bluuebunny/crossref_metadata_2025 huggingface dataset:
Disrupting the (Hidden) Curriculum: Anti-Racist Approaches to Student Instruction and Assignments
Authors: Peters April L. , Rangel Virginia , Anderson Anastasia
Published: June 2023

In an urban elementary school serving predominantly White and Latinx students, the second-grade teachers created an assignment that asked students to share how their families migrated to the United States. The mother of a Black student met with the teacher to discuss her discomfort with the assignment given that their family descended from enslaved Africans, not immigrants. The teacher was sympathetic but did not understand the issue and refused to omit the assignment. Unsatisfied, the mother requested a meeting with the principal to discuss the racist implications of this assignment and the potential trauma her son would experience.
Health and Wellness Coaching and Sustained Gains: A Rapid Systematic Review
Authors: Ahmann Elizabeth , Saviet Micah , Conboy Lisa , Smith Katherine , Iachini Barbara , DeMartin Ron
Published: June 2023

The Transtheoretical Model of Change identifies key stages in behavior change, including a maintenance stage occurring when a behavior has been upheld for at least 6 months. Health and wellness coaching has demonstrated support for health behavior change, but maintenance of gains has received little attention. Our rapid systematic literature review characterizes both the research exploring sustained gains with health and wellness coaching and what is known about sustained gains after the completion of a health and wellness coaching engagement. Guided by The Cochrane Rapid Reviews Methods Group “Interim Guidance,” we drew 231 studies from the 2018 and 2020 Sforzo et al “Compendium of the health and wellness coaching literature,” and “Addendum…” appendices. Initial screening and coding for inclusion and exclusion criteria yielded 28 studies for data extraction. We examined studies across outcome categories (physiological, behavioral, psychological, and health risk assessment) to determine whether outcome measures were: not sustained; partially sustained; fully sustained; or improved from immediate post-intervention to a later follow-up period. Twenty-five of the 28 studies reviewed demonstrated partially, or fully, sustained or improved outcomes in one or more variables studied, with sustained gains demonstrated across outcome categories, strengthening confidence in HWC as a facilitator of lasting change.
A comparison of different population-level summary measures for randomised trials with time-to-event outcomes, with a focus on non-inferiority trials
Authors: Quartagno Matteo , Morris Tim P , Gilbert Duncan C , Langley Ruth E , Nankivell Matthew G , Parmar Mahesh KB , White Ian R
Published: June 2023

Background

The population-level summary measure is a key component of the estimand for clinical trials with time-to-event outcomes. This is particularly the case for non-inferiority trials, because different summary measures imply different null hypotheses. Most trials are designed using the hazard ratio as summary measure, but recent studies suggested that the difference in restricted mean survival time might be more powerful, at least in certain situations. In a recent letter, we conjectured that differences between summary measures can be explained using the concept of the non-inferiority frontier and that for a fair simulation comparison of summary measures, the same analysis methods, making the same assumptions, should be used to estimate different summary measures. The aim of this article is to make such a comparison between three commonly used summary measures: hazard ratio, difference in restricted mean survival time and difference in survival at a fixed time point. In addition, we aim to investigate the impact of using an analysis method that assumes proportional hazards on the operating characteristics of a trial designed with any of the three summary measures.

Methods

We conduct a simulation study in the proportional hazards setting. We estimate difference in restricted mean survival time and difference in survival non-parametrically, without assuming proportional hazards. We also estimate all three measures parametrically, using flexible survival regression, under the proportional hazards assumption.

Results

Comparing the hazard ratio assuming proportional hazards with the other summary measures not assuming proportional hazards, relative performance varies substantially depending on the specific scenario. Fixing the summary measure, assuming proportional hazards always leads to substantial power gains compared to using non-parametric methods. Fixing the modelling approach to flexible parametric regression assuming proportional hazards, difference in restricted mean survival time is most often the most powerful summary measure among those considered.

Conclusion

When the hazards are likely to be approximately proportional, reflecting this in the analysis can lead to large gains in power for difference in restricted mean survival time and difference in survival. The choice of summary measure for a non-inferiority trial with time-to-event outcomes should be made on clinical grounds; when any of the three summary measures discussed here is equally justifiable, difference in restricted mean survival time is most often associated with the most powerful test, on the condition that it is estimated under proportional hazards.
Association between blood pressure and different antihypertensive drugs with outcome after ischemic stroke: A Mendelian randomization study
Authors: Liu Hanchen , Zhang Xiaoxi , Zhou Yu , Nguyen Thanh N , Zhang Lei , Xing Pengfei , Li Zifu , Shen Hongjian , Zhang Yongxin , Hua Weilong , Xu Hongye , Zhu Xuan , Chen Lei , Zuo Qiao , Zhao Rui , Li Qiang , Dai Dongwei , Zhang Yongwei , Xu Yi , Huang Qinghai , Liu Jianmin , Yang Pengfei
Published: June 2023

Background:

Observational studies suggest an association between blood pressure (BP) and functional outcomes in ischemic stroke patients but whether this is causal or due to confounding is uncertain. We used Mendelian randomization (MR) to assess causality, and also explore whether particular classes of anti-hypertensives were associated with a better outcome after ischemic stroke.

Methods:

We selected genetic variants associated with systolic and diastolic BP and BP-lowering variants in genes encoding antihypertensive drugs from genome-wide association studies (GWAS) on 757,601 individuals. The primary outcome was 3-month dependence or death defined as a modified Rankin Scale (mRS) of 3–6. The secondary outcome was disability or death after 90 days defined as mRS 2–6. Cochran’s Q statistic in the inverse variance weighted (IVW) model, the weighted median, MR-Egger regression, leave-one-single-nucleotide polymorphism (SNP)-out analysis, MR-Pleiotropy Residual Sum and Outlier methods were adopted as sensitivity analyses. To validate our primary results, we performed independent repeat analyses and Bi-directional MR analyses.

Results:

Genetic predisposition to higher systolic and diastolic BP was associated with disability or death after ischemic stroke in univariable IVW MR analysis (odds ratio (OR) 1.29, 95% confidence interval (CI): 1.05–1.59, p = 0.014; OR 1.27, 95% CI: 1.07–1.51, p = 0.006, respectively). Pulse pressure was associated with both dependence or death and disability or death after ischemic stroke (OR = 1.05, 95% CI: 1.02–1.08, p = 0.002; OR = 1.04, 95% CI = 1.01–1.07, p = 0.009, respectively). Angiotensin-converting enzyme inhibitor (ACEI) and calcium channel blocker (CCB) were significantly associated with improved functional outcomes (dependence or death, OR 0.76, 95% CI: 0.62–0.94, p = 0.009; OR 0.89, 95% CI: 0.83–0.97, p = 0.005). Proxies for β-blockers, angiotensin receptor blockers (ARB), and thiazides failed to show associations with functional outcomes ( p > 0.05).

Conclusion:

We provide evidence for an association of genetic predisposition to higher BP with a higher risk of 3-month functional dependence after ischemic stroke. Our findings support ACEI and CCB as promising antihypertensive drugs for improving functional outcomes in ischemic stroke.
Examining a Diabetes Self-Management Education and Support Telemedicine Model With High-Risk Patients in a Rural Community
Authors: Siminerio Linda , Krall Jodi , Johnson Patricia , Ruppert Kristine , Hammoudeh Rawan , Bandi Archana , Ng Jason M.
Published: June 2023

Background:

Ongoing support is critical to diabetes self-management education and support (DSMES) effectiveness, but difficult to realize, particularly in areas with limited resources. The objective of this feasibility study was to assess the impact of a virtual support model on diabetes outcomes and acceptability with high-risk patients with type 2 diabetes in a rural community.

Methods:

In a 12-month nonrandomized trial in federally qualified health centers (FQHCs), patients with hemoglobin A1c (HbA1c) >9% were referred to the Telemedicine for Reach, Education, Access, Treatment, and Ongoing Support (TREAT-ON) program where a Diabetes Care and Education Specialist provided DSMES through videoconferencing. HbA1c change was compared in 30 patients in the intervention group (IG) to a propensity score-matched retrospective control group (CG) of patients who received in-person DSMES delivered by a DCES. Changes in HbA1c, diabetes distress, empowerment, self-care and acceptability were assessed within the intervention group (IG) between those who did and did not meet self-management goals.

Results:

The IG experienced similar significant reductions in HbA1c as the CG. Most (64%) IG participants achieved their self-management goal. Goal attainers had a significant HbA1c decrease of 0.21% every 3 months as well as significant reduction in diabetes distress and improvement in general dietary intake. Regardless of goal attainment, IG participants reported high levels of acceptability with TREAT-ON.

Conclusions:

This feasibility study suggests that TREAT-ON was well-received and as effective as traditional in-person DSMES. While findings augment ample evidence regarding DSMES benefits, the TREAT-ON model offers additional advantages and provides validation for telehealth to inform future practice in reaching and supporting self-management for high-risk patients in underserved areas.

Trial Registration:

Clinicaltrials.gov, # NCT04107935.
Systemic monotherapy with acitretin for erythrodermic psoriasis: results of a retrospective study of 81 patients
Authors: Yu Chenyang , Wu Chao , Yang Yuyan , Jin Hongzhong
Published: June 2023

Background:

Erythrodermic psoriasis (EP) remains challenging to manage because it is rare and has complex complications. Although acitretin is recommended as an appropriate choice for EP, there is a lack of large-scale evidence.

Objectives:

This study aims to assess the efficacy and safety of acitretin as systemic monotherapy in EP patients.

Design:

We retrospectively analyzed data from patients with EP who received at least 3 months of acitretin as systemic monotherapy during hospitalization and out-patient follow-up from January 2005 to May 2021 at the Peking Union Medical College Hospital, China.

Methods:

The efficacy was clinically evaluated after 1, 2, 4, and 12 weeks of treatment, which was classified as a good response (>75% of lesions cleared), partial response (50%–75% cleared), moderate response (25–50% cleared), or no response (<25% cleared). Safety was assessed on the basis of physical examination results and significant changes in laboratory examination results after 12 weeks of treatment.

Results:

Overall, 81 patients (79.0% men; mean age, 47.9 years) were included. The acitretin dose ranged from 20 to 60 mg/day (0.3 to 0.8 mg/kg/day). The rates of good, partial, and moderate responses were 0.0%, 2.5%, and 42.0% at 1 week; 3.7%, 34.6%, and 61.7% at 2 weeks; 29.6%, 58.0%, and 12.4% at 4 weeks; and 85.2%, 13.6%, and 1.2% at 12 weeks after treatment initiation, respectively. EP patients transformed from psoriasis vulgaris showed a higher good/partial response rate compared with that of EP patients that developed from pustular or articular psoriasis (44.6% vs. 14.3%, p = 0.035). Patients with concurrent infection showed a lower rate of good/partial response compared with that of those without concurrent infection (16.7% vs. 44.4%, p = 0.049). Adverse effects were seen in 45 (55.6%) patients in 12 weeks, and dyslipidemia ( n = 31; 38.3%), xerosis ( n = 24; 29.6%), and elevated liver enzymes ( n = 6; 7.4%) were most commonly reported. Twenty-three patients were followed up for over 3 years, and six (26.1%) patients had EP recurrence.

Conclusions:

Acitretin as a systemic monotherapy showed satisfactory effectiveness for EP, especially in patients developed from psoriasis vulgaris and without infection.
Integrated health system to assess and manage frailty in community dwelling: Co-design and usability evaluation
Authors: Moral Cristian , Pérez-Rodríguez Rodrigo , Villalba-Mora Elena , Barrio-Cortes Jaime , Ferre Xavier , Rodríguez-Mañas Leocadio
Published: June 2023

Objective

We aimed to co-create and evaluate an integrated system to follow-up frailty in a community dwelling environment and provide a multi-modal tailored intervention. Frailty and dependency among the older population are a major challenge to the sustainability of healthcare systems. Special attention must be paid to the needs and particularities of frail older persons as a vulnerable group.

Methods

To ensure the solution fits all the stakeholders’ needs, we performed several participatory design activities with them, such as pluralistic usability walkthroughs, design workshops, usability tests and a pre-pilot. The participants in the activities were older people; their informal carers; and specialized and community care professionals. In total, 48 stakeholders participated.

Results

We created and evaluated an integrated system consisting of four mobile applications and a cloud server, which has been evaluated through a 6-months clinical trial, where secondary endpoints were both usability and user experience evaluation. In total, 10 older adults and 12 healthcare professionals participated in the intervention group using the technological system. Both patients and professionals have positively evaluated their applications.

Conclusion

Both older adults and healthcare professionals have considered the resulted system easy to use and learn, consistent and secure. In general terms, they also would like to keep using it in the future.
Incivility in Online Discussion: An Examination of Impolite and Intolerant Comments
Authors: Rega Rossella , Marchetti Rita , Stanziano Anna
Published: June 2023

Incivility in online political discussion represents one of the most widely debated issues among scholars. Much research focuses on the incivility disseminated by political elites on social media, paying less attention to the user incivility that spreads as a “bottom-up” reaction to politicians’ posts. To fill this gap, the article focuses on user comments on the Facebook pages of parliamentary candidates in the run-up to the Italian general election of 2018. Distinguishing between intolerant and impolite comments, we observed that the extent of the former in user discussions is limited, and linked to highly sensitive issues and radical right-wing populist communities. This would seem to counter the view that all political debate on social media is inherently toxic and harmful to democratic and deliberative processes. Impoliteness, on the contrary, is adopted by users to express mutual hostility and seems particularly based on feelings of partisanship, so that the issues disappear completely from the discussion and forms of participation “against the other” are activated.
Music and Boredom: A First Insight Into an Unexplored Relationship
Authors: Merrill Julia , Niedecken Tristan
Published: June 2023

While the positive effects of music listening have received much attention, insights into the negative effects are rare, such as the experience of boredom. In two consecutive online surveys using qualitative (N  =  266) and quantitative methods (N  =  719), participants were asked to retrospectively report their experience of boredom while listening to music. The experience of boredom depends on a combination of factors, such as musical features or styles combined with a certain situation, or the dislike of that music. Boredom is also accompanied by feelings of high and low arousal such as annoyance, anger, fatigue, and listlessness. Notably, boredom in the context of music does not only refer to an emotional state but is also used as a disparaging judgment of music. The associated musical features of “boring” music, such as repetition and monotony, go along with a perceived simplicity and uniformity in specific musical styles (e.g., German schlager, pop, EDM, or rap). Overall, the prevalence of boredom during music listening was low in the current sample, where 77% never or rarely experience boredom, but 46% report experiencing it moderately to very severely when it occurs. Participants with higher musical perceptual abilities report experiencing boredom more frequently and intensely, while a higher active engagement with music and higher agreeableness seem to prevent one from “musical” boredom. The results align with typical aspects of general boredom and contribute to the understanding of the variety of factors that compose an averse form of an aesthetic experience with music.
Return to Sport After Multiligament Knee Injury in Young Athletes
Authors: Fine River , Curtis William , Stevens Kaleb , Imada Allicia O. , Stein Elena R. , Treme Gehron , Schenck Robert C. , Richter Dustin L.
Published: June 2023

Background:

While return to sport (RTS) in young athletes after anterior cruciate ligament (ACL) reconstruction has been well studied, little is known regarding their rate of RTS after multiligament knee injury (MLKI).

Purpose:

To assess the level of and factors associated with RTS after MLKI in young athletes.

Study Design:

Case series; Level of evidence, 4.

Methods:

We retrospectively identified 116 patients aged ≤23 years who had sustained an injury to ≥2 knee ligaments and undergone operative reconstruction or repair of ≥1 ligament. Our primary outcome was self-reported RTS at the preinjury level or higher. We estimated the likelihood of RTS using binomial logistic regression. Secondary variables included the 2000 International Knee Documentation Committee Subjective Knee Form (IKDC-SF), ACL–Return to Sport after Injury (ACL-RSI), and 12-Item Short Form Health Survey (SF-12) physical and mental health summaries.

Results:

A total of 30 (25.9%) patients (24 men, 6 women; mean age, 18.1 ± 2.5 years) completed patient-reported outcome surveys at a mean follow-up of 7.8 years (median, 6.6 years [range, 1.1-19.5 years]). A total of 28 patients underwent surgical treatment of ≥2 ligaments. RTS was achieved by 90% of patients, and 43.3% returned to their preinjury level or higher. Patients who had played sports at a higher level before injury were more likely to RTS at their preinjury level or higher (odds ratio [OR], 3.516 [95% CI, 1.034-11.955]; P = .044), while those who played cutting sports were less likely to do so (OR, 0.013 [95% CI, 0.000-0.461; P = .017). Patients who achieved RTS at their preinjury level or higher had significantly higher IKDC-SF and ACL-RSI scores versus patients who did not ( P = .001 and P = .002, respectively). The number of ligaments injured, age, mental health diagnosis, and SF-12 scores were not associated with the ability to RTS at the preinjury or higher levels.

Conclusion:

Most young athletes who sustained MLKI were able to return to play at some level, but a minority returned to their preinjury level. Patients who did return at preinjury or higher levels had higher IKDC-SF and ACL-RSI scores than those who did not. Performance in cutting and/or pivoting sports was negatively associated with RTS.
Patient Journey Map: Metal Hypersensitivity
Authors: Lagura J. Adrienne , Dordunoo Dzifa , Mallidou Anastasia , Carey Jett , Borycki Elizabeth M. , Kushniruk Andre
Published: June 2023

In this study, we highlight patients’ experiences with metal hypersensitivity (MH) after receiving implantable medical devices (IMDs). We aim to identify gaps in clinical care and improve outcomes for individuals who have or may be sensitive to metals. Secondary data analysis from a previous interpretative phenomenological qualitative study was utilized. Using patient journey maps, we explored the experiences of 8 individuals from outpatient settings who received IMD and have first-hand experience with MH. We documented their journey from MH symptom recognition to diagnosis and subsequent IMD management. The results reveal that the time frames from device implantation to the treatment of MH varied from 17 to 228 months. The longest phase on the patient journey maps was the symptom recognition phase, which refers to the time between symptom emergence and MH diagnosis. Participants also required extensive healthcare utilization following their initial surgery. These findings emphasize that MH should be considered in differential diagnoses for patients with IMD. Early screening and detection of MH can enhance patient safety, alleviate distress, and reduce unnecessary healthcare utilization.
Telehealth for Comprehensive Care to Quarantine Residents: A Novel Approach and Lessons Learned
Authors: Curtis Stephanie J. , Taylor Ronnie , Perry Lynette , Trewin Abigail , Were Karen , Walsh Nick , McDermott Kathleen
Published: June 2023

Proactive engagement and care with regular and timely information are required to manage the health and well-being of people in quarantine. At Australia's Howard Springs International Quarantine Facility, a telehealth model was rapidly established using trained non-clinical Customer Service Officers (CSO's) with the aim to provide comprehensive care to residents, maximize staff safety, and reduce clinical workforce capacity pressures. We describe this model, whereby CSO's provided residents with daily COVID-19 symptom and well-being screening, weekly psychological screening, and ongoing linkage to additional clinical and administrative services. In addition, CSO's went beyond these duties to deliver personalized care through delivery of care packages and attendance of the departure point to farewell residents. From October 2020 to May 2021, across 7105 residents, we estimated that CSO's prevented over 75 000 face-to-face resident visits, which reduced workforce requirements and preserved staff safety through minimizing potential COVID-19 transmission and time spent in personal protective equipment in the challenging ambient environment. We share key lessons learned which may inform future telehealth models and guide a positive experience for quarantine residents.
Collaborative Learning Communities With Medical Students as Teachers
Authors: Yang Chenyi , Davis Konnor , Head Michael , Huck Nolan A. , Irani Tyler , Ovakimyan Andrew , Frank Aaron , Cuyegkeng Andrew , Stokes Lauren
Published: June 2023

In recent years, peer-assisted learning has emerged as a new and effective medical education modality. Near-peer tutoring utilizes a senior student serving as an instructor to a junior student. In 2019, the University of California, Irvine, School of Medicine (UCISOM) implemented a near-peer tutoring model beginning with first-year anatomy and physiology curricula. Following a successful pilot program, UCISOM launched a full-fledged near-peer tutoring program in 2020 named Collaborative Learning Communities (CLC) with Medical Students as Teachers. The rollout of CLC occurred in phases. In 2020, second-year medical students led the program for first-year students; in 2021, an additional program was led by third-year medical students for second-year students; in 2022, the program expanded to third-year medical students led by fourth-year students. Each program serves the unique learning needs of each student class, utilizing evidence-based teaching practices while allowing the opportunity for mentorship, interclass connectedness, and refinement of the tutor's teaching skills. In this paper, we describe the creation of CLC, its goals, leadership and curricular structure, and its various benefits, challenges, and limitations.
Chimeric antigen receptor T-cell therapy in a dialysis patient with lymphoma
Authors: Mire Muhammad , Collins Jennifer , Bonilla Marco , Riedell Peter A , Koyner Jay L
Published: June 2023

Chimeric antigen receptor T-cell (CAR-T) therapy has become a revolutionary cancer therapy for multiple subtypes of hematologic malignancies. Despite this progress, CAR-T use in End Stage Kidney Disease (ESKD) patients is limited. We describe the successful administration of CAR-T therapy in a patient with ESKD who had developed diffuse large B-cell lymphoma (DLBCL) from an underlying chronic lymphocytic leukemia. The patient received CAR-T therapy, preceded by lymphodepleting chemotherapy with dose-reduced fludarabine and cyclophosphamide, followed by intermittent hemodialysis on a modified basis. The treatment course was complicated by pancytopenia and Grade 2 cytokine release syndrome, managed with tocilizumab. The patient underwent an initial disease response assessment, which showed a complete response, and remains in remission 12 months after CAR-T infusion. This case report highlights the importance of individualized hemodialysis schedules and lymphodepleting chemotherapy dose adjustments in ESKD patients for a successful administration of CAR-T therapy.
Epichaperome inhibition targets TP53-mutant AML and AML stem/progenitor cells
Authors: Carter Bing Z. , Mak Po Yee , Muftuoglu Muharrem , Tao Wenjing , Ke Baozhen , Pei Jingqi , Bedoy Andrea D. , Ostermann Lauren B. , Nishida Yuki , Isgandarova Sevinj , Sobieski Mary , Nguyen Nghi , Powell Reid T. , Martinez-Moczygemba Margarita , Stephan Clifford , Basyal Mahesh , Pemmaraju Naveen , Boettcher Steffen , Ebert Benjamin L. , Shpall Elizabeth J. , Wallner Barbara , Morgan Robert A. , Karras Georgios I. , Moll Ute M. , Andreeff Michael
Published: June 2023

TP 53-mutant acute myeloid leukemia (AML) remains the ultimate therapeutic challenge. Epichaperomes, formed in malignant cells, consist of heat shock protein 90 (HSP90) and associated proteins that support the maturation, activity, and stability of oncogenic kinases and transcription factors including mutant p53. High-throughput drug screening identified HSP90 inhibitors as top hits in isogenic TP53–wild-type (WT) and -mutant AML cells. We detected epichaperomes in AML cells and stem/progenitor cells with TP53 mutations but not in healthy bone marrow (BM) cells. Hence, we investigated the therapeutic potential of specifically targeting epichaperomes with PU-H71 in TP53-mutant AML based on its preferred binding to HSP90 within epichaperomes. PU-H71 effectively suppressed cell intrinsic stress responses and killed AML cells, primarily by inducing apoptosis; targeted TP53-mutant stem/progenitor cells; and prolonged survival of TP53-mutant AML xenograft and patient-derived xenograft models, but it had minimal effects on healthy human BM CD34+ cells or on murine hematopoiesis. PU-H71 decreased MCL-1 and multiple signal proteins, increased proapoptotic Bcl-2-like protein 11 levels, and synergized with BCL-2 inhibitor venetoclax in TP53-mutant AML. Notably, PU-H71 effectively killed TP53-WT and -mutant cells in isogenic TP53-WT/TP53-R248W Molm13 cell mixtures, whereas MDM2 or BCL-2 inhibition only reduced TP53-WT but favored the outgrowth of TP53-mutant cells. Venetoclax enhanced the killing of both TP53-WT and -mutant cells by PU-H71 in a xenograft model. Our data suggest that epichaperome function is essential for TP53-mutant AML growth and survival and that its inhibition targets mutant AML and stem/progenitor cells, enhances venetoclax activity, and prevents the outgrowth of venetoclax-resistant TP53-mutant AML clones. These concepts warrant clinical evaluation.
Analysis and therapeutic targeting of the IL-1R pathway in anaplastic large cell lymphoma
Authors: Song Zhihui , Wu Wenjun , Wei Wei , Xiao Wenming , Lei Michelle , Cai Kathy Q. , Huang Da Wei , Jeong Subin , Zhang Jing-Ping , Wang Hongbo , Kadin Marshall E. , Waldmann Thomas A. , Staudt Louis M. , Nakagawa Masao , Yang Yibin
Published: June 2023

Anaplastic large cell lymphoma (ALCL), a subgroup of mature T-cell neoplasms with an aggressive clinical course, is characterized by elevated expression of CD30 and anaplastic cytology. To achieve a comprehensive understanding of the molecular characteristics of ALCL pathology and to identify therapeutic vulnerabilities, we applied genome-wide CRISPR library screenings to both anaplastic lymphoma kinase positive (ALK+) and primary cutaneous (pC) ALK− ALCLs and identified an unexpected role of the interleukin-1R (IL-1R) inflammatory pathway in supporting the viability of pC ALK− ALCL. Importantly, this pathway is activated by IL-1α in an autocrine manner, which is essential for the induction and maintenance of protumorigenic inflammatory responses in pC-ALCL cell lines and primary cases. Hyperactivation of the IL-1R pathway is promoted by the A20 loss-of-function mutation in the pC-ALCL lines we analyze and is regulated by the nonproteolytic protein ubiquitination network. Furthermore, the IL-1R pathway promotes JAK-STAT3 signaling activation in ALCLs lacking STAT3 gain-of-function mutation or ALK translocation and enhances the sensitivity of JAK inhibitors in these tumors in vitro and in vivo. Finally, the JAK2/IRAK1 dual inhibitor, pacritinib, exhibited strong activities against pC ALK− ALCL, where the IL-1R pathway is hyperactivated in the cell line and xenograft mouse model. Thus, our studies revealed critical insights into the essential roles of the IL-1R pathway in pC-ALCL and provided opportunities for developing novel therapeutic strategies.
Generating porous metal surfaces as a mean to incorporate thymol-loaded nanoparticles
Authors: Zemmour Chalom , Zakharova Sofya , Benny Ofra
Published: June 2023

Porous metals have gained interest in many fields such as biomedicine, electronics, and energy. Despite the many benefits that these structures may offer, one of the major challenges in utilizing porous metals is to incorporate active compounds, either small molecules or macromolecules, on these surfaces. Coatings that contain active molecules have previously been used for biomedical applications to enable the slow release of drugs, e.g., with drug-eluting cardiovascular stents. However, direct deposition of organic materials on metals by coatings is very difficult due to the challenge of obtaining uniform coatings, as well as issues related to layer adherence and mechanical stability. Our study describes an optimization of a production process of different porous metals, aluminum, gold, and titanium, using wet-etching. Pertinent physicochemical measurements were carried out to characterize the porous surfaces. Following the production of porous metal surface, a new methodology for incorporating active materials onto the metals by using mechanical entrapment of polymeric nanoparticles in metal pores was developed. To demonstrate our concept of active material incorporation, we produced an odor-releasing metal object with embedded particles loaded with thymol, an odoriferous molecule. Polymer particles were placed inside nanopores in a 3D-printed titanium ring. Chemical analysis, followed by smell tests, indicated that the smell intensity lasts significantly longer in the porous material containing the nanoparticles, compared with the free thymol.
Co-delivery of curcumin and si-STAT3 with a bioinspired tumor homing for polydopamine nanoparticles for synergistic osteosarcoma therapy
Authors: Wu Kunzhe , Zhou Zhongsheng , Liu Te , Liu Chunkang , Mu Xupeng , Jiang Jinlan
Published: June 2023

Purpose

Owing to the complexity of cancer, a synergistic combination of chemotherapy and gene therapy can be a promising therapeutic strategy. This study aimed to use stem cell membrane (SCM)-camouflaged polydopamine nanoparticles for simultaneous delivery of curcumin (CUR) and siRNA-targeting STAT3 (CPDA/siSTAT3@SCM NPs) for osteosarcoma (OS).

Methods

Transmission electron microscopy, UV–Vis absorbance spectra, zeta potential, cell co-localization, and Coomassie bright blue staining were used to characterize CPDA/siSTAT3@SCM NPs constructed by the self-assembly method. Drug release, cellular uptake, cell proliferation, apoptosis, wound healing, and transwell assays were evaluated in vitro. The expression levels of epithelial–mesenchymal transition (EMT)- and apoptosis-related proteins were measured by western blotting. Furthermore, the biodistribution, antitumor efficacy, and biosafety of CPDA/siSTAT3@SCM NPs in an MG63 xenograft mouse model were evaluated.

Results

CPDA/siSTAT3@SCM NPs were successfully synthesized to deliver CUR and siRNA simultaneously, and they showed osteosarcoma-targeting ability. Furthermore, it showed high cellular uptake and excellent synergistic antitumor effects in vitro. CPDA/siSTAT3@SCM NPs suppressed OS cell proliferation, migration, invasion, and EMT progression, and promoted the apoptotic process. In tumor-bearing mice, the treatment with CPDA/siSTAT3@SCM NPs showed an excellent antitumor effect with no side effects in major organs.

Conclusion

This study revealed that CPDA/siSTAT3@SCM NPs can target drug delivery by biomimetic multifunctional nanoparticles to treat OS through chemo-gene combined therapy.
PacBio single-molecule long-read sequencing provides new insights into the complexity of full-length transcripts in oriental river prawn, macrobrachium nipponense
Authors: Mou Cheng-Yan , Li Qiang , Huang Zhi-Peng , Ke Hong-Yu , Zhao Han , Zhao Zhong-Meng , Duan Yuan-Liang , Li Hua-Dong , Xiao Yu , Qian Zhou-Ming , Du Jun , Zhou Jian , Zhang Lu
Published: June 2023

Background

Oriental river prawn (Macrobrachium nipponense) is one of the most dominant species in shrimp farming in China, which is a rich source of protein and contributes to a significant impact on the quality of human life. Thus, more complete and accurate annotation of gene models are important for the breeding research of oriental river prawn.

Results

A full-length transcriptome of oriental river prawn muscle was obtained using the PacBio Sequel platform. Then, 37.99 Gb of subreads were sequenced, including 584,498 circular consensus sequences, among which 512,216 were full length non-chimeric sequences. After Illumina-based correction of long PacBio reads, 6,599 error-corrected isoforms were identified. Transcriptome structural analysis revealed 2,263 and 2,555 alternative splicing (AS) events and alternative polyadenylation (APA) sites, respectively. In total, 620 novel genes (NGs), 197 putative transcription factors (TFs), and 291 novel long non-coding RNAs (lncRNAs) were identified.

Conclusions

In summary, this study offers novel insights into the transcriptome complexity and diversity of this prawn species, and provides valuable information for understanding the genomic structure and improving the draft genome annotation of oriental river prawn.
Activation of astrocytes in the basal forebrain in mice facilitates isoflurane-induced loss of consciousness and prolongs recovery
Authors: Lin Jialing , Cheng Xuefeng , Wang Haoyuan , Du Lin , Li Xiangyu , Zhao Gaofeng , Xie Chuangbo
Published: June 2023

Objectives

General anesthesia results in a state of unconsciousness that is similar to sleep. In recent years, increasing evidence has reported that astrocytes play a crucial role in regulating sleep. However, whether astrocytes are involved in general anesthesia is unknown.

Methods

In the present study, the designer receptors exclusively activated by designer drugs (DREADDs) approach was utilized to specifically activate astrocytes in the basal forebrain (BF) and observed its effect on isoflurane anesthesia. One the other side, L-α-aminoadipic acid was used to selectively inhibit astrocytes in the BF and investigated its influence on isoflurane-induced hypnotic effect. During the anesthesia experiment, cortical electroencephalography (EEG) signals were recorded as well.

Results

The chemogenetic activation group had a significantly shorter isoflurane induction time, longer recovery time, and higher delta power of EEG during anesthesia maintenance and recovery periods than the control group. Inhibition of astrocytes in the BF delayed isoflurane-induced loss of consciousness, promoted recovery, decreased delta power and increased beta and gamma power during maintenance and recovery periods.

Conclusions

The present study suggests that astrocytes in the BF region are involved in isoflurane anesthesia and may be a potential target for regulating the consciousness state of anesthesia.
Classification based on event in survival machine learning analysis of cardiovascular disease cohort
Authors: Ahmad Shokh Mukhtar , Ahmed Nawzad Muhammed
Published: June 2023

The aim of this study is to assess the effectiveness of supervised learning classification models in predicting patient outcomes in a survival analysis problem involving cardiovascular patients with a significant cured fraction. The sample comprised 919 patients (365 females and 554 males) who were referred to Sulaymaniyah Cardiac Hospital and followed up for a maximum of 650 days between 2021 and 2023. During the research period, 162 patients (17.6%) died, and the cure fraction in this cohort was confirmed using the Mahler and Zhu test (P < 0.01). To determine the best patient status prediction procedure, several machine learning classifications were applied. The patients were classified into alive and dead using various machine learning algorithms, with almost similar results based on several indicators. However, random forest was identified as the best method in most indicators, with an Area under ROC of 0.934. The only weakness of this method was its relatively poor performance in correctly diagnosing deceased patients, whereas SVM with FP Rate of 0.263 performed better in this regard. Logistic and simple regression also showed better performance than other methods, with an Area under ROC of 0.911 and 0.909 respectively.
Traumatic cardiac arrest – a nationwide Danish study
Authors: Wolthers Signe Amalie , Jensen Theo Walther , Breindahl Niklas , Milling Louise , Blomberg Stig Nikolaj , Andersen Lars Bredevang , Mikkelsen Søren , Torp-Pedersen Christian , Christensen Helle Collatz
Published: June 2023

Background

Cardiac arrest following trauma is a leading cause of death, mandating urgent treatment. This study aimed to investigate and compare the incidence, prognostic factors, and survival between patients suffering from traumatic cardiac arrest (TCA) and non-traumatic cardiac arrest (non-TCA).

Methods

This cohort study included all patients suffering from out-of-hospital cardiac arrest in Denmark between 2016 and 2021. TCAs were identified in the prehospital medical record and linked to the out-of-hospital cardiac arrest registry. Descriptive and multivariable analyses were performed with 30-day survival as the primary outcome.

Results

A total of 30,215 patients with out-of-hospital cardiac arrests were included. Among those, 984 (3.3%) were TCA. TCA patients were younger and predominantly male (77.5% vs 63.6%, p =  < 0.01) compared to non-TCA patients. Return of spontaneous circulation occurred in 27.3% of cases vs 32.3% in non-TCA patients, p < 0.01, and 30-day survival was 7.3% vs 14.2%, p < 0.01. An initial shockable rhythm was associated with increased survival (aOR = 11.45, 95% CI [6.24 – 21.24] in TCA patients. When comparing TCA with non-TCA other trauma and penetrating trauma were associated with lower survival (aOR: 0.2, 95% CI [0.02–0.54] and aOR: 0.1, 95% CI [0.03 – 0.31], respectively. Non-TCA was associated with an aOR: 3.47, 95% CI [2.53 – 4,91].

Conclusion

Survival from TCA is lower than in non-TCA. TCA has different predictors of outcome compared to non-TCA, illustrating the differences regarding the aetiologies of cardiac arrest. Presenting with an initial shockable cardiac rhythm might be associated with a favourable outcome in TCA.
Qualitative study on the use of emergency services by people with serious mental disorder in Spain
Authors: Pérez-Milena Alejandro , Ramos-Ruiz Juan Andrés , Zafra-Ramirez Natalia , Noguera-Cuenca Carmen , Rodríguez-Bayón Antonina , Ruiz-Díaz Beatriz
Published: June 2023

Background

The population with severe mental disorders (SMD) is a frequent user of emergency services. Situations of psychiatric decompensation can have devastating consequence and can cause problems in getting urgent medical care. The objective was to study the experiences and needs of these patients and their caregivers regarding the demand for emergency care in Spain.

Methods

Qualitative methodology involving patients with SMD and their informal caregivers. Purposive sampling by key informants in urban and rural areas. Paired interviews were carried out until data saturation. A discourse analysis was conducted, obtaining a codification in categories by means of triangulation.

Results

Forty-two participants in twenty-one paired interviews (19 ± 7.2 min as mean duration). Three categories were identified. 1º Reasons for urgent care: poor self-care and lack of social support, as well as difficulties in accessibility and continuity of care in other healthcare settings. 2º Urgent care provision: trust in the healthcare professional and the information patients receive from the healthcare system is crucial, telephone assistance can be a very useful resource. 3º Satisfaction with the urgent care received: they request priority care without delays and in areas separated from the other patients, as well as the genuine interest of the professional who attends them.

Conclusions

The request for urgent care in patients with SMD depends on different psychosocial determinants and not only on the severity of the symptoms. There is a demand for care that is differentiated from the other patients in the emergency department. The increase in social networks and alternative systems of care would avoid overuse of the emergency departments.
Predictors of not maintaining regular medical follow-up after stroke
Authors: Springer Mellanie V. , Skolarus Lesli E. , Feng Chunyang , Burke James F.
Published: June 2023

Background

Regular medical follow-up after stroke is important to reduce the risk of post-stroke complications and hospital readmission. Little is known about the factors associated with stroke survivors not maintaining regular medical follow-up. We sought to quantify the prevalence and predictors of stroke survivors not maintaining regular medical follow-up over time.

Methods

We conducted a retrospective cohort study of stroke survivors in the National Health and Aging Trends Study (2011–2018), a national longitudinal sample of United States Medicare beneficiaries. Our primary outcome was not maintaining regular medical follow-up. We performed a cox regression to estimate predictors of not maintaining regular medical follow-up.

Results

There were 1330 stroke survivors included, 150 of whom (11.3%) did not maintain regular medical follow-up. Stroke survivor characteristics associated with not maintaining regular medical follow-up included not having restrictions in social activities (HR 0.64, 95% CI 0.41, 1.01 for having restrictions in social activities compared to not having restrictions in social activities), greater limitations in self-care activities (HR 1.13, 95% CI 1.03, 1.23), and probable dementia (HR 2.23, 95% CI 1.42, 3.49 compared to no dementia).

Conclusions

The majority of stroke survivors maintain regular medical follow-up over time. Strategies to retain stroke survivors in regular medical follow-up should be directed towards stroke survivors who do not have restrictions in social activity participation, those with greater limitations in self-care activities, and those with probable dementia.
Cesarean section rates according to the Robson Classification and its association with adequacy levels of prenatal care: a cross-sectional hospital-based study in Brazil
Authors: Piva Veridiana Monteiro Ramos , Voget Verena , Nucci Luciana Bertoldi
Published: June 2023

Background

The rate of Cesarean section (CS) deliveries has been increasing worldwide for decades. Brazil exhibits high rates of patient-requested CS deliveries. Prenatal care is essential for reducing and preventing maternal and child morbidity and mortality, ensuring women's health and well-being. The aim of this study was to verify the association between the level of prenatal care, as measured by the Kotelchuck (APNCU – Adequacy of the prenatal care utilization) index and CS rates.

Methods

We conducted a cross-sectional study based on data from routine hospital digital records and federal public health system databases (2014–2017). We performed descriptive analyses, prepared Robson Classification Report tables, and estimated the CS rate for the relevant Robson groups across distinct levels of prenatal care. Our analysis also considered the payment source for each childbirth – either public healthcare or private health insurers – and maternal sociodemographic data.

Results

CS rate by level of access to prenatal care was 80.0% for no care, 45.2% for inadequate, 44.2% for intermediate, 43.0% for adequate, and 50.5% for the adequate plus category. No statistically significant associations were found between the adequacy of prenatal care and the rate of cesarean sections in any of the most relevant Robson groups, across both public (n = 7,359) and private healthcare (n = 1,551) deliveries.

Conclusion

Access to prenatal care, according to the trimester in which prenatal care was initiated and the number of prenatal visits, was not associated with the cesarean section rate, suggesting that factors that assess the quality of prenatal care, not simply adequacy of access, should be investigated.
Cytokine quantification and association with cervical length in a prospective cohort of pregnant women
Authors: Herren Helmer , Marcolin Alessandra C. , Barbieri Marco A. , Bettiol Heloisa , Cardoso Viviane C. , Quintana Silvana M. , Cavalli Ricardo C.
Published: June 2023

Background

Preterm birth is a leading cause of infant morbidity and mortality; its multifactorial causes are an obstacle to understanding etiology and pathogenesis. The importance of cytokines and inflammation in its etiology and association with the short cervix is nowadays well-proven. To date, there are no reliable biological or biochemical markers to predict preterm birth; even though the length of the cervix has high specificity, its sensitivity with the cervix below 2.5 cm is low.

Objective

We study the association of plasma cytokine levels and cervical length in search of predictors of preterm birth.

Study design

We evaluated a total of 1400 pregnant women carrying a single fetus between 20 and 25 weeks of gestation, and 1370 of them after childbirth in a nested case–control study of a prenatal cohort. Eligible pregnant women were interviewed and submitted to obstetric morphological and transvaginal ultrasound with cervical length measurement, gynecological examination, and blood collection. Preterm birth occurred in 133 women, 129 included in the study, and a control group randomly selected at a 2:1 ratio. A total of 41 cytokines with a higher probability of being associated with preterm birth or being of significance during labor were determined.

Results

Cytokine and cervical length analysis by multivariate analysis of the conditional interference tree revealed that growth-related oncogene values of less than 2293 pg/mL were significantly associated with a cervical length of less than 2.5 cm.

Conclusions

As well as a cervical length shorter than 2.5 cm, growth-related oncogene levels of less than 2293 pg/ml may be associated with an increased risk of PB. Analysis based on the association of biomarkers and of the interaction between cytokines is a promising pathway in search of a predictor of preterm birth.