bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of Fractional CO2 Laser in Cleft Lip Scars
Authors: Shadad Mohamed , Ali Wagdi M. , Fayyaz Ghulam Qadir , El-Shazly Mohamed
Published: August 2020

Background

Whatever the technique of the surgical repair, the scar remains and it is the most common cause for parent's and patient's dissatisfaction. We aimed in this work to evaluate the efficacy of the fractional CO2 (FCO2) laser on the later appearance of cleft lip scars in general and to compare between the early and late use of this tool to know its ideal application time in particular. To our knowledge, there are no published reports about this objective with regard to the number of patients and the concerned designated study.

Patients and Methods

One hundred twenty patients complaining of cleft lip scar were divided into 3 groups. Group 1 started FCO2 application 3 weeks postoperatively, group 2 started it 3 months postoperatively, and group 3 applied local creams only as a control group. Fractional CO2 laser had been applied for 5 to 7 sessions. Vancouver scar scale was used for scar evaluation determining vascularity, pigmentation, pliability, and height. Visual analog scale was also used depending on 5 independent physicians and nonmedical personnel to rate results on a graded scale from 0 to 10. Moreover, the scar width had been assessed through studying the final images by Photoshop CS5 Extended Version, in 2 fixed points of the scar width.

Results

Patients showed a great degree of improvement in their lip scar after FCO2 laser sessions. Vancouver Scar Scale score had insignificant differences between studied groups at the baseline before applying either FCO2 or local cream, whereas after their applications, it was significantly lower in group 1 (1.92 ± 0.88) in comparison with group 2 (3.70 ± 1.11) and group 3 (4.05 ± 1.29). Regarding scar width assessment, it was significantly lower in group 1 (2.51 ± 0.64) in comparison with groups 2 (3.17 ± 0.54) and 3 (3.27 ± 0.48). The visual analog scale by the participating medical personnel indicated that the FCO2-induced improvement in the lip scar appearance in group 1 more than groups 2 and 3 with a mean score of 44.17 ± 3.45, 36.53 ± 4.43, and 30.40 ± 5.22, respectively. The same assessment by the participating nonmedical personnel was significantly higher in group 1 (43.52 ± 4.20) in comparison with group 2 (37.52 ± 4.73) and group 3 (33.55 ± 4.85).

Conclusions

We proved that using FCO2 is significantly better than using local creams in the postoperative management of cleft lip scars. More in depth, the early application of this tool is also significantly better than its delayed use.

Clinical Trials Registration Name: Assessment of Fractional CO2 Laser in Treatment of Post-surgical Scarring of Cleft Lip

URL:
https://clinicaltrials.gov/ct2/show/NCT03277287?cond=Assessment+of+Fractional+CO2+Laser+in+Treatment+of+Post-surgical+Scarring+of+Cleft+Lip&draw=2&rank=1

Clinical Trials ID: NCT03277287

Registration Date: June 9, 2017, retrospectively registered
Trauma-Hemorrhage Stimulates Immune Defense, Mitochondrial Dysfunction, Autophagy, and Apoptosis in Pig Liver at 72 h
Authors: Shi Yulong , Greven Johannes , Guo Weijun , Luo Peng , Xu Ding , Wang Weikang , Relja Borna , Vollrath Jan T. , Buhl Eva Miriam , Horst Klemens , Bolierakis Eftychios , Bläsius Felix , Hildebrand Frank
Published: August 2020

Hepatic dysfunction frequently occurs after trauma-hemorrhage, resulting in severe pathophysiological responses that include leukocyte shifting and self-mediated mechanisms of cells, such as autophagy and apoptosis. This in vivo study aimed to characterize mitochondrial morphology, leukocyte reaction, and the processes of autophagy and apoptosis after polytrauma hemorrhage (TH) in a long-term, large animal model.

Liver tissue was taken from a porcine TH model (hemorrhagic shock, blunt chest trauma, tibia fracture, and liver laceration) with an intensive care unit follow-up of 72 h. The ultrastructural changes of the liver tissue after TH were evaluated by transmission electron microscopy. The leukocyte phenotypes and autophagy and apoptosis pathways were elucidated by immunohistofluorescence, Western blot, and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL).

In addition to post-traumatic changes in the mitochondrial morphology, the biomarkers of anti-inflammatory macrophages (CD163) and reparative monocytes (CD11R3 and CD16) were upregulated, while the inducible nitric oxide synthase was downregulated after TH. Furthermore, the autophagy-related protein expressions of LC3 and Beclin-1 were upregulated, whereas the protein expression of P62 was downregulated after TH. Costaining showed that the macrophages were LC3 (or Beclin-1) positive and that CD163 was copositive and upregulated. Apoptosis biomarkers (cleaved-caspase-3/caspase-3 and Bcl-2) increased after TH, which is in line with TUNEL results.

In conclusion, the observed findings indicate that mitochondrial dysfunction might be one trigger of hepatic autophagy and apoptosis after TH. These processes occur together with the activation of anti-inflammatory leukocytes in liver tissue. Further studies are needed to elucidate the potential therapeutic effects of inhibiting mitochondrial swelling during autophagy or apoptosis.
Early Sequential Microcirculation Assessment In Shocked Patients as a Predictor of Outcome: A Prospective Observational Cohort Study
Authors: Holley Anthony D. , Dulhunty Joel , Udy Andrew , Midwinter Mark , Lukin Bill , Stuart Janine , Boots Robert , Lassig-Smith Melissa , Holley Robert B. , Paratz Jenny , Lipman Jeffrey
Published: August 2020

Objectives:

A dysfunctional microcirculation is universal in shock and is often dissociated from global hemodynamic parameters. Persistent microcirculatory derangements reflect ongoing tissue hypoperfusion and organ injury. The initial microcirculatory dysfunction and subsequent resolution could potentially guide therapy and predict outcomes. We evaluated the microcirculation early in a heterogenous shocked population. Microcirculatory resolution was correlated with measures of tissue perfusion and global hemodynamics. The relationship between the microcirculation over 24 h and outcome were evaluated.

Design:

We prospectively recruited patients with all forms of shock, based on global hemodynamics and evidence of organ hypoperfusion.

Setting:

A 30-bed adult intensive care unit (ICU).

Patients:

Eighty-two shocked patients.

Measurements and Main Results:

Following the diagnosis of shock, patients underwent a sublingual microcirculation examination using Sidestream Dark Field Imaging. The median age of patients was 66 years old (interquartile range [IQR] 54–71), with an Acute Physiology and Chronic Health Evaluation II of 27 (IQR 20–32). Microcirculatory parameters included Percentage Perfused Vessels (PPV), De Backer Score, and a heterogeneity index in patients with septic shock, according to the second consensus guidelines Additional parameters collected: temperature, heart rate and arterial pressure, cumulative fluid balance, and vasopressor use. Arterial blood samples were taken at the time of microcirculatory assessments, providing HCO3, lactate concentrations, PaO2, and PaCO2 measurements. A statistically significant improvement in PPV and the heterogeneity index was demonstrated. This improvement was mirrored by biomarkers of perfusion; however, the global hemodynamic parameter changes were not significantly different over the 24-h period. The early microcirculatory improvement was not predictive of an improvement in acute kidney injury, length of stay, ICU, or hospital mortality.

Conclusions:

Early sequential evaluation of the microcirculation in shocked patients, demonstrated statistically significant improvement in the PPV and microvascular heterogeneity with standard care. These improvements were mirrored by biomarkers of organ perfusion; however, the changes in global hemodynamics were not as pronounced in this early phase. Early improvement in the microcirculation did not predict clinical outcome.
Thrombin Generation Kinetics are Predictive of Rapid Transfusion in Trauma Patients Meeting Critical Administration Threshold
Authors: MacArthur Taleen A. , Spears Grant M. , Kozar Rosemary A. , Dong Jing-fei , Auton Matthew , Jenkins Donald H. , Bailey Kent R. , Ashrani Aneel A. , Ferrara Mike J. , Immermann Joseph M. , Halling Timothy M. , Park Myung S.
Published: August 2020

Introduction:

We hypothesize that a patient (pt) with accelerated thrombin generation, time to peak height (ttPeak), will have a greater odds of meeting critical administration threshold (CAT) criteria (> 3 packed red blood cell [pRBC] transfusions [Tx] per 60 min interval), within the first 24 h after injury, independent of international normalized ratio (INR).

Methods:

In a prospective cohort study, trauma patients were enrolled over a 4.5-year period and serial blood samples collected at various time points. We retrospectively stratified pts into three categories: CAT+, CAT− but receiving some pRBC Tx, receiving no Tx within the first 24 h. Blood collected prior to Tx was analyzed for thrombin generation parameters and prothrombin time (PT)/INR.

Results:

A total of 484 trauma pts were analyzed: injury severity score = 13 [7,22], age = 48 [28, 64] years, and 73% male. Fifty pts met criteria for CAT+, 64 pts CAT−, and 370 received no Tx. Risk factors for meeting CAT+: decreased arrival systolic blood pressure (OR 2.82 [2.17, 3.67]), increased INR (OR 2.09, [1.66, 2.62]) and decreased time to peak OR 2.27 [1.74, 2.95]). These variables remained independently associated with increased risk of requiring Tx in a multivariable logistic model, after adjusting for sex and trauma type.

Conclusions:

Pts in hemorrhagic shock, who meet CAT+ criteria, are characterized by accelerated thrombin generation. In our multivariable analysis, both ttPeak and PT/INR have a complementary role in predicting those injured patients who will require a high rate of Tx.
Resolved External Ophthalmoplegia and Hearing Loss in Wernicke's Encephalopathy With Thiamine Replacement
Authors: Nyce Maxwell Q. , Chisholm Joshua S. , Szmanda Julia A. , Boyce A. Katharina , Boczar Caroline M. , Kattah Jorge C.
Published: August 2020

Background:

Wernicke encephalopathy (WE) is classically described by a clinical triad consisting of confusion, ataxia, and ophthalmoplegia, but recent reports emphasize a history of malnutrition along with 2 elements of the WE triad (Caine's criteria) to enhance diagnostic sensitivity. The ophthalmoplegia, vestibular, and auditory expeditious improvement with intravenous thiamine usually confirms the diagnosis; serum levels generally provide additional diagnostic certainty.

Methods:

Here, we discuss the case of a woman with a distant history of gastric sleeve, poor nutrition and protracted vomiting, who developed acute confusion, imbalance, near-total external ophthalmoplegia (EO), and hearing loss. The baseline thiamine level was 28 πmol/L (Normal: 70–180 πmol/L). We performed serial neurological, vestibular, and audiological examination to document over 5 days, the effect of intravenous (IV) thiamine, and again at 3 months with continued oral supplementation. We provide serial documentation with photographs and video recording of oculomotor abnormalities, audiometric testing, and a video of horizontal head impulse testing, and imaging findings.

Results:

Over the course of 5 days of IV thiamine supplementation, we demonstrate our patient's resolution of near complete EO. We assessed vestibular paresis with horizontal head impulse testing, after complete resolution of the EO. The initially positive bilateral h-HIT showed decreased gain and overt corrective saccades, it clinically resolved by day 5, but video h-HIT testing demonstrated persistent decreased horizontal vestibulo-ocular reflex (VOR) gain and covert horizontal saccades, which persisted at the 3-month examination. By contrast, the vertical VOR gain was normal without corrective saccades. Bedside audiometry completed during the acute phase demonstrated severely restricted auditory speech comprehension, which normalized 3 months later. Severe truncal ataxia improved as well.

Conclusions:

This case is an example of how awareness of the variations in the clinical presentation of WE can be crucial in achieving an early diagnosis and obtaining better outcomes. A history of the poor nutritional status can be an important clue to aid in this early diagnosis.
Comprehensive evaluation of cardiovascular efficacy and safety outcomes of SGLT2 inhibitors in high risk patients of cardiovascular disease: systematic review and meta-analysis
Authors: Bhattarai Mukul , Salih Mohsin , Regmi Manjari , Al-akchar Mohammad , Koester Cameron , Ibrahim Abdisamad , Parajuli Priyanka , Garcia Odalys Lara , Bhandari Bishal , Rehman Anis , Siddique Momin
Published: August 2020

Objectives

To demonstrate a magnitude of the cardiovascular benefits, concomitantly analyzing the safety outcomes of sodium-glucose cotransporter 2 inhibitor (SGLT2-I) comprehensively, as a class effect in a larger sample size combined from recent randomized control trials.

Methods

We searched electronic databases using specific terms and evaluated 6 efficacy and 10 safety outcomes. Odds ratios (ORs) and 95% confidence interval (CI) were used to compare two interventions.

Results

Five studies (n = 41 267) were included, among which 23 539 received SGLT2-I. The SGLT2-I group favored reduction in major adverse cardiovascular events (OR, 0.78; 95% CI, 0.62–0.98; P = 0.03), cardiovascular death (CVD) or heart failure hospitalization (OR, 0.60; 95% CI, 0.46–0.80; P = 0.0004), rate of hospitalization for heart failure (OR, 0.56; 95% CI, 0.44–0.72; P < 0.00001), CVD (OR, 0.68; 95% CI, 0.50–0.93; P = 0.01), all-cause mortality (OR, 0.67; 95% CI, 0.48–0.93; P = 0.02) and myocardial infarction (OR, 0.79; 95% CI, 0.64–0.99; P = 0.04) when compared to the placebo group. Safety analysis showed higher diabetic ketoacidosis (DKA) rate in SGLT2-I group (OR, 2.33; 95% CI, 1.40–3.90; P = 0.001); in contrast, major hypoglycemic events were significantly lower (OR, 0.79; 95% CI, 0.73–0.87; P < 0.00001). AKI was significantly higher in the placebo group (OR, 0.76; 95% CI, 0.65–0.88; P = 0.0004). There were no statistically significant effects on other outcomes.

Conclusion

In selected high-risk patients of cardiovascular disease, the SGLT2-I is a potential effective class of drugs for improving cardiovascular outcomes and all-cause mortality without an increased risk of all other major complications except DKA on this meta-analysis.
SARS-CoV-2 growth, furin-cleavage-site adaptation and neutralization using serum from acutely infected hospitalized COVID-19 patients
Authors: Klimstra William B. , Tilston-Lunel Natasha L. , Nambulli Sham , Boslett James , McMillen Cynthia M. , Gilliland Theron , Dunn Matthew D. , Sun Chengun , Wheeler Sarah E. , Wells Alan , Hartman Amy L. , McElroy Anita K. , Reed Douglas S. , Rennick Linda J. , Duprex W. Paul
Published: August 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), emerged at the end of 2019 and by mid-June 2020 the virus had spread to at least 215 countries, caused more than 8 000 000 confirmed infections and over 450 000 deaths, and overwhelmed healthcare systems worldwide. Like severe acute respiratory syndrome coronavirus (SARS-CoV), which emerged in 2002 and caused a similar disease, SARS-CoV-2 is a betacoronavirus. Both viruses use human angiotensin-converting enzyme 2 (hACE2) as a receptor to enter cells. However, the SARS-CoV-2 spike (S) glycoprotein has a novel insertion that generates a putative furin cleavage signal and this has been postulated to expand the host range. Two low-passage (P) strains of SARS-CoV-2 (Wash1 : P4 and Munich : P1) were cultured twice in Vero E6 cells and characterized virologically. Sanger and MinION sequencing demonstrated significant deletions in the furin cleavage signal of Wash1 : P6 and minor variants in the Munich : P3 strain. Cleavage of the S glycoprotein in SARS-CoV-2-infected Vero E6 cell lysates was inefficient even when an intact furin cleavage signal was present. Indirect immunofluorescence demonstrated that the S glycoprotein reached the cell surface. Since the S protein is a major antigenic target for the development of neutralizing antibodies, we investigated the development of neutralizing antibody titres in serial serum samples obtained from COVID-19 human patients. These were comparable regardless of the presence of an intact or deleted furin cleavage signal. These studies illustrate the need to characterize virus stocks meticulously prior to performing either in vitro or in vivo pathogenesis studies.
ELISA detection of SARS-CoV-2 antibodies in saliva
Authors: MacMullan Melanie A. , Ibrayeva Albina , Trettner Kylie , Deming Laura , Das Sudipta , Tran Frances , Moreno Jose Ricardo , Casian Joseph G. , Chellamuthu Prithivi , Kraft Jeffrey , Kozak Kenneth , Turner Fred E. , Slepnev Vladimir I. , Le Page Lydia M.
Published: August 2020

To facilitate containment of the COVID-19 pandemic currently active in the United States and across the world, options for easy, non-invasive antibody testing are required. Here we have adapted a commercially available, serum-based ELISA for use with saliva samples, which will enable widespread, affordable testing for patients who experienced this disease.
Estimating Cumulative COVID-19 Infections by a Novel “Pandemic Rate Equation”
Authors: Hamilton David H.
Published: August 2020

A fundamental problem dealing with the Covid-19 pandemic has been to estimate the rate of infection, since so many cases are asymptomatic and contagious just for a few weeks. For example, in the US, estimate the proportion P(t) = N/330 where N is the US total who have ever been infected (in millions)at time t (months, t = 0 being March 20). This is important for decisions on social restrictions, and allocation of medical resources, etc. However, the demand for extensive testing has not produced good estimates. In the US, the CDC has used the blood supply to sample for anti-bodies. Anti-bodies do not tell the whole picture, according to the Karolinska Instituet [2], many post infection cases show T-cell immunity, but no anti-bodies. We introduce a method based on a difference-differential equation (dde) for P(t). We emphasize that this is just for the present, with no prediction on how the pandemic will evolve. The dde uses only x = x (s), which is the number/million testing positive, and y = y (s), the number/million who have been tested for all time 0 ≤ s ≤ t (months), with no assumptions on the dynamics of the pandemic. However, we need two parameters. First, ρ, the ratio of asymptomatic to symptomatic infected cases. Second, τ, the period of active infection when the virus can be detected. Both are random variables with distribution which can be estimated. For fixed ρ, we prove uniform bounds

are best possible, with range depending on τ. One advantage of our theory is being able to estimate P for many regions and countries where x and y is the only information available.
Generalizability of Polygenic Risk Scores for Breast Cancer in the Multiethnic eMERGE Study
Authors: Liu Cong , Zeinomar Nur , Chung Wendy K. , Kiryluk Krzysztof , Ghravi Ali G. , Hripcsak George , Crew Katherine D. , Shang Ning , Khan Atlas , Fasel David , Manolio Teri A. , Jarvik Gail P. , Rowley Robb , Justice Ann E. , Rahm Alanna K. , Fullerton Stephanie M. , Smoller Jordan W. , Larson Eric B. , Crane Paul K. , Dikilitas Ozan , Terry Mary Beth , Weng Chunhua
Published: August 2020

Background

The majority of polygenic risk scores (PRS) for breast cancer have been developed and validated using cohorts of European ancestry (EA). Less is known about the generalizability of these PRS in other ancestral groups.

Methods

The Electronic Medical Records and Genomics (eMERGE) network cohort dataset was used to evaluate the performance of seven previously developed PRS (three EA-based PRSs, and four non-EA based PRSs) in three major ancestral groups. Each PRS was separately evaluated in EA (cases: 3939; controls: 28840), African ancestry (AA) (cases: 121; controls: 1173) and self-reported LatinX ancestry (LA) (cases: 92; controls: 1363) women. We assessed the association between breast cancer risk and each PRS, adjusting forage, study site, breast cancer family history, and first three ancestry informative principal components.

Results

EA-based PRSs were significantly associated with breast cancer risk in EA women per one SD increase (odds ratio [OR] = 1.45, 95% confidence interval [CI] = 1.40–1.51), and LA women (OR = 1.41, 95% CI = 1.13–1.77), but not AA women (OR = 1.13, 95% CI = 0.92–1.40). There was no statistically significant association for the non-EA PRSs in all ancestry groups, LA including an LA-based PRS and an AA-based PRS.

Conclusion

We evaluated EA-derived PRS for estimating breast cancer risk using the eMERGE dataset and found they generalized well in LA women but not in AA women. For non-EA based PRSs, we did not replicate previously reported associations for the respective ancestries in the eMERGE cohort. Our results highlight the need to improve representation of diverse population groups, particularly AA women, in research cohorts.
A Deep Learning Model to Predict the Need for Mechanical Ventilation Using Chest X-Ray Images in Hospitalized COVID-19 Patients
Authors: Kulkarni Anoop , Athavale Ambarish M. , Sahni Ashima , Sukhal Shashvat , Sahni Abhimanyu , Itteera Mathew , Zhukovsky Sara , Vernik Jane , Abraham Mohan , Joshi Amit , Amarah Amatur , Ruiz Juan , Hart Peter D. , Kulkarni Hemant
Published: August 2020

Purpose

Early identification of a potentially deteriorating clinical course in hospitalized COVID-19 patients is critical since there exists a resource-demand gap for the ventilators.

Materials

We aimed to develop and validate a deep learning-based approach to predict the need for mechanical ventilation as early as at the time of initial radiographic evaluation. We exploited the well-established DenseNet121 deep learning architecture for this purpose on 663 X-ray images derived from 528 hospitalized COVID-19 patients. Two Pulmonary and Critical Care experts blindly and independently evaluated the same X-ray images for purpose of validation.

Results

We found that our deep learning model predicted the need for ventilation with a high accuracy, sensitivity and specificity (90.06%, 86.34% and 84.38%, respectively). This prediction was done approximately three days ahead of the actual intubation event. Our model also outperformed two Pulmonary and Critical Care experts who evaluated the same X-ray images and provided an incremental accuracy of 7.24–13.25%.

Conclusion

Our deep learning model accurately predicted the need for mechanical ventilation early during hospitalization of COVID-19 patients. Until effective preventive or treatment measures become widely available for COVID-19 patients, prognostic stratification as provided by our model is likely to be highly valuable.
DEEP LEARNING TO PREDICT DEGREE OF INTERSTITIAL FIBROSIS AND TUBULAR ATROPHY FROM KIDNEY ULTRASOUND IMAGES – AN ARTIFICIAL INTELLIGENCE APPROACH
Authors: Athavale Ambarish M. , Hart Peter D. , Itteera Mathew , Cimbaluk David , Patel Tushar , Alabka Anas , Dunea George , Arruda Jose , Singh Ashok , Rosenberg Avi , Kulkarni Hemant
Published: August 2020

Background

Interstitial fibrosis and tubular atrophy (IFTA) is a strong predictor of decline in kidney function. Non-invasive test to assess IFTA is not available.

Methods

We trained, validated and tested a deep learning (DL) system to classify IFTA grade from 6,135 ultrasound images obtained from 352 patients who underwent kidney biopsy. Of 6,135 ultrasound images, 5,523 were used for training (n = 5,122) and validation (n = 401) and 612 to test the accuracy of the DL system. IFTA grade scored by nephropathologist on trichrome stained kidney biopsy slide was used as reference standard.

Results

There were 159 patients (2,701 ultrasound images), 74 patients (1,239 ultrasound images), 41 patients (701 ultrasound images) and 78 patients (1,494 ultrasound images) with IFTA grades 1, 2, 3 and 4, respectively. The deep-learning classification system used masked images based on a 91% accurate kidney segmentation routine. The performance matrices for the deep learning classifier algorithm in the validation set showed excellent precision (90%), recall (76%), accuracy (84%) and F1-score (80%). In the independent test set also, performance matrices showed excellent precision (90%), recall (80%), accuracy (87%) and F1-score of (84%). Accuracy was highest for IFTA grade 1 (98%) and IFTA grade 4 (82%).

Conclusion

A DL system can accurately predict IFTA from kidney ultrasound image.
ARTIFICIAL INTELLIGENCE IN PERCUTANEOUS CORONARY INTERVENTION: IMPROVED PREDICTION OF PCI-RELATED COMPLICATIONS USING AN ARTIFICIAL NEURAL NETWORK
Authors: Kulkarni Hemant , Amin Amit P.
Published: August 2020

Importance

Complications after percutaneous coronary intervention (PCI) are common and costly. Risk models for predicting the likelihood of acute kidney injury (AKI), bleeding, stroke and death are limited by accuracy and inability to use non-linear relationships among predictors. Additionally, if non-linear relationships among predictors can be leveraged, then the prediction of any adverse event (i.e. “the patient who will not do well with PCI”) is perhaps of greater interest to clinicians than prediction of adverse events in isolation.

Objective

To develop and validate a set of artificial neural networks (ANN) models to predict five adverse outcomes after PCI – AKI, bleeding, stroke, death and one or more of these four (‘any adverse outcome’).

Design

Cross-sectional study, using institutional NCDR CathPCI data.

Setting and participants

28,005 patients undergoing PCI at five hospitals in the Barnes-Jewish Hospital system.

Main Outcome(s)

AKI, bleeding, stroke, death, and one or more of these four (‘any adverse outcome’). We divided 28,005 PCI patients into a training cohort of 21,004 (75%) and a test cohort of 7,001 (25%). We used an artificial neural network (ANN) multilayer perceptron (MLP) model to predict each outcome based on a set of 278 encoded and preprocessed variables. Model accuracy was tested using area under the receiver-operating-characteristic curve (AUC). Performance and validation of the MLP model was compared with existing regression models using integrated discrimination improvement (IDI) and continuous net reclassification index (NRI).

Results

The prevalence of AKI, bleeding, stroke and death in the study cohort was 4.6%, 3.6%, 0.3% and 1.1%, respectively. The fully trained MLP model achieved convergence quickly (< 10 epochs) and could predict accurately predict AKI (77.9%), bleeding (86.5%), death (90.3%) and any adverse outcome (80.6%) in the independent test set. However, prediction of stroke was not satisfactory (69.9%). Compared to the currently used models for AKI, bleeding and death prediction, our models showed a significantly higher AUC (range 1.6% – 5.6%), IDI (range 4.9% –7.2%) and NRI (range 0.07 – 0.61).

Conclusions and Relevance

By using neural network-based models, we accurately predict major adverse events after PCI. Larger studies for replicability and longitudinal studies for evidence of impact are needed to establish these artificial intelligence methods in current PCI practice.
Clinico-epidemiological characteristics of asymptomatic and symptomatic COVID-19-positive patients in Bangladesh
Authors: Hasan Mohammad Jahid , Chowdhury Sayeda Mukta , Khan Md. Abdullah Saeed , Rahaman Monjur , Fardous Jannatul , Adit Tanjir , Rahman Mustafizur , Hossain Md. Tarek , Yesmin Shakila , Raheem Enayetur , Amin Mohammad Robed
Published: August 2020

Background

As of August 15, 2020, Bangladesh lost 3591 lives since the first Coronavirus disease 2019 (COVID-19) case announced on March 8. The objective of the study was to report the clinical manifestation of both symptomatic and asymptomatic COVID-19-positive patients.

Methods

A online-based cross-sectional survey was conducted for initial recruitment of participants with subsequent telephone interview by the three trained physicians in 237 adults with confirmed COVID-19 infection in Bangladesh. The study period was between 27 April to 26th May, 2020. Consent was ensured before commencing the interview. Collected data were entered in a predesigned case report form and subsequently analyzed by SPSS 20.

Results

The mean age at presentation was 41.59±13.73 (SD) years and most of the cases were male (73%). A total of 90.29% of patients reside in urban areas. Among the positive cases, 13.1% (n = 31) were asymptomatic. Asymptomatic cases were significantly more common in households with 2 to 4 members (p = .008). Both symptomatic and asymptomatic patients shared similar ages of presentation (p = 0.23), gender differences (p = 0.30), and comorbidities (p = 0.11). Only 5.3% of patients received ICU care during their treatment. The most frequent presentation was fever (88.3%), followed by cough (69.9%), chest pain (34.5%), body ache (31.1%), and sore throat (30.1%). Thirty-nine percent (n = 92) of the patients had comorbidities, with diabetes and hypertension being the most frequently observed.

Conclusion

There has been an upsurge in COVID-19 cases in Bangladesh. Patients were mostly middle-aged and male. Typical presentations were fever and cough. Maintenance of social distancing and increased testing are required to meet the current public health challenge.
Mathematical modeling of metastasis, a feasible way to detect the weakness
Authors: Guerra A. , Silva E. , Mansilla R. , Nieto-Villar J. M.
Published: August 2020

Aim

Cancer is one of the main causes of death worldwide. 90% of deaths caused by this disease occur due to metastasis. Two models are proposed that rescue fundamental aspects of metastasis, such as EMT (epithelial-mesenchymal transition), extravasation and colonization.

Methods

To evaluate the complexity, the Lyapunov exponents, the eigenvalues of the Jacobian matrix (stability analysis) and the Kaplan York dimension were calculated.

Results

It was evidenced that the weakness of the metastasis lies in these stages, which indicates that they constitute potential targets in the search for an effective treatment.

Conclusion

The results suggest that strengthening the immune system during EMT as well as its specialization in the detection of DTCs (disseminated tumor cells) can be effective strategies in the treatment of metastasis.
An effective, safe and cost-effective cell-based chimeric vaccine against SARS-CoV2
Authors: Cheng Zhenguo , Zhang Danhua , Liu XiaoWen , Miao Jinxin , Wang Jianyao , Guo Haoran , Yan Wenli , Zhang Zhe , Zhang Na , Wang Jingjing , Lu Shuangshuang , Zhang Zhongxian , Liu Wei , Liu Hong , Zhang Yi , Zhang Lirong , Dong Jianzeng , Lemoine Nicholas R , Wang Yaohe
Published: August 2020

More than one hundred vaccines against SARS-CoV-2 have been developed and some of them have entered clinical trials, but the latest results revealed that these vaccines still face great challenges. Here, we developed a novel cell-based gp96-Ig-secreting chimeric vaccine which is composed of two viral antigens, the RBD of spike protein, and a truncated nucleocapsid protein that could induce epitope-specific cytotoxic T lymphocytes but low antibody response. Syrian hamsters immunized with the cell-based vaccine produced high level of SARS-CoV-2 specific NAbs and specific T cell immunity which could eliminate RBD-truncated N-expressing cells, without the induction of antibody against N protein and other observed toxicity. This study provides a proof of concept for clinical testing of this safe, effective and cost-effective vaccine against SARS-CoV2 infection.
Modulation of flight and feeding behaviours requires presynaptic IP3Rs in dopaminergic neurons
Authors: Sharma Anamika , Hasan Gaiti
Published: August 2020

Innate behaviours, though robust and hard wired, rely on modulation of neuronal circuits, for eliciting an appropriate response according to internal states and external cues.Drosophilaflight is one such innate behaviour that is modulated by intracellular calcium release through inositol 1,4,5-trisphosphate receptors (IP3Rs). Cellular mechanism(s) by which IP3Rs modulate neuronal function for specific behaviours remain speculative, in vertebrates and invertebrates. To address this, we generated an inducible dominant negative form of the IP3R (IP3RDN). Flies with neuronal expression of IP3RDNexhibit flight deficits. Spatiotemporal expression of IP3RDNhelped identify key flight-modulating dopaminergic neurons with axonal projections in the mushroom body. Attenuation of IP3R function in these presynaptic dopaminergic neurons resulted in flies with shortened flight bouts and a disinterest in seeking food, accompanied by reduced excitability and dopamine release upon cholinergic stimulation. Our findings suggest that the same neural circuit modulates the drive for food search and for undertaking longer flight bouts.
Enterococcus peptidoglycan remodeling promotes immune checkpoint inhibitor therapy
Authors: Griffin Matthew E. , Espinosa Juliel , Becker Jessica L. , Jha Jyoti K. , Fanger Gary R. , Hang Howard C.
Published: August 2020

The antitumor efficacy of cancer immunotherapy has been correlated with specific species within the gut microbiota. However, molecular mechanisms by which these microbes affect host response to immunotherapy remain elusive. Here we show that specific members of the bacterial genus Enterococcus can promote anti-PD-L1 immunotherapy in mouse tumor models. The active enterococci express and secrete orthologs of the NlpC/p60 peptidoglycan hydrolase SagA that generate immune-active muropeptides. Expression of SagA in non-protective E. faecalis was sufficient to promote antitumor activity of clinically approved checkpoint targets, and its activity required the peptidoglycan sensor Nod2. Notably, SagA-engineered probiotics or synthetic muropeptides also promoted checkpoint inhibitor antitumor activity. Our data suggest that microbiota species with unique peptidoglycan remodeling activity may enhance immunotherapy and could be leveraged for next-generation adjuvants.

One Sentence Summary

A conserved family of secreted NlpC/p60 peptidoglycan hydrolases from Enterococcus promote antitumor activity of immune checkpoint inhibitors.
Detection and Characterization of Magnetosome Chains In Magnetotactic Bacteria
Authors: Vinay Bharadhwaj , Vijay Bhavya , Raghunath Surya K
Published: August 2020

Aim

Magnetotactic bacteria are gram-negative, prokaryotic organisms which align themselves according to the Earth’s geomagnetic field. They contain organelles called magnetosomes which produce nano-magnetites by the mechanism of biomineralization. These nano-magnetites are arranged in the form of well-ordered chain called magnetosome chain, which are held together by intermolecular forces. The growth of these bacteria is stringent to specific oxygen gradient regions, where there is oxic-anoxic transition zone. In this paper, we report the cultivation and characterisation of magnetotactic bacteria that was accomplished under laboratory conditions and scanning electron microscope respectively.

Methodology

Bacterial soil samples were collected and cultivated under laboratory conditions using a precise and cost-effective media formulation using coffee bean extract and ferric chloride, which were to provide sufficient iron under the influence of external magnetic field. Experiments were conducted using media, deficient with ferric chloride and coffee bean solution, as control. Pour plate method was carried out for the growth of bacteria under the influence of external magnetic field provided on one-end of the petri-plate.

Result

We observed the growth of the cultivated bacteria in the proximity of the magnetic field only in the presence of iron in media. This emphasises that the media formulated was appropriate for the growth of bacteria under laboratory conditions. Scanning electron microscope analysis confirmed the presence of magnetosome chains in magnetotactic bacteria.

Interpretation

In this research, the bacteria were able to sustain in artificial oxygen-transition zones provided in the laboratory. The coffee bean solution contained quinic acid and succinic acid, which along with ferric chloride provided iron in the form of ferric quinate, and succinic acid which are the major sources of growth for the bacteria. Even though magnetosome research has shown promising advances, one of major limitations in its commercialization is its difficulty in cultivation under laboratory conditions.
Forces experienced by instrumented animals depend on lifestyle
Authors: Wilson Rory P , Rose Kayleigh A , Gunner Richard , Holton Mark , Marks Nikki J , Bennett Nigel C , Bell Stephen H. , Twining Joshua P , Hesketh Jamie , Duarte Carlos M. , Bezodis Neil , Scantlebury D. Michael
Published: August 2020

Animal-attached devices have transformed our understanding of vertebrate ecology. However, to be acceptable, researchers must minimize tag-related harm. The long-standing recommendation that tag masses should not exceed 3% of the animal’s body mass ignores tag forces generated by movement. We used collar-attached accelerometers on four free-ranging carnivores, spanning two orders of magnitude in mass, to reveal that during movement, forces exerted by ‘3%’ tags were generally equivalent to 4-19% of the animals’ masses, with a record of 54% in a hunting cheetah. Controlled studies on domestic dogs revealed how the tag forces are dictated by animal gait and speed but appear largely invariant of body mass. This fundamentally changes how acceptable tag mass limits should be determined, requiring cognizance of animal athleticism.

One Sentence Summary

There can be no universal rule for collar-tag masses as a percentage of carrier mass since tag forces depend on lifestyle.
Maternal factor PABPN1L is essential for maternal mRNA degradation during maternal-to-zygotic transition
Authors: Wang Ying , Feng Tianhao , Shi Xiaodan , Liu Siyu , Wang Zerui , Zhang Xin , Zhang Jintao , Zhao Shuqin , Zhang Junqiang , Ling Xiufeng , Liu Mingxi
Published: August 2020

Infertility affects 10% - 15% of families worldwide. However, the pathogenesis of female infertility caused by abnormal early embryonic development is not clear. We constructed a mouse model (Pabpn1l -/-) simulating the splicing abnormality of human PABPN1L and found that the female was sterile and the male was fertile. The Pabpn1l -/- oocytes can be produced, ovulated and fertilized normally, but cannot develop beyond the 2-cell stage. Using RNA-Seq, we found a large-scale upregulation of RNA in Pabpn1l -/- MII oocytes. Of the 2401 transcripts upregulated in Pabpn1l-/- MII oocytes, 1523 transcripts (63.4%) were also upregulated in Btg4 -/- MII oocytes, while only 53 transcripts (2.2%) were upregulated in Ythdf2 -/- MII oocytes. We documented that transcripts in zygotes derived from Pabpn1l -/- oocytes have a longer poly(A) tail than the control group, a phenomenon similar to that in Btg4-/- mice. Surprisingly, the poly(A) tail of these mRNAs was significantly shorter in the Pabpn1l -/- MII oocytes than in the Pabpn1l +/+. These results suggest that PABPN1L is involved in BTG4-mediated maternal mRNA degradation, and may antagonize poly(A) tail shortening in oocytes independently of its involvement in maternal mRNA degradation. Thus, PABPN1L variants could be a genetic marker of female infertility.
Activation of G-protein coupled receptors is thermodynamically linked to lipid solvation
Authors: Leonard Alison N. , Lyman Edward
Published: August 2020

Preferential lipid solvation of the G-protein coupled A2Aadenosine receptor (A2AR) is evaluated from 35μsec of all-atom molecular dynamics simulation. A coarse-grained transition matrix algorithm is developed to overcome slow equilibration of the first solvation shell, obtaining statistically robust estimates of the free energy of solvation by different lipids for the receptor in different activation states. Results indicate preference for solvation by unsaturated chains, which favors the active receptor. A model for lipid-dependent GPCR activity is proposed in which the chemical potential of lipids in the bulk membrane modulates receptor activity. The enthalpy and entropy associated with moving saturated vs. unsaturated lipids from bulk to A2AR’s first solvation shell are compared. In the simulated mixture, saturated chains are disordered (i.e., obtain a favorable entropic contribution) when partitioning to the receptor surface, but this is outweighed by a favorable enthalpic contribution for unsaturated chains to occupy the first solvation shell.
Deep learning for species identification of modern and fossil rodent molars
Authors: Miele Vincent , Dussert Gaspard , Cucchi Thomas , Renaud Sabrina
Published: August 2020

Reliable identification of species is a key step to assess biodiversity. In fossil and archaeological contexts, genetic identifications remain often difficult or even impossible and morphological criteria are the only window on past biodiversity. Methods of numerical taxonomy based on geometric morphometric provide reliable identifications at the specific and even intraspecific levels, but they remain relatively time consuming and require expertise on the group under study. Here, we explore an alternative based on computer vision and machine learning. The identification of three rodent species based on pictures of their molar tooth row constituted the case study. We focused on the first upper molar in order to transfer the model elaborated on modern, genetically identified specimens to isolated fossil teeth. A pipeline based on deep neural network automatically cropped the first molar from the pictures, and returned a prediction regarding species identification. The deep-learning approach performed equally good as geometric morphometrics and, provided an extensive reference dataset including fossil teeth, it was able to successfully identify teeth from an archaeological deposit that was not included in the training dataset. This is a proof-of-concept that such methods could allow fast and reliable identification of extensive amounts of fossil remains, often left unstudied in archaeological deposits for lack of time and expertise. Deep-learning methods may thus allow new insights on the biodiversity dynamics across the last 10.000 years, including the role of humans in extinction or recent evolution.
Targeted knockdown of ribulose-1, 5-bisphosphate carboxylase-oxygenase in rice mesophyll cells impact on photosynthesis and growth
Authors: Maheshwari Chirag , Coe Robert A , Karki Shanta , Covshoff Sarah , Tapia Ronald , Tyagi Aruna , Hibberd Julian M. , Furbank Robert T. , Quick W Paul , Lin Hsiang-Chun
Published: August 2020

We generated antisense constructs targeting two of the five Rubisco small subunit genes (OsRBCS2 and 4) which account for between 30-40% of the RBCS transcript abundance in leaf blades. The constructs were driven by a maize phosphoenolpyruvate carboxylase (PEPC) promoter known to have enriched expression in mesophyll cells (MCs). In the resulting lines leaf Rubisco protein content was reduced by between 30-50% and CO2assimilation rate was limited under photorespiratory and non-photorespiratory conditions. A relationship between Rubisco protein content and CO2assimilation rate was found. This was associated with a significant reduction in dry biomass accumulation and grain yield of between 37 to 70%. In addition to serving as a resource for reducing Rubisco accumulation in a cell-preferential manner, these lines allow us to characterize gene function and isoform specific suppression on photosynthesis and growth. Our results suggest that the knockdown of multiple genes is required to completely reduce Rubisco accumulation in MCs.
Functions of Gle1 are governed by two distinct modes of self-association
Authors: Mason Aaron C. , Wente Susan R.
Published: August 2020

Gle1 is a conserved, essential regulator of DEAD-box RNA helicases, with critical roles defined in mRNA export, translation initiation, translation termination, and stress granule formation. Mechanisms that specify which, where and when DDXs are targeted by Gle1 are critical to understand. In addition to roles for stress-induced phosphorylation and inositol hexakisphosphate (IP6) binding in specifying Gle1 function, Gle1 oligomerizes via its N-terminal domain in a phosphorylation-dependent manner. However, a thorough analysis of the role for Gle1 self-association is lacking. Here, we find that Gle1 self-association is driven by two distinct regions: a coiled-coil domain and a novel ten amino acid aggregation prone region, both of which are necessary for proper Gle1 oligomerization. By exogenous expression in HeLa cells, we tested the function of a series of mutations that impact the oligomerization domains of the Gle1A and Gle1B isoforms. Gle1 oligomerization is necessary for many, but not all aspects of Gle1A and Gle1B function, and the requirements for each interaction domain differ. Whereas the coiled-coil domain and aggregation prone region additively contribute to competent mRNA export and stress granule formation, both self-association domains are independently required for regulation of translation under cellular stress. In contrast, Gle1 self-association is dispensable for phosphorylation and non-stressed translation initiation. Collectively, we reveal self-association functions as an additional mode of Gle1 regulation to ensure proper mRNA export and translation. This work also provides further insight into the mechanisms underlying humangle1disease mutants found in prenatally lethal forms of arthrogryposis.
Current status and future opportunities for serial crystallography at MAX IV Laboratory
Authors: Shilova Anastasya , Lebrette Hugo , Aurelius Oskar , Nan Jie , Welin Martin , Kovacic Rebeka , Ghosh Swagatha , Safari Cecilia , Friel Ross J. , Milas Mirko , Matej Zdenek , Högbom Martin , Brändén Gisela , Kloos Marco , Shoeman Robert L. , Doak Bruce , Ursby Thomas , Håkansson Maria , Logan Derek T. , Mueller Uwe
Published: August 2020

Over the last decade, serial crystallography, a method to collect complete diffraction datasets from a large number of microcrystals delivered and exposed to an X-ray beam in random orientations at room temperature, has been successfully implemented at X-ray free-electron lasers and synchrotron radiation facility beamlines. This development relies on a growing variety of sample presentation methods, including different fixed target supports, injection methods using gas-dynamic virtual-nozzle injectors and high-viscosity extrusion injectors, and acoustic levitation of droplets, each with unique requirements. In comparison with X-ray free-electron lasers, increased beam time availability makes synchrotron facilities very attractive to perform serial synchrotron X-ray crystallography (SSX) experiments. Within this work, the possibilities to perform SSX at BioMAX, the first macromolecular crystallography beamline at  MAX IV Laboratory in Lund, Sweden, are described, together with case studies from the SSX user program: an implementation of a high-viscosity extrusion injector to perform room temperature serial crystallography at BioMAX using two solid supports – silicon nitride membranes (Silson, UK) and XtalTool (Jena Bioscience, Germany). Future perspectives for the dedicated serial crystallography beamline MicroMAX at MAX IV Laboratory, which will provide parallel and intense micrometre-sized X-ray beams, are discussed.