jimnoneill/paper-to-field-training huggingface dataset:
NATURAL SELECTION ALONG AN ENVIRONMENTAL GRADIENT: A CLASSIC CLINE IN MOUSE PIGMENTATION

Field: Agricultural and Biological Sciences (Life Sciences)

We revisited a classic study of morphological variation in the oldfield mouse (Peromyscus polionotus) to estimate the strength of selection acting on pigmentation patterns and to identify the underlying genes. We measured 215 specimens collected by Francis Sumner in the 1920s from eight populations across a 155-km, environmentally variable transect from the white sands of Florida's Gulf coast to the dark, loamy soil of southeastern Alabama. Like Sumner, we found significant variation among populations: mice inhabiting coastal sand dunes had larger feet, longer tails, and lighter pigmentation than inland populations. Most striking, all seven pigmentation traits examined showed a sharp decrease in reflectance about 55 km from the coast, with most of the phenotypic change occurring over less than 10 km. The largest change in soil reflectance occurred just south of this break in pigmentation. Geographic analysis of microsatellite markers shows little interpopulation differentiation, so the abrupt change in pigmentation is not associated with recent secondary contact or reduced gene flow between adjacent populations. Using these genetic data, we estimated that the strength of selection needed to maintain the observed distribution of pigment traits ranged from 0.0004 to 21%, depending on the trait and model used. We also examined changes in allele frequency of SNPs in two pigmentation genes, Mc1r and Agouti, and show that mutations in the cis-regulatory region of Agouti may contribute to this cline in pigmentation. The concordance between environmental variation and pigmentation in the face of high levels of interpopulation gene flow strongly implies that natural selection is maintaining a steep cline in pigmentation and the genes underlying it.
Wide Area Transepithelial Sampling With Computer-Assisted 3-Dimensional Analysis (WATS3D) and Forceps Biopsies Should Both Be Obtained to Maximize Detection of Intestinal Metaplasia Following Ablation of Barrett’s Esophagus

Field: Medicine (Health Sciences)

Introduction: Barrett’s esophagus (BE) is a precancerous condition characterized by esophageal intestinal metaplasia (IM). Endoscopic ablation is performed to decrease risk of progression to adenocarcinoma. Post-ablation surveillance is accomplished using the modified Seattle protocol, where 4-quadrant forceps biopsies (FB) are taken at least every 2 cm throughout the original BE segment. Prior studies have demonstrated the benefit of adjunctive use of WATS3D with FB to improve detection of residual or recurrent IM following endoscopic ablation. Our aim was to investigate discordance between post-ablation WATS3D and FB and determine demographic and endoscopic factors that predict disparate results. Methods: Patients undergoing follow-up endoscopy after BE ablation between June 2012 and May 2014 were evaluated. If there was no visual evidence of BE, WATS3D biopsies were obtained using the standard 2-brush technique (CDx Diagnostics, Suffern, NY). The squamocolumnar junction was sampled with its own brush kit, followed by separate brushings from the tubular esophagus for all patients with an original BE length of at least 2 cm. Samples were analyzed by a central laboratory using a neural network to identify IM. Four-quadrant FB were obtained during the same endoscopy and reviewed by an expert GI pathologist. Results from both data sets were compared. Statistical analysis using two-tailed T-tests was performed using patient demographic and endoscopic data. Results: Post-ablation biopsies were taken in 114 cases (78% male, mean age 62 years). Diagnostic agreement between WATS3D and FB was seen in 89 cases (78%). Of the 31 cases in which IM was detected, only 6 had positive results on both WATS3D and FB. Fifteen cases were detected by FB alone and 10 cases by WATS3D alone. Therefore, the adjunctive yield of WATS3D was 47.6% (10/21). Analysis demonstrated no statistically significant difference between patients with diagnostic agreement versus discordance with respect to age, gender, smoking status or mean number of ablative treatments to visually eradicate BE. However, mean hiatal hernia size was substantially larger when IM was detected only with WATS3D (3.6 cm versus 2.6 cm, p=0.08). Conclusion: Residual or recurrent IM detected following BE ablation was found with both WATS3D and FB in only 19.4% of cases. This high degree of discrepancy when IM persists underscores the importance of using both techniques to survey normal-appearing post-ablation mucosa. WATS3D seems to be most helpful when sampling in the presence of larger hiatal hernias. This may be due to a greater luminal circumference and/or reduced inspection capability. Further improvements in WATS3D brush technology and technique will only augment its benefit in post-ablation surveillance. Disclosure - Dr. Smith - Advisory Board Member and Research Support: CDx Diagnostics.
Phase 2 results of selinexor in advanced de-differentiated (DDLS) liposarcoma (SEAL) study: A phase 2/3, randomized, double blind, placebo controlled cross-over study.

Field: Medicine (Health Sciences)

11512 Background: Locally advanced DDLS is incurable with an overall survival of 11 – 20 mo with palliative therapies. Ideal imaging criteria for efficacy is currently undefined. Selinexor (S) is an oral, selective inhibitor of nuclear export that specifically blocks exportin 1, leading to the nuclear accumulation and reactivation of tumor suppressor proteins. S demonstrated anti-tumor activity against DDLS in preclinical studies and a Ph 1b study in patients (pts) with soft tissue sarcomas. Methods: Eligible pts had DDLS and progressive disease (PD) with ≥ 1 prior systemic therapy. Pts were randomized 1:1 to receive blinded S (60 mg) or placebo (P) twice weekly; 42 day cycle until PD or intolerability. Pts with PD on P may cross over to S. The primary endpoint was progression-free survival (PFS) by WHO criteria. Pre-specified analyses using RECIST v1.1 (R v1.1) was included. Results: Ph 2 enrollment is complete. 56 evaluable pts (33 M, 23 F) were randomized to S or P. Median age: 61 yrs and median prior treatments: 2 (1-9). Treatments for 51 pts were unblinded (24 S, 27 P). The main reason for ending blinded treatment was PD confirmed by Independent Central Radiological Review by WHO Criteria. Common AEs Grade 1/2 (S:P) were: nausea (85% : 31%), anorexia (62% : 14%), and fatigue (58% : 45%). Grade 3/4 AEs were: hyponatremia (15% : 0%), anemia (15% : 7%), and thrombocytopenia (12% : 0%). 12 pts on S had dose reductions due to AEs. There was no difference in median PFS by WHO. By R v1.1, median PFS on S: 5.6 mo; P: 1.8 mo, hazard ratio of 0.64 (p 0.21, not powered in Ph 2). (Table 1). Some pts ended treatment early with small changes in tumor burden due to PD by WHO criteria. Conclusions: R v1.1 may be better criteria than WHO to evaluate drug efficacy in DDLS. Improvement of PFS (R v1.1) is promising and supports continuation of the Ph 3 portion of S in DDLS. Clinical trial information: NCT02606461.Median PFS by R v1.1 and WHO criteria. Treatment Arm R v1.1 - PFS (mo) Hazard Ratio (95% CI) WHO - PFS (mo) Hazard Ratio (95% CI) Selinexor (N = 24) 5.6 0.64 (0.31, 1.32) p = 0.21 1.4 0.92 (0.52, 1.63) Placebo (N = 27) 1.8 1.4
Between the Lines of Boyer, Goodlad, and Sizer

Field: Arts and Humanities (Social Sciences)

Discussions of national reform reports have tended to focus on such amorphous proposals as raising standards of achievement or establishing schoolwide goals while ignoring what Mortimer Adler calls the heart of matter, quality of teaching in classroom. High School by Ernest Boyer, A Place Called School by John Goodlad, and Horace's Compromise by Theodore Sizer are three such reports that have something to say to classroom teachers. Woven through their carefully wrought descriptions of classrooms in action are four themes that should guide English teachers in our own personal search for excellence. These themes--engagement, inquiry, connection, and community-find their natural expression in English curriculum. They may even provide thread for uniting what Edmund Farrell calls now discordant priorities of reformers and students.
Phosphorus facilitation and covariation of root traits in steppe species

Field: Agricultural and Biological Sciences (Life Sciences)

Summary Different phosphorus (P)‐acquisition strategies may be relevant for species coexistence and plant performance in terrestrial communities on P‐deficient soils. However, how interspecific P facilitation functions in natural systems is largely unknown. We investigated the root physiological activities for P mobilization across 19 coexisting plant species in steppe vegetation, and then grew plants with various abilities to mobilize sorbed P in a microcosm in a glasshouse. We show that P facilitation mediated by rhizosphere processes of P‐mobilizing species promoted growth and increased P content of neighbors in a species‐specific manner. When roots interacted with a facilitating neighbor, Cleistogenes squarrosa and Bromus inermis tended to show greater plasticity of root proliferation or rhizosheath acid phosphatase activity compared with other non‐P‐mobilizing species. Greater variation in these root traits was strongly correlated with increased performance in the presence of a facilitator. The results also show, for the first time, that P facilitation was an important mechanism underlying a positive complementarity effect. Our study highlights that interspecific P‐acquisition facilitation requires that facilitated neighbors exhibit a better match of root traits with a facilitating species. It provides a better understanding of species coexistence in P‐limited communities.
Do I stay because I am happy or am I happy because I stay? Life satisfaction in migration, and the decision to stay permanently, return and out-migrate

Field: Economics, Econometrics and Finance (Social Sciences)

Mobility in the forms of permanent migration, return or out-migration can provide individuals with gainful employment, better jobs and a higher level of earnings. But as a growing number of studies are suggesting, the gains from migration should not be strictly evaluated from the utilitarian approach but subjective well-being indicators should be taken into consideration. The purpose of this study is to test how life satisfaction during the migration experience determines the preference to stay, return or out-migrate by controlling not only for economic but also for social and subjective well-being determinants. We aim to address this analysis by combining two streams of research: the one on migration and return decisions and the one on life satisfaction and subjective well-being literature so as to broaden the analytical framework to add to economic thinking also some of the main findings from other social sciences. The results of the study confirm that, once in the destination country, migration intentions such as to stay permanently, to move to another country or to return home are strongly linked to the assessment of life satisfaction through diverse social and economic drivers. For women life satisfaction is not only a good predictor of migration preferences but also a mediator, whereas for men this is not confirmed. Determinants that appear to be positively linked with life satisfaction are civic participation and housing which correlate with migrants’ reporting high levels of life satisfaction.
Age‐ and gender‐related variations in morphometric characteristics of thoracic spine pedicle

Field: Medicine (Health Sciences)

Transpedicular spinal fusion is the most commonly used fixation technique for the surgical treatment of vertebral disorders. However, the instrumentation of the thoracic spine using this technique continues to be controversial. The objective of the present study was to determine the morphometric characteristics of the thoracic pedicle and to establish how these characteristics vary with gender and age. Two hundred thoracic spines (4800 thoracic pedicles) from individuals of known gender and age were analyzed (in accordance with the order of vertebrae). The spines were divided into six groups according to age and gender. The horizontal and vertical diameters of the thoracic pedicle were determined for each piece. The mean and standard deviation of each variable were determined, and differences between age groups for each gender were evaluated using parametric correlation tests. The pedicle diameters of men and women differed significantly for most groups ( P < 0.05). The horizontal diameters decreased from T1 to T5 and increased up to T12. The vertical diameter followed a cephalocaudal pattern of development from T1‐T12. The pedicle diameters decreased with increasing age in women, while the opposite trend was observed in men. In men, the dimensions of the thoracic spine pedicle increase with increasing age; in women, they decrease. These differences should be taken into account when selecting the appropriate pedicle screw. Clin. Anat. 27:441–450, 2014. © 2013 Wiley Periodicals, Inc.
679 Flat-top talus after clubfoot treatment: a systematic review of aetiology, prevalence and management strategies

Field: Medicine (Health Sciences)

Aims

Flat-top talus (FTT) is a complication well-known to those treating clubfoot. Despite varying anecdotal opinions, its association with different treatments, especially the Ponseti method, remains uncertain. This systematic review aimed to establish the aetiology and prevalence of FTT, as well as detailing management strategies and their efficacy.

Methods

A systematic review was conducted according to PRISMA guidelines to search for articles using MEDLINE, EMBASE and Web of Science until November 2021. Studies with original data relevant to one of three questions were included: 1) Possible aetiology 2) Prevalence following different treatments 3) Management strategies and their outcomes.

Results

32 original studies were included, with a total of 1473 clubfeet. FTT may be a pre-existing feature of the pathoanatomy of some clubfeet as well as a sequela of treatment. It can be a radiological artefact due to positioning or other residual deformity. The Ponseti method is associated with a higher percentage of radiologically normal tali (57%) than both surgical methods (52%) and non-Ponseti casting (29%). Only one study was identified that reported outcomes after surgical treatment for FTT (anterior distal tibial hemiepiphysiodesis).

Conclusion

The cause of FTT remains unclear. It is seen after all treatment methods but the rate is lowest following Ponseti casting. Guided growth may be an effective treatment.
RNA Second Messengers and Riboswitches: Relics from the RNA World?

Field: Biochemistry, Genetics and Molecular Biology (Life Sciences)

Compelling evidence supports the hypothesis that modern cells descended from organisms whose components were made entirely of RNA. Scientists who helped formulate this “RNA World” hypothesis for the evolution of life have identified many characteristics of modern cells that strongly suggest RNA once ruled the planet. For example, the existence of self-cleaving and self-splicing ribozymes that cut and ligate RNAs demonstrates that at least some RNA-processing reactions can be catalyzed without the need for proteins. Also, the existence of ribosomal RNAs that build all genetically encoded proteins emphasizes the fact that today's organisms depend on RNA to carry out fundamental biochemical processes. Even many nucleotide-like coenzymes that are near universal in all life forms likely first appeared in RNA World organisms. The RNA World hypothesis is appealing because it helps explain the arcane characteristics of genetic and biochemical processes in modern cells. Why do all cells use ribosomal RNAs, and not protein enzymes, to stitch together amino acids to make polypeptides? Most likely, the ribosome's peptidyl transferase center is an evolutionary descendent of an ancient ribozyme that first catalyzed this reaction before protein enzymes evolved. Why do so many coenzymes, such as adenosylcobalamin (AdoCbl), thiamin pyrophosphate (TPP), flavin mononucleotide (FMN), S-adenosylmethionine (SAM), molybdenum cofactor (Moco), and tetrahydrofolate (THF), all carry recognizable fragments of RNA nucleotides or derive from nucleotide precursors? Perhaps these compounds served as coenzymes for metabolic ribozymes of the RNA World, and they have been preserved as legacies from a time before protein enzymes existed.
Purification of extracellular lipase from Pseudomonas aeruginosa

Field: Biochemistry, Genetics and Molecular Biology (Life Sciences)

Lipase (triacylglycerol acylhydrolase, EC 3.1.1.3) was excreted by Pseudomonas aeruginosa PAC1R during the late logarithmic growth phase. Characterization of cell-free culture supernatants by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed the presence of significant amounts of lipopolysaccharide, part of which seemed to be tightly bound to lipase. After concentration of culture supernatants by ultrafiltration, lipase-lipopolysaccharide complexes were dissociated by treatment with EDTA-Tris buffer and subsequent sonication in the presence of the zwitterionic detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate. The solubilized lipase was purified by isoelectric focusing in an agarose gel containing the same detergent; the lipase activity appeared in a single peak corresponding to a distinct band in the silver-stained gel. The isoelectric point was 5.8. Analysis of purified lipase by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and scanning revealed an apparent molecular weight of 29,000 and a specific activity of 760 mu kat/mg of protein. Estimations based on these data showed that a single P. aeruginosa cell excreted about 200 molecules of lipase, each having a molecular activity of 2.2 X 10(4) per s.
Additional file 3 of Whole-genome methylation analysis reveals epigenetic variation between wild-type and nontransgenic cloned, ASMT transgenic cloned dairy goats generated by the somatic cell nuclear transfer

Field: Biochemistry, Genetics and Molecular Biology (Life Sciences)

Additional file 3: Fig. S3. Genome-wide distribution of mean methylation rates (A, ASMT transgenic cloned goat (K2020); B, control goat (S2); C, Nontransgenic cloned goat (K03)).
A structural examination of the Crimean-Congo Hemorrhagic Fever Virus Otu protease domain in the presence of the Ubiquitin and ISG15 substrates

Field: Biochemistry, Genetics and Molecular Biology (Life Sciences)

Immune cytokines tumor necrosis factor alpha and type I interferons provide front-line defense against viral infection and are regulated in part by ubiquitin (Ub) and Ub-like molecules. Ubiquitin and Ub-like molecule ISG15 share a conserved C-terminal motif where a terminal glycine residue becomes attached to cellular target proteins. Nairoviruses and arteriviruses contain an ovarian tumor domain-containing protease (OTU protease) that was found to corrupt pathways by removing Ub or ISG15 from target proteins. This broad substrate specificity is unlike mammalian deubiquitinating enzymes, which cannot recognize both substrates. To understand how viral OTU domain-containing proteases remove Ub and ISG15, the crystal structure of the Crimean-Congo Heamorhaggic Fever nairovirus (CCHFV) was determined with Ub to 2.5 Å resolution. A computational model was built of the CCHFV Otu protease bound to ISG15 as well. The CCHFV Otu protease has several structural differences from known OTU proteases, manifesting in its broad substrate recognition capability.
The THE ROLE OF SELF-EFFICACY AND FAMILY SUPPORT IN STABILIZING BLOOD PRESSURE OF PATIENTS WITH HYPERTENSION

Field: Health Professions (Health Sciences)

Hypertension is a health problem for the majority of people in Indonesia. The Efforts to reduce the incidence rate of hypertension and controling blood pressure by changing the healthy lifestyle and by being in taking. To realize healthy lifestyle and behavior of hypertension, self-efficacy and support of the family as well as health care cooperation with the parties, the family, and society are required. The purpose of this research to know if self-efficacy and family support stabilizing blood pressure of patients with hypertension. This research is a pre-experimental research with One-Group Pre-Post test design approach. The study was conducted in 50 people with the stratified random sampling technique in Ketawang Village, Gondang Districtor 8 weeks. Measurement of the blood pressure was the Spignomanometer merk Onemed was given before and after the patients were given counseling self-efficacy and family support. The data was analyzed SPSS 21 Wilcoxon test. The Statistical test results obtained p value 0.000 to sistole and diatole so that there is a meaningful that self-efficacy counseling and family support stabilizing blood pressure of patients hypertension. Self-efficacy counseling and family support controling blood pressure for patients with hypertension, so they needs to be developed to reduce hypertension complications.
Data from Functional Analyses of Mutations in Receptor Tyrosine Kinase Genes in Non–Small Cell Lung Cancer: Double-Edged Sword of <i>DDR2</i>

Field: Biochemistry, Genetics and Molecular Biology (Life Sciences)

<div>Abstract<p><b>Purpose:</b> This study investigated whether mutations of receptor tyrosine kinase (RTK) genes detected using next-generation sequencing (NGS) are suitable therapeutic targets.</p><p><b>Experimental design:</b> Fifty surgically resected non–small cell lung cancer (NSCLC) samples were target resequenced using NGS. We then investigated the functions of the identified RTK gene mutations, including their oncogenic potential, <i>in vitro</i>.</p><p><b>Results:</b> Mutations in RTK genes were found in 20 samples (<i>EGFR</i>, 15; <i>ERBB4</i>, 1; <i>ALK</i>, 1; <i>DDR2</i>, 2; <i>FGFR1</i>, 1), mutations in MAPK pathway genes were found in nine samples (<i>KRAS</i>, 7; <i>NRAS</i>, 1; <i>BRAF</i>, 2), and mutations in PI3K pathway genes were found in three samples (<i>PIK3CA</i>, 1; <i>PTEN</i>, 3). Among the mutations in RTKs, the functions of four mutations were unclear (<i>ERBB4</i> D245G; <i>DDR2</i> H246R and E655K; <i>FGFR1</i> A263V). These mutations did not exhibit any transformational activities. Neither the phosphorylation nor the protein expressions of RTKs were changed by the <i>DDR2</i> H246R, <i>ERBB4</i> D245G, and <i>FGFR1</i> A263V mutations, although the expression level of the DDR2 protein harboring the E655K mutation was particularly low. Collagen stimulation decreased cellular proliferation through p38 activation in the <i>DDR2</i> wild-type–overexpressed cell lines, whereas the growth-suppressive effect was weakened in <i>DDR2</i> E655K–overexpressed cell lines. Furthermore, the <i>DDR2</i> E655K protein strongly bound to ubiquitin ligase E3 (Cbl-b), and the mutant protein expression was increased after treatment with a proteasome inhibitor.</p><p><b>Conclusions:</b> Our experimental findings suggest that RTK mutations are not always suitable as therapeutic targets. The <i>DDR2</i> E655K mutation can play a role in cancer progression by reducing the growth-inhibitory effect of collagen. <i>Clin Cancer Res; 22(14); 3663–71. ©2016 AACR</i>.</p></div>