bluuebunny/crossref_metadata_2025 huggingface dataset:
Luminol-conjugated cyclodextrin biological nanoparticles for the treatment of severe burn-induced intestinal barrier disruption
Authors: Song Yajun , Li Yang , Hu Wengang , Li Feng , Sheng Hao , Huang Chibing , Gou Xin , Hou Jingming , Zheng Ji , Xiao Ya
Published: March 2024

Background

The breakdown of intestinal barrier integrity occurs after severe burn injury and is responsible for the subsequent reactions of inflammation and oxidative stress. A new protective strategy for the intestinal barrier is urgently needed due to the limitations of the traditional methods. Recently, the application of nanoparticles has become one of the promising therapies for many inflammation-related diseases or oxidative damage. Herein, we developed a new anti-inflammatory and antioxidant nanoparticle named luminol-conjugated cyclodextrin (LCD) and aimed to evaluate its protective effects in severe burn-induced intestinal injury.

Methods

First, LCD nanoparticles, engineered with covalent conjugation between luminol and β-cyclodextrin (β-CD), were synthesized and examined. Then a mouse burn model was successfully established before the mouse body weight, intestinal histopathological manifestation, permeability, tight junction (TJ) expression and pro-inflammatory cytokines were determined in different groups. The proliferation, apoptosis, migration and reactive oxygen species (ROS) of intestinal epithelial cells (IECs) were assessed. Intraepithelial lymphocytes (IELs) were isolated and cultured for analysis by flow cytometry.

Results

LCD nanoparticle treatment significantly relieved the symptoms of burn-induced intestinal injury in the mouse model, including body weight loss and intestinal permeability abnormalities. Moreover, LCD nanoparticles remarkably recovered the mechanical barrier of the intestine after severe burn, renewed TJ structures, promoted IEC proliferation and migration, and inhibited IEC apoptosis. Mechanistically, LCD nanoparticles dramatically alleviated pro-inflammation factors (tumor necrosis factor-α, IL-17A) and ROS accumulation, which could be highly involved in intestinal barrier disruption. Furthermore, an increase in IL-17A and the proportion of IL-17A+Vγ4+ γδ T subtype cells was also observed in vitro in LPS-treated Vγ4+ γδ T cells, but the use of LCD nanoparticles suppressed this increase.

Conclusions

Taken together, these findings demonstrate that LCD nanoparticles have the protective ability to ameliorate intestinal barrier disruption and provide a therapeutic intervention for burn-induced intestinal injury.
Service Function Placement Optimization For Cloud Service With End-to-End Delay Constraints
Authors: Yan Guofeng , Su Zhengwen , Tan Hengliang , Du Jiao
Published: March 2024

Network function virtualization (NFV) has been proposed to enable flexible management and deployment of the network service in cloud. In NFV architecture, a network service needs to invoke several service functions (SFs) in a particular order following the service chain function. The placement of SFs has significant impact on the performance of network services. However, stochastic nature of the network service arrivals and departures as well as meeting the end-to-end Quality of Service(QoS) makes the SFs placement problem even more challenging. In this paper, we firstly provide a system architecture for the SFs placement of cloud service with end-to-end QoS deadline. We then formulate the end-to-end service placement as a Markov decision process (MDP) which aims to minimize the placement cost and the end-to-end delay. In our MDP, the end-to-end delay of active services in the network is considered to be the state of the system, and the placement (nonplacement or placement) of SF is considered as the action. Also, we discuss the rationality of our analytical model by analyzing the Markov stochastic property of the end-to-end service placement. To obtain the optimal placement policy, we then propose an algorithm (Algorithm 1) for dynamic SFs placement based on our model and use successive approximations, i.e. $\epsilon $-iteration algorithm (Algorithm 2) to obtain action distribution. Finally, we evaluate the proposed MDP by comparing our optimal method with DDQP, DRL-QOR, MinPath and MinDelay for QoS optimization, including acceptance probability, average delay, resource utilization, load-balancing and reliability.
An Improved Density Peaks Clustering Algorithm Based On Density Ratio
Authors: Zou Yujuan , Wang Zhijian , Xu Pengfei , Lv Taizhi
Published: March 2024

Density peaks clustering (DPC) is a relatively new density clustering algorithm. It is based on the idea that cluster centers always have relatively high local densities and are relatively far from the points with higher densities. With the aforementioned idea, a decision graph can be drawn, and cluster centers will be chosen easily with the aid of the decision graph. However, the algorithm has its own weaknesses. Because the algorithm calculates local density and allocates points based on the distances between certain points, the algorithm has difficulty in classifying points into proper groups with varying densities or nested structures. This paper proposes an improved density peaks clustering algorithm called Dratio-DPC to overcome this weakness. First, Dratio-DPC adjusts the original local density with a coefficient calculated with the density ratio. Second, Dratio-DPC takes density similarity into consideration to calculate the distances between one point and other points with higher local densities. We design and perform experiments on different benchmark datasets and compare the clustering results of Dratio-DPC, traditional clustering algorithms and three improved DPC algorithms. Comparison results show that Dratio-DPC is effective and applicable to a wider range of scenarios.
Concept Drift–Based Intrusion Detection For Evolving Data Stream Classification In IDS: Approaches And Comparative Study
Authors: Seth Sugandh , Chahal Kuljit Kaur , Singh Gurvinder
Published: March 2024

Static machine and deep learning algorithms are commonly used in intrusion detection systems (IDSs). However, their effectiveness is constrained by the evolving data distribution and the obsolescence of the static data sources used for model training. Consequently, static classifiers lose efficacy, necessitating expensive model retraining with time. The aim is to develop a dynamic and adaptable IDS that mitigates the limitations of static models, ensuring real-time threat detection and reducing the need for frequent, resource-intensive model retraining. This research proposes an approach that amalgamates the adaptive random forest (ARF) classifier with Hoeffding’s bounds and a moving average test for the early and accurate detection of network intrusions. The ARF can adapt in real time to shifting network conditions and evolving attack patterns, constantly refining its intrusion detection capabilities. Furthermore, the inclusion of Hoeffding’s bounds and the moving average test adds a dimension of statistical rigor to the system, facilitating the timely recognition of concept drift and distinguishing benign network variations from potential intrusions. The synergy of these techniques results in reduced false positives and false negatives, thereby enhancing the overall detection rate. The proposed method delivers outstanding results, with 99.95% accuracy and an impressive 99.96% recall rate on the latest CIC-IDS 2018 dataset, outperforming the results of existing approaches.
Identification and characterization of unknown disturbances in a structured population using high-throughput phenotyping data and measurement of robustness: application to growing pigs
Authors: Le Vincent , Rohmer Tom , David Ingrid
Published: March 2024

Improving the robustness of animals has become a priority in breeding due to climate change, new societal demands, and the agroecological transition. Components of animal robustness can be extracted from the analysis of the adaptive response of an animal to disturbance using longitudinal data. Nonetheless, this response is a function of animal robustness as well as of disturbance characteristics (intensity and duration). To correctly assess an animal’s robustness potential, it is therefore useful to know the characteristics of the disturbances it faces. The UpDown method, which detects and characterizes unknown disturbances at different levels of organization of the population (e.g., individual, pen, and batch disturbances), has been proposed for this purpose. Furthermore, using the outputs of the method, it is possible to extract proxies of the robustness of animals. In this context, the objective of the study was to evaluate the performances of the UpDown method to detect and characterize disturbances and quantify the robustness of animals in a genetic framework using different sets of simulations, and to apply this method to real pig longitudinal data recorded during the fattening period (body weight, cumulative feed intake, and feeding rate). Based on the simulations, the specificity of the UpDown method was high (>0.95). Its sensitivity increased with the level of organization exposed (from 0.23 to 0.32 for individual disturbances, from 0.45 to 0.59 for pen disturbances, and from 0.77 to 0.88 for batch disturbances). The UpDown method also showed a good ability to characterize detected disturbances. The average time interval between the estimated and true start date or duration of the disturbance was lower than 3 d. The correlation between the true and estimated intensity of the disturbance increased with the hierarchical level of organization (on average, 0.41, 0.78, and 0.83 for individual, pen, and batch disturbance, respectively). The accuracy of the estimated breeding values of the proxies for robustness extracted from the analysis of individual trajectories over time were moderate (lower than 0.33). Applied to real data, the UpDown method detected different disturbances depending on the phenotype analyzed. The heritability of the proxies of robustness were low to moderate (ranging from 0.11 to 0.20).
Endemic Coronavirus Infections are Associated with Strong Homotypic Immunity in a US Cohort of Children from Birth to 4 Years
Authors: Morrow Ardythe L , Payne Daniel C , Conrey Shannon C , McMorrow Meredith , McNeal Monica M , Niu Liang , Burrell Allison R , Schlaudecker Elizabeth P , Mattison Claire , Burke Rachel M , DeFranco Emily , Teoh Zheyi , Wrammert Jens , Atherton Lydia J , Thornburg Natalie J , Staat Mary A
Published: March 2024

Background

The endemic coronaviruses OC43, HKU1, NL63, and 229E cause cold-like symptoms and are related to SARS-CoV-2, but their natural histories are poorly understood. In a cohort of children followed from birth to 4 years, we documented all coronavirus infections, including SARS-CoV-2, to understand protection against subsequent infections with the same virus (homotypic immunity) or a different coronavirus (heterotypic immunity).

Methods

Mother–child pairs were enrolled in metropolitan Cincinnati during the third trimester of pregnancy in 2017-2018. Mothers reported their child’s sociodemographics, risk factors, and weekly symptoms. Mid-turbinate nasal swabs were collected weekly. Blood was collected at 6 weeks, 6, 12, 18, 24 months, and annually thereafter. Infections were detected by testing nasal swabs by an RT-PCR multi-pathogen panel and by serum IgG responses. Health care visits were documented from pediatric records. Analysis was limited to 116 children with high sample adherence. Reconsent for monitoring SARS-CoV-2 infections from June 2020 through November 2021 was obtained for 74 (64%) children.

Results

We detected 345 endemic coronavirus infections (1.1 infections/child-year) and 21 SARS-CoV-2 infections (0.3 infections/child-year). Endemic coronavirus and SARS-CoV-2 infections were asymptomatic or mild. Significant protective homotypic immunity occurred after a single infection with OC43 (77%) and HKU1 (84%) and after two infections with NL63 (73%). No heterotypic protection against endemic coronaviruses or SARS-CoV-2 was identified.

Conclusions

Natural coronavirus infections were common and resulted in strong homotypic immunity but not heterotypic immunity against other coronaviruses, including SARS-CoV-2. Endemic coronavirus and SARS-CoV-2 infections in this US cohort were typically asymptomatic or mild.
The dilemma of radiation necrosis from diagnosis to treatment in the management of brain metastases
Authors: Mayo Zachary S , Billena Cole , Suh John H , Lo Simon S , Chao Samuel T
Published: March 2024

Radiation therapy with stereotactic radiosurgery (SRS) or whole brain radiation therapy is a mainstay of treatment for patients with brain metastases. The use of SRS in the management of brain metastases is becoming increasingly common and provides excellent local control. Cerebral radiation necrosis (RN) is a late complication of radiation treatment that can be seen months to years following treatment and is often indistinguishable from tumor progression on conventional imaging. In this review article, we explore risk factors associated with the development of radiation necrosis, advanced imaging modalities used to aid in diagnosis, and potential treatment strategies to manage side effects.
Stereotactic body radiation therapy for spinal metastases: A new standard of care
Authors: Sacino Amanda N , Chen Hanbo , Sahgal Arjun , Bettegowda Chetan , Rhines Laurence D , Maralani Pejman , Redmond Kristin J
Published: March 2024

Advancements in systemic therapies for patients with metastatic cancer have improved overall survival and, hence, the number of patients living with spinal metastases. As a result, the need for more versatile and personalized treatments for spinal metastases to optimize long-term pain and local control has become increasingly important. Stereotactic body radiation therapy (SBRT) has been developed to meet this need by providing precise and conformal delivery of ablative high-dose-per-fraction radiation in few fractions while minimizing risk of toxicity. Additionally, advances in minimally invasive surgical techniques have also greatly improved care for patients with epidural disease and/or unstable spines, which may then be combined with SBRT for durable local control. In this review, we highlight the indications and controversies of SBRT along with new surgical techniques for the treatment of spinal metastases.
Novel radiotherapeutic strategies in the management of brain metastases: Challenging the dogma
Authors: Palmer Joshua D , Perlow Haley K , Lehrer Eric J , Wardak Zabi , Soliman Hany
Published: March 2024

The role of radiation therapy in the management of brain metastasis is evolving. Advancements in machine learning techniques have improved our ability to both detect brain metastasis and our ability to contour substructures of the brain as critical organs at risk. Advanced imaging with PET tracers and magnetic resonance imaging-based artificial intelligence models can now predict tumor control and differentiate tumor progression from radiation necrosis. These advancements will help to optimize dose and fractionation for each patient’s lesion based on tumor size, histology, systemic therapy, medical comorbidities/patient genetics, and tumor molecular features. This review will discuss the current state of brain directed radiation for brain metastasis. We will also discuss future directions to improve the precision of stereotactic radiosurgery and optimize whole brain radiation techniques to improve local tumor control and prevent cognitive decline without forming necrosis.
Composite antiferromagnetic and orbital order with altermagnetic properties at a cuprate/manganite interface
Authors: Sarkar Subhrangsu , Capu Roxana , Pashkevich Yurii G , Knobel Jonas , Cantarino Marli R , Nag Abhishek , Kummer Kurt , Betto Davide , Sant Roberto , Nicholson Christopher W , Khmaladze Jarji , Zhou Ke-Jin , Brookes Nicholas B , Monney Claude , Bernhard Christian
Published: March 2024

Heterostructures from complex oxides allow one to combine various electronic and magnetic orders as to induce new quantum states. A prominent example is the coupling between superconducting and magnetic orders in multilayers from high-Tc cuprates and manganites. A key role is played here by the interfacial CuO2 layer whose distinct properties remain to be fully understood. Here, we study with resonant inelastic X-ray scattering the magnon excitations of this interfacial CuO2 layer. In particular, we show that the underlying antiferromagnetic exchange interaction at the interface is strongly suppressed to J≈70 meV, when compared with J≈130 meV for the CuO2 layers away from the interface. Moreover, we observe an anomalous momentum dependence of the intensity of the interfacial magnon mode and show that it suggests that the antiferromagnetic order is accompanied by a particular kind of orbital order that yields a so-called altermagnetic state. Such a 2D altermagnet has recently been predicted to enable new spintronic applications and superconducting proximity effects.
Mutations in the SARS-CoV-2 spike receptor binding domain and their delicate balance between ACE2 affinity and antibody evasion
Authors: Xue Song , Han Yuru , Wu Fan , Wang Qiao
Published: March 2024

Intensive selection pressure constrains the evolutionary trajectory of SARS-CoV-2 genomes and results in various novel variants with distinct mutation profiles. Point mutations, particularly those within the receptor binding domain (RBD) of SARS-CoV-2 spike (S) protein, lead to the functional alteration in both receptor engagement and monoclonal antibody (mAb) recognition. Here, we review the data of the RBD point mutations possessed by major SARS-CoV-2 variants and discuss their individual effects on ACE2 affinity and immune evasion. Many single amino acid substitutions within RBD epitopes crucial for the antibody evasion capacity may conversely weaken ACE2 binding affinity. However, this weakened effect could be largely compensated by specific epistatic mutations, such as N501Y, thus maintaining the overall ACE2 affinity for the spike protein of all major variants. The predominant direction of SARS-CoV-2 evolution lies neither in promoting ACE2 affinity nor evading mAb neutralization but in maintaining a delicate balance between these two dimensions. Together, this review interprets how RBD mutations efficiently resist antibody neutralization and meanwhile how the affinity between ACE2 and spike protein is maintained, emphasizing the significance of comprehensive assessment of spike mutations.
Childhood Adversity and Incident Psychotic Experiences in Early Adulthood: Cognitive and Psychopathological Mediators
Authors: Cortes Hidalgo Andrea P , Hammerton Gemma , Heron Jon , Bolhuis Koen , Madley-Dowd Paul , Tiemeier Henning , van IJzendoorn Marinus H , Zammit Stanley , Jones Hannah J
Published: March 2024

Background and Hypothesis

Childhood adversity is often described as a potential cause of incident psychotic experiences, but the underlying mechanisms are not well understood. We aimed to examine the mediating role of cognitive and psychopathological factors in the relation between childhood adversity and incident psychotic experiences in early adulthood.

Study Design

We analyzed data from the Avon Longitudinal Study of Parents and Children, a large population-based cohort study. Childhood adversity was measured prospectively from birth to age 11 years, mediators (anxiety, depression, external locus of control [LoC], negative symptoms) were assessed at approximately 16 years of age, and incident psychotic experiences were assessed at ages 18 and 24 years. Mediation was examined via the counterfactual g-computation formula.

Study Results

In total, 7% of participants had incident suspected or definite psychotic experiences in early adulthood. Childhood adversity was related to more incident psychotic experiences (ORadjusted = 1.34, 95% CI = 1.21; 1.49), and this association was partially mediated via all mediators examined (proportion mediated: 19.9%). In separate analyses for each mediator, anxiety, depression, external LoC, and negative symptoms were all found to mediate the link between adversity and incident psychotic experiences. Accounting for potential confounders did not modify our results.

Conclusions

Our study shows that cognitive biases as well as mood symptomatology may be on the causal pathway between early-life adversity and the development of psychotic experiences. Future studies should determine which mediating factors are most easily modifiable and most likely to reduce the risk of developing psychotic experiences.
Genomic Insights into Combating Anthracnose with an Endophytic Bacillus amyloliquefaciens Strain
Authors: Zhang Haiyan , Zhang Jie , Tong Yao , Luan Zhiyuan , Hou Jiexi , Luan Fenggang
Published: March 2024

Anthracnose, caused by Colletotrichum spp., is a common disease of Camellia oleifera. In this study, a Bacillus amyloliquefaciens strain, GZY63, was isolated from fruit of the anthracnose-resistant cultivar of Ca. oleifera “Ganzhouyou7.” Plate confrontation assays and field experiments demonstrated the strong inhibitory effect of GZY63 on anthracnose, and this strain exhibited broad-spectrum resistance to nine pathogenic Colletotrichum spp. This strain shows potential as a fungicide alternative, but genetic information on this strain is critical for its optimal use. Combining Illumina and Nanopore sequencing, we assembled a high-quality circular genome of GZY63 that contained no plasmids. The GZY63 complete genome was approximately 3.93 Mb and had an average guanine-cytosine content of 46.5%. The genome comprised 4,024 predicted coding sequences and 12 types of gene clusters involved in secondary metabolite production. This genome information provides insights into the mechanism underlying the antagonistic impact of the GZY63 strain on anthracnose and its symbiotic relationship with Ca. oleifera.
Complete Circularized Genome Resources for Xylella fastidiosa subsp. sandyi Strains CO33 and CFBP8478
Authors: Velasco-Amo María Pilar , Arias-Giraldo Luis F. , Román-Écija Miguel , Giampetruzzi Annalisa , Saponari Maria , Landa Blanca B.
Published: March 2024

Xylella fastidiosa ( Xf) is a vascular phytopathogenic bacterium native to the Americas, known for causing severe diseases and significant economic losses in important crops. In Europe, Xf is considered a quarantine pathogen. Since its first detection in 2013 in Italy, mandatory surveys to search for Xf across Europe have revealed the presence of three Xf subspecies ( fastidiosa, multiplex, and pauca) in different outbreaks occurring in France, Spain, and Portugal. Xf subspecies sandyi and morus have not been associated with epidemic outbreaks in Europe; however, subspecies sandyi has been detected in intercepted plants imported from Costa Rica and Honduras. By combining data from the Oxford Nanopore Technologies and Illumina sequencing platforms, we obtained complete genomes for Xf strains CO33 and CFBP8478. Both strains belong to the subspecies sandyi and were isolated from coffee plants intercepted in Europe that were imported from Costa Rica. These two genome resources increase the scarce number of Xf genomes available belonging to the subspecies sandyi, which is crucial for comparative genomic analysis and population studies of this important plant-pathogenic bacterium.

[Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Pomalidomide improves the effectiveness of CAR-T treatment in the relapsed and refractory multiple myeloma or B-cell leukemia/lymphoma with extramedullary disease
Authors: Zhao Jie , Yang Hui , Ge Junnan , Li Linyu , Yao Qiong , He Shaolong , Zhu Qiujuan , Ren Ruiui , Li Chunrui , Ma Liangming , Tian Weiwei , Wei Jia
Published: March 2024

Relapsed and refractory multiple myeloma (RRMM) and B-cell leukemia/lymphoma with extramedullary disease (EMD) have poor prognosis and high mortality, lack of effective therapeutic approaches. We reported for the first time that 6 patients with malignant hematological diseases with EMD received chimeric antigen receptor (CAR)-T treatment combined with pomalidomide, and CAR-T cells were treated with pomalidomide in vitro to determine its killing activity and cytokine secretion. Three patients with RRMM were given B cell maturation antigen (BCMA)-CAR-T therapy. All 3 patients with B-cell leukemia/lymphoma received CD19/22-CAR-T sequential infusion. There were no treatment-related deaths. The maximum overall response rate (ORR) was 100%. Median follow-up was 211.5 days (75–407 days). Three patients (50%) experienced cytokine release syndrome, all of which were grade 1, and no neurotoxicity was observed. In vitro experiments showed that the killing activity did not differ significantly between BCMA-CAR-T cells with and without pomalidomide (10, 25, or 50 μg/mL) in 8226/U266 cell cocultures (P > .05). Tumor necrosis factor (TNF)-α and interferon (IFN)-γ secretion was significantly higher from 8226 and Raji cells cocultured with BCMA-CAR-T and cluster of differentiation (CD)19-CAR-T cells (P < .05). Based on the cocultures, adding pomalidomide significantly promoted IFN-γ and TNF-α secretion (P < .05). Based on the above clinical and in vitro studies demonstrating the co-administration of pomalidomide with CAR-T cell treatment demonstrated favorable tolerability and therapeutic effectiveness in RRMM or B-cell leukemia/lymphoma.
Understanding Eating Disorders and the Nurse's Role in Diagnosis, Treatment, and Support
Authors: Cole Britt
Published: March 2024

Eating disorders (EDs) are a severe type of mental illness that nurses in many settings may encounter. The three primary eating disorders—anorexia nervosa, bulimia nervosa, and binge eating disorder—are described here. Signs, symptoms, and treatment of eating disorders are outlined, along with the importance of nurses in early identification of EDs and developing therapeutic relationships with patients. A case study and elements of spiritual care are presented.
Improving Heart Failure Patient Engagement with Mobile Apps Using Nurse Navigators
Authors: Phelps Rachel E. , Buckner Ellen B.
Published: March 2024

Providing high-quality heart failure education through smartphone applications (apps) empowers patients to more successfully manage their disease process outside the hospital setting. The purpose of this project was to evaluate the addition of nurse navigators to increase engagement of newly-diagnosed heart failure patients with the GetWell Loop (GWL) technology program that assists patient learning and monitoring for self-care. Adding navigators increased patient engagement with the GWL over the use of the GWL without navigators.
The benefits of PCSK9 inhibitors in patients with acute coronary syndrome: a systematic review and meta-analysis
Authors: Zhang Guanzhao , Chang Shuting , Zhao Faming , Guan Xiangfeng , Nie Zifan , Liu Wenhao , Li Bo
Published: March 2024

Background

Proprotein convertase subtilisin/kexin 9 (PSCK9) inhibitors have been beneficial for many patients with hyperlipidemia. The objective of this study was to investigate the benefit of PSCK9 inhibitors in patients with acute coronary syndrome (ACS).

Methods

We systematically searched PubMed, EMBASE, and Cochrane Clinical Trials (published before January 2023; no language restriction) to compare the treatment of patients with ACS using PCSK9 inhibitors and placebo. The primary end points were major adverse cardiovascular events, nonfatal myocardial infarction, cardiogenic death, stroke, hospitalization for recurrent ACS, and coronary revascularization. Fixed- or random-effects models were used to assess the aggregated data.

Results

Of the 1686 identified studies, 5 were eligible and included in our analysis (of a total of 38,005 participants, 18,609 cases were placed in the PCSK9 inhibitor treatment group and 19,396 cases in the placebo group). Compared with the placebo group, PCSK9 inhibitors significantly reduced the major adverse cardiovascular events (odds ratio [OR]: 0.83; 95% confidence interval [CI]: 0.77–0.88; P < 0.00001) for patients following ACS. The incidence of nonfatal myocardial infarction (relative risk: 0.80; 95% CI: 0.74–0.87; P < 0.00001), cardiovascular death (OR: 0.96; 95% CI: 0.83–1.10; P = 0.56), stroke (OR: 0.74; 95% CI: 0.63–0.88; P = 0.0007), hospitalization for recurrent ACS (OR: 0.57; 95% CI: 0.40–0.83; P = 0.003), or coronary revascularization (OR: 0.82; 95% CI: 0.76–0.88; P < 0.00001) all demonstrated a significant decrease in the comparison between the 2 groups.

Conclusion

This meta-analysis demonstrated that treatment with PCSK9 inhibitors in patients with ACS reduced the probability of multiple cardiovascular events and improved patient prognosis.
Advocacy inquiry and circular questioning to maintain psychological safety in training, feedback, and conversations with residents
Authors: Lateef Fatimah
Published: March 2024

Training of emergency physicians through an emergency medicine residency program takes 5 years, that is, 3 years in junior residency and 2 years in senior residency. Throughout this period, residents will be exposed to a variety of educational methodologies and meet a spectrum of faculty, supervisors, and teachers, who will have different personalities, styles, and approaches to teaching and nurturing them. It is important to ensure the maintenance of psychological safety for these residents throughout their training journey and into the future years of practice s an emergency physician.

Communications, interactions (which involve questioning), and presentations will be an important part of this training program. This article looks at two modes of questioning: advocacy inquiry and circular questioning, which can be applied as appropriate. These two methods are examples in which faculty may consider adopting in their many interactions, follow-up, feedback, tutorials, facilitation, partnerships, and counseling sessions with residents. These two techniques offer options to maintain psychological safety, which can facilitate learners sharing and opening up. It can be included in the faculty’s armamentarium of questioning techniques and applied where applicable.
Comparative Study between Gluteal Artery Perforator Flaps and Local Fasciocutaneous Flaps in Reconstruction of Gluteal Pressure Ulcers
Authors: El Naggar Abdel Nasser Mohamed , Fathy Ibrahim Mostafa , Abdel Azeem Khaled Mohamed , Ibrahim Ahmed Hamdy Mahmoud , Mohamed Hawas Emad
Published: March 2024

Background:

Gluteal pressure ulcers are a common problem, associated with great morbidity and cost, and their surgical treatment includes debridement with complete bursectomy, followed by soft tissue coverage. Gluteal artery perforator flaps and gluteal fasciocutaneous flaps are commonly preferred for reconstruction because they preserve the gluteal muscle, allowing for revision in recurrent cases. The aim of this study was to evaluate the differences between these two flaps in the reconstruction of gluteal pressure ulcers regarding operative time, postoperative hospital stay, postoperative complications, and recurrence.

Methods:

This prospective comparative study was conducted on 30 patients who presented with stage IV gluteal pressure ulcers. Patients were randomly allocated into two equal groups: each group consisted of 15 patients. Cases in group A were reconstructed using gluteal artery perforator flaps, and those in group B were reconstructed using local fasciocutaneous flaps.

Results:

There was statistically significant long operative time and short postoperative hospital stay in gluteal artery perforator flaps when compared with local fasciocutaneous flaps. Also, the fasciocutaneous group reported a higher nonsignificant complication rate when compared with the gluteal perforator group. No recurrent cases were reported, and most patients had satisfactory outcomes in both groups.

Conclusion:

Both techniques are safe, reliable, and effective and can be considered as a first-line option in the reconstruction of gluteal pressure ulcers.
The cell fate regulator DACH1 modulates ferroptosis through affecting P53/SLC25A37 signaling in fibrotic disease
Authors: Guo Mei , Zhuang Yanshuang , Wu Yang , Zhang Chun , Cheng Xudong , Xu Dong , Zhang Zili
Published: March 2024

Background:

Dachshund homolog 1 (DACH1) is widely acknowledged for its involvement in regulating diverse cell fates, but its precise regulatory mechanism in ferroptosis remains elusive. In this study, we investigated whether DACH1 modulates ferroptosis through affecting P53/solute carrier family 25 member 37 (SLC25A37) signaling in hepatic fibrogenesis.

Methods:

CRISPR-Cas9 system was used to knockout DACH1 in HSC to determine the effect of DACH1 on ferroptosis. Immunoprecipitation, pulldown, and mouse model of hepatic fibrogenesis were used to analyze the potential molecular mechanism of ferroptosis regulation by DACH1.

Results:

We found that ferroptosis inducers increased the protein expression of DACH1 by suppressing the ubiquitin-proteasome signaling. DACH1 knockout can resist ferroptosis, whereas DACH1 knockin can enhance it. Interestingly, the upregulation of DACH1 resulted in the mitochondrial translocation of p53 by inducing phosphorylation at serine 392. The mutation of serine 392 can prevent the combination of DACH1 and p53, the mitochondrial translocation of p53, and DACH1-mediated ferroptosis. Moreover, SLC25A37 was identified as a candidate target for mitochondrial p53. The binding of p53 to SLC25A37 can enhance the iron uptake capacity of SLC25A37, which may cause an overload of iron in the mitochondria and hyperactive mitochondrial electron transport chain. Knockdown of SLC25A37 can impair p53-mediated mitochondrial iron overload and ferroptosis. Furthermore, treatment with erastin can induce HSC ferroptosis and relieve fibrotic lesion damage in the mouse model of hepatic fibrogenesis. HSC-specific knockdown of DACH1, p53, and SLC25A37 can abolish the induction of HSC ferroptosis and reversal of hepatic fibrogenesis by erastin treatment.

Conclusions:

Our findings suggest that the DACH1/P53/SLC25A37 signaling pathway is a promising target for fibrotic disorders and reveals new regulatory mechanisms of ferroptosis.
Chinese expert consensus on open irreversible electroporation ablation for locally advanced pancreatic cancer (version 2023)
Authors: He Chaobin , Wang Jun , Mao Yize , Lao Xiangming , Chen Yongliang , Li Xiaoyong , Wu Heshui , Qiu Yudong , Li Shengping
Published: March 2024

Pancreatic cancer is one of the most lethal malignancies, with increasing morbidity and mortality. Only 20% of all cases are candidates for surgical resection. Most locally advanced pancreatic cancer (LAPC) is deemed to be an unresectable disease because of the invasion of major vessels. Irreversible electroporation (IRE) is now increasingly applicable to treat LAPC. For the establishment of precise eligibility and the standardization of the IRE technique, a guideline is expected, aiming to improve safety, lead to reproducible outcomes, and facilitate further research into IRE. This article aimed to provide a set of technical recommendations for the treatment of LAPC by open IRE.
A case report and anesthetic implications of situs inversus totalis in video-assisted thoracoscopic pulmonary resection
Authors: Kor Benjamin T. , Kor Jennifer J. , Kor Todd M , He Amy Y. , Stewart Thomas M. , Sims Charles R. , Hofer Ryan E. , Kor Nathan T.
Published: March 2024

Introduction and importance:

Reports are limited on video-assisted thoracoscopic surgery (VATS) for lung malignancy of patients with situs inversus totalis (SIT). Patients with SIT have significant anatomic differences with implications that are important for surgery, anesthesia, and nursing to understand in order to provide care for this patient population.

Case presentation:

A 64-year-old man with SIT and lung adenocarcinoma needed flexible bronchoscopy and wedge resection of a 9×8-mm adenocarcinoma in the right upper lobe and underwent VATS.

Clinical discussion:

Pre-operative planning, including collaboration with the surgical team, allowed safe monitoring, induction of anesthesia, and airway isolation in this patient allowing them to have successful resection of their pulmonary malignancy. Post-operative care was enhanced by detailed communication and understanding of the patient’s anatomy and implications of this condition for post anesthesia care unit (PACU) nursing care.

Conclusion:

Patients with rare clinical conditions and backgrounds may require surgical and anesthetic intervention. We describe important anesthetic considerations of preoperative evaluation, airway management, cardiac monitoring, and vascular access that should be noted and taken into account for patients with SIT. Proper preparation, planning, and communication allow for patients with SIT to safely undergo surgical procedures.
Histotripsy - an innovative approach for minimally invasive tumor and disease treatment
Authors: Iqbal Muhammad Faheem , Shafique Muhammad Ashir , Abdur Raqib Moosa , Fadlalla Ahmad Tagwa Kalool , Haseeb Abdul , Mhjoob Abdulhadi M. A. , Raja Adarsh
Published: March 2024

Histotripsy is a noninvasive medical technique that uses high-intensity focused ultrasound (HIFU) to treat liver tumors. The two main histotripsy methods are Boiling Histotripsy and Cavitation Cloud Histotripsy. Boiling Histotripsy uses prolonged ultrasound pulses to create small boiling bubbles in the tissue, which leads to the breakdown of the tissue into smaller subcellular fragments. Cavitation Cloud Histotripsy uses the ultrasonic cavitation effect to disintegrate target tissue into precisely defined liquefied lesions. Both methods show similar treatment effectiveness; however, Boiling Histotripsy ensures treatment stability by producing a stable boiling bubble with each pulse. The therapeutic effect is ascribed to mechanical damage at the subcellular level rather than thermal damage. This article discusses the mechanisms, treatment parameters, and potential of histotripsy as a minimally invasive procedure that provides precise and controlled subcellular damage.
Study of caudal ropivacaine with or without dexmedetomidine for postoperative analgesia in pediatric genitourinary infraumbilical surgery: A double-blinded randomized controlled trial
Authors: Tamang Kaushal , Baral Bidur Kumar , Shah Malla Sadichhya , KC Brihaspati , Kuikel Sandip , Shrestha Diwan , Pathak Nibesh
Published: March 2024

Various studies have described the use of Dexmedetomidine with local anesthetic drugs in caudal blocks for the management of postoperative pain in children. This study was designed to determine the analgesic effect of caudal Dexmedetomidine with Ropivacaine in pediatric genitourinary infraumbilical surgeries. Postoperative analgesic effects of caudal Ropivacaine with or without Dexmedetomidine in pediatric genitourinary infraumbilical were evaluated. This study was a prospective, interventional, comparative study conducted after ethical approval from the institute. Informed expressed consent was taken from each patient’s guardians. The sample size was calculated to be 31 in each group. The two groups were randomly assigned and the intervention involved caudal epidural injection with either Ropivacaine combined with Dexmedetomidine or Ropivacaine with Normal Saline. Children receiving Ropivacaine with Dexmedetomidine had a significantly prolonged duration of analgesia compared to those receiving Ropivacaine alone (840.35 ± 149.97 minutes vs. 412.90 ± 93.46 minutes, P < 0.001). Postoperative rFLACC scores were consistently lower in the Dexmedetomidine group, indicating better pain control (P < 0.05 at 6, 12, and 24 hours). Total analgesic consumption was lower in the Dexmedetomidine group (500.67 ± 212.92 mg vs. 741.75 ± 268.06 mg, P < 0.01). No significant differences in adverse effects were observed between the groups. The addition of Dexmedetomidine to Ropivacaine in caudal epidural significantly prolongs analgesia, improves pain control, and reduces analgesic consumption in pediatric genitourinary infraumbilical surgeries.
A Structured Home Health and Hospice Clinical Rotation and Onboarding Model to Address the Nursing Shortage
Authors: Dias Nancy , White Michelle , Harmuth Susan , Horvick Savannah
Published: March 2024

North Carolina home health and hospice agencies are experiencing serious shortages of registered nurses (RNs), particularly in rural areas. These shortages can negatively impact patients and families by delaying access to care and possibly resulting in avoidable hospitalizations/rehospitalizations. Many home health and hospice agencies do not hire newly graduated RNs due to limited patient care experience, limited or no opportunity for home health/hospice clinical rotations, and the autonomous nature of providing care in the home. The Hospice and Home Care Foundation of North Carolina was awarded a $468,196 3-year grant, and, in collaboration with key stakeholders, developed a model for clinical rotation experiences in home health and hospice settings for RN students as well as an onboarding model for newly graduated RNs. Seven home health and hospice project partner agencies were selected to pilot the models. This article describes program implementation and evaluation. We used a survey method and site visit interviews to assess program effectiveness. Students provided positive feedback about the clinical rotation and more than 80% indicated their clinical rotation met “most” or “almost all” of their learning needs. The focus group interviews provided substantive anecdotal examples to validate the survey results.
Improving the Accuracy of Code Status Documentation in Home Care
Authors: Benedict Joanne
Published: March 2024

Advance care planning discussions require specialized skills to elicit goals and preferences from patients contending with life-limiting illness. Documentation forms which include Health Care Proxies, Medical Orders for Life Sustaining Treatments, or Physician Orders for Life Sustaining Treatments are meant to accompany patients through every transition of care. However, they are often forgotten between the hospital and the home setting. Home care clinicians have the obligation to ensure all providers involved in the patient's care are made aware of their code status and goals of care. Consequently, home care clinicians need education about advance care planning to support patients in achieving their care goals as they transition from hospital to home. This quality improvement project implemented three consecutive interventions including reminding clinicians to review code status orders, applying short educational interventions at daily nursing huddles via email, and finally, administering primary palliative education classes for home care clinicians. The purpose was to guide home care nurses in reviewing and reaffirming code status orders and advance care documentation at the initiation of the home care episode and to improve the consistency and accuracy of code status documentation at the transition of care. After implementing the interventions to improve code status documentation, compliance improved from 8% to 100% in a 10-month period.
The Spectrum of Non-neoplastic Changes Associated With Breast Implants
Authors: Marques-Piubelli Mario L. , Lyapichev Kirill A. , FNU Aakash , Adrada Beatriz , Stewart John , Hunt Kelly K. , Clemens Mark W. , Iyer Swaminathan , Wu Yun , El Hussein Siba , Xu Jie , Ok Chi Young , Li Shaoying , Pierson Diane M. , Ferrufino-Schmidt Maria C. , Nahmod Karen A. , Yoga Arthy , Hunsicker Lisa , Evans Mark G. , Resetkova Erika , Qiu Lianqun , Khanlari Mahsa , Garces Sofia A. , Bueso-Ramos Carlos E. , Medeiros L. Jeffrey , Miranda Roberto N.
Published: March 2024

Breast implant-associated anaplastic large cell lymphoma has been recognized as a distinct entity in the World Health Organization classification of hematolymphoid neoplasms. These neoplasms are causally related to textured implants that were used worldwide until recently. Consequently, there is an increased demand for processing periprosthetic capsules, adding new challenges for surgeons, clinicians, and pathologists. In the literature, the focus has been on breast implant-associated anaplastic large cell lymphoma; however, benign complications related to the placement of breast implants occur in up to 20% to 30% of patients. Imaging studies are helpful in assessing patients with breast implants for evidence of implant rupture, changes in tissues surrounding the implants, or regional lymphadenopathy related to breast implants, but pathologic examination is often required. In this review, we couple our experience with a review of the literature to describe a range of benign lesions associated with breast implants that can be associated with different clinical presentations or pathogenesis and that may require different diagnostic approaches. We illustrate the spectrum of the most common of these benign disorders, highlighting their clinical, imaging, gross, and microscopic features. Finally, we propose a systematic approach for the diagnosis and handling of breast implant specimens in general.
Tumor Budding, Poorly Differentiated Clusters, and Stroma Percentage in Uterine Endometrioid Carcinomas Are Morphologic Findings Associated With Adverse Clinical Outcomes
Authors: Christensen Daniel , Ghafoor Mariam , Goldberg Allison , De Cotiis Dan A. , Chan Joanna S.Y.
Published: March 2024

Uterine endometrioid carcinoma (UEC) has well-defined morphologic features that carry prognostic significance and guide treatment. In addition to the well-known features, tumor budding (TB), poorly differentiated clusters (PDCs), and amount of stroma within the invasive front are associated with a poor prognostic outcome in many carcinomas. Here, we evaluate TB, PDCs, and the stroma percentage in UEC and correlate these findings with morphologic features known to be associated with a poor clinical outcome and with recurrence-free survival (RFS). We performed a retrospective search of our institution’s EMR for cases of hysterectomy for UEC. We collected clinical data including disease recurrence, death, and data associated with poor patient outcomes. Cases were evaluated for TB, PDCs, and percent stroma by 2 pathologists. Ten 20× fields were examined, and the one with the most PDCs and TB was evaluated. Percent stroma was evaluated in a ×10 field of tumor at the area of deepest invasion. Less than 10% stroma was defined as stroma poor, and >10% stroma was defined as stroma rich. Statistical testing and analysis were conducted, and P-value was set at 0.05. One hundred thirteen cases were evaluated. Decreased RFS was seen with TB (P=0.03), at least 5 PDCs (P=0.01), and stroma-rich tumors (P=0.043). This study shows a statistically significant association between TB presence, at least 5 PDCs, stroma-rich tumors, and decreased RFS in UEC. We conclude that TB, PDCs and stromal evaluation are strong independent prognostic indicators in UEC and provide additional value to the currently used morphologic assessment of UEC.