bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effect of Chemotherapeutic Agents upon the Metabolism of Intact Human Cancer Cells
Authors: Katchman Bernard J , Zipf Robert E , Murphy James P F 
Published: January 2020

Abstract
The effect of certain chemotherapeutic agents upon the metabolism of human ascites and leukemic leukocytes was investigated. Human leukemic blast cells show 2-3 times the respiratory activity of "chronic" cells. From a study of the effects of eight chemotherapeutic drugs upon the respiration of human leukemic leukocytes and human ascites cells, relative index of cell sensitivity was obtained.
The alkaloid, vinblastine sulfate, and the alkylating agents, triethylenethiophosphoramide and nitrogen mustard, were found to be more toxic to human cancer cells than the antimetabolites, 6-mercaptopurine, 8-azaguanine, aminopterin, diazouracil, or prednisone. Stimulation of aerobic glycolysis was found for all chemicals except aminopterin (no effect) and nitrogen mustard (inhibition).
No correlation between stimulation of lactic acid production and inhibition of respiration was found. Stimulation of lactic acid production could be produced under conditions where respiration was unchanged. Only nitrogen mustard differed in that inhibition of respiration always accompanied inhibition of lactic acid production.
Most chemotherapeutic agents tested are Pasteur effect inhibitors.
An unusual stimulation of glucose disappearance to products unknown as yet was caused by 6-mercaptopurine in all cells tested. The potential usefulness of a cell sensitivity test in clinical chemotherapy is discussed.
Use of a Lyophilized Serum Enzyme Preparation in Quality Control
Authors: Hersey Melford Q , Hartwell Katherine , Doe Richard P 
Published: January 2020

Abstract
A purified preparation of alkaline phosphatase added to standardized lyophilized serum has been used by the Minneapolis Veterans Administration Reference Laboratory to evaluate the routine alkaline phosphatase method in use in the 10 laboratories in its reference area.
Evidence of a marked need for investigation of the routine method for alkaline phosphatase determination was found in 3 of the 10 laboratories.
A semiquantitative phosphatase method proved to be useful as an independent procedure for use in evaluation of the different laboratories.
Metabolic Disorders Leading to Mental Deficiency
Authors: Karlsson J L 
Published: January 2020

Abstract
A new approach is described for the detection of abnormal metabolites in the urine of patients with known or suspected metabolic disorders. Distribution curves are presented for nonurea organic carbon and nitrogen which form a basis for judging whether grossly abnormal amounts of organic materials are present in the urine.
Families with recurrent mental retardation have been identified whose mental defect may be on an unknown metabolic basis.
A Rabbit Serum Calcium Lowering Factor from the Pituitary
Authors: Natelson Samuel , Pincus Joseph B , Rannazzisi Gandolfo 
Published: January 2020

Abstract
A factor has been shown to exist in ACTH fractions of porcine pituitaries which lowers serum calcium levels markedly when injected intramuscularly in the fasting rabbit. The lowest value is usually reached in 1.5-2.5 hr. and returns to normal in 5-6 hr.
It has been demonstrated that the activity of this material is independent of the ACTH activity of the preparation and is distinct from the pituitary hormones TSH, LTH, STH, or oxytocin. This factor can lower serum calcium levels in rabbits to as low as 50% of its initial value, producing tetany and convulsions.
It has also been demonstrated that the action of this material is not mediated through the release of 1-adrenaline, 1-noradrenaline, insulin, glucagon, ascorbic acid, cortisone, hydrocortisone, or corticosterone, all of which substances are without significant effect. Parathormone raises serum calcium levels slowly in the rabbit. Commercial vasopressin preparations are active in lowering serum calcium levels but not to as low a level as the ACTH preparations.
It has also been demonstrated that under stress the rabbit's serum calcium is spontaneously lowered to a slight degrree (10%).
The Renal Clearance of Sodium Pentaborate in Mice and Men
Authors: Farr Lee E , Konikowski T 
Published: January 2020

Abstract
The renal blood clearance of sodium pentaborate was observed in 8 patients undergoing neutron capture therapy for intracranial malignant tumors and was found to average 39.1 ml./min. per 1.73 sq. m. surface area.
The renal blood clearance was calculated for mice receiving sodium pentaborate intravenously in dosages of 25 µ.g./gm. body weight and 100 µg./gm., calculated as boron. The average clearance for the mice receiving the larger dose was 0.207 ml./min. for a 21-gm. mouse. The average clearance for the mice receiving the smaller dose was 0.192 ml./min. per 21-gm. mouse.
For the mouse, clearance calculated for a surface area of 1.73 sq. m., as was used in man, averages 40 ml./min.
No toxic effects on renal function were observed in mice at the higher dosage.
Competition Between Calcium, Strontium, and Magnesium for Absorption in the Isolated Rat Intestine
Authors: Hendrix J Z , Alcock N W , Archibald R M 
Published: January 2020

Abstract
Rats 1-2 mo. old were placed on a low calcium or a low calcium and low magnesium diet. Absorption in isolated rat intestine was studied in vitro. Duodenal segments which actively took up and actively transported Ca45++ well, actively took up and actively transported Sr85++ well; where Ca45++ active uptake and active transport was poor, that of Sr85++ was low. The uptakes of Ca45++, Sr85++, and Mg28++ by the gut tissue were greater than the amounts transported. Ca++, Sr++, and Mg++ decreased the active uptake of Ca45++ and Sr85++ by the duodenum. Ca++ decreased the rate of active transport to the serosal media of Ca40++ and Sr85++. Ca++ was more effective in decreasing the active uptake of Sr55++ than was Sr++. The active uptake of Ca45++ by the ileum was reduced by Mg++ and Sr++. The active uptake of Mg28++ by the ileum was reduced by Ca++. The rate at which Mg28++ crosses and is taken up by the small intestine increases as one progresses from the proximal duodenum to the distal ileum. Ca++ was actively transported by the colon. Ca++, Sr++, and Mg++ appear to share a common pathway for absorption by the gut, but in the various areas of the intestine the rate of absorption of a particular divalent cation and the degree of competition between the divalent cations varies. Therefore, the absorption of a particular cation may involve also other pathways.
Sequencing Analysis of Plasma Epstein-Barr Virus DNA Reveals Nasopharyngeal Carcinoma-Associated Single Nucleotide Variant Profiles
Authors: Lam W K Jacky , Ji Lu , Tse O Y Olivia , Cheng Suk Hang , Jiang Peiyong , Lee P H Patrick , Lin S Vivien , Hui Edwin P , Ma Brigette B Y , Chan Anthony T C , Chan K C Allen , Chiu Rossa W K , Lo Y M Dennis 
Published: January 2020

Abstract

Background
Nasopharyngeal carcinoma (NPC) is strongly associated with Epstein-Barr virus (EBV) infection. Plasma EBV DNA is a validated screening tool for NPC. In screening, there are some individuals who do not have NPC but carry EBV DNA in plasma. Currently it is not known from screening if there may be any genotypic differences in EBV isolates from NPC and non-NPC subjects. Also, low concentrations of EBV DNA in plasma could pose challenge to such EBV genotypic analysis through plasma DNA sequencing.

Methods
In a training dataset comprised of plasma DNA sequencing data of NPC and non-NPC subjects, we studied the difference in the EBV single nucleotide variant (SNV) profiles between the two groups. The most differentiating SNVs across the EBV genome were identified. We proposed an NPC risk score to be derived from the genotypic patterns over these SNV sites. We subsequently analyzed the NPC risk scores in a testing set.

Results
A total of 661 significant SNVs across the EBV genome were identified from the training set. In the testing set, NPC plasma samples were shown to have high NPC risk scores, which suggested the presence of NPC-associated EBV SNV profiles. Among the non-NPC samples, there was a wide range of NPC risk scores. These results support the presence of diverse SNV profiles of EBV isolates from non-NPC subjects.

Conclusion
EBV genotypic analysis is feasible through plasma DNA sequencing. The NPC risk score may be used to inform the cancer risk based on the EBV genome-wide SNV profile.
GLEE: Geometric Laplacian Eigenmap Embedding
Authors: Torres Leo , Chan Kevin S , Eliassi-Rad Tina 
Published: January 2020

AbstractGraph embedding seeks to build a low-dimensional representation of a graph $G$. This low-dimensional representation is then used for various downstream tasks. One popular approach is Laplacian Eigenmaps (LE), which constructs a graph embedding based on the spectral properties of the Laplacian matrix of $G$. The intuition behind it, and many other embedding techniques, is that the embedding of a graph must respect node similarity: similar nodes must have embeddings that are close to one another. Here, we dispose of this distance-minimization assumption. Instead, we use the Laplacian matrix to find an embedding with geometric properties instead of spectral ones, by leveraging the so-called simplex geometry of $G$. We introduce a new approach, Geometric Laplacian Eigenmap Embedding, and demonstrate that it outperforms various other techniques (including LE) in the tasks of graph reconstruction and link prediction.
MTMR4 SNVs modulate ion channel degradation and clinical severity in congenital long QT syndrome: insights in the mechanism of action of protective modifier genes
Authors: Lee Yee-Ki , Sala Luca , Mura Manuela , Rocchetti Marcella , Pedrazzini Matteo , Ran Xinru , Mak Timothy S H , Crotti Lia , Sham Pak C , Torre Eleonora , Zaza Antonio , Schwartz Peter J , Tse Hung-Fat , Gnecchi Massimiliano 
Published: January 2020

Abstract

Aims
In long QT syndrome (LQTS) patients, modifier genes modulate the arrhythmic risk associated with a disease-causing mutation. Their recognition can improve risk stratification and clinical management, but their discovery represents a challenge. We tested whether a cellular-driven approach could help to identify new modifier genes and especially their mechanism of action.

Methods and results
We generated human-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) from two patients carrying the same KCNQ1-Y111C mutation, but presenting opposite clinical phenotypes. We showed that the phenotype of the iPSC-CMs derived from the symptomatic patient is due to impaired trafficking and increased degradation of the mutant KCNQ1 and wild-type human ether-a-go-go-related gene. In the iPSC-CMs of the asymptomatic (AS) patient, the activity of an E3 ubiquitin-protein ligase (Nedd4L) involved in channel protein degradation was reduced and resulted in a decreased arrhythmogenic substrate. Two single-nucleotide variants (SNVs) on the Myotubularin-related protein 4 (MTMR4) gene, an interactor of Nedd4L, were identified by whole-exome sequencing as potential contributors to decreased Nedd4L activity. Correction of these SNVs by CRISPR/Cas9 unmasked the LQTS phenotype in AS cells. Importantly, the same MTMR4 variants were present in 77% of AS Y111C mutation carriers of a separate cohort. Thus, genetically mediated interference with Nedd4L activation seems associated with protective effects.

Conclusion
Our finding represents the first demonstration of the cellular mechanism of action of a protective modifier gene in LQTS. It provides new clues for advanced risk stratification and paves the way for the design of new therapies targeting this specific molecular pathway.
Vascular effects of serelaxin in patients with stable coronary artery disease: a randomized placebo-controlled trial
Authors: Corcoran David , Radjenovic Aleksandra , Mordi Ify R , Nazir Sheraz A , Wilson Simon J , Hinder Markus , Yates Denise P , Machineni Surendra , Alcantara Jose , Prescott Margaret F , Gugliotta Barbara , Pang Yinuo , Tzemos Niko , Semple Scott I , Newby David E , McCann Gerry P , Squire Iain , Berry Colin 
Published: January 2020

Abstract

Aims
The effects of serelaxin, a recombinant form of human relaxin-2 peptide, on vascular function in the coronary microvascular and systemic macrovascular circulation remain largely unknown. This mechanistic, clinical study assessed the effects of serelaxin on myocardial perfusion, aortic stiffness, and safety in patients with stable coronary artery disease (CAD).

Methods and results
In this multicentre, double-blind, parallel-group, placebo-controlled study, 58 patients were randomized 1:1 to 48 h intravenous infusion of serelaxin (30 µg/kg/day) or matching placebo. The primary endpoints were change from baseline to 47 h post-initiation of the infusion in global myocardial perfusion reserve (MPR) assessed using adenosine stress perfusion cardiac magnetic resonance imaging, and applanation tonometry-derived augmentation index (AIx). Secondary endpoints were: change from baseline in AIx and pulse wave velocity, assessed at 47 h, Day 30, and Day 180; aortic distensibility at 47 h; pharmacokinetics and safety. Exploratory endpoints were the effect on cardiorenal biomarkers [N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hsTnT), endothelin-1, and cystatin C]. Of 58 patients, 51 were included in the primary analysis (serelaxin, n = 25; placebo, n = 26). After 2 and 6 h of serelaxin infusion, mean placebo-corrected blood pressure reductions of −9.6 mmHg (P = 0.01) and −13.5 mmHg (P = 0.0003) for systolic blood pressure and −5.2 mmHg (P = 0.02) and −8.4 mmHg (P = 0.001) for diastolic blood pressure occurred. There were no between-group differences from baseline to 47 h in global MPR (−0.24 vs. −0.13, P = 0.44) or AIx (3.49% vs. 0.04%, P = 0.21) with serelaxin compared with placebo. Endothelin-1 and cystatin C levels decreased from baseline in the serelaxin group, and there were no clinically relevant changes observed with serelaxin for NT-proBNP or hsTnT. Similar numbers of serious adverse events were observed in both groups (serelaxin, n = 5; placebo, n = 7) to 180-day follow-up.

Conclusion
In patients with stable CAD, 48 h intravenous serelaxin reduced blood pressure but did not alter myocardial perfusion.
Antiapoptotic activity of Chlamydia trachomatis Pgp3 protein involves activation of the ERK1/2 pathway mediated by upregulation of DJ-1 protein
Authors: Luo Fangzhen , Shu Mingyi , Gong Silu , Wen Yating , He Bei , Su Shengmei , Li Zhongyu 
Published: January 2020

ABSTRACT
Chlamydia trachomatis has evolved strategies to prevent host cell apoptosis to evade the host immune defense. However, the precise mechanisms of antiapoptotic activity of C. trachomatis still need to be clarified. Pgp3, one of eight plasmid proteins of C. trachomatis, has been identified to be closely associated with chlamydial virulence. In this study, we attempted to explore the effects and the mechanisms of Pgp3 protein on apoptosis in HeLa cells; the results showed that Pgp3 increased Bcl-2/Bax ratio and prevented caspase-3 activation to suppress apoptosis induced by TNF-α and cycloheximide (CHX) through ERK1/2 pathway activation. Downregulation of DJ-1 with siRNA-DJ-1(si-DJ-1) reduced ERK1/2 phosphorylation and elevated apoptotic rate significantly in Pgp3-HeLa cells. However, inhibition of ERK1/2 signal pathway with ERK inhibitor PD98059 had little effect on DJ-1 expression. These findings confirm that plasmid protein Pgp3 contributes to apoptosis resistance through ERK1/2 signal pathway mediated by upregulation of DJ-1 expression. Therefore, the present study provided novel insights into the role of Pgp3 in apoptosis and suggested that manipulation of the host apoptosis response could be a new approach for the prevention and treatment of C. trachomatis infection.
Towards Spatially Explicit Quantification of Pre- and Postfire Fuels and Fuel Consumption from Traditional and Point Cloud Measurements
Authors: Hudak Andrew T , Kato Akira , Bright Benjamin C , Loudermilk E Louise , Hawley Christie , Restaino Joseph C , Ottmar Roger D , Prata Gabriel A , Cabo Carlos , Prichard Susan J , Rowell Eric M , Weise David R 
Published: January 2020

Abstract
Methods to accurately estimate spatially explicit fuel consumption are needed because consumption relates directly to fire behavior, effects, and smoke emissions. Our objective was to quantify sparkleberry (Vaccinium arboretum Marshall) shrub fuels before and after six experimental prescribed fires at Fort Jackson in South Carolina. We used a novel approach to characterize shrubs non-destructively from three-dimensional (3D) point cloud data collected with a terrestrial laser scanner. The point cloud data were reduced to 0.001 m–3 voxels that were either occupied to indicate fuel presence or empty to indicate fuel absence. The density of occupied voxels was related significantly by a logarithmic function to 3D fuel bulk density samples that were destructively harvested (adjusted R2 = .32, P &lt; .0001). Based on our findings, a survey-grade Global Navigation Satellite System may be necessary to accurately associate 3D point cloud data to 3D fuel bulk density measurements destructively collected in small (submeter) shrub plots. A recommendation for future research is to accurately geolocate and quantify the occupied volume of entire shrubs as 3D objects that can be used to train models to map shrub fuel bulk density from point cloud data binned to occupied 3D voxels.
Hospitalization Rates in Older Adults With Albuminuria: The Cardiovascular Health Study
Authors: Barzilay Joshua I , Buzkova Petra , Shlipak Michael G , Bansal Nisha , Garimella Pranav , Mukamal Kenneth J 
Published: January 2020

Abstract

Background
Albuminuria is highly prevalent among older adults, especially those with diabetes. It is associated with several chronic diseases, but its overall impact on the health of older adults, as measured by hospitalization, has not been quantified.

Method
We followed up 3,110 adults, mean age 78 years, for a median 9.75 years, of whom 654 (21%) had albuminuria (≥30 mg albumin/gram creatinine) at baseline. Poisson regression models, adjusted for cardiovascular, renal, and demographic factors, were used to evaluate the association of albuminuria with all-cause and cause-specific hospitalizations, as defined by ICD, version 9, categories.

Results
The rates of hospitalization per 100 patient-years were 65.85 for participants with albuminuria and 37.55 for participants without albuminuria. After adjustment for covariates, participants with albuminuria were more likely to be hospitalized for any cause than participants without albuminuria (incident rate ratio, 1.39 [95% confidence intervals, 1.27. 1.53]) and to experience more days in hospital (incident rate ratio 1.56 [1.37, 1.76]). The association of albuminuria with hospitalization was similar among participants with and without diabetes (adjusted incident rate ratio for albuminuria versus no albuminuria: diabetes 1.37 [1.11, 1.70], no diabetes 1.40 [1.26, 1.55]; p interaction nonsignificant). Albuminuria was significantly associated with hospitalization for circulatory, endocrine, genitourinary, respiratory, and injury categories.

Conclusions
Albuminuria in older adults is associated with an increased risk of hospitalization for a broad range of illnesses. Albuminuria in the presence or absence of diabetes appears to mark a generalized vulnerability to diseases of aging among older adults.
The development of the privy council oath in Tudor England*
Authors: McGovern Jonathan 
Published: January 2020

Abstract
From the early thirteenth century to the present day, privy councillors have been required to swear an oath of office. This article demonstrates that at least four different council oaths were administered by chancery during the Tudor period, and that William Cecil drafted yet another revised oath in 1558, although this was never finished. The article compares the respective texts and explains the administrative and political reasons for each of the revisions. It goes on to examine evidence from these oaths that suggests developments in the conception of counsel in the sixteenth century. It concludes with transcriptions of the four operational oaths and the Cecilian draft.
Enteral immunonutrition versus enteral nutrition for patients undergoing oesophagectomy: a systematic review and meta-analysis
Authors: Li Xiao-Kun , Zhou Hai , Xu Yang , Cong Zhuang-Zhuang , Wu Wen-Jie , Luo Jing , Jiang Zhi-Sheng , Shen Yi 
Published: January 2020

Abstract

OBJECTIVES
According to retrospective studies, oesophageal carcinoma is the second deadliest gastrointestinal cancer after gastric cancer. Enteral immunonutrition (EIN) has been increasingly used to enhance host immunity and relieve the inflammatory response of patients undergoing oesophagectomy; however, conclusions across studies remain unclear. We aimed to evaluate the effect of EIN on the clinical and immunological outcomes of patients undergoing oesophagectomy.

METHODS
Four electronic databases (MEDLINE, Embase, Web of Science and Cochrane Library) were used to search articles in peer-reviewed, English-language journals. The mean difference, relative risk or standard mean difference with 95% confidence interval were calculated. Heterogeneity was assessed by the Cochran’s Q test and I2 statistic combined with the corresponding P-value. The analysis was carried out with RevMan 5.3.

RESULTS
Six articles were finally included, with a total of 320 patients with oesophageal cancer. The meta-analysis results showed that EIN did not improve clinical outcomes (such as infectious complications, pneumonia, surgical site infection, anastomotic leak and postoperative hospital stay) or immune indices [referring to C-reactive protein, interleukin (IL)-6, IL-8, tumour necrosis factor-α]. Descriptive analysis suggested that EIN also increased the serum concentrations of IgG and the percentage of the B-cell fraction. Thus, its impact on IL-8 and IL-6 remains inconsistent.

CONCLUSIONS
The early-stage impact of EIN on immunological status in patients undergoing oesophagectomy is still unclear. According to the results of this meta-analysis, whether EIN could improve the clinical outcomes or biological status after oesophagectomy compared to standard enteral nutrition is uncertain. Since the impact of EIN is unclear, current guidelines that strongly advise the use of EIN should be changed, as the utility of EIN is very uncertain. More appropriately powered clinical studies are warranted to confirm its effectiveness.