bluuebunny/crossref_metadata_2025_split huggingface dataset:
Three-dimensional environment sensitizes pancreatic cancer cells to the anti-proliferative effect of budesonide by reprogramming energy metabolism
Authors: Ibello Eduardo , Saracino Federica , Delle Cave Donatella , Buonaiuto Silvia , Amoroso Filomena , Andolfi Gennaro , Corona Marco , Guardiola Ombretta , Colonna Vincenza , Sainz Jr Bruno , Altucci Lucia , De Cesare Dario , Cobellis Gilda , Lonardo Enza , Patriarca Eduardo Jorge , D’Aniello Cristina , Minchiotti Gabriella 
Published: June 2024

Abstract
Background
Pancreatic ductal adenocarcinoma (PDAC) is the most lethal cancer with an aggressive metastatic phenotype and very poor clinical prognosis. Interestingly, a lower occurrence of PDAC has been described in individuals with severe and long-standing asthma. Here we explored the potential link between PDAC and the glucocorticoid (GC) budesonide, a first-line therapy to treat asthma.

Methods
We tested the effect of budesonide and the classical GCs on the morphology, proliferation, migration and invasiveness of patient-derived PDAC cells and pancreatic cancer cell lines, using 2D and 3D cultures in vitro. Furthermore, a xenograft model was used to investigate the effect of budesonide on PDAC tumor growth in vivo. Finally, we combined genome-wide transcriptome analysis with genetic and pharmacological approaches to explore the mechanisms underlying budesonide activities in the different environmental conditions.

Results
We found that in 2D culture settings, high micromolar concentrations of budesonide reduced the mesenchymal invasive/migrating features of PDAC cells, without affecting proliferation or survival. This activity was specific and independent of the Glucocorticoid Receptor (GR). Conversely, in a more physiological 3D environment, low nanomolar concentrations of budesonide strongly reduced PDAC cell proliferation in a GR-dependent manner. Accordingly, we found that budesonide reduced PDAC tumor growth in vivo. Mechanistically, we demonstrated that the 3D environment drives the cells towards a general metabolic reprogramming involving protein, lipid, and energy metabolism (e.g., increased glycolysis dependency). This metabolic change sensitizes PDAC cells to the anti-proliferative effect of budesonide, which instead induces opposite changes (e.g., increased mitochondrial oxidative phosphorylation). Finally, we provide evidence that budesonide inhibits PDAC growth, at least in part, through the tumor suppressor CDKN1C/p57Kip2.

Conclusions
Collectively, our study reveals that the microenvironment influences the susceptibility of PDAC cells to GCs and provides unprecedented evidence for the anti-proliferative activity of budesonide on PDAC cells in 3D conditions, in vitro and in vivo. Our findings may explain, at least in part, the reason for the lower occurrence of pancreatic cancer in asthmatic patients and suggest a potential suitability of budesonide for clinical trials as a therapeutic approach to fight pancreatic cancer.
Autoimmune thyroid disease and ovarian hypofunction: a review of literature
Authors: Wang Ru , Lv Youyuan , Dou Tao , Yang Qian , Yu Chunxiao , Guan Qingbo 
Published: June 2024

AbstractThyroid hormones(THs) are essential for the proper functioning of the ovaries, and multiple studies have shown that thyroid abnormalities, especially during adolescence and reproductive age, can lead to lifelong ovarian dysfunction. Autoimmune thyroid disease (AITD), one of the most common organ specific autoimmune diseases, is mainly mediated by cellular autoimmune reactions, and has strong inflammatory infiltration and immune active cells, including chemokines and cytokines, which are important components of ovarian aging. This suggests that autoimmune and inflammatory molecular processes may play a role in the emergence of ovarian dysfunction. The purpose of this review is to summarize recent in vivo and in vitro evidence of a complex relationship between AITD and ovarian dysfunction. AITD is closely related to the decline of ovarian function from the perspective of antibody, cytokine, oxidative stress, and genetic factors. Finally, some of the currently known treatments for AITD and hypo ovarian disease are summarized.
Modifiable risk factors for cancer among people with lynch syndrome: an international, cross-sectional survey
Authors: Power Robert F. , Doherty Damien E. , Horgan Roberta , Fahey Pat , Gallagher David J. , Lowery Maeve A. , Cadoo Karen A. 
Published: June 2024

Abstract
Background
Lynch syndrome is the most common cause of hereditary colorectal and endometrial cancer. Lifestyle modification may provide an opportunity for adjunctive cancer prevention. In this study, we aimed to characterise modifiable risk factors in people with Lynch syndrome and compare this with international guidelines for cancer prevention.

Methods
A cross-sectional study was carried out utilizing survey methodology. Following public and patient involvement, the survey was disseminated through patient advocacy groups and by social media. Self-reported demographic and health behaviours were collected in April 2023. Guidelines from the World Cancer Research Fund (WCRF) were used to compare percentage adherence to 9 lifestyle recommendations, including diet, physical activity, weight, and alcohol intake. Median adherence scores, as a surrogate for lifestyle risk, were calculated and compared between groups.

Results
156 individuals with Lynch syndrome participated from 13 countries. The median age was 51, and 54% were cancer survivors. The mean BMI was 26.7 and the mean weekly duration of moderate to vigorous physical activity was 90 min. Median weekly consumption of ethanol was 60 g, and 3% reported current smoking. Adherence to WCRF recommendations for cancer prevention ranged from 9 to 73%, with all but one recommendation having < 50% adherence. The median adherence score was 2.5 out of 7. There was no significant association between median adherence scores and age (p = 0.27), sex (p = 0.31), or cancer history (p = 0.75).

Conclusions
We have characterised the modifiable risk profile of people living with Lynch syndrome, outlining targets for intervention based on lifestyle guidelines for the general population. As evidence supporting the relevance of modifiable factors in Lynch syndrome emerges, behavioural modification may prove an impactful means of cancer prevention.
A do it yourself (DIY) point-of-care wrist ultrasound phantom for joint access training
Authors: Cheng Andrea , Zhou Justin , Chan Chun Hei Ryan , Chen Connie , Cheng Charlotte , Storm Kaitlyn , Zhou Anson , Mao Alan , Kuk Won Jun , Fong Tiffany C. , Villagran Ignacio , Miranda Constanza 
Published: June 2024

Abstract
Background
Joint access is essential for arthrocentesis, or joint aspiration of fluids. Joint treatments that are not performed properly can result in avoidable patient issues such as damage to the muscles, tendons, and blood vessels surrounding the joint. The use of ultrasound has become the gold standard for this procedure and proven to be a support in the skill learning process. However, success with this equipment, particularly in small joints like the wrist, depends on a clinician's capacity to recognize the crucial landmarks that guide these procedures. Prior to executing on a real patient, task trainers have proven to be an effective way for doctors to practice and prepare for procedures. However, shortcomings of current solutions include high purchase costs, incompatibility with ultrasound imaging, and low reusability. In addition, since this is a procedure that is not performed frequently, there may not be space or resources available in healthcare facilities to accommodate one at the point of care. This study aimed to close the existing gap by developing a DIY ultrasound compatible task trainer for wrist joint access training.

Results
We developed a novel ultrasound compatible wrist joint model that can be made from sustainable materials and reusable parts, thus reducing the costs for acquisition and environmental impact. Our model, which was produced utilizing small-batch production methods, is made up of 3D-printed bones enclosed in an ultrasound-compatible gelatin mixture. It can be easily remade after each practice session, removing needle tracks that are visible under ultrasound for conventional phantoms. The ultrasonic properties of this model were tested through pixel brightness analysis and visual inspection of simulated anatomical structures.

Conclusion
Our results report the advantages and limitations of the proposed model regarding production, practice, and ultrasound compatibility. While future work entails the transfer to patients of the same skill, this reusable and replicable model has proven, when presented to experts, to be successful in representing the physical characteristics and ultrasound profile of significant anatomical structures. This novel DIY product could be an effective alternative to teach procedures in the context of resource-restrained clinical simulation centers.
Effect of Otago exercise on fear of falling in older adults: a systematic review and meta-analysis
Authors: Han Jianlong , Wang Hongwei , Ding Yunxin , Li Qing , Zhai Huanqie , He Shuling 
Published: June 2024

Abstract
Background
Approximately 40–70% of older adults who have experienced falls develop fear of falling (FOF), with the incidence rate in nursing home residents reaching as high as 79.4%. An increasing number of studies have focused on the effect of the Otago Exercise Programme (OEP) on reducing FOF among older adults, yet comprehensive analysis is lacking due to regional and demographic variations. Therefore, this study integrates the relevant literature to provide evidence supporting interventions aimed at alleviating FOF among older adults.

Objective
To evaluate the impact of OEP on FOF in older adults through meta-analysis.

Methods
We searched ten databases using computer systems, covering all records up to May 1, 2024. Two researchers independently conducted the literature screening, bias risk assessment, and data extraction. We performed data analysis using RevMan 5.3 and Stata 15.0 software, assessed result stability through sensitivity analysis, and examined publication bias with funnel plots and Egger’s test.

Results
Sixteen RCTs were included. Meta-analysis revealed that the OEP significantly reduced FOF among older adults [SMD = 0.96, 95%CI (0.68, 1.23), P < 0.00001]. Subgroup analysis revealed that interventions lasting more than 16 weeks [SMD = 1.12, 95%CI (0.75, 1.49), P < 0.00001], with a frequency of more than twice a week [SMD = 0.99, 95%CI (0.64, 1.35), P < 0.00001], and for older adults in community and nursing institutions [SMD = 1.03, 95%CI (0.50, 1.57), P = 0.0002] were more effective. A comparison of the 16-week and 24-week interventions revealed that the latter had better outcomes [SMD = 0.87, 95%CI (0.66, 1.08), P = 0.0004].

Conclusion
Current evidence indicates that OEP effectively reduces FOF among older adults. It is recommended that interventions last for more than 24 weeks, occur more than twice a week, and suitable for application among older adults in community settings or elder care institutions.
Enhanced hippocampal LTP but normal NMDA receptor and AMPA receptor function in a rat model of CDKL5 deficiency disorder
Authors: Simões de Oliveira Laura , O’Leary Heather E. , Nawaz Sarfaraz , Loureiro Rita , Davenport Elizabeth C. , Baxter Paul , Louros Susana R. , Dando Owen , Perkins Emma , Peltier Julien , Trost Matthias , Osterweil Emily K. , Hardingham Giles E. , Cousin Michael A. , Chattarji Sumantra , Booker Sam A. , Benke Tim A. , Wyllie David J. A , Kind Peter C. 
Published: June 2024

Abstract
Background
Mutations in the X-linked gene cyclin-dependent kinase-like 5 (CDKL5) cause a severe neurological disorder characterised by early-onset epileptic seizures, autism and intellectual disability (ID). Impaired hippocampal function has been implicated in other models of monogenic forms of autism spectrum disorders and ID and is often linked to epilepsy and behavioural abnormalities. Many individuals with CDKL5 deficiency disorder (CDD) have null mutations and complete loss of CDKL5 protein, therefore in the current study we used a Cdkl5−/y rat model to elucidate the impact of CDKL5 loss on cellular excitability and synaptic function of CA1 pyramidal cells (PCs). We hypothesised abnormal pre and/or post synaptic function and plasticity would be observed in the hippocampus of Cdkl5−/y rats.

Methods
To allow cross-species comparisons of phenotypes associated with the loss of CDKL5, we generated a loss of function mutation in exon 8 of the rat Cdkl5 gene and assessed the impact of the loss of CDLK5 using a combination of extracellular and whole-cell electrophysiological recordings, biochemistry, and histology.

Results
Our results indicate that CA1 hippocampal long-term potentiation (LTP) is enhanced in slices prepared from juvenile, but not adult, Cdkl5−/y rats. Enhanced LTP does not result from changes in NMDA receptor function or subunit expression as these remain unaltered throughout development. Furthermore, Ca2+ permeable AMPA receptor mediated currents are unchanged in Cdkl5−/y rats. We observe reduced mEPSC frequency accompanied by increased spine density in basal dendrites of CA1 PCs, however we find no evidence supporting an increase in silent synapses when assessed using a minimal stimulation protocol in slices. Additionally, we found no change in paired-pulse ratio, consistent with normal release probability at Schaffer collateral to CA1 PC synapses.

Conclusions
Our data indicate a role for CDKL5 in hippocampal synaptic function and raise the possibility that altered intracellular signalling rather than synaptic deficits contribute to the altered plasticity.

Limitations
This study has focussed on the electrophysiological and anatomical properties of hippocampal CA1 PCs across early postnatal development. Studies involving other brain regions, older animals and behavioural phenotypes associated with the loss of CDKL5 are needed to understand the pathophysiology of CDD.
Phenotypic and ancestry-related assortative mating in autism
Authors: Zhang Jing , Weissenkampen J. Dylan , Kember Rachel L. ,   iPSYCH Consortium, Hougaard David M. , Bybjerg-Grauholm Jonas , Werge Thomas , Als Thomas D. , Rosengren Anders , Grove Jakob , Børglum Anders D. , Robinson Elise B. , Brodkin Edward S. , Almasy Laura , Bucan Maja , Sebro Ronnie 
Published: June 2024

Abstract
Background
Positive assortative mating (AM) in several neuropsychiatric traits, including autism, has been noted. However, it is unknown whether the pattern of AM is different in phenotypically defined autism subgroups [e.g., autism with and without intellectually disability (ID)]. It is also unclear what proportion of the phenotypic AM can be explained by the genetic similarity between parents of children with an autism diagnosis, and the consequences of AM on the genetic structure of the population.

Methods
To address these questions, we analyzed two family-based autism collections: the Simons Foundation Powering Autism Research for Knowledge (SPARK) (1575 families) and the Simons Simplex Collection (SSC) (2283 families).

Results
We found a similar degree of phenotypic and ancestry-related AM in parents of children with an autism diagnosis regardless of the presence of ID. We did not find evidence of AM for autism based on autism polygenic scores (PGS) (at a threshold of |r|> 0.1). The adjustment of ancestry-related AM or autism PGS accounted for only 0.3–4% of the fractional change in the estimate of the phenotypic AM. The ancestry-related AM introduced higher long-range linkage disequilibrium (LD) between single nucleotide polymorphisms (SNPs) on different chromosomes that are highly ancestry-informative compared to SNPs that are less ancestry-informative (D2 on the order of 1 × 10−5).

Limitations
We only analyzed participants of European ancestry, limiting the generalizability of our results to individuals of non-European ancestry. SPARK and SSC were both multicenter studies. Therefore, there could be ancestry-related AM in SPARK and SSC due to geographic stratification. The study participants from each site were unknown, so we were unable to evaluate for geographic stratification.

Conclusions
This study showed similar patterns of AM in autism with and without ID, and demonstrated that the common genetic influences of autism are likely relevant to both autism groups. The adjustment of ancestry-related AM and autism PGS accounted for < 5% of the fractional change in the estimate of the phenotypic AM. Future studies are needed to evaluate if the small increase of long-range LD induced by ancestry-related AM has impact on the downstream analysis.
Monogenic hypertriglyceridemia and recurrent pancreatitis in a homozygous carrier of a rare APOA5 mutation: a case report
Authors: Makhmudova Umidakhon , Schulze P. Christian , Lorkowski Stefan , März Winfried , Geiling J.-A. , Weingärtner Oliver 
Published: June 2024

Abstract
Background
Homozygous mutations in the APOA5 gene constitute a rare cause of monogenic hypertriglyceridemia, or familial chylomicronemia syndrome (FCS). We searched PubMed and identified 16 cases of homozygous mutations in the APOA5 gene. Severe hypertriglyceridemia related to monogenic mutations in triglyceride-regulating genes can cause recurrent acute pancreatitis. Standard therapeutic approaches for managing this condition typically include dietary interventions, fibrates, and omega-3-fatty acids. A novel therapeutic approach, antisense oligonucleotide volanesorsen is approved for use in patients with FCS.

Case presentation
We report a case of a 25-years old Afghani male presenting with acute pancreatitis due to severe hypertriglyceridemia up to 29.8 mmol/L caused by homozygosity in APOA5 (c.427delC, p.Arg143Alafs*57). A low-fat diet enriched with medium-chain TG (MCT) oil and fibrate therapy did not prevent recurrent relapses, and volanesorsen was initiated. Volanesorsen resulted in almost normalized triglyceride levels. No further relapses of acute pancreatitis occurred. Patient reported an improve life quality due to alleviated chronic abdominal pain and headaches.

Conclusions
Our case reports a rare yet potentially life-threatening condition—monogenic hypertriglyceridemia-induced acute pancreatitis. The implementation of the antisense drug volanesorsen resulted in improved triglyceride levels, alleviated symptoms, and enhanced the quality of life.
Wavelet analysis on a generalized helix space curves and its examples
Authors: Zhou Xiaohui 
Published: June 2024

AbstractIn this paper, wavelet transform on a generalized helix space curves are investigated, including of local continuous wavelet transform at some point and discrete wavelet transform on a class of helix curves. Firstly, a class of helix space curves are introduced and the parameter equations are given. Then the dilation operator and translation on the function $$\psi^{{(\xi_{{0}} )}}$$

ψ

(

ξ
0

)

is properly defined by the local projection at some point from a space curve on the unit sphere onto its tangent line. The local continuous wavelet transform and its reconstruction formula are deduced at some point of a space curve on the unit sphere. On the other hand, According to the discretization of length-preserving projection, discrete wavelet transform is lifted onto a helix space curve, such as a circular helix curve. Based on length-preserving projection, the some properties are discussed, such as two-scale sequences of scaling function and wavelet, orthogonality, decomposition formula and so on. Finally, two examples are given for our discussion. One example is illustrating the application of local continuous wavelet transform at some point of a space curve. The result shows the signal at some point of a space curve can be reconstructed by local continuous wavelet method. The norm of the error is 0.3783 between original signal and reconstructed signal in this example. The other numerical example is given for decomposing and reconstructing with the signal on a circular helix curve. The result shows the signal on a helix space curve can be decomposed and reconstructed by the length-preserving projection. The norm of the error is 8.0741 × 10−11 between original signal and reconstructed signal. The figures are shown for the simulation results.
Image quality comparison of AirDoc portable retina camera versus eyer in a diabetic retinopathy screening program
Authors: Brant Rodrigo , Nakayama Luis Filipe , de Oliveira Talita Virgínia Fernandes , de Oliveira Juliana Angelica Estevão , Ribeiro Lucas Zago , Richter Gabriela Dalmedico , Rodacki Rafael , Penha Fernando Marcondes 
Published: June 2024

Abstract
Background
Diabetic retinopathy (DR) stands as the foremost cause of preventable blindness in adults. Despite efforts to expand DR screening coverage in the Brazilian public healthcare system, challenges persist due to various factors including social, medical, and financial constraints. Our objective was to evaluate the quality of images obtained with the AirDoc, a novel device, compared to Eyer portable camera which has already been clinically validated.

Methods
Images were captured by two portable retinal devices: AirDoc and Eyer. The included patients had their fundus images obtained in a screening program conducted in Blumenau, Santa Catarina. Two retina specialists independently assessed image’s quality. A comparison was performed between both devices regarding image quality and the presence of artifacts.

Results
The analysis included 129 patients (mean age of 61 years), with 29 (43.28%) male and an average disease duration of 11.1 ± 8 years. In Ardoc, 21 (16.28%) images were classified as poor quality, with 88 (68%) presenting artifacts; in Eyer, 4 (3.1%) images were classified as poor quality, with 94 (72.87%) presenting artifacts.

Conclusions
Although both Eyer and AirDoc devices show potential as screening tools, the AirDoc images displayed higher rates of ungradable and low-quality images, that may directly affect the DR and DME grading. We must acknowledge the limitations of our study, including the relatively small sample size. Therefore, the interpretations of our analyses should be approached with caution, and further investigations with larger patient cohorts are warranted to validate our findings.