bluuebunny/crossref_metadata_2025 huggingface dataset:
Clarity from Chaos
Authors: Elliott Andrew C. A.
Published: September 2021

Experimentalists interpret their observations as a combination of effects arising from their models of understanding and residual errors. Successive refinements of theory can reduce the observed discrepancies in a systematic way. All experimental findings are provisional, and the associated uncertainty can be quantified. Correlation does not imply causation, but causation is what we really seek: how can it be established? The process of establishing cigarette smoking as a leading cause of lung cancer is taken as a case study. General approaches to understanding causation are described.
Shaping the Risk
Authors: Elliott Andrew C. A.
Published: September 2021

The board game backgammon illustrates that we can control the effects of risk by understanding chances, controlling our exposure to risk, and attending to the preparation of our responses. If we understand the risks we face in a financial context, hedging strategies can allow us to shape the overall risk by offsetting some or all of it, but this comes at a price. Financial futures and options are some of the tools that allow financial risks to be shaped in creative ways. Where risks are poorly understood, though, these financial engineering approaches may not always be effective, and have in the past led to financial difficulties.
What’s Coming Next?
Authors: Elliott Andrew C. A.
Published: September 2021

The need and desire for forecasts is explored, starting with the weather. A case study is made of the 2020 Primary process to select a Democratic Party presidential campaign, and how predictions were overturned by events. Predictions of doom are investigated, ranging from Malthus to the Millennium Bug. Some of the pressing threats that we face in current times are discussed in light of our incomplete understanding of uncertainty.
On the illocutionary force of exclamatives and non-canonical questions in German and Italian
Authors: Hinterhölzl Roland , Munaro Nicola
Published: September 2021

On the basis of evidence from German and Italian, it is argued that non-canonical wh-questions and wh-exclamatives involve the expression of surprise about an unexpected state of affairs; however, they exhibit a difference in illocutionary force: while non-canonical questions constitute directive speech acts which request the hearer to provide an explanation for the unexpected state of affairs, wh-exclamatives are more akin to assertions, since they are used to indicate the speaker’s surprise about the difference between the expected state of affairs and the actual one. These interpretive differences are syntactically codified by the presence and absence of Verb Second in German and by a difference in the final landing site of the wh-element in standard questions, non-canonical questions, and wh-exclamatives in Italian.
Connectors as emotive signs
Authors: Hanna Patrizia Noel Aziz
Published: September 2021

This chapter is a contribution to exploring the interrelations between syntactic position, semiotic status, and pragmatic function. Ways of identifying the kind of expressivity encoded by sentence-final connectors and related phenomena like the ‘et ceteras’ are discussed, focusing on German triple und ‘and so on’ from a cross-linguistic perspective. Expressivity is effected by an interplay of factors: the innovative sentence-final placement of a connector, the status of the sentence-final connector as emotive sign (Marty 1908), and its function as a general extender. This interplay leads to rigid ‘packages’ which surface in lexical entries like triple und and multiple et cetera. It is argued that und und und, like other sentence-final particles, belongs to the class of Wackernagel elements, which recently have emerged in sentence-final position. Triple und is linked to the on-going discussion of the functions of the left and right sentence peripheries.
Spanish ‘mirative future’
Authors: Escandell-Vidal Victoria , Leonetti Manuel
Published: September 2021

This chapter provides an account of the Spanish ‘mirative future.’ Starting from the assumption that the Spanish future is an inferential evidential (Escandell-Vidal 2010, 2014, 2020), it is argued that mirativity is contextually inferred as a result of a combination of multiple factors that constrain interpretation. These factors include restrictions on word order (only VS), intonational patterns (either fall-rise or high rise), and kind of predicates (individual-level, gradable, negative predicates). In addition, the speaker encodes that s/he has only indirect evidence, but the context of utterance makes it clear that this is not so. Given these conditions, mirative uses are essentially rhetorical questions. From this perspective, the Spanish mirative future reproduces a consistent pattern across languages: mirative interpretations are obtained when indirect or inferential evidential markers are used in contexts where the speaker has direct experience of the facts.
Introduction
Authors: George Erika
Published: September 2021

Incorporating Rights: Strategies to Advance Corporate Accountability begins with the stories of victims of human rights violations. The introduction invites the reader to imagine how circumstances could have been different if business enterprises were in the business of ensuring respect for human dignity beyond returning profits to investors.
International Law, Corporate Law, and Governance Gaps
Authors: George Erika
Published: September 2021

This chapter explains how domestic US corporate law ignores human rights considerations and contributes to governance gaps. It offers an overview of the conceptual foundations of the corporate form that serve to place rights at risk. It argues that voluntary corporate social responsibility initiatives, leadership on the part of management, and more inclusive configurations of corporate governance can contribute to creating better business practices consistent with respect for human rights. This chapter also explains how international human rights law is inadequate to address human rights abuses where corporate actors are implicated. It offers an overview of the conceptual foundations of international law that render global business enterprises difficult to regulate and hold to account for alleged abuses. It argues that a wide array of actors beyond states must be recognized as possessing the potential to participate in the creation of policies to regulate business practices with respect to human rights.
Competition, Choice, and Change
Authors: George Erika
Published: September 2021

Initiatives to promote information about business human rights impacts on the part of civil society activists demonstrate a shifting consciousness and increasing concern that could introduce moral considerations into capital and consumer markets at a scale sufficient to create an incentive for corporate actors to consider the risks particular business practices may present for human rights. This chapter considers how enforcement of corporate commitments to respect human rights could occur through the provision of actionable information on corporate performance to conscious constituencies of investors and consumers. It considers competitive pressures that could be brought to bear on particular industries by virtue of greater transparency, including the connected nature of communication enjoyed by a significant segment of consumers. A connected and concerned community of consumers and investors could leverage concerns into change. It contemplates ways to generate adverse market consequences for business activities that have adverse human rights consequences. Specifically, it considers the changes generated by shareholder activism on human rights issues and the advances achieved by a “worker driven, consumer powered and market enforced” fair food program. It also considers examples of corporations that have reaped rewards for responsible conduct consistent with the responsibility to respect human rights. This chapter argues that expectations on business with respect to avoiding adverse human rights impacts and complicity in abuses are increasing and that choices will reflect concerns aligned with rewarding responsible business conduct.
How Orbán won? Neoliberal disenchantment and the grand strategy of financial nationalism to reconstruct capitalism and regain autonomy
Authors: Sebők Miklós , Simons Jasper
Published: September 2021

Disenchantment with global finance in Central-Eastern Europe enabled financial nationalism to emerge as a counter-hegemonic strategy. In Hungary, Prime Minister Orbán put forth his explicit aim to increase domestic ownership in banking to over 50% and legitimized the ensuing re-nationalization of the financial sector with resentment over neoliberal banking practices. The article describes how the financial crisis created an opportunity for Orbán and his allies to usher in a new era of financial ownership structures. It provides a critical political economy analysis of how the Orbán government selected economic sectors to target and how it used a network of associated private actors in its quest to re-nationalize and then re-privatize major banks to a newly created elite, the ‘national capitalists’. In this, financial nationalism constituted a grand strategy to reconstruct Hungarian capitalism in order to regain autonomy and assure long-term political survival within a liberal EU context.
Expanding the ambit of Section 32 of the Trustee Act 1925? Womble Bond Dickinson (Trust Corporation) Limited v Glenn & Others [2021] EWHC 624; [2021] WTLR 737
Authors: Weaver Elizabeth
Published: September 2021

Where beneficiaries of a trust have a contingent or reversionary entitlement to capital, section 32 of the Trustee Act 1925 empowers trustees to accelerate their enjoyment of that interest by paying over part of their share to them, although only with the consent of beneficiaries with prior interests. Can that power be exercised where the trusts are in Hancock v Watson form, i.e. there is an apparently absolute gift to a beneficiary but trusts are then engrafted or imposed on the beneficiary’s interest giving them only a life interest? The article considers the judgment in Womble Bond Dickinson (Trust Corporation) Ltd v Glenn which is the first ever decision on this question.
Alternative Wound Management: Translating Science into Practice
Authors: Sathe Pushkar Satish , Prabhu Divyashree V. , Ravikumar Padmini , Bolton Laura L.
Published: September 2021

Effective wound healing is achieved by well-timed host, cell, and environment interactions involving hemostasis, inflammation, formation of repaired dermal structures, and epithelialization, followed by months to years of scar remodeling. Globally, various natural or synthetic agents or dressings are used to optimize wound environments, prolong drug release, aid in fluid absorption, provide favorable healing environments, and act as a mechanical barrier against wound trauma. In this scoping review of evidence from the PubMed and clinicaltrials.gov databases, authors examined clinical study evidence supporting the efficacy and safety of selected phytochemicals, vehicles, polymers, and animal products considered “naturally derived” or “alternative” wound interventions to provide a summary of preclinical evidence. Agents with the most clinical evidence were honey, alginates, polyurethane, gelatin, and dextran. Practice implications are described in the context of the TIMERS clinical paradigm.

GENERAL PURPOSE

To present a scoping review of preclinical and clinical trial evidence supporting the efficacy and/or safety of major alternative wound care agents to summarize their effects on validated elements of wound bed preparation and wound management paradigms.

TARGET AUDIENCE

This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care.

LEARNING OBJECTIVES/OUTCOMES

After participating in this educational activity, the participant will:

1. Differentiate the effectiveness of the topical wound care agents included in this review.

2. Compare the preventive efficacy of intravenous agents administered to trauma and surgical patients.

3. Select the effectiveness of products in this review that are left in place after surgical procedures.

4. Identify an oral agent that can be helpful in mitigating the effects of COVID-19.
Nonoperative Management of a Recurrent Postoperative Inguinal Lymphatic Leak via Negative-Pressure Wound Therapy: A Case Report
Authors: Cannata Aldo , Ordanini Marco , Sesana Giovanni , Russo Claudio Francesco
Published: September 2021

Lymphatic leaks are common following common femoral vessel exposure for cardiac surgical procedures. The management of this complication can be difficult and is often uncomfortable for the patient. This case report describes the successful nonoperative treatment of a recurrent lymphatic leak from an inguinal surgical wound via negative-pressure wound therapy. Negative pressure may be considered a minimally invasive, effective, and acceptable way to treat postoperative lymphatic leaks at the groin.
Overcoming the Challenge of Support Surface Selection: Utilization of Standards
Authors: Thurman Kristen , Deppisch Michelle , Morello Susan S. , Moseley Rachel , Slayton Stephanie , Sylvia Cynthia , Todd Jackie
Published: September 2021

Selecting the appropriate support surface for patients continues to challenge clinicians and facilities. The Support Surface Standards Committee has developed and published test methods that allow for informed comparisons among support surface characteristics. The first published standards address the performance characteristics of immersion/envelopment, shear/friction, and microclimate management. This article describes the full body support surface standards development and provides guidance on the use of the outcomes from those standard tests for clinicians and facilities to make more informed choices for patients and patient populations.
Acetabular remodeling after graft extrusion, rotation or impaction in Dega and Pemberton acetabuloplasties for developmental dysplasia of the hip
Authors: Bakarman Khalid A. , Rafiq Zulqurnain
Published: September 2021

Traditionally graft displacement following Pemberton and Dega acetabuloplasties involves internal fixation for treatment of developmental dysplasia of hip (DDH). This study was performed to assess the acetabular remodeling by conservative management of graft displacement among patients with DDH. This was a retrospective study of 20 patients 17 (85%) women and 3 (15%) men; mean age 22.90 ± 6.96 months with DDH who underwent Pemberton and Dega acetabuloplasties at King Khalid University Hospital, Riyadh between January 2013 and January 2018. All patients after losing acetabular correction during immediate postoperative period were treated by conservative management. The management involved application of Spica cast for 6 weeks that was trimmed to broomstick cast for an extended period of time and finally replaced by nocturnal abduction brace until normal acetabular index (AI) was achieved. The patients were followed up for a mean period of 44.60 ± 12.36 months. Out of the total, 18 (90%) patients with DDH were successfully treated by conservative management. The mean preoperative AI of 43.70° ± 5.91° improved to 21.35o ± 6.32o at the final follow-up (P < 0.001) which was no different when compared to the mean of unaffected hips (19.70o ± 2.96o; P < 0.44). The mean preoperative CEA of all the patients was negative that improved during the conservative treatment to 29.20° ± 10.0° which was no different when compared with the mean of unaffected (31.70° ± 4.64o; P = 0.32) hips at the final follow-up. doption of less aggressive approach for management of displaced, rotated or impacted autograft following acetabuloplasties among children with DDH was not only a useful conservative approach for remodeling of hips but also obviated the need for additional surgical intervention.
New scoring systems for predicting advanced proximal neoplasia in asymptomatic adults with or without knowing distal colorectal findings: a prospective, cross-sectional study
Authors: Imperiale Thomas F. , Monahan Patrick O. , Stump Timothy E. , Ransohoff David F.
Published: September 2021

Background

Models estimating risk for advanced proximal colorectal neoplasia (APN) may be used to select colorectal cancer (CRC) screening test, either prior to knowing distal colorectal findings or afterward. Current models have only fair discrimination and nearly all require knowing distal findings.

Objective

Derive and test risk prediction models for APN with and without distal findings.

Setting

Selected endoscopy centers within central Indiana, USA.

Participants

Average-risk persons undergoing first-time screening colonoscopy

Interventions

Demographics, personal and family medical history, lifestyle factors and physical measures were linked to the most advanced finding in proximal and distal colorectal segments. For both models, logistic regression identified factors independently associated with APN on a derivation set. Based on equation coefficients, points were assigned to each factor, and risk for APN was examined for each score. Scores with comparable risks were collapsed into risk categories. Both models and their scoring systems were tested on the validation set.

Main outcome

APN, defined as any adenoma or sessile serrated lesion ≥1 cm, one with villous histology or high-grade dysplasia, or CRC proximal to the descending colon.

Results

Among 3025 subjects in the derivation set (mean age 57.3 ± 6.5 years; 52% women), APN prevalence was 4.5%; 2859 (94.5%) had complete data on risk factors. Independently associated with APN were age, sex, cigarette smoking, cohabitation status, metabolic syndrome, non-steroidal anti-inflammatory drug use and physical activity. This model (without distal findings) was well-calibrated (P = 0.62) and had good discrimination (c-statistic = 0.73). In low-, intermediate- and high-risk groups that comprised 21, 58 and 21% of the sample, respectively, APN risks were 1.47% (95% CI, 0.67–2.77%), 3.09% (CI, 2.31–4.04%) and 11.6% (CI, 9.10–14.4%), respectively (P < 0.0001), with no proximal CRCs in the low-risk group and 2 in the intermediate-risk group. When tested in the validation set of 1455, the model retained good metrics (calibration P = 0.85; c-statistic = 0.83), with APN risks in low- (22%), intermediate- (56%) and high-risk (22%) subgroups of 0.62% (CI, 0.08–2.23%) 2.20% (CI, 1.31–3.46%) and 13.0% (CI, 9.50–17.2%), respectively (P < 0.0001). There were no proximal CRCs in the low-risk group, and two in the intermediate-risk group. The model with distal findings performed comparably, with validation set metrics of 0.18 for calibration, 0.76 for discrimination and APN risk (% sample) in low-, intermediate-, and high-risk groups of 1.1 (69%), 8.3 (22%) and 22.3% (9%).

Conclusion

These models stratify large proportions of average-risk persons into clinically meaningful risk groups, and could improve screening efficiency, particularly for noncolonoscopy-based programs.
Psychotropic prescribing rates and pharmacogenomic testing implications for autism in the Canadian primary care sentinel surveillance network
Authors: Ahmed Zeeshan , Hao Sylvia , Williamson Tyler , McMorris Carly A. , Bousman Chad A.
Published: September 2021

Objective

To estimate prescribing rates of psychotropic drugs to individuals with autism and the proportion of these individuals who could benefit from pharmacogenetic testing.

Methods

Prescribing data for 92 psychotropic drugs, including 31 antidepressants, 22 antipsychotics, 14 mood stabilizer/antiepileptics, 17 anxiolytic/hypnotics and eight antiadrenergic/psychostimulant were retrieved from medical records of 787 (613 males) autistic individuals who sought treatment from a primary care office enrolled in the Canadian Primary Care Sentinel Surveillance Network between 2012 and 2014. Each prescribed drug was cross-referenced with pharmacogenomic-based prescribing guidelines published by the Clinical Pharmacogenetics Implementation Consortium, the Dutch Pharmacogenetics Working Group, and the Canadian Pharmacogenomics Network for Drug Safety.

Results

More than half (58%) of the participants were prescribed a psychotropic drug and 37% were prescribed two or more psychotropic drugs concurrently. Among the 83 psychotropic drugs examined, 54 (65%) were prescribed to one or more participants during the study’s observation period. The ten most frequently prescribed psychotropics were methylphenidate (16.3%), risperidone (12.8%), lorazepam (12.1%), fluoxetine (7.9%), sertraline (7.1%), quetiapine (6.9%), aripiprazole (6.1%), lisdexamfetamine (5.8%), citalopram (5.6%) and clonazepam (4.8%). Seventeen (32%) of the 54 psychotropic drugs prescribed were linked to a pharmacogenomic-based prescribing guideline, including risperidone, sertraline, aripiprazole and citalopram.

Conclusions

Our findings suggest primary care providers in Canada prescribe a wide range of psychotropics to their patients with autism, some of which may benefit from the integration of pharmacogenomic information into their treatment planning.
Postoperative delirium and neurocognitive disorders
Authors: Migirov Allan , Chahar Praveen , Maheshwari Kamal
Published: September 2021

Purpose of review

Postoperative neurocognitive disorders (NCD) are significant causes of morbidity and mortality. In this paper, we will review our understanding and potential management of postoperative NCD.

Recent findings

Postoperative delirium, delayed neurocognitive recovery and postoperative cognitive dysfunction (POCD) are recognized as a part of the continuous spectrum of postoperative NCD. Although the pathophysiology is still poorly understood, there is renewed focus on improving neurocognitive outcomes of aging surgical population. Novel methods of neurocognitive screening are developed and research in the prevention and management of NCD has gained traction.

A spectrum of NCD exists in surgical patients ranging from postoperative delirium, delayed neurocognitive recovery, and POCD. Identification of patients at-risk for developing NCD can help target appropriate perioperative intervention. Also, specialized care teams and the implementation of standardized protocols are crucial for the successful management perioperative NCD. Finally, large, randomized, multicenter studies are needed to confirm benefits of preventive and treatment strategies
Management of patients with unilateral microtia and aural atresia: recent advances and updates
Authors: Ikeda Allison K. , Bhrany Amit D. , Sie Kathleen C.Y. , Bly Randall A.
Published: September 2021

Purpose of review

The management of patients with unilateral microtia and aural atresia is complex. Recent literature suggests significant strides in hearing habilitation and ear reconstruction.

Recent findings

Several options of hearing management are available and are associated with improved outcomes. Timelines for hearing habilitation and ear reconstruction vary by institution. We offer our timeline as a reference. Three dimensional (3D) printed models are increasingly used for training and reconstruction. Bioprinting is on the horizon, though safety and effectiveness studies are pending. Lastly, application of qualitative methods has provided a foundation on which to improve communication between physicians and patients and their families. Better understanding of the patient and family experiences will provide opportunities to target interventions to improve care.

Current developments include expanding options for hearing management, changing approaches to timing of atresiaplasty, utilization of 3D printed models, and focus on patient and family experience to improve reconstructive outcomes.
Clinical Practice Guidelines for the Management of Patients With Cleft Lip and Palate: A Systematic Quality Appraisal Using the Appraisal of Guidelines for Research and Evaluation II Instrument
Authors: Yver Christina M. , Chorath Kevin T. , Connolly John , Shah Mitali , Majmudar Tanmay , Moreira Alvaro G. , Rajasekaran Karthik
Published: September 2021

Patients with cleft lip and/or palate require complex and longitudinal care by a multidisciplinary cleft team. Unfortunately, delivery of cleft care is often fragmented, and care practices can vary significantly. Multiple clinical practice guidelines (CPGs) have been proposed to provide a standardized framework for cleft care delivery. As CPGs have gained popularity, there has been increasing demand to maintain the quality of existing guidelines. A comprehensive search of EMBASE, MEDLINE via PubMed, Scopus, Cochrane and grey literature sources published from January 1, 1990 to December 31, 2020 was conducted to identify CPGs for the care of cleft patients. The Appraisal of Guidelines for Research and Evaluation, 2nd edition II tool was used to assess the quality of selected CPGs. Intraclass coefficients were calculated to assess agreement among appraisers. Eleven guidelines were identified for study inclusion. One guideline was classified as “high” quality by Appraisal of Guidelines for Research and Evaluation II criteria, and the remaining guidelines were classified as “average” or “low” quality. The “Clarity of Presentation” domain achieved the highest mean score (76.9% ± 11.7%) across CPGs, whereas the “Rigor of Development” domain scored the lowest (35.6% ± 21.2%). Intraclass coefficients analysis reflected very good inter-rater reliability across all domains (0.853–0.987). These findings highlight significant variability in the quality of existing CPGs for the global management of patients with cleft lip and/or palate. The “Rigor of Development” domain reflects the greatest opportunity for improvement. Given these findings, future guidelines may prioritize incorporating a systematic review of existing evidence into recommendations.
A New Technique of Open Septal Reduction Using Polydioxanone Plates for Nasoseptal Fracture: Three-Dimensional Volumetric Analysis
Authors: Kim Kyubeom , Kim Jaehoon , Kim Junhyung , Yun Insik , Jo Taehee , Choi Jaehoon , Jeong Woonhyeok
Published: September 2021

Background:

In this study, we designed a new technique for open septal reduction using a polydioxanone (PDS) plate and compared it with closed reduction (CR).

Methods:

This study included 19 consecutive patients with nasoseptal fracture: 10 receiving open reduction with a PDS plate (PDS group) and 9 undergoing CR group. Open septal reduction was performed after CR for nasal bone fracture. A mucoperichondrial flap was unilaterally elevated, and the deviated septal cartilage was reduced. The PDS plate was inserted horizontally above the vomerine suture. Surgical outcome was analyzed with three-dimensional volumetry and with a quality-of-life scale for nasal obstruction (Nasal Obstruction Symptom Evaluation scale).

Results:

Complications included 1 case of septal perforation in the CR group and 1 case of PDS exposure and septal hematoma in the PDS group. In the three-dimensional volumetric analysis of the PDS group, the median value of the nasal cavity change significantly differed between 1.14 mL (interquartile range; 0.46–2.4) at the preoperative computed tomography scan and 0.33 mL (interquartile range; −0.22 to 1.29) at the postoperative computed tomography scan (∗∗
P = 0.0039). The Nasal Obstruction Symptom Evaluation scale revealed significant improvement in nasal obstruction postsurgically (median value, 42.5–7.5; ∗
P = 0.0139) in the PDS group.

Conclusions:

Polydioxanone plates potentially present a new concept of open septal reduction in terms of septal reinforcement compared with the subtractive approach of open septal reduction.
High-order fluxes in heat transfer with phonons and electrons: application towavepropagation
Authors: Carlomagno I. , Di Domenico M. , Sellitto A.
Published: September 2021

We propose a theoretical model to study heat transfer at the nanoscale by means of high-order thermodynamic fluxes. The model is fully compatible with the model of heat transfer of extended irreversible thermodynamics, represents a generalization of the Guyer–Krumhansl proposal (Guyer & Krumhansl 1966Phys. Rev.148) and is able to deal with relaxational and non-local effects. It also accounts for the role played by the different heat carriers (electrons and/or lattice vibrations) and captures different heat-carrier temperatures. The proposed model is hyperbolic and is used to investigate the propagation of thermal waves.
Phylogenetic diversity and activity screening of cultivable Actinobacteria isolated from marine sponges and associated environments from the western coast of India
Authors: Baig Ulfat , Dahanukar Neelesh , Shintre Neha , Holkar Ketki , Pund Anagha , Lele Uttara , Gujarathi Tejal , Patel Kajal , Jakati Avantika , Singh Ruby , Vidwans Harshada , Tamhane Vaijayanti , Deshpande Neelima , Watve Milind
Published: September 2021

The phylogenetic diversity of cultivable actinobacteria isolated from sponges (Haliclona spp.) and associated intertidal zone environments along the northern parts of the western coast of India were studied using 16S rRNA gene sequences. A subset of randomly selected actinobacterial cultures were screened for three activities, namely predatory behaviour, antibacterial activity and enzyme inhibition. We recovered 237 isolates from the phylum Actinobacteria belonging to 19 families and 28 genera, which could be attributed to 95 putative species using maximum-likelihood partition and 100 putative species using Bayesian partition in Poisson tree processes. Although the trends in the discovery of actinobacterial genera isolated from sponges were consistent with previous studies from different study areas, we provide the first report of nine actinobacterial species from sponges. We observed widespread non-obligate epibiotic predatory behaviour in eight actinobacterial genera and we provide the first report of predatory activity in

Brevibacterium

,

Glutamicibacter

,

Micromonospora

,

Nocardiopsis

,

Rhodococcus

and

Rothia

. Sponge-associated actinobacteria showed significantly more predatory behaviour than environmental isolates. While antibacterial activity by actinobacterial isolates mainly affected Gram-positive target bacteria with little or no effect on Gram-negative bacteria, predation targeted both Gram-positive and Gram-negative prey with equal propensity. Actinobacterial isolates from both sponges and associated environments produced inhibitors of serine proteases and angiotensin-converting enzyme. Predatory behaviour was strongly associated with inhibition of trypsin and chymotrypsin. Our study suggests that the sponges and associated environments of the western coast of India are rich in actinobacterial diversity, with widespread predatory activity, antibacterial activity and production of enzyme inhibitors. Understanding the diversity and associations among various actinobacterial activities – with each other and the source of isolation – can provide new insights into marine microbial ecology and provide opportunities to isolate novel therapeutic agents.
Reclassification of seven honey bee symbiont strains as Bombella apis
Authors: Smith Eric A. , Anderson Kirk E. , Corby-Harris Vanessa , McFrederick Quinn S. , Parish Audrey J. , Rice Danny W. , Newton Irene L. G.
Published: September 2021

Honey bees are important pollinators of many major crops and add billions of dollars annually to the US economy through their services. Recent declines in the health of the honey bee have startled researchers and lay people alike as honey bees are agriculture’s most important pollinator. One factor that may influence colony health is the microbial community. Although honey bee worker guts have a characteristic community of bee-specific microbes, the honey bee queen digestive tracts are colonized predominantly by a single acetic acid bacterium tentatively named ‘Parasaccharibacter apium’. This bacterium is related to flower-associated microbes such as

Saccharibacter floricola

, and initial phylogenetic analyses placed it as sister to these environmental bacteria. We used a combination of phylogenetic and sequence identity methods to better resolve evolutionary relationships among ‘P. apium’, strains in the genus

Saccharibacter

, and strains in the closely related genus

Bombella

. Interestingly, measures of genome-wide average nucleotide identity and aligned fraction, coupled with phylogenetic placement, indicate that many strains labelled as ‘P. apium’ and

Saccharibacter

species are all the same species as

Bombella apis

. We propose reclassifying these strains as

Bombella apis

and outline the data supporting that classification below.
Effect of immature tick-borne encephalitis virus particles on antiviral activity of 5-aminoisoxazole-3-carboxylic acid adamantylmethyl esters
Authors: Tuchynskaya Ksenia K. , Fomina Anastasiia D. , Nikitin Nikolai A. , Illarionova Viktoria V. , Volok Viktor P. , Kozlovskaya Liubov I. , Rogova Anastasia A. , Vasilenko Dmitry A. , Averina Elena B. , Osolodkin Dmitry I. , Karganova Galina G.
Published: September 2021

Tick-borne encephalitis virus (TBEV), a member of the genusFlavivirus, is common in Europe and Asia and causes a severe disease of the central nervous system. A promising approach in the development of therapy for TBEV infection is the search for small molecule antivirals targeting the flavivirus envelope protein E, particularly its β-n-octyl-d-glucoside binding pocket (β-OG pocket). However, experimental studies of candidate antivirals may be complicated by varying amounts and different forms of the protein E in the virus samples. Viral particles with different conformations and arrangements of the protein E are produced during the replication cycle of flaviviruses, including mature, partially mature, and immature forms, as well as subviral particles lacking genomic RNA. The immature forms are known to be abundant in the viral population. We obtained immature virion preparations of TBEV, characterized them by RT-qPCR, and assessedin vivoandin vitroinfectivity of the residual mature virions in the immature virus samples. Analysis of the β-OG pocket structure on the immature virions confirmed the possibility of binding of adamantylmethyl esters of 5-aminoisoxazole-3-carboxylic acid in the pocket. We demonstrated that the antiviral activity of these compounds in plaque reduction assay is significantly reduced in the presence of immature TBEV particles.
Quantitative measurement of infectious virus in SARS-CoV-2 Alpha, Delta and Epsilon variants reveals higher infectivity (viral titer:RNA ratio) in clinical samples containing the Delta and Epsilon variants
Authors: Despres Hannah W. , Mills Margaret G. , Shirley David J. , Schmidt Madaline M. , Huang Meei-Li , Jerome Keith R. , Greninger Alexander L. , Bruce Emily A.
Published: September 2021

Background

Novel SARS-CoV-2 Variants of Concern (VoC) pose a challenge to controlling the COVID-19 pandemic. Previous studies indicate that clinical samples collected from individuals infected with the Delta variant may contain higher levels of RNA than previous variants, but the relationship between viral RNA and infectious virus for individual variants is unknown.

Methods

We measured infectious viral titer (using a micro-focus forming assay) as well as total and subgenomic viral RNA levels (using RT-PCR) in a set of 165 clinical samples containing SARS-CoV-2 Alpha, Delta and Epsilon variants that were processed within two days of collection from the patient.

Results

We observed a high degree of variation in the relationship between viral titers and RNA levels. Despite the variability we observed for individual samples the overall infectivity differed among the three variants. Both Delta and Epsilon had significantly higher infectivity than Alpha, as measured by the number of infectious units per quantity of viral E gene RNA (6 and 4 times as much, p=0.0002 and 0.009 respectively) or subgenomic E RNA (11 and 7 times as much, p<0.0001 and 0.006 respectively).

Conclusion

In addition to higher viral RNA levels reported for the Delta variant, the infectivity (amount of replication competent virus per viral genome copy) may also be increased compared to Alpha. Measuring the relationship between live virus and viral RNA is an important step in assessing the infectivity of novel SARS-CoV-2 variants. An increase in the infectivity of the Delta variant may further explain increased spread and suggests a need for increased measures to prevent viral transmission.

SIGNIFICANCE STATEMENT

Current and future SARS-CoV-2 variants threaten our ability to control the COVID-19 pandemic. Variants with increased transmission, higher viral loads, or greater immune evasion are of particular concern. Viral loads are currently measured by the amount of viral RNA in a clinical sample rather than the amount of infectious virus. We measured both RNA and infectious virus levels directly in a set of 165 clinical specimens from Alpha, Epsilon or Delta variants. Our data shows that Delta is more infectious compared to Alpha, with ∼ six times as much infectious virus for the same amount of RNA. This increase in infectivity suggests increased measures (vaccination, masking, distancing, ventilation) are needed to control Delta compared to Alpha.
Impact of multiple sclerosis disease-modifying therapies on SARS-CoV-2 vaccine-induced antibody and T cell immunity
Authors: Sabatino Joseph J. , Mittl Kristen , Rowles William , Mcpolin Kira , Rajan Jayant V. , Zamecnik Colin R. , Dandekar Ravi , Alvarenga Bonny D. , Loudermilk Rita P. , Gerungan Chloe , Spencer Collin M. , Sagan Sharon A. , Augusto Danillo G. , Alexander Jessa , Hollenbach Jill A. , Wilson Michael R. , Zamvil Scott S. , Bove Riley
Published: September 2021

Vaccine-elicited adaptive immunity is an essential prerequisite for effective prevention and control of coronavirus 19 (COVID-19). Treatment of multiple sclerosis (MS) involves a diverse array of disease-modifying therapies (DMTs) that target antibody and cell-mediated immunity, yet a comprehensive understanding of how MS DMTs impact SARS-CoV-2 vaccine responses is lacking. We completed a detailed analysis of SARS-CoV-2 vaccine-elicited spike antigen-specific IgG and T cell responses in a cohort of healthy controls and MS participants in six different treatment categories. Two specific DMT types, sphingosine-1-phosphate (S1P) receptor modulators and anti-CD20 monoclonal antibodies (mAb), resulted in significantly reduced spike-specific IgG responses. Longer duration of anti-CD20 mAb treatment prior to SARS-CoV-2 vaccination were associated with absent antibody responses. Except for reduced CD4+ T cell responses in S1P-treated patients, spike-specific CD4+ and CD8+ T cell reactivity remained robust across all MS treatment types. These findings have important implications for clinical practice guidelines and vaccination recommendations in MS patients and other immunosuppressed populations.
Effects of short-term salinity exposure on haemolymph osmolality, gill morphology and Na+/K+ - ATPase activity in Solenaia oleivora
Authors: Yao Jingting , Zhang Ting , Xu Dongpo , Lv Guohua , Jin Wu , Ma Xueyan , Zhou Yanfeng , Gu Ruobo , Wen Haibo
Published: September 2021

In order to explore the physiological reaction to hyperosmotic environment, Solenaia oleivora were exposed to 2.23‰ salinity. In 48h, the hemolymph osmolality kept increasing, and the hemolymph protein concentration increased in the first 6h and then decreased significantly, while the free amino acid content increased in the first 24h and then kept stable (P < 0.05). The activity of Na+/K+-ATPase at 0h was significantly higher than other times in most organs except intestine, which was highest at 3h (P < 0.05). The ions concentration were also influenced. The concentration of Na+ rose in haemolymph, axe foot and intestine, but decreased in gill and hepatopancreas. In hemolymph, gill, hepatopancreases and adductor muscle, the K+ concentration was the highest at 0h, while in axe foot and intestine, it showed a positive tendency. The concentration of Cl- in haemolymph, adductor muscle, intestine and axe foot were positively correlated with treatment time, while hepatopancreas showed opposite tendency. High salinity stress caused a difference in the gill histological structure, the gill structure shrunk, the gill lamellas space and shrinking degree showed an enlarging trend with salinity treatment time.
Proton pump inhibitors use and risk of preeclampsia
Authors: Hussain Salman , Singh Ambrish , Antony Benny , Klugarová Jitka , Klugar Miloslav
Published: September 2021

Preeclampsia is one of the common complications of pregnancy and is characterized by high blood pressure. Proton pump inhibitors (PPIs) are commonly used for the management of gastroesophageal reflux disease among pregnant women. Recently, multiple epidemiological studies suggested the association between PPIs use and the risk of preeclampsia. This study aims to review the evidence and meta-analyse the pooled risk of preeclampsia in PPI users from epidemiological studies. Databases-MEDLINE, Embase, Scopus, Web of Science Core Collection, Emcare, and CINAHL (EBSCO) as well as sources of grey literature, ProQuest Dissertations & Theses Global,ClinicalTrials.govand WHO International Clinical Trials Registry Platform will be searched to identify the epidemiological studies assessing the association between PPIs use and the risk of preeclampsia. Study selection, data extraction, and quality assessment will be performed by two independent authors. The risk of bias among included studies will be evaluated by using the Newcastle-Ottawa scale. The pooled effect of PPIs use on the risk of preeclampsia in pregnant women is the primary outcome of interest. Meta-analysis will be performed using Review Manager version 5.4.
COVID-19 Vaccination and Healthcare Demand
Authors: Betti Matthew I. , Abouleish Amira Hassan , Spofford Victoria , Peddigrew Cory , Diener Alan , Heffernan Jane M.
Published: September 2021

One of the driving concerns during any epidemic is the strain on the healthcare system. As we have seen many times over the globe with the COVID-19 pandemic, hospitals and ICUs can quickly become overwhelmed by cases. While strict periods of public health mitigation have certainly helped decrease incidence and thus healthcare demand, vaccination is the only clear long-term solution. In this paper, we develop a two-module model to forecast the effects of relaxation of non-pharmaceutical intervention and vaccine uptake on daily incidence, and the cascade effects on healthcare demand. The first module is a simple epidemiological model which incorporates non-pharmaceutical intervention, the relaxation of such measures and vaccination campaigns to predict caseloads into the the Fall of 2021. This module is then fed into a healthcare module which can forecast the number of doctor visits, the number of occupied hospital beds, number of occupied ICU beds and any excess demand of these. From this module we can also estimate the length of stay of individuals in ICU. For model verification and forecasting, we use the four most populous Canadian provinces as a case study.
SARS-CoV-2 wastewater surveillance in Germany: long-term PCR monitoring, suitability of primer/probe combinations and biomarker stability
Authors: Ho Johannes , Stange Claudia , Suhrborg Rabea , Wurzbacher Christian , Drewes Jörg E. , Tiehm Andreas
Published: September 2021

In recent months, wastewater-based epidemiology (WBE) has been shown to be an important tool for early detection of SARS-CoV-2 circulation in the population. In this study, a detection methodology for SARS-CoV-2 RNA (wild-type and variants of concern) in wastewater was developed based on the detection of different target genes (E and ORF1ab) by PEG precipitation and digital droplet PCR. This methodology was used to determine the SARS-CoV-2 concentration and the proportion of N501Y mutation in raw sewage of the wastewater treatment plant of the city of Karlsruhe in southwestern Germany over a period of 1 year (June 2020 to July 2021). Comparison of SARS-CoV-2 concentrations with reported COVID-19 cases in the catchment area showed a significant correlation. Viral RNA titre trends appeared more than 12 days earlier than clinical data, demonstrating the potential of wastewater-based epidemiology as an early warning system. Parallel PCR analysis using seven primer and probe systems revealed similar gene copy numbers with E, ORF, RdRP2 and NSP9 assays. RdPP1 and NSP3 generally resulted in lower copy numbers, and in particular for N1 there was low correlation with the other assays due to outliers. The occurrence of the N501Y mutation in the wastewater of Karlsruhe was consistent with the occurrence of the alpha-variant (B.1.1.7) in the corresponding individual clinical tests. In batch experiments SARS-CoV-2 RNA was stable for several days under anaerobic conditions, but the copy numbers decreased rapidly in the presence of dissolved oxygen. Overall, this study shows that wastewater-based epidemiology is a sensitive and robust approach to detect trends in the spread of SARS-CoV-2 at an early stage, contributing to successful pandemic management.
Germinal center responses to SARS-CoV-2 mRNA vaccines in healthy and immunocompromised individuals
Authors: Lederer Katlyn , Parvathaneni Kalpana , Painter Mark M. , Bettini Emily , Agarwal Divyansh , Lundgreen Kendall A. , Weirick Madison , Goel Rishi R. , Xu Xiaoming , Drapeau Elizabeth M. , Gouma Sigrid , Greenplate Allison R. , Coz Carole Le , Romberg Neil , Jones Lisa , Rosen Mark , Besharatian Behdad , Kaminiski Mary , Weiskopf Daniela , Sette Alessandro , Hensley Scott E. , Bates Paul , Wherry E. John , Naji Ali , Bhoj Vijay , Locci Michela
Published: September 2021

Vaccine-mediated immunity often relies on the generation of protective antibodies and memory B cells, which commonly stem from germinal center (GC) reactions. An in-depth comparison of the GC responses elicited by SARS-CoV-2 mRNA vaccines in healthy and immunocompromised individuals has not yet been performed due to the challenge of directly probing human lymph nodes. In this study, through a fine-needle-aspiration-based approach, we profiled the immune responses to SARS-CoV-2 mRNA vaccines in lymph nodes of healthy individuals and kidney transplant (KTX) recipients. We found that, unlike healthy subjects, KTX recipients presented deeply blunted SARS-CoV-2-specific GC B cell responses coupled with severely hindered T follicular helper cells, SARS-CoV-2 receptor-binding-domain-specific memory B cells and neutralizing antibodies. KTX recipients also displayed reduced SARS-CoV-2-specific CD4 and CD8 T cell frequencies. Broadly, these data indicate impaired GC-derived immunity in immunocompromised individuals, and suggest a GC-origin for certain humoral and memory B cell responses following mRNA vaccination.