bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lessons learned from expanded reproductive carrier screening in self‐reported Ashkenazi, Sephardi, and Mizrahi Jewish patients
Authors: Akler Gidon , Birch Ashley H. , Schreiber‐Agus Nicole , Cai Xiaoqiang , Cai Guiqing , Shi Lisong , Yu Chunli , Larmore Anastasia M. , Mendiratta‐Vij Geetu , Elkhoury Lama , Dillon Mitchell W. , Zhu Jun , Mclellan Andrew S. , Suer Funda E. , Webb Bryn D. , Schadt Eric E. , Kornreich Ruth , Edelmann Lisa 
Published: December 2019

AbstractBackgroundNext‐generation sequencing (NGS)‐based panels have gained traction as a strategy for reproductive carrier screening. Their value for screening Ashkenazi Jewish (AJ) individuals, who have benefited greatly from population‐wide targeted testing, as well as Sephardi/Mizrahi Jewish (SMJ) individuals (an underserved population), has not been fully explored.MethodsThe clinical utilization by 6,805 self‐reported Jewish individuals of an expanded NGS panel, along with several ancillary assays, was assessed retrospectively. Data were extracted for a subset of 96 diseases that, during the panel design phase, were classified as being AJ‐, SMJ‐, or pan‐Jewish/pan‐ethnic‐relevant.Results64.6% of individuals were identified as carriers of one or more of these 96 diseases. Over 80% of the reported variants would have been missed by following recommended AJ screening guidelines. 10.7% of variants reported for AJs were in “SMJ‐relevant genes,” and 31.2% reported for SMJs were in “AJ‐relevant genes.” Roughly 2.5% of individuals carried a novel, likely pathogenic variant. One in 16 linked cohort couples was identified as a carrier couple for at least one of these 96 diseases.ConclusionFor maximal carrier identification, this study supports using expanded NGS panels for individuals of all Jewish backgrounds. This approach can better empower at‐risk couples for reproductive decision making.
Novel VAC14 variants identified in two Chinese siblings with childhood‐onset striatonigral degeneration
Authors: Liao Shuang , Chen Tingting , Dai Ying , Wang Yanqin , Wu Fangrui , Zhong Min 
Published: December 2019

AbstractBackgroundVAC14 is a component of a trimolecular complex that tightly regulates the level of phosphatidylinositol 3,5‐bisphosphate [PI (3,5) P2]. VAC14 pathogenic variants cause prominent vacuolation of neurons in basal ganglia of patients with childhood‐onset striatonigral degeneration (SNDC).MethodsWe identified two siblings with SNDC. Whole‐exome sequencing was performed for genetic molecular analysis in these probands.ResultsThe patients were compound heterozygotes for two novel variants in the VAC14 gene, p.Ala582Thr and p.Arg681His. The pathogenicity of these variants was indicated by a bioinformatic study and protein three‐dimensional modeling. Eight previously reported SNDC cases and a Yunis–Varón syndrome caused by VAC14 mutations were summarized and compared.ConclusionWe present novel compound heterozygous variants (c.1744G>A/c.2042G>A) in our proband, and these novel variants were predicted to be likely pathogenic. The affected siblings were clinically severe and lethal; their phenotypes were similar to the majority of previously reported SNDC cases, with the exception of two cases that showed mild clinical manifestations. VAC14 pathogenic variants may be associated with various phenotypes. Herein, we report the Chinese siblings with SNDC, they are the first Asian cases. Our results expanded the spectrum of VAC14 pathogenic variants and the ethnic backgrounds of the affected cases.
An analytical formalism for the assessment of dose uncertainties due to positioning uncertainties
Authors: Lechner Wolfgang , Georg Dietmar , Palmans Hugo 
Published: December 2019

PurposeTo present an analytical formalism for the in depth assessment of uncertainties of field output factors in small fields related to detector positioning based on dose profile measurements. Additionally, a procedure for the propagation of these uncertainties was developed.MethodsBased on the assumption that one dimensional and two dimensional second‐order polynomial functions can be fitted to dose profiles of small photon beams, equations for the calculation of the expectation value, the variance, and the standard deviation were developed. The following fitting procedures of the dose profiles were considered: A one‐dimensional case (1D), a quasi two‐dimensional case (2Dq) based on independently measured line profiles and a full 2D case (2Df) which also considers cross‐correlations in a two‐dimensional dose distribution. A rectangular and a Gaussian probability density function (PDF) characterizing the probability of possible positions of the detector relative to the maximum dose were used. Uncertainty components such as the finite resolution of the scanning water phantom, the reproducibility of the determination of the position of the maximum dose, and the reproducibility of the collimator system were investigated. This formalism was tested in a 0.5 x 0.5 cm2 photon field where dose profiles were measured using a radiochromic film, a synthetic diamond detector, and an unshielded diode detector. Additionally, the dose distribution measured with the radiochromic film was convoluted with a convolution kernel mimicking the active volume of the unshielded diode.ResultsAnalytic expressions for the calculation of uncertainties on field output factors were found for the 1D, the 2Dq, and the 2Df case. The uncertainty of the field output factor related to the relative position of the detector to the maximum dose increased quadratically with increasing limits of possible detector positions. Analysis of the radiochromic film showed that the 2Dq case gave a more conservative assessment of the uncertainty compared to the 2Df case with a difference of < 0.1%. The 2Dq case applied to the film measurements agreed well with the same approach as was applied to the unshielded diode. The investigated uncertainty components propagated to an uncertainty of the field output factors of 0.5% and 0.4% for the synthetic diamond and the unshielded diode, respectively. Additionally, the expectation value was lower than the maximum dose. The difference was 0.4% and 0.3% for the synthetic diamond and the unshielded diode, respectively.ConclusionsThe assessment of uncertainties of field output factors related to detector positioning is feasible using the proposed formalism. The 2Dq case is applicable when using online detectors. Accurate positioning in small fields is essential for accurate dosimetry as its related uncertainty increases quadratically. The observed drop of the expectation value needs to be considered in small field dosimetry.
Nursing research priorities based on CINAHL database: A scoping review
Authors: Hopia Hanna , Heikkilä Johanna 
Published: December 2019

AbstractAimTo analyse nursing research based on the CINAHL database to identify research priorities for nursing.DesignA scoping literature review was conducted. The CINAHL Plus (EBSCO) Full Text was searched between 2012–2018.MethodsOut of 1522 original publications, 91 fulfilled the inclusion criteria. The Joanna Briggs Institute critical appraisal tools were applied. Data were analysed by a thematic analysis method.ResultsA strong emphasis should be put on development and evaluation of nursing theories and, in addition, randomized controlled trial studies, meta‐synthesis, experimental and intervention studies are needed in nursing research. Development of competencies and skills in the nursing profession ought to be studied more extensively and research should be focused on variety fields of nursing practice.
Surgical tracheostomy in children with malignancy receiving intensive chemotherapy: A case series and review of literature
Authors: Manna Soumendu S. , Malik Rubina , Douthwaite Amy , Vaidya Sucheta 
Published: December 2019

AbstractWe retrospectively reviewed a paediatric intensive care unit database that supports a tertiary oncology service to explore safety and outcome of tracheostomy in oncology patients over a 12‐year period and reviewed literature. A total of 895 patients were admitted with a haematological or a solid tumour malignancy of which 222 were ventilated. Six of 222 (2.7%) ventilated children were tracheostomised. Four of six children tracheostomised for ventilatory support received intensive chemotherapy complicated by neutropenia and thrombocytopenia. There was no significant tracheostomy‐related complication. Tracheostomy improved patient comfort, reduced sedative requirement, and may have helped recovery. Tracheostomy should be considered early in selected children with haemato‐oncological diagnoses requiring prolonged ventilation.
Optimization of a clofarabine‐based drug combination regimen for the preclinical evaluation of pediatric acute lymphoblastic leukemia
Authors: Xie Jinhan , Span Miriam , van Maarseveen Erik , Langenhorst Jurgen , Boddy Alan V. , Sia Keith C.S. , Sutton Rosemary , Venn Nicola , Punt Arjen M. , Tyrrell Vanessa , Haber Michelle , Trahair Toby , Lau Loretta , Marshall Glenn M. , Lock Richard B. 
Published: December 2019

AbstractBackgroundThe aim of this study was to improve the predictive power of patient‐derived xenografts (PDXs, also known as mouse avatars) to more accurately reflect outcomes of clofarabine‐based treatment in pediatric acute lymphoblastic leukemia (ALL) patients.ProcedurePharmacokinetic (PK) studies were conducted using clofarabine at 3.5 to 15 mg/kg in mice. PDXs were established from relapsed/refractory ALL patients who exhibited good or poor responses to clofarabine. PDX engraftment and response to clofarabine (either as a single agent or in combinations) were assessed based on stringent objective response measures modeled after the clinical setting.ResultsIn naïve immune‐deficient NSG mice, we determined that a clofarabine dose of 3.5 mg/kg resulted in systemic exposures equivalent to those achieved in pediatric ALL patients treated with clofarabine‐based regimens. This dose was markedly lower than the doses of clofarabine used in previously reported preclinical studies (typically 30‐60 mg/kg) and, when scheduled consistent with the clinical regimen (daily × 5), resulted in 34‐fold lower clofarabine exposures. Using a well‐tolerated clofarabine/etoposide/cyclophosphamide combination regimen, we then found that the responses of PDXs better reflected the clinical responses of the patients from whom the PDXs were derived.ConclusionsThis study has identified an in vivo clofarabine treatment regimen that reflects the clinical responses of relapsed/refractory pediatric ALL patients. This regimen could be used prospectively to identify patients who might benefit from clofarabine‐based treatment. Our findings are an important step toward individualizing prospective patient selection for the use of clofarabine in relapsed/refractory pediatric ALL patients and highlight the need for detailed PK evaluation in murine PDX models.
A phase I study of sirolimus in combination with metronomic therapy (CHOAnome) in children with recurrent or refractory solid and brain tumors
Authors: Qayed Muna , Cash Thomas , Tighiouart Mourad , MacDonald Tobey J. , Goldsmith Kelly C. , Tanos Rachel , Kean Leslie , Watkins Benjamin , Suessmuth Yvonne , Wetmore Cynthia , Katzenstein Howard M. 
Published: December 2019

AbstractBackground/purposeTo determine the maximum tolerated dose, toxicities, and response of sirolimus combined with oral metronomic therapy in pediatric patients with recurrent and refractory solid and brain tumors.ProcedurePatients younger than 30 years of age with recurrent, refractory, or high‐risk solid and brain tumors were eligible. Patients received six‐week cycles of sirolimus with twice daily celecoxib, and alternating etoposide and cyclophosphamide every three weeks, with Bayesian dose escalation over four dose levels (NCT01331135).ResultsEighteen patients were enrolled: four on dose level (DL) 1, four on DL2, eight on DL3, and two on DL4. Diagnoses included solid tumors (Ewing sarcoma, osteosarcoma, malignant peripheral nerve sheath tumor, rhabdoid tumor, retinoblastoma) and brain tumors (glioblastoma multiforme [GBM], diffuse intrinsic pontine glioma, high‐grade glioma [HGG], medulloblastoma, ependymoma, anaplastic astrocytoma, low‐grade infiltrative astrocytoma, primitive neuroectodermal tumor, nongerminomatous germ cell tumor]. One dose‐limiting toxicity (DLT; grade 4 neutropenia) was observed on DL2, two DLTs (grade 3 abdominal pain and grade 3 mucositis) on DL3, and two DLTs (grade 3 dehydration and grade 3 mucositis) on DL4. The recommended phase II dose of sirolimus was 2 mg/m2 (DL3). Best response was stable disease (SD) in eight patients, and partial response (PR) in one patient with GBM. A patient with HGG was removed from the study with SD and developed PR without further therapy. Western blot analysis showed inhibition of phospho‐S6 kinase in all patients during the first cycle of therapy.ConclusionThe combination of sirolimus with metronomic chemotherapy is well tolerated in children. A phase II trial of this combination is ongoing.
BCOR‐CCNB3 fusion‐positive clear cell sarcoma of the kidney
Authors: Han Hyojeong , Bertrand Kelsey C. , Patel Kalyani R. , Fisher Kevin E. , Roy Angshumoy , Muscal Jodi A. , Venkatramani Rajkumar 
Published: December 2019

AbstractClear cell sarcoma of the kidney (CCSK) is the second most common malignant pediatric renal tumor. Two of the recurrent somatic alterations reported in CCSK are BCL‐6 corepressor (BCOR) internal tandem duplication (ITD) and YWHAE‐NUTM2B/E gene fusion. A minority of patients with CCSKs have other rare somatic alterations. We report two patients with CCSK showing BCOR‐CCNB3 (where CCNB3 is cyclin B3) fusion, who had similar clinical presentation of a large renal mass with tumor thrombus extending through the inferior vena cava into the right atrium and a favorable response to chemotherapy. We recommend BCOR‐CCNB3 fusion testing for all patients with CCSK who lack BCOR‐ITD or YWHAE‐NUTM2B/E gene fusions.
Dimensionless numbers to study cell wall deformation of stiff mutants of Phycomyces blakesleeanus
Authors: Munoz Cindy M. , Ortega Joseph K. E. 
Published: December 2019

AbstractThe sporangiophores of Phycomyces blakesleeanus are large cylindrical aerial cells that elongate vertically at rates between 10 μm/min and 60 μm/min. Wild‐type sporangiophores grow toward light, opposed to gravitational acceleration and away from solid barriers (tropic responses). Sporangiophores of stiff mutants C149 and C216 exhibit diminished tropic (bending) responses. Originally, it was thought that the altered genes affect the “stiffness” (elastic wall deformation) of the cell wall. Subsequent investigations employing the pressure probe demonstrated that the irreversible (plastic) wall deformation was smaller for the stiff mutants compared to wild type and could account for the diminished tropic responses. However, it was not shown whether the elastic wall deformation was altered in these stiff mutants. Recent theoretical studies have identified dimensionless numbers that can be used to quantitate the magnitudes of biophysical processes involved in expansive growth of walled cells. In this study, dimensionless numbers are used to determine the magnitudes of elastic deformation rate, plastic deformation rate, and stress relaxation rate of the cell wall during expansive growth of the stiff mutant sporangiophores. It is found that the altered genes reduce stress relaxation rates and plastic deformation rates of the wall, but do not significantly alter the magnitude of the elastic deformation rates of the wall. These results indicate that the mutant genes reduce wall loosening chemistry in these sporangiophores and the genetic mutation is not expressed in a change in “wall stiffness,” but in “wall viscosity” or “wall extensibility.”
Distress in cancer patients: Who are the main groups at risk?
Authors: Herschbach Peter , Britzelmeir Ingrid , Dinkel Andreas , Giesler Jürgen M. , Herkommer Kathleen , Nest Alexandra , Pichler Theresia , Reichelt Ralf , Tanzer‐Küntzer Sylvia , Weis Joachim , Marten‐Mittag Birgitt 
Published: December 2019

AbstractObjectivesPsychosocial distress is common in cancer patients and survivors and encompasses a broad range of concerns and psychological symptoms. The aim of the current study was to identify subgroups of respondents who experience a specific constellation of distress symptoms.MethodsThis study uses data from a large data base (n = 21 680) of cancer patients from diverse settings who provided data in the Questionnaire on Distress in Cancer Patients—Short Form (QSC‐R10). Cluster analysis was applied to identify subgroups with a distinct constellation of distress symptoms.ResultsThe results showed five distinct clusters: minimally distressed patients (46.6% of the sample), highly distressed patients (12.7%), mainly physically distressed patients (15.2%), mainly psychologically distressed patients (15.6%), and mainly socially distressed patients (9.9%). These groups differed with regard to age, sex, cancer site, treatment setting, and disease progression.ConclusionThe results revealed large heterogeneity in the experience of distress. Distress clusters were associated with socio‐demographic and clinical variables. These associations might aid a clinician to tailor interventions and to address specific types of distress.
Long‐term efficacy of meaning‐centered group psychotherapy for cancer survivors: 2‐Year follow‐up results of a randomized controlled trial
Authors: Holtmaat Karen , van der Spek Nadia , Lissenberg‐Witte Birgit , Breitbart William , Cuijpers Pim , Verdonck‐de Leeuw Irma 
Published: December 2019

AbstractObjectiveMeaning‐centered group psychotherapy for cancer survivors (MCGP‐CS) is an effective intervention to improve personal meaning, psychological well‐being, and depressive symptoms until 6 months after the intervention. In this study, the long‐term effects of MCGP‐CS (i.e., at 1‐ and 2‐year follow‐up) on meaning, psychological well‐being and posttraumatic growth were assessed, in comparison to supportive group psychotherapy (SGP) and care as usual (CAU).MethodsCancer survivors (n = 170) were randomized into MCGP‐CS, SGP, or CAU. Assessments were scheduled at baseline, 1 week, 3 months, 6 months, 1 year, and 2 years postintervention. Outcome measures were the Personal Meaning Profile, Ryff's Scales of Psychological Well‐Being (SPWB), the Posttraumatic Growth Inventory, and their subscales. Linear mixed models (LMM) were used and results were both reported on an intention‐to‐treat (ITT) basis, as well as for intervention completers only.ResultsLMM and post hoc analyses with Bonferroni correction revealed that MCGP‐CS participants reported more improvement on positive relations (subscale of SPWB) than CAU participants of 2‐year postintervention (ITT analysis, Cohen's d = .82). Completers also reported more personal growth (subscale of SPWB) after MCGP‐CS than after SGP 1‐year postintervention (Cohen's d = .94). No long‐term effects were found on the other outcome measures.ConclusionsIn the 2 years after MCGP‐CS, the short‐term significant effects on personal meaning and most positive effects related to psychological well‐being faded. However, MCGP‐CS had a long‐term positive effect on positive relations with others and on survivors' sense of personal growth.Trial registrationNetherlands Trial Register: NTR3571
Does a regular nurse‐led distress screening and discussion improve quality of life of breast cancer patients treated with curative intent? A randomized controlled trial
Authors: Ploos van Amstel Floortje K. , Peters Marlies E. W. J. , Donders Rogier , Schlooz‐Vries Margrethe S. , Polman Lenny J. M. , van der Graaf Winette T. A. , Prins Judith B. , Ottevanger Petronella B. 
Published: December 2019

AbstractObjectiveWe performed a randomized controlled trial (RCT) to investigate whether regular screening with the distress thermometer (DT) by a nurse improved global quality of life (QOL) of patients with breast cancer (BC) treated with curative intent.MethodsBC patients were randomized between regular screening for distress with a nurse‐led DT intervention (NDTI) and usual care (UC). Both groups filled out questionnaires at baseline, after each received treatment modality and at follow‐up visits up to 2 years. At these points, the intervention group received also the NDTI. The primary outcome was the global QOL of the EORTC QLQ C30 at 2 years after the end of treatment. Analyses were done on an intention‐to‐treat basis, using analysis of covariance (ANCOVA), generalized least squares, and interaction analyses.ResultsOf 194 randomized patients, 153 filled out the questionnaires up to 2 years after treatment. There was no significant difference between NDTI and UC in global QOL 2 years after the end of treatment (mean diff. = –1∙273, P = .610; 95% CI [−6.195; 3.649]). Subgroup analysis of patients who received multimodality treatment (surgery, radiotherapy, and chemotherapy, n = 66) showed a significant between‐group difference in global QOL over time (mean diff. = –10, P < .001; 95% CI [−14.835; −5.167]) together with other secondary outcome measures in favor of the NDTI.ConclusionNDTI did not lead to a significant improvement in global QOL 2 years after the end of treatment for patients with BC. However, the findings indicate that BC patients who received multimodality treatment may benefit from NDTI.
Structure of the full‐length Serratia marcescens acetyltransferase AAC(3)‐Ia in complex with coenzyme A
Authors: Popov Georgy , Evdokimova Elena , Stogios Peter J. , Savchenko Alexei 
Published: December 2019

ABSTRACTAcyl‐coenzyme A‐dependent N‐acetyltransferases (AACs) catalyze the modification of aminoglycosides rendering the bacteria carrying such enzymes resistant to this class of antibiotics. Here we present the crystal structure of AAC(3)‐Ia enzyme from Serratia marcescens in complex with coenzyme A determined to 1.8 Å resolution. This enzyme served as an architype for the AAC enzymes targeting the amino group at Position 3 of aminoglycoside main aminocyclitol ring. The structure of this enzyme has been previously determined only in truncated form and was interpreted as distinct from subsequently characterized AACs. The reason for the unusual arrangement of secondary structure elements of AAC(3)‐Ia was not further investigated. By determining the full‐length structure of AAC(3)‐Ia we establish that this enzyme adopts the canonical AAC fold conserved across this family and it does not undergo through significant rearrangement of secondary structure elements upon ligand binding as was proposed previously. In addition, our results suggest that the C‐terminal tail in AAC(3)‐Ia monomer forms intramolecular hydrogen bonds that contributes to formation of stable dimer, representing the predominant oligomeric state for this enzyme.