bluuebunny/crossref_metadata_2025 huggingface dataset:
It’s More Than Language: Cultural Adaptation of a Proven Dementia Care Intervention for Hispanic/Latino Caregivers
Authors: Parker Lauren J , Marx Katherine A , Nkimbeng Manka , Johnson Elma , Koeuth Sokha , Gaugler Joseph E , Gitlin Laura N
Published: August 2022

Although Hispanic/Latino older adults are at disproportionate and increased risk for Alzheimer’s disease and related dementias, few evidence-based supportive care interventions are specifically developed for or adapted for this population. Adapting a supportive care intervention requires more than Spanish language translation; it necessitates an understanding of cultural nuances and care preferences of Hispanic/Latino families and staff who implement the intervention. This article describes the cultural adaptation of the Adult Day Service Plus intervention for delivery by staff to Hispanic/Latino caregivers, which was guided by the cultural adaptation process model. Also, using the Framework for Reporting Adaptations and Modifications—Enhanced, we discuss (a) when modifications were made, (b) who determined the modifications needed, (c) what aspects of the intervention were modified, (d) the relationship to fidelity and how fidelity was maintained, and (e) reasons for modifications. Modifications to the delivery and content were changed to reflect the values and norms of both the Hispanic/Latino staff and the caregivers they serve. As supportive interventions for caregivers are developed and implemented into real-world settings, inclusion of cultural elements may enhance research participation among Hispanic/Latino provider sites, people living with dementia, and their caregivers. Cultural adaptation is an essential consideration when developing, adapting, and implementing previously tested evidence-based interventions. Cultural adaptation offers an important lens by which to identify contextual factors that influence successful adoption to assure equity in the reach of evidence-based programs.
A machine learning framework for discovery and enrichment of metagenomics metadata from open access publications
Authors: Nassar Maaly , Rogers Alexander B , Talo' Francesco , Sanchez Santiago , Shafique Zunaira , Finn Robert D , McEntyre Johanna
Published: August 2022

Metagenomics is a culture-independent method for studying the microbes inhabiting a particular environment. Comparing the composition of samples (functionally/taxonomically), either from a longitudinal study or cross-sectional studies, can provide clues into how the microbiota has adapted to the environment. However, a recurring challenge, especially when comparing results between independent studies, is that key metadata about the sample and molecular methods used to extract and sequence the genetic material are often missing from sequence records, making it difficult to account for confounding factors. Nevertheless, these missing metadata may be found in the narrative of publications describing the research. Here, we describe a machine learning framework that automatically extracts essential metadata for a wide range of metagenomics studies from the literature contained in Europe PMC. This framework has enabled the extraction of metadata from 114,099 publications in Europe PMC, including 19,900 publications describing metagenomics studies in European Nucleotide Archive (ENA) and MGnify. Using this framework, a new metagenomics annotations pipeline was developed and integrated into Europe PMC to regularly enrich up-to-date ENA and MGnify metagenomics studies with metadata extracted from research articles. These metadata are now available for researchers to explore and retrieve in the MGnify and Europe PMC websites, as well as Europe PMC annotations API.
Larval dispersal simulations and connectivity predictions for Mediterranean gorgonian species: sensitivity to flow representation and biological traits
Authors: Sciascia Roberta , Guizien Katell , Magaldi Marcello G
Published: August 2022

Larval dispersal enables demographic and genetic connectivity among marine populations. For many sessile species, it is the only natural mechanism for resilience after major population disturbances, as those that have been affecting Mediterranean gorgonian species inside and outside Marine Protected Areas (MPAs). Larval dispersal simulation is a powerful tool to anticipate connectivity among populations which might be altered by modelling choices. We assessed how flow representation (resolution and vertical turbulence) and larval traits (pelagic larval duration, release timing and duration, larval vertical behaviour) influenced populations connectivity among five coastal rocky locations in the northwestern Mediterranean, four of them being designated as MPAs. We used a finer (0.3 km) and coarser (1.5 km) flow resolution in two years to assess, using a hierarchical simulation approach, the sensitivity of connectivity patterns to the above parameters. Larval traits corresponded to two gorgonian species, the neutrally buoyant Eunicella singularis and the passive sinker Paramuricea clavata. Ocean model resolution was the most influential factor on resulting connectivity patterns. When using the finer flow model resolution, connectivity patterns were equally influenced by all larval traits while vertical turbulence could be neglected. Hence, advising the design of coastal MPAs with regional connectivity estimates requires adequate flow simulation resolution.
High-resolution post-release behaviour and recovery periods of two highly prized recreational sportfish: the blue marlin and sailfish
Authors: Logan Ryan K , Vaudo Jeremy J , Lowe Christopher G , Wetherbee Bradley M , Shivji Mahmood S
Published: August 2022

High recreational catch rates of istiophorid billfishes in the eastern tropical Pacific (ETP) have led to substantial eco-tourism derived economic benefits for the countries in the region, prompting many countries to mandate catch-and-release practices for recreational anglers. Previous estimates of billfish post-release behaviours and recovery periods after these physiologically stressful capture events, however, vary widely depending on the type of tag used. Using high-resolution, multi-sensor biologging tags, we provide a fine-scale, detailed view of the behaviour and recovery periods of blue marlin (Makaira nigricans; n = 9) and sailfish (Istiophorus platypterus, Istiophoridae; n = 9) caught in a typical recreational fishery in the ETP. Angling times ranged from 4 to 90 min, and fish were monitored for periods of 6–70 h after release. Blue marlin showed a characteristic long, deep dive immediately after release, with significantly greater duration associated with longer fight times, a behaviour not typical for sailfish. Diving depths were, however, much shallower than those previously reported for both species due to the shallow thermocline and oxycline present in the ETP. Data from 40 derived metrics from acceleration (i.e. tailbeat period, amplitude, pitch, etc.) and physical parameters (i.e. depth, speed, temperature, oxygen saturation, etc.) used to quantify a recovery period suggest blue marlin and sailfish recover 9.0 ± 3.2 and 4.9 ± 2.8 h after release, respectively. Our high-resolution assessment of post-release behaviour suggests that these billfish are capable of rapid physiological recovery after capture in recreational fisheries, and that catch-and-release practices like those used here can be an effective approach to conserve and sustain billfish populations in the ETP. Predicted climate change caused shallowing of the oxygen minimum zone, however, would increase the vertical habitat compression present in this region, potentially prolonging or inhibiting recovery.
CRISPR-RNAa: targeted activation of translation using dCas13 fusions to translation initiation factors
Authors: Otoupal Peter B , Cress Brady F , Doudna Jennifer A , Schoeniger Joseph S
Published: August 2022

Tools for synthetically controlling gene expression are a cornerstone of genetic engineering. CRISPRi and CRISPRa technologies have been applied extensively for programmable modulation of gene transcription, but there are few such tools for targeted modulation of protein translation rates. Here, we employ CRISPR-Cas13 as a programmable activator of translation. We develop a novel variant of the catalytically-deactivated Cas13d enzyme dCasRx by fusing it to translation initiation factor IF3. We demonstrate dCasRx-IF3’s ability to enhance expression 21.3-fold above dCasRx when both are targeted to the start of the 5′ untranslated region of mRNA encoding red fluorescent protein in Escherichia coli. Activation of translation is location-dependent, and we show dCasRx-IF3 represses translation when targeted to the ribosomal binding site, rather than enhancing it. We provide evidence that dCasRx-IF3 targeting enhances mRNA stability relative to dCasRx, providing mechanistic insights into how this new tool functions to enhance gene expression. We also demonstrate targeted upregulation of native LacZ 2.6-fold, showing dCasRx-IF3’s ability to enhance expression of endogenous genes. dCasRx-IF3 requires no additional host modification to influence gene expression. This work outlines a novel approach, CRISPR-RNAa, for post-transcriptional control of translation to activate gene expression.
SMG-6 mRNA cleavage stalls ribosomes near premature stop codons in vivo
Authors: Kim John H , Modena Matthew S , Sehgal Enisha , Courney Annie , Neudorf Celine W , Arribere Joshua A
Published: August 2022

Nonsense-mediated mRNA decay (NMD) protects cells from the toxic and potentially dominant effects of truncated proteins. Targeting of mRNAs with early stop codons is mediated by the ribosome and spatiotemporally aligned with translation termination. Previously we identified a novel NMD intermediate: ribosomes stalled on cleaved stop codons, raising the possibility that NMD begins even prior to ribosome removal from the stop codon. Here we show that this intermediate is the result of mRNA cleavage by the endonuclease SMG-6. Our work supports a model in which ribosomes stall secondary to SMG-6 mRNA cleavage in Caenorhabditis elegans and humans, i.e. that the novel NMD intermediate occurs after a prior ribosome elicits NMD. Our genetic analysis of C. elegans’ SMG-6 supports a central role for SMG-6 in metazoan NMD, and provides a context for evaluating its function in other metazoans.
The DEAD-box helicase Hlc regulates basal transcription and chromatin opening of stress-responsive genes
Authors: Jia Ruirui , Lin Jiamei , You Jin , Li Shi , Shan Ge , Huang Chuan
Published: August 2022

Stress-responsive genes are lowly transcribed under normal conditions and robustly induced in response to stress. The significant difference between basal and induced transcription indicates that the general transcriptional machinery requires a mechanism to distinguish each transcription state. However, what factors specifically function in basal transcription remains poorly understood. Using a classic model stress-responsive gene (Drosophila MtnA), we found that knockdown of the DEAD-box helicase Hlc resulted in a significant transcription attenuation of MtnA under normal, but not stressed, conditions. Mechanistically, Hlc directly binds to the MtnA locus to maintain the accessibility of chromatin near the transcriptional start site, which allows the recruitment of RNA polymerase II and subsequent MtnA transcription. Using RNA-seq, we then identified plenty of additional stress-responsive genes whose basal transcription was reduced upon knockdown of Hlc. Taken together, these data suggest that Hlc-mediated basal transcription regulation is an essential and widespread mechanism for precise control of stress-responsive genes.
Mobilization with reduced cyclophosphamide for autologous stem cell transplantation is feasible in patients with systemic sclerosis
Authors: Pecher Ann-Christin , Ach Katharina Renate , Vogel Wichard , Henes Joerg Christoph
Published: August 2022

Objectives

To assess the feasibility of reduced cyclophosphamide dosing in the setting of mobilization chemotherapy prior to high dose chemotherapy and autologous stem cell transplantation in patients with SSc. The primary end point was the occurrence of ‘poor mobilization’ when using different cyclophosphamide dosing. The second end point was to analyse potential risk factors for difficult stem cell mobilization in this cohort of patients with SSc.

Methods

This single-centre study retrospectively reviewed 32 patients with SSc who underwent autologous stem cell transplantation. We analysed the occurrence of ‘poor mobilization’ (defined as CD34+ progenitor cell count <2 × 106/kg body weight, the use of increasing G-CSF dose, the use of plerixafor, or leukapheresis on >2 consecutive days) in different cyclophosphamide mobilization regimens: We herein compared low dose (2 × 1–1.5 g/m2) cyclophosphamide vs high dose (2 × 2 g/m2) for mobilization.

Results

Higher dosing of cyclophosphamide seems not to be beneficial regarding stem cell collection as there was no significant difference in stem cell yield between high dose and reduced dose cyclophosphamide (6.2 vs 5.2 × 106/kg bodyweight after CD34+ enrichment). Furthermore, higher doses of cyclophosphamide might be associated with more side effects; this difference was, however, not statistically significant. Lower bodyweight and BMI (P < 0.001) as well as rituximab pre-therapy (P < 0.05) and cardiac involvement (P < 0.01) might negatively impact stem cell collection independently from the chosen regimen.

Conclusion

Our data demonstrate that a reduced cyclophosphamide mobilization regimen seems to be feasible. Risk factors for poor mobilization might be low bodyweight, prior rituximab therapy and cardiac involvement.
Sexual dysfunction in women with systemic autoimmune rheumatic disorders: a systematic review and meta-analysis
Authors: Minopoulou Ioanna , Pyrgidis Nikolaos , Tishukov Maksim , Sokolakis Ioannis , Baniotopoulos Pantelis , Kefas Aristeidis , Doumas Michael , Hatzichristodoulou Georgios , Dimitroulas Theodoros
Published: August 2022

Objectives

In women with systemic autoimmune rheumatic diseases (SARDs), female sexual dysfunction (SD) remains underestimated. We aimed to explore the prevalence and correlates of SD in females with SARDs.

Methods

We performed a systematic review and meta-analysis of studies assessing the prevalence of SD and the pooled Female Sexual Function Index (FSFI) scores in this setting (PROSPERO: CRD42021287346). We searched PubMed, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) databases and grey literature until February 2022. We evaluated the quality of the selected records using the Hoy Risk of Bias tool. A random-effects meta-analysis of proportions with the double arcsine transformation was conducted. Subgroup and sensitivity analyses, as well as meta-regression of important correlates, were conducted.

Results

We included 68 studies with 5457 females diagnosed with a SARD (mean age: 43.7 [12.9] years). The overall SD prevalence was 63% (95% CI: 56, 69%, I2 = 94%) and the overall FSFI total score was 19.7 points (95% CI: 18.4, 21, I2 = 97%). Including only sexually active females, the SD prevalence was estimated as 60% (95% CI: 53, 67%, I2 = 88%), whereas the FSFI total score was 22 points (95% CI: 20.8, 23.1, I2 = 93%). Across the different SARDs, women with Sjögren’s syndrome and systemic sclerosis reported the highest levels of SD (74%, 95% CI: 58, 87%, I2 = 84% and 69%, 95% CI: 54, 83%, I2 = 94%, respectively).

Conclusion

Sexual function in females with SARDs seems to be severely impaired, irrespective of the type of SARD. Screening and treatment of SD in females with SARDs should become an integral part of healthcare clinical practice.
Snoozing: an examination of a common method of waking
Authors: Mattingly Stephen M , Martinez Gonzalo , Young Jessica , Cain Meghan K , Striegel Aaron
Published: August 2022

Study Objectives

Snoozing was defined as using multiple alarms to accomplish waking, and considered as a method of sleep inertia reduction that utilizes the stress system. Surveys measured snoozing behavior including who, when, how, and why snoozing occurs. In addition, the physiological effects of snoozing on sleep were examined via wearable sleep staging and heart rate (HR) activity, both over a long time scale, and on the days that it occurs. We aimed to establish snoozing as a construct in need of additional study.

Methods

A novel survey examined snoozing prevalence, how snoozing was accomplished, and explored possible contributors and motivators of snoozing behavior in 450 participants. Trait- and day-level surveys were combined with wearable data to determine if snoozers sleep differently than nonsnoozers, and how snoozers and nonsnoozers differ in other areas, such as personality.

Results

57% of participants snoozed. Being female, younger, having fewer steps, having lower conscientiousness, having more disturbed sleep, and being a more evening chronotype increased the likelihood of being a snoozer. Snoozers had elevated resting HR and showed lighter sleep before waking. Snoozers did not sleep less than nonsnoozers nor did they feel more sleepiness or nap more often.

Conclusions

Snoozing is a common behavior associated with changes in sleep physiology before waking, both in a trait- and state-dependent manner, and is influenced by demographic and behavioral traits. Additional research is needed, especially in detailing the physiology of snoozing, its impact on health, and its interactions with observational studies of sleep.
Association betweenToxoplasma gondiiInfection and Nephrotic Syndrome Risk in Children: A Case–Control Study and Systematic Review
Authors: Sorkhi Hadi , Mollalo Abolfazl , Bijani Ali , Mehravar Saeed , Pournasrollah Mohammad , Sadr Moharerpour Sahar , Rostami Ali
Published: August 2022

Some evidence suggests toxoplasmosis as an etiology of nephrotic syndrome (NS) in children; however, no observational study evaluated this relationship. In a case–control study, we enrolled 35 children with NS and 37 healthy children. All participants were examined for anti-Toxoplasma immunoglobulin G and M (IgG and IgM) antibodies using enzyme-linked immunosorbent assay. We also systematically reviewed the literature to assess this relationship. Prevalence of anti-Toxoplasma IgG was 17.4% and 13.5% in cases and controls, respectively, indicating a non-significant association (adjusted odds ratio, 1.22, 95% confidence interval, 0.35–4.41). No subjects were seropositive for IgM. In a systematic review, we found that acute toxoplasmosis can induce NS in some children and anti-Toxoplasma treatment is effective in the remission of NS in these cases. In pediatrics with NS, acute toxoplasmosis should be considered as a neglected causative factor.
Examining the Impact of Dialogic Learning on Critically Reflective Practice
Authors: Boyd Victoria A. , Woods Nikki N. , Kumagai Arno K. , Kawamura Anne A. , Orsino Angela , Ng Stella L.
Published: August 2022

Purpose

While research is beginning to reveal the potential of dialogue in sparking critical reflection (critically reflective ways of seeing), additional research is needed to guide the teaching of critical reflection toward enabling critically reflective practice (critically reflective ways of seeing and doing). An experimental study was conducted to investigate the impact of dialogic learning on critically reflective practice, compared to discussion-based learning. The dialogic intervention integrated the theory of Mikhail Bakhtin with the theory of critical reflection and critical disability studies.

Method

In interprofessional groups of 4, medical, occupational therapy, and speech-language pathology students were randomly assigned to a learning condition that used a reflective discussion or critically reflective dialogue about a pediatric patient case. All participants were then randomly assigned a clinical report for a novel pediatric patient and asked to write a hypothetical clinical letter to the child’s school. Hierarchical logistic regression models were constructed to estimate the probabilities of sentences and letters being critically reflective.

Results

The probability of sentences being critically reflective was significantly higher for the dialogue condition (0.26, 95% CI [0.2, 0.33]), compared to the discussion condition (0.11, 95% CI [0.07, 0.15]). Likewise, the probability of letters being critically reflective was significantly higher for the dialogue condition (0.26, 95% CI [0.15, 0.4]), compared to the discussion condition (0.04, 95% CI [0.01, 0.16]). In both conditions, the probability of a letter being critically reflective was positively associated with the proportion of critically reflective sentences.

Conclusions

The results demonstrate dialogic learning prepared students to enact critically reflective practice when writing mock clinical letters. Students who participated in a dialogue engaged in a collaborative process of critical reflection and subsequently applied that way of seeing in the individual act of writing a letter. This study highlights how Bakhtin’s theory of dialogue can advance critical pedagogy.
Management of intradialytic hypertension: current evidence and future perspectives
Authors: Iatridi Fotini , Theodorakopoulou Marieta P. , Papagianni Aikaterini , Sarafidis Pantelis
Published: August 2022

Intradialytic hypertension (IDH), that is, a paradoxical rise in blood pressure (BP) during or immediately after a hemodialysis session, affects approximately 10–15% of the hemodialysis population. It is currently recognized as a phenomenon of major clinical significance as recent studies have shown that BP elevation extends to the whole interdialytic interval and associates with increased cardiovascular and all-cause mortality. The pathophysiology of IDH is complex involving volume and sodium overload, endothelial dysfunction, excess renin–angiotensin–aldosterone system and sympathetic nervous system activation, and other mechanisms. For several years, there was a scarcity of studies regarding IDH treatment; recently, however, several attempts to examine the effect of nonpharmacological and pharmacological measures on BP levels in IDH are made. This review attempts to summarize this latest evidence in the field of management of IDH and discuss areas for future research.
Variability of aldosterone, renin and the aldosterone-to-renin ratio in hypertensive patients without primary aldosteronism
Authors: Veldhuizen Gregory P. , Alnazer Rawan M. , Kroon Abraham A. , de Leeuw Peter W.
Published: August 2022

Objectives:

The aldosterone-to-renin ratio (ARR) is commonly used in the screening of primary aldosteronism. However, limited information is available with regard to the intra-patient variability in this ratio. Our objective is to determine whether ARR measurements are reliably consistent over both the short- and long-term.

Methods:

We assessed the short-term variability of the aldosterone-to-renin ratio in 116 unmedicated, essential hypertensive participants who had two blood samples taken in the morning of the same day for measurement of aldosterone and active plasma renin concentration. Long-term variability was studied in 22 unmedicated, essential hypertensive participants who had two blood samples taken approximately 1 year apart. All samples were taken under highly standardized conditions.

Results:

Our data show that renin, aldosterone and the aldosterone-to-renin ratio show marked variations, both when measured on the same day and when assessed at a longer interval. The ARR becomes increasingly variable as its mean value increases. Its degree of variability is similar in both the short-term and the long-term.

Conclusions:

Based on our findings, we conclude that the aldosterone-to-renin has acceptable short-term variability in the lower ranges, but increasingly dubious reliability as aldosterone-to-renin values rise. Thus, in a clinical context, great caution should be taken in interpreting point-measurements of moderate to high aldosterone-to-renin ratio values.
Predictive power of 24-h ambulatory pulse pressure and its components for mortality and cardiovascular outcomes in 11 848 participants recruited from 13 populations
Authors: Gavish Benjamin , Bursztyn Michael , Thijs Lutgarde , Wei Dong-Mei , Melgarejo Jesus D. , Zhang Zhen-Yu , Boggia José , Hansen Tine W. , Asayama Kei , Ohkubo Takayoshi , Kikuya Masahiro , Yang Wen-Yi , Stolarz-Skrzypek Katarzyna , Malyutina Sofia , Casiglia Edoardo , Lind Lars , Li Yan , Kawecka-Jaszcz Kalina , Filipovský Jan , Tikhonoff Valérie , Gilis-Malinowska Natasza , Dolan Eamon , Sandoya Edgardo , Narkiewicz Krzysztof , Wang Ji-Guang , Imai Yutaka , Maestre Gladys E. , O’Brien Eoin , Staessen Jan A.
Published: August 2022

Background:

The role of pulse pressure (PP) ‘widening’ at older and younger age as a cardiovascular risk factor is still controversial. Mean PP, as determined from repeated blood pressure (BP) readings, can be expressed as a sum of two components: ‘elastic PP’ (elPP) and ‘stiffening PP’ (stPP) associated, respectively, with stiffness at the diastole and its relative change during the systole. We investigated the association of 24-h ambulatory PP, elPP, and stPP (‘PP variables’) with mortality and composite cardiovascular events in different age classes.

Method:

Longitudinal population-based cohort study of adults with baseline observations that included 24-h ambulatory BP. Age classes were age 40 or less, 40–50, 50–60, 60–70, and over 70 years. Co-primary endpoints were total mortality and composite cardiovascular events. The relative risk expressed by hazard ratio per 1SD increase for each of the PP variables was calculated from multivariable-adjusted Cox regression models.

Results:

The 11 848 participants from 13 cohorts (age 53 ± 16 years, 50% men) were followed for up for 13.7 ± 6.7 years. A total of 2946 participants died (18.1 per 1000 person-years) and 2093 experienced a fatal or nonfatal cardiovascular event (12.9 per 1000 person-years). Mean PP, elPP, and stPP were, respectively, 49.7, 43.5, and 6.2 mmHg, and elPP and stPP were uncorrelated (r = −0.07). At age 50–60 years, all PP variables displayed association with risk for almost all outcomes. From age over 60 years to age over 70 years, hazard ratios of of PP and elPP were similar and decreased gradually but differently for pulse rate lower than or higher than 70 bpm, whereas stPP lacked predictive power in most cases. For age 40 years or less, elPP showed protective power for coronary events, whereas stPP and PP predicted stroke events. Adjusted and unadjusted hazard ratio variations were similar over the entire age range.

Conclusion:

This study provides a new basis for associating PP components with outcome and arterial properties in different age groups and at different pulse rates for both old and young age. The similarity between adjusted and unadjusted hazard ratios supports the clinical usefulness of PP components but further studies are needed to assess the prognostic significance of the PP components, especially at the young age.
Validation of Virtual Monochromatic Images and Effect of Body Size Obtained Using a Rapid kVp-switching Dual-energy Computed Tomography System: A Phantom Study
Authors: Wu Tung-Hsin , Ting Yun-Lung , Hwang Yi-Shuan , Chui Chen-Shou , Lin Cristopher K. J.
Published: August 2022

The objective of this paper is to validate virtual monochromatic computed tomography (CT) numbers and the effect of the body size of insert materials in phantoms on the findings of a dual-energy CT scanner. The material inserted in the phantom simulates human organs. This study investigated the effect of different body sizes on CT numbers to understand the accuracy of dual-energy CT. The effect of body size on virtual monochromatic CT numbers was investigated using a QRM phantom. The true monochromatic CT numbers of insert materials were calculated from coefficients obtained using NIST XCOM. The true Zeff values were supplied by phantom manufacturers or computed using Mayneord’s equation. The virtual monochromatic CT numbers of insert materials in both the phantoms varied with energy. The CT numbers of materials with a Zeff of >7.42 (water Zeff) and <7.42 decreased and increased with energy, respectively. The CT numbers were affected by phantom size as a function of energy. For water, tissues, and air, the CT numbers in the XL phantom were considerably larger than those in other phantom sizes at 40 keV. Body size affected the CT numbers, particularly for the XL size and at low energies. For all materials, the magnitude of difference between the measured and true CT numbers was related to the Zeff of the materials, potentially because the photoelectric effect is more prominent at low energies for materials with a higher Zeff. The difference in CT numbers appeared to be dependent on position. The true and measured Zeff agreed to within 6% for all the materials except the SR2 brain, for which the discrepancy was 25%.
Considerations for Radiation Safety Professionals to Prepare and Respond to the Next Pandemic
Authors: Emery R. J. , Patlovich S. J. , Gutierrez J. M. , Rios J.
Published: August 2022

The Health Physics Society’s stated mission is “excellence in the science and practice of radiation safety.” Why, then, should we discuss disease outbreaks, epidemics, and pandemics with radiation safety professionals? The answer is simple: all workers are impacted by infectious diseases—and, as safety professionals, we will inevitably be called upon to prepare for and respond to these events. The COVID-19 pandemic has disrupted every facet of life, including home, school, work, and leisure. Moreover, virtually all radiation safety professionals have been impacted by the pandemic either personally, academically, or professionally. Even if radiation safety professionals were not involved directly with COVID-19 response, they were impacted by school closures, remote schooling and work, testing regimes, temperature screenings, vaccination programs, and so forth. However, many radiation safety professionals have been intimately involved in COVID-19 response through activities such as the deployment of personal protective equipment, directional airflow verification for isolation areas, disinfection and decontamination efforts, the design and layout of testing and vaccine centers, and in many other ways. Yet, it is likely that many radiation safety professionals have not received formal training in epidemiology, disease control, or other related topics, and thus may not be attuned to the key aspects to consider when the next pandemic emerges—and it will.
ADP-dependent glucokinase (ADPGK) is not critical for the activation of human macrophages by LPS
Authors: Geiger Benjamin , Wang Bei-Tzu , Munteanu Bogdan , Riedel Jens , Zezina Ekaterina , Biesemann Nadine , Schmoll Dieter
Published: August 2022

Background:

Activated immune cells show an enhanced glucose metabolism, suggesting that the inhibition of this pathway selective in immune cells could be a potential approach to combat inflammatory diseases. We studied here whether ADP-dependent glucokinase (ADPGK), a glucose-phosphorylating enzyme predominantly expressed in immune cells, could be a suitable target for the inhibition of macrophage activation.

Methods:

The regulation and role of ADPGK in human primary macrophages differentiated from blood monocytes was studied using Real-time quantitative PCR (RT-qPCR), gene silencing, whole-cell MALDI-mass spectrometry (MS) imaging as well as immune-based and enzymatic medium analyzes.

Results:

The expression of ADPGK was induced in response to the activation of toll-like receptors (TLRs). The most robust effect was observed with the TLR4 ligand Lipopolysaccharide (LPS) leading to an approximately 4-fold increase of ADPGK RNA levels. For this induction, the activation of p38 MAPK and IKKε was important. Silencing of ADPGK expression using siRNAs had neither an effect on LPS-induced expression and release of proinflammatory cytokines nor on cellular ATP levels and lactate production. Untargeted metabolic cell profiling by whole-cell MALDI-MS imaging did not reveal any metabolic regulations after ADPGK down-regulation suggesting no specific metabolic pathway involvement.

Conclusions:

ADPGK neither catalyzes a rate-limiting step of glucose metabolism in LPS-activated macrophages nor is required for the proinflammatory phenotype of these cells in vitro. Our data do not indicate that ADPGK inhibition could be a pharmacological approach to modulate immunometabolism.
Severe infections in recipients of cancer immunotherapy: what intensivists need to know
Authors: Joseph Adrien , Lafarge Antoine , Mabrouki Asma , Abdel-Nabey Moustafa , Binois Yannick , Younan Romy , Azoulay Elie
Published: August 2022

Purpose of review

Given the increased number of cancer patients admitted in the ICU and the growing importance of immunotherapy in their therapeutic arsenal, intensivists will be increasingly confronted to patients treated with immunotherapies who will present with complications, infectious and immunologic.

Recent findings

Apart from their specific immunologic toxicities, cancer immunotherapy recipients also have specific immune dysfunction and face increased infectious risks that may lead to intensive care unit admission.

Chimeric antigen receptor T-cell therapy is associated with profound immunosuppression and the risks of bacterial, fungal and viral infections vary according to the time since infusion.

Immune checkpoint blockers are associated with an overall favorable safety profile but associations of checkpoint blockers and corticosteroids and immunosuppressive drugs prescribed to treat immune-related adverse events are associated with increased risks of bacterial and fungal infections.

The T-cell engaging bispecific therapy blinatumomab causes profound B-cell aplasia, hypogammaglobulinemia and neutropenia, but seems to be associated with fewer infectious adverse events compared with standard intensive chemotherapy.

Lastly, intravesical administration of Bacillus Calmette-Guérin (BCG) can lead to disseminated BCGitis and severe sepsis requiring a specific antibiotherapy, often associated with corticosteroid treatment.
Bone marrow fibrocytes: villain or white knight in thyroid-associated ophthalmopathy?
Authors: Proctor Erin S. , Smith Terry J.
Published: August 2022

Purpose of review

We attempt to provide an historical perspective on progress made in understanding the pathogenesis of thyroid-associated ophthalmopathy (TAO), focusing on the roles of orbital fibroblasts (OF) in the diseased orbit (termed GD-OF) and how these cells differ from those residing in the healthy orbit. GD-OF comprise both residential OF and those apparently derived from CD34+ fibrocytes.

Recent findings

CD34+ fibrocytes of the monocyte lineage putatively traffic to the TAO orbit from bone marrow. We believe that these fibroblastic cell populations dictate the activity and severity of TAO. Their impact on disease may be moderated by Slit2, a neuron axon guidance repellent synthesized by and released from residential CD34- OF. Approximately 50% of patients with GD develop clinically meaningful TAO. Relatively few require systemic medical and surgical therapies, while milder disease can be managed with conservative, local care. Determining the intrinsic properties of GD-OF and their expression of Slit2 may explain why some patients with GD develop severe, vision-threatening TAO while others virtually escape any of its manifestations. Such insights should allow for improved and better-tolerated therapies.

Identifying unique characteristics of fibrocytes and GD-OF subsets reveals their apparent roles in tissue activation, inflammation, and remodeling associated with TAO. Better understanding of these cells, their origins, behavior, and factors modulating their activities remains necessary for the development of more targeted, effective, and safe treatments.
Chlamydia Vaccination: Parent Opinions and Implications for Future Promotion Programs
Authors: Footman Alison , Kanney Nita , Niccolai Linda M. , Zimet Gregory D. , Overton Edgar Turner , Davies Susan L. , Van Der Pol Barbara
Published: August 2022

Background

Chlamydia vaccines are currently under development and have the potential to lower the incidence of infection and disease, which are highest among adolescents and young adults. Ideally, a chlamydia vaccine would be administered to adolescents before sexual debut, a time when parents are the primary vaccine decision makers. This study explores parent opinions about an adolescent chlamydia vaccine to understand barriers and facilitators to uptake.

Methods

Semistructured interviews were conducted with parents of adolescents. Topics included conversations parents have with their children about chlamydia, opinions on chlamydia vaccine development, and vaccine characteristics, such as efficacy and cost. Interviews were analyzed using a thematic analysis approach.

Results

From March to April 2021, 21 interviews were completed. Few parents discuss chlamydia with their children and sex education was seen as limited. Overall, 16 parents indicated that a chlamydia vaccine is needed. However, there were mixed opinions about vaccinating their own children, related to the need to vaccinate at a young age, vaccine efficacy, and confusion about benefits of vaccination. Finally, healthcare provider recommendations were seen as important before deciding to vaccinate a child.

Conclusions

Although parents think that chlamydia vaccines are needed, lack of awareness about infections and potential benefits of vaccination could serve as barriers to uptake. Healthcare provider recommendations can help to improve knowledge and vaccine uptake. However, there is a need for multilevel approaches to improve chlamydia awareness and ensure that vaccination initiation and completion rates remain high.
Estimating Chlamydia and Gonorrhea Burden Among US Army Soldiers From Military Health System Data: Mind the Gap
Authors: Jordan Nikki N. , Gaydos Joel C. , Garges Eric C.
Published: August 2022

Background

Reporting systems are commonly used for chlamydia and gonorrhea surveillance and community burden assessments. Estimates are conservative given high proportions of asymptomatic cases and underreporting. The military's unified health system, which includes laboratory and medical encounter data, could offer insight into surveillance gaps and improve burden analyses.

Methods

Confirmed chlamydia and gonorrhea cases reported among active component soldiers were merged with laboratory and medical encounter records indicative of infection to identify incident cases during 2015–2019. Case capture across data systems was assessed, and reported case rates were compared with those derived from the enhanced 3-source database. Attributable medical encounters for total cases were extrapolated using average visits for the subset of cases with supporting encounter data. Multivariable generalized linear models were generated to characterize infections.

Results

Approximately 83% and 76% of respective chlamydia and gonorrhea cases were identified through reporting, compared with 87% and 67% through laboratory records, and 58% for both through medical encounters. Rates from enhanced 3-source surveillance peaked at 2844 chlamydia and 517 gonorrhea cases per 100,000 person-years in 2019, reflecting 17% and 28% increases in respective rates compared with reported rates. Overall, 3163 cases of chlamydia and/or gonorrhea per 100,000 person-years were detected in 2019, affecting 13,004 soldiers and requiring an estimated 21,690 medical encounters. Soldiers who were younger, female, racial/ethnic minorities, nonmarried, enlisted, less educated, and Southern residents had significantly higher risk.

Conclusion

Integration of laboratory and medical encounter data substantially improved burden estimation over reporting alone. Rates generated remain conservative because they only reflect documented cases. Increasing rates support prevention prioritization, particularly among young soldiers.
Monkeypox and Herpes Simplex Virus Type 2 Coinfection: Case Report of Perianal Lesions in HIV-Positive Patient
Authors: Zlámal Milan , Bartovská Zofia , Burantová Anna , Zákoucká Hana , Jiřincová Helena , Chmel Martin , Holub Michal
Published: August 2022

We report a case of monkeypox and herpes simplex type 2 coinfection in an HIV-positive male patient who has sex with men. This case report describes a diagnostic approach for papular rash in the anal area of the male patient who has sex with men with a history of sexually transmitted disease. This is also the first documented case of monkeypox in the Czech Republic, which was confirmed after a retrospective review of swab samples from a previously hospitalized HIV-positive patient.
Building Consensus for a Shared Definition of Adverse Events: A Case Study in the Profession of Dentistry
Authors: Franklin Amy , Kalenderian Elsbeth , Hebballi Nutan , Delattre Veronique , Etoule Jini , White Joel , Vaderhobli Ram , Stewart Denice , Kent Karla , Yansane Alfa , Walji Muhammad
Published: August 2022

Background

To achieve high-quality health care, adverse events (AEs) must be proactively recognized and mitigated. However, there is often ambiguity in applying guidelines and definitions. We describe the iterative calibration process needed to achieve a shared definition of AEs in dentistry. Our alignment process includes both independent and consensus building approaches.

Objective

We explore the process of defining dental AEs and the steps necessary to achieve alignment across different care providers.

Methods

Teams from 4 dental institutions across the United States iteratively reviewed patient records after identification of charts using an automated trigger tool. Calibration across teams was supported through negotiated definition of AEs and standardization of evidence provided in review. Interrater reliability was assessed using descriptive and κ statistics.

Results

After 5 iterative cycles of calibration, the teams (n = 8 raters) identified 118 cases. The average percent agreement for AE determination was 82.2%. Furthermore, the average, pairwise prevalence and bias-adjusted κ (PABAK) was 57.5% (κ = 0.575) for determining AE presence. The average percent agreement for categorization of the AE type was 78.5%, whereas the PABAK was 48.8%. Lastly, the average percent agreement for categorization of AE severity was 82.2% and the corresponding PABAK was 71.7%.

Conclusions

Successful calibration across reviewers is possible after consensus building procedures. Higher levels of agreement were found when categorizing severity (of identified events) rather than the events themselves. Our results demonstrate the need for collaborative procedures as well as training for the identification and severity rating of AEs.
Critical Care Clinicians’ Experiences of Patient Safety During the COVID-19 Pandemic
Authors: Rosen Amanda , Carter Danielle , Applebaum Jo R. , Southern William N. , Brodie Daniel , Schwartz Joseph , Cornelius Talea , Shelton Rachel C. , Yip Natalie H. , Pincus Harold A. , Hwang Calvin , Cooke Joseph , Adelman Jason S.
Published: August 2022

Objective

It is unknown how hospital- and systems-level factors have impacted patient safety in the intensive care unit (ICU) during the COVID-19 pandemic. We sought to understand how the pandemic has exacerbated preexisting patient safety issues and created novel patient safety challenges in ICUs in the United States.

Methods

We performed a national, multi-institutional, mixed-methods survey of critical care clinicians to elicit experiences related to patient safety during the pandemic. The survey was disseminated via email through the Society of Critical Care Medicine listserv. Data were reported as valid percentages, compared by COVID caseload and peak of the pandemic; free-text responses were analyzed and coded for themes.

Results

We received 335 survey responses. On general patient safety, 61% felt that conditions were more hazardous when compared with the prepandemic period. Those who took care of mostly COVID-19 patients were more likely to perceive that care was more hazardous (odds ratio, 4.89; 95% CI, 2.49–9.59) compared with those who took care of mostly non–COVID-19 or no COVID-19 patients. In free-text responses, providers identified patient safety risks related to pandemic adaptations, such as ventilator-related lung injury, medication and diagnostic errors, oversedation, oxygen device removal, and falls.

Conclusions

Increased COVID-19 case burden was significantly associated with perceptions of a less safe patient care environment by frontline ICU clinicians. Results of the qualitative analysis identified specific patient safety hazards in ICUs across the United States as downstream consequences of hospital and provider strain during periods of the COVID-19 pandemic.
Teamwork Before and During COVID-19: The Good, the Same, and the Ugly…
Authors: Rehder Kyle J. , Adair K. Carrie , Eckert Erin , Lang Richard W. , Frankel Allan S. , Proulx Joshua , Sexton J. Bryan
Published: August 2022

Objectives

The COVID 19 pandemic placed unprecedented strain on healthcare systems and workers, likely also impacting patient safety and outcomes. This study aimed to understand how teamwork climate changed during that pandemic and how these changes affected safety culture and workforce well-being.

Methods

This cross-sectional observational study of 50,000 healthcare workers (HCWs) in 3 large U.S. health systems used scheduled culture survey results at 2 distinct time points: before and during the first year of the COVID 19 pandemic. The SCORE survey measured 9 culture domains: teamwork climate, safety climate, leadership engagement, improvement readiness, emotional exhaustion, emotional exhaustion climate, thriving, recovery, and work-life balance.

Results

Response rate before and during the pandemic was 75.45% and 74.79%, respectively. Overall, HCWs reporting favorable teamwork climate declined (45.6%–43.7%, P < 0.0001). At a facility level, 35% of facilities saw teamwork climate decline, while only 4% saw an increase in teamwork climate. Facilities with decreased teamwork climate had associated decreases in every culture domain, while facilities with improved teamwork climate maintained well-being domains and saw improvements in every other culture domain.

Conclusions

Healthcare worker teamwork norms worsened during the COVID-19 pandemic. Teamwork climate trend was closely associated with other safety culture metrics. Speaking up, resolving conflicts, and interdisciplinary coordination of care were especially predictive. Facilities sustaining these behaviors were able to maintain other workplace norms and workforce well-being metrics despite a global health crisis. Proactive team training may provide substantial benefit to team performance and HCW well-being during stressful times.
Endonasal Endoscopic Removal of Orbital Cavernous Venous Malformation With Optic Neuropathy
Authors: Park Jung Yul , Cho Kyu-sup , Son Yu Bin , Choi Hee-young
Published: August 2022

Several surgical methods have been employed, but the management of orbital cavernous venous malformations at the orbital apex remains challenging. The authors present an endonasal endoscopy-assisted removal of an orbital apex cavernous venous malformation compressing the optic nerve with the addition of an inferomedial conjunctival approach. A 43-year-old Asian man presented with an orbital cavernous venous malformation incidentally found radiographically with a history of decreased vision of 20/50 oculus dexter (OD). The patient’s visual field index was 22%, with signs of optic neuropathy. An endonasal endoscopic procedure combining transconjunctival and caruncular orbitotomies was adopted because of its deep posterior placement inside the orbit. The cavernous venous malformation was removed without complications, and the visual function of the patients recovered. For these challenging lesions, an endonasal endoscopic technique with an anterior orbitotomy may be a promising alternative. Simple packing material may adequately repair the medial orbital wall; there were no complications during the 12-month follow-up period.