bluuebunny/crossref_metadata_2025 huggingface dataset:
Bendamustine lymphodepletion before axicabtagene ciloleucel is safe and associates with reduced inflammatory cytokines
Authors: Ghilardi Guido , Paruzzo Luca , Svoboda Jakub , Chong Elise A. , Shestov Alexander A. , Chen Linhui , Cohen Ivan J. , Gabrielli Giulia , Nasta Sunita D. , Porazzi Patrizia , Landsburg Daniel J. , Gerson James N. , Carter Jordan , Barta Stefan K. , Yelton Rebecca , Pajarillo Raymone , Patel Vrutti , White Griffin , Ballard Hatcher J. , Weber Elizabeth , Napier Ellen , Chong Emeline R. , Fraietta Joseph A. , Garfall Alfred L. , Porter David L. , Milone Michael C. , O’Connor Roderick , Schuster Stephen J. , Ruella Marco
Published: December 2023

Lymphodepletion (LD) is an integral component of chimeric antigen receptor T-cell (CART) immunotherapies. In this study, we compared the safety and efficacy of bendamustine (Benda) to standard fludarabine/cyclophosphamide (Flu/Cy) LD before CD19-directed, CD28-costimulated CART axicabtagene ciloleucel (axi-cel) for patients with large B-cell lymphoma (LBCL) and follicular lymphoma (FL). We analyzed 59 patients diagnosed with LBCL (n = 48) and FL (n = 11) consecutively treated with axi-cel at the University of Pennsylvania. We also analyzed serum samples for cytokine levels and metabolomic changes before and after LD. Flu/Cy and Benda demonstrated similar efficacy, with complete remission rates of 51.4% and 50.0% (P = .981), respectively, and similar progression-free and overall survivals. Any-grade cytokine-release syndrome occurred in 91.9% of patients receiving Flu/Cy vs 72.7% of patients receiving Benda (P = .048); any-grade neurotoxicity after Flu/Cy occurred in 45.9% of patients and after Benda in 18.2% of patients (P = .031). In addition, Flu/Cy was associated with a higher incidence of grade ≥3 neutropenia (100% vs 54.5%; P < .001), infections (78.4% vs 27.3%; P < .001), and neutropenic fever (78.4% vs 13.6%; P < .001). These results were confirmed both in patients with LBCL and those with FL. Mechanistically, patients with Flu/Cy had a greater increase in inflammatory cytokines associated with neurotoxicity and reduced levels of metabolites critical for redox balance and biosynthesis. This study suggests that Benda LD may be a safe alternative to Flu/Cy for CD28-based CART CD19-directed immunotherapy with similar efficacy and reduced toxicities. Benda is associated with reduced levels of inflammatory cytokines and increased anabolic metabolites.
Prognostic risk signature in patients with acute myeloid leukemia treated with hypomethylating agents and venetoclax
Authors: Bataller Alex , Bazinet Alexandre , DiNardo Courtney D. , Maiti Abhishek , Borthakur Gautam , Daver Naval G. , Short Nicholas J. , Jabbour Elias J. , Issa Ghayas C. , Pemmaraju Naveen , Yilmaz Musa , Montalban-Bravo Guillermo , Takahashi Koichi , Loghavi Sanam , Garcia-Manero Guillermo , Ravandi Farhad , Kantarjian Hagop M. , Kadia Tapan M.
Published: December 2023

Hypomethylating agents (HMAs) and venetoclax (Ven) represent the standard of care for patients with acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy. However, the European LeukemiaNet (ELN) risk classifications have been validated for patients treated with intensive therapy. In this study, we validate a recently proposed new molecular prognostic risk signature (mPRS) for patients with AML treated with HMAs and Ven. This classification allocated patients to favorable, intermediate (N/KRAS or FLT3–internal tandem duplication mutations), and lower (TP53 mutations) benefit groups. We retrospectively analyzed 159 patients treated with HMA and Ven. The mPRS classification allocated 74 (47%), 31 (19%), and 54 (34%) patients to the higher, intermediate, and lower-benefit groups, respectively. The overall response rate was 71% (86%, 54%, and 59% in the higher, intermediate, and lower-benefit groups, respectively). The median overall survival (OS) and event-free survival (EFS) times were 30 and 19 months, respectively, in the higher-benefit group; 12 and 8 months in the intermediate-benefit group; and 5 and 4 months in the lower-benefit group (P < .001). The C-index for OS and EFS was higher when stratifying patients according to mPRS classification than with the ELN 2022 classification. The 2-year cumulative incidence of relapse was 35%, 70%, and 60% in the higher, intermediate, and lower-benefit groups, respectively (P = .005). The mPRS classification accurately segregated groups of patients with AML treated with HMA plus Ven. In these patients, N/KRAS and TP53 mutations appear to negatively affect outcomes; therefore, new treatment approaches are warranted.
MRD-driven treatment with venetoclax-R2 in mantle cell lymphoma: the Nordic Lymphoma Group MCL7 VALERIA trial
Authors: Jerkeman Mats , Kolstad Arne , Hutchings Martin , Pasanen Annika , Meriranta Leo , Niemann Carsten Utoft , Kragh Jørgensen Rasmus Rask , El-Galaly Tarec Christoffer , Riise Jon , Leppä Sirpa , Christensen Jacob Haaber , Sonnevi Kristina , Pedersen Lone Bredo , Wader Karin Fahl , Glimelius Ingrid
Published: December 2023

Despite improvements in treatment of mantle cell lymphoma (MCL), most patients eventually relapse. In this multicenter phase 1b/2 trial, we evaluated safety and efficacy of minimal residual disease (MRD)–driven venetoclax, lenalidomide, and rituximab (venetoclax-R2) in relapsed/refractory (R/R) MCL and explored the feasibility of stopping treatment in molecular remission. The primary end point was overall response rate (ORR) at 6 months. After dose escalation, the recommended phase 2 dose was lenalidomide 20 mg daily, days 1 to 21; venetoclax 600 mg daily after ramp-up; and rituximab 375 mg/m2 weekly for 4 weeks, then every 8 weeks. MRD monitoring by RQ-PCR was performed every 3 months. When MRD-negativity in the blood was reached, treatment was continued for another 3 months; if MRD-negativity was then confirmed, treatment was stopped. In total, 59 patients were enrolled, with a median age of 73 years. At 6 months, the ORR was 63% (29 complete remission [CR], 8 partial remission [PR]), and 40% (4 CR, 2 PR) for patients previously failing a Bruton tyrosine kinase (BTK) inhibitor. Median progression-free survival (PFS) was 21 months, with median overall survival of 31 months. TP53 mutation was associated with inferior PFS (P < .01). Overall, 28 patients (48%) discontinued treatment in molecular remission, and 25 remain MRD negative after a median of 17.4 months. Hematological toxicity was frequent, with 52 of 59 (88%) patients with G3-4 neutropenia and 21 of 59 (36%) patients with G3-4 thrombocytopenia. To conclude, MRD-driven venetoclax-R2 is feasible and tolerable and shows efficacy in R/R MCL, also after BTK inhibitor failure. This trial was registered at www.ClinicalTrials.gov as #NCT03505944.
Why and how should children be protected from the deluge of vaping related media and marketing overexposure?
Authors: White David , Bush Andrew , Smyth Alan R. , Bhatt Jayesh Mahendra
Published: December 2023

E-cigarettes are products delivering nicotineviainhalation and are devised to mimic tobacco smoking. While they were initially introduced as a device putatively to aid with smoking cessation, their use is now far broader than that. Use by children is significantly increasing. There is growing evidence of the potential harms of vaping. E-liquids used for e-cigarettes contain a wide range of harmful substances, and the clinical consequences of this are now being increasingly demonstrated, such as the rise in cases of e-cigarette- or vaping-associated lung injury. In addition, early use may result in long-term nicotine addiction. Vaping companies utilise marketing methods that distinctly target young people, and weak legislation in the UK allows them free rein to expose children to vaping.

In this review we demonstrate why children must be protected from vaping. We must have stringent legislation to prevent easy access to e-cigarettes, including banning the convenience and affordability disposable vapes provide, and prevent marketing that does not warn about the potential health effects. The Australia approach of prescription or pharmacy only access for smoking cessation should be considered to limit exposure of children and minimise use by nonsmokers.
The tuberculous pleural effusion
Authors: McNally Emma , Ross Clare , Gleeson Laura E.
Published: December 2023

Pleural tuberculosis (TB) is a common entity with similar epidemiological characteristics to pulmonary TB. It represents a spectrum of disease that can variably self-resolve or progress to TB empyema with severe sequelae such as chronic fibrothorax or empyema necessitans. Coexistence of and progression to pulmonary TB is high. Diagnosis is challenging, as pleural TB is paucibacillary in most cases, but every effort should be made to obtain microbiological diagnosis, especially where drug resistance is suspected. Much attention has been focussed on adjunctive investigations to support diagnosis, but clinicians must be aware that apparent diagnostic accuracy is affected both by the underlying TB prevalence in the population, and by the diagnostic standard against which the specified investigation is being evaluated. Pharmacological treatment of pleural TB is similar to that of pulmonary TB, but penetration of the pleural space may be suboptimal in complicated effusions. Evidence for routine drainage is limited, but evacuation of the pleural space is indicated in complicated disease.

Educational aims

To demonstrate that pleural TB incorporates a wide spectrum of disease, ranging from self-resolving lymphocytic effusions to severe TB empyema with serious sequelae.

To emphasise the high coexistence of pulmonary TB with pleural TB, and the importance of obtaining sputum for culture (induced if necessary) in all cases.

To explore the significant diagnostic challenges posed by pleural TB, and consequently the frequent lack of information about drug sensitivity prior to initiating treatment.

To highlight the influence of underlying TB prevalence in the population on the diagnostic accuracy of adjunctive investigations for the diagnosis of pleural TB.

To discuss concerns around penetration of anti-TB medications into the pleural space and how this can influence decisions around treatment duration in practice.
Use of exhaled nitric oxide in the diagnosis and monitoring of childhood asthma: myth or maxim?
Authors: Fraser Anna , Simpson Ruaraidh , Turner Steve
Published: December 2023

Asthma is a common condition in children. This review describes the evidence from the literature and international asthma guidelines for using fractional exhaled nitric oxide (FENO) in the diagnosis and monitoring of childhood asthma. The accuracy ofFENOmeasuring devices could be further improved, the difference inFENOresults between devices are equivalent to what is considered a clinically important difference. For diagnosing asthma no guideline currently recommendsFENOis used as the first test, but many recommendFENOas part of a series of tests. A cut-off of 35 ppb is widely recommended as being supportive of an asthma diagnosis, but evidence from children at risk of asthma suggests that a lower threshold of 25 ppb may be more appropriate. Nine randomised clinical trials including 1885 children have addedFENOto usual asthma care and find that exacerbations are reduced when care is guided byFENO(OR for exacerbation compared to usual care 0.77, 95% CI 0.62–0.94). What is not clear is what cut-off(s) ofFENOshould be used to trigger a change in treatment. After 30 years of intensive research there is not sufficient evidence to recommendFENOfor routine diagnosing and monitoring asthma in children.

Educational aims

To give the reader an overview of literature that supports and does not support the role ofFENOin diagnosing asthma in children.

To give the reader an overview of literature that supports and does not support the role ofFENOin monitoring asthma in children.

To give the reader an understanding of the role ofFENOin international guidelines for diagnosing and monitoring asthma in children.
Which inflammatory marker, between systemic immune-inflammation index and neutrophil to eosinophil ratio, is associated with Peyronie’s disease and are there any implications for a better understanding of its mechanisms?
Authors: Crocetto Felice , Imbimbo Ciro , Barone Biagio , Turchino Davide , Bracale Umberto Marcello , Peluso Antonio , Panagrosso Marco , Falcone Alfonso , Mirto Benito Fabio , De Luca Luigi , Sicignano Enrico , Del Giudice Francesco , Busetto Gian Maria , Lucarelli Giuseppe , Giampaglia Gaetano , Manfredi Celeste , Ferro Matteo , Tarantino Giovanni
Published: December 2023

Background

Peyronie’s disease affects up to 9% of men and is often accompanied by pain and/or erectile dysfunction. It is characterized by an inflammatory process that is the grassroots of the subsequent fibrosis stage. There is an unmet need to evaluate its onset and progression. Among the newly proposed biomarkers of inflammation, authors developed a novel systemic immune-inflammation index (SII) based on lymphocyte, neutrophil, and platelet counts. Similarly, a recent study reported that a neutrophil-to-eosinophil ratio (NER) represents systemic inflammation.

Results

A 49-patient group with Peyronie’s disease as confronted with 50 well-matched for age and BMI controls. As laboratory evaluation of inflammation, SII, NER and the eosinophil to neutrophil ratio (ENR) were studied. As a likely risk factor for the presence of Peyronie’s disease, a higher prevalence of hypercholesterolemia, hyperglycemia and hypertension was discovered in the patients compared to controls. A significant difference was found in the median values of the NER between the two selected groups, i.e., 32.5 versus 17.3 (p = 0.0021). As expected, also ENR was significantly different. The receiver operating characteristic curves for SII, ENR and NER were 0.55, 0.32 and 0.67, respectively, highlighting the best performance of NER. The cut-off for NER was 12.1, according to the Youden test.

Conclusions

According to our results, any evaluation of circulating eosinophil, evaluated as NER, beyond being a signature of immuno-inflammatory response, help assess tissue homeostasis, since eosinophils are now considered multifunctional leukocytes and give a picture of the inflammatory process and repair process belonging to Peyronie’s disease.
Natural clines and human management impact the genetic structure of Algerian honey bee populations
Authors: Salvatore Giovanna , Chibani Bahi Amar Amira , Canale-Tabet Kamila , Fridi Riad , Tabet Aoul Nacera , Saci Soumia , Labarthe Emmanuelle , Palombo Valentino , D’Andrea Mariasilvia , Vignal Alain , Faux Pierre
Published: December 2023

Background

The Algerian honey bee population is composed of two described subspecies A. m. intermissa and A. m. sahariensis, of which little is known regarding population genomics, both in terms of genetic differentiation and of possible contamination by exogenous stock. Moreover, the phenotypic differences between the two subspecies are expected to translate into genetic differences and possible adaptation to heat and drought in A. m. sahariensis. To shed light on the structure of this population and to integrate these two subspecies in the growing dataset of available haploid drone sequences, we performed whole-genome sequencing of 151 haploid drones.

Results

Integrated analysis of our drone sequences with a similar dataset of European reference populations did not detect any significant admixture in the Algerian honey bees. Interestingly, most of the genetic variation was not found between the A. m. intermissa and A. m. sahariensis subspecies; instead, two main genetic clusters were found along an East–West axis. We found that the correlation between genetic and geographic distances was higher in the Western cluster and that close-family relationships were mostly detected in the Eastern cluster, sometimes at long distances. In addition, we selected a panel of 96 ancestry-informative markers to decide whether a sampled bee is Algerian or not, and tested this panel in simulated cases of admixture.

Conclusions

The differences between the two main genetic clusters suggest differential breeding management between eastern and western Algeria, with greater exchange of genetic material over long distances in the east. The lack of detected admixture events suggests that, unlike what is seen in many places worldwide, imports of queens from foreign countries do not seem to have occurred on a large scale in Algeria, a finding that is relevant for conservation purposes. In addition, the proposed panel of 96 markers was found effective to distinguish Algerian from European honey bees. Therefore, we conclude that applying this approach to other taxa is promising, in particular when genetic differentiation is difficult to capture.
PAPerFly: Partial Assembly-based Peak Finder for ab initio binding site reconstruction
Authors: Faltejsková Kateřina , Vondrášek Jiří
Published: December 2023

Background

The specific recognition of a DNA locus by a given transcription factor is a widely studied issue. It is generally agreed that the recognition can be influenced not only by the binding motif but by the larger context of the binding site. In this work, we present a novel heuristic algorithm that can reconstruct the unique binding sites captured in a sequencing experiment without using the reference genome.

Results

We present PAPerFly, the Partial Assembly-based Peak Finder, a tool for the binding site and binding context reconstruction from the sequencing data without any prior knowledge. This tool operates without the need to know the reference genome of the respective organism. We employ algorithmic approaches that are used during genome assembly. The proposed algorithm constructs a de Bruijn graph from the sequencing data. Based on this graph, sequences and their enrichment are reconstructed using a novel heuristic algorithm. The reconstructed sequences are aligned and the peaks in the sequence enrichment are identified. Our approach was tested by processing several ChIP-seq experiments available in the ENCODE database and comparing the results of Paperfly and standard methods.

Conclusions

We show that PAPerFly, an algorithm tailored for experiment analysis without the reference genome, yields better results than an aggregation of ChIP-seq agnostic tools. Our tool is freely available at https://github.com/Caeph/paperfly/ or on Zenodo (https://doi.org/10.5281/zenodo.7116424).
Role of family factors in provision and perception of social support for older people in Iran: a cross-sectional survey
Authors: Tajvar Maryam , Grundy Emily , Fletcher Astrid , Allen Elizabeth , Karami Badriyeh
Published: December 2023

Background

Iran has experienced a very fast fertility transition. The process of demographic transition, coupled with modernization, has had considerable consequences for the structure and function of families. There is rising concern in Iran about a potential decline in family care and support for older people as a result of these changes. The main aim of this study was to provide a benchmark by examining current associations between family factors and older people’s social support, both perceived and received.

Methods

A cross-sectional survey of a random sample of 644 people aged 60 + years resident in Tehran was conducted using stratified cluster random sampling method in 2015. Outcome variables were perceived social support, as measured by Social Provision Scale, and received instrumental social support. Multilevel mixed-effects models were used to examine the hypotheses.

Results

The analyses showed that most of the family factors measured, including family size (p = 0.01), living arrangements (p = 0.05), and amount of contact with family members (p = 0.001) were associated with older people’s receipt of instrumental social support. Living arrangements and quality of relationships with family members were associated with older people’s perceptions of social support (p < 0.001). Also, a significant gender interaction was found in associations between family size and SPS (p = 0.03). Having a large size family was positively associated with higher SPS for women (Coef. = 3.9, p = 0.009) but not for men (Coef. = -0.4, p = 0.7).

Conclusion

findings of this study support the premise that most of family factors play an important role in provision and perception of social support for Iranian older people. Further policies should mostly be selective of those at higher risk of low support such as widowed, childless, those living alone, having poor relationship with their relatives and those with worse health status. The results of this study may be utilized to target older populations who are at higher risk of low support with innovative programs that focus on building social networks and enhancing social support.
Effectiveness and safety of adalimumab in patients with intestinal Behçet’s disease: a real-world prospective observational study in South Korea
Authors: Yu Jongwook , Shin Sung Jae , Park Yune-Jung , Kim Hyung Wook , Lee Bo-In , Ye Byong Duk , Kim Geun-Tae , Kim Sung Kook , Kim Joo Sung , Kim Young-Ho , Jeong Seonjeong , Cheon Jae Hee
Published: December 2023

Background

Intestinal Behçet’s disease (BD) is characterized by typical gastrointestinal ulcers in patients with BD followed by complications such as bleeding, perforation and fistula. Biologic agents are currently under active investigation to delay the disease course. Various data regarding infliximab are available, but there is relatively lack of data regarding adalimumab.

Methods

This was a multicenter, real-world prospective observational study to evaluate the effectiveness and safety of adalimumab in intestinal BD. The primary endpoint was disease activity at each follow up, including disease activity index for intestinal Behçet’s disease (DAIBD), serum C-reactive protein (CRP) level, and endoscopic findings. The secondary endpoint was the incidence of adverse drug reactions (ADRs).

Results

A total of 58 patients were enrolled and 8 of them were excluded. Adverse events were reported in 72.0% of patients with 122 events. ADRs were reported in 24.0% with 28 events. For adverse events, arthralgia was most commonly reported (13.1%: 16/122) and only one experienced critical adverse event (0.82%, 1/122: death due to stroke). On multivariable regression analysis, a longer disease duration was significantly associated with decreased ADRs [Odds ratio 0.976 (0.953–0.999, 95% CI); p = 0.042]. Clinical response rates as assessed by DAIBD were 90.9% at Week 12 and 89.7% at Week 56, respectively. The mean serum CRP level at baseline was significantly decreased after 12 weeks (3.91 ± 4.93 to 1.26 ± 2.03 mg/dL; p = 0.0002).

Conclusion

Adalimumab was found to be safe and effective in Korean patients with intestinal BD. A longer disease duration was significantly associated with decreased ADRs.
An evolutionary game-based simulation study of a multi-agent governance system for smart senior care services in China
Authors: Shi Qiannan , Yang Shumian , Wang Na , Zhang Shu-e , Wang Yanping , Wu Bing , Lu Xinyuan , She Yining , Yue Zhihao , Gao Lei , Zhang Zhong
Published: December 2023

Background

The competing interests of the government, smart senior care technology service providers, and older adults have led to a serious fragmentation of governance in China. This study aims to identify the collaboration mechanisms and evolutionary stabilization strategies for these agents.

Methods

An evolutionary game model is developed to analyze the strategic decisions made by the government, smart senior care technology service providers, and older adults. A sensitivity analysis is conducted using data from Anhui Province, China, to verify the effects of relevant parameters on the strategy decisions of each agent.

Results

The results of the simulation and sensitivity analysis indicated that, first, despite changes in the initial willingness values of the tripartite agents, the system eventually converges on 1. Second, the collaboration mechanism of the tripartite agents in the smart senior care system is related to government incentives, penalties, and subsidies, smart senior care service costs, and the additional benefits provided to smart senior care technology service providers.

Conclusion

The strategy decisions of the government, providers, and older adults interact with each other. To promote collaboration among the tripartite agents and improve governance effectiveness, the government should strengthen the regulations for providers, increase penalties for providers that engage in a breach of trust, provide moderate incentives and subsidies, and control smart senior care service costs.
A case of TM infection with challenging differential diagnosis from lymphoma post-renal transplant
Authors: Luo Sulin , Wang Xingxia , Ren Xue , Cheng Yamei , Guo Luying , Yan Pengpeng , Lv Junhao , Su Xinhui , Shen Jia , Zhao Kui , Sun Ke , Chen Jianghua , Wang Rending
Published: December 2023

Background

Lymphomas involving the gastrointestinal tract may be manifested as anti-inflammatory tract bleeding, abdominal lymph node enlargement, or even perforation of the gastrointestinal tract. After organ transplantation, the likelihood of post-transplant lymphoproliferative disorders increases, and some rare infections may also appear.

Case presentation

Herein, we report a living transplant patient with talaromycosis marneffei (TSM) or Talaromyces marneffei (TM) infection with gastrointestinal hemorrhage and systemic lymph node enlargement, which presented clinically as lymphoma.

Conclusion

This case is TSM in a kidney transplant patient, confirmed by lymph node biopsy and blood culture. The patient discharged from hospital successfully under the treatment of antifungal therapy and immunosuppressive therapy. Physicians should be aware that TSM can mimic lymphoma, and early diagnosis and treatment can benefit the outcomes.
The Carolina hysterectomy cohort (CHC): a novel case series of reproductive-aged hysterectomy patients across 10 hospitals in the US south
Authors: Haji-Noor Zakiya M. , Mathias Joacy G. , Beltran Theo Gabriel , Anderson Lauren G. , Wood Mollie E. , Howard Annie Green , Hinton Sharon Peacock , Doll Kemi M. , Robinson Whitney R.
Published: December 2023

Background

Hysterectomy is a common surgery among reproductive-aged U.S. patients, with rates highest among Black patients in the South. There is limited insight on causes of these racial differences. In the U.S., electronic medical records (EMR) data can offer richer detail on factors driving surgical decision-making among reproductive-aged populations than insurance claims-based data. Our objective in this cohort profile paper is to describe the Carolina Hysterectomy Cohort (CHC), a large EMR-based case-series of premenopausal hysterectomy patients in the U.S. South, supplemented with census and surgeon licensing data. To demonstrate one strength of the data, we evaluate whether patient and surgeon characteristics differ by insurance payor type.

Methods

We used structured and abstracted EMR data to identify and characterize patients aged 18–44 years who received hysterectomies for non-cancerous conditions between 10/02/2014–12/31/2017 in a large health care system comprised of 10 hospitals in North Carolina. We used Chi-squared and Kruskal Wallis tests to compare whether patients’ socio-demographic and relevant clinical characteristics, and surgeon characteristics differed by patient insurance payor (public, private, uninsured).

Results

Of 1857 patients (including 55% non-Hispanic White, 30% non-Hispanic Black, 9% Hispanic), 75% were privately-insured, 17% were publicly-insured, and 7% were uninsured. Menorrhagia was more prevalent among the publicly-insured (74% vs 68% overall). Fibroids were more prevalent among the privately-insured (62%) and the uninsured (68%). Most privately insured patients were treated at non-academic hospitals (65%) whereas most publicly insured and uninsured patients were treated at academic centers (66 and 86%, respectively). Publicly insured and uninsured patients had higher median bleeding (public: 7.0, uninsured: 9.0, private: 5.0) and pain (public: 6.0, uninsured: 6.0, private: 3.0) symptom scores than the privately insured. There were no statistical differences in surgeon characteristics by payor groups.

Conclusion

This novel study design, a large EMR-based case series of hysterectomies linked to physician licensing data and manually abstracted data from unstructured clinical notes, enabled identification and characterization of a diverse reproductive-aged patient population more comprehensively than claims data would allow. In subsequent phases of this research, the CHC will leverage these rich clinical data to investigate multilevel drivers of hysterectomy in an ethnoracially, economically, and clinically diverse series of hysterectomy patients.
Effect of empathy competence on moral sensitivity in Chinese student nurses: the mediating role of emotional intelligence
Authors: Liu Fang , Zhou Hengyu , Yuan Long , Cai Ying
Published: December 2023

Background

Ethical issues may pose challenges to nursing students entering clinical practice. Moral sensitivity can assist them in recognising existing moral situations and then taking adequate action. Identifying the variables associated with moral sensitivity may be useful in preparing to improve nursing students' moral sensitivity.

Objectives

This study investigated empathy, emotional intelligence, and moral sensitivity in Chinese student nurses to explore the association among these three factors and to verify the mediating function of emotional intelligence in determining the connection between empathy and moral sensitivity.

Design

This study used a cross-sectional correlational design.

Setting and participants

Through convenience sampling, 239 fourth-year nursing undergraduates at a university in Western China were enrolled in this study.

Methods

Nursing students who volunteered to participate in the study completed self-reported scales on empathy, emotional intelligence, and moral sensitivity between September and October 2022. The potential mediating effect was explored using the Process Macro and bootstrap method.

Results

The nursing students' average scores were 39.62 ± 5.27 on moral sensitivity, 108.21 ± 15.49 on empathy, and 124.41 ± 13.66 on EI. Moral sensitivity was positively correlated with emotional intelligence (r = 0.454, p < 0.001) and empathy (r = 0.545, p < 0.001). Furthermore, empathy exerted a substantial direct effect on nursing students' moral sensitivity (B = 0.1424, p < 0.001). Emotional intelligence could mediate the indirect path from empathy to moral sensitivity. (B = 0.0372, p < 0.001).

Conclusion

Emotional intelligence mediated the association between empathy and moral sensitivity. Thus, educational activities and programmes placing an emphasis on empathy and emotional intelligence may offer an alternative way to promote moral sensitivity in Chinese student nurses.

Implications

Nursing educators can organise programmes to improve nursing students' emotional competence and professional values. Early exposure to clinical practice benefits nursing students a lot in terms of building interactions with patients and increasing emotional resonance. In addition, nursing educators should develop situational teaching in nursing ethics courses to help students cope with ethical issues.
Clinical nurses’ compassion fatigue psychological experience process: a constructivist grounded theory study
Authors: Zhang Jie , Zou Jie , Wang Xiao , Luo Yaoyue , Zhang Jin , Xiong Zhiyao , Zhang Jingping
Published: December 2023

Background

Clinical nurses are susceptible to compassion fatigue when exposed to various types of traumatic events in patients for extended periods of time. However, the developmental process, staging, and psychological responses distinct to each stage of compassion fatigue in nurses are not fully clarified. This study aimed to explore the processes of compassion fatigue and the psychological experiences specific to each phase of compassion fatigue among clinical nurses.

Methods

Charmaz’s Constructivist Grounded Theory methodology was used in this qualitative research. Semi-structured interviews were conducted with 13 clinical nurses with varying degrees of compassion fatigue from December 2020 to January 2021. Interview data were analyzed using grounded theory processes.

Results

The data were categorized into five separate categories and 22 sub-categories. This study found that the process of compassion fatigue is dynamic and cumulative, which was classified into five phases: compassion experience period, compassion decrement period, compassion discomfort period, compassion distress period, and compassion fatigue period.

Conclusion

Clinical nurses who experience compassion fatigue may go through five stages that are stage-specific and predictable. The findings can shed light on local and global applications to better understand the problem of nurses’ compassion fatigue. The interventions for addressing compassion fatigue in clinical nurses should be stage-specific, targeted, and individualized.
Impact of maternal age and body mass index on the structure and function of the heart in newborns: a Copenhagen Baby Heart Study
Authors: Nørregaard Mette Marie Olsen , Basit Saima , Sillesen Anne-Sophie , Raja Anna Axelsson , Jørgensen Finn Stener , Iversen Kasper Karmark , Bundgaard Henning , Boyd Heather Allison , Vøgg Ruth Ottilia Birgitta
Published: December 2023

Background

Maternal obesity and advanced age have been associated with an increased risk of structural congenital heart defects in the offspring. Whether these factors may also cause abnormalities in infant cardiac dimension and function is unknown. This study investigates whether maternal body mass index (BMI) and maternal age are associated with changes in left ventricular (LV) dimensions and function in the newborn.

Methods

Infants enrolled in the Copenhagen Baby Heart Study (CBHS), who were born at term, and contributed with a transthoracic echocardiography (TTE) within 60 days of birth were included. The exposure variables were prepregnancy maternal BMI (kg/m2) < 18.5; 18.5–24.9 (reference); 25–29.9; 30–34.9 and ≥ 35 and maternal age (years) < 25; 25–29; 30–34 (reference); 35–39 and ≥ 40. Outcomes were LV parameters ascertained by 2D-echocardiography. Associations between each maternal factor and infant LV parameters were analysed with either a linear model adjusted for the child’s weight and length at birth, gestational age, sex, age at TTE, and maternal smoking, or a linear mixed model, further adjusted for random effects of analyst and month of analysis. Analyses investigating impact of maternal BMI were adjusted for maternal age, and vice versa.

Results

The study cohort included 24,294 infants. Compared with infants in the BMI reference group, infants born to women with a BMI ≥ 25 kg/m2 generally had smaller measures of LV internal diameters in end-diastole, reaching statistical significance for BMI 30–34.9 kg/m2 [-0.11 ± 0.04 mm, p = 0.01]. All groups of infants born to women with a BMI ≥ 25 kg/m2 had significantly smaller LV internal diameters in end-systole: BMI 25–29.9 kg/m2 [-0.04 ± 0.02 mm, p = 0.04], BMI 30–34.9 kg/m2 [-0.12 ± 0.03 mm, p = 0.001] and BMI ≥ 35 kg/m2 [-0.11 ± 0.05 mm, p = 0.03].

Compared with infants in the age reference group, infants born to women ≥ 40 years had significantly smaller LV internal diameters in end-diastole [-0.15 ± 0.04 mm, p = 0.001] and end-systole [-0.09 ± 0.04 mm, p = 0.009].

Conclusions

Systematic population-based echocardiography of infants showed that a maternal prepregnancy BMI ≥ 25 kg/m2 and maternal age ≥ 40 years were associated with smaller systolic and diastolic LV diameters. The long-term effects are unknown.

Clinical trial registration

April 2016, Copenhagen Baby Heart, NCT02753348.
Comparing variants related to chronic diseases from genome-wide association study (GWAS) and the cancer genome atlas (TCGA)
Authors: Jeon Soohyun , Park Chaewon , Kim Jineui , Lee Jung Hoon , Joe Sung-yune , Ko Young Kyung , Gim Jeong-An
Published: December 2023

Background

Several genome-wide association studies (GWAS) have been performed to identify variants related to chronic diseases. Somatic variants in cancer tissues are associated with cancer development and prognosis. Expression quantitative trait loci (eQTL) and methylation QTL (mQTL) analyses were performed on chronic disease-related variants in TCGA dataset.

Methods

MuTect2 calling variants for 33 cancers from TCGA and 296 GWAS variants provided by LocusZoom were used. At least one mutation was found in TCGA 22 cancers and LocusZoom 23 studies. Differentially expressed genes (DEGs) and differentially methylated regions (DMRs) from the three cancers (TCGA-COAD, TCGA-STAD, and TCGA-UCEC). Variants were mapped to the world map using population locations of the 1000 Genomes Project (1GP) populations. Decision tree analysis was performed on the discovered features and survival analysis was performed according to the cluster.

Results

Based on the DEGs and DMRs with clinical data, the decision tree model classified seven and three nodes in TCGA-COAD and TCGA-STAD, respectively. A total of 11 variants were commonly detected from TCGA and LocusZoom, and eight variants were selected from the 1GP variants, and the distribution patterns were visualized on the world map.

Conclusions

Variants related to tumors and chronic diseases were selected, and their geological regional 1GP-based proportions are presented. The variant distribution patterns could provide clues for regional clinical trial designs and personalized medicine.
DPY30 promotes colorectal carcinoma metastasis by upregulating ZEB1 transcriptional expression
Authors: Luo Chun-Ying , Su Wei-Chao , Jiang Hai-Feng , Luo Ling-Tao , Shen Dong-Yan , Su Guo-Qiang
Published: December 2023

DPY30 belongs to the core subunit of components of the histone lysine methyltransferase complex, which is implicated in tumorigenesis, cell senescence, and other biological events. However, its contribution to colorectal carcinoma (CRC) progression and metastasis has yet to be elucidated. Therefore, this study aimed to investigate the biological function of DPY30 in CRC metastasis both in vitro and in vivo. Herein, our results revealed that DPY30 overexpression is significantly positively correlated with positive lymph nodes, epithelial-mesenchymal transition (EMT), and CRC metastasis. Moreover, DPY30 knockdown in HT29 and SW480 cells markedly decreased EMT progression, as well as the migratory and invasive abilities of CRC cells in vitro and lung tumor metastasis in vivo. Mechanistically, DPY30 increased histone H3K4me3 level and promoted EMT and CRC metastasis by upregulating the transcriptional expression of ZEB1. Taken together, our findings indicate that DPY30 may serve as a therapeutic target and prognostic marker for CRC.

Graphical Abstract
Lonicera japonica Thunb extract ameliorates lipopolysaccharide-induced acute lung injury associated with luteolin-mediated suppression of NF-κB signaling pathway
Authors: Jia Qinyao , wen Jing , Yang Qi , Liu Shengming , Zhang Jianwu , Wang Tao , Cheng Yao
Published: December 2023

Objective

Lonicera japonica Thunb (LJT) is a commonly used herbal soup to treat inflammation-related diseases. However, the effect of LJT on ALI is unknown. The present study was aimed at investigating the protective effects of LJT extract (LTE) and its active ingredient luteolin (Lut) on lipopolysaccharide (LPS)-stimulated ALI and investigate its potential mechanism.

Materials and methods

The effects of LTE and Lut were explored in an ALI mouse model induced by intraperitoneal injection of lipopolysaccharide (LPS). Besides, the LPS-induced inflammation model in BEAS-2B cells was used to clarify the underlying mechanisms. The ALI pathological changes in lung tissues were tested through Haematoxylin and eosin (HE) staining. The apoptosis of cells in lung tissue and the cell model in vitro was evaluated by TUNEL assays, respectively. Meanwhile, the viability of cells in vitro was evaluated by Cell Counting Kit-8 (CCK-8) assay. The levels/concentrations of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β and IL-10 in BALF were detected by enzyme-linked immunosorbent assay (ELISA). Besides, through quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting, the expression of the above-mentioned inflammatory factors and key factors in the NF-κB signaling pathway was examined. The distribution of inflammatory factors in tissue was observed through immunohistochemistry (IHC) assays .

Results

In relative to LPS-stimulated group, the in vivo study showed that LTE and different concentrations of Lut dramatically alleviated LPS-evoked lung pathological injury and lung edema based on the changes in total protein levels and lung wet/dry (W/D) ratio in the bronchoalveolar lavage fluid (BALF) from ALI mice. LTE and different concentrations of Lut also suppressed the inflammatory response, as reflected by the variations of neutrophil accumulation and the production of proinflammatory and anti-inflammatory cytokines in the lung tissues and BALF of ALI mice. The in vitro research also demonstrated that LTE and Lut visibly facilitated cell viability and restrained the apoptosis of BEAS-2B cells stimulated by LPS. Lut hindered LPS-inducible activation of NF-κB pathway in BEAS-2B cells.

Conclusion

The present study proved that LTE might suppress LPS-induced acute injury and inflammation in mice and BEAS-2B cells through the Lut-caused suppression of NF-κB signal path (Figure 1).
Perceptions of fentanyl among African Americans who misuse opioids: implications for risk reduction
Authors: Rigg Khary K. , Kusiak Ethan S.
Published: December 2023

Background

Fentanyl is a powerful synthetic opioid that is 50 times more powerful than heroin and has become ubiquitous in the illicit drug supply in the USA. Studies show that among people who use drugs, fentanyl is sometimes viewed as a desirable substance due to its high potency and low cost, while others have an unfavorable perception because of its association with overdose. Unfortunately, studies on the perceptions of fentanyl are relatively rare and existing studies tend to rely on samples with little African American representation. The objective of this study, therefore, was to identify and describe perceptions of fentanyl among African Americans who misuse opioids, while capturing their motivations for seeking out or avoiding fentanyl.

Methods

In-depth interviews (n = 30) were conducted with a sample of African American adults who misuse opioids in Southwest Florida between August 2021 and February 2022. Audiotapes of interviews were transcribed, coded, and thematically analyzed.

Results

Analyses revealed the presence of three subtypes of fentanyl-related perceptions: (1) fentanyl as an avoided adulterant, (2) fentanyl as a tolerated adulterant, and (3) fentanyl as a drug of choice.

Conclusions

These findings show that African Americans’ perceptions of fentanyl are not monolithic and suggest the distribution of fentanyl test strips and naloxone may be an effective risk reduction strategy. Given that most studies on fentanyl rely on quantitative data from drug seizures and death certificates, this study uniquely contributes to the literature by capturing the voices of African Americans who use drugs.
Didymin alleviates metabolic dysfunction-associated fatty liver disease (MAFLD) via the stimulation of Sirt1-mediated lipophagy and mitochondrial biogenesis
Authors: Yang Jing-wen , Zou Ying , Chen Jun , Cui Chen , Song Jia , Yang Meng-meng , Gao Jing , Hu Hui-qing , Xia Long-qing , Wang Li-ming , Lv Xiao-yu , Chen Li , Hou Xin-guo
Published: December 2023

Background

Metabolic dysfunction-associated fatty liver disease (MAFLD) is one of the most prevalent metabolic syndromes worldwide. However, no approved pharmacological treatments are available for MAFLD. Chenpi, one kind of dried peel of citrus fruits, has traditionally been utilized as a medicinal herb for liver diseases. Didymin is a newly identified oral bioactive dietary flavonoid glycoside derived from Chenpi. In this study, we investigated the therapeutic potential of Didymin as an anti-MAFLD drug and elucidated its underlying mechanisms.

Methods

High-fat diet (HFD)-induced MAFLD mice and alpha mouse liver 12 (AML12) cells were utilized to evaluate the effects and mechanisms of Didymin in the treatment of MAFLD. Liver weight, serum biochemical parameters, and liver morphology were examined to demonstrate the therapeutic efficacy of Didymin in MAFLD treatment. RNA-seq analysis was performed to identify potential pathways that could be affected by Didymin. The impact of Didymin on Sirt1 was corroborated through western blot, molecular docking analysis, microscale thermophoresis (MST), and deacetylase activity assay. Then, a Sirt1 inhibitor (EX-527) was utilized to confirm that Didymin alleviates MAFLD via Sirt1. Western blot and additional assays were used to investigate the underlying mechanisms.

Results

Our results suggested that Didymin may possess therapeutic potential against MAFLD in vitro and in vivo. By promoting Sirt1 expression as well as directly binding to and activating Sirt1, Didymin triggers downstream pathways that enhance mitochondrial biogenesis and function while reducing apoptosis and enhancing lipophagy.

Conclusions

These suggest that Didymin could be a promising medication for MAFLD treatment. Furthermore, its therapeutic effects are mediated by Sirt1.
Transcriptomic analysis reveals impact of gE/gI/TK deletions on host response to PRV infection
Authors: Wang Xiaoli , Li Yingguang , Dong Shaoming , Wang Cong , Wang Yongming , Zhang Hongliang
Published: December 2023

Background

Pseudorabies virus (PRV) causes substantial losses in the swine industry worldwide. Attenuated PRV strains with deletions of immunomodulatory genes glycoprotein E (gE), glycoprotein I (gI) and thymidine kinase (TK) are candidate vaccines. However, the effects of gE/gI/TK deletions on PRV-host interactions are not well understood.

Methods

To characterize the impact of gE/gI/TK deletions on host cells, we analyzed and compared the transcriptomes of PK15 cells infected with wild-type PRV (SD2017), PRV with gE/gI/TK deletions (SD2017gE/gI/TK) using RNA-sequencing.

Results

The attenuated SD2017gE/gI/TK strain showed increased expression of inflammatory cytokines and pathways related to immunity compared to wild-type PRV. Cell cycle regulation and metabolic pathways were also perturbed.

Conclusions

Deletion of immunomodulatory genes altered PRV interactions with host cells and immune responses. This study provides insights into PRV vaccine design.