bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeted vs. full population screening costs for incident atrial fibrillation and AF-related stroke for a healthy population aged 65 years in the United Kingdom
Authors: Burdett Paul , Lip Gregory Y H
Published: February 2022

Aims

Atrial Fibrillation (AF) is the most common sustained heart arrhythmia and a major preventable cause of stroke. Stroke accounts for a large amount of health and social care funding and over the coming years is likely to place an increasing cost burden on the wider UK health care system. We therefore need to understand how an opportunistic AF screening programme would impact on healthcare costs of AF (and AF-related stroke) for the NHS.

Methods and results

Using UK population forecasts and prior published data we initially calculated the number of people to be screened, newly-diagnosed and treated for Atrial Fibrillation (AF), and the associated costs of such a programme for all 65 year olds and for just a ‘high risk’ group. The reduction in the number of stroke cases recorded and the associated cost savings were subsequently calculated, for 2020 and the projected estimates over the following decade. The number of newly diagnosed AF patients at 65 years old for the two groups (all 65 year olds and for just a ‘high risk’ group) would be in 6754 and 797 in 2020, rising to 9200 and 1086 in 2030, respectively. In 2020 the cost of the screening programme for the two options would be £14.3m and £1.7m. If AF is medicated and monitored then there would be a subsequent reduction in the number of stroke cases in 2020 by 4323 or 510 depending on the group screened, with associated savings of £394.2m and £46.5m,  respectively. Focussing on 2030 and should opportunistic screenings for AF be introduced at age 65, with subsequent treatment, it is predicted to reduce the number of stroke cases over the decade by 5888 if all 65 year olds are screened and 695 if just the high risk group are screened. If the number of strokes can be reduced by treating these screened AF patients, we would substantially reduce the health and social care costs of stroke by £654.6m and £77.3m,  respectively.

Conclusion

The number of newly diagnosed AF patients at age 65 will rise over the decade between 2020 and 2030. Screening and treatment of AF will substantially reduce the health and social care costs of AF-related stroke in the NHS.
Effect of irisin on the expression of osteoclast-related genes in cementoblasts
Authors: Zhao Chunyi , Wang Yunlong , Cao Zhengguo , Zhu Jiaqi , He Hong
Published: February 2022

Background and objectives

Cementoblasts can communicate with osteoclasts by synthesis and secretion of cytokines, such as RANKL, OPG, and M-CSF. Previously, we reported that irisin promotes the differentiation of cementoblasts, while the effect of irisin on cementoblast-mediated osteoclastogenesis remains inconclusive. This study aimed to explore the effect of irisin on the expression of osteoclastogenesis-related cytokines in cementoblasts.

Material and methods

An immortalized murine cementoblast cell line OCCM-30 was used. Immunofluorescence and Western Blot were performed to identify the expression of irisin receptor integrin alphaV and the activation of its downstream signals in OCCM-30 cells. Cells were treated with irisin (100 ng/ml) for various time lengths ranging from 0 to 72 hours, and then qRT-PCR was used to detect the expression of osteoclastogenesis-related genes, including RANKL, IL-6, M-CSF, OPG, Wnt5A, Sema3A. Cells were also incubated with irisin in a series of concentrations (0–200 ng/ml) for 24 hours, and then qRT-PCR and ELISA were performed to examine the above osteoclastogenesis-related cytokines.

Results

Irisin receptor integrin alphaV was expressed in OCCM-30 cells and its downstream signaling pathways were markedly activated by irisin. Both qRT-PCR and ELISA results revealed that RANKL and IL-6 were up-regulated by irisin while M-CSF, OPG, Wnt5A, Sema3A remained unaffected.

Conclusions

OCCM-30 cells were responsive to the stimulation of irisin. The expression of RANKL and IL-6 was significantly enhanced by irisin, suggesting a possible promotive effect on cementoblast-mediated osteoclastogenesis.
Effect of strigolactones on recruitment of the rice root-associated microbiome
Authors: Kim Bora , Westerhuis Johan A , Smilde Age K , Floková Kristýna , Suleiman Afnan K A , Kuramae Eiko E , Bouwmeester Harro J , Zancarini Anouk
Published: February 2022

Strigolactones are endogenous plant hormones regulating plant development and are exuded into the rhizosphere when plants experience nutrient deficiency. There, they promote the mutualistic association of plants with arbuscular mycorrhizal fungi that help the plant with the uptake of nutrients from the soil. This shows that plants actively establish—through the exudation of strigolactones—mutualistic interactions with microbes to overcome inadequate nutrition. The signaling function of strigolactones could possibly extend to other microbial partners, but the effect of strigolactones on the global root and rhizosphere microbiome remains poorly understood. Therefore, we analyzed the bacterial and fungal microbial communities of 16 rice genotypes differing in their root strigolactone exudation. Using multivariate analyses, distinctive differences in the microbiome composition were uncovered depending on strigolactone exudation. Moreover, the results of regression modeling showed that structural differences in the exuded strigolactones affected different sets of microbes. In particular, orobanchol was linked to the relative abundance of Burkholderia–Caballeronia–Paraburkholderia and Acidobacteria that potentially solubilize phosphate, while 4-deoxyorobanchol was associated with the genera Dyella and Umbelopsis. With this research, we provide new insight into the role of strigolactones in the interplay between plants and microbes in the rhizosphere.
Pathways to Justice: Historical Institutional Child Abuse and the Role of Activist Research
Authors: Lundy Patricia
Published: February 2022

This article contributes to the theorization of responses to historical institutional child abuse by critically analysing the role and utility of activist research. Drawing upon empirical research with survivors1 who participated in the Northern Ireland Historical Institutional Abuse Inquiry (HIAI or Hart Inquiry), including 43 in-depth interviews, five workshops and a survey, it shows that the Inquiry disempowered survivors, delimited voice, and fell short in meeting survivors’ justice needs. It further explores how activist research was used as a tool to empower survivors and achieve justice. The article begins with a detailed analysis of activist research principles, methodology and debates. It then uses a case study of the survivor-driven Panel of Experts on Redress to explore how, and to what effect, activist research was used to formulate pathways to justice. The article concludes that activist research has transformative potential. It gave voice to those historically marginalized and silenced, challenged powerful institutions, and brought about change to redress legislation. The amended legislation passed through Westminster in November 2019, significantly improving the Inquiry’s compensation package, thereby benefiting thousands of survivors in Northern Ireland and beyond. The article and findings provide lessons for those seeking to facilitate survivor participation in redress policy development and intervention strategies for historical harms.
Recognising Legal Parenthood in Chinese Same-sex Families: Obstacles, Conflicts, and Possible Resolutions
Authors: Weng Yi
Published: February 2022

Thousands of children are born to and raised by same-sex parents in China every year. However, Chinese law has not yet recognised the legitimacy of this new form of parent–child relationship. This article provides a comprehensive analysis of the legal obstacles and conflicts that same-sex parents are facing under Chinese law. The conclusion is that the missing connection of marital relationship, the impossibility of procreation in the natural way and the strong stance on public interests have created formidable barriers for same-sex parents to claim parenthood in China. The legal disconnect between intended parents and children is argued to be detrimental to children’s welfare and psychological health. In the end, solutions to alleviate the incongruence between social needs and the legal position are proposed for Chinese law to adopt.
Storified narrative: Awake photo archives in digital humanities
Authors: Zeng Jingyi , Xu Yongjun , Niu Li
Published: February 2022

The rise and development of digital humanities have brought new challenges and possibilities to the archival narrative. This article aims to explore the storified narrative path to awake photo archives in digital humanities. The authors clarify plot and plot unit definitions first, then focus on photo archives to analyze the path realization of the storified narrative. The authors also take the photo archives of Chinese Archivist Mr Wu Baokang, an example for a more specific explanation, which Mrs Wu Jiaqing authorizes. The plot-driven storified narrative path of photo archives involves two parts: story elements deconstruction and plot units representation, narrative clues construction, and plot generation. The plot-driven, storified narrative path can fully play the advantages of storifying and promoting the critical development of archival narrative under the research paradigm of digital humanities. By exploring the storified narrative path of archives, it is helpful to promote the activation, in-depth utilization, and widespread dissemination of archives, promote the integration of archival narrative with digital humanities, and provide support for digital humanities research.
A logic for biassed information diffusion by paranoid agents in social networks
Authors: Prandi Lorenzo , Primiero Giuseppe
Published: February 2022

Information transmission in social networks is riddled with issues of reliability and trustworthiness. One of the main sources of disinformation can be traced back to agents—human or artificial—whose political or cultural agenda is guided by conspiracy theories. Modelling and understanding the behaviour of such agents within social networks is therefore crucial to approach the disinformation problem. In the present paper, we formulate the logic (un)SecureNDsim*, equipped with a proof-theory and a relational semantics in which negative trust relations are defined formalizing the attitude of paranoid agents, i.e. agents distrusting any information originating from the authority and thereby spreading what can be characterized as the content of conspiracy theories. The logic is implemented in a multi-agent simulation aimed at analysing the effects of conspiracy theorists in networks of agents. In particular, we analyse consensus reaching scenarios and the ability of paranoid agents to induce the spread of potentially false information.
Cosmic Voids and BAO with relative baryon-CDM perturbations
Authors: Khoraminezhad Hasti , Vielzeuf Pauline , Lazeyras Titouan , Baccigalupi Carlo , Viel Matteo
Published: February 2022

We study the statistics of various large-scale structure tracers in gravity-only cosmological simulations including baryons and cold dark matter (CDM) initialized with two different transfer functions, and simulated as two distinct fluids. This allows us to study the impact of baryon-CDM relative perturbations on these statistics. In particular, we focus on the statistics of cosmic voids, as well as on the matter and halo real-space 2-point correlation function and baryon acoustic oscillations (BAO) peak. We find that the void size function is affected at the 1–2 per cent level at maximum, and that the impact is more important at higher redshift, while the void density profile and void bias are roughly unaffected. We do not detect a sizeable impact of relative baryon-CDM perturbations on the real-space correlation functions of matter and haloes or the BAO peak, which is in line with results from previous works. Our results imply that it would be hard to use voids or real-space correlation functions to constrain baryon-CDM relative perturbations, but also that we might not have to include them in models for the analysis of future cosmological surveys data.
Discovery of hot subdwarfs covered with helium-burning ash
Authors: Werner Klaus , Reindl Nicole , Geier Stephan , Pritzkuleit Max
Published: February 2022

Helium-rich subdwarf O stars (sdOs) are hot compact stars in a pre-white dwarf evolutionary state. Most of them have effective temperatures and surface gravities in the range Teff = 40 000–50 000 K and log g = 5.5–6.0. Their atmospheres are helium dominated. If present at all, C, N, and O are trace elements. The abundance patterns are explained in terms of nucleosynthesis during single star evolution (late helium core flash) or a binary He-core white dwarf merger. Here we announce the discovery of two hot hydrogen-deficient sdOs (PG1654+322 and PG1528+025) that exhibit unusually strong carbon and oxygen lines. A non-LTE model atmosphere analysis of spectra obtained with the Large Binocular Telescope and by the LAMOST survey reveals astonishingly high abundances of C ($\approx 20{{\ \rm per\ cent}}$) and O ($\approx 20{{\ \rm per\ cent}}$) and that the two stars are located close to the helium main sequence. Both establish a new spectroscopic class of hot H-deficient subdwarfs (CO-sdO) and can be identified as the remnants of a He-core white dwarf that accreted matter of a merging low-mass CO-core white dwarf. We conclude that the CO-sdOs represent an alternative evolutionary channel creating PG1159 stars besides the evolution of single stars that experience a late helium-shell flash.
Serial H3K27M cell-free tumor DNA (cf-tDNA) tracking predicts ONC201 treatment response and progression in diffuse midline glioma
Authors: Cantor Evan , Wierzbicki Kyle , Tarapore Rohinton S , Ravi Karthik , Thomas Chase , Cartaxo Rodrigo , Nand Yadav Viveka , Ravindran Ramya , Bruzek Amy K , Wadden Jack , John Vishal , May Babila Clarissa , Cummings Jessica R , Rahman Kawakibi Abed , Ji Sunjong , Ramos Johanna , Paul Alyssa , Walling Dustin , Leonard Marcia , Robertson Patricia , Franson Andrea , Mody Rajen , Garton Hugh J L , Venneti Sriram , Odia Yazmin , Kline Cassie , Vitanza Nicholas A , Khatua Soumen , Mueller Sabine , Allen Joshua E , Gardner Sharon L , Koschmann Carl
Published: February 2022

Background

Diffuse Midline Glioma (DMG) with the H3K27M mutation is a lethal childhood brain cancer, with patients rarely surviving 2 years from diagnosis.

Methods

We conducted a multi-site Phase 1 trial of the imipridone ONC201 for children with H3K27M-mutant glioma (NCT03416530). Patients enrolled on Arm D of the trial (n = 24) underwent serial lumbar puncture for cell-free tumor DNA (cf-tDNA) analysis and patients on all arms at the University of Michigan underwent serial plasma collection. We performed digital droplet polymerase chain reaction (ddPCR) analysis of cf-tDNA samples and compared variant allele fraction (VAF) to radiographic change (maximal 2D tumor area on MRI).

Results

Change in H3.3K27M VAF over time (“VAF delta”) correlated with prolonged PFS in both CSF and plasma samples. Nonrecurrent patients that had a decrease in CSF VAF displayed a longer progression free survival (P = .0042). Decrease in plasma VAF displayed a similar trend (P = .085). VAF “spikes” (increase of at least 25%) preceded tumor progression in 8/16 cases (50%) in plasma and 5/11 cases (45.4%) in CSF. In individual cases, early reduction in H3K27M VAF predicted long-term clinical response (>1 year) to ONC201, and did not increase in cases of later-defined pseudo-progression.

Conclusion

Our work demonstrates the feasibility and potential utility of serial cf-tDNA in both plasma and CSF of DMG patients to supplement radiographic monitoring. Patterns of change in H3K27M VAF over time demonstrate clinical utility in terms of predicting progression and sustained response and possible differentiation of pseudo-progression and pseudo-response.
Longitudinal Evaluation of Circulating Tumor DNA Using Sensitive Amplicon-Based Next-Generation Sequencing to Identify Resistance Mechanisms to Immune Checkpoint Inhibitors for Advanced Urothelial Carcinoma
Authors: Ravi Praful , Ravi Arvind , Riaz Irbaz B , Freeman Dory , Curran Catherine , Mantia Charlene , McGregor Bradley A , Kilbridge Kerry L , Pan Chong-Xian , Pek Michelle , Choudhury Yukti , Tan Min-Han , Sonpavde Guru P
Published: February 2022

Serial evaluation of circulating tumor DNA may allow noninvasive assessment of drivers of resistance to immune checkpoint inhibitors (ICIs) in advanced urothelial cancer (aUC). We used a novel, amplicon-based next-generation sequencing assay to identify genomic alterations (GAs) pre- and post-therapy in 39 patients with aUC receiving ICI and 6 receiving platinum-based chemotherapy (PBC). One or more GA was seen in 95% and 100% of pre- and post-ICI samples, respectively, commonly in TP53 (54% and 54%), TERT (49% and 59%), and BRCA1/BRCA2 (33% and 33%). Clearance of ≥1 GA was seen in 7 of 9 patients responding to ICI, commonly in TP53 (n = 4), PIK3CA (n = 2), and BRCA1/BRCA2 (n = 2). A new GA was seen in 17 of 20 patients progressing on ICI, frequently in BRCA1/BRCA2 (n = 6), PIK3CA (n = 3), and TP53 (n = 3), which seldom emerged in patients receiving PBC. These findings highlight the potential for longitudinal circulating tumor DNA evaluation in tracking response and resistance to therapy.
Policing White Supremacy: Asymmetry and Inequality in Protest Control
Authors: Cunningham David
Published: February 2022

Despite evident and oft-cited disparities in the policing of right-wing extremists and more progressive social movements, we understand much less about how such distinctions emerge and unfold as the police prepare for, and act within, protest events. How does the racial and political orientation of social movements affect how they are policed? What are the processes through which such effects are realized? In contrast with most existing studies of protest policing, which emphasize how the actions of authorities are conditioned by the degree of threat associated with, for example, the size or capacity for violence of a given protest target, the analysis here of a cluster of cases associated with the 2017 Unite the Right rally in Charlottesville, Virginia, recognizes the constructed nature of protest threats and highlights how those assumptions inform and interact with police planning and action. Findings emphasize how the degree of alignment between police and protesters shapes policing agents’ preparations for, and operational considerations within, protest events. This alignment provides a basis for asymmetric communication, differential assessment, and—ultimately—distinct treatment of different protest targets.
Temporal Variation and Factors Associated with Allergic Rhinitis in a Cohort of Rural Preschool Children from Sri Lanka
Authors: Rajapakse Shashanka , Amarasiri Lakmali , Yasaratne Duminda , Warnasekara Janith , Agampodi Suneth
Published: February 2022

Background

Allergic rhinitis is a common chronic childhood disease with a low diagnosis rate, causing poor quality of life, absenteeism, decreased school performance and significant healthcare cost. However, data on the prevalence of allergic rhinitis is sparse in preschoolers of rural geography, especially in developing countries.

Aim

To describe the epidemiology of allergic rhinitis in preschoolers from a rural geography of a developing country.

Methods

A population-based cross-sectional study was conducted in Anuradhapura district, Sri Lanka using the WHO-30 cluster methodology with probability proportionate to size sampling. The International Study of Asthma and Allergy in Childhood questionnaire was used to assess symptomatology.

Results

The response rate was 91.8%, with 548 (51.7%) male and 512 (48.3%) female participants. The mean age was 4.4 (± 0.7) years. Allergic rhinitis was reported in 123 (11.6%; 95% CI 9.7–13.5), and eye symptoms were reported in 41 (3.9%; 95% CI 2.8–5.2) children. Activities of daily living were disturbed due to nasal symptoms in 113 (10.7%; 95% CI 8.8–12.5). Allergic rhinitis was independently associated with severe asthma (OR 6.26; 95% CI 3.54–11.06), sleeping on the floor (OR 4.79; 95% CI 1.33–17.25) and having cats in the households (OR 1.86; 95% CI 1.18–2.91). Nasal symptoms were more common in January and August to October months. The standardized local highest monthly temperature, lowest monthly temperature, highest monthly humidity and dew point strongly predicted allergic rhinitis symptom exacerbation (F=4.8, p=0.036, adjusted R square=57.8%, VIF≤2.259, DW=2.1).

Conclusions

Allergic rhinitis affects 1 in 10 preschool children of rural Sri Lanka. The factors associated and environmental factor model developed to predict symptom exacerbation could be used to prevent allergic rhinitis exacerbations.
Propofol-induced Unresponsiveness Is Associated with a Brain Network Phase Transition
Authors: Pullon Rebecca M. , Warnaby Catherine E. , Sleigh Jamie W.
Published: February 2022

Background

The wakeful brain can easily access and coordinate a large repertoire of different states—dynamics suggestive of “criticality.” Anesthesia causes loss of criticality at the level of electroencephalogram waveforms, but the criticality of brain network connectivity is less well studied. The authors hypothesized that propofol anesthesia is associated with abrupt and divergent changes in brain network connectivity for different frequencies and time scales—characteristic of a phase transition, a signature of loss of criticality.

Methods

As part of a previously reported study, 16 volunteers were given propofol in slowly increasing brain concentrations, and their behavioral responsiveness was assessed. The network dynamics from 31-channel electroencephalogram data were calculated from 1 to 20 Hz using four phase and envelope amplitude–based functional connectivity metrics that covered a wide range of time scales from milliseconds to minutes. The authors calculated network global efficiency, clustering coefficient, and statistical complexity (using the Jensen–Shannon divergence) for each functional connectivity metric and compared their findings with those from an in silico Kuramoto network model.

Results

The transition to anesthesia was associated with critical slowing and then abrupt profound decreases in global network efficiency of 2 Hz power envelope metrics (from mean ± SD of 0.64 ± 0.15 to 0.29 ± 0.28 absolute value, P < 0.001, for medium; and from 0.47 ± 0.13 to 0.24 ± 0.21, P < 0.001, for long time scales) but with an increase in global network efficiency for 10 Hz weighted phase lag index (from 0.30 ± 0.20 to 0.72 ± 0.06, P < 0.001). Network complexity decreased for both the 10 Hz hypersynchronous (0.44 ± 0.13 to 0.23 ± 0.08, P < 0.001), and the 2 Hz asynchronous (0.73 ± 0.08 to 0.40 ± 0.13, P < 0.001) network states. These patterns of network coupling were consistent with those of the Kuramoto model of an order–disorder phase transition.

Conclusions

Around loss of behavioral responsiveness, a small increase in propofol concentrations caused a collapse of long time scale power envelope connectivity and an increase in 10 Hz phase-based connectivity—suggestive of a brain network phase transition.

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Racism and the Reproductive Health Experiences of U.S.-Born Black Women
Authors: Treder Kelly , White Katharine O. , Woodhams Elisabeth , Pancholi Rushina , Yinusa-Nyahkoon Leanne
Published: February 2022

OBJECTIVE:

To explore Black women's lived experiences of racism and the associated effects on reproductive health decisions and the reproductive health care experience.

METHODS:

We recruited participants through social media and community outreach. We conducted semi-structured individual interviews focusing on Black women's lived experiences of racism and their effects on reproductive health. We coded and analyzed interview transcripts using process coding methodology.

RESULTS:

Participants (N=21) were 21–45 years old and from Boston, Chicago, and Atlanta. Our primary themes were: 1) reproductive health racism across the life course, 2) anti-Black racism in the reproductive health care system, and 3) self-protective actions when interacting with the reproductive health care system. Reproductive racism across the life course included subthemes of early sexualization of Black women, heightened awareness of reproductive health inequities, and knowledge of reproductive oppression. Anti-Black racism in the reproductive health care system included subthemes of absence of shared decision making; vicarious reproductive health experiences; stereotyping, invalidation, and dismissal by reproductive health professionals; and medical mistrust. Participants guarded themselves against racism within reproductive health care by engaging in a variety of self-protective actions including seeking a health care professional of color, overpreparing for their appointments, enlisting advocates, seeking care only when desperate, and heightening symptoms to be heard.

CONCLUSION:

Personal, vicarious, and historical experiences of racism within reproductive health care triggered participants to perform self-protective actions when interacting with the reproductive health care system. These actions served to promote safety, autonomy and rehumanization within a system that has historically and contemporarily devalued Black reproductive health.
Validation of Respiratory Rate-Oxygenation Index in Patients With COVID-19–Related Respiratory Failure
Authors: Myers Laura C. , Mark Dustin , Ley Brett , Guarnieri Michael , Hofmeister Melinda , Paulson Shirley , Marelich Gregory , Liu Vincent X.
Published: February 2022

OBJECTIVES:

The respiratory rate-oxygenation (ROX) index is a fraction of oxygen saturation, Fio
2, and respiratory rate that has been validated to predict receipt of invasive mechanical ventilation in patients receiving high-flow nasal cannula (HFNC). This study aimed to validate ROX in a cohort of inpatients with COVID-19–related respiratory failure.

DESIGN:

Retrospective validation of the ROX index. We calculated sensitivity, specificity, positive predictive value, negative predictive value, and 95% CIs of ROX for invasive mechanical ventilation any time during hospitalization.

SETTING:

Twenty-one hospitals of Kaiser Permanente Northern California, an integrated healthcare delivery system.

PATIENTS:

We identified adults with positive severe acute respiratory syndrome coronavirus 2 polymerase chain reaction test within 3 weeks of, or during, hospitalization between February 1, 2020, and December 31, 2020. We calculated ROX at 12 hours after HFNC initiation. We grouped patients as low (≥ 4.88), intermediate (< 4.88 and ≥ 3.85), or high (< 3.85) risk using previously published thresholds.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

We identified 1,847 patients who had no limitation of life support. Of these, 525 (31.7%) received invasive mechanical ventilation any time during hospitalization and 511 died (27.7%). The sensitivity, specificity, positive predictive value, and negative predictive value of 12-hour ROX threshold (< 3.85) predicting invasive mechanical ventilation were 32.3% (95% CI, 28.5–36.3%), 89.8% (95% CI, 88.0–91.4%), 59.4% (95% CI, 53.8–64.9%), and 74.1% (95% CI, 71.8–76.3%), respectively.

CONCLUSIONS:

The 12-hour ROX index has a positive predictive value (59.4%) using threshold of less than 3.85 for COVID-19 patients needing invasive mechanical ventilation. Our health system has embedded ROX into the electronic health record to prioritize rounding during periods of inpatient surge.
Herpes Simplex Virus Encephalitis With Initial Negative Polymerase Chain Reaction in the Cerebrospinal Fluid: Prevalence, Associated Factors, and Clinical Impact*
Authors: de Montmollin Etienne , Dupuis Claire , Jaquet Pierre , Sarton Benjamine , Sazio Charline , Susset Vincent , Conrad Marie , Argaud Laurent , Demeret Sophie , Tadié Jean Marc , Barbier François , Wolff Michel , Timsit Jean-François , Visseaux Benoit , Sonneville Romain ,   the ENCEPHALITICA Study Group
Published: February 2022

OBJECTIVES:

To describe the prevalence, associated factors, and clinical impact of an initial negative herpes simplex virus (HSV) polymerase chain reaction (PCR) in critically ill patients with PCR-proven HSV encephalitis.

DESIGN:

Retrospective multicenter study from 2007 to 2017.

SETTING:

Forty-seven French ICUs.

PATIENTS:

Critically ill patients admitted to the ICU with possible/probable acute encephalitis and a positive cerebrospinal fluid (CSF) PCR for HSV.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

We included 273 patients with a median Glasgow Coma Scale score of 9 (6–12) at ICU admission. CSF HSV PCR was negative in 11 cases (4%), exclusively in lumbar punctures (LPs) performed less than 4 days after symptoms onset. Patients with an initial negative PCR presented with more frequent focal neurologic signs (4/11 [36.4%] vs 35/256 [13.7%]; p = 0.04) and lower CSF leukocytosis (4 cells/mm3 [3–25 cells/mm3] vs 52 cells/mm3 [12–160 cells/mm3]; p < 0.01). An initial negative PCR was associated with an increased delay between LP and acyclovir treatment (3 d [2–7 ] vs 0 d [0–0 d]; p < 0.01) and was independently associated with a poor neurologic outcome at hospital discharge (modified Rankin Scale score ≥ 4) (adjusted odds ratio, 9.89; 95% CI, 1.18–82.78).

CONCLUSIONS:

In severe herpes simplex encephalitis, initial negative CSF HSV PCR occurred in 4% of cases and was independently associated with worse neurologic outcome at hospital discharge. In these patients, a systematic multimodal diagnostic approach including early brain MRI and EEG will help clinicians avoid delayed acyclovir initiation or early inappropriate discontinuation.
Protein kinases in cardiovascular diseases
Authors: Chen Jiawen , Li Yafei , Du Chong , Wei Tianwen , Shan Tiankai , Wang Liansheng
Published: February 2022

Cardiovascular disease (CVD) remains the leading cause of death worldwide. Therefore, exploring the mechanism of CVDs and critical regulatory factors is of great significance for promoting heart repair, reversing cardiac remodeling, and reducing adverse cardiovascular events. Recently, significant progress has been made in understanding the function of protein kinases and their interactions with other regulatory proteins in myocardial biology. Protein kinases are positioned as critical regulators at the intersection of multiple signals and coordinate nearly every aspect of myocardial responses, regulating contractility, metabolism, transcription, and cellular death. Equally, reconstructing the disrupted protein kinases regulatory network will help reverse pathological progress and stimulate cardiac repair. This review summarizes recent researches concerning the function of protein kinases in CVDs, discusses their promising clinical applications, and explores potential targets for future treatments.
A Case of Congenital Syphilis—Focus on Histopathology and Literature Review
Authors: Balaban Alexandra , Al-Rohil Rami N.
Published: February 2022

Although a rare disease, the incidence of congenital syphilis is on the rise in the US. We report a case of early congenital syphilis in a 1-day-old premature boy with positive Rapid plasma reagin titer, respiratory insufficiency, disseminated intravascular coagulation, and encephalopathy, born to a mother with known syphilis infection. Skin examination showed diffuse truncal petechiae, desquamation of the distal extremities, and violaceous, retiform plaques on the buttocks and lower extremities. A biopsy was performed to rule out an infectious etiology or vasculitis. Histopathologic examination revealed irregular epidermal acanthosis with orthokeratosis and parakeratosis. There were foci of neutrophilic infiltrate forming rare pustules within the stratum corneum and focal intraepidermal eosinophils, neutrophils, and rare dyskeratotic keratinocytes. In the dermis, there was some minimal endothelial swelling with a perivascular, interstitial, and periadnexal infiltrate of lymphocytes, eosinophils, and rare plasma cells. A Treponema pallidum immunostain highlighted spirochetes present within the epidermis and within the eccrine ducts. Penicillin G therapy was administered for 10 days. The infant's Rapid plasma reagin titer trended downward until it was negative 6 months after birth. Literature review reveals 8 case reports within the last 20 years describing the histopathology of rashes in congenital syphilis. Herein we summarize the reported histopathology of rashes in congenital syphilis and compare it to the histopathology of rashes in secondary syphilis in adults.
Wells Syndrome-Like Histologic Pattern Caused by a Permanent Tattoo
Authors: Kazmi Maha , Elsensohn Ashley , Junkins-Hopkins Jacqueline M.
Published: February 2022

Tattoo reactions have become more common as tattoos gain visibility and popularity worldwide. A variety of inflammatory patterns have been described in association with tattoos— more commonly fibrosing, granulomatous, lichenoid, pseudolymphomatous, and spongiotic patterns. To date, there has been one case report of a Wells syndrome-like inflammatory pattern associated with a temporary Henna tattoo. Here we present the first case of a permanent tattoo with resulting flame figures, histologically resembling Wells syndrome. We believe this uncommon histologic pattern might be of interest for pathologists to be aware of.
Pilomatrical Acanthoma: An Extremely Rare Intraepidermal Variant of Pilomatricoma
Authors: He Lin , Hosler Gregory A.
Published: February 2022

Pilomatrical differentiation can be observed in a variety of benign and malignant tumors, with the most common prototype being pilomatricoma. Pilomatricoma often presents in the deep dermis or subcutis, and the sole involvement of epidermis is extremely rare. In our current case series, specimens from 5 patients were included with an average age of 68 years. All lesions presented as solitary verrucous or keratotic papules on the extremities, with 1 lesion having a prominent horn. All lesions have a variable mixture of basaloid matrical cells and shadow cells, and all lesions express β-catenin (strong nuclear and cytoplasmic), lymphoid enhancer–binding factor 1 within the matrical component, and pleckstrin homology-like domain family A member 1. The histomorphology and immunoprofile of all lesions are of pilomatrical differentiation, confined to the level of the epidermis. Based on these findings and analogous to the terminology used for other benign intraepidermal proliferations (hidroacanthoma simplex and epidermolytic acanthoma), we propose the term “pilomatrical acanthoma” for these rare lesions.
Ecological studies of COVID-19 and air pollution: How useful are they?
Authors: Villeneuve Paul J. , Goldberg Mark S.
Published: February 2022

Background:

Results from ecological studies have suggested that air pollution increases the risk of developing and dying from COVID-19. Drawing causal inferences from the measures of association reported in ecological studies is fraught with challenges given biases arising from an outcome whose ascertainment is incomplete, varies by region, time, and across sociodemographic characteristics, and cannot account for clustering or within-area heterogeneity. Through a series of analyses, we illustrate the dangers of using ecological studies to assess whether ambient air pollution increases the risk of dying from, or transmitting, COVID-19.

Methods:

We performed an ecological analysis in the continental United States using county-level ambient concentrations of fine particulate matter (PM2.5) between 2000 and 2016 and cumulative COVID-19 mortality counts through June 2020, December 2020, and April 2021. To show that spurious associations can be obtained in ecological data, we modeled the association between PM2.5 and the prevalence of human immunodeficiency virus (HIV). We fitted negative binomial models, with a logarithmic offset for county-specific population, to these data. Natural cubic splines were used to describe the shape of the exposure-response curves.

Results:

Our analyses revealed that the shape of the exposure-response curve between PM2.5 and COVID-19 changed substantially over time. Analyses of COVID-19 mortality through June 30, 2021, suggested a positive linear relationship. In contrast, an inverse pattern was observed using county-level concentrations of PM2.5 and the prevalence of HIV.

Conclusions:

Our analyses indicated that ecological analyses are prone to showing spurious relationships between ambient air pollution and mortality from COVID-19 as well as the prevalence of HIV. We discuss the many potential biases inherent in any ecological-based analysis of air pollution and COVID-19.
Precise characterization of a solitary pulmonary nodule using tumor shadow disappearance rate-corrected F-18 FDG PET and enhanced CT
Authors: Park Ki Seong , Seon Hyun Ju , Yun Ju-Sik , Yoo Su Woong , Lee Changho , Kang Sae-Ryung , Kim Jahae , Cho Sang-Geon , Song Ho-Chun , Bom Hee-Seung , Min Jung-Joon , Kwon Seong Young
Published: February 2022

We aimed to characterize solitary pulmonary nodule (SPN) using imaging parameters for F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) or enhanced CT corrected by tumor shadow disappearance rate (TDR) to reflect the tissue density.

We enrolled 51 patients with an SPN who underwent PET/CT and chest CT with enhancement. The FDG uptake of SPN was evaluated using maximum standardized uptake value (SUVmax) on PET/CT. The mean Hounsfield unit (HU) for each SPN was evaluated over the region of interest on nonenhanced and enhanced CT images. The change in mean HU (HUpeak-pre) was quantified by subtracting the mean HU of the preenhanced CT from that of the post-enhanced CT. TDR was defined as the ratio of the tumor area, which disappears at a mediastinal window, to the tumor area of the lung window. We investigated which parameters (SUVmax or HUpeak-pre) could contribute to the characterization of SPN classified by TDR value and whether diagnostic performance could be improved using TDR-corrected imaging parameters.

For SPN with higher tissue density (TDR <42%, n = 22), high value of SUVmax (≥3.1) was a significant factor to predict malignancy (P = .006). High value of HUpeak-pre (≥38) was a significant factor to characterize SPN (P = .002) with lower tissue density (TDR ≥42%, n = 29). The combined approach using TDR-corrected parameters had better predictive performance to characterize SPN than SUVmax only (P = .031).

Applying imaging parameters such as SUVmax or HUpeak-pre in consideration of tissue density calculated with TDR could contribute to accurate characterization of SPN.
The efficacy and safety of triptorelin-therapy following conservative surgery for deep infiltrating endometriosis
Authors: Zhu Libo , Guan Zheng , Huang Yan , Hua Keqin , Ma Liguo , Zhang Jian , Yang Dazhen , Perrot Valerie , Li Hongbo , Zhang Xinmei
Published: February 2022

Triptorelin is one of the most commonly used gonadotropin-releasing hormone agonists and has been used in the treatment of deep infiltrating endometriosis (DIE). This study aimed to evaluate the efficacy and safety of up to 24 weeks of triptorelin treatment after conservative surgery for DIE.

This prospective, non-interventional study was performed in 18 tertiary hospitals in China. Premenopausal women aged ≥18 years treated with triptorelin 3.75 mg once every 28 days for up to 24 weeks after conservative surgery for DIE were included. Endometriosis symptoms were assessed, using a visual analogue scale (0–10 cm) or numerical range (0–10), at baseline (pre-surgery) and routine visits 3, 6, 9, 12, 18, and 24 months after surgery. Changes in symptom intensity over time were primary outcome measures.

A total of 384 women (mean [standard deviation] age, 33.4 [6.2] years) were analyzed. Scores for all symptoms (pelvic pain, dysmenorrhea, ovulation pain, dyspareunia, menorrhagia, metrorrhagia, and gastrointestinal and urinary symptoms) assessed decreased from baseline over 24 months. Cumulative improvement rates in pelvic pain, dysmenorrhoa, ovulation pain, and dyspareunia were 74.4%, 83.6%, 55.1%, and 66.9%, respectively. The 24-month cumulative recurrence rate (≥1 symptom) was 22.2%. The risk of symptom recurrence was higher in patients with ≥2 versus 1 lesion (odds ratio [OR] 2.539; 95% CI: 1.458–4.423; P = .001) and patients with moderate (OR 5.733; 95% CI: 1.623–20.248; P = .007) or severe (OR 8.259; 95% CI: 2.449–27.851; P = .001) pain versus none/mild pain. Triptorelin was well tolerated without serious adverse events.

Triptorelin after conservative surgery for DIE improved symptoms over 24 months of follow up. The recurrence rate of symptoms was low and triptorelin was generally well tolerated.

Trial registration number: ClinicalTrials.gov, NCT01942369.
Clinical and genetic features of four patients with Pearson syndrome
Authors: Son Ji Soo , Seo Go Hun , Kim Yoon-Myung , Kim Gu-Hwan , Jin Hee Kyung , Bae Jae-sung , Im Ho Joon , Yoo Han-Wook , Lee Beom Hee
Published: February 2022

Pearson syndrome (PS) is a multisystem mitochondrial cytopathy arising from deletions in mitochondrial DNA. Pearson syndrome is a sporadic disease that affects the hematopoietic system, pancreas, eyes, liver, and heart and the prognosis is poor. Causes of morbidity include metabolic crisis, bone marrow dysfunction, sepsis, and liver failure in early infancy or childhood. Early diagnosis may minimize complications, but suspicion of the disease is difficult and only mitochondrial DNA gene testing can identify mutations. There is no specific treatment for PS, which remains supportive care according to symptoms; however, hematopoietic stem cell transplantation may be considered in cases of bone marrow failure.

We herein describe the clinical and genetic characteristics of four patients with PS. One patient presented with hypoglycemia, two developed pancytopenia, and the final patient had hypoglycemia and acute hepatitis as the primary manifestation. All patients had lactic acidosis. Additionally, all patients showed a variety of clinical features including coagulation disorder, pancreatic, adrenal, and renal tubular insufficiencies. Two patients with pancytopenia died in their early childhood. Our experience expands the phenotypic spectrum associated with PS and its clinical understanding.
Patterns of Concerns Among Hematological Cancer Survivors
Authors: Mayo Samantha J. , Brennenstuhl Sarah , Panesar Prabdeep , Bryant Ashley Leak
Published: February 2022

Background

Advances in treatment for hematological cancers warrant greater attention on survivorship concerns.

Objective

The aims of this study were to describe survivorship concerns among hematological cancer survivors, identify subgroups of survivors with distinct classes of concerns, and examine sociodemographic and clinical differences across subgroups.

Methods

We conducted a cross-sectional analysis of data from 1160 hematological cancer survivors, who rated their degree of concern regarding 20 physical, emotional, and practical changes. Clusters of concerns were identified using latent class analysis. Associations between respondent characteristics and cluster membership were calculated using multinomial logistic regression.

Results

Survivors had a mean of 7.5 concerns (SD, 4.6; range, 0–19), the most frequent being fatigue/tiredness (85.4%); anxiety, stress, and worry about cancer returning (70.2%); and changes to concentration/memory (55.4%). Three distinct classes of concerns were identified: class 1 (low, 47.0%), characterized by low endorsement of most concerns, apart from fatigue; class 2 (moderate, 32.3%), characterized by high endorsement of a combination of concerns across domains; and class 3 (high, 20.7%), characterized by the highest number of concerns out of the 3 identified classes, including greater endorsement of concerns relating to sexual well-being. Class membership was differentiated by survivor age, sex, marital status, and diagnosis.

Conclusions

Three distinct patterns of concerns were detected in a large sample of hematological cancer survivors. Patterns of concerns could be differentiated by survivor characteristics.

Implications for Practice

Our study highlights the concerns experienced by hematological cancer survivors and provides support for a tailored biopsychosocial approach to survivorship care in this context.
How Caregivers Cope and Adapt When a Family Member Is Diagnosed With a Hematologic Malignancy: Informing Supportive Care Needs
Authors: Albrecht Tara A. , Hoppe Rebecca , Winter Marcia A.
Published: February 2022

Background

Informal family caregivers (FCs) of adults with various diseases including hematologic malignancy (HM) experience low quality of life and psychological well-being. Although HMs are life-threatening cancers associated with high mortality, numerous symptoms, and lengthy hospitalizations and are therefore likely to be challenging for FCs to cope with, there is scant research exploring FC experiences.

Objective

The aim of this study was to describe the coping and adaptation of FCs of patients during diagnosis and treatment of HM.

Methods

This study used a qualitative descriptive design to analyze semi-structured interview responses from FCs (N = 28) within 3 months of the patients’ HM diagnosis. A content analysis was conducted to generate common themes.

Results

Family caregivers endorsed adaptive and maladaptive coping. Adaptive strategies included taking one day at a time, spirituality, engaging in pastimes, and utilizing emotional and instrumental family and community support. Maladaptive coping included wishful thinking, harmful habits, avoidance, and lacking or being unable to accept family and community support.

Conclusions

Findings highlight the complexities of caregiver burden as they support their loved ones with HM.

Implications for Practice

Family caregivers would benefit from receiving an interdisciplinary family-centered approach as their HM person is initiating treatment. Nurses should consider assessing the FCs’ psychosocial needs to help facilitate appropriate services, such as palliative care consultations, social work referrals, support groups, and/or counseling.
Orientation to the Operating Room
Authors: Olson Mary A. , Johnson Anastasia M.
Published: February 2022

A hospital system and a local college formed a partnership to create a customized orientation program for novice operating room nurses. Perioperative online modules, hands-on skills laboratories facilitated by qualified faculty, and clinical time with a preceptor were the foundations of the program. Outcomes included cost savings of 1.5 million dollars, increased nurse retention rates, and improved examination scores. Nursing professional development practitioners can utilize this model for operating room orientation best practice.
Building on Early Coronavirus (COVID-19) Pandemic Orientation Modifications to Improve Competency Validation for Newly Hired New-to-Practice and Experienced Nurses
Authors: Winslow Susan A. , Britt Cherika P. , Dorrell Jolene J. , Gentry Deborah J. , Gillis Debra D. , Hochmiller Kathy L. , Smith Catherine V. , McGee Genemarie W. , Wilkerson Julie S.
Published: February 2022

Nursing professional development and human resource leaders revised general nursing orientation content and structure based on changes because of COVID-19 in length, focus, and platforms from the early stages of the pandemic. The aim of this quality improvement project was to incorporate best of pandemic modifications with key stakeholders and new-to-practice and experienced nursing hire needs emerging from COVID-19 realities on the workforce. The benefit for nursing professional development practitioners is relatability of general nursing orientation revisions for sustainability of clinical excellence and safety.