bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-omics approach to reveal follicular metabolic changes and their effects on oocyte competence in PCOS patients
Authors: Chen Yuezhou , Xie Minyu , Wu Siyun , Deng Zehua , Tang Yan , Guan Yiqing , Ye Yun , He Qiandong , Li Lei 
Published: October 2024

BackgroundPolycystic ovary syndrome (PCOS) is a common heterogeneous disorder linked with endocrine and metabolic disturbances. The underlying mechanism of PCOS, especially its effect on oocyte competence, remains unclear. The study aimed to identify abnormal follicular metabolic changes using a multi-omics approach in follicular fluid from PCOS patients and to determine their effects on oocyte competence.MethodsA total of 36 women with PCOS and 35 women without PCOS who underwent in vitro fertilization and embryo transfer were included in the study. Cumulus cells and follicular fluid samples were collected. Follicular fluid samples underwent metabolomic analysis, while cumulus cell clusters from the same patients were assessed using transcriptomic analysis. Clinical information of patients and assisted reproductive technology (ART) results were recorded. Transcriptomics and metabolomics were integrated to identify disrupted pathways, and receiver operation characteristics (ROC) analysis was conducted to identify potential diagnostic biomarkers for PCOS. Pearson correlation analysis was conducted to assess the relationship between metabolites in follicular fluid and oocyte competence (fertilization and early embryo development potential).ResultsThrough multi-omics analysis, we identified aberrantly expressed pathways at both transcriptional and metabolic levels, such as the citrate cycle (TCA cycle), oxidative phosphorylation, the cAMP signaling pathway, the mTOR signaling pathway, and steroid hormone biosynthesis. Ten candidate metabolites were identified based on metabolic profiling data from these altered pathways. Phytic acid, succinic acid, 2’-deoxyinosine triphosphate, and 4-trimethylammoniobutanoic acid in the follicular fluid exhibited high specificity and sensitivity in distinguishing PCOS. Among these metabolites, L-arginine showed a negative correlation with the 2PN fertilization rate and cleavage rate, while estrone sulfate showed a negative correlation with the high-quality embryo rate in the in-vitro fertilization (IVF) cycle.ConclusionsWe have conducted a preliminary study of a novel metabolic signature in women with PCOS using a multi-omics approach. The alterations in key metabolic pathways may enhance our understanding of the pathogenesis of PCOS.
The impact of sleep problems on cerebral aneurysm risk is mediated by hypertension: a mediated Mendelian randomization study
Authors: Yan Xiaofei , Li Hongwu 
Published: October 2024

IntroductionCerebral aneurysm (CA) is a common vascular disease. The risk factors of CA include hypertension, smoking, and a family history of genetic predisposition. Although sleep-related problems have been found to have a strong association with cardiovascular disease, there is a lack of research regarding the causal relationship with cerebral aneurysms.MethodsIn this study, we investigated the causal relationship between four sleep-related problems, including snoring, insomnia, narcolepsy, and napping during the day, and CA using a two-sample Mendelian randomization (MR) analysis. Moreover, the potential confounders before sleep problems and CA were further analyzed by multivariate MR (MVMR).ResultsThe causal relationship between insomnia and CA was obtained analytically by means of six MR analyses. There was a strong causal effect relationship between insomnia and CA, which suggests this as a potential risk factor [odds ratio (OR) = 8.35, 95% confidence interval (CI) = 2.422–28.791, p = 7.772e-04]. On this basis, hypertension was identified as a mediator between insomnia and CA by MVMR, with a mediating effect of 52.538% (OR = 3.05, 95% CI = 1.549–4.55, p = 0.015).ConclusionThe causal relationship between insomnia and CA was predicted using genetic variance data, and insomnia was found to be a potential risk factor. Furthermore, hypertension is a mediator between insomnia and CA. Therefore, focusing on sleep problems and improving sleep quality may be an active and effective strategy to prevent CA.
Protein kinase D1 in myeloid lineage cells contributes to the accumulation of CXCR3+CCR6+ nonconventional Th1 cells in the lungs and potentiates hypersensitivity pneumonitis caused by S. rectivirgula
Authors: Snyder John D. , Yoon Tae Won , Lee Sangmin , Halder Priyanka , Fitzpatrick Elizabeth Ann , Yi Ae-Kyung 
Published: October 2024

IntroductionHypersensitivity pneumonitis (HP) is an extrinsic allergic alveolitis characterized by inflammation of the interstitium, bronchioles, and alveoli of the lung that leads to granuloma formation. We previously found that activation of protein kinase D1 (PKD1) in the lungs following exposures to Saccharopolyspora rectivirgula contributes to the acute pulmonary inflammation, IL-17A expression in the lungs, and development of HP. In the present study, we investigated whether PKD1 in myeloid-lineage cells affects the pathogenic course of the S. rectivirgula-induced HP.MethodsMice were exposed intranasally to S. rectivirgula once or 3 times/week for 3 weeks. The protein and mRNA expression levels of cytokines/chemokines were detected by enzyme-linked immunosorbent assay and quantitative real-time PCR, respectively. Flow cytometry was used to detect the different types of immune cells and the levels of surface proteins. Lung tissue sections were stained with hematoxylin and eosin, digital images were captured, and immune cells influx into the interstitial lung tissue were detected.ResultsCompared to control PKD1-sufficient mice, mice with PKD1 deficiency in myeloid-lineage cells (PKD1mKO) showed significantly suppressed expression of TNFα, IFNγ, IL-6, CCL2, CCL3, CCL4, CXCL1, CXCL2, and CXCL10 and neutrophilic alveolitis after single intranasal exposure to S. rectivirgula. Substantially reduced levels of alveolitis and granuloma formation were observed in the PKD1mKO mice repeatedly exposed to S. rectivirgula for 3 weeks. In addition, expression levels of the Th1/Th17 polarizing cytokines and chemokines such as IFNγ, IL-17A, CXCL9, CXCL10, CXCL11, and CCL20 in lungs were significantly reduced in the PKD1mKO mice repeatedly exposed to S. rectivirgula. Moreover, accumulation of CXCR3+CCR6+ nonconventional Th1 in the lungs were significantly reduced in PKD1mKO mice repeatedly exposed to S. rectivirgula.DiscussionOur results demonstrate that PKD1 in myeloid-lineage cells plays an essential role in the development and progress of HP caused by repeated exposure to S. rectivirgula by contributing Th1/Th17 polarizing proinflammatory responses, alveolitis, and accumulation of pathogenic nonconventional Th1 cells in the lungs.
Circulatory microRNAs and proinflammatory cytokines as predictors of lupus nephritis
Authors: ElFeky Dalia Saad , Omar Noha Mohamed , Shaker Olfat Gamil , Abdelrahman Walaa , Gheita Tamer A. , Nada Mona Gamal 
Published: October 2024

IntroductionLupus nephritis (LN) is one of the most prevalent severe organ manifestations of systemic lupus erythematosus (SLE), impacting 70% of SLE patients. MicroRNAs (miRNAs), are small non-coding RNA molecules which influence the expression of approximately one-third of human genes after the process of transcription. Dysregulation of miRNAs was documented in numerous disorders, including SLE and LN. Cytokines are the orchestrators of the immune response in autoimmune diseases. Our study aims to explore the variation in the levels of circulating miRNAs and proinflammatory cytokines as potential diagnostic biomarkers among LN and SLE patients without LN in comparison to controls.MethodsThe study involved 20 LN patients, 20 SLE patients without LN, and 10 healthy controls. Serum levels of IL-12 and IL-21 in addition to miR-124, miR-146a, miR-199a, and miR-21 were assessed using the enzyme-linked immunosorbent assay (ELISA) for cytokines and quantitative real-time PCR for miRNAs.ResultsA significant downregulation in miR-124 (p&lt;0.001) and a significant overexpression of miR-146a (p=0.005) were found in SLE patients without LN in comparison to controls. In comparison to SLE patients without LN and the control group, miR-199a, miR-21, and miR-146a were significantly upregulated in LN patients (p=&lt;0.001) with high diagnostic values of these miRNAs in discriminating LN from SLE patients without LN according to Receiver operating curve (ROC) analysis. Logistic regression analysis revealed that only miR-199a is an independent predictor of LN (OR 1.69; 95% CI: 1.1-2.6). The expression of miR-124 was reduced in LN patients in comparison to the control but increased in LN patients in comparison to SLE patients without LN. However, there was no statistically significant difference in either scenario. In comparison to both SLE patients without LN and controls, LN patients exhibited the highest serum levels of IL-12 and IL-21, with no statistically significant difference. Regression analysis revealed that only miR-146a was associated with creatinine levels and SLEDAI score (p= 0.009 and 0.03, respectively), while miR-124 was associated with hemoglobin level (p=0.03).ConclusionMiR-199a is an independent predictor for LN and might be used as a diagnostic biomarker for this disease. MiR-146a might play an important role in LN pathophysiology.
Clinical associations of complement-activating collectins, collectin-10, collectin-11 and mannose-binding lectin in preterm neonates
Authors: Gajek Gabriela , Hansen Soren W. K. , Jarych Dariusz , Kufelnicka-Babout Maja , Świerzko Anna S. , Kobiela Paulina , Szala-Poździej Agnieszka , Chojnacka Karolina , Sobczuk Katarzyna , Domżalska-Popadiuk Iwona , Mazela Jan , Kalinka Jarosław , Thiel Steffen , Cedzyński Maciej 
Published: October 2024

IntroductionPremature and low-birthweight infants are at especially high risk of perinatal complications, including impaired thermoregulation, infections and respiratory distress. Such adverse effects and the need for invasive procedures are associated with high mortality among preterms. This study focused on the influence of the innate immune system and tested the levels of collectins, collectin-10 (CL-10), collectin-11 (CL-11) and mannose-binding lectin (MBL) in preterm neonates.MethodsCord blood was collected from 535 preterms (born at gestational age ≤37 weeks). COLEC10 and COLEC11 polymorphisms were analyzed by real-time PCR and those of MBL2 by PCR/PCR-RFLP. The concentrations of collectins in sera from cord blood were determined with ELISA.FindingsLow concentrations of CL-10 in cord sera (&lt;462 ng/ml corresponding to the 10th percentile) were significantly associated with births at GA ≤32 weeks. Median levels of both CL-10 and CL-11 were significantly lower in preterms with very low birthweight (&lt;1500 g), low Apgar 1’ score and those who needed prolonged hospitalisation. Lower median CL-10 was also observed in fetal growth restriction cases. An important finding was the decreased concentrations of CL-10, CL-11 and MBL in respiratory distress syndrome (RDS). For CL-10 and CL-11, that relationship was confined to infants born at GA ≥33 weeks and/or with body mass at birth ≥1500 g. Only CL-10 was found to influence susceptibility to early-onset infections. COLEC11 heterozygosity for the activity-decreasing polymorphism (rs7567833, +39618 A&gt;G, His219Arg) was more common in preterm premature rupture of membranes (pPROM) cases, compared with corresponding reference groups. Furthermore, C/T or T/T genotypes at COLEC11 at rs3820897 (-9570 C&gt;T) as well as MBL deficiency-associated MBL2 gene variants were more common in preterms diagnosed with RDS than among unaffected newborns.ConclusionThe complement-activating collectins investigated here could be important for maintaining homeostasis in preterm neonates. Despite similar structure and specificity, MBL, CL-10 and CL-11 manifest a different spectrum of clinical associations.
Case report: Neoadjuvant-intent pembrolizumab resulted in complete response in a xeroderma pigmentosum patient with locally advanced resectable cutaneous squamous cell carcinoma of the nose
Authors: Zalaquett Nader G. , Kreidieh Lara , Youssef Bassem , Mourad Marc , Kreidieh Firas 
Published: October 2024

BackgroundAnti-PD1 antibodies have gained popularity in the treatment of skin cancers. These drugs have been FDA approved for treatment of cutaneous melanoma and unresectable/metastatic squamous cell carcinoma of the skin. However, the use of anti-PD1 antibodies is not established for resectable cutaneous squamous cell carcinoma, as the mainstay treatment is surgical excision.CaseA 49-year-old female with Xeroderma Pigmentosum presented with an ulcerating lateral nasal mass causing obstruction. Biopsy confirmed cutaneous squamous cell carcinoma and was staged as IVA (T2N2cM0) based on PET-CT findings, which showed a 2.7 × 2.3 cm left nasal mass and radiotracer-avid cervical lymph nodes. Despite surgical recommendations, the patient declined surgery due the expected morbidity and disfigurement. Instead, she received neoadjuvant Pembrolizumab (200 mg IV every 3 weeks). After two cycles, PET-CT and MRI showed significant reduction in the nasal mass and decreased cervical lymph node involvement. On physical exam, the nasal lesion had resolved. Multidisciplinary tumor board discussion recommended radiation therapy instead of neck dissection, considering the patient's clinical response and potential surgical morbidity. After a third Pembrolizumab cycle, she received 66 Gy in 33 fractions, followed by continued adjuvant immunotherapy.
Survival and prognostic factors for relapsed childhood acute lymphoblastic leukemia after treatment with the Chinese children’s cancer group ALL-2015 protocol: a single center results
Authors: Chen Xia , Yu Jie 
Published: October 2024

IntroductionThis retrospective study was conducted to assess the survival rates and prognostic factors in children with relapsed acute lymphoblastic leukemia (ALL) who were treated according to the Chinese Children’s Cancer Group ALL-2015 protocol at the Children’s Hospital of Chongqing Medical University.MethodsThe study cohort involving 852 evaluable children with ALL reported a total of 146 relapses during a median follow-up period of 53 months. The primary outcomes measured were the second complete remission (CR2) rates, and 5-year event-free survival (EFS) and overall survival (OS) for patients who received re-treatment post-relapse. Patient data were stratified by ALL subtype (B-ALL vs. T-ALL), age at relapse, site of relapse, and timing of relapse. Univariate and multivariate analyses were performed to identify factors significantly associated with EFS and OS.ResultsAs of March 31, 2023, 146 relapses were observed, including 128 B-ALL and 18 T-ALL cases. The 8-year CIR was (19.8 ± 1.6)%, with no significant difference between B-ALL and T-ALL (P=0.271). Among the 105 patients who underwent re-treatment, 70 achieved CR2, resulting in a CR2 rate of 67.6%. The 5-year EFS and OS rates for re-treated patients were (45.0 ± 5.4)% and (56.9 ± 5.2)%, respectively. Significant differences in 5-year OS and EFS were found between B-ALL and T-ALL relapses (P &lt; 0.001). The 5-year EFS and OS varied significantly with relapse timing and site of relapse. Factors significantly affecting EFS after relapse included the site of relapse, immunophenotyping, CR2 achievement, and hematopoietic stem cell transplantation (HSCT). Immunophenotyping, CR2 achievement, and HSCT were also identified as significant factors affecting OS after relapse.DiscussionDespite treatment with the CCCG-ALL-2015 protocol, a significant relapse rate was observed, with 72% of children opting for re-treatment post-relapse. The study highlights the importance of considering specific prognostic factors to inform tailored treatment strategies for relapsed childhood ALL. The findings emphasize the need for further research into improving therapeutic approaches for this patient population. This retrospective study was conducted to assess the survival rates and prognostic factors in children with relapsed acute lymphoblastic leukemia (ALL) who were treated according to the Chinese Children’s Cancer Group ALL-2015 protocol at the Children’s Hospital of Chongqing Medical University.
The cardiopulmonary benefits of physiologically based cord clamping persist for at least 8 hours in lambs with a diaphragmatic hernia
Authors: Riddington Paige J. , DeKoninck Philip L. J. , Thio Marta , Roberts Calum T. , Bhatia Risha , Dekker Janneke , Kashyap Aidan J. , Amberg Benjamin J. , Rodgers Karyn A. , Thiel Alison M. , Nitsos Ilias , Zahra Valerie A. , Hodges Ryan J. , Hooper Stuart B. , Crossley Kelly J. 
Published: October 2024

IntroductionInfants with congenital diaphragmatic hernia can suffer severe respiratory insufficiency and pulmonary hypertension after birth. Aerating the lungs before removing placental support (physiologically based cord clamping, PBCC) increases pulmonary blood flow (PBF) and reduces pulmonary vascular resistance (PVR) in lambs with a diaphragmatic hernia (DH). We hypothesized that these benefits of PBCC persist for at least 8 h after birth.MethodsAt ∼138 days of gestation age (dGA), 21 lambs with a surgically induced left-sided DH (∼86 dGA) were delivered via cesarean section. The umbilical cord was clamped either before ventilation onset (immediate cord clamping, ICC, n = 9) or after achieving a tidal volume of 4 ml/kg, with a maximum delay of 10 min (PBCC, n = 12). The lambs were ventilated for 8 h, initially with conventional mechanical ventilation, but were switched to high-frequency oscillatory ventilation after 30 min if required. Ventilatory parameters, cardiopulmonary physiology, and arterial blood gases were measured throughout the study.ResultsPBF increased after ventilation onset in both groups and was higher in the PBCC DH lambs than the ICC DH lambs at 8 h (5.2 ± 1.2 vs. 1.9 ± 0.3 ml/min/g; p &lt; 0.05). Measured over the entire 8-h ventilation period, PBF was significantly greater (p = 0.003) and PVR was significantly lower (p = 0.0002) in the PBCC DH lambs compared to the ICC DH lambs. A high incidence of pneumothoraces in both the PBCC (58%) and ICC (55%) lambs contributed to a reduced sample size at 8 h (ICC n = 4 and PBCC n = 4).ConclusionCompared with ICC, PBCC increased PBF and reduced PVR in DH lambs and the effects were sustained for at least 8 h after ventilation onset.
Exploring generative AI in higher education: a RAG system to enhance student engagement with scientific literature
Authors: Thüs Dominik , Malone Sarah , Brünken Roland 
Published: October 2024

IntroductionThis study explores the implementation and evaluation of OwlMentor, an AI-powered learning environment designed to assist university students in comprehending scientific texts. OwlMentor was developed participatorily and then integrated into a course, with development and evaluation taking place over two semesters. It offers features like document-based chats, automatic question generation, and quiz creation.MethodsWe used the Technology Acceptance Model to assess system acceptance, examined learning outcomes, and explored the influence of general self-efficacy on system acceptance and OwlMentor use.ResultsThe results indicated complex relationships between perceived ease of use, perceived usefulness, and actual use, suggesting the need for more dynamic models of system acceptance. Although no direct correlation between OwlMentor use and learning gains was found, descriptive results indicated higher gains among users compared to non-users. Additionally, general self-efficacy was strongly related to perceived usefulness, intention to use, and actual use of the system.DiscussionThese findings highlight the importance of aligning AI tools with students’ needs and existing learning strategies to maximize their educational benefits.
Diseño de sistemas de tuberías aplicando los principios básicos de la mecánica de fluidos
Authors: Ponce Anchundia Melanny Nohelia , Montero Vera Maily Mayerli , Vera Bustamante Johanna Elizabeth , Jacome Alarcón Luis Fernando 
Published: October 2024

Diseñar sistemas de tuberías que introducen principios de mecánica de fluidos ha sido esencial para crear sistemas eficientes y seguros. Los avances en modelado por computadora, nuevos materiales y tecnología de monitoreo continúan mejorando el rendimiento y la sostenibilidad de estos sistemas, permitiendo solucionar de manera más efectiva problemas persistentes y crear nuevas innovaciones en la industria. Este artículo tuvo como objetivo proporcionar una amplia comprensión de cómo se diseñan y operan los sistemas de tuberías y redes para el transporte de fluidos.
Para lograrlo, se estudiaron las propiedades físicas de los fluidos y se aplicaron los principios fundamentales de la mecánica de fluidos. Para la investigación se utilizó un enfoque descriptivo-explicativo donde se hizo una revisión bibliográfica de los diferentes conceptos relacionados a la mecánica de fluidos. El estudio concluyó que el diseño y la operación de sistemas de tuberías y redes fluidos es un campo de ingeniería que requiere de un conocimiento profundo científico y la aplicación de tecnología avanzada.
TRANSFORMASI SUMBER DAYA MANUSIA DAN ORGANISASI DALAM MENGHADAPI PERSAINGAN BISNIS
Authors: Nursiani Ni Putu 
Published: October 2024

Perubahan yang cepat dalam lingkungan organisasi merupakan kekuatan eksternal yang mengakibatkan transformasi dalam sebuah organisasi. Pada dasarnya, tujuan utama dari transformasi tersebut adalah merubah struktur organisasi agar menjadi lebih fleksibel dan mampu bersaing, dengan tingkat structural yang lebih kecil, serta jumlah manajer dan karyawan yang lebih sedikit. Transformasi tersebut harus menyeluruh, bagi para anggota organisasi agar tidak menghambat perubahan tersebut., sehingga organisasi harus mencari jalan untuk mengurangi hambatan-hambatan tersebut. Organisasi harus belajar keanekaragaman dari budaya dan nilai anggotanya, harus mengembangkan budaya organisasi sendiri melalui komunikasi yang baik dengan anggotanya. Untuk mendukung usaha mengembangkan budaya organisasi, harus ada perubaban pada kebijakan sumber daya manusia.

Kata kunci: Transformasi SDM, Transformasi Organisasi dan Persaingan Bisnis
ANALISIS HARGA TERHADAP TINGKAT HUNIAN HOTEL DALAM MENDUKUNG INDUSTRI PARIWISATA DI KOTA KUPANG
Authors: Nalle Faldio , Fanggidae Ronald P C , Amtiran Paulina Y 
Published: October 2024

Penelitian ini bertujuan untuk mengetahui pengaruh harga terhadap tingkat hunian hotel dalam mendukung industri pariwisata di Kota Kupang dengan menganalisis harga, tingkat hunian dan omset setiap tahun dari hotel-hotel yang menjadi objek penelitian bagi penulis. Penelitian ini merupakan penelitian kuantitatif dengan teknik pengumpulan data yaitu dengan proses wawancara. Teknik pengambilan sampel yang digunakan adalah Purposive Sampling dengan populasi hotel-hotel di kota kupang dan tiga hotel sebagai sampel penelitian. Hasil penelitian yang diperoleh oleh penulis yaitu, adanya pengaruh yang signifikan antara harga dan tingkat hunian dan diantara keduanya terdapat hubungan yang tak bisa terpisahkan. Terdapat tiga hotel yang menjadi objek penelitian utama yakni Aston Hotel Kupang & Convention Center, Kristal Hotel Kupang dan M Hotel Kupang. Peran hotel sangat penting bagi pemerintah daerah setempat, pengusaha perhotelan dan kelangsungan hidup masyarakat. Tingkat hunian hotel dapat naik atau turun sesuai dengan kebutuhan pengunjung, misalnya terdapat even-even tertentu maupun perlombaan dan acara lainnya, maka kamar hotel akan selalu banyak pesanan, dan dari hasil analisis data, tingkat hunian hotel selalu mengalami fluktuasi sesuai kondisi.
Kata Kunci : Pariwisata, Hotel, Tingkat Hunian