bluuebunny/crossref_metadata_2025_split huggingface dataset:
Isolation and anti-neuroinflammation activity of sesquiterpenoids from Artemisia argyi: computational simulation and experimental verification
Authors: La Caiwenjie , Li Menghe , Wang Zexu , Liu Tao , Zeng Qiongzhen , Sun Pinghua , Ren Zhe , Ye Cuifang , Liu Qiuying , Wang Yifei 
Published: July 2024

Abstract
Background
Artemisia argyi is a traditional herbal medicine belonging to the genus Artemisia that plays an important role in suppressing inflammation. However, the chemical constituents and underlying mechanisms of its therapeutic potential in neuroinflammation are still incompletely understood, and warrant further investigation.

Methods
Several column chromatography were employed to isolate and purify chemical constituents from Artemisia argyi, and modern spectroscopy techniques were used to elucidate their chemical structures. The screening of monomeric compounds with nitric oxide inhibition led to the identification of the most effective bioactive compound, which was subsequently confirmed for its anti-inflammatory capability through qRT‒PCR. Predictions of compound-target interactions were made using the PharmMapper webserver and the TargetNet database, and an integrative protein-protein interaction network was constructed by intersecting the predicted targets with neuroinflammation-related targets. Topological analysis was performed to identify core targets, and molecular docking and molecular dynamics simulations were utilized to validate the findings. The result of the molecular simulations was experimentally validated through drug affinity responsive target stability (DARTS) and Western blot experiments.

Results
Seventeen sesquiterpenoids, including fifteen known sesquiterpenoids and two newly discovered guaiane-type sesquiterpenoids (argyinolide S and argyinolide T) were isolated from Artemisia argyi. Bioactivity screening revealed that argyinolide S (AS) possessed the most potent anti-inflammatory activity. However, argyinolide T (AT) showed weak anti-inflammatory activity, so AS was the target compound for further study. AS may regulate neuroinflammation through its modulation of eleven core targets: protein kinase B 1 (AKT1), epidermal growth factor receptor (EGFR), proto-oncogene tyrosine-protein Kinase (FYN), Janus Kinase (JAK) 1, mitogen-activated protein (MAP) Kinase 1,8 and 14, matrix metalloproteinase 9 (MMP9), ras-related C3 botulinum toxin substrate 1 (RAC1), nuclear factor kappa-B p65 (RELA), and retinoid X receptor alpha (RXRA). Molecular dynamics simulations and DARTS experiments confirmed the stable binding of AS to JAK1, and Western blot experiments demonstrated the ability of AS to inhibit the phosphorylation of downstream Signal transducer and activator of transcription 3 (STAT3) mediated by JAK1.

Conclusions
The sesquiterpenoid compounds isolated from Artemisia argyi, exhibit significant inhibitory effects on inflammation in C57BL/6 murine microglia cells (BV-2). Among these compounds, AS, a newly discovered guaiane-type sesquiterpenoid in Artemisia argyi, has been demonstrated to effectively inhibit the occurrence of neuroinflammation by targeting JAK1.
Wealth-based disparities in the prevalence of short birth interval in India: insights from NFHS-5
Authors: Singh Aditya , Singh Anshika , Chakrabarty Mahashweta , Singh Shivani , Tripathi Pooja 
Published: July 2024

Abstract
Background
Short birth interval (SBI) has profound implications for the health of both mothers and children, yet there remains a notable dearth of studies addressing wealth-based inequality in SBI and its associated factors in India. This study aims to address this gap by investigating wealth-based disparities in SBI and identifying the underlying factors associated with SBI in India.

Methods
We used information on 109,439 women of reproductive age (15–49 years) from the fifth round of the National Family Health Survey (2019-21). We assessed wealth-based inequality in SBI for India and its states using the Erreygers Normalised Concentration Index (ECI). Additionally, we used a multilevel binary logistic regression to assess the factors associated with SBI in India.

Results
In India, the prevalence of SBI was 47.8% [95% CI: 47.4, 48.3] during 2019-21, with significant variation across states. Bihar reported the highest prevalence of SBI at 61.2%, while Sikkim the lowest at 18.1%. SBI prevalence was higher among poorer mothers compared to richer ones (Richest: 33.8% vs. Poorest: 52.9%). This wealth-based inequality was visible in the ECI as well (ECI= -0.13, p < 0.001). However, ECI varied considerably across the states. Gujarat, Punjab, and Manipur exhibited the highest levels of wealth-based inequality (ECI= -0.28, p < 0.001), whereas Kerala showed minimal wealth-based inequality (ECI= -0.01, p = 0.643). Multilevel logistic regression analysis identified several factors associated with SBI. Mothers aged 15–24 (OR: 12.01, p < 0.001) and 25–34 (2.92, < 0.001) were more likely to experience SBI. Women who married after age 25 (3.17, < 0.001) and those belonging to Scheduled Caste (1.18, < 0.001), Scheduled Tribes (1.14, < 0.001), and Other Backward Classes (1.12, < 0.001) also had higher odds of SBI. Additionally, the odds of SBI were higher among mothers in the poorest (1.97, < 0.001), poorer (1.73, < 0.001), middle (1.62, < 0.001), and richer (1.39, < 0.001) quintiles compared to the richest quintile. Women whose last child had passed away were also significantly more likely to have SBI (2.35, < 0.001). Furthermore, mothers from communities with lower average schooling levels (1.18, < 0.001) were more likely to have SBI. Geographically, mothers from eastern (0.67, < 0.001) and northeastern (0.44, < 0.001) regions of India were less likely to have SBI.

Conclusion
The significant wealth-based inequality in SBI in India highlights the need for targeted interventions focusing on economically disadvantaged women, particularly in states with high SBI prevalence. Special attention should be given to younger mothers and those from socially disadvantaged groups to enhance maternal and child health outcomes across the country.
Mesomelia-synostoses syndrome: contiguous deletion syndrome, SULF1 haploinsufficiency or enhancer adoption?
Authors: Bendas Feres Lima Ingrid , Fátima Marques de Moraes Lúcia de , Roberto da Fonseca Carlos , Clinton Llerena Junior Juan , Mehrjouy Mana , Tommerup Niels , Ferreira Bastos Elenice 
Published: July 2024

Abstract
Background
Mesomelia-Synostoses Syndrome (MSS)(OMIM 600,383) is a rare autosomal dominant disorder characterized by mesomelic limb shortening, acral synostoses and multiple congenital malformations which is described as a contiguous deletion syndrome involving the two genes SULF1 and SLCO5A1. The study of apparently balanced chromosomal rearrangements (BCRs) is a cytogenetic strategy used to identify candidate genes associated with Mendelian diseases or abnormal phenotypes. With the improved development of genomic technologies, new methods refine this search, allowing better delineation of breakpoints as well as more accurate genotype-phenotype correlation.

Case presentation
We present a boy with a global development deficit, delayed speech development and an ASD (Asperger) family history, with an apparently balanced “de novo” reciprocal translocation [t(1;8)(p32.2;q13)dn]. The cytogenetic molecular study identified a likely pathogenic deletion of 21 kb in the 15q12 region, while mate pair sequencing identified gene-truncations at both the 1p32.2 and 8q13 translocation breakpoints.

Conclusions
The identification of a pathogenic alteration on 15q12 involving GABRA5 was likely the main cause of the ASD-phenotype. Importantly, the chr8 translocation breakpoint truncating SLCO5A1 exclude SLCO5A1 as a candidate for MSS, leaving SULF1 as the primary candidate. However, the deletions observed in MSS remove a topological associated domain (TAD) boundary separating SULF1 and SLCO5A1. Hence, Mesomelia-Synostoses syndrome is either caused by haploinsufficiency of SULF1 or ectopic enhancer effects where skeletal/chrondrogenic SULF1 enhancers drive excopic expression of developmental genes in adjacent TADs including PRDM14, NCOA2 and/or EYA1.
A phase III randomized clinical trial comparing laparoscopic radical hysterectomy based on open state with abdominal radical hysterectomy in patients with early-stage cervical cancer
Authors: Zhao Xin , Liu Yansong , Niu Jumin , Shi Yulin 
Published: July 2024

Abstract
Background
Cervical cancer is the fourth most frequently diagnosed cancer and the fourth leading cause of cancer death in women, The standard treatment recommendation for women with early cervical cancer is radical hysterectomy with pelvic lymph node dissection, however, articles published in recent years have concluded that the treatment outcome of laparoscopic surgery for cervical cancer is inferior to that of open surgery. Thus, we choose a surgically new approach; the laparoscopic cervical cancer surgery in the open state is compared with the traditional open cervical cancer surgery, and we hope that patients can still have a good tumor outcome and survival outcome. This trial will investigate the effectiveness of laparoscopic cervical cancer surgery in the open-state treatment of early-stage cervical cancer.

Method and design
This will be an open-label, 2-armed, randomized, phase-III single-center trial of comparing laparoscopic radical hysterectomy based on open state with abdominal radical hysterectomy in patients with early-stage cervical cancer. A total of 740 participants will be randomly assigned into 2 treatment arms in a 1:1 ratio. Clinical, laboratory, ultrasound, and radiology data will be collected at baseline, and then at the study assessments and procedures performed at baseline and 1 week, 6 weeks, and 3 months, and follow-up visits begin at 3 months following surgery and continue every 3 months thereafter for the first 2 years and every 6 months until year 4.5. The primary aim is the rate of disease-free survival at 4.5 years. The secondary aims include treatment-related morbidity, costs and cost-effectiveness, patterns of recurrence, quality of life, pelvic floor function, and overall survival.

Conclusions
This prospective trial aims to show the equivalence of the laparoscopic cervical cancer surgery in the open state versus the transabdominal radical hysterectomy approach for patients with early-stage cervical cancer following a 2-phase protocol.

Trial registration
ChiCTR2300075118. Registered on August 25, 2023.
Congenital anomalies in pregnancies with overt and pregestational type 2 diabetes: a gray portrayal from a cohort in Brazil
Authors: Campos Maria Amélia A , Oppermann Maria Lúcia R , Sanseverino Maria Teresa V , Guerra Giulia L , Hirakata Vânia N , Reichelt Angela J 
Published: July 2024

Abstract
Objective
To describe the frequency and types of congenital anomalies and associated risk factors in Brazilian women with type 2 diabetes.

Methods
In this retrospective cohort study between 2005 and 2021, we included all pregnant participants with type 2 diabetes from the two major public hospitals in southern Brazil. We collected data from the electronic hospital records. Congenital anomalies were classified by the 10th revised International Classification of Diseases, Q chapter, enhanced by the EUROCAT registry classification, and categorized by type and gravity. We used multiple Poisson regression with robust estimates to estimate risks.

Results
Among 648 participants, we excluded 19, and 62 were lost to follow-up; therefore, we included 567 participants. Overt diabetes arose in 191 participants (33.7%, 95% CI 30.0% – 38.0%). Less than 20% of the participants supplemented folate. Congenital anomalies occurred in 78 neonates (13.8%, CI 11.0 − 16.9%), 73 babies (93.6%) presented major anomalies, and 20 (10.5%) cases occurred in participants with overt diabetes. Cardiac anomalies were the most frequent (43 isolated and 12 combined). Pre-eclampsia was associated with an increased risk in the analyses including all women (adjusted RR 1.87 (95% CI 1.23–2.85), p = 0.003), but not in analyses including only women with an HbA1c measured up to the 14th gestational age. HbA1c, either measured at any time in pregnancy (adjusted RR 1.21 (95% CI 1.10–1.33), p < 0.001) or up to the first 14 weeks (adjusted RR 1.22, 95% CI 1.10–1.35, p < 0.001) was the only sustained risk factor. Risk factors such as maternal age, obesity, diabetes diagnosis, or use of antidiabetic medications were not associated with congenital anomalies.

Conclusion
We found a high frequency of congenital anomalies associated with poor maternal glycemic control and revealed an almost universal lack of preconception care. An urgent call to action is mandatory for the reversal of this gray scenario.
Tribological and microstructural characteristics of Al2O3–LM6 semi-solid cast composite synthesized by dual mixed slurry process
Authors: Soni Bal Govind , Agarwal Mayank 
Published: July 2024

AbstractThe purpose of this work is to analyze the impact of reinforced Al2O3–LM6 aluminum composite made with dual mixed slurry for semi-solid casting with stirring, which is documented according to microstructure and wear properties. Under dry sliding pin-on-disk conditions, the composition and surface morphology of worn surfaces were carefully examined for the 10 N applied force, 1.2 m/s sliding speed, and sliding distances up to 750 m. Experimental findings indicate that Al2O3 reinforcement with semi-solid dual slurry effects give outstanding resistance against the adhesive wear. Microstructure, EDS, and XRD results from worn surface evaluation all show evidence of protective layers, which helps explain the reason for the rate of wear decreased due to processing. In this experiment, LM6 serves as the matrix material and Al2O3 as reinforcement. Al2O3–LM6 semi-solid cast composite was created via a dual mixed slurry technique with temperature control close to the solidus line for varying compositions. This work reports a substantial relationship between metallurgical and mechanical parameters. Mechanical properties and wear characteristics have been investigated.
An end-to-end workflow to study newly synthesized mRNA following rapid protein depletion in Saccharomyces cerevisiae
Authors: Ridenour John B. , Donczew Rafal 
Published: July 2024

Abstract
Background
Gene transcription by RNA polymerase II is a fundamental process in eukaryotic cells. The precise regulation of transcription is necessary for cellular growth and development and requires the coordinated activity of numerous proteins and protein complexes. Although significant progress has been made in understanding the mechanisms that regulate transcription, many questions remain unresolved. Accurately defining the direct effects of transcriptional regulators is critical to addressing these questions. An effective approach for identifying the direct targets of transcriptional regulators is combining rapid protein depletion and quantification of newly synthesized RNA. The auxin-inducible degron (AID) system and thiol (SH)-linked alkylation for the metabolic sequencing of RNA (SLAM-seq) are powerful methods to rapidly degrade a target protein and directly quantify newly synthesized RNA, respectively. Both methods have been widely applied to study transcriptional regulation. To address unresolved questions in transcription, we assembled an end-to-end workflow to deplete proteins of interest using the AID system and measure newly synthesized RNA using SLAM-seq in the model eukaryote, Saccharomyces cerevisiae.

Methods
We provide an open-source, step-by-step protocol to support the rapid implementation of this workflow. We include methods for targeted protein degradation, 4-thiouracil (4tU) incorporation, rapid methanol fixation, RNA purification, RNA alkylation, 3´ mRNA-seq library construction, and data analysis. Additionally, we demonstrate that this workflow can help define the direct effects of transcriptional regulators using the bromodomain and extra-terminal domain (BET) proteins, Bdf1 and Bdf2, as an example.

Discussion
We demonstrate that data generated using this workflow effectively quantifies 4tU-labeled transcripts and is robust to normalization using whole-cell spike-in or, at least in the case of Bdf1 and Bdf2 depletion, total read counts. We additionally demonstrate that this data correlates well with 4tU-seq data and identifies extensive differential expression due to the depletion of Bdf1 and Bdf2. Lastly, the workflow is modular and readily adaptable to other systems. Taken together, this workflow and supporting protocol will help address outstanding questions underlying the molecular basis of transcriptional regulation and other processes in S. cerevisiae and other eukaryotes.
Hematologic Malignancies Influence the Accuracy of Prediction of Survival in Patients With Solid Tumor Spinal Metastases Undergoing Surgery
Authors: Chanplakorn Pongsthorn , Budsayavilaimas Chanthong , Jaipanya Pilan , Pichyangkul Picharn , Siriyotha Sukanya , Lertudomphonwanit Thamrong 
Published: July 2024

PURPOSE There is no consensus on how to identify patients with multiple-level spinal metastases who would benefit from surgery. Previous studies have revealed that patients with hematologic malignancies have a significantly longer median survival time than those with solid tumor spinal metastases. We aimed to compare predictors and survival data between patients with spinal metastases, including hematologic malignancies (all-malignancies group), with only those with nonhematologic malignancies (nonhematologic malignancies group). MATERIALS AND METHODS This single-center retrospective study included all patients age >18 years who underwent surgery to treat spinal metastases in our department from 2008 to 2018. The patients' baseline characteristics, treatment modalities, and laboratory results were analyzed. Survival was calculated from the date of surgery to the date of confirmed death. Cox regression analysis was used to identify independent predictors of survival. RESULTS The study cohort comprised 186 patients with a mean age of 57.1 ± 13.4 years, 101 of whom were male and 18 of whom had hematologic malignancies. The median survival time was 201 days in the all-malignancies group and 168 days in the nonhematologic malignancies group. Independent predictors of survival differed between the two groups. Eastern Cooperative Oncology Group status and response to preoperative chemotherapy were identified as independent factors in both groups. However, radiosensitivity and CNS metastases were identified only in the all-malignancies group, and tumor growth potential, albumin status, and number of vertebrae were identified only in the nonhematologic malignancies group. The receiver operating characteristics were comparable in the two groups: 0.75 in the all-malignancies group and 0.77 in the nonhematologic malignancies group. CONCLUSION Longer survival in patients with hematologic malignancies influences the overall prediction of survival. Tumor-specific prognostic factors may improve the prediction of survival in patients with spinal metastases.
Dynamics of Long-Term Quality of Life After Treatment for Esophageal Cancer: A Community-Based Patient Study
Authors: Chen Lei , Wang Hui , Qi Zifan , Liang Linlin , Guo Chuanhai , He Yu , Liu Mengfei , Liu Zhen , Pan Yaqi , Liu Fangfang , Liu Ying , Hu Zhe , Chen Huanyu , He Zhonghu , Ke Yang 
Published: July 2024

PURPOSE To characterize the pattern of post-treatment quality of life (QoL) for esophageal cancer (EC) survivors and construct models predicting their long-term QoL. METHODS On the basis of a randomized trial in an EC high-risk region in China, we interviewed 363 EC survivors and 25,245 permanent residents matched with the survivors on age, sex, and township as the baseline. QoL was measured using three-level version of European Quality of Life 5-Dimensions instrument. We constructed piecewise mixed models estimating the QoL of EC survivors that varied by age, sex, patient type, hospital level, and therapy to ascertain QoL determinants. RESULTS The post-treatment QoL of EC survivors dropped by 15.7% within the first year and recovered by 9.3% between 1 and 9 years compared with the baseline. Therapy was found to be a determinant of QoL, and a series of therapy-specific models were fitted accordingly, which all showed the pattern of decreasing rapidly and recovering gradually. Endoscopic treatment had the least impact on post-treatment QoL (7.5% drop within 5 years) compared with esophagectomy (12.2% drop within 1 year) and chemoradiotherapy (37.8% drop within 2 years). The usual activities dimension showed the greatest impairment among those patients (34.4% drop within 1 year). CONCLUSION This community-based study described the long-term QoL trajectory for EC survivors after different therapeutic modalities and constructed models to predict therapy-specific QoL at different time points after treatment. It provided new insights into decision making in treatment for EC from the perspective of QoL protection, offering a convenient tool for estimating quality-adjusted life-years.
Node marking techniques and targeted axillary dissection in patients with cN1 disease undergoing neoadjuvant chemotherapy: Analysis of initial 500 participants in the ATNEC trial.
Authors: Goyal Amit , Elbeltagi Nada , Marshall Andrea , Nicholls Sophie , Hammonds Natalie , Elsberger Beatrix , Wheatley Duncan , Shaaban Abeer , Rose Janice , Edwards Helen Teresa , Nabi Zohal , Homer Tara , Ahmed Samreen , Dunn Janet ,   ATNEC Trial Management Group
Published: July 2024

609 Background: In the ongoing neoadjuvant ATNEC breast cancer trial (NCT04109079), cT1-3N1M0 patients receive neoadjuvant chemotherapy (NACT) followed by sentinel node biopsy (SNB) or targeted axillary dissection (TAD). If the sentinel nodes (SNs) convert to benign (ypN0), patients are randomized to receive Axillary Treatment vs. no Axillary Treatment. Standardized node marking procedures are promoted in this study. This study evaluates node marking techniques, rates of marked node identification, and concordance of the marked node with the sentinel node in the initial 500 participants. Methods: Data from 587 patients registered from December 2021 to January 1, 2024, across 77 UK centers were analyzed. These patients presented with cT1-3N1M0 breast cancer and received or planned to receive NACT. Results: The median age was 54 years (range 28-81), with a median of 4 nodes [interquartile range, 3-5] removed during SNB/TAD. Among 470 patients with node marking data, 72% (339) had the involved node marked. Sentinel node biopsy was performed using a combination of radioisotope and blue dye in 51%, blue dye only in 13%, radioisotope only in 10%, and Magtrace only in 9%. The marked node was successfully removed in 90% (305/339) of these patients, with the marked node being the sentinel node in 80% (243/305) of cases. In patients with complete pathological nodal response, the marked node did not show signs of downstaging (e.g. fibrosis) in 15% (46). Common techniques used for node marking included clip/coil only before NACT (29%), clip/coil before NACT with another wireless marker after NACT (26%), Magseed only before NACT (16%), and black dye only before NACT (15%). Conclusions: Notably, 72% of patients underwent node marking, with an intra-operative identification rate of 90%, demonstrating the successful implementation of node marking in the UK through the ATNEC trial. Clinical trial information: NCT04109079 .