bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: ASCO Clinical Practice Guideline Update—Integration of Results From TAILORx
Authors: Andre Fabrice , Ismaila Nofisat , Henry N. Lynn , Somerfield Mark R. , Bast Robert C. , Barlow William , Collyar Deborah E. , Hammond M. Elizabeth , Kuderer Nicole M. , Liu Minetta C. , Van Poznak Catherine , Wolff Antonio C. , Stearns Vered 
Published: May 2019

PURPOSE This focused update addresses the use of Onco type DX in guiding decisions on the use of adjuvant systemic therapy. METHODS ASCO uses a signals approach to facilitate guideline updating. For this focused update, the publication of the Trial Assigning Individualized Options for Treatment (TAILORx) evaluating noninferiority of endocrine therapy alone versus chemoendocrine therapy for invasive disease–free survival in women with Onco type DX scores provided a signal. An expert panel reviewed the results of TAILORx along with other published literature on the Onco type DX assay to assess for evidence of clinical utility. UPDATED RECOMMENDATIONS For patients with hormone receptor–positive, axillary node–negative breast cancer whose tumors have Onco type DX recurrence scores of less than 26, there is little to no benefit from chemotherapy, especially for patients older than age 50 years. Clinicians may recommend endocrine therapy alone for women older than age 50 years. For patients 50 years of age or younger with recurrence scores of 16 to 25, clinicians may offer chemoendocrine therapy. Patients with recurrence scores greater than 30 should be considered candidates for chemoendocrine therapy. Based on informal consensus, the panel recommends that oncologists may offer chemoendocrine therapy to these patients with recurrence scores of 26 to 30. Additional information can be found at www.asco.org/breast-cancer-guidelines .
Development and Implementation of a Cancer Quality Index in Queensland, Australia: A Tool for Monitoring Cancer Care
Authors: Walpole Euan T. , Theile David E. , Philpot Shoni , Youl Philippa H. ,   for Cancer Alliance Queensland
Published: May 2019

PURPOSE: Many cancer-specific assessment tools to measure health care performance have been developed. However, reporting on quality indicators at a population level is uncommon. We describe the development and implementation of a Cancer Quality Index (CQI) and examine the sensitivity of the index to detect change over time. METHODS: In developing the CQI, we reviewed existing indices, guidelines, and cancer care pathways. Our choice of indicators was additionally guided by the availability of population-wide data. A series of pilot indicators underwent trial use and were evaluated, and outcomes were discussed before a final set of indicators was established. The process was overseen by a clinician-led quality assurance committee that included hospital administrators and data custodians. RESULTS: The CQI includes five quality dimensions and 16 indicators for public and private cancer services using population-wide information. The following are the five indicators: Effective, Efficient, Safe, Accessible, and Equitable. We demonstrated the sensitivity of the CQI to measure change over time by examining outcomes such as time to first treatment and 30-day surgical mortality, using linked cancer registry and health administrative data for 99,728 patients with cancer diagnosed between 2005 and 2009 and 2010 and 2014. CONCLUSION: The CQI is a valuable tool to track progress in delivering safe, quality cancer care within health care services. Critical to its development and implementation has been the involvement of clinicians from several disciplines and the availability of population-based data. We found the CQI to be a sensitive tool able to detect changes over time.
Stress-Induced Suppression of Milk Protein Is Involved in a Noradrenergic Mechanism in the Mammary Gland
Authors: Chiba Takeshi , Maeda Tomoji , Fujita Yu , Takeda Rika , Kikuchi Akihiko , Kudo Kenzo 
Published: May 2019

Abstract
Stress decreases milk components such as milk protein and milk yield. The objective of this study was to investigate whether noradrenaline (NA) in milk constituted a factor associated with stress-induced changes in milk proteins such as β-casein. Breast milk obtained from eight healthy, nursing women contained NA at concentrations ranging from 12.7 to 115.5 nM. The expression of tyrosine hydroxylase (TH), a rate-limiting enzyme of NA synthesis, was observed in primary normal human mammary epithelial cells (HMECs), and in MCF-12A and MCF-10A cell lines. The mean NA concentration in culture medium used by MCF-12A transfected with TH small interfering RNA (siRNA) was significantly lower than that of cells transfected with control siRNA. NA concentration in milk in restraint-stressed nursing mice was significantly higher than that in nonstressed nursing mice, owing to elevated TH expression in the mammary epithelium. The mean β-casein concentration in milk in restraint-stressed mice was significantly lower than that in nonstressed mice. NA treatment resulted in a concentration-dependent decrease in β-casein expression in HMECs. β2 adrenergic receptor (ADRB2) expression was observed in HMECs, MCF-12A, and MCF-10A, and immunohistochemical analysis of ADRB2 using mammary epithelium sections obtained from mice at day 10 of lactation showed that ADRB2 was expressed at the apical membrane of mammary epithelium. Treatment with salbutamol, an ADRB2 stimulant, decreased β-casein expression in a concentration-dependent manner in MCF-12A. Our results showed that endogenous NA derived from mammary epithelial cells likely comprises one of the factors involved in stress-induced changes in milk proteins such as β-casein.
SREBP Plays a Regulatory Role in LH/hCG Receptor mRNA Expression in Human Granulosa-Lutein Cells
Authors: Li Yin-Xia , Guo Xingzi , Gulappa Thippeswamy , Menon Bindu , Menon K M J 
Published: May 2019

AbstractContextLH receptor (LHR) expression has been shown to be regulated posttranscriptionally by LHR mRNA binding protein (LRBP) in rodent and human ovaries. LRBP was characterized as mevalonate kinase. The gene that encodes mevalonate kinase is a member of a family of genes that encode enzymes involved in lipid synthesis and are regulated by the transcription factor sterol regulatory element binding proteins (SREBPs).ObjectiveThe current study examined the regulation of LHR mRNA expression in human granulosa-lutein cells in response to alterations in cholesterol metabolism.DesignUsing atorvastatin, an inhibitor of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase to inhibit cholesterol biosynthesis, we examined its effect on LHR mRNA expression. The effect of atorvastatin on SREBP and mRNA expression as well as LHR mRNA binding protein expression was examined. Finally, the effect of atorvastatin on human chorionic gonadotropin (hCG)–stimulated progesterone production and the expression of key steroidogenic enzymes was also examined.ResultsStatin treatment reduced LHR mRNA expression by increasing the levels of SREBP1a and SREBP2, leading to an increase in LRBP. RNA gel shift assay showed that increased binding of LHR mRNA to LRBP occurred in response to atorvastatin, leading to LHR mRNA degradation. The granulosa-lutein cells pretreated with atorvastatin also showed decreased responsiveness to hCG by decreasing the mRNA and protein expression of steroidogenic enzymes. Atorvastatin also attenuated LH/hCG-induced progesterone production.ConclusionThese results imply that LHR mRNA expression by the human granulosa-lutein cells is regulated by cholesterol, through a mechanism involving SREBP and SREBP cleavage activating protein serving as the cholesterol sensor.
Migration through physical constraints is enabled by MAPK-induced cell softening via actin cytoskeleton re-organization
Authors: Rudzka Dominika A. , Spennati Giulia , McGarry David J. , Chim Ya-Hua , Neilson Matthew , Ptak Aleksandra , Munro June , Kalna Gabriela , Hedley Ann , Moralli Daniela , Green Catherine , Mason Susan , Blyth Karen , Mullin Margaret , Yin Huabing , Olson Michael F. 
Published: May 2019

ABSTRACT
Cancer cells are softer than the normal cells, and metastatic cells are even softer. These changes in biomechanical properties contribute to cancer progression by facilitating cell movement through physically constraining environments. To identify properties that enabled passage through physical constraints, cells that were more efficient at moving through narrow membrane micropores were selected from established cell lines. By examining micropore-selected human MDA MB 231 breast cancer and MDA MB 435 melanoma cancer cells, membrane fluidity and nuclear elasticity were excluded as primary contributors. Instead, reduced actin cytoskeleton anisotropy, focal adhesion density and cell stiffness were characteristics associated with efficient passage through constraints. By comparing transcriptomic profiles between the parental and selected populations, increased Ras/MAPK signalling was linked with cytoskeleton rearrangements and cell softening. MEK inhibitor treatment reversed the transcriptional, cytoskeleton, focal adhesion and elasticity changes. Conversely, expression of oncogenic KRas in parental MDA MB 231 cells, or oncogenic BRaf in parental MDA MB 435 cells, significantly reduced cell stiffness. These results reveal that MAPK signalling, in addition to tumour cell proliferation, has a significant role in regulating cell biomechanics.
This article has an associated First Person interview with the first author of the paper.
Molecular mechanisms of chemotropism and cell fusion in unicellular fungi
Authors: Martin Sophie G. 
Published: May 2019

ABSTRACT
In all eukaryotic phyla, cell fusion is important for many aspects of life, from sexual reproduction to tissue formation. Fungal cells fuse during mating to form the zygote, and during vegetative growth to connect mycelia. Prior to fusion, cells first detect gradients of pheromonal chemoattractants that are released by their partner and polarize growth in their direction. Upon pairing, cells digest their cell wall at the site of contact and merge their plasma membrane. In this Review, I discuss recent work on the chemotropic response of the yeast models Saccharomyces cerevisiae and Schizosaccharomyces pombe, which has led to a novel model of gradient sensing: the cell builds a motile cortical polarized patch, which acts as site of communication where pheromones are released and sensed. Initial patch dynamics serve to correct its position and align it with the gradient from the partner cell. Furthermore, I highlight the transition from cell wall expansion during growth to cell wall digestion, which is imposed by physical and signaling changes owing to hyperpolarization that is induced by cell proximity. To conclude, I discuss mechanisms of membrane fusion, whose characterization remains a major challenge for the future.
Synthesis of the Soluble Precursors of Tetrabenzoporphyrin: Control of the Solubility and the Conversion Temperature
Authors: Okujima Tetsuo , Hashimoto Yusuke , Furuta Tomoya , Yamanaka Ritsuko , Jin Guangnan , Otsubo Saika , Aramaki Shinji , Mori Shigeki , Yamada Hiroko , Uno Hidemitsu , Ono Noboru 
Published: May 2019

Abstract
Novel thermally convertible precursors of tetrabenzoporphyrin (TBP) were synthesized by tetramerization of the corresponding bicyclo[2.2.2]octadiene(BCOD)-fused pyrroles. These precursors showed high solubility and were converted into TBPs by heating at 180–330 °C depending on the structure of BCOD moieties. This strategy provided easy access to pure PtTBP from the precursor with high conversion temperature in a good yield. Organic field effect transistors based on TBP were fabricated by thermal conversion after spin-coating of the precursors.
An Empirical Model for Stereochemical Control in the Cyclization of Cyclopropanetricarboxylic Acid Esters
Authors: Tanaka Kento , Manabe Hitomi , Irie Raku , Oikawa Masato 
Published: May 2019

Abstract
Here, we report an empirical model for diastereoselective cyclopropanation of fumarate/maleate diesters with chloroacetate, sulfonium ylide, or ammonium ylide. With symmetrical fumarate/maleate diesters, cyclopropanation was found to proceed with a high level of diastereoselectivity in favor of the chiral isomer. In contrast, production of the meso isomer was observed in 38–48% diastereoselectivity when unsymmetrical fumarate/maleate was employed. An improved synthesis of (N-desmethy)dysibetaine CPa in both racemic and enantiomerically pure forms was furthermore achieved. Configurational analysis by experimental and calculated 13C NMR data is also reported.
The Role of Customer Investor Involvement in Crowdfunding Success
Authors: Cornelius Philipp B. , Gokpinar Bilal 
Published: May 2019

Entrepreneurs increasingly use reward-based crowdfunding to finance innovation projects through a large number of customer investments. The existing academic literature has predominantly studied factors that drive crowd investments and whether crowdfunding predicts market success. However, we argue that the involvement of customers goes beyond the provision of capital. As investors, customers enter into a principal–agent relationship with entrepreneurs. Thus, entrepreneurs are often faced with a crowd of customer investors who try to influence product development. We show that entrepreneurs can benefit from this influence, because customer investors provide some of the support usually received from institutional investors. Greater involvement from customer investors thus increases funding success. This holds when we control for creator ability and project quality. The effect is driven by customers’ influence on product development and the reduction in agency costs for prospective customers. We also link the involvement of customer investors during crowdfunding to the crowdsourcing literature and show that its positive effect is augmented by the elicitation of external information through distant search. This paper was accepted by Lee Fleming, entrepreneurship and innovation.
Hip or spine surgery first?
Authors: Liu N. , Goodman S. B. , Lachiewicz P. F. , Wood K. B. 
Published: May 2019

Aims Patients may present with concurrent symptomatic osteoarthritis (OA) of the hip and degenerative disorders of the lumbar spine, with surgical treatment being indicated for both. Whether arthroplasty of the hip or spinal surgery should be performed first remains uncertain. Materials and Methods Clinical scenarios were devised for a survey asking the preferred order of surgery and the rationale for this decision for five fictional patients with both OA of the hip and degenerative lumbar disorders. These were symptomatic OA of the hip and: 1) lumbar spinal stenosis with neurological claudication; 2) lumbar degenerative spondylolisthesis with leg pain; 3) lumbar disc herniation with leg weakness; 4) lumbar scoliosis with back pain; and 5) thoracolumbar disc herniation with myelopathy. This survey was sent to 110 members of The Hip Society and 101 members of the Scoliosis Research Society. The choices of the surgeons were compared among scenarios and between surgical specialties using the chi-squared test. The free-text comments were analyzed using text-mining. Results Responses were received from 51 hip surgeons (46%) and 37 spine surgeons (37%). The percentages of hip surgeons recommending ‘hip first’ differed significantly among scenarios: 59% for scenario 1; 73% for scenario 2; 47% for scenario 3; 47% for scenario 4; and 10% for scenario 5 (p < 0.001). The percentages of spine surgeons recommending ‘hip first’ were 49% for scenario 1; 70% for scenario 2; 19% for scenario 3; 78% for scenario 4; and 0% for scenario 5. There were significant differences between the groups for scenarios 3 (more hip surgeons recommended ‘hip first’; p = 0.012) and 4 (more hip surgeons recommended ‘spine first’; p = 0.006). Conclusion In patients with coexistent OA of the hip and degenerative disorders of the spine, the question of ‘hip or spinal surgery first’ elicits relatively consistent answers in some clinical scenarios, but remains controversial in others, even for experienced surgeons. The nature of neurological symptoms can influence surgeons’ decision-making. Cite this article: Bone Joint J 2019;101-B(6 Supple B):37–44.
Can some early revision total hip arthroplasties be avoided?
Authors: Novikov D. , Mercuri J. J. , Schwarzkopf R. , Long W. J. , Bosco III J. A. , Vigdorchik J. M. 
Published: May 2019

Aims Studying the indications for revision total hip arthroplasty (THA) may enable surgeons to change their practice during the initial procedure, thereby reducing the need for revision surgery. The aim of this study was to identify and describe the potentially avoidable indications for revision THA within five years of the initial procedure. Patients and Methods A retrospective review of 117 patients (73 women, 44 men; mean age 61.5 years (27 to 88)) who met the inclusion criteria was conducted. Three adult reconstruction surgeons independently reviewed the radiographs and medical records, and they classified the revision THAs into two categories: potentially avoidable and unavoidable. Baseline demographics, perioperative details, and quality outcomes up to the last follow-up were recorded. Results A total of 60 revision THAs (51.3%) were deemed potentially avoidable and 57 (48.7%) were deemed unavoidable. The following were identified as avoidable factors: suboptimal positioning of the acetabular component (29; 48%), intraoperative fracture or a fracture missed on an intraoperative radiograph (20; 33%), early (less than two weeks) aseptic loosening (seven; 11.7%), and symptomatic leg length discrepancy of > 1 cm (four; 6.7%). Conclusion A surprisingly large proportion of acute revision THAs are potentially avoidable. Surgeons must carefully evaluate the indications for revision THAs in their practice and identify new methods to address these issues. Cite this article: Bone Joint J 2019;101-B(6 Supple B):97–103.
Increased conditional risk of recurring complications with contralateral total hip arthroplasty surgery
Authors: Roberts H. J. , Tsay E. L. , Grace T. R. , Vail T. P. , Ward D. T. 
Published: May 2019

Aims Increasingly, patients with bilateral hip arthritis wish to undergo staged total hip arthroplasty (THA). With the rise in demand for arthroplasty, perioperative risk assessment and counselling is crucial for shared decision making. However, it is unknown if complications that occur after a unilateral hip arthroplasty predict complications following surgery of the contralateral hip. Patients and Methods We used nationwide linked discharge data from the Healthcare Cost and Utilization Project between 2005 and 2014 to analyze the incidence and recurrence of complications following the first- and second-stage operations in staged bilateral total hip arthroplasty (BTHAs). Complications included perioperative medical adverse events within 30 to 60 days, and infection and mechanical complications within one year. Conditional probabilities and odds ratios (ORs) were calculated to determine whether experiencing a complication after the first stage of surgery increased the risk of developing the same complication after the second stage. Results A total of 13 829 patients (5790 men and 8039 women) who underwent staged BTHAs were analyzed. The mean age at first operation was 62.9 years (14 to 95). For eight of the 12 outcomes evaluated, patients who experienced the outcome following the first arthroplasty had a significantly increased probability and odds of developing that same complication following the second arthroplasty, compared with those who did not experience the complication after the first surgery. This was true for digestive complications (OR 25.67, 95% confidence interval (CI) 13.86 to 46.08; p < 0.001), urinary complications (OR 6.48, 95% CI 1.7 to 20.73; p = 0.01), haematoma (OR 12.17, 95% CI 4.55 to 31.14; p < 0.001), deep vein thrombosis (OR 4.82, 95% CI 2.34 to 9.65; p < 0.001), pulmonary embolism (OR 12.03, 95% CI 2.02 to 46.77; p = 0.01), deep hip infection (OR 534.21, 95% CI 314.96 to 909.25; p < 0.001), superficial hip infection (OR 1574.99, 95% CI 269.83 to 9291.81; p < 0.001), and mechanical malfunction (OR 117.49, 95% CI 91.55 to 150.34; p < 0.001). Conclusion The occurrence of certain complications after unilateral THA is associated with an increased risk of the same complication occurring after staged arthroplasty of the contralateral hip. Patients who experience these complications after unilateral hip arthroplasty should be appropriately counselled regarding their risk profile prior to undergoing staged contralateral hip arthroplasty. Cite this article: Bone Joint J 2019;101-B(6 Supple B):77–83.
Incidence and treatment of abductor deficiency during total hip arthroplasty using the posterior approach
Authors: Whiteside L. A. , Roy M. E. 
Published: May 2019

Aims The aims of this study were to assess the exposure and preservation of the abductor mechanism during primary total hip arthroplasty (THA) using the posterior approach, and to evaluate gluteus maximus transfer to restore abductor function of chronically avulsed gluteus medius and minimus. Patients and Methods A total of 519 patients (525 hips) underwent primary THA using the posterior approach, between 2009 and 2013. The patients were reviewed preoperatively and at two and five years postoperatively. Three patients had mild acute laceration of the gluteus medius caused by retraction. A total of 54 patients had mild chronic damage to the tendon (not caused by exposure), which was repaired with sutures through drill holes in the greater trochanter. A total of 41 patients had severe damage with major avulsion of the gluteus medius and minimus muscles, which was repaired with sutures through bone and a gluteus maximus flap transfer to the greater trochanter. Results Abductor strength was maintained in the normal hips, but lateral hip pain progressed significantly, five years postoperatively (p < 0.0001). In the 54 patients with mild abductor tendon damage treated with simple repair, lateral hip pain also increased significantly during follow-up (p = 0.002). In the 35 patients with severe avulsion but good muscle repaired using a gluteus maximus flap transfer, abductor function was restored. The six patients with complete avulsion and poor muscle did not regain strong abductor power, but lateral hip pain decreased. Conclusion The posterior approach offered excellent exposure and preservation of the abductor mechanism during primary THA. Augmentation of the repair with a gluteus maximus flap provided stable reconstruction of the abductor muscles and seemed to restore function in the hips with functioning muscles. Cite this article: Bone Joint J 2019;101-B(6 Supple B):116–122.