bluuebunny/crossref_metadata_2025_split huggingface dataset:
Engineered extracellular vesicles carrying let-7a-5p for alleviating inflammation in acute lung injury
Authors: Chen Sin-Yu , Chen Yi-Ling , Li Po-Chen , Cheng Tai-Shan , Chu Yeh-Shiu , Shen Yi-Shan , Chen Hsin-Tung , Tsai Wei-Ni , Huang Chien-Ling , Sieber Martin , Yeh Yuan-Chieh , Liu Hsiao-Sheng , Chiang Chi-Ling , Chang Chih-Hung , Lee Andrew S. , Tseng Yen-Han , Lee Ly James , Liao Hsiu-Jung , Yip Hon-Kan , Huang Chi-Ying F. 
Published: March 2024

Abstract
Background
Acute lung injury (ALI) is a life-threatening respiratory condition characterized by severe inflammation and lung tissue damage, frequently causing rapid respiratory failure and long-term complications. The microRNA let-7a-5p is involved in the progression of lung injury, inflammation, and fibrosis by regulating immune cell activation and cytokine production. This study aims to use an innovative cellular electroporation platform to generate extracellular vesicles (EVs) carring let-7a-5p (EV-let-7a-5p) derived from transfected Wharton’s jelly-mesenchymal stem cells (WJ-MSCs) as a potential gene therapy for ALI.

Methods
A cellular nanoporation (CNP) method was used to induce the production and release of EV-let-7a-5p from WJ-MSCs transfected with the relevant plasmid DNA. EV-let-7a-5p in the conditioned medium were isolated using a tangential flow filtration (TFF) system. EV characterization followed the minimal consensus guidelines outlined by the International Society for Extracellular Vesicles. We conducted a thorough set of therapeutic assessments, including the antifibrotic effects using a transforming growth factor beta (TGF-β)-induced cell model, the modulation effects on macrophage polarization, and the influence of EV-let-7a-5p in a rat model of hyperoxia-induced ALI.

Results
The CNP platform significantly increased EV secretion from transfected WJ-MSCs, and the encapsulated let-7a-5p in engineered EVs was markedly higher than that in untreated WJ-MSCs. These EV-let-7a-5p did not influence cell proliferation and effectively mitigated the TGF-β-induced fibrotic phenotype by downregulating SMAD2/3 phosphorylation in LL29 cells. Furthermore, EV-let-7a-5p regulated M2-like macrophage activation in an inflammatory microenvironment and significantly induced interleukin (IL)-10 secretion, demonstrating their modulatory effect on inflammation. Administering EVs from untreated WJ-MSCs slightly improved lung function and increased let-7a-5p expression in plasma in the hyperoxia-induced ALI rat model. In comparison, EV-let-7a-5p significantly reduced macrophage infiltration and collagen deposition while increasing IL-10 expression, causing a substantial improvement in lung function.

Conclusion
This study reveals that the use of the CNP platform to stimulate and transfect WJ-MSCs could generate an abundance of let-7a-5p-enriched EVs, which underscores the therapeutic potential in countering inflammatory responses, fibrotic activation, and hyperoxia-induced lung injury. These results provide potential avenues for developing innovative therapeutic approaches for more effective interventions in ALI.
Analysis of affordability differences for rare diseases in China: a comparison across disease types and regions
Authors: Chen Ye , Chen Xinyang , Deng Yi , Ding Jinxi 
Published: March 2024

Abstract
Background
China has implemented policies to make rare diseases more affordable. While previous studies evaluated overall affordability, few have examined affordability differences across regions and disease types. Given the vastness of China and varying medical policies across cities, this study assesses the affordability of rare diseases based on China’s First List of Rare Diseases (CFLRD), National Reimbursement Drug List (NRDL), and outpatient chronic and special disease policies in each prefecture.

Method
Six rare diseases were selected and the average annual treatment cost of all relevant drugs in NRDL was calculated for each disease. Based on the WHO/HAI standardized approach, the study analyzed 289 cities with outpatient chronic and special disease policies, measured the security levels by the actual reimbursement ratio of Basic Medical Insurance (BMI) and affordability by the ratio of individual expenses after reimbursement to the annual disposable income of urban residents in the province. The security levels and affordability differences across disease types and provinces were analyzed using the Mann-Whitney U test and the K-W test.

Result
The affordability of rare diseases varied significantly on the disease types and annual treatment cost. Diseases with an annual treatment cost below 100 000 yuan are affordable to all prefectures even with low reimbursement rates, while those with a higher treatment cost were not affordable in at least 80% of prefectures even though the reimbursement ratio is high. The affordability of the same disease varies significantly across provinces and municipalities. Outpatient chronic and special diseases insurance and critical illness insurance, and the inconsistencies between them, result in regional differences.

Conclusion
Although China has made progress in improving the affordability of rare diseases, significant differences persist between cities and diseases. The study suggests the optimization of the BMI system and explores independent funds and innovative insurance models to enhance the affordability of rare diseases, particularly those with extremely high treatment costs.
Organochlorine pesticides and risk of papillary thyroid cancer in U.S. military personnel: a nested case-control study
Authors: Rusiecki Jennifer A. , McAdam Jordan , Denic-Roberts Hristina , Sjodin Andreas , Davis Mark , Jones Richard , Hoang Thanh D. , Ward Mary H. , Ma Shuangge , Zhang Yawei 
Published: March 2024

Abstract
Background
The effects of organochlorine pesticide (OCP) exposure on the development of human papillary thyroid cancer (PTC) are not well understood. A nested case-control study was conducted with data from the U.S. Department of Defense Serum Repository (DoDSR) cohort between 2000 and 2013 to assess associations of individual OCPs serum concentrations with PTC risk.

Methods
This study included 742 histologically confirmed PTC cases (341 females, 401 males) and 742 individually-matched controls with pre-diagnostic serum samples selected from the DoDSR. Associations between categories of lipid-corrected serum concentrations of seven OCPs and PTC risk were evaluated for classical PTC and follicular PTC using conditional logistic regression, adjusted for body mass index category and military branch to compute odds ratios (OR) and 95% confidence intervals (CIs). Effect modification by sex, birth cohort, and race was examined.

Results
There was no evidence of associations between most of the OCPs and PTC, overall or stratified by histological subtype. Overall, there was no evidence of an association between hexachlorobenzene (HCB) and PTC, but stratified by histological subtype HCB was associated with significantly increased risk of classical PTC (third tertile above the limit of detection (LOD) vs. <LOD, OR = 1.61, 95% CI, 1.09, 2.38; p for trend = 0.05) and significantly decreased risk of follicular variant PTC (third tertile above the limit of detection (LOD) vs. <LOD, OR = 0.38, 95% CI, 0.16, 0.91; p for trend = 0.04). Further stratified by sex, risk of classical PTC was higher for females (third tertile above LOD vs. <LOD, OR = 2.23, 95% CI: 1.23, 4.06; p-trend = 0.02) than for males (OR = 1.22, 95%CI: 0.72–2.08; p-trend = 0.56), though the test for interaction by sex was not statistically significant (p-interaction = 0.30). Similarly, β-hexachlorocyclohexane (β-HCCH) was associated with a higher risk for classical PTC for women with concentrations ≥LOD versus <LOD (OR = 1.76, 95% CI: 1.07, 2.89), while the effects were null for men. There were no consistent trends when stratified by race or birth year.

Conclusions
The U.S. Environmental Protection Agency has classified HCB and other OCPs we studied here as probable human carcinogens. Our findings of increased risks for classical PTC associated with increased concentrations of HCB and β-HCCH, which were stronger among females, should be replicated in future studies of other populations.
Cre-LoxP and tamoxifen-induced deletion of ovarian quiescin sulfhydryl oxidase 2 showed disruption of ovulatory activity in mice
Authors: Chen Shih-Yun , Wang Tse-En , Lee Wei-Yun , Yang Ya-Yi , Lai Hong-Chun , Matsuda Fuko , Kosek Haruhiko , Chen You-Tzung , Li Sheng-Hsiang , Tsai Pei-Shiue 
Published: March 2024

Abstract
Background
Quiescin sulfhydryl oxidase 2 (QSOX2) is a flavin adenine dinucleotide-dependent sulfhydryl oxidase that is known to be involved in protein folding, cell growth regulation, and redox state modification through oxidative activities. Earlier studies demonstrated the tissue and cellular localization of QSOX2 in the male reproductive tract, as well as the highly-regulated mechanism of QSOX2 protein synthesis and expression through the coordinated action of testosterone and epididymal-enriched amino acid, glutamate. However, the presence and the functions of QSOX2 in female reproduction are unknown. In this study, we applied the Cre-loxP gene manipulation system to generate the heterozygous and homozygous Qsox2 knockout mice and examined its effects on ovarian function.

Results
We demonstrated that QSOX2 was detected in the follicle-supporting cells (granulosa and cumulus cells) of ovarian follicles of all stages but was absent in the corpus luteum, suggesting its supportive role in folliculogenesis. In comparison with reproductive organogenesis in wild-type mice, there was no difference in testicular and epididymal structure in male Qsox2 knockout; however, Qsox2 knockout disrupted the regular ovulation process in female mice as a drastic decrease in the formation of the corpus luteum was detected, and no pregnancy was achieved when mating males with homozygous Qsox2 knockout females. RNAseq analyses further revealed that Qsox2 knockout altered critical signaling pathways and genes that are responsible for maintaining ovarian functions.

Conclusion
Our data demonstrated for the first time that Qsox2 is critical for ovarian function in mice.
Monocyte state 1 (MS1) cells in critically ill patients with sepsis or non-infectious conditions: association with disease course and host response
Authors: Leite Giuseppe G. F. , de Brabander Justin , Michels Erik H. A. , Butler Joe M. , Cremer Olaf L. , Scicluna Brendon P. , Sweeney Timothy E. , Reyes Miguel , Salomao Reinaldo , Peters-Sengers Hessel , van der Poll Tom 
Published: March 2024

Abstract
Background
Sepsis is a life-threatening condition arising from an aberrant host response to infection. Recent single-cell RNA sequencing investigations identified an immature bone-marrow-derived CD14+ monocyte phenotype with immune suppressive properties termed “monocyte state 1” (MS1) in patients with sepsis. Our objective was to determine the association of MS1 cell profiles with disease presentation, outcomes, and host response characteristics.

Methods
We used the transcriptome deconvolution method (CIBERSORTx) to estimate the percentage of MS1 cells from blood RNA profiles of patients with sepsis admitted to the intensive care unit (ICU). We compared these profiles to ICU patients without infection and to healthy controls. Host response dysregulation was further studied by gene co-expression network and gene set enrichment analyses of blood leukocytes, and measurement of 15 plasma biomarkers indicative of pathways implicated in sepsis pathogenesis.

Results
Sepsis patients (n = 332) were divided into three equally-sized groups based on their MS1 cell levels (low, intermediate, and high). MS1 groups did not differ in demographics or comorbidities. The intermediate and high MS1 groups presented with higher disease severity and more often had shock. MS1 cell abundance did not differ between survivors and non-survivors, or between patients who did or did not acquire a secondary infection. Higher MS1 cell percentages were associated with downregulation of lymphocyte-related and interferon response genes in blood leukocytes, with concurrent upregulation of inflammatory response pathways, including tumor necrosis factor signaling via nuclear factor-κB. Previously described sepsis host response transcriptomic subtypes showed different MS1 cell abundances, and MS1 cell percentages positively correlated with the “quantitative sepsis response signature” and “molecular degree of perturbation” scores. Plasma biomarker levels, indicative of inflammation, endothelial cell activation, and coagulation activation, were largely similar between MS1 groups. In ICU patients without infection (n = 215), MS1 cell percentages and their relation with disease severity, shock, and host response dysregulation were highly similar to those in sepsis patients.

Conclusions
High MS1 cell percentages are associated with increased disease severity and shock in critically ill patients with sepsis or a non-infectious condition. High MS1 cell abundance likely indicates broad immune dysregulation, entailing not only immunosuppression but also anomalies reflecting exaggerated inflammatory responses.

Graphical abstract
Association between tranexamic acid administration and mortality based on the trauma phenotype: a retrospective analysis of a nationwide trauma registry in Japan
Authors: Tachino Jotaro , Seno Shigeto , Matsumoto Hisatake , Kitamura Tetsuhisa , Hirayama Atsushi , Nakao Shunichiro , Katayama Yusuke , Ogura Hiroshi , Oda Jun 
Published: March 2024

Abstract
Background
In trauma systems, criteria for individualised and optimised administration of tranexamic acid (TXA), an antifibrinolytic, are yet to be established. This study used nationwide cohort data from Japan to evaluate the association between TXA and in-hospital mortality among all patients with blunt trauma based on clinical phenotypes (trauma phenotypes).

Methods
A retrospective analysis was conducted using data from the Japan Trauma Data Bank (JTDB) spanning 2019 to 2021.

Results
Of 80,463 patients with trauma registered in the JTDB, 53,703 met the inclusion criteria, and 8046 (15.0%) received TXA treatment. The patients were categorised into eight trauma phenotypes. After adjusting with inverse probability treatment weighting, in-hospital mortality of the following trauma phenotypes significantly reduced with TXA administration: trauma phenotype 1 (odds ratio [OR] 0.68 [95% confidence interval [CI] 0.57–0.81]), trauma phenotype 2 (OR 0.73 [0.66–0.81]), trauma phenotype 6 (OR 0.52 [0.39–0.70]), and trauma phenotype 8 (OR 0.67 [0.60–0.75]). Conversely, trauma phenotypes 3 (OR 2.62 [1.98–3.47]) and 4 (OR 1.39 [1.11–1.74]) exhibited a significant increase in in-hospital mortality.

Conclusions
This is the first study to evaluate the association between TXA administration and survival outcomes based on clinical phenotypes. We found an association between trauma phenotypes and in-hospital mortality, indicating that treatment with TXA could potentially influence this relationship. Further studies are needed to assess the usefulness of these phenotypes.

Graphical abstract
DANCE: a deep learning library and benchmark platform for single-cell analysis
Authors: Ding Jiayuan , Liu Renming , Wen Hongzhi , Tang Wenzhuo , Li Zhaoheng , Venegas Julian , Su Runze , Molho Dylan , Jin Wei , Wang Yixin , Lu Qiaolin , Li Lingxiao , Zuo Wangyang , Chang Yi , Xie Yuying , Tang Jiliang 
Published: March 2024

AbstractDANCE is the first standard, generic, and extensible benchmark platform for accessing and evaluating computational methods across the spectrum of benchmark datasets for numerous single-cell analysis tasks. Currently, DANCE supports 3 modules and 8 popular tasks with 32 state-of-art methods on 21 benchmark datasets. People can easily reproduce the results of supported algorithms across major benchmark datasets via minimal efforts, such as using only one command line. In addition, DANCE provides an ecosystem of deep learning architectures and tools for researchers to facilitate their own model development. DANCE is an open-source Python package that welcomes all kinds of contributions.
Determine the factors affecting the time to recovery of children with bacterial meningitis at Jigjiga university referral hospital in the Somali Regional State of Ethiopia: using the parametric shared frailty and AFT models
Authors: Adawe Daud Hussein , Mengistie Dagne Tesfaye 
Published: March 2024

Abstract
Background
Neisseria meningitides, Streptococcus pneumonia, and hemophilic influenza type B are frequently linked to bacterial meningitis (BM) in children. It’s an infectious sickness that kills and severely mobilizes children. For a variety of reasons, bacterial meningitis remains a global public health concern; most cases and deaths are found in Sub-Saharan Africa, particularly in Ethiopia. Even though vaccination has made BM more preventable, children worldwide are still severely harmed by this serious illness. Age, sex, and co-morbidity are among the risk variables for BM that have been found. Therefore, the main objective of this study was to identify the variables influencing the time to recovery for children with bacterial meningitis at Jigjiga University referral hospital in the Somali regional state of Ethiopia.

Method
A retrospective cohort of 535 children with bacterial meningitis who received antibiotic treatment was the subject of this study. Parametric Shared Frailty ty and the AFT model were employed with log likelihood, BIC, and AIC methods of model selection. The frailty models all employed the patients' kebele as a clustering factor.

Results
The number of cases of BM declined in young children during the duration of the 2 year, 11 month study period, but not in the elderly. Streptococcus pneumonia (50%), hemophilic influenza (30.5%), and Neisseria meningitides (15%) were the most frequent causes of BM. The time to recovery of patients from bacteria was significantly influenced by the covariates male patients (ϕ = 0.927; 95% CI (0.866, 0.984); p-value = 0.014), patients without a vaccination history (ϕ = 0.898; 95% CI (0.834, 0.965); P value = 0.0037), and patients who were not breastfeeding (ϕ = 0.616; 95% CI (0.404, 0.039); P-value = 0.024). The recovery times for male, non-breastfed children with bacterial patients are 7.9 and 48.4% shorter, respectively. In contrast to children with comorbidity, the recovery time for children without comorbidity increased by 8.7%.

Conclusion
Age group, sex, vaccination status, co-morbidity, breastfeeding, and medication regimen were the main determinant factors for the time to recovery of patients with bacterial meningitis. Patients with co-morbidities require the doctor at Jigjiga University Referral Hospital to pay close attention to them.
Beneficial effects of cannabidiol from Cannabis
Authors: Lee Sullim , Lee Yunjeong , Kim Yunseo , Kim Hyunji , Rhyu Haerim , Yoon Kyoungmi , Lee Chang-Dae , Lee Sanghyun 
Published: March 2024

AbstractCannabis, traditionally used for recreation due to psychoactive compounds in its leaves, flowers, and seeds, has not been thoroughly explored for potential therapeutic benefits. Δ9-trans-Tetrahydrocannabinol, a key cannabinoid in cannabis, causes hallucinogenic effects and delirium symptoms. In contrast, cannabidiol (CBD) does not induce hallucinations and has shown effectiveness in treating symptoms of various rare, incurable diseases. Cannabis exhibits neuroprotective, anti-inflammatory, anti-thrombotic, anti-bacterial, analgesic, and antiepileptic properties, recently attracting more attention. This review aims to summarize comprehensively the impact of cannabis on human health, focusing on endocannabinoids and their receptors. It also delves into recent CBD research advancements, highlighting the compound’s potential medical applications. Overall, this paper provides valuable insights into the prospective development of medical cannabis, with a particular emphasis on CBD.
The potential value of ultrasound in predicting local refractory/relapse events in primary thyroid lymphoma patients
Authors: Ji Jiang , Gao Luying , Liu Ruifeng , Shi Xinlong , Ma Liyuan , Pan Aonan , Li Naishi , Liu Chunhao , Li Xiaoyi , Yang Meng , Xia Yu , Jiang Yuxin 
Published: March 2024

Abstract
Background
Primary thyroid lymphoma (PTL) is a rare malignant disorder, and ultrasound plays an important role in PTL diagnosis and follow-up surveillance. Prediction of refractory/relapse events in PTL patients is an essential issue, yet no ultrasonic PTL features have been discovered to be related to refractory/local relapse events.

Methods
From January 2008 to September 2022, newly diagnosed PTL patients in our center who underwent standard first-line treatment and received an ultrasound examination before treatment were enrolled. Data regarding patients’ clinical and sonographic features, as well as their therapeutic responses were collected. Subjects with an ideal prognosis were compared to those with refractory/relapse events.

Results
In total, 37 PTL patients were analyzed, including 26 with diffuse large B-cell lymphoma, 2 with follicular lymphoma and 9 with mucosa-associated lymphoid tissue lymphoma. During the median follow-up of 25 months, 30 patients obtained a complete response, 4 were refractory patients, and 3 experienced local relapse. No significant difference was detected in the baseline clinical characteristics between patients with an ideal prognosis and those with refractory/local relapse events. In terms of sonographic features, however, an event-free survival (EFS) curve comparison revealed that patients with bilobar enlargement (defined as an anterior-posterior diameter > 2.5 cm on both sides of thyroid lobes) had a poorer EFS than those without (P < 0.0001), and patients with diffuse type had a poorer EFS than those with mixed/nodular types (P = 0.043). No significant difference was observed in EFS between patients with or without signs of suspicious cervical lymph node metastasis, rich blood signal distribution or symptoms of trachea compression.

Conclusions
PTL patients with an anterior-posterior diameter > 2.5 cm for both thyroid lobes or PTL patients of the diffuse ultrasound type could be prone to refractory/local relapse events.
How is GPS used? Understanding navigation system use and its relation to spatial ability
Authors: Topete Alexis , He Chuanxiuyue , Protzko John , Schooler Jonathan , Hegarty Mary 
Published: March 2024

AbstractGiven how commonly GPS is now used in everyday navigation, it is surprising how little research has been dedicated to investigating variations in its use and how such variations may relate to navigation ability. The present study investigated general GPS dependence, how people report using GPS in various navigational scenarios, and the relationship between these measures and spatial abilities (assessed by self-report measures and the ability to learn the layout of a novel environment). GPS dependence is an individual’s perceived need to use GPS in navigation, and GPS usage is the frequency with which they report using different functions of GPS. The study also assessed whether people modulate reported use of GPS as a function of their familiarity with the location in which they are navigating. In 249 participants over two preregistered studies, reported GPS dependence was negatively correlated with objective navigation performance and self-reported sense of direction, and positively correlated with spatial anxiety. Greater reported use of GPS for turn-by-turn directions was associated with a poorer sense of direction and higher spatial anxiety. People reported using GPS most frequently for time and traffic estimation, regardless of ability. Finally, people reported using GPS less, regardless of ability, when they were more familiar with an environment. Collectively these findings suggest that people moderate their use of GPS, depending on their knowledge, ability, and confidence in their own abilities, and often report using GPS to augment rather than replace spatial environmental knowledge.