bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antihirudin antibodies in patients with heparin-induced thrombocytopenia treated with lepirudin: incidence, effects on aPTT, and clinical relevance
Authors: Eichler Petra , Friesen Heinz-Juergen , Lubenow Norbert , Jaeger Bernd , Greinacher Andreas 
Published: October 2019

Abstract
Hirudin, a potent and specific thrombin inhibitor, is a protein of nonhuman origin and therefore potentially immunogenic. The primary objectives of this investigation were to determine the incidence of antihirudin antibodies (ahir-ab) in patients with heparin-induced thrombocytopenia (HIT) who received lepirudin as parenteral anticoagulation and to determine the incidence of death, limb amputation, new thromboembolic complications (TECs), and major hemorrhage in patients who had ahir-ab, compared with patients who were ahir-ab negative. The investigation used data from 2 prospective multicenter studies with the same study protocol, in which HIT patients received 1 of 4 intravenous lepirudin dosage regimens. The treatment duration was 2 to 10 days. Ahir-ab were determined by a newly developed enzyme-linked immunosorbent assay (ELISA). Eighty-seven of 196 evaluable patients (44.4%) had ahir-ab of the IgG class. Development of ahir-ab was dependent on the duration of treatment (ahir-ab–positive patients 18.6 days vs ahir-ab–negative patients 11.8 days; P = .0001). Fewer ahir-ab–positive than ahir-ab–negative patients died (P = .001). Ahir-ab did not cause an increase in limb amputation (P = .765), new TECs (P &gt; .99), or major bleedings (P = .549). In 23 of 51 (45.1%) evaluable patients in whom ahir-ab developed during treatment with lepirudin ( = 12% of all lepirudin treated patients), the ahir-ab enhanced the anticoagulatory effect of lepirudin. Ahir-ab are frequent in patients treated with lepirudin for more than 5 days. Ahir-ab are the first example for a drug-induced immune response causing enhanced activity of a drug. Therefore, during prolonged treatment with lepirudin, anticoagulatory activity should be monitored daily to avoid bleeding complications.
Bone marrow transplantation versus chemotherapy in the treatment of very high–risk childhood acute lymphoblastic leukemia in first remission: results from Medical Research Council UKALL X and XI
Authors: Wheeler Kate A. , Richards Susan M. , Bailey Clifford C. , Gibson Brenda , Hann Ian M. , Hill Frank G. H. , Chessells Judith M. 
Published: October 2019

Abstract
The role of bone marrow transplantation (BMT) in first remission of children with high-risk acute lymphoblastic leukemia (ALL) remains unclear. There were 3676 patients (aged 1 to 15 years) entered into the United Kingdom (UK) Medical Research Council (MRC) trials UKALL X and XI from 1985 to 1997. Of these patients, 473 patients (13%) were classified as very high (VH) risk and were eligible for a transplantation from a matched histocompatible sibling donor (MSD). We tissue-typed 286 patients; 99 patients had a matched related donor, and 76 patients received transplantations. Additionally, 25 children received transplantations from a matched unrelated donor (MUD) despite trial guidelines for MSD transplantations only. The median time to transplantation was 5 months (range, 2 to 19 months), and the median follow-up was 8 years. The 10-year event-free survival (EFS) adjusted for the time to transplantation, diagnostic white blood cell (WBC) count, Ph chromosome status, and ploidy was 6.0% higher (95% confidence interval (CI), −10.5% to 22.5%) for 101 patients who received a first-remission transplantation (MSD and MUD) than for the 351 patients treated with chemotherapy (transplantation, 45.3%, vs chemotherapy, 39.3%). The transplantation group had fewer relapses (31%) compared to relapses in the chemotherapy group (55%); however, the transplantation group had more remission deaths (18%) compared to remission deaths in the chemotherapy group (3%). In contrast the adjusted 10-year EFS was 10.7% higher (95% CI, −2.6% to 24.0%) for patients without a human leukocyte antigen (HLA)–matched donor than for those patients with a donor (no donor, 50.4%, vs donor, 39.7%). In conclusion, for the majority of children with VH-risk ALL, the first-remission transplantation has not improved EFS.
In vivo CAMPATH-1H prevents graft-versus-host disease following nonmyeloablative stem cell transplantation
Authors: Kottaridis Panagiotis D. , Milligan Donald W. , Chopra Rajesh , Chakraverty Ronjon K. , Chakrabarti Suparno , Robinson Stephen , Peggs Karl , Verfuerth Stephanie , Pettengell Ruth , Marsh Judith C. W. , Schey Stephen , Mahendra Premini , Morgan Gareth J. , Hale Geoff , Waldmann Herman , de Elvira M. Carmen Ruiz , Williams Catherine D. , Devereux Stephen , Linch David C. , Goldstone Anthony H. , Mackinnon Stephen 
Published: October 2019

Abstract
A novel nonmyeloablative conditioning regimen was investigated in 44 patients with hematologic malignancies. The median patient age was 41 years. Many of the patients had high-risk features, including 19 patients with a previous failed transplant. Recipient conditioning consisted of CAMPATH-1H, 20 mg/day on days −8 to −4; fludarabine, 30 mg/m2 on days −7 to −3; and melphalan, 140 mg/m2 on day −2. Thirty-six recipients received unmanipulated granculocyte colony-stimulating factor–mobilized peripheral blood stem cells from HLA-identical siblings, and 8 received unmanipulated marrow from matched unrelated donors. GVHD prophylaxis was with cyclosporine A alone for 38 patients and cyclosporine A plus methotrexate for 6 sibling recipients. Forty-two of the 43 evaluable patients had sustained engraftment. Results of chimerism analysis using microsatellite polymerase chain reaction indicate that 18 of 31 patients studied were full-donor chimeras while the other patients were mixed chimeras in one or more lineages. At a median follow-up of 9 months (range 3 to 29 months), 33 patients remain alive in complete remission or with no evidence of disease progression. Seven patients relapsed or progressed post-transplantation, and 4 of them subsequently died. Four patients died of regimen-related complications. There were no cases of grades III-IV acute GVHD. Only 2 patients developed grade II acute GVHD, and only 1 had chronic GVHD. The estimated probability of nonrelapse mortality was 11%. Although longer follow-up is needed to establish the long-term remission rates, this study demonstrates that this nonmyeloablative preparative regimen is associated with durable engraftment, minimal toxicity, and low incidence of GVHD.
De novo factor VIII gene intron 22 inversion in a female carrier presents as a somatic mosaicism
Authors: Oldenburg Johannes , Rost Simone , El-Maarri Osman , Leuer Marco , Olek Klaus , Müller Clemens R. , Schwaab Rainer 
Published: October 2019

Abstract
The intron 22 inversion represents the most prevalentfactor VIII gene defect in severe hemophilia A, accounting for about 40% of all mutations. It is hypothesized that the inversion mutations occur almost exclusively in germ cells during meiotic cell division by intrachromosomal recombination between 1 of 2 telomeric copies of the Int22h region and its intragenic homologue. The majority of inversion mutations originate in male germ cells, where the lack of bivalent formation may facilitate flipping of the telomeric end of the single X chromosome. This is the first intron 22 inversion that presents as a somatic mosaicism in a female, affecting only about 50% of lymphocyte and fibroblast cells of the proposita. Supposing a post-zygotic de novo mutation as the usual cause of somatic mosaicism, the finding would imply that the intron 22 inversion mutation is not restricted to meiotic cell divisions but can also occur during mitotic cell divisions, either in germ cell precursors or in somatic cells.
Cyclin A transcriptional suppression is the major mechanism mediating homocysteine-induced endothelial cell growth inhibition
Authors: Wang Hong , Jiang XiaoHua , Yang Fan , Chapman Gary B. , Durante William , Sibinga Nicholas E. S. , Schafer Andrew I. 
Published: October 2019

Abstract
Previously, it was reported that homocysteine (Hcy) specifically inhibits the growth of endothelial cells (ECs), suppresses Ras/mitogen-activated protein (MAP) signaling, and arrests cell growth at the G1/S transition of the cell cycle. The present study investigated the molecular mechanisms underlying this cell-cycle effect. Results showed that clinically relevant concentrations (50 μM) of Hcy significantly inhibited the expression of cyclin A messenger RNA (mRNA) in ECs in a dose- and time-dependent manner. G1/S-associated molecules that might account for this block were not changed, because Hcy did not affect mRNA and protein expression of cyclin D1 and cyclin E. Cyclin D1- and E-associated kinase activities were unchanged. In contrast, cyclin A–associated kinase activity and CDK2 kinase activity were markedly suppressed. Nuclear run-on assay demonstrated that Hcy decreased the transcription rate of the cyclin A gene but had no effect on the half-life of cyclin A mRNA. In transient transfection experiments, Hcy significantly inhibited cyclin A promoter activity in endothelial cells, but not in vascular smooth muscle cells. Finally, adenovirus-transduced cyclin A expression restored EC growth inhibition and overcame the S phase block imposed by Hcy. Taken together, these findings indicate that cyclin A is a critical functional target of Hcy-mediated EC growth inhibition.
Remote homology searches identify bacterial homologues of eukaryotic lipid transfer proteins, including Chorein-N domains in TamB and AsmA and Mdm31p
Authors: Levine Timothy P. 
Published: October 2019

Abstract

Background
All cells rely on lipids for key functions. Lipid transfer proteins allow lipids to exit the hydrophobic environment of bilayers, and cross aqueous spaces. One lipid transfer domain fold present in almost all eukaryotes is the TUbular LIPid binding (TULIP) domain. Three TULIP families have been identified in bacteria (P47, OrfX2 and YceB), but their homology to eukaryotic proteins is too low to specify a common origin. Another recently described eukaryotic lipid transfer domain in VPS13 and ATG2 is Chorein-N, which has no known bacterial homologues. There has been no systematic search for bacterial TULIPs or Chorein-N domains.

Results
Remote homology predictions for bacterial TULIP domains using HHsearch identified four new TULIP domains in three bacterial families. DUF4403 is a full length pseudo-dimeric TULIP with a 6 strand β-meander dimer interface like eukaryotic TULIPs. A similar sheet is also present in YceB, suggesting it homo-dimerizes. TULIP domains were also found in DUF2140 and in the C-terminus DUF2993. Remote homology predictions for bacterial Chorein-N domains identified strong hits in the N-termini of AsmA and TamB in diderm bacteria, which are related to Mdm31p in eukaryotic mitochondria. The N-terminus of DUF2993 has a Chorein-N domain adjacent to its TULIP domain.

Conclusions
TULIP lipid transfer domains are widespread in bacteria. Chorein-N domains are also found in bacteria, at the N-terminus of multiple proteins in the intermembrane space of diderms (AsmA, TamB and their relatives) and in Mdm31p, a protein that is likely to have evolved from an AsmA/TamB-like protein in the endosymbiotic mitochondrial ancestor. This indicates that both TULIP and Chorein-N lipid transfer domains may have originated in bacteria.
Cortical pencil lining on SWI MRI in NBIA and healthy aging
Authors: van der Weijden Marlous C. M. , van Laar Peter Jan , Lambrechts Roald A. , Verbeek Dineke S. , Tijssen Marina A. J. 
Published: October 2019

AbstractBackgroundNeurodegeneration with brain iron accumulation (NBIA) is characterized by pathological iron accumulation in the subcortical nuclei and the cortex. As age-related iron accumulation studies in these structures are lacking in healthy aging, we aimed to characterize the dynamics of age-dependent iron accumulation in subcortical nuclei in healthy aging and selected NBIA cases. This is fundamental to understand the natural age-related iron deposition in the healthy brain prior to using this marker as a potential prognostic or diagnostic tool in neurodegenerative disorders.MethodsSusceptibility-weighted imaging (SWI) scans from 81 healthy volunteers (0-79 years) and four genetically confirmed patients suffering from NBIA (2-14 years) were obtained. We scored the presence or absence of pencil lining of the motor cortex and putamen and analyzed the normalized SWI signal intensity ratio (NSIR) in five subcortical nuclei.ResultsIn healthy subjects, an age-dependent increase of pencil lining occurred starting from the second decade of life and was present in all cases at the age of 50. In their first decade, NBIA patients showed no cortical pencil lining, but we did observe putaminal pencil lining at this stage. In healthy subjects, age and NSIR of all nuclei correlated positively and was particularly dynamic in early childhood until young adulthood in the globus pallidus, dentate nucleus and red nucleus, but not in the caudate nucleus and putamen. NBIA patients showed an increased NSIR in the globus pallidus only and not in the other subcortical nuclei compared to age-matched healthy subjects.ConclusionsCortical pencil lining is part of healthy aging. This should be considered when assessing this as a potential marker in NBIA diagnosis and prognosis. Putaminal pencil lining has the potential to become a specific marker for some subtypes of NBIA in the first decade of life, as it was only observed in NBIA and not in age-matched healthy subjects. NSIR in the subcortical nuclei during healthy aging was shown to be dynamic, accentuating the importance of having an age-dependent baseline.
Demyelinating syndrome in systemic sclerosis and neuromyelitis optica
Authors: Deeb Khaled , Eby Jessika , Labault-Santiago Jose 
Published: October 2019

Abstract

Background
This article reports a case diagnosis of a 44-year-old female who presented with intractable hiccups and vomit complicated with an acute onset of paraplegia. Transverse myelitis was evident on MRI and serological studies were consistent with Neuromyelitis Optica (NMO) based on NMO-IgG sero-positivity. Further studies revealed positive ANA, anti-RNA polymerase III autoantibodies, and Scl-70, leading to a concurrent diagnosis of systemic sclerosis (SSc). The coexistence of these two disease processes and their underlying clinical manifestations and therapeutic interventions are seldom reported in literature and are worth reporting.

Case presentation
The patient was treated with high dose steroids, and subsequently developed malignant hypertension and acute renal failure, later identified on biopsy as steroids-induced scleroderma renal crisis. Although Neuromyelitis Optica spectrum disorder (NMOSD) has often been associated with various collagen and autoimmune diseases, the coexistence of NMOSD and SSc presented a challenge where the patient underwent aggressive physical therapy and necessitated an intervention with Rituximab to achieve an appropriate clinical response.
We have received a written consent forms from the participant in our study, and we have them on file in case they are requested. We have also received the patient’s written consent for the data and images presented in this article.

Conclusion
This article expands on NMOSD associated autoimmune diseases. Systemic Sclerosis is an insidious disease that is often diagnosed late as not all patients often report skin manifestation. The finding suggests that patients presenting with acute neurological manifestations get tested for NMO-IgG/AQP-4 antibodies and other immunological studies based on clinical findings.
Identification of a novel splicing mutation in the SLC25A13 gene from a patient with NICCD: a case report
Authors: Zhang Linlin , Li Yingying , Shi Wenli , Gao Jinshuang , Tian Yuan , Li Ying , Guo Yaqing , Cui Shihong , Zhang Xiaoan 
Published: October 2019

Abstract

Background
Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is an autosomal recessive disorder and one of the most common inherent causes of cholestatic jaundice in Asian infants. Mutations in the SLC25A13 gene, which encodes citrin protein expressed in the liver, have been identified as the genetic cause for NICCD.

Case presentation
Here, we report a 4-month-old female with clinical features including jaundice, hyperbilirubinemia, hyperlactacidemia, and abnormal liver function. The patient was diagnosed with NICCD by differential diagnosis using genetic analysis. Mutations in 60 jaundice-related genes were tested by using amplicon sequencing, which was performed on an Ion S5XL genetic analyzer. A compound heterozygous mutation in the SLC25A13 gene was identified, consisting of a known deletion SLC25A13:c.852_855delTATG and a novel splicing mutation SLC25A13:c.1841 + 3_1841 + 4delAA. Sanger sequencing for the proband and her parents was performed to validate the result and reveal the source of mutations.

Conclusion
A compound heterozygous mutation in the SLC25A13 gene was identified in a 4-month-old female patient with NICCD. Our data suggest that amplicon sequencing is a helpful tool for the differential diagnosis of inherited diseases with similar symptoms. Further studies of the mutation spectrum of neonatal jaundice in China are warranted.
A systematic review of monitoring and evaluation indicators for sexual and reproductive health in humanitarian settings
Authors: Broaddus-Shea Elena T. , Kobeissi Loulou , Ummer Osama , Say Lale 
Published: October 2019

Abstract

Objective
To conduct a comprehensive mapping of published indicators for monitoring and evaluation (M&E) of sexual and reproductive health (SRH) services and outcomes in humanitarian settings.

Methods
A systematic search of the peer-reviewed and grey literature published between January 2008 and May 2018 was conducted to identify all references describing indicator sets for M&E of SRH services and outcomes in humanitarian settings. The databases MEDLINE, Web of Science, and Global Health, as well as 85 websites of relevant organizations involved in humanitarian response were searched. Characteristics of identified indicator sets and data from individual indicators was extracted.

Findings
Of 3278 records identified, 20 met the review’s inclusion criteria and 9 existing indicator sets were identified. A total of 179 relevant indicators were included in the mapping, and removal of duplicates yielded 132 unique indicators. Twenty-seven percent fell within the maternal health domain, followed by the HIV/AIDS domain (26%) and the gender-based violence domain (23%). The distribution of indicators by type (process/output, outcome, impact) was balanced overall but varied substantially across domains. The most commonly used data collection platforms were facility-based systems or population-based surveys. Domains covered and indicator definitions were inconsistent across indicator sets.

Conclusion
Results demonstrate the need to standardize data collection efforts for M&E of SRH services and outcomes in humanitarian settings and to critically appraise the extent to which different domains should be covered. A core list of indicators is essential for assessing response status over time as well as across countries.
A transcriptional response of Clostridium beijerinckii NRRL B-598 to a butanol shock
Authors: Sedlar Karel , Kolek Jan , Gruber Markus , Jureckova Katerina , Branska Barbora , Csaba Gergely , Vasylkivska Maryna , Zimmer Ralf , Patakova Petra , Provaznik Ivo 
Published: October 2019

AbstractBackgroundOne of the main obstacles preventing solventogenic clostridia from achieving higher yields in biofuel production is the toxicity of produced solvents. Unfortunately, regulatory mechanisms responsible for the shock response are poorly described on the transcriptomic level. Although the strainClostridium beijerinckiiNRRL B-598, a promising butanol producer, has been studied under different conditions in the past, its transcriptional response to a shock caused by butanol in the cultivation medium remains unknown.ResultsIn this paper, we present a transcriptional response of the strain during a butanol challenge, caused by the addition of butanol to the cultivation medium at the very end of the acidogenic phase, using RNA-Seq. We resequenced and reassembled the genome sequence of the strain and prepared novel genome and gene ontology annotation to provide the most accurate results. When compared to samples under standard cultivation conditions, samples gathered during butanol shock represented a well-distinguished group. Using reference samples gathered directly before the addition of butanol, we identified genes that were differentially expressed in butanol challenge samples. We determined clusters of 293 down-regulated and 301 up-regulated genes whose expression was affected by the cultivation conditions. Enriched term “RNA binding” among down-regulated genes corresponded to the downturn of translation and the cluster contained a group of small acid-soluble spore proteins. This explained phenotype of the culture that had not sporulated. On the other hand, up-regulated genes were characterized by the term “protein binding” which corresponded to activation of heat-shock proteins that were identified within this cluster.ConclusionsWe provided an overall transcriptional response of the strainC. beijerinckiiNRRL B-598 to butanol shock, supplemented by auxiliary technologies, including high-pressure liquid chromatography and flow cytometry, to capture the corresponding phenotypic response. We identified genes whose regulation was affected by the addition of butanol to the cultivation medium and inferred related molecular functions that were significantly influenced. Additionally, using high-quality genome assembly and custom-made gene ontology annotation, we demonstrated that this settled terminology, widely used for the analysis of model organisms, could also be applied to non-model organisms and for research in the field of biofuels.
Use of literature mining for early identification of emerging contaminants in freshwater resources
Authors: Hartmann Julia , Wuijts Susanne , van der Hoek Jan Peter , de Roda Husman Ana Maria 
Published: October 2019

AbstractChemical and microbial contaminants in the aquatic environment pose a potential threat to humans and to ecosystems. Humans may be exposed to contaminants in water resources when used for drinking water production, agriculture, aquaculture or recreation. Climatological, social and demographic changes, as well as the increasing sensitivity of analytical techniques, may result in the augmented detection of contaminants. Recent research has shown that it takes about 15 years from the time of the first scientific study mentioning the presence of a contaminant in the environment for the issue to peak in scientific attention and regulatory action. One possible factor influencing this lengthy period is that the first article becomes lost in the vast number of publications. In this study, we therefore developed a methodology using literature mining to identify the first scientific study which reports the presence of a contaminant in the aquatic environment. The developed semi-automated methodology enables health and environment agencies to inform policy makers about contaminants in the aquatic environment that could be significant for public and environmental health in national, international and river basin settings. The methodology thereby assists the proactive governance of emerging contaminants in the aquatic environment. This was illustrated by a retrospective analysis of the period of emergence in the Netherlands of: (1) perfluorooctanoic acid in surface water, and (2) biological industrial wastewater treatment systems as potential infection sources for Legionnaires´ disease.