bluuebunny/crossref_metadata_2025 huggingface dataset:
Classifying signals from a wearable accelerometer device to measure respiratory rate
Authors: Drummond Gordon B. , Fischer Darius , Lees Margaret , Bates Andrew , Mann Janek , Arvind D.K.
Published: March 2021

Background

Automatic measurement of respiratory rate in general hospital patients is difficult. Patient movement degrades the signal and variation of the breathing cycle means that accurate observation for ≥60 s is needed for adequate precision.

Methods

We studied acutely ill patients recently admitted to a teaching hospital. Breath duration was measured from a triaxial accelerometer attached to the chest wall and compared with a signal from a nasal cannula. We randomly divided the patient records into a training (n=54) and a test set (n=7). We used machine learning to train a neural network to select reliable signals, automatically identifying signal features associated with accurate measurement of respiratory rate. We used the test records to assess the accuracy of the device, indicated by the median absolute difference between respiratory rates, provided by the accelerometer and by the nasal cannula.

Results

In the test set of patients, machine classification of the respiratory signal reduced the median absolute difference (interquartile range) from 1.25 (0.56–2.18) to 0.48 (0.30–0.78) breaths per min. 50% of the recording periods were rejected as unreliable and in one patient, only 10% of the signal time was classified as reliable. However, even only 10% of observation time would allow accurate measurement for 6 min in an hour of recording, giving greater reliability than nurse charting, which is based on much less observation time.

Conclusion

Signals from a body-mounted accelerometer yield accurate measures of respiratory rate, which could improve automatic illness scoring in adult hospital patients.
Bioanalytical screening of low levels of dioxins and dioxin-like PCBs in pig meat (pork) for checking compliance with EU maximum and action levels using highly sensitive “third generation” recombinant H4L7.5c2 rat hepatoma cells
Authors: Haedrich Johannes , Stumpf Claudia , Denison Michael S.
Published: March 2021

Background

Low maximum and action levels set by the European Union for polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (DL-PCBs) in pig meat (pork) have led to a demand for reliable and cost-effective bioanalytical screening methods implemented upstream of gas chromatography/high-resolution mass spectrometry confirmatory technology, that can detect low levels of contamination in EU-regulated foods with quick turn-around times.

Results

Based on the Chemically Activated LUciferase gene eXpression (CALUX) bioassay, extraction and clean-up steps were optimized for recovery and reproducibility within working ranges significantly lower than in current bioassays. A highly sensitive “3rd generation” recombinant rat hepatoma cell line (H4L7.5c2) containing 20 dioxin responsive elements was exposed to pork sample extracts, and their PCDD/Fs and DL-PCBs levels were evaluated by measuring luciferase activity. The method was validated according to the provisions of Commission Regulation (EU) 2017/644 of 5 April 2017 with spiking experiments performed selectively for PCDD/Fs and DL-PCBs and individual calibration for PCDD/Fs, DL-PCBs and the calculated sum of PCDD/Fs and DL-PCBs. The resulting performance parameters met all legal specifications as confirmed by re-calibration using authentic samples. Cut-off concentrations for assessing compliance with low maximum levels and action levels set for PCDD/Fs and DL-PCBs within a range of 0.50–1.25 pg WHO-TEQ/g fat were derived, ensuring low rates of false-compliant results (ß-error < 1%) and keeping the rate of false-noncompliant results well under control (α-error < 12%).

Conclusions

We present a fast and efficient bioanalytical routine method validated according to the European Union’s legal requirements on the basis of authentic samples, allowing the analyst to reliably identify pork samples and any other EU-regulated foods of animal origin suspected to be noncompliant with a high level of performance and turn-around times of 52 h. This was facilitated in particular by a quick and efficient extraction step followed by selective clean-up, use of a highly sensitive “3rd generation” H4L7.5c2 recombinant rat hepatoma cell CALUX bioassay, and optimized assay performance with improved calibrator precision and reduced lack-of-fit errors. New restrictions are proposed for the calibrator bias and the unspecific background contribution to reportable results. The procedure can utilize comparably small sample amounts and allows an annual throughput of 840–1000 samples per lab technician. The described bioanalytical method contributes to the European Commission's objective of generating accurate and reproducible analytical results according to Commission Regulation (EU) 2017/644 across the European Union.
Chloroplast genome sequence of Chongming lima bean (Phaseolus lunatus L.) and comparative analyses with other legume chloroplast genomes
Authors: Tian Shoubo , Lu Panling , Zhang Zhaohui , Wu Jian Qiang , Zhang Hui , Shen Haibin
Published: March 2021

Background

Lima bean (Phaseolus lunatus L.) is a member of subfamily Phaseolinae belonging to the family Leguminosae and an important source of plant proteins for the human diet. As we all know, lima beans have important economic value and great diversity. However, our knowledge of the chloroplast genome level of lima beans is limited.

Results

The chloroplast genome of lima bean was obtained by Illumina sequencing technology for the first time. The Cp genome with a length of 150,902 bp, including a pair of inverted repeats (IRA and IRB 26543 bp each), a large single-copy (LSC 80218 bp) and a small single-copy region (SSC 17598 bp). In total, 124 unique genes including 82 protein-coding genes, 34 tRNA genes, and 8 rRNA genes were identified in the P. lunatus Cp genome. A total of 61 long repeats and 290 SSRs were detected in the lima bean Cp genome. It has a typical 50 kb inversion of the Leguminosae family and an 70 kb inversion to subtribe Phaseolinae. rpl16, accD, petB, rsp16, clpP, ndhA, ndhF and ycf1 genes in coding regions was found significant variation, the intergenic regions of trnk-rbcL, rbcL-atpB, ndhJ-rps4, psbD-rpoB, atpI-atpA, atpA-accD, accD-psbJ, psbE-psbB, rsp11-rsp19, ndhF-ccsA was found in a high degree of divergence. A phylogenetic analysis showed that P. lunatus appears to be more closely related to P. vulgaris, V.unguiculata and V. radiata.

Conclusions

The characteristics of the lima bean Cp genome was identified for the first time, these results will provide useful insights for species identification, evolutionary studies and molecular biology research.
Risk definition and outcomes with the application of the PEGASUS-TIMI 54 trial inclusion criteria to a “real world” STEMI population: results from the Italian “CARDIO-STEMI SANREMO” registry
Authors: Sanchez Federico , Boasi Valentina , Vercellino Matteo , Tacchi Chiara , Cannarile Pierpaolo , Pingelli Nicoletta , Perri Dino , Gomez Laura , Cattunar Stefano , Mascelli Giovanni
Published: March 2021

Background

The PEGASUS-TIMI 54 trial inclusion criteria effectively identified high-risk patients with recent myocardial infarction (MI) who would benefit from continuing dual antiplatelet therapy (DAPT) with ticagrelor for more than 12 months. It is unknown how many real-world patients meet these criteria during the acute phase of ST-elevation MI (STEMI), or the extent to which these criteria predict a patient's risk and prognosis. Study objectives were: (1) determine the proportion of PEGASUS-TIMI 54-like patients (PG-l) in a real-world cohort of patients hospitalized with STEMI and to assess their ischemic and hemorrhagic risk; (2) examine their ischemic and hemorrhagic in-hospital events (major adverse cardiovascular and cerebrovascular events [MACCE] and clinically relevant bleeding); (3) evaluate their long-term outcomes and the impact on the long-term prognosis of the type of DAPT prescribed at discharge.

Methods

This observational study was conducted in 1086 patients admitted to hospital with a diagnosis of STEMI between February 2011 and March 2018 and enrolled in the CARDIO-STEMI Sanremo registry. Patients’ demographic and clinical characteristics, procedural variables, and individual ischemic and hemorrhagic risk scores were assessed in-hospital. Four-year survival was also analyzed.

Results

The proportion of PG-I patients was 69.2%. Compared with non-PG-l patients, PG-l patients were older, had more multivessel disease and comorbidities, and experienced more frequent MACCE (8.3% vs. 3.6%, p = 0.005) and clinically significant bleeding events (6.7% vs. 2.7%, p = 0.008), a higher rate of in-hospital death (6.5% vs. 1.5%, p < 0.001), and higher follow-up mortality rate (14.8% vs. 7.7%; p = 0.002). Four-year survival was significantly lower in the PG-l group (83.9% vs. 91.8%; Log-rank = 0.001) and was related to the cumulative number of concurrent risk factors. In the unadjusted analysis, survival was greater in patients discharged on ticagrelor than on another P2Y12 inhibitor (90.2% vs. 76.7%, Log-rank = 0.001), and the difference was particularly evident in PG-l patients.

Conclusions

The risk of MACCE for PG-l patients increased with the number of concurrent PEGASUS-TIMI 54 risk features. Treatment with ticagrelor on discharge was associated with improved survival rates during 4 years of follow-up.
Positive and negative ageing perceptions account for health differences between older immigrant and native populations in the Netherlands
Authors: Nieboer Anna P. , van den Broek Thijs , Cramm Jane M.
Published: March 2021

Background

This study assessed the extent to which persistent differences in self-rated health (SRH) between older immigrants and natives are attributable to negative and positive ageing perceptions.

Methods

The study was conducted with three population groups in Rotterdam, the Netherlands: native Dutch people aged ≥70 years (n = 1150), Turkish immigrants aged ≥65 years (n = 680) and Moroccan immigrants aged ≥65 years (n = 292). To assess participants’ internal ageing representations, we used the short Aging Perceptions Questionnaire, which distinguishes negative (consequences, chronic and cyclical timeline awareness, and emotional representations) and positive (positive consequences, positive and negative control) dimensions and has been validated in native and immigrant populations. We analysed differences in ageing perceptions between immigrants and natives and the associations of ageing perceptions with SRH. We used Karlson–Holm–Breen decomposition to assess ageing perceptions’ mediation of the relationship between migration background and SRH.

Results

Older immigrants had stronger negative and weaker positive ageing perceptions (excepting the positive consequences of ageing) than did Dutch natives. Ageing perceptions mediated the relationship between migration background and SRH. SRH differences between Turkish immigrants and native Dutch older persons were explained mainly by differences in negative consequences and cyclical timeline awareness. SRH differences between Moroccan immigrants and native Dutch older persons were attributable mainly to differences in negative consequences and positive control.

Conclusions

Differences in positive and negative ageing perceptions between older immigrants and natives in the Netherlands largely explained SRH differences between these population groups.
Silencing of FTX suppresses pancreatic cancer cell proliferation and invasion by upregulating miR-513b-5p
Authors: Li Shan , Zhang Qian , Liu Wen , Zhao Chunbo
Published: March 2021

Background

Abnormal expression of long non-coding RNA (lncRNA) FTX (five prime to Xist), which is involved in X chromosome inactivation, has been reported in various tumors. However, the effect of FTX on the development of pancreatic cancer (PC) has not been elucidated. The purpose of this study was to explore the possible molecular mechanism of FTX in PC.

Methods

Quantitative real-time PCR (qRT-PCR) was used to measure the expression levels of FTX and miR-513b-5p in PC cell lines. Proliferation and apoptosis of PC cells were determined by CCK-8, Edu assay, and flow cytometry. Invasion and migration ability of PC cells were detected by Transwell assay and scratch test. Bioinformatics analysis, luciferase reporter gene assay, and RNA immunoprecipitation (RIP) assay were used to verify the direct binding between FTX and miR-513b-5p. The xenotransplantation mouse model was established to explore the effect of FTX and miR-513b-5p on the PC tumor growth in vivo.

Results

The expression levels of FTX were increased in PC cell lines, and silencing of FTX remarkably suppressed the invasion ability and cell viability. Besides, FTX could bind to miR-513b-5p as a competitive endogenous RNA, thus promoting the invasion and proliferation ability of PC cells. Moreover, knockdown of FTX inhibited the tumor growth and increased the expression levels of miR-513b-5p and apoptosis-related proteins in vivo.

Conclusions

FTX could directly combine with miR-513b-5p as a competitive endogenous RNA, thus promoting the occurrence and development of PC in vitro and in vivo.
Genome-wide association study identifies new loci associated with risk of HBV infection and disease progression
Authors:   the HBVstudy consortium, Zeng Zheng , Liu Hankui , Xu Huifang , Lu Haiying , Yu Yanyan , Xu Xiaoyuan , Yu Min , Zhang Tao , Tian Xiulan , Xi Hongli , Guan Liping , Zhang Jianguo , O’Brien Stephen J.
Published: March 2021

Background

Recent studies have identified susceptibility genes of HBV clearance, chronic hepatitis B, liver cirrhosis, hepatocellular carcinoma, and showed the host genetic factors play an important role in these HBV-related outcomes.

Methods

Collected samples from different outcomes of HBV infection and performed genotyping by Affymetrix 500 k SNP Array. GCTA tool, PLINK, and Bonferroni method were applied for analysis of genotyping and disease progression. ANOVA was used to evaluate the significance of the association between biomarkers and genotypes in healthy controls. PoMo, FST, Vcftools and Rehh package were used for building the racial tree and population analysis. FST statistics accesses 0.15 was used as a threshold to detect the signature of selection.

Results

There are 1031 participants passed quality control from 1104 participants, including 275 HBV clearance, 92 asymptomatic persistence infection (ASPI), 93 chronic hepatitis B (CHB), 188 HBV-related decompensated cirrhosis (DC), 214 HBV-related hepatocellular carcinoma (HCC) and 169 healthy controls (HC). In the case–control study, one novel locus significantly associated with CHB (SNP: rs1264473, Gene: GRHL2, P = 1.57 × 10−6) and HCC (SNP: rs2833856, Gene: EVA1C, P = 1.62 × 10−6; SNP: rs4661093, Gene: ETV3, P = 2.26 × 10−6). In the trend study across progressive stages post HBV infection, one novel locus (SNP: rs1537862, Gene: LACE1, P = 1.85 × 10−6), and three MHC loci (HLA-DRB1, HLA-DPB1, HLA-DPA2) showed significant increased progressive risk from ASPI to CHB. Underlying the evolutionary study of HBV-related genes in public database, the derived allele of two HBV clearance related loci, rs3077 and rs9277542, are under strong selection in European population.

Conclusions

In this study, we identified several novel candidate genes associated with individual HBV infectious outcomes, progressive stages, and liver enzymes. Two SNPs that show selective significance (HLA-DPA1, HLA-DPB1) in non-East Asian (European, American, South Asian) versus East Asian, indicating that host genetic factors contribute to the ethnic disparities of susceptibility of HBV infection. Taken together, these findings provided a new insight into the role of host genetic factors in HBV related outcomes and progression.
Factors supporting retention of health and wellbeing staff in Aboriginal health services: a strength-based case study
Authors: Deroy Sara , Schütze Heike
Published: March 2021

Background

Aboriginal Community Controlled Health Services are fundamental to improving the health and welfare of Aboriginal peoples. A key element that contributes to the effectiveness of these services are Aboriginal health and wellbeing staff. However, Aboriginal health and wellbeing staff often suffer high rates of stress and burnout. Current literature focuses on proposed strategies to increase staff retention in Aboriginal Health Services, yet, there is limited information available showcasing what has actually worked.

Method

This was an intrinsic strengths-based case study of one regional Aboriginal Community Controlled Health Service. Semi-structured research yarning interviews were conducted with past and present staff employed in health and wellbeing roles to highlight the factors that staff felt contributed to their retention.

Results

Ten interviews were conducted between February and April 2018. Six key themes emerged: social accountability, teamwork and collaboration, cultural safety, supervision, professional advancement, and recognition. We add to the literature by identifying the importance of bi-directional communication, and showing that social accountability, teamwork and collaboration, cultural safety, supervision, professional advancement, and recognition continue to be important factors that contribute to health and wellbeing staff retention in Aboriginal Health Services.

Conclusion

This exemplar Aboriginal Health Service may provide insights into future strategies to improve staff retention in other health services.
Systematic review of the correlates of outdoor play and time among children aged 3-12 years
Authors: Lee Eun-Young , Bains Ajaypal , Hunter Stephen , Ament Alyssa , Brazo-Sayavera Javier , Carson Valerie , Hakimi Shawn , Huang Wendy Y. , Janssen Ian , Lee Mikyung , Lim Heejun , Silva Diego Augusto Santos , Tremblay Mark S.
Published: March 2021

Background

Due to the myriad of benefits of children’s outdoor play and time, there is increasing concern over its decline. This systematic review synthesized evidence on the correlates of outdoor play and outdoor time among children aged 3-12 years.

Methods

A total of 12 electronic databases in five different languages (Chinese, English, Korean, Spanish, Portuguese) were searched between October 28, 2019 and July 27, 2020. Covidence software was used for screening and Microsoft Excel with a predesigned coding form was used for data extraction. Evidence was synthesized and correlates were categorized using the socioecological model framework.

Results

Based on 107 studies representing 188,498 participants and 422 childcare centers from 29 countries, 85 studies examined potential correlates of outdoor play while 23 studies examined that of outdoor time (one examined both). The duration of outdoor play and outdoor time ranged between 60 and 165 min/d and 42-240 min/d, respectively. Out of 287 (outdoor play) and 61 (outdoor time) potential correlates examined, 111 correlates for outdoor play and 33 correlates for outdoor time were identified as significant correlates. Thirty-three variables were identified as key/common correlates of outdoor play/time, including eight correlates at the individual level (e.g., sex/gender, race/ethnicity, physical activity), 10 correlates at the parental level (e.g., parental attitude/support/behavior, parenting practice), nine at the microsystem level (e.g., proximal home/social environment such as residence type, peer influence), three at the macrosystem/community level (e.g., availability of space children can play), and three at the physical ecology/pressure for macrosystem change level (e.g., seasonality, rurality). No key correlates were found at the institutional level.

Conclusions

Individual, parental, and proximal physical (home) and social environments appear to play a role in children’s outdoor play and time. Ecological factors (i.e., seasonality, rurality) also appear to be related to outdoor play/time. Evidence was either inconsistent or lacking at institutional and macrosystem/community levels. Standardizing terminology and measures of outdoor play/time is warranted. Future work should investigate the interactions and processes of multiple variables across different levels of socioecological modelling to better understand the mechanisms through which outdoor play/time opportunities can be optimized for children while paying special attention to varying conditions in which children are born, live, and play.
Stable, simultaneous and proportional 4-DoF prosthetic hand control via synergy-inspired linear interpolation: a case series
Authors: Lukyanenko Platon , Dewald Hendrik Adriaan , Lambrecht Joris , Kirsch Robert F. , Tyler Dustin J. , Williams Matthew R.
Published: March 2021

Background

Current commercial prosthetic hand controllers limit patients’ ability to fully engage high Degree-of-Freedom (DoF) prosthetic hands. Available feedforward controllers rely on large training data sets for controller setup and a need for recalibration upon prosthesis donning. Recently, an intuitive, proportional, simultaneous, regression-based 3-DoF controller remained stable for several months without retraining by combining chronically implanted electromyography (ciEMG) electrodes with a K-Nearest-Neighbor (KNN) mapping technique. The training dataset requirements for simultaneous KNN controllers increase exponentially with DoF, limiting the realistic development of KNN controllers in more than three DoF. We hypothesize that a controller combining linear interpolation, the muscle synergy framework, and a sufficient number of ciEMG channels (at least two per DoF), can allow stable, high-DoF control.

Methods

Two trans-radial amputee subjects, S6 and S8, were implanted with percutaneously interfaced bipolar intramuscular electrodes. At the time of the study, S6 and S8 had 6 and 8 bipolar EMG electrodes, respectively. A Virtual Reality (VR) system guided users through single and paired training movements in one 3-DoF and four different 4-DoF cases. A linear model of user activity was built by partitioning EMG feature space into regions bounded by vectors of steady state movement EMG patterns. The controller evaluated online EMG signals by linearly interpolating the movement class labels for surrounding trained EMG movements. This yields a simultaneous, continuous, intuitive, and proportional controller. Controllers were evaluated in 3-DoF and 4-DoF through a target-matching task in which subjects controlled a virtual hand to match 80 targets spanning the available movement space. Match Percentage, Time-To-Target, and Path Efficiency were evaluated over a 10-month period based on subject availability.

Results and conclusions

In 3-DoF, S6 and S8 matched most targets and demonstrated stable control after 8 and 10 months, respectively. In 4-DoF, both subjects initially found two of four 4-DoF controllers usable, matching most targets. S8 4-DoF controllers were stable, and showed improving trends over 7–9 months without retraining or at-home practice. S6 4-DoF controllers were unstable after 7 months without retraining. These results indicate that the performance of the controller proposed in this study may remain stable, or even improve, provided initial viability and a sufficient number of EMG channels. Overall, this study demonstrates a controller capable of stable, simultaneous, proportional, intuitive, and continuous control in 3-DoF for up to ten months and in 4-DoF for up to nine months without retraining or at-home use with minimal training times.
In vitro evaluation of cerebrospinal fluid velocity measurement in type I Chiari malformation: repeatability, reproducibility, and agreement using 2D phase contrast and 4D flow MRI
Authors: Williams Gwendolyn , Thyagaraj Suraj , Fu Audrey , Oshinski John , Giese Daniel , Bunck Alexander C. , Fornari Eleonora , Santini Francesco , Luciano Mark , Loth Francis , Martin Bryn A.
Published: March 2021

Background

Phase contrast magnetic resonance imaging, PC MRI, is a valuable tool allowing for non-invasive quantification of CSF dynamics, but has lacked adoption in clinical practice for Chiari malformation diagnostics. To improve these diagnostic practices, a better understanding of PC MRI based measurement agreement, repeatability, and reproducibility of CSF dynamics is needed.

Methods

An anatomically realistic in vitro subject specific model of a Chiari malformation patient was scanned three times at five different scanning centers using 2D PC MRI and 4D Flow techniques to quantify intra-scanner repeatability, inter-scanner reproducibility, and agreement between imaging modalities. Peak systolic CSF velocities were measured at nine axial planes using 2D PC MRI, which were then compared to 4D Flow peak systolic velocity measurements extracted at those exact axial positions along the model.

Results

Comparison of measurement results showed good overall agreement of CSF velocity detection between 2D PC MRI and 4D Flow (p = 0.86), fair intra-scanner repeatability (confidence intervals ± 1.5 cm/s), and poor inter-scanner reproducibility. On average, 4D Flow measurements had a larger variability than 2D PC MRI measurements (standard deviations 1.83 and 1.04 cm/s, respectively).

Conclusion

Agreement, repeatability, and reproducibility of 2D PC MRI and 4D Flow detection of peak CSF velocities was quantified using a patient-specific in vitro model of Chiari malformation. In combination, the greatest factor leading to measurement inconsistency was determined to be a lack of reproducibility between different MRI centers. Overall, these findings may help lead to better understanding for application of 2D PC MRI and 4D Flow techniques as diagnostic tools for CSF dynamics quantification in Chiari malformation and related diseases.
Astrocyte-specific hypoxia-inducible factor 1 (HIF-1) does not disrupt the endothelial barrier during hypoxia in vitro
Authors: Baumann Julia , Tsao Chih-Chieh , Huang Sheng-Fu , Gassmann Max , Ogunshola Omolara O.
Published: March 2021

Background

Astrocytes (AC) are essential for brain homeostasis. Much data suggests that AC support and protect the vascular endothelium, but increasing evidence indicates that during injury conditions they may lose their supportive role resulting in endothelial cell activation and BBB disturbance. Understanding the triggers that flip this switch would provide invaluable information for designing new targets to modulate the brain vascular compartment. Hypoxia-inducible factor-1 (HIF-1) has long been assumed to be a culprit for barrier dysfunction as a number of its target genes are potent angiogenic factors. Indeed AC themselves, reservoirs of an array of different growth factors and molecules, are frequently assumed to be the source of such molecules although direct supporting evidence is yet to be published. Being well known reservoirs of HIF-1 dependent angiogenic molecules, we asked if AC HIF-1 dependent paracrine signaling drives brain EC disturbance during hypoxia.

Methods

First we collected conditioned media from control and siRNA-mediated HIF-1 knockdown primary rat AC that had been exposed to normoxic or hypoxic conditions. The conditioned media was then used to culture normoxic and hypoxic (1% O2) rat brain microvascular EC (RBE4) for 6 and 24 h. Various activation parameters including migration, proliferation and cell cycling were assessed and compared to untreated controls. In addition, tight junction localization and barrier stability per se (via permeability assay) was evaluated.

Results

AC conditioned media maintained both normoxic and hypoxic EC in a quiescent state by suppressing EC metabolic activity and proliferation. By FACs we observed reduced cell cycling with an increased number of cells in G0 phase and reduced cell numbers in M phase compared to controls. EC migration was also blocked by AC conditioned media and in correlation hypoxic tight junction organization and barrier functionality was improved. Surprisingly however, AC HIF-1 deletion did not impact EC responses or barrier stability during hypoxia.

Conclusions

This study demonstrates that AC HIF-1 dependent paracrine signaling does not contribute to AC modulation of EC barrier function under normoxic or hypoxic conditions. Thus other cell types likely mediate EC permeability in stress scenarios. Our data does however highlight the continuous protective effect of AC on the barrier endothelium. Exploring these protective mechanisms in more detail will provide essential insight into ways to prevent barrier disturbance during injury and disease.
Comparison of the prognosis of four different treatment strategies for acute left malignant colonic obstruction: a systematic review and network meta-analysis
Authors: Tan Ling , Liu Zi-lin , Ran Meng-ni , Tang Ling-han , Pu Yan-jun , Liu Yi-lei , Ma Zhou , He Zhou , Xiao Jiang-wei
Published: March 2021

Background

There is controversy regarding the efficacy of different treatment strategies for acute left malignant colonic obstruction. This study investigated the 5-year overall survival (OS) and disease-free survival (DFS) of several treatment strategies for acute left malignant colonic obstruction.

Methods

We searched for articles published in PubMed, Embase (Ovid), MEDLINE (Ovid), Web of Science, and Cochrane Library between January 1, 2000, and July 1, 2020. We screened out the literature comparing different treatment strategies. Evaluate the primary and secondary outcomes of different treatment strategies. The network meta-analysis summarizes the hazard ratio, odds ratio, mean difference, and its 95% confidence interval.

Results

The network meta-analysis involved 48 articles, including 8 (randomized controlled trials) RCTs and 40 non-RCTs. Primary outcomes: the 5-year overall survival (OS) and disease-free survival (DFS) of the CS-BTS strategy and the DS-BTS strategy were significantly better than those of the ES strategy, and the 5-year OS of the DS-BTS strategy was significantly better than that of CS-BTS. The long-term survival of TCT-BTS was not significantly different from those of CS-BTS and ES. Secondary outcomes: compared with emergency resection (ER) strategies, colonic stent-bridge to surgery (CS-BTS) and transanal colorectal tube-bridge to surgery (TCT-BTS) strategies can significantly increase the primary anastomosis rate, CS-BTS and decompressing stoma-bridge to surgery (DS-BTS) strategies can significantly reduce mortality, and CS-BTS strategies can significantly reduce the permanent stoma rate. The hospital stay of DS-BTS is significantly longer than that of other strategies. There was no significant difference in the anastomotic leakage levels of several treatment strategies.

Conclusion

Comprehensive literature research, we find that CS-BTS and DS-BTS strategies can bring better 5-year OS and DFS than ER. DS-BTS strategies have a better 5-year OS than CS-BTS strategies. Without considering the hospital stays, DS-BTS strategy is the best choice.
Prediction of functional loss in emergency surgery is possible with a simple frailty screening tool
Authors: Zattoni Davide , Montroni Isacco , Saur Nicole Marie , Garutti Anna , Bacchi Reggiani Maria Letizia , Ghignone Federico , Taffurelli Giovanni , Ugolini Giampaolo
Published: March 2021

Background

Senior adults fear postoperative loss of independence the most, and this might represent an additional burden for families and society. The number of geriatric patients admitted to the emergency room requiring an urgent surgical treatment is rising, and the presence of frailty is the main risk factor for postoperative morbidity and functional decline. Frailty assessment in the busy emergency setting is challenging. The aim of this study is to verify the effectiveness of a very simple five-item frailty screening tool, the Flemish version of the Triage Risk Screening Tool (fTRST), in predicting functional loss after emergency surgery among senior adults who were found to be independent before surgery.

Methods

All consecutive individuals aged 70 years and older who were independent (activity of daily living (ADL) score ≥5) and were admitted to the emergency surgery unit with an urgent need for abdominal surgery between December 2015 and May 2016 were prospectively included in the study. On admission, individuals were screened using the fTRST and additional metrics such as the age-adjusted Charlson Comorbidity Index (CACI) and the ASA score. Thirty- and 90-day complications and postoperative decline in the ADL score where recorded. Regression analysis was performed to identify preoperative predictors of functional loss.

Results

Seventy-eight patients entered the study. Thirty-day mortality rate was 12.8% (10/78), and the 90-day overall mortality was 15.4% (12/78). One in every four patients (17/68) experienced a significant functional loss at 30-day follow-up. At 90-day follow-up, only 3/17 patients recovered, 2 patients died, and 12 remained permanently dependent. On the regression analysis, a statistically significant correlation with functional loss was found for fTRST, CACI, and age≥85 years old both at 30 and 90 days after surgery. fTRST≥2 showed the highest effectiveness in predicting functional loss at 90 days with AUC 72 and OR 6.93 (95% CI 1.71–28.05). The institutionalization rate with the need to discharge patients to a healthcare facility was 7.6% (5/66); all of them had a fTRST≥2.

Conclusion

fTRST is an easy and effective tool to predict the risk of a postoperative functional decline and nursing home admission in the emergency setting.
Real-time ultrasound for tip location of umbilical venous catheter in neonates: a pre/post intervention study
Authors: Rubortone Serena Antonia , Costa Simonetta , Perri Alessandro , D’Andrea Vito , Vento Giovanni , Barone Giovanni
Published: March 2021

Background

Recent guidelines advocate the use of real-time ultrasound to locate umbilical venous catheter tip. So far, training programs are not well established.

Methods

A pre/post interventional study was carried out in our tertiary neonatal intensive care unit centre to evaluate the efficacy of a training protocol in the use of real-time ultrasound. Primary outcome was the percentage in the use of real-time ultrasound.

Results

Fifty-four patients were enrolled. The use of real-time ultrasound for tip location significantly increased after the training program (15.3% vs 89.2%, p <  0.0001). After the training the tip of the catheters was more frequently placed at the junction of the inferior vena cava and right atrium (75% vs 30.7%, p = 0.0023). Twenty-two catheters were also evaluated with serial scans during the intervention phase to assess migration rate which was 50%.

Conclusion

a multimodal, targeted training on the use of real-time ultrasound for umbilical venous catheter placement is feasible. Real-time ultrasound is easily teachable, increases the number of umbilical venous catheters placed in a correct position, reduces the number of line manipulations and the need of chest-x-rays.
Galectin-3 in septic acute kidney injury: a translational study
Authors: Sun Haibing , Jiang Huiping , Eliaz Amity , Kellum John A. , Peng Zhiyong , Eliaz Isaac
Published: March 2021

Background

Galectin-3 (Gal-3) is a pleiotropic glycan-binding protein shown to be involved in sepsis and acute kidney injury (AKI). However, its role has never been elucidated in sepsis-associated AKI (S-AKI). We aimed to explore Gal-3’s role and its potential utility as a therapeutic target in S-AKI.

Methods

In 57 patients admitted to the intensive care unit (ICU) with sepsis, serum Gal-3 was examined as a predictor of ICU mortality and development of AKI. In a rat model of S-AKI induced by cecal ligation and puncture (CLP), 7-day mortality and serum Gal-3, Interleukin-6 (IL-6), and creatinine were examined at 2, 8, and 24 hours (h) post-CLP. Two experimental groups received the Gal-3 inhibitor modified citrus pectin (P-MCP) at 400 mg/kg/day and 1200 mg/kg/day, while the control group received water only (n = 18 in each group).

Results

Among 57 patients, 27 developed AKI and 8 died in the ICU. Serum Gal-3 was an independent predictor of AKI (OR = 1.2 [95% CI 1.1–1.4], p = 0.01) and ICU mortality (OR = 1.4 [95% CI 1.1–2.2], p = 0.04) before and after controlling for age, AKI, and acute physiology and chronic health evaluation (APACHE II) score. In the CLP rat experiment, serum Gal-3 peaked earlier than IL-6. Serum Gal-3 was significantly lower in both P-MCP groups compared to control at 2 h post-CLP (400 mg: p = 0.003; 1200 mg: p = 0.002), and IL-6 was significantly lower in both P-MCP groups at all time points with a maximum difference at 24 h post-CLP (400 mg: p = 0.015; 1200 mg: p = 0.02). In the Gal-3 inhibitor groups, 7-day mortality was significantly reduced from 61% in the control group to 28% (400 mg P-MCP: p = 0.03) and 22% (1200 mg P-MCP: p = 0.001). Rates of AKI per RIFLE criteria were significantly reduced from 89% in the control group to 44% in both P-MCP groups (400 mg: p = 0.007; 1200 mg: p = 0.007).

Conclusions

This translational study demonstrates the importance of Gal-3 in the pathogenesis of S-AKI, and its potential utility as a therapeutic target.

Graphic abstract
Magnetic resonance imaging and ultrasound for prediction of residual tumor size in early breast cancer within the ADAPT subtrials
Authors: Graeser Monika , Schrading Simone , Gluz Oleg , Strobel Kevin , Herzog Christopher , Umutlu Lale , Frydrychowicz Alex , Rjosk-Dendorfer Dorothea , Würstlein Rachel , Culemann Ralph , Eulenburg Christine , Adams Jascha , Nitzsche Henrik , Prange Anna , Kümmel Sherko , Grischke Eva-Maria , Forstbauer Helmut , Braun Michael , Potenberg Jochem , von Schumann Raquel , Aktas Bahriye , Kolberg-Liedtke Cornelia , Harbeck Nadia , Kuhl Christiane K. , Nitz Ulrike
Published: March 2021

Background

Prediction of histological tumor size by post-neoadjuvant therapy (NAT) ultrasound and magnetic resonance imaging (MRI) was evaluated in different breast cancer subtypes.

Methods

Imaging was performed after 12-week NAT in patients enrolled into three neoadjuvant WSG ADAPT subtrials. Imaging performance was analyzed for prediction of residual tumor measuring ≤10 mm and summarized using positive (PPV) and negative (NPV) predictive values.

Results

A total of 248 and 588 patients had MRI and ultrasound, respectively. Tumor size was over- or underestimated by < 10 mm in 4.4% and 21.8% of patients by MRI and in 10.2% and 15.8% by ultrasound. Overall, NPV (proportion of correctly predicted tumor size ≤10 mm) of MRI and ultrasound was 0.92 and 0.83; PPV (correctly predicted tumor size > 10 mm) was 0.52 and 0.61. MRI demonstrated a higher NPV and lower PPV than ultrasound in hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-positive and in HR−/HER2+ tumors. Both methods had a comparable NPV and PPV in HR−/HER2− tumors.

Conclusions

In HR+/HER2+ and HR−/HER2+ breast cancer, MRI is less likely than ultrasound to underestimate while ultrasound is associated with a lower risk to overestimate tumor size. These findings may help to select the most optimal imaging approach for planning surgery after NAT.

Trial registration

Clinicaltrials.gov, NCT01815242 (registered on March 21, 2013), NCT01817452 (registered on March 25, 2013), and NCT01779206 (registered on January 30, 2013).
Evaluation on immediate analgesic efficacy and safety of Kai-Hou-Jian spray (children’s type) in treating sore throat caused by acute pharyngitis and tonsillitis in children: study protocol for a randomized controlled trial
Authors: Ma Yan-ning , Zhong Cheng-liang , Hu Si-yuan , Cai Qiu-han , Guo Sheng-xuan
Published: March 2021

Background

Acute pharyngitis and tonsillitis are common respiratory diseases for which children seek medical care. Their main clinical manifestation is sore throat which interferes with patients’ quality of life. However, there is no proven effective or safe method to treat it. It is necessary to find an excellent strategy to reduce sore throat and reduce the burden of acute illness. We designed the randomized controlled trial with the characteristics of traditional Chinese medicine (TCM) to determine the clinical positioning of Kai-Hou-Jian spray (children’s type) (KHJS) through evidence-based research. This trial aims to evaluate the immediate analgesic efficacy of KHJS on sore throat caused by acute pharyngitis and tonsillitis (wind-heat syndrome/heat exuberance in lung and stomach syndrome) in children and to observe its safety.

Methods/design

This is a prospective, multicenter, randomized, double-blind, parallel-group, placebo-controlled trial. It will include 240 children with acute pharyngitis/tonsillitis from 7 study sites across China. All participants are randomly assigned to two parallel treatment groups, one with KHJS and the other with placebo sprays, for 5 consecutive days. The primary outcome is the time of analgesic onset. Secondary outcomes include duration of analgesic effect, area under time curve of 0–3 h Wong-Baker FACES Pain Rating Scale (WBS) score (AUC0-3 h), rate of analgesic onset, rate of disappearance of sore throat, changes of WBS score (in days), effective rate of pharyngeal signs, and effective rate of TCM syndrome. The incidence of adverse events during the trial is the primary safety outcome. In addition, vital signs and laboratory tests before and after medication are monitored.

Discussion

To our knowledge, this will be the first clinical trial to explore the immediate analgesic efficacy of a Chinese patent medicine spray for acute pharyngitis/tonsillitis induced sore throat in children in a multicenter, randomized, double-blinded, parallel-group, placebo-controlled manner. Not only might it prove the efficacy and safety of KHJS in the treatment of sore throat caused by acute pharyngitis/tonsillitis in children, but it might also provide evidence for the treatment of acute sore throat with Chinese herbal medicine.

Trial registration

A multicenter, randomized, double-blind, very low-dose, parallel controlled trial for the immediate analgesic effect and safety of Kai-Hou- Jian spray (children's type) in the treatment of sore throat caused by acute pharyngitis and tonsillitis in children. Chinese Clinical Trial RegistryChiCTR2000031599. Registered on 5 April 2020
Timing of antiretroviral therapy for HIV-infected patients with cytomegalovirus retinitis: study protocol of a multi-center prospective randomized controlled trial
Authors: He Xiao-Qing , Huang Yin-Qiu , Zeng Yan-Ming , Qin Yuan-Yuan , Tang Sheng-Quan , Xu Xiao-Lei , Harypursat Vijay , Lu Yan-Qiu , Liu Min , Yuan Jing , Chen Yao-Kai
Published: March 2021

Background

Cytomegalovirus retinitis (CMVR) is an important opportunistic infection (OI) occurring mainly in patients with acquired immunodeficiency syndrome (AIDS) and has the potential to cause severe visual impairment and blindness among AIDS patients. Subsequent to the adoption and implementation of widespread antiretroviral therapy (ART), the prognosis of AIDS-associated CMVR has been substantially improved. Nevertheless, the equivocal clinical evidence as regards the optimal timing for ART initiation in patients with an established CMVR diagnosis is required. We therefore designed the present study in order to investigate the optimal timing for ART initiation in AIDS/CMVR patients.

Methods

This will be a prospective, randomized controlled trial to be performed at 17 hospitals in mainland China. A total of 300 participants with CMVR will be randomly assigned to an early ART initiation group (ART initiation within 2 weeks after anti-CMV therapy), or a deferred ART initiation group (initiation of ART more than 2 weeks after anti-CMV therapy) at a 1:1 ratio. All participants will receive 48 weeks of follow-up after anti-CMV therapy initiation. Our primary outcome will be the incidence of visual loss (to a visual acuity worse than 20/40 or 20/200) in the two groups during the 48-week follow-up period. Secondary outcomes will include changes in HIV virological suppression and serum CD4+ T-cell counts, the incidence of mortality, retinitis progression (movement of the peripheral border of a CMV lesion ≥ ½ disc diameter, or occurrence of a new CMV lesion), retinal detachment, immune recovery uveitis (IRU), and other OIs and adverse events between the two study groups during the 48 weeks of follow-up.

Discussion

The study aims to investigate the optimal timing for ART initiation in AIDS/CMVR patients. We hope to be able to extract robust clinical evidence for use in optimal AIDS/CMVR management should our trial be successful.

Trial registration

This research was registered as one of the twelve clinical trials under the name of a general project “A study for precision diagnosing and treatment strategies in difficult-to-treat AIDS cases and HIV-infected patients with highly fatal or highly disabling opportunistic infections”, ChiCTR1900021195. Registered on 1 February 2019, http://www.chictr.org.cn/showproj.aspx?proj=35362.
High-elevational occurrence of two tick species, Ixodes ricinus and I. trianguliceps, at their northern distribution range
Authors: De Pelsmaeker Nicolas , Korslund Lars , Steifetten Øyvind
Published: March 2021

Background

During the last decades a northward and upward range shift has been observed among many organisms across different taxa. In the northern hemisphere, ticks have been observed to have increased their latitudinal and altitudinal range limit. However, the elevational expansion at its northern distribution range remains largely unstudied. In this study we investigated the altitudinal distribution of the exophilic Ixodes ricinus and endophilic I. trianguliceps on two mountain slopes in Norway by assessing larval infestation rates on bank voles (Myodes glareolus).

Methods

During 2017 and 2018, 1325 bank voles were captured during the spring, summer and autumn at ten trapping stations ranging from 100 m to 1000 m.a.s.l. in two study areas in southern Norway. We used generalized logistic regression models to estimate the prevalence of infestation of both tick species along gradients of altitude, considering study area, collection year and season, temperature, humidity and altitude interactions as extrinsic variables, and host body mass and sex as intrinsic predictor variables.

Results

We found that both I. ricinus and I. trianguliceps infested bank voles at altitudes up to 1000 m.a.s.l., which is a substantial increase in altitude compared to previous findings for I. ricinus in this region. The infestation rates declined more rapidly with increasing altitude for I. ricinus compared to I. trianguliceps, indicating that the endophilic ecology of I. trianguliceps may provide shelter from limiting factors tied to altitude. Seasonal effects limited the occurrence of I. ricinus during autumn, but I. trianguliceps was found to infest rodents at all altitudes during all seasons of both years.

Conclusions

This study provides new insights into the altitudinal distribution of two tick species at their northern distribution range, one with the potential to transmit zoonotic pathogens to both humans and livestock. With warming temperatures predicted to increase, and especially so in the northern regions, the risk of tick-borne infections is likely to become a concern at increasingly higher altitudes in the future.

Graphical Abstract