bluuebunny/crossref_metadata_2025_split huggingface dataset:
Delayed multiligament PCL reconstruction is associated with a higher prevalence of intraarticular injury and may influence treatment
Authors: Zsidai Bálint , Engler Ian D. , Narup Eric , Lin Ryan T. , Nazzal Ehab M. , Winkler Philipp W. , Samuelsson Kristian , Irrgang James J. , Musahl Volker 
Published: June 2023

Abstract
Background
The aim of this study was to investigate differences in concomitant injury patterns and their treatment in patients undergoing early (≤ 12 weeks) and delayed (> 12 weeks) primary multiligament posterior cruciate ligament (PCL) reconstruction (PCL-R).

Methods
This study was a retrospective chart review of patients undergoing primary multiligament PCL-R at a single institution between 2008 and 2020. Multiligament PCL-R was defined as PCL-R and concurrent surgical treatment of one or more additional knee ligament(s). Exclusion criteria included isolated PCL-R, PCL repair, and missing data for any variable. Patients were dichotomized into early (≤ 12 weeks) and delayed (> 12 weeks) PCL-R groups based on the time elapsed between injury and surgery. Between-group comparison of variables were conducted with the Chi-square, Fisher’s exact, and independent samples t-tests.

Results
A total of 148 patients were eligible for analysis, with 57 (38.5%) patients in the early and 91 (61.1%) patients in the delayed multiligament PCL-R groups. Concomitant LCL/PLC reconstruction (LCL-R/PLC-R) was performed in 55 (60%) of delayed multiligament PCL-Rs and 23 (40%) of early PCL-Rs (p = 0.02). Despite similar rates of meniscus injury, concomitant meniscus surgery was significantly more prevalent in the early (n = 25, 44%) versus delayed (n = 19, 21%) multiligament PCL-R group (p = 0.003), with a significantly greater proportion of medial meniscus surgeries performed in the early (n = 16, 28%) compared to delayed (n = 13, 14%) PCL-R group (p = 0.04). The prevalence of knee cartilage injury was significantly different between the early (n = 12, 24%) and delayed (n = 41, 46%) multiligament PCL-R groups (p = 0.01), with more frequent involvement of the lateral (n = 17, 19% vs. n = 3, 5%, respectively; p = 0.04) and medial (n = 31, 34% vs. n = 6, 11%, respectively; p = 0.005) femoral condyles in the delayed compared to the early PCL-R group.

Conclusions
Given higher rates of chondral pathology and medial meniscus surgery seen in delayed multiligament PCL-R, early management of PCL-based multiligament knee injury is recommended to restore knee stability and potentially prevent the development of further intraarticular injury.

Level of evidence
Level III.
Barriers and facilitators to the implementation of an early intervention in psychosis service in three demonstration sites in Ireland
Authors: Darker C.D. , Nicolson G. , Reddon H. , O’Connor K. , Jennings R. , O’Connell N. 
Published: June 2023

Abstract
Background
Programmes for early intervention (EIP) in psychosis for people experiencing a first episode of psychosis (FEP) have been found to be both clinically and cost effective. Following the publication of a new EIP model of care (MoC) in Ireland, the aim of this research is to describe how people participated in and responded to the MoC including service users, family members, HSE clinical staff and HSE management.

Methods
Qualitative design using the UK Medical Research Council’s process evaluation framework. Purposive sampling techniques were used. A total of N = 40 key informant semi-structured interviews were completed which included clinical staff (N = 22), health service managers and administrators (N = 9), service users (N = 8) and a family member (N = 1). Thematic analyses were conducted.

Results
Unique features of the EIP service (e.g., speed of referral/assessment, multidisciplinary approach, a range of evidence-based interventions and assertive MDT follow up) and enthusiasm for EIP were identified as two key factors that facilitated implementation. In contrast, obstacles to staff recruitment and budget challenges emerged as two primary barriers to implementation.

Conclusions
The findings from this research provide real world insights into the complexity of implementing an innovative service within an existing health system. Clear and committed financial and human resource processes which allow new innovations to thrive and be protected during their initiation and early implementation phase are paramount. These elements should be considered in the planning and implementation of EIP services both nationally in Ireland and internationally.
Exploring everyday work as a dynamic non-event and adaptations to manage safety in intraoperative anaesthesia care: an interview study
Authors: Olin Karolina , Klinga Charlotte , Ekstedt Mirjam , Pukk-Härenstam Karin 
Published: June 2023

Abstract
Background
Safety has been described as a dynamic non-event and as constantly present in professionals’ work processes. Investigating management of complex everyday situations may create an opportunity to elucidate safety management. Anaesthesia has been at the frontline of enhancing patient safety – testing and implementing knowledge from other high-reliability industries, such as aviation, in the complex, adaptive system of an operating room. The aim of this study was to explore factors supporting anaesthesia nurses and anaesthesiologists in managing complex everyday situations during intraoperative anaesthesia care processes.

Methods
Individual interviews with anaesthesia nurses (n = 9) and anaesthesiologists (n = 6) using cognitive task analysis (CTA) on case scenarios from previous prospective, structured observations. The interviews were analysed using the framework method.

Results
During intraoperative anaesthesia care, management of everyday complex situations is sustained through preparedness, support for mindful practices, and monitoring and noticing complex situations and managing them. The prerequisites are created at the organization level. Managers should ensure adequate resources in the form of trained personnel, equipment and time, team and personnel sustainability and early planning of work. Management of complex situations benefits from high-quality teamwork and non-technical skills (NTS), such as communication, leadership and shared situational awareness.

Conclusion
Adequate resources, stability in team compositions and safe boundaries for practice with shared baselines for reoccurring tasks where all viewed as important prerequisites for managing complex everyday work. When and how NTS are used in a specific clinical context depends on having the right organizational prerequisites and a deep expertise of the relevant clinical processes. Methods like CTA can reveal the tacit competence of experienced staff, guide contextualized training in specific contexts and inform the design of safe perioperative work practices, ensuring adequate capacity for adaptation.
Photomodulation alleviates cellular senescence of aging adipose-derived stem cells
Authors: Zhang Tao , He Yuqian , Shu Xin , Ma Xiaoyu , Wu Jiaqi , Du Zuoqin , Xu Jin , Chen Ni , You Jingcan , Liu Yaofang , Li Tian , Wu Jianbo 
Published: June 2023

Abstract
Background
Mesenchymal stem cells (MSCs) therapies are emerging as a promising approach to therapeutic regeneration. Therapeutic persistence and reduced functional stem cells following cell delivery remain critical hurdles for clinical investigation due to the senescence of freshly isolated cells and extensive in-vitro passage.

Methods
Cultured adipose-derived stem cells (ASCs) were derived from subcutaneous white adipose tissue isolated from mice fed a normal diet. We performed senescence-associated-β-galactosidase (SA-β-gal) staining, real-time PCR, and Westernblot to evaluate the levels related to cellular senescence markers.

Results
The mRNA expression levels of senescence markers were significantly increased in the later passage of ASCs. We show that light activation reduced the expression of senescent genes, and SA-β-Gal in all cells at passages. Moreover, the light-activated ASCs-derived exosomes decrease the expression of senescence, and SA-β-Gal in the later passage cells. We further investigated the photoreceptive effect of Opsin3 (Opn3) in light-activated ASCs. Deletion of Opn3 abolished the differences of light activation in reduced expression of senescent genes, increased Ca 2+ influx, and cAMP levels.

Conclusions
ASCs can undergo cellular senescence in-vitro passage. Photomodulation might be better preserved over senescence and Opn3-dependent activation in aged ASCs. Light-activated ASCs-derived exosomes could be served as e a new protective paradigm for cellular senescence in-vitro passage.
Oridonin promotes endoplasmic reticulum stress via TP53-repressed TCF4 transactivation in colorectal cancer
Authors: Zhou Fangyuan , Gao Haiyang , Shang Luorui , Li Jinxiao , Zhang Mengqi , Wang Shuhan , Li Runze , Ye Lin , Yang Shenglan 
Published: June 2023

Abstract
Background
The incidence of colorectal cancer and cancer death rate are increasing every year, and the affected population is becoming younger. Traditional Chinese medicine therapy has a unique effect in prolonging survival time and improving the prognosis of patients with colorectal cancer. Oridonin has been reported to have anti-cancer effects in a variety of tumors, but the exact mechanism remains to be investigated.

Methods
Cell Counting Kit-8 assay (CCK8) and 5-Ethynyl-2'-deoxyuridine (EdU) staining assay, Tranwell, and Wound healing assays were performed to measure cell proliferation, invasion, and migration capacities, respectively. The protein and mRNA expression levels of various molecules were reflected by Western blot and Reverse Transcription quantitative Polymerase Chain Reaction (qRT-PCR). Transcription Factor 4 (TCF4) and its target genes were analyzed by Position Weight Matrices (PWMs) software and the Gene Expression Omnibus (GEO) database. Immunofluorescence (IF) was performed to visualize the expression and position of Endoplasmic Reticulum (ER) stress biomarkers. The morphology of the ER was demonstrated by the ER tracker-red. Reactive Oxygen Species (ROS) levels were measured using a flow cytometer (FCM) or fluorescent staining. Calcium ion (Ca2+) concentration was quantified by Fluo-3 AM staining. Athymic nude mice were modeled with subcutaneous xenografts.

Results
Oridonin inhibited the proliferation, invasion, and migration of colorectal cancer, and this effect was weakened in a concentration-dependent manner by ER stress inhibitors. In addition, oridonin-induced colorectal tumor cells showed increased expression of ER stress biomarkers, loose morphology of ER, increased vesicles, and irregular shape. TCF4 was identified as a regulator of ER stress by PWMs software and GEO survival analysis. In vitro and in vivo experiments confirmed that TCF4 inhibited ER stress, reduced ROS production, and maintained Ca2+ homeostasis. In addition, oridonin also activated TP53 and inhibited TCF4 transactivation, further exacerbating the elevated ROS levels and calcium ion release in tumor cells and inhibiting tumorigenesis in colorectal cancer cells in vivo.

Conclusions
Oridonin upregulated TP53, inhibited TCF4 transactivation, and induced ER stress dysregulation in tumor cells, promoting colorectal cancer cell death. Therefore, TCF4 may be one of the important nodes for tumor cells to regulate ER stress and maintain protein synthesis homeostasis. And the inhibition of the TP53/TCF4 axis plays a key role in the anti-cancer effects of oridonin.
A systematic review of hemorrhage and vascular injuries in civilian public mass shootings
Authors: Nyberger Karolina , Strömmer Lovisa , Wahlgren Carl-Magnus 
Published: June 2023

Abstract
Background
Civilian public mass shootings (CPMSs) are a major public health issue and in recent years several events have occurred worldwide. The aim of this systematic review was to characterize injuries and mortality after CPMSs focusing on in-hospital management of hemorrhage and vascular injuries.

Method
A systematic review of all published literature was undertaken in Medline, Embase and Web of Science January 1st, 1968, to February 22nd, 2021, according to the PRISMA guidelines. Literature was eligible for inclusion if the CPMS included three or more people shot, injured or killed, had vascular injuries or hemorrhage.

Results
The search identified 2884 studies; 34 were eligible for inclusion in the analysis. There were 2039 wounded in 45 CPMS events. The dominating anatomic injury location per event was the extremity followed by abdomen and chest. The median number of operations and operated patients per event was 22 (5–101) and 10.5 (4–138), respectively. A total of 899 deaths were reported with a median mortality rate of 36.1% per event (15.9–71.4%) Thirty-eight percent (13/34) of all studies reported on vascular injuries. Vascular injuries ranged from 8 to 29%; extremity vascular injury the most frequent. Specific vascular injuries included thoracic aorta 18% (42/232), carotid arteries 6% (14/232), and abdominal aorta 5% (12/232). Vascular injuries were involved in 8.3%-10% of all deaths.

Conclusion
This systematic review showed an overall high mortality after CPMS with injuries mainly located to the extremities, thorax and abdomen. About one quarter of deaths was related to hemorrhage involving central large vessel injuries. Further understanding of these injuries, and structured and uniform reporting of injuries and treatment protocols may help improve evaluation and management in the future.
Level of Evidence Systematic review and meta-analysis, level III.
Pediatricians’ awareness of galenic drugs for children with special needs: a regional survey
Authors: Burlo Francesca , Zanon Davide , Minghetti Paola , Taucar Valentina , Benericetti Giulia , Bennati Giada , Barbi Egidio , De Zen Lucia 
Published: June 2023

AbstractThe prevalence of children with medical complexity is increasing, therefore drug formulations must be updated in accordance with their needs. Furthermore, a different drug formulation may be also needed for patients who require a very low dosage which is not easily reachable with those of the industrial products or for those following a ketogenic diet. Galenic (or compounded) drugs have been recently pointed out as effective in treating children. Nonetheless, their knowledge among healthcare providers is limited. We investigated how much did pediatricians know about galenic compounds by a short questionnaire administered to family and hospital pediatricians and pediatric residents in Friuli Venezia Giulia, Italy. We collected answers from 65 family pediatricians (57,5%), 39 hospital pediatricians (36,1%), and 47 pediatric residents (41,2%). Overall, both family and hospital pediatricians substantially know what is a galenic compound and the indications to its use. Of note, most of pediatricians ignore which is the legislation that allows the galenic compounds’ preparation and use, and which is the correct procedure to prescribe them. Moreover, half of the hospital pediatricians and one-third of the family ones erroneously stated that galenic formulations cost more or like the industrial products, and around the 15% of both categories affirmed that galenic compounds are less safe than the commercial product. In conclusion, the use of galenic drug may significantly improve children’s and caregivers’ quality of life. We believe that all pediatricians should be updated on this quite new and interesting topic.
BluePrint molecular subtypes predict response to neoadjuvant pertuzumab in HER2-positive breast cancer
Authors: Liefaard M. C. , van der Voort A. , van Ramshorst M. S. , Sanders J. , Vonk S. , Horlings H. M. , Siesling S. , de Munck L. , van Leeuwen A. E. , Kleijn M. , Mittempergher L. , Kuilman M. M. , Glas A. M. , Wesseling J. , Lips E. H. , Sonke G. S. 
Published: June 2023

Abstract
Background
The introduction of pertuzumab has greatly improved pathological complete response (pCR) rates in HER2-positive breast cancer, yet effects on long-term survival have been limited and it is uncertain which patients derive most benefit. In this study, we determine the prognostic value of BluePrint subtyping in HER2-positive breast cancer. Additionally, we evaluate its use as a biomarker for predicting response to trastuzumab-containing neoadjuvant chemotherapy with or without pertuzumab.

Methods
From a cohort of patients with stage II-III HER2-positive breast cancer who were treated with neoadjuvant chemotherapy and trastuzumab with or without pertuzumab, 836 patients were selected for microarray gene expression analysis, followed by readout of BluePrint standard (HER2, Basal and Luminal) and dual subtypes (HER2-single, Basal-single, Luminal-single, HER2-Basal, Luminal-HER2, Luminal-HER2-Basal). The associations between subtypes and pathological complete response (pCR), overall survival (OS) and breast cancer-specific survival (BCSS) were assessed, and pertuzumab benefit was evaluated within the BluePrint subgroups.

Results
BluePrint results were available for 719 patients. In patients with HER2-type tumors, the pCR rate was 71.9% in patients who received pertuzumab versus 43.5% in patients who did not (adjusted Odds Ratio 3.43, 95% CI 2.36–4.96). Additionally, a significantly decreased hazard was observed for both OS (adjusted hazard ratio [aHR] 0.45, 95% CI 0.25–0.80) and BCSS (aHR 0.46, 95% CI 0.24–0.86) with pertuzumab treatment. Findings were similar in the HER2-single subgroup. No significant benefit of pertuzumab was seen in other subtypes.

Conclusions
In patients with HER2-type or HER2-single-type tumors, pertuzumab significantly improved the pCR rate and decreased the risk of breast cancer mortality, which was not observed in other subtypes. BluePrint subtyping may be valuable in future studies to identify patients that are likely to be highly sensitive to HER2-targeting agents.
Characterization of novel loci controlling seed oil content in Brassica napus by marker metabolite-based multi-omics analysis
Authors: Li Long , Tian Zhitao , Chen Jie , Tan Zengdong , Zhang Yuting , Zhao Hu , Wu Xiaowei , Yao Xuan , Wen Weiwei , Chen Wei , Guo Liang 
Published: June 2023

Abstract
Background
Seed oil content is an important agronomic trait of Brassica napus (B. napus), and metabolites are considered as the bridge between genotype and phenotype for physical traits.

Results
Using a widely targeted metabolomics analysis in a natural population of 388 B. napus inbred lines, we quantify 2172 metabolites in mature seeds by liquid chromatography mass spectrometry, in which 131 marker metabolites are identified to be correlated with seed oil content. These metabolites are then selected for further metabolite genome-wide association study and metabolite transcriptome-wide association study. Combined with weighted correlation network analysis, we construct a triple relationship network, which includes 21,000 edges and 4384 nodes among metabolites, metabolite quantitative trait loci, genes, and co-expression modules. We validate the function of BnaA03.TT4, BnaC02.TT4, and BnaC05.UK, three candidate genes predicted by multi-omics analysis, which show significant impacts on seed oil content through regulating flavonoid metabolism in B. napus.

Conclusions
This study demonstrates the advantage of utilizing marker metabolites integrated with multi-omics analysis to dissect the genetic basis of agronomic traits in crops.
Analysis of Notch1 signaling in mammalian sperm development
Authors: Sambe Naoto , Yoshihara Masaharu , Nishino Teppei , Sugiura Ryosuke , Nakayama Takahiro , Louis Chandra , Takahashi Satoru 
Published: June 2023

Abstract
Objective
A mammalian Delta-Notch signaling component, Notch1, has been suggested for its expression during the normal sperm development although its conditional deletion caused no apparent abnormalities. Since we established our original transgenic mouse system that enabled labeling of past and ongoing Notch1 signaling at a cellular level, we tried to validate that observation in vivo. Our transgenic mouse system used Cre/loxP system to induce tandem dsRed expression upon Notch1 signaling.

Results
To our surprise, we were unable to observe tandem dsRed expression in the seminiferous tubules where the sperms developed. In addition, tandem dsRed expression was lacking in the somatic cells of the next generation in our transgenic mouse system, suggesting that sperms received no Notch1 signaling during their development. To validate this result, we conducted re-analysis of four single-cell RNA-seq datasets from mouse and human testes and showed that Notch1 expression was little in the sperm cell lineage. Collectively, our results posed a question into the involvement of Notch1 in the normal sperm development although this observation may help the interpretation of the previous result that Notch1 conditional deletion caused no apparent abnormalities in murine spermatogenesis.
European survey on the use of patient contact shielding during radiological examinations
Authors: Granata Claudio , Briers Erik , Candela-Juan Cristian , Damilakis John , De Bondt Timo , Faj Dario , Foley Shane , Frija Guy , de las Heras Gala Hugo , Hiles Peter , Pauwels Ruben , Sans Merce Marta , Simantirakis Georgios , Vano Eliseo , Gilligan Patrick ,   the ESR, ESPR, EFOMP, EFRS, and EURADOS
Published: June 2023

Abstract
Objectives
Contact shielding (CS) of patients during X-ray studies has been used for decades to protect radiosensitive organs. This practice has not changed much despite increasing evidence that CS is not useful in many cases. The Gonad And Patient Shielding (GAPS) group—founded by representatives of the main European bodies involved in radiology—promoted this survey to assess the current practice of CS among European radiology departments and the attitude towards a non-shielding policy.

Methods
Over a four-month period (15 May–15th September 2021) European Society of Radiology and European Society of Paediatric Radiology radiologist members were invited to respond to a web-based questionnaire consisting of 59 questions.

Results
225 centres from 35 countries responded to this survey. CS was routinely applied in at least one radiological modality in 49.2% of centres performing studies in adults, 57.5% of centres performing studies in children, and 47.8% of centres performing studies on pregnant women. CS was most frequently used in conventional radiography, where the most frequently shielded organs were the gonads, followed by thyroid, female breasts, and eye lens. 83.6% respondents would follow European recommendations on the use of CS when provided by the main European bodies involved in radiology.

Conclusions
This review shows that CS is still largely used across Europe. However, a non-shielding policy could be adopted in most departments if European professional societies provided recommendations. In this regard, a strong commitment by European and national professional societies to educate and inform practitioners, patients and carers is paramount.

Clinical relevance statement
According to this survey expectations of patients and carers, and skepticism among
professionals about the limited benefits of CS are the most important obstacles to the application of a no-shielding policy. A strong commitment from European and national professional societies to inform practitioners, patients and carers is fundamental.

Graphical Abstract