Miracle-dz/UniFAR-FTUs huggingface dataset:
Motivation for entry, occupational commitment and intent to remain: a survey regarding Registered Nurse retention.

AIM This paper is a report of a study of the relationships between Registered Nurses' motivation for entering the profession, occupational commitment and intent to remain with an employer until retirement. BACKGROUND Identifying and supporting nurses who are strongly committed to their profession may be the single most influential intervention in combating the nursing shortage. An understanding of the characteristics these individuals possess could lead to a decline in the high attrition rates plaguing the profession. METHOD Using a survey design, Registered Nurses enrolled at the school of nursing and/or employed at the associated university medical centre of a large, not-for-profit state university were polled in 2008. Logistic regression analysis was used to determine how the variables of motivation for entry and occupational commitment could indicate intent to remain. RESULTS The strongest indicators of intent to remain were normative commitment and age, with a 70% average rate of correctly estimating retention. Exp(B) values for normative commitment (1·09) and age (1·07) indicated that for each one-point increase on the normative commitment scale or one-point increase in age, the odds of remaining with an employer until retirement increased by 1·1%. CONCLUSION Transformational changes in healthcare environments and nursing schools must be made to encourage loyalty and obligation, the hallmarks of normative commitment. Retention strategies should accommodate mature nurses as well as promote normative commitment in younger nurses.
Studies of TBX4 and chromosome 17q23.1q23.2: An uncommon cause of nonsyndromic clubfoot

Clubfoot is a common birth defect characterized by inward posturing and rigid downward displacement of one or both feet. The etiology of syndromic forms of clubfoot is varied and the causes of isolated clubfoot are not well understood. A microduplication of 2.2 Mb on chromosome 17q23.1q23. 2 which includes T‐box 4 (TBX4), a hindlimb‐specific gene, and 16 other genes was recently identified in 3 of 66 families reported as nonsyndromic clubfoot, but additional non‐foot malformations place them in the syndromic clubfoot category. Our study assesses whether variation in or around TBX4 contributes to nonsyndromic clubfoot. To determine whether this microduplication was a common cause of nonsyndromic clubfoot, 605 probands (from 148 multiplex and 457 simplex families) with nonsyndromic clubfoot were evaluated by copy number and oligonucleotide array CGH testing modalities. Only one multiplex family (0.68%) that had 16 with clubfoot and 9 with other foot anomalies, had a 350 kb microduplication, which included the complete duplication of TBX4 and NACA2 and partial duplication of BRIP1. The microduplication was transmitted in an autosomal dominant pattern and all with the microduplication had a range of phenotypes from short wide feet and toes to bilateral clubfoot. Minimal evidence was found for an association between TBX4 and clubfoot and no pathogenic sequence variants were identified in the two known TBX4 hindlimb enhancer elements. Altogether, these results demonstrate that variation in and around the TBX4 gene and the 17q23.1q23. 2 microduplication are not a frequent cause of this common orthopedic birth defect and narrows the 17q23.1q23. 2 nonsyndromic clubfoot‐associated region. © 2012 Wiley Periodicals, Inc.
Cys-27 Variant of Human δ-Opioid Receptor Modulates Maturation and Cell Surface Delivery of Phe-27 Variant via Heteromerization*

Background: Human δ-opioid receptor (hδOR) carries F27C polymorphism in its extracellular domain. Results: HδOR-Cys-27 with inherently impaired maturation/intracellular trafficking forms heteromers with hδOR-Phe-27 in the endoplasmic reticulum and enhances its targeting to degradation. Conclusion: HδOR-Cys-27 impairs hδOR-Phe-27 cell surface delivery in a dominant negative manner. Significance: Homo/heteromerization early in the biosynthetic pathway governs the levels of functionally active receptors at the cell surface. The important role of G protein-coupled receptor homo/heteromerization in receptor folding, maturation, trafficking, and cell surface expression has become increasingly evident. Here we investigated whether the human δ-opioid receptor (hδOR) Cys-27 variant that shows inherent compromised maturation has an effect on the behavior of the more common Phe-27 variant in the early secretory pathway. We demonstrate that hδOR-Cys-27 acts in a dominant negative manner and impairs cell surface delivery of the co-expressed hδOR-Phe-27 and impairs conversion of precursors to the mature form. This was demonstrated by metabolic labeling, Western blotting, flow cytometry, and confocal microscopy in HEK293 and human SH-SY5Y neuroblastoma cells using differentially epitope-tagged variants. The hδOR-Phe-27 precursors that were redirected to the endoplasmic reticulum-associated degradation were, however, rescued by a pharmacological chaperone, the opioid antagonist naltrexone. Co-immunoprecipitation of metabolically labeled variants revealed that both endoplasmic reticulum-localized precursors and mature receptors exist as homo/heteromers. The existence of homo/heteromers was confirmed in living cells by bioluminescence resonance energy transfer measurements, showing that the variants have a similar propensity to form homo/heteromers. By forming both homomers and heteromers, the hδOR-Cys-27 variant may thus regulate the levels of receptors at the cell surface, possibly leading to altered responsiveness to opioid ligands in individuals carrying the Cys-27 variant.
Role of Runt-related Transcription Factor 3 (RUNX3) in Transcription Regulation of Natural Cytotoxicity Receptor 1 (NCR1/NKp46), an Activating Natural Killer (NK) Cell Receptor*

Background: The expression of the activating receptor NKp46/NCR1 is highly restricted to NK cells. Results: RUNX proteins bind identified cis-regulatory element and affect NCR1 expression. Conclusion: NCR1 is regulated by two key proximal cis-regulatory elements and by RUNX factors. Significance: Mapping regulatory components of NCR1 will contribute to a deeper understanding of NK biology. Natural cytotoxicity receptor 1 (NCR1), also known as NKp46, is a natural killer (NK) lymphocyte-activating receptor. It is involved in major aspects of NK immune function and shows a high degree of lineage specificity in blood and bone marrow. The nature of its NK-restricted expression is not well understood. In this study, we confirm that human NCR1 NK-specific expression is achieved at the mRNA level. We found two key cis-regulatory elements in the immediate vicinity upstream of the gene. One element acts as an essential promoter, whereas the other acts as a tissue-dependent enhancer/repressor. This latter regulatory element contains a runt related-transcription factor (RUNX) recognition motif that preferentially binds RUNX3. Interfering with RUNX proteins using a dominant negative form results in decreased Ncr1 expression. RUNX3 overexpression had the opposite effect. These findings shed light on the role of RUNX3 in the control of an important NK-activating receptor.
POSITIVE AND NEGATIVE PATHS FROM WORK-LIFE BALANCE PRACTICE USE:USING JAPANESE DATA OF FULLTIME WORKER

本論文は、育児休業施策と短時間勤務施策を利用する育児中の女性正社員を対象とし、 それぞれの施策効果がいかなる状況で得られるのかについて検討することを目的とする。 分析は、フルサンプル・育児休業施策利用者・短時間勤務施策利用者で行われ、ぞれぞれ のデータセットにおいて両立支援施策を利用することによるコスト意識と（ネガティブパ ス）組織からの支援（WPC、ポジティブパス）といった二つのメカニズムを探索的に検討 した。 分析結果、両立支援施策の利用によるコスト認識が組織支援によって解消される模 様と度合いにおいて、育児休業者と短時間勤務者の間に明確な違いがあった。 キャリア意 識の高低を示す代理変数として施策利用状況を解釈できるとするならば、本論文はキャリ ア観の違いに応じた組織からの個別的な取り組みについて議論する必要性を支持するもの である。 , While the academic attentions toward work-life balance (WLB) practice in Japan have been growing, there are not enough arguments using consensual theoretical framework. This paper depicts the both light and shadow effects attached in WLB practice use from the view of employees’ perception. The results using data from interview and survey shows two unconventional findings. 1) WLB practice use can has negative impact on employee’s perceived WLB and willingness to stay long for a standard Japanese fulltime worker, because of the cost perception which WLB practice use can draws losses of opportunities in internal labor market. 2) There is WLB domain-specific Psychological Contracts (WPC) and its fulfillment can has positive impact on employee outcomes. This study browse there is not the easy way from the introduction of WLB practice to employee outcomes, negative with positive paths coexisting practically and also theoretically. Further study focusing how WLB implement at workplace fit to overall Human Resource functions each other, is needed.
X-ray Structures of Progesterone Receptor Ligand Binding Domain in Its Agonist State Reveal Differing Mechanisms for Mixed Profiles of 11β-Substituted Steroids

Background: Understanding the molecular basis for the mixed profiles of progesterone receptor (PR) ligands will benefit future drug design. Results: Two differing mechanisms for the induction of mixed profiles by 11β-steroids are described. Conclusion: Subtle electrostatic and steric factors explain the differing PR activities of 11β-steroids. Significance: These observations will impact future drug-design strategies for PR and potentially other nuclear receptors. We present here the x-ray structures of the progesterone receptor (PR) in complex with two mixed profile PR modulators whose functional activity results from two differing molecular mechanisms. The structure of Asoprisnil bound to the agonist state of PR demonstrates the contribution of the ligand to increasing stability of the agonist conformation of helix-12 via a specific hydrogen-bond network including Glu723. This interaction is absent when the full antagonist, RU486, binds to PR. Combined with a previously reported structure of Asoprisnil bound to the antagonist state of the receptor, this structure extends our understanding of the complex molecular interactions underlying the mixed agonist/antagonist profile of the compound. In addition, we present the structure of PR in its agonist conformation bound to the mixed profile compound Org3H whose reduced antagonistic activity and increased agonistic activity compared with reference antagonists is due to an induced fit around Trp755, resulting in a decreased steric clash with Met909 but inducing a new internal clash with Val912 in helix-12. This structure also explains the previously published observation that 16α attachments to RU486 analogs induce mixed profiles by altering the binding of 11β substituents. Together these structures further our understanding of the steric and electrostatic factors that contribute to the function of steroid receptor modulators, providing valuable insight for future compound design.
Structural Basis for the Recognition of C20:2-αGalCer by the Invariant Natural Killer T Cell Receptor-like Antibody L363*

Background: Antibodies that recognize glycolipids presented by the antigen-presenting molecule CD1d are useful tools in studying natural killer T cell biology. Results: The CD1d-α-galactosylceramide specific antibody L363 has TCR-like binding properties. Conclusion: Glycolipid-reactive antibodies are more antigen-specific than the TCR of iNKT cells. Significance: This is the first crystal structure of a glycolipid-reactive TCR-like antibody. Natural killer T (NKT) cells express a semi-invariant Vα14 T cell receptor (TCR) and recognize structurally diverse antigens presented by the antigen-presenting molecule CD1d that range from phosphoglycerolipids to α- and β-anomeric glycosphingolipids, as well as microbial α-glycosyl diacylglycerolipids. Recently developed antibodies that are specific for the complex of the prototypical invariant NKT (iNKT) cell antigen αGalCer (KRN7000) bound to mouse CD1d have become valuable tools in elucidating the mechanism of antigen loading and presentation. Here, we report the 3.1 Å resolution crystal structure of the Fab of one of these antibodies, L363, bound to mCD1d complexed with the αGalCer analog C20:2, revealing that L363 is an iNKT TCR-like antibody that binds CD1d-presented αGalCer in a manner similar to the TCR. The structure reveals that L363 depends on both the L and H chains for binding to the glycolipid-mCD1d complex, although only the L chain is involved in contacts with the glycolipid antigen. The H chain of L363 features residue Trp-104, which mimics the TCR CDR3α residue Leu-99, which is crucial for CD1d binding. We characterized the antigen-specificity of L363 toward several different glycolipids, demonstrating that whereas the TCR can induce structural changes in both antigen and CD1d to recognize disparate lipid antigens, the antibody L363 can only induce the F′ roof formation in CD1d but fails to reorient the glycolipid headgroup necessary for binding. In summary, L363 is a powerful tool to study mechanism of iNKT cell activation for structural analogs of KRN7000, and our study can aid in the design of antibodies with altered antigen specificity.
Bacterial Degradation of Benzoate

Background: The specific transcriptional regulation of the box pathway for aerobic benzoate degradation is unknown. Results: The BoxR/benzoyl-CoA couple controls the induction of the box genes. Conclusion: BoxR is the regulator of the box pathway in bacteria. Significance: There is cross-regulation between anaerobic and aerobic benzoate degradation pathways. We have studied for the first time the transcriptional regulatory circuit that controls the expression of the box genes encoding the aerobic hybrid pathway used to assimilate benzoate via coenzyme A (CoA) derivatives in bacteria. The promoters responsible for the expression of the box cluster in the β-proteobacterium Azoarcus sp. , their cognate transcriptional repressor, the BoxR protein, and the inducer molecule (benzoyl-CoA) have been characterized. The BoxR protein shows a significant sequence identity to the BzdR transcriptional repressor that controls the bzd genes involved in the anaerobic degradation of benzoate. Because the boxR gene is present in all box clusters so far identified in bacteria, the BoxR/benzoyl-CoA regulatory system appears to be a widespread strategy to control this aerobic hybrid pathway. Interestingly, the paralogous BoxR and BzdR regulators act synergistically to control the expression of the box and bzd genes. This cross-regulation between anaerobic and aerobic pathways for the catabolism of aromatic compounds has never been shown before, and it may reflect a biological strategy to increase the cell fitness in organisms that survive in environments subject to changing oxygen concentrations.
Clinical nurse research consultant: a clinical and academic role to advance practice and the discipline of nursing.

AIMS This article presents a proposal for the Clinical Nurse Research Consultant, a new nursing role. BACKGROUND Although healthcare delivery continues to evolve, nursing has lacked highly specialized clinical and research leadership that, as a primary responsibility, drives evidence-based practice change in collaboration with bedside clinicians. DATA SOURCES International literature published over the last 25 years in the databases of CINAHL, OVID, Medline Pubmed, Science Direct, Expanded Academic, ESBSCOhost, Scopus and Proquest is cited to create a case for the Clinical Nurse Research Consultant. DISCUSSION The Clinical Nurse Research Consultant will address the research/practice gap and assist in facilitating evidence-based clinical practice. To fulfil the responsibilities of this proposed role, the Clinical Nurse Research Consultant must be a doctorally prepared recognized clinical expert, have educational expertise, and possess advanced interpersonal, teamwork and communication skills. This role will enable clinical nurses to maintain and share their clinical expertise, advance practice through research and role model the clinical/research nexus. IMPLICATIONS FOR NURSING Critically, the Clinical Nurse Research Consultant must be appointed in a clinical and academic partnership to provide for career progression and role support. CONCLUSION The creation of the Clinical Nurse Research Consultant will advance nursing practice and the discipline of nursing.
Predictors of actual turnover in a national sample of newly licensed registered nurses employed in hospitals.

AIM This paper is a report of a study of factors that affect turnover of newly licensed registered nurses in United States hospitals. BACKGROUND There is a large body of research related to nursing retention; however, there is little information specific to newly licensed registered nurse turnover. Incidence rates of turnover among new nurses are unknown because most turnover data are not from nationally representative samples of nurses. METHOD This study used a longitudinal panel design to obtain data from 1653 registered nurses who were recently licensed by examination for the first time. We mailed surveys to a nationally representative sample of hospital registered nurses 1 year apart. The analytic sample consisted of 1653 nurses who responded to both survey mailings in January of 2006 and 2007. RESULTS Full-time employment and more sprains and strains (including back injuries) result in more turnover. Higher intent to stay and hours of voluntary overtime and more than one job for pay reduces turnover. When we omitted intent to stay from the probit model, less job satisfaction and organizational commitment led to more turnover, confirming their importance to turnover. Magnet Recognition Award(®) hospitals and several other work attributes had no effect on turnover. CONCLUSION Turnover problems are complex, which means that there is no one solution to decreasing turnover. Multiple points of intervention exist. One specific approach that may improve turnover rates is hospital policies that reduce strains and sprains.
Clinical utility of the X‐chromosome array

Previous studies have limited the use of specific X‐chromosome array designed platforms to the evaluation of patients with intellectual disability. In this retrospective analysis, we reviewed the clinical utility of an X‐chromosome array in a variety of scenarios. We divided patients according to the indication for the test into four defined categories: (1) autism spectrum disorders and/or developmental delay and/or intellectual disability (ASDs/DD/ID) with known family history of neurocognitive disorders; (2) ASDs/DD/ID without known family history of neurocognitive disorders; (3) breakpoint definition of an abnormality detected by a different cytogenetic test; and (4) evaluation of suspected or known X‐linked conditions. A total of 59 studies were ordered with 27 copy number variants detected in 25 patients (25/59 = 42%). The findings were deemed pathogenic/likely pathogenic (16/59 = 27%), benign (4/59 = 7%) or uncertain (7/59 = 12%). We place particular emphasis on the utility of this test for the diagnostic evaluation of families affected with X‐linked conditions and how it compares to whole genome arrays in this setting. In conclusion, the X‐chromosome array frequently detects genomic alterations of the X chromosome and it has advantages when evaluating some specific X‐linked conditions. However, careful interpretation and correlation with clinical findings is needed to determine the significance of such changes. When the X‐chromosome array was used to confirm a suspected X‐linked condition, it had a yield of 63% (12/19) and was useful in the evaluation and risk assessment of patients and families. © 2012 Wiley Periodicals, Inc.
Evaluation of Tibial Osteopathy Occurrence in Neurofibromatosis Type 1 Italian Patients

Neurofibromatosis Type 1 (NF1) is a common autosomal dominant disorder characterized by high penetrance, widely variable expressivity and occurrence of specific skeletal changes such as tibial osteopathy (TO). We collected data on patients referred to the Italian Neurofibromatosis Study Group in order to compare clinical features between 49 NF1 patients with TO, and 98 age‐matched NF1 patients without TO, and to determine whether the presence of TO is associated with a different risk of developing the typical NF1 complications. We assessed both groups for: age at diagnosis of NF1, gender distribution, family history, gender inheritance, presence of scoliosis, sphenoid wing osteopathy, other skeletal abnormalities, macrocrania, hydrocephalus, plexiform neurofibromas, tumors, optic pathway gliomas, T2H (high‐signal intensity areas on T2 weighted brain MRI), epilepsy, headache, mental retardation, cardiovascular malformations, and Noonan phenotype. Patients of both groups were subdivided by gender and re‐evaluated for these items. Statistical comparison was carried out between the two groups of patients for each feature. We collected data on type of treatment and on the clinical conditions of NF1‐TO patients after follow‐up. Patient's age at NF1 diagnosis was significantly younger in NF1‐TO subjects compared with NF1 subjects without TO, and the incidence of T2H was significantly reduced in NF1‐TO males compared with NF1 males without TO. The presence of TO does not imply that there is an increased risk of developing typical complications of NF1 (e.g., optic pathway glioma, plexiform neurofibroma, etc.), however, it does allow us to make an earlier diagnosis of NF1. © 2013 Wiley Periodicals, Inc.
Seminal Plasma Accelerates Semen-derived Enhancer of Viral Infection (SEVI) Fibril Formation by the Prostatic Acid Phosphatase (PAP248–286) Peptide*

Background: SEVI is an amyloid fibril that enhances HIV infectivity. To date, it has been produced from its precursor peptide only under nonphysiologic conditions. Results: Seminal plasma (SP) accelerates SEVI formation and protects SEVI from proteolytic degradation. Conclusion: SEVI forms spontaneously from its precursor peptide under physiologic conditions in SP. Significance: These findings may explain the presence of SEVI in human semen. Amyloid fibrils contained in semen, known as SEVI, or semen-derived enhancer of viral infection, have been shown to increase the infectivity of HIV dramatically. However, previous work with these fibrils has suggested that extensive time and nonphysiologic levels of agitation are necessary to induce amyloid formation from the precursor peptide (a proteolytic cleavage product of prostatic acid phosphatase, PAP248–286). Here, we show that fibril formation by PAP248–286 is accelerated dramatically in the presence of seminal plasma (SP) and that agitation is not required for fibrillization in this setting. Analysis of the effects of specific SP components on fibril formation by PAP248–286 revealed that this effect is primarily due to the anionic buffer components of SP (notably inorganic phosphate and sodium bicarbonate). Divalent cations present in SP had little effect on the kinetics of fibril formation, but physiologic levels of Zn2+ strongly protected SEVI fibrils from degradation by seminal proteases. Taken together, these data suggest that in the in vivo environment, PAP248–286 is likely to form fibrils efficiently, thus providing an explanation for the presence of SEVI in human semen.