bluuebunny/crossref_metadata_2025 huggingface dataset:
The Combination of Tocilizumab and Methylprednisolone Along With Initial Lung Recruitment Strategy in Coronavirus Disease 2019 Patients Requiring Mechanical Ventilation: A Series of 21 Consecutive Cases
Authors: Hazbun Munir E. , Faust Andrew C. , Ortegon Anthony L. , Sheperd Lyndsay A. , Weinstein Gary L. , Doebele Rebecca L. , Weinmeister Kenney D. , Liddell Allison M. , Feldman Mark
Published: June 2020

Objective:

To describe the outcomes with use of a combination of tocilizumab and methylprednisolone administered around the time of endotracheal intubation in patients with confirmed coronavirus disease 2019-associated hypoxemic respiratory failure requiring mechanical ventilation.

Data Sources:

Retrospective chart review.

Study Selection/Data Extraction:

Twenty-one consecutive patients with confirmed coronavirus disease 2019-associated hypoxemic respiratory failure requiring mechanical ventilation. Initial ventilator parameters were positive end-expiratory pressure 14 cm H2
o and target plateau pressure 29 cm H2
o to maximize lung recruitment. Methylprednisolone (125 mg every 6hr for 24 hr with tapering to 60 mg every 12 hr) was administered shortly after patients were intubated (median 11 hr after intubation).

Data Synthesis:

No patient in the cohort died while hospitalized (mortality, 0%; 95% CI, 0%–18%) and 18 patients have been discharged from the acute care setting. Twenty of 21 patients (95%) have been liberated from mechanical ventilation after a median duration of 8 days (range, 4–30 d). Following 48 hours of methylprednisolone, the A-a o
2 gradient decreased from 455 ± 103 to 228 ± 109 mm Hg (difference 227 ± 108 mm Hg; p < 0.01).

Conclusions:

Our positive experience with tocilizumab in combination with methylprednisolone started early after endotracheal intubation may be one avenue for reducing the morbidity and mortality seen with severe coronavirus disease 2019 and merits further exploration in clinical studies.
Subcutaneous Enoxaparin Safely Facilitates Bedside Sustained Low-Efficiency Hemodialysis in Hypercoagulopathic Coronavirus Disease 2019 Patients—A Proof-of-Principle Trial
Authors: Neumann-Haefelin Elke , Widmeier Eugen , Bansbach Joachim , Kaufmann Kai , Heinrich Sebastian , Walz Gerd , Bürkle Hartmut , Kalbhenn Johannes
Published: June 2020

Objectives:

Renal replacement therapy in coronavirus disease 2019 patients is complicated by increased activation of the coagulation system. This may worsen the quality of hemodialysis and contribute to a shortage of dialysis machines as well as plastic disposables during the pandemic. This study describes a simple and safe protocol of anticoagulation with low-molecular-weight heparin in combination with bedside sustained low-efficiency hemodialysis in coronavirus disease 2019 patients.

Design:

Monocentric observational cross-over trial investigating sustained low-efficiency hemodialysis with unfractionated heparin following sustained low-efficiency hemodialysis with low-molecular-weight heparin.

Setting:

Coronavirus disease 2019-ICU in a German Tertiary Care University Hospital.

Patients:

Three consecutive severe coronavirus disease 2019 patients receiving nine sustained low-efficiency hemodialysis therapies with unfractionated heparin followed by 18 sustained low-efficiency hemodialysis therapies with low-molecular-weight heparin.

Interventions:

Switch from IV unfractionated heparin to subcutaneous low-molecular-weight heparin enoxaparin in therapeutic doses for patients receiving bedside sustained low-efficiency hemodialysis.

Measurements and Main Results:

Nine renal replacement therapy sessions in patients anticoagulated with high doses of unfractionated heparin had to be discontinuated prematurely because of clotting of tubes or membrane and poor quality of hemodialysis. In the same patients, the switch to anticoagulation with therapeutic doses of the low-molecular-weight heparin enoxaparin allowed undisturbed bedside sustained low-efficiency hemodialysis for at least 12 hours. Quality of hemodialysis was excellent, no bleeding event was observed.

Conclusions:

Systemic anticoagulation with subcutaneous enoxaparin provides an effective and safe renal replacement procedure in critically ill patients with coronavirus disease 2019 and hypercoagulability. The protocol reduces the risk of filter clotting, blood loss, and poor dialysis quality and may also prevent systemic thromboembolism.
Quantification of Iridotrabecular Contact in Primary Angle-Closure Disease
Authors: Gupta Barkha , Angmo Dewang , Yadav Suresh , Dada Tanuj , Gupta Viney , Sihota Ramanjit
Published: June 2020

Precis:

Iridotrabecular contact (ITC), a measure of angle closure, can be quantified along with other angle parameters on anterior segment optical coherence tomography (ASOCT). Hence, angle changes and angle closure mechanisms can be detected predicting the efficacy of iridotomy.

Purpose:

To assess 360-degree ITC and ocular parameter changes, after laser peripheral iridotomy (LPI), in primary angle-closure disease (PACD) subgroups.

Methodology:

This was a prospective observational study including 90 subjects, 30 each of primary angle-closure suspect (PACS), primary angle closure (PAC), and primary angle-closure glaucoma (PACG). Anterior segment OCT parameters were measured before and 3 weeks after LPI ITC: central anterior chamber depth, lens vault, angle-opening distance, angle recess area, trabecular iris space area, trabecular iris angle at 500 and 750 μm from scleral spur.

Results:

ITC was highest in PACG, 81.43%±22.39%, followed by PAC, 28.53%±21.30%, and PACS, 10.76%± 8.54% (P=0.011). There was a significant decrease in ITC in all 3 groups after iridotomy (P<0.001), with a residual ITC of 68.56%±26.44% in PACG, 18.23%±15.98% in PAC, and 5.13%±5.11% in PACS. A significant positive correlation was seen between the extent of ITC, baseline intraocular pressure, and visual field index. ITC was highest in eyes with exaggerated lens vault (77.3%±32.03%), as compared with eyes having a plateau iris configuration or relative pupillary block configuration (P<0.001).

Conclusions:

Iridotomy at any stage of PACD shows a significant decrease in ITC, with areas of residual ITC. Even in PACG, the iridotomy is effective in exposing parts of the trabecular meshwork that had contact earlier. Greater baseline ITC and postlaser ITC are a biomarker for higher intraocular pressure and greater visual field damage, which need lifelong review and appropriate management.
The Shape of Posterior Sclera as a Biometric Signature in Open-angle Glaucoma: An Intereye Comparison Study
Authors: Kim Yong Chan , Koo Yong Ho , Bin Hwang Hyung , Kang Kui Dong
Published: June 2020

Purpose:

To characterize intereye differences in posterior segment parameters and determine their significance in open-angle glaucoma patients with unilateral damage.

Methods:

Both eyes from 65 subjects without any nerve damage and 43 patients undergoing treatment for unilateral open-angle glaucoma were included in this study. A 12.0×9.0×2.6 mm volume of the posterior segment in each eye was scanned with swept-source optical coherence tomography. Coronally reconstructed optical coherence tomography images were analyzed to determine the deepest point of the eye (DPE), which we then calculated the distance (Disc-DPE distance), depth (Disc-DPE depth), angle (Disc-DPE angle) from the optic disc center to the DPE. Posterior pole shape was analyzed measuring the posterior pole-cross-sectional area, posterior pole-horizontal width (PP-HW), and posterior pole-vertical width) of the posterior pole. These measurements and their intereye absolute difference (IAD; absolute difference in measurements between the right and left eyes) values were compared between the healthy and unilateral glaucomatous patients.

Results:

The posterior sclera measurements, including the Disc-DPE distance, Disc-DPE depth, and posterior pole-cross-sectional area, were significantly different between the unilateral glaucoma eyes and contralateral healthy eyes (P=0.043, P=0.035, and P=0.049, respectively). By contrast, none of the intereye differences in optic nerve head parameters were significant in the unilateral glaucoma patients. In comparison with the IAD values, the baseline intraocular pressure and PP-HW of the posterior segment showed significant differences between the healthy and the unilateral glaucoma patients (P=0.019 and P=0.036, respectively). A multivariate analysis showed that a larger baseline intraocular pressure IAD [odds ratio (OR), 1.381; P=0.009)] and larger PP-HW IAD (OR, 1.324; P=0.032) were significantly associated with the presence of glaucoma.

Conclusions:

Compared with the fellow healthy eyes, glaucomatous eyes had larger and more steeply curved posterior poles, which represent a structural variation of the posterior sclera that might be associated with glaucomatous optic neuropathy.
Automated Gonioscopy Assessment of XEN45 Gel Stent Angle Location After Isolated XEN or Combined Phaco-XEN Procedures: Clinical Implications
Authors: Barão Rafael C. , José Patrícia , Teixeira Filipa J. , Ferreira Nuno P. , Sens Paula , Pinto Luis Abegão
Published: June 2020

Précis:

Angle location of the XEN implant both in isolated and in combined procedures did not appear to influence long-term outcomes. However, more posterior stent placements seem to be associated with increased early postoperative complications.

Purpose:

The purpose of this study was to assess success and safety outcomes of different levels of insertion of the XEN45 gel stent in the angle in standalone and combined procedures.

Methods:

This was a cross-sectional study of patients in whom XEN had been implanted without intraoperative gonioscopy. Automated gonioscopy was used for postoperative analysis of the XEN location, classified as anterior or posterior relative to the scleral spur. Absolute success was defined as ≥20% intraocular pressure decrease from baseline and ranging from 6 to 21 mm Hg without medication and qualified success if medicated. The need for additional drainage surgery was considered failure, but needling was allowed. Clinical data were retrieved from patient files.

Results:

Gonioscopy-assisted XEN location was performed on 42 eyes of 33 patients (14 isolated and 28 combined procedures) on average 18±9 months after surgery. Absolute (32% vs. 35%; P>0.99) and qualified (44% vs. 65%; P=0.22) success was similar in both anterior and posterior placements, respectively. Kaplan-Meier survival analysis yielded similar median survival times for both groups. The distribution of XEN insertion level in the angle was similar in standalone and combined procedures (P=0.75). Although overall safety outcome measures did not differ significantly, the proportion of intraoperative and early postoperative complications was higher in posterior XEN placements (P=0.03).

Conclusions:

Different locations of XEN45 did not seem to significantly impact late success and safety outcomes, although stents inserted more posteriorly may be associated with a higher rate of early complications. Combined implantation of XEN with phacoemulsification does not seem to influence stent location in the iridocorneal angle in a setting without intraoperative gonioscopy.
The Effects of L-Carnitine on Echocardiographic Changes in Patients With β-Thalassemia Major and Intermedia
Authors: Shahidi Mohsen , Hashemi Sayedeh Rozhin , Fattahi Nima , Roshani Daem , Vahedi Siamak , Sharifi Pezhman , Moradveisi Borhan
Published: June 2020

Introduction:

Heart failure, fatal arrhythmias, and cardiac dilatation because of anemia are common causes of β-thalassemia major–related deaths. The aim of this study was to determine the effect of L-carnitine on echocardiographic changes in β-thalassemia major and intermedia patients in Besat Hospital in Sanandaj, Iran.

Methods:

In a randomized clinical trial, 60 β-thalassemia patients who were eligible for L-carnitine administration were randomly divided into 2 placebo and study drug groups. The duration of the study was 6 months. Using echocardiography and blood tests, cardiac parameters including left ventricular dilatation, left ventricular hypertrophy, and a number of cardiac blood indices were examined before and after the intervention. The data were analyzed using SPSS V.23 software, χ2, and covariance statistical tests.

Results:

There was no significant difference between the 2 groups in terms of age and sex. Patients treated with L-carnitine have a reduced rate of left ventricular dilatation, left ventricular hypertrophy, and systolic blood pressure compared with controls (P<0.05). Cardiac output increased from 43.5 to 56.5 (P=0.002).

Conclusions:

The results of this study showed that the drug has a positive effect on the improvement of cardiac indices in β-thalassemia patients. Therefore, we suggest that further studies with more samples and other diagnostic modalities of the drug’s effect be investigated.
Behavioral Observation of Infants With Life-Threatening or Life-Limiting Illness in the Neonatal Intensive Care Unit
Authors: Fortney Christine A. , Sealschott Stephanie D. , Pickler Rita H.
Published: June 2020

Background

Infants in the neonatal intensive care unit experience aversive stimuli that cause pain and distress. Maintaining adequate relief from pain and distress is challenging because of infants’ varying ages and stages of development and their nonverbal status. Thus, pain and distress must be interpreted by a healthcare provider or other proxy from their own observations or perceptions. There is no standard research or clinical measure for pain and distress in infants.

Objective

The purpose of this analysis was to evaluate the use of the COMFORT Behavior (COMFORT-B) Scale as a measure of pain and distress in infants diagnosed with life-threatening or life-limiting illnesses in the neonatal intensive care unit in comparison with the nurse-documented Neonatal Pain, Agitation and Sedation Scale; the infants’ Technology Dependence Scale; and the mothers’ report of total perceived symptom scores.

Methods

Infants diagnosed with life-threatening or life-limiting illnesses and hospitalized in a Level IV neonatal intensive care unit in the Midwestern United States and their parents were included. Measurement of pain and distress in infants was collected weekly from enrollment through 12 weeks or until discharge, whichever occurred first. Observations for the COMFORT-B Scale were conducted before and after standard caregiving activities. Pearson r correlations were used to compare means between pain and distress, technology dependence, and mothers’ total perceived symptom scores over time.

Results

Data from 78 infants (46 male and 32 female infants) of ages 23–41 weeks of gestation at birth were analyzed. No correlations were found among the COMFORT-B Scale; the Neonatal Pain, Agitation and Sedation Scale; and mothers’ total perceived symptom scores. Moderate correlations were found among the Technology Dependence Scale; mothers’ total perceived symptom scores; and the Neonatal Pain, Agitation and Sedation Scale.

Discussion

Performing COMFORT-B observations can be challenging, and it is unclear whether the information obtained from the COMFORT-B Scale added to the assessment of the infant’s pain and distress that is typically recorded in the health record or from parents. Further evaluation is needed to determine if it is more reliable to collect the Neonatal Pain, Agitation and Sedation Scale scores rather than conduct observations using the COMFORT-B Scale in studies of infants with life-threatening and life-limiting illnesses in the neonatal intensive care unit.
Laparoscopic Total Extraperitoneal Inguinal Hernia Repair Under Epidural Anesthesia Versus General Anesthesia
Authors: Sürek Ahmet , Bozkurt Mehmet Abdussamet , Ferahman Sina , Gemici Eyüp , Dönmez Turgut
Published: June 2020

Introduction:

Laparoscopic total extraperitoneal (TEP) inguinal hernia repair is a well-known approach to inguinal hernia repair. The present study aims to compare the advantages and disadvantages of the TEP technique under general anesthesia (GA) and epidural anesthesia (EA).

Materials and Methods:

The patients were divided into 2 groups as those undergoing TEP under EA (Group 1) and those undergoing TEP under GA (Group 2). The 2 patient groups were compared in terms of sex, age, body mass index data, duration of surgery, total operation time, patient satisfaction, VAS scores (1, 4, 12, and 24 h), length of hospital stay, and postoperative complications.

Results:

The number of patients operated under EA (Group 1) was 30, and the number of patients operated under GA (Group 2) was 32. Only in the postoperative first hour VAS scores was statistically significantly less and the need for analgesia evaluated in both groups was found to be statistically significantly lower in Group 1 (P<0.001). The mean operation time was recorded as 62 and 46.50 minutes in Groups 1 and 2, respectively, which was statistically significantly shorter in Group 2 (P<0.001). There was no difference between the 2 groups regarding complications, hospital stay, recovery, or surgery time. Conversion rate is 0 in both groups.

Conclusions:

Lower postoperative VAS scores and lower postoperative VAS scores and lower analgesic used requirements of EA, it is thought that EA can be safely applied in the TEP procedure as an alternative in patients who cannot be administered GA.
Anatomic Indications for Using Actuator-driven Pulsed Water Jet for Hepatectomy
Authors: Kawasaki Yota , Iino Satoshi , Idichi Tetsuya , Sakoda Masahiko , Tanoue Kiyonori , Kurahara Hiroshi , Mataki Yuko , Maemura Kosei , Ueno Shinichi , Natsugoe Shoji
Published: June 2020

Background:

The clamp crushing method and the use of the Cavitron ultrasonic surgical aspirator (CUSA) are widely accepted techniques for hepatic parenchymal transection. The actuator-driven pulsed water jet (ADPJ) with high tissue selectivity is a new technology that was shown as a safe transection tool in preclinical models, although not much is known about its safety criteria in patients. Therefore, its strongest advantage, the best indications for its use, and its performance in comparison with other transection methods remain to be clarified. In this report, we present several representative cases to help answer these questions.

Methods:

We started using the ADPJ in December 2017, only in cases where the tumor was very close to major vessels or attached to them, along a considerable length, to preserve vessels and prevent postoperative liver failure. All the cases underwent highly demanding procedures. We avoided using this device in cases such as liver cirrhosis, where the hepatic parenchyma was very hard.

Results:

Six cases fulfilled our limited indications for using ADPJ. The median age and number of tumors were 55 years (10 to 69 y) and 2.5 years (1 to 4 y), respectively. The mean tumor size was 7.8 cm (2.8 to 21 cm), the minimum distance between the tumor and major vessels to be preserved was 0 mm (0 to 4 mm), and the contact length of the tumor and major vessels was 26 mm (19 to 40 mm). Regarding the surgical outcome, the median operation time and blood loss were 559 minutes (508 to 919 min) and 620 mL (230 to 860 mL), respectively. We achieved a negative surgical margin (R0 resection) in all cases.

Conclusions:

Using ADPJ, we could perform R0 hepatectomy in all cases, which preoperatively were considered to have a high chance of being margin positive. We consider the best indication for using ADPJ is when the tumor and vessels to be preserved are attached or very close over a long distance.
Neutral competition boosts cycles and chaos in simulated food webs
Authors: Rodríguez-Sánchez Pablo , van Nes Egbert H. , Scheffer Marten
Published: June 2020

Similarity of competitors has been proposed to facilitate coexistence of species because it slows down competitive exclusion, thus making it easier for equalizing mechanisms to maintain diverse communities. On the other hand, previous studies suggest that chaotic ecosystems can have a higher biodiversity. Here, we link these two previously unrelated findings, by analysing the dynamics of food web models. We show that near-neutrality of competition of prey, in the presence of predators, increases the chance of developing chaotic dynamics. Moreover, we confirm that chaotic dynamics correlate with a higher biodiversity.
Combining tissue engineering and optical imaging approaches to explore interactions along the neuro-cardiac axis
Authors: Sigalas Charalampos , Cremer Maegan , Winbo Annika , Bose Samuel J. , Ashton Jesse L. , Bub Gil , Montgomery Johanna M. , Burton Rebecca A. B.
Published: June 2020

Interactions along the neuro-cardiac axis are being explored with regard to their involvement in cardiac diseases, including catecholaminergic polymorphic ventricular tachycardia, hypertension, atrial fibrillation, long QT syndrome and sudden death in epilepsy. Interrogation of the pathophysiology and pathogenesis of neuro-cardiac diseases in animal models present challenges resulting from species differences, phenotypic variation, developmental effects and limited availability of data relevant at both the tissue and cellular level. By contrast, tissue-engineered models containing cardiomyocytes and peripheral sympathetic and parasympathetic neurons afford characterization of cellular- and tissue-level behaviours while maintaining precise control over developmental conditions, cellular genotype and phenotype. Such approaches are uniquely suited to long-term, high-throughput characterization using optical recording techniques with the potential for increased translational benefit compared to more established techniques. Furthermore, tissue-engineered constructs provide an intermediary between whole animal/tissue experiments and
in silico
models. This paper reviews the advantages of tissue engineering methods of multiple cell types and optical imaging techniques for the characterization of neuro-cardiac diseases.
Maternal and cohort effects modulate offspring responses to multiple stressors
Authors: Torres Gabriela , Thomas David N. , Whiteley Nia M. , Wilcockson David , Giménez Luis
Published: June 2020

Current concerns about climate change have led to intensive research attempting to understand how climate-driven stressors affect the performance of organisms, in particular the offspring of many invertebrates and fishes. Although stressors are likely to act on several stages of the life cycle, little is known about their action across life phases, for instance how multiple stressors experienced simultaneously in the maternal environment can modulate the responses to the same stressors operating in the offspring environment. Here, we study how performance of offspring of a marine invertebrate (shore crab
Carcinus maenas
) changes in response to two stressors (temperature and salinity) experienced during embryogenesis in brooding mothers from different seasons. On average, offspring responses were antagonistic: high temperature mitigated the negative effects of low salinity on survival. However, the magnitude of the response was modulated by the temperature and salinity conditions experienced by egg-carrying mothers. Performance also varied among cohorts, perhaps reflecting genetic variation, and/or maternal conditions prior to embryogenesis. This study contributes towards the understanding of how anthropogenic modification of the maternal environment drives offspring performance in brooders.
Towards reconciliation of the four world bird lists: hotspots of disagreement in taxonomy of raptors
Authors: McClure Christopher J. W. , Lepage Denis , Dunn Leah , Anderson David L. , Schulwitz Sarah E. , Camacho Leticia , Robinson Bryce W. , Christidis Les , Schulenberg Thomas S. , Iliff Marshall J. , Rasmussen Pamela C. , Johnson Jeff
Published: June 2020

There are currently four world bird lists referenced by different stakeholders including governments, academic journals, museums and citizen scientists. Consolidation of these lists is a conservation and research priority. In reconciling lists, care must be taken to ensure agreement in taxonomic concepts—the actual groups of individual organisms circumscribed by a given scientific epithet. Here, we compare species-level taxonomic concepts for raptors across the four lists, highlighting areas of disagreement. Of the 665 species-level raptor taxa observed at least once among the four lists, only 453 (68%) were consistent across all four lists. The Howard and Moore Checklist of the Birds of the World contains the fewest raptor species (528), whereas the International Ornithological Community World Bird List contains the most (580) and these two lists are in the most disagreement. Of the disagreements, 67% involved owls, and Indonesia was the country containing the most disagreed upon species (169). Finally, we calculated the amount of species-level agreement across lists for each avian order and found raptor orders spread throughout the rankings of agreement. Our results emphasize the need to reconcile the four world bird lists for all avian orders, highlight broad disagreements across lists and identify hotspots of disagreement for raptors, in particular.
Whatman FTA cards versus plasma specimens for the quantitation of HIV-1 RNA using two real-time PCR assays
Authors: Yacouba Abdourahamane , Congo Malika , Dioma Gérard Komonsira , Somlare Hermann , Coulidiaty David , Ouattara Kalifa , Sangare Lassana
Published: June 2020

Background. Several studies have compared the use of dried blot spot (DBS) as an alternative to plasma specimens, mainly using Whatman 903 cards as filter paper. The aim of this study was to evaluate the use of Whatman FTA card (FTA card) specimens for HIV-1 viral load testing compared to plasma specimens using two real-time PCR assays manufactured by Roche and Abbott.

Methodology. A cross-sectional study was conducted between April 2017 and September 2017 on HIV-1 patients admitted to Yalgado Ouédraogo Teaching Hospital. Paired FTA cards and plasma specimens were collected and analysed using the Abbott Real-Time HIV-1 assay (Abbott) and COBAS AmpliPrep/COBAS TaqMan v2.0 (Roche).

Results. In total, 107 patients were included. No statistical differences (P>0.05) were observed between the mean viral loads obtained from the FTA cards and those of the plasma specimens using the Roche and Abbott assays. In total, 29 samples with Roche and 15 samples with Abbott assay showed discrepant results. At viral loads of ≤1000 copies ml−1, the sensitivity and specificity of the FTA cards were 78.6 and 100% with Roche, and 92.3 and 95.9% with Abbott, respectively. Both the Roche and Abbott assays showed good correlation and agreement between the FTA cards and plasma values.

Conclusion. Our study demonstrates the feasibility of using FTA card filter paper for HIV-1 viral load testing. However, further studies will be required for the validation of the use of FTA card filter paper in HIV-1 treatment monitoring.
Genetic diversity of enterovirus G detected in faecal samples of wild boars in Japan: identification of novel genotypes carrying a papain-like cysteine protease sequence
Authors: Nagata Ayaka , Sekiguchi Yuya , Oi Toru , Sunaga Fujiko , Madarame Hiroo , Imai Ryo , Sano Kaori , Katayama Yukie , Omatsu Tsutomu , Oba Mami , Furuya Tetsuya , Shirai Junsuke , Okabayashi Tamaki , Misawa Naoaki , Oka Tomoichiro , Mizutani Tetsuya , Nagai Makoto
Published: June 2020

The genetic diversity of enterovirus G (EV-G) was investigated in the wild-boar population in Japan. EV-G-specific reverse transcription PCR demonstrated 30 (37.5 %) positives out of 80 faecal samples. Of these, viral protein 1 (VP1) fragments of 20 samples were classified into G1 (3 samples), G4 (1 sample), G6 (2 samples), G8 (4 samples), G11 (1 sample), G12 (7 samples), G14 (1 sample) and G17 (1 sample), among which 11 samples had a papain-like cysteine protease (PL-CP) sequence, believed to be the first discoveries in G1 (2 samples) or G17 (1 sample) wild-boar EV-Gs, and in G8 (2 samples) or G12 (6 samples) EV-Gs from any animals. Sequences of the non-structural protein regions were similar among EV-Gs possessing the PL-CP sequence (PL-CP EV-Gs) regardless of genotype or origin, suggesting the existence of a common ancestor for these strains. Interestingly, for the two G8 and two G12 samples, the genome sequences contained two versions, with or without the PL-CP sequence, together with the homologous 2C/PL-CP and PL-CP/3A junction sequences, which may explain how the recombination and deletion of the PL-CP sequences occured in the PL-CP EV-G genomes. These findings shed light on the genetic plasticity and evolution of EV-G.
Impact of Hypertension on Progression and Prognosis in Patients with COVID-19 A Retrospective Cohort Study in 1031 Hospitalized Cases in Wuhan, China
Authors: Zeng Hesong , Zhang Tianlu , He Xingwei , Du Yuxin , Tong Yan , Wang Xueli , Zhang Weizhong , Shen Yin
Published: June 2020

Objectives

The main aim of our study is to observe clinical characteristics and effects of antihypertensive drugs in different hospitalized populations, and to further provide evidence to explore causes and specific clinical markers of the aggravation of COVID-19 in patients with underlying hypertension.

Design

This was a retrospective cohort study focusing on the clinical data of COVID-19 inpatients admitted at the early stage of pandemic.

Setting

A single center study conducted in Tongji Hospital, Tongji Medical College of Huazhong university of Science and Technology (Wuhan, China).

Participants

All 1031 inpatients diagnosed with COVID-19 according to Prevention and control Scheme for Novel Coronavirus Pneumonia published by National Health Commission of the People’s Republic of China and WHO interim guidance in Tongji hospital (Wuhan, China), from January 27, 2020, to March 8, 2020 with the cutoff date being March 30, 2020, were included in this study.

Main outcome measures

Demographic data, medical history, clinical symptoms and signs, laboratory findings, chest computed tomography (CT), treatment, and clinical outcomes were extracted from electronic medical records.

Results

1031 COVID-19 inpatients were included in this study, of whom 866 were discharged and 165 were deceased in hospital. 73% of 165 deceased patients had chronic comorbidities. Patients with underlying diseases showed CFR 2.8 times as that of patients without. Senility and males were observed to be main risk factors for increased in-hospital case-fatality rate, with the odds ratio in multivariable regression being 2.94 (95%CI: 2.00 to 4.33; P <0.001) and 2.47 (95%CI: 1.65 to 3.70; P <0.001), respectively. The odds ratio of cases with composite endpoints for patients with simple hypertension was 1.53 (95%CI: 1.07 to 2.17; P=0.019). Senile patients with hypertension were proved to be at high risk early in the disease, which might be associated with the level of CRP, LDH, and eGFR. The odds ratio of case-fatality rate for patients with hypertension taking CCB group was 0.67 (95%CI: 0.37 to 1.20; P = 0.176). Among 271 severe cases without IKF, the odds ratio of case-fatality rate was 0.42 (95CI%: 0.18 to 0.99; P = 0.046) for patients in the CCB group after adjustment of age, sex, and underlying diseases.

Conclusions

Hypertension is not just a chronic underlying comorbidity, but also a risk factor affecting the severity of COVID-19 and does play a critical role in worsening patients’ clinical outcomes. Therefore, hypertension management in patients with COVID-19 should be regarded as a major challenge in the diagnostic and therapeutic strategies.

Trial registration

N.A.
Enhanced comparisons of COVID-19 mortality across populations
Authors: Rao Chalapati , Doi Suhail A. , Williams Gail
Published: June 2020

Background

The reported crude case fatality rate (CFR) for COVID-19 varies considerably across countries. Crude CFRs could by biased by larger proportions of older COVID-19 cases in population data, who are also at increased mortality risk. Such distorted age case structures are a common feature of selective COVID 19 testing strategies in many countries, and they potentially mask underlying differences arising from other important factors such as health system burden.

Methods

We used the method of direct case-age standardisation to evaluate the effects of age variations on CFRs. Data on cases and death by age from Italy, Spain, China, Australia and South Korea were analysed to derive standardised CFRs. Findings were compared across different case age distribution references as standards.

Results

Using the South Korean case age distribution as a standard, the fivefold higher crude CFR for Italy is reduced to less than two-fold after adjustment, while the crude CFR difference for Spain is virtually eliminated. The adjusted CFR for Australia is the lowest among all countries.

Discussion

Mortality differences based on crude CFRs are exaggerated by age structures, which are effectively controlled by case age standardization. Residual CFR differences could be attributed to health and health system factors. The South Korean case age distribution is an appropriate reference standard, given its robust case detection and contact tracing program. Till reliable population level indicators of incidence and mortality are available, the age-standardized CFR could be a viable option for international comparison of the impact of the COVID 19 epidemic.

The known

There are intense debates around the magnitude of and reasons for wide variations in observed case fatality rates (CFRs) from COVID 19 across countries. Age is commonly speculated as a reason, but this has not been technically quantified or explained.

The new

The technique of direct standardization using reference distributions of case age structures eliminates the effects of age on CFR, thus enhancing the comparability as well as understanding of differentials

The implications

Residual differences between adjusted CFRs can be used to infer health and health system factors that influence mortality in COVID 19 cases in different populations
Predicting mammalian hosts in which novel coronaviruses can be generated
Authors: Wardeh Maya , Baylis Matthew , Blagrove Marcus S.C.
Published: June 2020

Novel pathogenic coronaviruses – including SARS-CoV and SARS-CoV-2 – arise by homologous recombination in a host cell1,2. This process requires a single host to be infected with more than one type of coronavirus, which recombine to form novel strains of virus with unique combinations of genetic material. Identifying possible sources of novel coronaviruses requires identifying hosts (termed recombination hosts) of more than one coronavirus type, in which recombination might occur. However, the majority of coronavirus-host interactions remain unknown, and therefore the vast majority of recombination hosts for coronaviruses cannot be identified. Here we show that there are 11.5-fold more coronavirus-host associations, and over 30-fold more potential SARS-CoV-2 recombination hosts, than have been observed to date. We show there are over 40-fold more host species with four or more different subgenera of coronaviruses. This underestimation of both number and novel coronavirus generation in wild and domesticated animals. Our results list specific high-risk hosts in which our model predicts homologous recombination could occur, our model identifies both wild and domesticated mammals including known important and understudied species. We recommend these species for coronavirus surveillance, as well as enforced separation in livestock markets and agriculture.
COVID-19 IN INDIA: MODELLING, FORECASTING AND STATE-WISE COMPARISON
Authors: Jose Ankitha , Salim Ashid , Subhash Silpa , George Noel
Published: June 2020

COVID-19 has turned the whole world upside down economically and socially. COVID-19 pandemic has caused around five crores of cases and three lakhs deaths globally as of 27 May 2020. This paper adopts four mathematical growth models. Basic models are encouraged because these models can make predictions with the available data and variables in the current scenario of COVID-19 pandemic. The best-fitted model is identified in accordance with the value of the coefficient of determination. As per the best model, there might be greater than 16 lakhs cases at the infection end in India. After predicting the future size of the pandemic, we analyzed how the disease severity varies among the Indian states and union territories using Case Fatality Rates (CFR).
A Pilot Comparative Study of Dental Students’ Ability to Detect Enamel-only Proximal Caries in Bitewing Radiographs With and Without the use of AssistDent® Deep Learning Software
Authors: Devlin Hugh , Ashley Martin , Williams Tomos , Purvis Brian , Roudsari Reza
Published: June 2020

Enamel-only proximal caries, if detected, can be reversed by non-invasive treatments. Dental bitewing radiograph analysis is central to diagnosis and treatment planning and when used to detect enamel-only proximal caries it is an important tool in minimum intervention and preventive dentistry. However, the subtle patterns of enamel-only proximal caries visible in a bitewing radiographs are difficult to detect and often missed by dental practitioners. This pilot study measures the ability of a cohort of third-year dental students to detect enamel-only proximal caries in bitewing radiographs with and without the use of a deep learning assistive software AssistDent®. We demonstrate an increased ability in the detection of enamel-only proximal caries by the students using AssistDent, showing a mean sensitivity level of 0.80 (95%CI ± 0.04), increased from 0.50 (95%CI ± 0.13) p<0.01 shown by students not using AssistDent. This improvement in ability was achieved without an increase in false positives. Mean false positives per bitewing radiograph recorded by students when using AssistDent was 2.64 (95%CI ± 0.57), and by students without using AssistDent was 2.46 (95%CI ± 1.51). Based on these results we conclude that the AI-based software AssistDent significantly improves third-year dental students’ ability to detect enamel-only proximal caries and could be considered as a tool to support minimum intervention and preventive dentistry in teaching hospitals and general practice. We also discuss how the experience of conducting this pilot study can be used to inform the design and methodology of a follow-on study of AssistDent in dental practice use.
Self-reported food choices before and during COVID-19 lockdown
Authors: Mitchell E. Siobhan , Yang Qiuchen , Behr Heather , Deluca Laura , Schaffer Paul
Published: June 2020

Stressful situations can cause changes in individual food choices, most notably, choices of highly rewarding foods that are high in fat or sugar. Few studies have examined how a population’s food choices change during a country-wide stress-inducing event such as the beginning of the COVID-19 stay-at-home orders in the United States. Food data from a digital behavior change weight loss program, which includes an interface for logging meals, were analyzed to assess self-reported food choices from March 5-March 11 (“pre-COVID”) and during the first week of the COVID-19 lockdown (March 12-March 18; “during-COVID”). The final sample consisted of 381,564 participants: 318,076 (83.4%) females, the majority who were aged 45-65 years (45.2%). Results indicate that self-reported servings of fresh fruit and vegetable intake decreased from pre-to during-COVID, while intake of red meat and starchy vegetables increased. More men than women increased their intake of red meat and processed meat. There was less overall change in fruit and vegetable consumption in participants aged 66 and older, compared to younger participants (aged 18-35). The percentage of older participants who reported lean meat and starchy vegetable intake increased, but these groups had a negligible change in younger subjects. More subjects aged 18-35 years reduced their intake of caffeine, desserts, lean meat and salads compared to older participants. No changes were observed in terms of snack or alcoholic beverage intake logged. In conclusion, this study of 381,564 US participants revealed that intake of particular food groups were altered during the first weeks of COVID lockdown.
Modeling the Post-Containment Elimination of Transmission of COVID-19
Authors: Coelho Flávio Codeço , Carvalho Luiz Max , Lana Raquel M , Cruz Oswaldo G , Bastos Leonardo S , Codeço Claudia T , Gomes Marcelo F C , Villela Daniel
Published: June 2020

Roughly six months into the COVID-19 pandemic, many countries have managed to contain the spread of the virus by means of strict containment measures including quarantine, tracing and isolation of patients as well strong restrictions on population mobility. Here we propose an extended SEIR model to explore the dynamics of containment and then explore scenarios for the local extinction of the disease. We present both the deterministic and stochastic version fo the model and derive the ℛ0 and the probability of local extinction after relaxation (elimination of transmission) of containment, ℙ0. We show that local extinctions are possible without further interventions, with reasonable probability, as long as the number of active cases is driven to single digits and strict control of case importation is maintained. The maintenance of defensive behaviors, such as using masks and avoiding agglomerations are also important factors. We also explore the importance of population immunity even when above the herd immunity threshold.
Variable association of atypical femur fracture and osteonecrosis of jaw with bisphosphonates and denosumab use: Drug-safety surveillance study
Authors: Makunts Tigran , Anwar Lara S. , Abagyan Ruben
Published: June 2020

In the United States, there are over ten million adults diagnosed with osteoporosis and many more are at risk of developing the condition. Osteoporosis affects both males and females, mostly post-menopausal. Bisphosphonates and denosumab have been widely used globally to treat the condition. The use of bisphosphonates and denosumab had been associated with rare adverse effects including osteonecrosis of the jaw, ONJ, and atypical femur fracture, AFF. However, it remained unclear whether those side effects were class-wide or drug-specific. By analyzing over 230,000 osteoporosis patient reports from the FDA adverse event reporting system, FAERS, we confirmed the association of bisphosphonates and denosumab use with AFF and ONJ. Additionally, comparing each of the four frequently used bisphosphonates with denosumab-treated patients used as a control, we identified: (i) varying significance of association with ONJ and AFF for alendronate, risedronate, ibandronate and zoledronic acid, (ii) over two fold increase in risk of both side effects in alendronate patients, particularly in females, (iii) over a six fold increase in AFF risk in both males and females taking risedronate, and (iv) lower risk of both AFF and ONJ, for zoledronic acid patients compared to denosumab.

Key points

We performed a disproportionality analysis of over 230,000 post-marketing reports of patients treated for osteoporosis to measure the risk of developing atypical femur fracture (AFF) and osteonecrosis of the jaw (ONJ).

Alendronate, ibandronate, risedronate, zoledronic acid, and denosumab were all significantly associated with AFF and ONJ when compared to teriparatide.

When compared to denosumab, patients taking alendronate, ibandronate, risedronate, or zoledronic acid had a variable risk of ONJ and AFF, which correlated with the frequency of drug administration. The trend in variable risk was observed in both females and males.
Individual Differences in Peripheral Hearing and Cognition Reveal Sentence Processing Differences in Healthy Older Adults
Authors: Kurthen Ira , Meyer Martin , Schlesewsky Matthias , Bornkessel-Schlesewsky Ina
Published: June 2020

When viewed cross-sectionally, aging seems to negatively affect speech comprehension. However, aging is a heterogeneous process, and variability among older adults is typically large. In this study, we investigated language comprehension as a function of individual differences in older adults. Specifically, we tested whether hearing thresholds, working memory, inhibition, and individual alpha frequency would predict event-related potential amplitudes in response to classic psycholinguistic manipulations at the sentence level. Twenty-nine healthy older adults (age range 61-76 years) listened to English sentences containing reduced relative clauses and object-relative clauses while their electroencephalogram was recorded. We found that hearing thresholds and working memory predicted P600 amplitudes early during reduced relative clause processing, while individual alpha frequency predicted P600 amplitudes at a later point in time. The results suggest that participants with better hearing and larger working memory capacity simultaneously activated both the preferred and the dispreferred interpretation of reduced relative clauses, while participants with worse hearing and smaller working memory capacity only activated the preferred interpretation. They also suggest that participants with a higher individual alpha frequency had a higher likelihood of successfully reanalysing the sentence towards the reduced relative clause reading than participants with a lower individual alpha frequency. By contrast, we found no relationship between object-relative clause processing and working memory or hearing thresholds. Taken together, the results support the view that older adults employ different strategies during auditory sentence processing dependent on their hearing and cognitive abilities and that there is no single ability that uniformly predicts sentence processing outcomes.
Massive transient damage of the olfactory epithelium associated with infection of sustentacular cells by SARS-CoV-2 in golden Syrian hamsters
Authors: Bryche Bertrand , St Albin Audrey , Murri Severine , Lacôte Sandra , Pulido Coralie , Gouilh Meriadeg Ar , Lesellier Sandrine , Servat Alexandre , Wasniewski Marine , Picard-Meyer Evelyne , Monchatre-Leroy Elodie , Volmer Romain , Rampin Olivier , Le Goffic Ronan , Marianneau Philippe , Meunier Nicolas
Published: June 2020

Anosmia is one of the most prevalent symptoms of SARS-CoV-2 infection during the COVID-19 pandemic. However, the cellular mechanism behind the sudden loss of smell has not yet been investigated. The initial step of odour detection takes place in the pseudostratified olfactory epithelium (OE) mainly composed of olfactory sensory neurons surrounded by supporting cells known as sustentacular cells. The olfactory neurons project their axons to the olfactory bulb in the central nervous system offering a potential pathway for pathogens to enter the central nervous system by bypassing the blood brain barrier. In the present study, we explored the impact of SARS-COV-2 infection on the olfactory system in golden Syrian hamsters. We observed massive damage of the OE as early as 2 days post nasal instillation of SARS-CoV-2, resulting in a major loss of cilia necessary for odour detection. These damages were associated with infection of a large proportion of sustentacular cells but not of olfactory neurons, and we did not detect any presence of the virus in the olfactory bulbs. We observed massive infiltration of immune cells in the OE andlamina propriaof infected animals, which may contribute to the desquamation of the OE. The OE was partially restored 14 days post infection. Anosmia observed in COVID-19 patient is therefore likely to be linked to a massive and fast desquamation of the OE following sustentacular cells infection with SARS-CoV-2 and subsequent recruitment of immune cells in the OE andlamina propria.