bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of low fasting plasma glucose on mortality in the general population
Authors: Chevli Parag A , Ahmad Muhammad Imtiaz , Hari Krupal , Anees Muhammad Ali , Soliman Elsayed Z 
Published: June 2020

Background: While the association between hypoglycaemia and poor outcomes in diabetes is well established, it is unclear whether such an association is generalizable to those without diabetes. Methods: A total of 8497 participants free of cardiovascular disease and diabetes from the Third National Health and Nutrition Examination Survey were included. We examined the relationship between baseline low (<80 mg/dL) and high (⩾126 mg/dL) fasting plasma glucose compared to normal levels (80–99 mg/dL). Results: Over a median follow-up of 14 years, 2101 deaths occurred, of which 570 were due to cardiovascular disease. In a model adjusted for sociodemographic and cardiovascular disease risk factors, individuals with low fasting plasma glucose were at increased risk of cardiovascular disease and all-cause mortality [hazard ratio = 1.79 (95% confidence interval = 1.04–3.08) and hazard ratio = 1.35 (95% confidence interval = 1.02–1.78), respectively], compared to those with normal fasting plasma glucose. These associations were stronger among men than women for both cardiovascular disease mortality and all-cause mortality. Conclusion: Low fasting plasma glucose in individuals without diabetes is a risk factor for cardiovascular disease and all-cause mortality, especially in men.
Influence of CYP3A5 Genetic Polymorphism on Long-Term Renal Function in Chinese Kidney Transplant Recipients Using Limited Sampling Strategy and Abbreviated Area Under the Curve for Tacrolimus Monitoring
Authors: Cheung Chi Yuen , Chan Koon Ming , Wong Yuen Ting , Chak Wai Leung , Bekers Otto , van Hooff Johannes P. 
Published: June 2020

Introduction: Although the association between CYP3A5 gene polymorphism and tacrolimus dosing requirements was well established, the impact on how CYP3A5 genotype affects the acute rejection and long-term renal function in patients who received kidney transplants and were treated with tacrolimus remained controversial. Design: Sixty-seven Chinese patients with kidney transplants receiving de novo tacrolimus-based immunosuppressive therapy with known CYP3A5 genotype were divided into 2 groups. Those with at least 1 CYP3A5*1 allele were CYP3A5 expressers while homozygotes for the mutant allele CYP3A5*3 were nonexpressers. Instead of trough level, our center used abbreviated area under the curve for tacrolimus monitoring. Primary outcome was the long-term renal function between both groups while secondary outcomes included the weight-adjusted daily tacrolimus dose, graft survival, incidence of biopsy-proven acute rejection (BPAR), opportunistic infection, and cancer. Results: Thirty-five (52.2%) patients were CYP3A5 expressers while 32 were nonexpressers. Mean daily tacrolimus dose in the CYP3A5 expressers and nonexpressers was 0.08 (0.03) and 0.05 (0.02) mg/kg, respectively ( P < .01). Starting from 1-month posttransplant, the renal function was comparable between both groups, which persisted up to 10-year. Ten patients experienced BPAR rejection and there was no significant difference in the rejection-free survival between both groups ( P = .87). There was also no significant difference in the death-censored graft survival between both groups ( P = .86). Finally, the incidence of opportunistic infection and posttransplant cancer was similar between them. Discussion: There was no significant difference in renal function, graft survival, and acute rejection between CYP3A5 expressers and nonexpressers.
The reduction of concomitant glucocorticoids dosage following treatment with IL-1 receptor antagonist in adult onset Still’s disease. A systematic review and meta-analysis of observational studies
Authors: Ruscitti Piero , Ursini Francesco , Sota Jurgen , De Giorgio Roberto , Cantarini Luca , Giacomelli Roberto 
Published: June 2020

Background: Despite being burdened by significant adverse events, glucocorticoids (GCs) are frequently employed in managing adult onset Still’s disease (AOSD), prompting the need for GC-sparing agents. In this work, we performed a systematic review and meta-analysis to synthesize the evidence about the reduction of concomitant GCs dosage and the rate of GCs discontinuation in patients with AOSD who were treated with anakinra, a recombinant IL-1 receptor antagonist. Methods: A systematic review of the literature was completed to identify all available data concerning the reduction of concomitant GCs dosage following anakinra in AOSD and a meta-analysis was thus performed using a random-effects model. Results: A significant reduction of the GCs dosage was detected by pooled analysis with mean difference of –22.4 mg/day [95% confidence interval (CI): –28.8 to –16.1, p < 0.0001] at the last follow-up; the heterogeneity was moderate (Q = 11.67 with df = 7.00, p < 0.0001, I2 = 40.01%). Furthermore, the pooled analysis under a random effects model showed an overall rate of GCs discontinuation of 0.35 (95% CI: 0.28–0.41, p < 0.0001); the heterogeneity was low (Q = 5.99 with df = 6.00, p < 0.0001, I2 = 0.00%). Discussion: Taking together all these findings, the reduction of concomitant GCs dosage following anakinra could be suggested, leading to a further improvement of AOSD therapeutic strategy. Conclusion: In conclusion, the present systematic review and meta-analysis suggests the reduction of concomitant GCs dosage following treatment with anakinra. A percentage of patients are no longer required to be treated with GCs, discontinuing these drugs without a flare of the disease.
Impact of Accelerating Insulin on an Artificial Pancreas System Without Meal Announcement: An In Silico Examination
Authors: Colmegna Patricio , Cengiz Eda , Garcia-Tirado Jose , Kraemer Kristen , Breton Marc D. 
Published: June 2020

Background: Controlling postprandial blood glucose without the benefit of an appropriately sized premeal insulin bolus has been challenging given the delays in absorption and action of subcutaneously injected insulin during conventional and artificial pancreas (AP) system diabetes treatment. We aim to understand the impact of accelerating insulin and increasing aggressiveness of the AP controller as potential solutions to address the postprandial hyperglycemia challenge posed by unannounced meals through a simulation study. Methods: Accelerated rapid-acting insulin analogue is modeled within the UVA/Padova simulation platform by uniformly reducing its pharmacokinetic time constants (α multiplier) and used with a model predictive control, where the controller’s aggressiveness depends on α. Two sets of single-meal simulations were performed: (1) where we only tune the controller’s aggressiveness and (2) where we also accelerate insulin absorption and action to assess postprandial glycemic control during each intervention. Results: Mean percent of time spent within the 70 to 180 mg/dL postprandial glycemic range is significantly higher in set (2) than in set (1): 79.9, 95% confidence interval [77.0, 82.7] vs 88.8 [86.8, 90.9] ([Note to typesetter: Set all unnecessary math in text format and insert appropriate spaces between operators.] P < .05) for α = 2, and 81.4 [78.6, 84.3] vs 94.1 [92.6, 95.6] ( P < .05) for α = 3. A decrease in percent of time below 70 mg/dL is also detected: 0.9 [0.4, 2.2] vs 0.6 [0.2, 1.4] ( P = .23) for α = 2 and 1.4 [0.7, 2.8] vs 0.4 [0.1, 1.4] ( P < .05) for α = 3. Conclusion: These proof-of-concept simulations suggest that an AP without prandial insulin boluses combined with significantly faster insulin analogues could match the glycemic performance obtained with an optimal hybrid AP.
Color stability and degree of conversion of a novel dibenzoyl germanium derivative containing photo-polymerized resin luting cement
Authors: Alkhudhairy Fahad , Vohra Fahim , Naseem Mustafa , Owais Mosa Mohammed , Amer Abdulmajeed H Bin , Almutairi Khalid B 
Published: June 2020

Aim: To compare the color stability and degree of conversion (DC) of a resin cement containing a dibenzoyl germanium derivative photo-initiator (Variolink Esthetic) to resin cements containing conventional luting agents. Materials and Method: Spectrophotometry and Fourier transform infrared spectroscopy (FTIR) were used to compare the color stability and DC, respectively, of Variolink Esthetic compared to Calibra, Variolink-N, and NX3 resin cements. Ten specimens (1 × 2 mm2) of each resin cement were photo-polymerized and then subjected to color stability assessments. In addition, 30 samples of each of the four resin cements were prepared and then immersed in three staining solutions (tea, coffee, and distilled water) for two weeks. Changes in color for the immersed versus non-immersed specimens (control specimens) were determined by comparing ΔL (lightness), Δa, and Δb (color components), and an overall ΔE (color difference) obtained from spectrophotometry assays. One-way analysis of variance and a multiple comparison test (Tukey’s test) were used to analyze color stability and DC data. NX3 and Variolink Esthetic resin cements exhibited significantly lower values compared to the dual cured resin cements (Variolink-N and Calibra). Results: The highest DC values were observed among the photo-polymerized samples of Variolink Esthetic (87.18 ± 2.90%), while the lowest DC values were observed among the Variolink-N samples (44.55 ± 4.33%). Conclusion: The resin cement, Variolink Esthetic, containing a novel dibenzoyl germanium derivative photo-initiator exhibited superior color stability ( p < 0.05) and a higher DC than other resin cements containing conventional luting agents in an in vitro setting.
A novel hotspot and rare somatic mutation p.A138V, at TP53 is associated with poor survival of pancreatic ductal and periampullary adenocarcinoma patients
Authors: Saha Gourab , Singh Richa , Mandal Argha , Das Subrata , Chattopadhyay Esita , Panja Prasun , Roy Paromita , DeSarkar Navonil , Gulati Sumit , Ghatak Supriyo , Ghosh Shibajyoti , Banerjee Sudeep , Roy Bidyut , Ghosh Saurabh , Chaudhuri Dipankar , Arora Neeraj , Biswas Nidhan K. , Sikdar Nilabja 
Published: June 2020

Abstract
Background
Pancreatic Ductal Adenocarcinoma (PDAC) is a cancer of the exocrine pancreas and 5-year survival rates remain constant at 7%. Along with PDAC, Periampullary Adenocarcinoma (PAC) accounts for 0.5–2% of all gastrointestinal malignancies. Genomic observations were well concluded for PDAC and PACs in western countries but no reports are available from India till now.

Methods
Targeted Next Generation Sequencing were performed in 8 (5 PDAC and 3 PAC) tumour normal pairs, using a panel of 412 cancer related genes. Primary findings were replicated in 85 tumour samples (31 PDAC and 54 PAC) using the Sanger sequencing. Mutations were also validated by ASPCR, RFLP, and Ion Torrent sequencing. IHC along with molecular dynamics and docking studies were performed for the p.A138V mutant of TP53. Key polymorphisms at TP53 and its associated genes were genotyped by PCR-RFLP method and association with somatic mutations were evaluated. All survival analysis was done using the Kaplan-Meier survival method which revealed that the survival rates varied significantly depending on the somatic mutations the patients harboured.

Results
Among the total 114 detected somatic mutations, TP53 was the most frequently mutated (41%) gene, followed by KRAS, SMAD4, CTNNB1, and ERBB3. We identified a novel hotspot TP53 mutation (p.A138V, in 17% of all patients). Low frequency of KRAS mutation (33%) was detected in these samples compared to patients from Western counties. Molecular Dynamics (MD) simulation and DNA-protein docking analysis predicted p.A138V to have oncogenic characteristics. Patients with p.A138V mutation showed poorer overall survival (p = 0.01). So, our finding highlights elevated prevalence of the p53p.A138V somatic mutation in PDAC and pancreatobiliary PAC patients.

Conclusion
Detection of p.A138V somatic variant in TP53 might serve as a prognostic marker to classify patients. It might also have a role in determining treatment regimes. In addition, low frequency of KRAS hotspot mutation mostly in Indian PDAC patient cohort indicates presence of other early drivers in malignant transformation.
Laser capture microdissection coupled mass spectrometry (LCM-MS) for spatially resolved analysis of formalin-fixed and stained human lung tissues
Authors: Herrera Jeremy A. , Mallikarjun Venkatesh , Rosini Silvia , Montero Maria Angeles , Lawless Craig , Warwood Stacey , O’Cualain Ronan , Knight David , Schwartz Martin A. , Swift Joe 
Published: June 2020

Abstract
Background
Haematoxylin and eosin (H&E)—which respectively stain nuclei blue and other cellular and stromal material pink—are routinely used for clinical diagnosis based on the identification of morphological features. A richer characterization can be achieved by laser capture microdissection coupled to mass spectrometry (LCM-MS), giving an unbiased assay of the proteins that make up the tissue. However, the process of fixing and H&E staining of tissues provides challenges with standard sample preparation methods for mass spectrometry, resulting in low protein yield. Here we describe a microproteomics technique to analyse H&E-stained, formalin-fixed paraffin-embedded (FFPE) tissues.

Methods
Herein, we utilize heat extraction, physical disruption, and in column digestion for the analysis of H&E stained FFPE tissues. Micro-dissected morphologically normal human lung alveoli (0.082 mm3) and human lung blood vessels (0.094 mm3) from FFPE-fixed H&E-stained sections from Idiopathic Pulmonary Fibrosis (IPF) specimens (n = 3 IPF specimens) were then subject to a qualitative and then quantitative proteomics approach using BayesENproteomics. In addition, we tested the sensitivity of this method by processing and analysing a range of micro-dissected human lung blood vessel tissue volumes.

Results
This approach yields 1252 uniquely expressed proteins (at a protein identification threshold of 3 unique peptides) with 892 differentially expressed proteins between these regions. In accord with prior knowledge, our methodology approach confirms that human lung blood vessels are enriched with smoothelin, CNN1, ITGA7, MYH11, TAGLN, and PTGIS; whereas morphologically normal human lung alveoli are enriched with cytokeratin-7, -8, -18, -19, 14, and -17. In addition, we identify a total of 137 extracellular matrix (ECM) proteins and immunohistologically validate that laminin subunit beta-1 localizes to morphologically normal human lung alveoli and tenascin localizes to human lung blood vessels. Lastly, we show that this micro-proteomics technique can be applied to tissue volumes as low as 0.0125 mm3.

Conclusion
Herein we show that our multistep sample preparation methodology of LCM-MS can identify distinct, characteristic proteomic compositions of anatomical features within complex fixed and stained tissues.
The clinical application of microincision vein harvesting of the great saphenous vein in coronary artery bypass grafting
Authors: Zhang Shao-Zhong , Wang Guo-Xiang , Zhou Xiao-Tong 
Published: June 2020

Abstract
Background
The present study aimed to summarize the clinical application of microincision vein harvesting (MVH) of the great saphenous vein in coronary artery bypass grafting (CABG).

Methods
From July 2014 to October 2017, 160 patients underwent coronary artery bypass grafting. Among them, 80 patients received MVH of the great saphenous vein, and 80 received open venous harvesting (OVH). The results of the sampling operation, complications during hospitalization, and the long-term patency of the great saphenous vein were compared between the two groups.

Results
All the patients in both groups received successful operations. The difference in the length of the veins obtained and the injury of the veins was not statistically significant (P > 0.05). The difference in the long-term patency rate of the graft vessels between the two groups was not statistically significant. The in-hospital mortality rate was the same in both groups. The MVH group had noticeable advantages over the OVH group in terms of the vein collection times, the incision length, and the complications experienced when performing the leg incisions (P < 0.01). The time relating to the patients’ observed early out-of-bed activity was significantly longer in the MVH group. Furthermore, the patients’ hospitalization length was significantly shorter in the MVH group compared to the OVH group (P < 0.05). The MVH group had significant advantages in pain score and patient satisfaction, and this difference was also statistically significant (P < 0.05).

Conclusions
The MVH procedure met the requirements of CABG in vein grafting. When compared with OVH, MVH can significantly reduce leg incision complications and improve patients’ overall satisfaction with their hospital experience.
Isolation of Coxiella burnetii in patients with nonspecific febrile illness in South Korea
Authors: Lee Seung Hun , Lee Jae Hoon , Park Sungdo , Lee Hae Kyung , Do Hwang Seon , Jeong Hye Won , Heo Jung Yeon , Lee Yeong Seon 
Published: June 2020

Abstract
Background
The number of human Q fever cases in South Korea has been rapidly increasing since 2015. We report the first isolation of Coxiella burnetii in Korea in two patients who initially presented with non-specific febrile illness and were finally diagnosed with acute Q fever in South Korea.

Case presentation
Two adult patients with fever had serologic tests against C. burnetii initially negative, and polymerase chain reaction against 16S rRNA using whole blood was also negative. After bacterial amplification of C. burnetii in immune-depressed mice, we isolated C. burnetii from patients with acute Q fever. The isolates KZQ2 and KZQ3 were confirmed by polymerase chain reaction, nucleotide sequence analysis, and morphologic observation using a transmission electron microscope.

Conclusions
These results can help us understand the clinical and epidemiologic features of Q fever in South Korea.
Factors associated with occurrence of salmonellosis among children living in Mukuru slum, an urban informal settlement in Kenya
Authors: Mbae Cecilia , Mwangi Moses , Gitau Naomi , Irungu Tabitha , Muendo Fidelis , Wakio Zilla , Wambui Ruth , Kavai Susan , Onsare Robert , Wairimu Celestine , Ngetich Ronald , Njeru Frida , Van Puyvelde Sandra , Clemens John , Dougan Gordon , Kariuki Samuel 
Published: June 2020

Abstract
Background
In Kenya, typhoid fever and invasive non-typhoidal salmonellosis present a huge burden of disease, especially in poor-resource settings where clean water supply and sanitation conditions are inadequate. The epidemiology of both diseases is poorly understood in terms of severity and risk factors. The aim of the study was to determine the disease burden and spatial distribution of salmonellosis, as well as socioeconomic and environmental risk factors for these infections, in a large informal settlement near the city of Nairobi, from 2013 to 2017.

Methods
Initially, a house-to-house baseline census of 150,000 population in Mukuru informal settlement was carried out and relevant socioeconomic, demographic, and healthcare utilization information was collected using structured questionnaires. Salmonella bacteria were cultured from the blood and faeces of children < 16 years of age who reported at three outpatient facilities with fever alone or fever and diarrhea. Tests of association between specific Salmonella serotypes and risk factors were conducted using Pearson Chi-Square (χ2) test.

Results
A total of 16,236 children were recruited into the study. The prevalence of bloodstream infections by Non-Typhoidal Salmonella (NTS), consisting of Salmonella Typhimurium/ Enteriditis, was 1.3%; Salmonella Typhi was 1.4%, and this was highest among children < 16 years of age. Occurrence of Salmonella Typhimurium/ Enteriditis was not significantly associated with rearing any domestic animals. Rearing chicken was significantly associated with high prevalence of S. Typhi (2.1%; p = 0.011). The proportion of children infected with Salmonella Typhimurium/ Enteriditis was significantly higher in households that used water pots as water storage containers compared to using water directly from the tap (0.6%). Use of pit latrines and open defecation were significant risk factors for S. Typhi infection (1.6%; p = 0.048). The proportion of Salmonella Typhimurium/ Enteriditis among children eating street food 4 or more times per week was higher compared to 1 to 2 times/week on average (1.1%; p = 0.032).

Conclusion
Typhoidal and NTS are important causes of illness in children in Mukuru informal settlement, especially among children less than 16 years of age. Improving Water, Sanitation and Hygiene (WASH) including boiling water, breastfeeding, hand washing practices, and avoiding animal contact in domestic settings could contribute to reducing the risk of transmission of Salmonella disease from contaminated environments.
Malaria patterns across altitudinal zones of Mount Elgon following intensified control and prevention programs in Uganda
Authors: Siya Aggrey , Kalule Bosco John , Ssentongo Benard , Lukwa Akim Tafadzwa , Egeru Anthony 
Published: June 2020

AbstractBackgroundMalaria remains a major tropical vector-borne disease of immense public health concern owing to its debilitating effects in sub-Saharan Africa. Over the past 30 years, the high altitude areas in Eastern Africa have been reported to experience increased cases of malaria. Governments including that of the Republic of Uganda have responded through intensifying programs that can potentially minimize malaria transmission while reducing associated fatalities. However, malaria patterns following these intensified control and prevention interventions in the changing climate remains widely unexplored in East African highland regions. This study thus analyzed malaria patterns across altitudinal zones of Mount Elgon, Uganda.MethodsTimes-series data on malaria cases (2011–2017) from five level III local health centers occurring across three altitudinal zones; low, mid and high altitude was utilized. Inverse Distance Weighted (IDW) interpolation regression and Mann Kendall trend test were used to analyze malaria patterns. Vegetation attributes from the three altitudinal zones were analyzed using Normalized Difference Vegetation Index (NDVI) was used to determine the Autoregressive Integrated Moving Average (ARIMA) model was used to project malaria patterns for a 7 year period.ResultsMalaria across the three zones declined over the study period. The hotspots for malaria were highly variable over time in all the three zones. Rainfall played a significant role in influencing malaria burdens across the three zones. Vegetation had a significant influence on malaria in the higher altitudes. Meanwhile, in the lower altitude, human population had a significant positive correlation with malaria cases.ConclusionsDespite observed decline in malaria cases across the three altitudinal zones, the high altitude zone became a malaria hotspot as cases variably occurred in the zone. Rainfall played the biggest role in malaria trends. Human population appeared to influence malaria incidences in the low altitude areas partly due to population concentration in this zone. Malaria control interventions ought to be strengthened and strategically designed to achieve no malaria cases across all the altitudinal zones. Integration of climate information within malaria interventions can also strengthen eradication strategies of malaria in such differentiated altitudinal zones.