bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting macrophage migration inhibitory factor (MIF): a promising therapy for inflammatory ocular diseases
Authors: Vázquez Alicia , González Marisol I. , Reyes José L. 
Published: August 2023

AbstractInflammatory ocular diseases are characterized by the presence of a persistent inflammatory response which cause tissue injury, decrease visual acuity and in severe cases, blindness. Several cytokines represent a therapeutic opportunity since they are key amplifiers of these pathologies, and thus neutralizing agents against them have been developed. Amongst others, macrophage migration inhibitory factor (MIF), an early produced inflammatory cytokine, has consistently been found elevated in patients with distinct ocular diseases (inflammatory and autoimmune). Here, we present and discuss evidence showing that preclinical trials using diverse strategies to neutralize MIF resulted in significant attenuation of disease signs and therefore MIF blockage might be a promising therapy for ocular diseases.
Genetic mapping of craniofacial traits in the Mexican tetra reveals loci associated with bite differences between cave and surface fish
Authors: Powers Amanda K. , Hyacinthe Carole , Riddle Misty R. , Kim Young Kwang , Amaismeier Alleigh , Thiel Kathryn , Martineau Brian , Ferrante Emma , Moran Rachel L. , McGaugh Suzanne E. , Boggs Tyler E. , Gross Joshua B. , Tabin Clifford J. 
Published: August 2023

Abstract
Background
The Mexican tetra, Astyanax mexicanus, includes interfertile surface-dwelling and cave-dwelling morphs, enabling powerful studies aimed at uncovering genes involved in the evolution of cave-associated traits. Compared to surface fish, cavefish harbor several extreme traits within their skull, such as a protruding lower jaw, a wider gape, and an increase in tooth number. These features are highly variable between individual cavefish and even across different cavefish populations.

Results
To investigate these traits, we created a novel feeding behavior assay wherein bite impressions could be obtained. We determined that fish with an underbite leave larger bite impressions with an increase in the number of tooth marks. Capitalizing on the ability to produce hybrids from surface and cavefish crosses, we investigated genes underlying these segregating orofacial traits by performing Quantitative Trait Loci (QTL) analysis with F2 hybrids. We discovered significant QTL for bite (underbite vs. overbite) that mapped to a single region of the Astyanax genome. Within this genomic region, multiple genes exhibit coding region mutations, some with known roles in bone development. Further, we determined that there is evidence that this genomic region is under natural selection.

Conclusions
This work highlights cavefish as a valuable genetic model for orofacial patterning and will provide insight into the genetic regulators of jaw and tooth development.
Prehospital pulse pressure and mortality of septic shock patients cared for by a mobile intensive care unit
Authors: Jouffroy Romain , Gilbert Basile , Tourtier Jean Pierre , Bloch-Laine Emmanuel , Ecollan Patrick , Boularan Josiane , Bounes Vincent , Vivien Benoit , Gueye Papa 
Published: August 2023

Abstract
Background
Septic shock medical treatment relies on a bundle of care including antibiotic therapy and hemodynamic optimisation. Hemodynamic optimisation consists of fluid expansion and norepinephrine administration aiming to optimise cardiac output to reach a mean arterial pressure of 65mmHg. In the prehospital setting, direct cardiac output assessment is difficult because of the lack of invasive and non-invasive devices. This study aims to assess the relationship between 30-day mortality and (i) initial pulse pressure (iPP) as (ii) pulse pressure variation (dPP) during the prehospital stage among patients cared for SS by a prehospital mobile intensive care unit (MICU).

Methods
From May 09th, 2016 to December 02nd, 2021, septic shock patients requiring MICU intervention were retrospectively analysed. iPP was calculated as the difference between systolic blood pressure (SBP) and diastolic blood pressure (DBP) at the first contact between the patient and the MICU team prior to any treatment and, dPP as the difference between the final PP (the difference between SBP and DBP at the end of the prehospital stage) and iPP divided by prehospital duration. To consider cofounders, the propensity score method was used to assess the relationship between (i) iPP < 40mmHg, (ii) positive dPP and 30-day mortality.

Results
Among the 530 patients analysed, pulmonary, digestive, and urinary infections were suspected among 43%, 25% and 17% patients, respectively. The 30-day overall mortality rate reached 31%. Cox regression analysis showed an association between 30-day mortality and (i) iPP < 40mmHg; aHR of 1.61 [1.03–2.51], and (ii) a positive dPP; aHR of 0.56 [0.36–0.88].

Conclusion
The current study reports an association between 30-day mortality rate and iPP < 40mmHg and a positive dPP among septic shock patients cared for by a prehospital MICU. A negative dPP could be helpful to identify septic shock with higher risk of poor outcome despite prehospital hemodynamic optimization.
What are the factors affecting older adults’ experience of unmet healthcare needs amid the COVID-19 pandemic in Korea?
Authors: Kim Sujin , Hwang Jongnam 
Published: August 2023

Abstract
Background
Unmet healthcare need is a critical indicator, showing a plausible picture of how the healthcare system works in the unprecedented pandemic situation. It is important to understand what factors affect healthcare services of older adults in the midst of the outbreak, as this could help identify service- and performance-related challenges and barriers to the healthcare system. This study aimed to identify factors associated with unmet healthcare needs among the older Korean population amid the COVID-19 pandemic.

Methods
Cross-sectional data were used from the Experience Survey on Healthcare Use of Older Adults during the COVID-19 (COVID-19 Survey) in Korea (n = 1,917). Our main outcome, unmet healthcare need, was measured based on self-reported experience of overall, regular, and irregular outpatient care services-related unmet healthcare needs. Independent variables were selected based on previous studies on determinants of unmet healthcare need during the COVID-19 pandemic and Andersen’s expanded behavioural model, which theorizes that healthcare-seeking behaviours are driven by psychosocial, enabling, and need factors.

Results
Using multiple logistic regression models, we identified a good understanding of the nation’s health system was associated with lower likelihood of all types of unmet healthcare needs among older Korean adults (OR: 0.39, 95%CI: 0.25–0.61; OR: 0.36, 95%CI: 0.20–0.63; OR: 0.41, 95%CI: 0.23–0.75). Decreased social activities (i.e., shopping and visiting family members) and worsened psychological health issues (i.e., increased anxiety & nervousness and greater difficulty sleeping) were also factors affecting overall and irregular outpatient services-related unmet needs.

Conclusions
To ensure timely access to necessary healthcare services for older adults in the era of the COVID-19 outbreak, improving older adult’s understanding on how the healthcare system works is necessary. Moreover, changes in psychological condition and daily activities due to COVID-19 should be considered as possible barriers to healthcare services among older adults during the global pandemic.
Assessing cancer in people with profound and multiple disabilities
Authors: Satgé Daniel , Nishi Motoi , Trétarre Brigitte 
Published: August 2023

Abstract
Background
Cancers are as common in individuals with intellectual disabilities as in the general population (GP). For the subgroup of people with profound and multiple disabilities (PMD) who present with both severe intellectual disability and major motor disorders, the frequency and distribution of cancers are currently not known, preventing proper cancer surveillance.

Methods
We carried out a systematic and synthetic review of the medical literature, including a focused search of Japanese data.

Results
The total risk of cancer in individuals with PMD is thought to be lower than in the GP, possibly due to a shorter life expectancy. They have reduced exposure to cancer risk factors, such as alcohol, tobacco, sunlight, human papillomavirus infection, occupational toxins, and being overweight. On the other hand, individuals with PMD present a greater frequency of gastroesophageal reflux disease, Helicobacter pylori gastritis, chronic cystitis, and cryptorchidism, which increase the risk for cancer of the esophagus, stomach, urinary bladder, and testes. In addition, certain genetic disorders underlying compromised motor and cognitive functions are associated with higher risk of childhood cancers. An analysis of 135 cancers in persons with PMD in Japan suggested that they present a particular tumor profile, with certain cancers rarer than in the GP, whereas cancers of the digestive tract are frequent. Cancers of the digestive tract occurred significantly earlier than in the GP (colon: average age 48.3 years vs. 71.3 years in the GP, esophagus: 39 years vs. 72 years in the GP). An increasing number of therapeutic successes in children and adults with PMD have been reported in different countries when cancers are discovered early.

Conclusion
Individuals with PMD must be appropriately monitored for cancer. Screenings for breast and colon cancer, as well as regular monitoring of the esophagus, stomach, urinary bladder, and testicles, are necessary. Population-based epidemiological studies are needed to better understand risk factors, frequency, and distribution of cancers in the PMD population.
Euterpe oleracea extract (açaí) exhibits cardioprotective effects after chemotherapy treatment in a breast cancer model
Authors: Alessandra-Perini Jéssica , Machado Daniel Escorsim , Palmero Celia Yelimar , Claudino Marllow Caetano , de Moura Roberto Soares , Palumbo Junior Antônio , Perini Jamila Alessandra , Nasciutti Luiz Eurico 
Published: August 2023

Abstract
Background
Açaí, a Brazilian native fruit, has already been demonstrated to play a role in the progress of breast cancer and cardiotoxicity promoted by chemotherapy agents. Thus, the present study aimed to evaluate the combined use of açaí and the FAC-D chemotherapy protocol in a breast cancer model in vivo.

Methods
Mammary carcinogenesis was induced in thirty female Wistar rats by subcutaneous injection of 25 mg/kg 7,12-dimethylbenzanthracene (DMBA) in the mammary gland. After sixty days, the rats were randomized into two groups: treated with 200 mg/kg of either açaí extract or vehicle, via gastric tube for 45 consecutive days. The FAC-D protocol was initiated after 90 days of induction by intraperitoneal injection for 3 cycles with a 7-day break each. After treatment, blood was collected for haematological and biochemical analyses, and tumours were collected for macroscopic and histological analyses. In the same way, heart, liver, and kidney samples were also collected for macroscopic and histological analyses.

Results
Breast cancer was found as a cystic mass with a fibrotic pattern in the mammary gland. The histological analysis showed an invasive carcinoma area in both groups; however, in the saline group, there was a higher presence of inflammatory clusters. No difference was observed regarding body weight, glycaemia, aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, and urea in either group. However, açaí treatment decreased creatine kinase (CK), creatine kinase MB (CKMB), troponin I and C-reactive protein levels and increased the number of neutrophils and monocytes. Heart histopathology showed normal myocardium in the açaí treatment, while the saline group presented higher toxicity effects with loss of architecture of cardiac tissue. Furthermore, the açaí treatment presented greater collagen distribution, increased hydroxyproline concentration and lower H2AX immunostaining in the heart samples.

Conclusion
Açaí decreased the number of inflammatory cells in the tumor environment and exhibited protection against chemotherapy drug cardiotoxicity with an increased immune response in animals. Thus, açaí can be considered a promising low-cost therapeutic treatment that can be used in association with chemotherapy agents to avoid heart damage.
“METAPAD” (METAbolic PAthways Decoded) – a gaming innovation to ease the complexity of metabolic pathways by promoting self-directed, active, participatory learning in small groups
Authors: Surapaneni Krishna Mohan 
Published: August 2023

Abstract
Background
In medical education, the conventional didactic lectures make the learning process tedious and cause disinterest among students. To overcome this, an effective experiential learning integrated with game-based approach that intends to make the learning process fun filled, interesting and enhance the active participation of students to understand complex topics in a simple and optimum manner should be adopted.

Objectives
The purpose of this study is to assess the efficiency of a puzzle-based innovation, METAPAD (METAbolic PAthways Decoded) in understanding the complexity of biochemical pathways by enhancing the self-directed learning of students through active engagement in small groups

Methods
In this mixed-method study, 103 first professional year medical students in small groups were enrolled for the METAPAD gaming puzzle-based learning activity. The puzzles were integrated with a relevant clinical case study. Decoding the puzzle after identification of the metabolic pathway involved in the case was conducted in level 1,2 and 3 with increasing complexity of puzzles at every level. Following the puzzle activity, A 21-item questionnaire was administered to evaluate the usefulness of the innovation and students’ perceptions towards different learning styles. Also, students’ feedback was obtained through personal interviews for qualitative analysis and thematic analysis was performed.

Results
One hundred and three first year undergraduate medical students participated in the study. Most of the students perceived the METAPAD gaming puzzle to be an effective and innovative style of learning. There was not any significant association between age, gender and acceptance towards the METAPAD gaming puzzle. The predominant type of learning style among the students was multimodal (49.5%). Also, there was no great influence of the learning styles on the overall perception towards the METAPAD gaming puzzle. However, learners emphasized the need to focus more while solving the puzzles.

Conclusion
Students perceive the METAPAD gaming puzzle as an actively engaging teaching-learning method that enhances their creativity, critical thinking and problem-solving abilities. It promotes self-directed learning of complex pathways in biochemistry which helps in remembering and recalling information and improves their learning skills.
Morphological, radiographic, three-dimensional computed tomographic, and histological features of the primary upstroke and downstroke muscles and bones in the domestic duck (Anas platyrhynchos domesticus) and the cattle egret (Bubulcus ibis, Linnaeus, 1758), reflecting the evolutionary transition towards the irreversible flightlessness
Authors: El-Ghazali Hanaa M. , Abdelbaset-Ismail Ahmed , Goda Nehal I. A. , Aref Mohamed 
Published: August 2023

Abstract
Background
The purpose of this study was to explore whether domestication could lead to evolutionary changes towards flightlessness in the domestic duck (Anas platyrhynchos domesticus) compared to the cattle egret (Bubulcus ibis) as a nonflying and flying biological model, respectively. Bones of the pectoral girdle (scapula, clavicle, and coracoid) and the foramen triosseum were comparatively assessed using anatomical, radiographic, and 3D computed tomographic (CT) studies. Additionally, the muscles pectoralis and the supracoracoideus were histologically and immunohistochemically assessed.

Results
Among the differences observed, radiographically, the distance between the paired clavicles was significantly wider (p < 0.05) in the domestic duck (mean ± SD 1.43 ± 0.23 cm) compared with the cattle egret (0.96 ± 0.13 cm). Unlike cattle egrets, there was no connection between the sternum and the hypocladium of furcula in domestic ducks. The scapula, clavicle, coracoid, sternum, and humerus were considerably longer in domestic ducks than in cattle egrets. The foramen triosseum appeared significantly (p < 0.01) wider in domestic ducks (0.7 ± 1.17 cm) compared to cattle egrets (0.49 ± 0.03 cm). Histologically, compared to cattle egrets, the muscle fibers in domestic ducks were loosely connected and contained fewer nuclei and perimysial/endomysial spaces. A higher myoglobin expression was evident in cattle egrets compared with domestic ducks.

Conclusions
Results of this study indicate that the bones and muscles of the pectoral girdle generally show specific morphological and structural changes reflective of the loss of prerequisites associated with flight behavior in domestic ducks due to domestication effects compared to cattle egrets.
Subcutaneous adipose tissue alteration in aging process associated with thyroid hormone signaling
Authors: Zhang Wen-Na , Zhu Hao , Ma Zhen-Wu , Yu Jing , Yang Yun , Lu Xuan-Bei , Lv Yi-Fan , Wang Xiao-Dong 
Published: August 2023

Abstract
Background
Functional changes in subcutaneous adipose tissue (SAT) occur earlier in the aging process and play an important role in the occurrence and development of age-related metabolic diseases. The mechanism of this phenomenon is still unclear, and the change in adipose tissue with age is poorly understood.

Methods
We used transcriptome sequencing (RNA seq) to screen differentially expressed genes at the mRNA level, and analyzed the functional characteristics of the differential genes through GO and KEGG analysis in human SAT of all ages. In order to clarify the specific mechanism of the functional change, we analyzed the chromatin accessibility in the promoter region in the same SAT used in the RNA seq by the assay for transposase-accessible chromatin with high throughput sequencing (ATAC-seq) and obtained the functional genes in SAT changed with age. To verify these changes, we enlarged our sample content of human SAT. The primary mice adipocytes were extracted and stimulated by thyroid hormone of different concentration to construct an animal model, and the expression of the genes were determined through real-time Polymerase Chain Reaction(RT-PCR). The oxygen consumption test and immunofluorescence staining were used to determine the mitochondrial function of SAT.

Results
RNA-seq showed characteristic gene expression of young and old human SAT, in which 331 genes were up-regulated and 349 genes were down-regulated. ATAC-seq, RNA-seq, combined with the mouse prediction model, determined the functional changed characteristics of seven genes. All these genes expressed differently in SAT of different ages, in which, NCF1, NLRP3, DUOX1 showed positive correlation with age; The expression of IFI30, P2RX1, P2RX6, PRODH, however, decreased with age. And all these genes showed dose dependent alternations under treatment of triiodothyroxine in mice SAT. The oxygen consumption rate revealed significant changes of the mitochondrial function and ROS accumulation in human SAT of different ages.

Conclusion
In elderly individuals, the function, in addition to distribution, of SAT undergoes significant changes, primarily in mitochondria, which may be due to insensitivity to thyroid hormone signaling. These results identified seven novel genes regulated by thyroid hormone, exhibiting significant changes in SAT of different age, and are probably related to the dysfunction of the aged SAT due to the mitochondrial damage and ROS accumulation.
Intrinsic disorder in PRAME and its role in uveal melanoma
Authors: Antonietti Michael , Gonzalez David J. Taylor , Djulbegovic Mak , Dayhoff Guy W. , Uversky Vladimir N. , Shields Carol L. , Karp Carol L. 
Published: August 2023

Abstract
Introduction
The PReferentially expressed Antigen in MElanoma (PRAME) protein has been shown to be an independent biomarker for increased risk of metastasis in Class 1 uveal melanomas (UM). Intrinsically disordered proteins and regions of proteins (IDPs/IDPRs) are proteins that do not have a well-defined three-dimensional structure and have been linked to neoplastic development. Our study aimed to evaluate the presence of intrinsic disorder in PRAME and the role these structureless regions have in PRAME( +) Class 1 UM.

Methods
A bioinformatics study to characterize PRAME’s propensity for the intrinsic disorder. We first used the AlphaFold tool to qualitatively assess the protein structure of PRAME. Then we used the Compositional Profiler and a set of per-residue intrinsic disorder predictors to quantify the intrinsic disorder. The Database of Disordered Protein Prediction (D2P2) platform, IUPred, FuzDrop, fIDPnn, AUCpred, SPOT-Disorder2, and metapredict V2 allowed us to evaluate the potential functional disorder of PRAME. Additionally, we used the Search Tool for the Retrieval of Interacting Genes (STRING) to analyze PRAME's potential interactions with other proteins.

Results
Our structural analysis showed that PRAME contains intrinsically disordered protein regions (IDPRs), which are structureless and flexible. We found that PRAME is significantly enriched with serine (p-value < 0.05), a disorder-promoting amino acid. PRAME was found to have an average disorder score of 16.49% (i.e., moderately disordered) across six per-residue intrinsic disorder predictors. Our IUPred analysis revealed the presence of disorder-to-order transition (DOT) regions in PRAME near the C-terminus of the protein (residues 475–509). The D2P2 platform predicted a region from approximately 140 and 175 to be highly concentrated with post-translational modifications (PTMs). FuzDrop predicted the PTM hot spot of PRAME to be a droplet-promoting region and an aggregation hotspot. Finally, our analysis using the STRING tool revealed that PRAME has significantly more interactions with other proteins than expected for randomly selected proteins of the same size, with the ability to interact with 84 different partners (STRING analysis result: p-value < 1.0 × 10–16; model confidence: 0.400).

Conclusion
Our study revealed that PRAME has IDPRs that are possibly linked to its functionality in the context of Class 1 UM. The regions of functionality (i.e., DOT regions, PTM sites, droplet-promoting regions, and aggregation hotspots) are localized to regions of high levels of disorder. PRAME has a complex protein–protein interaction (PPI) network that may be secondary to the structureless features of the polypeptide. Our findings contribute to our understanding of UM and suggest that IDPRs and DOT regions in PRAME may be targeted in developing new therapies for this aggressive cancer.