bluuebunny/crossref_metadata_2025_split huggingface dataset:
Parenthood and risk of hip fracture: a 10-year follow-up prospective study of middle-aged women and men in China
Authors: Peng K. , Yao P. , Yang L. , Kartsonaki C. , Bennett D. , Tian M. , Guo Y. , Bian Z. , Chen Y. , Chen Z. , Woodward M. , Ivers R. , Clarke R. 
Published: December 2019

Abstract
Summary
This prospective study of Chinese adults demonstrated an inverse J-shaped association of number of children with risk of hip fracture in both men and postmenopausal women aged 50 years or older. Women with 2 or 3 children and men with 4 children had the lowest risk of hip fracture.

Introduction
Women have higher absolute risks of fracture than men, which is believed to reflect differences in oestrogen exposure. The aim of this study was to compare the associations of number of children with risk of hip fracture between men and women aged over 50 years.

Methods
The China Kadoorie Biobank (CKB) recruited 133,399 women and 110,296 men, aged 50 years or older between 2004 and 2008. During 10-year follow-up, 2068 participants (1394 women and 674 men) suffered a hip fracture. Cox regression analysis was used to estimate sex-specific adjusted hazard ratios (HRs) and 95% CI for incident hip fracture.

Results
Over 98% of both subsets of men and women aged 50 or older reported having children. Women who had 2 or 3 children had the lowest risks of hip fracture compared with other groups. Compared with nulliparous women, the adjusted HR for hip fracture were 0.89 (95% CI; 0.72, 1.10) for 1 child, 0.79 (0.70, 0.90) for 2 children, 0.79 (0.72, 0.87) for 3 children, 0.81 (0.72, 0.91) for 4 children, and 0.95 (0.83, 1.10) for those with 5 or more children. The associations of number of children with hip fracture were broadly consistent in men of a similar age.

Conclusions
The concordant effects of the number of children with risk of hip fracture between men and women suggest that the lower risks in multiparous women are not due to differences in oestrogen exposure or other biological effects, but may reflect residual confounding by socioeconomic or lifestyle factors.
Mechanisms of immune evasion in bladder cancer
Authors: Crispen Paul L. , Kusmartsev Sergei 
Published: December 2019

AbstractWith the introduction of multiple new agents, the role of immunotherapy is rapidly expanding across all malignancies. Bladder cancer is known to be immunogenic and is responsive to immunotherapy including intravesical BCG and immune checkpoint inhibitors. Multiple trials have addressed the role of checkpoint inhibitors in advanced bladder cancer, including atezolizumab, avelumab, durvalumab, nivolumab and pembrolizumab (all targeting the PD1/PD-L1 pathway). While these trials have demonstrated promising results and improvements over existing therapies, less than half of patients with advanced disease demonstrate clinical benefit from checkpoint inhibitor therapy. Recent breakthroughs in cancer biology and immunology have led to an improved understanding of the influence of the tumor microenvironment on the host’s immune system. It appears that tumors promote the formation of highly immunosuppressive microenvironments preventing generation of effective anti-tumor immune response through multiple mechanisms. Therefore, reconditioning of the tumor microenvironment and restoration of the competent immune response is essential for achieving optimal efficacy of cancer immunotherapy. In this review, we aim to discuss the major mechanisms of immune evasion in bladder cancer and highlight novel pathways and molecular targets that may help to attenuate tumor-induced immune tolerance, overcome resistance to immunotherapy and improve clinical outcomes.
Oral vinorelbine versus intravenous vinorelbine, in combination with epirubicin as first-line chemotherapy in Chinese patients with metastatic breast cancer
Authors: Huang Liang , Wang Xiaojia , Zhou Liheng , Di Lijun , Zheng Hongyu , Jiang Zefei , Wang Yongsheng , Song Xiangqun , Feng Jifeng , Yu Shiying , Liu Yunpeng , Zheng Hong , Shen Kunwei , Tong Zhongsheng , Shao Zhimin 
Published: December 2019

AbstractOral VRL offers easier administration, better quality of life, and cost saving. This study aimed to evaluate the treatment efficacy in terms of tumor response of the two formulations of vinorelbine (VRL, oral and IV) in combination with epirubicin (EPI); and the effect of EPI co-administration on VRL pharmacokinetics (PK) in Chinese patients with metastatic breast cancer (MBC) using a phase 2, open label, randomized trial. Patients were aged 18–70 years, had histologically confirmed MBC, Karnofsky Performance Status ≥ 70%, and life expectancy ≥ 12 weeks. The treatment consisted of 6 cycles of 3 weeks each. VRL dose was: (Oral-VRL) 60 mg/m2 for cycle 1, 80 mg/m2 for cycles 2–6, and (IV-VRL) 25 mg/m2 for cycle 1 and 30 mg/m2 for cycles 2–6. EPI dose of 75 mg/m2 was given on day 1 in both arms for all cycles. 133 patients were enrolled: 66 in Oral-VRL and 67 in IV-VRL arms. The median age for Oral-VRL and IV-VRL arms was 48.4 and 50.0 years, respectively. Objective response rates were 50.0% (95% CI 37.4–62.6%) for Oral-VRL and 53.7% (95% CI 41.1–66.0%) for IV-VRL. Both treatment arms met the efficacy objective target of at least 31 responses, demonstrating efficacy as first-line treatment for MBC. Similar blood PK profiles, exposures, and VRL clearance were observed between VRL + EPI vs VRL-only modalities for both arms. Oral VRL is comparable to IV VRL and an effective first-line treatment for Chinese patients with MBC. The activity of VRL + EPI combination is unaltered when VRL is given orally at recommended doses.
Time-saving opportunities in knee osteoarthritis: T2 mapping and structural imaging of the knee using a single 5-min MRI scan
Authors: Eijgenraam Susanne M. , Chaudhari Akshay S. , Reijman Max , Bierma-Zeinstra Sita M. A. , Hargreaves Brian A. , Runhaar Jos , Heijboer Frank W. J. , Gold Garry E. , Oei Edwin H. G. 
Published: December 2019

Abstract
Objectives
To assess the discriminative power of a 5-min quantitative double-echo steady-state (qDESS) sequence for simultaneous T2 measurements of cartilage and meniscus, and structural knee osteoarthritis (OA) assessment, in a clinical OA population, using radiographic knee OA as reference standard.

Methods
Fifty-three subjects were included and divided over three groups based on radiographic and clinical knee OA: 20 subjects with no OA (Kellgren-Lawrence grade (KLG) 0), 18 with mild OA (KLG2), and 15 with moderate OA (KLG3). All patients underwent a 5-min qDESS scan. We measured T2 relaxation times in four cartilage and four meniscus regions of interest (ROIs) and performed structural OA evaluation with the MRI Osteoarthritis Knee Score (MOAKS) using qDESS with multiplanar reformatting. Between-group differences in T2 values and MOAKS were calculated using ANOVA. Correlations of the reference standard (i.e., radiographic knee OA) with T2 and MOAKS were assessed with correlation analyses for ordinal variables.

Results
In cartilage, mean T2 values were 36.1 ± SD 4.3, 40.6 ± 5.9, and 47.1 ± 4.3 ms for no, mild, and moderate OA, respectively (p < 0.001). In menisci, mean T2 values were 15 ± 3.6, 17.5 ± 3.8, and 20.6 ± 4.7 ms for no, mild, and moderate OA, respectively (p < 0.001). Statistically significant correlations were found between radiographic OA and T2 and between radiographic OA and MOAKS in all ROIs (p < 0.05).

Conclusion
Quantitative T2 and structural assessment of cartilage and meniscus, using a single 5-min qDESS scan, can distinguish between different grades of radiographic OA, demonstrating the potential of qDESS as an efficient tool for OA imaging.

Key Points
• Quantitative T
2
values of cartilage and meniscus as well as structural assessment of the knee with a single 5-min quantitative double-echo steady-state (qDESS) scan can distinguish between different grades of knee osteoarthritis (OA).
• Quantitative and structural qDESS-based measurements correlate significantly with the reference standard, radiographic degree of OA, for all cartilage and meniscus regions.
• By providing quantitative measurements and diagnostic image quality in one rapid MRI scan, qDESS has great potential for application in large-scale clinical trials in knee OA.
Pre- and intraoperative acoustic and functional assessment of the novel APrevent® VOIS implant during routine medialization thyroplasty
Authors: Ho Guan-Yuh , Leonhard Matthias , Denk-Linnert Doris-Maria , Schneider-Stickler Berit 
Published: December 2019

AbstractPurposePersistent unilateral vocal fold paralysis (UFVP) with glottal insufficiency often requires type I medialization thyroplasty (MT). Previous implants cannot be adjusted postoperatively if necessary. The newly developed APrevent®VOIS implant (VOIS) can provide postoperative re-adjustment to avoid revision MT. The objective of this pilot study is to evaluate the VOIS intraoperatively concerning voice improvement, surgical feasibility and device handling.MethodsDuring routine MT, VOIS was applied short time in eight patients before the regular implantation of the Titanium Vocal Fold Medialization Implant (TVFMI™). In all patients, perceptual voice sound analysis using R(oughness)–B(reathiness)–H(oarseness)-scale, measurement of M(aximum)–P(honation)–T(ime) and glottal closure in videolaryngoscopy were performed before and after implanting VOIS/TVFMI™. Acoustic analyses of voice recordings were performed using freeware praat. Surgical feasibility, operative handling and device fitting of VOIS and TVFMI™ were assessed by the surgeon using V(isual)-A(nalog)-S(cale). Data were statistically analyzed with pairedttest.ResultAll patients showed significant improvement of voice sound parameters after VOIS/TVFMI™ implantation. The mean RBH-scale improved from preoperativeR = 2.1,B = 2.3,H = 2.5 toR = 0.6,B = 0.3,H = 0.8 after VOIS andR = 0.5,B = 0.3,H = 0.8 after TVFMI™ implantation. The mean MPT increased from preoperative 7.9 to 14.6 s after VOIS and 13.8 s after TVFMI™ implantation. VOIS/TVFMI™ achieved complete glottal closure in 7/8 patients. The satisfaction with intraoperative device fitting and device handling of VOIS was as good as that of TVFMI™.ConclusionThe novel APrevent®VOIS implant showed similar intraoperative voice improvement compared to routinely used TVFMI™ without adverse device events and with safe device fitting.
Current practices in children with severe acute asthma across European PICUs: an ESPNIC survey
Authors: Boeschoten Shelley , de Hoog Matthijs , Kneyber Martin , Merkus Peter , Boehmer Annemie , Buysse Corinne 
Published: December 2019

AbstractMost pediatric asthma guidelines offer evidence-based or best practice approaches to the management of asthma exacerbations but struggle with evidence-based approaches for severe acute asthma (SAA). We aimed to investigate current practices in children with SAA admitted to European pediatric intensive care units (PICUs), in particular, adjunct therapies, use of an asthma severity score, and availability of a SAA guideline. We designed a cross-sectional electronic survey across European PICUs. Thirty-seven PICUs from 11 European countries responded. In 8 PICUs (22%), a guideline for SAA management was unavailable. Inhaled beta-agonists and anticholinergics, combined with systemic steroids and IV MgSO4was central in SAA treatment. Seven PICUs (30%) used a loading dose of a short-acting beta-agonist. Eighteen PICUs (49%) used an asthma severity score, with 8 different scores applied. Seventeen PICUs (46%) observed an increasing trend in SAA admissions.Conclusion: Variations in the treatment of children with SAA mainly existed in the use of adjunct therapies and asthma severity scores. Importantly, in 22% of the PICUs, a SAA guideline was unavailable. Standardizing SAA guidelines across PICUs in Europe may improve quality of care. However, the limited number of PICUs represented and the data compilation method are constraining our findings.What is Known:•Recent reports demonstrate increasing numbers of children with SAA requiring PICU admission in several countries across the world.•Most pediatric guidelines offer evidence-based approaches to the management of asthma exacerbations, but struggle with evidence-based approaches for SAA beyond these initial steps.What is New:•A large arsenal of adjunct therapies and 8 different asthma scores were used.•In a large number of PICUs, a written guideline for SAA management is lacking.
Energy and protein requirements for children with CKD stages 2-5 and on dialysis–clinical practice recommendations from the Pediatric Renal Nutrition Taskforce
Authors: Shaw Vanessa , Polderman Nonnie , Renken-Terhaerdt José , Paglialonga Fabio , Oosterveld Michiel , Tuokkola Jetta , Anderson Caroline , Desloovere An , Greenbaum Laurence , Haffner Dieter , Nelms Christina , Qizalbash Leila , Vande Walle Johan , Warady Bradley , Shroff Rukshana , Rees Lesley 
Published: December 2019

AbstractDietary management in pediatric chronic kidney disease (CKD) is an area fraught with uncertainties and wide variations in practice. Even in tertiary pediatric nephrology centers, expert dietetic input is often lacking. The Pediatric Renal Nutrition Taskforce (PRNT), an international team of pediatric renal dietitians and pediatric nephrologists, was established to develop clinical practice recommendations (CPRs) to address these challenges and to serve as a resource for nutritional care. We present CPRs for energy and protein requirements for children with CKD stages 2–5 and those on dialysis (CKD2–5D). We address energy requirements in the context of poor growth, obesity, and different levels of physical activity, together with the additional protein needs to compensate for dialysate losses. We describe how to achieve the dietary prescription for energy and protein using breastmilk, formulas, food, and dietary supplements, which can be incorporated into everyday practice. Statements with a low grade of evidence, or based on opinion, must be considered and adapted for the individual patient by the treating physician and dietitian according to their clinical judgment. Research recommendations have been suggested. The CPRs will be regularly audited and updated by the PRNT.
Long-term all-cause mortality and cardiovascular outcomes in Scottish children after initiation of renal replacement therapy: a national cohort study
Authors: Galiyeva Dinara B. , Jackson Caroline A. , Wild Sarah H. , Burns Susan , Hughes David , Traynor Jamie P. , Metcalfe Wendy , Halbesma Nynke 
Published: December 2019

Abstract
Background
Data on long-term outcomes in children who have received renal replacement therapy (RRT) for end-stage renal disease are limited.

Methods
We studied long-term survival and incidence of fatal and nonfatal cardiovascular disease (CVD) events and determinants of these outcomes in children who initiated RRT between 1961 and 2013 using data from the Scottish Renal Registry (SRR). Linkage to morbidity records was available from 1981.

Results
A total of 477 children of whom 55% were boys, almost 50% had congenital urinary tract disease (CAKUT), 10% received a transplant as the first mode of RRT and almost 60% were over 11 years of age at start of RRT were followed for a median of 17.8 years (interquartile range (IQR) 8.7–26.6 years). Survival was 87.3% (95% confidence interval (CI) 84.0–90.1) at 10 years and 77.6% (95% CI 73.3–81.7) at 20 years. During a median follow-up of 14.96 years (IQR 7.1–22.9), 20.9% of the 381 patients with morbidity data available had an incident of CVD event. Age < 2 years at start of RRT, receiving dialysis rather than a kidney transplant and primary renal disease (PRD) other than CAKUT or glomerulonephritis (GN), were associated with a higher risk of all-cause mortality. Male sex, receiving dialysis rather than a kidney transplant and PRD other than CAKUT or GN, was associated with a higher risk of CVD incidence.

Conclusions
Mortality and CVD incidence among children receiving RRT are high. PRD and RRT modality were associated with increased risk of both all-cause mortality and CVD incidence.
Influence of mild-moderate hypocapnia on intracranial pressure slow waves activity in TBI
Authors: Beqiri Erta , Czosnyka Marek , Lalou Afroditi D. , Zeiler Frederick A. , Fedriga Marta , Steiner Luzius A. , Chieregato Arturo , Smielewski Peter 
Published: December 2019

Abstract
Background
In traumatic brain injury (TBI) the patterns of intracranial pressure (ICP) waveforms may reflect pathological processes that ultimately lead to unfavorable outcome. In particular, ICP slow waves (sw) (0.005–0.05 Hz) magnitude and complexity have been shown to have positive association with favorable outcome. Mild-moderate hypocapnia is currently used for short periods to treat critical elevations in ICP. Our goals were to assess changes in the ICP sw activity occurring following sudden onset of mild-moderate hypocapnia and to examine the relationship between changes in ICP sw activity and other physiological variables during the hypocapnic challenge.

Methods
ICP, arterial blood pressure (ABP), and bilateral middle cerebral artery blood flow velocity (FV), were prospectively collected in 29 adult severe TBI patients requiring ICP monitoring and mechanical ventilation in whom a minute volume ventilation increase (15–20% increase in respiratory minute volume) was performed as part of a clinical CO2-reactivity test. The time series were first treated using FFT filter (pass-band set to 0.005–0.05 Hz). Power spectral density analysis was performed. We calculated the following: mean value, standard deviation, variance and coefficient of variation in the time domain; total power and frequency centroid in the frequency domain; cerebrospinal compliance (Ci) and compensatory reserve index (RAP).

Results
Hypocapnia led to a decrease in power and increase in frequency centroid and entropy of slow waves in ICP and FV (not ABP). In a multiple linear regression model, RAP at the baseline was the strongest predictor for the decrease in the power of ICP slow waves (p < 0.001).

Conclusion
In severe TBI patients, a sudden mild-moderate hypocapnia induces a decrease in mean ICP and FV, but also in slow waves power of both signals. At the same time, it increases their higher frequency content and their morphological complexity. The difference in power of the ICP slow waves between the baseline and the hypocapnia period depends on the baseline cerebrospinal compensatory reserve as measured by RAP.
Soil Microbial Responses to 28 Years of Nutrient Fertilization in a Subarctic Heath
Authors: Hicks Lettice C. , Rousk Kathrin , Rinnan Riikka , Rousk Johannes 
Published: December 2019

AbstractArctic and subarctic soils are typically characterized by low nitrogen (N) availability, suggesting N-limitation of plants and soil microorganisms. Climate warming will stimulate the decomposition of organic matter, resulting in an increase in soil nutrient availability. However, it remains unclear how soil microorganisms in N-limited soils will respond, as the direct effect of inorganic N addition is often shown to inhibit microbial activity, while elevated N availability may have a positive effect on microorganisms indirectly, due to a stimulation of plant productivity. Here we used soils from a long-term fertilization experiment in the Subarctic (28 years at the time of sampling) to investigate the net effects of chronic N-fertilization (100 kg N ha−1 y−1, added together with 26 kg P and 90 kg K ha−1 y−1, as expected secondary limiting nutrients for plants) on microbial growth, soil C and N mineralization, microbial biomass, and community structure. Despite high levels of long-term fertilization, which significantly increased primary production, we observed relatively minor effects on soil microbial activity. Bacterial growth exhibited the most pronounced response to long-term fertilization, with higher rates of growth in fertilized soils, whereas fungal growth remained unaffected. Rates of basal soil C and N mineralization were only marginally higher in fertilized soils, whereas fertilization had no significant effect on microbial biomass or microbial community structure. Overall, these findings suggest that microbial responses to long-term fertilization in these subarctic tundra soils were driven by an increased flow of labile plant-derived C due to stimulated plant productivity, rather than by direct fertilization effects on the microbial community or changes in soil physiochemistry.
MRI compared with low-dose CT scanning in the diagnosis of axial spondyloarthritis
Authors: Ye Lusi , Liu Yuncai , Xiao Qinqin , Dong Ledan , Wen Caiyun , Zhang Zhang , Jin Mengmeng , Brown Matthew A. , Chen Dan 
Published: December 2019

Abstract
Objectives
To compare the performance of conventional radiography, ldCT, and MRI in the diagnosis of sacroiliitis in suspected axial spondyloarthritis (axSpA).

Methods
Patients presenting with > 3 months chronic back pain were assessed by axSpA-experienced rheumatologists and diagnosed as axSpA or not; axSpA patients were then considered nr-axSpA or AS using plain radiography. Non-axSpA patients were recruited as controls, and divided into non-inflammatory and inflammatory groups on the basis of inflammatory back pain and/or CRP/ESR elevation. Clinical variables, pelvic radiography, sacroiliac joint (SIJ) ldCT, and SIJ MRI were obtained.

Results
A total of 121 patients were included and had SIJ radiography and ldCT, of whom 71 additionally had an SIJ MRI. These included 23 non-inflammatory controls, 21 inflammatory controls, 32 nr-axSpA cases, and 45 AS cases. Fourteen of 32 (44%) nr-axSpA patients had positive ldCT scans, 21/24 (88%) had MRI-BMO, and 11/24 (46%) had MRI-structural lesions. ldCT had high specificity with only 1/23 (4%) non-inflammatory controls being positive. MRI-BMO had the highest sensitivity for nr-axSpA, but compared with ldCT lower specificity, with 5/15 (33%) of non-inflammatory controls being positive, and similar sensitivity for AS (20/22 (91%) vs 44/44 for ldCT).

Conclusions
ldCT identifies evidence of radiographic change in a significant proportion of nr-axSpA cases and is highly specific for axSpA. MRI-BMO lesions are more sensitive than either conventional radiography or MRI-structural assessment for axSpA. The relative position of these imaging modalities in screening for axSpA needs to be reconsidered, also taking into account the costs involved.Key Points• ldCT is more sensitive for erosions or sclerosis in axSpA than plain radiography, with 44% of patients with nr-axSpA having evidence of AS-related sacroiliac joint changes on ldCT.• MRI-structural lesions are no more sensitive but are less specific for AS than ldCT.• MRI-BMO is the most sensitive test for nr-axSpA of the modalities tested but is less specific for axSpA than for ldCT.