bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insulin resistance, kidney outcomes and effects of the endothelin receptor antagonist atrasentan in patients with type 2 diabetes and chronic kidney disease
Authors: Smeijer J. David , Kohan Donald E. , Rossing Peter , Correa-Rotter Ricardo , Liew Adrian , Tang Sydney C.W. , de Zeeuw Dick , Gansevoort Ron T. , Ju Wenjun , Lambers Heerspink Hiddo J. 
Published: September 2023

Abstract
Background
Insulin resistance (IR) is a pathophysiologic hallmark of type 2 diabetes and associated with the presence of chronic kidney disease (CKD). Experimental studies suggest that endothelin-1 increases IR. We assessed the association between IR and cardio-renal outcomes and the effect of the selective endothelin receptor antagonist atrasentan on IR in patients with type 2 diabetes and CKD.

Methods
We used data from the RADAR and SONAR trials that recruited participants with type 2 diabetes and CKD [eGFR 25–75 mL/min/1.73 m², urine albumin-to-creatinine ratio of 300–5000 mg/g]. IR was calculated using the homeostatic model assessment (HOMA-IR). The association between HOMA-IR and the pre-specified cardio-renal outcomes was assessed using multivariable Cox proportional hazards regression, and effects of atrasentan on HOMA-IR by a linear mixed effect model.

Results
In the SONAR trial, each log-unit increase in HOMA-IR was associated with an increased risk of the composite cardio-renal outcome [hazard ratio 1.32 (95%CI 1.09,1.60; p = 0.004)], kidney outcome [hazard ratio 1.30 (95%CI 1.00,1.68; p-value = 0.048)], and the kidney or all-cause mortality outcome [hazard ratio 1.25 (95%CI 1.01,1.55; p-value = 0.037)]. After 12 weeks treatment in the RADAR trial (N = 123), atrasentan 0.75 mg/day and 1.25 mg/day compared to placebo reduced HOMA-IR by 19.1 (95%CI -17.4, 44.3) and 26.7% (95%CI -6.4, 49.5), respectively. In the SONAR trial (N = 1914), atrasentan 0.75 mg/day compared to placebo reduced HOMA-IR by 9.6% (95%CI 0.6, 17.9).

Conclusions
More severe IR is associated with increased risk of cardio-renal outcomes. The endothelin receptor antagonist atrasentan reduced IR.

Trial registration
RADAR trial (Reducing Residual Albuminuria in Subjects With Diabetes and Nephropathy With AtRasentan): NCT01356849.
SONAR trial (The Study Of Diabetic Nephropathy With AtRasentan) NCT01858532.
ARF6 promotes hepatocellular carcinoma proliferation through activating STAT3 signaling
Authors: Hu Yabing , Huang Yongchu , Xie Xiaohang , Li Longshan , Zhang Yong , Zhang Xiaochao 
Published: September 2023

Abstract
Background
Hepatocellular Carcinoma (HCC) possesses the high mortality in cancers worldwide. Nevertheless, the concrete mechanism underlying HCC proliferation remains obscure. In this study, we show that high expression of ARF6 is associated with a poor clinical prognosis, which could boost the proliferation of HCC.

Methods
Immunohistochemistry and western blotting were used to detect the expression level of ARF6 in HCC tissues. We analyzed the clinical significance of ARF6 in primary HCC patients. We estimated the effect of ARF6 on tumor proliferation with in vitro CCK8, colony formation assay, and in vivo nude mouse xenograft models. Immunofluorescence was conducted to investigate the ARF6 localization. western blotting was used to detect the cell cycle-related proteins with. Additionally, we examined the correlation between ARF6 and STAT3 signaling in HCC with western blotting, immunohistochemistry and xenograft assay.

Results
ARF6 was upregulated in HCC tissues compared to adjacent normal liver tissues. The increased expression of ARF6 correlated with poor tumor differentiation, incomplete tumor encapsulation, advanced tumor TNM stage and poor prognosis. ARF6 obviously promoted HCC cell proliferation, colony formation, and cell cycle progression. In vivo nude mouse xenograft models showed that ARF6 enhanced tumor growth. Furthermore, ARF6 activated the STAT3 signaling and ARF6 expression was positively correlated with phosphorylated STAT3 level in HCC tissues. Furthermore, after intervening of STAT3, the effect of ARF6 on tumor-promoting was weakened, which demonstrated ARF6 functioned through STAT3 signaling in HCC.

Conclusions
Our results indicate that ARF6 promotes HCC proliferation through activating STAT3 signaling, suggesting that ARF6 may serve as potential prognostic and therapeutic targets for HCC patients.
Assessing the impact of the “malaria supporters project” intervention to malaria control in the Brazilian Amazon: an interrupted time-series analysis
Authors: Garcia Klauss Kleydmann Sabino , Soremekun Seyi , Bottomley Christian , Abrahão Amanda Amaral , de Miranda Cristiano Barreto , Drakeley Chris , Ramalho Walter Massa , Siqueira André M. 
Published: September 2023

Abstract
Background
In 2021, Brazil was responsible for more than 25% of malaria cases in the Americas. Although the country has shown a reduction of cases in the last decades, in 2021 it reported over 139,000 malaria cases. One major malaria control strategy implemented in Brazil is the “Malaria Supporters Project”, which has been active since 2012 and is directed to municipalities responsible for most Brazil’s cases. The objective of this study is to analyse the intervention effect on the selected municipalities.

Methods
An ecological time-series analysis was conducted to assess the “Malaria Supporters Project” effect. The study used data on Annual Parasitic Incidence (API) spanning the period from 2003 to 2020 across 48 intervention municipalities and 88 control municipalities. To evaluate the intervention effect a Prais–Winsten segmented regression model was fitted to the difference in malaria Annual Parasitic Incidence (API) between control and intervention areas.

Results
The intervention group registered 1,104,430 cases between 2012 and 2020, a 50.6% reduction compared to total cases between 2003 and 2011. In 2020 there were 95,621 cases, 50.4% fewer than in 2011. The number of high-risk municipalities (API > 50 cases/1000) reduced from 31 to 2011 to 17 in 2020. The segmented regression showed a significant 42.0 cases/1000 residents annual decrease in API compared to control group.

Conclusions
The intervention is not a silver bullet to control malaria, but it has reduced API in locations with high malaria endemicity. Furthermore, the model has the potential to be replicated in other countries with similar epidemiological scenarios.
Predictors of persisting pain in children with Juvenile Idiopathic Arthritis: a case control study nested in the ReACCh-Out cohort
Authors: McGrath Tara , Guzman Jaime , Tucker Lori , Shiff Natalie J. , Yaskina Maryna , Tupper Susan , Rumsey Dax G. ,   for the Research in Arthritis in Canadian Children Emphasizing Outcomes (ReACCh-Out) Investigators, Benseler Susanne , Berard Roberta , Boire Gilles , Bolaria Roxana , Cabral David , Cameron Bonnie , Campillo Sarah , Chan Mercedes , Chédeville Gaëlle , Chetaille Anne-Laure , Dancey Paul , Dorval Jean , Duffy Ciarán , Ellsworth Janet , Feldman Brian , Feldman Debbie , Gross Katherine , Haddad Ellie , Houghton Kristin , Huber Adam , Johnson Nicole , Jurencak Roman , Lang Bianca , Larché Maggie , Laxer Ronald , LeBlanc Claire , Levy Deborah , Luca Nadia , Miettunen Paivi , Morishita Kimberly , Oen Kiem , Petty Ross , Ramsey Suzanne , Rosenberg Alan , Roth Johannes , Saint-Cyr Claire , Schmeling Heinrike , Schneider Rayfel , Silverman Earl , Spiegel Lynn , Stringer Elizabeth , Scuccimarri Rosie , Tse Shirley , Turvey Stuart , Duffy Karen Watanabe , Yeung Rae 
Published: September 2023

Abstract
Background
To identify baseline predictors of persisting pain in children with Juvenile Idiopathic Arthritis (JIA), relative to patients with JIA who had similar baseline levels of pain but in whom the pain did not persist.

Methods
We used data from the Research in Arthritis in Canadian Children emphasizing Outcomes (ReACCh-Out) inception cohort to compare cases of ‘moderate persisting pain’ with controls of ‘moderate decreasing pain’. Moderate pain was defined as a Visual Analogue Scale (VAS) for pain measurement score of > 3.5 cm. Follow-up was minimum 3 years. Univariate and Multivariate logistic regression models ascertained baseline predictors of persisting pain.

Results
A total of 31 cases and 118 controls were included. Mean pain scores at baseline were 6.4 (SD 1.6) for cases and 5.9 (1.5) for controls. A greater proportion of cases than controls were females (77.4% vs 65.0%) with rheumatoid factor positive polyarthritis (12.9% vs 4.2%) or undifferentiated JIA (22.6% vs 8.5%). Oligoarthritis was less frequent in cases than controls (9.7% vs 33%). At baseline, cases had more active joints (mean of 11.4 vs 7.7) and more sites of enthesitis (4.6 vs 0.7) than controls. In the final multivariate regression model, enthesitis count at baseline (OR 1.40, CI 95% 1.19–1.76), female sex (4.14, 1.33–16.83), and the overall Quality of My Life (QoML) baseline score (0.82, 0.69–0.98) predicted development of persisting pain.

Conclusions
Among newly diagnosed children with JIA with moderate pain, female sex, lower overall quality of life, and higher enthesitis counts at baseline predicted development of persisting pain. If our findings are confirmed, patients with these characteristics may be candidates for interventions to prevent development of chronic pain.
Case report: a case of primary intracranial parasagittal meningeal angiosarcoma
Authors: Cao Jun , Fang Jincheng , Jiang Xiaochun , Di Guangfu , Shen Jun 
Published: September 2023

Abstract
Background
Angiosarcoma, also known as malignant hemangioendothelioma, is a rare vasogenic malignant tumor, commonly found on the skin of the head and neck, rarely occurring in the intracranial region. As for intracranial meningeal angiosarcoma, only 8 cases have been reported before and there is no clinical study with large sample size. We report here a case of parasagittal meningeal angiosarcoma.

Case description
A 48-year-old Chinese male patient was admitted to our hospital due to headache accompanied by bilateral lower limb weakness. On admission, CT showed a high-density mass on both sides of the sagittal sinus at the top of the frontal lobe. We performed exploratory surgical resection of the tumor. During the operation, it was found that the tumor originated from the dura mater and extensively invaded the surrounding brain tissue and skull, and the surrounding hemosiderin deposition was observed. Postoperative pathology suggested angiosarcoma.

Conclusions
Intracranial meningeal angiosarcoma is difficult to accurately diagnose before surgery, so radiologists and neurosurgeons need to strengthen their understanding of this disease. The presence of extensive superficial hemosiderin deposition during operation may contribute to the diagnosis, and immunohistochemistry is very important for the diagnosis of intracranial angiosarcoma.
Analgesic efficacy of collagen peptide in knee osteoarthritis: a meta-analysis of randomized controlled trials
Authors: Lin Chun-Ru , Tsai Sung Huang Laurent , Huang Ko-Yen , Tsai Po-An , Chou Hsuan , Chang Shu-Hao 
Published: September 2023

Abstract
Background
The management of knee osteoarthritis involves various treatment strategies. It is important to explore alternative therapies that are both safe and effective. Collagen peptides have emerged as a potential intervention for knee osteoarthritis. This study aims to evaluate the analgesic effects and safety of collagen peptide in patients diagnosed with knee osteoarthritis.

Methods
We conducted a systematic literature search following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Multiple databases including PubMed, Scopus, EMBASE, Web of Science, Cochrane, and ClinicalTrials.gov were searched for randomized controlled trials (RCTs) published up to 27 May 2023 that focused on the analgesic outcomes and adverse events associated with collagen peptides or hydrolyzed collagen in patients with osteoarthritis. We assessed the quality of the included studies and the strength of evidence using the Cochrane ROB 2.0 tool and Grading of Recommendations, Assessment, Development, and Evaluations.

Results
Four trials involving 507 patients with knee osteoarthritis were included and analyzed using the random-effects model. All these trials were considered to have a high risk of bias. Our results revealed a significant difference in pain relief between the collagen peptide group and the placebo group in patients with knee osteoarthritis (standardized mean difference: − 0.58; 95% CI − 0.98, − 0.18, p = 0.004; I2: 68%; quality of evidence: moderate). However, there was no significant difference in the risk of adverse events between collagen peptide and placebo (odds ratio: 1.66; 95% CI 0.99, 2.78, p = 0.05; I2: 0%; quality of evidence: very low).

Conclusions
Our findings demonstrate significant pain relief in patients with knee osteoarthritis who received collagen peptides compared to those who received placebo. In addition, the risk of adverse events did not differ significantly between the collagen peptide group and the placebo group. However, due to potential biases and limitations, well-designed randomized controlled trials are needed to validate and confirm these findings.
Experimental study of a 3D-printing technique combined with biphasic calcium phosphates to treat osteonecrosis of the femoral head in a canine model
Authors: Chen Zhian , Feng Fanzhe , Su Xixiong , Xu Yongqing , Zhang Ying , Tan Hongbo 
Published: September 2023

Abstract
Objective
This study was aimed to use a digital design of 3D-printing technology to create a surgical navigation template. At the same time, biphasic calcium phosphate (BCP) was applied to treat osteonecrosis of the femoral head (ONFH) in animal models, based on accurate positioning of necrotic lesions in the navigation templates and observation of its therapeutic effect.

Methods
Fifteen healthy adult male and female beagle dogs weighing 20 + 2 kg were randomly divided into three groups (n = 5) after establishing a model of ONFH using the liquid nitrogen freezing method. Each model underwent necrotic lesion creation and BPC implantations on one side of the femoral head and only necrotic lesion creation on the other side of the femoral head. Each group underwent CT examination, gross observation, histological examination and immunohistochemical staining at 6 weeks, 12 weeks and 18 weeks postoperatively.

Results
At weeks 6, 12, and 18, CT and gross examination showed that the necrotic area in the experimental group was basically intact and had been completely raised by BCP material. In the control group, there were signs of bone repair in the femoral head, but there were still large bone defects and cavities. At week 18, extensive collapse of the cartilage surface was observed. Through histological examination, in the experimental group at 12 and 18 weeks, a large number of new and reconstructed bone trabeculae containing a large amount of collagen fibres were observed (P < 0.05), while in the control group, there was extensive necrosis of the bone trabeculae without cellular structural areas. Immunohistochemical examination observation: A large number of CD31-positive cells were observed in the experimental group at 6 weeks, gradually decreasing at 12 and 18 weeks (P < 0.05), while a small number of CD31-positive cells were observed in the control group at 18 weeks.

Conclusion
The 3D-printed navigation template can accurately locate ONFH lesions. Implantation of BCP material can effectively play a supporting role, prevent the collapse of the loading surface, and induce bone formation and angiogenesis to some extent.
Cytogenetic profile of 1791 adult acute myeloid leukemia in India
Authors: Srivastava Vivi M. , Nair Sukesh Chandran , Sappani Marimuthu , Manipadam Marie-Therese , Kulkarni Uday P. , Devasia Anup J. , Fouzia N. A. , Korula Anu , Lakshmi Kavitha M. , Abraham Aby , Srivastava Alok 
Published: September 2023

Abstract
Background
Cytogenetic analysis continues to have an important role in the management of acute myeloid leukemia (AML) because it is essential for prognostication. It is also necessary to diagnose specific categories of AML and to determine the most effective form of treatment. Reports from South Asia are few because the availability of cytogenetic services is relatively limited.

Methods
We performed a retrospective analysis of the cytogenetic findings in adults with AML seen consecutively in a single centre in India. The results were categorised according to the 2022 World Health Organisation (WHO), International Consensus Classification (ICC) and European LeukemiaNet (ELN) classifications.

Results
There were 1791 patients aged 18–85 years (median age 42, 1086 males). Normal karyotypes were seen in 646 (36%) patients. The 1145 (64%) abnormal karyotypes comprised 585 (32.7%) with recurrent genetic abnormalities (RGA), 403 (22.5%) with myelodysplasia-related cytogenetic abnormalities (MRC), and 157 (8.8%) with other abnormalities. There were 567 (31.7%) patients with solitary abnormalities and 299 (16.7%) with two abnormalities. Among the 279 (15.6%) patients with ≥ 3 abnormalities, 200 (11.2%) had complex karyotypes (CK) as per the WHO/ICC and 184 (10.3%), as per the ELN definition. There were 158 (8.8%) monosomal karyotypes (MK). Patients with normal karyotypes had a higher median age (45 years) than those with abnormal karyotypes (40 years, p < 0.001), and those with ≥ 3 abnormalities (43 years), than those with fewer abnormalities (39 years, p = 0.005). Patients with CK (WHO/ICC) and monosomal karyotypes had a median age of 48 years. Those with RGA had a lower median age (35 years, p < 0.001) than MRC (46 years) or other abnormalities (44 years). The t(15;17) was the most common abnormality (16.7%),followed by trisomy 8 (11.6%), monosomy 7/del 7q (9.3%), t(8;21) (7.2%), monosomy 5/del 5q (6.7%) and monosomy 17/del 17p (5.2%).

Conclusion
Our findings confirm the lower age profile of AML in India and show similarities and differences with respect to the frequencies of individual abnormalities compared to the literature. The frequencies of the t(15;17), trisomy 8 and the high-risk abnormalities monosomy 7 and monosomy 5/del 5q were higher, and that of the inv(16), lower than in most reports.
Financial characteristics and security of podiatry work in Victoria: the PAIGE cross sectional study of Australian podiatrists
Authors: Couch Anna G. , Haines Terry , O'Sullivan Belinda , Menz Hylton B. , Williams Cylie M. 
Published: September 2023

AbstractBackgroundPodiatrists' earnings have an important influence on workforce dynamics. This includes the profession's ability to attract and retain workers so the population's healthcare needs can be met. This study aimed to describe financial characteristics of podiatry work and factors relating to a sense of financial security.MethodsThis was a cross sectional study using data from Victorian podiatrists who participated in Wave 1 of the Podiatrists in Australia: Investigating Graduate Employment (PAIGE) survey. Demographic and financial characteristics were described. The outcome measure, financial security, was collected through a self‐reported belief based on current financial situation and prospects, respondents' perception of having enough income to live on when they retire. Univariate logistic regression was used to determine associations with rural or metropolitan practice locations. Multiple ordered logistic regression was performed to explore associations between factors relating to financial security and retirement prospects.ResultsThere were 286 Victorian podiatrist (18% of n = 1,585 Victorian podiatrists) respondents. Of these, 206 (72% of n = 286) identified as female, 169 (59% of 286) worked in the private sector and the mean (SD) age was 33.4 (9.5) years. The mean (SD) annual gross income was $79,194 ($45,651) AUD, and 243 (87% of 279) made regular superannuation contributions. Multiple ordered logistic regression analyses identified factors associated with podiatrists' perception of having adequate retirement income. These included being an owner/partner of their main workplace (adj OR = 2.70, 95% CI = 1.49–4.76), growing up in a rural location (adj OR = 2.27, 95% CI = 1.38–3.70), perceiving a moderate overall health rating (adj OR = 2.03 95% CI = 1.51–2.75), not having financial debt related to education and training (adj OR = 2.02, 95% CI = 1.24–3.32) and regular contributions to a superannuation scheme (adj OR = 4.76, 95% CI = 2.27–10.00).ConclusionThis is the first known study to explore podiatrists' earnings and perceptions regarding financial security. Findings suggest modifiable ways to improve financial security of podiatrists including support and education about personal and business finances including debt management, understanding the importance of contributions to superannuation when self‐employed, and developing skills and supports for podiatrists to run their own businesses. This research is exploratory and is relevant for understanding the impact that income and financial security have on workforce dynamics.
Reducing antimicrobial overuse through targeted therapy for patients with community-acquired pneumonia: a study protocol for a cluster-randomized factorial controlled trial (CARE-CAP)
Authors: Deshpande Abhishek , Walker Ramara , Schulte Rebecca , Pallotta Andrea M. , Tereshchenko Larisa G. , Hu Bo , Kadri Sameer S. , Klompas Michael , Rothberg Michael B. 
Published: September 2023

Abstract
Background
Community-acquired pneumonia (CAP) is a significant public health concern and a leading cause of hospitalization and inpatient antimicrobial use in the USA. However, determining the etiologic pathogen is challenging because traditional culture methods are slow and insensitive, leading to prolonged empiric therapy with extended-spectrum antibiotics (ESA) that contributes to increased hospital length of stay, and antimicrobial resistance. Two potential ways to reduce the exposure to ESA are (a) rapid diagnostic assays that can provide accurate results within hours, obviating the need for empiric therapy, and (b) de-escalation following negative bacterial cultures in clinically stable patients.

Methods
We will conduct a large pragmatic 2 × 2 factorial cluster-randomized controlled trial across 12 hospitals in the Cleveland Clinic Health System that will test these two approaches to reducing the use of ESA in adult patients (age ≥ 18 years) with CAP. We will enroll over 12,000 patients and evaluate the independent and combined effects of routine use of rapid diagnostic testing at admission and pharmacist-led de-escalation after 48 h for clinically stable patients with negative cultures vs usual care. We hypothesize that both approaches will reduce days on ESA. Our primary outcome is the duration of exposure to ESA therapy, a key driver of antimicrobial resistance. Secondary outcomes include detection of respiratory viruses, treatment with anti-viral medications, positive pneumococcal urinary antigen test, de-escalation by 72 h from admission, re-escalation to ESA after de-escalation, total duration of any antibiotic, 14-day in-hospital mortality, intensive care unit transfer after admission, healthcare-associated C. difficile infection, acute kidney injury, total inpatient cost, and hospital length-of-stay.

Discussion
Our study aims to determine whether identifying an etiological agent early and pharmacist-led de-escalation (calling attention to negative cultures) can safely reduce the use of ESA in patients with CAP. If successful, our findings should lead to better antimicrobial stewardship, as well as improved patient outcomes and reduced healthcare costs. Our findings may also inform clinical guidelines on the optimal management of CAP.

Trial registration
ClinicalTrials.gov NCT05568654. Registered on October 4, 2022.