Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmaceutical Innovation and U.S. Cancer Survival, 1992-2003: Evidence from Linked SEER-MEDSTAT Data

This study examines the impact of pharmaceutical innovation and other factors on the survival of U.S. cancer patients during the period 1992-2003. In particular, it investigates whether cancer survival rates increased more for those cancer sites that had the largest increases in the proportion of chemotherapy treatments that were "new" treatments. We control for other types of medical innovation, i.e. other pharmaceutical innovation, and innovation in surgical procedures, diagnostic radiology procedures, and radiation oncology procedures.Data on observed survival rates, the number of people diagnosed, mean age at diagnosis, and stage distribution are obtained from the National Cancer Institutes SEER public-use data. Estimates of rates of innovation in chemotherapy and other treatment and diagnostic procedures are constructed from the MEDSTAT MarketScan database and other data sources. Treatment innovation indicators based on MEDSTAT data are likely to be useful, albeit noisy, indicators of the treatment innovation experienced by patients in SEER registries. This sampling error is likely to bias the coefficients on the treatment innovation measures towards zero.We compute weighted least-squares estimates of 6 versions of a survival model, based on different survival intervals and functional forms. The chemotherapy vintage coefficient is positive and significant in every model. This indicates that the cancer sites whose chemotherapy vintage (measured by the share of post-1990 treatments) increased the most during the period 1992-2003 tended to have larger increases in observed survival rates, ceteris paribus.We estimate how much lower the survival rate from all cancer sites combined would have been during 1993-2001 in the absence of post-1992 chemotherapy innovation. The estimates indicate that chemotherapy innovation accounted for 74% of the increase in the 1-year observed survival rate for all cancer sites combined during the period 1992-2001. Chemotherapy innovation accounted for smaller fractions of the increases in the 2-year and 3-year observed survival rates for all cancer sites combined during the same period: 51% and 29%, respectively.The coefficients on measures of non-pharmaceutical medical innovation (in radiation oncology, diagnostic radiology, and surgery innovation) are generally not significant. However these measures may be less reliable than the drug innovation measure. They were based upon the year in which the AMA established a new procedure code, which may be a far less meaningful indicator of innovation than the year in which the FDA first approved a drug. This topic warrants further research.
Water-Tolerant DUT-Series Metal-Organic Frameworks: A Theoretical-Experimental Study for the Chemical Fixation of CO2 and Catalytic Transfer Hydrogenation of Ethyl Levulinate to γ-Valerolactone.

A series of highly thermally and hydrolytically stable porous solid with intriguing properties of zirconium- and hafnium-based metal-organic frameworks (Dresden University of Technology (DUT) series) was synthesized. The DUT metal-organic frameworks were found to be effective catalysts for both epoxide-CO2 cycloaddition reactions and the catalytic transfer hydrogenation (CTH) of ethyl levulinate (EL). In particular, 12-connected DUT-52(Zr) showed higher catalytic activity than eight- and six-connected catalysts in the synthesis of cyclic carbonates as well as in the production of gamma-valerolactone (GVL). The secondary building unit connectivity, co-existence of moderate number of acidic and basic sites, Brunauer-Emmett-Teller surface area, and combined effects of the pores of the metal-organic frameworks seem to influence the catalytic activity. The reaction mechanism for the DUT-52(Zr) mediated cycloaddition reaction of CO2 and the catalytic transfer hydrogenation reactions were investigated in detail by using periodic-DFT calculations. To the best of our knowledge, this is the first detailed computational study for the formation of GVL from EL by using MOF as catalyst. In addition, Grand Canonical Monte Carlo (GCMC) simulations predicted the strong interaction of CO2 molecules with the DUT-52(Zr) framework. Remarkably, the DUT-series catalysts possess extraordinary tolerance towards water. Further, DUT-52(Zr) is recyclable and is an efficient catalyst for cycloaddition and CTH reactions for at least five uses without obvious reductions in the activity or structural integrity. Keywords: DUT, cyclic carbonate, CO2, biomass, gamma-valerolactone.
Identification of transgene integration site and anatomical properties of fluorescence intensity in a EGFP transgenic chicken line

Transgenic birds are commonly used for time‐lapse imaging and fate mapping studies in developmental biology. When researchers use transgenic birds expressing fluorescent protein, they need to understand the integration site of the transgene in the genome and the intensity of fluorescence in the tissues of interest. In this study, we determined the integration site of the transgene and fluorescence property of developing organs in our transgenic chicken line generated by lentivirus infection. The transgene was localized between exons 3 and 4 of MED27. Some homozygotes and heterozygotes appeared to be lethal at early embryonic stages. We performed histological analysis of EGFP expression in transgenic embryos at St. 14, 17, and 24 by immunohistochemistry with anti‐GFP antibody on paraffin sections. Next, we cut cryosections and quantified direct EGFP intensity from the transgene in each tissue without performing immunohistochemistry. These results revealed that EGFP intensity in each tissue was unique in developing embryos and changed according to developmental stages. Finally, we demonstrated that EGFP‐expressing cells in a micromass culture with co‐culturing wild‐type cells were clearly distinguishable via live cell imaging. These results provide essential information on the potential of our transgenic line and indicate that these transgenic chicken lines are useful for research associated with developmental biology.
How the Distance Between Drag-Cloth Checks Affects the Estimate of Adult and Nymphal Ixodes scapularis (Acari: Ixodidae) Density

Abstract Drag-cloth sampling is the most commonly used method to sample for ticks. A cloth is dragged along the ground and checked for ticks at regular intervals to count ticks before they drop off. The distance between drag-cloth checks differs between studies, which could result in lower density estimates for studies with greater distances between checks. Here, we measured this effect by 1) calculating the rate at which nymphal and adult Ixodes scapularis Say ticks drop off the cloth per meter dragged and 2) measuring tick density by drag-cloth sampling with three different drag-cloth check interval distances. We found a higher drop-off rate for adult ticks, 0.083/m, than nymphal ticks, 0.047/m. The estimated density of ticks decreased with increasing check interval distance. Our results not only highlight the importance of accounting for check interval distance when estimating tick density, but also provide the first estimate of nymphal I. scapularis drop-off rate.
Ferroelectric and dipole control of band alignment in the two dimensional InTe/In2Se3 heterostructure

Two dimensional (2D) ferroelectric materials are gaining growing attention due to their nontrival ferroelectricity, and the 2D ferroelectric heterostructures with tunable electronic, optoelectronic, or even magnetic properties, show many novel properties that do not exist in their constituents. In this work, by using the first-principles calculations, we investigate the ferroelectric and dipole control of electronic structures of the 2D ferroelectric heterostructure InTe/In2Se3. It is found that band alignment is closely dependent on the ferroelectric polarization of In2Se3. By switching the polarization of In2Se3, the band alignment of InTe/In2Se3 switches from a staggered (type II) to a straddling type (type I), and the band gap changes from indirect gap 0.76 eV to direct gap 0.15 eV. When the ferroelectric field of In2Se3 is reversed, the band alignment of InTe/In2Se3 switches from type-I to type-II, and the band gap changes from indirect gap 0.76 eV to direct gap 0.15 eV. In addition, we find that the interlayer dipole can also effectively modulate the band structure and induce the type-I to type-II band alignment transition. Our present results indicate that the 2D ferroelectric heterostructure with the tunable band alignment and band gap can be of great significance in the optoelectronic devices.
Transition from child to adult health services: A qualitative study of the views and experiences of families of young adults with intellectual disabilities.

AIMS AND OBJECTIVES To explore the experiences of the families of young adults with intellectual disabilities (ID) at the point of transition from child to adult health services. BACKGROUND The population of people with ID is changing rapidly, with young people with increasingly complex needs surviving into adulthood and requiring transition from child to adult health services. DESIGN An interpretative qualitative design. METHOD Semi-structured interviews were held with ten family carers of young adults with ID and complex care needs, who were in the process of or had recently completed a transition from child to adult health services in Scotland. Data was analysed using thematic analysis. The COREQ checklist was used. RESULTS Transition emerged asa highly emotional and challenging period for family carers.Their experiences were captured in five main themes: "a deep sense of loss", "an overwhelming process", "parents making transitions happen", "a shock to the adult healthcare system" and "the unbearable pressure". Nurses were often seen as instrumental to counteracting some of these challenges. CONCLUSION There is an urgent need to respond to the challenges experienced by carers at the point of transition and beyond, by ensuring early and coordinated planning, effective information sharing and communication and clear transition processes and guidelines. A person-centred and family-centred approach is required to minimise negative impact on the health and wellbeing of the young adult with ID and their carers. RELEVANCE TO CLINICAL PRACTICE Registered nurses have a key role in providing information and support, along with coordinating care at the time of transition from child to adult health services for young adults with complex ID. It is vital that their input is person-centred and responds effectively to the expert knowledge of family carers, whilst at the same time ensuring their needs for information and support are also addressed.
Factors associated with muscular fitness phenotypes in Australian children: A cross-sectional study

ABSTRACT To help inform strategies aimed at increasing muscular fitness levels, we examined factors associated with childhood muscular fitness (strength and power) that preceded the recently observed secular decline. Data were available from a nationally representative sample of Australian children aged 7–15 years in 1985 (n = 8469). Muscular fitness measures included strength (right and left grip, shoulder extension and flexion, and leg strength) and power (standing long jump distance). Anthropometric (adiposity, fat-free mass), cardiorespiratory fitness (CRF), flexibility, speed capability, physical activity (individual and parental), dietary quality and intake (fruit, vegetable, protein) and sociodemographic (area-level socioeconomic status (SES), school type) data were available. Statistical analyses included sex-stratified linear regression. Of all examined factors, measures of adiposity, fat-free mass, CRF, flexibility and speed capability were associated with muscular fitness at levels that met Cohen’s threshold for important effects (r-squared = 0.02 to 0.28). These findings highlight the multifactorial relationship between muscular fitness and its determinants. Collectively, these factors were powerful in explaining muscular strength (females: r-squared = 0.32; males: r-squared = 0.41) and muscular power (females: r-squared = 0.36; males: r-squared = 0.42). These findings highlight modifiable and environmental factors that could be targeted to increase childhood muscular fitness.
Changing perspectives on how the permeation pathway through potassium channels is regulated

The primary means by which ion permeation through potassium channels is controlled, and the key to selective intervention in a range of pathophysiological conditions, is the process by which channels switch between non‐conducting and conducting states. Conventionally, this has been explained by a steric mechanism in which the pore alternates between two conformations: a ‘closed’ state in which the conduction pathway is occluded and an ‘open’ state in which the pathway is sufficiently wide to accommodate fully hydrated ions. Recently, however, ‘non‐canonical’ mechanisms have been proposed for some classes of K+ channels. The purpose of this review is to illuminate structural and dynamic relationships underpinning permeation control in K+ channels, indicating where additional data might resolve some of the remaining issues.
OPIOID CODRUGS FOR PAIN MANAGEMENT

OF DISSERTATION OPIOID CODRUGS FOR PAIN MANAGEMENT Pain is an unpleasant sensory and emotional experience associated with actual or potential tissus damage or described in terms of such damage. Opioids are effective in treating moderate to severe pain, but opioid alone therapy is associated with several adverse effects, development of tolerance and addiction potential. One way to solve these problems is to administer opioids with adjuvant drugs. In this project several opioid molecules were combined with other adjuvant drugs in a single chemical entity to form a codrug. A series of codrugs were prepared by conjugation of an opioid with S-(-)-nornicotine, ketamine, norketamine and gabapentin. Several of the synthesized codrugs were evaluated for analgesic activity in the rats after oral administration. Codeine-S-(-)nornicotine, 3-O-acetylmorphine-S-(-)-nornicotine, and N-ethoxycarbonylgabapentincodeine codrugs showed greater effectiveness as well as prolonged pain management properties as compared to the parent drugs. Stabilities of several synthesized codrugs were studied in aqueous solutions from pH 1.3-7.4, in simulated gastrointestinal fluids, in rat plasma and in brain homogenate. Only the ester-linked codrugs showed sign of hydrolysis in different solutions. Carbamate-linked codrugs didn’t cleave under any hydrolytic condition. Pharmacokinetic study was performed on the following three codrugs: 3-O-acetylmorphine-S-(-)-nornicotine, N-acetylgabapentin-codeine, and Nethoxycarbonylgabapentin-codeine. The carbamate linkage in 3-O-acetylmorphine-S-(-)nornicotine codrug did not cleave in vivo to produce parent drugs. The ester linkage in Nacetylgabapentin-codeine codrug cleaved in vivo to produce codeine and Nacetylgabapentin, but N-acetylgabapentin did not undergo hydrolysis to produce gabapentin. The ester linkage in N-ethoxycarbonylgabapentin-codeine codrug hydrolyzed slowly in plasma to produce N-ethoxycarbonylgabapentin and codeine and then the carbamate linkage in N-ethoxycarbonylgabapentin hydrolyzed even slowly to produce gabapentin. Produced codeine also metabolized to generate some amount of morphine. Thus, the design and synthesis of an opiate and gabapentin codrug was achieved which was stable enough in the gastrointestinal tract, showed enhanced analgesic effects as compared to the physical mixture of the parent drugs, and also produced the two parent drugs in blood plasma.
Rotation and propulsion in 3D active chiral droplets

Significance Chirality plays an important role in many biological systems. Biomolecules, such as DNA, actin, or microtubules, form helical structures, which at sufficiently high density and in the absence of active forces, tend to self-assemble into twisted cholesteric phases. We study the effect of activity on a droplet of chiral matter, finding a surprisingly rich range of dynamical behaviors ranging from spontaneous rotations to screw-like motion. The phenomena that we uncover require both thermodynamic chirality and activity and are linked to the nontrivial topology of the defects that form by necessity at the droplet surface. It would be of interest to look for analogues of the motility modes found here in chiral microorganisms occurring in nature or in synthetic active matter. Chirality is a recurrent theme in the study of biological systems, in which active processes are driven by the internal conversion of chemical energy into work. Bacterial flagella, actomyosin filaments, and microtubule bundles are active systems that are also intrinsically chiral. Despite some exploratory attempt to capture the relations between chirality and motility, many features of intrinsically chiral systems still need to be explored and explained. To address this gap in knowledge, here we study the effects of internal active forces and torques on a 3-dimensional (3D) droplet of cholesteric liquid crystal (CLC) embedded in an isotropic liquid. We consider tangential anchoring of the liquid crystal director at the droplet surface. Contrary to what happens in nematics, where moderate extensile activity leads to droplet rotation, cholesteric active droplets exhibit more complex and variegated behaviors. We find that extensile force dipole activity stabilizes complex defect configurations, in which orbiting dynamics couples to thermodynamic chirality to propel screw-like droplet motion. Instead, dipolar torque activity may either tighten or unwind the cholesteric helix and if tuned, can power rotations with an oscillatory angular velocity of 0 mean.
Lipopolysaccharide induces epithelial–mesenchymal transition of alveolar epithelial cells cocultured with macrophages possibly via the JAK2/STAT3 signaling pathway

Epithelial–mesenchymal transition (EMT) plays a key role in the process of pulmonary fibrosis (PF). Increasing evidences have shown that exaggerated EMT in recurrent pulmonary injury mediates the early pathogenesis of PF. This study aimed to evaluate EMT of human alveolar epithelial cells (A549) when cocultured with human macrophages Tohoku hospital pediatrics-1 (THP-1) induced by lipopolysaccharide (LPS) and investigate the role of Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway. Firstly, we detected the inflammatory and EMT biomarkers in A549 cells monoculture and A549/THP-1 cells coculture in the presence or absence of LPS. Then, the activation of JAK2/STAT3 signaling pathway was determined in coculture. Interestingly, inflammatory markers, such as interleukin (IL)-6, matrix metalloproteinase (MMP)-9, transforming growth factor (TGF)-β, and collagen type 1 (COL-1), were enhanced in LPS treated coculture. Besides, the expression of E-cadherin decreased but α-smooth muscle actin expression increased, indicating the presence of EMT in A549 cells when cocultured with THP-1 macrophages. However, these phenotypes could not be observed in LPS-treated A549 cells monoculture. Meanwhile, JAK2/STAT3 signaling pathway was activated, and the STAT3 DNA-binding and inflammatory markers were inhibited by Stattic. Together, these findings demonstrate the key role of JAK2/STAT3 signaling pathway in LPS promoted EMT of A549 in the presence of THP-1 macrophages as an in vitro PF model.
Beginning Head Start Children Families and Programs in Fall 2006

The Head Start Family and Child Experiences Survey (FACES), a tool for measuring Head Start program performance at the national level, collects data on successive nationally representative cohorts of the children, their families, classrooms, and programs. It also examines developmental progress of children and their families during and after Head Start participation. In fall 2006, approximately 458,000 children were newly enrolled in 14,400 Head Start centers across the U.S. Just over a third were Hispanic/Latino; another third were African American. On average, children scored below the national norms on most measures of language, literacy, and math development, but mean standard scores for the highest quartile of children were at the national averages in letter recognition and early writing skills.
Brilliant Blue as an alternative dye to Fast Green for in ovo electroporation

Chick embryo electroporation is a powerful tool for the introduction of transgenes into tissues of interest for the study of developmental biology. This method often uses Fast Green to visualize the injected area by staining the solution containing DNA green. Here, we show that Fast Green fluoresces in a red color after electroporation, suggesting that researchers need to be cautious when detecting red fluorescence. Fast Green solution did not show any fluorescence before injection into chick embryos, but fluoresced red within 3 min post‐injection into chick embryos. We identified Brilliant Blue as suitable alternative dye for use as an indicator of injection sites in ovo electroporation. We found that 0.2% of Brilliant Blue was sufficient to track the area of DNA injection. In addition, this chemical did not show red fluorescence after electroporation. Our findings demonstrate that Brilliant Blue can be used for detecting red fluorescent proteins introduced into chick embryos by electroporation. Our study also shows useful examples for the application of Brilliant Blue for the precise quantification of two fluorescence intensities after EGFP and mCherry co‐electroporation.
Emergence of an NDM-5-Producing Hypervirulent Klebsiella pneumoniae Sequence Type 35 Strain with Chromosomal Integration of an Integrative and Conjugative Element, ICEKp1

Here, we report an NDM-5-producing sequence type 35 (ST35) hypervirulent Klebsiella pneumoniae strain, isolated from the blood of a male patient. It showed a remarkable resistance to serum killing and neutrophil phagocytosis and high virulence in a mouse peritonitis infection model. ABSTRACT Here, we report an NDM-5-producing sequence type 35 (ST35) hypervirulent Klebsiella pneumoniae strain, isolated from the blood of a male patient. It showed a remarkable resistance to serum killing and neutrophil phagocytosis and high virulence in a mouse peritonitis infection model. Instead of carrying a pLVPK-like virulence plasmid, chromosomal integration of ICEKp1 (∼76 kb) was identified in a specific asparagine-tRNA gene, harboring the iron acquisition system salmochelin genes (iroBCDN), a yersiniabactin gene, and a variant of the rmpA gene.