bluuebunny/crossref_metadata_2025_split huggingface dataset:
UJI EFEKTIVITAS ANTIINFLAMASI EKSTRAK ETANOL KOMBINASI DAUN KEMANGI LOMBOK (Ocimum sanctum) DAN DAUN SALAM (Syzygium polyanthum) PADA TIKUS JANTAN
Authors: Putri Susi Windi Ana , Pertiwi Ajeng Dian , Rahmawati Sri , Idawati Sri 
Published: March 2024

Inflamasi merupakan respon tubuh terhadap cedera jaringan dan infeksi, sehingga menginaktifasi atau merusak organisme yang menyerang. Menghilangkan zat iritan, dan mengatur derajat perbaikan jaringan. Lima khas cirri dari inflamasi atau biasa dikenal sebagai tanda-tanda utama inflamasi yaitu kemerahan (rubor), panas (kalor), pembekakan (tumor), nyeri/sakit (dolor) dan hilangnya fungsi (fungsiolaesa)
Penelitian ini bertujuan untuk mengetaui efek dari inflmasi ekstrak etanol kombinasi daun kemangi lombok (Ocimum Sanctum) daun salam (Syzygium Polyanthum) pada tikus jantan yang dinduksi dengan caragen 0,1%. Penelitian ini melakukan 15 ekor tikus jantan dan dibagi menjadi 5 kelompok, kelompok I diberikan Nacmc sebagai kontrol (positif), kelompok II diberikan Natrium Diclofenac sebagai kontrol (Negatif), kelompok III diberikan estrak etanol kombinasi daun kemangi lombok dan daun salam dengan dosis 125:125 mg/ kg bb, kelompok IV diberikan ekstrak etanol kombinasi daun kemangi lombok dan daun salam dengan dosis 125:75mg/ kg bb, dan kelompok V diberikan ekstrak etanol kombinasi daun kemangi lombok dan daun salam dengan dosis 250:75mg/ kg bb. Seluruh pemberian dilakukan secara oral, dan pengukuran kaki tikus jantan dilakukan setiap 30 menit sampai 150 menit. Data dianalisis secara statistik menggunakan one way anova dilanjutkan dengan uji LSD untuk melihat antar perlakuan. Hasil penelitian menunjukan bahwa dosis 250:75 memiliki efek untuk menurunkan jumlah volume udem yang terjadi pada tikus jantan.
Life cycle assessment of iron-biomass supported catalyst for Fischer Tropsch synthesis
Authors: Amin Muhammad , Shah Hamad Hussain , Naveed Abdul Basit , Iqbal Amjad , Gamil Yaser , Najeh Taoufik 
Published: March 2024

The iron-based biomass-supported catalyst has been used for Fischer-Tropsch synthesis (FTS). However, there is no study regarding the life cycle assessment (LCA) of biomass-supported iron catalysts published in the literature. This study discusses a biomass-supported iron catalyst’s LCA for the conversion of syngas into a liquid fuel product. The waste biomass is one of the source of activated carbon (AC), and it has been used as a support for the catalyst. The FTS reactions are carried out in the fixed-bed reactor at low or high temperatures. The use of promoters in the preparation of catalysts usually enhances C5+ production. In this study, the collection of precise data from on-site laboratory conditions is of utmost importance to ensure the credibility and validity of the study’s outcomes. The environmental impact assessment modeling was carried out using the OpenLCA 1.10.3 software. The LCA results reveals that the synthesis process of iron-based biomass supported catalyst yields a total impact score in terms of global warming potential (GWP) of 1.235E + 01 kg CO2 equivalent. Within this process, the AC stage contributes 52% to the overall GWP, while the preparation stage for the catalyst precursor contributes 48%. The comprehensive evaluation of the iron-based biomass supported catalyst’s impact score in terms of human toxicity reveals a total score of 1.98E−02 kg 1,4-dichlorobenzene (1,4-DB) equivalent.
Effects of irrigation dams on riverine biota in mountain streams
Authors: Rocha Pompeu Cássia , Peñas Francisco J. , Barquín José 
Published: March 2024

Mountain streams harbor unique biodiversity and provide essential ecosystem services to human societies. Yet, these ecosystems face numerous threats, such as the construction of dams and land use changes, leading to rapid habitat degradation, water pollution, and biodiversity loss. In this study, we assess the effect of irrigation dams on mountain riverine biota using traditional biotic indices and trait-based approaches. We selected diatom and macroinvertebrate communities surveyed between 2015 and 2017 in mountain streams located in different regions in northern Spain (Cantabrian Cordillera, Iberian System, and Pyrenees) under natural and altered flow conditions (i.e., downstream of irrigation dams). Hydrological and biological changes related to the presence of dams, the mountain range, and the interaction between these two factors were identified. Summer flows, frequency of high flow events, and minimum annual flows timing were significantly affected by irrigation dams, independently of the region. Winter flows, the magnitude of high flow extremes, and the number of flow rises and falls varied significantly with the dam-mountain range interaction. The frequency and duration of flow pulses depended on the mountain range only. In the Cantabrian Cordillera, a region with larger reservoirs (&gt;150 hm3), impacted sites showed a marked inversion of the seasonal flow patterns (i.e., increased summer flows but reduced winter flows). In the other mountain ranges, reservoirs had smaller storage volumes and multiple purposes, causing significant flow change frequency variations. Diatom traits, taxonomic richness, diversity, and IPS score varied with dam presence and mountain ranges, while macroinvertebrate traits and biotic indices responded weakly. These findings suggest that diatom communities might be more sensitive to hydrological alteration, while macroinvertebrates might be more influenced by space-related factors, such as biogeography and dispersal, overriding dam-related impacts. Furthermore, dam-related changes in ecosystems may depend not only on the presence of dams and their characteristics (e.g., reservoir size and operation), but also on local conditions and biogeography. Our findings emphasize that, when using pre-existing biomonitoring datasets, although some dam-related patterns emerge (e.g., with diatoms), other patterns may be constrained by the datasets’ low spatio-temporal coverage and taxonomic resolution, highlighting the need of well-structured study designs.
Construction and validation of a machine learning-based nomogram to predict the prognosis of HBV associated hepatocellular carcinoma patients with high levels of hepatitis B surface antigen in primary local treatment: a multicenter study
Authors: Xiong Yiqi , Qiao Wenying , Wang Qi , Li Kang , Jin Ronghua , Zhang Yonghong 
Published: March 2024

BackgroundHepatitis B surface antigen (HBsAg) clearance is associated with improved long-term outcomes and reduced risk of complications. The aim of our study was to identify the effects of levels of HBsAg in HCC patients undergoing TACE and sequential ablation. In addition, we created a nomogram to predict the prognosis of HCC patients with high levels of HBsAg (≥1000U/L) after local treatment.MethodThis study retrospectively evaluated 1008 HBV-HCC patients who underwent TACE combined with ablation at Beijing Youan Hospital and Beijing Ditan Hospital from January 2014 to December 2021, including 334 patients with low HBsAg levels and 674 patients with high HBsAg levels. The high HBsAg group was divided into the training cohort (N=385), internal validation cohort (N=168), and external validation cohort (N=121). The clinical and pathological features of patients were collected, and independent risk factors were identified using Lasso-Cox regression analysis for developing a nomogram. The performance of the nomogram was evaluated by C-index, receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) curves in the training and validation cohorts. Patients were classified into high-risk and low-risk groups based on the risk scores of the nomogram.ResultAfter PSM, mRFS was 28.4 months (22.1-34.7 months) and 21.9 months (18.5-25.4 months) in the low HBsAg level and high HBsAg level groups (P&lt;0.001). The content of the nomogram includes age, BCLC stage, tumor size, globulin, GGT, and bile acids. The C-index (0.682, 0.666, and 0.740) and 1-, 3-, and 5-year AUCs of the training, internal validation, and external validation cohorts proved good discrimination of the nomogram. Calibration curves and DCA curves suggested accuracy and net clinical benefit rates. The nomogram enabled to classification of patients with high HBsAg levels into low-risk and high-risk groups according to the risk of recurrence. There was a statistically significant difference in RFS between the two groups in the training, internal validation, and external validation cohorts (P&lt;0.001).ConclusionHigh levels of HBsAg were associated with tumor progression. The nomogram developed and validated in the study had good predictive ability for patients with high HBsAg levels.
Cooperative interaction of interferon regulatory factor -1 and bromodomain—containing protein 4 on RNA polymerase activation for intrinsic innate immunity
Authors: Xu Xiaofang , Qiao Dianhua , Brasier Allan R. 
Published: March 2024

IntroductionThe human orthopneumovirus, Respiratory Syncytial Virus (RSV), is the causative agent of severe lower respiratory tract infections (LRTI) and exacerbations of chronic lung diseases. In immune competent hosts, RSV productively infects highly differentiated epithelial cells, where it elicits robust anti-viral, cytokine and remodeling programs. By contrast, basal cells are relatively resistant to RSV infection, in part, because of constitutive expression of an intrinsic innate immune response (IIR) consisting of a subgroup of interferon (IFN) responsive genes. The mechanisms controlling the intrinsic IIR are not known.MethodsHere, we use human small airway epithelial cell hSAECs as a multipotent airway stem cell model to examine regulatory control of an intrinsic IIR pathway.ResultsWe find hSAECs express patterns of intrinsic IIRs, highly conserved with pluri- and multi-potent stem cells. We demonstrate a core intrinsic IIR network consisting of Bone Marrow Stromal Cell Antigen 2 (Bst2), Interferon Induced Transmembrane Protein 1 (IFITM1) and Toll-like receptor (TLR3) expression are directly under IRF1 control. Moreover, expression of this intrinsic core is rate-limited by ambient IRF1• phospho-Ser 2 CTD RNA Polymerase II (pSer2 Pol II) complexes binding to their proximal promoters. In response to RSV infection, the abundance of IRF1 and pSer2 Pol II binding is dramatically increased, with IRF1 complexing to the BRD4 chromatin remodeling complex (CRC). Using chromatin immunoprecipitation in IRF1 KD cells, we find that the binding of BRD4 is IRF1 independent. Using a small molecule inhibitor of the BRD4 acetyl lysine binding bromodomain (BRD4i), we further find that BRD4 bromodomain interactions are required for stable BRD4 promoter binding to the intrinsic IIR core promoters, as well as for RSV-inducible pSer2 Pol II recruitment. Surprisingly, BRD4i does not disrupt IRF1-BRD4 interactions, but disrupts both RSV-induced BRD4 and IRF1 interactions with pSer2 Pol II.ConclusionsWe conclude that the IRF1 functions in two modes- in absence of infection, ambient IRF1 mediates constitutive expression of the intrinsic IIR, whereas in response to RSV infection, the BRD4 CRC independently activates pSer2 Pol II to mediates robust expression of the intrinsic IIR. These data provide insight into molecular control of anti-viral defenses of airway basal cells.
Clinicopathologic analysis of nodal T-follicular helper cell lymphomas, a multicenter retrospective study from China
Authors: Ma Shanshan , Li Suxiao , Zuo Xiaona , Li Wencai , Wang Lifu , Liu Weiping , Wang Zhe , Sang Wei , Wang Yanjie , Zhang Xudong , Zhang Mingzhi 
Published: March 2024

BackgroundNodal T-follicular helper cell lymphomas (nTFHLs) represent a new family of peripheral T-cell lymphomas (PTCLs), and comparative studies of their constituents are rare.MethodsThis study retrospectively enrolled 10 patients with nTFHL-F and 30 patients with nTFHL-NOS diagnosed between December 2017 and October 2023 at six large comprehensive tertiary hospitals; 188 patients with nTFHL-AI were diagnosed during the same period at the First Affiliated Hospital of Zhengzhou University for comparison.ResultsCompared with nTFHL-AI, nTFHL-NOS patients exhibited better clinical manifestations, lower TFH expression levels, and a lower Ki-67 index. However, no differences in clinicopathological features were observed between nTFHL-F and nTFHL-AI patients as well as nTFHL-NOS patients. According to the survival analysis, the median OS for patients with nTFHL-NOS, nTFHL-AI, and nTFHL-F were 14.2 months, 10 months, and 5 months, respectively, whereas the median TTP were 14 months, 5 months, and 3 months, respectively. Statistical analysis revealed differences in TTP among the three subtypes(P=0.0173). Among the population of patients receiving CHOP-like induction therapy, there were significant differences in the OS and TTP among the nTFHL-NOS, nTFHL-AI, and nTFHL-F patients (P=0.0134, P=0.0205). Both the GDPT and C-PET regimens significantly improved the ORR, OS, and PFS in nTFHL patients.ConclusionThere are significant differences in the clinical manifestations, pathology, and survival outcomes among the three subtypes of nTFHLs. However, further research with a larger sample size, and involving clinical pathology and molecular genetics is needed to determine the distinctive biological characteristics of these tumors.
Choosing T-cell sources determines CAR-T cell activity in neuroblastoma
Authors: García-García Lorena , G. Sánchez Elena , Ivanova Mariya , Pastora Keren , Alcántara-Sánchez Cristina , García-Martínez Jorge , Martín-Antonio Beatriz , Ramírez Manuel , González-Murillo África 
Published: March 2024

IntroductionThe clinical success of chimeric antigen receptor-modified T cells (CAR-T cells) for hematological malignancies has not been reproduced for solid tumors, partly due to the lack of cancer-type specific antigens. In this work, we used a novel combinatorial approach consisting of a versatile anti-FITC CAR-T effector cells plus an FITC-conjugated neuroblastoma (NB)-targeting linker, an FITC-conjugated monoclonal antibody (Dinutuximab) that recognizes GD2.MethodsWe compared cord blood (CB), and CD45RA-enriched peripheral blood leukapheresis product (45RA) as allogeneic sources of T cells, using peripheral blood (PB) as a control to choose the best condition for anti-FITC CAR-T production. Cells were manufactured under two cytokine conditions (IL-2 versus IL-7+IL-15+IL-21) with or without CD3/CD28 stimulation. Immune phenotype, vector copy number, and genomic integrity of the final products were determined for cell characterization and quality control assessment. Functionality and antitumor capacity of CB/45RA-derived anti-FITC CAR-T cells were analyzed in co-culture with different anti-GD2-FITC labeled NB cell lines.ResultsThe IL-7+IL-15+IL-21 cocktail, in addition to co-stimulation signals, resulted in a favorable cell proliferation rate and maintained less differentiated immune phenotypes in both CB and 45RA T cells. Therefore, it was used for CAR-T cell manufacturing and further characterization. CB and CD45RA-derived anti-FITC CAR-T cells cultured with IL-7+IL-15+IL-21 retained a predominantly naïve phenotype compared with controls. In the presence of the NB-FITC targeting, CD4+ CB-derived anti-FITC CAR-T cells showed the highest values of co-stimulatory receptors OX40 and 4-1BB, and CD8+ CAR-T cells exhibited high levels of PD-1 and 4-1BB and low levels of TIM3 and OX40, compared with CAR-T cells form the other sources studied. CB-derived anti-FITC CAR-T cells released the highest amounts of cytokines (IFN-γ and TNF-α) into co-culture supernatants. The viability of NB target cells decreased to 30% when co-cultured with CB-derived CAR-T cells during 48h.ConclusionCB and 45RA-derived T cells may be used as allogeneic sources of T cells to produce CAR-T cells. Moreover, ex vivo culture with IL-7+IL-15+IL-21 could favor CAR-T products with a longer persistence in the host. Our strategy may complement the current use of Dinutuximab in treating NB through its combination with a targeted CAR-T cell approach.
Modular design of bi- and multi-specific knob domain fusions
Authors: Kuravsky Mikhail , Gibbons Glyn F. , Joyce Callum , Scott-Tucker Anthony , Macpherson Alex , Lawson Alastair D. G. 
Published: March 2024

IntroductionThe therapeutic potential of bispecific antibodies is becoming widely recognised, with over a hundred formats already described. For many applications, enhanced tissue penetration is sought, so bispecifics with low molecular weight may offer a route to enhanced potency. Here we report the design of bi- and tri-specific antibody-based constructs with molecular weights as low as 14.5 and 22 kDa respectively.MethodsAutonomous bovine ultra-long CDR H3 (knob domain peptide) modules have been engineered with artificial coiled-coil stalks derived from Sin Nombre orthohantavirus nucleocapsid protein and human Beclin-1, and joined in series to produce bi- and tri-specific antibody-based constructs with exceptionally low molecular weights.ResultsKnob domain peptides with coiled-coil stalks retain high, independent antigen binding affinity, exhibit exceptional levels of thermal stability, and can be readily joined head-to-tail yielding the smallest described multi-specific antibody format. The resulting constructs are able to bind simultaneously to all their targets with no interference.DiscussionCompared to existing bispecific formats, the reduced molecular weight of the knob domain fusions may enable enhanced tissue penetration and facilitate binding to cryptic epitopes that are inaccessible to conventional antibodies. Furthermore, they can be easily produced at high yield as recombinant products and are free from the heavy-light chain mispairing issue. Taken together, our approach offers an efficient route to modular construction of minimalistic bi- and multi-specifics, thereby further broadening the therapeutic scope for knob domain peptides.
Electroacupuncture regulates gut microbiota to reduce depressive-like behavior in rats
Authors: Wang Junying , Zhu Haohan , Song Xingke , Zhao Jun , Zhang Jianliang , Zhang Jinling , Li Shaoyuan , Rong Peijing 
Published: March 2024

Background and objectivesGrowing studies show that gut microbiota is closely associated with depression. Acupuncture treatment could regulate the gut microbiota of many diseases. Here, we aim to observe the effect of electroacupuncture (EA) on gut microbiota in rats that showed depressive-like behavior.Materials and methodsThe rats were randomly divided into normal group, chronic unpredictable mild stress model (CUMS) group, CUMS + electroacupuncture (EA) group, and CUMS + sham-electroacupuncture (Sham) group. The CUMS+EA rats were treated with EA stimulation at bilateral Zusanli (ST36) and Tianshu (ST25) acupoints for 2 weeks (0.7 mA, 2/100 Hz, 30 min/day). The rats in the sham EA group were treated with the same conditions without inserting needles and electrical stimulation. Behavioral tests were conducted by forced swimming test (FST), open field test (OFT), and sucrose preference test (SPT) to assess depression-like behavior in rats. The relative abundance of intestinal bacteria in rat feces was detected by 16S rRNA analysis. The expression of calcitonin-gene-related peptide (CGRP), vasoactive intestinal peptide (VIP), somatostatin (SST), and adrenocorticotropic hormone (ACTH) in serum was detected by ELISA kit, and VIP, CGRP, and SST in the colon were detected by qRT-PCR and Western blot.ResultsChronic unpredictable mild stress model rats exhibited depressive-like behaviors and had differential abundance vs. control rats. CUMS significantly decreased the relative abundance of Bifidobacterium and Streptococcus at the genus level, CGRP in plasma (p &lt; 0.05), and significantly increased the intestine propulsion rate, the mRNA and protein expression of VIP, SST, and mRNA in the colon, and ATCH in plasma (p &lt; 0.05). EA rats with microbial profiles were distinct from CUMS rats. EA markedly reduced the depressive-like behaviors, significantly increased the intestine propulsion rate, the relative abundance of Bacteroidetes, Proteobacteria, and Actinobacteria at the phylum level, Bifidobacterium and Streptococcus at the genus level, and VIP and CGRP in plasma (p &lt; 0.05), and significantly decreased Firmicutes, the ratio of Firmicutes to Bacteroidetes at the phylum level, ACTH and SST in plasma, and SST mRNA in the colon (p &lt; 0.05).ConclusionThe antidepressant effect of EA at ST36 and ST25 is related to regulating intestinal flora and the neurotransmitter system. Our study suggests that EA contributes to the improvement of depression, and gut microbiota may be one of the mechanisms of EA effect.
Using a k-means clustering to identify novel phenotypes of acute ischemic stroke and development of its Clinlabomics models
Authors: Jiang Yao , Dang Yingqiang , Wu Qian , Yuan Boyao , Gao Lina , You Chongge 
Published: March 2024

ObjectiveAcute ischemic stroke (AIS) is a heterogeneous condition. To stratify the heterogeneity, identify novel phenotypes, and develop Clinlabomics models of phenotypes that can conduct more personalized treatments for AIS.MethodsIn a retrospective analysis, consecutive AIS and non-AIS inpatients were enrolled. An unsupervised k-means clustering algorithm was used to classify AIS patients into distinct novel phenotypes. Besides, the intergroup comparisons across the phenotypes were performed in clinical and laboratory data. Next, the least absolute shrinkage and selection operator (LASSO) algorithm was used to select essential variables. In addition, Clinlabomics predictive models of phenotypes were established by a support vector machines (SVM) classifier. We used the area under curve (AUC), accuracy, sensitivity, and specificity to evaluate the performance of the models.ResultsOf the three derived phenotypes in 909 AIS patients [median age 64 (IQR: 17) years, 69% male], in phenotype 1 (N = 401), patients were relatively young and obese and had significantly elevated levels of lipids. Phenotype 2 (N = 463) was associated with abnormal ion levels. Phenotype 3 (N = 45) was characterized by the highest level of inflammation, accompanied by mild multiple-organ dysfunction. The external validation cohort prospectively collected 507 AIS patients [median age 60 (IQR: 18) years, 70% male]. Phenotype characteristics were similar in the validation cohort. After LASSO analysis, Clinlabomics models of phenotype 1 and 2 were constructed by the SVM algorithm, yielding high AUC (0.977, 95% CI: 0.961–0.993 and 0.984, 95% CI: 0.971–0.997), accuracy (0.936, 95% CI: 0.922–0.956 and 0.952, 95% CI: 0.938–0.972), sensitivity (0.984, 95% CI: 0.968–0.998 and 0.958, 95% CI: 0.939–0.984), and specificity (0.892, 95% CI: 0.874–0.926 and 0.945, 95% CI: 0.923–0.969).ConclusionIn this study, three novel phenotypes that reflected the abnormal variables of AIS patients were identified, and the Clinlabomics models of phenotypes were established, which are conducive to individualized treatments.