bluuebunny/crossref_metadata_2025 huggingface dataset:
Customized toric intraocular lens implantation in cornea plana
Authors: Fogla Rajesh , Indumathy Thazethaeveetil R.
Published: August 2020

A 50-year-old woman with cornea plana had reduced visual acuity due to development of lenticular changes. Flat keratometry with high astigmatism, shallow anterior chamber depth, and short axial length made it challenging both for intraocular lens (IOL) power calculation and cataract surgery. Surgery was planned for the right eye because the left eye was densely amblyopic. IOL power required was beyond the commercially available lenses; hence, a customized toric IOL was obtained. Phacoemulsification was successfully performed along with in-the-bag implantation of the toric IOL, which resulted in improved visual acuity with satisfactory refractive outcome. Cataract surgery with a customized IOL improved visual acuity in an eye with cornea plana.
Ten-year safety follow-up and post-explant analysis of an anterior chamber phakic IOL
Authors: Kohnen Thomas , Maxwell Andrew , Holland Simon , Lane Stephen , Von Tress Mark , Salem Craig , LaFontaine Laura
Published: August 2020

Purpose:

To assess endothelial cell loss (ECL) rate and collect safety data in patients with AcrySof L-series Cachet phakic intraocular lens (pIOL) up to 10 years post-implantation.

Setting:

Clinical settings in the United States, European Union, and Canada.

Design:

Nonrandomized, observational, open-label safety study.

Methods:

Central and peripheral endothelial cell density was evaluated and compared with 6-month post-implantation baseline. Nonlinear analysis was performed to identify factors affecting post-explantation ECL. Additional evaluations included uncorrected visual acuity (UCVA), corrected distance visual acuity (CDVA), adverse device effects (ADEs), and serious adverse events (SAEs).

Results:

The study included 1123 implanted eyes (mean age, 37.5 years). At 10 years, mean central and peripheral ECL was 16% (1.7% annualized). Explantations were performed in 10% of eyes (n = 136/1323). For eyes with pIOL explantation because of ECL (7%), annualized ECL rate post-explantation was numerically lower compared with the overall rate in eyes that underwent explantation for any reason (annualized rate, −1.65% vs −2.03%, respectively; n = 96) and compared with pre-explantation ECL. Mean ± SD CDVA and UCVA were −0.12 ± 0.11 and 0.03 ± 0.22 logarithm of the minimum angle of resolution, respectively. Common ocular ADEs included ECL (10%), pIOL extraction (9%), iris adhesion (7%), and pupillary deformity (2%). Common SAEs included pIOL extraction (11%), ECL (9%), and iris adhesions (8%).

Conclusions:

Cachet pIOLs were associated with long-term ECL in some cases. Overall, only 10% of all implanted eyes underwent explantation during 10-year follow-up. In patients requiring explantation because of ECL, the annualized ECL rates decreased post-explantation in some eyes. Continued monitoring of patients regardless of explantation is recommended.
Cataract induced by eyelid cosmetic treatment with intense focused ultrasound
Authors: Roditi Eduardo , Wasser Lauren M. , Gelman Evgeny , Zadok David
Published: August 2020

A 45-year-old woman, immediately after receiving a cosmetic treatment with intense focused ultrasound (IFUS) over the eyelids, developed an acute, progressive, severe cataract with a unique shape as an adverse effect of the IFUS esthetic treatment. At examination of the lens in the right eye, 4 drop-like dense lens opacities aligned consecutively in a horizontal line together with a posterior capsular opacity in a stellate-shaped fashion. It rapidly progressed into a dense posterior cataract, leaving the patient with an uncorrected distance visual acuity (UDVA), from 20/20 prior to the event, to 20/160 4 days later. Phacoemulsification and intraocular lens implantation were performed, restoring her UDVA to 20/25. Cosmetic and ophthalmic healthcare providers should be aware of the potentially damaging effect of IFUS.
Differential optical density of fluid in capsular bag distension syndrome
Authors: Oli Avadhesh , Malik Robin , Waikar Shrikant
Published: August 2020

Capsular bag distension syndrome (CBDS) is a rare complication of cataract surgery due to collection of fluid behind the intraocular lens (IOL). Nd:Yag laser capsulotomy is commonly performed to release the fluid collection; however, the potential risk of infection and inflammation has led to adaptation of numerous surgical procedures. Clinical examination in an established case of CBDS reveals opalescent fluid behind the IOL with ballooning of the posterior capsule, which has different reflectivity on optical coherence tomography. However, the exact optical properties of this fluid are still unknown. A case of delayed CBDS with induced myopia due to change in IOL position because of fluid collection behind the IOL is presented.
The Influence of Physicians' Physical Activity Prescription on Indicators of Health Service Quality
Authors: Asiamah Nestor , Kouveliotis Kyriakos , Opoku Emmanuel
Published: August 2020

Introduction

Many researchers are of the opinion that the incorporation of physical activity prescription (PAP) into healthcare is a move that can add value to healthcare, but there are others who think this move would rather disrupt clinical practice. This study, therefore, examined the influence of physicians' PAP (PPAP) on healthcare quality indicators.

Methods

The study adopted a correlational approach and was performed at a primary care facility. Participants were 605 patients in wards and the outpatient department of a district healthcare facility. A self-reported questionnaire was used to gather data. Structural equation modeling was used to present findings.

Results

The study found that PPAP has a positive influence on care quality (β = 0.4, critical ratio = 10.59, and p = .000), patient satisfaction, and patient loyalty. Physical activity prescription also has a positive indirect influence on patient loyalty through patient satisfaction.

Conclusions:

Physicians' physical activity prescription in healthcare can improve healthcare quality indicators. A key implication of our results is that the incorporation of PPAP into healthcare could be in harmony with the key mission of hospitals. Physical activity prescription in healthcare could be a way to satisfy and retain patients.
Loperamide Abuse and Its Sequelae
Authors: Strzyzewski Lauren , Key Phillip , Jones Prentiss , Prahlow Joseph A.
Published: August 2020

Introduction

Loperamide is an opioid available over the counter and in prescription form. Loperamide functions as a μ-agonist within the enteric nervous system to slow intestinal motility. Its antidiarrheal properties and primarily peripheral activity make loperamide an important tool in the management of inflammatory bowel disease.

Case Report

A 42-year-old man was found unconscious in cardiac arrest, and emergency medical personnel restored normal sinus rhythm. Family reported complaints of abdominal pain and that he “went through a lot” of loperamide. In the emergency department, the patient exhibited symptoms consistent with an opioid overdose. Mental status improved after administration of naloxone, an opioid antagonist. An electrocardiogram revealed a prolonged QTc interval, which progressed into Torsades de Pointes rhythm during admission. The patient succumbed from hypoxic brain injury, and there was evidence of acute pancreatitis at autopsy. Loperamide and desmethylloperamide (loperamide metabolite) were detected in blood samples. Cause of death was ruled loperamide toxicity.

Discussion

Because of reduced central nervous system activity and associated euphoria at therapeutic doses, loperamide abuse is rarely reported. This case demonstrates that an overdose on loperamide can occur in patients seeking symptom alleviation, and may mimic the presentation of opioid overdose.
Traumatic Decapitation of the Fetus During Birth
Authors: Vojtíšek Tomáš , Pohlová Kučerová Štěpánka , Duchaňová Svatava , Krajsa Jan , Hejna Petr
Published: August 2020

Serious intrapartum fetal injuries are unfortunate events that confer severe consequences on medical personnel. Most birth traumas are noncritical and resolve for a few days. Permanent effects or fatal outcomes occur infrequently. We report an unusual case of intrapartum complete fetal decapitation. The labor was complicated by shoulder dystocia, with resultant repeated mechanical trauma to the fetal neck and, finally, decapitation. The tragic results of biological processes in human organisms do not automatically confirm medical malpractice. However, there may be grave ethical and forensic outcomes.
Non-relativistic limits and three-dimensional coadjoint Poincaré gravity
Authors: Bergshoeff Eric , Gomis Joaquim , Salgado-Rebolledo Patricio
Published: August 2020

We show that a recently proposed action for three-dimensional non-relativistic gravity can be obtained by taking the limit of a relativistic Lagrangian that involves the coadjoint Poincaré algebra. We point out the similarity of our construction with the way that three-dimensional Galilei gravity and extended Bargmann gravity can be obtained by taking the limit of a relativistic Lagrangian that involves the Poincaré algebra. We extend our results to the anti-de Sitter case and we will see that there is a chiral decomposition at both the relativistic and non-relativistic level. We comment on possible further generalizations.
Coral evolutionary responses to microbial symbioses
Authors: van Oppen Madeleine J. H. , Medina Mónica
Published: August 2020

This review explores how microbial symbioses may have influenced and continue to influence the evolution of reef-building corals (Cnidaria; Scleractinia). The coral holobiont comprises a diverse microbiome including dinoflagellate algae (Dinophyceae; Symbiodiniaceae), bacteria, archaea, fungi and viruses, but here we focus on the Symbiodiniaceae as knowledge of the impact of other microbial symbionts on coral evolution is scant. Symbiosis with Symbiodiniaceae has extended the coral's metabolic capacity through metabolic handoffs and horizontal gene transfer (HGT) and has contributed to the ecological success of these iconic organisms. It necessitated the prior existence or the evolution of a series of adaptations of the host to attract and select the right symbionts, to provide them with a suitable environment and to remove disfunctional symbionts. Signatures of microbial symbiosis in the coral genome include HGT from Symbiodiniaceae and bacteria, gene family expansions, and a broad repertoire of oxidative stress response and innate immunity genes. Symbiosis with Symbiodiniaceae has permitted corals to occupy oligotrophic waters as the algae provide most corals with the majority of their nutrition. However, the coral–Symbiodiniaceae symbiosis is sensitive to climate warming, which disrupts this intimate relationship, causing coral bleaching, mortality and a worldwide decline of coral reefs.

This article is part of the theme issue ‘The role of the microbiome in host evolution’.
In the beginning: egg–microbe interactions and consequences for animal hosts
Authors: Nyholm Spencer V.
Published: August 2020

Microorganisms are associated with the eggs of many animals. For some hosts, the egg serves as the ideal environment for the vertical transmission of beneficial symbionts between generations, while some bacteria use the egg to parasitize their hosts. In a number of animal groups, egg microbiomes often perform other essential functions. The eggs of aquatic and some terrestrial animals are especially susceptible to fouling and disease since they are exposed to high densities of microorganisms. To overcome this challenge, some hosts form beneficial associations with microorganisms, directly incorporating microbes and/or microbial products on or in their eggs to inhibit pathogens and biofouling. Other functional roles for egg-associated microbiomes are hypothesized to involve oxygen and nutrient acquisition. Although some egg-associated microbiomes are correlated with increased host fitness and are essential for successful development, the mechanisms that lead to such outcomes are often not well understood. This review article will discuss different functions of egg microbiomes and how these associations have influenced the biology and evolution of animal hosts.

This article is part of the theme issue ‘The role of the microbiome in host evolution’.
Microbial control of host gene regulation and the evolution of host–microbiome interactions in primates
Authors: Grieneisen Laura , Muehlbauer Amanda L. , Blekhman Ran
Published: August 2020

Recent comparative studies have found evidence consistent with the action of natural selection on gene regulation across primate species. Other recent work has shown that the microbiome can regulate host gene expression in a wide range of relevant tissues, leading to downstream effects on immunity, metabolism and other biological systems in the host. In primates, even closely related host species can have large differences in microbiome composition. One potential consequence of these differences is that host species-specific microbial traits could lead to differences in gene expression that influence primate physiology and adaptation to local environments. Here, we will discuss and integrate recent findings from primate comparative genomics and microbiome research, and explore the notion that the microbiome can influence host evolutionary dynamics by affecting gene regulation across primate host species.

This article is part of the theme issue ‘The role of the microbiome in host evolution’.
The study of host–microbiome (co)evolution across levels of selection
Authors: Koskella Britt , Bergelson Joy
Published: August 2020

Microorganismal diversity can be explained in large part by selection imposed from both the abiotic and biotic environments, including—in the case of host-associated microbiomes—interactions with eukaryotes. As such, the diversity of host-associated microbiomes can be usefully studied across a variety of scales: within a single host over time, among host genotypes within a population, between populations and among host species. A plethora of recent studies across these scales and across diverse systems are: (i) exemplifying the importance of the host genetics in shaping microbiome composition; (ii) uncovering the role of the microbiome in shaping key host phenotypes; and (iii) highlighting the dynamic nature of the microbiome. They have also raised a critical question: do these complex associations fit within our existing understanding of evolution and coevolution, or do these often intimate and seemingly cross-generational interactions follow novel evolutionary rules from those previously identified? Herein, we describe the known importance of (co)evolution in host–microbiome systems, placing the existing data within extant frameworks that have been developed over decades of study, and ask whether there are unique properties of host–microbiome systems that require a paradigm shift. By examining when and how selection can act on the host and its microbiome as a unit (termed, the holobiont), we find that the existing conceptual framework, which focuses on individuals, as well as interactions among individuals and groups, is generally well suited for understanding (co)evolutionary change in these intimate assemblages.

This article is part of the theme issue ‘The role of the microbiome in host evolution’.
Time to negative PCR from symptom onset in COVID-19 patients on Hydroxychloroquine and Azithromycin - A real-world experience
Authors: Saleemi Sarfraz , Alrajhi Abdulrahman , Alhajji Mohammed , Alfattani Areej , Albaiz Faisal
Published: August 2020

Background

The role of hydroxychloroquine (HCQ) and azithromycin in the treatment of COVID-19 and its effect on SARS-CoV-2 viral clearance is not known.

Methods

This is a retrospective observational study to assess the effect of HCQ and Azithromycin on duration from symptom onset to negative SARS-CoV-2 PCR using nasopharyngeal swab in hospitalized patient with COVID-19. Eighty-five patients were included in the study, 65 in HCQ (Hydroxychloroquine + Azithromycin) and 20 in non-HCQ group. Measurement of duration from symptom onset to negative PCR and effect of gender, age and disease severity on time to viral clearance was measured.

Results

Median time to negative PCR in HCQ group was 23 days (IQR: 9, Mean 24+8, N=65) compared with non-HCQ group, 19 days (IQR: 8, Mean 18±6, N=20), (p <0.05). Forty-one (63%) patients in HCQ group and all patients (100%) in non-HCQ group had mild disease. Multivariate regression model (F=6.8, P<0.002, R2=0.20) shows that being in HCQ group would delay the time to negative PCR by 7 days (95%CI: 2-12) and with every year increase in the age, the time to negative PCR would be delayed by 0.12 days (95%CI: 0.017-0.22). Among HCQ sub-groups, gender and disease severity had no effect on duration (p 0.142 and 0.156 respectively) but older patients ≥60 year had longer duration compared to patients <60 year of age although p value did not reach significance (p 0.073). Median time to negative PCR in mild- HCQ group (23 days, IQR: 9, Mean 23+8, N=41) was longer when compared with non-HCQ group (p <0.05). On day 28, all patients in non-HCQ group had negative PCR while only 50/65 (77%) were negative in HCQ group.

Conclusion

Hydroxychloroquine (HCQ) and azithromycin delay SARS-CoV-2 virus clearance in hospitalized patients with COVID-19 and it is correlated with older age. Larger studies are needed to confirm this finding.
Indirect Impact of the COVID-19 Pandemic on Activity and Outcomes of Transcatheter and Surgical Treatment of Severe Aortic Stenosis in England
Authors: Martin Glen P. , Curzen Nick , Goodwin Andrew T. , Nolan James , Balacumaraswami Lognathen , Ludman Peter , Kontopantelis Evangelos , Wu Jianhua , Gale Chris , de Belder Mark A , Mamas Mamas A.
Published: August 2020

Background

Aortic stenosis requires timely treatment with either surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR). This study aimed to investigate the indirect impact of COVID-19 on national SAVR and TAVR activity and outcomes.

Methods

The UK TAVR Registry and the National Adult Cardiac Surgery Audit were used to identify all TAVR and SAVR procedures in England, between January 2017 and June 2020. The number of isolated AVR, AVR+coronary artery bypass graft (CABG) surgery, AVR+other surgery and TAVR procedures per month was calculated. Separate negative binomial regression models were fit to monthly procedural counts, with functions of time as covariates, to estimate the expected change in activity during COVID-19.

Results

We included 13376 TAVR cases, 12328 isolated AVR cases, 7829 AVR+CABG cases, and 6014 AVR+Other cases. Prior to March 2020 (UK lockdown), monthly TAVR activity was rising, with a slight decrease in SAVR activity during 2019. We observed a rapid and significant drop in TAVR and SAVR activity during the COVID-19 pandemic, especially for elective cases. Cumulatively, over the period March to June 2020, we estimated an expected 2294 (95% CI 1872, 2716) cases of severe aortic stenosis who have not received treatment.

Conclusion

This study has demonstrated a significant decrease in TAVR and SAVR activity in England following the COVID-19 outbreak. This situation should be monitored closely, to ensure that monthly activity rapidly returns to expected levels. There is potential for significant backlog in the near-to-medium term, and potential for increased mortality in this population.
Decoding distinctive features of plasma extracellular vesicles in amyotrophic lateral sclerosis
Authors: Pasetto Laura , Callegaro Stefano , Corbelli Alessandro , Fiordaliso Fabio , Ferrara Deborah , Brunelli Laura , Sestito Giovanna , Pastorelli Roberta , Bianchi Elisa , Cretich Marina , Chiari Marcella , Potrich Cristina , Moglia Cristina , Corbo Massimo , Sorarù Gianni , Lunetta Christian , Calvo Andrea , Chiò Adriano , Mora Gabriele , Pennuto Maria , Quattrone Alessandro , Rinaldi Francesco , D’Agostino Vito Giuseppe , Basso Manuela , Bonetto Valentina
Published: August 2020

Background

Amyotrophic lateral sclerosis (ALS) is a multifactorial, multisystem motor neuron disease for which currently there is no effective treatment. There is an urgent need to identify biomarkers to tackle the disease’s complexity and help in early diagnosis, prognosis, and therapy. Extracellular vesicles (EVs) are nanostructures released by any cell type into body fluids. Their biophysical and biochemical characteristics vary with the parent cell’s physiological and pathological state and make them an attractive source of multidimensional data for patient classification and stratification.

Methods

We analyzed plasma-derived EVs of ALS patients (n= 106) and controls (n=96), and SOD1G93Aand TDP-43Q331Kmouse models of ALS. We purified plasma EVs by nickel-based isolation, characterized their EV size distribution and morphology respectively by nanotracking analysis and transmission electron microscopy, and analyzed EV markers and protein cargos by Western blot and proteomics. We used machine learning techniques to predict diagnosis and prognosis.

Results

Our procedure resulted in high-yield isolation of intact and polydisperse plasma EVs, with minimal lipoprotein contamination. There were more particles in the plasma of ALS patients and the two mouse models of ALS while their average diameter was smaller. HSP90 was differentially represented in ALS patients and mice compared to the controls. In terms of disease progression, the levels of cyclophilin A, with the EV size distribution, distinguished fast and slow disease progressors, suggesting a new means for patient stratification. We also measured the levels of phosphorylated TDP-43 and showed that is not an intravesicular cargo of plasma-derived EVs.

Conclusions

Our analysis unmasked features in plasma EVs of ALS patients with potential straightforward clinical application. We conceived an innovative mathematical model based on machine learning which, by integrating EV size distribution data with protein cargoes, gave very high prediction rates for disease diagnosis and prognosis.
Natural Polymorphisms in Mycobacterium tuberculosis Conferring Resistance to Delamanid in Drug-naïve Patients
Authors: Reichmuth Martina L. , Hoemke Rico , Zürcher Kathrin , Sander Peter , Avihingsanon Anchalee , Collantes Jimena , Loiseau Chloé , Borrell Sonia , Reinhard Miriam , Wilkinson Robert J. , Yotebieng Marcel , Fenner Lukas , Böttger Erik C. , Gagneux Sebastien , Egger Matthias , Keller Peter M.
Published: August 2020

Mutations in the genes of the F420 signaling pathway, including dnn, fgd1, fbiA, fbiB, fbiC, and fbiD, of Mycobacterium tuberculosis (Mtb) complex can lead to delamanid resistance. We searched for such mutations among 129 Mtb strains from Asia, South-America, and Africa using whole-genome sequencing; 70 (54%) strains had at least one mutation in one of the genes. For ten strains with mutations, we determined the minimum inhibitory concentration (MIC) of delamanid. We found one strain from a delamanid-naïve patient carrying the natural polymorphism Tyr29del (ddn) that was associated with a critical MIC to delamanid.
Mask-associated de novo headache in healthcare workers during the Covid-19 pandemic
Authors: Ramírez-Moreno José M , Ceberino David , González-Plata Alberto , Rebollo Belen , Macías-Sedas Pablo , Ramchandani Roshu Hariranami , Roa Ana M , Constantino Ana B
Published: August 2020

Introduction

The pandemic caused by the new coronavirus (COVID-19) has led to changes in the development of health care activities by health professionals. We analysed whether there is an association between the appearance of “de novo” headache according to the type of mask used, the related factors, as well as the impact of the headache on health professionals.

Method

cross-sectional study in a tertiary hospital in Extremadura, Spain. We administered an online questionnaire to healthcare workers during the period of maximum incidence of COVID-19 in our setting.

Results

n=306, 244 women (79.7%), with an average age of 43 years (range 23-65). Of the total, 129 (42.2%) were physicians, 112 (36.6%) nurses and 65 (21.2%) other health workers. 208 (79.7%) used surgical masks and 53 (20.3%) used filtering masks. Of all those surveyed, 158 (51.6%) presented “de novo” headache. The occurrence of headache was independently associated with the use of a filtering mask, OR 2.14 (IC95% 1.07-4.32), being a nurse OR 2.09 (IC95% 1.18-3.72) or another health worker OR 6.94 (IC95% 3.01-16.04) or having a history of asthma OR 0.29 (IC95% 0.09-0.89). Depending on the type of mask used there were differences in headache intensity. And the impact of headache in the subjects who used a filtering mask was worse in the all aspects evaluated.

Conclusions

The appearance of “de novo” headache is associated with the use of filtering masks and is more frequent in certain health care workers, causing a greater occupational, family, personal and social impact.
Reflux Esophagitis is Associated with Higher Risks of Acute Stroke and Transient Ischemic Attacks in Patients Hospitalized with Atrial Fibrillation: A Nationwide Inpatient Sample Analysis
Authors: Jiang Yi , Damiris Konstantinos , Suero-Abreu Giselle A. , Ahlawat Sushil
Published: August 2020

Objective

Reflux esophagitis (RE) is a subset of gastroesophageal reflux disease (GERD) with endoscopic evidence of esophageal inflammation, which has been linked to an increased incidence of atrial fibrillation (AF). However, data on the effect of RE on patient outcomes is limited. We sought to examine the potential association of RE with outcomes of patients with AF in a nationwide study.

Methods

The National Inpatient Sample (NIS) database was queried to identify hospitalized adult patients with AF and RE between 2010 and 2014. Primary outcomes included inpatient mortality, length of stay (LOS), and total hospital charges. AF related complications such as acute stroke, transient ischemic attack (TIA) and acute heart failure were assessed as secondary outcomes. Propensity score matching and multivariate regression analysis were used.

Results

667,520 patients were admitted for primary diagnosis of AF out of which 5,396 had a secondary diagnosis of RE. In the AF with RE cohort, the average age was 73.6 years, 41.5% were male, and 79.9% were Caucasian. There was a greater prevalence of concomitant dyslipidemia, chronic liver disease and chronic pulmonary disease (p <0.01) when compared to the AF without RE cohort. Patients with AF and RE also had higher incidence of acute strokes and TIAs (p<0.05), longer LOS (p<0.001), and higher hospital charges (p<0.05) with no difference in acute heart failure (p=0.08), hospital mortality (p=0.12), or CHA2DS2-VAS score (p=0.67).

Conclusion

In hospitalized patients with AF, RE was associated with a higher rate of acute stroke and TIA, longer LOS, and greater hospital charges.
Retrospective study on the clinicogenomic characteristics of EGFR mutant and wildtype NSCLC
Authors: Dhar Chirag
Published: August 2020

Background

Lung cancer is among the leading causes of mortality. Nearly 90% of all lung cancers are histologically classified as non-small cell lung cancer (NSCLC). A subset of these tumors harbor mutations on the epidermal growth factor receptor gene (EGFR) and such patients are candidates for targeted therapy with EGFR tyrosine kinase inhibitors (EGFR TKIs).

Aim

To compare and contrast the clinicogenomic characteristics of EGFR mutant and wildtype NSCLC.

Methods and results

A retrospective cohort study design was used to analyze publicly available data on cBioPortal.org. Patients with EGFR mutations were more likely to be female, of Asian ethnicity, never-smokers, and diagnosed with lung adenocarcinoma. Metastasis to the pleura, pleural fluid, and liver were common in patients with EGFR mutant NSCLC. On the other hand, lymph node, brain and adrenal gland metastases were more common in patients with other mutations. While the median overall survival was about the same in the two groups, progression free survival was significantly shorter in the EGFR mutant group. The mutational landscape was significantly different in the two groups with EGFR mutant NSCLCs having a lower mutational burden. Differences in copy number alterations between the two groups were also noted.

Conclusions

The clinicogenomic profiles of EGFR mutant and EGFR wildtype significantly differ. Further studies on these differences and underlying mechanisms are likely to lead to new “druggable” targets that overcome EGFR TKI resistance.
In-depth Analysis of Laboratory Parameters Reveals the Interplay Between Sex, Age and Systemic Inflammation in Individuals with COVID-19
Authors: ten-Caten Felipe , Gonzalez-Dias Patrícia , Castro Ícaro , Ogava Rodrigo L T , Giddaluru Jeevan , Silva Juan Carlo S , Martins Felipe , Gonçalves André N A , Costa-Martins André G , Araujo José D. , Viegas Ana Carolina , Cunha Fernando Q , Farsky Sandra , Bozza Fernando A , Levin Anna S , Pannaraj Pia S , de Silva Thushan I , Minoprio Paola , Andrade Bruno B , da Silva Fabiano Pinheiro , Nakaya Helder I
Published: August 2020

Introduction

The progression and severity of the coronavirus disease 2019 (COVID-19), an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), varies significantly in the population. While the hallmarks of SARS-CoV-2 and severe COVID-19 within routine laboratory parameters are emerging, little is known about the impact of sex and age on these profiles.

Methods

We performed multidimensional analysis of millions of records of laboratory parameters and diagnostic tests for 178,887 individuals, of which 33,266 tested positive for SARS-CoV-2. These included complete blood cell count, electrolytes, metabolites, arterial blood gases, enzymes, hormones, cancer biomarkers, and others.

Results

COVID-19 induced similar alterations in the laboratory parameters in males compared to females. Biomarkers of inflammation, such as C-reactive protein (CRP) and ferritin, were increased especially in older men with COVID-19, whereas other markers such as abnormal liver function tests were common across several age groups, except for young women. Low peripheral blood basophils and eosinophils were also more common in the elderly with COVID-19. Both male and female COVID-19 patients admitted to the intensive care unit (ICU) displayed alterations in the coagulation system, and higher levels of neutrophils, CRP, lactate dehydrogenase (LDH), among others.

Discussion

Our study uncovers the laboratory profile of a large cohort of COVID-19 patients that underly discrepancies influenced by aging and biological sex. These profiles directly link COVID-19 disease presentation to an intricate interplay between sex, age and the immune response.

One Sentence Summary

Big Data analysis of laboratory results from a large number of COVID-19 patients and controls reveals distinct disease profiles influenced by age and sex which may underly occurrence of severe disease.

Key messages

- What is the key question?

Little is known about the impact of sex and age on the routine laboratory parameters measured in COVID-19 patients.

- What is the bottom line?

Our in-depth analysis unraveled distinct disease profiles influenced by age and sex which may underly occurrence of severe disease.

- Why read on?

This work will help physicians to interpret the disease presentation in COIVD-19 patients according to their age and sex.
Population perspective comparing COVID-19 to all and common causes of death in seven European countries
Authors: Olabi Bayanne , Bagaria Jayshree , Bhopal Sunil S. , Curry Gwenetta D. , Villarroel Nazmy , Bhopal Raj
Published: August 2020

Background

Mortality statistics on the COVID-19 pandemic have led to widespread concern and fear. To contextualise these data, we compared mortality related to COVID-19 with all and common causes of death, stratifying by age and sex. We also calculated deaths as a proportion of the population by age and sex.

Methods

COVID-19 related mortality and population statistics from seven European countries were extracted: England and Wales, Italy, Germany, Spain, France, Portugal and Netherlands. Available data spanned 14-16 weeks since the first recorded deaths in each country, except Spain, where only comparable stratified data over an 8-week time period was available. The Global Burden of Disease database provided data on all deaths and those from pneumonia, cardiovascular disease combining ischaemic heart disease and stroke, chronic obstructive pulmonary disease, cancer, road traffic accidents and dementia.

Findings

Deaths related to COVID-19, while modest overall, varied considerably by age. Deaths as a percentage of all cause deaths during the time period under study ranged from <0.01% in children in Germany, Portugal and Netherlands, to as high as 41.65% for men aged over 80 years in England and Wales. The percentage of the population who died from COVID-19 was less than 0.2% in every age group under the age of 80. In each country, over the age of 80, these proportions were: England and Wales 1.27% males, 0.87% females; Italy 0.6% males, 0.38% females; Germany 0.13% males, 0.09% females; France 0.39% males, 0.2% females; Portugal 0.2% males, 0.15% females; and Netherlands 0.6% males, 0.4% females.

Interpretation

Mortality rates from COVID-19 remains low including when compared to other common causes of death and will likely decline further while control measures are maintained. These data may help people contextualise their risk and policy makers in decision-making.
Compound risks of hurricane evacuation amid the COVID-19 pandemic in the United States
Authors: Pei Sen , Dahl Kristina A. , Yamana Teresa K. , Licker Rachel , Shaman Jeffrey
Published: August 2020

Current projections and unprecedented storm activity to date suggest the 2020 Atlantic hurricane season will be extremely active and that a major hurricane could make landfall during the global COVID-19 pandemic. Such an event would necessitate a large-scale evacuation, with implications for the trajectory of the pandemic. Here we model how a hypothetical hurricane evacuation from four counties in southeast Florida would affect COVID-19 case levels. We find that hurricane evacuation increases the total number of COVID-19 cases in both origin and destination locations; however, if transmission rates in destination counties can be kept from rising during evacuation, excess evacuation-induced case numbers can be minimized by directing evacuees to counties experiencing lower COVID-19 transmission rates. Ultimately, the number of excess COVID-19 cases produced by the evacuation depends on the ability of destination counties to meet evacuee needs while minimizing virus exposure through public health directives.
Reproducibility in systems biology modelling
Authors: Tiwari Krishna , Kananathan Sarubini , Roberts Matthew G , Meyer Johannes P , Sharif Shohan Mohammad Umer , Xavier Ashley , Maire Matthieu , Zyoud Ahmad , Men Jinghao , Ng Szeyi , Nguyen Tung V N , Glont Mihai , Hermjakob Henning , Malik-Sheriff Rahuman S.
Published: August 2020

The reproducibility crisis has emerged as an important concern across many fields of science including life science, since many published results failed to reproduce. Systems biology modelling, which involves mathematical representation of biological processes to study complex system behaviour, was expected to be least affected by this crisis. While lack of reproducibility of experimental results and computational analysis could be a repercussion of several compounded factors, it was not fully understood why systems biology models with well-defined mathematical expressions fail to reproduce and how prevalent it is. Hence, we systematically attempted to reproduce455kinetic models of biological processes published in peer-reviewed research articles from152journals; which is collectively a work of about1400scientists from49countries. Our investigation revealed that about half (49%) of the models could not be reproduced using the information provided in the published manuscripts. With further effort, an additional 12% of the models could be reproduced either by empirical correction or support from authors. The other 37% remained non-reproducible models due to missing parameter values, missing initial concentration, inconsistent model structure, or a combination of these factors. Among the corresponding authors of the non-reproducible model we contacted, less than30%responded. Our analysis revealed that models published in journals across several fields of life science failed to reproduce, revealing a common problem in the peer-review process. Hence, we propose an 8-point reproducibility scorecard that can be used by authors, reviewers and journal editors to assess each model and address the reproducibility crisis.
Dach1 extends artery networks and protects against cardiac injury
Authors: Raftrey Brian , Williams Ian , Rios Coronado Pamela E. , Chang Andrew H. , Zhao Mingming , Roth Robert , Racelis Raquel , D’Amato Gaetano , Phansalkar Ragini , Gonzalez Karen M. , Zhang Yue , Bernstein Daniel , Red-Horse Kristy
Published: August 2020

Coronary artery disease (CAD) is the leading cause of death worldwide, but there are currently no available methods to stimulate growth or regeneration of artery networks in diseased hearts. Studying how arteries are built during embryonic development could illuminate strategies for re-building these vessels in the setting of ischemic heart disease. We previously found, using loss-of-function experiments, that the transcription factorDach1is required for coronary artery development in mouse embryos. Here, we report thatDach1overexpression in endothelial cells (ECs) extended coronary arteries and improved survival and heart function in adult mice following myocardial infarction (MI).Dach1overexpression increased the length and number of arterial end branches, in both heart and retinal vasculature, by causing additional capillary ECs to differentiate into arterial ECs and contribute to growing arteries. Single-cell RNA sequencing (scRNAseq) of ECs undergoingDach1-induced arterial specification indicated that it potentiated normal artery differentiation, rather than functioning as a master regulator of artery cell fate. ScRNAseq also showed that normal arterial differentiation is accompanied by repression of lipid metabolism genes, which were also repressed by Dach1 prior to arterialization. Together, these results demonstrate that increasing the expression level ofDach1is a novel pathway for driving specification of artery ECs and extending arterial vessels, which could be explored as a means of increasing artery coverage to mitigate the effects of CAD.
Dynamics of infection in a novel group of promiscuous phages and hosts of multiple bacterial genera retrieved from river communities
Authors: Cazares Daniel , Cazares Adrian , Figueroa Wendy , Guarneros Gabriel , Edwards Robert A. , Vinuesa Pablo
Published: August 2020

Phages are generally described as species- or even strain-specific viruses, implying an inherent limitation for some to be maintained and spread in diverse bacterial communities. Moreover, phage isolation and host range determination rarely consider the phage ecological context, likely biasing our notion on phage specificity. Here we identified and characterized a novel group of promiscuous phages existing in rivers by using diverse bacteria isolated from the same samples, and then used this biological system to investigate infection dynamics in distantly related hosts. We assembled a diverse collection of over 600 native bacterial strains and used them to isolate six podophages, named Atoyac, from different geographic origin and capable of infecting six genera in the Gammaproteobacteria. Atoyac phage genomes are highly similar to each other but not to those currently available in the genome and metagenome public databases. Detailed comparison of the phage’s infectivity in diverse hosts and trough hundreds of interactions revealed variation in plating efficiency amongst bacterial genera, implying a cost associated with infection of distant hosts, and between phages, despite their sequence similarity. We show, through experimental evolution in single or alternate hosts of different genera, that plaque production efficiency is highly dynamic and tends towards optimization in hosts rendering low plaque formation. Complex adaptation outcomes observed in the evolution experiments differed between highly similar phages and suggest that propagation in multiple hosts may be key to maintain promiscuity in some viruses. Our study expands our knowledge of the virosphere and uncovers bacteria-phage interactions overlooked in natural systems.

Importance

In natural environments, phages co-exist and interact with a broad variety of bacteria, posing a conundrum for narrow-host-range phages maintenance in diverse communities. This context is rarely considered in the study of host-phage interactions, typically focused on narrow-host-range viruses and their infectivity in target bacteria isolated from sources distinct to where the phages were retrieved from. By studying phage-host interactions in bacteria and viruses isolated from river microbial communities, we show that novel phages with promiscuous host range encompassing multiple bacterial genera can be found in the environment. Assessment of hundreds of interactions in diverse hosts revealed that similar phages exhibit different infection efficiency and adaptation patterns. Understanding host range is fundamental in our knowledge of bacteria-phage interactions and their impact in microbial communities. The dynamic nature of phage promiscuity revealed in our study has implications in different aspects of phage research such as horizontal gene transfer or phage therapy.
A Validated Measure of Rigidity in Parkinson’s Disease Using Alternating Finger Tapping on an Engineered Keyboard
Authors: Trager Megan H , Wilkins Kevin B , Koop Mandy Miller , Bronte-Stewart Helen
Published: August 2020

Introduction

Reliable and accurate measures of rigidity have remained elusive in remote assessments of Parkinson’s disease (PD). This has severely limited the utility of telemedicine in the care and treatment of people with PD. It has also had a large negative impact on the scope of available outcomes, and on the costs, of multicenter clinical trials in PD. The goal of this study was to determine if quantitative measures from an engineered keyboard were sensitive and related to clinical measures of rigidity.

Methods

Sixteen participants with idiopathic PD, off antiparkinsonian medications, and eleven age-matched control participants performed a 30 second repetitive alternating finger tapping task on an engineered keyboard and were assessed with the Unified Parkinson’s Disease Rating Scale – motor (UPDRS-III).

Results

The speed of the key release was significantly slower in the PD compared to control cohorts (p <0.0001). In the PD cohort key release speed correlated with the lateralized upper extremity UPDRS III rigidity score (r = - 0.58, p < 0.0001), but not with the lateralized upper extremity tremor score (r = 0.14, p = 0.43).

Conclusions

This validated measure of rigidity complements our previous validation of temporal metrics of the repetitive alternating finger tapping task with the UPDRS III, bradykinesia and with the ability to quantify tremor, arrhythmicity and freezing episodes, and suggests that thirty seconds of alternating finger tapping on a portable engineered keyboard could transform the treatment of PD with telemedicine and the precision of multicenter clinical trials.
Comparative Clinical Outcomes and Mortality in Prisoner and Non-Prisoner Populations Hospitalized with COVID-19: A Cohort from Michigan
Authors: Altibi Ahmed M. , Pallavi Bhargava , Liaqat Hassan , Slota Alexander A. , Sheth Radhika , Al Jebbawi Lama , George Matthew E. , LeDuc Allison , Abdallah Enas , Russel Luke R. , Jain Saniya , Shirvanian Nariné , Masri Ahmad , Kak Vivek
Published: August 2020

Background

Prisons in the United States have become a hotbed for spreading Covid-19 among incarcerated individuals. Covid-19 cases among prisoners are on the rise, with more than 46,000 confirmed cases to date. However, there is paucity of data addressing clinical outcomes and mortality in prisoners hospitalized with Covid-19.

Methods

An observational study of all patients hospitalized with Covid-19 between March 10 and May 10, 2020 at two Henry Ford Health System hospitals in Michigan. Clinical outcomes were compared amongst hospitalized prisoners and non-prisoner patients. The primary outcomes were intubation rates, in-hospital mortality, and 30-day mortality. Multivariable logistic regression and Cox-regression models were used to investigate primary outcomes.

Results

Of the 706 hospitalized Covid-19 patients (mean age 66.7 ± 16.1 years, 57% males, and 44% black), 108 were prisoners and 598 were non-prisoners. Compared to non-prisoners, prisoners were more likely to present with fever, tachypnea, hypoxemia, and markedly elevated inflammatory markers. Prisoners were more commonly admitted to the intensive care unit (ICU) (26.9% vs. 18.7%), required vasopressors (24.1% vs. 9.9%), and intubated (25.0% vs. 15.2%). Prisoners had higher unadjusted inpatient mortality (29.6% vs. 20.1%) and 30-day mortality (34.3% vs. 24.6%). In the adjusted models, prisoner status was associated with higher in-hospital death (odds ratio, 1.95; 95% confidence interval (CI), 1.07 to 3.57) and 30-day mortality (hazard ratio, 1.92; 95% CI, 1.24 to 2.98).

Conclusions

In this cohort of hospitalized Covid-19 patients, prisoner status was associated with more severe clinical presentation, higher rates of ICU admissions, vasopressors requirement, intubation, inhospital mortality, and 30-day mortality.