bluuebunny/crossref_metadata_2025 huggingface dataset:
Al-Andalus
Authors: Cressier Patrice , Lloret Sonia Gutiérrez
Published: November 2020

The archaeology of al-Andalus did not emerge as a discipline until the end of the 1970s, slightly later than medieval archaeology in Northern Europe. Its spectacular development in subsequent decades goes hand in hand with the revision, sometimes conflicting, of a historiography which traditionally underestimated and sometimes even denied the societal transformations following the Arab-Berber conquest of 711. The principal themes of controversy relate to the degree of transformation that occurred, the existence of ruptures, and the “Oriental” character of the new political, social, and familial structures that emerged. Focusing on the materiality of historical processes, archaeology has made it possible to approach these debates from different perspectives and to give new meaning to the concepts of Islamization and Arabization. This chapter examines some of the most significant research themes in the archaeology of al-Andalus.
Eastern African Coast
Authors: Wynne-Jones Stephanie , Fleisher Jeffrey
Published: November 2020

This chapter offers an overview of historical and archaeological research on Islam and Islamic practice on the pre-colonial eastern African coast during the late first and early second millennium ce. Due to the visible remains of mosques, tombs, and other stylistic elements influenced by the Islamic heartlands, researchers have always regarded Islam as important to the emergence of Swahili coastal towns. In this way, the archaeology of the Swahili has always been an archaeology of Islam. Archaeological research during the past thirty years, however, has challenged the way an earlier generation of archaeologists characterized Swahili society as resulting from immigrant settlers from the Arab world. These debates, which continue today, are centered on how researchers position the Swahili within the dar al-Islam: Are they increasingly marginalized descendants of early colonists or the result of cosmopolitan engagements of local communities? Uncovering the first-millennium roots of east African Islam has allowed archaeologists to explore the development of coastal Islam, its particular material legacy, and its possible sectarian associations. Building on this research, the authors argue for a shift in research emphasis, from the study of Islamic presence to that of Islamic practice and demonstrate how research on mosques, burials, and coins can provide insights into the way coastal residents enacted Islam in their daily lives.
Ethiopia and the Horn of Africa
Authors: Insoll Timothy
Published: November 2020

The Islamic archaeology of Ethiopia and the Horn of Africa remains largely unexplored. This chapter reviews research that has been completed in Djibouti, Eritrea, Ethiopia, Somalia, and Somaliland, providing a survey of the main sites that have been investigated. Relevant research themes that have emerged such as rural and urban landscapes, Islamization, trade, diet, and epigraphy are also considered within these geographical sections. The main routes for Muslim contacts from the coast to the interior are evaluated. Primary focus is given to research in eastern Ethiopia, exploring Islamization via archaeological evidence. This is indicating significantly entangled inter-African and international connections as well as allowing reconstruction of regional settlement and trade patterns involving the transfer of material, objects, technologies, and ideas. The importance of results of recent archaeological analysis in Somaliland is also highlighted in facilitating understanding of various categories of sites and particularly in relation to past nomad lifeways. Finally, future directions for research are considered.
Heritage Management and Community Development
Authors: de Vries Bert
Published: November 2020

This section deals with the incipient practice of heritage management in Islamic archaeology through the deliberate engagement of local communities in the preservation of Islamic material culture. This growing expansion of the nature of the academic Islamic Archaeology has been enabled by the maturation of the discipline. An it was encouraged by a post-colonial activist agenda among some scholars to restore the rightful access of previously by excluded local communities to their own archaeological and architectural heritage. This thematic introduction will treat the emergence and nature of this process, and the ensuing chapters will give diverse instances of its practice.
The Islamic West
Authors: Fenwick Corisande
Published: November 2020

This text provides a brief introduction to the chapters focusing on the Islamic West. Long neglected by Anglophone academics, this region was pivotal in the development of Islamic art history and archaeology as a discipline, but, over the course of the 20th century it came to be regarded as peripheral to broader debates in Islamic archaeology. Since the 1970s, a new generation of Islamic archaeologists working in Europe, North Africa, and the Sahara has transformed our understanding of the region, though the amount and quality of research remains uneven in different countries.
Sub-Saharan Africa
Authors: Insoll Timothy
Published: November 2020

The chapters in this section are introduced and the main archaeological research themes considered, such as the presence and practice of Islam, Islamization, the role of commerce in spreading Islam, indigenization, and syncretism. The reasons for the regional disparity in archaeological research are identified: for example, political instability.
Persia
Authors: Rante Rocco
Published: November 2020

Long the stepchild of the study of Ancient, Classical, and Late Antique civilizations, the archaeology of Islamic-era Persia is a relatively new discipline, and one that has been dominated by the exploration of urban forms and the documentation of monuments. This chapter, then, uses the evolution of cities as a window on medieval Islamic societies in the region. The reorganization of old fortified settlements, the constitution of new well-organized quarters as rabads, and the creation of cities ex novo show the major contribution of Islamic culture to Iranian urbanization. What we know archaeologically about the rural hinterland, its relationship to the “urban,” and industry is summarized here, placing scholarship on the Islamic Persian city into a larger perspective.
Medieval Turkey
Authors: Redford Scott
Published: November 2020

In this chapter, Islamic archaeology of the medieval (11th–14th centuries) period in Turkey is related to international as well as national developments in the late Ottoman Empire and the Republic of Turkey in areas like cultural policy, economic development, and tourism. These and other factors directly impacted the choice of sites to be excavated, thereby affecting the archaeological record. The author also examines Islamic archaeology in Turkey in relation to that of other historical periods there and raises cases in which the archaeology of this period can address the cultural and economic shift that accompanied the establishment of Turco-Islamic states in former Byzantine lands.
Ifriqiya and the Central Maghreb
Authors: Fenwick Corisande
Published: November 2020

North Africa played a pivotal part in the development of Islamic archaeology as a discipline through the important French excavations at the Qal’a of the Beni Hammad in Algeria in the late 19th century, one of the earliest excavations at an Islamic site by European archaeologists anywhere in the Islamic world. Despite this early promise, for most of the 20th century, the Islamic period was the preserve of art historians, with only a handful of small-scale excavations conducted at the spectacular palatial-cities, mosques, ribats, and fortresses of Algeria, Tunisia, and Libya. Since the 1990s, there has been a significant rise in the number of projects and amount of evidence available, as well as a new interest in revisiting old questions and models for the Islamic period. This chapter charts the development of Islamic archaeology and lays out the key scholarly debates in Ifriqiya and the central Maghreb, broadly understood as encompassing modern-day Tunisia, Algeria, and western coastal Libya.
Subclinical synovitis in arthralgia: how often does it result in clinical arthritis? Reflecting on starting points for disease-modifying anti-rheumatic drug treatment
Authors: Rogier Cleo , Wouters Fenne , van Boheemen Laurette , van Schaardenburg Dirkjan , de Jong Pascal H P , van der Helm-van Mil Annette H M
Published: November 2020

Objectives

According to guidelines, clinical arthritis is mandatory for diagnosing RA. However, in the absence of clinical synovitis, imaging-detected subclinical synovitis is increasingly used instead and is considered as a starting point for DMARD therapy. To search for evidence we studied the natural course of arthralgia patients with subclinical synovitis from three longitudinal cohorts and determined the frequencies of non-progression to clinically apparent inflammatory arthritis (IA) (i.e. ‘false positives’).

Methods

Subclinical synovitis in the hands or feet of arthralgia patients was visualized with US (two cohorts; definition: greyscale ≥2 and/or power Doppler ≥1) or MRI (one cohort; definition: synovitis score ≥1 by two readers). Patients were followed for 1  year on for IA development; two cohorts also had 3  year data. Analyses were stratified for ACPA.

Results

Subclinical synovitis at presentation was present in 36%, 41% and 31% in the three cohorts. Of the ACPA-positive arthralgia patients with subclinical synovitis, 54%, 44% and 68%, respectively, did not develop IA. These percentages were even higher in the ACPA-negative arthralgia patients: 66%, 85% and 89%, respectively. Similar results were seen after 3 years of follow-up.

Conclusion

Replacing clinical arthritis with subclinical synovitis to identify RA introduces a high false-positive rate (44–89%). These data suggest an overestimation regarding the value of ACPA positivity in combination with the presence of subclinical synovitis in patients with arthralgia, which harbours the risk of overtreatment if DMARDs are initiated in the absence of clinical arthritis.
Impacts of commingling cattle from different sources on their physiological, health, and performance responses during feedlot receiving
Authors: Wiegand Jacob B , Cooke Reinaldo F , Brandão Alice P , Schubach Kelsey M , Colombo Eduardo A , Daigle Courtney L , Duff Glenn C , Gouvêa Vinicius N
Published: November 2020

This experiment compared physiological, health, and performance responses of beef heifers assigned to different commingling schemes (one, two, or four sources per pen) during a 56-d feedlot receiving period. Ninety-six recently weaned Angus-influenced heifers were obtained from an auction facility. Heifers originated from four cow-calf ranches, and were reared in the same herd within each ranch since birth. Heifers were loaded into two livestock trailers at the auction yard (two sources per trailer; d −2), arranged in two sections of each trailer according to source, and transported for 10 h to stimulate the stress of a long-haul. Heifers were not mixed with cohorts from other sources prior to and at the auction yard. Upon arrival (d −2), shrunk body weight (BW) was recorded and heifers were maintained in four paddocks by source with ad libitum access to a complete starter feed and water for 36 h. On d 0, heifers were ranked by source and shrunk BW and allocated to 1 of 24 drylot pens (four heifers per pen) containing: 1) heifers from a single source (1SRC, n = 8), 2) heifers from two sources (2SRC, n = 8), or 3) heifers from four sources (4SRC, n = 8). From d 0 to d 55, heifers had free-choice access to the complete starter feed and water. Heifers were assessed daily for symptoms of bovine respiratory disease (BRD), and feed intake was recorded from each pen daily. Blood samples were collected on d 0, d 6, d 13, d 27, d 41, and d 55, and shrunk BW (after 16 h of water and feed withdrawal) was recorded on d 56 for average daily gain (ADG). No treatment differences were noted (P ≥ 0.56) for heifer ADG (mean ± SE = 0.853 ± 0.043 kg/d), final shrunk BW, feed intake, and feed efficiency. No treatment differences were noted (P ≥ 0.27) for plasma concentrations of cortisol and haptoglobin, and serum concentrations of antibodies against BRD viruses and Mannheimia haemolytica. No treatment differences were noted (P ≥ 0.17) for incidence of BRD (mean ± SE = 59.3 ± 5.0%) or mortality. The proportion of heifers diagnosed with BRD that required three antimicrobial treatments to regain health increased linearly (P = 0.03) according to the number of sources (0.0, 12.3, and 20.8% of 1SRC, 2SRC, and 4SRC heifers, respectively; SEM = 7.0). Hence, commingling heifers from different sources did not impact performance, physiological responses, and BRD incidence during a 56-d receiving period, although recurrence of BRD after the second antimicrobial treatment increased according to commingling level.
Risk Factors of Stenotrophomonas maltophilia Blood Stream Infections: Comparison With Other Gram-Negative Blood Stream Infections in Children
Authors: Gayretli Aydιn Zeynep Gökçe , Tanir Gonul , Bayhan Gulsum Iclal , Aydin Teke Turkan , Metin Akçan Ozge , Kaman Ayse , Yasar Durmus Sevgi , Oz Fatma Nur
Published: November 2020

Background:

Stenotrophomonas maltophilia, is a nonfermentative, aerobic, Gram-negative bacilli which is intrinsically resistance to several antibiotics. Treatment options for this bacteria are quite different from the other Gram-negative bacilli, which can represent a therapeutic challenge. To initiate appropriate empiric treatment and to reduce mortality, differentiation of S. maltophilia from other Gram-negative bacteria is critically important. The aim of this study is to distinguish the risk factors of S. maltophilia blood stream infections (BSI) from other Gram-negative BSI.

Methods:

This was a retrospective, case-control study. Patients with S. maltophilia BSI were selected as cases and patients with non-S. maltophilia Gram-negative BSI were selected as controls. Demographic and clinical characteristics of patients were recorded.

Results:

Forty-eight cases with S. maltophilia BSI and 144 controls were enrolled in the study. Risk factors for S. maltophilia BSI compared with the control group includes prior use of antibiotics, especially carbapenem, pediatric intensive care unit stay, mechanical ventilator use, indwelling catheters and duration of hospitalization.

Conclusions:

Breakthrough infection by S. maltophilia can occur in severely ill patients being treated with carbapenem. In the presence of risk factors, to reduce morbidity and mortality, S. maltophilia should be kept in mind when starting empiric treatment.
Prevention of veteran suicide in community settings: Patient safety resources
Authors: Yackel Edward E.
Published: November 2020

As a recently retired Army Nurse Corps officer with almost 30 years of service to my country, I want to ensure that my fellow nurse practitioners (NPs) are aware of their role in ensuring high quality and safe patient care to all veterans who are accessing care outside of the Veterans Health Administration (VHA). Specifically, NPs who work outside the VHA have an opportunity to participate in patient safety efforts aimed at reducing veteran suicide. On June 6, 2018, Congress passed Public Law 115–182 or the Veterans Affairs Maintaining Internal Systems and Strengthening Integrated Outside Networks (MISSION) Act. A goal of the MISSION Act is to ensure that veterans have access to health care by streamlining eligibility criteria for community care. A veteran who drives more than 30 minutes or waits more than 20 days for a primary care or mental health appointment may be eligible to be sent to a community care provider such as an NP. Therefore, NPs and other providers who work in community settings have an obligation to know more about the mental and physical health care needs of veterans as well as the resources that have been developed by the VHA to assist them.
Female warfighters' perceptions of urogenital health in operational settings
Authors: Kostas-Polston Elizabeth A. , Braun Lisa A. , Miedema Joy
Published: November 2020

Background:

An increased incidence in hygiene-related urogenital infections (bacterial vaginitis, vulvovaginal candidiasis, and urinary tract) has been reported in female warfighters serving in austere environments with decreased availability of water and sanitation resources, and when personal safety outweighs concerns for hygiene. Knowledge and access to an innovative kit designed for the female warfighter to self-test, self-identify, and self-treat common urogenital symptoms is critical to force health.

Purpose:

The purpose of this descriptive, cross-sectional, exploratory qualitative study was to explore female warfighters': 1) confidence in seeking sex-specific health care in field and deployment environments and 2) acceptance and willingness to self-test, self-identify, and self-treat urogenital symptoms and infections.

Methodological orientation:

Qualitative data for this thematic analysis were collected during administration of the Military Women's Readiness Urogenital Health Questionnaire. Participants provided open-ended comments associated with three survey questions. Braun and Clarke's inductive thematic analysis method guided the narrative analysis.

Sample:

Our sample included a diverse group of US Army women (USAW; n = 152) from a large, military installation.

Results:

Narratives and themes demonstrate USAW's desire and need for the availability of a self-test and self-treatment kit. Access, time, mission, and prevention of self-harm by quicker resolve of symptoms are cited as key reasons in support of such a kit.

Conclusions and practice implications:

Nurse practitioners (NPs) are ideally positioned to provide sex-specific educational interventions and anticipatory guidance that supports physical health, to include urogenital conditions. As urogenital self-testing becomes available for female warfighters, NPs are the model healthcare provider for educating women on their use.
Headache management in a Veteran population: First considerations
Authors: Williams Karen A.
Published: November 2020

It is estimated that almost half the general population has a headache disorder. The majority of these are considered tension-type headaches. Migraines and chronic daily headache (CDH) are not as common but are much more debilitating. Although CDH/chronic migraine (CM) occurs in about 3% of the population, it has been found to be 20% or higher in the post 9/11 combat Veteran population. Data from the Veterans Health Administration show that more than 380,000 Veterans, younger than 50 years, received care for a headache in 2017. Approximately 75% of the headache care was from a primary care provider. The purpose of the article is to review physical examination for the veteran with a history of a headache disorder, discuss contributing factors and comorbid conditions, as well as give an overview of current treatment options, with a focus on the post‐9/11 combat Veteran who has CDH/CM.
Simultaneous Superiorly Based Pharyngeal Flap and Tonsillectomy: Evaluation of Speech and Pain Outcomes
Authors: Hon Heidi H. , DeLuna Devin , Akhter Haris M. , Brosnihan Paul J. , Samson Kaeli , Diaz Jennifer , Miller Jason J.
Published: November 2020

Controversy remains whether to perform a pharyngeal flap simultaneously with a tonsillectomy in patients with velopharyngeal insufficiency. The aim of this study is to revisit the speech outcomes and complications associated with the combined superiorly based pharyngeal flap and tonsillectomy procedure, while comparing pain outcomes. We hypothesize that the combined procedure will improve speech outcomes with minimal complications, but patients will experience more pain in the combined procedure.

A 5-year retrospective review of registry data from Boys Town National Research Hospital was conducted from 2014 to 2019. Data collection included age, surgeries performed, length of stay, pain medication administration occurrences, immediate postoperative complications, postoperative speech outcomes specifically related to articulation (audible nasal airway emissions) and resonance (hypernasality).

Eighty-eight patients had a superiorly based pharyngeal flap over this 5-year period. Eighteen patients (20%) had a simultaneous procedure performed. There were no patients who had immediate postoperative complications such as upper airway obstruction or bleeding complications that necessitated a reoperation. One of the patients had a pharyngeal flap dehiscence that required a revision pharyngeal flap in the combined group. Nasal airway emissions and hypernasality were eliminated in 58.3% and 75%of the combined patients, respectively. The total number of narcotic administration occurrences were significantly higher in the combined group than the pharyngeal flap only group (9.0 versus 7.0; P = 0.03).

A number of velopharyngeal patients will present with hypertrophied tonsils. We believe that it is safe and beneficial to perform the combined procedure in the same setting.
Sleep in disorders of consciousness: diagnostic, prognostic, and therapeutic considerations
Authors: Gottshall Jackie L. , Rossi Sebastiano Davide
Published: November 2020

Purpose of review

Sleep is important in the evaluation of patients with disorders of consciousness (DOC). However, it remains unclear whether reconstitution of sleep could enable consciousness or vice versa. Here we synthesize recent evidence on natural recovery of sleep in DOC, and sleep-promoting therapeutic interventions for recovery of consciousness.

Recent findings

In subacute DOC, physiological sleep--wake cycles and complex sleep patterns are related to better outcomes. Moreover, structured rapid-eye-movement (REM), non-REM (NREM) stages, and presence of sleep spindles correlate with full or partial recovery. In chronic DOC, sleep organization may reflect both integrity of consciousness-supporting brain networks and engagement of those networks during wakefulness. Therapeutic strategies have integrated improvement of sleep and sleep--wake cycles in DOC patients; use of bright light stimulation or drugs enhancing sleep and/or vigilance, treatment of sleep apneas, and neuromodulatory stimulations are promising tools to promote healthy sleep architecture and wakeful recovery.

Sleep features and sleep--wake cycles are important prognostic markers in subacute DOC and can provide insight into covert recovery in chronic DOC. Although large-scale studies are needed, preliminary studies in limited patients suggest that therapeutic options restoring sleep and/or sleep--wake cycles may improve cognitive function and outcomes in DOC.
Seroprevalence of parechovirus A1, A3 and A4 antibodies in Yamagata, Japan, between 1976 and 2017
Authors: Mizuta Katsumi , Komabayashi Kenichi , Aoki Yoko , Itagaki Tsutomu , Ikeda Tatsuya
Published: November 2020

Introduction. Although new parechovirus A (PeVA) types, including parechovirus A3 (PeVA3) and PeVA4, have been reported in this century, there have not yet been any seroepidemiological studies on PeVA over a period of several decades.

Hypothesis/Gap Statement. The authors hypothesize that PeVA3 and PeVA4 emerged recently.

Aims. The aim was to clarify changes in the seroprevalence of PeVA1, PeVA3 and PeVA4.

Methodology. Neutralizing antibodies (NT Abs) were measured among residents in Yamagata, Japan in 1976, 1983, 1985, 1990, 1999 and 2017.

Results. The total NT Ab-positive rate for PeVA1 was between 90.7 and 100 % for all years analysed, with that for PeVA3 increasing from 39.6 % in 1976 to 69.6 % in 2017, and that for PeVA4 decreasing from 93.9 % in 1976 to 49.1 % in 2017. The distribution of NT Ab titres for PeVA1, PeVA3 and PeVA4 among those aged less than 20 years old was as follows: those ≥1 : 32 for PeVA1 were between 68.0–89.2 % for all years analysed; those ≥1 : 32 for PeVA3 was 15.4 % in 1976, 44.3–54.9 % in 1983–1990 and 64.8–68.0 % in 1999–2017; and those ≥1 : 32 for PeVA4 were between 49.1–67.2 % in 1976–1990, 41.3 % in 1999 and 23.8 % in 2017.

Conclusions. Our findings in this seroepidemiological study over four decades suggested that PeVA1 has been stably endemic, while PeVA3 appeared around 1970s and has spread since then as an emerging disease, and occasional PeVA4 infections were common in 1970s and 1980s but have been decreasing for several decades in our community.
High mortality by nosocomial infections caused by carbapenem-resistant P. aeruginosa in a referral hospital in Brazil: facing the perfect storm
Authors: Urzedo Jane Eire , de Paula Menezes Ralciane , Porto Juliana Pena , Ferreira Melina Lorraine , Gonçalves Iara Rossi , de Brito Cristiane Silveira , Gontijo-Filho Paulo P. , Ribas Rosineide Marques
Published: November 2020

Introduction. Carbapenem-resistant

Pseudomonas aeruginosa

is responsible for increased patient mortality.

Gap Statement. Five and 30 day in-hospital all-cause mortality in patients with

P. aeruginosa

infections were assessed, followed by evaluations concerning potential correlations between the type III secretion system (TTSS) genotype and the production of metallo-β-lactamase (MBL).

Methodology. This assessment comprised a retrospective cohort study including consecutive patients with carbapenem-resistant infections hospitalized in Brazil from January 2009 to June 2019. PCR analyses were performed to determine the presence of TTSS-encoding genes and MBL genes.

Results. The 30-day and 5-day mortality rates for 262 patients were 36.6 and 17.9 %, respectively. The unadjusted survival probabilities for up to 5 days were 70.55 % for patients presenting exoU-positive isolates and 86 % for those presenting exo-negative isolates. The use of urinary catheters, as well as the presence of comorbidity conditions, secondary bacteremia related to the respiratory tract, were independently associated with death at 5 and 30 days. The exoS gene was detected in 64.8 % of the isolates, the presence of the exoT and exoY genes varied and exoU genes occurred in 19.3 % of the isolates. The exoU genotype was significantly more frequent among multiresistant strains. MBL genes were not detected in 92 % of the isolates.

Conclusions. Inappropriate therapy is a crucial factor regarding the worse prognosis among patients with infections caused by multiresistant

P. aeruginosa

, especially those who died within 5 days of diagnosis, regardless of the genotype associated with TTSS virulence.
Epigenomics, genomics, resistome, mobilome, virulome and evolutionary phylogenomics of carbapenem-resistant Klebsiella pneumoniae clinical strains
Authors: Kopotsa Katlego , Mbelle Nontombi M. , Osei Sekyere John
Published: November 2020

Carbapenem-resistant

Klebsiella pneumoniae

(CRKP) remains a major clinical pathogen and public health threat with few therapeutic options. The mobilome, resistome, methylome, virulome and phylogeography of CRKP in South Africa and globally were characterized. CRKP collected in 2018 were subjected to antimicrobial susceptibility testing, screening by multiplex PCR, genotyping by repetitive element palindromic (REP)-PCR, plasmid size, number, incompatibility and mobility analyses, and PacBio’s SMRT sequencing (n=6). There were 56 multidrug-resistant CRKP, having bla
OXA-48-like and bla
NDM-1/7 carbapenemases on self-transmissible IncF, A/C, IncL/M and IncX3 plasmids endowed with prophages, traT, resistance islands, and type I and II restriction modification systems (RMS). Plasmids and clades detected in this study were respectively related to globally established/disseminated plasmids clades/clones, evincing transboundary horizontal and vertical dissemination. Reduced susceptibility to colistin occurred in 23 strains. Common clones included ST307, ST607, ST17, ST39 and ST3559. IncFIIk virulent plasmid replicon was present in 56 strains. Whole-genome sequencing of six strains revealed least 41 virulence genes, extensive ompK36 mutations, and four different K- and O-loci types: KL2, KL25, KL27, KL102, O1, O2, O4 and O5. Types I, II and III RMS, conferring m6A (G
A
TC, G
A
TGNNNNNNTTG, CA
A
NNNNNNCATC motifs) and m4C (C
C
WGG) modifications on chromosomes and plasmids, were found. The nature of plasmid-mediated, clonal and multi-clonal dissemination of blaOXA-48-like and blaNDM-1 mirrors epidemiological trends observed for closely related plasmids and sequence types internationally. Worryingly, the presence of both bla
OXA-48 and bla
NDM-1 in the same isolates was observed. Plasmid-mediated transmission of RMS, virulome and prophages influence bacterial evolution, epidemiology, pathogenicity and resistance, threatening infection treatment. The influence of RMS on antimicrobial and bacteriophage therapy needs urgent investigation.
Performance of qualitative and quantitative antigen tests for SARS-CoV-2 in early symptomatic patients using saliva
Authors: Yokota Isao , Sakurazawa Takayo , Sugita Junichi , Iwasaki Sumio , Yasuda Keiko , Yamashita Naoki , Fujisawa Shinichi , Nishida Mutsumi , Konno Satoshi , Teshima Takanori
Published: November 2020

Background

The rapid detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an urgent need for the prevention and containment of disease outbreaks in communities. Although the gold standard is polymerase chain reaction (PCR), antigen tests such as immunochromatographic assay (ICA) and chemiluminescent enzyme immunoassay (CLEIA) that can yield results within 30 minutes.

Methods

We evaluated performance of ICA and CLEIA using 34 frozen PCR-positive specimens (17 saliva and 17 nasopharyngeal swab) and 307 PCR-negative samples.

Results

ICA detected SARS-CoV-2 in only 14 (41%) samples, with positivity of 24% in saliva and 59% in NPS. Notably, ICA detected SARS-CoV-2 in 5 (83%) of 6 samples collected within 4 days after symptom onset. CLEIA detected SARS-CoV-2 in 31 (91%) samples, with positivity of 82% in saliva and 100% in NPS. CLEIA was negative in 3 samples with low viral load by PCR.

Conclusions

These results suggest that use of ICA should be limited to earlier time after symptom onset and CLEIA is more sensitive and can be used in situations where quick results are required.
A saliva-based RNA extraction-free workflow integrated with Cas13a for SARS-CoV-2 detection
Authors: Azmi Iqbal , Faizan Md Imam , Kumar Rohit , Yadav Siddharth Raj , Chaudhary Nisha , Singh Deepak Kumar , Butola Ruchika , Ganotra Aryan , Joshi Gopal Datt , Jhingan Gagan Deep , Iqbal Jawed , Joshi Mohan C , Ahmad Tanveer
Published: November 2020

A major bottleneck in scaling-up COVID-19 testing is the need for sophisticated instruments and well-trained healthcare professionals, which are already overwhelmed due to the pandemic. Moreover, the high-sensitive SARS-CoV-2 diagnostics are contingent on an RNA extraction step, which, in turn, is restricted by constraints in the supply chain. Here, we present CASSPIT (Cas13 Assisted Saliva-based & Smartphone Integrated Testing), which will allow direct use of saliva samples without the need for an extra RNA extraction step for SARS-CoV-2 detection. CASSPIT utilizes CRISPR-Cas13a based SARS-CoV-2 RNA detection, and lateral-flow assay (LFA) readout of the test results. The sample preparation workflow includes an optimized chemical treatment and heat inactivation method, which, when applied to COVID-19 clinical samples, showed a 97% positive agreement with the RNA extraction method. With CASSPIT, LFA based visual limit of detection (LoD) for a given SARS-CoV-2 RNA spiked into the saliva samples was ∼200 copies; image analysis-based quantification further improved the analytical sensitivity to ∼100 copies. Upon validation of clinical sensitivity on RNA extraction-free saliva samples (n=76), a 98% agreement between the lateral-flow readout and RT-qPCR data was found (Ct<35). To enable user-friendly test results with provision for data storage and online consultation, we subsequently integrated lateral-flow strips with a smartphone application. We believe CASSPIT will eliminate our reliance on RT-qPCR by providing comparable sensitivity and will be a step toward establishing nucleic acid-based point-of-care (POC) testing for COVID-19.
Identifying Barriers to Disclosure to Overcome Barriers to ART Initiation: An explanatory qualitative study on PMTCT in Zambia
Authors: Kanguya Tukiya , Koyuncu Aybüke , Sharma Anjali , Kusanathan Thankian , Mubanga Martha , Chi Benjamin H. , Vinikoor Michael J. , Mubiana-Mbewe Mwangelwa
Published: November 2020

Background

Though antiretroviral therapy (ART) is widely available, HIV positive pregnant women in Zambia are less likely to start and remain on therapy throughout pregnancy and after delivery. This study sought to understand readiness to start ART among HIV pregnant women from the perspectives of both women and men in order to suggest more holistic programs to support women to continue life-long ART after delivery.

Methods

We conducted a qualitative study with HIV positive pregnant women before and after ART initiation, and men with female partners, to understand readiness to start lifelong ART. We conducted a total of 28 in-depth interviews among women and 2 focus group discussions among male partners. Data was transcribed verbatim and analyzed in NVivo 12 using thematic analysis. Emerging themes from the data were organized using the social ecological framework.

Results

Men thought of their female partners as young and needing their supervision to initiate and stay on ART. Women agreed that disclosure and partner support were necessary preconditions to ART initiation and adherence and expressed fear of divorce as a prominent barrier to disclosure. Maternal love and desire to look after one’s children instilled a sense of responsibility among women which motivated them to overcome individual, interpersonal and health system level barriers to initiation and adherence. Women preferred adherence strategies that were discrete, the effectiveness of which, depended on women’s intrinsic motivation.

Conclusion

The results support current policies in Zambia to encourage male engagement in ART care. To appeal to male partners, messaging on ART should be centered on emphasizing the importance of male involvement to ensure women remain engaged in ART care. Programs aimed at supporting postpartum ART adherence should design messages that appeal to both men’s role in couples’ joint decision-making and women’s maternal love as motivators for adherence.
Machine learning analysis of naïve B-cell receptor repertoires stratifies celiac disease patients and controls
Authors: Shemesh Or , Polak Pazit , Lundin Knut E.A. , Sollid Ludvig M. , Yaari Gur
Published: November 2020

Celiac disease (CeD) is a common autoimmune disorder caused by an abnormal immune response to dietary gluten proteins. The disease has high heritability. HLA is the major susceptibility factor, and the HLA effect is mediated via presentation of deamidated gluten peptides by disease-associated HLA-DQ variants to CD4+ T cells. In addition to gluten-specific CD4+ T cells the patients have antibodies to transglutaminase 2 (autoantigen) and deamidated gluten peptides. These disease-specific antibodies recognize defined epitopes and they display common usage of specific heavy and light chains across patients. Interactions between T cells and B cells are likely central in the pathogenesis, but how the repertoires of naïve T and B cells relate to the pathogenic effector cells is unexplored. To this end, we applied machine learning classification models to naïve B cell receptor (BCR) repertoires from CeD patients and healthy controls. Strikingly, we obtained a promising classification performance with an F1 score of 85%. Clusters of heavy and light chain sequences were inferred and used as features for the model, and signatures associated with the disease were then characterized. These signatures included amino acid (AA) 3-mers with distinct bio-physiochemical characteristics and enriched V and J genes. We found that CeD-associated clusters can be identified and that common motifs can be characterized from naïve BCR repertoires. The results may indicate a genetic influence by BCR encoding genes in CeD. Analysis of naïve BCRs as presented here may become an important part of assessing the risk of individuals to develop CeD. Our model demonstrates the potential of using BCR repertoires and in particular, naïve BCR repertoires, as disease susceptibility markers.
A Scalable, Open-Source Implementation of a Large-Scale Mechanistic Model for Single Cell Proliferation and Death Signaling
Authors: Erdem Cemal , Mutsuddy Arnab , Bensman Ethan M. , Dodd William B. , Saint-Antoine Michael M. , Bouhaddou Mehdi , Blake Robert C. , Gross Sean M. , Heiser Laura M. , Alex Feltus F. , Birtwistle Marc R.
Published: November 2020

Mechanistic models of how single cells respond to different perturbagens can help integrate disparate big data sets or predict response to varied drug combinations. However, the construction and simulation of such models have proved challenging. Our lab previously constructed one of the largest mechanistic models for single mammalian cell regulation of proliferation and death (774 species, 141 genes, 8 ligands, 2400 reactions). However, this, as many other large-scale models, was written using licensed software (MATLAB) with intricate programming structure, impeding alteration, expansion, and sharing. Here, we generated a new foundation for this model, which includes a python-based creation and simulation pipeline converting a few structured text files into an SBML-compatible format. This new open-source model (named SPARCED) is high-performance- and cloud-computing compatible and enables the study of virtual cell population responses at the single-cell level. We applied this new model to a subset of the LINCS MCF10A Data Cube, which observed that IFNγ acts as an anti-proliferative factor, but the reasons why were unknown. After expanding the SPARCED model with an IFNγ signaling module (to 950 species, 150 genes, 9 ligands, 2500 reactions), we ran stochastic single-cell simulations for two different putative crosstalk mechanisms and looked at the number of cycling cells in each case. Our model-based analysis suggested, and experiments support that these observations are better explained by IFNγ-induced SOCS1 expression sequestering activated EGF receptors, thereby downregulating AKT activity, as opposed to direct IFNγ-induced upregulation of p21 expression. This work forms a foundation for increased mechanistic model-based data integration on a single-cell level, an important building block for clinically predictive mechanistic models.
Exendin-4 improves neuron protection and functional recovery in experimental spinal cord injury in rats through regulating PCBP2 expression
Authors: Luo Huaichao , Wang Qingwei , Wang Lei
Published: November 2020

Aims

In the present research, we assessed the therapeutic effects of Exendin-4 (Ex-4) on rat models with spinal cord injury (SCI).

Materials and methods

36 male Sprague–Dawley rats were randomly allocated into three groups, including sham operation group, SCI group and SCI+Ex-4 group (Ex-4 treatment (10 µg/rat) after SCI, i.p.). In the SCI group, a laminectomy was performed at the T10 vertebrae, followed by weight-drop contusion of the spinal cord. In the sham group, a laminectomy was carried out without SCI contusion.

Key findings

Our results showed that Basso-Beattie-Bresnahan scale scores were significantly decreased after SCI, and were obviously improved in SCI rats with Ex-4 administration. Additionally, the water content of spinal cord in SCI group was dramatically increased than that in sham group, and after Ex-4 treatment, degree of edema of spinal cord was remarkably reduced. And also, concentration levels of inflammatory cytokines (IL-1α, IL-1β, IL-6 and TNF-α) in the spinal cord were significantly elevated after SCI, and were remarkably reduced in SCI rats with Ex-4 administration. Subsequently, cell apoptosis rate in the injured spinal cord was significantly increased, and after Ex-4 treatment, cell apoptosis rate was remarkably decreased. We also revealed that levels of PCBP2 mRNA and protein were significantly up-regulated after SCI, and were dramatically dropped in SCI rats with Ex-4 administration.

Significance

Take altogether, our findings disclosed that Ex-4 plays a role in promoting neurological function recovery and inhibiting neuronal apoptosis through effecting PCBP2 expression in SCI rat models.
Association analysis of repetitive elements and R-loop formation across species
Authors: Zeng Chao , Onoguchi Masahiro , Hamada Michiaki
Published: November 2020

Genomes are known to have a large number of repetitive elements. Emerging evidence suggests that these non-coding elements may play an important regulatory role. However, few studies have investigated the effect of repetitive elements on R-loop formation. In this study, we found different repetitive elements related to R-loop formation in various species. By controlling length and genomic distributions, we observed that satellites, long interspersed nuclear elements (LINEs), and DNAs were each specifically enriched for R-loops in humans, fruit flies, andArabidopsis thaliana, respectively. R-loops also tended to arise in regions of low-complexity or simple repeats across species. We also found that the repetitive elements associated with R-loop formation differ according to developmental stage. For instance, LINEs and long terminal repeats (LTRs) are more likely to contain R-loops in embryos (fruit fly) and then turn out to be low-complexity and simple repeats in post-developmental S2 cells. Our results indicate that repetitive elements may have species-specific or development-specific regulatory effects on R-loop formation. This work advances our understanding of repetitive elements and R-loop biology.
Structure of the TELO2-TTI1-TTI2 complex and its function in TOR recruitment to the R2TP chaperone
Authors: Pal Mohinder , Muñoz-Hernandez Hugo , Bjorklund Dennis , Zhou Lihong , Degliesposti Gianluca , Skehel J. Mark , Hesketh Emma L. , Thompson Rebecca F. , Pearl Laurence H. , Llorca Oscar , Prodromou Chrisostomos
Published: November 2020

The R2TP (RUVBL1-RUVBL2-RPAP3-PIH1D1) complex, in collaboration with HSP90, functions as a chaperone for the assembly and stability of protein complexes, including RNA polymerases, snRNPs and PI3 kinase-like kinases (PIKK) such as TOR and SMG1. PIKK stabilisation depends on an additional complex of TELO2, TTI1 and TTI2 (TTT), whose structure and function are poorly understood. We have now determined the cryo-EM structure of the human R2TP-TTT complex that together with biochemical experiments reveals the mechanism of TOR recruitment to the R2TP-TTT chaperone. The HEAT-repeat TTT complex binds the kinase domain of TOR, without blocking its activity, and delivers TOR to the R2TP chaperone. In addition, TTT regulates the R2TP chaperone by inhibiting RUVBL1-RUVBL2 ATPase activity and by modulating the conformation and interactions of the PIH1D1 and RPAP3 components of R2TP. Together, our results show how TTT couples the recruitment of TOR to R2TP with the regulation of this chaperone system.
The structural heterogeneity of α-synuclein is governed by several distinct subpopulations with interconversion times slower than milliseconds
Authors: Chen Jiaxing , Zaer Sofia , Drori Paz , Zamel Joanna , Joron Khalil , Kalisman Nir , Lerner Eitan , Dokholyan Nikolay V.
Published: November 2020

The intrinsically disordered protein, α-synuclein, implicated in synaptic vesicle homeostasis and neurotransmitter release, is also associated with several neurodegenerative diseases. The different roles of α-synuclein are characterized by distinct structural states (membrane-bound, dimer, tetramer, oligomer, and fibril), which are originated from its various monomeric conformations. The pathological states, determined by the ensemble of α-synuclein monomer conformations and dynamic pathways of interconversion between dominant states, remain elusive due to their transient nature. Here, we use inter-dye distance distributions from bulk time-resolved Förster resonance energy transfer as restraints in discrete molecular dynamics simulations to map the conformational space of the α-synuclein monomer. We further confirm the generated conformational ensemble in orthogonal experiments utilizing far-UV circular dichroism and cross-linking mass spectrometry. Single-molecule protein-induced fluorescence enhancement measurements show that within this conformational ensemble, some of the conformations of α-synuclein are surprisingly stable, exhibiting conformational transitions slower than milliseconds. Our comprehensive analysis of the conformational ensemble reveals essential structural properties and potential conformations that promote its various functions in membrane interaction or oligomer and fibril formation.
Loss of histone H3.3 results in DNA replication defects and altered origin dynamics in C. elegans
Authors: Strobino Maude , Wenda Joanna M. , Padayachy Laura , Steiner Florian A.
Published: November 2020

Histone H3.3 is a replication-independent variant of histone H3 with important roles in development, differentiation, and fertility. Here, we show that loss of H3.3 results in replication defects in Caenorhabditis elegans embryos at elevated temperatures. To characterize these defects, we adapt methods to determine replication timing, map replication origins, and examine replication fork progression. Our analysis of the spatiotemporal regulation of DNA replication shows that despite the very rapid embryonic cell cycle, the genome is replicated from early and late firing origins and is partitioned into domains of early and late replication. We find that under temperature stress conditions, additional replication origins become activated. Moreover, loss of H3.3 results in altered replication fork progression around origins, which is particularly evident at stress-activated origins. These replication defects are accompanied by replication checkpoint activation, a delayed cell cycle, and increased lethality in checkpoint-compromised embryos. Our comprehensive analysis of DNA replication in C. elegans reveals the genomic location of replication origins and the dynamics of their firing, and uncovers a role of H3.3 in the regulation of replication origins under stress conditions.