bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel molecular subtypes of intracranial germ cell tumors expand therapeutic opportunities
Authors: Li Bo , Zhao Shuang , Li Shouwei , Li Chunde , Liu Wei , Li Lin , Cui Bowen , Liu Xing , Chen Huiyuan , Zhang Jing , Ren Yin , Liu Fei , Yang Ming , Jiang Tao , Liu Yu , Qiu Xiaoguang
Published: March 2024

Background

Intracranial germ cell tumors (IGCTs) are a rare group of malignancies that are clinically classified as germinomas and nongerminomatous germ cell tumors (NGGCTs). Previous studies have found that somatic mutations involving the mitogen-activated protein kinase/mTOR signaling pathway are common early events. However, a comprehensive genomic understanding of IGCTs is still lacking.

Methods

We established a cohort including over 100 IGCTs and conducted genomic and transcriptomic sequencing.

Results

We identified novel recurrent driver genomic aberrations, including USP28 truncation mutations and high-level copy number amplification of KRAS and CRKL caused by replication of extrachromosomal DNA. Three distinct subtypes associated with unique genomic and clinical profiles were identified with transcriptome analysis: Immune-hot, MYC/E2F, and SHH. Both immune-hot and MYC/E2F were predominantly identified in germinomas and shared similar mutations involving the RAS/MAPK signaling pathway. However, the immune-hot group showed an older disease onset age and a significant immune response. MYC/E2F was characterized by a younger disease onset age and increased genomic instability, with a higher proportion of tumors showing whole-genome doubling. Additionally, the SHH subtype was mostly identified in NGGCTs.

Conclusions

Novel genomic aberrations and molecular subtypes were identified in IGCTs. These findings provide molecular basis for the potential introduction of new treatment strategies in this setting.
Plasma ctDNA liquid biopsy of IDH1, TERTp, and EGFRvIII mutations in glioma
Authors: Jones Jordan J , Nguyen Hong , Wong Stephen Q , Whittle James , Iaria Josie , Stylli Stanley , Towner James , Pieters Thomas , Gaillard Frank , Kaye Andrew H , Drummond Katharine J , Morokoff Andrew P
Published: March 2024

Background

Circulating tumor DNA has emerging clinical applications in several cancers; however, previous studies have shown low sensitivity in glioma. We investigated if 3 key glioma gene mutations IDH1, TERTp, and EGFRvIII could be reliably detected in plasma by droplet digital polymerase chain reaction (ddPCR) thereby demonstrating the potential of this technique for glioma liquid biopsy.

Methods

We analyzed 110 glioma patients from our biobank with a total of 359 plasma samples (median 4 samples per patient). DNA was isolated from plasma and analyzed for IDH1, TERTp, and EGFRvIII mutations using ddPCR.

Results

Total cfDNA was significantly associated with tumor grade, tumor volume, and both overall and progression-free survival for all gliomas as well as the grade 4 glioblastoma subgroup, but was not reliably associated with changes in tumor volume/progression during the patients’ postoperative time course. IDH1 mutation was detected with 84% overall sensitivity across all plasma samples and 77% in the preoperative samples alone; however, IDH1 mutation plasma levels were not associated with tumor progression or survival. IDH1m plasma levels were not associated with pre- or postsurgery progression or survival. The TERTp C228T mutation was detected in the plasma ctDNA in 88% but the C250T variant in only 49% of samples. The EGFRvIII mutation was detected in plasma in 5 out of 7 patients (71%) with tissue EGFRvIII mutations in tumor tissue.

Conclusions

Plasma ctDNA mutations detected with ddPCR provide excellent diagnostic sensitivity for IDH1, TERTp-C228T, and EGFRvIII mutations in glioma patients. Total cfDNA may also assist with prognostic information. Further studies are needed to validate these findings and the clinical role of ctDNA in glioma.
An Analysis of Social Determinants of Health and Their Implications for Hepatitis C Virus Treatment in People Who Inject Drugs: The Case of Baltimore
Authors: Gonzalez Corro Luis A , Zook Katie , Landry Miles , Rosecrans Amanda , Harris Robert , Gaskin Darrell , Falade-Nwulia Oluwaseun , Page Kathleen R , Lucas Gregory M
Published: March 2024

Background

Sixty-eight percent of the nearly 3.5 million people living with hepatitis C virus (HCV) in the United States are people who inject drugs (PWID). Despite effective treatments, uptake remains low in PWID. We examined the social determinants of health (SDoH) that affect the HCV care cascade.

Methods

We conducted a secondary analysis of data from 720 PWID in a cluster-randomized trial. We recruited PWID from 12 drug-affected areas in Baltimore. Inclusion criteria were injection in the prior month or needle sharing in the past 6 months. Intake data consisted of a survey and HCV testing. Focusing on SDoH, we analyzed self-report of (1) awareness of HCV infection (in those with active or previously cured HCV) and (2) prior HCV treatment (in the aware subgroup). We used descriptive statistics and logistic regression for statistical analyses.

Results

The 342 participants were majority male and Black with a median age of 52 years. Women were more likely to be aware of their status but less likely to be treated. Having a primary care provider and HIV-positive status were associated with increased awareness and treatment. Unhoused people had 51% lower odds of HCV treatment. People who reported that other PWID had shared their HCV status with them had 2.3-fold higher odds of awareness of their own status.

Conclusions

Further study of gender disparities in HCV treatment access is needed. Increased social support was associated with higher odds of HCV treatment, suggesting an area for future interventions. Strategies to identify and address SDoH are needed to end HCV.
A Machine Learning-Based Thermobarometer for Magmatic Liquids
Authors: Weber Gregor , Blundy Jon
Published: March 2024

Experimentally calibrated models to recover pressures and temperatures of magmas are widely used in igneous petrology. However, large errors, especially in barometry, limit the capacity of these models to resolve the architecture of crustal igneous systems. Here, we apply machine learning to a large experimental database to calibrate new regression models that recover P–T of magmas based on melt composition plus associated phase assemblage. The method is applicable to compositions from basalt to rhyolite, pressures from 0.2 to 15 kbar, and temperatures of 675°C to 1400°C. Testing and optimisation of the model with a filter that removes estimates with standard deviation above the 50th percentile show that pressures can be recovered with root-mean-square-error (RMSE) of 1.1 to 1.3 kbar and errors on temperature estimates of 21°C. Our findings demonstrate that, given constraints on the coexisting mineral assemblage, melt chemistry is a reliable recorder of magmatic variables. This is a consequence of the relatively low thermodynamic variance of natural magma compositions despite their relatively large number of constituent oxide components. We apply our model to two contrasting cases with well-constrained geophysical information: Mount St. Helens volcano (USA), and Askja caldera in Iceland. Dacite whole-rocks from Mount St Helens erupted 1980 to 1986, inferred to represent liquids extracted from cpx–hbl–opx–plag–mt–ilm mush, yield melt extraction source pressures of 5.1 to 6.7 kbar in excellent agreement with geophysical constraints. Melt inclusions and matrix glasses record lower pressures (0.7–3.8 kbar), consistent with magma crystallisation within the upper reaches of the imaged geophysical anomaly and during ascent. Magma reservoir depth estimates for historical eruptions from Askja match the location of seismic wave speed anomalies. Vp/Vs anomalies at 5 to 10 km depth correspond to hot (~990°C) rhyolite source regions, while basaltic magmas (~1120°C) were stored at 7 to 17 km depth under the caldera. These examples illustrate how our model can link petrology and geophysics to better constrain the architecture of volcanic feeding systems. Our model (MagMaTaB) is accessible through a user-friendly web application (https://igdrasil.shinyapps.io/MagmaTaBv4/).
AraLeTA: An Arabidopsis leaf expression atlas across diurnal and developmental scales
Authors: Vong Gina Y W , McCarthy Kayla , Claydon Will , Davis Seth J , Redmond Ethan J , Ezer Daphne
Published: March 2024

Mature plant leaves are a composite of distinct cell types, including epidermal, mesophyll, and vascular cells. Notably, the proportion of these cells and the relative transcript concentrations within different cell types may change over time. While gene expression data at a single-cell level can provide cell-type-specific expression values, it is often too expensive to obtain these data for high-resolution time series. Although bulk RNA-seq can be performed in a high-resolution time series, RNA-seq using whole leaves measures average gene expression values across all cell types in each sample. In this study, we combined single-cell RNA-seq data with time-series data from whole leaves to assemble an atlas of cell-type-specific changes in gene expression over time for Arabidopsis (Arabidopsis thaliana). We inferred how the relative transcript concentrations of different cell types vary across diurnal and developmental timescales. Importantly, this analysis revealed 3 subgroups of mesophyll cells with distinct temporal profiles of expression. Finally, we developed tissue-specific gene networks that form a community resource: an Arabidopsis Leaf Time-dependent Atlas (AraLeTa). This allows users to extract gene networks that are confirmed by transcription factor–binding data and specific to certain cell types at certain times of day and at certain developmental stages. AraLeTa is available at https://regulatorynet.shinyapps.io/araleta/.
The role of long noncoding RNA MEG3 in fibrosis diseases
Authors: Wu Wenlong , Zhou Sijing , Fei Guanghe , Wang Ran
Published: March 2024

Fibrosis is a prevalent pathological condition observed in various organs and tissues. It primarily arises from the excessive and abnormal accumulation of the extracellular matrix, resulting in the structural and functional impairment of tissues and organs, which can culminate in death. Many forms of fibrosis, including liver, cardiac, pulmonary, and renal fibrosis, are considered irreversible. Maternally expressed gene 3 (MEG3) is an imprinted RNA gene. Historically, the downregulation of MEG3 has been linked to tumor pathogenesis. However, recent studies indicate an emerging association of MEG3 with fibrotic diseases. In this review, we delve into the current understanding of MEG3’s role in fibrosis, aiming to shed light on the molecular mechanisms of fibrosis and the potential of MEG3 as a novel therapeutic target.
Characteristics of long COVID in patients with autoimmune rheumatic diseases: a systematic review and meta-analysis
Authors: Chen Der-Yuan , Huang Po-I , Tang Kuo-Tung
Published: March 2024

Objectives

Numerous cases of long coronavirus disease (long COVID) have been reported in patients with autoimmune rheumatic diseases (ARDs). Despite the reviews on clinical manifestations of long COVID in the general population, systematic reviews on ARD patients are scarce. Herein, we conducted a systematic review and meta-analysis on the prevalence and characteristics of long COVID in ARD patients.

Methods

We searched the literature in PubMed and Embase as of 27 December 2022. Cohort, cross-sectional and case–control studies relevant to long COVID in ARD patients were collected. Stratification based on the severity of COVID infection and subtypes of rheumatic diseases [systemic autoimmune rheumatic disease (SARD) vs non-autoimmune rheumatic disease (NARD)] was also undertaken. A random-effects model was used in the meta-analysis.

Results

A total of 15 relevant studies were identified from the literature. The prevalence of long COVID was 56% (95% CI 34, 76) in 2995 patients. Hospitalized COVID patients had a higher proportion of long COVID than non-hospitalized patients. The prevalence of long COVID was similar between SARD and NARD patients. In terms of symptoms, fatigue, arthralgia and pain were commonly reported in long COVID patients with ARDs.

Conclusion

The characteristics of long COVID in ARD patients are generally similar to those in the general population despite a higher prevalence and a higher proportion of arthralgia and pain.
Inclusion-body myositis associated with Sjögren’s disease: clinical characteristics and comparison with other Sjögren-associated myositis
Authors: Astouati Quentin , Machet Thomas , Houssais Camille , Noury Jean-Baptiste , Allenbach Yves , Gallay Laure , Quere Baptiste , Assan Florence , Benveniste Olivier , Broner Jonathan , Duffau Pierre , Espitia Alexandra , Grasland Anne , Hayem Gilles , Le Guern Véronique , Martis Nihal , Mariampillai Kuberaka , Nocturne Gaëtane , Mariette Xavier , Meyer Alain , Mulleman Denis , Devauchelle-Pensec Valérie , Collet Aurore , Launay David , Hachulla Eric , Cornec Divi , Guellec Dewi , Sanges Sébastien
Published: March 2024

Objectives

To describe the characteristics of patients with Sjögren’s disease (SjD) and inclusion-body myositis (IBM), and how they compare to SjD patients with other inflammatory myopathies (IM).

Methods

Patients were retrospectively recruited from 13 French centres and included if they met the ACR/EULAR criteria for SjD and for IM. They were categorized as SjD-IBM if sub-criteria for IBM were met, or as SjD-other IM if not.

Results

SjD-IBM patients (n = 22) were mostly females (86%), with a median [Q1; Q3] age of 54 [38.5; 64] years at SjD diagnosis, and 62 [46.5; 70] years at first IBM symptoms. Although most patients displayed glandular and immunological abnormalities, additional extra-glandular manifestations were uncommon, resulting in moderate disease activity at SjD diagnosis (ESSDAI 5.5 [1; 7.8]). Classic IBM features were frequent, such as progressive symptom onset (59%), asymmetrical (27%) and distal (32%) involvements, dysphagia (41%), low CPK (386.5 [221.8; 670.5] UI/l) and CRP (3.0 [3; 8.5] mg/l) levels. Immunosuppressants were reported as efficient in 55% of cases. Compared with SjD-IBM patients, SjD patients with other IM (n = 50) were significantly younger, displayed more frequent additional extra-glandular disease, higher ESSDAI score (11 [3; 30]), shorter delay between SjD diagnosis and myositis onset (0 [−0.5; 26]), more frequent CPK values over 1000 UI/l (36%), and less frequent classic IBM features.

Conclusion

IBM can occur in SjD patients, with muscle features reminiscent of classic sporadic IBM characteristics, but mostly affecting women. In SjD patients with muscle involvement, extra-glandular manifestations, high ESSDAI score, elevated CPK values and shorter delay after SjD diagnosis plead against IBM.
Loneliness in the Daily Lives of People With Mood and Psychotic Disorders
Authors: Moran Erin K , Shapiro Madelyn , Culbreth Adam J , Nepal Subigya , Ben-Zeev Dror , Campbell Andrew , Barch Deanna M
Published: March 2024

Background and Hypothesis

Loneliness, the subjective experience of feeling alone, is associated with physical and psychological impairments. While there is an extensive literature linking loneliness to psychopathology, limited work has examined loneliness in daily life in those with serious mental illness. We hypothesized that trait and momentary loneliness would be transdiagnostic and relate to symptoms and measures of daily functioning.

Study Design

The current study utilized ecological momentary assessment and passive sensing to examine loneliness in those with schizophrenia (N = 59), bipolar disorder (N = 61), unipolar depression (N = 60), remitted unipolar depression (N = 51), and nonclinical comparisons (N = 82) to examine relationships of both trait and momentary loneliness to symptoms and social functioning in daily life.

Study Results

Findings suggest that both trait and momentary loneliness are higher in those with psychopathology (F(4,284) = 28.00, P < .001, ηp2 = 0.27), and that loneliness significantly relates to social functioning beyond negative symptoms and depression (β = −0.44, t = 6.40, P < .001). Furthermore, passive sensing measures showed that greater movement (β = −0.56, t = −3.29, P = .02) and phone calls (β = −0.22, t = 12.79, P = .04), but not text messaging, were specifically related to decreased loneliness in daily life. Individuals higher in trait loneliness show stronger relationships between momentary loneliness and social context and emotions in everyday life.

Conclusions

These findings provide further evidence pointing to the importance of loneliness transdiagnostically and its strong relation to social functioning. Furthermore, we show that passive sensing technology can be used to measure behaviors related to loneliness in daily life that may point to potential treatment implications or early detection markers of loneliness.
An online behavioral self-help intervention rapidly improves acute insomnia severity and subjective mood during the coronavirus disease-2019 pandemic: a stratified randomized controlled trial
Authors: Elder Greg J , Santhi Nayantara , Robson Amelia R , Alfonso-Miller Pamela , Spiegelhalder Kai , Ellis Jason G
Published: March 2024

Study Objectives

Stressful life events, such as the coronavirus disease-2019 (COVID-19) pandemic, can cause acute insomnia. Cognitive behavioral therapy for acute insomnia is effective but is both time and resource-intensive. This study investigated if an online behavioral self-help intervention, which has been successfully used alongside sleep restriction for acute insomnia, reduced insomnia severity and improved mood in acute insomnia. This study also assessed good sleepers to explore if a “sleep vaccination” approach was feasible.

Methods

In this online stratified randomized controlled trial, 344 participants (103 good sleepers and 241 participants with DSM-5 acute insomnia) were randomized to receive the intervention/no intervention (good sleepers) or intervention/intervention after 28 days (poor sleepers). Insomnia severity was assessed using the ISI (primary outcome), and anxiety and depression using the GAD-7/PHQ-9 (secondary outcomes) at baseline, 1 week, 1 month, and 3-month follow-up.

Results

In people with acute insomnia, relative to baseline, there were significant reductions in ISI (dz = 1.17), GAD-7 (dz = 0.70), and PHQ-9 (dz = 0.60) scores at 1-week follow-up. ISI, GAD-7, and PHQ-9 scores were significantly lower at all follow-up time points, relative to baseline. Subjective diary-derived sleep continuity was unaffected. No beneficial effects on sleep or mood were observed in good sleepers.

Conclusions

An online behavioral self-help intervention rapidly reduces acute insomnia severity (within 1 week), and benefits mood in people with acute insomnia. These beneficial effects are maintained up to 3 months later. Although the use of the intervention is feasible in good sleepers, their subjective sleep was unaffected.

Clinical Trial registration

Testing an early online intervention for the treatment of disturbed sleep during the COVID-19 pandemic; prospectively registered at ISRCTN on 8 April 2020 (identifier: ISRCTN43900695).
HDAC3 promotes Sertoli cell maturation and maintains the blood–testis barrier dynamics
Authors: Liu Mengrou , He Qing , Yuan Zihan , Chen Niuniu , Ren Sen , Du Qian , Wang Yanfeng , Han Shenglin , Xu Chen , Lu Luyang , Sun Zheng , Guan Yongjuan , Xie Jie , Guan Yichun , Ye Lan
Published: March 2024

Germ cell development depends on the capacity of somatic Sertoli cells to undergo differentiation into a mature state and establish a germ cell‐specific blood–testis barrier (BTB). The BTB structure confers an immunological barrier for meiotic and postmeiotic germ cells, and its dynamic permeability facilitates a transient movement of preleptotene spermatocytes through BTB to enter meiosis. However, the regulatory factors involved in Sertoli cell maturation and how BTB dynamics coordinate germ cell development remain unclear. Here, we found a histone deacetylase HDAC3 abundantly expresses in Sertoli cells and localizes in both cytoplasm and nucleus. Sertoli cell‐specific Hdac3 knockout in mice causes infertility with compromised integrity of blood–testis barrier, leading to germ cells unable to traverse through BTB and an accumulation of preleptotene spermatocytes in juvenile testis. Mechanistically, nuclear HDAC3 regulates the expression program of Sertoli cell maturation genes, and cytoplasmic HDAC3 forms a complex with the gap junction protein Connexin 43 to modulate the BTB integrity and dynamics through regulating the distribution of tight junction proteins. Our findings identify HDAC3 as a critical regulator in promoting Sertoli cell maturation and maintaining the homeostasis of the blood–testis barrier.
Phenotypic and functional exhaustion of circulating CD3+CD56+NKT‐like cells in colorectal cancer patients
Authors: Cao Kangli , Wang Xiaowei , Wang Hui , Xu Cairui , Ma Along , Zhang Yuntao , Zheng Meijuan , Xu Yuanhong , Tang Ling
Published: March 2024

CD3+CD56+ NKT‐like cells are crucial to antitumor immune surveillance and defense. However, research on circulating NKT‐like cells in colorectal cancer (CRC) patients is limited. This investigation selected 113 patients diagnosed with primary CRC for preoperative peripheral blood collection. The blood from 106 healthy donors at the physical examination center was acquired as a healthy control (HC). The distribution of lymphocyte subsets, immunophenotype, and functional characteristics of NKT‐like cells was comprehensively evaluated. Compared to HC, primary CRC patients had considerably fewer peripheral NKT‐like cells in frequency and absolute quantity, and the fraction of NKT‐like cells was further reduced in patients with vascular invasion compared to those without. The NKT‐like cells in CRC patients had a reduced fraction of the activating receptor CD16, up‐regulated expression of inhibitory receptors LAG‐3 and NKG2A, impaired production of TNF‐α and IFN‐γ, as well as degranulation capacity. Moreover, the increased frequency of NKG2A+ NKT‐like cells and the decreased expression of activation‐related molecules were significantly correlated with tumor progression. In detail, NKG2A+ NKT‐like cells indicated increased PD‐1 and Tim‐3 and reduced TNF‐α than NKG2A− subgroup. Blocking NKG2A in vitro restored cytokine secretion capacity in NKT‐like cells from CRC patients. Altogether, this research revealed that circulating NKT‐like cells in CRC patients exhibited suppressive phenotype and functional impairment, which was more pronounced in NKG2A+ NKT‐like cells. These findings suggest that NKG2A blockade may restore anti‐tumor effector function in NKT‐like cells, which provides a potential target for immunotherapy in CRC patients.
Lipolysis inhibition improves the survival of fat grafts through ameliorating lipotoxicity and inflammation
Authors: Niu Xingtang , Zhang Yuchen , Lai Zhuhao , Huang Xiaoqi , Guo Lingling , Lu Feng , Yuan Yi , Gao Jianhua , Chang Qiang
Published: March 2024

Fat grafting is a promising technique for correcting soft tissue abnormalities, but oil cyst formation and graft fibrosis frequently impede the therapeutic benefit of fat grafting. The lipolysis of released oil droplets after grafting may make the inflammation and fibrosis in the grafts worse; therefore, by regulating adipose triglyceride lipase (ATGL) via Atglistatin (ATG) and Forskolin (FSK), we investigated the impact of lipolysis on fat grafts in this study. After being removed from the mice and chopped into small pieces, the subcutaneous fat from wild‐type C57BL/6J mice was placed in three different solutions for two hours: serum‐free cell culture medium, culture medium+FSK (50 μM), and culture medium+ATG (100 μM). Following centrifugation to remove water and free oil droplets, 0.3 mL of the fat particles per mouse was subcutaneously injected into the back of mice. Additionally, the subcutaneous fat grafting area was immediately injected with PBS (control group), ATG (30 mg/kg), and FSK (15 mg/kg) following fat transplantation. Detailed cellular events after grafting were investigated by histological staining, real‐time polymerase chain reaction, immunohistochemistry/immunofluorescent staining, and quantification. Two weeks after grafting, grafts treated with ATG showed lower expression of ATGL and decreased mRNA levels of TNFα and IL‐6. In contrast, grafts treated with ATG showed elevated expression levels of IL‐4 and IL‐13 compared to the control grafts. In addition, fewer apoptotic cells and oil cysts were observed in ATG grafts. Meanwhile, a higher CD206+/CD68+ ratio of macrophages and more CD31+ vascular endothelial cells existed in the 2‐month ATG grafts. In comparison to the control, ATG treatment improved the volume retention of grafts, and decreased graft fibrosis and oil cyst formation. By preventing oil droplet lipolysis, pharmacological suppression of ATGL shielded adipocytes from lipotoxicity following grafting. Additionally, ATG ameliorated the apoptosis and inflammation brought on by adipocyte death and oil droplet lipolysis in grafted fat. These all indicate that lipolysis inhibition improved transplanted fat survival and decreased the development of oil cysts and graft fibrosis, offering a potential postoperative pharmacological intervention for bettering fat grafting.
Effects of hypoxic compound exercise to promote HIF‐1α expression on cardiac pumping function, sleep activity behavior, and exercise capacity in Drosophila
Authors: Ping Xu , Li Qiufang , Ding Meng , Wang Xiaoya , Tang Chao , Yu Zhengwen , Yi Qin , He Yupeng , Zheng Lan
Published: March 2024

Alteration of HIF‐1α expression levels under hypoxic conditions affects the sequence of its downstream target genes thereby producing different effects. In order to investigate whether the effect of hypoxic compound exercise (HE) on HIF‐1α expression alters cardiac pumping function, myocardial structure, and exercise capacity, we developed a suitable model of hypoxic exercise using Drosophila, a model organism, and additionally investigated the effect of hypoxic compound exercise on nocturnal sleep and activity behavior. The results showed that hypoxic compound exercise at 6% oxygen concentration for five consecutive days, lasting 1 h per day, significantly improved the cardiac stress resistance of Drosophila. The hypoxic complex exercise promoted the whole‐body HIF‐1α expression in Drosophila, and improved the jumping ability, climbing ability, moving speed, and moving distance. The expression of HIF‐1α in the heart was increased after hypoxic exercise, which made a closer arrangement of myofilaments, an increase in the diameter of cardiac tubules, and an increase in the pumping function of the heart. The hypoxic compound exercise improved the sleep quality of Drosophila by increasing its nocturnal sleep time, the number of deep sleeps, and decreasing its nocturnal awakenings and activities. Therefore, we conclude that hypoxic compound exercise promoted the expression of HIF‐1α to enhance the exercise capacity and heart pumping function of Drosophila, and improved the quality of sleep.
Alterations of SARS-CoV-2 Evolutionary Dynamics by Pharmaceutical Factors
Authors: Halma Matthew
Published: March 2024

The outbreak of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has been influenced by the human response to the virus. These responses have undoubtedly impacted the evolutionary dynamics of the virus in ways distinct from a scenario lacking a widespread response. Two important pharmaceutical interventions, vaccination and the utilization of medications, particularly molnupiravir, known to have mutagenic properties, were the focus of this article. The impact of molnupiravir on human health was evaluated through 3 mechanisms: viral resistance, mutagenesis of SARS-CoV-2, and mutagenesis occurring in patients undergoing treatment with molnupiravir. These mechanisms, as well as the impact of vaccination, have inadvertently given rise to unforeseen challenges in the management of the COVID-19 crisis. Taking a systems view in future pandemic responses, and taking into account the evolution of the pandemic virus, may be critical to ending the pandemic at an earlier date.
A novel predictive formula for highly accurate discrimination between truly Helicobacter pylori-uninfected and currently infected/spontaneously eradicated individuals for gastric cancer screening
Authors: Takayama Takako , Suzuki Hideo , Okada Kosuke , Akiyama Shintaro , Narasaka Toshiaki , Maruo Kazushi , Sakamoto Taku , Seo Emiko , Tsuchiya Kiichiro
Published: March 2024

The ABC classification, which categorizes gastric cancer risk based on serum Helicobacter pylori (H pylori) antibody and pepsinogen levels, has a limitation of potentially misclassifying high-risk individuals as low risk. To overcome the problem, we previously developed a 4-parameter predictive formula (age, serum H pylori antibody, PGI, and PGII) using logistic regression analysis to accurately identify low-risk truly H pylori-uninfected status. Our predictive formula demonstrated superior sensitivity and specificity in distinguishing between low-risk truly uninfected individuals and high-risk currently/spontaneously eradicated status individuals, compared to the modified ABC classification based on latex immunoassay kits (traditional 3-parameter model). This study aimed to revalidate the diagnostic accuracy of the predictive formula in a new and different study population. We applied the predictive formula to the target population and compared the sensitivity and specificity with those of the traditional 3-parameter model. A total of 788 enrollees were analyzed: 703 were classified as truly uninfected, 45 as currently infected, and 40 as spontaneously eradicated according to the results of stool antigen testing and endoscopic findings. The sensitivities and specificities of the predictive formula and the traditional 3-parameter model were 89.5% and 87.1% versus 89.8% and 80.0%, respectively. The specificity of the predictive formula was superior in the 70 to 89 age range and H pylori antibody < 3 U/mL groups. The predictive formula had higher specificity than the traditional 3-parameter model. The results should contribute to efficient gastric cancer screening by predicting H pylori infection status.
Role of Flt3l and Rps15 in ketamine anesthesia
Authors: Zhang Lin , Xu Lingyan
Published: March 2024

Ketamine is the only intravenous narcotic that has sedative, analgesic, and anesthetic effects. However, the role of Flt3l and ribosomal protein S15 (Rps15) in ketamine anesthesia remains unclear. GSE26364 and GSE93041 were downloaded from gene expression omnibus. Multiple datasets were merged and batched. Differentially expressed genes (DEGs) were screened and weighted gene co-expression network analysis was performed. Construction and analysis of protein–protein interaction network. Gene ontology (GO) and Kyoto Encyclopedia of Gene and Genome were performed. A heat map of gene expression was drawn. TargetScan was used to screen miRNAs regulating DEGs. 882 DEGs were identified. According to the GO analysis, these DEGs were mainly enriched in cell differentiation, extracellular region, and cytoplasm. The Kyoto Encyclopedia of Gene and Genome analysis revealed enrichment in pathways such as the PPAR signaling pathway, TNF signaling pathway, Hippo signaling pathway, and IL-17 signaling pathway. In the Metascape enrichment analysis, GO enrichment categories included leukocyte differentiation, negative regulation of CREB transcription factor activity, and positive regulation of cell cycle. The protein–protein interaction network showed 10 core genes (Rpl7, Rpl18, Rps15, Rpl7l1, Flt3l, Rps16, Eprs, Rps19, Rps28, Rplp2).Gene expression heatmap showed that core genes (Rplp2, Flt3l, Rps15) were highly expressed in samples treated with ketamine anesthesia. Flt3l and Rps15 are highly expressed during ketamine anesthesia, and may be molecular targets.
Patient delay of patients with pulmonary tuberculosis in Yantai, China, 2013 to 2022: Analysis of a case series
Authors: Zhu Sijin , Wang Yuelei , Chu Tianci , Jin Xiaoxiang , Wei Fei , Hu Naibao
Published: March 2024

Patient delay increases the morbidity and mortality due to tuberculosis (TB). This study aimed to assess patient delay among patients with pulmonary tuberculosis in Yantai from 2013 to 2022, and to analyze factors related to patient delay. Data of patients with pulmonary tuberculosis in Yantai City from 2013 to 2022 were obtained from the Tuberculosis Management Information System of the Chinese Disease Prevention and Control System. Statistical analyses were performed using the SPSS.26.0 software. The trend in patient delay rate was tested using the chi-square trend test. Univariate analyses were performed using the chi-square test, and factors with statistically significant differences in the univariate analysis were included in the binary logistic regression analysis to identify the factors affecting patient delay. Patient delay was defined as an interval of more than 14 days between the onset of clinical symptoms and the patient first visit to a healthcare facility. From 2013 to 2022, the median delay time for patients with pulmonary tuberculosis in Yantai was 28 ± 52 days and the patient delay rate was 69.5%. There was an overall increasing trend in the rate of patient delay as the number of years increased. Univariate analyses revealed statistically significant differences in patient delay in terms of age, occupation, patient source, domicile, pathogenetic results, and the presence of comorbidities (all P < .05). The results of logistic regression analysis showed that the age was 20 to 39, 40 to 59, and ≥ 60 years (OR = 1.365, 95%CI: 1.156–1.612; OR = 1.978, 95%CI: 1.660–2.356; OR = 1.767, 95%CI: 1.480–2.110), occupation was domestic and un-employed (OR = 1.188, 95%CI: 1.071–1.317), domicile as mobile population (OR = 1.212, 95%CI: 1.099–1.337), and positive pathogenic results (OR = 1.242, 95%CI: 1.015–1.520) were risk factors for patient delay. Patient delays were serious among pulmonary tuberculosis patients in Yantai City, 2013 to 2022, and patient delay was related to factors such as age, occupation, domicile, patient source, and pathogenetic results.
Time interval of esomeprazole and dual antiplatelet therapy in patients with cardiocerebrovascular diseases
Authors: Kim Hyunsoo , Park Moon-Hwa , Kim Joon-Tae
Published: March 2024

Dual antiplatelet therapy (DAPT) with the combination of clopidogrel and aspirin is recommended for preventing secondary ischemic events in patients with acute coronary syndrome (ACS) or acute ischemic stroke (AIS). Proton pump inhibitors (PPIs) are suggested as preventive treatment for these patients. Due to clopidogrel-PPI interactions, separating their administration might be considered. However, a paucity of studies has been conducted to investigate the outcome differences between concurrent and interval-based use in ACS and AIS patients. Our study aimed to evaluate clinical outcomes based on administration timing. This study included patients with ACS or AIS onset or recurrence of within the last month. Patients who were expected to receive DAPT for at least 6 months and who were currently taking or planning to take esomeprazole were included. Patients were divided into Group 1 (interval administration group, IA group) and Group 2 (concurrent administration group, CA group) according to the interval between esomeprazole and DAPT administration. The time interval was based on 12 hours. The primary outcome was the occurrence of major adverse cardiocerebrovascular events (MACCEs), and safety outcomes were defined as major bleeding, minor bleeding and gastrointestinal bleeding and intracranial hemorrhage. A total of 3600 patients completed this study. The proportions of patients in the 2 groups were as follows: CA group, 99% (n = 3489) and IA group, 1% (n = 111). The primary outcome occurred in 0.9% of patients in the IA group and 1.8% of patients in the CA group (P = .51). There was no significant distinction in the overall bleeding risk of the CA group compared to that of the IA group (2.75% in the CA group and 2.70% in the IA group). Additionally, there was no significant difference observed between the 2 groups for safety outcomes. This multicenter, prospective, observational study that enrolled patients with ACS or AIS demonstrated that there was no significant difference in the occurrence of MACCEs and bleeding issues within 6 months according to the medication administration interval. The majority of patients with DAPT were taking PPIs simultaneously in real-world practice.
Exploration of Ginkgo biloba leaves on non-small cell lung cancer based on network pharmacology and molecular docking
Authors: Wang Mingxiao , Li Ruochen , Bai Moiuqi , Zhou Xun
Published: March 2024

Background:

Pharmacological studies have found Ginkgo biloba leaves have the effect of inhibiting neoplasms, it is clinically used in treating various neoplasms. However, the mechanism of Ginkgo biloba leaves in treating non-small cell lung cancer (NSCLC) remains unclear.

Methods:

The active components and corresponding targets of Ginkgo biloba leaves were obtained from the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) database, and the targets of NSCLC were obtained from the GeneCards, OMIM, TTD, and DrugBank databases. The common targets of NSCLC and Ginkgo biloba leaves were obtained from VENNY 2.1.0. The STRING database was utilized to construct protein-protein intersections, by using the Cytoscape 3.7.1 software, the protein-protein intersection was optimized and the drug-disease network diagram was constructed. The DAVID database was utilized to perform GO and KEGG analysis. Finally, The Autodock Vina software was used to perform molecular docking of core components and targets.

Results:

The key components of Ginkgo biloba leaves in treating NSCLC include quercetin, luteolin, and kaempferol, which may act on Tp53, AKT1, and TNF. Bioinformatic annotation analysis results suggest that Ginkgo biloba leaves may implicated in PI3K-AKT and MAPK signaling pathways. The molecular docking results show the firm affinity between key ingredients and targets.

Conclusion:

The potential mechanism of Ginkgo biloba leaves in treating NSCLC has been discussed in this study, which provides a theoretical basis for the clinical treatment of NSCLC and further experimental validation.
The relationship between disease activity with pan-immune-inflammatory value and systemic immune-inflammation index in rheumatoid arthritis
Authors: Başaran Pinar Özge , Dogan Murat
Published: March 2024

Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease. Immune system cells have an important role in RA. Our aim was to investigate the relationship between disease activity, systemic immune-inflammation index (SII), and pan-immune-inflammation value (PIV) levels in RA patients. We planned to investigate whether these 2 measurements have an advantage over each other. About 67 patients diagnosed with RA and 49 healthy controls included in this study. RA was diagnosed based on 2010 ACR classification criteria. In this cross-sectional study, peripheral blood tests, C-reactive protein (CRP), hemogram, and erythrocyte sedimentation rate levels were noted after the physical examination of all participants. PIV was calculated with the formula: (neutrophil count × platelet count × monocyte count) / lymphocyte count. SII was calculated as follows: (neutrophil count × monocytes count) / lymphocyte count. The disease activity score 28 (DAS28) were noted in patients with RA. CRP values of active RA group were significantly higher than remission RA and control groups (P < .001), control and remission RA groups were similar (P = .86). PIV and SII are significantly higher in active RA than remission RA and control (P < .001, P < .001) higher in remission RA than control (P < .001, P < .001). Receiver operating characteristic curve analysis in predicting remission compared to the control group, CRP was not significant, PIV and SII was significant and PIV has higher sensitivity and sensitivity, a PIV value of > 217.31 have sensitivity 75.0% and specificity 85.7%. CRP, PIV, and SII are statistically significant in predicting active RA compared to the remission RA and control group. Our findings show that PIV, and SII are easy, inexpensive and reliable markers predicting remission in RA patients. CRP was not significant compared to remission RA and control group, PIV and SII was significant and PIV has higher sensitivity and specificity than SII in the remission group in RA. Patients with high disease activity, PIV, SII, and CRP levels were effective in showing disease activity compared to RA remission group and healthy controls.
Current use of antithymoglobulin as induction regimen in kidney transplantation: A review
Authors: Park Byung Hwa , Kim Ye Na , Shin Ho Sik , Jung Yeonsoon , Rim Hark
Published: March 2024

Currently, various immunosuppressive drugs are used in organ transplantation. In particular, antithymoglobulin is a widely used drug in kidney transplantation in Korea, accounting for 20% of all induction therapy. According to existing studies, antithymoglobulin induction therapy has several advantages and disadvantages compared with other immunotherapies depending on the kidney transplant situation (dead donor, living donor, low-risk recipient, and high-risk recipient) or antithymoglobulin dose. In this review, we summarize the research conducted so far on antithymoglobulin and hope that antithymoglobulin research on kidney transplantation will be actively conducted in the future.
Reliability and validity of the PROMIS-29 health profile in Ankylosing Spondylitis patients: A cross-sectional study
Authors: Hwang Mark C. , Bell Cynthia , Farran Yvette , Ogdie Alexis , Green Charles , Reveille John
Published: March 2024

The Patient-Reported Outcomes Measurement Information System 29-Item Health Profile (PROMIS-29) is a generic measure of health-related quality of life that is not well-studied in Ankylosing Spondylitis (AS) patients. Our objective was to investigate the reliability and validity of the PROMIS-29 in AS. About 169 consecutive AS patients were enrolled from 2017 to 2022 with 167/169 patients fully completing the PROMIS-29 in this cross-sectional study. Test–retest reliability and internal consistency was assessed using intraclass correlation coefficients (ICC) and Cronbach alpha, respectively. We studied structural validity with confirmatory factor analysis (CFA) of our hypothesized and general population models. We evaluated model fit by Chi-squared goodness-of-fit-test (χ2), comparative fit index, and root mean square error of approximation. A χ2 test was used to compare nested models. PROMIS-29 convergent validity was studied by Spearman correlation coefficients with AS-legacy measures. PROMIS-29 domains showed good test–retest reliability (intraclass correlation coefficients (ICC) > 0.7) and excellent internal consistency with Cronbach alpha > 0.9 in all subscales. CFA of only the general population model met our model fit cutoffs (χ2 goodness-of-fit P-value of 0.21, comparative fit index of 0.99, and root mean square error of approximation of 0.05). Furthermore, a nested χ2 test was not significantly different between our hypothesized (full) and general (reduced) model [χ2 (1) = 0.754, P > .38]. AS legacy measures showed a strong correlation (rho > |0.7|) with the extracted physical health factor. The PROMIS-29 demonstrated good reliability and construct validity in AS patients with the general population model. Further study is required to determine its clinical and research utility in AS patients.
Top-50 cited articles on cysticercosis and neurocysticercosis
Authors: Gonzalez-Alcaide Gregorio , Sosa Nestor , Valero-Samper Fatima , Belinchon-Romero Isabel , Ramos-Rincon Jose-Manuel
Published: March 2024

Background:

Identifying the most highly cited papers in a given field can help researchers and professionals understand the milestones and research areas that are generating the most impact. This study aimed to identify and describe the 50 most frequently cited manuscripts on cysticercosis and neurocysticercosis.

Methods:

We identified the 50 most cited papers (articles and reviews) on cysticercosis and neurocysticercosis from the MEDLINE database and indexed in Web of Science-Core Collection, analyzing their bibliographic and content characteristics.

Results:

The most cited documents comprised 29 (58%) original articles and 21 (42%) reviews, the bulk of which were narrative reviews (n = 17), with a negligible presence of other types of reviews with high-level scientific evidence. Six journals published 42% of the articles. In addition to the USA, Mexico and Peru were prominent countries of origin among leading researchers. The main research topics were the central nervous system and epilepsy on the one hand, and diagnostic and therapeutic approaches on the other.

Conclusion:

Our findings shed light on the dissemination of knowledge about cysticercosis and neurocysticercosis in recent decades, identifying the most highly cited contributions that have driven research in the field.
Fourteen-year trends in prescribing patterns for patients with bipolar mania discharged from a public psychiatric hospital in Taiwan
Authors: Chiu Huei-Ping , Shih YuJu , Lin Ching-Hua
Published: March 2024

Bipolar disorder is a complex mental illness. Pharmacological therapy, including antipsychotics and mood stabilizers, is the primary treatment approach for manic episode. The study aimed to analyze prescribing patterns over a 14-year period for patients with bipolar mania discharged from a psychiatric hospital in Taiwan. Patients with bipolar mania discharged from the study hospital between 2006 and 2019 (n = 2956) were included in the analysis. Prescribed drugs for the treatment of manic episode, included mood stabilizers (i.e., lithium, valproate, carbamazepine) and any antipsychotics (i.e., second- and first-generation antipsychotics; SGAs & FGAs). Monotherapy, simple polypharmacy, and complex polypharmacy were also examined. Simple polypharmacy was defined as being prescribed 2 different bipolar drugs (lithium, valproate, carbamazepine, and any antipsychotics), while complex polypharmacy at least 3 bipolar drugs. Temporal trends of each prescribing pattern were analyzed using the Cochran-Armitage Trend test. The prescription rates of valproate, SGAs, and complex polypharmacy significantly increased over time, whereas the prescription rates of any mood stabilizers, FGAs, and simple polypharmacy significantly decreased. Prescription rates of lithium and monotherapy did not significantly change. The study highlights the shifts in prescribing practices for bipolar mania. SGAs were prescribed more while FGAs declined, likely due to SGAs’ favorable properties. Complex polypharmacy increased, reflecting the complexity of treating bipolar disorder. Long-term outcomes of these changes require further research.