bluuebunny/crossref_metadata_2025_split huggingface dataset:
Providing holistic end-of-life care for people with a history of problem substance use: a mixed methods cohort study of interdisciplinary service provision and integrated care
Authors: Webb Lucy , Yarwood Gemma , Witham Gary , Wright Sam , Galvani Sarah 
Published: April 2024

AbstractHarmful use of illicit drugs and/or alcohol is linked to life-limiting illness and complex health and social care needs, but people who use substances and have complex needs do not receive timely palliative care and fail to achieve quality standards for a good death. They and their families often require support from multiple health and social care services which are shown to be poorly integrated and fail to deliver interdisciplinary care. This study aimed to identify the existing barriers and facilitators within and between services in providing this population with a good death. Using a mixed methods approach of survey, focus groups and semi-structured interviews, we explored the perspectives of practitioner and management staff across a range of health and social disciplines and organisations in one combined authority in a large city in the north west of England. Our findings indicate that practitioners want to provide better care for this client group, but face structural, organisational and professional boundary barriers to delivering integrated and shared care. Differences in philosophy of care, piecemeal commissioning and funding of services, and regulatory frameworks for different services, lead to poor and inequitable access to health and social care services. Ways forward for improving care are suggested as bespoke hostel-based accommodation for palliative care for this client group, and specialist link workers who can transcend professional and organisational boundaries to support co-ordination of services and support. We conclude that it is no longer adequate to call for more training, better communication and improved joint working. Complex care at the end of life requires creative and cohesive systemic responses that enable multi-disciplinary practitioners to provide the care they wish to give and enables individuals using substances to get the respect and quality service they deserve.
Effects of hysteroscopic septum incision versus expectant management on IVF outcomes in women with complete septate uterus: a retrospective study
Authors: Zhang Jiajia , Kang Jia , Song Xueling , Yang Shuo , Yang Yan , Qiao Jie , Ma Caihong 
Published: March 2024

Abstract
Objective
This retrospective study aimed to assess the impact of hysteroscopic septum incision on in vitro fertilization (IVF) outcomes among infertile women diagnosed with a complete septate uterus and no history of recurrent pregnancy loss.

Methods
The study was conducted at a tertiary reproductive center affiliated with a university hospital and involved 78 women with a complete septate uterus. Among them, 34 women underwent hysteroscopic septum incision, while 44 women opted for expectant management. The primary outcome measure was the live birth rate, while secondary outcomes included clinical pregnancy rate, preterm birth rate, miscarriage rate, and ongoing pregnancy rate.

Results
Women who underwent hysteroscopic septum incision demonstrated a comparable likelihood of achieving a live birth compared to those managed expectantly (25% vs. 25%, Relative Risk (RR): 1.000, 95% Confidence Interval (CI): 0.822 to 1.216). No preterm births occurred in either group. The clinical pregnancy rate, ongoing pregnancy rate, and miscarriage rate showed no significant differences between the surgical group and the expectant management group. Subgroup analyses based on the type of embryo transferred also revealed no significant differences in outcomes.

Conclusions
Hysteroscopic septum incision does not appear to yield improved IVF outcomes compared to expectant management in infertile women with a complete septate uterus and no history of recurrent pregnancy loss.
Relationship between depression and burnout among nurses in Intensive Care units at the late stage of COVID-19: a network analysis
Authors: Zhang Yinjuan , Wu Chao , Ma Jin , Liu Fang , Shen Chao , Sun Jicheng , Ma Zhujing , Hu Wendong , Lang Hongjuan 
Published: April 2024

Abstract
Background
Mental health problems are critical and common in medical staff working in Intensive Care Units (ICU) even at the late stage of COVID-19, particularly for nurses. There is little research to explore the inner relationships between common syndromes, such as depression and burnout. Network analysis (NA) was a novel approach to quantified the correlations between mental variables from the perspective of mathematics. This study was to investigate the interactions between burnout and depression symptoms through NA among ICU nurses.

Method
A cross-sectional study with a total of 616 Chinese nurses in ICU were carried out by convenience sampling from December 19, 2022 to January19, 2023 via online survey. Burnout symptoms were measured by Maslach Burnout Inventory-General Survey (MBI-GS) (Chinese version), and depressive symptoms were assessed by the 9-item Patient Health Questionnaire (PHQ-9). NA was applied to build interactions between burnout and depression symptoms. We identified central and bridge symptoms by R package qgraph in the network model. R package bootnet was used to examined the stability of network structure.

Results
The prevalence of burnout and depressive symptoms were 48.2% and 64.1%, respectively. Within depression-burnout network, PHQ4(Fatigue)-MBI2(Used up) and PHQ4(Fatigue)-MBI5(Breakdown) showed stronger associations. MBI2(Used up) had the strongest expected influence central symptoms, followed by MBI4(Stressed) and MBI7 (Less enthusiastic). For bridge symptoms. PHQ4(Fatigue), MBI5(Breakdown) and MBI2(Used up) weighed highest. Both correlation stability coefficients of central and bridge symptoms in the network structure were 0.68, showing a high excellent level of stability.

Conclusion
The symptom of PHQ4(Fatigue) was the bridge to connect the emotion exhaustion and depression. Targeting this symptom will be effective to detect mental disorders and relieve mental syndromes of ICU nurses at the late stage of COVID-19 pandemic.
Genetic toolbox for Photorhabdus and Xenorhabdus: pSEVA based heterologous expression systems and CRISPR/Cpf1 based genome editing for rapid natural product profiling
Authors: Rill Alexander , Zhao Lei , Bode Helge B. 
Published: April 2024

Abstract
Background
Bacteria of the genus Photorhabdus and Xenorhabdus are motile, Gram-negative bacteria that live in symbiosis with entomopathogenic nematodes. Due to their complex life cycle, they produce a large number of specialized metabolites (natural products) encoded in biosynthetic gene clusters (BGC). Genetic tools for Photorhabdus and Xenorhabdus have been rare and applicable to only a few strains. In the past, several tools have been developed for the activation of BGCs and the deletion of individual genes. However, these often have limited efficiency or are time consuming. Among the limitations, it is essential to have versatile expression systems and genome editing tools that could facilitate the practical work.

Results
In the present study, we developed several expression vectors and a CRISPR-Cpf1 genome editing vector for genetic manipulations in Photorhabdus and Xenorhabdus using SEVA plasmids. The SEVA collection is based on modular vectors that allow exchangeability of different elements (e.g. origin of replication and antibiotic selection markers with the ability to insert desired sequences for different end applications). Initially, we tested different SEVA vectors containing the broad host range origins and three different resistance genes for kanamycin, gentamycin and chloramphenicol, respectively. We demonstrated that these vectors are replicative not only in well-known representatives, e.g. Photorhabdus laumondii TTO1, but also in other rarely described strains like Xenorhabdus sp. TS4. For our CRISPR/Cpf1-based system, we used the pSEVA231 backbone to delete not only small genes but also large parts of BGCs. Furthermore, we were able to activate and refactor BGCs to obtain high production titers of high value compounds such as safracin B, a semisynthetic precursor for the anti-cancer drug ET-743.

Conclusions
The results of this study provide new inducible expression vectors and a CRISPR/CPf1 encoding vector all based on the SEVA (Standard European Vector Architecture) collection, which can improve genetic manipulation and genome editing processes in Photorhabdus and Xenorhabdus.
“Metabolic burden” explained: stress symptoms and its related responses induced by (over)expression of (heterologous) proteins in Escherichia coli
Authors: Snoeck Sofie , Guidi Chiara , De Mey Marjan 
Published: March 2024

Abstract
Background
Engineering bacterial strains to redirect the metabolism towards the production of a specific product has enabled the development of industrial biotechnology. However, rewiring the metabolism can have severe implications for a microorganism, rendering cells with stress symptoms such as a decreased growth rate, impaired protein synthesis, genetic instability and an aberrant cell size. On an industrial scale, this is reflected in processes that are not economically viable.

Main text
In literature, most stress symptoms are attributed to “metabolic burden”, however the actual triggers and stress mechanisms involved are poorly understood. Therefore, in this literature review, we aimed to get a better insight in how metabolic engineering affects Escherichia coli and link the observed stress symptoms to its cause. Understanding the possible implications that chosen engineering strategies have, will help to guide the reader towards optimising the envisioned process more efficiently.

Conclusion
This review addresses the gap in literature and discusses the triggers and effects of stress mechanisms that can be activated when (over)expressing (heterologous) proteins in Escherichia coli. It uncovers that the activation of the different stress mechanisms is complex and that many are interconnected. The reader is shown that care has to be taken when (over)expressing (heterologous) proteins as the cell’s metabolism is tightly regulated.
Circulating ceramide levels and ratios in Emirati youth under 18 years: associations with cardiometabolic risk factors
Authors: Shalaby Youssef M. , Al-Zohily Bashar , Raj Anjana , Yasin Javed , Al Hamad Sania , Antoniades Charalambos , Akawi Nadia , Aburawi Elhadi H. 
Published: April 2024

Abstract
Background
Circulating ceramide (Cer) drives various pathological processes associated with cardiovascular diseases, liver illness, and diabetes mellitus. Although recognized as predictors of cardiometabolic diseases (CMD) in research and clinical settings, their potential for predicting CMD risk in individuals under 18 remains unexplored.

Objectives
This study was designed to utilize Liquid Chromatography-Mass Spectrometry (LC-MS/MS) methodology to determine the biological reference ranges for Cer in plasma samples of Emirati children and develop a risk assessment score (CERT-1) based on Cer concentrations.

Methods
Using LC-MS/MS, we developed a method to measure five Cer species in plasma samples of 582 Emirati participants aged 5–17. We used the circulating concentrations of these Cer to determine their reference intervals in this population. We employed traditional statistical analyses to develop a risk score (CERT-1) and assess the association between Cer levels and conventional biomarkers of CMD.

Results
We validated a high-throughput methodology using LC–MS/MS to quantify five Cer species in human plasma. Reference values for this population (n = 582) were quantified: CerC16:0 (0.12–0.29 µmol/L), CerC18:0 (0.019–0.067 µmol/L), CerC22:0 (0.102–0.525 µmol/L), CerC24:0 (0.65–1.54 µmol/L) and CerC24:1 (0.212–0.945 µmol/L). We devised a risk assessment score (CERT-1) based on plasma Cer content in the study participants, showing that 72.5% have low to moderate risk and 9.3% are at a higher risk of developing CMD. Our analyses also revealed a significant correlation (P < 0.05) between this score and the conventional risk factors linked to CMD, indicating its potential clinical implication.

Conclusion
This study presents a clinical-scaled LC–MS/MS methodology for assessing clinically relevant Cer, setting reference ranges, and developing a risk score (CERT-1) for young Emirati individuals. Our findings can enhance primary risk prediction and inform the management and follow-up of CMD from an early age.
Acceptability of a pilot motivational interviewing intervention at public health facilities to improve the HIV treatment cascade among people who inject drugs in Indonesia
Authors: Wongso Lydia V. , Rahadi Arie , Sukmaningrum Evi , Handayani Miasari , Wisaksana Rudi 
Published: April 2024

Abstract
Background
HIV-positive people who inject drugs (PWID) experience challenges in initiating and adhering to antiretroviral treatment (ART). Counselling using motivational interviewing (MI) techniques may help them formulate individualised strategies, and execute actions to address these challenges collaboratively with their providers. We evaluated the acceptability of MI from a pilot implementation at three public health facilities in Indonesia.

Methods
Adapting the acceptability constructs developed by Sekhon (2017) we assessed the acceptability to HIV-positive PWID clients (n = 12) and providers (n = 10) in four synthesised constructs: motivation (attributes that inspire engagement); cost consideration (sacrifices made to engage in MI); learned understanding (mechanism of action); and outcomes (ability to effect change with engagement). We included all providers and clients who completed ≥ 2 MI encounters. Qualitative analysis with an interpretive paradigm was used to extract and categorise themes by these constructs.

Results
In motivation, clients valued the open communication style of MI, while providers appreciated its novelty in offering coherent structure with clear boundaries. In cost consideration, both groups faced a challenge in meeting MI encounters due to access or engagement in other health care areas. In learned understanding, clients understood that MI worked to identify problematic areas of life amenable to change to support long-term ART, with reconciliation in family life being the most targeted change. By contrast, providers preferred targeting tangible health outcomes to such behavioural proxies. In outcomes, clients were confident in their ability to develop behaviours to sustain ART uptakes, whereas providers doubted the outcome of MI on younger PWID or those with severe dependence.

Conclusions
There is broad acceptability of MI in motivating engagement for both actors. Relative to providers, clients were more acceptable in its mechanism and had greater confidence to perform behaviours conducive to ART engagement. Design innovations to improve the acceptability of MI for both actors are needed.
MicroRNA-21a-5p inhibition alleviates systemic sclerosis by targeting STAT3 signaling
Authors: Park Jin-Sil , Kim Chongtae , Choi JeongWon , Jeong Ha Yeon , Moon Young-Mee , Kang Hoin , Lee Eun Kyung , Cho Mi-La , Park Sung-Hwan 
Published: April 2024

Abstract
Background
MicroRNA (miRNA)-21-5p participates in various biological processes, including cancer and autoimmune diseases. However, its role in the development of fibrosis in the in vivo model of systemic sclerosis (SSc) has not been reported. This study investigated the effects of miRNA-21a-5p overexpression and inhibition on SSc fibrosis using a bleomycin-induced SSc mouse model.

Methods
A murine SSc model was induced by subcutaneously injecting 100 μg bleomycin dissolved in 0.9% NaCl into C57BL/6 mice daily for 5 weeks. On days 14, 21, and 28 from the start of bleomycin injection, 100 μg pre-miRNA-21a-5p or anti-miRNA-21a-5p in 1 mL saline was hydrodynamically injected into the mice. Fibrosis analysis was conducted in lung and skin tissues of SSc mice using hematoxylin and eosin as well as Masson’s trichrome staining. Immunohistochemistry was used to examine the expression of inflammatory cytokines, phosphorylated signal transducer and activator of transcription-3 (STAT3) at Y705 or S727, and phosphatase and tensin homologue deleted on chromosome-10 (PTEN) in skin tissues of SSc mice.

Results
MiRNA-21a-5p overexpression promoted lung fibrosis in bleomycin-induced SSc mice, inducing infiltration of cells expressing TNF-α, IL-1β, IL-6, or IL-17, along with STAT3 phosphorylated cells in the lesional skin. Conversely, anti-miRNA-21a-5p injection improved fibrosis in the lung and skin tissues of SSc mice, reducing the infiltration of cells secreting inflammatory cytokines in the skin tissue. In particular, it decreased STAT3-phosphorylated cell infiltration at Y705 and increased the infiltration of PTEN-expressing cells in the skin tissue of SSc mice.

Conclusion
MiRNA-21a-5p promotes fibrosis in an in vivo murine SSc model, suggesting that its inhibition may be a therapeutic strategy for improving fibrosis in SSc.
Bilateral juvenile osteochondrosis dissecans in monozygotic twins: a case report
Authors: Bausch Luca , Probst Monika , Fritsch Lorenz , Mehl Julian , Siebenlist Sebastian , Willinger Lukas 
Published: April 2024

Abstract
Introduction
The etiology of osteochondrosis dissecans (OCD), a chondropathy associated with detachment of the subchondral bone and the overlaying cartilage, is not yet fully understood. While repetitive physical exercise-related stress is usually assumed to be the main risk factor for the occurrence of OCD, genetic predisposition could have an underestimated influence on the development of the disease.

Case report
We report a case of monozygotic twins with almost identical stages of bilateral osteochondrosis dissecans of the knee joint. In both patients, initially, a unilateral lesion occurred; despite restricted physical exercise, in the further course of the disease a lesion also developed on the contralateral side. While the lesion found most recently demonstrated an ongoing healing process at a 6-month follow-up, the other three lesions showed a natural course of healing under conservative treatment with significant clinical as well as radiological improvements after one year and complete consolidation in magnetic resonance imaging (MRI) after 2 years.

Conclusion
There could be a genetic component to the development of OCD, although this has not yet been proven. Based on a two-year MRI follow-up, we were able to show the self-limiting characteristics of juvenile osteochondrosis dissecans.
Experimental assessment of pelvis slipping during postless traction for orthopaedic applications
Authors: Daghero Marco , Borrelli Simone , Vieira Taian M. , Cannito Francesco , Aprato Alessandro , Audisio Andrea , Bignardi Cristina , Terzini Mara 
Published: April 2024

Abstract
Background
The application of lower limb traction during hip arthroscopy and femur fractures osteosynthesis is commonplace in orthopaedic surgeries. Traditional methods utilize a perineal post on a traction table, leading to soft tissue damage and nerve neuropraxia. A postless technique, using high-friction pads, has been considered as a potential damage-free alternative. However, whether these pads sufficiently prevent patient displacement remains unknown. Thus, this study systematically assesses the efficacy of commercial high-friction pads (PinkPad and CarePad) in restraining subject displacement, for progressively increasing traction loads and different Trendelenburg angles.

Methods
Three healthy male subjects were recruited and tested in supine and Trendelenburg positions (5° and 10°), using a customized boot-pulley system. Ten load disks (5 kg) were dropped at 15s intervals, increasing gradually the traction load up to 50 kg. Pelvis displacement along the traction direction was measured with a motion capture system. The displacement at 50 kg of traction load was analyzed and compared across various pads and bed inclinations. Response to varying traction loads was statistically assessed with a quadratic function model.

Results
Pelvis displacement at 50 kg traction load was below 60 mm for all conditions. Comparing PinkPad and CarePad, no significant differences in displacement were observed. Finally, similar displacements were observed for the supine and Trendelenburg positions.

Conclusions
Both PinkPad and CarePad exhibited nearly linear behavior under increasing traction loads, limiting displacement to 60 mm at most for 50 kg loads. Contrary to expectations, placing subjects in the Trendelenburg position did not increase adhesion.
An attachment-based pilot program to promote adolescent adjustment to parental divorce
Authors: Tay-Karapas Karla , Guzmán-González Mónica , Gómez Fabiola , Comino Priscila , Salaberria Karmele , Bahamondes Joaquín 
Published: March 2024

AbstractThe study aimed to assess the impact of an attachment-based intervention on adolescent adaptation to parental divorce. The Adolescent Adjustment Pilot Program to Parental Divorce (AAPPD) employed an experimental group format, targeting improvements in various adaptation indicators (life satisfaction, positive affect, and negative affect). The sample comprised 30 Chilean adolescents aged 12 to 16 (M = 13.6, SD = 1.35), with 60% females and 40% males. After the intervention, the adolescents showed a decrease in negative affect at 6 and 12 months. However, no differences were identified in other dimensions of subjective well-being considered as indicators of divorce adaptation. The findings prompt discussion on theoretical and clinical implications.
Identification of genetic modifiers enhancing B7-H3-targeting CAR T cell therapy against glioblastoma through large-scale CRISPRi screening
Authors: Li Xing , Sun Shiyu , Zhang Wansong , Liang Ziwei , Fang Yitong , Sun Tianhu , Wan Yong , Ma Xingcong , Zhang Shuqun , Xu Yang , Tian Ruilin 
Published: April 2024

Abstract
Background
Glioblastoma multiforme (GBM) is a highly aggressive brain tumor with a poor prognosis. Current treatment options are limited and often ineffective. CAR T cell therapy has shown success in treating hematologic malignancies, and there is growing interest in its potential application in solid tumors, including GBM. However, current CAR T therapy lacks clinical efficacy against GBM due to tumor-related resistance mechanisms and CAR T cell deficiencies. Therefore, there is a need to improve CAR T cell therapy efficacy in GBM.

Methods
We conducted large-scale CRISPR interference (CRISPRi) screens in GBM cell line U87 MG cells co-cultured with B7-H3 targeting CAR T cells to identify genetic modifiers that can enhance CAR T cell-mediated tumor killing. Flow cytometry-based tumor killing assay and CAR T cell activation assay were performed to validate screening hits. Bioinformatic analyses on bulk and single-cell RNA sequencing data and the TCGA database were employed to elucidate the mechanism underlying enhanced CAR T efficacy upon knocking down the selected screening hits in U87 MG cells.

Results
We established B7-H3 as a targetable antigen for CAR T therapy in GBM. Through large-scale CRISPRi screening, we discovered genetic modifiers in GBM cells, including ARPC4, PI4KA, ATP6V1A, UBA1, and NDUFV1, that regulated the efficacy of CAR T cell-mediated tumor killing. Furthermore, we discovered that TNFSF15 was upregulated in both ARPC4 and NDUFV1 knockdown GBM cells and revealed an immunostimulatory role of TNFSF15 in modulating tumor-CAR T interaction to enhance CAR T cell efficacy.

Conclusions
Our study highlights the power of CRISPR-based genetic screening in investigating tumor-CAR T interaction and identifies potential druggable targets in tumor cells that confer resistance to CAR T cell killing. Furthermore, we devised targeted strategies that synergize with CAR T therapy against GBM. These findings shed light on the development of novel combinatorial strategies for effective immunotherapy of GBM and other solid tumors.