bluuebunny/crossref_metadata_2025_split huggingface dataset:
The preliminary report about the modified supramalleolar tibial osteotomy for asymmetric ankle osteoarthritis
Authors: Koo Ja Wook , Park Sang Hoon , Kim Ki Chun , Sung Il-Hoon 
Published: February 2019

Objective: Supramalleolar tibial osteotomy (SMO) for asymmetric ankle osteoarthritis (OA) is known to lead to satisfactory. Here, authors present a preliminary report on SMO surgical treatment in patients with asymmetric ankle arthritis. Materials and Methods: We reviewed cases of asymmetric ankle OA treated by modified SMO between January 2011 and October 2015. Clinical assessment was performed with the use of the ankle and hindfoot score of the American Orthopedic Foot and Ankle Society (AOFAS), foot function index, and visual analogue scale (VAS). Patient satisfaction with surgery and postoperative subjective symptoms were examined. Radiographic evaluation included preoperative and postoperative tibial anterior surface angle (TAS angle), talar tilt angle (TT angle), and tibial lateral surface angle (TLS angle). Takakura stage was measured. Results: The average follow-up period was 46.3 months. The AOFAS score was 55.7 ± 6.03 preoperatively and 76.0 ± 4.73 postoperatively. Foot function index was 60.7 ± 8.78 preoperatively and 30.8 ± 7.59 postoperatively. VAS was 7.2 ± 0.53 before surgery and 1.9 ± 0.85 after surgery. Clinical evaluations showed statistically significant improvement. The majority of patients reported satisfactory results in the subjective satisfaction evaluation. TAS angle was 84.6 ± 1.82 preoperatively and 94.0 ± 2.79 postoperatively. TLS angle was 78.8 ± 2.11 preoperatively and 81.8 ± 1.80 postoperatively. TT angle was 3.6 ± 1.26 before surgery and 2.1 ± 0.79 after surgery. Thirteen cases showed radiographic improvement of Takakura stage. Complications were not observed. Conclusion: Modified SMO is a useful procedure that provides for the union and stability of osteotomy with the advantages of the existing SMO and can be performed without bone graft.
Impact of the 7-Day Disabled List Rule Change on Economics and Performance After Reported Concussion Injuries in Major League Baseball
Authors: Chatha Kiran , Al-Mansoori Ahmed , Guo Eric , Whaley James D. , Sabesan Vani J. 
Published: February 2019

Background: The incidence of concussions is increasing in Major League Baseball (MLB), and the cost of these injuries in 2008 was reportedly as high as US$423 million. Team officials are more aware of concussion injuries, and one measure to address this issue was the creation of a concussion-specific 7-day disabled list (DL) in 2011. Purpose: To evaluate concussion trends among MLB players and the impact of concussion-specific 7-day DL status on postinjury player performance and team financials. Study Design: Descriptive epidemiology study. Methods: From 2005 to 2016, a total of 112 players placed on the DL because of a concussion were identified using the MLB website and were verified using established news databases. Salary information for players was collected using MLB published data, and cost was calculated with a previously published formula utilizing the injured player’s salary per game and adding the cost of his replacement. Performance metrics were compared before and after the rule change. Results: The mean number of days on the DL decreased from 38.8 before 2011 to 29.2 after 2011. The mean annual cost per player before 2011 was $1.1 million and decreased to $565,000 after the rule change. Regression analyses demonstrated a downward trend in the mean cost ( R = –0.61, P < .001). A comparison of postinjury performance metrics showed no significant differences with decreased time on the DL. Conclusion: The minimum 7-day DL change has not had a negative impact on reporting; instead, it has demonstrated decreased time on the DL and lower associated team costs. Performance metrics demonstrated no differences compared with before the rule change, suggesting that players are not negatively affected by decreased time on the DL.
Bilateral Ischemic Optic Neuropathy Following Intravenous Immunoglobulin
Authors: Ansari Waseem H. , Patrick Brittany K. , Smith Bradley T. 
Published: February 2019

Purpose: The purpose of this work is to report an association between intravenous immunoglobulin (IVIG) infusions and the development of bilateral ischemic optic neuropathy. Methods: A case report is described. Results: A 76-year-old male receiving IVIG infusions developed loss of vision in the left eye and was diagnosed with ischemic optic neuropathy. Two months later, he developed another episode of ischemic optic neuropathy in the contralateral eye. The investigation for giant-cell arteritis, vasculopathy, and infiltrative processes was negative. The patient had minimal improvement in visual acuity over several months of follow-up. Conclusions: Bilateral ischemic optic neuropathy was likely caused by IVIG infusion in this case, given the temporal relationship and the negative workup for other risk factors.
The global clonal complexity of the murine blood system declines throughout life and after serial transplantation
Authors: Ganuza Miguel , Hall Trent , Finkelstein David , Wang Yong-Dong , Chabot Ashley , Kang Guolian , Bi Wenjian , Wu Gang , McKinney-Freeman Shannon 
Published: February 2019

AbstractAlthough many recent studies describe the emergence and prevalence of “clonal hematopoiesis of indeterminate potential” in aged human populations, a systematic analysis of the numbers of clones supporting steady-state hematopoiesis throughout mammalian life is lacking. Previous efforts relied on transplantation of “barcoded” hematopoietic stem cells (HSCs) to track the contribution of HSC clones to reconstituted blood. However, ex vivo manipulation and transplantation alter HSC function and thus may not reflect the biology of steady-state hematopoiesis. Using a noninvasive in vivo color-labeling system, we report the first comprehensive analysis of the changing global clonal complexity of steady-state hematopoiesis during the natural murine lifespan. We observed that the number of clones (ie, clonal complexity) supporting the major blood and bone marrow hematopoietic compartments decline with age by ∼30% and ∼60%, respectively. Aging dramatically reduced HSC in vivo–repopulating activity and lymphoid potential while increasing functional heterogeneity. Continuous challenge of the hematopoietic system by serial transplantation provoked the clonal collapse of both young and aged hematopoietic systems. Whole-exome sequencing of serially transplanted aged and young hematopoietic clones confirmed oligoclonal hematopoiesis and revealed mutations in at least 27 genes, including nonsense, missense, and deletion mutations in Bcl11b, Hist1h2ac, Npy2r, Notch3, Ptprr, and Top2b.
Carbon ion radiotherapy boost in the treatment of glioblastoma: a randomized phase I/III clinical trial
Authors: Kong Lin , Gao Jing , Hu Jiyi , Lu Rong , Yang Jing , Qiu Xianxin , Hu Weixu , Lu Jiade J. 
Published: February 2019

AbstractBackgroundGlioblastoma (GBM) is a highly virulent tumor of the central nervous system, with a median survival < 15 months. Clearly, an improvement in treatment outcomes is needed. However, the emergence of these malignancies within the delicate brain parenchyma and their infiltrative growth pattern severely limit the use of aggressive local therapies. The particle therapy represents a new promising therapeutic approach to circumvent these prohibitive conditions with improved treatment efficacy.Methods and designPatients with newly diagnosed malignant gliomas will have their tumor tissue samples submitted for the analysis of the status of O‐6‐methylguanine‐DNA methyltransferase (MGMT) promoter methylation. In Phase I, the patients will undergo an induction carbon ion radiotherapy (CIRT) boost followed by 60 GyE of proton irradiation with concurrent temozolomide (TMZ) at 75 mg/m2. To determine the maximal dose of safe induction boost, the tolerance, and acute toxicity rates in a dose‐escalation manner from 9 to 18 GyE in three fractions will be used. In Phase III, GBM‐only patients will be randomized to receive either 60 GyE (2 GyE per fraction) of proton irradiation with concurrent TMZ (control arm) or a CIRT boost (dose determined in Phase I of this trial) followed by 60 GyE of proton irradiation with concurrent TMZ. The primary endpoints are overall survival (OS) and toxicity rates (acute and long‐term). Secondary endpoints are progression‐free survival (PFS), and tumor response (based upon assessment with C‐methionine/fluoro‐ethyl‐tyrosine positron emission tomography [MET/FET PET] or magnetic resonance imaging [MRI] and detection of serologic immune markers). We hypothesize that the induction CIRT boost will result in a greater initial tumor‐killing ability and prime the tumor microenvironment for enhanced immunologic tumor clearance, resulting in an expected 33% improvement in OS rates.DiscussionThe prognosis of GBM remains grim. The mechanism underpinning the poor prognosis of this malignancy is its chronic state of tumor hypoxia, which promotes both immunosuppression/immunologic evasion and radio‐resistance. The unique physical and biological properties of CIRT are expected to overcome these microenvironmental limitations to confer an improved tumor‐killing ability and anti‐tumor immune response, which could result in an improvement in OS with minimal toxicity.Trial registration number This trial has been registered with the China Clinical Trials Registry, and was allocated the number ChiCTR‐OID‐17013702.
West German Study PlanB Trial: Adjuvant Four Cycles of Epirubicin and Cyclophosphamide Plus Docetaxel Versus Six Cycles of Docetaxel and Cyclophosphamide in HER2-Negative Early Breast Cancer
Authors: Nitz Ulrike , Gluz Oleg , Clemens Michael , Malter Wolfram , Reimer Toralf , Nuding Benno , Aktas Bahriye , Stefek Andrea , Pollmanns Anke , Lorenz-Salehi Fatemeh , Uleer Christoph , Krabisch Petra , Kuemmel Sherko , Liedtke Cornelia , Shak Steven , Wuerstlein Rachel , Christgen Matthias , Kates Ronald E. , Kreipe Hans H. , Harbeck Nadia ,   on behalf of the West German Study Group PlanB Investigators
Published: February 2019

PURPOSE The West German Study Group PlanB trial evaluated an anthracycline-free chemotherapy standard (six cycles of docetaxel and cyclophosphamide [TC]) in the routine treatment of human epidermal growth factor receptor 2–negative early breast cancer (EBC). PATIENTS AND METHODS Patients with pT1 to pT4c, all pN+, and pN0/high-risk EBC were eligible. High-risk pN0 was defined by one or more of the following: pT greater than 2, grade 2 to 3, high urokinase-type plasminogen activator/plasminogen activator inhibitor-1, hormone receptor (HR) negativity, and less than 35 years of age. After an early amendment, all HR-positive tumors underwent recurrence score (RS) testing, with chemotherapy omission recommended in RS less than or equal to 11 pN0 to pN1 disease. Patients were randomly assigned to four cycles of epirubicin (E)90/cyclophoshamide (C)600 followed by four cycles of docetaxel (T)100 or six cycles of T75C600 (administered once every 3 weeks). The primary end point was disease-free survival (DFS); secondary end points were overall survival (OS) and safety. The protocol specified P = .05 for a noninferiority margin of 4.4% for all patients combined. RESULTS Of the 3,198 registered patients, 348 (RS ≤ 11) omitted chemotherapy, and 401 were not randomly assigned. The intention-to-treat population included 2,449 patients (1,227 EC-T v 1,222 TC: postmenopausal, 62.2% v 60.8%; pN0, 58.2% v 59.5%; pT1, 57.6% v 52.3%; HR positive, 81.4% v 82.2%; RS greater than 25 [in HR-positive patients], 26.2% v 27.5%). Within the safety population (1,167 v 1,178 patients), 87.5% v 93.0% completed therapy. After a 60-month median follow-up, 5-year outcomes were similar in the EC-T and TC arms (DFS, 89.6% [95% CI, 87.9% to 91.5%] v 89.9% [95% CI, 88.1% to 91.8%]; OS, 94.5% [95% CI, 93.1% to 95.9%] v 94.7% [95% CI, 93.3% to 96.1%]). The DFS difference was within the noninferiority margin of the original trial design. Five treatment-related deaths were reported for TC (one for EC-T), despite a trend toward more-severe adverse events in the latter. Interaction analysis revealed no predictive trends with respect to key factors, including triple-negative, luminal A/B-like, pN, age, and RS status. CONCLUSION In the West German Study Group PlanB trial, 5-year outcomes for TC and EC-T were equally excellent. Six cycles of TC is an effective/safe option in human epidermal growth factor receptor 2–negative EBC with pN0 high genomic risk or pN1 EBC with genomically intermediate- to high-risk disease.
Maintenance Defactinib Versus Placebo After First-Line Chemotherapy in Patients With Merlin-Stratified Pleural Mesothelioma: COMMAND—A Double-Blind, Randomized, Phase II Study
Authors: Fennell Dean A. , Baas Paul , Taylor Paul , Nowak Anna K. , Gilligan David , Nakano Takashi , Pachter Jonathan A. , Weaver David T. , Scherpereel Arnaud , Pavlakis Nick , van Meerbeeck Jan P. , Cedrés Susana , Nolan Luke , Kindler Hedy , Aerts Joachim G.J.V. 
Published: February 2019

PURPOSE Inhibition of focal adhesion kinase has been shown to selectively kill mesothelioma cells that express low levels of moesin-ezrin-radixin-like protein (merlin). On this basis, we designed a randomized, phase II trial to investigate whether defactinib as maintenance therapy after standard first-line chemotherapy could improve progression-free survival (PFS) in patients with malignant pleural mesothelioma (MPM). METHODS This global, double-blind, randomized, placebo-controlled trial was conducted in patients with advanced MPM and disease control after at least four cycles of first-line chemotherapy. Patients were stratified for merlin and then randomly assigned (in a 1:1 fashion) to receive either oral defactinib or placebo until disease progression, unacceptable toxicity, or withdrawal occurred. The coprimary end points were PFS and overall survival (OS). Quality of life (QoL) was assessed using the Lung Cancer Symptom Scale for Mesothelioma tool. RESULTS Three hundred forty-four patients were randomly assigned to receive either defactinib (n = 173) or placebo (n = 171). The median PFS was 4.1 months (95% CI, 2.9 to 5.6 months) for defactinib versus 4.0 months (95% CI, 2.9 to 4.2 months) for placebo. The median OS was 12.7 months (95% CI, 9.1 to 21 months) for defactinib versus 13.6 months (95% CI, 9.6 to 21.2 months) for placebo (hazard ratio, 1.0; 95% CI, 0.7 to 1.4). Although shorter survival for both defactinib- and placebo-treated patients was observed, in the patients who had merlin-low MPM compared with the patients who had merlin-high MPM, there were no statistical differences in response rate, PFS, OS, or QoL between the treatment groups. The most common grade 3 or worse adverse events were nausea, diarrhea, fatigue, dyspnea, and decreased appetite. CONCLUSION Neither PFS nor OS was improved by defactinib after first-line chemotherapy in patients with merlin-low MPM. Defactinib cannot be recommended as maintenance therapy for advanced MPM.
A Simplified Approach to Reducing Cardiovascular Risk
Authors: Schade David S , Eaton R Philip 
Published: February 2019

Abstract

Context
Cardiovascular disease remains the number one cause of morbidity and mortality in the United States, despite major advances in our understanding of its pathogenesis and prevention. One reason for this continued epidemic is the poor adherence to treatment guidelines by caregivers and the lack of understanding by patients relative to its reversibility with treatment. Current guidelines are complex and often contradictory; there are at least 21 organizations publishing guidelines.

Objective
This article proposes a simplified approach that is based on the low-density lipoprotein (LDL) hypothesis stating that the lower the LDL cholesterol (LDL-C), the less the cardiovascular disease. This goal focuses on obtaining a plasma LDL-C <50 mg/dL.

Design
A positive coronary artery calcium scan in conjunction with an intermediate online cardiovascular risk score will identify individuals with substantial cardiovascular disease risk. With lifestyle improvements (including a low cholesterol diet) and low-dose hypolipemic generic oral medications, this LDL-C concentration is readily achievable in the majority of asymptomatic patients at risk for atherosclerosis.

Conclusion
Controlling the cardiovascular epidemic will require participation of both the patient and the physician caregiver. By simplifying the therapeutic regimen, patient compliance will increase, and an important reduction in cardiovascular morbidity and mortality will follow.
Gene-environment interaction impacts on heart development and embryo survival
Authors: Moreau Julie L. M. , Kesteven Scott , Martin Ella M. M. A. , Lau Kin S. , Yam Michelle X. , O'Reilly Victoria C. , del Monte-Nieto Gonzalo , Baldini Antonio , Feneley Michael P. , Moon Anne M. , Harvey Richard P. , Sparrow Duncan B. , Chapman Gavin , Dunwoodie Sally L. 
Published: February 2019

ABSTRACT
Congenital heart disease (CHD) is the most common type of birth defect. In recent years, research has focussed on identifying the genetic causes of CHD. However, only a minority of CHD cases can be attributed to single gene mutations. In addition, studies have identified different environmental stressors that promote CHD, but the additive effect of genetic susceptibility and environmental factors is poorly understood. In this context, we have investigated the effects of short-term gestational hypoxia on mouse embryos genetically predisposed to heart defects. Exposure of mouse embryos heterozygous for Tbx1 or Fgfr1/Fgfr2 to hypoxia in utero increased the incidence and severity of heart defects while Nkx2-5+/− embryos died within 2 days of hypoxic exposure. We identified the molecular consequences of the interaction between Nkx2-5 and short-term gestational hypoxia, which suggest that reduced Nkx2-5 expression and a prolonged hypoxia-inducible factor 1α response together precipitate embryo death. Our study provides insight into the causes of embryo loss and variable penetrance of monogenic CHD, and raises the possibility that cases of foetal death and CHD in humans could be caused by similar gene-environment interactions.
Global CO2 emission reduction policies and West African electricity system: Case for transformational access
Authors: Momodu Abiodun Suleiman , Addo Ahmad 
Published: February 2019

Based on the UN Human Development Index, the West African sub-region holds one of lowest indices in development around the world. There is a glaring need for the sub-region to increase its electricity capacity; however, stringent global CO2 policies have ‘choking’ effects on the growth of the electricity sector in energy deprived countries, like the West African Member States. This study examines the West Africa electric power sector under a range of technological, economic, and policy-related uncertainties, positing that there is the need to frame policies from the premise of ‘need’ rather than a ‘circumstantial’ perspective, which, in this study, relates to the global policies on CO2 emission reduction. Though CO2 is the inevitable by-product of combusting fossil fuels to generate electricity, it should also be viewed from the perspective of its significant benefits as regards provision of social welfare of individuals. This study evaluated the broad strategies in policy formulation and implementation (top-down versus bottom-up analysis) and applied these strategies to examine investment decision versus pricing regime and electricity system value chain (upstream versus downstream analysis). System dynamics principles were used to forecast what future consumption will look like, which shows that there would be marked increase in demand followed by increased emission without intervention. This study concludes that global CO2 policy would need to be re-considered such that energy deprived countries, like those in West Africa, would be able to implement a sustainable development agenda through growth strategy of bottom-up approach to ‘free’ their electricity system for improved living standard, irrespective of climate change issues.
The second generation of The Avon Longitudinal Study of Parents and Children (ALSPAC-G2): a cohort profile
Authors: Lawlor Deborah A. , Lewcock Melanie , Rena-Jones Louise , Rollings Claire , Yip Vikki , Smith Daniel , Pearson Rebecca M. , Johnson Laura , Millard Louise A. C. , Patel Nashita , Skinner Andy , Tilling Kate ,   ALSPAC Executive
Published: February 2019

Background: The Avon Longitudinal Study of Parents and Children-Generation 2 (ALSPAC-G2) was set up to provide a unique multi-generational cohort. It builds on the existing ALSPAC resource, which recruited 14,541 pregnancies to women resident in the South West of England who were expected to deliver between 01/04/1991 and 31/12/1992. Those women and their partners (Generation 0; ALSPAC-G0) and their offspring (ALSPAC-G1) have been followed for the last 26 years. This profile describes recruitment and data collection on the next generation (ALSPAC-G2)—the grandchildren of ALSPAC-G0 and children of ALSPAC-G1. Recruitment: Recruitment began on the 6th of June 2012 and we present details of recruitment and participants up to 30th June 2018 (~6 years). We knew at the start of recruitment that some ALSPAC-G1 participants had already become parents and ALSPAC-G2 is an open cohort; we recruit at any age. We hope to continue recruiting until all ALSPAC-G1 participants have completed their families. Up to 30th June 2018 we recruited 810 ALSPAC-G2 participants from 548 families. Of these 810, 389 (48%) were recruited during their mother’s pregnancy, 287 (35%) before age 3 years, 104 (13%) between 3-6 years and 30 (4%) after 6 years. Over 70% of those invited to early pregnancy, late pregnancy, second week of life, 6-, 12- and 24-month assessments (whether for their recruitment, or a follow-up, visit) have attended, with attendance being over 60% for subsequent visits up to 7 years (to few are eligible for the 9- and 11-year assessments to analyse). Data collection: We collect a wide-range of social, lifestyle, clinical, anthropometric and biological data on all family members repeatedly. Biological samples include blood (including cord-blood), urine, meconium and faeces, and placental tissue. In subgroups detailed data collection, such as continuous glucose monitoring and videos of parent-child interactions, are being collected.
Reducing emergency admissions for primary constipation: a pilot study to cut costs in an acute hospital trust
Authors: Blythin Sandra , McAteer Julie , Crook Zoe , Walker Mike 
Published: February 2019

Background: Constipation is a common condition that impacts quality of life, often causing psychological distress and incurring considerable healthcare costs in terms of unnecessary emergency admissions due to poor management. Aintree University Hospital has a healthy bowel clinic for treating patients presenting with functional bowel disorders, including constipation, in an outpatient setting. From December 2013 to November 2014, 301 patients were admitted to hospital with a primary diagnosis of constipation, 216 of these through the accident and emergency department, with an average length of stay of 3.3 days. Methods: To prevent unnecessary admission, a successful bid provided £16 000 to fund a 12-month pilot study to develop a new emergency constipation pathway, including an emergency constipation clinic and linked to the main healthy bowel clinic. Results: Over the pilot study period, more than 70 patients were seen through the new pathway, which saved 231 bed days. At an average cost per bed day of £400, this equates to a total annual saving of £92 400. Conclusion: A new emergency pathway linked to an already established outpatient clinic prevented admission of patients presenting with primary constipation.