bluuebunny/crossref_metadata_2025_split huggingface dataset:
The potential role of veterinary technicians in promoting antimicrobial stewardship
Authors: Redding Laurel E. , Reilly Katherine , Radtke Bridget , Bartholomew Stacy , Cole Stephen D. 
Published: September 2023

Abstract
Background
A core principle of antimicrobial stewardship (AMS) in veterinary settings is the need for engagement of all stakeholders; however, no studies have addressed the role of veterinary technicians in AMS specifically. The objective of this study was to qualitatively assess knowledge, opinions, and practices related to AMS among technicians. Semi-structured interviews were conducted with 33 veterinary technicians with varied backgrounds, experience and roles. Interviews centered on participants work experience and interactions with their employer, perceptions of antimicrobial resistance and overuse in veterinary medicine, observed application of AMS principles, opinions on potential opportunities for technicians to contribute to AMS and concomitant potential barriers to these opportunities. Transcripts of interviews were coded thematically by two authors, then organized into a hierarchical framework, and the characterization of codes was compared across different categories of respondents.

Results
Most veterinary technicians were knowledgeable about antimicrobial drugs but could not provide a complete definition of antimicrobial resistance or AMS. Most veterinary technicians could identify examples of antimicrobial misuse. Participants identified areas of client education and discussion with veterinarians as potential areas to contribute to AMS. Barriers identified included hierarchical structures of veterinary practices and time-constraints. Most participants expressed a personal interest in participating in AMS.

Conclusions
There is a possible appetite among some veterinary technicians to participate in AMS and they already play applicable roles in practices. Barriers such as educational needs, hierarchical structures of veterinary practices and time constraints will need to be addressed if technicians are included in AMS efforts.
The role of oxidative stress in diabetes mellitus-induced vascular endothelial dysfunction
Authors: An Ying , Xu Bu-tuo , Wan Sheng-rong , Ma Xiu-mei , Long Yang , Xu Yong , Jiang Zong-zhe 
Published: September 2023

AbstractDiabetes mellitus is a metabolic disease characterized by long-term hyperglycaemia, which leads to microangiopathy and macroangiopathy and ultimately increases the mortality of diabetic patients. Endothelial dysfunction, which has been recognized as a key factor in the pathogenesis of diabetic microangiopathy and macroangiopathy, is characterized by a reduction in NO bioavailability. Oxidative stress, which is the main pathogenic factor in diabetes, is one of the major triggers of endothelial dysfunction through the reduction in NO. In this review, we summarize the four sources of ROS in the diabetic vasculature and the underlying molecular mechanisms by which the pathogenic factors hyperglycaemia, hyperlipidaemia, adipokines and insulin resistance induce oxidative stress in endothelial cells in the context of diabetes. In addition, we discuss oxidative stress-targeted interventions, including hypoglycaemic drugs, antioxidants and lifestyle interventions, and their effects on diabetes-induced endothelial dysfunction. In summary, our review provides comprehensive insight into the roles of oxidative stress in diabetes-induced endothelial dysfunction.
Left ventricular remodeling response to SGLT2 inhibitors in heart failure: an updated meta-analysis of randomized controlled studies
Authors: Carluccio Erberto , Biagioli Paolo , Reboldi Gianpaolo , Mengoni Anna , Lauciello Rosanna , Zuchi Cinzia , D’Addario Sandra , Bardelli Giuliana , Ambrosio Giuseppe 
Published: September 2023

Abstract
Background
Randomized controlled trials (RCTs) reported contrasting results about reverse left ventricular remodeling (LVR) after sodium-glucose co-transporter-2 inhibitors (SGLT2i) therapy in patients with heart failure (HF).

Methods and results
We performed a metanalysis of RCTs of SGLT2i administration in HF outpatients published until June 2022 searching four electronic databases. The protocol has been published in PROSPERO. Primary LVR outcome was change in absolute LV end-diastolic (LVEDV) and end-systolic volume (LVESV) from baseline to study endpoint. Secondary outcomes included changes in LVEDV and LVESV indexed to body surface area, LV Mass index (LVMi), LV ejection fraction (LVEF), and N-terminal pro-B-type natriuretic peptide (NTproBNP). Mean differences (MDs) with 95% CIs were pooled. A total of 9 RCTs (1385 patients) were analyzed. All of them reported data on LVEF. Six trials reported data on LVESV and LVEDV (n = 951); LVMi was available in 640. SGLT2i treatment significantly reduced LVEDV [MD= -10.59 ml (-17.27; -3.91), P = 0.0019], LVESV [MD= -8.80 ml (-16.91; -0.694), P = 0.0334], and LVMI [MD= -5.34 gr/m2 (-9.76; -0.922), P = 0.0178], while LVEF significantly increased [MD = + 1.98% (0.67; 0.306), P = 0.0031]. By subgroup analysis, the beneficial effects of SGLT2i on LVEF did not differ by imaging method used, time to follow-up re-evaluation, or HF phenotype. Reduction in LV volumes tended to be greater in HF with reduced EF (HFrEF) than in those with preserved EF (HFpEF), while the opposite was observed for LVMi.

Conclusions
Treatment with SGLT2i significantly reversed cardiac volumes, improving LV systolic function and LV mass, particularly in HFrEF patients.
Association between the insulin resistance and all-cause mortality in patients with moderate and severe aortic stenosis: a retrospective cohort study
Authors: Huang Rihua , Xu Xinghao , Xu Chaoguang , Zhang Shaozhao , Xiong Zhenyu , Liu Menghui , Huang Yiquan , Wen Han , Guo Yue , Liao Xinxue , Zhuang Xiaodong 
Published: September 2023

Abstract
Background
The triglyceride-glucose (TyG) index is a reliable surrogate marker of insulin resistance (IR). However, whether the TyG index has prognostic value in patients with moderate to severe aortic stenosis (AS) remains unclear.

Methods
This study enrolled 317 patients with moderate to severe AS at the First Affiliated Hospital of Sun Yat-Sen University. The patients were grouped according to the cut-off value of the TyG index. Cox regression with Firth’s penalized maximum likelihood method and restricted cubic splines regression were conducted to assess the association between the TyG index and all-cause mortality. The added value of the TyG index included in the traditional risk factors model for outcome prediction was also analyzed.

Results
Among 317 patients (mean age 67.70 years, 62.8% male), there was 84 all-cause mortality during a median 38.07 months follow-up. After fully adjusting for confounders, a per-unit increase in the TyG index was associated with a 62% higher all-cause mortality risk (HR 1.622, 95% CI 1.086–2.416, p = 0.018). The restricted cubic splines regression model revealed a linear association between the TyG index and the risk of all-cause mortality (p for nonlinearity = 0.632). The addition of the TyG index in the basic risk model has an incremental effect on the prediction of mortality [C-statistic change from 0.755 to 0.768; continuous net reclassification improvement (95% CI): 0.299 (0.051–0.546), p = 0.017; integrated discrimination improvement: 0.017 (0.001–0.033), p = 0.044].

Conclusions
Higher IR assessed by the TyG index was associated with a higher risk of all-cause mortality in patients with moderate and severe AS.
The regulation of simulated artificial oro-gastrointestinal transit stress on the adhesion of Lactobacillus plantarum S7
Authors: Chen Dawei , Chen Chunmeng , Guo Congcong , Zhang Hui , Liang Yating , Cheng Yue , Qu Hengxian , Wa Yunchao , Zhang Chenchen , Guan Chengran , Qian Jianya , Gu Ruixia 
Published: September 2023

Abstract
Background
Oro-gastrointestinal stress in the digestive tract is the main stress to which orally administered probiotics are exposed. The regulation of oro-gastrointestinal transit (OGT) stress on the adhesion and survival of probiotics under continuous exposure to simulated salivary-gastric juice-intestinal juice was researched in this study.

Results
Lactobacillus plantarum S7 had a higher survival rate after exposure to simulated OGT1 (containing 0.15% bile salt) stress and OGT2 (containing 0.30% bile salt) stress. The adhesion ability of L. plantarum S7 was significantly increased by OGT1 stress (P < 0.05) but was not changed significantly by OGT2 stress (P > 0.05), and this trend was also observed in terms of the thickness of the surface material of L. plantarum S7 cells. The expression of surface proteins of L. plantarum S7, such as the 30 S ribosomal proteins, mucus-binding protein and S-layer protein, was significantly downregulated by OGT stress (P < 0.05); meanwhile, the expression of moonlight proteins, such as glyceraldehyde-3-phosphate dehydrogenase (GAPDH), phosphoglycorate kinase (PGK), beta-phosphoglucomutase (PGM1), GroEL and glucose-6-phosphate isomerase (PGI), was significantly upregulated (P < 0.05). However, the upregulation of GAPDH, PGK, PGM1 and PGI mediated by OGT1 stress was greater than those mediated by OGT2 stress. The quorum sensing pathway of L. plantarum S7 was changed significantly by OGT stress compared with no OGT stress cells (P < 0.05), and the expression of Luxs in the pathway was significantly upregulated by OGT1 stress (P < 0.05). The ABC transportation pathway was significantly altered by OGT1 stress (P < 0.05), of which the expression of the peptide ABC transporter substrate-binding protein and energy-coupling factor transporter ATP-binding protein EcfA was significantly upregulated by OGT stress (P < 0.05). The glycolide metabolism pathway was significantly altered by OGT1 stress compared with that in response to OGT2 stress (P < 0.05).

Conclusion
L. plantarum S7 had a strong ability to resist OGT stress, which was regulated by the proteins and pathways related to OGT stress. The adhesion ability of L. plantarum S7 was enhanced after continuous exposure to OGT1 stress, making it a potential probiotic with a promising future for application.
Progranulin promoted the proliferation, metastasis, and suppressed apoptosis via JAK2-STAT3/4 signaling pathway in papillary thyroid carcinoma
Authors: Dong Yanxu , Tan Hao , Wang Lidong , Liu Zhen 
Published: September 2023

Abstract
Background
Progranulin (PGRN), a glycoprotein secreted by a wide range of epithelial cells and plays an important role in inflammatory mechanisms and tumor progression. In this study, the expression, and functions of PGRN in papillary thyroid carcinoma (PTC) was examined to explore the potential pathogenesis of PTC.

Methods
Western blotting and qRT-PCR were used to detect the relationship between PGRN expression and clinicopathological characteristics of patients with PTC. PTC cell lines with PGRN overexpression and with PGRN knockdown were established to explore their effects on the biological behavior. Western blotting was used to detect the changes of relevant molecules and JAK2-STAT3/4 signaling pathway. Moreover, rescue experiments validated the involvement of the JAK2-STAT3/4 signaling pathway. And statistical analyses were analyzed using SPASS 21.0 and graph generation were performed using GraphPad Prism 8.0.

Results
PGRN was overexpressed in PTC tissue and increased by 75% at mRNA level and 161% at relative protein level in the patients with lymph node metastasis compared to without lymph node metastasis. Besides, PGRN regulated and promoted PTC cell proliferation, migration, invasion, and inhibited cell apoptosis. With PGRN overexpressed, relevant molecules including the expression of BCL2/BAX, BCL2/BAD, CyclinD1, MMP2, vimentin and N-cadherin were increased, the expression level of E-cadherin was decreased, and the phosphorylation of JAK2 and STAT3/4 were increased. JAK inhibitor (JSI-124) rescued these changes of PTC cells induced by overexpressed PGRN.

Conclusions
These findings revealed that PGRN promote the progression of PTC through the JAK2-STAT3/4 pathway, and PGRN could be served as a potential therapeutic target for PTC.
Icariin-Curcumol promotes docetaxel sensitivity in prostate cancer through modulation of the PI3K-Akt signaling pathway and the Warburg effect
Authors: Xu Wenjing , Ding Jin , Kuang Shida , Li Bonan , Sun Tiansong , Zhu Congxu , Liu Juan , Zhu Lemei , Li Yingqiu , Sheng Wen 
Published: September 2023

Abstract
Background
Docetaxel (DTX) resistance reduces therapeutic efficacy in prostate cancer (PCa). Accumulating reports support the role of phytochemicals in the reversal of DTX resistance. This study aimed to determine whether Epimedium brevicornu and Curcuma zedoaria extracts (ECe), specially icariin-curcumol, attenuates DTX resistance and explore their potential mechanisms.

Methods
Regulatory pathways were predicted between ECe active ingredients and PCa using network pharmacology. DTX-resistant cell LNCaP/R were established based on DTX-sensitive LNCaP, and xenograft models were further established. Active ingredients in ECe by HLPC-MS were identified. The binding of icariin and curcumol to the target was analyzed by molecular docking. Biochemical experiments were applied to determine the possible mechanisms by which Icariin-Curcumol regulates DTX sensitivity.

Results
Akt1 and the PI3K-Akt signaling pathway were predicted as the primary functional target between drug and PCa. ECe and DTX inhibited xenograft tumor growth, inflammation, cell viability and promoted apoptosis. Icariin and curcumol were detected in ECe, and icariin and curcumol docked with Akt1. ECe, Icariin-Curcumol and DTX downregulated AR, PSA, PI3K, Akt1, mTOR, and HIF-1ɑ. Moreover, ECe, Icariin-Curcumol and DTX increased glucose and PDH, decreased lactic acid, ATP and LDH, and downregulated c-Myc, hnRNPs, VEGF, PFK1, and PKM2. Notably, the anti-PCa effect of DTX was attenuated compared to ECe or Icariin-Curcumol in the LNCaP/R model. The combined effect of Icariin-Curcumol and DTX was superior to that of DTX.

Conclusion
Our data support that Icariin-Curcumol reverses DTX resistance by inhibiting the PI3K-Akt signaling and the Warburg effect, providing new ideas for improving therapeutic measures for PCa.
Lipoprotein(a) is a new prognostic factor in patients with psoriasis and coronary artery disease: a retrospective cohort study
Authors: Zhao Lin , Sun Lin , Zhang ZengLei , Yang KunQi , Li ZuoZhi , Wang Man , Zeng Yan , Zhou XianLiang , Yang WeiXian 
Published: September 2023

Abstract
Background
The prognostic value of lipoprotein (Lp) (a) in patients who have suffered from coronary artery disease (CAD) has not been fully studied, and the results are inconsistent. This study was conducted to evaluate whether increased Lp(a) concentrations cause differences in clinical adverse outcomes in patients with psoriasis who have already suffered from CAD.

Methods
This retrospective cohort study included consecutive patients with psoriasis and CAD between January 2017 and May 2022 in our hospital. The clinical records were collected, and comparisons were made between patients in the low Lp(a) and high Lp(a) groups. Cox proportional hazard analysis and log-rank tests were used to evaluate the association between variables.

Results
Among 295 patients, 148 patients were in the low Lp(a) group, and 147 were in the high Lp(a) group. These two groups did not differ significantly in age, gender or body mass index. Compared with the low Lp(a) group, the levels of platelet counts (P = 0.038) and high sensitivity C reactive protein (P = 0.012) were higher in the high Lp(a) group. Patients in the high Lp(a) group had higher total cholesterol levels (P = 0.029) and lower triglyceride levels (P = 0.037). Among the whole cohort, clinical adverse events were not correlated with Lp(a) concentrations after a median follow-up of 3 years. However, in the subgroup analysis, there were significant differences in all-cause death (log rank P = 0.036) and rehospitalization (log rank P = 0.037) between the two groups in patients with diabetes; a difference in rehospitalization (log rank P = 0.042) was also found between the two groups in men.

Conclusions
In patients with psoriasis and CAD, high levels of Lp(a) were related to a poor prognosis, especially in patients with diabetes and in men. These results will provide valuable information for the risk stratification of patients with psoriasis and CAD.
Piezoelectric enhanced sulfur doped graphdiyne nanozymes for synergistic ferroptosis–apoptosis anticancer therapy
Authors: Wang Jianxin , Chu Yinzhu , Zhao Zhiyu , Zhang Cong , Chen Qi , Ran Haitao , Cao Yang , Wu Changjun 
Published: September 2023

AbstractGraphdiyne has excellent potential due to its enzymatic properties. Metal-free sulfur-doped Graphdiyne (S-GDY) has piezoelectric characteristics, and ultrasonic excitation of S-GDY enhances peroxidase activity. It can turn hydrogen peroxide into toxic hydroxyl radicals and induce apoptosis in 4T1 cells. More importantly, the ultrasound (US) enhanced nanozyme induced 4T1 cell ferroptosis by promoting an imbalanced redox reaction due to glutathione depletion and glutathione peroxidase 4 inactivation. S-GDY exhibited enhanced nanozyme activity in vitro and in vivo that may directly trigger apoptosis-ferroptosis for effective tumor therapy. Altogether, this study was expected to provide new insights into the design of piezoelectric catalytic nanozyme and expand their application in the catalytic therapy of tumors.
Graphical Abstract
Availability of telehealth-based services at syringe services programs under the COVID-19 Public Health Emergency
Authors: Bartholomew Tyler S. , Tookes Hansel E. , Chueng Teresa A. , Bluthenthal Ricky N. , Wenger Lynn D. , Kral Alex H. , Lambdin Barrot H. 
Published: September 2023

Abstract
Introduction
The expanded capacity of syringe services programs (SSPs) in the USA to integrate telehealth services was largely related to flexibility of buprenorphine prescription in response to the COVID-19 pandemic. SSPs demonstrated the potential of using telehealth to reach participants with both medical and non-medical services. The present study examines the implementation of medical and non-medical telehealth-based health services in 2020 at SSPs in the USA and organizational characteristics associated with adopting specific telehealth services.

Methods
We administered a cross-sectional survey among all known SSPs operating in the USA as of 2021. The two primary study outcomes were (1) implementation of medical telehealth and (2) implementation of non-medical telehealth in 2020. Medical services included HIV counseling/care, hepatitis C virus (HCV) counseling/care, and buprenorphine. Non-medical services included wellbeing/check-ins, overdose prevention training, health navigation, harm reduction and psychological counseling. Bivariate and multivariable mixed effects logistic regression models were used to directly estimate the odds ratio associated with organizational characteristics on the implementation of telehealth-based health services.

Results
Thirty percent of programs (n = 290) reported implementing telehealth-based health services. In multivariable logistic regression models, community-based organization SSPs had higher odds of implementing medical (aOR = 4.69, 95% CI [1.96, 11.19]) and non-medical (aOR = 2.18, 95% CI [1.10, 4.31]) health services compared to public health department SSPs. SSPs that received governmental funding had higher odds of implementing medical services via telehealth (aOR = 2.45, 95% CI [1.35, 4.47]) compared to programs without governmental funding.

Conclusion
Community-based organization SSPs and those with government funding had the highest odds of telehealth implementation in response to the COVID-19 Public Health Emergency. Federal, state, and local governments must increase funding for low-barrier venues like SSPs to support telehealth implementation to serve the needs of people who use drugs.
TSLP in DRG neurons causes the development of neuropathic pain through T cells
Authors: Ino Yuka , Maruyama Motoyo , Shimizu Masumi , Morita Rimpei , Sakamoto Atsuhiro , Suzuki Hidenori , Sakai Atsushi 
Published: September 2023

Abstract
Background
Peripheral nerve injury to dorsal root ganglion (DRG) neurons develops intractable neuropathic pain via induction of neuroinflammation. However, neuropathic pain is rare in the early life of rodents. Here, we aimed to identify a novel therapeutic target for neuropathic pain in adults by comprehensively analyzing the difference of gene expression changes between infant and adult rats after nerve injury.

Methods
A neuropathic pain model was produced in neonatal and young adult rats by spared nerve injury. Nerve injury-induced gene expression changes in the dorsal root ganglion (DRG) were examined using RNA sequencing. Thymic stromal lymphopoietin (TSLP) and its siRNA were intrathecally injected. T cells were examined using immunofluorescence and were reduced by systemic administration of FTY720.

Results
Differences in changes in the transcriptome in injured DRG between infant and adult rats were most associated with immunological functions. Notably, TSLP was markedly upregulated in DRG neurons in adult rats, but not in infant rats. TSLP caused mechanical allodynia in adult rats, whereas TSLP knockdown suppressed the development of neuropathic pain. TSLP promoted the infiltration of T cells into the injured DRG and organized the expressions of multiple factors that regulate T cells. Accordingly, TSLP caused mechanical allodynia through T cells in the DRG.

Conclusion
This study demonstrated that TSLP is causally involved in the development of neuropathic pain through T cell recruitment.