bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exosome-mediated delivery of super-repressor IκBα alleviates inflammation and joint damages in rheumatoid arthritis
Authors: Lee Hae-In , Ahn Min-Joo , Yoo Jae-Kwang , Ahn So-Hee , Park Seon Young , Seo Hyangmi , Kim Moon-Ju , Lee Yu Jeong , Jang Hyun Hee , Shim Seung Cheol , Won Eun Jeong , Park Cheolhyoung , Choi Chulhee , Kim Tae-Jong 
Published: January 2024

Abstract
Background
This study aims to investigate the potential anti-inflammatory effects of exosomes engineered to carry super-repressor IκB (Exo-srIκB), an exosome-based NF-κB inhibitor, in the context of RA.

Methods
Peripheral blood mononuclear cells (PBMCs) and synovial fluid mononuclear cells (SFMCs) were collected from patients diagnosed with RA and treated with Exo-srIκB to test the therapeutic potential. Flow cytometry analysis was performed to assess the production of inflammatory cytokines (IL-17A and GM-CSF) by the cells. ELISA was utilized to measure the levels of TNF-α, IL-17A, IL-6, and GM-CSF. Arthritis was induced in SKG mice by intraperitoneal injection of curdlan. DBA/1 J mice were used in collagen-induced arthritis (CIA) experiments. After the development of arthritis, mice were injected with either Exo-Naïve (control exosome) or Exo-srIκB. Arthritis scores were recorded biweekly, and histological observations of the ankle joint were conducted using H&E and safranin-O staining. Additionally, bone erosion was evaluated using micro-CT imaging.

Results
In the ex vivo study involving human PBMCs and SFMCs, treatment with Exo-srIκB demonstrated a notable reduction in inflammatory cytokines. Furthermore, in both the SKG and CIA models, Exo-srIκB treatment exhibited significant reductions in inflammation, cartilage destruction, and bone erosion within the joint tissues when compared to the Exo-Naive control group. Additionally, the radiographic score assessed through microCT showed a significant decrease compared to the Exo-Naive control group.

Conclusion
Overall, these findings suggest that Exo-srIκB possesses anti-inflammatory properties in human RA cells and animal models, making it a promising therapeutic candidate for the treatment of RA.
Causal relationship between systemic lupus erythematosus and primary liver cirrhosis based on two-sample bidirectional Mendelian randomization and transcriptome overlap analysis
Authors: Wu Linyong , Li Songhua , Wu Chaojun , Wu Shaofeng , Lin Yan , Wei Dayou 
Published: January 2024

Abstract
Background
Overlapping cases of systemic lupus erythematosus (SLE) and primary biliary cirrhosis (PBC) are rare and have not yet been fully proven to be accidental or have a common genetic basis.

Methods
Two-sample bidirectional Mendelian randomization (MR) analysis was applied to explore the potential causal relationship between SLE and PBC. The heterogeneity and reliability of MR analysis were evaluated through Cochran’s Q-test and sensitivity test, respectively. Next, transcriptome overlap analysis of SLE and PBC was performed using the Gene Expression Omnibus database to identify the potential mechanism of hub genes. Finally, based on MR analysis, the potential causal relationship between hub genes and SLE or PBC was validated again.

Results
The MR analysis results indicated that SLE and PBC were both high-risk factors for the occurrence and development of the other party. On the one hand, MR analysis had heterogeneity, and on the other hand, it also had robustness. Nine hub genes were identified through transcriptome overlap analysis, and machine learning algorithms were used to verify their high recognition efficiency for SLE patients. Finally, based on MR analysis, it was verified that there was no potential causal relationship between the central gene SOCS3 and SLE, but it was a high-risk factor for the potential risk of PBC.

Conclusion
The two-sample bidirectional MR analysis revealed that SLE and PBC were high-risk factors for each other, indicating that they had similar genetic bases, which could to some extent overcome the limitation of insufficient overlap in case samples of SLE and PBC. The analysis of transcriptome overlapping hub genes provided a theoretical basis for the potential mechanisms and therapeutic targets of SLE with PBC overlapping cases.
Causality between rheumatoid arthritis and the risk of cognitive impairment: a Mendelian randomization study
Authors: Duan Lincheng , Li Shiyin , Li Haoming , Shi Yue , Xie Xiaolong , Feng Yue 
Published: January 2024

Abstract
Background
There is mounting proof that rheumatoid arthritis (RA) and cognitive decline are related. These studies, however, have not all been uniform, and others have not discovered such a correlation. It is essential to investigate the link between RA and cognitive decline.

Method
We conducted a Mendelian randomization analysis utilizing three different publicly accessible RA GWAS summary datasets and a variety of meticulously verified instrumental variables. We mostly used inverse variance weighting (IVW), as well as MR-Egger, weighted median, MR-PRESSO, and several sensitivity analyses, to figure out the link between RA and cognitive impairment (CI).

Results
Our MR study identified the causality between RA and declining cognitive performance (β = − 0.010, 95% CI of − 0.017 to − 0.003, P = 4.33E−03) and cognitive function (β = − 0.029, 95% CI of − 0.053 to − 0.005, P = 1.93E−02). The consistent direction of the connection is revealed by sensitivity analysis utilizing the weighted median and the MR-Egger method. Furthermore, we reproduced our findings across two additional RA datasets and found identical outcomes, strengthening the validity of our findings.

Conclusion
This study offers proof of causality between RA and an increased risk of CI. Our findings highlight the importance of examining RA patients for cognitive ability, which may open up fresh ideas for the prevention of CI.
Effects of single and repeated bouts of flywheel exercise on jump performance and muscle damage in athletes and non athletes
Authors: Shimizu Takashi , Tsuchiya Yosuke , Ueda Hisashi , Izumi Shigeki , Ochi Eisuke 
Published: January 2024

Abstract
Background
Although recent studies have investigated the effects of flywheel (FW) training on muscle function, the effects of transient FW exercise on jump performance in athletes are unknown. This study examined the effects of single and repeated bouts of FW squat exercises on jump performance and muscle damage in male collegiate basketball players.

Methods
The participants were 10 healthy college-age men (nonathletes) and 11 male basketball players (athletes). The intervention involved 100 squat exercises (10 repetitions × 10 sets) using an FW device. To examine the repeated-bout effects, the protocol was conducted again after a 2-week interval. Squat jumps, countermovement jumps, drop jumps, and rebound jumps were evaluated as jump performance, while isometric maximal voluntary contraction (MVC) torque in knee extension, muscle soreness, range of motion, thigh circumference, muscle thickness, and echo intensity were evaluated as markers of muscle damage. Measurements were taken at baseline, immediately after exercise, 24 h later, and 72 h later.

Results
The jump performance of nonathletes decreased after exercise (p < 0.05), while that of the athletes did not. The results were similar for muscle soreness. MVC torque decreased significantly after the first exercise in both groups (p < 0.05) and was significantly lower in the nonathletes versus athletes. Significant repeated-bout effects were found for muscle soreness in nonathletes but not athletes.

Conclusions
These results suggest that a single bout of FW exercise reduces jump performance in male nonathletes but not basketball players.
Physical and autonomic functionality in women with breast cancer pre and post chemotherapy: a case control study
Authors: Sousa Bruna Lorena Soares Cavalcante , dos Santos Rosa Thiago , Silvino Valmir Oliveira , Barros Esmeralda Maria Lustosa , de Luca Corrêa Hugo , do Prado Danilo Marcelo Leite , Veras-Silva Acácio Salvador , de Souza Mariana Duarte , de Lima Carlos Eduardo Batista , de Oliveira Luciano Fonseca Lemos , dos Santos Marcos Antonio Pereira 
Published: January 2024

Abstract
Background
Breast cancer (BC) is one of the most incident types of cancer among women in the world. Although chemotherapy is an effective way to treat several types of cancer, it may also cause serious complications, including cardiotoxicity. This study aimed to identify the impact of chemotherapy on functional capacity, muscle strength and autonomic function.

Methods
Ten breast cancer patients in therapeutic follow-up (TG) and ten women without comorbidities (CG) participated in the study (46±8.87 years old). Both groups were evaluated at two time points, before and 20 weeks after the start of chemotherapy. Functional capacity and muscle strength were assessed by 6-minute walk test (6MWT) and handgrip test, respectively. Autonomic function was assessed by heart rate variability analysis.

Results
TG presented greater reductions in the handgrip test for the non-dominant hand (TG ↓15.2%; CG: ↑1.1%, p<0.05) compared to GC. However, no significant differences were found regarding VO2max (p>0.05) and 6MWT total distance (p>0.05). Regarding the heart rate variability variables before and after follow-up period, rMSSD (CG= 39.15±37.66; TG= 14.89±8.28, p= 0.01) and SDNN (CG= 55.77±40.03; TG= 26.30±10.37, p= 0.02) showed effect in the group and time interaction, whereas the LF/HF ratio presented significant difference only in the time analysis (CG= 2.24±2.30; TG= 2.84±1.82, p= 0.04).

Conclusion
Chemotherapy used in the treatment of breast cancer patients resulted in decreased muscle strength and autonomic imbalance. The data suggests that chemotherapy may carry the risk of developing cardiovascular disease.

Trial registration
Registration not required.
Casearia tomentosa fruit extracts exposed larvicidal activity and morphological alterations in Culex quinquefasciatus and Aedes albopictus under in vitro and semi field conditions
Authors: Mandal Priyanka , Chandra Goutam 
Published: January 2024

AbstractMosquitoes are notorious insects that transmit a wide range of infectious diseases, including zika, malaria, chikungunya, filariasis, and dengue. The overuse and incorrect application of synthetic pesticides to control mosquitoes has resulted in resistance development and environmental contamination, both of which have had a negative impact on human health. To address this issue, the larvicidal and pupicidal potential of acetone extract from Casearia tomentosa fruits was investigated. The extract was evaluated in a lab setting against all larval instars and pupa of Culex quinquefasciatus and Aedes albopictus, as well as against third instar larvae in a semi-field condition. Purified compounds through TLC were also tested against 3rd instar larvae of both mosquito and non-target organisms. The FT-IR and GC-MS analyses were used to characterise the extract. Morphological aberration caused by the acetone extract was observed using FESEM. The anal gills and respiratory siphon of both mosquitoes showed significant deformation from their normal state. 100 ppm was found to cause 100% larval mortality at 24 h of exposure in case of Cx. quinquefasciatus and at 72 h of exposure in Ae. albopictus larvae. After 72 h of exposure under in vitro conditions, the extract demonstrated considerable larvicidal activity with LC50 values of 38.33 and 47.56 against 3rd instar larvae of Culex quinquefasciatus and Aedes albopictus, respectively. The acetone extract can be considered as a highly effective mosquito larvicidal agent that is safe for the environment.
Graphical abstract
Digital Clock and Recall is superior to the Mini-Mental State Examination for the detection of mild cognitive impairment and mild dementia
Authors: Jannati Ali , Toro-Serey Claudio , Gomes-Osman Joyce , Banks Russell , Ciesla Marissa , Showalter John , Bates David , Tobyne Sean , Pascual-Leone Alvaro 
Published: January 2024

Abstract
Background
Disease-modifying treatments for Alzheimer’s disease highlight the need for early detection of cognitive decline. However, at present, most primary care providers do not perform routine cognitive testing, in part due to a lack of access to practical cognitive assessments, as well as time and resources to administer and interpret the tests. Brief and sensitive digital cognitive assessments, such as the Digital Clock and Recall (DCR™), have the potential to address this need. Here, we examine the advantages of DCR over the Mini-Mental State Examination (MMSE) in detecting mild cognitive impairment (MCI) and mild dementia.

Methods
We studied 706 participants from the multisite Bio-Hermes study (age mean ± SD = 71.5 ± 6.7; 58.9% female; years of education mean ± SD = 15.4 ± 2.7; primary language English), classified as cognitively unimpaired (CU; n = 360), mild cognitive impairment (MCI; n = 234), or probable mild Alzheimer’s dementia (pAD; n = 111) based on a review of medical history with selected cognitive and imaging tests. We evaluated cognitive classifications (MCI and early dementia) based on the DCR and the MMSE against cohorts based on the results of the Rey Auditory Verbal Learning Test (RAVLT), the Trail Making Test-Part B (TMT-B), and the Functional Activities Questionnaire (FAQ). We also compared the influence of demographic variables such as race (White vs. Non-White), ethnicity (Hispanic vs. Non-Hispanic), and level of education (≥ 15 years vs. < 15 years) on the DCR and MMSE scores.

Results
The DCR was superior on average to the MMSE in classifying mild cognitive impairment and early dementia, AUC = 0.70 for the DCR vs. 0.63 for the MMSE. DCR administration was also significantly faster (completed in less than 3 min regardless of cognitive status and age). Among 104 individuals who were labeled as “cognitively unimpaired” by the MMSE (score ≥ 28) but actually had verbal memory impairment as confirmed by the RAVLT, the DCR identified 84 (80.7%) as impaired. Moreover, the DCR score was significantly less biased by ethnicity than the MMSE, with no significant difference in the DCR score between Hispanic and non-Hispanic individuals.

Conclusions
DCR outperforms the MMSE in detecting and classifying cognitive impairment—in a fraction of the time—while being not influenced by a patient’s ethnicity. The results support the utility of DCR as a sensitive and efficient cognitive assessment in primary care settings.

Trial registration
ClinicalTrials.gov identifier NCT04733989.
Critical contribution of mitochondria in the development of cardiomyopathy linked to desmin mutation
Authors: Hovhannisyan Yeranuhi , Li Zhenlin , Callon Domitille , Suspène Rodolphe , Batoumeni Vivien , Canette Alexis , Blanc Jocelyne , Hocini Hakim , Lefebvre Cécile , El-Jahrani Nora , Kitsara Maria , L’honoré Aurore , Kordeli Ekaterini , Fornes Paul , Concordet Jean-Paul , Tachdjian Gérard , Rodriguez Anne-Marie , Vartanian Jean-Pierre , Béhin Anthony , Wahbi Karim , Joanne Pierre , Agbulut Onnik 
Published: January 2024

Abstract
Background
Beyond the observed alterations in cellular structure and mitochondria, the mechanisms linking rare genetic mutations to the development of heart failure in patients affected by desmin mutations remain unclear due in part, to the lack of relevant human cardiomyocyte models.

Methods
To shed light on the role of mitochondria in these mechanisms, we investigated cardiomyocytes derived from human induced pluripotent stem cells carrying the heterozygous DESE439K mutation that were either isolated from a patient or generated by gene editing. To increase physiological relevance, cardiomyocytes were either cultured on an anisotropic micropatterned surface to obtain elongated and aligned cardiomyocytes, or as a cardiac spheroid to create a micro-tissue. Moreover, when applicable, results from cardiomyocytes were confirmed with heart biopsies of suddenly died patient of the same family harboring DESE439K mutation, and post-mortem heart samples from five control healthy donors.

Results
The heterozygous DESE439K mutation leads to dramatic changes in the overall cytoarchitecture of cardiomyocytes, including cell size and morphology. Most importantly, mutant cardiomyocytes display altered mitochondrial architecture, mitochondrial respiratory capacity and metabolic activity reminiscent of defects observed in patient’s heart tissue. Finally, to challenge the pathological mechanism, we transferred normal mitochondria inside the mutant cardiomyocytes and demonstrated that this treatment was able to restore mitochondrial and contractile functions of cardiomyocytes.

Conclusions
This work highlights the deleterious effects of DESE439K mutation, demonstrates the crucial role of mitochondrial abnormalities in the pathophysiology of desmin-related cardiomyopathy, and opens up new potential therapeutic perspectives for this disease.
Knocking out Fkbp51 decreases CCl4-induced liver injury through enhancement of mitochondrial function and Parkin activity
Authors: Qiu Bin , Zhong Zhaohui , Dou Longyu , Xu Yuxue , Zou Yi , Weldon Korri , Wang Jun , Zhang Lingling , Liu Ming , Williams Kent E. , Spence John Paul , Bell Richard L. , Lai Zhao , Yong Weidong , Liang Tiebing 
Published: January 2024

AbstractBackground and aimsPreviously, we found that FK506 binding protein 51 (Fkbp51) knockout (KO) mice resist high fat diet-induced fatty liver and alcohol-induced liver injury. The aim of this research is to identify the mechanism ofFkbp51in liver injury.MethodsCarbon tetrachloride (CCl4)-induced liver injury was compared betweenFkbp51KO and wild type (WT) mice. Step-wise and in-depth analyses were applied, including liver histology, biochemistry, RNA-Seq, mitochondrial respiration, electron microscopy, and molecular assessments. The selective FKBP51 inhibitor (SAFit2) was tested as a potential treatment to ameliorate liver injury.ResultsFkbp51knockout mice exhibited protection against liver injury, as evidenced by liver histology, reduced fibrosis-associated markers and lower serum liver enzyme levels. RNA-seq identified differentially expressed genes and involved pathways, such as fibrogenesis, inflammation, mitochondria, and oxidative metabolism pathways and predicted the interaction of FKBP51, Parkin, and HSP90. Cellular studies supported co-localization of Parkin and FKBP51 in the mitochondrial network, and Parkin was shown to be expressed higher in the liver of KO mice at baseline and after liver injury relative to WT. Further functional analysis identified that KO mice exhibited increased ATP production and enhanced mitochondrial respiration. KO mice have increased mitochondrial size, increased autophagy/mitophagy and mitochondrial-derived vesicles (MDV), and reduced reactive oxygen species (ROS) production, which supports enhancement of mitochondrial quality control (MQC). Application of SAFit2, an FKBP51 inhibitor, reduced the effects of CCl4-induced liver injury and was associated with increased Parkin, pAKT, and ATP production.ConclusionsDownregulation of FKBP51 represents a promising therapeutic target for liver disease treatment.Graphical Abstract
Classification of drought severity in contiguous USA during the past 21 years using fractal geometry
Authors: Azizi Sepideh , Azizi Tahmineh 
Published: January 2024

AbstractDrought is characterized by a moisture deficit that can adversely impact the environment, economy, and society. In North America, like many regions worldwide, predicting the timing of drought events is challenging. However, our novel study in climate research explores whether the Drought Monitor database exhibits fractal characteristics, represented by a single scaling exponent. This database categorizes drought areas by intensity, ranging from D0 (abnormally dry) to D4 (exceptional drought). Through vibration analysis using power spectral densities (PSD), we investigate the presence of power-law scaling in various statistical moments across different scales within the database. Our multi-fractal analysis estimates the multi-fractal spectrum for each category, and the Higuchi algorithm assesses the fractal complexity, revealing that D4 follows a multi-fractal pattern with a wide range of exponents, while D0 to D3 exhibit a mono-fractal nature with a narrower range of exponents.
Building capacity for network meta-analysis in Sub-Saharan Africa: reflections and future direction
Authors: Rohwer Anke , Ngah Veranyuy , Mavridis Dimitris , Young Taryn , McCaul Michael 
Published: January 2024

AbstractRobust, relevant, comprehensive, and up-to-date evidence syntheses are the cornerstone for evidence-informed healthcare decisions. When considering multiple treatment options, network meta-analysis (NMA) systematic reviews play a key role in informing impactful decisions and clinical practice guidelines. However, the capacity and literacy to conduct NMA systematic reviews and interpret its results remains out of reach for many clinicians and review authors, especially in low-to-middle-income countries. Despite ample resources and guides, NMA capacity and training opportunities remain limited to non-existent in Sub-Saharan Africa. Towards solutions and strengthening evidence synthesis and NMA capacity in the Sub-Saharan African region, we describe and reflect on two courses that build NMA capacity and aim to address NMA literacy in Sub-Saharan Africa.The Primer in NMA systematic reviews aimed for participants to be able to find, appraise, interpret, and consider the use of NMA SRs of intervention effects. It is a 6-week online course for clinicians, policy-makers, and researchers wanting to learn more about using NMA systematic reviews. The Global NMA Masterclass workshop aimed for participants to be able to understand and apply pairwise and NMA in STATA and R, evaluate NMA assumptions and confidence in NMA results, and appropriately report NMA results. This course was offered over 5 weeks to clinicians, biostatisticians, and researchers with basic knowledge of epidemiology and biostatics. Although the bulk of learning occurred through self-study, we had weekly, synchronous question-and-answer sessions for both courses. Using relevant examples throughout the courses helped to enable an authentic learning environment.This was the first NMA training developed in Africa for Africa. Development of the courses was a collaborative effort from a multi-disciplinary team. Both NMA courses were well received and attended by a diverse group of participants spread across Sub-Saharan African countries. Participants felt the courses were applicable to their setting. Although most participants appreciated the benefits of online learning, we also experienced some challenges. There is great potential to conduct NMA systematic reviews in Sub-Saharan Africa. The NMA Primer and NMA workshop can play an essential role in expanding and developing NMA SR capacity and literacy in SSA.