bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of genetic variants related to combined lipid-lowering and antihypertensive therapies with risk of cardiovascular disease: 2 × 2 factorial Mendelian randomization analyses
Authors: Li Ying , Liu Hongwei , Shen Chong , Li Jianxin , Liu Fangchao , Huang Keyong , Gu Dongfeng , Li Yun , Lu Xiangfeng
Published: May 2024

Background

Lipid-lowering drugs and antihypertensive drugs are commonly combined for cardiovascular disease (CVD). However, the relationship of combined medications with CVD remains controversial. We aimed to explore the associations of genetically proxied medications of lipid-lowering and antihypertensive drugs, either alone or both, with risk of CVD, other clinical and safety outcomes.

Methods

We divided 423,821 individuals in the UK Biobank into 4 groups via median genetic scores for targets of lipid-lowering drugs and antihypertensive drugs: lower low-density lipoprotein cholesterol (LDL-C) mediated by targets of statins or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, lower systolic blood pressure (SBP) mediated by targets of β-blockers (BBs) or calcium channel blockers (CCBs), combined genetically lower LDL-C and SBP, and reference (genetically both higher LDL-C and SBP). Associations with risk of CVD and other clinical outcomes were explored among each group in factorial Mendelian randomization.

Results

Independent and additive effects were observed between genetically proxied medications of lipid-lowering and antihypertensive drugs with CVD (including coronary artery disease, stroke, and peripheral artery diseases) and other clinical outcomes (ischemic stroke, hemorrhagic stroke, heart failure, diabetes mellitus, chronic kidney disease, and dementia) (P > 0.05 for interaction in all outcomes). Take the effect of PCSK9 inhibitors and BBs on CVD for instance: compared with the reference, PCSK9 group had a 4% lower risk of CVD (odds ratio [OR], 0.96; 95%CI, 0.94–0.99), and a 3% lower risk was observed in BBs group (OR, 0.97; 95%CI, 0.94–0.99), while combined both were associated with a 6% additively lower risk (OR, 0.94; 95%CI, 0.92–0.97; P = 0.87 for interaction).

Conclusions

Genetically proxied medications of combined lipid-lowering and antihypertensive drugs have an independent and additive effects on CVD, other clinical and safety outcomes, with implications for CVD clinical practice, subsequent trials as well as drug development of polypills.
Ruxolitinib plus standard of care in severe hospitalized adults with severe fever with thrombocytopenia syndrome (SFTS): an exploratory, single-arm trial
Authors: Wen Sai , Xu Nannan , Zhao Lianhui , Yang Lulu , Yang Hui , Chang Caiyun , Wang Shanshan , Qu Chunmei , Song Li , Zou Wenlu , He Yishan , Wang Gang
Published: May 2024

Background

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease, and its morbidity and mortality are increasing. At present, there is no specific therapy available. An exacerbated IFN-I response and cytokine storm are related to the mortality of patients with SFTS. Ruxolitinib is a Janus kinase (JAK) 1/2 inhibitor that can block proinflammatory cytokines and inhibit the type I IFN pathway. We aimed to explore the use of ruxolitinib plus standard of care for severe SFTS.

Methods

We conducted a prospective, single-arm study of severe SFTS. We recruited participants aged 18 years or older who were admitted to the hospital with laboratory-confirmed severe SFTS and whose clinical score exceeded 8 points within 6 days of symptom onset. Participants received oral ruxolitinib (10 mg twice a day) for up to 10 days. The primary endpoint was 28-day overall survival. The secondary endpoints included the proportion of participants who needed intensive care unit (ICU) admission, total cost, changes in neurologic symptoms and clinical laboratory parameters, and adverse events (AEs) within 28 days. A historical control group (HC group, n = 26) who met the upper criteria for inclusion and hospitalized from April 1, 2021, to September 16, 2022, was selected and 1:1 matched for baseline characteristics by propensity score matching.

Results

Between Sep 16, 2022, and Sep 16, 2023, 26 participants were recruited into the ruxolitinib treatment group (RUX group). The 28-day overall mortality was 7.7% in the RUX group and 46.2% in the HC group (P = 0.0017). There was a significantly lower proportion of ICU admissions (15.4% vs 65.4%, p < 0.001) and total hospitalization cost in the RUX group. Substantial improvements in neurologic symptoms, platelet counts, hyperferritinemia, and an absolute decrease in the serum SFTS viral load were observed in all surviving participants. Treatment-related adverse events were developed in 6 patients (23.2%) and worsened in 8 patients (30.8%), and no treatment-related serious adverse events were reported.

Conclusions

Our findings indicate that ruxolitinib has the potential to increase the likelihood of survival as well as reduce the proportion of ICU hospitalization and being tolerated in severe SFTS. Further trials are needed.

Trail registration

ChiCTR2200063759, September 16, 2022.
ABO and Rhesus blood groups and multiple health outcomes: an umbrella review of systematic reviews with meta-analyses of observational studies
Authors: Liu Fang-Hua , Guo Jia-Kai , Xing Wei-Yi , Bai Xue-Li , Chang Yu-Jiao , Lu Zhao , Yang Miao , Yang Ying , Li Wen-Jing , Jia Xian-Xian , Zhang Tao , Yang Jing , Chen Jun-Tong , Gao Song , Wu Lang , Zhang De-Yu , Liu Chuan , Gong Ting-Ting , Wu Qi-Jun
Published: May 2024

Background

Numerous studies have been conducted to investigate the relationship between ABO and Rhesus (Rh) blood groups and various health outcomes. However, a comprehensive evaluation of the robustness of these associations is still lacking.

Methods

We searched PubMed, Web of Science, Embase, Scopus, Cochrane, and several regional databases from their inception until Feb 16, 2024, with the aim of identifying systematic reviews with meta-analyses of observational studies exploring associations between ABO and Rh blood groups and diverse health outcomes. For each association, we calculated the summary effect sizes, corresponding 95% confidence intervals, 95% prediction interval, heterogeneity, small-study effect, and evaluation of excess significance bias. The evidence was evaluated on a grading scale that ranged from convincing (Class I) to weak (Class IV). We assessed the certainty of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation criteria (GRADE). We also evaluated the methodological quality of included studies using the A Measurement Tool to Assess Systematic Reviews (AMSTAR). AMSTAR contains 11 items, which were scored as high (8–11), moderate (4–7), and low (0–3) quality. We have gotten the registration for protocol on the PROSPERO database (CRD42023409547).

Results

The current umbrella review included 51 systematic reviews with meta-analysis articles with 270 associations. We re-calculated each association and found only one convincing evidence (Class I) for an association between blood group B and type 2 diabetes mellitus risk compared with the non-B blood group. It had a summary odds ratio of 1.28 (95% confidence interval: 1.17, 1.40), was supported by 6870 cases with small heterogeneity (I2 = 13%) and 95% prediction intervals excluding the null value, and without hints of small-study effects (P for Egger’s test > 0.10, but the largest study effect was not more conservative than the summary effect size) or excess of significance (P < 0.10, but the value of observed less than expected). And the article was demonstrated with high methodological quality using AMSTAR (score = 9). According to AMSTAR, 18, 32, and 11 studies were categorized as high, moderate, and low quality, respectively. Nine statistically significant associations reached moderate quality based on GRADE.

Conclusions

Our findings suggest a potential relationship between ABO and Rh blood groups and adverse health outcomes. Particularly the association between blood group B and type 2 diabetes mellitus risk.
KDM5 family as therapeutic targets in breast cancer: Pathogenesis and therapeutic opportunities and challenges
Authors: Li Chang-Yun , Wang Wanhe , Leung Chung-Hang , Yang Guan-Jun , Chen Jiong
Published: May 2024

Breast cancer (BC) is the most frequent malignant cancer diagnosis and is a primary factor for cancer deaths in women. The clinical subtypes of BC include estrogen receptor (ER) positive, progesterone receptor (PR) positive, human epidermal growth factor receptor 2 (HER2) positive, and triple-negative BC (TNBC). Based on the stages and subtypes of BC, various treatment methods are available with variations in the rates of progression-free disease and overall survival of patients. However, the treatment of BC still faces challenges, particularly in terms of drug resistance and recurrence. The study of epigenetics has provided new ideas for treating BC. Targeting aberrant epigenetic factors with inhibitors represents a promising anticancer strategy. The KDM5 family includes four members, KDM5A, KDM5B, KDM5C, and KDMD, all of which are Jumonji C domain-containing histone H3K4me2/3 demethylases. KDM5 proteins have been extensively studied in BC, where they are involved in suppressing or promoting BC depending on their specific upstream and downstream pathways. Several KDM5 inhibitors have shown potent BC inhibitory activity in vitro and in vivo, but challenges still exist in developing KDM5 inhibitors. In this review, we introduce the subtypes of BC and their current therapeutic options, summarize KDM5 family context-specific functions in the pathobiology of BC, and discuss the outlook and pitfalls of KDM5 inhibitors in this disease.
Bio-nanoparticles loaded with synovial-derived exosomes ameliorate osteoarthritis progression by modifying the oxidative microenvironment
Authors: Cao Haifei , Li Wanxin , Zhang Hao , Hong Lihui , Feng Xiaoxiao , Gao Xuzhu , Li Hongye , Lv Nanning , Liu Mingming
Published: May 2024

Background and aims

Osteoarthritis (OA) is a prevalent degenerative joint disorder, marked by the progressive degeneration of joint cartilage, synovial inflammation, and subchondral bone hyperplasia. The synovial tissue plays a pivotal role in cartilage regulation. Exosomes (EXOs), small membrane-bound vesicles released by cells into the extracellular space, are crucial in mediating intercellular communication and facilitating the exchange of information between tissues. Our study aimed to devise a hydrogel microsphere infused with SOD3-enriched exosomes (S-EXOs) to protect cartilage and introduce a novel, effective approach for OA treatment.

Materials and methods

We analyzed single-cell sequencing data from 4247 cells obtained from the GEO database. Techniques such as PCR, Western Blot, immunofluorescence (IF), and assays to measure oxidative stress levels were employed to validate the cartilage-protective properties of the identified key protein, SOD3. In vivo, OA mice received intra-articular injections of S-EXOs bearing hydrogel microspheres, and the effectiveness was assessed using safranine O (S.O) staining and IF.

Results

Single-cell sequencing data analysis suggested that the synovium influences cartilage via the exocrine release of SOD3. Our findings revealed that purified S-EXOs enhanced antioxidant capacity of chondrocytes, and maintained extracellular matrix metabolism stability. The S-EXO group showed a significant reduction in mitoROS and ROS levels by 164.2% (P < 0.0001) and 142.7% (P < 0.0001), respectively, compared to the IL-1β group. Furthermore, the S-EXO group exhibited increased COL II and ACAN levels, with increments of 2.1-fold (P < 0.0001) and 3.1-fold (P < 0.0001), respectively, over the IL-1β group. Additionally, the S-EXO group showed a decrease in MMP13 and ADAMTS5 protein expression by 42.3% (P < 0.0001) and 44.4% (P < 0.0001), respectively. It was found that S-EXO-containing hydrogel microspheres could effectively deliver SOD3 to cartilage and significantly mitigate OA progression. The OARSI score in the S-EXO microsphere group markedly decreased (P < 0.0001) compared to the OA group.

Conclusion

The study demonstrated that the S-EXOs secreted by synovial fibroblasts exert a protective effect on chondrocytes, and microspheres laden with S-EXOs offer a promising therapeutic alternative for OA treatment.
Deficiency of UCHL1 results in insufficient decidualization accompanied by impaired dNK modulation and eventually miscarriage
Authors: Zhang Jie , Xue Mingxing , Huang Jiefang , He Shan , Zhu Lingqiao , Zhao Xiaonan , Wang Bei , Jiang Tingwang , Zhang Yanyun , Miao Changhong , Zhou Guoqiang
Published: May 2024

Background

Miscarriage is a frustrating complication of pregnancy that is common among women of reproductive age. Insufficient decidualization which not only impairs embryo implantation but disturbs fetomaternal immune-tolerance, has been widely regarded as a major cause of miscarriage; however, the underlying mechanisms resulting in decidual impairment are largely unknown.

Methods

With informed consent, decidual tissue from patients with spontaneous abortion or normal pregnant women was collected to detect the expression profile of UCHL1. Human endometrial stromal cells (HESCs) were used to explore the roles of UCHL1 in decidualization and dNK modulation, as well as the mechanisms involved. C57/BL6 female mice (7–10 weeks old) were used to construct pregnancy model or artificially induced decidualization model to evaluate the effect of UCHL1 on mice decidualization and pregnancy outcome.

Results

The Ubiquitin C-terminal hydrolase L1 (UCHL1), as a deubiquitinating enzyme, was significantly downregulated in decidua from patients with miscarriage, along with impaired decidualization and decreased dNKs. Blockage of UCHL1 led to insufficient decidualization and resultant decreased expression of cytokines CXCL12, IL-15, TGF-β which were critical for generation of decidual NK cells (dNKs), whereas UCHL1 overexpression enhanced decidualization accompanied by increase in dNKs. Mechanistically, the promotion of UCHL1 on decidualization was dependent on its deubiquitinating activity, and intervention of UCHL1 inhibited the activation of JAK2/STAT3 signaling pathway, resulting in aberrant decidualization and decreased production of cytokines associated with dNKs modulation. Furthermore, we found that inhibition of UCHL1 also disrupted the decidualization in mice and eventually caused adverse pregnancy outcome.

Conclusions

UCHL1 plays significant roles in decidualization and dNKs modulation during pregnancy in both humans and mice. Its deficiency indicates a poor pregnancy outcome due to defective decidualization, making UCHL1 a potential target for the diagnosis and treatment of miscarriage.

Graphical Abstract
Activated phosphoinositde 3-kinase (PI3Kδ) syndrome: an Italian point of view on diagnosis and new advances in treatment
Authors: Lougaris Vassilios , Piane Federico Le , Cancrini Caterina , Conti Francesca , Tommasini Alberto , Badolato Raffaele , Trizzino Antonino , Zecca Marco , De Rosa Antonio , Barzaghi Federica , Pignata Claudio
Published: May 2024

Activated phosphoinositide 3-kinase (PI3Kδ) Syndrome (APDS) is an inborn error of immunity (IEI) with a variable clinical presentation, characterized by infection susceptibility and immune dysregulation that may overlaps with other Primary Immune Regulatory Disorders (PIRDs). The rarity of the disease, its recent discovery, and the multiform /multifaced clinical presentation make it difficult to establish a correct diagnosis, especially at an early stage. As a result, the true prevalence of the pathology remains unknown. There is no treatment protocol for APDS, and drug therapy is primarily focused on treating symptoms. The most common therapies include immunoglobulin replacement therapy, antimicrobial prophylaxis, and immunosuppressive drugs. Hematopoietic stem cell transplantation (HSCT) has been used in some cases, but the risk-benefit balance remains unclear. With the upcoming introduction of specific medications, such as selective inhibitors for PI3Kδ, clinicians are shifting their attention towards target therapy.

This review provides a comprehensive overview of APDS with a focus on diagnostic and treatments procedures available. This review may be useful in implementing strategies for a more efficient patients’ management and therapeutic interventions.

Main Text.
Targeted temperature control following traumatic brain injury: ESICM/NACCS best practice consensus recommendations
Authors: Lavinio Andrea , Coles Jonathan P. , Robba Chiara , Aries Marcel , Bouzat Pierre , Chean Dara , Frisvold Shirin , Galarza Laura , Helbok Raimund , Hermanides Jeroen , van der Jagt Mathieu , Menon David K. , Meyfroidt Geert , Payen Jean-Francois , Poole Daniele , Rasulo Frank , Rhodes Jonathan , Sidlow Emily , Steiner Luzius A. , Taccone Fabio Silvio , Takala Riikka
Published: May 2024

Aims and scope

The aim of this panel was to develop consensus recommendations on targeted temperature control (TTC) in patients with severe traumatic brain injury (TBI) and in patients with moderate TBI who deteriorate and require admission to the intensive care unit for intracranial pressure (ICP) management.

Methods

A group of 18 international neuro-intensive care experts in the acute management of TBI participated in a modified Delphi process. An online anonymised survey based on a systematic literature review was completed ahead of the meeting, before the group convened to explore the level of consensus on TTC following TBI. Outputs from the meeting were combined into a further anonymous online survey round to finalise recommendations. Thresholds of ≥ 16 out of 18 panel members in agreement (≥ 88%) for strong consensus and ≥ 14 out of 18 (≥ 78%) for moderate consensus were prospectively set for all statements.

Results

Strong consensus was reached on TTC being essential for high-quality TBI care. It was recommended that temperature should be monitored continuously, and that fever should be promptly identified and managed in patients perceived to be at risk of secondary brain injury. Controlled normothermia (36.0–37.5 °C) was strongly recommended as a therapeutic option to be considered in tier 1 and 2 of the Seattle International Severe Traumatic Brain Injury Consensus Conference ICP management protocol. Temperature control targets should be individualised based on the perceived risk of secondary brain injury and fever aetiology.

Conclusions

Based on a modified Delphi expert consensus process, this report aims to inform on best practices for TTC delivery for patients following TBI, and to highlight areas of need for further research to improve clinical guidelines in this setting.
Synergistic effect of umbilical cord extracellular vesicles and rhBMP-2 to enhance the regeneration of a metaphyseal femoral defect in osteoporotic rats
Authors: Deluca Amelie , Wagner Andrea , Heimel Patrick , Deininger Christian , Wichlas Florian , Redl Heinz , Rohde Eva , Tempfer Herbert , Gimona Mario , Traweger Andreas
Published: May 2024

Background

The aim of this study was to evaluate potential synergistic effects of a single, local application of human umbilical cord MSC-derived sEVs in combination with a low dose of recombinant human rhBMP-2 to promote the regeneration of a metaphyseal femoral defect in an osteoporotic rat model.

Methods

6 weeks after induction of osteoporosis by bilateral ventral ovariectomy and administration of a special diet, a total of 64 rats underwent a distal femoral metaphyseal osteotomy using a manual Gigli wire saw. Defects were stabilized with an adapted Y-shaped mini-locking plate and were subsequently treated with alginate only, or alginate loaded with hUC-MSC-sEVs (2 × 109), rhBMP-2 (1.5 µg), or a combination of sEVs and rhBMP-2 (n = 16 for each group). 6 weeks post-surgery, femora were evaluated by µCT, descriptive histology, and biomechanical testing.

Results

Native radiographs and µCT analysis confirmed superior bony union with callus formation after treatment with hUC-MSC-sEVs in combination with a low dose of rhBMP-2. This finding was further substantiated by histology, showing robust defect consolidation 6 weeks after treatment. Torsion testing of the explanted femora revealed increased stiffness after application of both, rhBMP-2 alone, or in combination with sEVs, whereas torque was only significantly increased after treatment with rhBMP-2 together with sEVs.

Conclusion

The present study demonstrates that the co-application of hUC-MSC-sEVs can improve the efficacy of rhBMP-2 to promote the regeneration of osteoporotic bone defects.
Fuzzy cognitive mapping in participatory research and decision making: a practice review
Authors: Sarmiento Iván , Cockcroft Anne , Dion Anna , Belaid Loubna , Silver Hilah , Pizarro Katherine , Pimentel Juan , Tratt Elyse , Skerritt Lashanda , Ghadirian Mona Z. , Gagnon-Dufresne Marie-Catherine , Andersson Neil
Published: May 2024

Background

Fuzzy cognitive mapping (FCM) is a graphic technique to describe causal understanding in a wide range of applications. This practice review summarises the experience of a group of participatory research specialists and trainees who used FCM to include stakeholder views in addressing health challenges. From a meeting of the research group, this practice review reports 25 experiences with FCM in nine countries between 2016 and 2023.

Results

The methods, challenges and adjustments focus on participatory research practice. FCM portrayed multiple sources of knowledge: stakeholder knowledge, systematic reviews of literature, and survey data. Methodological advances included techniques to contrast and combine maps from different sources using Bayesian procedures, protocols to enhance the quality of data collection, and tools to facilitate analysis. Summary graphs communicating FCM findings sacrificed detail but facilitated stakeholder discussion of the most important relationships. We used maps not as predictive models but to surface and share perspectives of how change could happen and to inform dialogue. Analysis included simple manual techniques and sophisticated computer-based solutions. A wide range of experience in initiating, drawing, analysing, and communicating the maps illustrates FCM flexibility for different contexts and skill bases.

Conclusions

A strong core procedure can contribute to more robust applications of the technique while adapting FCM for different research settings. Decision-making often involves choices between plausible interventions in a context of uncertainty and multiple possible answers to the same question. FCM offers systematic and traceable ways to document, contrast and sometimes to combine perspectives, incorporating stakeholder experience and causal models to inform decision-making. Different depths of FCM analysis open opportunities for applying the technique in skill-limited settings.
Single-cell analysis of a progressive Rosai–Dorfman disease affecting the cerebral parenchyma: a case report
Authors: Huang Guo-Hao , Liu Guo-Long , Huang De-Zhi , Diao Xin-Wei , Lv Sheng-Qing
Published: May 2024

Neurologic Rosai–Dorfman disease (RDD) is a rare type of non-Langerhans cell histiocytosis that affects the central nervous system. Most neurologic RDDs grow like meningiomas, have clear boundaries, and can be completely resected. However, a few RDDs are invasive and aggressive, and no effective treatment options are available because the molecular mechanisms involved remain unknown. Here, we report a case of deadly and glucocorticoid-resistant neurologic RDD and explore its possible pathogenic mechanisms via single-cell RNA sequencing. First, we identified two distinct but evolutionarily related histiocyte subpopulations (the C1Q+ and SPP1+ histiocytes) that accumulated in the biopsy sample. The expression of genes in the KRAS signaling pathway was upregulated, indicating gain-of-function of KRAS mutations. The C1Q+ and SPP1+ histiocytes were highly differentiated and arrested in the G1 phase, excluding the idea that RDD is a lympho-histio-proliferative disorder. Second, although C1Q+ histiocytes were the primary RDD cell type, SPP1+ histiocytes highly expressed several severe inflammation-related and invasive factors, such as WNT5A, IL-6, and MMP12, suggesting that SPP1+ histiocytes plays a central role in driving the progression of this disease. Third, oligodendrocytes were found to be the prominent cell type that initiates RDD via MIF and may resist glucocorticoid treatment via the MDK and PTN signaling pathways. In summary, in this case, we report a rare presentation of neurologic RDD and provided new insight into the pathogenic mechanisms of progressive neurologic RDD. This study will also offer evidence for developing precision therapies targeting this complex disease.
Acid-catalyzed transformation of orange waste into furfural: the effect of pectin degree of esterification
Authors: Rivera-Cedillo Eva E. , González-Chávez Marco M. , Handy Brent E. , Quintana-Olivera María F. , López-Mercado Janneth , Cárdenas-Galindo María-Guadalupe
Published: May 2024

The transformation of biomasses from agro-industrial waste can significantly impact the production of green chemicals from sustainable resources. Pectin is a biopolymer present in lignocellulosic biomass as Orange Peel Waste (OPW) and has possibilities for making platform compounds such as furfural for sustainable chemistry. In this work, we studied the transformation to furfural of OPW, pectins, and d-galacturonic acid (D-GalA), which is the main component (65 wt%) of pectin. We analyzed pectins with different degrees of esterification (45, 60 and 95 DE) in a one-pot hydrolysis reaction system and studied the differences in depolymerization and dehydration of the carbohydrates. The results show that the production of furfural decreases as the DE value increases. Specifically, low DE values favor the formation of furfural since the decarboxylation reaction is favored over deesterification. Interestingly, the furfural concentration is dependent upon the polysaccharide composition of pentoses and uronic acid. The obtained concentrations of furfural (13 and 14 mmol/L), d-xylose (6.2 and 10 mmol/L), and L-arabinose (2.5 and 2.7 mmol/L) remained the same when the galacturonic acid was fed either as a polymer or a monomer under the same reaction conditions (0.01 M SA, 90 min and 433 K). OPW is proposed as a feedstock in a biorefinery, in which on a per kg OPW dry basis, 90 g of pectin and 15 g of furfural were produced in the most favorable case. We conclude that the co-production of pectin and furfural from OPW is economically feasible.

Graphical Abstract
Exploring direct and indirect cultural experiences: a study of global consumers’ Hanbok experience and engagement mediated via YouTube
Authors: Lee Jungsoon , Lee Ha Kyung
Published: May 2024

With the rapid development of technology and media, people’s experiences of other cultures have shifted from direct only to a combination of direct and virtual experiences. This study investigated how global consumers directly and indirectly experience other cultures, mediated by YouTube. It focused on the consumer experience of the Korean traditional costume, the Hanbok. YouTube content focusing on Hanbok experiences was collected to understand the direct Hanbok experiences, while viewers’ reactions to YouTube content (i.e., views, likes, and comments) were collected to understand indirect Hanbok experiences. The analysis involved two steps. First, the latent Dirichlet allocation topic modeling algorithm in Python was used to extract topics from direct and indirect Hanbok experiences. Second, simple regression analysis was conducted using numerical data derived from textual data through linguistic inquiry and word count to examine the relationship between direct Hanbok experiences via YouTube and viewer engagement as an indicator of indirect Hanbok experiences. The results showed that YouTubers’ Hanbok experiences were categorized into seven topics, namely novelty, sensory, daily, cultural, trial, pleasing, and intellectual experiences. Indirect Hanbok experiences were identified based on dimensions of consumer engagement, such as social, cognitive, learning, behavioral, and affective engagement. The regression analysis results revealed that cultural and affective Hanbok experiences significantly impacted consumer engagement. This study expanded the scope of research by exploring indirect cultural experiences mediated by a media platform.
P. gingivalis in oral-prostate axis exacerbates benign prostatic hyperplasia via IL-6/IL-6R pathway
Authors: Wang Shuang-Ying , Cai Yi , Hu Xiao , Li Fei , Qian Xin-Hang , Xia Ling-Yun , Gao Bo , Wu Lan , Xie Wen-Zhong , Gu Jia-Min , Deng Tong , Zhu Cong , Jia Hai-Chang , Peng Wan-Qi , Huang Jiao , Fang Cheng , Zeng Xian-Tao
Published: May 2024

Background

Benign prostatic hyperplasia (BPH) is the most common disease in elderly men. There is increasing evidence that periodontitis increases the risk of BPH, but the specific mechanism remains unclear. This study aimed to explore the role and mechanism of the key periodontal pathogen Porphyromonas gingivalis (P. gingivalis) in the development of BPH.

Methods

The subgingival plaque (Sp) and prostatic fluid (Pf) of patients with BPH concurrent periodontitis were extracted and cultured for 16S rDNA sequencing. Ligature-induced periodontitis, testosterone-induced BPH and the composite models in rats were established. The P. gingivalis and its toxic factor P. gingivalis lipopolysaccharide (P.g-LPS) were injected into the ventral lobe of prostate in rats to simulate its colonization of prostate. P.g-LPS was used to construct the prostate cell infection model for mechanism exploration.

Results

P. gingivalis, Streptococcus oralis, Capnocytophaga ochracea and other oral pathogens were simultaneously detected in the Pf and Sp of patients with BPH concurrent periodontitis, and the average relative abundance of P. gingivalis was found to be the highest. P. gingivalis was detected in both Pf and Sp in 62.5% of patients. Simultaneous periodontitis and BPH synergistically aggravated prostate histological changes. P. gingivalis and P.g-LPS infection could induce obvious hyperplasia of the prostate epithelium and stroma (epithelial thickness was 2.97- and 3.08-fold that of control group, respectively), and increase of collagen fibrosis (3.81- and 5.02-fold that of control group, respectively). P. gingivalis infection promoted prostate cell proliferation, inhibited apoptosis, and upregulated the expression of inflammatory cytokines interleukin-6 (IL-6; 4.47-fold), interleukin-6 receptor-α (IL-6Rα; 5.74-fold) and glycoprotein 130 (gp130; 4.47-fold) in prostatic tissue. P.g-LPS could significantly inhibit cell apoptosis, promote mitosis and proliferation of cells. P.g-LPS activates the Akt pathway through IL-6/IL-6Rα/gp130 complex, which destroys the imbalance between proliferation and apoptosis of prostate cells, induces BPH.

Conclusion

P. gingivalis was abundant in the Pf of patients with BPH concurrent periodontitis. P. gingivalis infection can promote BPH, which may affect the progression of BPH via inflammation and the Akt signaling pathway.
Doping Prevalence among U.S. Elite Athletes Subject to Drug Testing under the World Anti-Doping Code
Authors: Davoren Ann Kearns , Rulison Kelly , Milroy Jeff , Grist Pauline , Fedoruk Matthew , Lewis Laura , Wyrick David
Published: May 2024

Background

Determining the prevalence of doping within an elite athlete population is challenging due to the extreme sensitivity of the topic; however, understanding true doping prevalence is important when designing anti-doping programs and measuring their effectiveness. The objective of this study was to estimate the prevalence of doping among Olympic, Paralympic, World, and National-level competitive athletes in the United States subject to the World Anti-Doping Code. All athletes who were subject to the U.S. Anti-Doping Agency’s Protocol for Olympic and Paralympic Movement Testing, a World Anti-Doping Code (“Code”)-compliant anti-doping program, were invited to complete a web-delivered survey. Using a direct questioning approach, the survey items asked athletes whether they had used each specific category of banned substance / method on the World Anti-Doping Agency’s Prohibited List. Multiple strategies to encourage honest reporting (e.g., protecting anonymity by collecting minimal demographic information; using an outside organization to administer the survey) and to detect inconsistent responses were used.

Results

Depending on the method of calculation, 6.5–9.2% of the 1,398 respondents reported using one or more prohibited substances or methods in the 12 months prior to survey administration. Specific doping prevalence rates for each individual substance / method categories ranged from 0.1% (for both diuretics / masking agents and stem cell / gene editing) to 4.2% for in-competition use of cannabinoids.

Conclusion

Determining the prevalence of doping within different athlete populations is critical so that sport governing bodies can evaluate their anti-doping efforts and better tailor their programming. By measuring doping prevalence of specific categories of substances and methods, rather than just the overall prevalence of doping, this study also highlights where sport governing bodies should focus their future educational and detection efforts.
Exploring the feasibility of conducting a randomised controlled trial of group-based pregnancy care and education: a pilot randomised controlled trial in Melbourne, Australia
Authors: Forster Della A. , Matthews Robyn , Hyde Rebecca , Fox Deborah , Dyson Kaye , Ryan Trish
Published: May 2024

Background

In group-based pregnancy models, antenatal care and childbirth/parenting education are provided in groups of eight to 10 women, usually with two midwives, and six to eight sessions. Current evidence is inconclusive regarding potential benefit or harm. We aimed to explore the feasibility of implementing an adequately powered randomised controlled trial (RCT).

Methods

A two-arm pilot RCT was conducted in a tertiary maternity hospital in Melbourne, Australia. Women were randomly allocated to either the intervention to receive group-based antenatal care and education (group care) or to usual care, which included hospital-based midwife, caseload midwifery, team midwifery, or GP shared care. Participants were English-speaking, primiparous, low risk, and < 24 weeks gestation at booking. Data collection: feasibility measures throughout pilot, baseline questionnaire at recruitment, clinical outcome data from the medical record, and a telephone-administered questionnaire 6 weeks postpartum. A focus group explored midwives’ views.

Results

Seventy-four women were recruited from May to June 2017 (group care = 40, usual care = 34). Study uptake was 35%. Women allocated to group care rated their overall pregnancy care more highly (88% good/very good vs 77% in usual care). There was no evidence of harm related to group care. Overarching themes from the midwives were that group care helped ‘build connections’ and ‘empower women’. All midwives would work in the model again and believed it should be expanded.

Conclusion

Group care was acceptable to both women and midwives with no evidence of harm. The pilot demonstrated the feasibility of undertaking a large adequately powered RCT, important given the inconclusive evidence on clinical outcomes regarding the model, and its current relatively widespread implementation.

Trial registration

Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12623000858695.
Exploring EFL learners’ actions during the use of lecture materials in Chinese tertiary classrooms from a transactional view
Authors: Dan Wei , Li Ming
Published: May 2024

Learners’ interaction with lecture materials has remained underexplored despite the growing body of studies on the use of materials. The current study explored the actions EFL learners employed during the use of lecture materials in tertiary classrooms in China through the lens of a transactional view. This empirical study involved forty-two students in two classes as well as two instructors enrolled in the Comprehensive English Course. Qualitative analysis revealed five levels of learner actions during interactions initiated by lectures: awareness, involvement, intervention, creation, and autonomy. The study further highlighted three factors that significantly influence these actions: learners’ intrinsic motivation to participate in classroom interactions, discourse space for participation, and the cultural model of learning. Pedagogical implications for enhancing learner autonomy and contributions during lecture materials use were discussed based on results.
A machine learning approach towards reviewing the role of ‘Internet of Things’ in the shipping industry
Authors: Gerakoudi Kelly , Kokosalakis Georgios , Stavroulakis Peter J.
Published: May 2024

The technology of the Internet of Things (IoT) represents a cornerstone of the fourth industrial revolution. We adopt a machine learning approach to examine the effect of IoT technology on shipping business operations. Text mining and the probabilistic latent Dirichlet allocation are applied for an unsupervised topic modelling analysis of two hundred and twenty-eight academic papers. Our findings reveal the potential of IoT to provide more efficient approaches to business operations and improve the quality of services, highlighting the value of instant and secure information flow among all parties involved. Problematic areas of the new technology are also identified, in reference to issues of standardization and interoperability. Relatively few studies have used machine learning techniques to elicit insights into the holistic effect of emerging IoT technology in the shipping industry. The research findings highlight the potential of IoT technology to transform shipping operations, offering useful and practical implications to academics and professionals.
The characteristics and corrections of ventral support interferences in the transonic-speed wind tunnel for the blended-wing-body aircraft
Authors: Qiu Aoxiang , Sang Weimin , Du Shuya , An Bo , Li Dong , Zhang Binqian
Published: May 2024

For the problem of ventral support interference in a transonic-speed wind tunnel with the blended-wing-body aircraft NPU-BWB-300 installed, the numerical simulation method based on Reynolds-averaged Navier–Stokes (RANS) equations is used to study the influence law of aerodynamic characteristic interference with the variation of Mach numbers and angles of attack. Moreover, the characteristics of ventral support interference for blended-wing-body aircraft and conventional aircraft are compared. The relevant mechanism of the generation and change of ventral support interference is revealed by employing analysis of the body surface pressure, the shock wave of the strut, and the separation area between the strut and the aircraft. The aerodynamic characteristic interference obtained from the numerical simulation is linearized based on the principle of the least square method. Afterward, a numerical simulation correction method of ventral support interference in the transonic-speed wind tunnel for the blended-wing-body aircraft is developed. Finally, the test results after the corrections of ventral support interferences in the transonic-speed wind tunnel for NPU-BWB-300 are obtained, which is significant for the evaluation of current aerodynamic performances and subsequent optimization designs.
Enhanced Whale Optimization Algorithm for task scheduling in cloud computing environments
Authors: Zhang Yanfeng , Wang Jiawei
Published: May 2024

The escalation of cloud services, driven by their accessibility, improved performance, and cost-effectiveness, has led cloud service providers to consistently seek methods to expedite job completion, thereby boosting profits and reducing energy consumption expenses. Despite developing numerous scheduling algorithms, many of these techniques address only a specific objective within the scheduling process. To efficiently achieve better optimization results for the cloud task scheduling problem, a novel approach, the Enhanced Whale Optimization Algorithm (EWOA), is proposed. EWOA integrates the WOA with the Lévy flight. The incorporation of Lévy flight is tailored to broaden the search space of WOA, expediting convergence with adaptive crossover. The EWOA model is simulated using the Cloudsim tool and evaluated under diverse test conditions. The effectiveness of EWOA is assessed by employing various parameters and comparing them with existing algorithms. The results demonstrate that EWOA outperforms other algorithms in resource utilization, energy consumption, and execution cost, establishing its superiority in addressing the complexities of multi-objective cloud task scheduling.
Breaking the Mold: Trailblazing Melanoma Therapy Beyond Checkpoint Through Innovative Approaches
Authors: Kidwai Neiha , Chen Monica , Postow Michael A. , Hassel Jessica , Callahan Margaret
Published: May 2024

Melanoma has long been a difficult malignancy to treat with low response rates to standard chemotherapies. In recent years, the use of immune checkpoint inhibitors have demonstrated promising results, paving the way for the use of the rapidly developing novel immune targeting therapies. In this review, we look beyond immune checkpoint inhibitor treatments and summarize several emerging treatment strategies for melanoma, including neoantigen vaccines, conventional antibody drug-conjugates, and bispecific T-cell engager therapies.
State-of-the-Art Management of Colorectal Cancer: Treatment Advances and Innovation
Authors: Pathak Priyadarshini S. , Chan Gloria , Deming Dustin A. , Chee Cheng Ean
Published: May 2024

Colorectal cancer (CRC) remains a significant global health challenge, ranking among the leading causes of cancer-related morbidity and mortality worldwide. Recent advancements in molecular characterization have revolutionized our understanding of the heterogeneity within colorectal tumors, particularly in the context of tumor sidedness. Tumor sidedness, referring to the location of the primary tumor in either the right or left colon, has emerged as a critical factor influencing prognosis and treatment responses in metastatic CRC. Molecular underpinnings of CRC, the impact of tumor sidedness, and how this knowledge guides therapeutic decisions in the era of precision medicine have led to improved outcomes and better quality of life in patients. The emergence of circulating tumor DNA as a prognostic and predictive tool in CRC heralds promising advancements in the diagnosis and monitoring of the disease. This innovation facilitates better patient selection for exploration of additional treatment options. As the field progresses, with investigational agents demonstrating potential as future treatments for refractory metastatic CRC, new avenues for enhancing outcomes in this challenging disease are emerging.
Biochemical Control in Cushing's Syndrome: Outcomes of the Treatment in a Large Single Center Cohort
Authors: Ritzel Katrin , Fazel Julia , August Leah , Fedtke Vanessa , Nowak Elisabeth , Vogel Frederick , Braun Leah , Zopp Stephanie , Then Cornelia , Künzel Heike , Reisch Nicole , Zimmermann Petra , Thorsteinsdottir Jun , Schopohl Jochen , Bidlingmaier Martin , Beuschlein Felix , Reincke Martin , Rubinstein German
Published: May 2024

Background

Normalization of hypercortisolism is essential to reduce morbidity and mortality in patients with Cushing's syndrome (CS). The aim of this analysis was to assess biochemical control rates in patients with Cushing's disease (CD), ectopic Cushing's syndrome (ECS), and adrenal Cushing's syndrome (ACS).

Methods

Patients with confirmed CS (n = 296) treated in a single tertiary care center were retrospectively analyzed (185 CD, 27 ECS, 84 uni- and bilateral ACS).

Results

First-line treatment led to biochemical control in 82% of the patients. Time to biochemical control (median, interquartile range) was longer in CD (11.0 weeks, 5.6-29.8; P < .05) than in ACS (7.7 weeks, 4.1-17.1) and ECS (5.6 weeks, 4.1-23.3). Disease persistence or recurrence after first-line therapy was observed more often in CD (24% and 18%; P < .05) than in ECS (15% and 15%) and ACS (6% and 4%). Total time in hypercortisolism since diagnosis was significantly shorter in patients with CD diagnosed since 2013, after specialized patient care was implemented, compared to patients diagnosed before 2013 (13.5 weeks vs 26.1 weeks; P < .0070). Control of hypercortisolism at last follow-up (76 months, 38-163) was achieved in 94% of patients with ACS, 100% of patients with ECS, and 92% of patients with CD.

Conclusion

Biochemical control can be achieved in most patients with different subtypes of CS within a reasonable time frame. Control of hypercortisolism has improved over time.
Gαz-independent and -dependent Improvements With EPA Supplementation on the Early Type 1 Diabetes Phenotype of NOD Mice
Authors: Fenske Rachel J , Wienkes Haley N , Peter Darby C , Schaid Michael D , Hurley Liam D , Pennati Andrea , Galipeau Jacques , Kimple Michelle E
Published: May 2024

Prostaglandin E2 (PGE2) is a key mediator of inflammation and is derived from the omega-6 polyunsaturated fatty acid, arachidonic acid (AA). In the β-cell, the PGE2 receptor, Prostaglandin EP3 receptor (EP3), is coupled to the unique heterotrimeric G protein alpha subunit, Gɑz to reduce the production of cyclic adenosine monophosphate (cAMP), a key signaling molecule that activates β-cell function, proliferation, and survival pathways. Nonobese diabetic (NOD) mice are a strong model of type 1 diabetes (T1D), and NOD mice lacking Gɑz are protected from hyperglycemia. Therefore, limiting systemic PGE2 production could potentially improve both the inflammatory and β-cell dysfunction phenotype of T1D. Here, we sought to evaluate the effect of eicosapentaenoic acid (EPA) feeding, which limits PGE2 production, on the early T1D phenotype of NOD mice in the presence and absence of Gαz. Wild-type and Gαz knockout NOD mice were fed a control or EPA-enriched diet for 12 weeks, beginning at age 4 to 5 weeks. Oral glucose tolerance, splenic T-cell populations, islet cytokine/chemokine gene expression, islet insulitis, measurements of β-cell mass, and measurements of β-cell function were quantified. EPA diet feeding and Gɑz loss independently improved different aspects of the early NOD T1D phenotype and coordinated to alter the expression of certain cytokine/chemokine genes and enhance incretin-potentiated insulin secretion. Our results shed critical light on the Gαz-dependent and -independent effects of dietary EPA enrichment and provide a rationale for future research into novel pharmacological and dietary adjuvant therapies for T1D.