bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficient detection and monitoring of pediatric brain malignancies with liquid biopsy based on patient-specific somatic mutation screening
Authors: Kojic Marija , Maybury Mellissa K , Waddell Nicola , Koufariotis Lambros T , Addala Venkateswar , Millar Amanda , Wood Scott , Pearson John V , Hansford Jordan R , Hassall Tim , Wainwright Brandon J
Published: February 2023

Background

Brain cancer is the leading cause of cancer-related death in children. Early detection and serial monitoring are essential for better therapeutic outcomes. Liquid biopsy has recently emerged as a promising approach for detecting these tumors by screening body fluids for the presence of circulating tumor DNA (ctDNA). Here we tested the limits of liquid biopsy using patient-specific somatic mutations to detect and monitor primary and metastatic pediatric brain cancer.

Methods

Somatic mutations were identified in 3 ependymoma, 1 embryonal tumor with multilayered rosettes, 1 central nervous system neuroblastoma, and 7 medulloblastoma patients. The mutations were used as liquid biomarkers for serial assessment of cerebrospinal fluid (CSF) samples using a droplet digital PCR (ddPCR) system. The findings were correlated to the imaging data and clinical assessment to evaluate the utility of the approach for clinical translation.

Results

We developed personalized somatic mutation ddPCR assays which we show are highly specific, sensitive, and efficient in detection and monitoring of ctDNA, with a positive correlation between presence of ctDNA, disease course, and clinical outcomes in the majority of patients.

Conclusions

We demonstrate the feasibility and clinical utility of personalized mutation-based liquid biopsy for the surveillance of brain cancer in children. However, even with this specific and sensitive approach, we identified some potential false negative analyses. Overall, our results indicate that changes in ctDNA profiles over time demonstrate the great potential of our specific approach for predicting tumor progression, burden, and response to treatment.
A critical analysis of neuro-oncology clinical trials
Authors: Kim Yeonju , Armstrong Terri S , Gilbert Mark R , Celiku Orieta
Published: February 2023

Background

Limitations in trial design, accrual, and data reporting impact efficient and reliable drug evaluation in cancer clinical trials. These concerns have been recognized in neuro-oncology but have not been comprehensively evaluated. We conducted a semi-automated survey of adult interventional neuro-oncology trials, examining design, interventions, outcomes, and data availability trends.

Methods

Trials were selected programmatically from ClinicalTrials.gov using primary malignant central nervous system tumor classification terms. Regression analyses assessed design and accrual trends; effect size analysis utilized survival rates among trials investigating survival.

Results

Of 3038 reviewed trials, most trials reporting relevant information were nonblinded (92%), single group (65%), nonrandomized (51%), and studied glioblastomas (47%) or other gliomas. Basic design elements were reported by most trials, with reporting increasing over time (OR = 1.24, P < .00001). Trials assessing survival outcomes were estimated to assume large effect sizes of interventions when powering their designs. Forty-two percent of trials were completed; of these, 38% failed to meet their enrollment target, with worse accrual over time (R = −0.94, P < .00001) and for US versus non-US based trials (OR = 0.5, P < .00001). Twenty-eight percent of completed trials reported partial results, with greater reporting for US (34.6%) versus non-US based trials (9.3%, P < .00001). Efficacy signals were detected by 15%–23% of completed trials reporting survival outcomes.

Conclusion

Low randomization rates, underutilization of controls, and overestimation of effect size, particularly pronounced in early-phase trials, impede generalizability of results. Suboptimal designs may be driven by accrual challenges, underscoring the need for cooperative efforts and novel designs. The limited results reporting highlights the need to incentivize data reporting and harmonization.
Multi-omics analysis reveals spatiotemporal regulation and function of heteromorphic leaves in Populus
Authors: Wu Zhihua , Jiang Zhenbo , Li Zhijun , Jiao Peipei , Zhai Juntuan , Liu Shuo , Han Xiaoli , Zhang Shanhe , Sun Jianhao , Gai Zhongshuai , Qiu Chen , Xu Jindong , Liu Hong , Qin Rui , Lu Rui
Published: February 2023

Despite the high economic and ecological importance of forests, our knowledge of the adaptive evolution of leaf traits remains very limited. Euphrates poplar (Populus euphratica), which has high tolerance to arid environment, has evolved four heteromorphic leaf forms, including narrow (linear and lanceolate) and broad (ovate and broad-ovate) leaves on different crowns. Here, we revealed the significant functional divergence of four P. euphratica heteromorphic leaves at physiological and cytological levels. Through global analysis of transcriptome and DNA methylation across tree and leaf developmental stages, we revealed that gene expression and DNA epigenetics differentially regulated key processes involving development and functional adaptation of heteromorphic leaves, such as hormone signaling pathways, cell division, and photosynthesis. Combined analysis of gene expression, methylation, ATAC-seq, and Hi-C-seq revealed longer interaction of 3D genome, hypomethylation, and open chromatin state upregulates IAA-related genes (such as PIN-FORMED1 and ANGUSTIFOLIA3) and promotes the occurrence of broad leaves while narrow leaves were associated with highly concentrated heterochromatin, hypermethylation, and upregulated abscisic acid pathway genes (such as Pyrabactin Resistance1-like10). Therefore, development of P. euphratica heteromorphic leaves along with functional divergence was regulated by differentially expressed genes, DNA methylation, chromatin accessibility, and 3D genome remodeling to adapt to the arid desert. This study advances our understanding of differential regulation on development and functional divergence of heteromorphic leaves in P. euphratica at the multi-omics level and provides a valuable resource for investigating the adaptive evolution of heteromorphic leaves in Populus.
Dynamic GOLVEN-ROOT GROWTH FACTOR 1 INSENSITIVE signaling in the root cap mediates root gravitropism
Authors: Xu Ke , Jourquin Joris , Xu Xiangyu , De Smet Ive , Fernandez Ana I , Beeckman Tom
Published: February 2023

Throughout the exploration of the soil, roots interact with their environment and adapt to different conditions. Directional root growth is guided by asymmetric molecular patterns but how these become established or are dynamically regulated is poorly understood. Asymmetric gradients of the phytohormone auxin are established during root gravitropism, mainly through directional transport mediated by polarized auxin transporters. Upon gravistimulation, PIN-FORMED2 (PIN2) is differentially distributed and accumulates at the lower root side to facilitate asymmetric auxin transport up to the elongation zone where it inhibits cell elongation. GOLVEN (GLV) peptides function in gravitropism by affecting PIN2 abundance in epidermal cells. In addition, GLV signaling through ROOT GROWTH FACTOR 1 INSENSITIVE (RGI) receptors regulates root apical meristem maintenance. Here, we show that GLV-RGI signaling in these 2 processes in Arabidopsis (Arabidopsis thaliana) can be mapped to different cells in the root tip and that, in the case of gravitropism, it operates mainly in the lateral root cap (LRC) to maintain PIN2 levels at the plasma membrane (PM). Furthermore, we found that GLV signaling upregulates the phosphorylation level of PIN2 in an RGI-dependent manner. In addition, we demonstrated that the RGI5 receptor is asymmetrically distributed in the LRC and accumulates in the lower side of the LRC after gravistimulation. Asymmetric GLV-RGI signaling in the root cap likely accounts for differential PIN2 abundance at the PM to temporarily support auxin transport up to the elongation zone, thereby representing an additional level of control on the asymmetrical auxin flux to mediate differential growth of the root.
An intrinsically disordered region-containing protein mitigates the drought–growth trade-off to boost yields
Authors: Liu Jun , Liu Jing , Deng Linbin , Liu Hongmei , Liu Hongfang , Zhao Wei , Zhao Yuwei , Sun Xingchao , Fan Shihang , Wang Hanzhong , Hua Wei
Published: February 2023

Drought stress poses a serious threat to global agricultural productivity and food security. Plant resistance to drought is typically accompanied by a growth deficit and yield penalty. Herein, we report a previously uncharacterized, dicotyledon-specific gene, Stress and Growth Interconnector (SGI), that promotes growth during drought in the oil crop rapeseed (Brassica napus) and the model plant Arabidopsis (Arabidopsis thaliana). Overexpression of SGI conferred enhanced biomass and yield under water-deficient conditions, whereas corresponding CRISPR SGI mutants exhibited the opposite effects. These attributes were achieved by mediating reactive oxygen species (ROS) homeostasis while maintaining photosynthetic efficiency to increase plant fitness under water-limiting environments. Further spatial-temporal transcriptome profiling revealed dynamic reprogramming of pathways for photosynthesis and stress responses during drought and the subsequent recovery. Mechanistically, SGI represents an intrinsically disordered region-containing protein that interacts with itself, catalase isoforms, dehydrins, and other drought-responsive positive factors, restraining ROS generation. These multifaceted interactions stabilize catalases in response to drought and facilitate their ROS-scavenging activities. Taken altogether, these findings provide insights into currently underexplored mechanisms to circumvent trade-offs between plant growth and stress tolerance that will inform strategies to breed climate-resilient, higher yielding crops for sustainable agriculture.
Liking or Needing? Theorizing on the Role of Affect in Network Behavior
Authors: van der Heijden Machiel
Published: February 2023

Informal networks are crucial for the functioning of public organizations and the quality of government service. Because of this, public administration scholars increasingly theorize on what drives informal network behavior, particularly in terms of whom public officials contact for information or advice. However, existing studies provide a rather rational and strategic account of how such networking occurs, pointing to factors, such as preference similarity, resource availability, and social capital as its main drivers. This article critiques the microfoundations of existing theoretical models, arguing that they (a) potentially require too extensive information-processing capabilities on behalf of individual decision-makers and (b) discount the role that affect and emotive responses are likely to play in the social activity of networked interaction. In response, this article proposes three lines of theorizing on how (interpersonal) affect can be incorporated into theorizing about the network behavior of public officials: (1) affect as a fallback strategy; (2) affect in the driver’s seat; and (3) affect as a decision distorter. Several methods are discussed to empirically pursue the presented lines of theorizing.
Quasilinear approach to bump-on-tail instability using non-Maxwellian distributions
Authors: Sheikh A , Zaheer S , Noreen N , Shah H A
Published: February 2023

Spacecraft observations provide evidence about the existence of various waves and kinetic instabilities in solar wind plasmas. These instabilities and waves play an important role in the dynamics of the solar wind. In the present work, bump-on-tail (BOT) instability is revisited by employing the κ and then the modified (r, κ) distributions using a quasilinear approach. The evolution of bump-on-tail instability is studied analytically and numerically by using the solar wind data. The growth rate of BOT instability for varying ratios of temperature and number density is also observed. It is observed that the maximum growth rate increases with increasing number density and decreases with increasing electron temperature in the bump. The effect of spectral indices κ in the kappa distribution and r and κ in the modified (r, κ) distribution functions ultimately contributes towards the shoulder and tail of the distribution functions and the results appear to have been modified. Stimulation of wave energy density shows rapid variation in the quasilinear evolution of bump-on-tail instability as compared to the simple linear model.
Silicone matrices for controlled dexamethasone release: toward a better understanding of the underlying mass transport mechanisms
Authors: Rongthong Thitiphorn , Qnouch Adam , Maue Gehrke Maria , Paccou Laurent , Oliveira Paulo , Danede Florence , Verin Jeremy , Vincent Christophe , Willart Jean-Francois , Siepmann Florence , Siepmann Juergen
Published: February 2023

Dexamethasone-loaded silicone matrices offer an interesting potential as innovative drug delivery systems, e.g. for the treatment of inner ear diseases or for pacemakers. Generally, very long drug release periods are targeted: several years/decades. This renders the development and optimization of novel drug products cumbersome: experimental feedback on the impact of the device design is obtained very slowly. A better understanding of the underlying mass transport mechanisms can help facilitating research in this field. A variety of silicone films were prepared in this study, loaded with amorphous or crystalline dexamethasone. Different polymorphic drug forms were investigated, the film thickness was altered and the drug optionally partially/completely exchanged by much more water-soluble dexamethasone ‘phosphate’. Drug release studies in artificial perilymph, scanning electron microscopy, optical microscopy, differential scanning calorimetry, X-ray diffraction and Raman imaging were used to elucidate the physical states of the drugs and polymer, and of the systems’ structure as well as dynamic changes thereof upon exposure to the release medium. Dexamethasone particles were initially homogeneously distributed throughout the systems. The hydrophobicity of the matrix former very much limits the amounts of water penetrating into the system, resulting in only partial drug dissolution. The mobile drug molecules diffuse out into the surrounding environment, due to concentration gradients. Interestingly, Raman imaging revealed that even very thin silicone layers (<20 µm) can effectively trap the drug for prolonged periods of time. The physical state of the drug (amorphous, crystalline) did not affect the resulting drug release kinetics to a noteworthy extent.
Diminished Auditory Cortex Dynamic Range and its Clinical Correlates in First Episode Psychosis
Authors: Sklar Alfredo L , Ren Xi , Chlpka Lydia , Curtis Mark , Coffman Brian A , Salisbury Dean F
Published: February 2023

Background and Hypothesis

There is growing appreciation for the contribution of sensory disruptions to disease morbidity in psychosis. The present study examined auditory cortex (AC) dynamic range: the scaling of neurophysiological responses to stimulus intensity, among individuals with a schizophrenia spectrum illness (FESz) and its relationship to clinical outcomes at disease onset.

Study Design

Magnetoencephalography (MEG) was recorded from 35 FESz and 40 healthy controls (HC) during binaural presentation of tones at three intensities (75 dB, 80 dB, and 85 dB). MRIs were obtained to enhance cortical localization of MEG sensor-level activity. All participants completed the MATRICS cognitive battery (MCCB) and Global Functioning: Role and Social scales (GFR/GFS). Patients were administered the Positive and Negative Syndrome Scale (PANSS).

Study Results

FESz exhibited reduced AC response relative to HC. Enhancement of AC activity to tones of increasing intensity was blunted in FESz relative to HC. Reduced dynamic range (85–75 dB AC response) was associated with lower GFS (r = .58) and GFR (r = .45) scores, worse MCCB performance (r = .45), and increased PANSS Negative symptom subscale scores (r = −.55) among FESz, relationships not observed with AC responses to individual tones.

Conclusion

Beyond an impaired AC response to pure tones, FESz exhibit reduced dynamic range relative to HC. This impairment was correlated with markers of disease morbidity including poorer community functioning as well as cognitive and negative symptoms. The relationship with impaired social functioning may reflect the role of AC dynamic range in decoding the emotional content of language and highlights its importance to future therapeutic sensory remediation protocols.
Missions as boundary objects for transformative change: understanding coordination across policy, research, and stakeholder communities
Authors: Janssen Matthijs J , Wesseling Joeri , Torrens Jonas , Weber K Matthias , Penna Caetano , Klerkx Laurens
Published: February 2023

Recent times have seen the rediscovery and adaptation of mission-oriented innovation policies (MIPs) for driving transformative change. While such policies seek to mobilise and align stakeholders, little is known about how missions feature in policy coordination processes. We argue that to facilitate the still troublesome operationalisation of MIPs, it is essential to understand missions as ‘boundary objects’ that have some shared meanings among the participants they convene, yet are open enough to be interpreted differently by distinct actors gathering in four interconnected policy arenas—i.e. a strategic, programmatic, implementation, and performance arena. By studying the European Commission’s Horizon Europe missions, we unravel how missions as boundary objects enable and disable the coordination of heterogeneous communities. The resulting analytical perspective highlights three key mechanisms for coordinating mission meanings across communities and arenas: convergence–divergence, passage, and reflexive learning. We conclude with research avenues for studying missions as boundary objects for facilitating concerted action.
Glutamate Positively Regulates Chitinase Activity and the Biocontrol Efficacy of Pseudomonas protegens
Authors: Takeuchi Kasumi , Ogiso Masayo , Morohoshi Tomohiro , Seo Shigemi
Published: February 2023

Broad-spectrum biocontrol by Pseudomonas protegens CHA0 and other fluorescent pseudomonads is achieved through the generation of various secondary metabolites with antibiotic activities against not only other microbes but, also, nematodes and insects present in the rhizosphere. A previous metabolomic study demonstrated that intracellular low–molecular weight effectors, such as guanosine tetraphosphate and γ-aminobutyrate, function as important signals in niche adaptation by strain CHA0 to plant roots. We investigated the role of amino acids in the biocontrol trait of P. protegens Cab57 towards Pythium damping off and root rot in cucumber. Among the 11 amino acids tested, only glutamate markedly enhanced the efficacy of biocontrol. An RNA-Seq analysis revealed that glutamate upregulated the expression of a chitinase gene cluster (c21370-c21380, in which the c21370 gene was annotated as a gene encoding the chitin-binding protein cbp and the c21380 gene encoded chitinase chiC) in strain CHA0. Glutamate upregulated the expression of the regulatory small RNA rsmZ but reduced the production levels of other Gac/Rsm-regulated biocontrol factors, such as 2,4-diacetylphloroglucinol and pyoluteorin. The promoter activity of cbp and chitinase activity were characterized in detail; their activities were up-regulated in response to glutamate and their expression was under the control of GacA. Therefore, glutamate appears to be essential for biocontrol activity in which chitinase production is regulated in response to glutamate.

[Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
A review of organizing pneumonia
Authors: Ketchersid Kimberlee
Published: February 2023

Organizing pneumonia is a clinical and pathological syndrome that describes a lung injury caused by an inflammatory reaction in the alveolar connective tissue. Classified as an interstitial lung disease, it can be secondary to infection, drug toxicity, connective tissue disorders, inhalation injuries (cocaine), organ transplant, or radiotherapy, and also can be idiopathic. Although organizing pneumonia is not a new phenomenon, it has been noted to be a complication of COVID-19, and should be considered in patients who have had COVID-19 and have atypical chest imaging, because treatment includes corticosteroids instead of antimicrobials.
Inflammasomes in Human Immunodeficiency Virus Type 1 Infection
Authors: Wang Qiankun , Shan Liang
Published: February 2023

Innate immune responses are the host's first line of defense against human immunodeficiency virus type 1 (HIV-1) infection, with pattern recognition receptors detecting viral specific pathogen-associated molecular patterns and initiating antiviral responses. In response to HIV-1 nucleic acids or proteins, some pattern recognition receptors have the ability to assemble a large multiprotein complex called the inflammasome, which triggers pro-inflammatory cytokine release and a form of lytic programmed cell death called pyroptosis. Here, we review our current understanding of the mechanism of the inflammasome in sensing HIV-1 infection. Furthermore, we discuss the contribution of inflammasome activation in HIV-1 pathogenesis as well as potential strategies of targeting inflammasome activation for the treatment of HIV-1 infection.
IMB-0523 Inhibits Enterovirus 71 Replication by Activating Signal Transducer and Activator of Transcription 3 Signaling to Upregulate Interferon-Stimulated Genes Expression
Authors: Wang Huiqiang , Ge Miao , Li Yanping , Li Yuhuan , Li Zhuorong
Published: February 2023

Background

Hand, foot, and mouth disease caused by enterovirus 71 (EV71) infection is prevalent in the Asia-Pacific region in recent years. Currently, no drug is available for the prevention and treatment of EV71 infection. IMB-0523, a N-phenylbenzamide derivative, inhibits hepatitis B virus replication by upregulating the expression of APOBEC3G. In the present study, the effect of IMB-0523 on EV71 replication and related mechanism were investigated.

Methods

The cytotoxicity of IMB-0523 was determined by cell counting kit. Quantitative real-time polymerase chain reaction and Western blot assay were used to detect the effect of IMB-0523 on EV71 replication and related mechanism. Cytopathic effect assay was used to investigate the effect of IMB-0523 on different EV71 strains, coxsackievirus A16, and coxsackieviruses of group B.

Results

The results showed that IMB-0523 could dose-dependently inhibit EV71 replication. Preliminary mechanism studies showed that IMB-0523 could activate STAT3 signaling to upregulate the expression of interferon-stimulated genes to play an antiviral role. In addition, IMB-0523 inhibited the replication of different EV71 strains, coxsackievirus A16, and coxsackieviruses of group B.

Conclusions

IMB-0523 inhibits EV71 replication by activating the STAT3 signaling pathway to upregulate interferon-stimulated gene expression. IMB-0523 has broad-spectrum antiviral potential and may be used as a lead compound for the development of broad spectrum antiviral drugs.
Retrospective Analysis of the Duration of Hospitalization of Imported Patients Infected with SARS-CoV-2 in Guangzhou, 2021
Authors: Xie Zhiwei , Tang Guofang , Li Lu , Shi Jingrong , Gan Qingxin , Zheng Xiaowen , Tang Jingyan , Zeng Huimin , Zhang Chuyu , Chen Sisi , Cui Jianping , Lin Zishi , Lin Lihua , Li Youxia , Liu Jinxin , Li Feng , Hu Fengyu , Tang Xiaoping , Deng Xilong
Published: February 2023

The pandemic of coronavirus disease 2019 is “not over,” in fact, the “dynamic clearing” policy for SARS-CoV-2 control and prevention in China has been firmly enforced. This study aimed to analyze the clinical symptoms and dynamic viral RNA changes in 2021 at Guangzhou Eighth People’s Hospital. This study showed that 31.4% of the patients (695/2212) tested negative for viral RNA from admission to the final release from quarantine. Of all negative cases, 86.5% (601/695) remained in the hospital for no more than 5 days and were asymptomatic or mild. Among the remaining 402 patients who stayed for no more than 5 days, 76.4% (307/402) were viral RNA retest positive during the isolation stage. However, 96.4% of the peak viral RNA (296/307) was over Ct = 33 cycles during the isolation stage.
Outpatient Parenteral Antibiotic Therapy for Diabetic Foot Osteomyelitis in an Uninsured and Underinsured Cohort
Authors: Schechter Marcos C. , Yao Yutong , Patel Manish , Andruski Rebecca , Rab Saira , Wong Jordan R. , Santamarina Gabriel , Fayfman Maya , Rajani Ravi , Kempker Russell R.
Published: February 2023

Background

Diabetic foot osteomyelitis (DFO) is usually treated with prolonged outpatient parenteral antibiotic therapy (OPAT). Evaluation and treatment of nonantibiotic aspects of DFO (eg, peripheral artery disease) are also recommended. There are limited data regarding OPAT practice patterns and outcomes for DFO.

Methods

Single-center observational study of patients receiving OPAT for DFO in a large United States public hospital between January 2017 and July 2019. We abstracted data regarding microbiology test, antibiotics, clinical outcomes, and nonantibiotic DFO management.

Results

Ninety-six patients were included and some had >1 DFO-OPAT course during the study period (106 DFO-OPAT courses included). No culture was obtained in 40 (38%) of courses. Methicillin-resistant Staphylococcus aureus was cultured in 15 (14%) and Pseudomonas aeruginosa in 1 (1%) of DFO-OPAT courses. An antibiotic with methicillin-resistant S. aureus activity (vancomycin or daptomycin) was used in 79 (75%) of courses, and a parenteral antibiotic with antipseudomonal activity was used in 7 (6%) of courses. Acute kidney injury occurred in 19 (18%) DFO-OPAT courses. An ankle-brachial index measurement was obtained during or 6 months before the first DFO-OPAT course for 44 (49%) of patients. Forty-two patients (44%) died or had an amputation within 12 months of their initial hospital discharge.

Conclusions

We found high rates of empiric antibiotic therapy for DFO and low uptake of the nonantibiotic aspects of DFO care. Better implementation of microbiological tests for DFO in addition to stronger integration of infectious disease and noninfectious diseases care could improve DFO outcomes.
Central Venous Catheter–Associated Infection: An Experience of a High Complexity Hospital
Authors: Gómez Boada Diego , Parra Amaris Camilo , Tuta-Quintero Eduardo , Bastidas-Goyes Alirio
Published: February 2023

Background

Central line–associated bloodstream infections (CLABSIs) are among the pathologies that increase mortality and morbidity in hospitalized patients with some type of device.

Objective

The aim of this study was to describe the clinical, microbiological, therapeutic characteristics, and economic costs associated with CLABSI.

Methodology

This study is a retrospective cohort study in subjects hospitalized at the Central Military Hospital of Bogotá, Colombia, describing the clinical, microbiological, and therapeutic characteristics in patients undergoing the insertion of a central venous catheter (CVC) and comparing them between subjects who did or did not develop infection. Central line–associated bloodstream infections were defined based on the criteria of the Infectious Diseases Society of America, a significant P < 0.05 was considered.

Results

A total of 821 patients were evaluated, of which 75 had a diagnosis of CLABSI, reaching a frequency of 9.1%. Patients with CVC infection were 12 years younger on average compared with the control group (55 vs 67 years; P = 0.001), 85.3% of the population with CVC-associated infection were men compared with 62.0% (P = 0.023) of the group without CLABSI. The CVC anatomical insertion sites with the highest proportion in both study groups were at the jugular and right subclavian levels (P = 0.001). The overall mortality of the study population was 24.6%, reaching 32% in the population with CLABSI compared with 23.9% in the control group (P = 0.254). Patients with CLABSI present higher associated costs during hospitalization (P = 0.013) and total costs (P = 0.028).

Conclusions

The younger population, the male sex, and the anatomical insertion of the CVC at the jugular and right subclavian levels presented a higher proportion of CLABSI. The costs associated with hospitalization and total costs were higher in the group of patients with CLABSI.
Limitation of Interpreting a Single COVID Cycle Threshold Value
Authors: Chen Alice , Leung Anthony K.
Published: February 2023

The United States reported its first case of coronavirus disease 2019 (COVID-19) in January 2020. There was limited testing capacity at the time, and the causative agent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was indeed extremely infectious. Testing, therefore, has become a vital part of controlling the COVID-19 pandemic. Nucleic acid amplification tests, such as polymerase chain reaction platform, a value called cycle threshold (Ct) is reported. This number represents the number of polymerase chain reaction test cycles it takes for the sample to become positive. It is inversely proportional to the amount of viral RNA present in the sample. Therefore, a high Ct value infers a low quantity of viral RNA, and conversely, a low Ct value implies high viral RNA, which in turn correlates with infectivity. When interpreted appropriately with the right clinical context, it could be used to assess the infectiousness of an individual. In September 2021, a 73-year-old man who previously completed a primary series of Moderna vaccine (2 injections) presented to the hospital with chest pain. Cardiac catheterization showed multivessel coronary artery disease and was deemed to have unstable angina. The plan was to undergo coronary aortic bypass graft surgery. Preoperative routine testing revealed a positive COVID-19 polymerase chain reaction test with a high Ct value. During the hospital stay, it was shown that he had a decreased Ct value and thus was determined to have an acute case of asymptomatic COVID-19 infection. His surgery was delayed according to the isolation protocol per Centers for Disease Control and Prevention for safety precautions. He eventually underwent coronary aortic bypass graft after completion of isolation and had an uneventful postoperative course. It was also documented that he had serological seroconversion consistent with acute COVID-19 infection. This case illustrates that reporting Ct values is useful in a certain clinical context, but clinicians need to be familiar with the transmissibility and history of SARS-CoV-2 infection as well as understanding the interpretation of positive tests. The appropriate clinical approach and management should be assessed based on exposure history, epidemiology, physical examination, radiographic assessment, and laboratory studies.
Overall survival, late mortality, and cancer-directed surgery among children and adolescents with ultra-rare pediatric pancreatoblastoma in the United States, 1975–2018
Authors: Li Peiyi , Kong Yujia , Wan Lin , Guo Jing , Li Weimin , Zhang Hui , Yang Guang , Zhang Bo
Published: February 2023

Background:

Pediatric pancreatoblastoma is an extremely rare malignant tumor, posing diagnostic and treatment difficulties for pediatric surgeons. Using the Surveillance, Epidemiology, and End Results (SEER) database, we present an up-to-date report of the epidemiology, clinicopathological features, survival rates, and prognosis of pancreatoblastoma in pediatric patients.

Methods:

All pediatric patients diagnosed with pancreatoblastoma between 1975 and 2018 were identified in the SEER registries (SEER 8 registries and SEER 17 registries). We conducted a survival analysis to assess overall survival and 1- and 5-year late mortality rates. Descriptive statistics and log-rank test were performed.

Results:

A total of 22 children and adolescents with pancreatoblastoma were identified. In this cohort, 12 of 22 were male (54.55%), 14 were White (63.64%), and 11 were diagnosed between the ages of 1 and 4 years (50.0%). Among the 22 patients, 11 (50.0%) had distant metastases, whereas 7 (31.82%) had localized, and 4 (18.18%) had a regional disease. A total of 5 children and adolescents died during the study period, with cumulative survival rates of 14 of 17 (82.35%) and 10 of 11 (90.95%) among 1- and 5-year survivors, respectively. Cancer-directed surgery was significantly associated with an increased life expectancy (log-rank test, P = .018).

Conclusion:

Pediatric pancreatoblastoma is a rare entity. Cases that underwent surgery had a greater likelihood of overall survival and reduced late mortality.
Running Gait Retraining in the Management of a Multiparous Runner With Chronic Stress Urinary Incontinence: A Case Study
Authors: Steimling Michael , Roberto Michael , Steimling Melinda
Published: February 2023

Background:

Stress urinary incontinence (SUI) is highly prevalent in the postpartum population and can result from injury or capacity deficits of the pelvic floor musculature. Impact forces seen during running increase demand on the pelvic floor musculature, resulting in a higher incidence of SUI. Running gait retraining, with emphasis on reducing impact, may reduce symptoms of SUI.

Case Description:

A 43-year-old woman was evaluated for chronic SUI when coughing, sneezing, and running since the birth of her second child 8 years ago. Initial interventions focused on pelvic floor, hip, and abdominal muscle training, and after 3 visits over 4 weeks, her SUI symptoms with coughing and sneezing resolved. She continued to complain of SUI during running. After a 2-dimensional video running gait assessment, running gait retraining was initiated in the form of verbal feedback to reduce the sound intensity of the foot striking the ground.

Outcomes:

After 2 visits of gait retraining over 2 weeks, the patient's SUI symptoms with running resolved. Gait reassessment revealed decreased sound intensity with foot strike. Eight weeks post-treatment, the patient remained symptom-free, and their Pelvic Floor Distress Inventory-20 (PFDI-20) total score decreased from 51.04/300 to 4.16/300.

Discussion:

This patient experienced meaningful improvements in symptoms of SUI following standard pelvic physical therapy treatment of pelvic floor, abdominal, and hip muscle training but only achieved resolution of symptoms with running after individualized running gait modification. Running gait retraining to reduce sound intensity during foot strike may have resulted in a decrease in impact and improvements in SUI symptoms while running.
The state of acute care postgraduate training: Faculty observations
Authors: Tennyson Carolina D. , Chen Leon L.
Published: February 2023

The benefits to postgraduate training programs (PTPs) for nurse practitioners (NPs) in all populations are being well established in the literature. As health care systems and teams evolve, acute care NPs (neonatal, pediatric, and adult-gerontology) are providing more specialized care to increasingly complex patients. As educators and clinicians, we recognize that acute care PTPs are playing an important role in preparing NPs to work to the top of their scope and training. This article provides our perspectives on the merits of PTPs for adult-gerontology acute care NPs and provides guidance for counseling NPs who are interested in acute care PTPs.
Pneumocystis pneumonia in a patient with diabetes mellitus: A case report
Authors: Li Ziling , Xu Shuyun , Shi Jing , Zhang Yong
Published: February 2023

Rationale:

Pneumocystis pneumonia (PCP) is an opportunistic infection of patients with congenital or acquired immunodeficiency. It is most frequently occurred in human immunodeficiency virus (HIV) infection, organ transplantation, leukemia, and immunosuppressive therapy. Here we describe the rare case of PCP in a non-HIV-infected diabetic patient and find possible reasons for the association through a literature review.

Patient concerns:

A 65-years-old male was admitted to our hospital due to a 10-year history of abnormal blood glucose levels and edema of both lower extremities for half a month. However, the patient developed a high fever and progressive dyspnea during hospitalization.

Diagnoses:

The patient had elevated blood sugar levels, a low white blood cell count within normal limits, and severe lymphopenia. His blood G test and lactate dehydrogenase levels increased significantly. Multiple sputa and bronchoalveolar lavage fluid specimens for Pneumocystis jirovecii (PJ) nucleic acid detection were positive. Chest computed tomography scan demonstrated hazy patchy shadows in the lungs suspected to be pulmonary infections. No tumor, transplantation, or an autoimmune disease was found in the examinations. The patient was diagnosed with PCP finally.

Interventions:

A combination of oral trimethoprim-sulfamethoxazole and intravenous caspofungin was administered immediately against PJ. The patient was also treated with noninvasive ventilator-assisted ventilation, subcutaneous insulin, and hemodialysis therapy.

Outcomes:

The patient was discharged home finally with a fair general condition and was followed up without respiratory symptoms.

Lessons:

The compromised immunity in HIV-negative patients with diabetes may be related to lymphocyte decrease and dysfunction, which may cause diabetic patients prone to PJ. Although PCP is rare in diabetes, it should be paid attention to the high rate of misdiagnosis and missed diagnosis.
Comparison of the effects of 2 frequencies of application of photobiomodulation on facial rejuvenation: Controlled, randomized, and double-blind clinical trial
Authors: Bragato Erick Frank , Pires Jefferson André , Momolli Marcos , Guerra Marina Bertoni , Paisano Adriana Fernandes , Ferrari Raquel Agnelli Mesquita , Bussadori Sandra Kalil , Motta Lara Jansiski , Fernandes Kristianne Porta Santos
Published: February 2023

Introduction:

Skin aging is an irreversible, slow and progressive process, mainly influenced by age, but also by external factors such as ultraviolet radiation, smoking, and alcohol, among others. It is increasingly common to look for procedures that slow down skin aging by limiting or hiding its effects on appearance. Studies have shown the benefits of photobiomodulation (PBM) for the skin, especially with the use of red light-emitting diodes. However, there is a high level of variability in the treatment parameters and frequency of application.

Methods and analysis:

The objective of this study is to compare the effects of PBM with a light-emitting diode mask (660 nm, 6.4 mW/ cm², 8,02 J/ cm², 5.02 mW, 21 minutes) on facial rejuvenation using 2 frequency applications for 4 weeks: one group will receive PBM application on the face, twice a week and another group will receive PBM application 3 times a week. A group with simulated PBM applied twice a week for 4 weeks will be used as a control. The treatment will be performed on female participants aged between 45 and 60 years. After 4 weeks, evaluations of photographic images by specialists (Wrinkle Assessment Scale) as well as the quantitative analysis of the wrinkle size by the Image J software, the depth and width of wrinkles (assessment of face impressions by optical coherence tomography) and the level of Satisfaction with Facial Appearance Overall will be compared with data collected before the start of the study. All data will be analyzed statistically according to their distribution, seeking a level of statistical significance of 0.05.

Ethics and dissemination:

This protocol was approved by the Research Ethics Committee of the Nove de Julho University (acceptance number: 4.365.565). This trial has been registered in ClinicalTrials.gov (ID: NCT04911140). This study is recruiting.
Predicting 6-month mortality of patients from their medical history: Comparison of multimorbidity index to Deyo–Charlson index
Authors: Alemi Farrokh , Avramovic Sanja , Schwartz Mark
Published: February 2023

While every disease could affect a patient’s prognosis, published studies continue to use indices that include a selective list of diseases to predict prognosis, which may limit its accuracy. This paper compares 6-month mortality predicted by a multimorbidity index (MMI) that relies on all diagnoses to the Deyo version of the Charlson index (DCI), a popular index that utilizes a selective set of diagnoses. In this retrospective cohort study, we used data from the Veterans Administration Diabetes Risk national cohort that included 6,082,018 diabetes-free veterans receiving primary care from January 1, 2008 to December 31, 2016. For the MMI, 7805 diagnoses were assigned into 19 body systems, using the likelihood that the disease will increase risk of mortality. The DCI used 17 categories of diseases, classified by clinicians as severe diseases. In predicting 6-month mortality, the cross-validated area under the receiver operating curve for the MMI was 0.828 (95% confidence interval of 0.826–0.829) and for the DCI was 0.749 (95% confidence interval of 0.748–0.750). Using all available diagnoses (MMI) led to a large improvement in accuracy of predicting prognosis of patients than using a selected list of diagnosis (DCI).
Association of traditional Chinese medicine body constitution and cold syndrome with leukocyte mitochondrial functions: An observational study
Authors: Ma Guangyin , Li Caixia , Ji Peng , Chen Yanjie , Li Ang , Hu Qingchuan , Song Zehua , Tang Bruce Qing , Jia Dexian , Wei Yulong , Li Tongju
Published: February 2023

Body constitution in traditional Chinese medicine (TCM) refers to the holistic and relatively durable state of an individual, based on the qi and blood assessment, and TCM syndrome is defined as the theoretical abstraction of disease-symptom profiles. The biological basis as related to mitochondria, which produce most of the cellular energy, has not been well studied. This study aimed to elucidate the association of mitochondrial function with TCM body constitution and cold syndrome. Body constitution and cold syndrome in TCM were assessed using the Constitution in Chinese Medicine Questionnaire (CCMQ). The mitochondrial function of peripheral leukocytes was evaluated based on oxygen consumption rate (OCR) and enzyme activity; OCR reflects mitochondrial activity and the capacity to produce adenosine triphosphate (ATP). Cellular adenosine nucleotides and malondialdehyde levels were determined using high-performance liquid chromatography to assess the potential bioenergetic mechanisms. A total of 283 adults participated in this study. Leukocytes from subjects with a balanced constitution had higher OCRs than those with unbalanced constitutions. Yang deficiency and cold syndrome also demonstrated lower energy metabolism, as indicated by reduced basal metabolic rate and cellular levels of ATP and malondialdehyde. Decreased mitochondrial enzyme activity has been observed in individuals with the cold syndrome. Unbalanced body constitutions in TCM impair mitochondrial function in leukocytes, which may contribute to the high disease susceptibility. Cold syndrome is characterized by reduced mitochondrial mass, which may explain its symptoms of low-energy metabolism and cold intolerance.
Multiple evanescent white dot syndrome in highly myopic eye in which fundus autofluorescence was diagnostically useful: A case report
Authors: Harada Sumine , Kato Kumiko , Matsui Yoshitsugu , Sugimoto Masahiko , Matsubara Hisashi , Kondo Mineo
Published: February 2023

Rationale:

Multiple evanescent white dot syndrome (MEWDS) is characterized by multiple white dots in the posterior pole of the eye, but its diagnosis can be difficult in cases when the white dots are not visible. We report an atypical case of MEWDS that developed in pathologic myopia.

Patient concern:

A 42-year-old woman presented with floater and reduced and distorted vision in the right eye that she noted 3 days earlier.

Diagnosis:

The right eye was highly myopic at -17.0 diopters, and her decimal best-corrected visual acuity was reduced to 0.2 (20/100). Fundus examinations revealed no abnormalities other than myopic fundus changes and previous laser photocoagulation spots. However, fundus autofluorescence (FAF) showed multiple hyperfluorescent dots, and optical coherence tomography showed a high reflective lesion on the retinal pigmental epithelium at the fovea. Adjustments of the brightness and contrast of the conventional fundus images revealed white dots in the same location as the hyperfluorescent spots seen in the FAF images. We diagnosed her with MEWDS.

Interventions:

We treated her with systemic administration of 20 mg prednisolone and the dose of prednisolone was reduced by 5 mg every 4 weeks.

Outcomes:

The optical coherence tomography and FAF findings gradually normalized, and 5 months later, her decimal visual acuity was restored to 1.0 (20/20).

Lessons:

It was suggested that white dots typical to MEWDS may not be evident in pathologic myopia, and FAF images and the brightness and contrast adjustment of fundus images were useful in the diagnosis of atypical MEWDS.
The effect of seamless nursing combined with Roy adaptive psychological nursing on self-efficacy and bad mood of patients after acute abdomen surgery
Authors: Nie Chang , Chen Xiaoxue , Wang Lifei , Li Ling , Rao Danfeng , Wei Xi , Zhang Guilian
Published: February 2023

To explore the effect of seamless nursing combined with Roy adaptive psychological nursing on self-efficacy and bad mood of patients after acute abdomen surgery. According to the digital table method, 120 patients with acute abdomen who were treated and nursed in our hospital from June 2019 to June 2021 were selected as prospective research objects, and they were divided into a control group and an observation group with 60 cases each. Among them, the control group carried out seamless nursing, and the observation group carried out Roy adaptive psychological nursing on this basis, and compared the effects of self-efficacy, nursing ability and bad mood of the 2 groups of patients after surgery. Before nursing, the self-efficacy scale, quality of life scores, nursing ability scores, as well as bad mood were not statistically significant between the 2 groups (P > .05). After nursing, the self-efficacy scale and nursing ability scores in the observation group were significantly higher than that in the control group (P < .05); the social interaction score, anxiety score and depression score were significantly lower than that in the control group (P < .001). Seamless nursing combined with Roy adaptive psychological nursing can effectively improve the quality of life of patients after acute abdomen surgery, reduce unhealthy emotions, and improve the nursing ability and self-efficacy of patients after surgery. It has a certain reference for the nursing of patients after acute abdomen surgery.