bluuebunny/crossref_metadata_2025 huggingface dataset:
Fine Mapping of the Ph-2 Gene Conferring Resistance to Late Blight (Phytophthora infestans) in Tomato
Authors: Zhi Xiaona , Shu Jinshuai , Zheng Zheng , Li Tao , Sun Xiaorong , Bai Jinrui , Cui Yanan , Wang Xiaoxuan , Huang Zejun , Guo Yanmei , Du Yongchen , Yang Yuhong , Liu Lei , Li Junming
Published: October 2020

Late blight is a devastating tomato disease. Breeding new varieties with multiple resistance (R) genes is highly effective for preventing late blight. The Ph-2 gene mediates resistance to Phytophthora infestans race T1 in tomato. In this study, we used an F2 population derived from a cross between Solanum lycopersicum Moboline (resistant) and LA3988 (susceptible) cultivars for the fine mapping of Ph-2. Two flanking markers, CAPS-1 and CC-Ase, mapped Ph-2 to a 141-kb genomic region containing 21 projected genes, 5 of which were identified as putative R genes. The Solyc10g085460 coding sequence varied significantly between the parents. The markers developed and candidate genes identified in this study shall be useful for the molecular breeding of tomato exhibiting increased late blight resistance and for the cloning of the Ph-2 gene.
Cultivar Susceptibility and Environmental Parameters Affecting Symptom Expression of Red Leaf Blotch of Almond in Spain
Authors: Miarnau Xavier , Zazurca Lourdes , Torguet Laura , Zúñiga Erick , Batlle Ignasi , Alegre Simó , Luque Jordi
Published: October 2020

Red leaf blotch (RLB) of almond, caused by Polystigma amygdalinum, is an important foliar disease of this nut tree in the Mediterranean basin and Middle East regions. In recent years, the incidence of this disease has increased in Spain, corresponding to increases in the area of newly planted orchards and the use of susceptible cultivars. In 2009, an experimental orchard including 21 almond cultivars was planted at Les Borges Blanques, Lleida, in northeastern Spain. No fungicide treatments were applied during the 10-year experimental period (2009 to 2018) in order to allow natural disease development. Cultivar susceptibility to RLB was assessed each year, from 2011 to 2018, through visual observations of symptoms in naturally infected trees. The experimental results led us to classify the cultivars into five susceptibility groups. The most susceptible were Tarraco, Guara, Tuono, Marinada, Desmayo Largueta, and Soleta, whereas Mardía was the most tolerant. The annual incidence of disease was positively correlated with accumulated rainfall in spring, and especially in April, while it was negatively correlated with high spring and summer temperatures, especially in May. These findings could be used to improve disease management strategies by identifying the most susceptible cultivars and improving the timing of fungicide application.
Comparative Studies on the Disease Prevalence and Population Dynamics of Ginger Blotch and Brown Blotch Pathogens of Button Mushrooms
Authors: Taparia Tanvi , Hendrix Ed , Hendriks Marc , Krijger Marjon , de Boer Wietse , van der Wolf Jan
Published: October 2020

Bacterial blotch is one of the most economically important diseases of button 'mushroom. Knowledge of mechanisms of disease expression, inoculum thresholds, and disease management is limited to the most well-known pathogen, Pseudomonas tolaasii. Recent outbreaks in Europe have been attributed to ‘P. gingeri’ and P. salomonii for ginger and brown blotch, respectively. Information about their identity, infection dynamics, and pathogenicity is largely lacking. The disease pressure in an experimental mushroom cultivation facility was evaluated for ‘P. gingeri’ and P. salomonii over varying inoculation densities, casing soil types, environmental humidity, and cultivation cycles. The pathogen population structures in the casing soils were simultaneously tracked across the cropping cycle using highly specific and sensitive TaqMan-quantitative PCR assays. ‘P. gingeri’ caused disease outbreaks at lower inoculum thresholds (104CFU/g) in the soil than P. salomonii (105CFU/g). Ginger blotch generically declined in later harvest cycles, although brown blotch did not. Casing soils were differentially suppressive to blotch diseases, based on their composition and supplementation. Endemic pathogen populations increased across the cultivation cycle although the inoculated pathogen populations were consistent between the first and second flush. In conclusion, ‘P. gingeri’ and P. salomonii have unique infection and population dynamics that vary over soil types. Their endemic populations are also differently abundant in peat-based casing soils. This knowledge is essential for interpreting diagnostic results from screening mushroom farms and designing localized disease control strategies.
Rubbery Taproot Disease of Sugar Beet in Serbia Associated with ‘Candidatus Phytoplasma solani’
Authors: Ćurčić Živko , Stepanović Jelena , Zübert Christina , Taški-Ajduković Ksenija , Kosovac Andrea , Rekanović Emil , Kube Michael , Duduk Bojan
Published: October 2020

Rubbery taproot disease (RTD) of sugar beet was observed in Serbia for the first time in the 1960s. The disease was already described in neighboring Bulgaria and Romania at the time but it was associated with abiotic factors. In this study on RTD of sugar beet in its main growing area of Serbia, we provide evidence of the association between ‘Candidatus Phytoplasma solani’ (stolbur phytoplasma) infection and the occurrence of typical RTD symptomatology. ‘Ca. P. solani’ was identified by PCR and the sequence analyses of 16S ribosomal RNA, tuf, secY, and stamp genes. In contrast, the causative agent of the syndrome “basses richesses” of sugar beet—namely, ‘Ca. Arsenophonus phytopathogenicus’—was not detected. Sequence analysis of the stolbur strain’s tuf gene confirmed a previously reported and a new, distinct tuf stolbur genotype (named ‘tuf d’) that is prevalent in sugar beet. The sequence signatures of the tuf gene as well as the one of stamp both correlate with the epidemiological cycle and reservoir plant host. This study provides knowledge that, for the first time, enables the differentiation of stolbur strains associated with RTD of sugar beet from closely related strains, thereby providing necessary information for further epidemiological work seeking to identify insect vectors and reservoir plant hosts. The results of this study indicate that there are differences in hybrid susceptibility. Clarifying the etiology of RTD as a long-known and economically important disease is certainly the first step toward disease management in Serbia and neighboring countries.
Imaging in Vaping-associated Lung Injury: Beyond the Haze
Authors: Vilanilam George Koshy , Purushothaman Rangarajan , Baskaran Naveen Prasath , Vohra Ishaan , Raghavan Sairam , Bean Brian , Sajovitz Lisa
Published: October 2020

E-cigarette or vaping, product associated lung injury is a rampant public health issue with a total of 2807 reported hospitalized patients in the United States as of February 18, 2020. Limited data, non-specific symptoms, non-responsiveness to antibiotics, and the lack of a specific biomarker, make it a diagnosis of exclusion. Overlap of clinical and imaging findings with other ongoing respiratory illness (MERS, SARS and COVID-19) poses a challenge in accurate diagnosis. We compiled 3 cases of patients hospitalized with confirmed vaping-associated lung injury and analyzed their imaging patterns, which revealed bilateral consolidation, ground-glass opacities and pleural effusions. We also reviewed the available literature on pathophysiology, imaging findings of EVALI and other respiratory illness.
Venous Thromboembolism in Hip Fracture Patients: A Subanalysis of the FAITH and HEALTH Trials
Authors: MacDonald David R. W. , Neilly David , Schneider Prism S. , Bzovsky Sofia , Sprague Sheila , Axelrod Daniel , Poolman Rudolf W. , Frihagen Frede , Bhandari Mohit , Swiontkowski Marc , Schemitsch Emil H. , Stevenson Iain M. ,   on behalf of the FAITH and HEALTH Investigators
Published: October 2020

Background:

The primary objective of this study was to determine the incidence of symptomatic venous thromboembolism (VTE), including pulmonary embolism (PE) and deep vein thrombosis (DVT), in the hip fracture population. Secondary objectives included determining timing of VTE diagnosis, VTE thromboprophylaxis given, and identifying any factors associated with VTE.

Methods:

Using data from the FAITH and HEALTH trials, the incidence of VTE, including DVT and PE, and the timing of VTE were determined. A multivariable Cox regression analysis was used to determine which factors were associated with increased risk of VTE, including age, treatment for comorbidity, thromboprophylaxis, time to surgery, and method of fracture management.

Results:

2520 hip fracture patients were included in the analysis. Sixty-four patients (2.5%) had a VTE [DVT: 36 (1.4%), PE: 28 (1.1%)]. Thirty-five (54.7%) were diagnosed less than 6 weeks postfracture and 29 (45.3%) more than 6 weeks postfracture. One thousand nine hundred ninety-three (79%) patients received thromboprophylaxis preoperatively and 2502 (99%) received thromboprophylaxis postoperatively. The most common method of preoperative (46%) and postoperative (73%) thromboprophylaxis was low molecular weight heparin. Treatment with arthroplasty compared to internal fixation was the only variable associated with increased risk of VTE (hazard ratio 2.67, P = 0.02).

Conclusions:

The incidence of symptomatic VTE in hip fracture patients recruited to the 2 trials was 2.5%. Although over half of the cases were diagnosed within 6 weeks of fracture, VTE is still prevalent after this period. The majority of patients received thromboprophylaxis. Treatment with arthroplasty rather than fixation was associated with increased incidence of VTE.

Level of Evidence:

Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.
Association of Serotype With Antimicrobial Resistance Patterns Among Shigella flexneri Isolates From Pakistan: The Importance of Serotype 2b
Authors: Nisa Iqbal , Haroon Mohammad , Qasim Muhammad , Driessen Arnold , Nijland Jeroen , Yasin Nusrat , Jalal Abdullah , Ali Nawab , Ullah Waheed , Khan Taj Ali , Begum Asia , Rahman Hazir
Published: October 2020

Background:

Shigella flexneri is an emerging threat in low socioeconomic countries including Pakistan. No previous data is available on the association between S. flexneri serotypes and antimicrobial resistance in Pakistan.

Objectives:

The objective of the present study was to assess the association between serotypes and antimicrobial resistance patterns among S. flexneri isolated from clinical and nonclinical samples.

Methods:

A total of 199 S. flexneri isolates were subjected to molecular serotyping and antibiotic resistance.

Results:

The most prevalent S. flexneri serotype was 2b (38%) followed by 1b (24%), 7a (20%), 2a (11%), 1d (5%) and Y (2%). The phylogenetic reconstruction showed 12 clades among which the clades II, III, V, VIII, IX and XI have consisted of serotypes that were found both in human population and environment samples. A high level of multidrug resistance (MDR) was observed in serotype 2b (37.68%) followed by 1b (19.5%) and 7a (19.5%), 2a (11.5%), 1d (5%) and Y (2%). All isolates of serotype 2b showed high level of resistance to amoxicillin/clavulanic acid (100%) followed by quinolone (74.6%) and trimethoprim-sulfamethoxazole (54.6%). Interestingly, none of the serotype was resistant to piperacillin-tazobactam, imipenem and amikacin. The most frequently detected resistance genes among serotype 2b were bla

OXA
(100%) followed by qnrS (88%), cat (81%) and sul2 (63%).

Conclusion:

The most frequent S. flexneri serotype was 2b while 1d and Y was first time reported in Pakistan. High frequency of MDR serotypes of S. flexneri is a serious threat in diarrhea endemic regions and thus require urgent strategies for its continuous monitoring and prevention.
Resistance to Antibiotics of Uropathogen Bacteria Isolated From Urine and Blood in Pediatric Cancer Patients
Authors: Landi Francesca , Bandettini Roberto , Rotulo Gioacchino Andrea , Mesini Alessio , Saffioti Carolina , Amoroso Loredana , Pierri Filomena , Guardo Daniela , Castagnola Elio
Published: October 2020

Resistant pathogens have become a major healthcare problem in children with cancer, causing different kinds of infections such as the bloodstream ones, most common, and most frequently described and the urinary tract ones, of which less data are available. We analyzed and compared the proportions, and the trends of resistance in pathogens isolated from blood and urines in children with cancer followed in IRCCS Istituto Giannina Gaslini, Genova, Italy, from January 2007 to December 2018. Overall, 345 strains detected in urines and 282 in bloodstream infections were analyzed. Enterobacteriales were the most frequently isolated pathogens. During the study period in urines, there was a significant increase of resistance to ceftazidime, ciprofloxacin, piperacillin/tazobactam, and trimethoprim-sulfamethoxazole, but pathogens from blood were significantly more frequently resistant to amikacin, piperacillin/tazobactam, and combination therapy piperacillin/tazobactam+amikacin, even if with a decreasing trend during the study period. These data confirm the importance of surveillance of isolated microorganism and antibiotic resistance in cancer children.
A Multicentered Study of the Clinical and Molecular Epidemiology of TEM- and SHV-type Extended-Spectrum Beta-Lactamase Producing Enterobacterales Infections in Children
Authors: Logan Latania K. , Rispens Jared R. , Medernach Rachel L. , Domitrovic T. Nicholas , Hujer Andrea M. , Marshall Steven H. , Rudin Susan D. , Qureshi Nadia K. , Zheng Xiaotian , Hayden Mary K. , Weinstein Robert A. , Bonomo Robert A.
Published: October 2020

Background:

Extended-spectrum β-lactamase (ESBL)-producing Enterobacterales-(Ent) infections are increasing in pediatrics. Before CTX-M ESBL emerged, the most common infection-associated ESBL genes were TEM and SHV-type ESBLs. We sought to define the current epidemiology of Ent infections in children due to bla
TEM and bla
SHV (TEM-SHV-Ent).

Methods:

A retrospective case-control analysis of children with TEM-SHV-Ent infections at 3 Chicago-area hospitals was performed. Cases had extended-spectrum-cephalosporin (ESC)-resistant infections due to bla
TEM or bla
SHV. DNA analysis assessed β-lactamase (bla) genes, multilocus sequence types, and E. coli phylogenetic grouping. Controls had ESC-susceptible Ent infections, matched 3:1 to cases by age, source, and hospital. Clinical-epidemiologic infection predictors were assessed.

Results:

Of 356 ESC-R-Ent isolates from children (median 4.3 years), 38 (10.7%) were positive solely for bla
TEM-ESBL (26%) or bla
SHV-ESBL genes (74%). Predominant organisms were Klebsiella (34.2%) and E. coli (31.6%); 67% of E. coli were phylogroup B2. Multilocus sequence types revealed multiple strains, 58% resistant to ≥3 antibiotic classes. On multivariable analysis, children with TEM-SHV-Ent infections more often had recent inpatient care (OR, 8.2), yet were diagnosed mostly as outpatients (OR, 25.6) and less in Neonatal Intensive Care Units (OR, 0.036) than controls. TEM-SHV-Ent patients had more gastrointestinal (OR, 23.7) and renal comorbidities (OR, 4.2). Differences in demographics, antibiotic exposure, and foreign bodies were not found.

Conclusion:

TEM-SHV-Ent are commonly linked to inpatient exposures in children with chronic conditions but most often present in outpatient settings. Clinicians should be aware of the potential increased risk for TEM-SHV-Ent infections in outpatients with gastrointestinal and renal comorbidities and histories of prolonged hospital stays.
Utilization of High-Intensity Statins in Patients at Risk for Cardiovascular Events: A National Cross-Sectional Study
Authors: Moorman John M. , Boyle Jaclyn , Bruno Leah , Dugan Sara , Everly Lukas , Gustafson Kyle , Hartzler Caleb , Homan Nathan , Joshi Dankesh , King Cynthia , King Kevin , King Philip K. , Pesce Anthony , Sadana Prabodh , Schneider Harold , Toth Jennifer , Unruh Amy , Walkerly Autumn
Published: October 2020

Background:

The 2013 American College of Cardiology/American Heart Association cholesterol guidelines, which identified four groups of patients at risk for atherosclerotic cardiovascular disease events, departed from the target-based approach to managing cholesterol. The impact of these guidelines on high-intensity statin use across the United States is unclear.

Study Question:

The primary objective was to evaluate the rate of high-intensity potential (HIP) statin use before and after the 2013 guidelines. The secondary objective was to identify predictors of HIP statin use within the study population.

Study Design:

A national cross-sectional study was conducted using data from the National Ambulatory Medical Care Survey. Office visits involving patients aged 21–75 years where criteria for HIP statin therapy were met were included. Visits involving pregnant patients were excluded.

Measures and Outcomes:

Prescribing trends of HIP statins were measured from National Ambulatory Medical Care Survey data before and after the 2013 guidelines. Multivariate logistic regression identified variables associated with prescribing HIP statins.

Results:

A total of 48,884 visits were included, representing more than 940 million office visits nationally. HIP statins were listed in 9.5% and 16.5% of visits before and after 2013, respectively (odds ratio [OR] 1.88; 95% confidence interval [CI] 1.62–2.20). The strongest predictors of HIP statin use were antihypertensive use (OR 5.38, 95% CI 4.67–6.20), comorbid hyperlipidemia (OR 2.93, 95% CI 2.62–3.29), Black race (OR 0.63, 95% CI 0.49–0.81), and Hispanic ethnicity (OR 0.65, 95% CI 0.52–0.80).

Conclusions:

Prescribing rates for HIP statins increased after the release of the 2013 guidelines. The prescribing rates were lower than expected, especially in Black and Hispanic patients. These observations signify opportunities to improve the quality of care for patients who are at risk for atherosclerotic cardiovascular disease events in the United States.
Comprehensive Review of Numerical Chromosomal Aberrations in Chromophobe Renal Cell Carcinoma Including Its Variant Morphologies
Authors: Alaghehbandan Reza , Trpkov Kiril , Tretiakova Maria , Luis Ana S. , Rogala Joanna D. , Hes Ondrej
Published: October 2020

Chromophobe renal cell carcinoma (ChRCC) accounts for 5% to 7% of all renal cell carcinomas. It was thought for many years that ChRCC exhibits a hypodiploid genome. Recent studies using advanced molecular genetics techniques have shown more complex and heterogenous pattern with frequent chromosomal gains. Historically, multiple losses of chromosomes 1, 2, 6, 10, 13, 17, and 21 have been considered a genetic hallmark of ChRCC, both for classic and eosinophilic ChRCC variants. In the last 2 decades, multiple chromosomal gains in ChRCCs have also been documented, depicting a considerably broader genetic spectrum than previously thought. Studies of rare morphologic variants including ChRCC with pigmented microcystic adenomatoid/multicystic growth, ChRCC with neuroendocrine differentiation, ChRCC with papillary architecture, and renal oncocytoma-like variants also showed variable chromosomal numerical aberrations, including multiple losses (common), gains (less common), or chromosomal changes overlapping with renal oncocytoma. Although not the focus of the review, The Cancer Genome Atlas (TCGA) data in ChRCC show TP53, PTEN, and CDKN2A to be the most mutated genes. Given the complexity of molecular genetic alterations in ChRCC, this review analyzed the existing published data, aiming to present a comprehensive up-to-date survey of the chromosomal abnormalities in classic ChRCC and its variants. The potential role of chromosomal numerical aberrations in the differential diagnostic evaluation may be limited, potentially owing to its high variability.
SRF Fusions Other Than With RELA Expand the Molecular Definition of SRF-fused Perivascular Tumors
Authors: Karanian Marie , Kelsey Anna , Paindavoine Sandrine , Duc Adeline , Vanacker Helene , Hook Liz , Weinbreck Nicolas , Delfour Christophe , Minard Veronique , Baillard Pauline , Blay Jean-Yves , Pissaloux Daniel , Tirode Franck
Published: October 2020

Pericytic tumors encompass several entities sharing morphologic and immunohistochemical features. A subset of perivascular myoid tumors associated with theSRF-RELAfusion gene was previously described. Herein, we report a series of 13 tumors belonging to this group, in which we have identified new fusion genes by RNA-sequencing, thus expanding the molecular spectrum of this entity. All patients except 1 were children and infants. The tumors, frequently located in the head (n=8), had a mean size of 38 mm (range 10 to 150 mm) and were mostly (n=9) well-circumscribed. Exploration of the follow-up data (ranging from 3 to 68 mo) confirmed the benign behavior of these tumors. These neoplasms presented a spectrum of morphologies, ranging from perivascular patterns to myoid appearance. Tumor cells presented mitotic figures but without marked atypia. Some of these tumors could mimic sarcoma. The immunohistochemical profiles confirmed a pericytic differentiation with the expression of the smooth muscle actin and the h-caldesmon, as well as the frequent positivity for pan-cytokeratin. The molecular analysis identified the expectedSRF-RELAfusion gene, in addition to other genetic alterations, all involvingSRFfused toCITED1,CITED2,NFKBIE, orNCOA2. The detection ofSRF-NCOA2fusions in spindle cell rhabdomyosarcoma of the infant has previously been described, representing a risk of misdiagnosis, although the cases reported herein did not express MyoD1. Finally, clustering analyses confirmed that this group ofSRF-fused perivascular myoid tumors forms a distinct entity, different from other perivascular tumors, spindle cell rhabdomyosarcomas of the infant, and smooth muscle tumors.
Prevalence and Outcomes of Congenital Heart Disease in Very Low Birth Weight Preterm Infants: An Observational Study From the Brazilian Neonatal Network Database
Authors: Anderson Daniela , Aragon Davi Casale , Gonçalves-Ferri Walusa A. , Manso Paulo H. , Leal Gabriela , Krebs Vera L. J. , Caldas Jamil P. S. , Almeida João H. C. L. , Ribeiro Manoel A. S. , Silveira Rita C. , Duarte José L. M. B. , Penido Márcia G. , Ferreira Daniela M. L. M. , Alves José M. S. , Sakano Karen M. K. , Santos Juliana P. F. , Gimenes Carolina B. , Silva Nathalia M. M. , Melo Fernanda P. G. , Venzon Paulyne S. , Meneses Jucille , Marques Patrícia F. , Rugolo Ligia M. S. S. , Testoni Daniela , Carmona Fabio
Published: October 2020

Objectives:

To evaluate the prevalence of congenital heart disease and their outcomes in a Brazilian cohort of very low birth weight preterm infants.

Design:

Post hoc analysis of data from the Brazilian Neonatal Network database, complemented by retrospective data from medical charts and a cross-sectional survey.

Setting:

Twenty public tertiary-care university hospitals.

Patients:

A total of 13,955 newborns weighing from 401 to 1,499 g and between 22 and 36 weeks of gestational age, born from 2010 to 2017.

Interventions:

None.

Measurements and Main Results:

The prevalence of congenital heart disease was 2.45% (95% CI, 2.20–2.72%). In a multivariate regression analysis, risk factors associated with congenital heart disease were maternal diabetes (relative risk, 1.55; 95% CI, 1.11–2.20) and maternal age above 35 years (relative risk, 2.09; 95% CI, 1.73–2.51), whereas the protection factors were maternal hypertension (relative risk, 0.54; 95% CI, 0.43–0.69), congenital infection (relative risk, 0.45; 95% CI, 0.21–0.94), and multiple gestation (relative risk, 0.73; 95% CI, 0.55–0.97). The pooled standardized mortality ratio in patients with congenital heart disease was 2.48 (95% CI, 2.22–2.80), which was significantly higher than in patients without congenital heart disease (2.08; 95% CI, 2.03–2.13). However, in multiple log-binomial regression analyses, only the presence of major congenital anomaly, gestational age (< 29 wk; relative risk, 2.32; 95% CI, 2.13–2.52), and Score for Neonatal Acute Physiology and Perinatal Extension II (> 20; relative risk, 3.76; 95% CI, 3.41–4.14) were independently associated with death, whereas the effect of congenital heart disease was spotted only when a conditional inference tree approach was used.

Conclusions:

The overall prevalence of congenital heart disease in this cohort of very low birth weight infants was higher and with higher mortality than in the general population of live births. The occurrence of a major congenital anomaly, gestational age (< 29 wk), and Score for Neonatal Acute Physiology and Perinatal Extension II (> 20) were significantly and independently associated with death, whereas the association of congenital heart disease and death was only evident when a major congenital anomaly was present.
The Value of DICER1 Mutation Analysis in “Subtle” Diagnostically Challenging Embryonal Rhabdomyosarcomas of the Uterine Cervix
Authors: Yoon Ju-Yoon , Apellaniz-Ruiz Maria , Chong Anne-Laure , Slim Zena , Salfinger Stuart G. , Clarke Blaise A. , Stewart Colin J.R. , Foulkes William D. , McCluggage W. Glenn
Published: October 2020

Embryonal rhabdomyosarcoma of the uterine cervix is a rare neoplasm which is almost invariably associated with pathogenic somatic or germline DICER1 mutations; patients with germline mutations have DICER1 syndrome. We report 2 subtle cervical embryonal rhabdomyosarcoma, one occurring in a 21-yr-old woman with a known history of DICER1 syndrome and the other in a 19-yr-old woman with no history of DICER1 syndrome or DICER1-associated neoplasms. Both neoplasms focally involved otherwise benign endocervical polyps and were characterized histologically by subtle areas of increased stromal cellularity, nuclear atypia and mitotic activity; there was focal nuclear staining of these areas with the skeletal muscle markers myogenin and myoD1. In both cases, demonstration of a somatic DICER1 RNase IIIb mutation in the tumor was instrumental in establishing the diagnosis. We believe these neoplasms represent the earliest discernible phase of cervical embryonal rhabdomyosarcoma. Pathologists should have a high index of suspicion when atypical stromal elements are present in endocervical polyps and immunohistochemistry together with DICER1 sequencing will assist in diagnosis.
Asymptomatic Malaria Co-infection of HIV-Infected Adults in Nigeria: Prevalence of and Impact on Cognition, Mood, and Biomarkers of Systemic Inflammation
Authors: Bharti Ajay R. , McCutchan John Allen , Umlauf Anya , Okwuegbuna Oluwakemi K. , Letendre Scott , Cherner Mariana , Burdo Tricia , Jumare Jibreel , Williams Kenneth , Blattner William , Royal Walter
Published: October 2020

Background:

HIV and malaria are associated with immunological perturbations and neurocognitive disorders even when asymptomatic. However, the effect of asymptomatic malaria (AM) in HIV-infected adults on neurocognitive impairment (NCI) is not well understood. This study investigated the biomarkers of systemic inflammation and neurocognition in dually infected Nigerian adults.

Methods:

We assessed the HIV and AM status of 269 adults and measured their global and domain-specific neurocognition and depression using standardized measures. Blood levels of sCD14 and sCD163 were also measured.

Results:

The mean age of the participants (n = 269) was 33 years, 62% were women, and AM among HIV+ and HIV− was similar (36% versus 37%). NCI was found in 23% (62/269) of participants. HIV+/AM+ had a higher prevalence of impaired learning and executive functions and were more depressed than HIV−/AM− or HIV+/AM−. HIV+ with CD4+ T-cell counts ≤200/µL were more impaired in the learning domain than those with >200/µL. HIV+/AM+ group had higher levels of sCD14 compared to the other 3 groups and higher levels of sCD163 than the HIV−/AM− group. Higher levels of sCD14 and sCD163 were each associated with NCI. The sCD163 (log10) levels were higher for those with 1+ versus 2+ parasitemia level.

Conclusions:

HIV and AM coinfection was associated with an increased risk of reduced learning and executive functions, and elevated systemic inflammation. Mood was more depressed in HIV patients with than those without AM. The mechanisms and long-term effects on neurocognition and depression among HIV+/AM+ individuals should be studied because this coinfection is common globally.
Highly Effective Inactivation of SARS-CoV-2 by Conjugated Polymers and Oligomers
Authors: Monge Florencia A. , Jagadesan Pradeepkumar , Bondu Virginie , Donabedian Patrick L. , Ista Linnea , Chi Eva Y. , Schanze Kirk S. , Whitten David G , Kell Alison M.
Published: October 2020

The current Covid-19 Pandemic caused by the highly contagious SARS-CoV-2 virus has proven extremely difficult to prevent or control. Currently there are few treatment options and very few long-lasting disinfectants available to prevent the spread. While masks and protective clothing and “social distancing” may offer some protection, their use has not always halted or slowed the spread. Several vaccines are currently undergoing testing; however there is still a critical need to provide new methods for inactivating the virus before it can spread and infect humans. In the present study we examined the inactivation of SARS-CoV-2 by synthetic conjugated polymers and oligomers developed in our laboratories as antimicrobials for bacteria, fungi and non-enveloped viruses. Our results show that we can obtain highly effective light induced inactivation with several of these oligomers and polymers including irradiation with near-UV and visible light. With both the oligomers and polymers, we can reach several logs of inactivation with relatively short irradiation times. Our results suggest several applications involving the incorporation of these materials in wipes, sprays, masks and clothing and other Personal Protection Equipment (PPE) that can be useful in preventing infections and the spreading of this deadly virus and future outbreaks from similar viruses.
SARS-CoV-2 Inactivation Potential of Metal Organic Framework Induced Photocatalysis
Authors: Ornstein Jason , Ozdemir Ray O.K. , Boehme Anne , Nouar Farid , Serre Christian , Ackerman Daniel N. , Herrera Vicki L. , Santarpia Joshua L.
Published: October 2020

As the world recovers from the lockdown imposed by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic, returning to shared indoor spaces is considered a formidable risk. It is now clear that transmission of SARS-CoV-2 is driven by respiratory microdroplets expelled by infected persons, which can become suspended in the air. Several layering technologies are being explored to mitigate indoor transmission in the hopes of re-opening business, schools and transportation systems. Here we coupled the water adsorptive and photocatalytic capacity of novel Metal Organic Frameworks (MOFs) to demonstrate the capture and inactivation of SARS-CoV-2. Discussion is given on the methods of analysis and the differences between the photocatalytic activity of several MOFs, and the difference between MOF induced photocatalysis and ultra violet photolysis of SARS-CoV-2. Our results are intended to provide support to industry looking for alternative methods secure indoor spaces.
Combined Metabolic Activators accelerates recovery in mild-to-moderate COVID-19
Authors: Altay Ozlem , Arif Muhammad , Li Xiangyu , Yang Hong , Aydın Mehtap , Alkurt Gizem , Kim Woonghee , Akyol Dogukan , Zhang Cheng , Dinler-Doganay Gizem , Turkez Hasan , Shoaie Saeed , Nielsen Jens , Borén Jan , Olmuscelik Oktay , Doganay Levent , Uhlén Mathias , Mardinoglu Adil
Published: October 2020

There is a need to treat COVID-19 patients suffering from respiratory problems, resulting in decreased oxygen levels and thus leading to mitochondrial dysfunction and metabolic abnormalities. Here, we investigated if a high oral dose of a mixture of Combined Metabolic Activators (CMA) can restore metabolic function and thus aid the recovery of COVID-19 patients. We conducted a placebo-controlled, open-label phase 2 study and a double-blinded phase 3 clinical trials to investigate the time of symptom-free recovery on ambulatory patients using a mixture of CMA consisting of NAD+ and glutathione precursors. The results of both studies showed that the time to complete recovery was significantly shorter in the CMA group (6.6 vs 9.3 days) in phase 2 and (5.7 vs 9.2 days) in phase 3 trials. A comprehensive analysis of the blood metabolome and proteome showed that the plasma levels of proteins and metabolites associated with inflammation and antioxidant metabolism are significantly improved in patients treated with the metabolic activators as compared to placebo. The results show that treating patients infected with COVID-19 with a high dose of CMAs leads to a more rapid symptom-free recovery, suggesting a role for such a therapeutic regime in the treatment of infections leading to respiratory problems.
Microbial Population Shift and Metabolic Characterization of Silver Diamine Fluoride Treatment Failure on Dental Caries
Authors: Paul Bidisha , Sierra Maria A , Xu Fangxi , Crystal Yasmi O , Li Xin , Saxena Deepak , Ruff Ryan Richard
Published: October 2020

Objectives

The objective of this pilot study was to describe the microbial profiles present in the plaque and saliva of children who continued to develop new carious lesions following treatment with silver diamine fluoride (“nonresponders”) compared to caries active, cariesfree, and children immediately receiving SDF treatment for untreated carie s in order to identify potential microbial differences that may relate to a re-incidence of caries.

Methods

Saliva and plaque samples from infected and contralateral sites were obtained from twenty children who were either caries free, had active carious lesions, were caries active and received SDF treatment immediately before sampling, or had previously received SDF treatment and developed new caries. In total, 8,057,899 Illumina-generated sequence reads from 60 samples were obtained. Reads were processed using the Quantitative Insights Into Microbial Ecology pipeline. Group differences were assessed using Analysis of Variance Models and Tukey Honest Significant Differences. To identify significant taxa between treatment groups, Linear discriminant analysis Effect Size (LefSe) and Analysis of Differential Abundance Taking Sample Variation Into Account were used.

Results

Differential abundant analysis indicated that members of the Lachnospiraceae family were significantly enriched in non-responders and the genus Tannerella and species Granulicatella adiances were also highly abundant in this group. LefSe analysis between nonresponders and SDF-treated groups revealed that genera Leptotrichia and Granulicatella were enriched in non-responders. We observed the highest abundance of phosphotransferase system and lowest abundance of lipopolysaccharide synthesis in non-responders.

Discussion

The microbiome in dental biofilms is responsible for initiation and progression of dental caries. SDF has been shown to be effective in arresting the progression carious lesions, in part due to to its antimicrobial properties. Findings suggest that the differential abundance of select microbiota and specific pathway functioning in individuals that present with recurrent decay after SDF treatment may contribute to a potential failure of silver diamine fluoride to arrest dental caries.
Impact of pathogen reduction methods on immunological properties of the COVID-19 convalescent plasma
Authors: Kostin Alexander I. , Lundgren Maria N. , Bulanov Andrey Y. , Ladygina Elena A. , Chirkova Karina S. , Gintsburg Alexander L. , Logunov Denis Y. , Dolzhikova Inna V. , Shcheblyakov Dmitry V. , Borovkova Natalia V. , Godkov Mikhail A. , Bazhenov Alexey I. , Shustov Valeriy V. , Bogdanova Alina S. , Kamalova Alina R. , Ganchin Vladimir V. , Dombrovskiy Eugene A. , Volkov Stanislav E. , Drozdova Nataliya E. , Petrikov Sergey S.
Published: October 2020

Background and Objectives

COVID-19 convalescent plasma is an experimental treatment against SARS-CoV-2. The aim of this study is to assess the impact of different pathogen reduction methods on the levels and virus neutralizing activity of the specific antibodies against SARS-CoV2 in convalescent plasma.

Materials and Methods

A total of 140 plasma doses collected by plasmapheresis from COVID-19 convalescent donors were subjected to pathogen reduction by three methods: methylene blue (M)/visible light, riboflavin (R)/UVB, and amotosalen (A)/UVA. To conduct a paired comparison, individual plasma doses were divided into 2 samples that were subjected to one of these methods. The titres of SARS-CoV2 neutralizing antibodies (NtAbs) and levels of specific immunoglobulins to RBD, S- and N- proteins of SARS-CoV-2 were measured before and after pathogen reduction.

Results

The methods reduced NtAbs titres differently: among units with the initial titre 80 or above, 81% of units remained unchanged and 19% decreased by one step after methylene blue; 60% were unchanged and 40% decreased by one step after amotosalen; after riboflavin 43% were unchanged and 50% (7% respectively) had a one- step (two-step respectively) decrease. Paired two-sample comparisons (M vs A, M vs R and A vs R) revealed that the largest statistically significant decrease in quantity and activity of the specific antibodies resulted from the riboflavin treatment.

Conclusion

Pathogen reduction with methylene blue or with amotosalen provides the greater likelihood of preserving the immunological properties of the COVID-19 convalescent plasma compared to riboflavin.
Antigen-based testing but not real-time PCR correlates with SARS-CoV-2 virus culture
Authors: Pekosz Andrew , Cooper Charles K. , Parvu Valentin , Li Maggie , Andrews Jeffrey C. , Manabe Yukari C. , Kodsi Salma , Leitch Jeffry , Gary Devin S. , Roger-Dalbert Celine
Published: October 2020

Individuals can test positive for SARS-CoV-2 by real-time polymerase chain reaction (RT-PCR) after no longer being infectious.1-8 Positive SARS-CoV-2 antigen-based testing exhibits a temporal pattern that corresponds with active, replicating virus and could therefore be a more accurate predictor of an individual’s potential to transmit SARS-CoV-2.2,3,9 Using the BD Veritor System for Rapid Detection of SARS-CoV-2 later flow antigen detection test, we demonstrate a higher concordance of antigen-positive test results with the presence of cultured, infectious virus when compared to RT-PCR. When compared to infectious virus isolation, the sensitivity of antigen-based testing is similar to RT-PCR. The correlation between SARS-CoV-2 antigen and SARS-CoV-2 culture represents a significant advancement in determining the risk for potential transmissibility beyond that which can be achieved by detection of SARS-CoV-2 genomic RNA. Coupled with a rapid time-to-result, low cost, and scalability, antigen-based testing should facilitate effective implementation of testing and public health interventions that will better contain COVID-19.
COVID-19 severity in asthma patients: A multi-center matched cohort study
Authors: Robinson Lacey B. , Wang Liqin , Fu Xiaoqing , Wallace Zachary S. , Long Aidan A. , Zhang Yuqing , Camargo Carlos A. , Blumenthal Kimberly G.
Published: October 2020

Objective

The evidence pertaining to the effects of asthma on Coronavirus disease 2019 outcomes has been unclear. To improve our understanding of the clinically important association of asthma and Coronavirus disease 2019.

Methods

A matched cohort study was performed using data from the Mass General Brigham Health Care System (Boston, MA). Adult (age ≥ 18 years) patients with confirmed Coronavirus disease 2019 and without chronic obstructive pulmonary disease, cystic fibrosis, or interstitial lung disease between March 4, 2020 and July 2, 2020 were analyzed. Up to 5 non-asthma comparators were matched to each asthma patient based on age (within 5 years), sex, and date of positive test (within 7 days). The primary outcomes were hospitalization, mechanical ventilation, and death, using multivariable Cox-proportional hazards models accounting for competing risk of death, when appropriate. Patients were followed for these outcomes from diagnosis of Coronavirus disease 2019 until July 2, 2020.

Results

Among 562 asthma patients, 199 (21%) were hospitalized, 15 (3%) received mechanical ventilation, and 7 (1%) died. Among the 2686 matched comparators, 487 (18%) were hospitalized, 107 (4%) received mechanical ventilation, and 69 (3%) died. The adjusted Hazard Ratios among asthma patients were 0.99 (95% Confidence Internal 0.80, 1.22) for hospitalization, 0.69 (95% Confidence Internal 0.36, 1.29) for mechanical ventilation, and 0.30 (95% Confidence Internal 0.11, 0.80) for death.

Conclusions

In this matched cohort study from a large Boston-based healthcare system, asthma was associated with comparable risk of hospitalization and mechanical ventilation but a lower risk of mortality.
Investigating the potential benefit that requiring travellers to self-isolate on arrival may have upon the reducing of case importations during international outbreaks of influenza, SARS, Ebola virus disease and COVID-19
Authors: Bays Declan , Bennett Emma , Finnie Thomas
Published: October 2020

With the advent of rapid international travel, disease can now spread between nations faster than ever. As such, when outbreaks occur in foreign states, pressure mounts to reduce the risk of importing cases to the home nation. In a previous paper, we developed a model to investigate the potential effectiveness of deploying screening at airports during outbreaks of influenza, SARS, and Ebola. We also applied the model to the current COVID-19 outbreak. This model simulated the testing of travellers (assumed not to be displaying symptoms prior to boarding their flight) as they arrived at their destination. The model showed that the reduction in risk of case importation that screening alone could deliver was minimal across most scenarios considered, with outputs indicating that screening alone could detect at most 46.4%, 12.9%, and 4.0% of travellers infected with influenza, SARS and Ebola respectively, while the model also reported a detection rate of 12.0% for COVID-19. In this paper, we present a brief modification to this model allowing us to assess the added impact that quarantining incoming travelers for various periods may have on reducing the risk of case importation. Primary results show that requiring all travellers to undergo 5 days of self-isolation on arrival, after which they are tested again, has the potential to increase rates of detection to 100%, 87.6%, 81.7% and 41.3% for travellers infected with influenza, SARS, COVID-19 and Ebola respectively. Extending the period of self-isolation to 14 days increases these potential detection rates to 100%, 100%, 99.5% and 91.8% respectively.
Effect of water intake and storage time on protein concentration and enzyme AChE activity in erythrocyte and plasma blood samples of healthy individuals
Authors: Jovičić Snežana
Published: October 2020

Background

Storage time influence concentration levels of blood biomarker. This study aimed to assess the effect of water intake prior sampling and storage time on protein concentration, enzyme AChE activity, inhibitor efficacy and to build an efficient inhibitor calibration curve in healthy individuals.

Methods

Data analysis was performed on 11 participants. Study utilizes substrate acetylcholine chloride and inhibitors BW284c51 (0.01mM) and GUK-987 (0.1mM). Calibration curve ranging from 10-1 to 10-38 mM was build for inhibitor GUK-987 and GDK-510.

Data analysis is carried out with Microsoft Excel 2007. Data analysis was performed via IBM SPSS Statistical Software v23.0. Descriptive statistics and parametric statistical tests were assessed for 0, 90, 91 and 92 days of storage in Plasma and Erythrocyte samples. Workflow of building calibration curve and the most efficient inhibition concentration is assessed.

Results

Water intake and storage time have effect on in vitro protein concentration, activation/inhibition of enzyme AChE activity in Plasma and Erythrocyte samples. However, 100% inhibitor efficacy is maintained for inhibitor GUK-987 in Plasma samples and inhibitor BW284c51 in Erythrocyte samples. The most efficient inhibitor concentration is determined.

Conclution

Significant changes and variable association have been estimated between protein concentration, activation/inhibition of enzyme AChE activity, as a cause of water intake and storage time. Taking all these factors into account for further research is important for disease prevention and human wellbeing.
A haemagglutination test for rapid detection of antibodies to SARS-CoV-2
Authors: Townsend Alain , Rijal Pramila , Xiao Julie , Tan Tiong Kit , Huang Kuan-Ying A , Schimanski Lisa , Huo Jiangdong , Gupta Nimesh , Rahikainen Rolle , Matthews Philippa C , Crook Derrick , Hoosdally Sarah , Street Teresa , Rudkin Justine , Stoesser Nicole , Karpe Fredrik , Neville Matthew , Ploeg Rutger , Oliveira Marta , Roberts David J , Lamikanra Abigail A , Tsang Hoi Pat , Bown Abbie , Vipond Richard , Mentzer Alexander J , Knight Julian C , Kwok Andrew , Screaton Gavin , Mongkolsapaya Juthathip , Dejnirattisai Wanwisa , Supasa Piyada , Klenerman Paul , Dold Christina , Baillie Kenneth , Moore Shona C , Openshaw Peter JM , Semple Malcolm G , Turtle Lance CW , Ainsworth Mark , Allcock Alice , Beer Sally , Bibi Sagida , Clutterbuck Elizabeth , Espinosa Alexis , Mendoza Maria , Georgiou Dominique , Lockett Teresa , Martinez Jose , Perez Elena , Sanchez Veronica , Scozzafava Giuseppe , Sobrinodiaz Alberto , Thraves Hannah , Joly Etienne
Published: October 2020

Serological detection of antibodies to SARS-CoV-2 is essential for establishing rates of seroconversion in populations, detection of seroconversion after vaccination, and for seeking evidence for a level of antibody that may be protective against COVID-19 disease. Several high-performance commercial tests have been described, but these require centralised laboratory facilities that are comparatively expensive, and therefore not available universally. Red cell agglutination tests have a long history in blood typing, and general serology through linkage of reporter molecules to the red cell surface. They do not require special equipment, are read by eye, have short development times, low cost and can be applied as a Point of Care Test (POCT). We describe a red cell agglutination test for the detection of antibodies to the SARS-CoV-2 receptor binding domain (RBD). We show that the Haemagglutination Test (“HAT”) has a sensitivity of 90% and specificity of 99% for detection of antibodies after a PCR diagnosed infection. The HAT can be titrated, detects rising titres in the first five days of hospital admission, correlates well with a commercial test that detects antibodies to the RBD, and can be applied as a point of care test. The developing reagent is composed of a previously described nanobody to a conserved glycophorin A epitope on red cells, linked to the RBD from SARS-CoV-2. It can be lyophilised for ease of shipping. We have scaled up production of this reagent to one gram, which is sufficient for ten million tests, at a cost of ∼0.27 UK pence per test well. Aliquots of this reagent are ready to be supplied to qualified groups anywhere in the world that need to detect antibodies to SARS-CoV-2, but do not have the facilities for high throughput commercial tests.