bluuebunny/crossref_metadata_2025_split huggingface dataset:
Causal inference of sex hormone-binding globulin on venous thromboembolism: evidence from Mendelian randomisation
Authors: Wang Shuping , Wang Yongxiang , Bai Ming , Peng Yu , Zhou Dan , Lei Peng , Zhou Binpeng , Zhang Piyi , Zhang Zheng 
Published: October 2023

Abstract
Background
Previous cohort studies have shown that exogenous sex hormone use, such as testosterone replacement therapy and oestrogen-containing contraceptives, can increase the risk of venous thromboembolism (VTE). However, the relationship between endogenous sex hormone levels and VTE remains unclear. The goal of the present study was to explore the causal roles of endogenous sex hormones, including hormone-binding globulin (SHBG), bioactive testosterone (BT), and total testosterone (TT), in VTE and its two subgroups, deep vein thrombosis (DVT) and pulmonary embolism (PE).

Methods
We used a genome-wide association study of sex hormones as exposure data and Finnish VTE data as the outcome. Inverse variance weighting, MR-Egger, and weighted median were used for two-sample Mendelian randomisation (MR). Sensitivity analyses included MR-Egger, MR-PRESSO, Cochrane Q test, MR Steiger, leave-one-out analysis, and funnel plot, combined with multivariate MR and replicated MR analyses using larger VTE data from the global biobank meta-analysis initiative. Linkage disequilibrium score regression (LDSC) was used to determine genetic associations and estimate sample overlap.

Results
Our findings genetically predicted that an increase in serum SHBG levels by one standard deviation (SD) caused 25% higher odds for VTE (OR: 1.25, 95% CI: 1.01−1.55) and 58% higher odds for PE (OR: 1.58, 95% CI: 1.20−2.08). LDSC supported the genetic correlation between these two traits and replicated analyses confirm SHBG’s genetic effect on VTE in both sexes (OR: 1.46, 95% CI: 1.20−1.78) and in females (OR: 1.49, 95% CI: 1.17−1.91). In addition, an increase in serum TT levels by one SD caused 32% higher odds for VTE (OR: 1.32, 95% CI: 1.08−1.62) and 31% higher odds for DVT (OR: 1.31, 95% CI: 1.01−1.69); however, LDSC and replicated analyses did not find a genetic correlation between TT and VTE or its subtypes. No significant correlation was observed between BT and all three outcome traits.

Conclusion
Our study provides evidence that elevated serum SHBG levels, as predicted by genetics, increase VTE risk. However, the causal effect of testosterone levels on VTE requires further investigation.
Association between ventricular CSF biomarkers and outcome after shunt surgery in idiopathic normal pressure hydrocephalus
Authors: Grønning Rebecca , Jeppsson Anna , Hellström Per , Laurell Katarina , Farahmand Dan , Zetterberg Henrik , Blennow Kaj , Wikkelsø Carsten , Tullberg Mats 
Published: October 2023

Abstract
Introduction
The relationship between neurochemical changes and outcome after shunt surgery in idiopathic normal pressure hydrocephalus (iNPH), a treatable dementia and gait disorder, is unclear. We used baseline ventricular CSF to explore associations to outcome, after shunting, of biomarkers selected to reflect a range of pathophysiological processes.

Methods
In 119 consecutive patients with iNPH, the iNPH scale was used before and after shunt surgery to quantify outcome. Ventricular CSF was collected perioperatively and analyzed for biomarkers of astrogliosis, axonal, amyloid and tau pathology, and synaptic dysfunction: glial fibrillary acidic protein (GFAP), chitinase-3-like protein 1 (YKL40/CHI3L1), monocyte chemoattractant protein-1 (MCP-1) neurofilament light (NfL), amyloid beta 38 (Aβ38), Aβ40, Aβ42, amyloid beta 42/40 ratio (Aβ42/40), soluble amyloid precursor protein alfa (sAPPα), sAPPβ, total tau (T-tau), phosphorylated tau (P-tau), growth-associated protein 43 (GAP43), and neurogranin.

Results
The neurogranin concentration was higher in improved (68%) compared to unimproved patients (median 365 ng/L (IQR 186–544) vs 330 (205–456); p = 0.046). A linear regression model controlled for age, sex and vascular risk factors including neurogranin, T-tau, and GFAP, resulted in adjusted R2 = 0.06, p = 0.047. The Aβ42/40 ratio was bimodally distributed across all samples, as well as in the subgroups of improved and unimproved patients but did not contribute to outcome prediction. The preoperative MMSE score was lower within the low Aβ ratio group (median 25, IQR 23–28) compared to the high subgroup (26, 24–29) (p = 0.028). The T-Tau x Aβ40/42 ratio and P-tau x Aβ40/42 ratio did not contribute to shunt response prediction. The prevalence of vascular risk factors did not affect shunt response.

Discussion
A higher preoperative ventricular CSF level of neurogranin, which is a postsynaptic marker, may signal a favorable postoperative outcome. Concentrations of a panel of ventricular CSF biomarkers explained only 6% of the variability in outcome. Evidence of amyloid or tau pathology did not affect the outcome.
Patterns of use of wild food plants by Brazilian local communities: systematic review and meta-analysis
Authors: Gomes Lailson César Andrade , Medeiros Patrícia Muniz de , Prata Ana Paula do Nascimento 
Published: October 2023

Abstract
Background
This systematic review and meta-analysis sought to investigate the patterns of use of native wild food plants of Brazil (native and non-cultivated).

Methods
We searched ethnobiological works with food plants in Web of Science, Scielo, Scopus and PubMed using different sets of keywords. Initially, the studies were evaluated based on inclusion criteria (systematic data collection instruments, such as interviews; specification of methods for data collection; and the presence of a species list). The methodological quality of each study was evaluated to define the risk of bias. A total of 20 articles met all criteria and were included in the review.

Results
The results showed that there was a predominance of consumption of fruits, followed by leaves and seeds, which together represented 85.8% of the total parts. As for the meta-analysis, there was a predominance of use of plant parts classified as reproductive, non-persistent, non-destructive and parts of woody plants. There was no interference from the type of ecosystem (seasonally dry x moist). The results did not support the seasonality hypothesis.

Conclusions
The concentration of studies in the Northeast, Southeast and South regions of Brazil and in the Atlantic Forest and Caatinga biomes points to the need for a greater effort in terms of quantitative ethnobotanical research in other regions and biomes. The predominance of fruits and plant parts classified as reproductive, non-persistent and non-destructive points to the high potential for implementation of sustainable management strategies aimed at these plants in the country.
Evaluation of the serum tRNA-derived fragment tRF-5022B as a potential biomarker for the diagnosis of osteoarthritis
Authors: Ni Yingchen , Wu Anqi , Li Jianxin , Zhang Weidong , Wang Youhua 
Published: October 2023

AbstractOsteoarthritis (OA) is a degenerative disease. It is common in middle-aged and elderly people and is one of the main causes of disability. Currently, the etiology of OA is unclear, and no specific biomarkers for the diagnosis of OA have been identified. Therefore, finding a highly sensitive biomarker is essential for a proper diagnosis.TRNA-derived fragments (tRFs) and tRNA-derived stress-induced RNAs (tiRNAs) are newly discovered classes of noncoding RNAs. tRF has been proven in several studies to have significant associations with tumor diagnosis, making it a promising biomarker in cancer research. However, the diagnostic utility of tRF in OA patients and the correlation between OA progression and trf differential expression have yet to be elaborated. The purpose of this research was to identify tRFs with differential expression in OA to assess their potential as OA biomarkers. To determine the tRF-5022B expression level in this research, real-time fluorescence quantitative PCR has been employed. Agarose gel electrophoresis, Sanger sequencing, and other investigations have been employed for evaluating tRF-5022B's molecular properties. Receiver operating characteristic curve analysis has been utilized for assessing the diagnostic effectiveness of the tRF-5022B. The findings demonstrated that tRF-5022B expression was considerably lower in OA serum. The Kellgren–Lawrence grading scale was shown to correspond with serum expression levels. The ROC curve confirmed that tRF-5022B serum expression levels might differentiate OA cases from healthy individuals and RA patients. According to the aforementioned findings, tRF-5022B may be employed as a novel biomarker for OA diagnosis due to its excellent diagnostic value.
Autocrine regulation of tumor cell repopulation by Hsp70-HMGB1 alarmin complex
Authors: Sverchinsky Dmitry V. , Alhasan Bashar A. , Mikeladze Marina A. , Lazarev Vladimir F. , Kuznetcova Liubov S. , Morshneva Alisa V. , Nikotina Alina D. , Ziewanah Amr , Koludarova Lidia V. , Starkova Tatiana Y. , Margulis Boris A. , Guzhova Irina V. 
Published: October 2023

Abstract
Background
Cancer recurrence is regulated by a variety of factors, among which is the material of dying tumor cells; it is suggested that remaining after anti-cancer therapy tumor cells receive a signal from proteins called damage-associated molecular patterns (DAMPs), one of which is heat shock protein 70 (Hsp70).

Methods
Two models of tumor repopulation were employed, based on minimal population of cancer cells and application of conditioned medium (CM). To deplete the CMs of Hsp70 affinity chromatography on ATP-agarose and immunoprecipitation were used. Cell proliferation and the dynamics of cell growth were measured using MTT assay and xCELLigence technology; cell growth markers were estimated using qPCR and with the aid of ELISA for prostaglandin E detection. Immunoprecipitation followed by mass-spectrometry was employed to identify Hsp70-binding proteins and protein-protein interaction assays were developed to reveal the above protein complexes.

Results
It was found that CM of dying tumor cells contains tumor regrowth-initiating factors and the removal of one of them, Hsp70, caused a reduction in the relapse-activating capacity. The pull out of Hsp70 alone using ATP-agarose had no effect on repopulation, while the immunodepletion of Hsp70 dramatically reduced its repopulation activity. Using proteomic and immunochemical approaches, we showed that Hsp70 in conditioned medium binds and binds another abundant alarmin, the High Mobility Group B1 (HMGB1) protein; the complex is formed in tumor cells treated with anti-cancer drugs, persists in the cytosol and is further released from dying tumor cells. Recurrence-activating power of Hsp70-HMGB1 complex was proved by the enhanced expression of proliferation markers, Ki67, Aurka and MCM-10 as well as by increase of prostaglandin E production and autophagy activation. Accordingly, dissociating the complex with Hsp70 chaperone inhibitors significantly inhibited the pro-growth effects of the above complex, in both in vitro and in vivo tumor relapse models.

Conclusions
These data led us to suggest that the abundance of the Hsp70-HMGB1 complex in the extracellular matrix may serve as a novel marker of relapse state in cancer patients, while specific targeting of the complex may be promising in the treatment of cancers with a high risk of recurrence.
Antibody drug conjugates: hitting the mark in pancreatic cancer?
Authors: Wittwer Nicole L. , Brown Michael P. , Liapis Vasilios , Staudacher Alexander H. 
Published: October 2023

AbstractPancreatic cancer is one of the most common causes of cancer-related death, and the 5-year survival rate has only improved marginally over the last decade. Late detection of the disease means that in most cases the disease has advanced locally and/or metastasized, and curative surgery is not possible. Chemotherapy is still the first-line treatment however, this has only had a modest impact in improving survival, with associated toxicities. Therefore, there is an urgent need for targeted approaches to better treat pancreatic cancer, while minimizing treatment-induced side-effects. Antibody drug conjugates (ADCs) are one treatment option that could fill this gap. Here, a monoclonal antibody is used to deliver extremely potent drugs directly to the tumor site to improve on-target killing while reducing off-target toxicity. In this paper, we review the current literature for ADC targets that have been examined in vivo for treating pancreatic cancer, summarize current and on-going clinical trials using ADCs to treat pancreatic cancer and discuss potential strategies to improve their therapeutic window.
The inhibitory effect of Gremlin-2 on adipogenesis suppresses breast cancer cell growth and metastasis
Authors: Jung Jiwoo , Kim Na Hui , Kwon Minji , Park Jayeon , Lim Dayeon , Kim Youjin , Gil World , Cheong Ye Hwang , Park Sin-Aye 
Published: October 2023

Abstract
Background
Gremlin-1 (GREM1) and Gremlin-2 (GREM2) are bone morphogenetic protein antagonists that play important roles in organogenesis, tissue differentiation, and tissue homeostasis. Although GREM1 has been reported to be involved in promoting various cancers, little has been reported about effects of GREM2 on cancer. Recently, it has been reported that GREM2 can inhibit adipogenesis in adipose-derived stromal/stem cells. However, as an inhibitor of adipogenesis, the role of GREM2 in cancer progression is not well understood yet.

Methods
Pre-adipocyte 3T3-L1 cells overexpressing mock or Grem2 were established using a lentiviral transduction system and differentiated into adipocytes-mock and adipocytes-Grem2, respectively. To investigate the effect of adipocyte-Grem2 on breast cancer cells, we analyzed the proliferative and invasion abilities of spheroids using a 3D co-culture system of breast cancer cells and adipocytes or conditioned medium (CM) of adipocytes. An orthotopic breast cancer mouse model was used to examine the role of adipocytes-Grem2 in breast cancer progression.

Results
Grem2 overexpression suppressed adipogenesis of 3T3-L1 cells. Proliferative and invasion abilities of spheroids formed by co-culturing MTV/TM-011 breast cancer cells and adipocytes-Grem2 were significantly reduced compared to those of spheroids formed by co-culturing MTV/TM-011 cells and adipocytes-mock. Compared to adipocytes-mock, adipocytes-Grem2 showed decreased mRNA expression of several adipokines, notably IL-6. The concentration of IL-6 in the CM of these cells was also decreased. Proliferative and invasive abilities of breast cancer cells reduced by adipocytes-Grem2 were restored by IL-6 treatment. Expression levels of vimentin, slug, and twist1 in breast cancer cells were decreased by treatment with CM of adipocytes-Grem2 but increased by IL-6 treatment. In orthotopic breast cancer mouse model, mice injected with both MTV/TM-011 cells and adipocytes-Grem2 showed smaller primary tumors and lower lung metastasis than controls. However, IL-6 administration increased both the size of primary tumor and the number of metastatic lung lesions, which were reduced by adipocytes-Grem2.

Conclusions
Our study suggests that GREM2 overexpression in adipocytes can inhibit adipogenesis, reduce the expression and secretion of several adipokines, including IL-6, and ultimately inhibit breast cancer progression.
Cercopithifilaria spp. of dogs: little known but prevalent filarioids beneath the skin
Authors: Bezerra-Santos Marcos Antonio , Dantas-Torres Filipe , Ramos Rafael Antonio Nascimento , Brianti Emanuele , Otranto Domenico 
Published: October 2023

AbstractFilarioids of the genus Cercopithifilaria are little studied, yet widespread parasites, that are relatively unique in being one of the very few nematodes transmitted by hard ticks. These filarioids live in the subcutis while microfilariae are found in the dermis. Definitive hosts include domestic dogs as well as a wide range of vertebrates, such as ruminants, non-human primates, murids, marsupials, porcupines, viverrids, bears and lagomorphs. The genus Cercopithifilaria contains three taxa (i.e. C. bainae, C. grassii and a yet undescribed species, namely Cercopithifilaria sp. II) that are known to infect dogs worldwide, with their occurrence overlapping the distribution of the main tick vector, Rhipicephalus sanguineus sensu lato. In recent decades, more attention has focused on these filarioids since they have been associated with clinical signs of infection, such as dermatitis, chronic polyarthritis and cutaneous cysts, and possibly with facilitating infections caused by other tick-borne pathogens. Nevertheless, these parasites remain largely underdiagnosed in clinical practice due to the lack of awareness of veterinary practitioners and to major obstacles to their diagnosis. In this review, we have assessed currently available data on Cercopithifilaria spp. infecting dogs worldwide and discussed the biological, clinical and epidemiological aspects of these filarioids, with the overall aim to gain a better understanding of their potential role in skin diseases.
Graphical abstract
Contrast media extravasation injury: a prospective observational cohort study
Authors: Liu Wanli , Wang Pinghu , Zhu Hui , Tang Hui , Guan Hongmei , Wang Xiaoying , Wang Chengxiang , Qiu Yao , He Lianxiang 
Published: October 2023

Abstract
Objective
To identify the risk factors for moderate and severe contrast media extravasation and provide effective guidance to reduce the degree of extravasation injuries.

Methods
We observed 224 adult patients who underwent contrast media extravasation at Xiangya Hospital of Central South University, Hunan Provincial Maternal and Child Healthcare Hospital, and Xiangya Changde Hospital, Hunan Province between January 1, 2018 and December 31, 2022. Risk factors for moderate extravasation injuries were evaluated using univariate and multivariate logistic regression.

Results
Among 224 patients, 0 (0%) had severe, 18 (8.0%) had moderate, and 206 (92.0%) had mild contrast media extravasation injury. Multivariate logistic regression analysis revealed malignant tumors (odds ratio [OR] = 6.992, 95% confidence interval [CI]: 1.674–29.208), Iohexol (OR = 9.343, 95% CI 1.280–68.214), large-volume (> 50 mL) extravasation (OR = 5.773, 95% CI 1.350‒24.695), and injection site (back of the hand) (OR = 13.491, 95% CI 3.056–59.560) as independent risk factors for moderate injury.

Conclusion
Risk factors for moderate contrast media extravasation injury are malignant tumors, iohexol, large-volume (> 50 mL) extravasation, and back-of-the-hand injection. Analysis of these risk factors can help reduce the degree of injury after extravasation.

Clinical relevance statement
High-risk patients with extravasation support should choose the appropriate contrast media type, avoiding back-of-the-hand injections. We recommend that patients with cancer be implanted with a high-pressure resistant central venous catheter and receive effective measures to timely detect and reduce extravasation.
Ethnicity as a risk factor for gambling disorder: a large-scale study linking data from the Norwegian patient registry with the Norwegian social insurance database
Authors: Aarestad Sarah Helene , Erevik Eilin Kristine , Smith Otto Robert Frans , Griffiths Mark D. , Leino Tony Mathias , Mentzoni Rune Aune , Pallesen Ståle 
Published: October 2023

Abstract
Background
The study investigated ethnicity as a risk factor for gambling disorder (GD), controlling for demographics, citizenship, and years of residency in Norway.

Methods
The sample comprised 65,771 individuals from a national patient registry (n = 35,607, age range 18–88 years) and a national social insurance database in Norway (n = 30,164, age rage 18–98 years). The data covered the period from 2008 to 2018.

Results
The results showed that when controlling for age and sex, ethnic minorities were overall less likely than those born in Norway to be diagnosed with GD (odds ratio [OR] ranging from 0.293 to 0.698). After controlling for citizenship and years of residency in Norway, the results were reversed and indicated that ethnic minorities were overall more likely to be diagnosed with GD (OR ranging from 1.179 to 3.208).

Conclusion
The results suggest that citizenship and years of residency are important variables to account for when assessing the relationship between ethnicity and being diagnosed with GD. Our results may be explained by people from ethnic minority groups being more likely to experience gambling problems but less likely to seek contact with healthcare services for gambling problems.
Diminazene aceturate or losartan ameliorates the functional, radiological and histopathological alterations in knee osteoarthritis rodent model: repurposing of the ACE2/Ang1‐7/MasR cascade
Authors: Habib Yasser H. , Sheta Eman , Khattab Mahmoud , Gowayed Mennatallah A. 
Published: October 2023

AbstractPurposeCurrent therapies for osteoarthritis (OA) are limited to analgesics and anti‐inflammatory drugs. Considering the importance of oxidative stress and inflammatory mediators in OA etiology, we tested the hypothesis that targeting the renin–angiotensin–aldosterone system (RAAS) can improve OA anomalies. Diminazene (DIZE), an activator of angiotensin‐converting enzyme 2 and the angiotensin 2 type‐1 receptor blocker losartan (LOS) were used for this purpose.MethodsOA was induced by a single intra‐articular injection of monosodium iodoacetate. The effects of exposure to DIZE or LOS for 21 days on OA anomalies in rats’ knees were investigated. Evaluation of motor function, nociception, and inflammatory response was done using rotarod, knee bend and knee swelling tests. Markers of knee joint inflammation, and cellular oxidation in addition to the RAAS biomarkers, were assessed in knee tissues, along with radiological and histopathological investigations.ResultsElevations in inflammatory and oxidative markers in knee tissues of OA rats were mostly improved by the two therapeutic drugs. Such effect was also reflected in the rotarod, knee bend and knee swelling tests. Treatment with DIZE has shown a more prominent effect than LOS in controlling OA‐associated inflammation and cellular oxidation. Markers of RAAS have also shown better responsiveness to DIZE over LOS.ConclusionsDIZE has shown a prominent increase in the angiotensin 1–7 amount, highlighting the involvement of the signaling pathway in the immunomodulatory effect. The radiological and histopathology examination came to confirm the outcome of biochemical markers, nominating diminazene aceturate as a possible therapeutic option for OA.