bluuebunny/crossref_metadata_2025_split huggingface dataset:
MSC-derived mitochondria promote axonal regeneration via Atf3 gene up-regulation by ROS induced DNA double strand breaks at transcription initiation region
Authors: Zhang Yingchi , Xu Tao , Xie Jie , Wu Hua , Hu Weihua , Yuan Xuefeng 
Published: April 2024

Abstract
Background
The repair of peripheral nerve injury poses a clinical challenge, necessitating further investigation into novel therapeutic approaches. In recent years, bone marrow mesenchymal stromal cell (MSC)-derived mitochondrial transfer has emerged as a promising therapy for cellular injury, with reported applications in central nerve injury. However, its potential therapeutic effect on peripheral nerve injury remains unclear.

Methods
We established a mouse sciatic nerve crush injury model. Mitochondria extracted from MSCs were intraneurally injected into the injured sciatic nerves. Axonal regeneration was observed through whole-mount nerve imaging. The dorsal root ganglions (DRGs) corresponding to the injured nerve were harvested to test the gene expression, reactive oxygen species (ROS) levels, as well as the degree and location of DNA double strand breaks (DSBs).

Results
The in vivo experiments showed that the mitochondrial injection therapy effectively promoted axon regeneration in injured sciatic nerves. Four days after injection of fluorescently labeled mitochondria into the injured nerves, fluorescently labeled mitochondria were detected in the corresponding DRGs. RNA-seq and qPCR results showed that the mitochondrial injection therapy enhanced the expression of Atf3 and other regeneration-associated genes in DRG neurons. Knocking down of Atf3 in DRGs by siRNA could diminish the therapeutic effect of mitochondrial injection. Subsequent experiments showed that mitochondrial injection therapy could increase the levels of ROS and DSBs in injury-associated DRG neurons, with this increase being correlated with Atf3 expression. ChIP and Co-IP experiments revealed an elevation of DSB levels within the transcription initiation region of the Atf3 gene following mitochondrial injection therapy, while also demonstrating a spatial proximity between mitochondria-induced DSBs and CTCF binding sites.

Conclusion
These findings suggest that MSC-derived mitochondria injected into the injured nerves can be retrogradely transferred to DRG neuron somas via axoplasmic transport, and increase the DSBs at the transcription initiation regions of the Atf3 gene through ROS accumulation, which rapidly release the CTCF-mediated topological constraints on chromatin interactions. This process may enhance spatial interactions between the Atf3 promoter and enhancer, ultimately promoting Atf3 expression. The up-regulation of Atf3 induced by mitochondria further promotes the expression of downstream regeneration-associated genes and facilitates axon regeneration.
Pan-cancer analysis implicates novel insights of lactate metabolism into immunotherapy response prediction and survival prognostication
Authors: Chen Dongjie , Liu Pengyi , Lu Xiongxiong , Li Jingfeng , Qi Debin , Zang Longjun , Lin Jiayu , Liu Yihao , Zhai Shuyu , Fu Da , Weng Yuanchi , Li Hongzhe , Shen Baiyong 
Published: April 2024

Abstract
Background
Immunotherapy has emerged as a potent clinical approach for cancer treatment, but only subsets of cancer patients can benefit from it. Targeting lactate metabolism (LM) in tumor cells as a method to potentiate anti-tumor immune responses represents a promising therapeutic strategy.

Methods
Public single-cell RNA-Seq (scRNA-seq) cohorts collected from patients who received immunotherapy were systematically gathered and scrutinized to delineate the association between LM and the immunotherapy response. A novel LM-related signature (LM.SIG) was formulated through an extensive examination of 40 pan-cancer scRNA-seq cohorts. Then, multiple machine learning (ML) algorithms were employed to validate the capacity of LM.SIG for immunotherapy response prediction and survival prognostication based on 8 immunotherapy transcriptomic cohorts and 30 The Cancer Genome Atlas (TCGA) pan-cancer datasets. Moreover, potential targets for immunotherapy were identified based on 17 CRISPR datasets and validated via in vivo and in vitro experiments.

Results
The assessment of LM was confirmed to possess a substantial relationship with immunotherapy resistance in 2 immunotherapy scRNA-seq cohorts. Based on large-scale pan-cancer data, there exists a notably adverse correlation between LM.SIG and anti-tumor immunity as well as imbalance infiltration of immune cells, whereas a positive association was observed between LM.SIG and pro-tumorigenic signaling. Utilizing this signature, the ML model predicted immunotherapy response and prognosis with an AUC of 0.73/0.80 in validation sets and 0.70/0.87 in testing sets respectively. Notably, LM.SIG exhibited superior predictive performance across various cancers compared to published signatures. Subsequently, CRISPR screening identified LDHA as a pan-cancer biomarker for estimating immunotherapy response and survival probability which was further validated using immunohistochemistry (IHC) and spatial transcriptomics (ST) datasets. Furthermore, experiments demonstrated that LDHA deficiency in pancreatic cancer elevated the CD8+ T cell antitumor immunity and improved macrophage antitumoral polarization, which in turn enhanced the efficacy of immunotherapy.

Conclusions
We unveiled the tight correlation between LM and resistance to immunotherapy and further established the pan-cancer LM.SIG, holds the potential to emerge as a competitive instrument for the selection of patients suitable for immunotherapy.
Assessment of the in vitro acaricidal activity of Bravecto® (fluralaner) and a proposed orange oil-based formulation vehicle for the treatment of Sarcoptes scabiei
Authors: Takano Kotaro , Carver Scott , Vermaak Yolandi , Fischer Katja , Harvey Robert J. , Mounsey Kate E. 
Published: April 2024

AbstractBackgroundSarcoptic mange is a serious animal welfare concern in bare-nosed wombats (Vombatus ursinus). Fluralaner (Bravecto®) is a novel acaricide that has recently been utilised for treating mange in wombats. The topical ‘spot-on’ formulation of fluralaner can limit treatment delivery options in situ, but dilution to a volume for ‘pour-on’ delivery is one practicable solution. This study investigated the in vitro acaricidal activity of Bravecto, a proposed essential oil-based diluent (Orange Power®), and two of its active constituents, limonene and citral, againstSarcoptes scabiei.MethodsSarcoptes scabieiwere sourced from experimentally infested pigs. In vitro assays were performed to determine the lethal concentration (LC50) and survival time of the mites when exposed to varying concentrations of the test solutions.ResultsAll compounds were highly effective at killing mites in vitro. The LC50values of Bravecto, Orange Power, limonene and citral at 1 h were 14.61 mg/ml, 4.50%, 26.53% and 0.76%, respectively. The median survival times of mites exposed to undiluted Bravecto, Orange Power and their combination were 15, 5 and 10 min, respectively. A pilot survival assay of mites collected from a mange-affected wombat showed survival times of < 10 min when exposed to Bravecto and Orange Power and 20 min when exposed to moxidectin.ConclusionsThese results confirm the acaricidal properties of Bravecto, demonstrate acaricidal properties of Orange Power and support the potential suitability of Orange Power and its active constituents as a diluent for Bravecto. As well as killing mites via direct exposure, Orange Power could potentially enhance the topical delivery of Bravecto to wombats by increasing drug penetration in hyperkeratotic crusts. Further research evaluating the physiochemical properties and modes of action of Orange Power and its constituents as a formulation vehicle would be of value.Graphical Abstract
Sex-specific disparities in disease activity scores among patients with axial spondyloarthritis and their implications for evaluating the response to tumor necrosis factor alpha inhibitor therapy
Authors: Lee Seulkee , Kang Seonyoung , Kim Hyungjin , Lee Jaejoon , Kim Min-Ji , Cha Hoon-Suk 
Published: April 2024

Abstract
Background
We aimed to investigate whether there are sex differences in disease activity measures among patients with axial spondyloarthritis (axSpA) and to determine any potential impact on the assessment of treatment responses to tumor necrosis factor alpha inhibitors (TNFi).

Methods
Using the Korean College of Rheumatology Biologics and Targeted Therapy (KOBIO) registry data, we compared sex differences in changes in the Bath Ankylosing Spondylitis Disease Activity Score (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS) levels at baseline and one year after TNFi initiation in patients with axSpA.

Results
This study included 1,753 patients with axSpA who started or changed TNFi, of whom 1,343 (76.6%) were male. At baseline, the mean BASDAI and ASDAS scores of all patients were 5.98 and 3.6, respectively. The BASDAI changes between baseline and the one-year follow-up were independently associated with sex (𝛽 = 0.343, p = 0.011), whereas ASDAS was not (𝛽 = 0.079, p = 0.235). When judging the effect of TNFi at one-year of treatment, male patients were more likely to be assessed as effective by the BASDAI-based criterion (ΔBASDAI ≥ 50% or ≥ 2; OR 1.700, 95% CI 1.200–2.406), while the ASDAS-based criterion (ΔASDAS ≥ 1.1) showed no significant difference between sexes (OR 0.993, 95% CI 0.678–1.455), after adjusting for other baseline characteristics.

Conclusions
The changes in disease activity before and after TNFi use were significantly different between sexes when measured by BASDAI, but not ASDAS. TNFi treatment effects may be interpreted differently between sexes depending on the disease activity measure used.
Effect of the SARS-CoV-2 pandemic on metabolic control in patients with type 2 diabetes: a 5-year cohort follow-up managed by a dynamic multidisciplinary team in Northeastern Mexico
Authors: Morales-Rodriguez Devany Paola , González-Cantú Arnulfo , Garza-Silva Arnulfo , Rivera-Cavazos Andrea , Fernández-Chau Iván Francisco , Cepeda-Medina Andrea Belinda , Sanz-Sánchez Miguel Angel , del Rio-Parra Gerardo Francisco , Torres-Fuentes María Angelina , Rodriguez-Puente Miguel Assael , Romero-Ibarguengoitia Maria Elena 
Published: April 2024

Abstract
Background
The SARS-CoV-2 pandemic brought a radical shift in the healthcare system and suboptimal care for vulnerable patients, such as those with Type 2 Diabetes Mellitus (T2D). Therefore, we compared metabolic control and macro/microvascular complications of patients with T2D before and throughout the three-year SARS-CoV-2 pandemic.

Research design and methods
A retrospective observational cohort of subjects with T2D studied from 2018 to 2022 in Northern Mexico was treated by a dynamic multidisciplinary team. Levels of Glycated hemoglobin (HbA1c), fasting serum glucose (FG), LDL-Cholesterol (LDL-C), blood pressure (BP), albuminuria, triglycerides, Body Mass Index (BMI), and FIB-4 score, micro and macrovascular complications were evaluated.

Results
A total of 999 patients were studied, 51.7% males with a mean (SD) age of 60.1 (12.7) years. Adequate glycemic control based on HbA1c increased by 15.2% and 42.3% in FSG (p < 0.001) between the beginning 2018 and the end of 2022. LDL-C control decreased by 5.1% between 2018 and 2022 (p < 0.001). Systolic BP control decreased by 2.6% (p < 0.001), whereas diastolic BP control increased by 1.8% (p = 0.01) between 2018 and 2022. Albuminuria control increased by 8.5% (p = 0.002). When comparing the Area Under the Curve (AUC) of metabolic parameters between patients who developed SARS-CoV-2 vs. those who did not, AUC was statistically higher in those who developed SARS-CoV-2 (p < 0.05). Diabetic neuropathy was the most prevalent microvascular complication (n = 35; 3.6%); ischemic heart disease was the most frequent macrovascular complication (n = 11;1.1%).

Conclusions
A multidisciplinary dynamic team that adapts to the pandemic SARS-CoV-2 maintains and increases metabolic control in subjects with type 2 diabetes in Mexico. This represents a low percentage of chronic complications. The AUC of metabolic parameters of subjects with SARS-CoV-2 infection is higher, reflecting more variability in metabolic control.

Graphical Abstract
Evaluating Night-Eating Syndrome in bariatric surgery patients: A cross-sectional study
Authors: Almuammar Sarah , Aljaaly Elham , Alqarni Lama , Alazwari Hadeel , Alsubhi Ruba , Alatawi Nouf 
Published: April 2024

Abstract
Background
Night-Eating Syndrome (NES) is a complex eating disorder that has gained recognition in the context of bariatric surgery. However, its prevalence and associated factors in this specific patient population remain understudied, particularly in the Saudi Arabian context.

Methods
This cross-sectional study was conducted at King Abdulaziz University Hospital in Jeddah, Saudi Arabia, from June to November 2022. Adult patients who had undergone bariatric surgery with a postoperative follow-up of 6 months were included. NES was assessed using the Night Eating Questionnaire (NEQ).

Results
A total of 154 patients were enrolled in the study, with a mean age of 38.8 ± 11.4 years. The mean BMI before surgery was 44.8 ± 8.2 kg/m2, which reduced to 28.9 ± 5.8 kg/m2 post-surgery. Of these, 52 patients (33.8%) met the criteria for NES based on NEQ scores. The prevalence of NES was significantly higher among female patients, with 35 out of 83 females (42.2%) compared to 17 out of 71 males (23.9%) experiencing NES. While NES was not significantly associated with age, nationality, diet adherence, BMI, or surgery type, chronic diseases—particularly diabetes—emerged as significant risk factors for NES in post-bariatric surgery patients.

Conclusion
NES is a prevalent concern among post-bariatric surgery patients, with distinct associations with gender and chronic diseases, particularly diabetes. This study provides valuable insights into NES prevalence and its risk factors in the Saudi Arabian context, highlighting the importance of addressing eating disorders within the framework of bariatric surgery care.
A study about the impact of indoor air pollution on cognitive function among middle-aged and older adult people in India
Authors: Saha Subhadeep , Das Priya , Das Tanu , Das Partha , Roy Tamal Basu 
Published: April 2024

Abstract
Background
In the 21st century, people still use solid fuel for cooking at home, resulting in poor indoor air quality. Prolonged exposure to such conditions may negatively affect one’s cognitive function. So, the present study examines the possible association between IAP and the cognitive function of individuals aged 45 years or above in India.

Methods
The study utilizes secondary data, procured from the longitudinal ageing study in India (2017-18). Treatment effects through regression-adjusted models were applied to represent the association between IAP and cognitive health and the results are represented by beta coefficient (β). Three separate models with a 95% confidence interval adjusting with the other factors like housing environment, individual and behavioural were framed.

Results
The study revealed that households without a separate kitchen (β = -0.64; 95%CI: -0.90 to -0.39) and electricity (β = -0.97; 95%CI: -1.34 to -0.61) significantly affect cognitive strength. Cognitive decline is likely more pronounced among older adults (β = -1.19; 95%CI: -1.42 to -0.96) than the middle-aged population. Moreover, the cognitive ability of rural residents (β = -1.11; 95%CI: -1.49 to -0.73) and women (β = -2.05; 95%CI: -2.29 to -1.81) is negatively associated with IAP exposure. Older adults with no reading habits (β = -6.28; 95%CI: -6.72; to -5.85) and physical inactivity (β = -0.96; 95%CI: -1.22 to -0.70) had a sign of notable decline in cognitive ability.

Conclusions
Findings revealed that cognitive function is negatively associated with IAP, demanding a deep intervention plan to minimize the detrimental effect.
Phytoplankton-derived polysaccharides and microbial peptidoglycans are key nutrients for deep-sea microbes in the Mariana Trench
Authors: Dang Yan-Ru , Cha Qian-Qian , Liu Sha-Sha , Wang Shu-Yan , Li Ping-Yi , Li Chun-Yang , Wang Peng , Chen Xiu-Lan , Tian Ji-Wei , Xin Yu , Chen Yin , Zhang Yu-Zhong , Qin Qi-Long 
Published: April 2024

Abstract
Background
The deep sea represents the largest marine ecosystem, driving global-scale biogeochemical cycles. Microorganisms are the most abundant biological entities and play a vital role in the cycling of organic matter in such ecosystems. The primary food source for abyssal biota is the sedimentation of particulate organic polymers. However, our knowledge of the specific biopolymers available to deep-sea microbes remains largely incomplete. One crucial rate-limiting step in organic matter cycling is the depolymerization of particulate organic polymers facilitated by extracellular enzymes (EEs). Therefore, the investigation of active EEs and the microbes responsible for their production is a top priority to better understand the key nutrient sources for deep-sea microbes.

Results
In this study, we conducted analyses of extracellular enzymatic activities (EEAs), metagenomics, and metatranscriptomics from seawater samples of 50–9305 m from the Mariana Trench. While a diverse array of microbial groups was identified throughout the water column, only a few exhibited high levels of transcriptional activities. Notably, microbial populations actively transcribing EE genes involved in biopolymer processing in the abyssopelagic (4700 m) and hadopelagic zones (9305 m) were primarily associated with the class Actinobacteria. These microbes actively transcribed genes coding for enzymes such as cutinase, laccase, and xyloglucanase which are capable of degrading phytoplankton polysaccharides as well as GH23 peptidoglycan lyases and M23 peptidases which have the capacity to break down peptidoglycan. Consequently, corresponding enzyme activities including glycosidases, esterase, and peptidases can be detected in the deep ocean. Furthermore, cell-specific EEAs increased at 9305 m compared to 4700 m, indicating extracellular enzymes play a more significant role in nutrient cycling in the deeper regions of the Mariana Trench.

Conclusions
Transcriptomic analyses have shed light on the predominant microbial population actively participating in organic matter cycling in the deep-sea environment of the Mariana Trench. The categories of active EEs suggest that the complex phytoplankton polysaccharides (e.g., cutin, lignin, and hemicellulose) and microbial peptidoglycans serve as the primary nutrient sources available to deep-sea microbes. The high cell-specific EEA observed in the hadal zone underscores the robust polymer-degrading capacities of hadal microbes even in the face of the challenging conditions they encounter in this extreme environment. These findings provide valuable new insights into the sources of nutrition, the key microbes, and the EEs crucial for biopolymer degradation in the deep seawater of the Mariana Trench.
Assessing intersectional gender analysis in Nepal’s health management information system: a case study on tuberculosis for inclusive health systems
Authors: Parajuli Ayuska , Kakchapati Sampurna , Arjyal Abriti , Joshi Deepak , Kharel Chandani , Otmani del Barrio Mariam , Baral Sushil C 
Published: April 2024

Abstract
Background
Tuberculosis (TB) remains a major public health problem in Nepal, high in settings marked by prevalent gender and social inequities. Various social stratifiers intersect, either privileging or oppressing individuals based on their characteristics and contexts, thereby increasing risks, vulnerabilities and marganilisation associated with TB. This study aimed to assess the inclusiveness of gender and other social stratifiers in key health related national policies and the Health Management Information System (HMIS) of National Tuberculosis Programme (NTP) by conducting an intersectional analysis of TB cases recorded via HMIS.

Methods
A desk review of key policies and the NTP’s HMIS was conducted. Retrospective intersectional analysis utilized two secondary data sources: annual NTP report (2017–2021) and records of 628 TB cases via HMIS 6.5 from two TB centres (2017/18–2018/19). Chi-square test and multi-variate analysis was used to assess the association between social stratifers and types of TB, registration category and treatment outcome.

Results
Gender, social inclusion and concept of intersectionality are incorporated into various health policies and strategies but lack effective implementation. NTP has initiated the collection of age, sex, ethnicity and location data since 2014/15 through the HMIS. However, only age and sex disaggregated data are routinely reported, leaving recorded social stratifiers of TB patients static without analysis and dissemination. Furthermore, findings from the intersectional analysis using TB secondary data, showed that male more than 25 years exhibited higher odds [adjusted odds ratio (aOR) = 4.95, 95% confidence interval (CI): 1.60–19.06, P = 0.01)] of successful outcome compared to male TB patients less than 25 years. Similarly, sex was significantly associated with types of TB (P < 0.05) whereas both age (P < 0.05) and sex (P < 0.05) were significantly associated with patient registration category (old/new cases).

Conclusions
The results highlight inadequacy in the availability of social stratifiers in the routine HMIS. This limitation hampers the NTP’s ability to conduct intersectional analyses, crucial for unveiling the roles of other social determinants of TB. Such limitation underscores the need for more disaggregated data in routine NTP to better inform policies and plans contributing to the development of a more responsive and equitable TB programme and effectively addressing disparities.
Unveiling the dynamics of "scenes changing as steps move" in a Chinese classical garden: a case study of Jingxinzhai Garden
Authors: Chen Yujia , Gu Yang , Liu Yaxin , Cao Lei 
Published: April 2024

Abstract
Chinese classical gardens are a significant cultural heritage in the history of world gardening, with their central architectural principle of "scenes changing as steps move" (步移景异) embodying traditional Chinese aesthetic ideals. This study employed the variation of visual complexity during a tour as a representation of this principle, using Jingxinzhai (静心斋) Garden as a case study. The visual environmental characteristics were quantified using the Fraclab box-counting, Canny edge detection, and DeepLab V3 + model, and the spatial distribution of fractal dimension and visual index of landscape elements were analyzed. Through partial correlation analysis, hierarchical regression analysis, and one-way ANOVA, the relevant factors (BVI, RVI, GVI, WVI) and influencing factors (BVI, RVI, GVI) and the differences among landscape element combinations of visual complexity were identified. Furthermore, the distribution patterns and causes of visual complexity in Chinese classical gardens were then discussed. This study proposes an effective method for quantifying the visual environmental characteristics of Chinese classical gardens and provides an explanation of the concept of "scenes changing as steps move" from the perspective of visual environment. It offers important references for a deeper understanding of Chinese classical garden design and planning.