bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of hepatocellular carcinoma in treated and untreated patients with chronic hepatitis B virus infection
Authors: Lin Chih-Lin , Kao Jia-Horng
Published: February 2023

Hepatitis B virus (HBV) is responsible for more than 50% of hepatocellular carcinoma (HCC) in HBV hyperendemic areas, such as the Asia-Pacific region. Several hepatitis B viral factors are involved in HBV-related hepatocarcinogenesis. Hepatitis B viral load is the most important risk factor of HCC development. In addition, HBV integration, HBV genotype C, and core-promoter mutations are also associated with a risk of HCC development. For untreated chronic hepatitis B (CHB) patients, the estimated HCC incidence rates per 100 patient-years were 0.03–0.17 in inactive carriers, 0.07–0.42 in asymptomatic carriers, 0.12–0.49 in chronic hepatitis, and 2.03–3.37 in cirrhosis. Complementary to HBV DNA, serum levels of the hepatitis B surface antigen and hepatitis B core-related antigen (HBcrAg) can predict the occurrence of HCC for untreated patients with low and intermediate viral loads, respectively. For patients receiving antiviral therapy, the risks of HCC occurrence 40–60% lower than those for untreated patients. Patients treated with residual detectable HBV DNA or intrahepatic cccDNA still have a risk of HCC. Serum levels of HBcrAg, M2BPGi and fibrosis-4 are predictive of the risk of HCC development in treated patients. Several well-developed HCC risk scores can help clinicians identify high-risk CHB patients for HCC surveillance, regardless of treatment status. These strategies can help minimize the threat of HCC and prolong survival in CHB patients.
Analisis Sistem Antrian pada Bank Negara Indonesia Kantor Cabang Kawasan Industri Medan
Authors: Sirait Paskah Riny , Gultom Parapat
Published: February 2023

The problem that occurs at Bank Negara Indonesia of Medan Industrial Area Branch Office is the occurrence of unemployed tellers at certain hours. The purpose of this study is to determine the queue system at Bank Negara Indonesia of Medan Industrial Area Branch Office and to find out the optimal number of tellers at the bank. The structure of the queue model that occurs at Bank Negara Indonesia of The Medan Industrial Area Branch Office is a Multi Channel-Single Phase by applying the discipline of the First Come First Serve queue. The bank has 4 tellers with an average customer arrival value (λ) of 20 people per hour and an average service level (μ) of 22 people per hour. The results of data processing show the arrival pattern of Poisson-distributed customers and the general distribution service pattern. This study resulted in a queueing model (M / G / 4): (FCFS / ∞ / ∞). The optimal number of tellers in providing customer service is to reduce 1 teller. Based on the calculation results with only 3 tellers, it can reduce the probability of the teller being unemployed from the initial one by 40.25% to 39.97%.
PENGARUH TEMPERATUR PELAT-LANDASAN PADA JIG HOT-GAS WELDING DAN SUDUT V-GROOVE TERHADAP KEKUATAN TARIK SAMBUNGAN LAS HDPE SHEET
Authors: Setiawan Agus , Witono Kris , Gumono Gumono
Published: February 2023

Proses pengelasan telah berkembang pesat saat ini, baik untuk material logam maupun non logam. Salah satu material non logam yang disambung dengan proses pengelasan adalah plastik. Pada saat ini penggunaan produk berbahan material plastik semakin meningkat, maka untuk proses pengelasan material plastik menggunakan metode Hot-Gas Welding (HGW). Diketahui bahwa dalam proses pengelasan konduktifitas material sangat mempengaruhi kwalitas sambungan las, semakin tinggi konduktifitas maka kwalitas hasil pengelasan akan semakin baik. Di sisi lain diketahui bahwa material plastik memiliki tingkat konduktivitas yang rendah, maka dalam proses pengelasan plastik tersebut akan menjadi kendala. Tujuan dari penelitian ini adalah melakukan studi untuk meningkatkan kwalitas sambungan las material plastik yang dikhususkan pada material HDPE, yaitu mengetahui pengaruh temperatur pelat-landasan pada Jig Hot-Gas Welding dan sudut V-groove terhadap kekuatan tarik sambungan las HDPE sheet. Metode penelitian yang digunakan adalah eksperimental dengan variasi temperatur pelat landasan 30°C, 70°C, 110°C, dan 150°C, sedangkan variasi sudut V-groove yang digunakan 40°, 60°, dan 75°. Standar uji tarik mengunakan standar ASTM D 638-03, sebagai data penunjang dilakukan foto makrostruktur dari masing-masing sambungan las. Hasil penelitian ini diperoleh temperatur pelat landasan dan sudut V-groove berpengaruh tinggi terhadap kekuatan tarik lasan HDPE sheet selama proses hot-gas welding. Hasil interaksi antara variasi temperatur pelat landasan dan variasi sudut v-groove diperoleh bahwa pada temperatur pelat landasan 150°C dan sudut V-groove 60° didapatkan nilai maksimum kekuatan tarik lasan 18,8 MPa atau 87,5% terhadap kekuatan tarik material HDPE sheet tanpa sambungan.
Analysis of Fiber Metal Composite Shear Strength Using Independent Variables of Fiber Angle Orientation and Metal Surface Roughness
Authors: Firmansyah Hilmi Iman , Wirawan Wirawan , Hariyanto Moh Nasir
Published: February 2023

Fiber Metal Laminates (FML) is a classification of metallic materials consisting of several thin layers of metal combined with composite materials. The constraint of FML is the weak bond between the layer material and the core composite. The weak bond between the layer material and the core composite can be influenced by several things, including the absence of an interlock system between the layer material and the core composite so that the strength of the FML composite decreases. In this study, a study was conducted on the shear strength of FML composites using the independent variables of surface roughness and fiber angle orientation. The highest shear strength in FML composite with fiber angle orientation of 45/45° and with a surface roughness value of 2.128 m with a shear strength value of 2.7 MPa
ANALISIS TEMPERATUR PELAT LANDASAN HOT-GAS WELDING DAN BENTUK BEVEL TERHADAP KEKUATAN TARIK LASAN HDPE
Authors: Witono Kris , Setiawan Agus , Susilo Sugeng Hadi
Published: February 2023

Welding has developed rapidly at this time, both for metallic and non-metallic materials, one of the methods used for plastic welding is Hot-Gas Welding. Plastic is a very difficult material to weld due to its low thermal conductivity. The quality of the mechanical properties of the existing plastic welded joints is not close to the strength of plastic objects without welding. The purpose of this study was to determine the effect of variations in the temperature of the base plate and variations in the shape of the bevel during the Hot-Gas Welding process on the tensile strength of HDPE sheet welded joints, to determine the conditions of the interaction between variations in the temperature of the base plate and variations in the shape of the bevel during the Hot-Gas Welding process. HDPE sheet welded joints that produce maximum tensile strength values. In this study, two independent variables were used, namely the base plate temperature (30,70,110,150 C), variations in bevel shape (V, X, U) and three controlled variables which included HDPE plastic material with a thickness of 5mm, using added filler material in the form of HDPE plastic with a diameter of 4 mm and a hot gun airflow heating temperature of 250℃. The tensile test standard uses the ASTM D 638-03 standard and for data processing is done by DOE factorial, as supporting data macrostructural photos of each weld joint are carried out. The results showed that the maximum tensile strength of HDPE welded joints was obtained at the temperature of the base plate of 150°C and the V bevel shape with a value of 18.46 MPa or 84.22% of the parent material
Bayesian logical neural networks for human-centered applications in medicine
Authors: Diaz Ochoa Juan G. , Maier Lukas , Csiszar Orsolya
Published: February 2023

Background: Medicine is characterized by its inherent uncertainty, i.e., the difficulty of identifying and obtaining exact outcomes from available data. Electronic Health Records aim to improve the exactitude of health management, for instance using automatic data recording techniques or the integration of structured as well as unstructured data. However, this data is far from perfect and is usually noisy, implying that epistemic uncertainty is almost always present in all biomedical research fields. This impairs the correct use and interpretation of the data not only by health professionals but also in modeling techniques and AI models incorporated in professional recommender systems.

Method: In this work, we report a novel modeling methodology combining structural explainable models, defined on Logic Neural Networks which replace conventional deep-learning methods with logical gates embedded in neural networks, and Bayesian Networks to model data uncertainties. This means, we do not account for the variability of the input data, but we train single models according to the data and deliver different Logic-Operator neural network models that could adapt to the input data, for instance, medical procedures (Therapy Keys depending on the inherent uncertainty of the observed data.

Result: Thus, our model does not only aim to assist physicians in their decisions by providing accurate recommendations; it is above all a user-centered solution that informs the physician when a given recommendation, in this case, a therapy, is uncertain and must be carefully evaluated. As a result, the physician must be a professional who does not solely rely on automatic recommendations. This novel methodology was tested on a database for patients with heart insufficiency and can be the basis for future applications of recommender systems in medicine.
Artificial intelligence-based non-small cell lung cancer transcriptome RNA-sequence analysis technology selection guide
Authors: Joo Min Soo , Pyo Kyoung-Ho , Chung Jong-Moon , Cho Byoung Chul
Published: February 2023

The incidence and mortality rates of lung cancer are high worldwide, where non-small cell lung cancer (NSCLC) accounts for more than 85% of lung cancer cases. Recent non-small cell lung cancer research has been focused on analyzing patient prognosis after surgery and identifying mechanisms in connection with clinical cohort and ribonucleic acid (RNA) sequencing data, including single-cell ribonucleic acid (scRNA) sequencing data. This paper investigates statistical techniques and artificial intelligence (AI) based non-small cell lung cancer transcriptome data analysis methods divided into target and analysis technology groups. The methodologies of transcriptome data were schematically categorized so researchers can easily match analysis methods according to their goals. The most widely known and frequently utilized transcriptome analysis goal is to find essential biomarkers and classify carcinomas and cluster NSCLC subtypes. Transcriptome analysis methods are divided into three major categories: Statistical analysis, machine learning, and deep learning. Specific models and ensemble techniques typically used in NSCLC analysis are summarized in this paper, with the intent to lay a foundation for advanced research by converging and linking the various analysis methods available.
A review on the role of long non-coding RNA prostate androgen-regulated transcript 1 (PART1) in the etiology of different disorders
Authors: Ghafouri-Fard Soudeh , Harsij Atefeh , Hussen Bashdar Mahmud , Abdullah Snur Rasool , Baniahmad Aria , Taheri Mohammad , Sharifi Guive
Published: February 2023

LncRNA prostate androgen-regulated transcript 1 (PART1) is an important lncRNA in the carcinogenesis whose role has been firstly unraveled in prostate cancer. Expression of this lncRNA is activated by androgen in prostate cancer cells. In addition, this lncRNA has a role in the pathogenesis intervertebral disc degeneration, myocardial ischemia-reperfusion injury, osteoarthritis, osteoporosis and Parkinson’s disease. Diagnostic role of PART1 has been assessed in some types of cancers. Moreover, dysregulation of PART1 expression is regarded as a prognostic factor in a variety of cancers. The current review provides a concise but comprehensive summary of the role of PART1 in different cancers and non-malignant disorders.
MAPping tubulin mutations
Authors: Cushion Thomas D. , Leca Ines , Keays David A.
Published: February 2023

Microtubules are filamentous structures that play a critical role in a diverse array of cellular functions including, mitosis, nuclear translocation, trafficking of organelles and cell shape. They are composed of α/β-tubulin heterodimers which are encoded by a large multigene family that has been implicated in an umbrella of disease states collectively known as the tubulinopathies. De novo mutations in different tubulin genes are known to cause lissencephaly, microcephaly, polymicrogyria, motor neuron disease, and female infertility. The diverse clinical features associated with these maladies have been attributed to the expression pattern of individual tubulin genes, as well as their distinct Functional repertoire. Recent studies, however, have highlighted the impact of tubulin mutations on microtubule-associated proteins (MAPs). MAPs can be classified according to their effect on microtubules and include polymer stabilizers (e.g., tau, MAP2, doublecortin), destabilizers (e.g., spastin, katanin), plus-end binding proteins (e.g., EB1-3, XMAP215, CLASPs) and motor proteins (e.g., dyneins, kinesins). In this review we analyse mutation-specific disease mechanisms that influence MAP binding and their phenotypic consequences, and discuss methods by which we can exploit genetic variation to identify novel MAPs.
EWSR1 prevents the induction of aneuploidy through direct regulation of Aurora B
Authors: Kim Haeyoung , Park Hyewon , Schulz Evan T. , Azuma Yoshiaki , Azuma Mizuki
Published: February 2023

EWSR1 (Ewing sarcoma breakpoint region 1) was originally identified as a part of an aberrant EWSR1/FLI1 fusion gene in Ewing sarcoma, the second most common pediatric bone cancer. Due to formation of the EWSR1/FLI1 fusion gene in the tumor genome, the cell loses one wild type EWSR1 allele. Our previous study demonstrated that the loss of ewsr1a (homologue of human EWSR1) in zebrafish leads to the high incidence of mitotic dysfunction, of aneuploidy, and of tumorigenesis in the tp53 mutant background. To dissect the molecular function of EWSR1, we successfully established a stable DLD-1 cell line that enables a conditional knockdown of EWSR1 using an Auxin Inducible Degron (AID) system. When both EWSR1 genes of DLD-1 cell were tagged with mini-AID at its 5′-end using a CRISPR/Cas9 system, treatment of the (AID-EWSR1/AID-EWSR1) DLD-1 cells with a plant-based Auxin (AUX) led to the significant levels of degradation of AID-EWSR1 proteins. During anaphase, the EWSR1 knockdown (AUX+) cells displayed higher incidence of lagging chromosomes compared to the control (AUX-) cells. This defect was proceeded by a lower incidence of the localization of Aurora B at inner centromeres, and by a higher incidence of the protein at Kinetochore proximal centromere compared to the control cells during pro/metaphase. Despite these defects, the EWSR1 knockdown cells did not undergo mitotic arrest, suggesting that the cell lacks the error correction mechanism. Significantly, the EWSR1 knockdown (AUX+) cells induced higher incidence of aneuploidy compared to the control (AUX-) cells. Since our previous study demonstrated that EWSR1 interacts with the key mitotic kinase, Aurora B, we generated replacement lines of EWSR1-mCherry and EWSR1:R565A-mCherry (a mutant that has low affinity for Aurora B) in the (AID-EWSR1/AID-EWSR1) DLD-1 cells. The EWSR1-mCherry rescued the high incidence of aneuploidy of EWSR1 knockdown cells, whereas EWSR1-mCherry:R565A failed to rescue the phenotype. Together, we demonstrate that EWSR1 prevents the induction of lagging chromosomes, and of aneuploidy through the interaction with Aurora B.
The synthesis and highly effective antibacterial properties of Cu-3, 5-dimethy l-1, 2, 4-triazole metal organic frameworks
Authors: Xu Xiaolin , Ding Mengna , Liu Kaiquan , Lv Fujian , Miao Yingchun , Liu Yanmi , Gong Ying , Huo Yuning , Li Hexing
Published: February 2023

The influence of metal ions, the state of metal salt, and ligands on the sterilization ability of (Metalorganic frameworks) MOFs to effectively achieve sterilization has been investigated in this study. Initially, the MOFs were synthesized by elements of Zn, Ag, and Cd for the same periodic and main group of Cu. This illustrated that the atomic structure of Cu was more beneficial for coordinating with ligands. To further induce the maximum amount of Cu2+ ions in the Cu-MOFs to achieve the highest sterilization, various Cu-MOFs synthesized by the different valences of Cu, various states of copper salts, and organic ligands were performed, respectively. The results demonstrated that Cu-MOFs synthesized by 3, 5-dimethyl-1, 2, 4-triazole and tetrakis (acetonitrile) copper(I) tetrafluoroborate presented the largest inhibition-zone diameter of 40.17 mm towards Staphylococcus Aureus (S. aureus) under dark conditions. The proposed mechanism of Cu (Ⅱ) in MOFs could significantly cause multiple toxic effects, such as the generation of reactive oxygen species, and lipid peroxidation in S. aureus cells, when the bacteria was anchored by the Cu-MOFs via electrostatic interaction. Finally, the broad antimicrobial properties of Cu-MOFs against Escherichia coli (E. coli), Acinetobacter baumannii (A. baumannii), and S. aureus were demonstrated. In conclusion, the Cu-3, 5-dimethyl-1, 2, 4-triazole MOFs appeared to be potential antibacterial catalysts in the antimicrobial field.
Why intervention in Afghan media failed to provide support for peace talks
Authors: Lynch Jake , Freear Matt
Published: February 2023

This article presents and discusses data from two research methods on journalism in Afghanistan before the Taliban takeover of power in August 2021. News reports from the time of the intra-Afghan peace talks in September 2020 were analyzed using the Peace Journalism model. These were found to be predominantly War Journalism, leaving audiences cognitively primed for violent conflict responses and likely to overlook or fail to value peace initiatives. Interviews with 16 Afghan journalists revealed this pattern to be at odds with their aspirations and role perceptions. They wanted to report more in the style of Peace Journalism: revealing backgrounds and contexts; highlighting successes and achievements; giving a voice to all rival parties, and covering peace initiatives from whatever level. The constraints they identified, as impeding their preferred reporting approaches, were categorized using Reese and Shoemaker's Hierarchy of Influences model. Some were attributed to the commercial competitive market structure of Afghan media under the internationally supported government, after an initial infusion of development aid was reduced. In any such intervention in future, it is argued, news can play a positive role in building a constituency for peace—but only if aid interventions ensure that media are not left to operate on a purely commercial basis.
Implications of Russia’s invasion of Ukraine for the governance of biodiversity conservation
Authors: Gallo-Cajiao Eduardo , Dolšak Nives , Prakash Aseem , Mundkur Taej , Harris Paul G. , Mitchell Ronald B. , Davidson Nick , Hansen Birgita , Woodworth Bradley K. , Fuller Richard A. , Price Melissa , Petkov Nicky , Mauerhofer Volker , Morrison Tiffany H. , Watson James E. M. , Chowdhury Sayam U. , Zöckler Christoph , Widerberg Oscar , Yong Ding Li , Klich Daniel , Smagol Vitaliy , Piccolo John , Biggs Duan
Published: February 2023

Maintaining peace and conserving biodiversity hinge on an international system of cooperation codified in institutions, but Russia’s invasion of Ukraine brings recent progress to a crossroads. Against this backdrop, we address some implications of Russia’s invasion of Ukraine for the governance of biodiversity conservation both within and beyond Russia. The Russian invasion of Ukraine threatens the governance system for biodiversity conservation, as it pertains to Russia and beyond, due to three interacting factors: (i) isolation of Russia from the international system, (ii) halt and delay of international cooperation, and (iii) changes in international and domestic policy priorities. We recommend making the existing international system of governance for conserving biodiversity more resilient and adaptable, while aligning security agendas with biodiversity conservation goals.
Impact of subway shield tunnel construction on deformation of existing utility tunnel
Authors: Wei Shi , Zenglin Hong , Min Yang , Ning Li , Tianxiang Tan
Published: February 2023

In recent years, the development of urban underground space in China, especially the construction and operation of subway tunnels, has greatly relieved the pressure of urban traffic. Due to the imperfect planning of urban facility, many subway tunnels have to be built under the existing utility tunnels (pipe galleries). Nevertheless, shield construction of subway tunnel has a great adverse impact on the deformation and safety of the existing pipe gallery. Therefore, this paper takes Xi’an Metro Line 2 as an example, and studies the safety depth for subway tunnel shield construction under different regional conditions in Xi’an through numerical simulation. The results show that the deformation of the existing pipe gallery and its influence range decrease with the rising buried depth of the double-line subway tunnel when the soil properties are good. For example, in the loess tableland area, when the buried depth of the subway tunnel is greater than 12 m, the settlement deformation of the pipe gallery basically meets the control standard. When the soil properties are poor or the soil properties vary greatly, the subway tunnel excavation has a great impact on the safety of the pipe gallery. For example, in the first-level alluvial fan area with sand layer, when the buried depth of the subway tunnel is less than 24 m and more than 12 m, the deformation standard cannot be satisfied. In addition, in the first-level alluvial fan area with sand layer, the lower soil layer should be treated or the construction parameters should be optimized before the excavation of subway tunnel. The research results can provide reference for similar engineering construction.
Causation of the heavy rainfall in Kyushu in early July 2020: A perspective of the depression that originated over the Tibetan Plateau
Authors: Li Lun , Huang Honghui , Zhu Congwen
Published: February 2023

Heavy rain fell in Kyushu, Japan, in early July 2020, which caused huge life and economic losses. The present work reports that a Tibetan Plateau vortex (TPV) generated over the Tibetan Plateau transformed into a trough at the eastern edge of the Tibetan Plateau, and the trough continued to move eastward and was responsible for the heavy rainfall in Kyushu. Accordingly, the maintenance and eastward movement of the trough and the influencing mechanism of the trough on the rainfall in Kyushu are explored based on the final analysis data (FNL) from NCEP and the JRA-55 reanalysis from JMA. Diagnoses of the potential vorticity (PV) tendency equation indicate that the horizontal PV flux convergence east of the trough is the primary contributor to the eastward movement and maintenance of the trough. Furthermore, the trough is proved to have important effects on the moisture condition and the ascending motion around Kyushu. That is, the trough increases the moisture in Kyushu by intensifying the eastward moisture transportation to Kyushu; the positive vorticity and warm center, as well as the wind perturbation related to the trough, are in favor of stronger ascending motion in Kyushu. The findings in this work provide extended knowledge on the causation of rainfall in Japan, which is beneficial for further precipitation prediction.
Bariatric Surgery: Targeting pancreatic β cells to treat type II diabetes
Authors: Liu Tiantong , Zou Xi , Ruze Rexiati , Xu Qiang
Published: February 2023

Pancreatic β-cell function impairment and insulin resistance are central to the development of obesity-related type 2 diabetes mellitus (T2DM). Bariatric surgery (BS) is a practical treatment approach to treat morbid obesity and achieve lasting T2DM remission. Traditionally, sustained postoperative glycemic control was considered a direct result of decreased nutrient intake and weight loss. However, mounting evidence in recent years implicated a weight-independent mechanism that involves pancreatic islet reconstruction and improved β-cell function. In this article, we summarize the role of β-cell in the pathogenesis of T2DM, review recent research progress focusing on the impact of Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG) on pancreatic β-cell pathophysiology, and finally discuss therapeutics that have the potential to assist in the treatment effect of surgery and prevent T2D relapse.
DNA methylation profiling reveals novel pathway implicated in cardiovascular diseases of diabetes
Authors: Hu Shengqing , Chen Lulu , Zeng Tianshu , Wang Wenyi , Yan Yan , Qiu Kangli , Xie Yajuan , Liao Yunfei
Published: February 2023

Objective

Epigenetics was reported to mediate the effects of environmental risk factors on disease pathogenesis. We intend to unleash the role of DNA methylation modification in the pathological process of cardiovascular diseases in diabetes.

Methods

We screened differentially methylated genes by methylated DNA immunoprecipitation chip (MeDIP-chip) among the enrolled participants. In addition, methylation-specific PCR (MSP) and gene expression validation in peripheral blood of participants were utilized to validate the DNA microarray findings.

Results

Several aberrantly methylated genes have been explored, including phospholipase C beta 1 (PLCB1), cam kinase I delta (CAMK1D), and dopamine receptor D5 (DRD5), which participated in the calcium signaling pathway. Meanwhile, vascular endothelial growth factor B (VEGFB), placental growth factor (PLGF), fatty acid transport protein 3 (FATP3), coagulation factor II, thrombin receptor (F2R), and fatty acid transport protein 4 (FATP4) which participated in vascular endothelial growth factor receptor (VEGFR) signaling pathway were also found. After MSP and gene expression validation in peripheral blood of participants, PLCB1, PLGF, FATP4, and VEGFB were corroborated.

Conclusion

This study revealed that the hypomethylation of VEGFB, PLGF, PLCB1, and FATP4 might be the potential biomarkers. Besides, VEGFR signaling pathway regulated by DNA methylation might play a role in the cardiovascular diseases’ pathogenesis of diabetes.
Hyperglycemia in Turner syndrome: Impact, mechanisms, and areas for future research
Authors: Mitsch Cameron , Alexandrou Eirene , Norris Andrew W. , Pinnaro Catherina T.
Published: February 2023

Turner syndrome (TS) is a common chromosomal disorder resulting from complete or partial absence of the second sex chromosome. Hyperglycemia, ranging from impaired glucose tolerance (IGT) to diabetes mellitus (DM), is common in TS. DM in individuals with TS is associated with an 11-fold excess in mortality. The reasons for the high prevalence of hyperglycemia in TS are not well understood even though this aspect of TS was initially reported almost 60 years ago. Karyotype, as a proxy for X chromosome (Xchr) gene dosage, has been associated with DM risk in TS – however, no specific Xchr genes or loci have been implicated in the TS hyperglycemia phenotype. The molecular genetic study of TS-related phenotypes is hampered by inability to design analyses based on familial segregation, as TS is a non-heritable genetic disorder. Mechanistic studies are confounded by a lack of adequate TS animal models, small and heterogenous study populations, and the use of medications that alter carbohydrate metabolism in the management of TS. This review summarizes and assesses existing data related to the physiological and genetic mechanisms hypothesized to underlie hyperglycemia in TS, concluding that insulin deficiency is an early defect intrinsic to TS that results in hyperglycemia. Diagnostic criteria and therapeutic options for treatment of hyperglycemia in TS are presented, while emphasizing the pitfalls and complexities of studying glucose metabolism and diagnosing hyperglycemia in the TS population.
Roles of endoplasmic reticulum stress in the pathophysiology of polycystic ovary syndrome
Authors: Koike Hiroshi , Harada Miyuki , Kusamoto Akari , Xu Zixin , Tanaka Tsurugi , Sakaguchi Nanoka , Kunitomi Chisato , Azhary Jerilee M. K. , Takahashi Nozomi , Urata Yoko , Osuga Yutaka
Published: February 2023

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among reproductive-age women, affecting up to 15% of women in this group, and the most common cause of anovulatory infertility. Although its etiology remains unclear, recent research has revealed the critical role of endoplasmic reticulum (ER) stress in the pathophysiology of PCOS. ER stress is defined as a condition in which unfolded or misfolded proteins accumulate in the ER because of an imbalance in the demand for protein folding and the protein-folding capacity of the ER. ER stress results in the activation of several signal transduction cascades, collectively termed the unfolded protein response (UPR), which regulates various cellular activities. In principle, the UPR restores homeostasis and keeps the cell alive. However, if the ER stress cannot be resolved, it induces programmed cell death. ER stress has recently been recognized to play diverse roles in both physiological and pathological conditions of the ovary. In this review, we summarize current knowledge of the roles of ER stress in the pathogenesis of PCOS. ER stress pathways are activated in the ovaries of both a mouse model of PCOS and in humans, and local hyperandrogenism in the follicular microenvironment associated with PCOS is responsible for activating these. The activation of ER stress contributes to the pathophysiology of PCOS through multiple effects in granulosa cells. Finally, we discuss the potential for ER stress to serve as a novel therapeutic target for PCOS.
Obesity-associated cardiometabolic complications in polycystic ovary syndrome: The potential role of sodium-glucose cotransporter-2 inhibitors
Authors: Pruett Jacob E. , Romero Damian G. , Yanes Cardozo Licy L.
Published: February 2023

Polycystic Ovary Syndrome (PCOS) is the most common endocrine disorder in reproductive-age women. PCOS is characterized by androgen excess, oligo/anovulation, and polycystic appearance of the ovaries. Women with PCOS have an increased prevalence of multiple cardiovascular risk factors such as insulin resistance, hypertension, renal injury, and obesity. Unfortunately, there is a lack of effective, evidence-based pharmacotherapeutics to target these cardiometabolic complications. Sodium-glucose cotransporter-2 (SGLT2) inhibitors provide cardiovascular protection in patients with and without type 2 diabetes mellitus. Although the exact mechanisms of how SGLT2 inhibitors confer cardiovascular protection remains unclear, numerous mechanistic hypotheses for this protection include modulation of the renin-angiotensin system and/or the sympathetic nervous system and improvement in mitochondrial function. Data from recent clinical trials and basic research show a potential role for SGLT2 inhibitors in treating obesity-associated cardiometabolic complications in PCOS. This narrative review discusses the mechanisms of the beneficial effect of SGLT2 inhibitors in cardiometabolic diseases in PCOS.
Numerical study of extreme waves driven by synthetic tropical cyclones in the northwest Pacific Ocean
Authors: Du Shengtao , Yan Zhiduo
Published: February 2023

Extreme waves induced by extreme tropical cyclones (TCs) with a very strong intensity threaten marine production and transportation. In this paper, six tropical cyclones with a typical track and extremely strong intensity were synthesized to study the extreme waves. The data on TC tracks were extracted from the China Meteorological Administration. The historic TCs from 1949 to 2018 were classified into six groups according to their tracks, and a representative track was synthesized for each group of TCs. We applied an extremely strong intensity to the tracks for studying the extreme wave field. The synthesized track of typical track cyclones (TTCs) was based on the maximum probability of the translation distance and direction of the TC center according to historical data. The central pressure (Pc) was used to represent the TC intensity and was studied at the recurrence periods of 100, 1,000, and 10,000 years. The synthetic TC with a representative track and extremely strong intensity was called a typical tropical cyclone (TTC). The extreme wave fields driven by TTCs were simulated by Simulating Waves Nearshore (SWAN). The wind field driving the waves was calculated using the Holland parametric wind model and was well-verified with observations. This paper calculated the extreme Hs and Tp values of the return periods of 100, 1,000, and 10,000 years for six types of TTCs. It was found that the extreme Hs values were very different for each TTC. The highest Hs could reach 31.3 m in the recurrence period of 10,000 years. Followed by TTC-I with 18 m, TTC-VI was the weakest with less than 10 m. The TC track position frequency and its spatial variation of extreme intensity were discussed. The synthetic tracks were representative, and the intensity could be influenced by spatial variation. In the end, four historical typhoons with great intensity, wide impact, and serious disaster-causing effects were selected to compare with TTC. This paper can provide guidance for maritime planners.
A novel SEMA6B variant causes adult-onset progressive myoclonic epilepsy-11 in a Chinese family: A case report and literature review
Authors: Chen Yirao , Yang Xingyan , Yan Xinxiang , Shen Lu , Guo Jifeng , Xu Qian
Published: February 2023

This study describes a patient with progressive myoclonic epilepsy-11 (EPM-11), which follows autosomal dominant inheritance caused by a novel SEMA6B variant. Most patients develop this disease during infancy or adolescence with action myoclonus, generalized tonic-clonic seizures (GTCS), and progressive neurological deterioration. No cases of adult-onset EPM-11 have been reported yet. Here, we present one case of adult-onset EPM-11 who experienced gait instability, seizures, and cognitive impairment, and harbored a novel missense variant, c.432C>G (p.C144W). Our findings provide a foundation for a better understanding of the phenotypic and genotypic profiles of EPM-11. Further functional studies are recommended to elucidate the pathogenesis of this disease.
Pre-transplant CRP–albumin ratio as a biomarker in patients receiving haploidentical allogeneic hematopoietic transplantation: Developing a novel DRCI-based nomogram
Authors: Wang Kejing , Jian Xing , Xu Ziwei , Wang Huafang
Published: February 2023

Background

In allogeneic hematopoietic stem cell transplantation (allo-HSCT), prognostic indicators effectively predict survival. The Disease conditions prior to transplantation dramatically affects the outcome of HSCT. Optimization of the pre-transplant risk assessment is critical for enhancing allo-HSCT decision-making. Inflammation and nutritional status play significant roles in cancer genesis and progression. As a combined inflammatory and nutritional status biomarker, the C-reactive protein/albumin ratio (CAR) can accurately forecast the prognosis in various malignancies. This research sought to examine the predictive value of CAR and develop a novel nomogram by combining biomarkers and evaluating their importance following HSCT.

Methods

Analyses were conducted retroactively on a cohort of 185 consecutive patients who underwent haploidentical hematopoietic stem cell transplantation (haplo-HSCT) at Wuhan Union Medical College Hospital during the period from February 2017 to January 2019. Of these patients, 129 were randomly assigned to the training cohort, and the remaining 56 patients constituted the internal validation cohort. Univariate and multivariate analyses were carried out to examine the predictive significance of clinicopathological factors in the training cohort. Subsequently, the survival nomogram model was developed and compared with the disease risk comorbidity index (DRCI) using the concordance index (C-index), calibration curve, receiver operating characteristics (ROC) curve, and decision curve analysis (DCA).

Results

Patients were separated into low and high CAR groups using a cutoff of 0.087, which independently predicted overall survival (OS). Based on risk factors, CAR, the Disease Risk Index(DRI), and the Hematopoietic Cell Transplantation–specific Comorbidity Index(HCT-CI), the nomogram was developed to predict OS. The C-index and area under the ROC curve confirmed the improved predictive accuracy of the nomogram. The calibration curves revealed that the observed probabilities agreed well with those predicted by the nomogram in training, validation and entire cohort. It was confirmed by DCA that the nomogram offered greater net benefits than DRCI among all cohorts.

Conclusion

CAR is an independent prognostic indicator for haplo-HSCT outcomes. Higher CAR was related to worse clinicopathologic characteristics and poorer prognoses in patients underwent haplo-HSCT. This research provided an accurate nomogram for predicting the OS of patients following haplo-HSCT, illustrating its potential clinical utility.
Interleukin-32 as a biomarker in rheumatic diseases: A narrative review
Authors: Kwon Oh Chan , Park Min-Chan , Kim Yong-Gil
Published: February 2023

Interleukin-32 (IL-32) is an important cytokine involved in the innate and adaptive immune responses. The role of IL-32 has been studied in the context of various diseases. A growing body of research has investigated the role of IL-32 in rheumatic diseases including inflammatory arthritides (rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis) and connective tissue diseases (systemic lupus erythematosus, systemic sclerosis, granulomatosis and polyangiitis, and giant cell arteritis). IL-32 has been shown to play different roles according to the type of rheumatic diseases. Hence, the putative role of IL-32 as a biomarker is also different in each rheumatic disease: IL-32 could serve as a biomarker for disease activity in some diseases, whereas in other diseases it could be a biomarker for certain disease manifestations. In this narrative review, we summarize the associations between IL-32 and various rheumatic diseases and discuss the putative role of IL-32 as a biomarker in each disease.
Large-scale nano-biosensing technologies
Authors: Tzouvadaki Ioulia , Prodromakis Themis
Published: February 2023

Nanoscale technologies have brought significant advancements to modern diagnostics, enabling unprecedented bio-chemical sensitivities that are key to disease monitoring. At the same time, miniaturized biosensors and their integration across large areas enabled tessellating these into high-density biosensing panels, a key capability for the development of high throughput monitoring: multiple patients as well as multiple analytes per patient. This review provides a critical overview of various nanoscale biosensing technologies and their ability to unlock high testing throughput without compromising detection resilience. We report on the challenges and opportunities each technology presents along this direction and present a detailed analysis on the prospects of both commercially available and emerging biosensing technologies.
The interplay between T helper cells and brain barriers in the pathogenesis of multiple sclerosis
Authors: Angelini Gabriele , Bani Alessandro , Constantin Gabriela , Rossi Barbara
Published: February 2023

The blood–brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB) represent two complex structures protecting the central nervous system (CNS) against potentially harmful agents and circulating immune cells. The immunosurveillance of the CNS is governed by immune cells that constantly patrol the BCSFB, whereas during neuroinflammatory disorders, both BBB and BCSFB undergo morphological and functional alterations, promoting leukocyte intravascular adhesion and transmigration from the blood circulation into the CNS. Multiple sclerosis (MS) is the prototype of neuroinflammatory disorders in which peripheral T helper (Th) lymphocytes, particularly Th1 and Th17 cells, infiltrate the CNS and contribute to demyelination and neurodegeneration. Th1 and Th17 cells are considered key players in the pathogenesis of MS and its animal model, experimental autoimmune encephalomyelitis. They can actively interact with CNS borders by complex adhesion mechanisms and secretion of a variety of molecules contributing to barrier dysfunction. In this review, we describe the molecular basis involved in the interactions between Th cells and CNS barriers and discuss the emerging roles of dura mater and arachnoid layer as neuroimmune interfaces contributing to the development of CNS inflammatory diseases.
Characterization of patients with IgA nephropathy with and without associated minimal change disease
Authors: Guo Wei-yi , Sun Li-jun , Dong Hong-rui , Wang Guo-qin , Xu Xiao-yi , Cheng Wen-rong , Zhao Zhi-rui , Ye Nan , Liu Yun , Cheng Hong
Published: February 2023

Introduction

Immunoglobulin A nephropathy (IgAN) presents various clinical manifestations and pathological phenotypes. Approximately 5% of patients with IgAN present with early onset nephrotic syndrome, mild mesangial lesions, and diffuse foot process effacement of podocytes, which resemble minimal change disease (MCD). These patients are defined as MCD-IgAN. Whether MCD-IgAN is a special type of IgAN or simply MCD accompanied by IgA deposition remains controversial.

Methods

A total of 51 patients diagnosed with MCD-IgAN at Beijing Anzhen Hospital from January 2010 to September 2022 were recruited. The clinical and pathological characteristics of IgA-MCD were analyzed. Patients with IgAN but without MCD (non-MCD-IgAN) and healthy participants were enrolled as controls. Galactose-deficient immunoglobulin A1 (Gd-IgA1) and complement C3 were detected both in the circulation and in renal tissues.

Results

We found that the levels of serum Gd-IgA1 were lower in participants with MCD-IgAN than in those with non-MCD-IgAN, but higher than in healthy participants. Gd-IgA1 was rarely deposited in the glomeruli of participants with MCD-IgAN, with a positive rate of only 13.7% (7/51); in contrast, the positive rate in participants with non-MCD-IgAN was 82.4% (42/51). Among renal Gd-IgA1-positive patients, Gd-IgA1 and immunoglobulin A (IgA) colocalized along the glomerular mesangial and capillary areas. Interestingly, we found that the circulating levels of complement C3 were significantly higher in participants with MCD-IgAN than in participants with non-MCD-IgAN. In addition, the intensity of C3c in glomeruli in participants with MCD-IgAN was significantly weaker than in participants with non-MCD-IgAN.

Conclusions

Our study suggests that, in MCD-IgAN, most of the IgA that is deposited on glomeruli is not the same pathogenic Gd-IgA1 as found in general IgAN. Complement activation both in the circulation and in the renal locality was much weaker in MCD-IgAN than in non-MCD-IgAN. Our study suggests that IgAN with MCD might be MCD with coincidental IgA deposition.
Case report: First manifestation of multiple sclerosis temporally correlated with COVID-19 vaccination
Authors: Czarnowska Agata , Kapica-Topczewska Katarzyna , Tarasów Eugeniusz , Tarasiuk Joanna , Chorąży Monika , Kochanowicz Jan , Kułakowska Alina
Published: February 2023

There are several case reports describing a temporal correlation between the first clinical manifestation of multiple sclerosis (MS) and the occurrence of relapses with vaccination against SARS-CoV-2. Here we report a case of a 33-year-old male who developed partial right upper and lower extremities numbness 2 weeks after receiving Johnson & Johnson's Janssen COVID-19 vaccine. The brain MRI performed during diagnostics in the Department of Neurology detected several demyelinating lesions, one with enhancement. Oligoclonal bands were present in the cerebrospinal fluid. The patient was treated with high-dose glucocorticoid therapy with improvement and the diagnosis of MS was made. It seems plausible that the vaccination revealed the underlying autoimmune condition. Cases like the one we reported here are rare, and—based on current knowledge—the benefits of vaccination against SARS-CoV-2 far outweigh the potential risks.
Abnormal resting-state functional connectivity underlies cognitive and clinical symptoms in patients with schizophrenia
Authors: Jia Yingxin , Jariwala Namasvi , Hinkley Leighton B. N. , Nagarajan Srikantan , Subramaniam Karuna
Published: February 2023

Introduction

The cognitive and psychotic symptoms in patients with schizophrenia (SZ) are thought to result from disrupted brain network connectivity.

Methods

We capitalize on the high spatiotemporal resolution of magnetoencephalography imaging (MEG) to record spontaneous neuronal activity in resting state networks in 21 SZ compared with 21 healthy controls (HC).

Results

We found that SZ showed significant global disrupted functional connectivity in delta-theta (2–8 Hz), alpha (8–12 Hz), and beta (12–30 Hz) frequencies, compared to HC. Disrupted global connectivity in alpha frequencies with bilateral frontal cortices was associated with more severe clinical psychopathology (i.e., positive psychotic symptoms). Specifically, aberrant connectivity in beta frequencies between the left primary auditory cortex and cerebellum, was linked to greater hallucination severity in SZ. Disrupted connectivity in delta-theta frequencies between the medial frontal and left inferior frontal cortex was associated with impaired cognition.

Discussion

The multivariate techniques employed in the present study highlight the importance of applying our source reconstruction techniques which leverage the high spatial localization abilities of MEG for estimating neural source activity using beamforming methods such as SAM (synthetic aperture morphometry) to reconstruct the source of brain activity, together with functional connectivity assessments, assayed with imaginary coherence metrics, to delineate how neurophysiological dysconnectivity in specific oscillatory frequencies between distinct regions underlie the cognitive and psychotic symptoms in SZ. The present findings employ powerful techniques in spatial and time-frequency domains to provide potential neural biomarkers underlying neuronal network dysconnectivity in SZ that will inform the development of innovations in future neuromodulation treatment development.
The disruptive relationship among circadian rhythms, pain, and opioids
Authors: Bumgarner Jacob R. , McCray Evan W. , Nelson Randy J.
Published: February 2023

Pain behavior and the systems that mediate opioid analgesia and opioid reward processing display circadian rhythms. Moreover, the pain system and opioid processing systems, including the mesolimbic reward circuitry, reciprocally interact with the circadian system. Recent work has demonstrated the disruptive relationship among these three systems. Disruption of circadian rhythms can exacerbate pain behavior and modulate opioid processing, and pain and opioids can influence circadian rhythms. This review highlights evidence demonstrating the relationship among the circadian, pain, and opioid systems. Evidence of how disruption of one of these systems can lead to reciprocal disruptions of the other is then reviewed. Finally, we discuss the interconnected nature of these systems to emphasize the importance of their interactions in therapeutic contexts.