Miracle-dz/UniFAR-FTUs huggingface dataset:
Gemigliptin: Newer Promising Gliptin for Type 2 Diabetes Mellitus

The dipeptidyl peptidase-4 (DPP-4) inhibitors have facilitated the management of type 2 diabetes mellitus (T2DM) owing to their superior efficacy and safety with low incidence of adverse effects. Gemigliptin is a new member of this family of drugs, and studies have revealed certain advantages of gemigliptin use compared to its previous congeners. Besides, this drug has also been studied for the treatment of T2DM as monotherapy, in combination with metformin or other oral antidiabetic drugs and in T2DM with moderate-to-severe renal failure. In this review, we explore the published data highlighting the pharmacology, efficacy, and safety of gemigliptin along with its recommendations for use in patients with T2DM.
Distinguishing between population bottleneck and population subdivision by a Bayesian model choice procedure

Although most natural populations are genetically subdivided, they are often analysed as if they were panmictic units. In particular, signals of past demographic size changes are often inferred from genetic data by assuming that the analysed sample is drawn from a population without any internal subdivision. However, it has been shown that a bottleneck signal can result from the presence of some recent immigrants in a population. It thus appears important to contrast these two alternative scenarios in a model choice procedure to prevent wrong conclusions to be made. We use here an Approximate Bayesian Computation (ABC) approach to infer whether observed patterns of genetic diversity in a given sample are more compatible with it being drawn from a panmictic population having gone through some size change, or from one or several demes belonging to a recent finite island model. Simulations show that we can correctly identify samples drawn from a subdivided population in up to 95% of the cases for a wide range of parameters. We apply our model choice procedure to the case of the chimpanzee (Pan troglodytes) and find conclusive evidence that Western and Eastern chimpanzee samples are drawn from a spatially subdivided population.
An update on the genotoxicity and carcinogenicity of marketed pharmaceuticals with reference to in silico predictivity

Information from the 1999 through 2008 Physicians' Desk Reference (PDR) was used to evaluate the genotoxicity of marketed drugs. Where available, data regarding the rodent carcinogenicity results were included (PDR and Gold potency database). In addition, computational predictivity of genotoxicity (DEREK, MC4PC) is included and expanded upon from two previous reviews. The present paper contains genotoxicity data on 545 marketed drugs. Excluded from analysis were most cytotoxic anti‐cancer and antiviral drugs, nucleosides (all with known mechanistic genotoxicity), steroids with class‐specific genotoxicity and biologicals or peptide‐based drugs. Per assay type, the percentage of positive drugs was: Bacterial mutagenesis assay: 38/525 (7.1%), in vitro chromosome aberrations: 88/380 (26.1%); mouse lymphoma assays (MLA): 32/163 (19.1%), in vivo cytogenetics: 49/438 (11.1%). The relationship among positive genetic toxicity findings, rodent carcinogenicity, and in silico prediction is discussed. Finally, supporting evidence is presented for the idea that the presence of an N‐dialkyl group or piperidine aryl ketone may somehow be associated with genotoxicity, perhaps through DNA intercalation and consequent DNA topoisomerase II inhibition. Environ. Mol. Mutagen. 2009. © 2009 Wiley‐Liss, Inc.
Adiponectin is produced by lymphocytes and is a negative regulator of granulopoiesis

Lymphocytes have long been established to play an important role in the regulation of hematopoiesis and produce many cytokines that act on hematopoietic progenitor cells. Previous studies by our group have shown that normal, unstimulated lymphocytes produce a protein that inhibits normal bone marrow GM colony formation. Adiponectin is an adipokine that has been demonstrated to act as a negative regulator of hematopoiesis and immune function. This study aimed to determine if the inhibitory molecule that we described previously was adiponectin. Here, we show transcription, translation, and secretion of adiponectin from lymphocytes and demonstrate that its receptors, AdipoR1 and AdipoR2, are expressed by bone marrow MNCs. We show that although the adiponectin expression is low in lymphocytes, it is sufficient to induce a significant inhibitory effect on GM precursors (CFU‐GM) and activate the AMPK pathway in these cells. The regulation of adiponectin production by lymphocytes and its detailed function in suppressing GM colony formation need to be elucidated now. Our findings suggest a functional role for adiponectin as a negative regulator of granulopoiesis.
Anthropometric analysis of palpebral fissure dimensions and its position in South Indian ethnic adults.

OBJECTIVES The morphology and anatomical relationship of periorbital features vary according to age, sex and ethnicity. Standard database regarding periorbital region is available for other ethnic groups. Since there is no data available in the literature, specifically for south Indian ethnic adults, the present study was carried out to determine the normal average values for South Indian ethnic population related to gender. METHODS Anthropometric measurements of both eyes were done on standardized frontal view photograph of 200 South Indian ethnic adults aged 18 to 26 years. Parameters included were palpebral fissure width (PFW), palpebral fissure height (PFH), palpebral fissure inclination (PFI), outercanthal distance (OCD), interpupillary distance (IPD), intercanthal distance (ICD) and comparisons were made between the genders using the independent t test. RESULTS Significant sexual dimorphism was noted in the given parameters. Palpebral fissure width (male: 31.08 mm; female: 29.90 mm), palpebral fissure inclination (male: 5.053°; female: 6.102°), outercanthal distance (male: 95.55 mm; female: 92.44 mm) and interpupillary distance (male: 66.72 mm; female: 62.59 mm). The palpebral fissure height (male: 11.30 mm; female: 11.58 mm) and intercanthal distance (male: 34.27 mm; female: 33.41 mm) showed no significant sexual differences. CONCLUSION Statistically significant differences were found between South Indian ethnic males and female in certain key parameters. The present study suggests that ethnicity and gender should be considered in orbital surgery. To individualize the treatment planning and diagnosis, it is important for the surgeons to have knowledge of these local norms.
Growth hormone deficiency in 'little' mice results in aberrant body composition, reduced insulin-like growth factor-I and insulin-like growth factor-binding protein-3 (IGFBP-3), but does not affect IGFBP-2, -1 or -4.

Although GH is known to regulate somatic growth during development, its role in regulating adult body composition is less well defined. The effects of GH on individual body compartments--water, fat, protein and mineral--are achieved both by the action of GH and by a GH-induced hormone, insulin-like growth factor-I (IGF-I). We used a genetic model of GH deficiency, the 'little' (gene symbol lit) mouse, to determine the GH regulation of IGF-I and its insulin-like growth factor-binding proteins (IGFBPs) and to define the interaction between these hormones and each body compartment in adults. Our results showed that GH-deficient lit/lit mice had reduced levels of serum IGF-I (range 38-130 micrograms/l) compared with normal lit/+ littermates (range 432-567 micrograms/l) between 2 and 52 weeks of age. The lit/lit mice did not experience the fivefold increase in IGF-I between 2 and 4 weeks of age that was seen in lit/+ mice. In lit/lit serum, overall binding of 125I-labelled IGF-I to the four IGFBPs was reduced, solely in response to a reduced amount of IGFBP-3. No overall differences were found between lit/lit and lit/+ mice in the binding of 125I-labelled IGF-I to IGFBP-2, -1 or -4. Age-related declines in IGF-I and IGFBPs were seen in lit/lit mice. However, adult levels of IGF-I were maintained in lit/+ mice to at least 52 weeks of age, as were levels of IGFBP-1 and -4, while IGFBP-3 and -2 declined with age. With respect to body composition, comparison of lit/lit with lit/+ mice showed that the lit/lit mice were characterized by abnormally large adipose tissue stores and reduced body water, protein and mineral from 2 weeks onward. These changes occurred despite normal energy intake in lit/lit mice up to 52 weeks of age, indicating that neither undernutrition nor hyperphagia is characteristic of this GH-induced model of obesity. Furthermore, lit/lit males accrued more body fat beginning at an earlier age than lit/lit females. With advancing age, the per cent body fat increased in both lit/lit and lit/+ mice, while the per cent body water and mineral declined. In lit/lit but not lit/+ mice, per cent protein also declined with age. The changes in body water and fat are attributable to lack of adequate GH in the genetically GH-deficient lit/lit mouse. On the other hand, the changes in body protein are more likely to be effects of IGF-I. (ABSTRACT TRUNCATED AT 400 WORDS)
Parental Fever Attitude and Management: Influence of Parental Ethnicity and Child's Age

Objective: The objective was to study parental fever management and attitude toward fever from the perspective of the child's ethnicity and age. Patients and Setting: Children with fever presenting at the pediatric emergency department (PED) of the Erasmus MC-Sophia Children's Hospital, Rotterdam, the Netherlands, in the period from February 2002 to March 2004. Design: Prospective observational. Main Outcome Measures: Parental fever attitude and management assessed by a questionnaire. Results: Two hundred eleven children with fever (median age, 1.2 years; interquartile range, 0.7-2.0 years) were included, of whom 108 (55%) were boys. One hundred fourteen children (54%) were self-referrals at the PED. Accompanying symptoms were reported in 95% (50% had ≥3); median temperature measured at PED was 39.5°C (interquartile range, 38.9°C-40.8°C). One hundred fifty-five parents (74%) had used antipyretics to reduce fever, and 155 parents (74%) were worried about fever and its possible complications. Differences between Dutch and non-Dutch ethnicities were seen in temperature-reducing techniques, self-referral, and parental anxiety of fever and its complications. Age did not influence parental fever attitude and management. Conclusions: For most children in our population, the use of antipyretics was justified, as the majority of our children visiting the PED for an acute febrile episode are young infants, in particular with a high degree of fever and accompanying symptoms. We confirm and extend previous findings of ethnicity influencing parental fever management.
Complete mitochondrial DNA sequence, gene organization and genetic variation of control regions in Parargyrops edita

The complete necleotide sequence of the mitochondrial genome of Parargyrops edita was determined by gene amplification using long polymerase chain reaction and direct sequencing techniques. The genome with 16 640 bp contained 37 genes (two ribosomal RNA, 22 transfer RNA, and 13 protein-coding genes). The content and order of genes was identical to those in typical teleosts. The major non-coding region of 964 bp in length with several conserved sequence features were identified as the control region (CR). Both COI and ND4 began with a GTG start codon, which is unusual in other fishes. The genetic variation of the CR from 27 wild samples was evaluated. A total of 536 bp consensus sequence of CR was aligned and 26 unique haplotypes were identified. The haplotype diversity (h) was estimated to be 0.997 (standard deviation [SD] 0.011) and nucleotide diversity (π) was 0.014 (SD 0.008) for the sample collected from coastal waters of Guangdong Province. It showed a very high level of genetic variation in the sample and also suggested that mtDNA CR sequence analysis can be use to evaluate the genetic deversity and genetic structure of P. edita.
CCR2 Chemokines Bind Selectively to Acetylated Heparan Sulfate Octasaccharides*

Chemokines participate in well documented interactions with glycosaminoglycans (GAGs). Although many chemokine amino acid residues involved in binding have been identified, much less is known about the bound regions of GAG. Heparan sulfate (HS) is the predominant cell surface GAG, and its heterogeneous nature offers proteins a variety of structural motifs with which to interact. In the present study, we describe the interactions of three CC chemokines, MCP-1/CCL2, MCP-2/CCL8, and MCP-3/CCL7, with HS-derived oligosaccharides. To this end, we generated and characterized a complex HS octasaccharide library containing 17 different octasaccharide compositions based on acetyl and sulfate group content. Electrospray ionization mass spectrometry was used to detect chemokine-HS octasaccharide complexes in the bound state, and an affinity purification protocol was used to select and identify chemokine-binding octasaccharides from the complex mixture. The results indicate that HS octasaccharide sulfation is the foremost requirement for chemokine binding. However, within octasaccharides of constant charge density, acetylation is also observed to augment binding, suggesting that there may be as yet undiscovered specificity in the chemokine-HS interaction.
Target Antigens Determine Graft-versus-Host Disease Phenotype

Chronic graft-vs-host disease (cGVHD) is an increasingly frequent complication of allogeneic stem cell transplantation. Phenotypically, cGVHD differs from patient to patient; in particular, a subset of patients develops extensive cutaneous fibrosis. Similarly, graft-vs-host disease (GVHD) is distinct in inbred murine donor:recipient pairings, indicating a genetic component to disease phenotype. The B10.D2 → BALB/c (H-2d) strain pairing uniquely recapitulates key pathologic features of fibrotic human cutaneous cGVHD. To distinguish whether this genetic component is due to differences in genes that modulate immune responses or to the specific Ags targeted, we asked whether skin-dominant cGVHD also develops in the B10 → BALB.B (H-2b) and B10.BR → BALB.K (H-2k) MHC-congenic pairings. Because each MHC haplotype presents different peptides and selects different T cell repertoires, GVHD in each donor:recipient pair undoubtedly targets different Ags. We found that, in contrast to BALB/c recipients, BALB.B mice never manifested skin disease while BALB.K mice developed a modified form of skin disease. Instead, BALB.B and BALB.K recipients developed systemic GVHD which was absent in BALB/c mice. Moreover, in (B10 × B10.D2)F1 → (BALB.B × BALB/c)F1 H-2b/d transplants, recipients developed both cutaneous and systemic disease. Thus, the selection of immunodominant Ags determines the target and character of GVHD, providing insight into the genetic basis for different forms of GVHD.
Iron, folate and cobalamin deficiency in anaemic pregnant females in tertiary care centre at Rawalpindi.

BACKGROUND Anaemia in pregnancy is a common clinical problem contributing to increased maternal and foetal morbidity. This study was carried out to determine frequency of iron, folate and cobalamin deficiency and associated risk factors in the anaemic pregnant females who reported first time during second and third trimester for antenatal check-up in the tertiary care hospital at Rawalpindi. METHODS This case control study was carried out in a tertiary care hospital at Rawalpindi. Two hundred and fifty pregnant women (age: 19-43 years) consisting of 125 anaemic (Hb < 110 g/L) and 125 non-anaemic who reported first time at antenatal clinic were included. Data on socio-demographic characteristics, parity and dietary intake were collected. Complete blood counts were done. Serum ferritin, folate and cobalamin assays were performed by using DPC kits on Immulite-1000. RESULTS The pregnant women were categorised having mild (Hb up to 54%), moderate (Hb up to 36%), or severe (Hb up to 10%) anaemia during antennal visit. They had significantly lower median (range) levels of haemoglobin 96 (40-110) g/L, ferritin 8 (3-142) microg/L, folate 15 (3-54) etamol/L and cobalamin 171 (111-629) etamolL than controls (p = < 0.01). Micronutrient analysis revealed secondary pregnancy related deficiency of Iron (57%), folate (20%). combined iron and folate (19%) and cobalamin (4%) in the female Among the risk factors, low income (OR: 7.69), multiparty (OR: 2.93), lack of iron/folate supplementation (OR 2.91) and inadequate dietary intakes (OR 2.51) were associated with anaemia. CONCLUSION The pregnant anaemic women had iron (57%); folate (20%), followed by combined iron folate (19%) and cobalamin (4%) deficiency during first antenatal visit. Low income, multiparty, poor diet and lack of supplements are the main contributor in development of anaemia during pregnancy.
Flow cytometric DNA content analysis of 185 soft tissue neoplasms indicates that S-phase fraction is a prognostic factor for sarcomas. French Federation of Cancer Centers (FNCLCC) Sarcoma Group.

BACKGROUND The authors determined the flow cytometric (FCM) DNA characteristics of 53 benign tumors and 132 malignant (71 primary, 61 recurrent) soft tissue sarcomas to investigate their heterogeneity and to evaluate the prognostic values of DNA ploidy status and S-phase fraction (SPF). METHODS One to 11 frozen samples were collected from 185 tumors at 10 participating centers of the French Federation of Cancer Centers (FNCLCC). All FCM analyses were performed in the same laboratory. Histologic diagnoses were collegially reviewed, and grade was assessed by the pathologists of the FNCLCC Sarcoma Group. Relationships between FCM, clinical, and pathologic data were investigated using univariate and multivariate analyses for risks of mortality and metastasis. RESULTS All except 2 of the 53 benign lesions were DNA diploid. One schwannoma and one desmoid tumor exhibited small abnormal DNA peaks. SPF was low in all benign lesions. One-third of the sarcomas were DNA diploid, whereas two-thirds were DNA aneuploid. Relationships were found between aneuploidy and mitotic count, grade, and histologic subtype of malignant fibrous histiocytoma. DNA ploidy status did not influence the clinical outcome. Multiple sampling performed in 32 sarcomas showed both diploid and aneuploid samples in 6 tumors. Heterogeneity was related to tumor size. SPF evaluated in 85 sarcomas was related to DNA ploidy status, mitotic count, and grade. SPF > or = 4% was significantly associated with a low overall survival rate. In a multivariate analysis performed for the whole group of 132 patients, the single factors with independent prognostic value for patient mortality were disease free status after the treatment course (P < 0.0001) and SPF (P = 0.03). In the subgroup of patients who were initially free of metastases and free of tumor after the treatment course, SPF remained the only factor that significantly influenced the overall survival rate (P = 0.021). CONCLUSIONS Despite its high failure rate, SPF is an independent factor in the prognosis of soft tissue sarcoma and should be considered when patients with a high mortality risk need to be selected for adjuvant chemotherapy.
Phage‐display and correlated mutations identify an essential region of subdomain 1C involved in homodimerization of Escherichia coli FtsA

FtsA plays an essential role in Escherichia coli cell division and is nearly ubiquitous in eubacteria. Several evidences postulated the ability of FtsA to interact with other septation proteins and with itself. To investigate these binding properties, we screened a phage‐display library with FtsA. The isolated peptides defined a degenerate consensus sequence, which in turn displayed a striking similarity with residues 126–133 of FtsA itself. This result suggested that residues 126–133 were involved in homodimerization of FtsA. The hypothesis was supported by the analysis of correlated mutations, which identified a mutual relationship between a group of amino acids encompassing the ATP‐binding site and a set of residues immediately downstream to amino acids 126–133. This information was used to assemble a model of a FtsA homodimer, whose accuracy was confirmed by probing multiple alternative docking solutions. Moreover, a prediction of residues responsible for protein‐protein interaction validated the proposed model and confirmed once more the importance of residues 126–133 for homodimerization. To functionally characterize this region, we introduced a deletion in ftsA, where residues 126–133 were skipped. This mutant failed to complement conditional lethal alleles of ftsA, demonstrating that amino acids 126–133 play an essential role in E. coli. Proteins 2003;50:192–206. © 2002 Wiley‐Liss, Inc.
Metals in aquatic systems.

In this article we address the general question of whether we can yet predict metal-scavenging residence times in natural systems based on current knowledge about metal behavior as derived from laboratory studies. Although we will show that our ability to predict metal behavior is still relatively limited, such a conclusion should not be construed as a criticism of the reductionist approach. Rather, it should be seen that a number of challenges remain for surface chemists interested in the natural environment.
Intrinsic deviations in fluorescence yield detected x-ray absorption spectroscopy: the case of the transition metal L2,3 edges

Fluorescence yield (FY) detected x-ray absorption spectra (XAS) of 3d transition metal ions are calculated from the integrated 2p3d resonant x-ray emission spectra. The resulting FY-XAS spectra are compared with the normal XAS spectra corresponding to the absorption cross section and significant deviations between the two spectra are found. This implies that the assumption that the FY-XAS spectrum identifies with the XAS spectrum is disproved. Especially for the early transition metal systems the differences between the FY-XAS and XAS are large, due to the opening of inelastic decay channels from selected x-ray absorption final states. The theoretical calculations show that the difference between FY detection and XAS is largest for the detection in depolarized geometry. The calculations are compared with experimental spectra for oxides and coordination compounds for Fe2+, Co2+ and Ni2+ systems. The implications for the sum rules in XAS and magnetic circular dichroism experiments are discussed.
Patterns and frequencies of acquired and constitutional uniparental isodisomies in pediatric and adult B‐cell precursor acute lymphoblastic leukemia

Single nucleotide polymorphism (SNP) arrays are increasingly being used in clinical routine for genetic analysis of pediatric B‐cell precursor acute lymphoblastic leukemias (BCP ALL). Because constitutional DNA is not readily available as a control at the time of diagnosis, it is important to be able to distinguish between acquired and constitutional aberrations in a diagnostic setting. In the present study we focused on uniparental isodisomies (UPIDs). SNP array analyses of 143 pediatric and 38 adult B‐cell precursor acute lymphoblastic leukemias and matched remission samples revealed acquired whole chromosome or segmental UPIDs (wUPIDs, sUPIDs) in 32 cases (18%), without any age‐ or gender‐related frequency differences. Acquired sUPIDs were larger than the constitutional ones (mean 35.3 Mb vs. 10.7 Mb; P < 0.0001) and were more often terminally located in the chromosomes (69% vs. 4.5%; P < 0.0001). Chromosomes 3, 5, and 9 were most often involved in acquired wUPIDs, whilst recurrent acquired sUPIDs targeted 6p, 9p, 9q, and 14q. The majority (56%) of sUPID9p was associated with homozygous CDKN2A deletions. In pediatric ALL, all wUPIDs were found in high hyperdiploid (51–67 chromosomes) cases and an extended analysis, also including unmatched diagnostic samples, revealed a higher frequency of wUPID‐positivity in higher modal number (56–67 chromosomes) than in lower modal number (51–55 chromosomes) high hyperdiploid cases (34% vs. 11%; P = 0.04), suggesting different underlying mechanisms of formation of these subtypes of high hyperdiploidy. © 2016 Wiley Periodicals, Inc.