bluuebunny/crossref_metadata_2025 huggingface dataset:
The efficacy and safety of acupuncture for patients with post-percutaneous coronary intervention depression
Authors: Liu Yong , Dai Disha , Huang Kailin , Zhuang Rui , Ma Liyong , Liu Birong , Pan Yi , Zhang Lijing
Published: December 2020

Background:

Percutaneous coronary intervention (PCI) has been increasingly applied as an effective revascularization strategy in patients with coronary artery disease (CAD). However, recent studies had indicated a higher incidence of depression on post-PCI patients. Acupuncture therapy is effective for depression. However, the treatment effect of depression on post-PCI patients is still not clear. Therefore, this systematic review and meta-analysis protocol is planned to evaluate the efficacy and safety of acupuncture for depression in post-PCI patients.

Methods:

Six English databases (PubMed, Web of science, Medline, EMBASE, Springer Cochrane Library and WHO International Clinical Trials Registry Platform) and 4 Chinese databases (Wan fang Database, Chinese Scientific Journal Database, China National Knowledge Infrastructure Database (CNKI) and Chinese Biomedical Literature Database) will be searched normatively according to the rule of each database from the inception to August 1, 2020. Two reviewers will independently conduct article selection, data collection, and risk of bias evaluation. Any disagreement will be resolved by discussion with the third reviewer. Either the fixed-effects or random-effects model will be used for data synthesis based on the heterogeneity test. The change in the scores on the Hamilton depression scale (HAMD) and the Self-rating depression scale (SDS) will be used as the main outcome measure. All-cause mortality, cardiac mortality, Major Adverse Cardiovascular Events (MACEs), rehospitalisation rate and Quality of Life Scale (SF-36) as the secondary outcome. Treatment Emergent Symptom Scale (TESS), General physical examination (temperature, pulse, respiration, blood pressure), Routine examination of blood, urine and stool, Electrocardiogram, Liver and kidney function examination as the security indexs. RevMan5.3.5 will be used for meta-analysis.

Results:

This study will provide high-quality evidence to assess the efficacy and safety of acupuncture for depression in post-PCI patients.

Conclusion:

This systematic review will explore whether acupuncture is an effective and safe intervention for depression in post-PCI patients.
Hemiarthroplasty versus total hip arthroplasty for displaced femoral neck fracture in patients older than 80 years
Authors: Peng Lin , Liu Hongyu , Hu Xiaoyi , Liu Jianqiang
Published: December 2020

Background:

The forms of treatment which are available for these patients include internal fixation, hemiarthroplasty (HA), or total hip arthroplasty (THA). Both HA and THA are widely used methods of hip replacement after displaced femoral neck fracture (DFNF). Our purpose is to analyze the long-term outcomes of these 2 different forms of treatment, which are suitable for active patients with femoral neck intracapsular fractures ≥80 years of age without advanced osteoarthritis or rheumatoid arthritis.

Methods:

This study is designed as a single-center randomized controlled trial. The participants will be randomly assigned to either the THA group or the HA group. Information will be collected from all participants after obtaining written informed consent in accordance with the Declaration of Helsinki and ethical board approval. Inclusion criteria include: displaced intracapsular femoral neck fracture, capability to obtain informed consent, no known metastatic disease, no contraindications to anesthesia, age ≥80 years, and ability to understand written Chinese. Patients will be evaluated at 3 months, 6 months, 1 year, and 3 years after surgery. At the time of the final follow-up, patients were assessed with use of the Harris hip score (HHS) and walking distance. Secondary outcomes of interest include postoperative complications, including 90-day medical complications (acute myocardial infarction, deep vein thrombosis, pulmonary embolism, intestinal obstruction, renal failure, and pneumonia) and surgical complications within 1 year (dislocation, infection, and revision replacement).

Results:

This trial is expected to be the largest randomized trial assessing the efficacy of THA and HA and powered to detect a potential difference in the primary outcome.

Trial registration:

This study protocol has been registered in Research Registry (researchregistry6203).
Polyserositis as a primary clinical manifestation of CD7+ acute myelogenous leukemia with myeloid sarcoma
Authors: Pi Yubo , Wang Beining , Wang Lihong , Ren Hanyun
Published: December 2020

Rationale:

Myeloid sarcomas (MS) are defined as rare extramedullary masses composed of immature myeloid cells. MS mostly develops in patients with acute myeloid leukemia (AML), and involves primarily the skin, soft tissues, bones, and lymph nodes. Pleura and pericardium involvement of MS are extremely uncommon. Polyserositis is also a very rare extramedullary presentation of acute myeloid leukemia (AML).

Patient concerns:

A 30-year-old woman with a complaint of right neck mass combined with coughing for 2 months as well as fever and systemic edema for the last 10 days, was admitted to our center on July 11, 2019. Initial positron emission tomography (PET) scan indicated systemic lymphadenopathy, bilateral pleural effusion, and pericardial effusion.

Diagnosis:

The initial pathological diagnosis of lymph nodes was MS. Subsequent bone marrow analysis confirmed AML.

Interventions:

Conventional IA induction regimen followed by high-dose cytarabine (HiDAC) regimen.

Outcomes:

Complete absorption of pericardial and pleural effusion after the first cycle of IA induction chemotherapy.

Lessons:

Polyserositis can be an extramedullary presentation of AML. Patients with polyserositis should undergo routine flow cytometric analysis. For AML with extamedullary infiltration, systemic chemotherapy should be administered in all confirmed cases.
Chinese herbal medicine for previous cesarean scar defect
Authors: Deng Jiashuai , Li Sixuan , Peng Yangzhi , Chen Zhaoxing , Wang Changhong , Fan Zhipeng , Zhao Mao , Jiang Yuchang , Wang Zhaodi , Jiang Yong
Published: December 2020

Background

: Previous cesarean scar defect (PCSD) is a gynecological disease that can cause bleeding after intercourse, prolonging menstrual period, intermenstrual bleeding, dysmenorrhea, and even lead to infertility. Chinese herbal medicine plays an important role in the treatment of gynecological diseases in China and East Asia. This study aims to assess the efficacy and safety of Chinese herbal medicine for PCSD.

Methods

: We search the following databases: PubMed, the Cochrane Library, Chinese Biomedical Literature Database (CB), Chinese Science and Technique Journals Database (VIP), EMBASE, Chinese National Knowledge Infrastructure Database (CNKI), and the Wanfang Database. Other sources will also be searched like Google Scholar and gray literature. All databases mentioned above are searched from the start date to the latest version. Randomized controlled trials will be included which recruiting PCSD participants to assess the efficacy and safety of Chinese herbal medicines against controls (placebo or other therapeutic agents). Primary outcomes will include the size of PCSD, menstrual cycle, menstrual phase, menstrual volume, duration of disease, security index. Two authors will independently scan the searched articles, extract the data from attached articles, and import them into Endnote X8 and use Microsoft Excel 2013 to manage data and information. We will assess the risk of bias by Cochrane tool of risk of bias. Disagreements will be resolved by consensus or the participation of a third party. All analysis will be performed based on the Cochrane Handbook for Systematic Reviews of Interventions. The meta-analysis in this review will use RevMan 5.3 software.

Results

: The study aims to evaluate the efficacy and safety of the treatment that Chinese herbal medicine for PCSD.

Conclusion

: This study of the meta-analysis could provide evidence for clinicians and help patients to make a better choice.

INPLASY registration number:

INPLASY202090080
The quality assessment of intraabdominal infection guidelines/consensuses in 2 decades - which are better and any changes?
Authors: Wang Yu , Guo Jun , Xiong Tingting , Wang Fangfang , Kou Guoxian , Ning Hong
Published: December 2020

Background and aim:

Intraabdominal infection (IAI) is a common and important disease worldwide. An increasing number of related guidelines/consensuses have been published in recent years, the quality evaluation for these guidelines/consensuses is necessary to identify lower-quality documents and explore the quality distribution in different time range and areas in this field.

Methods:

The Appraisal of Guidelines for Research & Evaluation Instrument tool was adopted to assess the quality of IAI guidelines/consensuses by 3 researchers independently. Intraclass correlation coefficients (ICCs) among the researchers were retrieved to reflect reliability. The quality differences of these guidelines/consensuses issued before and after May 2009, both international and non-international, were compared by a Mann–Whitney U test.

Results:

Fourteen IAI guidelines/consensuses published in English were obtained following a literature search. The ICCs among the researchers were all above 0.75, indicating satisfactory reliability. This outcome showed that the overall quality of these guidelines/consensuses was mediocre and considered acceptable in all items. A few guidelines/consensuses were better in their scientific and methodological characteristics than the others. Moreover, there were no significant differences in the scores between the guidelines/consensuses issued before and after May 2009 or between international vs regional guidelines/consensuses.

Conclusions:

Overall, the quality of the IAI guidelines/consensuses was generally acceptable and applicable, with a few deficiencies. Therefore, continuous improvement is essential. The guideline assessment tools should be applied in guideline/consensus development both widely and strictly to improve the methodological quality.
Time to sputum culture conversion and its predictors among patients with multidrug-resistant tuberculosis in Hangzhou, China
Authors: Li Qingchun , Lu Min , Hsieh Evelyn , Wu Limin , Wu Yifei , Wang Meng , Wang Le , Zhao Gang , Xie Li , Qian Han-Zhu
Published: December 2020

The objective is to investigate the time to initial sputum culture conversion (SCC) and its predictors among multidrug-resistant tuberculosis (MDR-TB) patients in Hangzhou, China.

A retrospective cohort study was conducted among patients who initiated MDR-TB treatment from 2011 to 2015 in Hangzhou, China. Successful achievement of initial SCC was defined as 2 consecutive negative cultures taken at least 30 days apart after initiation of treatment of MDR-TB. Successful treatment outcomes included being cured and completing treatment, while poor treatment outcomes included treatment failure, loss to follow-up, and death. Time to initial SCC was analyzed using the Kaplan–Meier method, and Cox proportional hazards regression was used to identify predictors of SCC.

Among 384 patients enrolled with MDR-TB, 359 (93.5%) successfully achieved initial SCC after a median of 85 days (interquartile range, 40–112 days). A higher rate of SCC was observed in participants with successful treatment outcomes than those with poor treatment outcomes (P<.01). Multivariate analysis showed that age 25 to 64 years (compared with age<25; adjusted odds ratio [AOR], 0.7; 95% confidence interval [CI], 0.5–0.9; P 
< .01), age ≥65 years (compared with age < 25; AOR, 0.5; 95% CI, 0.3–0.8; P < .01), and household registration in Hangzhou (compared with non-Hangzhou registration; AOR, 1.3; 95% CI, 1.0–1.5; P 
< .05) were found to be associated with SCC.

Although high SCC and treatment success rates were observed among MDR-TB patients in Hangzhou, the prolonged duration to initial SCC underscores the importance of emphasizing measures for infection control. A new policy of shifting outpatient treatment to inpatient treatment in China may reduce the risk of transmission from patients in the time window prior to SCC.
Metal artifacts reduction in computed tomography: A phantom study to compare the effectiveness of metal artifact reduction algorithm, model-based iterative reconstruction, and virtual monochromatic imaging
Authors: Ishikawa Takuya , Suzuki Shigeru , Harashima Shingo , Fukui Rika , Kaiume Masafumi , Katada Yoshiaki
Published: December 2020

The purpose of this study was to compare the effectiveness of a metal artifact reduction algorithm (MAR), model-based iterative reconstruction (MBIR), and virtual monochromatic imaging (VMI) for reducing metal artifacts in CT imaging.

A phantom study was performed for quantitatively evaluating the dark bands and fine streak artifacts generated by unilateral hip prostheses. Images were obtained by conventional scanning at 120 kilovolt peak, and reconstructed using filtered back projection, MAR, and MBIR. Furthermore, virtual monochromatic images (VMIs) at 70 kilo-electron volts (keV) and 140 keV with/without use of MAR were obtained by dual-energy CT. The extents and mean CT values of the dark bands and the differences in the standard deviations and location parameters of the fine streak artifacts evaluated by the Gumbel method in the images obtained by each of the methods were statistically compared by analyses of variance.

Significant reduction of the extent of the dark bands was observed in the images reconstructed using MAR than in those not reconstructed using MAR (all, P < .01). Images obtained by VMI at 70 keV and 140 keV with use of MAR showed significantly increased mean CT values of the dark bands as compared to those obtained by reconstructions without use of MAR (all, <.01). Significant reduction of the difference in the standard deviations used to evaluate fine streak artifacts was observed in each of the image sets obtained with VMI at 140 keV with/without MAR and conventional CT with MBIR as compared to the images obtained using other methods (all, P < .05), except between VMI at 140 keV without MAR and conventional CT with MAR. The location parameter to evaluate fine streak artifacts was significantly reduced in CT images obtained using MBIR and in images obtained by VMI at 140 keV with/without MAR as compared to those obtained using other reconstruction methods (all, P < .01).

In our present study, MAR appeared to be the most effective reconstruction method for reducing dark bands in CT images, and MBIR and VMI at 140 keV appeared to the most effective for reducing streak artifacts.
Determination of the optimal time for N95 respirator for aerosol infection control
Authors: Du Jian , Zhang Lijie , Liu Yuhong , Shu Wei , Ma Yan , Gao Jingtao , Li Liang
Published: December 2020

The transmission of tuberculosis has been declared as an important occupational hazard for health care workers of tuberculosis dispensary. Here, we evaluated the filtration efficiency and respiratory resistance of different respirators along with the increase of wear time.

Filter efficiency and breathing resistance were tested to determine the performance of different types of respirators, and the N95 respirator were simulatively worn by volunteers to determine the optimal time for N95 respirator as a tuberculosis control measure.

N95 respirator had the highest filtration efficiency (97.4% ± 0.3%), whereas the surgical mask could only prevent 18.4% of aerosol particles to penetrate inside the respirator. In addition, N95 respirator and surgical mask had the highest and lowest exhalation resistance (13.8 ± 0.9 mmH2O vs. 1.8 ± 0.2 mmH2O), respectively. When the volunteers wore the N95 respirator for 3 days, the average filtration efficiency was 97.0%. In addition, there were no significant differences in the exhalation resistance of N95 respirator, ranging from 13.8 ± 0.9 mmH2O of 0 day to 11.6 ± 0.9 mmH2O of 14 days.

Our results demonstrate that only N95 respirator provides promising protective efficiency for health care workers against tuberculosis. In addition, N95 respirator could produce adequate protective efficacy after 3-day wear time.
The efficacy and safety of fire needle for the treatment of lumbar disc herniation
Authors: Wang Meiyuan , Zheng Beisi , Wu Cunshu , Yi Shixiong
Published: December 2020

Background:

A very large acceleration in clinical studies on the efficacy of fire needle to treat lumbar disc herniation (LDH) are increasing, while studies on the assessment of its efficacy are still lacking. Therefore, this study will demonstrate the efficacy of fire needle in the treatment of LDH combining with the meta-analysis.

Methods:

The studies on randomized controlled trials (RCTs) will be searched at the databases of China National Knowledge Infrastructure (CNKI), WANFANG database (Chinese Medicine Premier), Chinese Scientific Journal Database (VIP), Chinese Biomedical Literature database (CBM), PubMed, EMBASE, and Cochrane Library from their inception to May 1, 2020.

Results:

This authentic and multi-dimensional study will shed light on the referable information for the treatment of LDH with fire needle.

Conclusion:

This study will evaluate the efficacy of fire needle in the treatment of LDH.

Registration:

PROSPERO (registration number CRD42020158596).
Assessment of early oxidative stress following the use of radiotheranostics agents 177Lu-PSMA for prostate cancer and 177Lu-DOTATATE for neuroendocrine tumors; radioprotective effect of vitamin C
Authors: Jafari Esmail , Ahmadzadehfar Hojjat , Bagheri Dara , Amini Abdullatif , Assadi Majid
Published: December 2020

Background:

We aimed first to evaluate the early oxidative stress following radionuclide therapy (RNT) with 177Lu-PSMA and 177Lu-DOTATATE and second to evaluate the protective effect of vitamin C on oxidative stress.

Materials and methods:

Prostate cancer and neuroendocrine tumor (NET) patients referred to therapy with 177Lu-PSMA and 177Lu-DOTATATE, respectively, were enrolled in this study. The patients divided into the control group underwent routine RNT without any intervention and the intervention group was asked to take effervescent tablets (500 mg) of vitamin C for two days prior to the RNT (three tablets per day). To measure oxidative stress, blood samples were taken immediately before treatment and 48 h after treatment, and the serums were separated and frozen. To evaluate oxidative stress, the serum levels of malondialdehyde (MDA) and glutathione (GSH) and the activity of glutathione reductase were measured before and two days after treatment.

Results:

In total, 61 RNT cycles were evaluated in 34 patients with age of 65 ± 2.83 (median ± SE) years (range of 27–99); this total included 20 (59%) prostate cancer patients [35 cycles (57.4%)] and 14 patients (41%) with NET [26 cycles (42.6%)]. Of the 61 evaluated cycles, 27 cycles were given in the control group and 34 cycles were given in the intervention group. The serum level of MDA was significantly increased after treatment compared to before treatment (P = 0.02) in the control group, while no significant change in the serum level of MDA was observed in the intervention group (P = 0.52). The serum level of GSH was insignificantly decreased after treatment compared to before treatment in the control group and slightly increased after treatment in the intervention group (P > 0.05). The serum level of glutathione reductase was insignificantly increased in all groups of patients after treatment (P > 0.05).

Conclusion:

According to the results of this study, RNT with Lu-PSMA and Lu-DOTATATE may induce oxidative stress via the generation of free radicals and reactive oxygen species. Consumption of vitamin C prior to RNT may ameliorate this oxidative stress. These preliminary results have positive implications for clinical practice. Verification of these noteworthy results is needed and can be conducted with larger randomized controlled trials with longer time points.
Before Disaster Strikes
Authors: Donahue Andrew , Brown Seth , Singh Suhkvir , Shokur Nikita , Burns J. Bracken , Duvall Kathryn L. , Tuell Dawn S.
Published: December 2020

Objective

Because training in pediatric disaster medicine (PDM) is neither required nor standardized for pediatric residents, we designed and integrated a PDM course into the curriculum of a pediatric residency program and assessed if participation increased participants' knowledge of managing disaster victims.

Methods

We adapted and incorporated a previously studied PDM course into a small-sized pediatric residency program. The curriculum consisted of didactic lectures and experiential learning via simulation with structured debriefing. With IRB approval, the authors conducted a longitudinal series of pretests and posttests to assess knowledge and perceptions.

Results

Sixteen eligible residents completed the intervention. Before the course, none of the residents reported experience treating disaster victims. Pairwise comparison of scores revealed a 35% improvement in scores immediately after completing the course (95% confidence interval, 22.73%–47.26%; P < 0.001) and a 23.73% improvement 2 months later (95% confidence interval, 7.12%–40.34%; P < 0.01).

Conclusions

Residents who completed this course increased their knowledge of PDM with moderate retention of knowledge gained. There was a significant increase in perceived ability to manage patients in a disaster situation after this educational intervention and the residents' confidence was preserved 2 months later. This PDM course may be used in future formulation of a standardized curriculum.
Identifying influential neighbors in social networks and venue affiliations among young MSM: a data science approach to predict HIV infection
Authors: Xiang Yang , Fujimoto Kayo , Li Fang , Wang Qing , Del Vecchio Natascha , Schneider John , Zhi Degui , Tao Cui
Published: December 2020

Objective:

Young MSM (YMSM) bear a disproportionate burden of HIV infection in the United States and their risks of acquiring HIV may be shaped by complex multilayer social networks. These networks are formed through not only direct contact with social/sex partners but also indirect anonymous contacts encountered when attending social venues. We introduced a new application of a state-of-the-art graph-based deep learning method to predict HIV infection that can identify influential neighbors within these multiple network contexts.

Design and methods:

We used empirical network data among YMSM aged 16–29 years old collected from Houston and Chicago in the United States between 2014 and 2016. A computational framework GAT-HIV (Graph Attention Networks for HIV) was proposed to predict HIV infections by identifying influential neighbors within social networks. These networks were formed by multiple relations constituted of social/sex partners and shared venue attendances, and using individual-level variables. Further, GAT-HIV was extended to combine multiple social networks using multigraph GAT methods. A visualization tool was also developed to highlight influential network members for each individual within the multiple social networks.

Results:

The multigraph GAT-HIV models obtained average AUC values of 0.776 and 0.824 for Chicago and Houston, respectively, performing better than empirical predictive models (e.g. AUCs of random forest: 0.758 and 0.798). GAT-HIV on single networks also delivered promising prediction performances.

Conclusion:

The proposed methods provide a comprehensive and interpretable framework for graph-based modeling that may inform effective HIV prevention intervention strategies among populations most vulnerable to HIV.
Efficacy and Safety of Intra-articular Sacroiliac Glucocorticoid Injections in Ankylosing Spondylitis
Authors: Nam Bora , Kim Tae-Hwan , Lee Sung Won , Kim Hyunah , Kim Yun Jin , Jun Jae-Bum , Lee Seunghun
Published: December 2020

Background/Aims

To assess the efficacy and safety of intra-articular sacroiliac glucocorticoid injection in ankylosing spondylitis (AS).

Methods

Patients with AS undergoing fluoroscopy-guided intra-articular sacroiliac glucocorticoid injection were enrolled between 2012 and 2018. Efficacy was assessed by numeric pain rating scale, acute phase reactants, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index, and Ankylosing Spondylitis Disease Activity Score (ASDAS). Patients who started biologics within 3 months despite the intervention were compared with those not starting biologics, hence: the nonbiologic group.

Results

A total of 96 patients were treated, with a total of 107 injections. After intervention, there were significant decreases in numeric pain rating scale (7.8 ± 1.8 vs. 3.3 ± 2.2, p < 0.001) and acute phase reactants level (erythrocyte sedimentation rate [ESR] 23.0 mm/h [10.0–47.0 mm/h] vs. 13.0 mm/h [4.0–27.0 mm/h], p < 0.001; C-reactive protein [CRP] 1.0 mg/dL [0.2–2.7 mg/dL] vs. 0.2 mg/dL [0.2–0.9 mg/dL], p < 0.001). Disease activity scores also decreased for BASDAI (6.2 ± 1.8 vs. 4.5 ± 2.5, p = 0.001), Bath Ankylosing Spondylitis Functional Index (5.5 [4.1–7.0] vs. 1.8 [0.5–4.1], p = 0.001), ASDAS-CRP (2.9 ± 1.0 vs. 2.3 ± 1.3, p = 0.046), and ASDAS-ESR (3.7 ± 1.1 vs. 2.4 ± 1.3, p < 0.001). However, 12 patients (12.5%) started biologics within 3 months. These patients showed higher ESR (91.0 mm/h [IQR 21.0–113.0 mm/h] vs. 21.5 mm/h [IQR 9.5–43.0 mm/h], p = 0.010), CRP (8.0 mg/dL [IQR 1.11–17.1 mg/dL] vs. 0.8 mg/dL [IQR 0.2–1.8 mg/dL], p = 0.002), BASDAI (7.4 ± 1.2 vs. 5.9 ± 1.8, p = 0.027), and ASDAS-CRP (4.0 ± 0.5 vs. 2.8 ± 1.0, p = 0.004) than the nonbiologic group. There was no serious adverse event.

Conclusions

Intra-articular sacroiliac glucocorticoid injection can be a safe and effective treatment option for active sacroiliitis in AS.
In Vivo Ultrasound Imaging of the Spinal Cord and Subarachnoid Space at the C1-C2 Level in Healthy Adult Subjects
Authors: Beland Michael D. , McElroy Abigail W. , Brinker Thomas , Gokaslan Ziya L. , Klinge Petra M.
Published: December 2020

Ultrasound (US) imaging of the spinal canal is applied in early infants before formation of posterior spine bony elements. Here, we demonstrate for the first time in adult healthy subjects that excellent visualization of intrathecal structures at the level of C1-C2 is possible by transcutaneous US in flexion, extension, and neutral head positions through the soft tissue US window between C1-C2. We show with US that the posterior subarachnoid space increases significantly in head extension. Accordingly, C1-C2 US guidance can facilitate cervical myelography. In addition, we suggest that US of the C1-C2 spine level may offer an adjunct tool to diagnosing structural abnormalities in the setting of traumatic, congenital, or degenerative pathologies of the craniocervical junction.
Red Blood Cells Elicit Platelet-Dependent Neutrophil Recruitment Into Lung Airspaces
Authors: Arnold Stephanie , Shah Sajeel A. , Cleary Simon J. , O'Shaughnessy Blaze G. , Amison Richard T. , Arkless Kate , Page Clive P. , Pitchford Simon C.
Published: December 2020

Hemolysis that occurs in intravascular hemolytic disorders, such as sickle cell disease and malaria, is associated with inflammation and platelet activation. Alveolar hemorrhage, for example following primary blast lung injury or acute respiratory distress syndrome, results in the escape of erythrocytes (RBCs) into alveolar spaces, where they subsequently lyse and release their intracellular contents. However, the inflammatory effects of RBCs in the airways are not fully understood. We hypothesized that RBCs in the airway induce an inflammatory response, associated with platelet activation. By instilling whole RBCs or lysed RBCs into the airways of mice, we have demonstrated that whole RBCs elicit macrophage accumulation in the lung. On the other hand, lysed RBCs induce significant inflammatory cell recruitment, particularly neutrophils and this was associated with a 50% increase in circulating platelet neutrophil complexes. Platelet depletion prior to lysed RBC exposure in the lung resulted in reduced neutrophil recruitment, suggesting that the presence of intracellular RBC components in the airways can elicit inflammation that is platelet dependent. To identify specific platelet-dependent signaling pathways involved in neutrophil recruitment, anti-P-selectin ligand and anti-PSGL1 blocking antibodies were tested; however, neither affected neutrophil recruitment. These findings implicate an involvement for other, as yet unidentified platelet-dependent signaling and adhesion mechanisms. Further understanding of how platelets contribute to lung inflammation induced by the presence of RBCs could offer novel therapeutic approaches to attenuate inflammation that occurs in conditions associated with alveolar hemorrhage.
SARS Coronavirus-2 microneutralisation and commercial serological assays correlated closely for some but not all enzyme immunoassays
Authors: Walker Gregory J , Naing Zin , Stella Alberto Ospina , Yeang Malinna , Caguicla Joanna , Ramachandran Vidiya , Isaacs Sonia R , Agapiou David , Bull Rowena A , Stelzer-Braid Sacha , Daly James , Gosbell Iain B , Hoad Veronica C , Irving David O , Pink Joanne M , Turville Stuart , Kelleher Anthony D , Rawlinson William D
Published: December 2020

Background

Serological testing for SARS-CoV-2 specific antibodies provides important research and diagnostic information relating to COVID-19 prevalence, incidence, and host immune response. A greater understanding of the relationship between functionally neutralising antibodies detected using microneutralisation assays and binding antibodies detected using scalable enzyme immunoassays (EIA) is needed in order to address protective immunity post-infection or vaccination, and assess EIA suitability as a surrogate test for screening of convalescent plasma donors. We assessed whether neutralising antibody titres correlated with signal cut-off ratios in five commercially available EIAs, and one in-house assay based on expressed spike protein targets.

Methods

Sera from individuals recovered from patients or convalescent plasma donors who reported laboratory-confirmed SARS-CoV-2 infection (n=200), and negative control sera collected prior to the COVID-19 pandemic (n=100) were assessed in parallel. Performance was assessed by calculating EIA sensitivity and specificity with reference to microneutralisation.

Results

Neutralising antibodies were detected in 166 (83%) samples. Compared with this, the most sensitive EIAs were the Cobas Elecsys Anti-SARS-CoV-2 (98%) and Vitros Immunodiagnostic Anti-SARS-CoV-2 (100%), which detect total antibody targeting the N and S1 antigens, respectively. The assay with the best quantitative relationship with microneutralisation was the Euroimmun IgG.

Conclusions

These results suggest the marker used (total Ab vs IgG vs IgA), and the target antigen are important determinants of assay performance. The strong correlation between microneutralisation and some commercially available assays demonstrate their potential for clinical and research use in assessing protection following infection or vaccination, and use as a surrogate test to assess donor suitability for convalescent plasma donation.
Feeding Experimentation Device version 3 (FED3): An open-source home-cage compatible device for measuring food intake and operant behavior
Authors: Matikainen-Ankney Bridget A. , Earnest Thomas , Ali Mohamed , Casey Eric , Sutton Amy K. , Legaria Alex , Barclay Kia , Murdaugh Laura B. , Norris Makenzie R. , Chang Yu-Hsuan , Nguyen Katrina P. , Lin Eric , Reichenbach Alex , Clarke Rachel E. , Stark Romana , Conway Sineadh M. , Carvalho Filipe , Al-Hasani Ream , McCall Jordan G. , Creed Meaghan C. , Cazares Victor , Buczynski Matthew W. , Krashes Michael J. , Andrews Zane , Kravitz Alexxai V.
Published: December 2020

Feeding is critical for survival and disruption in the mechanisms that govern food intake underlie disorders such as obesity and anorexia nervosa. It is important to understand both food intake and food motivation to reveal mechanisms underlying feeding disorders. Operant behavioral testing can be used to measure the motivational component to feeding, but most food intake monitoring systems do not measure operant behavior. Here, we present a new solution for monitoring both food intake and motivation: The Feeding Experimentation Device version 3 (FED3). FED3 measures food intake and operant behavior in rodent home-cages, enabling longitudinal studies of feeding behavior with minimal experimenter intervention. It has a programmable output for synchronizing behavior with optogenetic stimulation or neural recordings. Finally, FED3 design files are open-source and freely available, allowing researchers to modify FED3 to suit their needs. In this paper we demonstrate the utility of FED3 in a range of experimental paradigms.

In Brief

Using a novel, high-throughput home cage feeding platform, FED3, Matikainen-Ankney et al. quantify food intake and operant learning in groups of mice conducted at multiple institutions across the globe. Results include rates of operant efficiency, circadian feeding patterns, and operant optogenetic self-stimulation.

Highlights

The Feeding Experimentation Device version 3(FED3) records food intake and operant behavior in rodent home cages.

Analysis of food intake includes total intake, meal pattern analysis, and circadian analysis of feeding patterns.

FED3 also allows for operant behavioral assays to examine food learning and motivation.
Systems-informed genome mining for electroautotrophic microbial production
Authors: Abel Anthony J. , Hilzinger Jacob M. , Arkin Adam P. , Clark Douglas S.
Published: December 2020

Microbial electrosynthesis (MES) systems can store renewable energy and CO2in many-carbon molecules inaccessible to abiotic electrochemistry. Here, we develop a multiphysics model to investigate the fundamental and practical limits of MES enabled by direct electron uptake and we identify organisms in which this biotechnological CO2-fixation strategy can be realized. Systematic model comparisons of microbial respiration and carbon fixation strategies revealed that, under aerobic conditions, the CO2fixation rate is limited to <6 μmol/cm2/hr by O2mass transport despite efficient electron utilization. In contrast, anaerobic nitrate respiration enables CO2fixation rates >50 μmol/cm2/hr for microbes using the reductive tricarboxylic acid cycle. Phylogenetic analysis, validated by recapitulating experimental demonstrations of electroautotrophy, uncovered multiple probable electroautotrophic organisms and a significant number of genetically tractable strains that require heterologous expression of <5 proteins to gain electroautotrophic function. The model and analysis presented here will guide microbial engineering and reactor design for practical MES systems.
Trends in Phase II trials for cancer therapies
Authors: Azam Faruque , Vazquez Alexei
Published: December 2020

Background

Drug combinations are the standard of care in cancer treatment. Identifying effective cancer drug combinations has become more challenging because of the increasing number of drugs. However, a substantial number of cancer drugs stumble at Phase III clinical trials despite exhibiting favourable efficacy in the earlier Phase.

Methods

We analysed recent Phase II cancer trials comprising 2,165 response rates to uncover trends in cancer therapies and used a null model of non-interacting agents to infer synergistic and antagonistic drug combinations. We compared our latest efficacy dataset with a previous dataset to assess the progress of cancer therapy.

Results

We demonstrate that targeted therapies should be used in combination with cytotoxic drugs to reach high response rates. We identify 4 synergistic and 10 antagonistic combinations based on the observed and expected response rates. We also demonstrate that recent targeted agents have not significantly increased the response rates.

Conclusions

We conclude either we are not making progress or response rate measured by tumour shrinkage is not a reliable surrogate endpoint for the targeted agents.
Advanced in silico validation framework for three-dimensional Traction Force Microscopy and application to an in vitro model of sprouting angiogenesis
Authors: Barrasa-Fano J. , Shapeti A. , de Jong J. , Ranga A. , Sanz-Herrera J.A. , Van Oosterwyck H.
Published: December 2020

In the last decade, cellular forces in three-dimensional hydrogels that mimic the extracellular matrix have been calculated by means of Traction Force Microscopy (TFM). However, characterizing the accuracy limits of a traction recovery method is critical to avoid obscuring physiological information due to traction recovery errors. So far, 3D TFM algorithms have only been validated using simplified cell geometries, bypassing image processing steps or arbitrarily simulating focal adhesions. Moreover, it is still uncertain which of the two common traction recovery methods, i.e., forward and inverse, is more robust against the inherent challenges of 3D TFM. In this work, we established an advanced in silico validation framework that is applicable to any 3D TFM experimental setup and that can be used to correctly couple the experimental and computational aspects of 3D TFM. Advancements relate to the simultaneous incorporation of complex cell geometries, simulation of microscopy images of varying bead densities and different focal adhesion sizes and distributions. By measuring the traction recovery error with respect to ground truth solutions, we found that while highest traction recovery errors occur for cases with sparse and small focal adhesions, our implementation of the inverse method improves two-fold the accuracy with respect to the forward method (average error of 23% vs. 50%). This advantage was further supported by recovering cellular tractions around angiogenic sprouts in an in vitro model of angiogenesis. The inverse method recovered more realistic traction patterns than the forward method, showing higher traction peaks and a clearer pulling pattern at the sprout protrusion tips.
Using weapons instead of perfume – chemical association strategies of the myrmecophilous bugScolopostethus pacificus(Rhyparochromidae)
Authors: Brückner Adrian
Published: December 2020

A vast diversity of parasites associate with ants. Living in and around ant nests these organisms must overcome ant colony defenses. As ant defensive behavior is mainly mediated by species-specific cuticular hydrocarbons (CHCs) or alarm pheromones, ant-associated parasites can either crack their hosts chemical communication code by modifying their own CHC-profiles or use pro-active strategies like chemical weaponry for distraction and repellency. While the chemical nature of ant-parasite interactions has been intensively studied for highly host specific parasites, the chemical-deceptive strategies of the rather rare ant-resembling Heteropterans are unknown. To gain insight into this system, I studied the bugScolopostethus pacificus(Barber 1918) which can be found near the nests of the ecologically dominant and aggressive velvety tree ant (Liometopum occidentale, Emery 1895). Using behavioral, chemical and molecular approaches I disentangled the relationship ofS. pasificusand its host ant. Chemical profiling of the bug and the ant revealed that the bug does not make use of CHC insignificance or mimicry, but instead uses a cocktail of volatile compounds released from its metathoracic glands that likely moderates encounters with its aggressive host. Feeding trials with armed and artificially disarmed bugs revealed a defensive function of the gland exudates. Targeted molecular gut barcoding showed thatS. pasificusdoes not feed onL. occidentale. These results suggest that chemical weaponry, rather than a chemical code-cracking CHC matching or chemical insignificance, enablesS. pasificusto get along with and live in close proximity to its host ant.
Fractional response analysis reveals logarithmic cytokine responses in cellular populations
Authors: Nienałtowski Karol , Rigby Rachel E. , Walczak Jarosław , Zakrzewska Karolina E. , Rehwinkel Jan , Komorowski Michał
Published: December 2020

Although we can now measure single-cell signaling responses with multivariate, high-throughput techniques our ability to interpret such measurements is still limited. Even interpretation of dose-response based on single-cell data is not straightforward: signaling responses can differ significantly between cells, encompass multiple signaling effectors, and have dynamic character. Here, we use probabilistic modeling and information-theory to introduce fractional response analysis (FRA), which quantifies changes in fractions of cells with given response levels. FRA can be universally performed for heterogeneous, multivariate, and dynamic measurements and, as we demonstrate, uncovers otherwise hidden patterns in single-cell data. In particular, we show that fractional responses to type I interferon in human peripheral blood mononuclear cells are very similar across different cell types, despite significant differences in mean or median responses and degrees of cell-to-cell heterogeneity. Further, we demonstrate that fractional responses to cytokines scale linearly with the log of the cytokine dose, which uncovers that cellular populations are sensitive to fold-changes in the dose, as opposed to additive changes.
Assessment of microbial communities in Nakivubo wetland and its catchment areas in Lake Victoria Basin, Uganda
Authors: Kanoi Bernard N. , Gamboa Maribet , Ngonzi Doris , Egwang Thomas G.
Published: December 2020

Microbial community structure changes are key in detecting and characterizing the impacts of anthropogenic activities on aquatic ecosystems. Here, we evaluated the effect of river pollution of industrial and urban sites on the microbial community composition and distribution in the Nakivubo wetland and its catchment areas in Lake Victoria basin, Uganda. Samples were collected from two industrial and one urban polluted sites and the microbial diversity was analyzed based on a 16S rRNA gene clone library. Differences in microbial diversity and community structure were observed at different sampling points. Bacteria associated with bioremediation were found in sites receiving industrial waste, while a low proportion of important human-pathogenic bacteria were seen in urban polluted sites. WhileEscherichiaspp. was the most dominant genus of bacteria for all sites, three unique bacteria,Bacillus sp., Pseudomonas sp., Thermomonas sp., which have been reported to transform contaminants such as heavy metals and hydrocarbons (such as oils) by their metabolic pathways were also identified. Our results may serve as a basis for further studies assessing microbial community structure changes among polluted sites at Nakivubo Water Channel for management and monitoring. The diversity of natural microbial consortia could also be a rich bioprospecting resource for novel industrial enzymes, medicinal and bioactive compounds.
Demographic analysis of IsraeliCarpobrotuspopulations: management strategies and future directions
Authors: Bogdan Ana , Levin Sam C. , Salguero-Gómez Roberto , Knight Tiffany M.
Published: December 2020

Carpobrotusspecies are harmful invaders to coastal areas throughout the world, particularly in Mediterranean habitats. Demographic models are ideally suited to identify and understand population processes and stages in the life cycle of the species that could be most effectively targeted with management. However, parameterizing these models has been limited by the difficulty in accessing the cliff-side locations where its populations are typically found, as well as accurately measuring the growth and spread individuals, which form large, dense mats. This study uses small unmanned aerial vehicles (UAVs, drones) to collect demographic data and parameterize an Integral Projection Model of an IsraeliCarpobrotuspopulation. We validated our data set with ground targets of known size. Through the analysis of asymptotic growth rates and population sensitivities and elasticities, we demonstrate that the population at the study site is demographically stable, and that reducing the survival and growth of the largest individuals would have the greatest effect on reducing overall population growth rate. Our results provide a first evaluation of the demography ofCarpobrotus,a species of conservation and economic concern, and provide the first stage-based population model of a representative of the Aizoaceae family, thus contributing to our global knowledge on plant population dynamics. In addition, we demonstrate the advantages of using drones for collecting demographic data in understudied habitats such as coastal ecosystems.
Temperature-induced compensatory growth inC. elegansis regulated by a thermosensitive TRP channel and influences reproductive rate
Authors: Sekajova Zuzana , Rosa Elena , Spagopoulou Foteini , Zervakis Panagiotis-Ioannis , Lind Martin I.
Published: December 2020

Animals are often not growing at the maximum rate, but can compensate for a bad start of life by subsequently increasing growth rate. While this compensatory growth is widespread, its direct fitness consequences are seldom investigated and its genetic basis is unknown.

We investigated the genetic regulation, as well as fitness and lifespan consequences of compensatory growth in response to temperature, usingC. elegansknockout of the thermo-sensitive TRP ion channel TRPA-1, involved in temperature recognition. We exposed juvenile worms to cold, favourable (intermediate) or warm temperatures in order to delay or speed up development.

Wild-type worms initially exposed to cold temperature experienced slower growth but after being switched to a more favourable temperature, they expressed compensatory growth and caught up in size. Those initially reared at warmer temperatures than favourable experienced slower growth and attained smaller adult size after being switched to the most favourable temperature.

Compensatory growth also altered the reproductive schedule. While rate-sensitive individual fitness decreased by cold juvenile temperatures, as a direct effect of the substantial developmental delay, once worms returned to more favourable temperature, they shifted their reproductive schedule towards early reproduction. Therefore, when focusing on the post-treatment period, the reproductive rate increased even though lifetime reproductive success was unaffected. Surprisingly, compensatory growth did not reduce adult lifespan. In contrast to the findings for wild-type worms, juvenile temperature did not induce compensatory or slowed-down growth in thetrpa-1knockout mutants.

We thus show that thetrpa-1is involved in the network regulating temperature-induced compensatory growth inC. elegansand that this compensatory growth can influence the reproductive rate.
The temperature-dependent predatory strike of Odonata larvae
Authors: Koehnsen Alexander , Tröger Hannah-Lena , Gorb Stanislav N , Büsse Sebastian
Published: December 2020

The larvae of Odonata are limnic predators capable of catching their prey using a highly modified mouthpart – the labium. Driven by a unique dual catapult mechanism, the apparatus can reach peak accelerations of up to 114.5m/s2. Yet little is known about the kinematics of the predatory strike in an ecological context. Here we show how different ambient temperatures affect the predatory strike and the avoidance reaction of prey items of Odonata larvae. We found that the extension velocity of the labial mask decreases significantly with the ambient temperature both in dragonflies and damselflies. However, temperature has lesser impact on the predatory strike itself than on directly muscle driven movements in both the predator and prey items. This contradicts the previous assumption that catapult mechanisms in insects are unaffected by temperature. Our results indicate that the prehensile labial mask is driven by a series-elastic catapult; a mechanism similar to the temperature dependent jump of frogs, where muscle and spring action are tightly linked. Our study provides novel insights into the predatory strike of Odonata larvae and offers a new ecological perspective on catapult mechanisms in arthropods in general.