Miracle-dz/UniFAR-FTUs huggingface dataset:
Real-world evaluation of glycemic control among patients with type 2 diabetes mellitus treated with canagliflozin versus dipeptidyl peptidase-4 inhibitors

Abstract Objective To evaluate glycemic control among patients with type 2 diabetes mellitus (T2DM) treated with canagliflozin (CANA) vs. dipeptidyl peptidase-4 (DPP-4) inhibitors. Methods Using integrated claims and lab data from a US health plan of commercial and Medicare Advantage enrollees, this matched-control cohort study assessed adult T2DM patients receiving treatment with CANA or DPP-4 inhibitors (1 April 2013–31 December 2013). Cohorts were chosen hierarchically; the first pharmacy claim for CANA was identified as the index date; then the first pharmacy claim for a DPP-4 inhibitor was identified and index date set. Eligible patients had 6 months of continuous health plan enrollment before the index date (baseline) and 9 months after (follow-up) and no evidence of index drug in baseline. Patients were matched 1:1 using propensity score matching. Changes in glycated hemoglobin (HbA1c) and percentages of patients with HbA1c <8% and <7% during the follow-up were evaluated. Results The matched CANA and DPP-4 inhibitor cohorts (53.2% treated with sitagliptin) included 2766 patients each (mean age: 55.7 years). Among patients with baseline and follow-up HbA1c results, mean baseline HbA1c values were similar, 8.62% and 8.57% (p = 0.615) for the CANA (n = 729) and DPP-4 inhibitor (n = 710) cohorts, respectively. Change in HbA1c was greater among patients in the CANA cohort than for those in the DPP-4 inhibitor cohort (−0.92% vs. −0.63%, p < 0.001), and also among the subset of patients with baseline HbA1c ≥7% (-1.07% [n = 624] vs. −0.79% [n = 603], p = 0.004). During follow-up, greater percentages of the CANA cohort relative to the DPP-4 inhibitor cohort achieved HbA1c of <8% (66.0% vs. 58.6%, p = 0.004) and <7% (35.4% vs. 29.9%, p = 0.022). Limitations This study was observational and residual confounding remains a possibility. Conclusions In this real-world study of patients with T2DM, CANA use was associated with greater HbA1c reduction and higher percentages of patients attaining HbA1c goals than those treated with DPP-4 inhibitors.
Folding and misfolding pathways of G-quadruplex DNA

G-quadruplexes adopt various folding topologies, but information on their folding pathways remains scarce. Here, we used electrospray mass spectrometry to detect and quantify the specifically bound potassium ions, and circular dichroism to characterize the stacking topology of each ensemble. For human telomeric (hTel) sequences containing the d((GGGTTA)3GGG) core, K+ binding affinity and cooperativity strongly depends on the chosen construct. The shortest sequences bind only one K+ at low KCl concentration, and this 2-quartet G-quadruplex is antiparallel. Flanking bases increase the K+ binding cooperativity. To decipher the folding pathways, we investigated the kinetics of K+ binding to telomeric (hybrid) and c-myc (parallel) G-quadruplexes. G-quadruplexes fold via branched pathways with multiple parallel reactions. Up to six states (one ensemble without K+, two ensembles with 1-K+ and three ensembles with 2-K+) are separated based on their formation rates and ion mobility spectrometry. All G-quadruplexes first form long-lived misfolded structures (off-pathway compared to the most stable structures) containing one K+ and two quartets in an antiparallel stacking arrangement. The results highlight the particular ruggedness of G-quadruplex nucleic acid folding landscapes. Misfolded structures can play important roles for designing artificial G-quadruplex based structures, and for conformational selection by ligands or proteins in a biological context.
[Anterior corpectomy combined with intervertebral decompression and fusion for multilevel cervical spondylotic myelopathy].

OBJECTIVE To investigate the clinical outcomes of anterior corpectomy combined with anterior intervertebral decompression and fusion for multilevel cervical spondylotic myelopathy. METHODS The clinical data of 28 patients with multilevel cervical spondylotic myelopathy who underwent surgery from October 2012 to June 2014 were retrospectively analyzed. There were 18 males and 10 females, aged from 45 to 77 years old with an average of (60.11±9.37) years. Three levels were involved in 27 cases, while four levels were involved in 1 case. The preoperative JOA score was 8.89±1.87; the fusion segments angles was (4.87±4.56)°; and the cervical curvature was (11.68±1.25)°. Anterior hybrid decompression and fusion were performed in 28 patients. The fusion segments angles and the cervical curvature were assessed by X-rays at 1, 12 months after operation, respectively. JOA score was used to evaluate the clinical effect. RESULTS The operative time was 163 min on average (ranged from 120 to 205 min), and intraoperative bleeding was 198 ml on average(ranged from 100 to 300 ml). Hoarseness occurred in 1 case and got recovery at 3 weeks after operation and choke cough occurred in 1 case, and got improvement at 1 week after operation. All the patients were regularly followed for 12-24 months with an average of(18.46±3.20) months. Graft bone obtained fusion at 12 months after operation and the position of internal fixation was good. The fusion segments angles, the cervical curvature and JOA scores were significantly improved at 1, 12 months after operation(P<0.05). The improvement rate of JOA score was(46.46±20.26)% at 12 months after operation, 12 cases got excellent results, 14 good and 2 fair. CONCLUSIONS Anterior corpectomy combined with anterior intervertebral decompression and fusion is safe and effective and can get satisfactory effects for multilevel cervical spondylotic myelopathy.
A New Paradigm for Practical Application of Behavioral Finance

The authors believe that the next phase in the practical application of behavioral finance is to correlate established investor biases with the psychographic and gender profiles of specific investors. They ask, “Are certain personality types or genders susceptible to biases identified in the behavioral finance literature? If so, can this information be helpful to investors and advisors? ” Their study examines the responses of 100 investors given a detailed Myers-Briggs Type Indicator® personality test and a questionnaire designed to reveal investor biases. They find that personality types and genders are differentially susceptible to numerous investor biases; accordingly, they introduce a new paradigm of practical application of behavioral finance that leverages their findings.
Text/Graphics Separation in Color Maps

Text/graphics separation in document image analysis is one of the main concerns in present research work. The complexity enhances when both text and graphics overlap in the context of maps in color images. This paper discusses a number of improvements to text/graphics separation methods to make it suitable for maps. Emphasize is given to the overlapping regions of text and graphics. It also discusses a method of color separation using clustering method for the purpose of text/graphics separation
Diet-dependent changes in the intestinal DNA methylome after introduction of enteral feeding in preterm pigs.

AIM To examine how enteral feeding affects the intestinal epigenome and gene expression just after preterm birth. MATERIALS & METHODS Intestinal tissue from preterm pigs, modeling preterm infants, was collected at birth and 5 days after gradual introduction of infant formula or bovine colostrum. The intestinal tissue was analyzed by reduced representation bisulfite sequencing and real-time qPCR. RESULTS Relative to colostrum, formula increased bacterial epithelial adherence and lipopolysaccharide binding protein (LBP) expression, which was regulated by promoter methylation. Diet-dependent changes in DNA methylation and/or mRNA expression were related to innate immune response, hypoxia, angiogenesis and epithelial-mesenchymal transition pathways (e.g., TTC38, IL8, C3, HIF1A and VEGFR1). CONCLUSION Epigenetic changes may mediate important effects of the first feeding on intestinal development in preterm neonates.
Isolation of Brucella pinnipedialis from Grey Seals (Halichoerus grypus) in the Baltic Sea

Abstract Brucella infection in seals was reported for the first time in 1994 around the coast of Scotland. Since then, marine mammal Brucella infections were found to be widely distributed in the northern hemisphere. Two Brucella species affect marine mammals: Brucella pinnipedialis in pinnipeds and Brucella ceti in cetaceans. We examined the livers of Baltic grey seals (Halichoerus grypus) from the Finnish coast (n=122) hunted, found dead, or killed as by-catch in fishing gear in 2013–15 as part of population health monitoring. We detected B. pinnipedialis in the livers of three grey seals. The bacterium was isolated from livers displaying parasitic cholangitis. We also detected Brucella DNA in liver flukes (Pseudamphistomum truncatum) obtained from a Brucella-infected grey seal, suggesting that flukes might be possible vectors of this pathogen in the marine environment.
Reduced AQP1, -2, and -3 levels in kidneys of rats with CRF induced by surgical reduction in renal mass.

Urinary concentration characteristically decreases in response to a reduction in renal mass in chronic renal failure (CRF). In the present study, we examined whether there are changes in the expression of aquaporins in rats where CRF was induced by 5/6 nephrectomy. Plasma creatinine levels were significantly elevated consistent with significant CRF: 135.7 ± 15.1 ( n = 17, CRF) vs. 33.9 ± 1.1 μmol/l ( n = 11, sham), P < 0.05. Two weeks after 5/6 nephrectomy, the remnant kidneys were hypertrophied, and total renal mass increased to 65 ± 3% of sham levels ( P < 0.05). Urine production increased markedly from 40 ± 2 to 111 ± 3 μl ⋅ min-1 ⋅ kg-1in CRF rats ( P < 0.05), whereas urine osmolality and solute-free water reabsorption decreased significantly. Quantitative immunoblotting of total kidney membrane fractions revealed a significant decrease in total kidney AQP2 expression in CRF rats to 43 ± 12% of sham levels ( P < 0.05). A similar reduction was observed for AQP1 and AQP3. Furthermore, the increased urine output and decreased urine osmolality persisted in CRF rats despite 7 days treatment with 1-desamino-[8-d-arginine]vasopressin (DDAVP, 0.1 μg/h sc) compared with untreated sham-operated controls. Also, there was no change in AQP2 expression (which remained at 38 ± 3% of sham levels, P < 0.05), urine output, or urine osmolality between CRF rats with or without DDAVP treatment. Immunocytochemistry confirmed the decreased AQP2 expression in collecting duct principal cells in CRF rats, with a predominant apical labeling. In conclusion, the results demonstrated that there was a significant vasopressin-resistant downregulation of AQP2 and AQP3 as well as downregulation of AQP1 associated with the polyuria in CRF rats.
Oncogenic regulation of tumor metabolic reprogramming

Development of malignancy is accompanied by a complete metabolic reprogramming closely related to the acquisition of most of cancer hallmarks. In fact, key oncogenic pathways converge to adapt the metabolism of carbohydrates, proteins, lipids and nucleic acids to the dynamic tumor microenvironment, conferring a selective advantage to cancer cells. Therefore, metabolic properties of tumor cells are significantly different from those of non-transformed cells. In addition, tumor metabolic reprogramming is linked to drug resistance in cancer treatment. Accordingly, metabolic adaptations are specific vulnerabilities that can be used in different therapeutic approaches for cancer therapy. In this review, we discuss the dysregulation of the main metabolic pathways that enable cell transformation and its association with oncogenic signaling pathways, focusing on the effects of c-MYC, hypoxia inducible factor 1 (HIF1), phosphoinositide-3-kinase (PI3K), and the mechanistic target of rapamycin (mTOR) on cancer cell metabolism. Elucidating these connections is of crucial importance to identify new targets and develop selective cancer treatments that improve response to therapy and overcome the emerging resistance to chemotherapeutics.
An ultra-wide range (0.01-240 Gbps) transmitter with latched AC-coupled driver and dummy data transient generator

: This paper proposes an ultra-wide range transmitter with a latched AC-coupled driver (LACD) and a dummy data transient generator (DDTG). The LACD expands the low-frequency range by preventing the capacitor discharge issue of the high-speed AC-coupled driver and the DDTG enhances the high-frequency range by generating a dummy transient pattern to stabilize the power node ﬂ uctuation induced by the dense and sparse pattern dependency in the case of coding-less application. A 24-channel test chip designed with 40-nm CMOS technology achieved an ultra-wide frequency range (0.01 – 10 Gbps / channel) and ultra-wide bandwidth from 0.01 Gbps (0.01 Gbps × 1 channel) to 240 Gbps (10 Gbs × 24 channels) and a high area e ﬃ ciency (0.0027 mm 2 / Gbps / channel). At the data rates of 5 and 10 Gbps, the jitters with DDTG were 50% lower than attained without DDTG.
Risk Factors for Diabetic Retinopathy Among Homeless Veterans

Homeless patients have high rates of visual impairment and lower rates of glycemic control than housed patients. Although diabetic retinopathy (DR) is the most common cause of new visual impairment and legal blindness in the developed world, little is known about differential risk factors for and rates of DR in homeless versus housed populations. This study aimed to compare the rates of DR between homeless and housed patients with diabetes at the Greater Los Angeles Veterans Affairs Health care System (GLA) and identify clinical and psychosocial predictors of DR rates. We performed secondary database analyses of veterans with diabetes who received care at GLA between October 1, 2013 and September 30, 2015. We described differences in demographic, clinical, and psychosocial characteristics associated with DR in homeless versus housed patients, and created a logistic regression model to identify independent predictors of DR. We found that diabetic veterans who were homeless, as compared with those who were housed, had higher rates of substance use disorders and mental health diagnoses, more primary care and mental health visits, and were more likely to have had diabetic retinopathy eye screening according to guidelines. Multiple logistic regression modeling predicting having DR, revealed that having DR was independently associated with not being homeless (i.e., being housed), older age, having had retinal screening, anemia, higher systolic blood pressure, insulin use, microalbuminuria, and higher HbA1c. Homeless diabetic veterans’ lower rates of DR may be due to the GLA VA’s tailored and intensive psychological and medical resources for homeless veteran patients.
Cloning, functional characterization, and localization of a rat renal Na+-dicarboxylate transporter.

We report here the isolation, functional characterization, tissue distribution, and membrane localization of rat renal Na+-dicarboxylate transporter (rNaDC-1). rNaDC-1 consists of 2,245 nucleotides, and the deduced amino acid sequence showed 73% and 75% identity to rabbit and human NaDC-1, respectively. When expressed in Xenopus laevis oocytes, rNaDC-1 mediated sodium-dependent uptake of di- and tricarboxylates. Substrates of rNaDC-1 evoked inward currents in oocytes expressed with rNaDC-1; succinate, α-ketoglutarate, and glutarate were relatively high-affinity substrates, and citrate was a low-affinity substrate of rNaDC-1. The coupling ratio of citrate to charge was determined to be 1:1 at pH 7.4; influx of one positive charge per citrate molecule suggests a symport of three Na+with a divalent citrate. Expression of rNaDC-1 mRNA was detected in the kidney and the small and large intestines. Immunohistochemistry using polyclonal antibodies raised against the 14 amino acids at the COOH terminus of rNaDC-1 revealed that rNaDC-1 is localized exclusively in the luminal membrane of S2 and S3.
Mechanism of action of cholera toxin on the opossum internal anal sphincter smooth muscle.

Cholera toxin (CTX), an activator of Gs protein, is an important pharmacological tool in G protein research. The effect and the mechanism of action of CTX in the gastrointestinal smooth muscle, including the internal anal sphincter (IAS), are not known. The present investigation was carried out to examine the effects of CTX on the signal transduction associated with the adenylate cyclase (AC) pathway on the basal tone of the IAS smooth muscle. CTX caused a prompt and dose-dependent fall in the basal tone of the IAS that was not affected by the neurotoxins TTX and ω-conotoxin or the nitric oxide synthase inhibitor N G-nitro-l-arginine. The cyclooxygenase inhibitor indomethacin, cAMP-dependent protein kinase inhibitor Rp-8-bromoadenosine 3',5' cyclic monophosphorothioate inhibited CTX-induced IAS smooth muscle relaxation. Furthermore, CTX caused a concentration-dependent relaxation of the isolated smooth muscle cells (SMC) of the IAS, which was blocked by Gsα antibody (Gsα-Ab). The IAS smooth muscle relaxation was accompanied with an increase in the GTPase activity that was also specifically blocked by Gsα-Ab. We conclude that a major part of the inhibitory action of CTX in the IAS is via the direct response of the SMC that is linked with Gs protein to the AC pathway. A part of the inhibitory action of CTX on the smooth muscle occurs via the activation of cyclooxygenase pathway. The relative contribution of such actions of CTX in the smooth muscle in the gastrointestinal motility disturbances following cholera infection remains to be determined.
Receptor-mediated inhibition of renal Na+-K+-ATPase is associated with endocytosis of its α- and β-subunits.

The mechanisms involved in receptor-mediated inhibition of Na+-K+-ATPase remain poorly understood. In this study, we evaluate whether inhibition of proximal tubule Na+-K+-ATPase activity by dopamine is linked to its removal from the plasma membrane and internalization into defined intracellular compartments. Clathrin-coated vesicles were isolated by sucrose gradient centrifugation and negative lectin selection, and early and late endosomes were separated on a flotation gradient. Inhibition of Na+-K+-ATPase activity by dopamine, in contrast to its inhibition by ouabain, was accompanied by a sequential increase in the abundance of the α-subunit in clathrin-coated vesicles (1 min), early endosomes (2.5 min), and late endosomes (5 min), suggesting its stepwise translocation between these organelles. A similar pattern was found for the β-subunit. The increased incorporation of both subunits in all compartments was blocked by calphostin C. The results demonstrate that the dopamine-induced decrease in Na+-K+-ATPase activity in proximal tubules is associated with internalization of its α- and β-subunits into early and late endosomes via a clathrin-dependent pathway and that this process is protein kinase C dependent. The presence of Na+-K+-ATPase subunits in endosomes suggests that these compartments may constitute normal traffic reservoirs during pump degradation and/or synthesis.
Well‐paid nurses are good nurses

Some recent articles suggest that increasing wage in the nursing market with the aim of reducing shortage can negatively impact on the average ability and motivation of applicants attracted and, in turn, on the average quality of care. This finding is at odds with empirical evidence and has been criticized on the grounds that nurses' motivation is modeled in an overly simplistic way. This paper provides a novel theoretical framework where the orientation of nurses' motivation-intrinsic versus extrinsic-is taken into account, and the precise distinction between intrinsic and extrinsic motivation is delineated on the basis of self-determination and person-environment fit theories. Conditions are derived under which high wages attract able and motivated individuals, thus maximizing the average quality of care.
Glucagon-like peptide-1 inhibits gastropancreatic function by inhibiting central parasympathetic outflow.

Glucagon-like peptide (GLP)-1 inhibits acid secretion and gastric emptying in humans, but the effect on acid secretion is lost after vagotomy. To elucidate the mechanism involved, we studied its effect on vagally stimulated gastropancreatic secretion and motility in urethan-anesthetized pigs with cut splanchnic nerves, in which insulin-induced hypoglycemia elicited a marked stimulation of gastropancreatic secretion and antral motility. In addition, we studied vagally stimulated motility and pancreatic secretion in isolated perfused preparations of the porcine antrum and pancreas. GLP-1 infusion (2 pmol ⋅ kg-1 ⋅ min-1) strongly and significantly inhibited hypoglycemia-induced antral motility, gastric acid secretion, pancreatic bicarbonate and protein secretion, and pancreatic polypeptide (PP) secretion. GLP-1 (at 10-10-10-8mol/l) did not inhibit vagally induced antral motility, pancreatic exocrine secretion, or gastrin and PP secretion in isolated perfused antrum and pancreas. We conclude that the inhibitory effect of peripheral GLP-1 on upper gastrointestinal secretion and motility is exerted via interaction with centers in the brain or afferent neural pathways relaying to the vagal motor nuclei.
II. Regulation of CFTR by small molecules including[Formula: see text].

Cystic fibrosis (CF) affects a number of epithelial tissues, including those in the gastrointestinal tract. The goal of this review is to summarize data related to regulation of the protein product of the CF gene, CF transmembrane conductance regulator (CFTR), by a variety of small molecules. There has been a surge of interest in discovering small molecules that could be exogenously added to cells and tissues to regulate CFTR and could potentially be used alone or in combination with genetic approaches for therapy in CF. We will discuss the apparent mechanisms of action of genistein, milrinone, 8-cyclopentyl-1,3-dipropylxanthine, IBMX, and NS-004; several of which appear to interact directly with one or both nucleotide binding domains of CFTR. We also discuss how [Formula: see text]interacts with CFTR as both a permeating anion and a potential regulator of Cl- permeation through the CFTR ion channel. It is likely that there are complicated interactions between Cl- and[Formula: see text] in the secretion of both ions through the CFTR and the anion exchanger in intestinal cells, and these may yield a role of CFTR in regulation of intestinal[Formula: see text] secretion as well as of intra- and extracellular pH.