bluuebunny/crossref_metadata_2025 huggingface dataset:
Using the Lateral Pontine Safe Entry Zone for Resection of Deep-Seated Cavernous Malformations in the Lateral Pons: 2-Dimensional Operative Video
Authors: Cavalcanti Daniel D , Catapano Joshua S , Niemeyer Filho Paulo
Published: May 2020

The retrosigmoid approach is one of the main approaches used in the surgical management of pontine cavernous malformations. It definitely provides a lateral route to large central lesions but also makes possible resection of some ventral lesions as an alternative to the petrosal approaches. However, when these vascular malformations do not emerge on surface, one of the safe corridors delimited by the origin of the trigeminal nerve and the seventh-eight cranial nerve complex can be used.
1-5

 Baghai et al
2
described the lateral pontine safe entry zone in 1982, as an alternative to approaches through the floor of the fourth ventricle when performing tumor biopsies. They advocated a small neurotomy performed right between the emergence of the trigeminal nerve and the facial-vestibulocochlear cranial nerves complex. Accurate image guidance, intraoperative cranial nerve monitoring, and comprehensive anatomical knowledge are critical for this approach.
4,5

 Knowing the natural history of a brainstem cavernous malformation after bleeding,
6
we sought to demonstrate in this video: (1) the use of the retrosigmoid craniotomy in lateral decubitus for resection of deep-seated pontine cavernous malformations; (2) the wide opening of arachnoid membranes and dissection of the superior petrosal vein complex to improve surgical freedom and prevent use of fixed cerebellar retraction; and (3) the opening of the petrosal fissure and exposure of the lateral pontine zone for gross total resection of a cavernous malformation in a 19-yr-old female with a classical crossed brainstem syndrome. She had full neurological recovery after 3 mo of follow-up.

 The patient consented in full to the surgical procedure and publication of the video and manuscript.
MEASUREMENT OF OPERATIONAL DOSIMETRY QUANTITIES FOR NUCLEAR MEDICINE STAFF
Authors: Dehghan Nahid , Sina Sedigheh
Published: May 2020

According to the ALARA principle, exposure to radiation should be reduced as low as reasonably achievable. This principle is very important in nuclear medicine (NM), and different investigations have been performed by establishing protocols and standards for staff protection. This study aims to measure the operational quantities, personal dose equivalent, Hp (10), Hp (0.07) and Hp (3) for NM staff in Shiraz hospitals, and comparison with dose limits. Two types of dosimeters, TLD-100 and GR-200, were used in this study. In the first step, the calibration of dosimeters was performed using different phantoms. Then, a group of dosimeters was prepared and used for 1 month on the heads, wrists and chests of the staff for measurement of Hp (3), Hp (0.07) and Hp (10), respectively. The obtained values of Hp (10) were compared with the results of their personal dosimetry, film badge. The results of this study show good consistency in the measurements using the two dosimeters.
Narcolepsy type 1: what have we learned from genetics?
Authors: Ollila Hanna M
Published: May 2020

Type-1 narcolepsy is a severe neurological disorder with distinct characteristic of loss of hypocretin neurotransmitter. Genetic analysis in type-1 narcolepsy have revealed a unique signal pointing toward autoimmune, rather than psychiatric origin. While type-1 narcolepsy has been intensively studied, the other subtypes of hypersomnolence, narcolepsy, and hypersomnia are less thoroughly understood. This review summarizes the latest breakthroughs in the field in narcolepsy. The goal of this article is to help the reader to understand better the risk from genetic factors and their interplay with immune, genetic, and epidemiological aspects in narcolepsy.
Society of Behavioral Medicine Update: retain support for the National Colorectal Cancer Roundtable’s call to action to reach 80% colorectal cancer screening
Authors: Tussing-Humphreys Lisa , Buscemi Joanna , Kanoon Jacqueline M , Watts Elizabeth A , Watson Karriem , Fitzgibbon Marian , Jung Barbara , Winn Robert
Published: May 2020

Colorectal cancer (CRC) remains the third most commonly diagnosed cancer and the third leading cause of cancer-related death in the USA. CRC can be prevented through regular screening and removal of precancerous polyps. However, roughly one third of eligible adults in the USA are not up to date with recommended CRC screening. To increase timely CRC screening uptake in the USA, in 2014, the National Colorectal Cancer Roundtable (NCCRT) launched 80% by 2018. This multilevel effort involved more than 1,500 pledged organizations targeting patients, providers, health care systems, and policymakers to increase U.S. CRC screening rates to 80% by 2018. Concurrent with this campaign, between 2012 and 2018, CRC screening rates increased nationwide by 3.6% from 65.2% to 68.8%, meaning that about 9.3 million more U.S. adults are being screened. NCCRT attributes these successes to widespread implementation of center- and system-wide evidence-based interventions to increase screening uptake, including direct patient communication, provider reminders via electronic health records, and patient navigation, among others. Moving beyond 2018, NCCRT has rebranded the initiative as the 80% Pledge and has since identified several targeted campaigns, including increased outreach to Hispanics, Latinos, and Asians, whose CRC screening uptake remains less than 50%; encouragement of Medicaid outreach activities around CRC screening in all 50 states; and advocacy for screening right at 50 years of age. Society of Behavioral Medicine continues to support NCCRT and encourages policymakers to do the same by taking legislative action to assure funding for Medicaid outreach, research innovations, and clinical quality improvement that supports the 80% Pledge.
11Science and Medicine
Authors: Chico Tita
Published: May 2020

The titles reviewed in this chapter concern science and medicine studies. They represent work drawn from a variety of contexts and disciplinary perspectives, including science and technology, the history of science, literary studies, critical race theory, public health, the philosophy of science, law, ethnography, anthropology, architecture, and geology. The chapter has five sections: 1. Histories and Historicity; 2. Epistemology and Dissemination; 3. Institutions and Praxis; 4. Bodies and Subjectivities; and 5. Conversations (Journals).
Prevention of Platinum-Induced Hearing Loss in Children with Cancer
Authors: Navarro-Ruiz Nancy Evelyn
Published: May 2020

Editor's note: The mission of Cochrane Nursing is to provide an international evidence base for nurses involved in delivering, leading, or researching nursing care. Cochrane Corner provides summaries of recent systematic reviews from the Cochrane Library. For more information, see https://nursing.cochrane.org.
First Oral Immunotherapy for Peanut Allergy
Authors: Aschenbrenner Diane S.
Published: May 2020

Peanut (Arachis hypogaea) allergen powder-dnfp (Palforzia) is the first oral immunotherapy for children ages four to 17 years who have been diagnosed with a peanut allergy.

Like subcutaneous forms of immunotherapy, Palforzia introduces the allergen in increasing doses and risks inducing allergic responses, including anaphylaxis.
Reducing Waste in the Clinical Setting
Authors: Wohlford Sara , Esteves-Fuentes Nathalia , Carter Kimberly Ferren
Published: May 2020

Nurses have the capacity and opportunity to alter their organization's environmental footprint. This article addresses how they can strengthen efficiency and environmental sustainability initiatives in their facilities by engaging in, monitoring, and supporting environmentally friendly clinical practices and programs at the point of care. Included are practical tips and examples of projects in which nurses identified sources of waste—the relaundering of unused linens; disposal of unused products; and improper sorting of pharmaceutical waste, recycling, and regulated medical waste—and realized significant cost savings as well as improved efficiency and environmental sustainability.
Automated CT Biomarkers Predict Cardiovascular Events and Survival Better than Clinical Parameters
Authors: Rosenberg Karen
Published: May 2020

According to this study:

In asymptomatic adults, fully automated quantitative tissue biomarkers derived from computed tomography (CT) scans can perform better than established clinical parameters in predicting future cardiovascular events and overall survival.

These data support the added value of abdominal CT scans performed for other indications.
Tear Levels of IGFBP-3: A Potential Biomarker for Diabetic Nerve Changes in the Cornea
Authors: Stuard Whitney L. , Titone Rossella , Robertson Danielle M.
Published: May 2020

Introduction:

Type 2 diabetes mellitus has reached epidemic levels in the United States and worldwide. Ocular complications from this disease include diabetic retinopathy and keratopathy, both of which can lead to significant vision loss. While frequently underappreciated, diabetic keratopathy is associated with painful ocular surface disorders, including corneal erosions and delayed wound healing. Recent work in our laboratory has focused on the role of the insulin-like growth factor (IGF) system in diabetic corneal disease.

Methods:

Here, we review recent findings on the presence of IGF-1, insulin, and the insulin-like binding protein (IGFBP-3) in human tear fluid and evaluate their potential use as biomarkers in diabetes. We further examine clinical evidence using in vivo confocal microscopy as an important imaging biomarker in diabetes and discuss associations between tear film changes in diabetes and corneal nerve loss.

Results:

IGFBP-3 was the only tear film marker significantly associated with nerve loss in type 2 diabetes, whereas tear levels of IGF-1 were associated with aging. Interestingly, tear levels of IGFBP-3 were not directly related to serum levels of HbA1c, suggesting that hyperglycemia alone is not driving increased secretion of this protein.

Conclusions:

Overwhelming evidence supports the use of in vivo confocal microscopy as a tool to evaluate corneal nerve and epithelial changes induced by diabetes in research settings. The newly identified relationship between morphological changes in the corneal subbasal nerve plexus in diabetes and the increase in tear levels of IGFBP-3 suggest that this protein may represent an innovative new biomarker to assess risk of ocular and nonocular complications in type 2 diabetes mellitus.
Management of Post-DALK Recipient Posterior Stromal Scarring: A Novel Approach
Authors: Sharma Vijay K. , Trehan Hemant S. , Kurumkattil Raji , Dhar Sanjay K.
Published: May 2020

Aim:

Management of recipient posterior stromal scarring following deep anterior lamellar keratoplasty (DALK) by a novel approach.

Methods:

A side port knife bent at the tip is used to make a linear incision in the host posterior stroma. Plane between host posterior stroma and DALK tissue is separated using a reverse sinskey hook and multiple radial incisions are made using microvitroretinal scissors. The recipient posterior stromal wedges are removed using 20G vitrector with a cut rate of 800 cuts/min. A Descemet stripping endothelial keratoplasty lenticule is inserted into the anterior chamber and apposed to the posterior surface of DALK tissue using air tamponade.

Result:

This technique was used in 10 patients who showed clearing of the scarring after the surgery with good apposition of the donor graft to the previous DALK tissue. Conclusion: This is a sutureless, relatively simple, inexpensive, and effective novel surgical technique that avoids complications of open sky procedure and can be replicated in any ophthalmologic operation theatre setup.
Passive Verification: A Flawed System Putting Patients' Sight at Risk
Authors: Yupari Renato J. , Steinemann Thomas L.
Published: May 2020

Objective:

To assess the rate of erroneous or expired (invalid) contact lens prescriptions submitted for passive verification at two practice sites in Cleveland, OH.

Methods:

Passive verification facsimile (FAX) requests were collected from office staff at a county hospital (MetroHealth [MH]), and at a private ophthalmology group office (University Ophthalmology Associates [UOA]) in Cleveland, Ohio, from January 2013 to January 2018.

Results:

A total of 415 verification requests were evaluated (339 MH, 75 UOA), 28.2% (104 MH, 13 UOA) were expired, 11.8% (48 MH, one UOA) were not under the care of the doctor to whom the request was directed, 8.9% (32 MH, 5 UOA) were incorrect, and 3.9% (16 MH, 0 UOA) did not complete fitting. The total rate of invalid prescriptions was 52.8% (200 MH, 19 UOA).

Conclusions:

There is a high rate of invalid prescriptions presented for passive verification. Although the majority of prescriptions are simply expired, there is a fraction of prescriptions that contain incorrect specification of lens parameters or no record of prescription by that doctor. The current mechanism of passive verification, with the burden on the provider for denial within a short time window, makes it likely that such prescriptions would be filled, potentially putting patient comfort and safety at risk.
Constipation Treatment
Authors: Lammers Emily , Srivastava Sneha Baxi
Published: May 2020

Constipation seems like a ubiquitous condition, something people of all ages experience and many complain about. It is often associated with infrequent bowel movements; however, in reality, constipation has a wide array of symptoms including hard stools, feeling of incomplete evacuation, abdominal discomfort, bloating, distension, excessive straining, sensation of anorectal blockage, or need for manual maneuvers during defecation. Determining the cause of the constipation is essential to ensure the appropriate treatment approach. The patient evaluation consists of collecting subjective and objective information. Constipation has many different treatment options, with many treatments available as over-the-counter products as well as prescription medications. For most types of constipation, nonpharmacological and dietary changes are typically recommended as first-line treatment. Prescription medications are available with indications for specific types of constipation. Both nonpharmacological and pharmacological interventions have a key role, and follow-up is important to ensure treatment is appropriate and adequate.
Risk of HIV infection among adolescent girls and young women in age-disparate relationships in sub-Saharan Africa
Authors: Bajunirwe Francis , Semakula Daniel , Izudi Jonathan
Published: May 2020

Objective:

To determine the association between age-disparate relationships and risk of HIV infection among adolescent girls and young women (AGYW) aged 15–24 years.

Design:

Systematic review and meta-analysis of published studies until January 5, 2020 in sub Saharan Africa (SSA).

Methods:

We searched several electronic databases, grey literature, and hand searched reference list of included studies to identify eligible studies for data abstraction. We assessed the quality of included studies using Newcastle–Ottawa Scale for nonrandomized studies. The DerSimonian–Laird random effects model was used to pool the overall results using risk ratios (RR), presented in a forest plot with 95% confidence interval (CI) and predictive interval. Heterogeneity was assessed with Cochrane's Q-test and quantified with I
2 values. Publication bias was checked with funnel plots and Egger's test.

Results:

We included 24 studies with an overall sample size of 33 390. Data show that age-disparate relationships were significantly associated with unprotected sexual intercourse (pooled RR, 1.57; 95% CI, 1.34–1.83; 95% predictive interval, 1.22–2.02), and higher risk for HIV infection (pooled RR, 1.39; 95 CI, 1.21–1.60; 95% predictive interval, 0.80–2.42). Studies included in pooling risk of unprotected sexual intercourse were largely homogeneous (I
2-value= 0.0, P = 0.79) whereas those for HIV infection were heterogeneous (I
2- value = 89.0%, P < 0.01). We found no publication bias and no study influenced the meta-analytic results.

Conclusion:

Age-disparate relationships among AGYW are associated with increased risk of unprotected sexual intercourse and HIV infection in SSA. HIV prevention interventions should target this sub-population.
A data-driven method to detect the flattening of the COVID-19 pandemic curve and estimating its ending life-cycle using only the time-series of new cases per day.
Authors: Gupta Dr. Praveen , Sharma Prof. K.K. , Joshi Prof. S.D. , Goyal Dr. S.
Published: May 2020

The novel Coronavirus-19 disease (COVID-19) has emerged as a pandemic and has presented itself as an unprecedented challenge to the majority of countries worldwide. The containment measures for this disease such as the requirement of health care facilities greatly rely on estimating the future dynamics and flattening of the COVID-19 curve. However, it is always challenging to estimate the future trends and flattening of the COVID-19 curve due to the involvement of many real-life variables. Recently, traditional methods based on SIR and SEIR have been presented for predictive monitoring and detection of flattening of the COVID-19 curve. In this paper, a novel method for detection of flattening of the COVID-19 curve and its ending life-cycle using only the time-series of new cases per day is presented. Simulation results are compared to the SIR based methods in three different scenarios using COVID-19 curves for South Korea, the United States of America, and India. In this study, simulations, performed on the 26th April 2020 show that the peak of the COVID-19 curve in the USA has already arrived and situated on the 14th of April 2020, while the peak of the COVID-19 curve for India has yet to arrive.
Assessing the impact of dental and periodontal statuses on the salivary microbiome: a global oral health scale
Authors: Relvas Marta , Regueira-Iglesias Alba , Balsa-Castro Carlos , Salazar Filomena , Pacheco Jose Julio , Cabral Cristina , Henriques Corsina , Tomas Inmaculada
Published: May 2020

Very few 16S rRNA-based studies have conducted a simultaneous analysis to identify the impact of various dental and periodontal parameters and determine which of them have the greatest repercussion for the salivary microbiota. Consequently, this study used 16S rRNA gene amplicon sequencing to assess the impact on salivary microbiome of different grades of dental, periodontal and global oral disease.
Our global oral health scale was used to produce a convenience sample of 81 patients from 270 who were initially recruited. These subjects were assigned the following grades: 47 had a periodontal grade (PG) of 0 and dental grades (DGs) between 0-3, and 46 had a DG of 0 and PGs between 0-3. Saliva samples were collected from each participant. Sequencing was performed in Illumina MiSeq with 2 x 300 bp reads, while the raw reads were processed according to the Mothur pipeline. The statistical analysis of the 16S rDNA sequencing data at the species level was conducted using the Phyloseq, DESeq2 and Microbiome packages. The impact on the salivary microbiota of the different DGs, PGs and global oral grades (GGs) was investigated in relation to: 1) indicators of alpha diversity and the structure of the bacterial community; and 2) the composition of the core microbiome and the results of differential abundance tests.
The simultaneous presence of dental and periodontal pathology has a potentiating effect on the richness and diversity of the salivary microbiota. The structure of the bacterial community in oral health differs from that present in dental, periodontal or global oral disease, especially in high grades. The non-specific microbiome core contains a greater number of more abundant species than the specific core of a particular dental or periodontal condition (health or pathology). The number of taxa in the salivary microbiota with differential abundances between the DGs, PGs or GGs represents, at most, a quarter of the bacterial community and are mainly non-core species. Supragingival dental parameters influence the microbiota`s abundance more than subgingival periodontal parameters, with the former making a greater contribution to the impact that global oral health has on salivary microbiome.
Acquired fluoroquinolone resistance genes in corneal isolates ofPseudomonas aeruginosa
Authors: Khan Mahjabeen , Summers Stephen , Rice Scott A , Stapleton Fiona , Willcox Mark D P , Subedi Dinesh
Published: May 2020

Fluroquinolones are widely used as an empirical therapy for pseudomonal ocular infections. Based on increasing reports on acquired fluroquinolone resistance genes in clinical isolates ofPseudomonas aeruginosa, we investigated 33 strains ofP. aeruginosaisolated from the cornea of microbial keratitis patients in India and Australia between 1992 and 2018 to understand the prevalence of acquired fluroquinolone resistance genes in ocular isolates and to assess whether the possession of those genes was associated with fluoroquinolone susceptibility. We obtained the whole genome sequence of 33 isolates using Illumina MiSeq platform and investigated the prevalence of two fluoroquinolone resistance genescrpPandqnrVC1. To examine the associated mobile genetic elements ofqnrVC1positive strains, we obtained long read sequences using Oxford Nanopore MinION and performed hybrid assembly to combine long reads with Illumina short sequence reads. We further assessed mutations in QRDRs and antibiotic susceptibilities to ciprofloxacin, levofloxacin and moxifloxacin to examine the association between resistance genes and phenotype. Twenty strains possessedcrpPin genetic islands characterised by possession of integrative conjugative elements. TheqnrVC1gene was carried by four isolates on class I integrons and Tn3transposons along with aminoglycoside and beta-lactam resistance genes. We did not observe any evidence of plasmids carrying fluroquinolone resistance genes. Resistance to fluroquinolones was observed in those strains which possessedcrpP, qnrVC1and that had QRDRs mutations. The presence ofcrpPwas not a sole cause of fluroquinolone resistance.
Human Antibodies Targeting a Transporter Mediate Protection Against Tuberculosis
Authors: Watson Avia , Li Hao , Ma Bingting , Weiss Ronen , Bendayan Danielle , Abramovitz Lilach , Mor Michael , Pinko Erica , Bar-Oz Michal , Wang Zhenqi , Du Fengjiao , Lu Yu , Rybniker Jan , Huang Hairong , Barkan Daniel , Xiang Ye , Javid Babak , Freund Natalia T
Published: May 2020

Evidence has emerged that some healthy individuals with a history of exposure to Mycobacterium tuberculosis (Mtb) can develop protective antibody responses. However, it is not known whether patients with active tuberculosis elicit protective antibodies, and if they do, which bacterial antigens are targeted. To investigate the B cell responses during active infection, we generated a panel of monoclonal antibodies isolated from memory B cells of one patient. The antibodies, members of four distinct B cell clones, were directed against the Mtb phosphate transporter subunit PstS1. Antibodies p4–36 and p4–163 from two different B cell clones showed protective efficacy against Mtb and Mycobacterium bovis-BCG in an ex vivo human whole blood growth inhibition assay. Germline versions of p4–36 and p4–163 could no longer bind Mtb, implying that affinity maturation was vital for their activity. Crystal structures of p4–36 and a closely related clonal variant of p4–163, p4–170, complexed to PstS1 were determined at a resolution of 2.1Å and 2.4Å and revealed that the two antibodies recognize two distinctive epitopes on PstS1. As a proof of principle, p4–36 and p4–163 were used in a passive vaccination setting in aerosol Mtb-infected Balb/c mice, where both antibodies reduced bacterial lung burden by 50% after a single injection prior to Mtb infection. Our study shows that inhibitory B cell responses arise during active tuberculosis and identifies PstS1 as a target for elicitation of anti-Mtb antibodies.
High Filtration Efficiency Face Masks made from Sterilization Wraps
Authors: Walawalkar Sachin , Khattry Navin , Sapra B.K. , Khan Arshad , Joshi Manish , Mohan Lalit , Srivastava S.P. , Naresh Chital , Badwe Rajendra , Gupta Sudeep
Published: May 2020

COVID-19 pandemic has spawned the need for mass production of N-95 respirators. We used Sterilization Wraps to produce face masks which maintained 93% particle capture efficacy post sterilization. This ubiquitously available material could be explored for production of high quality face masks at a cost less than 30 US cents.
A DISSYMMETRY IN THE FIGURES RELATED TO THE COVID-19 PANDEMIC IN THE WORLD: WHAT FACTORS EXPLAIN THE DIFFERENCE BETWEEN AFRICA AND THE REST OF THE WORLD?
Authors: Faye Cheikh , Wade CheikhTidiane , Dione Ibrahima Demba
Published: May 2020

Humanity has experienced outbreaks for millennia, from epidemics limited to pandemics that have claimed many victims and changed the course of civilizations. The advent of vaccines has eradicated some of the serious pathogens and reduced many others. However, pandemics are still part of our modern world, as we continue to have pandemics as devastating as HIV and as alarming as severe acute respiratory syndrome, Ebola and the Middle East respiratory syndrome. The Covid-19 epidemic with 0-exponential contamination curves reaching 3 million confirmed cases should not have come as a surprise, nor should it have been the last pandemic in the world. In this article, we try to summarize the lost opportunities as well as the lessons learned, hoping that we can do better in the future. The objective of this study is to relate the situation of Covid-19 in African countries with those of the countries most affected by the pandemic. It also allows us to verify how, according to the observed situation, the African ecosystem seems to be much more resilient compared to that of other continents where the number of deaths is in the thousands. To verify this, the diagnosed morbidity and mortality reported for different states of the world are compared to the ages of life and the average annual temperature of these states. The results show that the less dramatic balance of the African continent compared to other continents is partly linked to the relatively high temperatures on the continent but also to the relatively young character of its population.
PROTOCOL: Are clinical trial participants informed about potential benefits and harms? A comparison of informed consent materials and trial protocols
Authors: Paludan-Mueller Asger Sand , Joergensen Karsten J , Goetzsche Peter C
Published: May 2020

This is a protocol for the project entitled: 'Are clinical trial participants informed about potential benefits and harms? A comparison of informed consent materials and trial protocols.'
Comparative Efficacy and Safety of Pharmacological Managements for Hospitalized COVID-19 Patients: Protocol for Systematic Review and Trade-Off Network Meta-Analysis.
Authors: Kim Min Seo , Kim Won Jun , An Min Ho
Published: May 2020

Coronavirus-Disease 2019 (COVID-19) is the clinical disease caused by the SARS-CoV-2 virus, the infectious agent causing the ongoing pandemic that has impacted the lives of hundreds of millions of people in almost every nation worldwide. It is a potentially fatal disease to many vulnerable patients including the elderly and those with chronic illnesses; but because this virus is a novel one, there are no firmly established treatment protocols. Many treatment methods are being investigated worldwide, and scientific conclusions drawn from these endeavors are crucial for healthcare professionals in combating this disease. In this network meta-analysis, we focus specifically on the pharmacologic agents that have been investigated for the treatment of COVID-19 and aim to produce a comprehensive picture of the evidence from current data in order to produce relevant insights on the comparative efficacy and safety profiles of various pharmacologic agents against COVID-19.
Do COVID-19 patients admitted to the ICU require anti-Pneumocystis jirovecii prophylaxis?
Authors: Alanio Alexandre , Voicu Sebastian , Delliere sarah , Megarbane Bruno , Bretagne Stephane
Published: May 2020

We are currently facing a frightening increase in COVID-19 patients admitted to the ICU.
Aiming at screening for secondary pneumonia, we collected the data of our first twelve ICU patients who underwent bronchoalveolar lavage (BAL). Surprisingly, four were detected with Pneumocystis jirovecii (Pj) DNA and RNA, resulting in Pj prevalence of 17%.

Pj is a ubiquitous ascomycetes fungus that thrives at the surface of type-I pneumocytes, specifically in human alveoli, leading to pneumocystosis in immunocompromised patients. Interestingly, none of our patients was immunocompromised per se before admission, while all presented the recognized risk factors for life-threatening COVID-19 infection.

Observing such high prevalence in COVID-infected patients was unexpected.
Almost all patients developed ARDS and received high-dose steroids to prevent worsening, as suggested by reports from China. In Pj-positive patients requiring steroids, prophylaxis was given to avoid the risk of pneumocystosis and increased lung inflammation that may compromise the outcome.

We are strongly convinced that testing deep lung specimens for Pj in severe COVID-19 patients should be recommended and Pj-positive patients treated with steroids, and given anti-Pj prophylaxis. This message is important, given the high mortality rate of COVID-19 patients in the ICU.
Exploring the spread dynamics of COVID-19 in Morocco
Authors: NAJI Mohamed
Published: May 2020

Despite some similarities of the dynamic of COVID−19 spread in Morocco and other countries, the infection, recovery and death rates remain very variable.
In this paper, we analyze the spread dynamics of COVID−19 in Morocco within a standard susceptible−exposed−infected−recovered−death (SEIRD) model. We have combined SEIRD model with a time−dependent infection rate function, to fit the real data of i) infection counts and ii) death rates due to COVID−19, for the period between March 2nd and Mai 15th 2020. By fitting the infection rate, SEIRD model placed the infection peak on 04/24/2020 and could reproduce it to a large extent on the expense of recovery and death rates. Fitting the SEIRD
model to death rates gives rather satisfactory predictions with a maximum of infections on 04/06/2020. Regardless of the low peak position, the peak position, confirmed cases and transmission rate were well reproduced.
Did I imagine that? The functional role of paracingulate cortex in reality monitoring
Authors: Garrison JR , Saviola F , Morgenroth E , Barker H , Lührs Michael , Simons JS , Fernyhough C , Allen P
Published: May 2020

Reality monitoring describes our ability to distinguish between internally and externally generated experiences. Individuals show significant variation in this ability and impaired reality monitoring has been linked to the experience of hallucinations. We undertook two studies to investigate the association between reality monitoring and morphology of the paracingulate region of medial prefrontal cortex. In Study 1 we compared reality monitoring accuracy and functional connectivity within paracingulate cortex in groups of healthy controls (N=20) and patients with schizophrenia and hallucinations (N=19). Controls showed greater reality monitoring accuracy that was associated with resting-state functional connectivity between paracingulate, precuneus and occipital cortices, while reality monitoring in patients was associated with more lateral functional connectivity. In Study 2 we used real-time fMRI neurofeedback to obtain causal evidence for the role of the paracingulate cortex in reality monitoring. Healthy individuals received Active feedback from paracingulate cortex (N=21) or Sham feedback based on randomised signal (N=18). Active-group participants showed a specific behavioural effect of improved reality monitoring for Imagined items, as well as increases in both activity within the paracingulate region, and its posterior functional connectivity with precuneus and lateral parietal cortices, and occipital cortex.

Our findings suggest reality monitoring in healthy individuals is causally supported by a paracingulate mediated flexible network including the precuneus. Network connectivity can be enhanced using neurofeedback and tracks with improved reality monitoring ability. In contrast, patients with schizophrenia may utilise a distinct and more lateral network which may explain observed sub-optimal reality monitoring accuracy, contributing to the experience of hallucinations.

Significance Statement

Reality monitoring refers to our ability to distinguish imagination from our experiences in the outside world, and is linked both to hallucinations in schizophrenia as well as to the morphology of paracingulate cortex area of the brain. Here, we revealed less paracingulate involvement in the functional reality monitoring networks in patients with schizophrenia compared to healthy individuals. Thereafter, we used real-time fMRI neurofeedback to show that healthy individuals can learn to upregulate brain activity within the paracingulate cortex, with this resulting in both improved reality monitoring ability and changes in paracingulate functional connectivity. This suggests that paracingulate cortex activity and connectivity play a causal role in reality monitoring, with implications for both the understanding and treatment of hallucinations.
Effect of Heat inactivation on Real-Time Reverse Transcription PCR of the SARS-COV-2 Detection
Authors: liu yanxia , cao zhengan , chen mei , zhong Yan , luo yuhao , shi gang , Xiang Hongxia , Luo Jianping , Zhou Hongwei
Published: May 2020

Background: Real-time reverse transcription PCR (rRT-PCR) is commonly used to diagnose SARS-CoV-2 infection. Heat inactivation prior to nucleic acid isolation may allow safe testing, while the effects of heat inactivation on SARS-CoV-2 rRT-PCR detection result need to be determined.
Methods: 14 positive nasopharyngeal swab specimens were inactivated at 56°C for 30min, 56°C for 60min, 60°C for 30min, 60°C for 75min, and 100°C for 10min, and another 2 positive nasopharyngeal swab specimens were also inactivated at 100°C for 10min, 100°C for 30min, 100°C for 60min, after which the samples were isolated and detected by rRT-PCR.
Results: All 14 heat treated samples remained positive. The range of threshold cycle (Ct) values observed when detecting ORF1a/b was 27.228-34.011 in heat-treated samples, while 25.281-34.861 in unheated samples, and the range of threshold cycle (Ct) values observed at the time of detecting N was 25.777-33.351 in heat-treated samples, while 24.1615-35.433 in unheated samples, on basis of which it showed no statistical difference otherwise a good correlation of Ct values between the heat-inactivated samples and the untreated samples. However, the 2 samples inactivated at 100°C 30min, 100°C 60min turned into negative.
Conclusions: Heat inactivation at 56°C for 30min, 56°C for 60min, 60°C for 30min, 60°C for 75min, and 100°C for 10min shall not affect the detection results of Real-Time Reverse Transcription PCR of the SARS-COV2. Furthermore, it is recommended to inactive nasopharyngeal swab specimens 10min at 100°C before RNA extraction in consideration of efficiency and reliable results.
Key Words: SARS-CoV-2, Heat Inactivation, rRT-PCR, Comparison
Clinical predictors of COVID-19 mortality
Authors: Yadaw Arjun S. , Li Yan-chak , Bose Sonali , Iyengar Ravi , Bunyavanich Supinda , Pandey Gaurav
Published: May 2020

Background: The coronavirus disease 2019 (COVID-19) pandemic has affected over millions of individuals and caused hundreds of thousands of deaths worldwide. It can be difficult to accurately predict mortality among COVID-19 patients presenting with a spectrum of complications, hindering the prognostication and management of the disease.

Methods: We applied machine learning techniques to clinical data from a large cohort of 5,051 COVID-19 patients treated at the Mount Sinai Health System in New York City, the global COVID-19 epicenter, to predict mortality. Predictors were designed to classify patients into Deceased or Alive mortality classes and were evaluated in terms of the area under the receiver operating characteristic (ROC) curve (AUC score).

Findings: Using a development cohort (n=3,841) and a systematic machine learning framework, we identified a COVID-19 mortality predictor that demonstrated high accuracy (AUC=0.91) when applied to test sets of retrospective (n= 961) and prospective (n=249) patients. This mortality predictor was based on five clinical features: age, minimum O2 saturation during encounter, type of patient encounter (inpatient vs. various types of outpatient and telehealth encounters), hydroxychloroquine use, and maximum body temperature.

Interpretation: An accurate and parsimonious COVID-19 mortality predictor based on five features may have utility in clinical settings to guide the management and prognostication of patients affected by this disease.
Detecting radiographic sacroiliitis using deep learning with expert-level accuracy in axial spondyloarthritis
Authors: Bressem Keno K. , Vahldiek Janis L. , Adams Lisa C. , Niehues Stefan M. , Haibel Hildrun , Rodriguez Valeria Rios , Torgutalp Murat , Protopopov Mikhail , Proft Fabian , Rademacher Judith , Sieper Joachim , Rudwaleit Martin , Hamm Bernd , Makowski Marcus R. , Hermann Kay Geert A. , Poddubnyy Denis
Published: May 2020

Conventional radiographs of sacroiliac joints from two independent cohorts of patients with axial spondyloarthritis (axSpA) were used to develop and validate an artificial neural network for the detection of definite radiographic sacroiliitis as a manifestation of the disease. The first cohort consisting of 1669 radiographs labelled by three experts was used for training. From the second cohort 100 radiographs labelled by two experts were randomly selected for the test dataset. The neural network achieved an excellent performance in detection of definite radiographic sacroiliitis with an area under the receiver operating characteristics curve of 0.97 and 0.96 for the validation and test datasets, respectively. Sensitivity and specificity for the cut-off weighting both measurements equally were 0.90 and 0.93 for the validation and 0.87 and 0.97 for the test set. The Cohen’s kappa between the neural network and the reference judgements were 0.80 for both validation and test sets, and the absolute agreement on the classification yielded 91% and 90%, respectively.
Rdh54/Tid1 Inhibits Rad51-Rad54-Mediated D-loop Formation and Limits D-loop Length
Authors: Shah Shanaya Shital , Hartono Stella , Piazza Aurèle , Som Vanessa , Wright William , Chédin Frédéric , Heyer Wolf-Dietrich
Published: May 2020

Displacement loops (D-loops) are intermediates formed during homologous recombination that play a pivotal role in the fidelity of repair. Rdh54 (a.k.a. Tid1), a Rad54 paralog inSaccharomyces cerevisiae, is well-known for its role with Dmc1 recombinase during meiotic recombination. Yet contrary to Dmc1, Rdh54 is also present in somatic cells where its function is less understood. While Rdh54 enhances the Rad51 DNA strand invasion activityin vitro, it is unclear how it interplays with Rad54-mediated invasions. Here, we show that Rdh54 inhibits D-loop formation by Rad51 and Rad54 in an ATPase-independent manner. Using a novel D-loop Mapping Assay, we further demonstrate that Rdh54 uniquely restricts the lengths of Rad54-mediated D-loops. The alterations in D-loop properties appear to be important for cell survival and mating-type switch in haploid yeast, whereas Rdh54 expression is suppressed in diploids. We propose that Rdh54 and Rad54 compete for potential binding sites within the Rad51 filament, where Rdh54 acts as a physical roadblock to Rad54’s translocation activity, limiting D-loop formation and D-loop length.
The Hybrid Forecasting Method SVR-ESAR for Covid-19
Authors: Frausto-Solis Juan , Olvera Vazquez Jose Enrique , Gonzalez-Barbosa Juan Javier , Castilla-Valdez Guadalupe , Sanchez-Hernandez Juan Paulo , Perez-Ortega Joaquin
Published: May 2020

We know that SARS-Cov2 produces the new COVID-19 disease, which is one of the most dangerous pandemics of modern times. This pandemic has critical health and economic consequences, and even the health services of the large, powerful nations may be saturated. Thus, forecasting the number of infected persons in any country is essential for controlling the situation. In the literature, different forecasting methods have been published attempting to solve the problem. However, a simple and accurate forecasting method is required for its implementation in any part of the world. This paper presents a precise and straightforward forecasting method named SVR-ESAR (Support Vector regression hybridized with the classical Exponential smoothing and ARIMA). We applied this method to the infected time series in four scenarios: the Whole World, China, the US, and Mexico. We compared our results with those of the literature showing the proposed method has the best accuracy.
Immunization with the receptor–binding domain of SARS-CoV-2 elicits antibodies cross-neutralizing SARS-CoV-2 and SARS-CoV without antibody-dependent enhancement
Authors: Zang Jinkai , Gu Chenjian , Zhou Bingjie , Zhang Chao , Yang Yong , Xu Shiqi , Zhang Xueyang , Zhou Yu , Bai Lulu , Wu Yang , Sun Zhiping , Zhang Rong , Deng Qiang , Yuan Zhenghong , Tang Hong , Qu Di , Lavillette Dimitri , Xie Youhua , Huang Zhong
Published: May 2020

Recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the ongoing coronavirus disease 2019 (COVID-19) pandemic. Currently, there is no vaccine available for preventing SARS-CoV-2 infection. Like closely related severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV-2 also uses its receptor-binding domain (RBD) on the spike (S) protein to engage the host receptor, human angiotensin-converting enzyme 2 (ACE2), facilitating subsequent viral entry. Here we report the immunogenicity and vaccine potential of SARS-CoV-2 RBD (SARS2-RBD)-based recombinant proteins. Immunization with SARS2-RBD recombinant proteins potently induced a multi-functional antibody response in mice. The resulting antisera could efficiently block the interaction between SARS2-RBD and ACE2, inhibit S-mediated cell-cell fusion, and neutralize both SARS-CoV-2 pseudovirus entry and authentic SARS-CoV-2 infection. In addition, the anti-RBD sera also exhibited cross binding, ACE2-blockade, and neutralization effects towards SARS-CoV. More importantly, we found that the anti-RBD sera did not promote antibody-dependent enhancement of either SARS-CoV-2 pseudovirus entry or authentic virus infection of Fc receptor-bearing cells. These findings provide a solid foundation for developing RBD-based subunit vaccines for SARS-CoV2.
HetL provides immunity to HetR against PatS inhibition, and promotes pattern formation in the cyanobacteriumNostocPCC 7120
Authors: Xu Xiaomei , Risoul Véronique , Byrne Deborah , Champ Stéphanie , Douzi Badredinne , Latifi Amel
Published: May 2020

Local activation and long-range inhibition are mechanisms conserved in self-organizing systems leading to biological patterns. A number of them involve the production by the developing cell of an inhibitory morphogen, but how this cell gets immune to self-inhibition is rather unknown. Under combined nitrogen starvation, the multicellular cyanobacteriumNostocPCC 7120 develops nitrogen-fixing heterocysts with a pattern of a heterocyst every 10-12 vegetative cells. Cell differentiation is regulated by HetR which activates the synthesis of its own inhibitory morphogen (PatS), which diffusion establishes the differentiation pattern. Here we show that HetR interacts with HetL at the same interface as PatS, and that this interaction is required to suppress inhibition and to differentiate heterocysts.hetLexpression is induced under nitrogen-starvation and is activated by HetR, suggesting that HetL provides immunity to the heterocyst. This protective mechanism might be conserved in other differentiating cyanobacteria as HetL homologues are spread across the phylum.
COX-1 – lipid interactions: arachidonic acid, cholesterol, and phospholipid binding to the membrane binding domain of COX-1
Authors: Sejdiu Besian I. , Tieleman D. Peter
Published: May 2020

Cyclooxygenases carry out the committed step in prostaglandin synthesis and are the target of NSAIDs, the most widely used class of drugs in alleviating pain, fever, and inflammation. While extensively studied, one aspect of their biology that has been neglected is their interaction with membrane lipids. Such lipid-protein interactions have been shown to be a driving force behind membrane protein function and activity. Cyclooxygenases (COX-1 and COX-2) are bound on the luminal side of the endoplasmic reticulum membrane. The entrance to their active site is formed by a long hydrophobic channel which is used by the cyclooxygenase natural substrate, arachidonic acid, to access the enzyme. Using atomistic and coarse-grained simulations, we show that several membrane lipids are capable of accessing the same hydrophobic channel. We observe the preferential binding of arachidonic acid, cholesterol and glycerophospholipids with residues lining the cavity of the channel. We find that the membrane binding domain (MBD) of COX-1 is usually in a lipid-bound state and not empty. This orthosteric binding by other lipids suggests a potential regulatory role of membrane lipids with the possibility of affecting the COX-1 turnover rate. We also observed the unbiased binding of arachidonic acid to the MBD of COX-1 allowing us to clearly delineate its binding pathway. We identified a series of arginine residues as being responsible for guiding arachidonic acid towards the binding site. Finally, we were also able to identify the mechanism by which COX-1 induces a positive curvature on the membrane environment.
Hydrothermal synthesis and crystal structure of poly[bis(μ3-3,4-diaminobenzoato)manganese], a layered coordination polymer
Authors: Khosa Muhammad Kaleem , Wood Paul T. , Humphrey Simon M. , Harrison William T. A.
Published: May 2020

The hydrothermal synthesis and crystal structure of the title two-dimensional coordination polymer, poly[bis(μ3-3,4-diaminobenzoato-κ3
N
3,O,O′)manganese(II)], [Mn(C7H7N2O2)2]
n
, are described. The Mn2+ cation (site symmetry \overline{1}) adopts a tetragonally elongated trans-MnN2O4 octahedral coordination geometry and the μ3-N,O,O′ ligand (bonding from both carboxylate O atoms and the meta-N atom) links the metal ions into infinite (10\overline{1}) layers. The packing is consolidated by intra-layer N—H...O and inter-layer N—H...N hydrogen bonds. The structure of the title compound is compared with other complexes containing the C7H7N2O2
− anion and those of the related M(C8H8NO2)2 (M = Mn, Co, Ni, Zn) family, where C8H8NO2
− is the 3-amino-4-methylbenzoate anion.