bluuebunny/crossref_metadata_2025_split huggingface dataset:
Higher pulse wave velocity in young adult offspring of mothers with type 1 diabetes: a case–control study
Authors: Korpijaakko Cedric A. , Eriksson Mia D. , Wasenius Niko S. , Klemetti Miira M. , Teramo Kari , Kautiainen Hannu , Eriksson Johan G. , Laine Merja K. 
Published: September 2022

Abstract
Background
Offspring of mothers with type 1 diabetes have an increased risk for acquiring early onset cardiovascular disease (CVD). Arterial stiffness, measured as pulse wave velocity (PWV), is a non-invasive biomarker for CVD risk assessment. Our aim is to determine whether PWV is increased in young adult offspring of mothers with type 1 diabetes.

Methods
This is a case–control study carried out in the hospital district of Helsinki and Uusimaa, Finland. 75 offspring of mothers with type 1 diabetes (cases) and 84 offspring of mothers without diabetes (controls), aged 18–23 years, were enrolled in this study. All participants attended clinical assessments, including questionnaires and laboratory tests. Carotid-femoral PWV (cfPWV), carotid-radial PWV (crPWV), and PWV ratio were measured from each participant using the Complior Analyse mechanotransducer (Alam Medical, France). Student’s t-test and chi-squared test were used to assess differences between the groups. Stata 17.0, StataCorp LP (College Station, TX, USA) statistical package was used for the analysis.

Results
We did not observe any differences in conventional CVD risk factors: systolic blood pressure, LDL, HbA1c, and smoking between cases and controls. We detected higher cfPWV in cases 6.5 (SD ± 1.2) m/s than in controls 6.2 (SD ± 0.7) m/s, p = 0.049, after adjustments for BMI, smoking, mean arterial pressure, height, and pulse rate was made. We did not observe any difference between cases and controls regarding crPWV or PWV ratio. Additionally, we detected no sex differences.

Conclusions
We report a novel finding of signs of increased arterial stiffness already in young adult offspring of mothers with type 1 diabetes compared to matched offspring of mothers without diabetes. Our finding suggests that exposure to an adverse intrauterine environment of type 1 diabetes mothers may affect the vascular health of offspring already in young adulthood. Additional research within this topic is warranted.
TRIM36 inhibits tumorigenesis through the Wnt/β-catenin pathway and promotes caspase-dependent apoptosis in hepatocellular carcinoma
Authors: Tong Qing , Yi Mingyu , Kong Panpan , Xu Lin , Huang Wukui , Niu Yue , Gan Xiaojing , Zhan Huan , Tian Rui , Yan Dong 
Published: September 2022

Abstract
Background
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and has an extremely poor prognosis. We aimed to determine the latent relationships between TRIM36 regulation of apoptosis and the Wnt/β-catenin pathway in HCC.

Methods
Immunohistochemistry and western blotting were used to characterize the aberrant expression of TRIM36 in HCC and adjacent tissues. Clinical information was analyzed using Kaplan–Meier and Cox methods. RNA-seq of potential targets was conducted to detect the regulation of TRIM36. Apoptosis assays and cellular proliferation, invasion and migration were conducted in a loss- and gain-of-function manner in cultured cells to determine the biological functions of TRIM36. A rescue experiment was conducted to confirm the role of Wnt/β-catenin signaling in TRIM36 regulation. Finally, in vivo experiments were conducted using cell line-derived xenografts in nude mice to validate the central role of TRIM36 in HCC.

Results
TRIM36 expression was significantly downregulated in HCC tissues compared to adjacent non-tumor tissues. TRIM36 repressed the proliferation, migration, and invasion of Huh7 and HCCLM3 cells, whereas it stimulated apoptosis. Wnt/β-catenin signaling was inhibited by TRIM36, and rescue experiments highlighted its importance in HCC proliferation, migration, and invasion. In vivo experiments further confirmed the effects of sh-TRIM36 on HCC tumorigenesis, inhibition of apoptosis, and promotion of Wnt/β-catenin signaling.

Conclusion
Our study is the first to indicate that TRIM36 acts as a tumor suppressor in HCC. TRIM36 activates apoptosis and inhibits cellular proliferation, invasion, and migration via the Wnt/β-catenin pathway, which may serve as an important biomarker and promising therapeutic target for HCC.
Anopheline diversity in urban and peri-urban malaria foci: comparison between alternative traps and seasonal effects in a city in the Western Brazilian Amazon
Authors: Meireles Anne Caroline Alves , da Silva Lucas Rosendo , Simplício Marlon Ferreira , de Lima Alzemar Alves , Rios Flávia Geovana Fontineles , de Menezes Carla Augusta , Feitoza Luiz Henrique Maciel , Julião Genimar Rebouças 
Published: September 2022

Abstract
Background
Continuous vector surveillance and sustainable interventions are mandatory in order to prevent anopheline proliferation (or spread to new areas) and interrupt malaria transmission. Anopheline abundance and richness were evaluated in urban and peri-urban malaria foci at a medium-sized city in the Brazilian Amazon, comparing the protected human landing catch technique (PHLC) and alternative sampling methods over different seasonal periods. Additional information was assessed for female feeding behaviour and faunal composition.

Methods
Anophelines were sampled bimonthly in four urban and peri-urban sites in the city of Porto Velho, state of Rondônia, Brazil. The average number of captured mosquitoes was compared between an PHLC (gold standard), a tent trap (Gazetrap), and a barrier screen by means of generalized linear mixed models (GLMM), which also included season and environment (peri-urban/urban) as predictors.

Results
Overall, 2962 Anopheles individuals belonging to 12 species and one complex were caught; Anopheles darlingi represented 86% of the individuals. More mosquitoes were captured in the peri-urban setting, and the urban setting was more diverse. The model estimates that significantly more anophelines were collected by PHLC than by the Screen method, and Gazetrap captured fewer individuals. However, the Screen technique yielded more blood-engorged females. The peak hours of biting activity were from 6 to 7 p.m. in urban areas and from 7 to 8 p.m. in peri-urban areas.

Conclusions
Although peri-urban settings presented a greater abundance of anophelines, Shannon and Simpson diversities were higher in urban sites. Each technique proved to be useful, depending on the purpose: PHLC was more effective in capturing the highest anopheline densities, Gazetrap caught the greatest number of species, and the barrier screen technique captured more engorged individuals. There was no seasonal effect on Anopheles assemblage structure; however, a more diverse fauna was caught in the transitional season. Biting activity was more intense from 6 to 8 p.m., with a predominance of An. darlingi.
Activation of NMDA receptors in brain endothelial cells increases transcellular permeability
Authors: Kim Kyu-Sung , Jeon Min Tae , Kim Eun Seon , Lee Chan Hee , Kim Do-Geun 
Published: September 2022

AbstractNeurovascular coupling is a precise mechanism that induces increased blood flow to activated brain regions, thereby providing oxygen and glucose. In this study, we hypothesized that N-methyl-D-aspartate (NMDA) receptor signaling, the most well characterized neurotransmitter signaling system which regulates delivery of essential molecules through the blood–brain barrier (BBB). Upon application of NMDA in both in vitro and in vivo models, increased delivery of bioactive molecules that was mediated through modulation of molecules involved in molecular delivery, including clathrin and caveolin were observed. Also, NMDA activation induced structural changes in the BBB and increased transcellular permeability that showed regional heterogeneity in its responses. Moreover, NMDA receptor activation increased endosomal trafficking and facilitated inactivation of lysosomal pathways and consequently increased molecular delivery mediated by activation of calmodulin-dependent protein kinase II (CaMKII) and RhoA/protein kinase C (PKC). Subsequent in vivo experiments using mice specifically lacking NMDA receptor subunit 1 in endothelial cells showed decreased neuronal density in the brain cortex, suggesting that a deficiency in NMDA receptor signaling in brain endothelial cells induces neuronal losses. Together, these results highlight the importance of NMDA-receptor-mediated signaling in the regulation of BBB permeability that surprisingly also affected CD31 staining.
In vivo measurement of intradiscal pressure changes related to thrust and non-thrust spinal manipulation in an animal model: a pilot study
Authors: Reed William R. , Liebschner Michael A. K. , Lima Carla R. , Singh Harshvardhan , Hurt Christopher P. , Martins Daniel F. , Cox James M. , Gudavalli Maruti R. 
Published: September 2022

Abstract
Background
The intervertebral disc is a known back pain generator and is frequently the focus of spinal manipulative therapy evaluation and treatment. The majority of our current knowledge regarding intradiscal pressure (IDP) changes related to spinal manual therapy involves cadaveric studies with their inherent limitations. Additional in vivo animal models are needed to investigate intervertebral disc physiological and molecular mechanisms related to spinal manipulation and spinal mobilization treatment for low back disorders.

Methods
Miniature pressure catheters (Millar SPR-1000) were inserted into either the L4-L5 or L5-L6 intervertebral disc of 3 deeply anesthetized adult cats (Oct 2012-May 2013). Changes in IDP were recorded during delivery of instrument-assisted spinal manipulation (Activator V® and Pulstar®) and motorized spinal flexion with/without manual spinous process contact.

Results
Motorized flexion of 30° without spinous contact decreased IDP of the L4-L5 disc by ~ 2.9 kPa, while physical contact of the L4 spinous process decreased IDP an additional ~ 1.4 kPa. Motorized flexion of 25° with L5 physical contact in a separate animal decreased IDP of the L5-L6 disc by ~ 1.0 kPa. Pulstar® impulses (setting 1–3) increased IDP of L4-L5 and L5-L6 intervertebral discs by ~ 2.5 to 3.0 kPa. Activator V® (setting 1–4) impulses increased L4-L5 IDP to a similar degree. Net changes in IDP amplitudes remained fairly consistent across settings on both devices regardless of device setting suggesting that viscoelastic properties of in vivo spinal tissues greatly dampen superficially applied manipulative forces prior to reaching deep back structures such as the intervertebral disc.

Conclusions
This study marks the first time that feline in vivo changes in IDP have been reported using clinically available instrument-assisted spinal manipulation devices and/or spinal mobilization procedures. The results of this pilot study indicate that a feline model can be used to investigate IDP changes related to spinal manual therapy mechanisms as well as the diminution of these spinal manipulative forces due to viscoelastic properties of the surrounding spinal tissues. Additional investigation of IDP changes is warranted in this and/or other in vivo animal models to provide better insights into the physiological effects and mechanisms of spinal manual therapy at the intervertebral disc level.
Systemic injection of nicotinic acetylcholine receptor antagonist mecamylamine affects licking, eyelid size, and locomotor and autonomic activities but not temporal prediction in male mice
Authors: Kaneko Shohei , Niki Yasuyuki , Yamada Kota , Nasukawa Daiki , Ujihara Yusuke , Toda Koji 
Published: September 2022

AbstractNicotinic acetylcholine receptors are thought to be associated with a wide range of phenomena, such as movement, learning, memory, attention, and addiction. However, the causal relationship between nicotinic receptor activity and behavior remains unclear. Contrary to the studies that examined the functions of muscarinic acetylcholine receptors, the role of the nicotinic acetylcholine receptors on behavior has not been examined as extensively. Here, we examined the effects of intraperitoneal injection of mecamylamine, a nicotinic acetylcholine receptor antagonist, on the performance of male mice in a head-fixed temporal conditioning task and a free-moving open-field task. The head-fixed experimental setup allowed us to record and precisely quantify the licking response while the mice performed the behavioral task with no external cues. In addition, by combining the utility of the head-fixed experimental design with computer vision analysis based on deep learning algorithms, we succeeded in quantifying the eyelid size of awake mice. In the temporal conditioning task, we delivered a 10% sucrose solution every 10 s using a blunt-tipped needle placed within the licking distance of the mice. After the training, the mice showed increased anticipatory licking toward the timing of sucrose delivery, suggesting that the mice could predict the timing of the reward. Systemic injection of mecamylamine decreased licking behavior and caused eye closure but had no effect on learned conditioned predictive behavior in the head-fixed temporal conditioning task. In addition, the injection of mecamylamine decreased spontaneous locomotor activity in a dose-dependent manner in the free-moving open-field task. The results in the open-field experiments further revealed that the effect of mecamylamine on fecal output and urination, suggesting the effects on autonomic activities. Our achievement of successful eyelid size recording has potential as a useful approach in initial screening for drug discovery. Our study paves a way forward to understanding the role of nicotinic acetylcholine receptors on learning and behavior.
Hypoxia-induced exosomal circPDK1 promotes pancreatic cancer glycolysis via c-myc activation by modulating miR-628-3p/BPTF axis and degrading BIN1
Authors: Lin Jiewei , Wang Xinjing , Zhai Shuyu , Shi Minmin , Peng Chenghong , Deng Xiaxing , Fu Da , Wang Jiancheng , Shen Baiyong 
Published: September 2022

Abstract
Background
circRNA has been established to play a pivotal role in tumorigenesis development in a variety of cancers; nevertheless, the biological functions and molecular mechanisms of hypoxia-induced exosomal circRNAs in pancreatic cancer remain largely unknown.

Methods
Differentially expressed circRNAs in exosomes between hypoxic exosomes and normoxic exosomes in PC cells were verified by RNA sequencing. The expression of circPDK1 in PC tumors and PC patients was evaluated by qRT-PCR and ISH, and the biological functions of circPDK1 in PC were verified through a series of in vitro and in vivo experiments. Using Western blotting, Co-IP, RNA pull-down, ChIP, RIP, dual-luciferase assays, and rescue experiments, the underlying mechanism of circPDK1 was verified.

Results
CircPDK1 was highly abundant in PC tumor tissues and serum exosomes and was associated with poor survival. Exosomal circPDK1 significantly promoted PC cell proliferation, migration, and glycolysis both in vitro and in vivo. Mechanistically, circPDK1 could be activated by HIF1A at the transcriptional level and sponges miR-628-3p to activate the BPTF/c-myc axis. In addition, circPDK1 serves as a scaffold that enhances the interaction between UBE2O and BIN1, inducing the UBE2O-mediated degradation of BIN1.

Conclusions
We found that circPDK1 was activated by HIF1A at the transcriptional level by modulating the miR-628-3p/BPTF axis and degrading BIN1. Exosomal circPDK1 is a promising biomarker for PC diagnosis and prognosis and represents a potential therapeutic target for PC.
Administration of vitamin D and its metabolites in critically ill adult patients: an updated systematic review with meta-analysis of randomized controlled trials
Authors: Menger Johannes , Lee Zheng-Yii , Notz Quirin , Wallqvist Julia , Hasan M. Shahnaz , Elke Gunnar , Dworschak Martin , Meybohm Patrick , Heyland Daren K. , Stoppe Christian 
Published: September 2022

Abstract
Background
The clinical significance of vitamin D administration in critically ill patients remains inconclusive. The purpose of this systematic review with meta-analysis was to investigate the effect of vitamin D and its metabolites on major clinical outcomes in critically ill patients, including a subgroup analysis based on vitamin D status and route of vitamin D administration.

Methods
Major databases were searched through February 9, 2022. Randomized controlled trials of adult critically ill patients with an intervention group receiving vitamin D or its metabolites were included. Random-effect meta-analyses were performed to estimate the pooled risk ratio (dichotomized outcomes) or mean difference (continuous outcomes). Risk of bias assessment included the Cochrane tool for assessing risk of bias in randomized trials.

Results
Sixteen randomized clinical trials with 2449 patients were included. Vitamin D administration was associated with lower overall mortality (16 studies: risk ratio 0.78, 95% confidence interval 0.62–0.97, p = 0.03; I2 = 30%), reduced intensive care unit length of stay (12 studies: mean difference − 3.13 days, 95% CI − 5.36 to − 0.89, n = 1250, p = 0.006; I2 = 70%), and shorter duration of mechanical ventilation (9 studies: mean difference − 5.07 days, 95% CI − 7.42 to − 2.73, n = 572, p < 0.0001; I2 = 54%). Parenteral administration was associated with a greater effect on overall mortality than enteral administration (test of subgroup differences, p = 0.04), whereas studies of parenteral subgroups had lower quality. There were no subgroup differences based on baseline vitamin D levels.

Conclusions
Vitamin D supplementation in critically ill patients may reduce mortality. Parenteral administration might be associated with a greater impact on mortality. Heterogeneity and assessed certainty among the studies limits the generalizability of the results.
Trial registration: PROSPERO international prospective database of systematic reviews (CRD42021256939—05 July 2021).
The iHealth-T2D study: a cluster randomised trial for the prevention of type 2 diabetes amongst South Asians with central obesity and prediabetes—a statistical analysis plan
Authors: Muilwijk Mirthe , Loh Marie , Mahmood Sara , Palaniswamy Saranya , Siddiqui Samreen , Silva Wnurinham , Frost Gary S. , Gage Heather M. , Jarvelin Marjo-Riitta , Rannan-Eliya Ravindra P. , Ahmad Sajjad , Jha Sujeet , Kasturiratne Anuradhani , Katulanda Prasad , Khawaja Khadija I. , Kooner Jaspal S. , Wickremasinghe Ananda R. , van Valkengoed Irene G. M. , Chambers John C. 
Published: September 2022

AbstractBackgroundSouth Asians are at high risk of type 2 diabetes (T2D). Lifestyle modification is effective at preventing T2D amongst South Asians, but the approaches to screening and intervention are limited by high costs, poor scalability and thus low impact on T2D burden. An intensive family-based lifestyle modification programme for the prevention of T2D was developed. The aim of the iHealth-T2D trial is to compare the effectiveness of this programme with usual care.MethodsThe iHealth-T2D trial is designed as a cluster randomised controlled trial (RCT) conducted at 120 sites across India, Pakistan, Sri Lanka and the UK. A total of 3682 South Asian men and women with age between 40 and 70 years without T2D but at elevated risk for T2D [defined by central obesity (waist circumference ≥ 95 cm in Sri Lanka or ≥ 100 cm in India, Pakistan and the UK) and/or prediabetes (HbA1c ≥ 6.0%)] were included in the trial. Here, we describe in detail the statistical analysis plan (SAP), which was finalised before outcomes were available to the investigators. The primary outcome will be evaluated after 3 years of follow-up after enrolment to the study and is defined as T2D incidence in the intervention arm compared to usual care. Secondary outcomes are evaluated both after 1 and 3 years of follow-up and include biochemical measurements, anthropometric measurements, behavioural components and treatment compliance.DiscussionThe iHealth-T2D trial will provide evidence of whether an intensive family-based lifestyle modification programme for South Asians who are at high risk for T2D is effective in the prevention of T2D. The data from the trial will be analysed according to this pre-specified SAP.Ethics and disseminationThe trial was approved by the international review board of each participating study site. Study findings will be disseminated through peer-reviewed publications and in conference presentations.Trial registrationEudraCT2016–001,350-18. Registered on 14 April 2016. ClinicalTrials.govNCT02949739. Registered on 31 October 2016.
Prevalence of major digestive and respiratory helminths in dogs and cats in France: results of a multicenter study
Authors: Bourgoin Gilles , Callait-Cardinal Marie-Pierre , Bouhsira Emilie , Polack Bruno , Bourdeau Patrick , Roussel Ariza Clarisse , Carassou Lisa , Lienard Emmanuel , Drake Jason 
Published: September 2022

AbstractBackgroundThe local distribution of helminths in dogs and cats and the evaluation of risk of contamination represent an important challenge for veterinarians due to their effects on animal health and their potential zoonotic risk. The overall goal of this study was to estimate the prevalence of the digestive and respiratory helminths infecting client-owned dogs and cats in France.MethodsFaecal samples were collected from 414 pet dogs and 425 pet cats at 20 study sites during 2017–2018 and analysed by coproscopy. The samples included specimens collected from animals of both genders and various breeds and ages from a variety of living environments, and with different lifestyles and feeding regimes. Associations between parasitic infection and qualitative factors were explored.ResultsOverall, 125 (14.9%) samples (15.2% in dogs and 14.6% in cats) were positive for at least one of the species of helminths identified. Infection rates were highest forToxocara canisandToxocara cati(8.5% and 11.3%, respectively), whileToxascaris leoninawas found only in one cat (0.2%). The apparent prevalence ofAncylostoma caninumandUncinaria stenocephalain dogs was 1.7% and 4.3%, respectively. No hookworms were found in cats. Whipworms (Trichuris vulpis) were identified in 2.7% of the dogs. Tapeworms (Dipylidium caninumand Taeniidae) were rarely found (< 1% in dogs and < 3% in cats). The prevalence ofAngiostrongylus vasorum Crenosoma vulpis, andStrongyloides stercoralis in dogs,Aelurostrongylus abstrususin cats andEucoleus spp./Capillaria spp.in both dogs and cats was < 1%. Significantly higher fecal parasite emission rates were identified in young individuals, in animals with outdoor access, in animals living in the countryside and in intact animals (especially in cats). In addition, cats not fed exclusively with commercial diets and living with other animals (dogs and/or cats) were at higher risk for parasites. For dogs, hunting/herding and walking off-leash were found to be additional risk factors. Furthermore, pets with no reported history of deworming or dewormed > 1 year before the study were positive for parasites significantly more often than pets dewormed < 1 year before study participation.ConclusionsThe overall prevalence of helminths (some of which are zoonotic), the risk factors and the reportedly low deworming frequencies identified in this study (20.5% animals having never been dewormed and only 26.4% dewormed ≥ 3 times/year) illustrate the need for improving pet owners’ adherence to anthelmintic guidelines in France.Graphical Abstract