bluuebunny/crossref_metadata_2025 huggingface dataset:
Restriction of visits to neonatal intensive care units in the COVID‐19 pandemic
Authors: Cigdem Zerrin , Guler Selver , Yavas Celik Melike
Published: July 2024

Aims

The aim of this study, it examine how visits to neonatal intensive care units were made during the COVID‐19 process and how mothers were affected by this process.

Methods

In this phenomenological study, interviews were conducted with semi‐structured questions and face‐to‐face interviews with the participants. While collecting the data, both observation and interview techniques were used. A content analysis technique was used to analyse the data.

Results

The findings of the study were gathered under two themes: ‘mothers' recommendations about visits in neonatal intensive care units’ and ‘mothers' fear of transmitting COVID‐19’.

Conclusion

As a result, visitor restrictions implemented during the pandemic period hurt on newborns. During the pandemic period, visitor restrictions were imposed in neonatal intensive care units around the world. Unfortunately, in our study, it was determined that this restriction was made. This situation may have adversely affected the mother‐infant attachment and the growth and development of the baby and may have led to irreversible problems. Therefore, newborn nurses should give more importance to mother‐infant interaction and continue their treatment and care without separating infants from their mothers.
The mirage of a “paradox” of dehumanization: How to affirm the reality of dehumanization
Authors: Kronfeldner Maria
Published: July 2024

This paper argues that the so‐called ‘paradox’ of dehumanization is a mirage arising from misplaced abstraction. The alleged ‘paradox’ is taken as a challenge that arises from a skeptical stance. After reviewing the history of that skeptical stance, it is reconstructed as an argument with two premises. With the help of an epistemologically structured but pluralistic frame it is then shown how the two premises of the Skeptic's argument can both be debunked. As part of that it emerges that there are a couple of ways how dehumanization can be realized, and one such realization can be sufficient for affirming the reality of dehumanization for a specific case.
Critical reflection in team‐based practice: A narrative review
Authors: Edelist Tracey , Friesen Farah , Ng Stella , Fernandez Nicolas , Bélisle Marilou , Lechasseur Kathleen , Rochette Annie , Vachon Brigitte , Caty Marie‐Ève
Published: July 2024

Introduction

Research on critical reflection (a process of recognising and challenging assumptions that frame health care practice) has demonstrated strong potential for making health care more collaborative and equitable, yet its enactment within team‐based health care remains underexplored. We conducted a narrative review to advance understanding of how critical reflection develops, occurs in and impacts team‐based practice and care.

Methods

We searched three databases (Medline, CINAHL and Scopus) for articles related to the concepts of critical reflection and/or critically reflective practice in the context of team‐based health care and examined how teams engage with those theoretical concepts, to inform ideas for a new approach to support critically reflective practice.

Findings

The search identified 974 citations of which nine articles showed elements of critical reflection in team‐based practice. However, since only one of the nine included articles explicitly used the term ‘critical reflection’ in their research, critical reflection as a theoretical concept was found to be largely missing from the current team‐based health care literature. Instead, aspects of critical reflection were evident in terms of challenging power hierarchies and questioning practice assumptions through dialogue, with a goal of collaborative practice. This sharing of knowledge and skills allowed teams to push boundaries and innovate together in practice. The included articles also emphasised the importance of creating a purposeful environment for open dialogue and practice change to occur.

Conclusion

To support equitable care through collaborative practices, we suggest dialogue as and for critical reflection should be explicitly developed and researched within team‐based health care.
Priority analysis of educational needs for new nurses in the intensive care unit: A cross‐sectional study
Authors: Chang Sung Ok , Chaung Seung‐Kyo , Sohng Kyeong‐Yae , Kim Kyunghee , Won Jongsoon , Choi Min‐Jung
Published: July 2024

Background

New intensive care unit (ICU) nurses often experience stress because of concerns about potentially harming their patients in a work environment that demands the rapid development of several skills in a limited training period.

Aim

This study aimed to investigate the prioritisation of educational needs within adult ICUs, focusing on how new nurses evaluate their current knowledge and perceive the most critical competencies.

Study Design

A cross‐sectional study was conducted among a convenience sample of 102 new ICU nurses in general and tertiary hospitals in South Korea. Educational needs were assessed using a structured questionnaire for new ICU nurses. This study investigated educational needs using paired t‐tests, Borich's assessment model and the Locus for Focus model.

Results

Only 48% of participants were satisfied with their education. The highest‐rated educational content included preparing to use a defibrillator (95% CI = 2.44–3.28, p < .001), administering emergency drugs for cardiopulmonary resuscitation (CPR) (95% CI = 2.09–2.91, p < .001), starting and maintaining continuous renal replacement therapy (95% CI = 1.50–2.42, p < .001), applying and maintaining a ventilator (95% CI = 1.42–2.08, p < .001), preparing for intubation (95% CI = 1.23–1.97, p < .001), reporting to the emergency team, preparing equipment for CPR (95% CI = 1.12–1.94, p < .001) and drug calculation (95% CI = 0.87–1.53, p < .001).

Conclusions

These findings indicate that educational programmes for new ICU nurses should be developed considering the aforementioned priorities. Furthermore, nurse educators should adopt a practical and active instructional method to repeatedly clarify content, prioritising the improvement of knowledge and performance of new ICU nurses.

Relevance to Clinical Practice

This study guides clinical educators and managers in focusing on areas where new ICU nurses need additional training. Effective nurse residency programmes tailored to the specific needs of new ICU nurses can enhance their confidence and ability to handle ICU nursing challenges.
Political action in nursing and medical codes of ethics
Authors: Essex Ryan , Mainey Lydia , Dillard‐Wright Jess , Richardson Sarah
Published: July 2024

Political action has a long history in the health workforce. There are multiple historical examples, from civil disobedience to marches and even sabotage that can be attributed to health workers. Such actions remain a feature of the healthcare community to this day; their status with professional and regulatory bodies is far less clear, however. This has created uncertainty for those undertaking such action, particularly those who are engaged in what could be termed ‘contentious’ forms of action. This study explored how advocacy and activism were presented in nursing and medical codes of ethics, comparing disciplinary and temporo‐spatial differences to understand how such action may be promoted or constrained by codes. The data for this study comes from 217 codes of ethics. Because of the size of the corpus and to facilitate analysis, natural language processing was utilised, which allowed for an automated exploration of the data and for comparisons to be drawn between groups. This was complemented by a manual search and contextualisation of the data. While there were noticeable differences between medical and nursing codes, overall, advocacy, activism and even politics were rarely discussed explicitly in most codes. When such action was spoken about, this was often vague and imprecise with codes speaking of ‘political action’ and ‘advocacy’ in general terms. While some codes were far more forthright in what they meant about advocacy or broader political action (i.e., Nursing codes in Denmark, Norway, Canada) more forceful language that spoke in specific terms or in terms of oppositional or specific actions (e.g., civil disobedience or marches) was almost completely avoided. These results are discussed in relation to the broader literature on codes and the normative questions they raise, namely whether such action should be included in codes of ethics at all.
The potential contributions of bouillon fortification to meeting micronutrient requirements among women and preschool children in Senegal: A modeling study using household consumption and expenditure survey data
Authors: Adams Katherine P. , Vosti Stephen A. , Tarini Ann , Beye Maguette , Pachón Helena , Kiselova Sophia , Engle‐Stone Reina
Published: July 2024

To reduce micronutrient deficiencies, Senegal mandates the fortification of refined oil with vitamin A and wheat flour with iron and folic acid. Expanding Senegal's large‐scale food fortification programs to include fortified bouillon could help fill the remaining gaps in dietary micronutrient requirements. Using 7‐day household food consumption data collected between 2018 and 2019, we assessed the potential contributions of bouillon fortified with vitamin A (40–250 μg/g bouillon), folic acid (20–120 μg/g), vitamin B12 (0.2–2 μg/g), iron (0.6–5 mg/g), and zinc (0.6–5 mg/g) for meeting micronutrient requirements of women of reproductive age (WRA; 15–49 years old) and children (6–59 months old). Most households (90%) reported consuming bouillon, including poor and rural households. At modeled fortification levels, bouillon fortification reduced the national prevalence of inadequacy by up to ∼20 percentage points (pp) for vitamin A, 34 pp (WRA) and 20 pp (children) for folate, 20 pp for vitamin B12, 38 pp (WRA) and 30 pp (children) for zinc, and ∼8 pp for iron. Predicted reductions in inadequacy were generally larger among poor and rural populations, especially for vitamins A and B12. Our modeling suggests that bouillon fortification has the potential to substantially reduce dietary inadequacy of multiple micronutrients and could also help address inequities in dietary micronutrient inadequacies in Senegal.
Autophagy is suppressed by low temperatures and is dispensable for cold acclimation in Arabidopsis
Authors: Sato Akito , Inayoshi Sena , Kitawaki Kohei , Mihara Ryota , Yoneda Kosei , Ito‐Inaba Yasuko , Inaba Takehito
Published: July 2024

Plants have evolved various mechanisms to adapt to the ever‐changing external environment. Autophagy is one such mechanism and has been suggested to play a key role in responding to and adapting to abiotic stresses in plants. However, the role of autophagy in adaptation to cold and freezing stresses remains to be characterized in detail. Here, we investigated the role of autophagy in the low‐temperature response of Arabidopsis using atg mutants. Both the atg5‐1 and atg10‐1 mutants exhibited normal freezing tolerance, regardless of cold acclimation. A comparison of fresh weights indicated that the difference in growth between the wild‐type and atg plants under cold conditions was rather small compared with that under normal conditions. Analysis of COLD‐REGULATED gene expression showed no significant differences between the atg mutants and wild type. Treatment with 3‐methyladenine, an inhibitor of autophagy, did not impair the induction of COR15Apro::LUC expression upon exposure to low temperature. Evaluation of autophagic activity using transgenic plants expressing RBCS‐mRFP demonstrated that autophagy was rarely induced by cold exposure, even in the dark. Taken together, these data suggest that autophagy is suppressed by low temperatures and is dispensable for cold acclimation and freezing tolerance in Arabidopsis.
LncRNA cis‐ and trans‐regulation provides new insight into drought stress responses in wild barley
Authors: Cheng Bingyun , Pei Wenyu , Wan Kui , Pan Rui , Zhang Wenying
Published: July 2024

Drought is one of the most common abiotic stresses that affect barley productivity. Long noncoding RNA (lncRNA) has been reported to be widely involved in abiotic stress, however, its function in the drought stress response in wild barley remains unclear. In this study, RNA sequencing was performed to identify differentially expressed lncRNAs (DElncRNA) among two wild barley and two cultivated barley genotypes. Then, the cis‐regulatory networks were according to the chromosome position and the expression level correction. The GO annotation indicates that these cis‐target genes are mainly involved in “ion transport transporter activity” and “metal ion transport transporter activity”. Through weighted gene co‐expression network analysis (WGCNA), 10 drought‐related modules were identified to contract trans‐regulatory networks. The KEGG annotation demonstrated that these trans‐target genes were enriched for photosynthetic physiology, brassinosteroid biosynthesis, and flavonoid metabolism. In addition, we constructed the lncRNA‐mediated ceRNA regulatory network by predicting the microRNA response elements (MREs). Furthermore, the expressions of lncRNAs were verified by RT‐qPCR. Functional verification of a candidate lncRNA, MSTRG.32128, demonstrated its positive role in drought response and root growth and development regulation. Hormone content analysis provided insights into the regulatory mechanisms of MSTRG.32128 in root development, revealing its involvement in auxin and ethylene signal transduction pathways. These findings advance our understanding of lncRNA‐mediated regulatory mechanisms in barley under drought stress. Our results will provide new insights into the functions of lncRNAs in barley responding to drought stress.
Emotional labor in decision making: Gender, race, and relational practices in the White House
Authors: Beauregard Philippe
Published: July 2024

Relational and emotional practices intensive in emotional labor play an essential role for high‐level decision making, even though this labor is often devalued or unseen. United States presidents can often present themselves as rational and emotionally detached because they delegate emotional work to other members of their team. The burden of such work is unequally distributed along gender and racial lines. It involves expressing empathic concern, repairing relations, anticipating others' emotional responses, protecting marginalized colleagues, speaking hard truths, and providing emotional support to help others regulate their emotions. This article contributes to research on emotions in decision making, public administration, and presidency studies. Case studies of Nancy Reagan and Valerie Jarrett—who played important roles in the Reagan and Obama administrations, respectively—illustrate the article's main argument.
Titian's Bacchus and his two loves
Authors: Luskin Fern
Published: July 2024

Titian's Bacchus and Ariadne represents not only Bacchus' attraction to Ariadne, as has long been recognized, but also his infatuation with a boy‐satyr, Ampelos, who struts at the centre of the composition. The little satyr's identity, recognized in the seventeenth century, but overlooked by modern scholars, is confirmed by newly revealed pentimenti. Titian was probably the first to embed this homoerotic love story in a painting depicting the Bacchus and Ariadne myth. The textual impetus for Titian's inclusion of the Ampelos myth was Nonnos' Dionysiaca. Guided by Nonnos' text, Titian alludes not only to Bacchus' love for Ampelos, but to the boy's transformation into a grapevine. His metamorphosis prompted Bacchus' discovery of wine, which precipitated his identity as the god of wine, hence his prominent position in the painting. Titian's portrayal of Bacchus' overwhelming ardour for the negligently dressed Ariadne, along with his former dalliance with the engaging, rosy‐cheeked boy‐satyr Ampelos, was never meant to represent celestial or marital love as has been claimed. Such an ennobling interpretation is disproved through an analysis of contemporary descriptions of the picture and its ancient literary sources.
First transition dynamics of reaction–diffusion equations with higher order nonlinearity
Authors: Şengül Taylan , Tiryakioglu Burhan , Yıldız Akıl Esmanur
Published: July 2024

In this study, the dynamics of a reaction–diffusion equation on a bounded interval at the first dynamic transition point is investigated. The main difference of this study from the existing ones in the dynamic transition literature is that in this work, no specific form of the nonlinear operator is assumed except that it is an analytic function of and . The linear operator is also assumed to be a general operator with sinusoidal eigenvectors. Moreover, we assume that there is a first transition as a real simple eigenvalue changes sign. With this general framework, we make a rigorous analysis of the dependence of the first transition dynamics on the coefficients of the Taylor expansion of the nonlinear operator. The main tool we use in this study is the center manifold reduction combined with the classification of the dynamic transition theory. This study is a generalization of a recent work where the nonlinear operator contains only low‐order (quadratic and cubic) nonlinearities. The current generalization requires certain technical difficulties such as the validity of the genericity conditions on the Taylor coefficients of the nonlinear operator and a bootstrapping argument using these genericity conditions. The results of this work can be generalized in various directions, which are discussed in the conclusions section.
Assessment of autoantibodies associated with intravenous immunoglobulin replacement therapy in children with primary immunodeficiency
Authors: Özer Murat , Tekeli Seher , Doğan Selçuk , Çetin Sema , Selen Rıdvan , Aytekin Caner
Published: July 2024

While it is known that immunoglobulin replacement therapy (IgRT) used in the treatment of primary immunodeficiency disorders (PIDs) can lead to the passive transfer of autoantibodies, there is no data indicating that these antibodies can cause clinical symptoms in patients. This study aimed to investigate the presence of autoantibodies and their clinical correlation in patients diagnosed with PIDs receiving IgRT. Paediatric patients who were diagnosed with PIDs, and administered IgRT at our immunology clinic between 1 January 2012 and 31 December 2021, were included in the study. The medical records of these patients were retrospectively analysed, and autoantibodies were screened. Autoantibody screening was conducted at least once in 48 cases. Among these cases, 29 cases (60.4%) demonstrated positivity for at least one of the autoantibodies screened in the study. Among these cases, 23 tested positive for anti‐TPO, 9 for anti‐TG and 2 for both anti‐TPO and anti‐TG. Only two of these patients were confirmed to have Hashimoto's thyroiditis. In 30 cases, autoantibodies related to Celiac disease (CD) were screened, with at least one being positive in five different cases; CD was not confirmed. The results of our study suggest that passive transfer of autoantibodies to patients with IgRT does not cause any significant clinical findings. In addition, in cases of PID, autoantibodies detected in the blood passed to patients with IgRT can lead to misdiagnosis. Screening for autoantibodies in patients with PID undergoing IgRT may not yield accurate results in terms of detecting autoimmune diseases.
Revisiting the charmed circle: A reflexive examination of unanswered questions in the infidelity literature
Authors: Weiser Dana A. , Shrout M. Rosie
Published: July 2024

Infidelity is a common experience in romantic relationships, and as such, relationships researchers have amassed a large infidelity literature. In the current manuscript, we provide a brief overview of the infidelity literature, specifically focusing on how infidelity is defined, infidelity attitudes, predictors of infidelity, and infidelity outcomes. Next, we introduce readers to the “Charmed Circle,” a theoretical perspective that conceptualizes monogamous sex as part of society's view of “good, normal, and natural” sex, otherwise known as mononormativity. As scholars, we are equally socialized in a system that endorses and reinforces mononormativity. In this article, we call on scholars to engage in reflexivity and consider how mononormativity has shaped the infidelity literature and their approach to research. We highlight pressing questions within the infidelity literature and argue that by questioning our own biases, assumptions, and methodologies, we will be able to further advance our understanding of infidelity.
Effect of gap size in grass cover on the percentage and rate of dandelion achene germination
Authors: Martinková Zdenka , Honěk Alois
Published: July 2024

In Central Europe, Taraxacum officinale Weber ex Wiggers (dandelion) is an economically important admixture in grasslands. Its spread is supported by its ability to germinate in gaps in grass stands. In a 5‐year experiment, we examined the effect of gap size on the germination rate and percentage of dandelion achenes. Each year, achenes were sown in late spring and mid‐summer in 90 square plots of six sizes, ranging from 2.5 × 2.5 cm to 80 × 80 cm. The plots were placed on a 2 × 6 m experimental area covered with low‐cut lawn. The course of germination varied among individual replicates depending on the weather. In each replicate, however, the rate of germination increased, and the percentage of germinated achenes decreased with increasing gap size. Differences in germination paralleled differences in the microclimate on the soil surface of plots where humidity decreased and temperature increased with plot size. The ultimate cause of this difference was the variance among gaps of different sizes in proportion to which the total area of the gap surface is insolated during the day. The colonization of lawns by dandelion is supported by the formation of small gaps in grass stands.
First record of an ixodid tick (Acari: Ixodidae) parasitic on the genus Pseudagkistrodon Van Denburgh (Squamata: Colubridae: Natricinae)
Authors: Amarga Ace Kevin , Robbins Richard G. , Lin Si-min
Published: July 2024

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Building better habitats: Spatiotemporal signaling cues in 3D biointerfaces for tailored cellular functionality
Authors: Ghorbani Sadegh , Sutherland Duncan S.
Published: July 2024

A promising research direction in the field of biological engineering is the design and functional programming of three-dimensional (3D) biointerfaces designed to support living cell functionality and growth in vitro, offering a route to precisely regulate cellular behaviors and phenotypes for addressing therapeutic challenges. While traditional two-dimensional (2D) biointerfaces have provided valuable insights, incorporating specific signaling cues into a 3D biointeractive microenvironment at the right locations and time is now recognized as crucial for accurately programming cellular decision-making and communication processes. This approach aims to engineer cell-centric microenvironments with the potential to recapitulate complex biological functions into a finite set of growing cellular organizations. Additionally, they provide insights into the hierarchical logic governing the relationship between molecular components and higher-order multicellular functionality. The functional live cell-based microenvironment engineered through such innovative biointerfaces has the potential to be used as an in vitro model system for expanding our understanding of cellular behaviors or as a therapeutic habitat where cellular functions can be reprogrammed.
Antibiotic duration and route for treatment of adults with uncomplicated streptococcal bloodstream infections: a retrospective study in a large healthcare system
Authors: Clutter Dana S. , Samiezade-Yazd Zahra , Champsi Jamila H. , Schapiro Jeffrey , Silverberg Michael J.
Published: July 2024

Data guiding the duration and route of streptococcal bloodstream infection (BSI) treatment are lacking. We conducted a retrospective cohort study of adults hospitalized with uncomplicated streptococcal BSI in a large integrated healthcare system from 2013 to 2020. The exposures of interest were antibiotic duration (5–10 days vs. 11–15 days) and antibiotic route (oral switch vs. entirely intravenous). The primary outcome was a composite 90-day outcome comprised of all-cause mortality, recurrent streptococcal BSI, or readmission. We performed non-inferiority analyses for each exposure. Separate multivariable Cox proportional hazards regression models were constructed for each exposure. The antibiotic duration analysis included 1,407 patients (5–10 days,
n
= 246; 11–15 days,
n
= 1,161). We found that 5–10-day courses were non-inferior to 11–15-day courses (
P
= 0.047). The antibiotic route analysis included 1,461 patients (oral switch,
n
= 1,112; entirely intravenous,
n
= 349). Oral step-down therapy did not meet the criteria for non-inferiority (
P
= 0.06). In the adjusted models, no significant difference was found in the primary outcome rate by antibiotic duration or antibiotic route at discharge. We found that 5–10-day courses were non-inferior to longer courses, and thus may be a safe and effective treatment option in the treatment of uncomplicated streptococcal bacteremia. Randomized controlled trials are needed to confirm the equivalent outcomes with shorter regimens and to definitively determine the optimal antibiotic route on discharge.
Developing microbiology literacy in biology education college: future teacher candidates
Authors: Fidiastuti Hasminar Rachman , Lestari Sri Rahayu , ‌ Suhadi , Prabaningtyas Sitoresmi
Published: July 2024

Recently, several articles have reflected on the existence of microorganisms in supporting the life and health of living creatures as the beginning of the emergence of microbiology literacy. In the curriculum, understanding the activity of microorganisms has been studied from pre-school, elementary school, and middle school to college. The presence of microorganisms is often associated as a cause of disease. As a result, most students know the negative impact of microorganisms but have not discovered the fundamental role of microorganisms in their lives. Special attention needs to be given as a form of effort to strengthen microbiology literacy. Several studies state that students have an important role in disseminating the concept of sterilization, maintaining a safe distance, and using masks as generally applicable protocols during the pandemic. Therefore, with the aim that microorganisms have an important role, both directly and indirectly and to curb negative perceptions of microorganisms, we propose microbiology competencies among biology education students, who are future teaching candidates. This article identifies the complex challenges of 21st-century microbiology learning and the OECD framework. This approach includes the use of pedagogical interventions with the main objectives: (i) knowledge (to teach fundamental microbiology knowledge, (ii) skills (to increase awareness in recognizing and solving real-life problems), and (iii) attitudes and values (to explain the contribution of microbiology in supporting life).
The cellular Notch1 protein promotes KSHV reactivation in an Rta-dependent manner
Authors: DeCotiis-Mauro Jennifer , Han Sun M. , Mello Helena , Goyeneche Corey , Marchesini-Tovar Giuseppina , Jin Lianhua , Bellofatto Vivian , Lukac David M.
Published: July 2024

The cellular Notch signal transduction pathway is intimately associated with infections by Kaposi’s sarcoma-associated herpesvirus (KSHV) and other gamma-herpesviruses. RBP-Jk, the cellular DNA binding component of the canonical Notch pathway, is the key Notch downstream effector protein in virus-infected and uninfected animal cells. Reactivation of KSHV from latency requires the viral lytic switch protein, Rta, to form complexes with RBP-Jk on numerous sites within the viral DNA. Constitutive Notch activity is essential for KSHV pathophysiology in models of Kaposi’s sarcoma (KS) and Primary Effusion Lymphoma (PEL), and we demonstrate that Notch1 is also constitutively active in infected Vero cells. Although the KSHV genome contains >100 RBP-Jk DNA motifs, we show that none of the four isoforms of activated Notch can productively reactivate the virus from latency in a highly quantitative trans-complementing reporter virus system. Nevertheless, Notch contributed positively to reactivation because broad inhibition of Notch1-4 with gamma-secretase inhibitor (GSI) or expression of dominant negative mastermind-like1 (dnMAML1) coactivators severely reduced production of infectious KSHV from Vero cells. Reduction of KSHV production is associated with gene-specific reduction of viral transcription in both Vero and PEL cells. Specific inhibition of Notch1 by siRNA partially reduces the production of infectious KSHV, and NICD1 forms promoter-specific complexes with viral DNA during reactivation. We conclude that constitutive Notch activity is required for the robust production of infectious KSHV, and our results implicate activated Notch1 as a pro-viral member of a MAML1/RBP-Jk/DNA complex during viral reactivation.

IMPORTANCE

Kaposi's sarcoma-associated herpesvirus (KSHV) manipulates the host cell oncogenic Notch signaling pathway for viral reactivation from latency and cell pathogenesis. KSHV reactivation requires that the viral protein Rta functionally interacts with RBP-Jk, the DNA-binding component of the Notch pathway, and with promoter DNA to drive transcription of productive cycle genes. We show that the Notch pathway is constitutively active during KSHV reactivation and is essential for robust production of infectious virus progeny. Inhibiting Notch during reactivation reduces the expression of specific viral genes yet does not affect the growth of the host cells. Although Notch cannot reactivate KSHV alone, the requisite expression of Rta reveals a previously unappreciated role for Notch in reactivation. We propose that activated Notch cooperates with Rta in a promoter-specific manner that is partially programmed by Rta’s ability to redistribute RBP-Jk DNA binding to the virus during reactivation.
Metabolic changes in
Toxoplasma gondii
-infected host cells measured by autofluorescence imaging
Authors: Gallego-López Gina M. , Contreras Guzman Emmanuel , Desa Danielle E. , Knoll Laura J. , Skala Melissa C.
Published: July 2024

Toxoplasma gondii,
the causative agent of toxoplasmosis, is an obligate intracellular parasite that infects warm-blooded vertebrates across the world. In humans, seropositivity rates of
T. gondii
range from 10% to 90% across communities. Despite its prevalence, few studies address how
T. gondii
infection changes the metabolism of host cells. In this study, we investigate how
T. gondii
manipulates the host cell metabolic environment by monitoring the metabolic response over time using noninvasive autofluorescence lifetime imaging of single cells, metabolite analysis, extracellular flux analysis, and reactive oxygen species (ROS) production. Autofluorescence lifetime imaging indicates that infected host cells become more oxidized and have an increased proportion of bound NAD(P)H compared to uninfected controls. Over time, infected cells also show decreases in levels of intracellular glucose and lactate, increases in oxygen consumption, and variability in ROS production. We further examined changes associated with the pre-invasion “kiss and spit” process using autofluorescence lifetime imaging, which also showed a more oxidized host cell with an increased proportion of bound NAD(P)H over 48 hours compared to uninfected controls, suggesting that metabolic changes in host cells are induced by
T. gondii
kiss and spit even without invasion.

IMPORTANCE

This study sheds light on previously unexplored changes in host cell metabolism induced by
T. gondii
infection using noninvasive, label-free autofluorescence imaging. In this study, we use optical metabolic imaging (OMI) to measure the optical redox ratio (ORR) in conjunction with fluorescence lifetime imaging microscopy (FLIM) to noninvasively monitor single host cell response to
T. gondii
infection over 48 hours. Collectively, our results affirm the value of using autofluorescence lifetime imaging to noninvasively monitor metabolic changes in host cells over the time course of a microbial infection. Understanding this metabolic relationship between the host cell and the parasite could uncover new treatment and prevention options for
T. gondii
infections worldwide.
De novo genome assembly of endophytic fungus
Nemania diffusa
strain YAFEF818, isolated from
Artemisia argyi
Authors: Yu Jiaojun , Yuan Xiaolong , Kui Yan , Li Yunqin , Bi Wei , Wang Yi
Published: July 2024

Here, we report a draft genome sequence of endophytic fungus
Nemania diffusa
YAFEF818, isolated from
Artemisia argyi
. Oxford Nanopore Technologies PromethION and Illumina NovaSeq sequence reads were assembled using NECAT and polished using pilon to yield a 55.63 Mb genome.
Complete genome sequence of
Enterococcus faecalis
B05
Authors: Li Jiahao , Wu Xiuyun , Meng Jing
Published: July 2024

Enterococcus faecalis
, a gram-positive bacterium, is the main intestinal bacteria in humans and animals. We report here the complete genome sequence of
E. faecalis
B05, whose genome length is 2,745,741 bp, containing 2,503 protein-coding genes, with a GC content of 37.64%.
Impact of diet change on the gut microbiome of common marmosets (
Callithrix jacchus
)
Authors: Tang-Wing Cassandra , Mohanty Ipsita , Bryant MacKenzie , Makowski Katherine , Melendez Daira , Dorrestein Pieter C. , Knight Rob , Caraballo-Rodríguez Andrés Mauricio , Allaband Celeste , Jenné Keith
Published: July 2024

Gastrointestinal diseases are the most frequently reported clinical problems in captive common marmosets (
Callithrix jacchus
), often affecting the health and welfare of the animal and ultimately their use as a research subject. The microbiome has been shown to be intimately connected to diet and gastrointestinal health. Here, we use shotgun metagenomics and untargeted metabolomics in fecal samples of common marmosets collected before, during, and after a dietary transition from a biscuit to a gel diet. The overall health of marmosets, measured as weight recovery and reproductive outcome, improved after the diet transition. Moreover, each marmoset pair had significant shifts in the microbiome and metabolome after the diet transition. In general, we saw a decrease in
Escherichia coli
and
Prevotella
species and an increase in
Bifidobacterium
species. Untargeted metabolic profiles indicated that polyamine levels, specifically cadaverine and putrescine, were high after diet transition, suggesting either an increase in excretion or a decrease in intestinal reabsorption at the intestinal level. In conclusion, our data suggest that
Bifidobacterium
species could potentially be useful as probiotic supplements to the laboratory marmoset diet. Future studies with a larger sample size will be beneficial to show that this is consistent with the diet change.

IMPORTANCE

Appropriate diet and health of the common marmoset in captivity are essential both for the welfare of the animal and to improve experimental outcomes. Our study shows that a gel diet compared to a biscuit diet improves the health of a marmoset colony, is linked to increases in
Bifidobacterium
species, and increases the removal of molecules associated with disease. The diet transition had an influence on the molecular changes at both the pair and time point group levels, but only at the pair level for the microbial changes. It appears to be more important which genes and functions present changed rather than specific microbes. Further studies are needed to identify specific components that should be considered when choosing an appropriate diet and additional supplementary foods, as well as to validate the benefits of providing probiotics. Probiotics containing
Bifidobacterium
species appear to be useful as probiotic supplements to the laboratory marmoset diet, but additional work is needed to validate these findings.
Evaluation of concordance of new QuantiFERON-TB Gold Plus platforms for
Mycobacterium tuberculosis
infection diagnosis in a prospective cohort of household contacts
Authors: Ruiz-Tagle Cinthya , García Patricia , Hernández Mariluz , Balcells María Elvira
Published: July 2024

Interferon-gamma (IFN-γ) release assays play a pivotal role in tuberculosis infection (TBI) diagnosis, with QuantiFERON-TB Gold Plus—an enzyme-linked immunosorbent assay (ELISA)—among the most widely utilized. Newer QuantiFERON-TB platforms with shorter turnaround times were recently released. We aimed to evaluate these platforms’ agreement in the diagnosis of TBI. Blood samples from a prospective cohort of tuberculosis household contacts were collected at baseline and after 12 weeks of follow-up, and tested with LIAISON, an automated chemiluminescence immunoassay (CLIA) system, QIAreach, a lateral flow (QFT-LF) semi-automated immunoassay, and the ELISA QuantiFERON-TB Gold Plus platform. Test concordances were analyzed. ELISA vs CLIA overall agreement was 83.3% for all tested samples (120/144) [Cohen’s kappa coefficient (κ): 0.66 (95% CI: 0.54–0.77)]. Samples positive with CLIA provided consistently higher IFN-γ levels than with ELISA (
P
< 0.001). Twenty-four (16.7%) discordant pairs were obtained, all CLIA-positive/ELISA-negative: 15 (62.5%) had CLIA IFN-γ levels within borderline values (0.35–0.99 IU/mL) and 9 (37.5%) >0.99 IU/mL. QFT-LF showed only 76.4% (68/89) overall agreement with ELISA [κ: 0.53 (95% CI: 0.37–0.68)] with 21 (23.6%) discordant results obtained, all QFT-LF-positive/ELISA-negative. Overall concordance between ELISA and CLIA platforms was substantial, and only moderate between ELISA and QFT-LF. The CLIA platform yielded higher IFN-γ levels than ELISA, leading to an almost 17% higher positivity rate. The techniques do not seem interchangeable, and validation against other gold standards, such as microbiologically-confirmed tuberculosis disease, is required to determine whether these cases represent true new infections or whether CLIA necessitates a higher cutoff.

IMPORTANCE

Tuberculosis is an airborne infectious disease caused by
Mycobacterium tuberculosis
that affects over 10 million people annually, with over 2 billion people carrying an asymptomatic tuberculosis infection (TBI) worldwide. Currently, TBI diagnosis includes tuberculin skin test and the blood-based interferon-gamma (IFN-γ) release assays, with Qiagen QuantiFERON-TB Gold Plus (QFT) being among those most widely utilized. We evaluated Qiagen's newer QFT platforms commercially available in a prospective cohort of tuberculosis contacts. A substantial agreement was obtained between the current QFT-enzyme-linked immunosorbent assay (ELISA) and the new QFT-chemiluminescence immunoassay (CLIA) platform, although QFT-CLIA provided higher concentrations of IFN-γ, leading to a 16.6% higher positivity rate. We highlight that both platforms may not be directly interchangeable and that further validation is required.
New and emerging treatments for major depressive disorder
Authors: Njenga Cecilia , Ramanuj Parashar Pravin , de Magalhães Frederico Jose Coelho , Pincus Harold Alan
Published: July 2024

Major depressive disorder (MDD) affects a substantial portion of the population; however, much is still unknown about the pathophysiology of this disorder. Treatment resistance highlights the heterogeneous nature of MDD and the need for treatments to target more than monoamine neurotransmission. This review summarizes research into the new and emerging targets of MDD. These include drugs such as psychedelics, antibiotics, opioid modulators, neuropeptides, and onabotulinumtoxin. Neuromodulatory treatments such as light based therapies and neuromodulation involving either magnetic or electrical stimulation are also discussed. Almost all interventions, pharmacological and neuromodulation, were trialed as adjunctive treatments to an antidepressant. Most research has been conducted on psychedelics, with trials suggesting rapid antidepressant and anti-suicidal effects. Trial findings, tolerability, study design limitations and quality of research have been considered throughout this review. There remains challenges in forming recommendations with the current research at present. With there being considerable interest into the research of new and emerging treatments—in particular, psychedelics—there may be scope in the future to form more robust recommendations.
Evolution of serious and life-threatening COVID-19 pneumonia as the SARS-CoV-2 pandemic progressed: an observational study of mortality to 60 days after admission to a 15-hospital US health system
Authors: Murthy Sudish C , Gordon Steven M , Lowry Ashley M , Blackstone Eugene H
Published: July 2024

Objective

In order to predict at hospital admission the prognosis of patients with serious and life-threatening COVID-19 pneumonia, we sought to understand the clinical characteristics of hospitalised patients at admission as the SARS-CoV-2 pandemic progressed, document their changing response to the virus and its variants over time, and identify factors most importantly associated with mortality after hospital admission.

Design

Observational study using a prospective hospital systemwide COVID-19 database.

Setting

15-hospital US health system.

Participants

26 872 patients admitted with COVID-19 to our Northeast Ohio and Florida hospitals from 1 March 2020 to 1 June 2022.

Main outcome measures

60-day mortality (highest risk period) after hospital admission analysed by random survival forests machine learning using demographics, medical history, and COVID-19 vaccination status, and viral variant, symptoms, and routine laboratory test results obtained at hospital admission.

Results

Hospital mortality fell from 11% in March 2020 to 3.7% in March 2022, a 66% decrease (p<0.0001); 60-day mortality fell from 17% in May 2020 to 4.7% in May 2022, a 72% decrease (p<0.0001). Advanced age was the strongest predictor of 60-day mortality, followed by admission laboratory test results. Risk-adjusted 60-day mortality had all patients been admitted in March 2020 was 15% (CI 3.0% to 28%), and had they all been admitted in May 2022, 12% (CI 2.2% to 23%), a 20% decrease (p<0.0001). Dissociation between observed and predicted decrease in mortality was related to temporal change in admission patient profile, particularly in laboratory test results, but not vaccination status or viral variant.

Conclusions

Hospital mortality from COVID-19 decreased substantially as the pandemic evolved but persisted after hospital discharge, eclipsing hospital mortality by 50% or more. However, after accounting for the many, even subtle, changes across the pandemic in patients’ demographics, medical history and particularly admission laboratory results, a patient admitted early in the pandemic and predicted to be at high risk would remain at high risk of mortality if admitted tomorrow.
Exploring fidelity of enactment in a cluster randomised controlled trial testing the effectiveness of ‘gatekeeper’ training for pesticide vendors in reducing self-poisoning in rural Sri Lanka: protocol for a multimethod qualitative study
Authors: Kanapathy Rajaratnam , Agampodi Thilini , Eddleston Michael , Konradsen Flemming , Pearson Melissa , Sanjula Bimali , Malalasekara Charuni , Naseer Nasman , Agampodi Suneth , Weerasinghe Manjula
Published: July 2024

Introduction

Pesticide self-poisoning causes severe health and socioeconomic hardship in low- and middle-income countries, including Sri Lanka. A stepped-wedge cluster randomised controlled trial (cRCT) has been designed to test whether ‘gatekeeper’ training for pesticide vendors reduces pesticide self-poisoning in rural Sri Lanka (Vendor cRCT). Ensuring intervention fidelity in RCTs is essential for consistently replicating interventions, accurately assessing their impact and improving outcomes. Thus, the overarching goal of this proposed study is to explore to what extent the pesticide vendors use the ‘gatekeeper’ strategies.

Methods and analysis

A multimethod qualitative research design is being used to explore the pesticide-selling behaviours of vendors after the ‘gatekeeper’ training. A subsample of the Vendor cRCT Study population is being recruited using a stratified purposive sampling method in all six intervention districts in Sri Lanka to ensure that the sample is representative of the pesticide vendors in the study area. Participant diaries, observations and focus group discussions are being adopted to collect data. Data triangulation will be performed and data will be analysed thematically.

Ethics and dissemination

The study was approved by the Ethics and Research Committee, Faculty of Medicine and Allied Sciences, at the Rajarata University of Sri Lanka (ERC/2023/09). All participants will provide informed consent. Findings will be disseminated in scientific peer-reviewed journals and conference presentations.
EASIER trial (Erector-spinAe analgeSia for hepatopancreaticobiliary pain In the Emergency Room): a single-centre open-label cohort-based randomised controlled trial analysing the efficacy of the ultrasound-guided erector-spinae plane block compared with intravenous morphine in the treatment of acute hepatopancreaticobiliary pain in the emergency department
Authors: David Sandeep Nathanael , Murali Vignesh , Kattumala Pradeep Daniel , Abhilash Kundavaram Paul Prabhakar , Thomas Ajith , Chowdury Sudipta Dhar , Karuppusami Reka
Published: July 2024

Background

Ultrasound-guided (USG) erector-spinae plane block (ESPB) may be better than intravenous opioids in treating acute hepatopancreaticobiliary (HPB) pain in the ED.

Methods

This open-label randomised controlled trial was conducted in the ED of a tertiary-care hospital between March and August 2023. All adult patients with severe HPB pain were recruited during times that a primary investigator was present. Unconsenting patients, numeric rating scale (NRS) ≤6, age ≤18 and ≥80 years, pregnant, unstable or with allergies to local anaesthetics or opioids were excluded. Patients in the intervention arm received bilateral USG ESPB with 0.2% ropivacaine at T7 level, by a trained ED consultant, and those in the control arm received 0.1 mg/kg intravenous morphine. Pain on a 10-point NRS was assessed by the investigators at presentation and at 1, 3, 5 and 10 hours after intervention by the treatment team, along with rescue analgesia requirements and patient satisfaction. Difference in NRS was analysed using analysis of co-variance (ANCOVA) and t-tests.

Results

70 participants were enrolled, 35 in each arm. Mean age was 40.4±13.2 years, mean NRS at presentation in the intervention arm was 8.0±0.9 and 7.6±0.6 in the control arm. NRS at 1 hour was significantly lower in the ESPB group (ANCOVA p<0.001). At 1, 3, 5 and 10 hours, reduction of NRS in the intervention arm (7±1.6, 6.7±1.9, 6.6±1.8, 6.1±1.9) was significantly greater than the control arm (4.4±2, 4.6±1.8, 3.7±2.2, 3.8±1.8) (t-test, p<0.001). Fewer patients receiving ESPB required rescue analgesia at 5 (t-test, p=0.031) and 10 hours (t-test, p=0.04). More patients were ‘very satisfied’ with ESPB compared with receiving only morphine at each time period (p<0.001).

Conclusion

ESPB is a promising alternative to morphine in those with HPB pain.

Trial registration number

CTRI/2023/03/050595.