bluuebunny/crossref_metadata_2025_split huggingface dataset:
Growth patterns and associated risk factors of congenital malformations in twins
Authors: Piro Ettore , Schierz Ingrid Anne Mandy , Serra Gregorio , Puccio Giuseppe , Giuffrè Mario , Corsello Giovanni 
Published: May 2020

AbstractBackgroundThe rate of twinning continues to increase due to the combined effect of a rise in parental age and increased use of assisted reproductive technology. The risk of congenital anomalies in twins is higher than in singletons, but it is less well reported in relation to growth patterns. We focused to the auxological outcome of twin pregnancies when one or both of twins are affected by one or more malformations.MethodsWe conducted a retrospective observational study reviewing the clinical charts of twins admitted in the period between January 2003 and December 2018 at the University Hospital of Palermo. The associations between malformations and anthropometric variables at birth were analyzed by comparison within each twin pair and regarding each variable as ordered difference between the two twins.ResultsWe studied data of 488 neonates (52% females) from 244 pregnancies. The rate of major congenital anomalies was 11%, affecting significantly the smaller twin (p = .00018; Odds ratio 3.21; 95% CI 1.65 6.59). Malformation class distribution was as following: genitourinary (24%), gastrointestinal (20%), cardiovascular (18.5%), musculoskeletal (11%), central nervous system (9%), syndromic (9%), ocular (5.5%) and diaphragmatic hernia (2%). The most predictive value, the Birthweight (BW) difference mean ratio in malformed versus not malformed neonates (− 0.31 vs 0.02;p = .0016) was distributed equally lower than zero in all malformed twins, except for those with congenital heart defects (p = .0000083).Microcephaly (head circumference < 2 standard deviation, SD) was present in 3% of symmetrically smaller twin, and severe microcephaly (< 3 SD) was present in 0.6%. We found that an intertwin BW discordance of 18% or greater identified 50% of neonates with microcephaly, but only 11% of malformed twins.ConclusionsIn case of one twin with a BW < 10th centile, a concomitant intertwin BW discordance ≥18% could reveal an increased risk for microcephaly but not for malformation. Lower values of BW, Ponderal index, Body mass index but above all negative value of BW difference mean ratio are associated with malformations in twin pairs.
Effect of mechanical power on intensive care mortality in ARDS patients
Authors: Coppola Silvia , Caccioppola Alessio , Froio Sara , Formenti Paolo , De Giorgis Valentina , Galanti Valentina , Consonni Dario , Chiumello Davide 
Published: May 2020

Abstract
Background
In ARDS patients, mechanical ventilation should minimize ventilator-induced lung injury. The mechanical power which is the energy per unit time released to the respiratory system according to the applied tidal volume, PEEP, respiratory rate, and flow should reflect the ventilator-induced lung injury. However, similar levels of mechanical power applied in different lung sizes could be associated to different effects. The aim of this study was to assess the role both of the mechanical power and of the transpulmonary mechanical power, normalized to predicted body weight, respiratory system compliance, lung volume, and amount of aerated tissue on intensive care mortality.

Methods
Retrospective analysis of ARDS patients previously enrolled in seven published studies. All patients were sedated, paralyzed, and mechanically ventilated.
After 20 min from a recruitment maneuver, partitioned respiratory mechanics measurements and blood gas analyses were performed with a PEEP of 5 cmH2O while the remaining setting was maintained unchanged from the baseline. A whole lung CT scan at 5 cmH2O of PEEP was performed to estimate the lung gas volume and the amount of well-inflated tissue.
Univariate and multivariable Poisson regression models with robust standard error were used to calculate risk ratios and 95% confidence intervals of ICU mortality.

Results
Two hundred twenty-two ARDS patients were included; 88 (40%) died in ICU. Mechanical power was not different between survivors and non-survivors 14.97 [11.51–18.44] vs. 15.46 [12.33–21.45] J/min and did not affect intensive care mortality. The multivariable robust regression models showed that the mechanical power normalized to well-inflated tissue (RR 2.69 [95% CI 1.10–6.56], p = 0.029) and the mechanical power normalized to respiratory system compliance (RR 1.79 [95% CI 1.16–2.76], p = 0.008) were independently associated with intensive care mortality after adjusting for age, SAPS II, and ARDS severity. Also, transpulmonary mechanical power normalized to respiratory system compliance and to well-inflated tissue significantly increased intensive care mortality (RR 1.74 [1.11–2.70], p = 0.015; RR 3.01 [1.15–7.91], p = 0.025).

Conclusions
In our ARDS population, there is not a causal relationship between the mechanical power itself and mortality, while mechanical power normalized to the compliance or to the amount of well-aerated tissue is independently associated to the intensive care mortality. Further studies are needed to confirm this data.
Towards a fasting-mimicking diet for critically ill patients: the pilot randomized crossover ICU-FM-1 study
Authors: Van Dyck Lisa , Vanhorebeek Ilse , Wilmer Alexander , Schrijvers An , Derese Inge , Mebis Liese , Wouters Pieter J. , Van den Berghe Greet , Gunst Jan , Casaer Michaël P. 
Published: May 2020

Abstract
Background
In two recent randomized controlled trials, withholding parenteral nutrition early in critical illness improved outcome as compared to early up-to-calculated-target nutrition, which may be explained by beneficial effects of fasting. Outside critical care, fasting-mimicking diets were found to maintain fasting-induced benefits while avoiding prolonged starvation. It is unclear whether critically ill patients can develop a fasting response after a short-term nutrient interruption. In this randomized crossover pilot study, we investigated whether 12-h nutrient interruption initiates a metabolic fasting response in prolonged critically ill patients. As a secondary objective, we studied the feasibility of monitoring autophagy in blood samples.

Methods
In a single-center study in 70 prolonged critically ill patients, 12-h up-to-calculated-target feeding was alternated with 12-h fasting on day 8 ± 1 in ICU, in random order. Blood samples were obtained at the start of the study, at the crossover point, and at the end of the 24-h study period. Primary endpoints were a fasting-induced increase in serum bilirubin and decrease in insulin requirements to maintain normoglycemia. Secondary outcomes included serum insulin-like growth factor I (IGF-I), serum urea, plasma beta-hydroxybutyrate (BOH), and mRNA and protein markers of autophagy in whole blood and isolated white blood cells. To obtain a healthy reference, mRNA and protein markers of autophagy were assessed in whole blood and isolated white blood cells of 23 matched healthy subjects in fed and fasted conditions. Data were analyzed using repeated-measures ANOVA, Fisher’s exact test, or Mann–Whitney U test, as appropriate.

Results
A 12-h nutrient interruption significantly increased serum bilirubin and BOH and decreased insulin requirements and serum IGF-I (all p ≤ 0.001). Urea was not affected. BOH was already increased from 4 h fasting onwards. Autophagic markers in blood samples were largely unaffected by fasting in patients and healthy subjects.

Conclusions
A 12-h nutrient interruption initiated a metabolic fasting response in prolonged critically ill patients, which opens perspectives for the development of a fasting-mimicking diet. Blood samples may not be a good readout of autophagy at the tissue level.

Trial registration
ISRCTN, ISRCTN98404761. Registered 3 May 2017.
Comparison of the therapeutic effects of 15 mg and 30 mg initial dosage of prednisolone daily in patients with subacute thyroiditis: protocol for a multicenter, randomized, open, parallel control study
Authors: Xu Shaoyong , Jiang Yuxin , Jia Aihua , Zhang Juan , Gao Bin , Xu Jing , Jing Xiaorui , Jiao Yang , Wei Jia , Xu Wenlei , Chen Ruikun , Gao Ling , Shang Lei 
Published: May 2020

Abstract
Background
Subacute thyroiditis (SAT) is the most common cause of thyroid pain. Several clinical guidelines recommend that patients who fail to respond to full doses of non-steroidal anti-inflammatory drugs (NSAIDs) should be treated instead with oral corticosteroid therapy. However, albeit strong recommendations, the treatment protocol is based on low-quality evidence and high-quality clinical trials are lacking with respect to the optimal initiation dosage and usage of corticosteroid. We aimed to evaluate whether 15 mg/day of prednisolone (PSL) as the initial dosage could provide non-inferiority effectiveness but with lower risk and more safety compared with 30 mg/day of PSL as the initial dosage.

Methods/design
This is a multicenter, open-label, randomized, parallel trial that will be conducted at five academic hospitals in China. A total of 90 adult patients diagnosed with SAT who present moderate to severe pain or fail to respond to full doses of NSAIDs will be randomly assigned with a 1:1 ratio to the low initial PSL dosage group (15 mg daily) and standard initial PSL dosage group (30 mg daily). The primary endpoint is the time period (days) required for PSL treatment (including PSL treatment for recurrence).

Discussion
Our randomized controlled trial will try to determine the optimal protocol in the treatment of SAT by providing high-quality evidence.

Trials registration
Chinese Clinical Trial Register, ChiCTR1900023884. Registered on 15 June 2019.
Combined use of apatinib mesylate and vinorelbine versus vinorelbine alone in recurrent or metastatic triple-negative breast cancer: study protocol for a randomized controlled clinical trial
Authors: Wu Shuo , Zhang Liang , Li Huan , Xu Junnan , Jiang Cui , Sun Tao 
Published: May 2020

Abstract
Background
The emergence of new molecular targeted drugs provides new prospects for the treatment of advanced breast cancer; the future therapeutic trend includes chemotherapy combined with molecular targeted therapy. Apatinib mesylate, a novel, small anti-angiogenic agent, highly selectively inhibits the activity of vascular endothelial growth factor receptor-2 tyrosine kinase. Apatinib mesylate also blocks the signaling of vascular endothelial growth factor binding to its receptor, thereby strongly inhibiting tumor angiogenesis and exerting an anti-tumor effect. However, there have been no reports of a randomized controlled clinical trial of apatinib combined with vinorelbine for the treatment of triple-negative breast cancer (TNBC). We will compare the therapeutic effect of vinorelbine alone or in combination with apatinib mesylate, in patients with recurrent or metastatic TNBC in North China who have received at least two drug treatments, including anthracyclines and taxanes.

Methods/analysis
This study is a triple-blind, randomized, placebo-controlled, parallel-group clinical trial. We plan to include 238 female patients with locally recurrent or metastatic TNBC, admitted to the Liaoning Cancer Hospital & Institute, Northeast China. All enrolled patients will be randomized to oral vinorelbine alone (40 mg, thrice a week (Mondays, Wednesdays, and Fridays) in each 3-week cycle), or in combination with oral apatinib mesylate (500 mg, once daily in each 3-week cycle). Radiographic assessment will be performed every 6 weeks for 36 weeks and every 9 weeks thereafter. The primary outcome is progression-free survival and secondary outcomes include overall survival, disease control rate, objective response rate, and incidence of adverse events at grades 3 and 4, as defined by the National Cancer Institute Common Toxicity Criteria Version 4.0. Outcome measures will be evaluated at baseline (< 2 weeks before starting treatment), every 6 weeks during treatment, and at 4 weeks and every 3 months after treatment discontinuation.

Discussion
Based on the data from this trial, we hope to identify a treatment plan that is suitable for female patients with TNBC, who have been treated with anthracyclines and taxanes, in Northeast China.

Trial registration
ClinicalTrials.gov: NCT03932526. Registered on 30 April 2019.
Evaluation of the efficacy and safety of intravenous remdesivir in adult patients with severe COVID-19: study protocol for a phase 3 randomized, double-blind, placebo-controlled, multicentre trial
Authors: Wang Yeming , Zhou Fei , Zhang Dingyu , Zhao Jianping , Du Ronghui , Hu Yi , Cheng Zhenshun , Gao Ling , Jin Yang , Luo Guangwei , Fu Shouzhi , Lu Qiaofa , Du Guanhua , Wang Ke , Lu Yang , Fan Guohui , Zhang Yi , Liu Ying , Ruan Shunan , Liu Wen , Jaki Thomas , Hayden Frederick G. , Horby Peter W. , Cao Bin , Wang Chen 
Published: May 2020

Abstract
Background
Coronavirus disease 2019 (COVID-19), caused by a novel corinavirus (later named SARS-CoV-2 virus), was fistly reported in Wuhan, Hubei Province, China towards the end of 2019. Large-scale spread within China and internationally led the World Health Organization to declare a Public Health Emergency of International Concern on 30th January 2020. The clinical manifestations of COVID-19 virus infection include asymptomatic infection, mild upper respiratory symptoms, severe viral pneumonia with respiratory failure, and even death. There are no antivirals of proven clinical efficacy in coronavirus infections. Remdesivir (GS-5734), a nucleoside analogue, has inhibitory effects on animal and human highly pathogenic coronaviruses, including MERS-CoV and SARS-CoV, in in vitro and in vivo experiments. It is also inhibitory against the COVID-19 virus in vitro. The aim of this study is to assess the efficacy and safety of remdesivir in adult patients with severe COVID-19.

Methods
The protocol is prepared in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. This is a phase 3, randomized, double-blind, placebo-controlled, multicentre trial. Adults (≥ 18 years) with laboratory-confirmed COVID-19 virus infection, severe pneumonia signs or symptoms, and radiologically confirmed severe pneumonia are randomly assigned in a 2:1 ratio to intravenously administered remdesivir or placebo for 10 days. The primary endpoint is time to clinical improvement (censored at day 28), defined as the time (in days) from randomization of study treatment (remdesivir or placebo) until a decline of two categories on a six-category ordinal scale of clinical status (1 = discharged; 6 = death) or live discharge from hospital. One interim analysis for efficacy and futility will be conducted once half of the total number of events required has been observed.

Discussion
This is the first randomized, placebo-controlled trial in COVID-19. Enrolment began in sites in Wuhan, Hubei Province, China on 6th February 2020.

Trial registration
ClinicalTrials.gov: NCT04257656. Registered on 6 February 2020.
Optimal partner wavelength combination method applied to NIR spectroscopic analysis of human serum globulin
Authors: Han Yun , Zhong Yun , Zhou Huihui , Kuang Xuesong 
Published: May 2020

AbstractHuman serum globulin (GLB), which contains various antibodies in healthy human serum, is of great significance for clinical trials and disease diagnosis. In this study, the GLB in human serum was rapidly analyzed by near infrared (NIR) spectroscopy without chemical reagents. Optimal partner wavelength combination (OPWC) method was employed for selecting discrete information wavelength. For the OPWC, the redundant wavelengths were removed by repeated projection iteration based on binary linear regression, and the result converged to stable number of wavelengths. By the way, the convergence of algorithm was proved theoretically. Moving window partial least squares (MW-PLS) and Monte Carlo uninformative variable elimination PLS (MC-UVE-PLS) methods, which are two well-performed wavelength selection methods, were also performed for comparison. The optimal models were obtained by the three methods, and the corresponding root-mean-square error of cross validation and correlation coefficient of prediction (SECV, RP,CV) were 0.813 g L−1 and 0.978 with OPWC combined with PLS (OPWC-PLS), and 0.804 g L−1 and 0.979 with MW-PLS, and 1.153 g L−1 and 0.948 with MC-UVE-PLS, respectively. The OPWC-PLS and MW-PLS methods achieved almost the same good results. However, the OPWC only contained 28 wavelengths, so it had obvious lower model complexity. Thus it can be seen that the OPWC-PLS has great prediction performance for GLB and its algorithm is convergent and rapid. The results provide important technical support for the rapid detection of serum.
Cartilage-binding antibodies initiate joint inflammation and promote chronic erosive arthritis
Authors: Li Yanpeng , Tong Dongmei , Liang Peibin , Lönnblom Erik , Viljanen Johan , Xu Bingze , Nandakumar Kutty Selva , Holmdahl Rikard 
Published: May 2020

AbstractBackgroundAntibodies binding to cartilage proteins are present in the blood and synovial fluid of early rheumatoid arthritis patients. In order to develop animal models mimicking the human disease, we have characterized the arthritogenic capacity of monoclonal antibodies directed towards different joint proteins in the cartilage.MethodsPurified antibodies specific to unmodified or citrullinated collagen type II (CII), collagen type XI (CXI), and cartilage oligomeric matrix protein (COMP) were produced as culture supernatant, affinity purified, pooled as antibody cocktails (Cab3 and Cab4), and injected intravenously into mice to induce arthritis. An adjuvant (lipopolysaccharide or mannan) was subsequently injected intraperitoneally on either day 5 or day 60 to enhance arthritis. Antibody binding and complement activation on the cartilage surface were analyzed by immunohistochemical methods. Bone erosions and joint deformations were analyzed by histological assessments, enzyme-linked immunosorbent assays, and micro-CT. Luminex was used to detect CII-triple helical epitope-specific antibody responses.ResultsThe new cartilage antibody cocktails induced an earlier and more severe disease than anti-CII antibody cocktail. Many of the mouse strains used developed severe arthritis with 3 antibodies, binding to collagen II, collagen XI, and cartilage oligomeric matrix protein (the Cab3 cocktail). Two new models of arthritis including Cab3-induced LPS-enhanced arthritis (lpsCAIA) and Cab3-induced mannan-enhanced arthritis (mCAIA) were established, causing severe bone erosions and bone loss, as well as epitope spreading of the B cell response. Cab4, with addition of an antibody to citrullinated collagen II, induced arthritis more efficiently in moderately susceptible C57BL/6 J mice.ConclusionsThe new mouse model for RA induced with cartilage antibodies allows studies of chronic development of arthritis and epitope spreading of the autoimmune response and bone erosion.
Effects of dihydrotestosterone on osteoblast activity in curdlan-administered SKG mice and osteoprogenitor cells in patients with ankylosing spondylitis
Authors: Jo Sungsin , Lee Eun-Ju , Nam Bora , Kang Juyeon , Lee Seunghun , Youn Jeehee , Park Ye-Soo , Kim Yong-Gil , Kim Tae-Hwan 
Published: May 2020

Abstract
Background
Ankylosing spondylitis (AS) is characteristically male-predominant, and progressive spinal ankylosis affects male patients more severely; however, the hormonal effects in males with AS are poorly understood.

Methods
In the present study, the regulatory effects of dutasteride, a 5-α reductase inhibitor that blocks the conversion of testosterone to dihydrotestosterone (DHT), were examined in curdlan-administered male SKG mice to determine spinal bone formation, bone metabolism-related markers, and interleukin (IL)-17A cytokine and T cell populations. In addition, the effects of DHT on primary osteoprogenitors from the facet joints of AS patients were assessed based on osteoblast-related parameters. DHT level was measured, and the correlation with modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) was analyzed in AS patients.

Results
In curdlan-administered SKG mice, dutasteride treatment resulted in an increased accumulation of hydroxyapatite in the spine which was positively correlated with serum IL-17A levels. In the analysis of bone metabolism-related molecules, a decrease in sclerostin levels was observed in the sera in the dutasteride group. Continuous exposure to DHT resulted in fewer calcium deposits in AS osteoprogenitors during osteoblast differentiation. DHT-treated AS osteoprogenitors showed decreased osteocalcin and increased DKK1 and SOST1 mRNA expression, supporting the results of the in vivo experiments. Treatment with dutasteride upregulated bone formation in the spine of curdlan-administered SKG mice and DHT treatment downregulated osteoblast differentiation in vitro.

Conclusions
Treatment with dutasteride affected the bone formation in the spine of curdlan-treated SKG mice, and DHT treatment attenuated osteoblast differentiation in vitro. Therefore, contrary to what could be expected if osteoblasts contributed to spinal ankylosis, DHT inhibition might increase rather than decrease the progression of spinal ankylosis despite the higher levels of DHT observed in many AS patients.
Point-of-care ultrasound to complete physical exam and to reach the diagnosis in a young man with syncope
Authors: Rasooli Fatemeh , Zahraie Mehrnoosh Aligholi , Bahreini Maryam 
Published: May 2020

AbstractBackgroundCardiac syncope can result from an atrial myxoma due to outflow obstruction. Myxoma is the most common primary cardiac tumor that may cause sudden death and the nonspecific symptoms may make early diagnosis difficult.Case presentationA 27-year-old man presented to our emergency department after two episodes of syncope and severe fatigue. He had no complaint of fever, weight loss, sweating, chest pain or dyspnea. Vital signs were within normal limits. A loud heart S1 was detected and normal neck veins. Other systemic examinations including neurological assessment were normal. Electrocardiography showed normal sinus rhythm. An obvious variability in heart rate was noticed on cardiac monitor changing by the patient’s position. Point-of-care ultrasonography (PoCUS) showed a large hyperechoic lesion with a well-defined stalk originating from the left atrium (LA). Thus, the patient was transferred to a cardiac surgery center for surgical intervention. Histopathology reported an LA mass compatible with myxoma.ConclusionsEmergency physicians should be familiar with the vague presentations of cardiac tumors to improve patient outcomes. It is beneficial to take advantage of bedside ultrasound for prompt diagnosis and subsequent treatment.