bluuebunny/crossref_metadata_2025_split huggingface dataset:
Automated closed-loopversusstandard manual oxygen administration after major abdominal or thoracic surgery: an international multicentre randomised controlled study
Authors: L'Her Erwan , Jaber Samir , Verzilli Daniel , Jacob Christophe , Huiban Brigitte , Futier Emmanuel , Kerforne Thomas , Pateau Victoire , Bouchard Pierre-Alexandre , Consigny Maëlys , Lellouche François 
Published: August 2020

IntroductionHypoxaemia and hyperoxaemia may occur after surgery, with related complications. This multicentre randomised trial evaluated the impact of automated closed-loop oxygen administration after high-risk abdominal or thoracic surgeries in terms of optimising the oxygen saturation measured by pulse oximetry time within target range.MethodsAfter extubation, patients with an intermediate to high risk of post-operative pulmonary complications were randomised to “standard” or “automated” closed-loop oxygen administration. The primary outcome was the percentage of time within the oxygenation range, during a 3-day frame. The secondary outcomes were the time with hypoxaemia and hyperoxaemia under oxygen.ResultsAmong the 200 patients, time within range was higher in the automated group, both initially (≤3 h; 91.4±13.7%versus40.2±35.1% of time, difference +51.0% (95% CI −42.8–59.2%); p<0.0001) and during the 3-day period (94.0±11.3%versus62.1±23.3% of time, difference +31.9% (95% CI 26.3–37.4%); p<0.0001). Periods of hypoxaemia were reduced in the automated group (≤3 days; 32.6±57.8 min (1.2±1.9%)versus370.5±594.3 min (5.0±11.2%), difference −10.2% (95% CI −13.9–−6.6%); p<0.0001), as well as hyperoxaemia under oxygen (≤3 days; 5.1±10.9 min (4.8±11.2%)versus177.9±277.2 min (27.0±23.8%), difference −22.0% (95% CI −27.6–−16.4%); p<0.0001). Kaplan–Meier analysis depicted a significant difference in terms of hypoxaemia (p=0.01) and severe hypoxaemia (p=0.0003) occurrence between groups in favour of the automated group. 25 patients experienced hypoxaemia for >10% of the entire monitoring time during the 3 days within the standard group, as compared to the automated group (p<0.0001).ConclusionAutomated closed-loop oxygen administration promotes greater time within the oxygenation target, as compared to standard manual administration, thus reducing the occurrence of hypoxaemia and hyperoxaemia.
Should the number of acute exacerbations in the previous year be used to guide treatments in COPD?
Authors: Sadatsafavi Mohsen , McCormack James , Petkau John , Lynd Larry D. , Lee Tae Yoon , Sin Don D. 
Published: August 2020

BackgroundIn contemporary management of chronic obstructive pulmonary disease (COPD), the frequent exacerbator phenotype, based on a 12-month history of acute exacerbation of COPD (AECOPD), is a major determinant of therapeutic recommendations. However, there is considerable debate as to the stability of this phenotype over time.MethodsWe used fundamental principles in time-to-event analysis to demonstrate that variation in the frequent exacerbator phenotype has two major sources: variability in the underlying AECOPD rate and randomness in the occurrence of individual AECOPDs. We re-analysed data from two large cohorts, the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study and the SubPopulations and InteRmediate OutcoMes In COPD Study (SPIROMICS), using a Bayesian model that separated these sources of variability. We then evaluated the stability of the frequent exacerbator phenotype based on these results.ResultsIn both cohorts, the pattern of AECOPDs strongly supported the presence of an individual-specific underlying AECOPD rate which is stable over time (Bayes Factor less than 0.001). Despite this, the observed AECOPD rate can vary markedly year-to-year within individual patients. For those with an underlying rate of 0.8–3.1 events·year−1, the frequent exacerbator classification, based on the observed rate, changes more than 30% of the time over two consecutive years due to chance alone. This value increases to more than 45% for those with an underlying rate of 1.2–2.2 events·year−1.ConclusionsWhile the underlying AECOPD rate is a stable trait, the frequent exacerbator phenotype based on observed AECOPD patterns is unstable, so much so that its suitability for informing treatment decisions should be questioned. Whether evaluating AECOPD history over longer durations or using multivariate prediction models can result in more stable phenotyping needs to be evaluated.
Compound Impedance Control of a Hydraulic Driven Parallel 3UPS/S Manipulator
Authors: Wang Lihang , Cui Shaofei , Ma Chong , Zhang Lijie 
Published: August 2020

AbstractThe hydraulic parallel manipulator combines the high-power density of the hydraulic system and high rigidity of the parallel mechanism with excellent load-carrying capacity. However, the high-precision trajectory tracking control of the hydraulic parallel manipulator is challenged by the coupling dynamics of the parallel mechanism and the high nonlinearities of the hydraulic system. In this study, the trajectory control of a 3-DOF symmetric spherical parallel 3UPS/S manipulator is evaluated. Focusing on the highly coupling and nonlinear system dynamics, a compound impedance control method for a hydraulic driven parallel manipulator is proposed, which combines impedance control with the spatial motion characteristics of a parallel manipulator. The control strategy is divided into the inner and outer loops. The inner loop controls the impedance of the actuator in the joint space, and the outer loop controls the impedance of the entire platform in the task space to compensate the coupling of the actuators and improve the tracking accuracy of the moving platform. Compound impedance control does not require force or pressure sensors and is less dependent on modeling precision. The experimental results show that the compound impedance control effectively improves the tracking accuracy of the moving platform. This research proposes a compound impedance control strategy for a 3-DOF hydraulic parallel manipulator, which has high tracking precision with a simple and cheap system configuration.
Nitrogen soil surface budgets for districts in Germany 1995 to 2017
Authors: Häußermann Uwe , Klement Laura , Breuer Lutz , Ullrich Antje , Wechsung Gabriele , Bach Martin 
Published: August 2020

Abstract
Background
Nitrogen (N) as a key input for crop production has adverse effects on the environment through emissions of reactive nitrogen. Less than 20% of the fertiliser nitrogen applied to agricultural land is actually consumed by humans in meat. Given this situation, nitrogen budgets have been introduced to quantify potential losses into the environment, to raise awareness in nutrient management, and to enforce and monitor nutrient mitigation measures. The surplus of the N soil surface budget has been used for many years for the assessment of potentially water pollution with nitrate from agriculture.

Results
For the 402 districts in Germany, nitrogen soil surface budgets were calculated for the time series 1995 to 2017. For the first time, biogas production in agriculture and the transfer of manure between districts were included in the budget. Averaged for all districts, the recent N supply to the utilised agricultural area (UAA) totals 227 kg N ha−1 UAA (mean 2015–2017), among them 104 kg N ha−1 UAA mineral fertiliser, 59 kg N ha−1 UAA manure, 33 kg N ha−1 UAA digestate, 14 kg N ha−1 UAA from gross atmospheric deposition, 13 kg N ha−1 UAA biological N fixation, and 1 kg N ha−1 UAA from seed and planting material. The withdrawal with harvested products accounts for 149 kg N ha−1 UAA, resulting in an N soil surface budget surplus of 77 kg N ha−1 UAA. The N surpluses per district (mean 2015–2017) vary considerably between 26 and 162 kg N ha−1 UAA and the nitrogen use efficiency of crop production ranges from 0.53 to 0.79 in the districts. The N surplus in Germany as a whole has remained nearly constant since 1995, but the regional distribution has changed significantly. The N surplus has decreased in the arable farming regions, but increased in the districts with high livestock density. Some of this surplus, however, is relocated to other districts through the transfer of manure.

Conclusions
The 23-year time series forms a reliable basis for further interpretation of N soil surface surplus in Germany. Agri-environmental programmes such as the limitation of the N surplus through the Fertiliser Ordinance and the promotion of biogas production have a clear effect on the N surplus in Germany as a whole and its regional distribution.
Dynamic RMST curves for survival analysis in clinical trials
Authors: Liao Jason J. Z. , Liu G. Frank , Wu Wen-Chi 
Published: August 2020

Abstract
Background
The data from immuno-oncology (IO) therapy trials often show delayed effects, cure rate, crossing hazards, or some mixture of these phenomena. Thus, the proportional hazards (PH) assumption is often violated such that the commonly used log-rank test can be very underpowered. In these trials, the conventional hazard ratio for describing the treatment effect may not be a good estimand due to the lack of an easily understandable interpretation. To overcome this challenge, restricted mean survival time (RMST) has been strongly recommended for survival analysis in clinical literature due to its independence of the PH assumption as well as a more clinically meaningful interpretation. The RMST also aligns well with the estimand associated with the analysis from the recommendation in ICH E-9 (R1), and the test/estimation coherency. Currently, the Kaplan Meier (KM) curve is commonly applied to RMST related analyses. Due to some drawbacks of the KM approach such as the limitation in extrapolating to time points beyond the follow-up time, and the large variance at time points with small numbers of events, the RMST may be hindered.

Methods
The dynamic RMST curve using a mixture model is proposed in this paper to fully enhance the RMST method for survival analysis in clinical trials. It is constructed that the RMST difference or ratio is computed over a range of values to the restriction time τ which traces out an evolving treatment effect profile over time.

Results
This new dynamic RMST curve overcomes the drawbacks from the KM approach. The good performance of this proposal is illustrated through three real examples.

Conclusions
The RMST provides a clinically meaningful and easily interpretable measure for survival clinical trials. The proposed dynamic RMST approach provides a useful tool for assessing treatment effect over different time frames for survival clinical trials. This dynamic RMST curve also allows ones for checking whether the follow-up time for a study is long enough to demonstrate a treatment difference. The prediction feature of the dynamic RMST analysis may be used for determining an appropriate time point for an interim analysis, and the data monitoring committee (DMC) can use this evaluation tool for study recommendation.
The quality of primary care in community health centers: comparison among urban, suburban and rural users in Shanghai, China
Authors: Shi Jianwei , Jin Hua , Shi Leiyu , Chen Chen , Ge Xuhua , Lu Yuan , Zhang Hanzhi , Wang Zhaoxin , Yu Dehua 
Published: August 2020

Abstract
Objective
Following World Health Organization’s initiatives to advance primary care, China put forth forceful policies including the Personal Family Doctor Contract to ensure that every family sign up with a qualified doctor in a community health center (CHC) ever since its 2009 New Health Reform. We used the Johns Hopkins-designed Primary Care Assessment Tool (PCAT) to assess primary care quality experienced by the contracted residents and compare this across different socioeconomic regions.

Methods
Using a multistage sampling method, four CHCs each were randomly selected from urban, suburban and rural districts of Shanghai, a metropolitan with 24 million residents. ANOVA and Multivariate analyses were used to assess the association between location of CHC and the quality of primary care experience.

Findings
A total of 2404 CHC users completed our survey. Except for the domain of coordination (information systems), users from suburban CHCs reported best primary care experiences in all other domains, followed by users of rural CHCs. After controlling for covariates, suburban CHC users were more likely to report higher total PCAT scores (ß = 1.57, P <  0.001) compared with those from urban CHCs.

Conclusion
That contracted residents from suburban CHCs reporting better primary care experience than those from urban CHCs demonstrates the unique value of CHCs in relatively medical-underserved areas. In particular, urban CHCs could further strengthen first contact (utilization), first contact (accessibility), coordination (referral system), comprehensiveness (available), and community orientation aspects of primary care performance. However, all CHCs could improve coordination (information system).
Highly proliferative anal neuroendocrine carcinoma: molecular and clinical features of a rare, recurrent case in complete remission
Authors: Juhlin Carl Christofer , Falhammar Henrik , Kjellman Magnus , Åhlén Jan , Welin Staffan , Calissendorff Jan 
Published: August 2020

Abstract
Background
Poorly differentiated anal neuroendocrine carcinomas (ANECs) are rare lesions with poor prognosis, and the molecular etiology is only partially understood.

Case presentation
At our institution, we have treated and followed a patient with such a rare ANEC. He had primarily surgery followed by three rounds of repeated surgery for loco-regional recurrences. He also received three different combinations of chemotherapy and external beam radiation. At last follow-up 13 years since the primary diagnosis, the patient had been in complete remission for nine years.
The patient’s medical files were re-examined, including laboratory, radiology and clinical examinations. Histopathology was re-assessed, and expanded immunohistochemistry was performed from tissue specimens from the four surgical procedures. In addition, the molecular genetic status was evaluated through next-generation sequencing.
The initial tumor was consistent with a 59 mm small cell neuroendocrine cancer with a Ki-67 index of 80%. Regional lymph node metastases were evident, and immunohistochemistry supported a neuroendocrine origin. A PCR screening detected human papilloma virus type 45 DNA (high-risk subtype), and focused next-generation sequencing found a missense mutation in the Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha (PIK3CA) gene. In tissues representing subsequent recurrences, the Chromogranin A expression was lost, and the Ki-67 index increased to 90%.

Conclusions
For the first time, we report the detection of HPV45 in a case of ANEC. To our belief, PIK3CA mutations have also not been previously demonstrated in this tumor entity. In highly malignant ANECs, cure can in rare cases be achieved. Although speculative, expression of HPV45 and/or the PIK3CA mutation may have contributed to the favorable outcome.
A cohort study investigating the relationship between patient reported outcome measures and pre-operative frailty in patients with operable, non-palliative colorectal cancer
Authors: Knight J. , Ayyash K. , Colling K. , Dhesi J. , Ewan V. , Danjoux G. , Kothmann E. , Mill A. , Taylor S. , Yates D. , Ayyash Reema 
Published: August 2020

Abstract
Background
Frailty refers to the reduction in homeostatic reserve resulting from an accumulation of physiological deficits over a lifetime. Frailty is common in older patients undergoing surgery and is an independent risk factor for post-operative mortality, morbidity and increased length of hospital stay. In frail individuals, stressors, such as surgery, can precipitate an acute deterioration in health, manifesting as delirium, falls, reduction in mobility or continence, rendering these individuals at an increased risk of adverse perioperative outcomes. However, little is known about how frailty affects the patient experience, functional ability and quality of life (QoL) after surgery. In addition, the distribution of frailty in this population is unknown.

Methods
We will conduct a multi-centre observational trial to investigate the relationship between patient reported outcome measures and preoperative frailty. We aim to recruit approximately two-hundred patients with operable, potentially curative colorectal cancer. Eligible patients will be identified at three hospital sites. QoL and functional ability (measured using EORTC QLQ-C30 and WHO-DAS 2.0 respectively) will be recorded at the pre-operative assessment clinic, and at 6 and 12 weeks postoperatively. Frailty scores including the Edmonton Frail Scale (EFS) and Rockwood clinical frailty scale (CFS) will be calculated both preoperatively, and at 12 weeks post-operatively. Secondary outcome measures including post-operative morbidity and mortality will be measured using Clavien Dindo classification and 90-day mortality.

Discussion
This observational feasibility study seeks to define the prevalence of frailty in older (> 65 years) colorectal cancer patients and understand how frailty impacts on patient reported outcome measures. This information will help to inform larger studies relating to treatment decision algorithms and promote shared decision making in this population.
Increased physiological dead space in mechanically ventilated COVID-19 patients recovering from severe acute respiratory distress syndrome: a case report
Authors: Xia Jingen , Feng Yingying , Li Min , Yu Xin , Zhang Yi , Duan Jun , Zhan Qingyuan 
Published: August 2020

Abstract
Background
An ongoing outbreak of coronavirus disease 2019 (COVID-19) is spreading globally. Recently, several articles have mentioned that the early acute respiratory distress syndrome (ARDS) caused by COVID-19 significantly differ from those of ARDS due to other causes. Actually, we newly observed that some mechanically ventilated COVID-19 patients recovering from severe ARDS (more than 14 days after invasive ventilation) often experienced evidently gradual increases in CO2 retention and minute ventilation. However, the underlying mechanics remain unclear.

Case presentation
To explain these pathophysiological features and discuss the ventilatory strategy during the late phase of severe ARDS in COVID-19 patients, we first used a metabolic module on a General Electric R860 ventilator (Engstrom Carestation; GE Healthcare, USA) to monitor parameters related to gas metabolism, lung mechanics and physiological dead space in two COVID-19 patients. We found that remarkably decreased ventilatory efficiency (e.g., the ratio of dead space to tidal volume 70–80%, arterial to end-tidal CO2 difference 18–23 mmHg and ventilatory ratio 3–4) and hypermetabolism (oxygen consumption 300–400 ml/min, CO2 elimination 200–300 ml/min) may explain why these patients experienced more severe respiratory distress and CO2 retention in the late phase of ARDS caused by COVID-19.

Conclusion
During the recovery period of ARDS among mechanically-ventilated COVID-19 patients, attention should be paid to the monitoring of physiological dead space and metabolism. Tidal volume (8–9 ml/kg) could be increased appropriately under the limited plateau pressure; however, barotrauma should still be kept in mind.
Differential diagnosis between hepatic alveolar echinococcosis and intrahepatic cholangiocarcinoma with conventional ultrasound and contrast-enhanced ultrasound
Authors: Wa Zeng-Cheng , Du Ting , Li Xian-Feng , Xu Hui-Qing , Suo-Ang Qiu-Cuo , Chen Li-Da , Hu Hang-Tong , Wang Wei , Lu Ming-De 
Published: August 2020

Abstract
Background
Misclassifications of hepatic alveolar echinococcosis (HAE) as intrahepatic cholangiocarcinoma (ICC) may lead to inappropriate treatment strategies. The aim of this study was to explore the differential diagnosis with conventional ultrasound and contrast-enhanced ultrasound (CEUS).

Methods
Sixty HAE lesions with 60 propensity score-matched ICC lesions were retrospectively collected. The 120 lesions were randomly divided into a training set (n = 80) and a testing set (n = 40). In the training set, the most useful independent conventional ultrasound and CEUS features was selected for differentiating between HAE and ICC. Then, a simplified US scoring system for diagnosing HAE was constructed based on selected features with weighted coefficients. The constructed US score for HAE was validated in both the training set and the testing set, and diagnostic performance was evaluated.

Results
Compared with ICC lesions, HAE lesions were mostly located in the right lobe and had mixed echogenicity, a pseudocystic appearance and foci calcifications on conventional ultrasound. On CEUS, HAE lesions showed more regular rim-like enhancement than ICC lesions and had late washout with a long enhancement duration. The simplified US score consisted of echogenicity, pseudocystic/calcification, bile duct dilatation, enhancement pattern, enhancement duration, and marked washout. In the testing set, the sensitivity, specificity, LR+, LR- and the area under the ROC curve for the score to differentiate HAE from ICC were 80.0, 81.3%, 4.27, 0.25 and 0.905, respectively.

Conclusions
The US score based on typical features from both conventional ultrasound and CEUS could accurately differentiate HAE from ICC.
Molecular abnormalities in autopsied brain tissue from the inferior horn of the lateral ventricles of nonagenarians and Alzheimer disease patients
Authors: Pearson Andrew , Ajoy Rosa , Crynen Gogce , Reed Jon M. , Algamal Moustafa , Mullan Michael , Purohit Dushyant , Crawford Fiona , Ojo Joseph O. 
Published: August 2020

Abstract
Background
The ventricular system plays a vital role in blood-cerebrospinal fluid (CSF) exchange and interstitial fluid-CSF drainage pathways. CSF is formed in the specialized secretory tissue called the choroid plexus, which consists of epithelial cells, fenestrated capillaries and the highly vascularized stroma. Very little is currently known about the role played by the ventricles and the choroid plexus tissue in aging and Alzheimer’s disease (AD).

Methods
In this study, we used our state-of-the-art proteomic platform, a liquid chromatography/mass spectrometry (LC-MS/MS) approach coupled with Tandem Mass Tag isobaric labeling to conduct a detailed unbiased proteomic analyses of autopsied tissue isolated from the walls of the inferior horn of the lateral ventricles in AD (77.2 ± 0.6 yrs), age-matched controls (77.0 ± 0.5 yrs), and nonagenarian cases (93.2 ± 1.1 yrs).

Results
Ingenuity pathway analyses identified phagosome maturation, impaired tight-junction signaling, and glucose/mannose metabolism as top significantly regulated pathways in controls vs nonagenarians. In matched-control vs AD cases we identified alterations in mitochondrial bioenergetics, oxidative stress, remodeling of epithelia adherens junction, macrophage recruitment and phagocytosis, and cytoskeletal dynamics. Nonagenarian vs AD cases demonstrated augmentation of oxidative stress, changes in gluconeogenesis-glycolysis pathways, and cellular effects of choroidal smooth muscle cell vasodilation. Amyloid plaque score uniquely correlated with remodeling of epithelial adherens junctions, Fc γ-receptor mediated phagocytosis, and alterations in RhoA signaling. Braak staging was uniquely correlated with altered iron homeostasis, superoxide radical degradation and phagosome maturation.

Conclusions
These changes provide novel insights to explain the compromise to the physiological properties and function of the ventricles/choroid plexus system in nonagenarian aging and AD pathogenesis. The pathways identified could provide new targets for therapeutic strategies to mitigate the divergent path towards AD.