bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thalidomide-Associated Thrombocytopenia
Authors: Duyvendak Michiel , Naunton Mark , Kingma Bert J , Brouwers Jacobus RBJ 
Published: October 2005

OBJECTIVE To report thrombocytopenia in a patient prescribed thalidomide for multiple myeloma (MM). CASE SUMMARY A 70-year-old woman was diagnosed in 2003 with MM. At diagnosis, melphalan 0.25 mg/kg/day and prednisolone 2 mg/kg/day were started; however, the patient became refractory to therapy. Melphalan and prednisolone were discontinued, and monotherapy with dexamethasone 40 mg for 12 days per month was started. The patient's hematologic condition deteriorated again after about one year; dexamethasone was discontinued, and treatment with oral thalidomide 200 mg/day was initiated. About 2 weeks after thalidomide administration, the woman developed disabling adverse effects (flu-like symptoms, swollen fingers, rash and hematoma on her legs, shortness of breath, dry mouth, multiple petechiae). Laboratory testing showed neutropenia (neutrophils 0.4 × 109/L) and thrombocytopenia (platelets 58 × 109/L). Thalidomide was promptly discontinued; within 3 weeks, the laboratory values returned to pretreatment levels (1.3 × 109/L and 267 × 109/L, respectively) and her symptoms disappeared. DISCUSSION Thrombocytopenia is a rarely reported hematologic adverse consequence of thalidomide therapy. A recent report identified 5 patients who developed thrombocytopenia while undergoing monotherapy with thalidomide for MM. According to the Naranjo probability scale, thalidomide was classified as the probable cause of thrombocytopenia in our patient. CONCLUSIONS Unlike other antineoplastic drugs, thalidomide is rarely reported to cause severe hematologic toxicity. We present this case to increase clinicians’ awareness for the potential of thalidomide to adversely affect platelet counts, particularly because its effectiveness in MM will likely result in expansion of its clinical use.
Pharmacist Impact on Clinical Outcomes in a Diabetes Disease Management Program via Collaborative Practice
Authors: Kiel Patrick J , McCord Amie D 
Published: October 2005

BACKGROUND Clinical outcomes resulting from pharmaceutical care have been incompletely addressed in the diabetes population. We conducted a retrospective study evaluating clinical outcomes in a diabetes disease management program in which clinical pharmacists possessed collaborative practice agreements. OBJECTIVE To evaluate changes in clinical outcomes for patients enrolled in a pharmacist-coordinated diabetes management program. METHODS Medical records of 157 patients enrolled in the diabetes management program between June 2003 and April 2004 were retrospectively reviewed. Data collection included baseline and follow-up values for hemoglobin A1C (A1C) and lipids as well as frequency of adherence to preventive care, including annual foot and eye examinations and daily aspirin therapy. RESULTS For patients with both baseline and follow-up data, the mean A1C reduction was 1.6% (n = 109; p < 0.001). For patients with an initial A1C of ≥8.5%, the mean reduction was 2.7% (n = 57; p < 0.001). The percentage of patients with A1C ≤7% increased from 19% at baseline to 50% at follow-up (p < 0.001). The mean low-density lipoprotein (LDL) reduction observed was 16 mg/dL (n = 73; NS) and the percentage of patients with LDL values ≤100 mg/dL increased from 30% at baseline to 56% at follow-up (p < 0.001). The frequency of microalbumin screening increased by 27% (p < 0.001), and the number of patients with annual eye and foot examinations increased by 27% (p < 0.05) and 15% (p < 0.05), respectively. The percentage of patients who had a positive microalbumin test and were taking a renal protective agent rose 19% from baseline to follow-up (NS). The percentage of patients taking daily aspirin increased from 42% at baseline to 80% at follow-up (p < 0.01). CONCLUSIONS The pharmacist-coordinated diabetes management program was effective in improving clinical markers for enrolled patients. Significant improvements were observed in A1C and LDL values as well as the frequency of adherence to preventive care.
Azo Dye Tautomeric Structures Determined by Laser-Raman Spectroscopy
Authors: Trotter P. J. 
Published: October 2005

Raman spectra of a number of azo dye structures have been analyzed. In azonaphthol and azopyrazol dyes, hydroxyazo to keto-hydrazone tautomerizations, [Formula: see text] were observed in aqueous basic and acidic media. Observations of azo and ring vibrations, as well as hydrazone (C=N plus C=0) bands, were made. It was noted that the azo-anions (examined at pH 12) convert to the protonated neutral hydrazone (keto) form in aqueous acid (run at pH 2). Infrared spectra were used to confirm the presence of the C=0 group in keto-tautomeric forms.
Novel bacterial molybdenum and tungsten enzymes: three-dimensional structure, spectroscopy, and reaction mechanism
Authors: Boll Matthias , Schink Bernhard , Messerschmidt Albrecht , Kroneck Peter M.H. 
Published: October 2005

Abstract
The molybdenum enzymes 4-hydroxybenzoyl-CoA reductase and pyrogallol-phloroglucinol transhydroxylase and the tungsten enzyme acetylene hydratase catalyze reductive dehydroxylation reactions, i.e., transhydroxylation between phenolic residues and the addition of water to a triple bond. Such activities are unusual for this class of enzymes, which carry either a mononuclear Mo or W center. Crystallization and subsequent structural analysis by high-resolution X-ray crystallography has helped to resolve the reaction centers of these enzymes to a degree that allows us to understand the interaction of the enzyme and the respective substrate(s) in detail, and to develop a concept for the respective reaction mechanism, at least in two cases.
Growth Defect and Mutator Phenotypes of RecQ-Deficient Neurospora crassa Mutants Separately Result From Homologous Recombination and Nonhomologous End Joining During Repair of DNA Double-Strand Breaks
Authors: Kato Akihiro , Inoue Hirokazu 
Published: October 2005

Abstract
RecQ helicases function in the maintenance of genome stability in many organisms. The filamentous fungus Neurospora crassa has two RecQ homologs, QDE3 and RECQ2. We found that the qde-3 recQ2 double mutant showed a severe growth defect. The growth defect was alleviated by mutation in mei-3, the homolog of yeast RAD51, which is required for homologous recombination (HR), suggesting that HR is responsible for this phenotype. We also found that the qde-3 recQ2 double mutant showed a mutator phenotype, yielding mostly deletions. This phenotype was completely suppressed by mutation of mus-52, a homolog of the human KU80 gene that is required for nonhomologous end joining (NHEJ), but was unaffected by mutation of mei-3. The high spontaneous mutation frequency in the double mutant is thus likely to be due to NHEJ acting on an elevated frequency of double-strand breaks (DSBs) and we therefore suggest that QDE3 and RECQ2 maintain chromosome stability by suppressing the formation of spontaneous DSBs.
Unequal Contribution of Sexes in the Origin of Dog Breeds
Authors: Sundqvist A-K , Björnerfeldt S , Leonard J A , Hailer F , Hedhammar Å , Ellegren H , Vilà C 
Published: October 2005

AbstractDogs (Canis familiaris) were domesticated from the gray wolf (Canis lupus) at least 14,000 years ago, and there is evidence of dogs with phenotypes similar to those in modern breeds 4000 years ago. However, recent genetic analyses have suggested that modern dog breeds have a much more recent origin, probably &lt;200 years ago. To study the origin of contemporaneous breeds we combined the analysis of paternally inherited Y chromosome markers with maternally inherited mitochondrial DNA and biparentally inherited autosomal microsatellite markers in both domestic dogs and their wild ancestor, the gray wolf. Our results show a sex bias in the origin of breeds, with fewer males than females contributing genetically, which clearly differs from the breeding patterns in wild gray wolf populations where both sexes have similar contributions. Furthermore, a comparison of mitochondrial DNA and Y chromosome diversity in dog groups recognized by the World Canine Organization, as well as in groups defined by the breeds' genetic composition, shows that paternal lineages are more differentiated among groups than maternal lineages. This demonstrates a lower exchange of males than of females between breeds belonging to different groups, which illustrates how breed founders may have been chosen.
Directional Positive Selection on an Allele of Arbitrary Dominance
Authors: Teshima Kosuke M , Przeworski Molly 
Published: October 2005

Abstract
Most models of positive directional selection assume codominance of the beneficial allele. We examine the importance of this assumption by implementing a coalescent model of positive directional selection with arbitrary dominance. We find that, for a given mean fixation time, a beneficial allele has a much weaker effect on diversity at linked neutral sites when the allele is recessive.
No Patrigenes Required for Femaleness in the Haplodiploid Wasp Nasonia vitripennis
Authors: Beukeboom Leo W , Kamping Albert 
Published: October 2005

Abstract
The parasitoid wasp Nasonia vitripennis is an emerging model organism for developmental and behavioral genetics. It reproduces by haplodiploidy; males typically develop parthenogenetically from haploid eggs and females from fertilized diploid eggs. A polyploid mutant strain is available in which females are triploid and lay haploid and diploid eggs that normally develop into males when unfertilized. In contrast to previous reports, ∼2% of triploid females were found to occasionally produce daughters as well as gynandromorphs from diploid unfertilized eggs. Daughter production increased with age and differed among familial lineages. This is the first report of parthenogenetic female development in Nasonia. The results show that a paternally provided genome is not required for femaleness and call for modifications of existing models of sex determination in Nasonia.
Genetic Analysis of Saccharomyces cerevisiae H2A Serine 129 Mutant Suggests a Functional Relationship Between H2A and the Sister-Chromatid Cohesion Partners Csm3–Tof1 for the Repair of Topoisomerase I-Induced DNA Damage
Authors: Redon Christophe , Pilch Duane R , Bonner William M 
Published: October 2005

Abstract
Collision between a topoisomerase I-DNA intermediate and an advancing replication fork represents a unique form of replicative damage. We have shown previously that yeast H2A serine 129 is involved in the recovery from this type of damage. We now report that efficient repair also requires proteins involved in chromatid cohesion: Csm3; Tof1; Mrc1, and Dcc1. Epistasis analysis defined several pathways involving these proteins. Csm3 and Tof1 function in a same pathway and downstream of H2A. In addition, the pathway involving H2A/Csm3/Tof1 is distinct from the pathways involving the Ctf8/Ctf18/Dcc1 complex, the Rad9 pathway, and another involving Mrc1. Our genetic studies suggest a role for H2A serine 129 in the establishment of specialized cohesion structure necessary for the normal repair of topoisomerase I-induced DNA damage.
DNA Polymerase 4 of Saccharomyces cerevisiae Is Important for Accurate Repair of Methyl-Methanesulfonate-Induced DNA Damage
Authors: Sterling Catherine H , Sweasy Joann B 
Published: October 2005

Abstract
The DNA polymerase 4 protein (Pol4) of Saccharomyces cerevisiae is a member of the X family of DNA polymerases whose closest human relative appears to be DNA polymerase λ. Results from previous genetic studies conflict over the role of Pol4 in vivo. Here we show that deletion of Pol4 in a diploid strain of the SK1 genetic background results in sensitivity to methyl methanesulfonate (MMS). However, deletion of Pol4 in other strain backgrounds and in haploid strains does not yield an observable phenotype. The MMS sensitivity of a Pol4-deficient strain can be rescued by deletion of YKu70. We also show that deletion of Pol4 results in a 6- to 14-fold increase in the MMS-induced mutation frequency and in a significant increase in AT-to-TA transversions. Our studies suggest that Pol4 is critical for accurate repair of DNA lesions induced by MMS.
Accumulation of NonfunctionalS-Haplotypes Results in the Breakdown of Gametophytic Self-Incompatibility in Tetraploid Prunus
Authors: Hauck Nathanael R , Yamane Hisayo , Tao Ryutaro , Iezzoni Amy F 
Published: October 2005

AbstractThe transition from self-incompatibility (SI) to self-compatibility (SC) is regarded as one of the most prevalent transitions in Angiosperm evolution, having profound impacts on the genetic structure of populations. Yet, the identity and function of mutations that result in the breakdown of SI in nature are not well understood. This work provides the first detailed genetic description of the breakdown of S-RNase-mediated gametophytic self-incompatibility (GSI) in a polyploid species that exhibits genotype-dependent loss of SI. Genetic analyses of six natural sour cherry (Rosaceae, Prunus cerasus) selections identified seven independent, nonfunctional S-haplotypes with disrupted pistil component (stylar-S) and/or pollen component (pollen-S) function. A genetic model demonstrating that the breakdown of SI in sour cherry is due to the accumulation of a minimum of two nonfunctional S-haplotypes within a single individual is developed and validated. Our finding that sour cherry is SI when only one nonfunctional S-haplotype is present has significant evolutionary implications since nonfunctional S-haplotypes would be maintained in the population without causing an abrupt shift to SC. Furthermore, we demonstrate that heteroallelic sour cherry pollen is self-incompatible, which is counter to the well-documented phenomenon in the Solanaceae where SC accompanying polyploidization is frequently due to the SC of heteroallelic pollen.
Intragenic Suppression of Gal3C Interaction With Gal80 in the Saccharomyces cerevisiae GAL Gene Switch
Authors: Diep Cuong Q , Peng Gang , Bewley Maria , Pilauri Vepkhia , Ropson Ira , Hopper James E 
Published: October 2005

Abstract
Gal4-mediated activation of GAL gene transcription in Saccharomyces cerevisiae requires the interaction of Gal3 with Gal80, the Gal4 inhibitor protein. While it is known that galactose and ATP activates Gal3 interaction with Gal80, neither the mechanism of activation nor the surface that binds to Gal80 is known. We addressed this through intragenic suppression of GAL3C alleles that cause galactose-independent Gal3–Gal80 interaction. We created a new allele, GAL3SOC, and showed that it suppressed a new GAL3C allele. We tested the effect of GAL3SOC on several newly isolated and existing GAL3C alleles that map throughout the gene. All except one GAL3C allele, D368V, were suppressible by GAL3SOC. GAL3SOC and all GAL3C alleles were localized on a Gal3 homology model that is based on the structure of the highly related Gal1 protein. These results provide evidence for allosterism in the galactose- and ATP-activation of Gal3 binding to Gal80. In addition, because D368V and residues corresponding to Gal80-nonbinder mutations colocalized to a domain that is absent in homologous proteins that do not bind to Gal80, we suggest that D368 is a part of the Gal80-binding surface.
Drosophila Target of Rapamycin Kinase Functions as a Multimer
Authors: Zhang Yong , Billington Charles J , Pan Duojia , Neufeld Thomas P 
Published: October 2005

Abstract
Target of rapamycin (TOR) is a conserved regulator of cell growth and metabolism that integrates energy, growth factor, and nutrient signals. The 280-kDa TOR protein functions as the catalytic component of two large multiprotein complexes and consists of an N-terminal HEAT-repeat domain and a C-terminal Ser/Thr kinase domain. Here we describe an allelic series of mutations in the Drosophila Tor gene and show that combinations of mutations in the HEAT and kinase domains of TOR display the rare genetic phenomenon of intragenic complementation, in which two or more defective proteins assemble to form a functional multimer. We present biochemical evidence that TOR self-associates in vivo and show that this multimerization is unaffected by positive or negative signals upstream of TOR. Consistent with multimerization of TOR, recessive mutations in the HEAT and kinase domains can dominantly interfere with wild-type TOR function in cells lacking TSC1 or TSC2. TOR multimerization thus partially accounts for the high apparent molecular weight of TOR complexes and offers novel therapeutic strategies for pathologies stemming from TOR hyperactivity.
Neonatal Intensive Care Unit Resource Use for Infants at 22 Weeks’ Gestation in the US, 2008-2021
Authors: Rysavy Matthew A. , Bennett Monica M. , Ahmad Kaashif A. , Patel Ravi M. , Shah Zubin S. , Ellsbury Dan L. , Clark Reese H. , Tolia Veeral N. 
Published: February 2024

ImportanceDuring the past decade, clinical guidance about the provision of intensive care for infants born at 22 weeks’ gestation has changed. The impact of these changes on neonatal intensive care unit (NICU) resource utilization is unknown.ObjectiveTo characterize recent trends in NICU resource utilization for infants born at 22 weeks’ gestation compared with other extremely preterm infants (≤28 weeks’ gestation) and other NICU-admitted infants.Design, Setting, and ParticipantsThis is a serial cross-sectional study of 137 continuously participating NICUs in 29 US states from January 1, 2008, through December 31, 2021. Participants included infants admitted to the NICU. Data analysis was performed from October 2022 to August 2023.ExposuresYear and gestational age at birth.Main Outcomes and MeasuresMeasures of resource utilization included NICU admissions, NICU bed-days, and ventilator-days.ResultsOf 825 112 infants admitted from 2008 to 2021, 60 944 were extremely preterm and 872 (466 [53.4%] male; 18 [2.1%] Asian; 318 [36.5%] Black non-Hispanic; 218 [25.0%] Hispanic; 232 [26.6%] White non-Hispanic; 86 [9.8%] other or unknown) were born at 22 weeks’ gestation. NICU admissions at 22 weeks’ gestation increased by 388%, from 5.7 per 1000 extremely preterm admissions in 2008 to 2009 to 27.8 per 1000 extremely preterm admissions in 2020 to 2021. The number of NICU admissions remained stable before the publication of updated clinical guidance in 2014 to 2016 and substantially increased thereafter. During the study period, bed-days for infants born at 22 weeks increased by 732%, from 2.5 per 1000 to 20.8 per 1000 extremely preterm NICU bed-days; ventilator-days increased by 946%, from 5.0 per 1000 to 52.3 per 1000 extremely preterm ventilator-days. The proportion of NICUs admitting infants born at 22 weeks increased from 22.6% to 45.3%. Increases in NICU resource utilization during the period were also observed for infants born at less than 22 and at 23 weeks but not for other gestational ages. In 2020 to 2021, infants born at less than or equal to 23 weeks’ gestation comprised 1 in 117 NICU admissions, 1 in 34 of all NICU bed-days, and 1 in 6 of all ventilator-days.Conclusions and RelevanceIn this serial cross-sectional study of 137 US NICUs from 2008 to 2021, an increasing share of resources in US NICUs was allocated to infants born at 22 weeks’ gestation, corresponding with changes in national clinical guidance.
Prioritizing Maternal Mental Health in Addressing Morbidity and Mortality
Authors: Wisner Katherine L. , Murphy Caitlin , Thomas Megan M. 
Published: February 2024

ImportanceThe rate of maternal mortality in the United States is 2-fold to 3-fold greater than that in other high-income countries. While many national initiatives have been developed to combat maternal mortality, these efforts often fail to include mental illness.ObjectiveTo highlight the underrecognized contribution of mental illness to maternal mortality, which is nearly double that of postpartum hemorrhage.Evidence ReviewA topic outline was developed to include challenges in measuring perinatal mental conditions and mortality rates; contributions of social determinants of health to mental conditions and mortality; perinatal psychiatric disorder characterization; mechanisms by which maternal mental illness increases mortality, specifically, suicide and addictive disorders; access limitations and care “deserts”; prenatal stress and its impact on reproductive outcomes; increasing clinician expertise through cross-disciplinary education; intervention sites and models; and asserting that mental health is fundamental to maternal health. Publications in the last 3 years were prioritized, particularly those relating to policy. References were selected through consensus. Sources were PubMed, Ovid, direct data published on government websites, and health policy sources such as the Policy Center for Maternal Mental Health.FindingsPriority was given to recent sources. Citations from 2022-2023 numbered 26; within the last 5 years, 14; and historical references, 15. Recommendations to address each topic area serve as concluding statements for each section. To mitigate the contributions of mental illness to the maternal mortality risk, a coordinated effort is required across professional and governmental organizations.Conclusions and RelevanceConcrete programmatic and policy changes are needed to reduce perinatal stress and address trauma, standardize the collection of social determinant of health data among perinatal patients, increase access to reproductive psychiatry curricula among prescribers, reduce perinatal mental health and obstetrical deserts, institute paid parental leave, and support seamless integration of perinatal and behavioral health care. Moreover, instead of focusing on a relatively minor portion of the contributors to health that current medical practice targets, fortifying the social foundation strengthens the prospects for the health of families for our current and future generations.
Plasmonic Au3Cu Ordered Nanocrystals Induced Phase Transformation in 2D‐MoS2 for Efficient Hydrogen Evolution
Authors: Qamar Ummiya , Roy Sayak , Kumar Sooraj , Mukherjee Bratindranath , Devi Assa Aravindh Sasikala , Goswami Ankur , Maiti Pralay , Das Santanu 
Published: February 2024

AbstractThe synthesis of ordered gold‐copper (Au3Cu) alloy nanocrystals (≈10 nm) is reported and used in the semiconductor (2H) to metallic (1T) phase transformation of an atomically thin large‐area 2D‐MoS2 grown via CVD technique. The ordered Au3Cu nanocrystals are dispersed over 2D‐MoS2, and the phase transformation is confirmed via Raman spectroscopy followed by X‐ray photoelectron spectroscopy (XPS), while the surface properties of the Au3Cu/2D‐MoS2 is determined by the XPS valence band analysis and ultra‐violet photoemission spectroscopy (UPS). By comparing overpotential and Tafel slopes for Hydrogen Evolution Reaction (HER), a decrease is observed in overpotential by 83.2 mV and Tafel slope by ≈58.25 mV per decade for Au3Cu/MoS2 on light irradiation. This electrocatalytic enhancement of Au3Cu/MoS2 refers to the transformation of semiconducting 2D‐MoS2 to metallic phase under light illumination, thereby altering the surface electronic structures, improving carrier concentrations, lowering the valence band edge, and lowering the free energy of H* adsorption/desorption. Density functional theory (DFT) calculations, along with other surface characterizations, further illustrate that the ordered nanocrystal‐induced phase transformation in 2D‐MoS2 leads to a more durable metallic characteristic, thus, enhancing the surface electrical conductivity, reducing surface potential and Gibbs free energy, and improving the kinetics of photoelectrocatalytic performance of the hybrid structure.