bluuebunny/crossref_metadata_2025 huggingface dataset:
Analisis Penentuan Jalur Evakuasi Bencana Tanah Longsor pada Kawasan Permukiman
Authors: Firdaus Muhammad Iqbal , Widyasamratri Hasti , Yuliani Eppy
Published: December 2024

ENGLISHIndonesia is an archipelagic country located on the equator. This causes rainfall in Indonesia to be quite high, around 2.898mm/year. Sukorejo Subdistrict, especially Bringinsari Village, which is located on the slopes of Mount Prau, has a high level of slope and rain intensity. With the high intensity of rain and changing weather conditions in Indonesia, Indonesia is an area prone to hydrometeorological disasters. Landslides are one of the hydrometeorological disasters. Landslides usually occur in areas with a high slope and have a high intensity of rain. The potential for landslide disasters in Bringinsari Village, especially in residential areas, makes disaster mitigation efforts something to pay attention to. Currently, there are no pre-disaster mitigation efforts, especially evacuation routes in Bringinsari Village, because mitigation efforts are only carried out when disasters occur and after disasters occur. Based on the analysis that has been carried out, six settlement points are prone to landslides and five evacuation points are located in Sumenet, Sumilir, Plalar, Gandring, and Balong. This evacuation point is in an open location in the form of a football field in each of these hamlets. The vulnerable points and evacuation points are connected with pre-disaster evacuation routes as a pre-disaster mitigation effort. INDONESIAIndonesia adalah negara kepulauan yang berada pada garis khatulistiwa, hal ini menyebabkan curah hujan di Indonesia cukup tinggi sekitar 2.898 mm/tahun. Kecamatan Sukorejo, khususnya Desa Bringinsari yang berada di lereng Gunung Prau memiliki tingkat kemiringan lereng dan intensitas hujan tinggi. Tingginya intensitas hujan dan kondisi cuaca di Indonesia yang berubah-ubah membuat Indonesia menjadi wilayah yang rawan mengalami bencana hidrometeorologi. Tanah longsor adalah salah satu bencana hidrometeorologi. Tanah longsor biasanya terjadi pada kawasan dengan kemiringan lereng yang tinggi dan memiliki intensitas hujan yang tinggi. Potensi bencana tanah longsor di Desa Bringinsari khususnya pada kawasan permukiman menjadikan upaya mitigasi bencana menjadi sesuatu yang diperhatikan. Saat ini, belum terdapat upaya mitigasi pra bencana khususnya jalur evakuasi di Desa Bringinsari karena upaya mitigasi hanya dilakukan saat bencana terjadi dan setelah bencana terjadi. Berdasarkan analisis yang telah dilakukan dihasilkan 6 (enam) titik permukiman rawan bencana longsor dan 5 (lima) titik evakuasi yang berlokasi pada Dusun Sumenet, Dusun Sumilir, Dusun Plalar, Dusun Gandring, dan Dusun Balong. Titik evakuasi ini berada pada lokasi terbuka berupa lapangan sepakbola di setiap masing-masing dusun tersebut. Titik rawan dan titik evakuasi tersebut dihubungkan dengan jalur evakuasi yang telah ditentukan sebagai upaya mitigasi prabencana.
Characterizing Fatty Acid Profiles and Evaluating Antibacterial Activity of Edible Yellow Puffer Fish, Xenopterus naritus
Authors: MOHAMAD SAMSUR , NOR AZMI NUR EQMAL DINIE , AHMAD NASIR AHMAD SYAFIQ , RANSANGAN JULIAN , NI RABUYAH
Published: December 2024

Puffer fish oil extracted from Xenopterus naritus represents a beneficial source of bioactive compounds with health-promoting properties. Despite the known benefits of puffer fish oil, there is a lack of detailed information on its fatty acid composition. This study aimed to fill this gap by investigating the fatty acid profiles of puffer fish oil extracted from the liver and muscle tissues. The oil was extracted using the solvent Bligh & Dyer method, and the samples were derivatized into fatty acid methyl esters (FAME) before being analyzed via Shimadzu QP2010 Plus gas chromatography-mass spectrometry (GC-MS). This analysis highlighted the prevalence of omega-3 fatty acids, particularly Docosahexaenoic acid (DHA) (8.28 ± 0.08% in liver, 6.15 ± 0.33% in muscle oil) and Eicosapentaenoic acid (EPA) (3.29 ± 0.12% in liver and 2.16 ± 0.06% in muscle oil), along with the abundance of omega-6 and omega-9 fatty acids, including arachidonic and oleic acid. Additionally, the antimicrobial properties of these fish oils were assessed against Gram-negative and Gram-positive bacteria using the Minimum Inhibitory Concentration (MIC) method, revealing promising inhibitory effects, with liver oil demonstrating greater efficacy. These findings suggest that puffer fish oil is rich in beneficial fatty acids and possesses antimicrobial properties that could find applications in food preservation, medicine, and agriculture, thereby offering a fresh perspective on the functional and nutritional value of Xenopterus naritus.
Antagonistic Potential of a Phosphate Solubilizing Bacteria (B. cereus PS1.1, B. cereus PS1.2, B. cereus PS1.4) Against the Patogent Fungus Ganoderma sp. Isolated from Basal Stem of Oil Palm (Elaeis guineensis Jacq.) with Rot Disease
Authors: KHOTIMAH SITI , RAHMAWATI  , MUKARLINA  , INDRIANI ADE
Published: December 2024

Ganoderma sp. is a pathogenic fungus whose attack can cause basal stem rot disease of oil palm (Elaeis guineensis Jacq.). Disease control using phosphate solubilizing bacteria (PSB), namely Bacillus cereus can be an alternative to biological control. The purpose of this study was to determine the antagonistic ability of PSB (B. cereus PS1.1, B. cereus PS1.2, B. cereus PS1.4) in inhibiting the growth of Ganoderma sp. BP1 and changes in hyphal morphology of Ganoderma sp. BP1 after antagonistic testing. The research was conducted from January to May 2023 at the Microbiology Laboratory, Department of Biology, Faculty of Mathematics and Natural Sciences, Tanjungpura University, Pontianak.  Antagonist testing used a completely randomized design (CRD) with the treatments consisted of Ganoderma sp. BP1 (negative control), 1% hexaconazole fungicide (positive control), PSB isolates PS1.1, PS1.2 and PS1.4. The test method used the dual culture on Sabouraud Dextrose Agar (SDA) media with each treatment repeated four times so that 20 experimental units were obtained. The results showed that PSB isolate PS1.4 had strong inhibition with an inhibition zone diameter of 11.01 mm, while isolates PS1.1 and PS1.2 had moderate inhibition with inhibition zone diameters of 9.43 mm and 9.45 mm, respectively, against Ganoderma sp. BP1. Hyphal morphology changes in of Ganoderma sp. BP1 that occurred after the antagonist test consist of lysed hyphae, twisted hyphae, hook-like hyphal tips, curly hyphae, bulbous hyphae, branched hyphae and bent hyphal ends.
Optimizing Silicon Application for Enhancing Growth and Chlorophyll Concentration in Pepper Plants (Piper nigrum L.) Cultivar Kuching
Authors: NUR AINU FARHAH RABAE  , JIN XIAOLEI , NG LEE CHUEN , MOHAMED SIDIQU SITI NORDAHLIAWATE
Published: December 2024

Silicon is known to play a central role in regulating various aspects of plant growth and development, including nutrient uptake, root formation, and growth. Silicon is the second most abundant element found in soil primarily as neutral, monomeric silicic acid, which is the biologically available form for plant uptake. Although silicon is not considered an essential nutrient for the basic life cycle of most plants, its availability can significantly benefits to plant health, growth, and stress tolerance. However, previous research has mainly focused on plants grown in silicon, and silicon occurs naturally as silicon dioxide (SiO2), and is not in a form that is easily absorbed by plants. Therefore, this study investigates the effects of silicon (Si) in silicic acid form (H4O4Si) on the growth and chlorophyll concentration of pepper (Piper nigrum L.) seedlings, particularly the Kuching variety. The Si application had been applied once a week with five different concentrations via root applications; T1 [0.5% Si (v/v)], T2 [1.5% Si (v/v)], T3 [2.0% Si (v/v)], T4 [1.5% potassium silicate (v/v)] as positive control and T5 [negative control (without silicon)] on pepper cutting-grown plants. Growth parameters such as plant height, stem diameter and chlorophyll concentration were observed and collected. Our results showed that the treatment with Si nutrients is promising, as the Si-treated pepper clones showed faster and more robust growth compared to the control plants in the early growth stages. The results indicate that a 0.5% Si concentration (v/v) effectively maintains the high chlorophyll content over four weeks, in contrast to the decreasing trend observed in the control group. This study thus presents the first report on the application of Si in P. nigrum L., demonstrating the feasibility of Si uptake and growth enhancement in pepper plants. The results suggest a stepwise application of Si, starting with low concentrations (0.5% Si v/v) via the root in the early growth stages to strengthen young plants before transplanting to the field. However, foliar spraying could also be considered in future studies as the silicon is absorbed faster compared to root application. Further studies on the passive defence structure (physical barriers such as cuticle, wax, and trichomes) are needed to prove that it can repel pathogens and insects.
Wildfire Pollution And Cognitive Function: A Hidden Effect Of The Climate Crisis
Authors: Buckhouse Talia
Published: December 2024

As global temperature and other symptoms of climate change increase, the threat of wildfires has risen globally. In particular, the western United States has faced detrimental levels of wildfire exposure to particulate matter released by wildfire smoke. Previous research has established the negative respiratory impacts of exposure to wildfire smoke (PM2.5). Further literature has also found associations between pollution and PM2.5 and decreased cognitive function. As such, efforts to establish widespread policy action to decrease exposure to wildfire smoke are paramount to the health of millions.
Financial Management in Guyangan Village in The Indonesian State Financial System
Authors: Septianto A.
Published: December 2024

Law No. 22 of 1999 and Law No. 25 of 1999, as well as Law No. 32 of 2004 and Law No. 33 of 2004, changed the ties between the central authority and the regional authorities. These two laws became the legal basis for the decentralisation method in Indonesia by distributing a significant position to the regional authorities (district or city). Since the enactment of these two laws, the Indonesian government has undergone a significant change from a centralised government to a decentralised government. The benefits of autonomy are carried out starting from provinces, districts/cities to villages. The purpose of this research is to find out how financial management in the village in the Indonesian state financial system
Musculoskeletal model predicted paraspinal loading may quick estimate the effect of exercise on spine BMD
Authors: Liu Shizhong , Xia Xiaoyu , Nie Yinxia , Huang Mengen , Meng Lin , Du Juan
Published: December 2024

Purpose

Spine is the most commonly found fracture site due to osteoporosis. Combined exercise including high-impact and resistance exercise shows the potential to improve bone mineral density (BMD) in the spine. However, the mechanical loading introduced by exercise, which is the mechanism of BMD changes, has not been investigated. The purpose of this study is to provide a new insight to investigate the mechanical stimuli of exercise induced bone remodelling.

Methods

Ten postmenopausal women with osteopenia who finalized a 6-month combined exercise of high-impact and resistance intervention were included. The changes in BMD were analyzed based on QCT images obtained from pre and post intervention. A modified full-body musculoskeletal model was built to estimate paravertebral muscle force (MF) and intervertebral compression force (ICF) during daily activities (walking and heel drop) and combined exercise including high-impact (jumping) and resistance exercise (pulling elastic bands).

Results

The paravertebral MF and ICF during jumping and pulling elastic bands exercise were all significantly greater than walking and heel drop exercise with up to 1.22–8.18 times. Spine BMD remained at the same level with no significant decline observed, especially at L1 (pre 247.95 ± 26.77 mg/cm3 and post 245.49 ± 22.04 mg/cm3). Comparing with daily activities, significant correlations were observed between the changes of BMD and the sum of spinal loadings generated by combined exercise at both global and segmental level (r = 0.687, p < 0.05).

Conclusion

It has been proved that paravertebral muscle forces and intervertebral compression forces generated by the combined exercise, rather than daily exercise, were the main reasons for the improvement of spine BMD. This study contributes into the understanding of exercise induced spine adaptation as well as a potential in fast prediction to evaluate the effect of physical exercise therapy.
Citri reticulate pericranium-derived extracellular vesicles exert antioxidant and anti-inflammatory properties and enhance the bioactivity of nobiletin by forming EVs-nob nanoparticles
Authors: Ma Ling , Ye Zimao , Guo Dongqin , Nie Chao , Zhou Zhiqin
Published: December 2024

Plant-driven extracellular vesicles (PEVs) have attracted significant interest due to their natural origin, remarkable bioactivity, and efficacy in drug encapsulation and target delivery. In our work, extracellular vesicles from Citri Reticulate Pericranium (CEVs) were isolated and investigated their physicochemical characteristics and biological activities. We identified the vesicle structures as regular, with a particle size of approximately 200 nm. We also detected large quantities of lipids, proteins, carbohydrates, as well as total phenols and total flavonoids. The rich content of CEVs endows them with significant antioxidant and anti-inflammatory effects, which can notably increase the levels of GSH and effectively promote the activity of antioxidant markers such as SOD, CAT, and GR. Additionally, they can inhibit the level of inflammatory markers like NO and inflammatory biological factors (IL-6, IL-1β and TNF-α). In addition, we successfully synthesized EVs-nob nanoparticles with a 83.75% ± 2.83% encapsulation rate and 2.79% ± 0.02% drug loading, which may enhance the antioxidant and anti-inflammatory effects of nobiletin. Our research provides critical insights into the bioactivity of CEVs and demonstrates the significant potential of PEVs in nanocarrier creation, thereby promoting the advancement of more PEVs for biomedical applications.
A systematic review and meta-analysis of health-related quality of life among patients with cardiovascular diseases in Ethiopia
Authors: Tassew Worku Chekol , Zeleke Agerie Mengistie , Woldie Samson Sisay , Ferede Yeshiwas Ayale
Published: December 2024

Introduction

Despite Ethiopia's best efforts, the physical, psychological, social, and environmental aspects of quality of life among patients with cardiovascular illnesses such as hypertension have not received adequate consideration. The quality of life among patients with cardiovascular diseases in Ethiopia has not been thoroughly examined; therefore, this study aimed to assess the prevalence and factors associated with health-related quality of life among patients with cardiovascular diseases.

Methods

The results of this systematic review and meta-analysis were reported in accordance with the International Recommended Reporting items for Systematic Review and Meta-analysis guidelines. A thorough search of published literature was conducted utilizing reliable databases (PubMed) and web-based search platforms (Science Direct, African Journals Online, and Google Scholar). The extracted data were imported to STATA version 11 to determine the pooled prevalence of health-related quality of life. The heterogeneity among the results of the primary studies was analyzed using Cochran's Q test and quantified using I2 statistics. A funnel plot and Egger's test were used to determine the presence of publication bias.

Results

This systematic review and meta-analysis included 10 published articles. The pooled prevalence of health-related quality of life among patients with cardiovascular diseases in Ethiopia was 45.32% [95% confidence interval (CI): 37.44–53.20, P < 0.001]. Age older than 60 years [odds ratio (OR) = 3.71, 95% CI: 2.81–4.89], presence of chronic comorbidities (OR: 2.87, 95% CI: 1.72–3.4.79), and rural residence (OR = 15.31, 95% CI: 2.82–83.26) were associated with poor health-related quality of life.

Conclusion

According to the findings of this study, a large number of patients with cardiovascular diseases in Ethiopia experience poor health-related quality of life. Furthermore, age above 60 years, presence of comorbidities, and rural residence were found to have substantial impacts on the quality of life of patients. As a result, this review recommends that quality-of-life evaluation be included in routine patient treatment regimens.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=573993, identifier (CRD42024573993).
Endovascular treatment of postoperative aortic coarctation aneurysms—a single center experience
Authors: Dimitrova Iva N. , Simeonov Peyo
Published: December 2024

Background

Formation of local type aortic aneurysm years after surgical repair of coarctation (CoA) occurs in 10% of patients independent of the surgical technique and is a potentially life-threatening condition if left untreated with a high risk of aortic rupture. Redo open surgery is associated with 14% in-hospital mortality and a high risk of complications. Endovascular treatment appears to be a feasible alternative with a high success rate and low morbidity and mortality, but data concerning long-term results is still mandatory. We describe the single center experience of a series of patients treated with endovascular stent grafting for large aneurysms after previous surgery for CoA.

Methods

This series involves 12 consecutive patients treated with endovascular stent grafting from April 2003 to January 2022 for late aneurysm at the site of previous surgical repair for CoA. Data on baseline characteristics, clinical, computed tomography (CT), procedural features, and in-hospital and long-term results were analyzed. All patients signed institutional informed consent for the procedure.

Results

A total of 12 patients (average age 38.5 ± 10.2 years) underwent endovascular repair. The average interval between the initial surgical intervention and the aneurysm repair was 24.1 ± 9.1 years and the majority (83.3%) underwent synthetic patch aortoplasty as previous intervention. All patients were symptomatic at presentation with an average maximum diameter of the aneurysm 67.2 mm (ranging from 44 to 110 mm). Stent-graft placement was successful in all cases without procedural, in-hospital, 30-day, and one-year mortality or major complications. The average hospital stay was 9.3 days (range 7–19 days). For a mean follow-up period of 87 months (range, 23–168 months), all patients demonstrated positive aneurysm remodeling with cavity thrombosis and aneurysm diameter reduction to 54.9 mm (±16,6). For the entire follow-up period, we observed one aneurysm-related death and three deaths of heart failure.

Conclusion

Endovascular stent-graft treatment of patients with thoracic aneurysms after repair of CoA is an acceptable treatment of choice. It has shown promising results with high technical success and low immediate, short—and mid-term morbidity and mortality. Still, randomised control trials (RCTs) are needed to define the long-term outcome of this approach. Routine surveillance and screening of patients with previous CoA repair are mandatory.
Artificial intelligence in respiratory care
Authors: Karthika Manjush , Sreedharan Jithin K. , Shevade Madhuragauri , Mathew Chris Sara , Ray Santosh
Published: December 2024

The evolution of artificial intelligence (AI) has revolutionised numerous aspects of our daily lives, with profound implications across various sectors, including healthcare. Although the concept of AI in healthcare was introduced in the early 1970s, the integration of this technology in healthcare is still in the evolution phase. Despite barriers, the current decade is witnessing an increased utility of AI into diverse specialities of the medical field to enhance precision medicine, predict diagnosis, therapeutic results, and prognosis; this includes respiratory medicine, critical care, and in their allied specialties. AI algorithms are widely studied in areas like mechanical ventilation, sleep medicine, lung ultrasound, and pulmonary function diagnostics and the results are found to be promising. The quality of patient care and safety can be greatly enhanced if respiratory care professionals fully understand the concept and importance of AI, as they are already incorporating various aspects of this technology into their clinical practice. Awareness of AI in the clinical field is essential during this phase; hence, it is desirable to establish widely accepted standards presented in a clear and accessible language. This article aims to describe the existing and prospective role of AI in the field of respiratory care and allied areas.
Transarterial therapy combined with bevacizumab plus immune checkpoint inhibitors as a neoadjuvant therapy for locally advanced HCC
Authors: Yang Zhenyun , Wang Qianyu , Hu Li , Sima Xiaoxian , Wang Juncheng , Hu Dandan , Zhou Zhongguo , Chen Minshan , Zhang Yaojun , Fu Yizhen
Published: December 2024

Background

Transarterial therapy (TAT), bevacizumab (Bev), and immune checkpoint inhibitors (ICIs) have individually exhibited efficacy in treating advanced-stage hepatocellular carcinoma (HCC). This study aimed to assess the efficacy and safety of the combination of these three treatments as a neoadjuvant modality in patients with locally advanced HCC.

Methods

The primary endpoint is overall survival (OS). The second endpoint is progression free survival (PFS), objective response rate (ORR), pathological response rate and safety.

Results

A total of 54 patients received standard systemic therapy comprising Bev combined with ICIs (Bev-ICIs group), 113 patients received direct surgery (Surgery group), and 273 patients received neoadjuvant therapy of TAT combined Bev plus ICIs, among which 79 patients (28.9%) underwent surgical resection after successful tumor downstaging (Neo-surgery group) while the remaining 194 patients (71.1%) received maintenance systemic therapies (Neo-maintenance group). Neoadjuvant following surgery demonstrated a prolonged OS in contrast to direct surgery, with a median OS time not reached in the Neo-surgery group and 30.6 (95% CI: 26.4-34.7) months in the Surgery group (hazard ratio (HR)=0.29, P=0.0058). The median PFS time in the Neo-surgery and Surgery groups stood at 19.2 (95% CI: 16.1-22.2) and 6.3 (95% CI:4.7-8) months, respectively (HR=0.25, P<0.0001). In patients failed to receiving resection after neoadjuvant therapy, the median OS was 22.8 (95% CI: 22.3-23.1) months, whereas that for the standard care population was 19.7 (95% CI: 15.9-24) month (HR=0.53, P=0.023). The median PFS time in Neo-maintenance group and Bev-ICIs groups was 11.2 (95% CI: 10.4-11.9) and 6.4 (95% CI: 4.4-8.5) months (HR=0.60, P=0.024). The ORR and disease control rate (DCR) across all patients received TAT-Bev-ICIs were 38.8% and 89.4%, respectively. Additionally, the pathological complete response (pCR) rate and the major pathological response (MPR) rate were 22.8% and 48.1% in the Neo-surgery group. As for safety, neoadjuvant therapy did not increase the perioperative complications when compared to direct surgery, and demonstrated similar incidences and severity of AEs when compared to the standard systemic therapy.

Conclusion

The triple therapy regimen comprising TAT-Bev-ICIs emerged as a promising therapeutic strategy for locally advanced hepatocellular carcinoma (HCC) as a neoadjuvant intervention.
Identification and experimental validation of diagnostic and prognostic genes CX3CR1, PID1 and PTGDS in sepsis and ARDS using bulk and single-cell transcriptomic analysis and machine learning
Authors: Jiang Jijin , Chen Yan , Su Yue , Zhang Li , Qian Hao , Song Xinmiao , Xu Jin-Fu
Published: December 2024

Background

Sepsis is an uncontrolled reaction to infection that causes severe organ dysfunction and is a primary cause of ARDS. Patients suffering both sepsis and ARDS have a poor prognosis and high mortality. However, the mechanisms behind their simultaneous occurrence are unclear.

Methods

We acquired sepsis and ARDS datasets from GEO and Arrayexpress databases and screened hub genes by WGCNA and machine learning algorithm. For diagnosis and prognosis, ROC curve and survival analysis were used. We performed GO, KEGG, GSEA, immune cell infiltration, drug prediction, molecular docking, transcription factor prediction, and constructed PPI and ceRNA networks to explore these genes and the common mechanisms of sepsis and ARDS. Single-cell data analysis compared immune cell profiles and hub gene localization. Finally, RT-qPCR and H&E staining confirmed the reliability of hub genes using PBMCs samples and mouse models.

Results

We identified 242 common differentially expressed genes in sepsis and ARDS. WGCNA analysis showed that the turquoise module in GSE95233 is strongly linked to sepsis occurrence and poor prognosis, while the black module in GSE10474 is associated with ARDS. Using WGCNA and three machine learning methods (LASSO, random forest and Boruta), we identified three key genes CX3CR1, PID1 and PTGDS. Models built with them showed high AUC values in ROC curve evaluations and were validated by external datasets, accurately predicting the occurrence and mortality. We further explored the immunological landscape of these genes using immune infiltration and single-cell analysis. Then, the ceRNA, predicted drugs and molecular docking were analyzed. Ultimately, we demonstrated that these genes are expressed differently in human and mouse samples with sepsis and ARDS.

Conclusion

This study identified three molecular signatures (CX3CR1, PID1 and PTGDS) linked to the diagnosis and poor prognosis of sepsis and ARDS, validated by RT-qPCR and H&E staining in both patient and mouse samples. This research may be valuable for identifying shared biological mechanisms and potential treatment targets for both diseases.
Durvalumab and pembrolizumab in advanced biliary tract cancer: a reconstructed patient-level mimic head-to-head comparative analysis
Authors: Wang Bi-Cheng , Kuang Bo-Hua , Lin Guo-He , Fu Chen
Published: December 2024

Background

The addition of durvalumab or pembrolizumab to gemcitabine and cisplatin (GP) has been approved to statistically improve survival outcomes in patients with advanced biliary tract cancer. However, since the survival time was only prolonged by about two months, doubts have been raised. In this analysis, we aimed to evaluate the efficacy of combining durvalumab or pembrolizumab with GP chemotherapy.

Methods

Records were identified through a formal search of PubMed and Web of Science. The TOPAZ-1 and KEYNOTE-966 trials were definitively included. Patient-level overall survival (OS) and progression-free survival (PFS) data were reconstructed and analyzed using a one-stage approach.

Results

The immunotherapy plus GP chemotherapy group showed superiority over the GP chemotherapy group (OS: HR 0.83, p < 0.001; PFS: HR 0.88, p = 0.009). The survival outcomes were similar between the durvalumab and pembrolizumab groups (OS: HR 1.02, p = 0.83; PFS: HR 0.95, p = 0.53). In the subgroup analysis, the gemcitabine-maintenance group significantly prolonged the OS compared to the gemcitabine-limited-to-8-cycles group (OS: HR 0.86, p = 0.007). Neither the durvalumab nor pembrolizumab groups statistically improved the OS compared to the gemcitabine-maintenance group. In contrast, the durvalumab and pembrolizumab groups significantly improved OS compared to the gemcitabine-limited-to-8-cycles group.

Conclusions

Based on this mimic head-to-head analysis, we are convinced that durvalumab and pembrolizumab benefit patients with biliary tract cancer. However, despite the statistically significant differences, the moderate progress made in OS and PFS might still be considered inadequate. It is crucial for clinicians to identify the precise subgroup population that could benefit most from immunotherapy and develop more strategies for those who might not respond well to immunotherapy.
SQLE-mediated squalene metabolism promotes tumor immune evasion in pancreatic cancer
Authors: Pan Junchen , Liang Haixi , Zhou Lin , Lu Wenhua , Huo Bitao , Liu Rui , Huang Peng
Published: December 2024

Background

Squalene epoxidase (SQLE) is a key enzyme in cholesterol biosynthesis and has been shown to negatively affect tumor immunity and is associated with poor outcomes of immunotherapy in various cancers. While most research in this area has focused on the impact of cholesterol on immune functions, the influence of SQLE-mediated squalene metabolism within the tumor immune microenvironment (TIME) remains unexplored.

Methods

We established an immune-competent mouse model (C57BL/6) bearing mouse pancreatic cancer xenografts (KPC cells) with or without stable SQLE-knockdown (SQLE-KD) to evaluate the impact of SQLE-mediated metabolism on pancreatic cancer growth and immune functions. The effect of squalene on tumor growth and immune cells was tested by direct administration of squalene to C57BL/6 mice bearing KPC tumors. Flow cytometry analysis and immunohistochemical (IHC) staining of immune cells from the tumor tissues were performed to evaluate changes in immune function. We also employed RNA-sequencing to analyze the gene expression profiles in pancreatic cancer cells (PANC-1) treated with or without squalene. RT-PCR and Western blot analyses were used to investigate the relevant molecular mechanisms.

Results

We show that SQLE is significantly overexpressed in pancreatic cancer, and abrogation of SQLE results in a significant increase in squalene accumulation within tumor cells. The elevated squalene inhibits CXCL1 transcription through its impact on the NF-κB pathway via p65, and thus reduces the recruitment of myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) into the tumor microenvironment. Silencing of SQLE also leads to an increased proportion of CD8+ T cells in the tumor tissues and suppresses tumor growth in vivo. Importantly, direct administration of squalene, the metabolic substrate of SQLE, to immune-competent mice bearing KPC pancreatic cancer tumors causes a substantial decrease in CD206+ TAMs and MDSCs, thus releasing immune suppression and inhibiting tumor growth.

Conclusion

Our study shows that squalene is an important immune-modulating metabolite that inhibits the infiltration of immune-suppressive cells in TIME, and that SQLE exerts its tumor immune evasion effect by metabolic removal of squalene. Thus, SQLE-mediated squalene metabolic pathway could be a potential target to enhance antitumor immunity in pancreatic cancer.
Latitudinal influences on sound scattering layer characteristics in the Southwestern Indian Ocean: insights into oceanographic environmental interactions
Authors: Kang Myounghee , Simanungkalit Fredrich , Kang Dongha , Jung Jihoon , Kim Joohyang , Song Somang , Kim Yeseul , Kang Dong-Jin , Nam SungHyun
Published: December 2024

Sound scattering layers (SSLs) are vital components of marine ecosystems, yet their morphometric and distributional characteristics remain understudied. This study investigates the SSL core in the southwestern Indian Ocean using a 38 kHz echosounder, focusing on its attributes across latitudinal gradients (20–4°S, 65°E) and three depth layers: epipelagic (0–100 m), intermediate (100–300 m), and mesopelagic (300–600 m). Our findings reveal the highest average acoustic values in the epipelagic layer (–72.9 dB), followed by the mesopelagic layer (–77.8 dB) and the intermediate layer (–82.5 dB). The SSL core was more prominent in northern latitudes (NLS) and showed greater depth variability in southern latitudes (SLS), with vertical profile peaks at 42.2 m and 431.1 m. In the NLS, the SSL core was longer (18,358 m > 6,788 m), thicker (13.8 m > 11.7 m), and more concentrated (aggregation index: 0.0053 m−1 > 0.004 m−1), as well as more dispersed from the center (inertia: 269.9 m² > 112.7 m²). Notably, depth and acoustic fluctuations were more pronounced over circadian cycles in the SLS than in the NLS. Multiple regression analysis revealed that oceanographic factors influencing acoustic values varied by depth, highlighting the complex interactions within SSL ecosystems. These insights enhance our understanding of SSL dynamics and their implications for long-term monitoring and climate influence assessment.
Reduced portal vein blood flow velocity in acute fatty liver of pregnancy
Authors: Zhao Yang , Zhang Er-ke , Li Dan-Hua , Zhou Yu-Jing , Jiang Hui , Jia Xiao-Chao , Qin Chuan
Published: December 2024

Purpose

Acute fatty liver of pregnancy (AFLP) is a severe complication that can occur in the third trimester or immediately postpartum, characterized by rapid hepatic failure. This study aims to explore the changes in portal vein blood flow velocity and liver function during pregnancy, which may assist in the early diagnosis and management of AFLP.

Methods

This longitudinal study was conducted at a tertiary healthcare center with participants recruited from routine antenatal check-ups. The study included healthy women aged 20–40 years with singleton pregnancies. Doppler ultrasonography was used to assess portal vein flow and velocity, complemented by standard laboratory tests to monitor liver function. A nomogram model integrating the clinical features and Doppler ultrasonography parameters was constructed using logistic regression analysis for differentiating AFLP from normal controls.

Results

A total of 135 women were enrolled, divided into control and AFLP groups. The AFLP group demonstrated a significant reduction in portal vein flow velocity and alterations in liver dimensions. Laboratory tests indicated elevated liver enzymes and altered lipid profiles in the AFLP group. Statistical analysis showed that portal vein flow velocity could be a sensitive marker for predicting liver dysfunction in AFLP. The area under the receiver operating characteristic (ROC) curves (AUC) of the nomogram model were 0.88 (95% confidence interval [CI]: 0.82–0.95) with specificity, sensitivity, negative predictive value, and positive predictive value of 67.8, 95.0, 95.0, and 67.8, respectively, in the training cohort and 0.86 (95% CI: 0.72–0.98) and 86.9, 75.0, 83.3, and 80.0 in the test cohort, respectively. The calibration curves demonstrated good agreement between the predicted and observed probability for predicting AFLP.

Conclusion

The study underscores the potential of using portal vein flow velocity as an early diagnostic marker for AFLP in pregnant women. Further research is required to establish standardized diagnostic thresholds for portal vein flow measurements.
WhiA transcription factor provides feedback loop between translation and energy production in a genome-reduced bacterium
Authors: Fisunov Gleb Y. , Tsvetkov Vladimir B. , Tsoy Ekaterina A. , Evsyutina Daria V. , Vedyaykin Alexey D. , Garanina Irina A. , Semashko Tatiana A. , Manuvera Valentin A. , Varizhuk Anna M. , Kovalchuk Sergey I. , Zubov Alexander I. , Barinov Nicolay A. , Pobeguts Olga V. , Govorun Vadim M.
Published: December 2024

Introduction

WhiA is a conserved protein found in numerous bacteria. It consists of an HTH DNA-binding domain linked with a homing endonuclease (HEN) domain. WhiA is one of the most conserved transcription factors in reduced bacteria of the class Mollicutes. Its function in Mollicutes is unknown, while it is well-characterized in Streptomyces. Here, we focused on WhiA protein from Mycoplasma gallisepticum.

Methods

We used a combination molecular dynamics, EMSA, MST and AFM to study the DNA-binding and ATP-binding properties of WhiA from M. gallisepticum. The transcriptional repressor function of WhiA was demonstrated using gene knockdown, reporter constructs and proteome analysis.

Results

We demonstrate that WhiA homolog from M. gallisepticum binds a conserved sequence of the GAYACRCY core (Y = C or T, R = A or G), which is located in the promoter of an operon coding for ribosomal proteins and adenylate kinase (rpsJ operon). We show that WhiA in M. gallisepticum is a repressor of rpsJ operon and a sensor of ATP. HTH domain binds to the core motif and HEN domain binds to the auxiliary motif GTTGT that is located downstream to the core motif. We show that binding by both domains to DNA is required to fulfill the transcription repressor function. Knockdown of whiA does not affect actively growing M. gallisepticum, but leads to the growth retardation after freezing.

Discussion

We propose the following model for M. gallisepticum WhiA function. WhiA remains bound to the core motif at any conditions. At low ATP concentrations (starvation) HEN domain binds auxiliary motif and represses rpsJ operon transcription. At high ATP concentrations (nutrient-rich conditions) HEN domain binds ATP and releases auxiliary motif. It leads to the de-repression of rpsJ operon and increased production of ribosomal proteins.
Effect of conjugative transfer of antibiotic resistance genes mediated by plasmids on the microecology of different intestinal segments
Authors: Ding Chengshi , Yan Li , Zhang Kai , Liu Xiangxiang , Liu Ziyu , Hou Shaowei , Ma Jing , Wu Zhiping , Wei Hongfei
Published: December 2024

Introduction

The conjugative transfer of antibiotic resistance genes (ARGs) mediated by plasmids occurred in different intestinal segments of mice was explored.

Methods

The location of ARG donor bacteria and ARGs was investigated by qPCR, flow cytometry, and small animal imaging. The resistant microbiota was analyzed by 16S rRNA gene amplification sequencing.

Results

The small intestine was the main site for the location of ARG donor bacteria and ARGs. The intestinal microbiota richness of the small intestine (duodenum and jejunum) and the large intestine (cecum, colon, and rectum) increased, and the ileum microbiota richness decreased under the action of donor bacteria. The differences in the number of bacteria in the small intestine and the large intestine, as well as the relative richness of Firmicutes from the small intestine to the large intestine, decreased. By contrast, the relative abundance of Proteobacteria increased. The intake of resistant plasmids alleviated the impact of antibiotics on intestinal microbiota, particularly increasing the proportion of Proteobacteria and Bacteroides, which were presumed to be susceptible to ARGs.

Discussion

The acquisition of ARGs by intestinal microbes is an important reason why infectious diseases are difficult to cure, which brings risks to human health and intestinal microecology.
Untargeted metabolomics profiling of gestational diabetes mellitus: insights into early diagnosis and metabolic pathway alterations
Authors: Aleidi Shereen M. , Al Fahmawi Hiba , AlMalki Reem H. , Al Mogren Maha , Alwahsh Mohammad , Mujammami Muhammad , Costanzo Michele , Abdel Rahman Anas
Published: December 2024

Introduction

Gestational Diabetes Mellitus (GDM) is a metabolic disorder marked by Q10 hyperglycemia that can negatively affect both mothers and newborns. The increasing prevalence of GDM and the limitations associated with the standard diagnostic test highlight the urgent need for early screening strategies that promote timely interventions.

Methods

This study aims to investigate the metabolic profile associated with GDM through an untargeted metabolomic analysis using mass spectrometry (MS)- based omics. Serum samples were collected from 40 pregnant women at weeks 24–28 of gestation based on the 2-h 75-g oral glucose tolerance test (OGTT); 50% were diagnosed with GDM (n = 20), and the remaining were considered a control group.

Results and discussion

The results showed distinct metabolic differences between women with GDM and those without, with 222 significantly dysregulated metabolites, 120 up- and 102 downregulated in GDM compared to the control group. Key metabolic pathways, such as tryptophan, inositol phosphate, phenylalanine, and histidine metabolism, were notably dysregulated in GDM. The study also found that specific metabolites, like N-Acetylproline and Serylmethionine, with area under the curve (AUC) of 0.978 and 0.968, respectively, showed high accuracy in distinguishing between GDM and non-GDM women. This study would enhance our understanding of metabolic alterations in GDM and could contribute to early prediction and management strategies.
Adult neurogenesis in the ventral hippocampus decreased among animal models of neurodevelopmental disorders
Authors: Sun Lihao , Ohashi Nobuhiko , Mori Takuma , Mizuno Yuka , Zang Weichen , Guo Qi , Kouyama-Suzuki Emi , Shirai Yoshinori , Tabuchi Katsuhiko
Published: December 2024

Introduction

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social interaction and communication, along with restricted and repetitive behaviors. Both genetic and environmental factors contribute to ASD, with prenatal exposure to valproic acid (VPA) and nicotine being linked to increased risk. Impaired adult hippocampal neurogenesis, particularly in the ventral region, is thought to play a role in the social deficits observed in ASD.

Methods

In this study, we investigated social behavior and adult hippocampal neurogenesis in C57BL/6J mice prenatally exposed to VPA or nicotine, as well as in genetically modified ASD models, including IQSEC2 knockout (KO) and NLGN3-R451C knock-in (KI) mice. Sociability and social novelty preference were evaluated using a three-chamber social interaction test. Adult hippocampal neurogenesis was assessed by BrdU and DCX immunofluorescence to identify newborn and immature neurons.

Results

VPA-exposed mice displayed significant deficits in social interaction, while nicotine-exposed mice exhibited mild impairment in social novelty preference. Both IQSEC2 KO and NLGN3-R451C KI mice demonstrated reduced adult neurogenesis, particularly in the ventral hippocampus, a region associated with social behavior and emotion. Across all ASD mouse models, a significant reduction in BrdU+/NeuN+ cells in the ventral hippocampus was observed, while dorsal hippocampal neurogenesis remained relatively unaffected. Similar reductions in DCX-positive cells were identified in VPA, nicotine, and NLGN3-R451C KI mice, indicating impaired proliferation or differentiation of neuronal progenitors.

Discussion

These findings suggest that impaired adult neurogenesis in the ventral hippocampus is a common hallmark across ASD mouse models and may underlie social behavior deficits. This study provides insight into region-specific neurogenic alterations linked to ASD pathophysiology and highlights potential targets for therapeutic interventions.
Evolocumab for early reduction of LDL-C levels in patients with acute ischemic stroke: a randomized controlled trial
Authors: Qiu Xiaohui , Liang Yeyuan , Wei Yunfei , Lu Mengru , Mei Yujia , Tang Shiting , Tang Jian , Liang Jinyu , Liang Junli
Published: December 2024

Background

Low-density lipoprotein cholesterol (LDL-C) has been determined as an established risk factor for acute ischemic stroke (AIS). Despite the recommendation for in-hospital initiation of high-intensity statin therapy in AIS patients, achieving the desired target LDL-C levels remains challenging. Evolocumab, a highly effective and quickly acting agent for reducing LDL-C levels, has yet to undergo extensively exploration in the acute phase of AIS. The aim was to assess the LDL-C reduction efficacy and safety of early application of evolocumab during the in-hospital phase of AIS patients.

Methods

An unblinded, single-center, prospective randomized controlled trial involving hospitalized AIS patients was conducted in the Second Affiliated Hospital of Guangxi Medical University in China. Patients were randomly assigned 1:1 to receive evolocumab 420 mg every 4 weeks or not, on top of standard of care (SOC) treatment (atorvastatin 40 mg/day and ezetimibe 10 mg/day), administered in-hospital until after 8 weeks. The primary outcome was the absolute change of LDL-C levels and the rate of achieving targeted lipid control at 8 weeks.

Results

Totally, 120 patients were recruited from January 2023 to December 2023. Mean LDL-C levels decreased from 3.15 mmol/L to 0.85 mmol/L in the evolocumab group, and from 3.17 mmol/L to 2.22 mmol/L in the control group, with the difference in mean change from baseline was −1.37 [95% confidence interval (CI) = −1.70 to −1.04, p < 0.001] at week 8. The rate of patients achieving targeted LDL-C <1.4 mmol/L was 81.67% in evolocumab group as compared with 13.33% in control group. Adverse events were similar in both groups.

Conclusion

Our study indicated that evolocumab added to high-intensity statin and ezetimibe therapy resulted in substantial reduction in LDL-C levels in early AIS patients and was well tolerated.

Clinical trial registration

ClinicalTrials.gov, identifier NCT05697185.
Multiple burr hole and erythropoietin combination therapy: optimal early surgical intervention for patients with acute stroke episode of moyamoya disease or moyamoya syndrome
Authors: Lee Yeonhu , Lee Jin Soo , Lee Seong-Joon , Hong Ji Man , Lim Yong Cheol
Published: December 2024

Objective

The optimal timing of bypass surgery for patients with moyamoya disease (MMD) or moyamoya syndrome (MMS) following an acute stroke episode remains unclear, mainly owing to the risk of postoperative complications. In this study, we aim to validate the safety and efficacy of early intervention using multiple burr hole (MBH) and erythropoietin (EPO) therapy, thereby refining the management strategy for patients with acute stroke episode of MMD or MMS.

Methods

We retrospectively analyzed data from 70 patients with MMD or MMS who underwent MBH and EPO therapy. The cohort was divided based on the time interval between the latest neurological deterioration and surgery: early (<30 days) and later (≥30 days) groups. We evaluated and compared perioperative clinical parameters and the extent of neovascularization on a 6-month postoperative angiography. Long-term clinical outcomes, including transient ischemic attack (TIA), infarction, hemorrhage, and seizure, were also analyzed during the follow-up period.

Results

In the cohort, 36 patients (51.4%) were in the early group, whereas 34 (48.6%) were in the later group. The 6-month follow-up angiography demonstrated that 34/47 hemispheres (72.3%) in the early group exhibited successful neovascularization (≥2/3 of MCA territories) compared with the 19/44 (43.2%) hemispheres in the later group (odds ratio [OR] = 3.44; 95% confidence interval [CI]: 1.46–8.45; p < 0.01). In addition, a notable reduction (≥50%) in basal moyamoya vessels was observed in 30/47 hemispheres (63.8%) from the early group vs. 12/44 (27.3%) hemispheres from the later group (OR = 4.71; 95% CI: 1.97–11.82; p < 0.001). During the average follow-up of 56.5 months, only six patients experienced infarction or hemorrhage.

Conclusion

Our dataset suggests that MBH and EPO combination therapy is an effective, minimally invasive, and acceptable treatment, even in the early period of patients with MMD or MMS following an acute stroke episode.