bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understandings, attitudes, practices and responses to GHB overdose among GHB consumers
Authors: Freestone Jack , Ezard Nadine , Bourne Adam , Brett Jonathan , Roberts Darren M. , Hammoud Mohamed , Nedanoski Anthony , Prestage Garrett , Siefried Krista J. 
Published: September 2023

Abstract
Background
Gamma-hydroxybutyrate (GHB) is used at disproportionately high rates within sexuality and gender diverse communities and carries a high risk of overdose. GHB overdose can result in death. Internationally, recent increases in GHB overdoses have been observed. Coronial reviews of GHB-related death highlight the pivotal roles that bystanders to GHB overdose play in preventing fatality. No research has examined, in detail, how bystanders respond to GHB overdose. This qualitative study was conducted among people who use GHB and explored how they responded upon witnessing a GHB overdose experienced by someone else.

Methods
Interviews were conducted with 31 sexuality and gender diverse Australian residents reporting three or more occasions of GHB use in the previous 12 months. Participants were asked questions about witnessed GHB overdose, their actions and decision-making processes throughout overdose. Data were analysed thematically.

Results
Participants described witnessing GHB overdose, commonly in private settings involving sexualized GHB use. Variable definitions of GHB overdose were reported, ranging from GHB-induced symptoms of distress to comatose intoxication. Drastic actions to keep someone alert and responsive post-GHB ingestion were reported; these included the administration of stimulant substances and citrus. Decisions to call or not call for emergency medical services (EMS) were influenced by many circumstantial variables. In most instances, an EMS call was resisted and response practices deviated from established first aid protocols.

Conclusions
GHB overdose prevention and response training programs targeting people who use GHB are urgently required. These education interventions ought to address inaccuracies that inform street remedies for GHB overdose, teach people how to safely check breathing and response, promote basic first aid principles and address barriers to contacting EMS.
Association between 5-year change in cardiovascular risk and the incidence of atherosclerotic cardiovascular diseases: a multi-cohort study
Authors: Yi Jiayi , Wang Lili , Guo Xinli , Ren Xiangpeng 
Published: September 2023

Abstract
Background
The influence of the historical cardiovascular risk status on future risk of atherosclerotic cardiovascular disease (ASCVD) is poorly understood. We aimed to investigate the association between 5-year changes in cardiovascular risk and ASCVD incidence.

Methods
We analyzed pooled data from seven community-based prospective cohort studies with up to 20 years of follow-up data. The study populations included White or Black participants aged 40–75 years without prevalent ASCVD. Cardiovascular risk was assessed using the pooled cohort equation and was categorized into non-high (< 20%) or high risk (≥ 20%). Changes in cardiovascular disease (CVD) risk over a 5-year interval were recorded. The main outcome was incident ASCVD.

Results
Among 11,026 participants (mean [SD] age, 60.0 [8.1] years), 4272 (38.7%) were female and 3127 (28.4%) were Black. During a median follow-up period of 9.9 years, 2560 (23.2%) ASCVD events occurred. In comparison with individuals showing a consistently high CVD risk, participants whose CVD risk changed from non-high to high (hazard ratio [HR], 0.67; 95% confidence interval [CI] 0.59–0.77) or high to non-high (HR, 0.57; 95% CI 0.41–0.80) and those with a consistently non-high risk (HR, 0.33; 95% CI 0.29–0.37) had a lower risk of incident ASCVD. In comparison with individuals showing a consistently non-high CVD risk, participants whose CVD risk changed from high to non-high (HR, 1.74; 95% CI 1.26–2.41) or from non-high to high risk (HR, 2.04; 95% CI 1.84–2.27) and those with a consistently high risk (HR 3.03; 95% CI 2.69–3.42) also showed an increased risk of incident ASCVD.

Conclusions
Individuals with the same current CVD risk status but different historical CVD risks exhibited varying risks of future ASCVD incidents. Dynamic risk evaluation may enable more accurate cardiovascular risk stratification, and decision-making regarding preventive interventions should take the historical risk status into account.

Graphical Abstract
Mesenchymal-derived extracellular vesicles enhance microglia-mediated synapse remodeling after cortical injury in aging Rhesus monkeys
Authors: Zhou Yuxin , Bhatt Hrishti , Mojica Chromewell A. , Xin Hongqi , Pessina Monica A. , Rosene Douglas L. , Moore Tara L. , Medalla Maria 
Published: September 2023

AbstractUnderstanding the microglial neuro-immune interactions in the primate brain is vital to developing therapeutics for cortical injury, such as stroke or traumatic brain injury. Our previous work showed that mesenchymal-derived extracellular vesicles (MSC-EVs) enhanced motor recovery in aged rhesus monkeys following injury of primary motor cortex (M1), by promoting homeostatic ramified microglia, reducing injury-related neuronal hyperexcitability, and enhancing synaptic plasticity in perilesional cortices. A focal lesion was induced via surgical ablation of pial blood vessels over lying the cortical hand representation of M1 of aged female rhesus monkeys, that received intravenous infusions of either vehicle (veh) or EVs 24 h and again 14 days post-injury. The current study used this same cohort to address how these injury- and recovery-associated changes relate to structural and molecular interactions between microglia and neuronal synapses. Using multi-labeling immunohistochemistry, high-resolution microscopy, and gene expression analysis, we quantified co-expression of synaptic markers (VGLUTs, GLURs, VGAT, GABARs), microglia markers (Iba1, P2RY12), and C1q, a complement pathway protein for microglia-mediated synapse phagocytosis, in perilesional M1 and premotor cortices (PMC). We compared this lesion cohort to age-matched non-lesion controls (ctr). Our findings revealed a lesion-related loss of excitatory synapses in perilesional areas, which was ameliorated by EV treatment. Further, we found region-dependent effects of EVs on microglia and C1q expression. In perilesional M1, EV treatment and enhanced functional recovery were associated with increased expression of C1q + hypertrophic microglia, which are thought to have a role in debris-clearance and anti-inflammatory functions. In PMC, EV treatment was associated with decreased C1q + synaptic tagging and microglia–spine contacts. Our results suggest that EV treatment may enhance synaptic plasticity via clearance of acute damage in perilesional M1, and thereby preventing chronic inflammation and excessive synaptic loss in PMC. These mechanisms may act to preserve synaptic cortical motor networks and a balanced normative M1/PMC synaptic function to support functional recovery after injury.
Review of cone beam computed tomography based online adaptive radiotherapy: current trend and future direction
Authors: Liu Hefei , Schaal David , Curry Heather , Clark Ryan , Magliari Anthony , Kupelian Patrick , Khuntia Deepak , Beriwal Sushil 
Published: September 2023

AbstractAdaptive radiotherapy (ART) was introduced in the late 1990s to improve the accuracy and efficiency of therapy and minimize radiation-induced toxicities. ART combines multiple tools for imaging, assessing the need for adaptation, treatment planning, quality assurance, and has been utilized to monitor inter- or intra-fraction anatomical variations of the target and organs-at-risk (OARs). Ethos™ (Varian Medical Systems, Palo Alto, CA), a cone beam computed tomography (CBCT) based radiotherapy treatment system that uses artificial intelligence (AI) and machine learning to perform ART, was introduced in 2020. Since then, numerous studies have been done to examine the potential benefits of Ethos™ CBCT-guided ART compared to non-adaptive radiotherapy. This review will explore the current trends of Ethos™, including improved CBCT image quality, a feasible clinical workflow, daily automated contouring and treatment planning, and motion management. Nevertheless, evidence of clinical improvements with the use of Ethos™ are limited and is currently under investigation via clinical trials.
Hemivertebra resection after age three produces the similar results but with less complications compared to earlier surgery: a minimum of 5-year follow-up
Authors: Wang Yu , Sun Xu , Li Wenhan , Shi Benlong , Liu Zhen , Wang Bin , Qiu Yong , Zhu Zezhang 
Published: September 2023

Abstract
Background
The optimal timing for hemivertebra resection remains controversial. Early intervention before 3 years of age seems being able to get better correction with less fusion segments. However, it was also reported that early surgery may be associated with more complications. The purpose of this study is to investigate correction outcomes and complications of delayed hemivertebra resection (between 3 and 5 years of age), in comparison with earlier surgery (before 3 years of age).

Methods
Patients who had undergone thoracolumbar hemivertebra resection at a single level before 5 years of age and had more than 5 years of follow-up were reviewed. Twenty-four patients had hemivertebra resection surgery below 3 years of age (early surgery, Group E), and 33 patients received surgery between 3 and 5 years of age (delayed surgery, Group D). Radiographs from preoperative, immediately postoperative, and the latest follow-up visits were reviewed to investigate the correction outcomes. Complications were recorded and compared between these two groups.

Results
The patients of Group E had shorter operation time and less blood loss than those of Group D (P = 0.003 and P = 0.006). Notably, the fusion segments were 2.3 ± 0.7 and 3.1 ± 1.2 in group E and group D (P = 0.005), respectively, indicating group E averagely saved 0.8 motion segments. At the time of surgery, group E had smaller main curve magnitude either in the coronal or in the sagittal plane than group D and experienced similar correction rates of scoliosis (83.3 ± 21.6% vs. 81.2 ± 20.1%, P = 0.707) and kyphosis (65.1 ± 23.8% vs. 71.7 ± 24.9%, P = 0.319). However, group E had relatively higher complication rates than group D and relatively greater correction loss in either coronal or sagittal plane during follow-up.

Conclusions
Hemivertebra resection resulted in similar correction results in both age groups. However, the rate of complications was lower for Group D than Group E. Thus, for non-kyphotic hemivertebra, surgery may be delayed till 3 to 5 years of age.
Learning curve of tibial cortex transverse transport: a cumulative sum analysis
Authors: Liu Jun-Peng , Yao Xing-Chen , Xu Zi-Yu , Du Xin-Ru , Zhao Hui 
Published: September 2023

Abstract
Objective
This study aimed to describe the learning curve of surgeons performing tibial cortex transverse transport (TTT) and explore its safety and effectiveness during the initial stages of surgeon’s learning.

Methods
The clinical data of patients with diabetic foot ulcers classified as Wagner grade ≥ 2, who underwent TTT at our hospital from January 2020 to July 2021, were included in this retrospective analysis. The same physician performed all procedures. Patients were numbered according to the chronological order of their surgery dates. The cumulative sum and piecewise linear regression were used to evaluate the surgeon's learning curve, identify the cut-off point, and divide the patients into learning and mastery groups. A minimum follow-up period of 3 months was ensured for all patients. Baseline data, perioperative parameters, complications, and efficacy evaluation indicators were recorded and compared between the two groups.

Results
Sixty patients were included in this study based on the inclusion and exclusion criteria. After completing 20 TTT surgeries, the surgeon reached the cut-off point of the learning curve. Compared to the learning group, the mastery group demonstrated a significant reduction in the average duration of the surgical procedure (34.88 min vs. 54.20 min, P < 0.05) along with a notable decrease in intraoperative fluoroscopy (9.75 times vs. 16.9 times, P < 0.05) frequency, while no significant difference was found regarding intraoperative blood loss (P = 0.318). Of the patients, seven (11.7%) experienced complications, with three (15%) and four cases (10%) occurring during the learning phase and the mastery phase, respectively. The postoperative ulcer area was significantly reduced, and the overall healing rate was 94.8%. Significant improvements were observed in postoperative VAS, ABI, and WIFI classification (P < 0.05). There were no significant differences in the occurrence of complications or efficacy indicators between the learning and mastery groups (P > 0.05).

Conclusion
Surgeons can master TTT after completing approximately 20 procedures. TTT is easy, secure, and highly efficient for treating foot ulcers. Furthermore, TTT’s application by surgeons can achieve almost consistent clinical outcomes in the initial implementation stages, comparable to the mastery phase.
Prognostic value of pathogenic variants in Lafora Disease: systematic review and meta-analysis of patient-level data
Authors: Pondrelli Federica , Minardi Raffaella , Muccioli Lorenzo , Zenesini Corrado , Vignatelli Luca , Licchetta Laura , Mostacci Barbara , Tinuper Paolo , Vander Kooi Craig W. , Gentry Matthew S. , Bisulli Francesca 
Published: September 2023

Abstract
Background
Lafora disease (LD) is a fatal form of progressive myoclonic epilepsy caused by biallelic pathogenic variants in EPM2A or NHLRC1. With a few exceptions, the influence of genetic factors on disease progression has yet to be confirmed. We present a systematic review and meta-analysis of the known pathogenic variants to identify genotype–phenotype correlations.

Methods
We collected all reported cases with genetically-confirmed LD containing data on disease history. Pathogenic variants were classified into missense (MS) and protein-truncating (PT). Three genotype classes were defined according to the combination of the variants: MS/MS, MS/PT, and PT/PT. Time-to-event analysis was performed to evaluate survival and loss of autonomy.

Results
250 cases described in 70 articles were included. The mutated gene was NHLRC1 in 56% and EPM2A in 44% of cases. 114 pathogenic variants (67 EPM2A; 47 NHLRC1) were identified. The NHLRC1 genotype PT/PT was associated with shorter survival [HR 2.88; 95% CI 1.23–6.78] and a trend of higher probability of loss of autonomy [HR 2.03, 95% CI 0.75–5.56] at the multivariable Cox regression analysis. The population carrying the homozygous p.Asp146Asn variant of NHLRC1 genotype was confirmed to have a more favourable prognosis in terms of disease duration.

Conclusions
This study demonstrates the existence of prognostic genetic factors in LD, namely the genotype defined according to the functional impact of the pathogenic variants. Although the reasons why NHLRC1 genotype PT/PT is associated with a poorer prognosis have yet to be fully elucidated, it may be speculated that malin plays a pivotal role in LD pathogenesis.
“A turn in the road, but still a rough journey” - Parent and child perspectives of outcomes after pre-adolescent inpatient psychiatric admission
Authors: Swart Tania T , Davids Eugene L , de Vries Petrus J 
Published: September 2023

Abstract
Background
Research regarding the outcomes of child and adolescent psychiatric inpatients appears insufficient and neglected. Where data are available, the majority of studies focus on adolescents. This study aimed (a) to describe child and parental perspectives of short-, medium- and long-term outcomes of children who have had a pre-adolescent inpatient psychiatric admission, and (b) to analyse these dyadic experiential data to identify outcome variables of importance to families and service users that could be used in future outcomes-based research.

Methods
The study employed a qualitative methodology, using semi-structured in-depth interviews of ten parent-child dyads to (a) collect the perspectives of children who have had an inpatient psychiatric admission at a pre-adolescent unit and their parents, and (b) to analyse the experiences of inpatient admission and perceived outcomes after discharge using thematic analysis.

Results
Overall, inpatient psychiatric admission was viewed as a positive and empowering experience by parents and children. Clear short-term benefits were reported as a result of new diagnoses, medications and new skills gained through the admission process. More than half of parent-child dyads reported long-term benefits, but many families commented on ongoing challenges. Thematic analysis identified diagnostic certainty, acquisition of cognitive and behavioural skills, appropriate educational environment, peer relationships, sustained follow-up and medication management, and parent-child relationships, as important contributors to outcomes. Importantly, the presence or lack of these elements influenced outcomes.

Conclusions
The study explored parent-child dyadic perspectives about their experiences of inpatient mental health admissions for pre-adolescents and perceived outcomes after admission. The majority of families found inpatient admission positive and helpful, and thematic analysis identified a number of functional variables that may predict outcome. However, positive outcomes were associated with ongoing difficulties over time, as indicated by the theme “a turn in the road, but still a rough journey”.
FBXW7 in breast cancer: mechanism of action and therapeutic potential
Authors: Chen Siyu , Leng Ping , Guo Jinlin , Zhou Hao 
Published: September 2023

AbstractBreast cancer is one of the frequent tumors that seriously endanger the physical and mental well-being in women. F-box and WD repeat domain-containing 7 (FBXW7) is a neoplastic repressor. Serving as a substrate recognition element for ubiquitin ligase, FBXW7 participates in the ubiquitin–proteasome system and is typically in charge of the ubiquitination and destruction of crucial oncogenic proteins, further performing a paramount role in cell differentiation, apoptosis and metabolic processes. Low levels of FBXW7 cause abnormal stability of pertinent substrates, mutations and/or deletions in the FBXW7 gene have been reported to correlate with breast cancer malignant progression and chemoresistance. Given the lack of an effective solution to breast cancer's clinical drug resistance dilemma, elucidating FBXW7's mechanism of action could provide a theoretical basis for targeted drug exploration. Therefore, in this review, we focused on FBXW7's role in a range of breast cancer malignant behaviors and summarized the pertinent cellular targets, signaling pathways, as well as the mechanisms regulating FBXW7 expression. We also proposed novel perspectives for the exploitation of alternative therapies and specific tumor markers for breast cancer by therapeutic strategies aiming at FBXW7.
The role of OIP5 in the carcinogenesis and progression of ovarian cancer
Authors: Zhang Xin , Gu Wenjie , Lin Aiqin , Duan Renjie , Lian Likai , Huang Yuanyuan , Li Tiechen , Sun Qing 
Published: September 2023

Abstract
Background
Opa interacting protein 5 (OIP5), which is a cancer/testis-specific gene, plays a cancer-promoting role in various types of human cancer. However, the role of OIP5 in the carcinogenesis and progression of ovarian cancer remains unknown.

Methods
We first analyzed the expression of OIP5 in ovarian cancer and various human tumors with the Sangerbox online analysis tool. GSE12470, GSE14407 and GSE54388 were downloaded from the Gene Expression Omnibus (GEO) database, and GEO2R was used to screen differentially expressed genes in ovarian cancer tissues. Gene Ontology (GO) enrichment analysis was used to explore the related biological processes. Receiver operating characteristic (ROC) curve was generated to evaluate the predictive ability of OIP5 for ovarian cancer. Next, RT–PCR, immunohistochemistry and Western blotting were utilized to evaluate the expression of OIP5 in ovarian cancer. CCK8, EdU proliferation assays and colony formation assays were used to measure cell proliferation, cell cycle progression was examined by PI staining and flow cytometry, and cell apoptosis was examined by Caspase3/7 activity assays. The effect of OIP5 on the migration and invasion of ovarian cancer cells was analyzed with Transwell assays.

Results
We found that OIP5 is highly expressed in ovarian cancer through bioinformatics analysis, and importantly, OIP5 may be an important biomarker for the prognosis and diagnosis of ovarian cancer. RT–PCR assays, immunohistochemistry and Western blotting were also used to confirm the high expression of OIP5 in ovarian cancer. Subsequently, we demonstrated that the proliferation and migration of the ovarian cancer cell line A2780 were significantly inhibited after OIP5 gene silencing, apoptosis was increased and cell cycle progression was arrested at the G1 phase.

Conclusion
This study indicated that OIP5 was highly expressed in ovarian cancer and that downregulation of OIP5 inhibited the proliferation, migration and invasion of ovarian cancer cells, induced cell cycle arrest and promoted cell apoptosis. Therefore, OIP5 may be an important biomarker for the early diagnosis and potential target for treatment of ovarian cancer.
The effect of perioperative of dexamethasone on postoperative complications after pancreaticoduodenectomy (PANDEX): a study protocol for a pragmatic multicenter randomized controlled trial
Authors: Chen Haoda , Wang Ying , Wang Chao , Lu Xiaojian , Li Yilong , Sun Bei , Jiang Kuirong , Qiu Yudong , Chen Rufu , Cao Liping , Chen Shi , Luo Yan , Shen Baiyong 
Published: September 2023

Abstract
Background
Pancreaticoduodenectomy (PD) nowadays serves as a standard treatment for patients with disorders of the pancreas, intestine, and bile duct. Although the mortality rate of patients undergoing PD has decreased significantly, postoperative complication rates remain high. Dexamethasone, a synthetic glucocorticoid with potent anti-inflammatory and metabolic effects, has been proven to have a favorable effect on certain complications. However, the role it plays in post-pancreatectomy patients has not been systematically evaluated. The aim of this study is to assess the effect of dexamethasone on postoperative complications after PD.

Methods
The PANDEX trial is an investigator-initiated, multicentric, prospective, randomized, double-blinded, placebo-control, pragmatic study. The trial is designed to enroll 300 patients who are going to receive elective PD. Patients will be randomized to receive 0.2 mg/kg dexamethasone or saline placebo, administered as an intravenous bolus within 5 min after induction of anesthesia. The primary outcome is the Comprehensive Complication Index (CCI) score within 30 days after the operation. The secondary outcomes include postoperative major complications (Clavien-Dindo≥3), postoperative pancreatic fistula (POPF), post-pancreatectomy acute pancreatitis (PPAP), infection, and unexpected relaparotomy, as well as postoperative length of stay, 30-day mortality, and 90-day mortality.

Discussion
The PANDEX trial is the first randomized controlled trial concerning the effect of dexamethasone on postoperative complications of patients undergoing PD, with the hypothesis that the intraoperative use of dexamethasone can reduce the incidence of postoperative complications and improve short-term outcomes after PD. The results of the present study will guide the perioperative use of dexamethasone and help improve the clinical management of post-pancreatectomy patients.

Trial registration
ClinicalTrials.gov NCT05567094. Registered on 30 September 30 2022