bluuebunny/crossref_metadata_2025 huggingface dataset:
Cost of Illness Study in Thyroid Patients: A Systematic Review
Authors: Junita Miru Seisye , Libriansyah  , Mufarrihah  , Yunita Nita
Published: May 2023

Background: The thyroid has a vital role in growth, neurodevelopment, reproduction, and metabolism. About 300 million people around the world had been reported to be suffering from thyroid disorders, but more than half were unaware. The factors of sex, age, weight of disease, and other accompanying conditions should be considered, otherwise, it will cause a long time treatment period in which the cost will become higher from year to year. Purpose: The systematic review aims to provide an overview of the financial burden caused by thyroid disease for the communities, governments and health care providers. Method: A systematic review of publications in several databases, namely PUBMED, SCIENCE DIRECT, DOAJ, SCOPUS and GOOGLE SCHOLAR. Results: Six research articles were obtained from publications selected for systematic review. The reviewed articles show overviews of the cost of thyroid disease in several countries. The financial burden of thyroid patients in some countries varies, with different perspectives. The lowest to highest cost ranges from 0.125 USD/patient – 8106 USD/patient. Conclusion: The study in this review illustrates the various costs in different countries; the cost of screening, and thyroid surgery has the largest contribution compared to other costs; research on the financial burden suffered by thyroid patients in the future must be carried out continuously and periodically to be able to estimate the cost of therapy more appropriately to provide a useful data for health care providers, governments and the community. Direct medical costs are the largest proportion.
Cowper’s syringocele (bulbourethral gland cyst)
Authors:   Institute for Urology and Reproductive Health, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation, Shpot E.V. , Chinenov D.V. ,   Institute for Urology and Reproductive Health, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation, Chernov Ya.N. ,   Institute for Urology and Reproductive Health, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation, Kharchilava R.R. ,   Institute for Urology and Reproductive Health, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation, Kurbanov A.A. ,   Institute for Urology and Reproductive Health, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation, Votyakov A.Yu. ,   Institute for Urology and Reproductive Health, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation, Tsukkiev Z.K. ,   Institute for Urology and Reproductive Health, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation
Published: May 2023

This article presents a clinical case of a 30-year-old patient with a closed cystic lesion in the bulbourethral gland, whose clinical presentation was masked as acute prostatitis. Cowper’s syringocele is a cystic dilation (deformity) of the main duct of the bulbourethral (Cowper’s) gland. This disease is not uncommon, but is rarely identified; it is often asymptomatic, and its clinical manifestations are highly variable, depending mainly on its type (open, closed) and are similar to lower urinary tract symptoms (perineal pain, post-micturition dribble, recurrent urinary tract infection, dysuria, etc.). A syringocele should be included in the examination algorithms for boys, adolescents, and men with signs of inflammatory diseases of the urogenital system or symptoms of infravesical obstruction. Ultrasonography is informative for closed cysts (a fluid-filled cavity may be identified); a pelvic MRI scan, supplemented by ureteroscopy, allows to visualize the cyst cavity and to determine its association with the urethra. Ureteroscopy is a preferable option for surgical treatment in most cases. Key words: bulbourethral gland cyst, lower urinary tract symptoms, Cowper’s syringocele, ureteroscopy
PENGARUH INFLASI, KEBEBASAN EKONOMI DAN PERKEMBANGAN SEKTOR INDUSTRI HALAL TERHADAP PERTUMBUHAN EKONOMI NEGARA
Authors: Quddus Muhammad Fathrul
Published: May 2023

Umat muslim saat ini memiliki kesadaran yang lebih besar untuk mendapatan produk-produk yang halal baik barang maupun jasa. Optimalisasi perkembangan sektor industri halal bisa meningkat melalui peran keuangan Islam secara langsung untuk menghidupi sektor rill atau dengan membiayai industri halal untuk menciptakan produktivitas dalam pertumbuhan ekonomi. Tujuan penelitian pada penelitian ini adalah untuk mengetahui pengaruh variabel inflasi, kebebasan ekonomi dan perkembangan sektor industri halal terhadap pertumbuhan ekonomi di negara yang selalu menjadi 10 negara terbaik dalam State Global Islamic Economic Report 2014-2019. Metode yang di gunakan pada penelitian ini adalah metode Vector Auto Regression (VAR). Data yang digunakan dalam penelitian ini adalah data panel sekunder yang diperoleh dari berbagai sumber seperti World Bank untuk data inflasi dan pertumbuhan ekonomi, The Heritage Foundation untuk data kebebasan ekonomi, serta State Global Islamic Economic Report untuk data perkembangan sektor industri halal. Hasil dari penelitian ini menunjukan bahwa variabel perembangan sektor industri halal berpengaruh secara signifikan kepada pertumbuhan ekonomi. Untuk variabel inflasi dan kebebasan ekonomi berdasarkan hasil penelitian tidak berpengaruh secara signifikan terhadap pertumbuhan ekonomi. Implikasi dari penelitian ini diharapkan dapat bermanfaat untuk berbagai kalangan. Untuk regulator di 10 negara yang dijadikan sampel dapat menjadi salah satu referensi dalam menentukan kebijakan. Untuk akademisi diharapkan berguna untuk pengembangan ilmu pengetahuan. Dan untuk masyarakat umum sebagai tambahan informasi dan sarana literasi.
Pembiasaan Kegiatan Keagamaan di Madrasah Ibtidaiyah untuk Membentuk Karakter Religius Siswa Perspektif Empirisme
Authors: Maulidya Difa , Cahyadi Ani
Published: May 2023

This study aims to describe the habituation of religious activities to shape the religious character of students in ibtidaiyah madrasahs based on the perspective of empiricist philosophy. This research uses a descriptive qualitative approach. Data collection techniques in this study are interviews, observations, and documentation. The data analysis technique in this study uses the miles and huberman model which is divided into three activities in data analysis, namely data reduction, data presentation, and data verification. the philosophy of empiricism states that the environment greatly influences the formation of character and knowledge. The religious activities carried out will be experience and knowledge. Experience or knowledge that is carried out repeatedly will be a habituation that is expected to continue to be applied not only in the secluded but also in the home or community.
Dynamic and multivalent engagement determines context-dependent nucleosomal deacetylation by the Rpd3S complex
Authors: Li Haitao , Guan Haipeng , Wang Pei , Zhang Pei , Ruan Chun , Ou Yutian , Peng Bo , Zheng Xiangdong , Lei Jianlin , Li Bing , Yan Chuangye
Published: May 2023

Context-dependent dynamic histone modifications constitute a key epigenetic mechanism in gene regulation. The Rpd3S complex recognizes H3K36 trimethylation (H3K36me3) and deacetylates histones H3 and H4 at multiple sites across transcribed regions. Here we solved the cryo-EM structures of yeast Rpd3S in its free and H3K36me3-nucleosome bound states. We demonstrated a unique architecture of Rpd3S, in which two copies of Eaf3-Rco1 heterodimers are asymmetrically assembled with Rpd3 and Sin3 to form a catalytic core complex. Multivalent recognition of two H3K36me3 marks, nucleosomal and linker DNAs by Eaf3, Sin3 and Rco1 positions the catalytic center of Rpd3 next to the histone H4 N-terminal tail for deacetylation. In an alternative catalytic mode, combinatorial readout of unmethylated H3K4 and H3K36me3 by Rco1 and Eaf3 directs histone H3-specific deacetylation except for the registered H3K9ac. Collectively, our work illustrates dynamic and diverse modes of multivalent nucleosomal engagement and methylation-guided deacetylation by Rpd3S, highlighting the exquisite complexity of epigenetic regulation with delicately designed multi-subunit enzymatic machineries in transcription and beyond.
U-Pb constraints Late Miocene Hipparionine fauna stratigraphic age at 7.26 Ma
Authors: Zhang Pu , Li Fanyang , Zhu Guangyou , Edwards R. Lawrence
Published: May 2023

This paper presents the first application of U-Pb dating to resolve the geological age of the Late Miocene mammalian fauna. Five fossil beds containing late Miocene mammalian fauna can be found in northern China, which include fossil specimens ofHipparion chiai,is most fixed time indicator fossil. However, the geological age of the fossil belt is still unresolved. Absolute dating of sedimentary rocks and fossils from the late Miocene is still rare, mainly due to the difficulties arising from suitable absolute dating technique and sample diagenetic changes. Biological Apatite (carbonated Hydroxyapatite) in the teeth fossils ofHipparion chiaicontain Uranium, high μ value (the initial value of238U/204Pbi), limited Th content and remain relatively unchanged due to their resistance to diagenetic alterations. Here, we first derived six fossil teeth ofHipparion chiaiwere sampled from the Wangdafuliang section in Fugu, in the Shaanxi Province, and were dated using the U/Pb method to obtain an absolute age. The U-Pb dates obtained from the six fossil teeth ofHipparion chiaivaried, ranging from 6.87±0.13 Ma to 7.71±0.39 Ma (2 s), with an average of 7.26 Ma. This result provides a new basis for determining the age of theHipparion chiai-Dinocrocuta gigantean-Hezhengia-Shaanxispirastandard fossil belt (index fossil assemblage) from the Late Miocene in northern China. The belt is probably 7.26 Ma, rather than previous estimates of 10–9 Ma. The absolute dating of fossils, in turn, bring about a new revolution in Biostratigraphy and establish the geochronology of sedimentary sequences at sub-millennial timescales, especially those early Cenozoic stratigraphy that is absent of an suitable absolute dating technique.
JAK2 Genetic Variation Potentially Associated with Susceptibility to Severe A(H1N1) Influenza
Authors: Cheng Zhong-shan , Zhou Jie
Published: May 2023

Genetic variation in JAK2, a key player in cytokine signaling, may affect the severity of influenza. We sought to identify single nucleotide polymorphisms (SNPs) of JAK2 predisposing to severe A(H1N1) influenza. A pilot genome wide association study (GWAS) of A(H1N1) influenza harvested 15 highly linked SNPs of JAK2 that were differentially distributed in severe cases and mild controls. Four SNPs, including a promoter SNP rs1887429 and its high linkage disequilibrium (LD) SNP rs7034539 (R2 = 0.49 in Asian population), as well as other two high LD SNPs (rs17425819 and rs7850484; R2 = 0.88) associated with JAK2 expression in Chinese lymphoblastoid cell lines (n = 45), were evaluated in an extension cohort (n = 343). The four SNPs of JAK2 were significantly associated with the severe influenza in both combined analysis (n = 463) and meta-analysis (all p-values < 0.01). A potential functional enhancer harboring one SNP rs59384377 and an indel rs527982744 (-/19T-repeat) were identified to be in high LD to rs17425819 and rs7850484, and the enhancer was predicted to regulate the promoter activity of JAK2. Reporter gene luciferase assay demonstrated that rs59384377 and rs527982744 encoded regulatory polymorphisms for the enhancer activity. Furthermore, JAK2 expression was upregulated by A(H1N1) virus infection, and the inhibition of JAK2 by the inhibitor NVP-BSK805 attenuated the A(H1N1) virus-triggered induction of two important influenza immune response genes, IP-10 and IL-8. In conclusion, the genetic association study together with molecular and cellular experiments support JAK2 as a potential host factor in the pathogenesis of severe A(H1N1) influenza, but further replication of the association is warranted.
A new family of Polak-Ribière-Polyak conjugate gradient method for impulse noise removal
Authors: Mousavi Ali , Esmaeilpour Mansour , Sheikhahmadi Amir
Published: May 2023

In this paper, impulse noise removal problem is formulated as an unconstrained optimization problem with smooth objective function. It can be solved by conjugate gradient methods with desired properties (low memory and strong global convergence) in high dimensions. Accordingly, a family of the Polak-Ribi`ere-Polyak (PRP) conjugate gradient directions is constructed for which the descent condition holds. In other words, we introduce four improved versions of PRP method three of which are based on a regularization and one of which is the combination of Fletcher-Reeves and PRP conjugate gradient parameters. Using several images, it is shown that the new methods are very robust and efficient in comparison with other competitive methods for impulse noise removal, especially in terms of the peak signal to noise ratio (PSNR).
Mathematics Subject Classification (2000) 90C30a . 90C25 . 90C90 . 68U10 . 03D15
Electric Field Sensing of Etchless Lithium Niobate Heterostructure with Low Driving Voltage based on Quasibound States in the Continuum
Authors: Huang Zhijin , Wang Junzhong , Yuan Lifang , Shen Kaixiang , Li Qianqian , Wang Juan
Published: May 2023

Realizing lithium niobate-based electric field (E-field) sensor for low driving voltage has been attractive extensive attention in field of extremely weak electric field detection, wireless communications, and even astronomical observations. However, lithium niobate (LN) is difficult to be etched with high accuracy. Here, we theoretically proposed a heterostructure E-field sensor consisted of etchless LN thin film and metagratings to support Fabry-Perot-like BIC mode, which has not only ultrahigh quality (Q) factor but also large extinction ratio. Due to the loss of electrodes, the BIC mode transitions into quasi-BIC resonance with Q factor of 2050. This quasi-BIC resonance is utilized to confine electromagnetic field inside the LN layer leading to an optical field enhancement factor to 14.2 times normalized to unpatterned thin film LN. And this resonance also boosts the strong interaction among optical field, EO material and applied electric field. Numerical simulations are carried out to demonstrate the Fabry-Perot-like quasi-BIC resonance is sensitive to the refractive index change Δn of LN material. As a result, we construct the relationship between the Δn and the applied electric field and successfully obtained a tuning sensitivity of 40.8 nm/V and low driving voltage of 18.9 mV with wavelength resolution of 0.38 nm. Meanwhile, we estimate the 3dB bandwidth of the E-field sensor should exceed 154 GHz after considering the low parasitic capacitance of LN material and high conductivity of electrodes. And we believe that the LN-based heterostructure has potential applications in ultralow driving voltage E-field sensors.
Stratospheric Ozone Recovery Increases Summer Precipitation in Siberia
Authors: Xie Fei , Niu Yingli , Xia Yan , Tian Wenshou , Chipperfield Martyn , Liu Na , Feng Wuhu , Han Yuanyuan
Published: May 2023

Siberia is one of the world's major food production bases areas and a climate-sensitive region, where summer precipitation has shown decreasing, increasing, and renewed decreasing trends in recent decades. However, the external factors driving the long-term trend in precipitation are not yet understood. Here we find that summer precipitation in Siberia is closely related to stratospheric ozone changes in both observations and simulations. An increase in the lowermost stratospheric ozone heats the upper troposphere and lower stratosphere (UTLS) of the mid-high latitudes in summer. The warming-induced divergence in the UT accelerates the polar circulation, which enhances convergence and upwelling in the lower troposphere and leads to more precipitation. A 20% increase in stratospheric ozone may have contributed ~50% of the summer precipitation variations over Siberia from 1990 to 2010. Our results suggest that stratospheric ozone recovery will drive Siberia to become wetter and wetter in the context of global warming.
The Role of Dietary Fiber on Preventing Gestational Diabetes Mellitus in an At-Risk Group of High Triglyceride-Glucose Index Women: A Randomized Controlled Trial
Authors: Zhang Dongyao , Sheng Jing , Chen Li , Jiang Ying , Cheng Decui , Su Yao , Yu Yuexin , Jia Haoyi , He Pengyuan , Wang Li , Cao Yannan , xu xianming
Published: May 2023

Background Pregnant women with a high triglyceride-glucose (TyG) index during early pregnancy may increase the risk of gestational diabetes mellitus (GDM), and dietary fiber could play an important role in glucose and lipid metabolism. However, no trials have tested the effects of dietary fiber on preventing GDM in women with a high TyG index. This study aims to investigate whether GDM can be prevented by dietary fiber supplementation in women with a TyG index ≥ 8.5 during early pregnancy (< 20 weeks).Methods A randomized clinical trial was performed among 295 women with a TyG index ≥ 8.5 before 20 weeks of gestation, divided into a fiber group (24 g dietary fiber powder/day) or a control group (usual care). The intervention was conducted from 20 to 24+ 6 gestational weeks, and both groups received guidance on exercise and diet. The primary outcomes were the incidence of GDM diagnosed by a 75 g oral glucose tolerance test (OGTT) at 25–28 gestational weeks, and levels of maternal blood glucose, lipids. Secondary outcomes include gestational hypertension, postpartum haemorrhage, preterm birth, and other maternal and neonatal complications.Results GDM occurred at 11.2% (10 of 89) in the fiber group, which was significantly lower than 23.7 (44 of 186) in the control group (P = 0.015). The mean gestational weeks increased dramatically in the fiber group compared with the control group (38.58 ± 1.44 weeks vs. 39.07 ± 1.08 weeks, P = 0.016). The incidence of preterm birth was 2.3% (2 of 86) of women randomized to the fiber group compared with 9.4% (17 of 181) in the control group (P = 0.032). The concentrations of 2 hour postprandial blood glucose showed statistically higher in the control group compared with the intervention group (6.69 ± 1.65 mmol/L vs. 6.45 ± 1.25 mmol/L, P = 0.026);. There were no other significant differences between groups in lipid profile values, or other secondary outcomes.Conclusion An intervention with dietary fiber supplementation during pregnancy may prevent GDM and preterm birth in women with a TyG index ≥ 8.5 before 20 weeks of gestation.
Winter, spring, summer or fall: Temporal patterns in placenta-mediated pregnancy complications – an exploratory analysis
Authors: Jeppegaard Maria , Rasmussen Steen Christian , Anhøj Jacob , Krebs Lone
Published: May 2023

Purpose: Placenta-mediated pregnancy complications, like growth restriction and hypertensive disorders, are leading causes of maternal, fetal and neonatal morbidity and mortality in high-income countries. The purpose is to investigate if there is a seasonal variation in placenta-mediated pregnancy complications (small for gestational age, intrauterine growth restriction, preeclampsia, preterm birth and intrauterine fetal death).
Methods: This is a Danish cohort study including all singleton deliveries at gestational week 22 up to and including week 41 conceived from December 2006 to November 2016 (N=555,459). We used statistical process control charts to visualize data and to test for patterns of non-random variation in data over time for pregnancies with risk factors (BMI, diabetes, in vitro fertilization, maternal age >40 years, primipara, previous caesarean and smoking) and each outcome: fetal growth restriction, hypertensive disorders, preterm birth and intrauterine fetal death. The study was approved by the Danish Data Protection agency; REG-039-2019.
Results: We found a seasonal pattern in hypertensive disorders during pregnancy with dips in pregnancies conceived in the fall season and highest risk by conception in the spring and summer season. We found no apparent seasonality in cases of preterm delivery, small for gestational age and intrauterine mortality. Individual risk factors (e.g. smoking and obesity) for placenta-mediated complicated over time were in consistency with the general trends.
Conclusions: We found a significant seasonal variation in the risk of hypertensive disorders of pregnancy with highest risk by conception in the spring and summer season. This study found no seasonal variation in other placenta-mediated complications.
ncRNAs-mediated high express of LPCAT1 correlates with poor prognosis and expression of tumor-related signaling pathway and tumor-related gene in breast cancer
Authors: Zhang Yuezhou , Fan Yu , siyuan Zheng , Zhao Minjie , Luo Jiefu , Liu Junyan , Ma Rong , Mu Junhao
Published: May 2023

Breast cancer is the most common malignant tumor and ranks as the leading cause of cancer-related death among women. Although endocrine and targeted therapy have obtained positive curative effects, the high recurrence rate and mortality associated with drug resistance remain obstacles. Solid evidence indicates that lysophosphatidylcholine acyltransferase 1 (LPCAT1) plays a key role during tumorigenesis. Notably, LPCAT1 upregulates cancer-related Erbb signaling pathways by affecting the lipid microenvironment around the cell membrane. However, its function and mechanism in breast cancer are still elusive. The regulation of long noncoding RNAs (lncRNAs) on multiple molecules is closely related to the occurrence and development of breast cancer. At present, most studies contend that lncRNAs facilitate downstream target gene expression by regulating ceRNAs, while others suggest that lncRNAs may function as upstream modulators, inhibiting gene expression by promoting splicing of per-miRNAs. In this study, the expression and prognosis of LPCAT1 and noncoding RNA (LINC01176) were analyzed in multiple tumors. Data in The Genotype-Tissue Expression (GTEx) indicated that LPCAT1 may be a potential oncogene in breast cancer, while LINC01176, as a new noncoding RNA, may have an inhibitory effect on breast cancer. A series of bioinformatic analyses, including expression, correlation, and prognostic analyses, confirmed that the expression of LPCAT1 is related to the regulation of the noncoding RNA (lncRNA) LINC01176. Finally, the LINC01176/hsa-miR-218-5p/LPCAT1 axis was identified as the most likely upstream lncRNA-related pathway for LPCAT1 in breast cancer. Mechanistically, we found that LPCAT1, LINC01176, and hsa-miR-218-5p are related to various tumor-related signaling pathways by KEGG enrichment analysis, including the Erbb signaling pathway, which is closely related to breast cancer, and tumor angiogenesis-related VEGF and Notch signaling pathways. Moreover, the LPCAT1 level was significantly positively associated with HER2, PC, VEGF, and NOTCH, while LINC was significantly negatively associated with HER2, PC, and NOTCH. In summary, our study suggests that LPCAT1 contributes to poor prognosis in breast cancer and that we can improve the prognosis of breast cancer by regulating the LINC01176/hsa-miR-218-5p/LPCAT1 axis.
Energy-economy-environment assessments of refrigerants R152a and R134a in a vapour compression refrigeration system using a variable displacement oil-free linear compressor
Authors: Fang Xueliang , Chiong Meng-Choung , Jiang Xinyue , Yu Lih Jiun , Chen Xinwen , Muhieldeen Mohammed W. , Al-Talib Ammar Abdulaziz Majeed , Lim Wei Hong , Wong Keng Yinn
Published: May 2023

In light of the adverse environmental impact of the R134a refrigerant, replacing it with a more environmentally friendly refrigerant has become imperative than ever. This study presents an experimental investigation into the utilization of R152a and R134a refrigerants in a vapor compression refrigeration (VCR) system employing a variable displacement oil-free linear compressor. The potential for the replacement of R134a with R152a was examined based on energy, environmental, and economic performance analyses. The outcomes indicated that R152a exhibited a higher coefficient of performance (COP) in comparison to R134a under identical operating conditions. Specifically, when the pressure ratio was 2.0 and the piston stroke was 11 mm, R152a's COP was 13.0% higher than R134a. It was also discovered that reducing the operating stroke and increasing the pressure ratio could effectively lower CO2 emissions and total costs. Under the 2.0 pressure ratio and 9 mm piston stroke, R134a produced 1082.4 kg more CO2 emissions than R152a, representing a 209% increase. Additionally, In addition, the R152a and R134a total cost was reduced by 8.3% with the 2.5 pressure ratio and 11 mm piston stroke. Notably, the results of the current study demonstrated that R152a outperformed R134a in energy consumption, environmental friendliness, and economy in oil-free linear compressor refrigeration systems. R152a used less electric power, generated fewer CO2 emissions, and naturally reduced predicted running costs in order to maintain the same COP.
Is the information infrastructure construction policy necessary to move towards a green production world?
Authors: He Xiaolong , Liang Yufan , Liang Dong , Deng Hong
Published: May 2023

While achieving economic growth, China's cities have also experienced severe environmental pollution problems. To achieve the goal of green production, this paper first measures the green total factor productivity (GTFP) of Chinese prefecture-level cities using the super Slacks-Based Measure and the global Malmquist-Luenberger index (SBM-GML) model and then explores the paths affecting GTFP from the perspective of information infrastructure construction policy (IICP) using a time-varying Difference-in-Difference (time-varying DID) model. The results show that the information infrastructure construction policy significantly contributes to urban GTFP growth overall, and the implementation of the policy leads to an average increase of 0.209 in pilot cities relative to non-pilot cities. The information infrastructure construction policy contributes to urban GTFP growth through green technology diffusion effects and the improvement of employment structure.
Importance of cross-shore transport and eddies in promoting large scale response to urban eutrophication
Authors: Kessouri Faycal , Sutula Martha , Bianchi Daniele , Ho Minna , Damien Pierre , McWilliams James , Frieder Christina , Renault Lionel , Frenzel Hartmut , McLaughlin Karen , Deutsch Curtis
Published: May 2023

A key control on the magnitude of coastal eutrophication is the degree to which currents quickly transport nitrogen away from the coast to the open ocean before eutrophication symptoms develop. In the Southern California Bight (SCB), an upwelling-dominated eastern boundary current ecosystem, anthropogenic nitrogen inputs increase algal productivity and cause subsurface acidification and deoxygenation along the coast. However, the extent of anthropogenic influence beyond the coastal band, and the physical transport mechanisms responsible these effects, were not previously documented. Here, we use a submesoscale-resolving numerical model to investigate the transport of anthropogenic nitrogen and its effects on SCB offshore habitats. Anthropogenic nutrient inputs promoted an increase in productivity and respiration offshore, with recurrent oxygen loss and pH decline in a region located 30 – 90 km from the mainland. Over 2013 to 2017, peak losses up to 14.2 mmol m-3 O2 persisted 4 to 6 months of the year over an area of 278,400 km2 (~30\% of SCB area). These recurrent features are associated with eddy cross-shore transport of nutrients and plankton biomass, and their accumulation and retention within persistent eddies offshore counteract the dilution and dispersion by mean currents that transport nitrogen and organic matter out of the SCB.
Efficient differential expression analysis of large-scale single cell transcriptomics data using dreamlet
Authors: Hoffman Gabriel , Lee Donghoon , Bendl Jaroslav , Fnu Prashant , Hong Aram , Casey Clara , Alvia Marcela , Shao Zhiping , Argyriou Stathis , Therrien Karen , Venkatesh Sanan , Voloudakis Georgios , Haroutunian Vahram , Fullard John , Roussos Panos
Published: May 2023

Advances in single-cell and -nucleus transcriptomics have enabled generation of increasingly large-scale datasets from hundreds of subjects and millions of cells. These studies promise to give unprecedented insight into the cell type specific biology of human disease. Yet performing differential expression analyses across subjects remains difficult due to challenges in statistical modeling of these complex studies and scaling analyses to large datasets. Our open-source R package dreamlet (DiseaseNeurogenomics.github.io/dreamlet) uses a pseudobulk approach based on precision-weighted linear mixed models to identify genes differentially expressed with traits across subjects for each cell cluster. Designed for data from large cohorts, dreamlet is substantially faster and uses less memory than existing workflows, while supporting complex statistical models and controlling the false positive rate. We demonstrate computational and statistical performance on published datasets, and a novel dataset of 1.4M single nuclei from postmortem brains of 150 Alzheimer’s disease cases and 149 controls.
An investigation into the effects of 6-Gingerol on glucose and glutamine metabolism in breast cancer cell lines
Authors: Ghorbani Mahboobe , Shafiee Seyed Mohammad , Dianati-Nassab Aria , Behbahani Sara Edalat , Honardar Zohreh , Khoshdel Zahra
Published: May 2023

Background One of the most significant signs of cancer is reprogramming of energy metabolism, especially enhancement of glycolysis and glutaminolysis to support the speedy growth of tumor cells.Purpose As [6]-gingerol may play a beneficial role in cancer cells metabolism, in this study, we investigated whether the [6]‐gingerol would be able to induce changes catalytic activities of lactate dehydrogenase A (LDHA) and glutamate dehydrogenase (GDH) in MCF-7 and SKBR3 breast cancer cells. We also wanted to test whether the glutamic acid transporters like SLC1A5 (ASCT2) and SLC7A5 (LAT1) are targets of [6]‐gingerol to block glutamine import into cancer cells.Methods and results Our results showed for the first time that [6]‐gingerol resulted in reduced LDHA and GDH enzyme activities. Our data also revealed a significant down-regulation of GDH, LDHA, SLC7A5, SLC1A5 gene expression after treatment of MCF-7 and SKBR3 cells with [6]-gingerol.Conclusion These findings indicated that [6]‐gingerol acts as metabolic antagonist for breast cancer cells, and any reduction in cell growth was associated with reduced LDHA, GDH enzymes activities and down-regulation of SLC1A5 and SLC7A5 gene expression, so this suggests that [6]‐gingerol has the potential to block certain glutamine transporters and deprive the tumor cells of these important tumor promoting amino acids. Therefore, [6]‐gingerol can antagonize the development of breast cancer cells via inhibition of aerobic glycolysis and glutaminolysis .
Predicting Saddle-Node Bifurcations Using Transient Dynamics: A Model-Free Approach
Authors: Habib Giuseppe
Published: May 2023

This paper proposes a novel method for predicting the presence of saddle-node bifurcations in dynamical systems. The method exploits the effect that saddle-node bifurcations have on transient dynamics in the surrounding phase space and parameter space, and does not require any information about the steady-state solutions associated with the bifurcation. Specifically, trajectories of a system obtained for parameters close to the saddle-node bifurcation present local minima of the logarithmic decrement trend in the vicinity of the bifurcation. By tracking the logarithmic decrement for these trajectories, the saddle-node bifurcation can be accurately predicted. The method does not strictly require any mathematical model of the system, but only a few time series, making it directly implementable for gray- and black-box models and experimental apparatus. The proposed algorithm is tested on various systems of different natures, including a single-degree-of-freedom system with nonlinear damping, the mass-on-moving-belt, a time-delayed inverted pendulum, and a pitch-and-plunge wing profile. Benefits, limitations, and future perspectives of the method are also discussed. The proposed method has potential applications in various fields, such as engineering, physics, and biology, where the identification of saddle-node bifurcations is crucial for understanding and controlling complex systems.
Differences clinical characteristics and factors in intrinsic and extrinsic adenomyosis
Authors: Liang Yan , Shi Wei , Sun Feng , Zhu Minjiao , Liu Yuan , Zhang Jian
Published: May 2023

Adenomyosis (AM) is a common gynecological condition that can be classified into different subtypes. This study aimed to evaluate the clinical characteristics, factors and treatment effect in women who diagnosed with intrinsic or extrinsic AM by MRI and underwent hysterectomies. A total of 181 women were enrolled in the study. Among these, 77 of which were identified to be in the intrinsic AM group (intrinsic group) and 54 in the extrinsic AM group (extrinsic group). Our results show that gravidity (P < 0.0001), parity (P < 0.0001), number of abortion (P < 0.0013) and endometrial curettage (P = 0.0167) were significantly higher in the intrinsic group, while the education level was lower in the intrinsic group (P = 0.0118). Women in the extrinsic group had earlier menarches (P = 0.0257) and were more coexist with ovarian endometrioma (OMA) (P < 0.0001) and deep infiltrating endometriosis (DIE) (P < 0.0001). In terms of clinical features, dysmenorrhea was more serious in the extrinsic group (P = 0.0091), whereas women in the intrinsic group had heavier menstrual volume (P < 0.0001). Surgery duration (P < 0.0001), surgical bleeding (P < 0.0013), hospitalization cost (P < 0.0001), and postoperative medical therapy (P < 0.001) were significantly higher in the extrinsic group than in the intrinsic group. In the multivariate analysis we performed, education level, gravidity and number of endometrial curettage were significantly associated with intrinsic AM. OMA and DIE were closely related to extrinsic AM. These results suggest that intrinsic and extrinsic AM have specific clinic characteristics, are associated with different factors, and may have different pathogenesis.
CLCLSA: Cross-omics Linked embedding with Contrastive Learning and Self Attention for multi-omics integration with incomplete multi-omics data
Authors: Zhou Weihua , Zhao Chen , Liu Anqi , Zhang Xiao , Cao Xuewei , Ding Zhengming , Sha Qiuying , Shen Hui , Deng Hong-Wen
Published: May 2023

Integration of heterogeneous and high-dimensional multi-omics data is becoming increasingly important in understanding genetic data. Each omics technique only provides a limited view of the underlying biological process and integrating heterogeneous omics layers simultaneously would lead to a more comprehensive and detailed understanding of diseases and phenotypes. However, one obstacle faced when performing multi-omics data integration is the existence of unpaired multi-omics data due to instrument sensitivity and cost. Studies may fail if certain aspects of the subjects are missing or incomplete. In this paper, we propose a deep learning method for multi-omics integration with incomplete data by Cross-omics Linked unified embedding with Contrastive Learning and Self Attention (CLCLSA). Utilizing complete multi-omics data as supervision, the model employs cross-omics autoencoders to learn the feature representation across different types of biological data. The multi-omics contrastive learning, which is used to maximize the mutual information between different types of omics, is employed before latent feature concatenation. In addition, the feature-level self-attention and omics-level self-attention are employed to dynamically identify the most informative features for multi-omics data integration. Extensive experiments were conducted on four public multi-omics datasets. The experimental results indicated that the proposed CLCLSA outperformed the state-of-the-art approaches for multi-omics data classification using incomplete multiomics data.
Predictive value of adipokines for the severity of acute pancreatitis: a meta-analysis
Authors: Yu Xuehua , Zhang Ning , Wu Jing , Zhao Yunhong , Liu Chengjiang , Liu Gaifang
Published: May 2023

Background Severe acute pancreatitis (SAP) is a dangerous condition with a high mortality rate. Many studies have found an association between adipokines and the development of SAP, but the results are controversial. Therefore, we performed a meta-analysis of the association of inflammatory adipokines with SAP.
Methods We screened PubMed, EMBASE, Web of Science and Cochrane Library for articles on adipokines and SAP published before March 2, 2023. The quality of the literature was assessed using QUADAS criteria. Standardised mean differences (SMD) with 95% confidence intervals (CI) were calculated to assess the combined effect. Subgroup analysis, sensitivity analysis and publication bias tests were also performed on the information obtained.
Result Fifteen eligible studies included 936 patients with acute pancreatitis (AP). Pooled analysis showed that patients with SAP had significantly higher levels of circulating resistin (SMD = 0.55, 95% CI:0.15 to 0.94, z = 2.70, P = 0.007). The difference in circulating leptin and adiponectin levels between SAP and MAP patients was not significant (SMD = 0.31, 95% CI: -0.11 to 0.73, z = 1.44, P = 0.149 and SMD = -0.07, 95% CI: -0.30 to 0.16, z = 0.57, P = 0.570). Subgroup analyses identified mean age of the patients as possible sources of circulating resistin level heterogeneity.
Conclusion Elevated levels of circulating resistin levels are associated with the development of SAP. Resistin may be potential biomarkers and therapeutic targets for SAP. However, the age of the patient may influence these results.
Turing pattern of an SIRI model on large-scale homogeneous and heterogeneous networks
Authors: He Le , Su Haijun
Published: May 2023

Taking into account the spatial flow and relapse behaviors, this paper establishes a network-organized reaction-diffusion system for disease spreading with Laplacian matrices. In this paper, the Turing branch of the system is studied, and the derivation of the necessary conditions for Turing instability is extended from homogeneous networks to heterogeneous diffusion environment. Here, it has been demonstrated that the system cannot exhibit Turing instability under conditions of constant growth, linear growth, and Logistic growth in susceptible individuals. Further, we assume that the susceptible satisfy the Logistic growth model with Allen effects, and investigate the system's Turing pattern by numerical methods. The simulation results for homogeneous networks show that the infection rate can significantly change the population distribution patterns on lattice networks. The results for heterogeneous networks show that the diffusion environments of susceptible population and infected population play a dominant role in the formation of network Turing patterns, and the difference between their average degrees shows a positive correlation with the difficulty of pattern formation.
Alcohol Consumption and Endometrial Cancer: A Mendelian Randomization Study
Authors: Yang Jie , Chang Hui , Jiang Fan , zhang Jinru , Yan Lijuan , Ning Peng
Published: May 2023

Background Endometrial cancer (EC) is a common gynecological tumor in females with an increasing incidence over the past few decades. Alcohol consumption has been linked to the occurrence of various cancers; however, epidemiological studies have shown inconsistent associations between alcohol consumption and EC risk. This study aimed to investigate whether there is a causal relationship between alcohol consumption and EC.Methods Mendelian randomization (MR) analysis was conducted using publicly available summary-level data from genome-wide association studies (GWAS). Fifty-seven single nucleotide polymorphisms (SNPs) were extracted as instrumental variables for alcohol exposure from the Social Science Genetic Association Consortium (SSGAC) GWAS summary data involving 941,287 participants of European ancestry. SNPs for EC were obtained from the Endometrial Cancer Association Consortium, the Endometrial Cancer Epidemiology Consortium, and the UK Biobank, involving 121,885 European participants. The inverse variance weighted (IVW) method was used as the primary method to estimate the causal effect, and the MR-Egger regression and weighted median method were used as supplementary methods. Sensitivity analyses were conducted using the Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) global test, MR-Egger intercept test, and leave-one-out analysis to evaluate the impact of pleiotropy on causal estimates.Results An increase of 1 standard deviation (SD) of genetically predicted log-transformed alcoholic drinks per day was associated with a 43% reduction in EC risk (odds ratio [OR], 0.57; 95% confidence interval [CI], 0.41–0.79; P༜0.001). Subgroup analysis of EC revealed that alcohol consumption was a protective factor for endometrioid endometrial cancer (EEC) (OR, 0.56; 95% CI, 0.38–0.83; P = 0.004) but not for non-endometrioid endometrial cancer (NEC) (OR, 1.36; 95% CI, 0.40–4.66; P = 0.626). The MR-Egger regression and weighted median method yielded consistent causal effects with the IVW method. The consistent results of sensitivity analyses indicated the reliability of our causal estimates. Additionally, alcohol consumption was associated with decreased human chorionic gonadotropin (HCG) and insulin-like growth factor 1 (IGF1) levels.Conclusion This study suggests that alcohol consumption is a protective factor for EC, particularly for EEC, and this protective effect may be mediated through the reduction of HCG and IGF1.
Identification of biomarkers functioning in the lipid-induced IBS symptoms
Authors: Ran Yamei , Wu Kangqi , Hu Chenglin , Liang Renzheng , Zhang Li , Xiao Juan , Peng Yongmei , Sun Wenjing
Published: May 2023

Background: Fat intake is one of the most important triggers for symptom development in patients with irritable bowel syndrome (IBS). But long-term restriction in fatty foods ingestion may lead to nutritional inadequacies. In this study, we aim to identify the vital genes that function in lipid-induced gastrointestinal symptoms, contributing to precise management of fat control for IBS patients.
Methods: The clinical characteristics of the subjects were collected by questionnaire investigation and analyzed using multivariate logistic regression. Differentially expressed genes (DEG) and signaling pathways were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The infiltrated immune cells in the small intestinal mucosa were analyzed using ImmuInfiltration and CIBERSORT packages. Random forest and SVM-RFE algorithms were used to select hub genes. A receiver operating characteristic curve (ROC) was performed to evaluate the diagnostic significance of each hub gene. Gene Set Enrichment Analysis (GSEA) was conducted to clarify the possible molecular mechanisms of hub genes in the pathogenesis of IBS after lipid infusion.
Results: Fat intake was positively associated with the risk, severity, and quality of life (QOL) of IBS patients. A total of 116 robust DEGs were identified in patients with IBS after lipid infusion using the GSE166869 dataset and were mainly clustered in the immune and inflammatory pathways. The infiltration levels of Neutrophils, CD4+T cells and M1 Macrophages were significantly higher in IBS patients compared to the healthy controls. Furthermore, infiltration levels of Neutrophils and resting memory CD4+ T cells were inversely related to the expression of hub genes (IGKV1D-43, IGKV1-12, APOD, FCGR2A and IGKV2-29). GSEA results of each hub gene suggested the importance of pro-inflammatory pathways in IBS pathogenesis after lipid infusion. After verification, only APOD and FCGR2A were stably down-regulated in both small intestinal mucosa and plasma of IBS patients. The area under the curve of APOD combined with FCGR2A expression was 0.9.
Conclusions: APOD and FCGR2A may act as promising biomarkers for discriminating lipid-sensitive IBS patients and IBS diagnosis. Their potential roles in the immune microenvironment of the small intestinal mucosa may provide a vital clue to IBS precision therapy.
Clinical failure of anti-tau and anti-synuclein antibodies in neurodegeneration: a quantitative systems pharmacology model analysis
Authors: Geerts Hugo , Bergeler Silke , Walker Mike , Graaf Piet van der , Courade Jean-Philippe
Published: May 2023

Misfolded proteins in Alzheimer’s disease (AD) and Parkinson’s disease (PD) follow a well-defined connectomics-based spatial progression. Several anti-tau and anti-alpha synuclein (aSyn) antibodies have failed to provide clinical benefit in clinical trials despite substantial target engagement in the experimentally accessible cerebrospinal fluid (CSF). The proposed mechanism of action is reducing neuronal uptake of seed-competent protein from the synaptic cleft. We built a quantitative systems pharmacology (QSP) model to quantitatively simulate intrasynaptic secretion, diffusion and antibody capture in the synaptic cleft, postsynaptic membrane binding and internalization of monomeric and seed-competent tau and aSyn proteins. Integration with a physiologically based pharmacokinetic (PBPK) model allowed us to simulate clinical trials of anti-tau antibodies gosuranemab, tilavonemab, semorinemab, and anti-aSyn antibodies cinpanemab and prasineuzumab. Maximal target engagement for monomeric tau was simulated as 45% (semorinemab) to 99% (gosuranemab) in CSF, 30% to 99% in ISF but only 1% to 3% in the synaptic cleft, leading to a reduction of less than 1% in uptake of seed-competent tau. Simulations for prasineuzumab and cinpanemab suggest target engagement of free monomeric aSyn of only 6-8% in CSF, 4-6% and 1-2% in the ISF and synaptic cleft, while maximal target engagement of aggregated aSyn was predicted to reach 99% and 80% in the synaptic cleft with similar effects on neuronal uptake. The study generates optimal values of selectivity, sensitivity and PK profiles for antibodies. The study identifies a gradient of decreasing target engagement from CSF to the synaptic cleft as a key driver of efficacy, quantitatively identifies various improvements for drug design and emphasizes the need for QSP modelling to support the development of tau and aSyn antibodies. Trial registration : N/A