bluuebunny/crossref_metadata_2025_split huggingface dataset:
Screening canine sources for novel antimicrobials reveals the circular broad-spectrum bacteriocin, caledonicin, produced by Staphylococcus caledonicus
Authors: O’Connor Michelle , O’Connor Paula M. , Hourigan David , Murray Ellen , de Farias Felipe Miceli , Field Des , Hill Colin , Ross R. Paul 
Published: August 2024

IntroductionAntimicrobial-resistant pathogens present an ongoing threat to human and animal health, with deaths linked to antimicrobial resistance (AMR) predicted to increase annually. While the misuse and overuse of antibiotics in humans undoubtedly contribute to this escalation, antibiotic use in the veterinary field, including companion animals, also plays a contributing role. Pet owners’ desire to improve the quality of life of their pets is likely to support antibiotic use in this field. Consequently, there is a need for antibiotic alternatives to treat bacterial infections. This study set out to screen for antimicrobial peptides known as bacteriocins from bacterial isolates of aerobic/microaerophilic environments of canine sources and determine their potential as antibiotic alternatives against clinically relevant pathogens.MethodsFollowing a laboratory-based protocol, 22 bacterial isolates were subjected to whole-genome sequencing (WGS), and a total of 14 putative novel bacteriocins were identified from both class I and II bacteriocin classes. One particular bacteriocin, herein named caledonicin, was identified via in silico analysis from a Staphylococcus caledonicus strain and partially purified for further in vitro evaluation.ResultsCaledonicin is a 64-amino acid (IAANLGVSSGTAYS MANALNNISNVATA LTIIGTFTGVGTIGSGIA ATILAILKKKGVAAAAAF) novel circular bacteriocin most closely related to enterocin_NKR-5-3B based on core peptide alignment (39.1%), with a molecular weight of 6077.1 Da. Caledonicin exhibits a broad-spectrum of activity against a range of pathogenic bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus pseudintermedius (MRSP), and Listeria monocytogenes; and the gut-related bacterium associated with Crohn’s disease, Mediterraneibacter gnavus ATCC 29149 (previously Ruminococcus gnavus ATCC 29149).DiscussionThis represents the first bacteriocin screening study involving bacteria from canine sources and confirms this is a rich environment for bacteriocin-producing strains. This study also identifies and characterises the first novel bacteriocin from the staphylococcal species, Staphylococcus caledonicus.
Association of cardiovascular risk factors and intraplaque neovascularization in symptomatic carotid plaque
Authors: Liu Zehao , Zhang Lianlian , Sun Bing , Ding Yasuo 
Published: August 2024

Background and purposeCardiovascular risk factors are known to contribute to the formation of atherosclerotic plaques, which can result in carotid stenosis. However, the extent to which these factors are associated with intraplaque neovascularization, a key indicator of plaque vulnerability, remains unclear. To investigate this relationship, a study was conducted utilizing contrast-enhanced ultrasound (CEUS) to assess intraplaque neovascularization in symptomatic patients.MethodsA cohort of 157 symptomatic patients underwent evaluation using Contrast-Enhanced Ultrasound (CEUS) imaging to assess carotid intraplaque neovascularization, which was quantified based on the degree of plaque enhancement. The collected data encompassed baseline patient characteristics, results from biochemical examinations, cardiovascular risk factors, and medication usage history. Regression analyses were conducted to elucidate the relationship between carotid plaque neovascularization and various cardiovascular risk factors.ResultsPatients with intraplaque neovascularization were more prone to have diabetes mellitus (OR 3.81, 95% CI 1.94–7.46, p &lt; 0.001), dyslipidemia (OR 2.36, 95% CI 1.22–4.55, p = 0.011) and hypertension (OR 2.92, 95% CI 1.50–5.71, p = 0.002). Smoking increased the risk of having intraplaque neovascularization (OR 2.25, 95% CI 1.12–4.54, p = 0.023). Treatment with statins was significantly lower in patients with intraplaque neovascularization (OR 0.37, 95% CI 0.19–0.72, p = 0.003). In the multivariate analysis, diabetes mellitus (OR 3.27, 95% CI 1.10–9.78, p = 0.034) was independently related to the presence of intraplaque neovascularization. Meanwhile, compared to the patients in the first tertile of serum glucose (&lt; 6.20 mmol/L), the patients in the third tertile (&gt; 13.35 mmol/L) had the most significance of intraplaque neovascularization (OR 5.55, 95% CI 1.85–16.66, p = 0.002).ConclusionThe findings indicated that diabetes mellitus is a significant cardiovascular risk factor that is strongly associated with carotid intraplaque neovascularization.
Ovariectomy exacerbates the disturbance of excitation- inhibition balance in the brain of APP/PS-1/tau mice
Authors: Liu Fuwang , Liu Yanman , Shen Xuri , Du Jiarui , Zhang Hanting , Hou Xueqin 
Published: August 2024

IntroductionThe prevalence of Alzheimer’s disease (AD) is significantly gender-differentiated, with the number of female AD patients far exceeding that of males, accounting for two-thirds of the total prevalence. Although postmenopausal AD mice have been shown to have more prominent pathologic features and memory impairments than normal AD mice, the relevant molecular mechanisms leading to these outcomes have not been well elucidated. In the present study, we used the disturbance of excitation-inhibition balance in the postmenopausal brain as an entry point to explore the link between estrogen deficiency, disorders of the glutamatergic-GABAergic nervous system, and memory impairment.MethodsWild-type (WT) mice and APP/PS1/tau (3 × Tg-AD) mice (10 months old) were randomly divided into four groups: WT+Sham group, WT+OVX group, 3 × Tg-AD+Sham group and 3 × Tg-AD+OVX group. Ovariectomy (OVX) was performed in the WT+OVX group and the 3 × Tg-AD+OVX group, and sham surgery was performed in the WT+Sham group and the 3 × Tg-AD+Sham group. The learning and memory ability and the anxiety and depression-like behavior changes of mice were evaluated by behavioral experiments, and the association between estrogen-estrogen receptors pathway and glutamatergic/GABAergic nervous system and female AD was evaluated by neurochemical experiments.ResultsIn WT and 3 × Tg-AD mice, OVX resulted in impaired learning and memory abilities and anxiety and depression-like behaviors; reduced estrogen levels and downregulated the expression of estrogen receptors; upregulated the expression of amyloid-β, amyloid precursor protein, presenilin 1, and p-tau; upregulated the expression of Bcl-2-associated X protein and downregulated the expression of B-cell lymphoma-2, promoting cell apoptosis; reduced the number of neuronal dendrites and downregulated the expression of postsynaptic density protein-95; more importantly, OVX increased brain glutamate levels but downregulated the expression of N-methyl-D-aspartate receptor-2B, excitatory amino acid transporter 1, excitatory amino acid transporter 2, γ-aminobutyric acid receptor-A and γ-aminobutyric acid receptor-B.ConclusionOur results suggested that OVX-induced estrogen-estrogen receptors pathway disruption caused learning and memory impairment and anxiety and depression-like behaviors, upregulated the expression of AD pathological markers, promoted apoptosis, destroyed neuronal structure, and most importantly, caused glutamatergic/GABAergic nervous system disorders.
Predicting radiotherapy efficacy and prognosis in tongue squamous cell carcinoma through an in-depth analysis of a radiosensitivity gene signature
Authors: Lai Jinzhi , Yang Hainan , Chen Junjun , Chen Shoubo , Chen Xiaofang 
Published: August 2024

BackgroundTongue squamous cell carcinoma (TSCC) is a prevalent tumor that affects many people worldwide. Radiotherapy is a common treatment option, but its efficacy varies greatly. This study seeks to validate the identified gene signature associated with radiosensitivity in TSCC, and its potential in predicting radiotherapy response and prognosis.MethodsWe analyzed 122 TSCC patients from TCGA database using the radiosensitivity signature and classified them into radiosensitive (RS) and radioresistant (RR) groups. Immune infiltration analysis methods were applied to investigate the immune status between different subgroups. Immunophenotype Score (IPS) and pRRophetic algorithm were employed to estimate the efficiency of treatment. A radioresistant TSCC cell line was established by gradually increasing radiation doses. Cell radiosensitivity was evaluated using the CCK-8 and colony formation assays. The expression of radiosensitivity-related genes was validated by qRT-PCR.ResultsOur study validated the predictive capacity of a previously identified “31-gene signature” in the TCGA-TSCC cohort, which effectively stratified patients into RS and RR groups. We observed that the RS group exhibited superior overall survival and progression-free survival rates relative to the RR group when treated with radiotherapy. The RS group was significantly enriched in most immune-related hallmark pathways, and may therefore benefit from immune checkpoint inhibitors. However, the RS group displayed lower sensitivity to first-line chemotherapy. A radioresistant TSCC cell line (CAL-27R) exhibited increased clonogenic potential and cell viability following irradiation, accompanied by downregulation of three radiosensitivity-related genes compared to its parental non-resistant cell (CAL-27). In addition, we constructed and validated a radiosensitivity-related prognostic index (PI) using 4 radiosensitivity-related genes associated with TSCC prognosis.ConclusionWe assessed the ability of the radiosensitivity gene signature to predict outcomes in TSCC patients. our research provided valuable insights into the molecular pathways associated with radiosensitivity in TSCC and offered clinicians a practical tool to predict patient radiotherapy effectiveness and prognosis.
Proportion trends, cancer stage, and survival of patients with cancer diagnosed through emergency and nonemergency departments: a nationwide cohort study
Authors: Lin Ying-Chao , Kuo Wei-Yin , Kung Pei-Tseng , Tsai Wen-Chen 
Published: August 2024

IntroductionTo reduce mortality, the Taiwan government has vigorously promoted free cancer screening and preventive health screening services. Cancers are usually advanced by the time they are discovered in the emergency department. Through this study, we aimed to understand the characteristics of cancer patients diagnosed through the emergency department and thus identify high-risk populations by comparing cancer staging and survival rates in patients diagnosed in the emergency department and those diagnosed in the non-emergency department.MethodsThe retrospective study enrolled a total of 389,043 patients over the age of 20 who were newly diagnosed with one of the five major cancers (including lung cancer, colorectal cancer, breast cancer, prostate cancer, and oral cancer) between 2008 and 2017 and analyzed their diagnostic pathway, cancer stage at diagnosis, and survival time.ResultsOf the study participants, 59,423 patients (about 15.3%) were diagnosed with cancer through the emergency department. We found that a sizable proportion of older people and patients with low education and low incomes were diagnosed through emergency department visits, and those with a health condition comorbidity severity of 3 had the highest proportion diagnosed by the emergency department, advanced stages at diagnosis, and risk of death. These can be classified as high-risk groups. In addition, 76.4% of patients diagnosed in the emergency department had advanced cancer, and the risk of death was 1.46 times higher than that of patients diagnosed in the non-emergency department. Although cancer screening is available, it does not reduce the proportion of patients with advanced cancer who are diagnosed through or at the time of diagnosis in the emergency department.ConclusionsThe present study found that the government’s cancer screening did not affect the proportion or number of cancers diagnosed through emergency department visits. Therefore, the government should focus on more cancer screening, health education in high-risk groups, and strengthening the link between emergency and oncology departments to reduce the risk of death for patients diagnosed through emergency department visits.
Acute-phase plasma proteomics of rabbit lung VX2 tumors treated by image-guided microwave ablation
Authors: Cheng Lin , Peng Jin-zhao , Li Sheng-wei , Bie Zhi-xin , Li Xiao-Guang 
Published: August 2024

PurposeTo explore the plasma proteomic changes of rabbit lung VX2 tumors treated by microwave ablation, and to explore the molecular pathway mechanisms that may be involved.MethodsNew Zealand white rabbits were inoculated with VX2 tumor cell suspension in the right lower lung and treated with microwave ablation after 2-3 weeks of tumor formation. Blood was collected at 5 time points (TP1~TP5) before and after ablation by cardiac blood sampling and pre-treated before proteomic analysis. The plasma proteome was analyzed by Data-Independent Acquisition (DIA).ResultsDifferent molecular pathways were activated at different time points:(i) TP1vsTP2: more proteins were down-regulated and enrichment analysis showed that the proteasome pathway was activated. The abnormal protein folding process involved in this pathway is closely related to the process of tumor development. (ii) TP2vsTP3: more proteins were up-regulated although the number of differentially differentiated proteins was lower and enrichment analysis showed that the phagosome pathway was activated. After microwave ablation inactivates tumor cells, it activates the phagosomal pathway for immune clearance of necrotic tumor tissue. (iii) TP3vsTP4: more down-regulated proteins, enrichment analysis showed that cysteine and methionine metabolism pathway was activated. Decreased metabolism of these amino acids suggests that cancer progression may be blocked after microwave ablation therapy. (iv) TP4vsTP5: the number of differential proteins was less and more down-regulated proteins, enrichment analysis showed that glutathione metabolism and metabolism of xenobiotics by cytochrome P450 pathway were activated. The down-regulated proteins in this pathway may suggest that microwave ablation may have reduced resistance to certain chemotherapeutic agents following.ConclusionsIn the process of lung cancer treatment by microwave ablation, the changes of proteins on the possible molecular pathways at each time point are related to lung cancer, and not only involve some simple inflammatory reactions, and some of the proteins released by destroying the tumor cells can be used as possible drug binding sites and reduce drug resistance.
Case report: Surgical treatment and literature review of a recurrent case of glucagonoma
Authors: Liu Zhipeng , Yang Faji , Hao Yijie , Jiang Qirong , Zhang Yisu , Zheng Qixuan , Jiang Yupeng , Lu Jun , Gao Hengjun 
Published: August 2024

A 40-year-old male patient was admitted due to abdominal distension and discomfort in the upper abdomen persisting for three days. Enhanced CT of the upper abdomen revealed an irregularly dense soft tissue area in the body and tail of the pancreas, approximately 7.6 × 3.1 cm in size, with blurred boundaries, and indistinct separation from the splenic artery and vein. Multiple liver lesions of varying sizes and slightly lower densities were also observed. Liver tumor biopsy considering a neuroendocrine tumor G2, combined with the medical history, led to a diagnosis of pancreatic neuroendocrine tumor G2 with liver metastasis. Physical examination showed mild tenderness in the upper abdomen but no other significant positive signs. During treatment, the patient developed multiple red papular rashes around the mouth, on both lower limbs, and the perineum, accompanied by itching. The glucagon level was 1138.3 pg/L. The patient underwent resection of the pancreatic body and tail, splenectomy, partial liver tumor resection, and cholecystectomy. Within five days post-surgery, the skin lesions began to crust and flake off. On the 14th day post-surgery, the serum glucagon level was rechecked at 136.4 pg/L. As of April 2024, progression of liver lesions was noted, with no significant skin symptoms during the period.
Comparative complications of prepectoral versus subpectoral breast reconstruction in patients with breast cancer: a meta-analysis
Authors: Wu Yongxiao , Yu Lizhi , Huang Miaoyan , Huang Yanping , Li Chunyan , Liang Yiwen , Liang Weiming , Qin Tian 
Published: August 2024

IntroductionThis meta-analysis aims to evaluate the complications associated with prepectoral breast reconstruction (PBR) compared to subpectoral breast reconstruction (SBR) in patients diagnosed with breast cancer.Materials and methodsA comprehensive search was performed in four databases, including Medline, Embase, Web of Science and CENTRAL, to collect literature published up until December 31, 2024. In addition, we conducted a thorough manual examination of the bibliographies of the identified papers, as well as pertinent reviews and meta-analyses. We conducted a search on three clinical trial registries, namely ClinicalTrials.gov, Controlled-trials.com, and Umin.ac.jp/ctr/index.htm. Meta-analyses were conducted on total complications, hematoma, infection, wound healing issues, necrosis, capsular contracture, rippling, animation deformity, and reoperation.ResultsA total of 40 studies were included in the meta-analysis. Compared with SBR, PBR significantly reduced the incidence of animated malformations (OR=0.37, 95% CI: 0.19 to 0.70, P=0.003, I ²=12%), but increased the incidence of ripples (OR=2.39, 95% CI: 1.53 to 3.72, P=0.0001, I ²=10%) and seroma (OR=1.55, 95% CI: 1.02 to 2.35, P=0.04, increasing I ²=70%).ConclusionsOur findings indicate that PBR and SBR have comparable safety profiles, with similar total complication rates. Specifically, PBR is more likely to cause rippling and seroma, whereas SBR is more prone to causing animation deformity.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024565837, identifier CRD42024565837.
Application of tissue pneumoperitoneum technique around lymph nodes in thoracoscopic lung cancer resection
Authors: Wang Fangqing , Chen Gang , Ruan Weimin , Wang Binkui , Zhu Zhaowang , Hu Weijian , Chen Sheng , Zang Lin 
Published: August 2024

BackgroundThoracoscopic surgery is a primary treatment for lung cancer, with lobectomy and mediastinal lymph node dissection being the predominant surgical approaches for invasive lung cancer. While many thoracic surgeons can proficiently perform lobectomy, thorough and standardized lymph node dissection remains challenging. This study aimed to explore a safer and more efficient surgical method for mediastinal lymph node dissection in lung cancer.MethodsA prospective randomized controlled study was conducted, involving 100 patients with right lung cancer who were admitted to our hospital from January 2021 to April 2024 and met the inclusion criteria. These patients were randomly divided into an observation group (tissue pneumoperitoneum technique around lymph nodes group) and a control group (conventional surgery group). Thoracoscopic lobectomy and mediastinal lymph node dissection were performed. Intraoperative and postoperative related indicators were observed to validate the effectiveness and safety of the tissue pneumoperitoneum technique around lymph nodes.ResultsThe observation group showed a significantly shorter lymph node dissection surgery time compared to the control group, with a statistically significant difference (p &lt; 0.05). The number of lymph nodes dissected in the observation group was significantly higher than that in the control group, with a statistically significant difference (p &lt; 0.05). Although the observation group had slightly more mediastinal lymph node stations dissected than the control group, the difference was not statistically significant (p &gt; 0.05). The total drainage volume within three days postoperatively was comparable between the two groups, with no statistically significant difference (p &gt; 0.05). The observation group had shorter chest tube indwelling time and postoperative hospital stay than the control group, with statistically significant differences (p &lt; 0.05). The incidence of surgical complications was similar between the two groups, and there were no perioperative deaths.ConclusionThe tissue pneumoperitoneum technique around lymph nodes is a more efficient method for mediastinal lymph node dissection in lung cancer, demonstrating safety and feasibility, and is worthy of promotion.
Large animal model species in pluripotent stem cell therapy research and development for retinal diseases: a systematic review
Authors: Bellingrath Julia-Sophia , Li Kang V. , Aziz Kanza , Izzi Jessica M. , Liu Ying V. , Singh Mandeep S. 
Published: August 2024

AimRetinal cell therapy modalities, in the category of advanced therapy medicinal products (ATMPs), are being developed to target several retinal diseases. Testing in large animal models (LAMs) is a crucial step in translating retinal ATMPs into clinical practice. However, challenges including budgetary and infrastructure constraints can hinder LAM research design and execution. Here, to facilitate the comparison of the various LAMs in pluripotent retinal cell therapy research, we aimed to systematically evaluate the species distribution, reported scientific utility, and methodology of a range of LAMs.MethodsA systematic search using the words retina, stem cell, transplantation, large animal, pig, rabbit, dog, and nonhuman primate was conducted in the PubMed, Embase, Science Direct and GoogleScholar databases in February 2023.ResultsWe included 22 studies involving pluripotent stem cells (induced pluripotent stem cells or human embryonic stem cells) in LAMs, including non-human primates (NHP), pigs, dogs, and rabbits. Nearly half of the studies utilized wild-type animal models. In other studies, retinal degeneration features were simulated via laser, chemical, or genetic insult. Transplants were delivered subretinally, either as cell suspensions or pre-formed monolayers (with or without biodegradable scaffolding). The transplanted cells dose per eye varied widely (40,000 – 4,000,000 per dose). Cells were delivered via vitrectomy surgery in 15 studies and by an “ab externo” approach in one study. Structural outcomes were assessed using confocal scanning laser ophthalmoscopy imaging. Functional outcomes included multifocal electroretinogram and, in one case, a measure of visual acuity. Generally, cell suspension transplants exhibited low intraretinal incorporation, while monolayer transplants incorporated more efficiently. Immune responses posed challenges for allogeneic transplants, suggesting that autologous iPSC-derived transplants may be required to decrease the likelihood of rejection.ConclusionThe use of appropriate LAMs helps to advance the development of retinal ATMPs. The anatomical similarity of LAM and human eyes allows the implementation of clinically-relevant surgical techniques. While the FDA Modernization Act 2.0 has provided a framework to consider alternative methods including tissue-on-a-chip and human cell culture models for pharmacologic studies, LAM testing remains useful for cell and tissue replacement studies to inform the development of clinical trial protocols.