bluuebunny/crossref_metadata_2025 huggingface dataset:
Advances in immunotherapy for triple-negative breast cancer
Authors: Liu Yang , Hu Yueting , Xue Jinqi , Li Jingying , Yi Jiang , Bu Jiawen , Zhang Zhenyong , Qiu Peng , Gu Xi
Published: September 2023

Background

Immunotherapy has recently emerged as a treatment strategy which stimulates the human immune system to kill tumor cells. Tumor immunotherapy is based on immune editing, which enhances the antigenicity of tumor cells and increases the tumoricidal effect of immune cells. It also suppresses immunosuppressive molecules, activates or restores immune system function, enhances anti-tumor immune responses, and inhibits the growth f tumor cell. This offers the possibility of reducing mortality in triple-negative breast cancer (TNBC).

Main body

Immunotherapy approaches for TNBC have been diversified in recent years, with breakthroughs in the treatment of this entity. Research on immune checkpoint inhibitors (ICIs) has made it possible to identify different molecular subtypes and formulate individualized immunotherapy schedules. This review highlights the unique tumor microenvironment of TNBC and integrates and analyzes the advances in ICI therapy. It also discusses strategies for the combination of ICIs with chemotherapy, radiation therapy, targeted therapy, and emerging treatment methods such as nanotechnology, ribonucleic acid vaccines, and gene therapy. Currently, numerous ongoing or completed clinical trials are exploring the utilization of immunotherapy in conjunction with existing treatment modalities for TNBC. The objective of these investigations is to assess the effectiveness of various combined immunotherapy approaches and determine the most effective treatment regimens for patients with TNBC.

Conclusion

This review provides insights into the approaches used to overcome drug resistance in immunotherapy, and explores the directions of immunotherapy development in the treatment of TNBC.
NIR diagnostic imaging of triple-negative breast cancer and its lymph node metastasis for high-efficiency hypoxia-activated multimodal therapy
Authors: Pan Yi , Liu Longcai , He Yichen , Ye Luyi , Zhao Xin , Hu Zhiming , Mou Xiaozhou , Cai Yu
Published: September 2023

Background

Triple-negative breast cancer (TNBC) possesses special biological behavior and clinicopathological characteristics, which is highly invasive and propensity to metastasize to lymph nodes, leading to a worse prognosis than other types of breast cancer. Thus, the development of an effective therapeutic method is significant to improve the survival rate of TNBC patients.

Results

In this work, a liposome-based theranostic nanosystem (ILA@Lip) was successfully prepared by simultaneously encapsulating IR 780 as the photosensitizer and lenvatinib as an anti-angiogenic agent, together with banoxantrone (AQ4N) molecule as the hypoxia-activated prodrug. The ILA@Lip can be applied for the near-infrared (NIR) fluorescence diagnostic imaging of TNBC and its lymph node metastasis for multimodal therapy. Lenvatinib in ILA@Lip can inhibit angiogenesis by cutting oxygen supply, thereby leading to enhanced hypoxia levels. Meanwhile, large amounts of reactive oxygen species (ROS) were produced while IR 780 was irradiated by an 808 nm laser, which also rapidly exhausted oxygen in tumor cells to worsen tumor hypoxia. Through creating an extremely hypoxic in TNBC, the conversion of non-toxic AQ4N to toxic AQ4 was much more efficiency for hypoxia-activated chemotherapy. Cytotoxicity assay of ILA@Lip indicated excellent biocompatibility with normal cells and tissues, but showed high toxicity in hypoxic breast cancer cells. Also, the in vivo tumors treated by the ILA@Lip with laser irradiation were admirably suppressed in both subcutaneous tumor model and orthotopic tumor models.

Conclusion

Utilizing ILA@Lip is a profound strategy to create an extremely hypoxic tumor microenvironment for higher therapeutic efficacy of hypoxia-activated chemotherapy, which realized collective suppression of tumor growth and has promising potential for clinical translation.
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

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

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

Understanding 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

Adaptive 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

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

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

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

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

Breast 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

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

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
Oxidation characteristic and thermal runaway of isoprene
Authors: Liang Min , Dai Suyi , Cheng Haijun , Yu Chang , Li Weiguang , Lai Fang , Yang Kang , Ma Li , Liu Xiongmin
Published: September 2023

In this study, the oxidation characteristics of isoprene were investigated using a custom-designed mini closed pressure vessel test (MCPVT). The results show that isoprene is unstable and polymerization occurs under a nitrogen atmosphere. Under an oxygen atmosphere, the oxidation process of isoprene was divided into three stages: (1) isoprene reacts with oxygen to produce peroxide; (2) Peroxides produce free radicals through thermal decomposition; (3) Free radicals cause complex oxidation and thermal runaway reactions. The oxidation of isoprene conforms to the second-order reaction kinetics, and the activation energy was 86.88 kJ·mol−1. The thermal decomposition characteristics of the total oxidation product and purified peroxide mixture were determined by differential scanning calorimetry (DSC). The initial exothermic temperatures Ton were 371.17 K and 365.84 K, respectively. And the decomposition heat QDSC were 816.66 J·g−1 and 991.08 J·g−1, respectively. It indicates that high concentration of isoprene peroxide has a high risk of thermal runaway. The results of thermal runaway experiment showed that the temperature and pressure of isoprene oxidation were prone to rise rapidly, which indicates that the oxidation reaction was dangerous. The reaction products of isoprene were analyzed by gas chromatography-mass spectrometry (GC–MS). The main oxidation products were methyl vinyl ketone, methacrolein, 3-methylfuran, etc. The main thermal runaway products were dimethoxymethane, 2,3-pentanedione, naphthalene, etc. Based on the reaction products, the possible reaction pathway of isoprene was proposed.
Effect of C-reactive protein deficiency on insulin resistance reversal in rats with polycystic ovary syndrome through augmented leptin action
Authors: Li Ke , Hu Lingling , Li Xinrun , Yuan Zhibin , He Jia , Liu Dongfang , Yang Gangyi , Yuan Lei
Published: September 2023

Background

C-reactive protein(CRP), is an inflammatory marker that weaken leptin bioavailability and insulin sensitivity to disturb energy and glucose metabolism. Polycystic ovary syndrome (PCOS) exhibit a metabolic component consisting of higher plasma CRP levels, hyperinsulinemic and hyperleptinemia. The ability of leptin to regulation of hepatic glucose production (HGP) in the absence of CRP in PCOS remain unknown.

Methods

Dehydroepiandrosterone (DHEA) was used to induce PCOS in rats. We assessed the effects of CRP gene knockout in PCOS model rats on body weight, energy expenditure glucose metabolism and insulin sensitivity. We conducted experiments involving the administration of leptin to both the peripheral and central systems in PCOS model rats with CRP knockout, and studied the effects on changes in glucose kinetics during hyperinsulinemic-euglycemic clamps.

Results

In female PCOS rats, the lack of CRP resulted in decreased leptin resistance and weight gain, increased energy expenditure, and improved insulin sensitivity. Additionally, the deletion of the CRP gene strengthened the HGP-lowering effects of leptin when administered peripherally or centrally. This effect was accompanied by a decrease in the expression of hepatic gluconeogenic enzymes and an increase in hepatic insulin signaling. Finally, inhibition of glucose production was also enhanced for central leptin administration during lipid infusion in PCOS rats.

Conclusions

Our findings highlight the therapeutic potential of targeting CRP to restore glucose homeostasis and insulin sensitivity for leptin in PCOS.
A systematic review of the measures that have been used to assess surface characteristics in relation to their impact on walking and falling
Authors: Lawson Rebecca , Thomas Nicholas D. A.
Published: September 2023

We investigated whether an impediment to progress in understanding the environmental factors that cause falls may be the difficulty in comparing results across studies because walking surfaces are poorly defined and underspecified. We conducted a systematic review of 384 studies from 370 articles that tested how different surfaces influenced human walking and falling. For each study, we report which categories of surfaces were used (indoor, outdoor, treadmill, virtual reality and qualitative), the nature of each surface (stairs, slopes, slippery, compliant, rough or default) and how information about each surface was measured. We found that minimal information was provided for many surfaces, making it impossible to meaningfully compare results for different types of surfaces across studies. We conclude that most published studies of walking and falling provide insufficient data to describe the surfaces that they used and we provide recommendations about how to improve the reporting of walking surfaces.
Development of machine learning models for the detection of surgical site infections following total hip and knee arthroplasty: a multicenter cohort study
Authors: Wu Guosong , Cheligeer Cheligeer , Southern Danielle A. , Martin Elliot A. , Xu Yuan , Leal Jenine , Ellison Jennifer , Bush Kathryn , Williamson Tyler , Quan Hude , Eastwood Cathy A.
Published: September 2023

Background

Population based surveillance of surgical site infections (SSIs) requires precise case-finding strategies. We sought to develop and validate machine learning models to automate the process of complex (deep incisional/organ space) SSIs case detection.

Methods

This retrospective cohort study included adult patients (age ≥ 18 years) admitted to Calgary, Canada acute care hospitals who underwent primary total elective hip (THA) or knee (TKA) arthroplasty between Jan 1st, 2013 and Aug 31st, 2020. True SSI conditions were judged by the Alberta Health Services Infection Prevention and Control (IPC) program staff. Using the IPC cases as labels, we developed and validated nine XGBoost models to identify deep incisional SSIs, organ space SSIs and complex SSIs using administrative data, electronic medical records (EMR) free text data, and both. The performance of machine learning models was assessed by sensitivity, specificity, positive predictive value, negative predictive value, F1 score, the area under the receiver operating characteristic curve (ROC AUC) and the area under the precision–recall curve (PR AUC). In addition, a bootstrap 95% confidence interval (95% CI) was calculated.

Results

There were 22,059 unique patients with 27,360 hospital admissions resulting in 88,351 days of hospital stay. This included 16,561 (60.5%) TKA and 10,799 (39.5%) THA procedures. There were 235 ascertained SSIs. Of them, 77 (32.8%) were superficial incisional SSIs, 57 (24.3%) were deep incisional SSIs, and 101 (42.9%) were organ space SSIs. The incidence rates were 0.37 for superficial incisional SSIs, 0.21 for deep incisional SSIs, 0.37 for organ space and 0.58 for complex SSIs per 100 surgical procedures, respectively. The optimal XGBoost models using administrative data and text data combined achieved a ROC AUC of 0.906 (95% CI 0.835–0.978), PR AUC of 0.637 (95% CI 0.528–0.746), and F1 score of 0.79 (0.67–0.90).

Conclusions

Our findings suggest machine learning models derived from administrative data and EMR text data achieved high performance and can be used to automate the detection of complex SSIs.
hsa_circ_0003596, as a novel oncogene, regulates the malignant behavior of renal cell carcinoma by modulating glycolysis
Authors: Xie QingZhi , Qin FuQiang , Luo LiHui , Deng ShaoQuan , Zeng Ke , Wu YunChou , Liao DunMing , Luo Lin , Wang KangNing
Published: September 2023

Background

This research was planned to analyze hsa_circ_0003596 (circCOL5A1) and glycolysis-focused mechanisms in renal cell carcinoma (RCC).

Methods

circCOL5A1, miR-370-5p, and PRKCSH levels were determined in RCC tissues and selected cell lines by RT-qPCR and/or Western blot. RCC cells after corresponding transfection were tested by colony formation assay, EdU assay, Transwell assay, and flow cytometry to analyze cell proliferation, invasion, migration, and apoptosis. Meanwhile, glycolysis in cells was evaluated by measuring glucose consumption, lactic acid, and ATP production, as well as immunoblotting for HK2 and PKM2. In addition, circCOL5A1 knockdown was performed in animal experiments to observe tumor growth and glycolysis. Finally, the ceRNA network between circCOL5A1, miR-370-5p, and PRKCSH was studied by luciferase reporter assay and RIP experiment.

Results

circCOL5A1 and PRKCSH were highly expressed and miR-370-5p was poorly expressed in RCC. circCOL5A1 knockdown depressed RCC proliferation, invasion, migration, and glycolysis, and enhanced apoptosis. circCOL5A1 competitively adsorbed miR-370-5p. Artificial upregulation of miR-370-5p saved the pro-tumor effect of circCOL5A1 on RCC cells, as evidenced by suppression of tumor malignancy and glycolysis. miR-370-5p targeted PRKCSH. PRKCSH overexpression contributed to a reversal of the anti-tumor effect of circCOL5A1 silencing. Silencing circCOL5A1 inhibited RCC tumor growth and glycolysis.

Conclusions

circCOL5A1 regulates the malignant behavior of RCC by modulating glycolysis.
Variations of bile bacterial community alongside gallstone disease progression and key taxa involved in poor outcomes after endoscopic surgery
Authors: Cai Xunchao , Peng Yao , Gong Yajie , Huang Xiuting , Liu Lu , Chen Yifan , Du Jingfeng , Dai Zhongming , Qian Yun , Xu Long
Published: September 2023

Gallstone disease is a prevalent biliary disease worldwide, and bacteria play vital roles in the disease development and progression, as well as the prognosis after endoscopic surgery. However, there have been limited studies to explore the key taxa involved. In this study, bile samples from healthy controls (HCs, liver donors without hepatobiliary disease) and three diseased groups, namely patients with gallbladder stones (GBS), patients with common bile duct stones (CBDS), and patients with stricture in the common bile duct (SCBD), were collected and analyzed. Bacterial community characterization based on 16S rRNA amplicon sequencing showed that bacterial diversities did not change significantly alongside gallstone disease development and progression. The predominant phyla in each group were Proteobacteria, Firmicutes, Bacteroidota, and Fusobacteriota, representing over 80% in abundance of the biliary bacteria community. Specifically, the abundance of Proteobacteria decreased greatly while that of Firmicutes and Bacteroidota increased greatly in the diseased groups when compared to that in HCs. Moreover, linear discriminant analysis identified several genera highly represented in the diseased groups. Among them, Klebsiella, Prevotella, Pseudomonas and Veillonella are persistent in both the HCs group and the diseased groups, indicating an enrichment of local bile bacteria in the diseased bile; while Lachnoanerobaculum, Atopobium, Oribacterium, and Stomatobaculum, those aligned to oral cavity taxa, are persistent in the diseased groups but are transient in the HCs group, and their abundances sequentially increased with the disease development and progression (HCs→GBS→CBDS→SCBD), implying a translocation and colonization of the oral cavity bacteria in the diseased bile. Moreover, co-occurrence network analysis revealed that bacterial infection (e.g., Photobacterium and Plesiomonas) from the intestine was developed during endoscopic surgery with reduced bile bacteria diversity. The results of this study revealed that the bile bacterial community is relatively stable and dominated by a few persistent taxa. Moreover, we hypothesized that translocation and colonization of specific bacteria from the oral cavity happens alongside gallstone disease development and progression, and bacterial infection from the intestinal tract results in poor outcomes after endoscopic surgery.
Translation and psychometric evaluation of the Persian version of “good death inventory- short Form” from the perspective of family-members of cancer patients
Authors: Roshan Hosein Mohammadi , Ebadi Abbas , Karimi Leila , Barasteh Salman
Published: September 2023

Introduction

Achieving good death is among the objectives of palliative care in patients with cancer. There should be an instrument for evaluating the quality of palliative care provided by family members at the end of life. This study was done to assess the psychometric properties of good death inventory- short form according to the perspective of family of patients with cancer.

Method

This methodological study was done in 2022 at two hospitals in Tehran. The translation was done via forward-backward method. Face validity was examined through cognitive interviewing with 10 family members. The content validation, were used by assessment the opinions of 10 palliative care specialists. The construct validity was explored through exploratory factor analysis and examination of convergent validation with care evaluation scale 2.0, as well as inspection of correlation by answering two general questions of satisfaction with treatment and end of life quality of life. The scale’s reliability, internal consistency was calculated using Cronbach’s alpha coefficient and stability via test-retest.

Results

Overall, 204 family members of patients with cancer were included. In the exploratory factor analysis, three factors of peace, hope, and value as well as quality of care were extracted with cumulative variance of 41.8%.A significant and suitable correlation between the total scores of the participants Good death inventory-short form and care evaluation scale2.0 (r = 0.459, P < 0.001) and general satisfaction with end-of-life care (r = 0.423, p < 0.001) as well as the patient’s general quality of life (r = 0.539, p < 0.001). The Cronbach’s alpha coefficient for the questionnaire was found 0.842, and the stability was confirmed with Intra cluster correlation coefficient = 0.851.

Conclusion

the Persian version of good death inventory-short form is a valid and reliable questionnaire which can investigate the factors associated with good death according to patients’ family members’ perspective.
Cerebrovascular disease case identification in inpatient electronic medical record data using natural language processing
Authors: Pan Jie , Zhang Zilong , Peters Steven Ray , Vatanpour Shabnam , Walker Robin L. , Lee Seungwon , Martin Elliot A. , Quan Hude
Published: September 2023

Background

Abstracting cerebrovascular disease (CeVD) from inpatient electronic medical records (EMRs) through natural language processing (NLP) is pivotal for automated disease surveillance and improving patient outcomes. Existing methods rely on coders’ abstraction, which has time delays and under-coding issues. This study sought to develop an NLP-based method to detect CeVD using EMR clinical notes.

Methods

CeVD status was confirmed through a chart review on randomly selected hospitalized patients who were 18 years or older and discharged from 3 hospitals in Calgary, Alberta, Canada, between January 1 and June 30, 2015. These patients’ chart data were linked to administrative discharge abstract database (DAD) and Sunrise™ Clinical Manager (SCM) EMR database records by Personal Health Number (a unique lifetime identifier) and admission date. We trained multiple natural language processing (NLP) predictive models by combining two clinical concept extraction methods and two supervised machine learning (ML) methods: random forest and XGBoost. Using chart review as the reference standard, we compared the model performances with those of the commonly applied International Classification of Diseases (ICD-10-CA) codes, on the metrics of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).

Result

Of the study sample (n = 3036), the prevalence of CeVD was 11.8% (n = 360); the median patient age was 63; and females accounted for 50.3% (n = 1528) based on chart data. Among 49 extracted clinical documents from the EMR, four document types were identified as the most influential text sources for identifying CeVD disease (“nursing transfer report,” “discharge summary,” “nursing notes,” and “inpatient consultation.”). The best performing NLP model was XGBoost, combining the Unified Medical Language System concepts extracted by cTAKES (e.g., top-ranked concepts, “Cerebrovascular accident” and “Transient ischemic attack”), and the term frequency-inverse document frequency vectorizer. Compared with ICD codes, the model achieved higher validity overall, such as sensitivity (25.0% vs 70.0%), specificity (99.3% vs 99.1%), PPV (82.6 vs. 87.8%), and NPV (90.8% vs 97.1%).

Conclusion

The NLP algorithm developed in this study performed better than the ICD code algorithm in detecting CeVD. The NLP models could result in an automated EMR tool for identifying CeVD cases and be applied for future studies such as surveillance, and longitudinal studies.
Design of chimeric GLP-1A using oligomeric bile acids to utilize transporter-mediated endocytosis for oral delivery
Authors: Kweon Seho , Lee Jun-Hyuck , Yang Seong-Bin , Park Seong Jin , Subedi Laxman , Shim Jung-Hyun , Cho Seung-Sik , Choi Jeong Uk , Byun Youngro , Park Jooho , Park Jin Woo
Published: September 2023

Background

Despite the effectiveness of glucagon-like peptide-1 agonist (GLP-1A) in the treatment of diabetes, its large molecular weight and high hydrophilicity result in poor cellular permeability, thus limiting its oral bioavailability. To address this, we developed a chimeric GLP-1A that targets transporter-mediated endocytosis to enhance cellular permeability to GLP-1A by utilizing the transporters available in the intestine, particularly the apical sodium-dependent bile acid transporter (ASBT).

Methods

In silico molecular docking and molecular dynamics simulations were used to investigate the binding interactions of
mono
-,
bis
-, and
tetra
-deoxycholic acid (DOCA) (
mono
DOCA,
bis
DOCA, and
tetra
DOCA) with ASBT. After synthesizing the chimeric GLP-1A-conjugated oligomeric DOCAs (
m
D-G1A,
b
D-G1A, and
t
D-G1A) using a maleimide reaction, in vitro cellular permeability and insulinotropic effects were assessed. Furthermore, in vivo oral absorption in rats and hypoglycemic effect on diabetic
db/db
mice model were evaluated.

Results

In silico results showed that
tetra
DOCA had the lowest interaction energy, indicating high binding affinity to ASBT. Insulinotropic effects of GLP-1A-conjugated oligomeric DOCAs were not different from those of GLP-1A-Cys or exenatide. Moreover,
b
D-G1A and
t
D-G1A exhibited improved in vitro Caco-2 cellular permeability and showed higher in vivo bioavailability (7.58% and 8.63%) after oral administration. Regarding hypoglycemic effects on
db/db
mice,
t
D-G1A (50 μg/kg) lowered the glucose level more than
b
D-G1A (50 μg/kg) compared with the control (35.5% vs. 26.4%).

Conclusion

GLP-1A was conjugated with oligomeric DOCAs, and the resulting chimeric compound showed the potential not only for glucagon-like peptide-1 receptor agonist activity but also for oral delivery. These findings suggest that oligomeric DOCAs can be used as effective carriers for oral delivery of GLP-1A, offering a promising solution for enhancing its oral bioavailability and improving diabetes treatment.

Graphical Abstract
Joint aspiration for diagnosis of chronic periprosthetic joint infection: when, how, and what tests?
Authors: Quinlan Nicole Durig , Jennings Jason M.
Published: September 2023

Diagnosing chronic periprosthetic joint infection (PJI) requires clinical suspicion in combination with both serological and synovial fluid tests, the results of which are generally applied to validated scoring systems or consensus definitions for PJI. As no single “gold standard” test exists, the diagnosis becomes challenging, especially in the setting of negative cultures or equivocal test results. This review aims to address the workup of chronic PJI and considerations for clinical evaluation to guide treatment. Following aspiration of the joint in question, a multitude of tests has been developed in an attempt to assist with diagnosis, including cell synovial white blood cell count, gram stain, cultures, leukocyte esterase, alpha-defensin, synovial C-reactive protein, multiplex polymerase chain reaction, next-generation sequencing, and interleukins. Each test has advantages and disadvantages and should be used in conjunction with the overall clinical picture to guide further clinical evaluation and treatment in this complex patient population.