bluuebunny/crossref_metadata_2025_split huggingface dataset:
Driving and exceptional cases: Supporting relicensing evaluation in patients whose visual fields fail to meet standards
Authors: Harper Robert A. , Parkes Jeremy A. , Dickinson Christine M. 
Published: June 2022

AbstractPurposeThe UK Driver and Vehicle Licensing Agency's (DVLA) visual field criteria mean that homonymous defects close to fixation are not usually acceptable for driving. Here, we illustrate cases where patients with field defects failing to meet standards had their licences revoked but subsequently were permitted to drive again through exceptional case provisions.MethodsClinical assessment of two patients with homonymous loss: a 62‐year‐old man (PWT) with a dense left upper homonymous quadrantanopia secondary to a right occipital lobe stroke and a 48‐year‐old woman (JC), only aware of right upper homonymous quadrantanopia following routine primary care assessment and subsequently attributed to left middle cerebral artery stroke from perinatal intracranial haemorrhage.ResultsPWT's Esterman test showed a significant central defect failing to meet the standard. His subsequent ophthalmic examination was otherwise unremarkable with excellent visual functions. Clinical evidence was provided supporting his relicensing application, and in time, a practical DVLA driving assessment indicated adaptation had been successful, and his licence was restored. JC's defect also failed to meet the standard, and her licence was revoked. Her ophthalmic examination was otherwise unremarkable, and her condition was attributed to a nonprogressive, isolated perinatal event. The DVLA accepted supporting clinical evidence; her subsequent practical driving assessment demonstrated successful adaptation and her licence was also restored.ConclusionsConventional visual field tests are not necessarily predictive of real‐world driving performance, with drivers' adaptive strategies not being accommodated. In the UK, individuals with visual field loss failing to meet the standard may be eligible for relicensing as exceptional cases if specific criteria can be met. For exceptional cases potentially licensable under these criteria, the DVLA requires clinician support and a satisfactory practical driving assessment. Similar provisions exist internationally. Clinicians need to be aware of the role they may play in such scenarios.
Celecoxib‐tramadol co‐crystal in patients with moderate‐to‐severe pain following bunionectomy with osteotomy: A phase 3, randomized, double‐blind, factorial, active‐ and placebo‐controlled trial
Authors: Viscusi Eugene R. , de Leon‐Casasola Oscar , Cebrecos Jesús , Jacobs Adam , Morte Adelaida , Ortiz Esther , Sust Mariano , Vaqué Anna , Gottlieb Ira , Daniels Stephen , Gimbel Joseph S. , Muse Derek , Winkle Peter , Kuss Michael E. , Videla Sebastián , Gascón Neus , Plata‐Salamán Carlos 
Published: June 2022

AbstractBackgroundCelecoxib‐tramadol co‐crystal (CTC) is a first‐in‐class analgesic co‐crystal of celecoxib and racemic tramadol with an improved pharmacologic profile, conferred by the co‐crystal structure, compared with its active constituents administered alone/concomitantly.AimWe evaluated CTC in moderate‐to‐severe acute postoperative pain.Materials and MethodsThis randomized, double‐blind, factorial, active‐ and placebo‐controlled phase 3 trial (NCT03108482) was conducted at 6 US clinical research centers. Adults with moderate‐to‐severe acute pain following bunionectomy with osteotomy were randomized to oral CTC (200 mg [112 mg celecoxib/88 mg rac‐tramadol hydrochloride] every 12 h), tramadol (50 mg every 6 h), celecoxib (100 mg every 12 h), or placebo for 48 h. Patients, investigators, and personnel were blinded to assignment. The primary endpoint was the 0–48 h sum of pain intensity differences (SPID0–48) in all randomized patients. Pain intensity was assessed on a 0–10 numerical rating scale (NRS). Safety was analyzed in patients who received study medication. Funded by ESTEVE Pharmaceuticals.ResultsIn 2017 (March to November), 1323 patients were screened and 637 randomized to CTC (n = 184), tramadol (n = 183), celecoxib (n = 181), or placebo (n = 89). Mean baseline NRS was 6.7 in all active groups. CTC had a significantly greater effect on SPID0–48 (least‐squares mean: −139.1 [95% confidence interval: −151.8, −126.5]) than tramadol (−109.1 [−121.7, −96.4]; p < 0.001), celecoxib (−103.7 [−116.4, −91.0]; p < 0.001), or placebo (−74.6 [−92.5, −56.6]; p < 0.001). Total treatment‐emergent adverse events (TEAEs) were 358 for CTC and 394 for tramadol. Drug‐related TEAEs occurred in 37.7% patients in the CTC group, compared with 48.6% in the tramadol group. There were no serious TEAEs/deaths.ConclusionCTC provided greater analgesia than comparable daily doses of tramadol and celecoxib, with similar tolerability to tramadol. CTC is approved in the United States.
Cardiac magnetic resonance diastolic indices correlate with ventricular filling pressures in pediatric heart transplant recipients
Authors: Belay Wubishet , Godown Justin , Chan Kak‐Chen , Bearl David W. , George‐Durrett Kristen , Slaughter James C. , Crum Kimberly , Dodd Debra A. , Chrisant Maryanne , Hernandez Lazaro , Soslow Jonathan 
Published: June 2022

AbstractBackgroundAtrial and ventricular filling pressures are routinely used in pediatric heart transplant (PHTx) recipients to assess graft function. We hypothesized that cardiac magnetic resonance (CMR) diastolic indices correlate with filling pressures, providing a noninvasive method of hemodynamic assessment.MethodsPediatric heart transplant recipients were prospectively enrolled at the time of cardiac catheterization. Pulmonary capillary wedge pressure (PCWP) and right atrial pressure (RAP) were measured. CMR included standard volumetric analysis. Filling curves were calculated by contouring every phase in the short‐axis stack. Global longitudinal and circumferential strain (GLS, GCS) were calculated using feature tracking. Atrial volumes and ejection fraction were calculated from 4‐chamber and 2‐chamber cine images. Correlations were analyzed using Spearman's Rho; modeling was performed with multivariable logistic regression.ResultsA total of 35 patients with a mean age of 15.5 years were included, 12 with acute rejection. The median time post‐transplant was 6.2 years. Peak filling rate (PFR) and peak LV ejection rate/end‐diastolic volume (PER/EDV) correlated with PCWP (rho = 0.48 p = .005, and rho = −0.35 p = .046, respectively) as did GLS and GCS (rho = 0.52 p = .002, and 0.40 p = .01). Indexed maximum and minimum left atrial (LA) volume correlated with PCWP (rho = 0.41, p = .01, rho = 0.41 p = .01), and LA ejection fraction inversely correlated with PCWP (rho = −0.40, p = .02). GLS and GCS correlated with RAP (rho = 0.55, p = .001 and rho = 0.43, p = .01). A model including LV GLS and PFR estimated PCWP ≥12 mmHg with an area under the curve of 0.84.ConclusionsCardiac magnetic resonance can be a useful noninvasive modality to assess for signs of diastolic dysfunction after PHTx.
Maladaptation to the transition period and consequences on fertility of dairy cows
Authors: Pascottini Osvaldo Bogado , Leroy Jo L. M. R. , Opsomer Geert 
Published: June 2022

AbstractAfter parturition, dairy cows undergo a plethora of metabolic, inflammatory, and immunologic changes to adapt to the onset of lactation. These changes are mainly due to the homeorhetic shift to support milk production when nutrient demand exceeds dietary intake, resulting in a state of negative energy balance. Negative energy balance in postpartum dairy cows is characterized by upregulated adipose tissue modelling, insulin resistance, and systemic inflammation. However, half of the postpartum cows fail to adapt to these changes and develop one or more types of clinical and subclinical disease within 5 weeks after calving, and this is escorted by impaired reproductive performance in the same lactation. Maladaptation to the transition period exerts molecular and structural changes in the follicular and reproductive tract fluids, the microenvironment in which oocyte maturation, fertilization, and embryo development occur. Although the negative effects of transition diseases on fertility are well‐known, the involved pathways are only partially understood. This review reconstructs the mechanism of maladaptation to lactation in the transition period, explores their key (patho)physiological effects on reproductive organs, and briefly describes potential carryover effects on fertility in the same lactation.
Effects of long‐term phosphorus fertilizer inputs and seasonal conditions on organic soil phosphorus cycling under grazed pasture
Authors: Touhami Driss , Condron Leo M. , McDowell Richard W. , Moss Ray 
Published: June 2022

AbstractSoil microbes and phosphatase enzymes play a critical role in organic soil phosphorus (P) cycling. However, how long‐term P inputs influence microbial P transformations and phosphatase enzyme activity under grazed pastures remains unclear. We collected top‐soil (0–75 mm) from a grazed pasture receiving contrasting P inputs (control, 188 kg ha−1 year−1 of single super phosphate [SSP], and 376 kg ha−1 year−1 of SSP) for more than 65 years. Olsen P, microbial biomass P, and acid and alkaline phosphatase enzyme activities were measured regularly over a 2‐year period. Pasture dry matter and soil chemical properties were also investigated. Results showed that long‐term P inputs significantly increased pasture dry matter, total N, and the concentrations of –N but significantly decreased soil pH and the concentrations of –N. Total C was not affected by P fertilization. Although Olsen P significantly increased with increasing long‐term P inputs, microbial biomass P was similar under P fertilized treatments. Long‐term P inputs decreased acid phosphatase activity but increased alkaline phosphatase activity. Microbial biomass P was similar across seasons in the control but decreased in spring and autumn while increased in summer and winter under P fertilized treatments. Acid and alkaline phosphatase activities were significantly affected by season and followed similar seasonal trends being maximum in summer and minimum in winter regardless of P treatment. Correlation and principal component analysis revealed that acid and alkaline phosphatase activities were significantly positively correlated with soil temperature and significantly negatively correlated with soil moisture. In contrast, Olsen P and microbial biomass P were weakly correlated with environmental conditions. The findings of this study highlight the intertwined relationship between organic P cycling and the availability of C and N in soil systems and the need to integrate both soil moisture and temperature in models predicting organic P mineralization, especially in the context of global climate change.
Limited soil carbon storage under long‐term organic fertilization in solar greenhouses
Authors: Zhang Yueqi , Hagedorn Frank , Guidi Claudia , Yang Lijuan 
Published: June 2022

AbstractEnvironmental conditions, fertilization systems and cultivation practices in greenhouses differ from those in arable soil. Despite being a widespread intensive management practice, large uncertainties exist on the effects of long‐term fertilization on soil organic carbon (SOC) in greenhouse cultivation. The objective of this study was to explore the effects of 11‐year‐long fertilization on carbon (C) stocks in soil aggregates (>2 mm; 2–0.25 mm; 0.25–0.053 mm; <0.053 mm) and SOC fractions (free light fraction (free LF), intra‐aggregate particulate organic carbon (iPOC), mineral‐associated organic carbon (mAOC)) at 0–20 cm and 20–40 cm depth in a solar greenhouse. Five treatments were examined: control (no fertilizer), chicken manure (M), chicken manure plus straw (M + S), chicken manure plus lime (M + Ca), chicken manure plus straw and lime (M + S + Ca). Over the 11 years of continuous intensive organic fertilization, SOC contents of all fertilization treatments first increased sharply and then stabilized after 5 years. The M + S + Ca treatment increased the proportion of aggregate masses, SOC concentrations as well as SOC stocks of soil aggregates >2 mm, 2–0.25 mm, but straw or lime application alone had no significant effects. The M + S + Ca treatment increased the SOC stock of free LF, fine iPOC, coarse iPOC and mAOC by 97%, 38%, 22% and 25% compared with the M treatment, respectively. Straw treatment alone only significantly increased the soil labile C stock (free LF, iPOC). At 0–40 cm depth, the regression between the C stock and the C input had the steepest slope in bulk soil (slope = 0.223, R2 = 0.87**). After 11 years, about 15% of the C inputs were sequestered in the soils. As the mAOC remained largely unaffected, the increase in SOC seems only short‐lived and reaches a new equilibrium within a few years when C inputs are balanced out by mineralization. Consequently, the intensive fertilization and management practices in greenhouse cultivation allowing obtaining high tomato yields results in an overall negative C balance.
Birth Weight and Other Risk Factors for Acute Leukemia in the Jerusalem Perinatal Study Cohort
Authors: Paltiel Ora , Harlap Susan , Deutsch Lisa , Knaanie Ariella , Massalha Sausan , Tiram Efrat , Barchana Micha , Friedlander Yehiel 
Published: June 2022

Abstract
Objectives: To assess the effect of birth weight of children and their siblings and other perinatal/parental factors on the risk of acute leukemia. Methods: We linked data from the Jerusalem Perinatal Study, a population-based research cohort (n = 88,829) of offspring born 1964 to 1976, with Israel's Cancer Registry. Risk factors for acute leukemia were assessed using univariate and multivariate proportional hazards models. Results: Leukemias developed in 65 individuals [24 acute myeloid leukemias (AML) and 41 acute lymphoblastic leukemias (ALL)]. A positive linear relation was found between gender-adjusted birth weight and all leukemias [hazard ratio (HR) 1.85, 95% confidence interval (95% CI) 1.1-3.0] and AML (HR 2.9, 95% CI 1.3-6.4). The association between birth weight and AML was especially notable among infants (HR 8.14, 95% CI 1.8-38.9 for age 0 to 1 year) but was also observed among subjects ages &gt;14 years at diagnosis. The relation was particularly strong among females (P = 0.001). Other risk factors for AML risk on univariate analysis were maternal origin, socioeconomic status, birth weight of sibling &gt; 3,500 g, and family size. On multivariate analysis, only birth weight retained borderline significance (adjusted HR 2.38 per kg, 95% CI 1.0-5.7). Significant predictors for ALL in both univariate and multivariate analyses were male sex (adjusted HR 1.92, 95% CI 1.0-3.7) and birth weight categories ≥ 3,000 g introduced into the model as nonlinear terms. Conclusion: Birth weight is associated with an increased risk of acute leukemia in infants, children, and young adults. Perinatal factors play a role in the development of childhood leukemias, but the patterns of association vary by leukemia type.
The P2X7 Receptor Gene A1513C Polymorphism Does Not Contribute to Risk of Familial or Sporadic Chronic Lymphocytic Leukemia
Authors: Sellick Gabrielle S. , Rudd Matthew , Eve Paul , Allinson Ruth , Matutes Estella , Catovsky Daniel , Houlston Richard S. 
Published: June 2022

Abstract
The P2X7 receptor, a plasma membrane ATP-gated ion channel that plays a role in lymphocyte apoptosis, has been suggested to be involved in the development of chronic lymphocytic leukemia (CLL). P2X7 is polymorphic with 1513A and 1513C alleles encoding fully active and nonfunctional proteins, respectively. We evaluated the significance of the P2X7-A1513C polymorphism on CLL risk by genotyping 424 patients and 428 healthy controls. To empower detection of an association, we included in our analysis 106 familial cases. Allele frequencies were identical in cases and controls irrespective of whether cases were familial or sporadic (frequency of the C allele was 0.17 and 0.17, respectively). The odds ratio of CLL associated with the C allele was 1.03 (95% confidence interval: 0.80-1.31). A meta-analysis of this study and five other smaller published studies provides no evidence of relationship between this P2X7 polymorphism and risk of CLL (odds ratio = 0.99, 95% confidence interval: 0.74-1.32).
Targeting Angiogenesis for Mammary Cancer Prevention: Factors to Consider in Experimental Design and Analysis
Authors: Thompson Henry J. , McGinley John N. , Wolfe Pamela , Spoelstra Nicole S. , Knott Katrina K. 
Published: June 2022

Abstract
An experimental model developed to investigate premalignant stages of breast cancer was used to establish a rationale for designing experiments that target angiogenesis for cancer prevention. Blood vessels were identified via CD31 immunostaining, and all vessels that occurred in a 50 μm wide region circumscribing each pathology were counted using a digital imaging technique. The blood vessel density associated with terminal end buds was unaffected by carcinogen treatment, whereas vessel density was higher in intraductal proliferations and ductal carcinoma in situ than in terminal end buds (P &lt; 0.001) and total vascularity increased with morphologic progression. In comparison with intraductal proliferation or ductal carcinoma in situ, mammary carcinomas had higher vascular density in the tissue surrounding the cancer with a marked increase in the number of blood vessels &lt;25 μm2. These data suggest that antiangiogenic chemopreventive agents would inhibit cancer occurrence if initiated at any premalignant stage of the carcinogenic process. Because increased vascular density observed during premalignancy could be explained by the size expansion of the lesion and its encroachment on a preexisting blood supply, by pathology-associated vessel expansion, and/or by angiogenesis, it remains to be determined if antiangiogenic agents will reduce the prevalence of premalignant lesions or cause their accumulation by blocking conversion to carcinomas. Failure to recognize the patterns of vascularization that accompany morphologic progression could limit the success of efforts to target angiogenesis for cancer prevention and lead to misinformation about how agents that affect blood vessel formation or growth inhibit the carcinogenic process.
Consumption of the Putative Chemopreventive Agent Curcumin by Cancer Patients: Assessment of Curcumin Levels in the Colorectum and their Pharmacodynamic Consequences
Authors: Garcea Giuseppe , Berry David P. , Jones Donald J.L. , Singh Raj , Dennison Ashley R. , Farmer Peter B. , Sharma Ricky A. , Steward William P. , Gescher Andreas J. 
Published: June 2022

Abstract
Curcumin, a constituent of the spice turmeric, has been shown to reduce the adenoma burden in rodent models of colorectal cancer accompanied by a reduction of levels of the oxidative DNA adduct 3-(2-deoxy-β-di-erythro-pentafuranosyl)-pyr[1,2-α]-purin-10(3H)one (M1G) and of expression of the enzyme cyclooxygenase-2 (COX-2). We tested the hypothesis that pharmacologically active levels of curcumin can be achieved in the colorectum of humans as measured by effects on levels of M1G and COX-2 protein. Patients with colorectal cancer ingested curcumin capsules (3,600, 1,800, or 450 mg daily) for 7 days. Biopsy samples of normal and malignant colorectal tissue, respectively, were obtained at diagnosis and at 6 to 7 hours after the last dose of curcumin. Blood was taken 1 hour after the last dose of curcumin. Curcumin and its metabolites were detected and quantitated by high-performance liquid chromatography with detection by UV spectrophotometry or mass spectrometry. M1G levels and COX-2 protein expression were measured by immunoslot blot and Western blotting, respectively. The concentrations of curcumin in normal and malignant colorectal tissue of patients receiving 3,600 mg of curcumin were 12.7 ± 5.7 and 7.7 ± 1.8 nmol/g, respectively. Curcumin sulfate and curcumin glucuronide were identified in the tissue of these patients. Trace levels of curcumin were found in the peripheral circulation. M1G levels were 2.5-fold higher in malignant tissue as compared with normal tissue (P &lt; 0.05 by ANOVA). Administration of curcumin (3,600 mg) decreased M1G levels from 4.8 ± 2.9 adducts per 107 nucleotides in malignant colorectal tissue to 2.0 ± 1.8 adducts per 107 nucleotides (P &lt; 0.05 by ANOVA). COX-2 protein levels in malignant colorectal tissue were not affected by curcumin. The results suggest that a daily dose of 3.6 g curcumin achieves pharmacologically efficacious levels in the colorectum with negligible distribution of curcumin outside the gut.
Effect of Folic Acid Supplementation on the Folate Status of Buccal Mucosa and Lymphocytes
Authors: Basten Graham P. , Hill Marilyn H. , Duthie Susan J. , Powers Hilary J. 
Published: June 2022

AbstractFolate deficiency may be associated with an increased risk of cancer at certain sites. There is a need to measure folate status and putative biomarkers of cancer risk in the same target tissue, or in surrogate tissues. A study was carried out to develop a method for the rapid measurement of folate in human buccal mucosa and lymphocytes and to evaluate the responsiveness of this measurement in both tissues to folic acid supplementation in healthy subjects, relative to conventional markers of folate status. Three hundred and twenty-three adults, ages between 20 and 60 years, were screened for RBC folate concentrations. Sixty-five subjects with red cell folate between 200 and 650 nmol/L participated in a randomized, double blind, placebo-controlled, folic acid (1.2 mg) intervention trial, lasting 12 weeks. As anticipated, a significant baseline correlation (r = 0.36, P &lt; 0.01) was observed between red cell folate and plasma 5-methyltetrahydrofolate (5-MeTHF). Lymphocyte total folate was significantly associated with plasma 5-MeTHF (r = 0.28, P &lt; 0.05) and plasma total homocysteine concentration (r = −0.34, P &lt; 0.05). Buccal mucosa total folate showed no correlation with either red cell folate or 5-MeTHF, but was significantly associated with lymphocyte total folate (r = 0.35, P &lt; 0.01). Supplementation elicited a significant increase in lymphocyte total folate (P &lt; 0.01), and this was strongly associated with the increase in RBC total folate (P &lt; 0.01) and plasma 5-MeTHF (P &lt; 0.01). Buccal mucosa total folate was not influenced by folate supplementation. Methods have been developed for the rapid measurement of lymphocyte and buccal mucosal total folate. Lymphocyte folate is sensitive to folate intake and is reflected by plasma 5-MeTHF.