bluuebunny/crossref_metadata_2025 huggingface dataset:
Attributable Mortality of Candida Bloodstream Infections in the Modern Era: A Propensity Score Analysis
Authors: Mazi Patrick B , Olsen Margaret A , Stwalley Dustin , Rauseo Adriana M , Ayres Chapelle , Powderly William G , Spec Andrej
Published: January 2022

Background

This study quantifies the mortality attributable to Candida bloodstream infections (BSI) in the modern era of echinocandins.

Methods

We conducted a retrospective cohort study of adult patients admitted to Barnes Jewish Hospital, a 1368-bed tertiary care academic hospital, in Saint Louis, Missouri, from 1 February 2012 to 30 April 2019. We identified 626 adult patients with Candida BSI that were frequency-matched with 6269 control patients that had similar Candida BSI risk-factors. The 90-day all-cause mortality attributable to Candida BSI was calculated using three methods—propensity score matching, matching by inverse weighting of propensity score, and stratified analysis by quintile.

Results

The 90-day crude mortality was 42.4% (269 patients) for Candida BSI cases and 17.1% (1083 patients) for frequency-matched controls. Following propensity score-matching, the attributable risk difference for 90-day mortality was 28.4% with hazard ratio (HR) of 2.12 (95% confidence interval [CI], 1.98–2.25, P < .001). In the stratified analysis, the risk for mortality at 90 days was highest in patients in the lowest risk quintile to develop Candida BSI (hazard ratio [HR] 3.13 (95% CI, 2.33–4.19). Patients in this lowest risk quintile accounted for 81(61%) of the 130 untreated patients with Candida BSI. Sixty-nine percent of untreated patients (57/83) died versus 35% of (49/127) of treated patients (P < .001).

Conclusions

Patients with Candida BSI continue to experience high mortality. Mortality attributable to Candida BSI was more pronounced in patients at lowest risk to develop Candida BSI. A higher proportion of these low-risk patients went untreated, experienced higher mortality, and should be the target of aggressive interventions to ensure timely, effective treatment.
Incidence and Predictors of Community-Acquired Pneumonia in Patients With Hematological Cancers Between 2016 and 2019
Authors: Certan Maria , Garcia Garrido Hannah M , Wong Gino , Heijmans Jarom , Grobusch Martin P , Goorhuis Abraham
Published: January 2022

Background

Patients with hematological cancers (HC) are at high risk of infections, in particular community-acquired pneumonia (CAP). Recent data on incidence and predictors of CAP among patients with HC are scarce.

Methods

We performed a cohort study (2016–2019) in 2 hospitals in the Netherlands among adults with HC to calculate incidence rates (IRs) of CAP. In addition, we performed a nested case-control study to identify predictors of CAP.

Results

We identified 275 CAP cases during 6264 patient-years of follow-up. The IR of CAP was 4390/100 000 patient-years of follow-up. Compared with the general population, IR ratios ranged from 5.4 to 55.3 for the different HCs. The case fatality and intensive care unit (ICU) admission rates were 5.5% and 9.8%, respectively. Predictors for CAP in patients with HC were male sex, anemia, lymphocytopenia, chronic kidney disease, cardiovascular disease, autologous and allogeneic stem cell transplantation, treatment with immunosuppressive medication for graft-vs-host disease, treatment with rituximab in the past year, and treatment with immunomodulators (lenalidomide, thalidomide, pomalidomide and/or methotrexate) in the past month. Independent predictors of a severe disease course (death or ICU admission) included neutropenia (odds ratio, 4.14 [95% confidence interval, 1.63–10.2]), pneumococcal pneumonia (10.24 [3.48–30.1]), chronic obstructive pulmonary disease (6.90 [2.07–23.0]), and the use of antibacterial prophylaxis (2.53 [1.05–6.08]).

Conclusions

The burden of CAP in patients with HC is high, with significant morbidity and mortality rates. Therefore, vaccination against respiratory pathogens early in the disease course is recommended, in particular before starting certain immunosuppressive therapies.
Effect of Influenza Vaccination on Risk of Coronavirus Disease 2019: A Prospective Cohort Study of 46 000 Healthcare Workers
Authors: Kristensen Jonas Henrik , Bo Hasselbalch Rasmus , Pries-Heje Mia , Nielsen Pernille Brok , Dehlbæk Knudsen Andreas , Fogh Kamille , Boesgaard Norsk Jakob , Eiken Aleksander , Andersen Ove , Fischer Thea Kølsen , Juul Jensen Claus Antonio , Torp-Pedersen Christian , Rungby Jørgen , Ditlev Sisse Bolm , Hageman Ida , Møgelvang Rasmus , Gybel-Brask Mikkel , Dessau Ram Benny , Sørensen Erik , Harritshøj Lene , Folke Fredrik , Engel Møller Maria Elizabeth , Benfield Thomas , Ullum Henrik , Sværke Jørgensen Charlotte , Rye Ostrowski Sisse , Dam Nielsen Susanne , Bundgaard Henning , Iversen Kasper
Published: January 2022

Background

The purpose of this study was to assess whether influenza vaccination has an impact on the risk of coronavirus disease 2019 (COVID-19).

Methods

A cohort of 46 112 healthcare workers were tested for antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and filled in a survey on COVID-19 symptoms, hospitalization, and influenza vaccination.

Results

The risk ratio of hospitalization due to SARS-CoV-2 for influenza vaccinated compared with unvaccinated participants was 1.00 for the seasonal vaccination in 2019/2020 (confidence interval, .56–1.78, P = 1.00). Likewise, no clinical effect of influenza vaccination on development of antibodies against SARS-CoV-2 was found.

Conclusions

The present findings indicate that influenza vaccination does not affect the risk of SARS-CoV-2 infection or COVID-19.
Modelling dynamic behaviour of agents in a multiagent world: Logical analysis of Wh-questions and answers
Authors: Číhalová Martina , Duží Marie
Published: January 2022

In a multiagent and multi-cultural world, the fine-grained analysis of agents’ dynamic behaviour, i.e. of their activities, is essential. Dynamic activities are actions that are characterized by an agent who executes the action and by other participants of the action. Wh-questions on the participants of the actions pose a difficult particular challenge because the variability of the types of possible answers to such questions is huge. To deal with the problem, we propose the analysis and classification of Wh-questions apt for agents’ communication in a multiagent system (MAS). Our proposal of such a system consists of agents who communicate with their fellow agents by messaging so that each autonomous agent, though resource-bounded, can make less or more rational decisions to meet its own and collective goals. In addition, by communicating with other fellow agents and their environment, agents can learn new concepts and enrich their ontology so that their behaviour is dynamic. We aim to make a general proposal of the system so that the ‘envelope’ of agents’ messages can be formalized in any MAS standard, be it The Foundation for Intelligent Physical Agents - Agent Communication Language (FIPA-ACL) or Knowledge Query and Manipulation Language (KQML). Yet, the content of messages is encoded in a formalized natural language. To this end, we apply Transparent Intensional Logic (TIL) with its procedural semantics which is particularly apt for a fine-grained analysis in which all the semantically salient features of natural language can be plausibly formalized. In this paper, we concentrate on analysing the content of query messages, particularly the content of those that encode Wh-questions and the answers to them. We also summarize TIL deduction system that makes it possible to answer such questions in an intelligent way. Linguists distinguish several subtypes of Wh-questions. Though the linguistic classification is helpful, it is not always suitable for agents’ communication and reasoning. We need the classification based on a logical analysis of Wh-questions so that the agents can infer possible answers to such questions rather than only looking for them by keywords. This paper aims to apply an appropriate classification of the logical types of Wh-questions and the analysis of such questions; we concentrate in particular on questions concerning the participants of activities. The application of these results to the analysis of processes and events based on verb valency frames is another novelty of the paper.
“To Abjure Popish Heresys”: Crafting a Borderlands Gospel during Queen Anne’s War at St. James Parish, South Carolina, 1701–20
Authors: Fritz Timothy David
Published: January 2022

In 1706, local authorities institutionalized the Church of England in South Carolina hoping to bring Carolinian social practice into conformity with that of the metropole. Anglican missionaries worked to install religious instruction as a pillar of community identity in this contested space. Employing the specter of war and popery—and the associated fear of slave rebellion—helped ministers Samuel Thomas and Francis LeJau articulate a borderland-specific conception of race, place, and paternal responsibility in an aggressively expanding colony from 1701 to 1720. Utilizing correspondence surrounding the activities of the Society for the Propagation of the Gospel (SPG), this article asserts that rather than serving as a link to English society, the Anglican missions of the SPG functioned as an ideological space for creating a distinct regional identity. Thomas and LeJau crafted a community-specific application of Anglican beliefs, working out their conceptions of religious practice concerning the threats presented by Spanish attempts to secure the loyalty of Yamasees Indians and enslaved Africans. Understanding how fear operated in the southeastern borderlands provides a nuanced understanding of how colonialism operated in the southern colonies.
Assessment of the accuracy of measures in the 1829 southern double star catalogue of James Dunlop
Authors: Letchford Roderick R , White Graeme L , Brown Carolyn J
Published: January 2022

In 1829 James Dunlop published the first southern double star catalogue of some 253 double stars. The accuracy of this catalogue has been determined by using Aladin to cross-match them with Gaia DR2 and estimate their positional (right ascension, declination, position angle, and separation) and magnitude accuracy. Seven per cent could not be identified using Aladin and 14 were single stars. We found 13 double stars (5 per cent) not currently listed in the Washington Double Star Catalog. The catalogue equinox was determined as B1826.0. Overall, 1σ uncertainties in right ascension were within 1 sidereal minute and declinations within 10 arcmin. We also identified and corrected a number of Quadrant errors in the position angles and quantified the separations. Apparent visual magnitude estimates were generally within 1 mag. Dunlop’s overall uncertainties were larger than those of his contemporaries, nevertheless the little known catalogue remains valuable as the earliest source of over 200 double star astrometric and visual magnitude estimates.
IDH-mutated gliomas promote epileptogenesis through d-2-hydroxyglutarate-dependent mTOR hyperactivation
Authors: Mortazavi Armin , Fayed Islam , Bachani Muzna , Dowdy Tyrone , Jahanipour Jahandar , Khan Anas , Owotade Jemima , Walbridge Stuart , Inati Sara K , Steiner Joseph , Wu Jing , Gilbert Mark , Yang Chun Zhang , Larion Mioara , Maric Dragan , Ksendzovsky Alexander , Zaghloul Kareem A
Published: January 2022

Background

Uncontrolled seizures in patients with gliomas have a significant impact on quality of life and morbidity, yet the mechanisms through which these tumors cause seizures remain unknown. Here, we hypothesize that the active metabolite d-2-hydroxyglutarate (d-2-HG) produced by the IDH-mutant enzyme leads to metabolic disruptions in surrounding cortical neurons that consequently promote seizures.

Methods

We use a complementary study of in vitro neuron-glial cultures and electrographically sorted human cortical tissue from patients with IDH-mutant gliomas to test this hypothesis. We utilize micro-electrode arrays for in vitro electrophysiological studies in combination with pharmacological manipulations and biochemical studies to better elucidate the impact of d-2-HG on cortical metabolism and neuronal spiking activity.

Results

We demonstrate that d-2-HG leads to increased neuronal spiking activity and promotes a distinct metabolic profile in surrounding neurons, evidenced by distinct metabolomic shifts and increased LDHA expression, as well as upregulation of mTOR signaling. The increases in neuronal activity are induced by mTOR activation and reversed with mTOR inhibition.

Conclusion

Together, our data suggest that metabolic disruptions in the surrounding cortex due to d-2-HG may be a driving event for epileptogenesis in patients with IDH-mutant gliomas.
Trends in Cigarette Marketing Expenditures, 1975–2019: An Analysis of Federal Trade Commission Cigarette Reports
Authors: Ma Haijing , Reimold Alexandria E , Ribisl Kurt M
Published: January 2022

Introduction

With tightened regulations on cigarette marketing and decreased smoking, the major tobacco companies quickly shifted their marketing expenditures in recent decades to maintain profits. We investigated cigarette marketing expenditures in the United States from 1975 through 2019 to examine the trends in cigarette marketing expenditures over the past 45 years.

Aims and Methods

Cigarette marketing expenditure data were obtained from the Federal Trade Commission (FTC) cigarette reports, 1975–2019. Based on individual expenditure categories included in the FTC reports, we created seven aggregate categories for marketing expenditures: Retail; Print; Out of home; Free tobacco products and gifts; Sports, public entertainment, and sponsorships; Telephone and digital; and Other. Dollar amounts and percentages by category were examined to assess trends in marketing expenditures.

Results

Cigarette marketing expenditures increased since 1975 and peaked in 2003 at $21.1 billion (adjusted dollars); afterward, they declined dramatically until 2010 and remained stable at around $9 billion through 2019. While all other expenditures decreased, retail expenditures increased, comprising more than 50% of expenditures in 1988 and reaching about 98% in 2019. In the retail category, tobacco companies spent the most on promotional allowances, coupons, and retail-value-added bonuses between 1988 and 2003, after which price discounts dominated retail spending.

Conclusions

Overall, cigarette marketing expenditures peaked in 2003 and retail first became the leading category in 1988. Tobacco companies adapted their marketing strategies in retail and allocated most of their retail spending on price discounts since 2003 to lower cigarette prices.

Implications

The major US tobacco companies directed the bulk of their vast spending on the retail environment since 1988. Moreover, they have dramatically shifted their marketing strategies within the retail category from cigarette advertising before 2003 to customer-directed price discounts since then. This shift may imply a change in focus from recruiting new smokers to retaining current smokers, in response to tax increases and government regulations. Accordingly, restrictions on price-related promotions in retail and nontax strategies should be implemented to counter tobacco companies’ marketing efforts in retail.
Efficacy and Safety of Apatinib in Patients with Recurrent or Refractory Melanoma
Authors: Yuan Shumin , Fu Qiang , Zhao Lingdi , Fu Xiaomin , Li Tiepeng , Han Lu , Qin Peng , Ren Yingkun , Huo Mingke , Li Zhimeng , Lu Chaomin , Yuan Long , Gao Quanli , Wang Zibing
Published: January 2022

Background

The prognosis of patients with metastatic malignant melanoma is very poor and partly due to resistance to conventional chemotherapies. The study’s objectives were to assess the activity and tolerability of apatinib, an oral small molecule anti-angiogenesis inhibitor, in patients with recurrent advanced melanoma.

Methods

This was a single-arm, single-center phase II trial. The primary endpoint was progression-free survival (PFS) and the secondary endpoints were objective response rate (ORR), disease control rate (DCR), and overall survival (OS). Eligible patients had received at least one first-line therapy for advanced melanoma and experienced recurrence. Apatinib (500 mg) was orally administered daily.

Results

Fifteen patients (V660E BRAF status: 2 mutation, 2 unknown, 11 wild type) were included in the analysis. The median PFS was 4.0 months. There were two major objective responses, for a 13.3% response rate. Eleven patients had stable disease, with a DCR of 86.7%. The median OS was 12.0 months. The most common treatment-related adverse events of any grade were hypertension (80.0%), mucositis oral (33.3%), hand-foot skin reaction (26.7%), and liver function abnormalities, hemorrhage, diarrhea (each 20%). The only grade ≥3 treatment-related adverse effects that occurred in 2 patients was hypertension (6.7%) and mucositis (6.7%). No treatment-related deaths occurred.

Conclusion

Apatinib showed antitumor activity as a second- or above-line therapy in patients with malignant melanoma. The toxicity was manageable.

ClinicalTrials.gov Identifier

NCT03383237
ROOT HAIR DEFECTIVE 2 vesicular delivery to the apical plasma membrane domain during Arabidopsis root hair development
Authors: Kuběnová Lenka , Tichá Michaela , Šamaj Jozef , Ovečka Miroslav
Published: January 2022

Arabidopsis (Arabidopsis thaliana) root hairs develop as long tubular extensions from the rootward pole of trichoblasts and exert polarized tip growth. The establishment and maintenance of root hair polarity is a complex process involving the local apical production of reactive oxygen species generated by A. thaliana nicotinamide adenine dinucleotide phosphate (NADPH) oxidase respiratory burst oxidase homolog protein C/ROOT HAIR-DEFECTIVE 2 (AtRBOHC/RHD2). Loss-of-function root hair defective 2 (rhd2) mutants have short root hairs that are unable to elongate by tip growth, and this phenotype is fully complemented by GREEN FLUORESCENT PROTEIN (GFP)-RHD2 expressed under the RHD2 promoter. However, the spatiotemporal mechanism of AtRBOHC/RHD2 subcellular redistribution and delivery to the plasma membrane (PM) during root hair initiation and tip growth are still unclear. Here, we used advanced microscopy for detailed qualitative and quantitative analysis of vesicular compartments containing GFP-RHD2 and characterization of their movements in developing bulges and growing root hairs. These compartments, identified by an independent molecular marker mCherry-VTI12 as the trans-Golgi network (TGN), deliver GFP-RHD2 to the apical PM domain, the extent of which corresponds with the stage of root hair formation. Movements of TGN/early endosomes, but not late endosomes, were affected in the bulging domains of the rhd2-1 mutant. Finally, we revealed that structural sterols might be involved in the accumulation, docking, and incorporation of TGN compartments containing GFP-RHD2 to the apical PM of root hairs. These results help in clarifying the mechanism of polarized AtRBOHC/RHD2 targeting, maintenance, and recycling at the apical PM domain, coordinated with different developmental stages of root hair initiation and growth.
Decreasing Postoperative Opioid Prescriptions After Orthopedic Trauma Surgery: The “Lopioid” Protocol
Authors: Landes Emma K , Leucht Philipp , Tejwani Nirmal C , Ganta Abhishek , McLaurin Toni M , Lyon Thomas R , Konda Sanjit R , Egol Kenneth A
Published: January 2022

Objective

To assess the effectiveness of a multimodal analgesic regimen containing “safer” opioid and non-narcotic pain medications in decreasing opioid prescriptions after surgical fixation in orthopedic trauma.

Design

Retrospective cohort study.

Setting

One urban, academic medical center.

Subjects

Patients with traumatic fracture from 2018 (n=848) and 2019 (n=931).

Methods

In 2019, our orthopedic trauma division began a standardized protocol of postoperative pain medications that included 50 mg of tramadol four times daily, 15 mg of meloxicam once daily, 200 mg gabapentin twice daily, and 1 g of acetaminophen every 6 hours as needed. This multimodal regimen was dubbed the “Lopioid” protocol. We compared patients who received this protocol with all patients from the prior year who had followed a standard protocol that included Schedule II narcotics.

Results

Greater mean morphine milligram equivalents were prescribed at discharge from fracture surgery under the standard protocol than under the Lopioid protocol (252.3 vs 150.0; P < 0.001), and there was a difference in the type of opioid medication prescribed (P < 0.001). There was a difference in the number of refills filled for patients discharged with opioids after surgical treatment between the standard and Lopioid cohorts (0.31 vs 0.21; P = 0.002). There were no differences in the types of medication-related complications (P = 0.710) or the need for formal pain management consults (P = 0.199), but patients in the Lopioid cohort had lower pain scores at discharge (2.2 vs 2.7; P = 0.001).

Conclusions

The Lopioid protocol was effective in decreasing the amount of Schedule II narcotics prescribed at discharge and the number of opioid refills after orthopedic surgery for fractures.
The Bureaucratic Ethos in Street-Level Work: Revitalizing Weber’s Ethics of Office
Authors: Møller Anne Mette , Pedersen Kirstine Zinck , Pors Anja Svejgaard
Published: January 2022

Despite the centrality of bureaucracy to both the theory and the realities of street-level bureaucracy, street-level scholars have rarely engaged with the concept of bureaucracy as such. We argue that Weber’s perspective on bureaucracy represents an indispensable source that may help us align the theoretical foundation of street-level scholarship with its empirical findings and bring attention to aspects of street-level work that are often overlooked. Drawing on a value-based reading of Weber, we propose an ethics of office-approach that allows us to see frontline workers’ discretionary practices as an integrated aspect of their bureaucratic ethos, which enables them to handle complex demands and multiple obligations. The ethics of office-approach further recognizes that their actual possibilities for doing so are related to their training and expertise within specific life orders characterized by different purposes and ethical codes. The approach therefore calls for contextual sensitivity. To develop our argument, and demonstrate the analytical range and usefulness of the ethics of office-approach, we present three case examples based on ethnographic studies of midwifery care, child protection, and citizen services.
Physical Therapists in Oncology Settings: Experiences in Delivering Cancer Rehabilitation Services, Barriers to Care, and Service Development Needs
Authors: Brennan Louise , Sheill Grainne , O’Neill Linda , O’Connor Louise , Smyth Emily , Guinan Emer
Published: January 2022

Objective

Physical therapist-delivered rehabilitation aims to manage the side effects of cancer and its treatments. Although access to cancer rehabilitation is not yet a standard of care in many countries, physical therapists practice in many types of cancer services with different cancer populations. The purpose of this study was to explore the experiences of physical therapists in cancer care practice with regard to their role, the factors influencing service delivery and development, and physical therapists’ professional development needs.

Methods

In this qualitative study with semistructured interviews, physical therapists in cancer care settings in the Republic of Ireland were interviewed via telephone. Participants (n = 17) represented a variety of clinical settings and roles. Two researchers performed thematic analysis of transcriptions using a semantic, inductive approach. Key themes and codes were identified and illustrative quotes were selected.

Results

Six main themes were found: the need for more services, barriers to service development and delivery, a lack of awareness of the role of physical therapy, facilitators to service development, goals for the future of oncology physical therapy, and training needs of staff.

Conclusions

Physical therapists provide valuable interventions across the spectrum of cancer care but experience barriers to the delivery and development of services. Investment in oncology physical therapy and developing international standards of care will allow physical therapists to meet the rehabilitation needs of survivors of cancer.

Impact

As international guidelines increasingly recommend development of cancer rehabilitation programs, it is important to understand physical therapists’ experiences of working in cancer care to assist in the development of effective oncology physical therapy services. This study demonstrates that physical therapist–led cancer rehabilitation services need investment and public promotion to enable the provision of optimal services to all patients with cancer and to meet standards of care.
Landscaping the Three-Volume Novel: Jane Austen’s Pride and Prejudice and Mansfield Park
Authors: Sharren Kandice
Published: January 2022

The importance to Jane Austen’s writing of the picturesque theory that emerged in the second half of the eighteenth century has been well established, from how it influenced stylistic choices to the commentary she offers on land ownership. This article reconsiders the relationship between picturesque theory and plot as it relates to the material forms that shaped the novel in the early nineteenth century, namely the three-volume structure that became the norm in the 1810s. This article argues that, in Pride and Prejudice and Mansfield Park, the metaphorical landscape of the plot is shaped in response to this three-volume structure; considering her novels through the lens of prospects and boundaries that correspond to volumes reveals the extent to which her narrative practice responds to the increasingly standard three-volume structure. But whereas the plot of Pride and Prejudice is naturalized within the structure of its volumes, resulting in a plot that conforms to the picturesque’s aim of concealing artifice, Mansfield Park uses landscapes and geographical locations to limit the reader’s perspective, resulting in an abrupt conclusion that draws attention to the boundaries of the book, thereby denaturalizing the plot within it and the ubiquity of the marriage plot more generally.
The coronavirus disease 2019 pandemic: the disruptor that maintenance dialysis never anticipated
Authors: Weinhandl Eric D.
Published: January 2022

Purpose of review

The novel coronavirus 2019 (COVID-19) pandemic has upended maintenance dialysis in the United States. I review changes in prevalence, incidence, mortality, and other clinical outcomes among patients undergoing dialysis since March 2020, highlighting vulnerabilities in the current system and opportunities for improved care in the future.

Recent findings

The number of dialysis patients in the United States declined between March 2020 and March 2021, an unprecedented year-over-year drop in the census. Some of the decline can be attributed to an early drop in patients initiating dialysis but most of the decline can be attributed to excess mortality. Kidney transplants also declined during the early part of the pandemic. Home dialysis utilization increased during 2020 but that increase was largely in line with secular trends. The rate of hospitalization for causes other than COVID-19 fell significantly during 2020.

The epidemiology of dialysis in the United States is clearly modifiable, as it reflects decisions to initiate treatment, prescribe home therapies, and hospitalize patients with acute medical needs. On the other hand, some outcomes are powerfully guided by health outcomes in the general population, thus limiting the ability of dialysis providers and nephrologists to influence outcomes.
Cholangiopathies and the noncoding revolution
Authors: Gradilone Sergio , Brunetti-Pierri Nicola , Piccolo Pasquale
Published: January 2022

Purpose of review

Noncoding RNAs (ncRNAs), including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) among others, have attracted a great deal of attention for their potential role as master regulators of gene expression and as therapeutic targets. This review focuses on recent advances on the role of ncRNAs in the pathogenesis, diagnosis and treatment of diseases of the cholangiocytes (i.e. cholangiopathies).

Recent findings

In the recent years, there has been an exponential growth in the knowledge on ncRNAs and their role in cholangiopathies, particularly cholangiocarcinoma.

Although several studies focused on miRNAs as noninvasive biomarkers for diagnosis and staging, several studies also highlighted their functions and provided new insights into disease mechanisms.
Patients' Perspective of the Impacts of Group Psychoeducation for Bipolar Disorder
Authors: Weiner Luisa , Li Chen Che Muriel , Bertschy Gilles , Weibel Sébastien
Published: January 2022

Little is known regarding the mechanisms involved in the clinical improvement of patients with bipolar disorder (BD) after group psychoeducation. We aimed at investigating these mechanisms by focusing on their subjective experience. Thirteen patients with BD aged 35.54 (SD, 12.06) were recruited. Interviews were analyzed using thematic analysis. Four high-order themes were identified: a) relationship among patients, b) effect of the facilitation style, c) program-related factors, and d) subjective impacts. “Relationships among patients” included a lower-ordered theme evoked by all participants, that is, “shared experiences.” Shared experiences included acknowledging that BD has a neurobiological substrate and that its manifestations are similar in BD; the social support and empowering message of those who have managed to exert control over the illness were also highlighted. Our results shed some light on the mechanisms underlying the effectiveness of group psychoeducation. The shared experience of patients seems to play an important role, probably through destigmatization.
Ketofol for Procedural Sedation and Analgesia in the Pediatric Population
Authors: Iqbal Ammarah U. , Shuster Megan E. , Baum Carl R.
Published: January 2022

The combination of ketamine and propofol, commonly referred to as ketofol, is sometimes used for procedural sedation and analgesia in the pediatric emergency department. This article reviews the pharmacology, dosing, and indications, as well as adverse effects and contraindications of ketamine, propofol, and ketofol.
Invasive aspergillosis in coronavirus disease 2019: a practical approach for clinicians
Authors: Lamoth Frederic
Published: January 2022

Purpose of review

Invasive pulmonary aspergillosis (IPA) can affect patients with severe coronavirus disease 2019 (COVID-19), but many questions remain open about its very variable incidence across the world, the actual link between the viral infection and the fungal superinfection, the significance of Aspergillus recovery in a respiratory sample, and the management of such cases. This review addresses these questions and aims at providing some clues for the practical diagnostic and therapeutic approaches of COVID-19-associated pulmonary aspergillosis (CAPA) in a clinical perspective.

Recent findings

Definitions have been proposed for possible/probable/proven CAPA, but distinction between colonization and invasive fungal infection is difficult and not possible in most cases in the absence of histopathological proof or positive galactomannan in serum. Most importantly, the recovery of an Aspergillus by a direct (culture, PCR) or indirect (galactomannan) test in a respiratory sample is an indicator of worse outcome, which justifies a screening for early detection and initiation of preemptive antifungal therapy in such cases.

The COVID-19 pandemic has increased our awareness of IPA among ICU patients. Although current recommendations are mainly based on experts’ opinions, prospective studies are needed to get more evidence-based support for the diagnostic approach and management of CAPA.
Epidermoid Cyst of the Floor of the Mouth
Authors: Erol Behçet , Laçin Nihat
Published: January 2022

Epidermoid cysts are rare, slow-growing, benign, developmental cysts that are derived from abnormally situated ectodermal tissue. Epidermoid cysts may grow anywhere on the body and about 7% of them are located in the head and neck region. They are usually asymptomatic over years but can be symptomatic due to secondary changes or the growing size. Clinically, the lesion presents as a slow-growing asymptomatic mass, usually located in the midline, above or below the mylohyoid muscle. Surgical excision from the floor of the mouth is indicated to relieve symptoms and prevent possible infection. This swelling on the floor of the mouth can sometimes cause serious problems with difficulty for swallowing and speaking. The purpose of this report is to present a case of sublingual epidermoid cyst of the floor of the mouth.
Integrated Autolysis, DNA Hydrolysis and Precipitation Enables an Improved Bioprocess for Q-Griffithsin, a Broad-Spectrum Antiviral and Clinical-Stage anti-COVID-19 Candidate
Authors: Decker John S. , Menacho-Melgar Romel , Lynch Michael D.
Published: January 2022

Across the biomanufacturing industry, innovations are needed to improve efficiency and flexibility, especially in the face of challenges such as the COVID-19 pandemic. Here we report an improved bioprocess for Q-Griffithsin, a broad-spectrum antiviral currently in clinical trials for COVID-19. Q-Griffithsin is produced at high titer inE. coliand purified to anticipated clinical grade without conventional chromatography or the need for any fixed downstream equipment. The process is thus both low-cost and highly flexible, facilitating low sales prices and agile modifications of production capacity, two key features for pandemic response. The simplicity of this process is enabled by a novel unit operation that integrates cellular autolysis, autohydrolysis of nucleic acids, and contaminant precipitation, giving essentially complete removal of host cell DNA as well as reducing host cell proteins and endotoxin by 3.6 and 2.4 log10units, respectively. This unit operation can be performed rapidly and in the fermentation vessel, such that Q-GRFT is obtained with 100% yield and >99.9% purity immediately after fermentation and requires only a flow-through membrane chromatography step for further contaminant removal. Using this operation or variations of it may enable improved bioprocesses for a range of other high-value proteins inE. coli.

Highlights

Integrating autolysis, DNA hydrolysis and precipitation enables process simplification

Autolysis reduces endotoxin release and burden to purification

Q-Griffithsin recovered from fermentation vessel at >99.9% purity and 100% yield

Q-Griffithsin purified to anticipated clinical grade without conventional chromatography

The resulting bioprocess is 100% disposables-compatible, scalable, and low-cost
Nonself Mutations in the Spike Protein Suggest an Increase in the Antigenicity and a Decrease in the Virulence of the Omicron Variant of SARS-CoV-2
Authors: Otaki Joji M. , Nakasone Wataru , Nakamura Morikazu
Published: January 2022

Despite extensive worldwide vaccination, the current COVID-19 pandemic caused by SARS-CoV-2 continues. The Omicron variant is a recently emerged variant of concern and is now taking over the Delta variant. To characterize the potential antigenicity of the Omicron variant, we examined the distributions of SARS-CoV-2 nonself mutations (in reference to the human proteome) as 5 amino acid stretches of short constituent sequences (SCSs) in the Omicron and Delta proteomes. The number of nonself SCSs did not differ much throughout the Omicron, Delta, and Reference Sequence (RefSeq) proteomes but markedly increased in the receptor binding domain (RBD) of the Omicron spike protein compared to those of the Delta and RefSeq proteins. In contrast, the number of nonself SCSs decreased in non-RBD regions in the Omicron spike protein, compensating for the increase in the RBD. Several nonself SCSs were tandemly present in the RBD of the Omicron spike protein, likely as a result of selection for higher binding affinity to the ACE2 receptor (and hence higher infectivity and transmissibility) at the expense of increased antigenicity. Taken together, the present results suggest that the Omicron variant has evolved to have higher antigenicity and less virulence in humans despite increased infectivity and transmissibility.
Combining antigenic data from public sources gives an early indication of the immune escape of emerging virus variants
Authors: Netzl Antonia , Tureli Sina , LeGresley Eric , Mühlemann Barbara , Wilks Samuel H. , Smith Derek J.
Published: January 2022

The rapid spread of the Omicron BA.1 (B.1.1.529.1) SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) variant in 2021 resulted in international efforts to quickly assess its escape from immunity generated by vaccines and previous infections. Numerous laboratories published BA.1 neutralization data as preprints and reports. We collated this data in real time and regularly presented updates of the aggregated results in US, European and WHO research and advisory settings. Here, we retrospectively analyzed the accuracy of these aggregations from 85 different sources published during a time period from 2021/12/08 up to 2022/08/14. We found that the mean titer fold change from wild type-like variants to BA.1, a standard measure of a variant's immune escape, remained stable after the first 15 days of data reporting in people who were twice vaccinated, and incoming data increased the confidence in this quantity. Further, it is possible to build reliable, stable antigenic maps from this collated data already after one month of incoming data. We here demonstrate that combining early reports from variable, independent sources can rapidly indicate a new virus variant's immune escape and can therefore be of immense benefit for public health.
Schild analysis of the interaction between parthenolide and cocaine suggests an allosteric relationship for their effects on planarian motility
Authors: Kakuturu Jyothi , O’Brien Mary , Pagán Oné R.
Published: January 2022

The freshwater planarian is an emerging animal model in neuropharmacology due to its close parallels with the nervous system of vertebrates. Cocaine is a naturally occurring compound and an abused drug, as well as the ‘founding member’ of the local anesthetic family. Sesquiterpene lactones of the parthenolide class are naturally occurring products that act as behavioral and physiological antagonists of cocaine in planarians and rats, respectively. One of the best-characterized planarian behaviors induced by various compounds is the change in locomotor velocity. Previous work from our laboratory showed that both parthenolide and cocaine reduced planarian motility and that parthenolide reversed the cocaine-induced motility decrease at concentrations where parthenolide does not affect the movement of the worms. However, the exact mechanism of the cocaine/parthenolide antagonism is unknown. Here, we report the results of a Schild analysis to explore the parthenolide/cocaine relationship in the planarian Girardia tigrina. The Schild slopes of the Δ parthenolide ± cocaine and Δ cocaine ± parthenolide were -0.33 and -0.43, respectively. These slopes were not statistically different from each other, and both were statistically different from -1, suggesting an allosteric relationship between these two compounds. To the best of our knowledge, this is the first study aimed at studying the mechanism of action of the antagonism between cocaine and parthenolide.
Nearly maximal information gain due to time integration in central dogma reactions
Authors: Sarkar Swarnavo , Rammohan Jayan
Published: January 2022

Living cells process information about their environment through the central dogma processes of transcription and translation, which drive the cellular response to stimuli. Here, we study the transfer of information from environmental input to the transcript and protein expression levels. Evaluation of both experimental and analogous simulation data reveals that transcription and translation are not two simple information channels connected in series. Instead, we show that the central dogma reactions often create a time-integrating information channel, where the translation channel receives and integrates multiple outputs from the transcription channel. This information channel model of the central dogma provides new information-theoretic selection criteria for the central dogma rate constants. Using the data for four well-studied species we show that their central dogma rate constants achieve information gain due to time integration while also keeping the loss due to stochasticity in translation relatively low (< 0.5 bits).
Increasing adult density compromises anti-bacterial defense in Drosophila melanogaster
Authors: Das Paresh Nath , Basu Aabeer , Prasad Nagaraj Guru
Published: January 2022

The density-dependent prophylaxis hypothesis predicts that risk of pathogen transmission increases with increase in population density, and in response to this, organisms mount a prophylactic immune response when exposed to high density. This prophylactic response is expected to help organisms improve their chances of survival when exposed to pathogens. Alternatively, organisms living at high densities can exhibit compromised defense against pathogens due to lack of resources and density associated physiological stress; the density stress hypothesis. We housed adult Drosophila melanogaster flies at different densities and measured the effect this has on their post-infection survival and resistance to starvation. We find that flies housed at higher densities show greater mortality after being infected with bacterial pathogens, while also exhibiting increased resistance to starvation. Our results are more in line with the density-stress hypothesis that postulates a compromised immune system when hosts are subjected to high densities.
Mapping the antigenic diversification of SARS-CoV-2
Authors: van der Straten Karlijn , Guerra Denise , van Gils Marit J. , Bontjer Ilja , Caniels Tom G. , van Willigen Hugo D.G. , Wynberg Elke , Poniman Meliawati , Burger Judith A. , Bouhuijs Joey H. , van Rijswijk Jacqueline , Olijhoek Wouter , Liesdek Marinus H. , Lavell A. H. Ayesha , Appelman Brent , Sikkens Jonne J. , Bomers Marije K. , Han Alvin X. , Nichols Brooke E. , Prins Maria , Vennema Harry , Reusken Chantal , de Jong Menno D. , de Bree Godelieve J. , Russell Colin A. , Eggink Dirk , Sanders Rogier W.
Published: January 2022

Large-scale vaccination campaigns have prevented countless hospitalizations and deaths due to COVID-19. However, the emergence of SARS-CoV-2 variants that escape from immunity challenges the effectiveness of current vaccines. Given this continuing evolution, an important question is when and how to update SARS-CoV-2 vaccines to antigenically match circulating variants, similar to seasonal influenza viruses where antigenic drift necessitates periodic vaccine updates. Here, we studied SARS-CoV-2 antigenic drift by assessing neutralizing activity against variants-of-concern (VOCs) of a unique set of sera from patients infected with a range of VOCs. Infections with D614G or Alpha strains induced the broadest immunity, while individuals infected with other VOCs had more strain-specific responses. Omicron BA.1 and BA.2 were substantially resistant to neutralization by sera elicited by all other variants. Antigenic cartography revealed that Omicron BA.1 and BA.2 are antigenically most distinct from D614G, associated with immune escape and likely requiring vaccine updates to ensure vaccine effectiveness.
Nurses’ Perceptions regarding Current Skills in Minimizing Patient’s Aggression at a selected Psychiatric hospital in Lesotho
Authors: Rathobei Libuseng Moureen , Nyangu Isabel , Dube Makhosazane Barbara
Published: January 2022

Background

Meta-analysis of international literature indicate high frequencies of aggression in mental health setting. Several studies indicate that among professional health workers, nurses are more likely than other staff members to experience aggressive incidences from patients. Furthermore, based on cause, nurses apply range of interventions in managing aggression, however, despite their perceived value of their intervention in managing aggression, no single intervention is sufficient for handling aggressive patients to stay in control in wards. Despite high priority placed on patient aggression management, insufficient research studies have been conducted on nurses’ perceptions regarding current skills in minimizing patient’s aggression.

Objectives

The purpose of the study was to describe nurses’ perceptions regarding current assessment skills in minimizing patient’s aggression at selected Psychiatric hospital.

Methodology

Non-experimental, exploratory, descriptive research design was used to guide research process. All-inclusive sampling method was used with 119 nurses as respondents. Data was collected by means of a questionnaire, analyzed using SPSS version 25. Descriptive statistics procedure was used to present findings of the study.

Results

Minority of respondents, (n=27) 22.7% agreed that their current assessment skills for minimizing patients’ aggression were good compared to majority of respondents, (n=92) 77.3%, who expressed a different opinion. This suggests that there is limited current assessment skills in identifying high risk aggressive patients in a selected Psychiatric hospital.

Conclusion

The findings of study indicate that there is limited current assessment skills in minimizing patients’ aggression at selected Psychiatric hospital. Therefore, there is need to provide comprehensive information on nurses’ current skills in minimizing patients’ aggression to obtain richer information.