bluuebunny/crossref_metadata_2025 huggingface dataset:
Anastrozole monotherapy further improves near-adult height after the initial combined treatment with leuprorelin and anastrozole in early-maturing girls with compromised growth prediction: results from the second phase of the GAIL study
Authors: Papadimitriou Dimitrios T. , Dermitzaki Eleni , Christopoulos Panagiotis , Livadas Sarantis , Grivea Ioanna N. , Mastorakos George
Published: April 2024

Background

The first phase of the GAIL study (“Girls treated with an Aromatase Inhibitor and Leuprorelin,” ISRCTN11469487) has shown that the combination of anastrozole and leuprorelin for 24 months is safe and effective in improving the predicted adult height (PAH) in girls with early puberty and compromised growth prediction by +1.21 standard deviation score (SDS; +7.51 cm) compared to inhibition of puberty alone, +0.31 SDS (+1.92 cm).

Objectives and hypotheses

In the second phase of the GAIL study, we assessed the adult height (AH)/near-adult height (NAH) at the end of the first phase and, in addition, the efficacy of anastrozole monotherapy thereafter in further improving NAH.

Methods

We measured the AH (age 16.5 years)/NAH [bone age (BA), 15 years] of the 40 girls included, divided into two matched groups: group A (20 girls on anastrozole + leuprorelin) and group B (20 girls on leuprorelin alone). Group A was further randomized into two subgroups: A1 and A2. Group A1 (n = 10), after completion of the combined therapy, received anastrozole 1 mg/day as monotherapy until BA 14 years, with a 6-month follow-up. Group A2 (n = 10) and group B (n = 20), who received only the combined treatment and leuprorelin alone, respectively, were recalled for evaluation of AH/NAH.

Results

AH or NAH exceeded the PAH at the completion of the 2-year initial phase of the GAIL study in all groups, but the results were statistically significant only in group A1: NAH–PAH group A1, +3.85 cm (+0.62 SDS, p = 0.01); group A2, +1.6 cm (+0.26 SDS, p = 0.26); and group B, +1.7 cm (+0.3 SDS, p = 0.08). The gain in group A1 was significantly greater than that in group A2 (p = 0.04) and in group B (p = 0.03). Anastrozole was determined to be safe even as monotherapy in Group A1.

Conclusions

In early-maturing girls with compromised growth potential, the combined treatment with leuprorelin and anastrozole for 2 years or until the age of 11 years resulted in a total gain in height of +9.7 cm when continuing anastrozole monotherapy until the attainment of NAH, as opposed to +7.4 cm if they do not continue with the anastrozole monotherapy and +3.6 cm when treated with leuprorelin alone. Thus, the combined intervention ends at the shortest distance from the target height if continued with anastrozole monotherapy until BA 14 years.
Transcriptome organization of white blood cells through gene co-expression network analysis in a large RNA-seq dataset
Authors: Forabosco Paola , Pala Mauro , Crobu Francesca , Diana Maria Antonietta , Marongiu Mara , Cusano Roberto , Angius Andrea , Steri Maristella , Orrù Valeria , Schlessinger David , Fiorillo Edoardo , Devoto Marcella , Cucca Francesco
Published: April 2024

Gene co-expression network analysis enables identification of biologically meaningful clusters of co-regulated genes (modules) in an unsupervised manner. We present here the largest study conducted thus far of co-expression networks in white blood cells (WBC) based on RNA-seq data from 624 individuals. We identify 41 modules, 13 of them related to specific immune-related functions and cell types (e.g. neutrophils, B and T cells, NK cells, and plasmacytoid dendritic cells); we highlight biologically relevant lncRNAs for each annotated module of co-expressed genes. We further characterize with unprecedented resolution the modules in T cell sub-types, through the availability of 95 immune phenotypes obtained by flow cytometry in the same individuals. This study provides novel insights into the transcriptional architecture of human leukocytes, showing how network analysis can advance our understanding of coding and non-coding gene interactions in immune system cells.
The role of B-1 cells in cancer progression and anti-tumor immunity
Authors: Rodríguez-Zhurbenko Nely , Hernández Ana M.
Published: April 2024

In recent years, in addition to the well-established role of T cells in controlling or promoting tumor growth, a new wave of research has demonstrated the active involvement of B cells in tumor immunity. B-cell subsets with distinct phenotypes and functions play various roles in tumor progression. Plasma cells and activated B cells have been linked to improved clinical outcomes in several types of cancer, whereas regulatory B cells have been associated with disease progression. However, we are only beginning to understand the role of a particular innate subset of B cells, referred to as B-1 cells, in cancer. Here, we summarize the characteristics of B-1 cells and review their ability to infiltrate tumors. We also describe the potential mechanisms through which B-1 cells suppress anti-tumor immune responses and promote tumor progression. Additionally, we highlight recent studies on the protective anti-tumor function of B-1 cells in both mouse models and humans. Understanding the functions of B-1 cells in tumor immunity could pave the way for designing more effective cancer immunotherapies.
Natural killer T cells in allergic asthma: implications for the development of novel immunotherapeutical strategies
Authors: Gutiérrez-Vera Cristián , García-Betancourt Richard , Palacios Pablo A. , Müller Marioly , Montero David A. , Verdugo Carlos , Ortiz Francisca , Simon Felipe , Kalergis Alexis M. , González Pablo A. , Saavedra-Avila Noemi A. , Porcelli Steven A. , Carreño Leandro J.
Published: April 2024

Allergic asthma has emerged as a prevalent allergic disease worldwide, affecting most prominently both young individuals and lower-income populations in developing and developed countries. To devise effective and curative immunotherapy, it is crucial to comprehend the intricate nature of this condition, characterized by an immune response imbalance that favors a proinflammatory profile orchestrated by diverse subsets of immune cells. Although the involvement of Natural Killer T (NKT) cells in asthma pathology is frequently implied, their specific contributions to disease onset and progression remain incompletely understood. Given their remarkable ability to modulate the immune response through the rapid secretion of various cytokines, NKT cells represent a promising target for the development of effective immunotherapy against allergic asthma. This review provides a comprehensive summary of the current understanding of NKT cells in the context of allergic asthma, along with novel therapeutic approaches that leverage the functional response of these cells.
Identification of diagnostic biomarkers and immune cell infiltration in coronary artery disease by machine learning, nomogram, and molecular docking
Authors: Jiang Xinyi , Luo Yuanxi , Li Zeshi , Zhang He , Xu Zhenjun , Wang Dongjin
Published: April 2024

Background

Coronary artery disease (CAD) is still a lethal disease worldwide. This study aims to identify clinically relevant diagnostic biomarker in CAD and explore the potential medications on CAD.

Methods

GSE42148, GSE180081, and GSE12288 were downloaded as the training and validation cohorts to identify the candidate genes by constructing the weighted gene co-expression network analysis. Functional enrichment analysis was utilized to determine the functional roles of these genes. Machine learning algorithms determined the candidate biomarkers. Hub genes were then selected and validated by nomogram and the receiver operating curve. Using CIBERSORTx, the hub genes were further discovered in relation to immune cell infiltrability, and molecules associated with immune active families were analyzed by correlation analysis. Drug screening and molecular docking were used to determine medications that target the four genes.

Results

There were 191 and 230 key genes respectively identified by the weighted gene co-expression network analysis in two modules. A total of 421 key genes found enriched pathways by functional enrichment analysis. Candidate immune-related genes were then screened and identified by the random forest model and the eXtreme Gradient Boosting algorithm. Finally, four hub genes, namely, CSF3R, EED, HSPA1B, and IL17RA, were obtained and used to establish the nomogram model. The receiver operating curve, the area under curve, and the calibration curve were all used to validate the accuracy and usefulness of the diagnostic model. Immune cell infiltrating was examined, and CAD patients were then divided into high- and low-expression groups for further gene set enrichment analysis. Through targeting the hub genes, we also found potential drugs for anti-CAD treatment by using the molecular docking method.

Conclusions

CSF3R, EED, HSPA1B, and IL17RA are potential diagnostic biomarkers for CAD. CAD pathogenesis is greatly influenced by patterns of immune cell infiltration. Promising drugs offers new prospects for the development of CAD therapy.
Shallow-water temperature seasonality in the middle Cretaceous mid-latitude northwestern Pacific
Authors: Ichimura Shunta , Takayanagi Hideko , Iryu Yasufumi , Takahashi Satoshi , Oji Tatsuo
Published: April 2024

Temperature seasonality during the middle Cretaceous provides vital information about climate dynamics and ecological traits of organisms under the conditions of the “supergreenhouse” Earth. However, sub-annual scale paleotemperature records in the mid-latitude region remain limited. In this study, sclerochronological and stable oxygen isotope (δ18O) analyses of bivalve fossils from the northwestern Pacific (paleolatitude: 44°N) were used to estimate their life history and sub-annual scale temperature patterns of the middle Cretaceous. The materials studied included Cucullaea (Idonearca) delicatostriata and Aphrodina pseudoplana recovered from middle Turonian (middle Cretaceous) shallow marine deposits in Hokkaido, northern Japan. Growth increment width and shell δ18O of C. (I.) delicatostriata revealed that the growth rate was temporally maximized and then minimized, which can be interpreted as representing spring and winter growth, respectively. Approximately 25 fortnightly growth increments occurred within that cycle, suggesting that shell formation proceeded continuously throughout the year. Based on shell δ18O values, shallow-water temperatures from 28°C to 35°C with 7°C seasonality were estimated, under the assumption that seawater δ18O values were annually invariant at −1‰ relative to VSMOW. This temperature seasonality in the middle Cretaceous is more than 5°C smaller than the seasonality of modern shallow-water environments at the same latitudes. These findings, taken together with previous studies of other oceanic regions, suggest that the Northern Hemisphere had low seasonal shallow-water temperature variation of up to 10°C in the middle Cretaceous.
Efficient deletion of microRNAs using CRISPR/Cas9 with dual guide RNAs
Authors: Ijee Smitha , Chambayil Karthik , Chaudhury Anurag Dutta , Bagchi Abhirup , Modak Kirti , Das Saswati , Benjamin Esther Sathya Bama , Rani Sonam , Paul Daniel Zechariah , Nath Aneesha , Roy Debanjan , Palani Dhavapriya , Priyanka Sweety , Ravichandran Rakshini , Kumary Betty K. , Sivamani Yazhini , S. Vijayanand , Babu Dinesh , Nakamura Yukio , Thamodaran Vasanth , Balasubramanian Poonkuzhali , Velayudhan Shaji R.
Published: April 2024

MicroRNAs (miRNAs) are short non-coding RNAs that play crucial roles in gene regulation, exerting post-transcriptional silencing, thereby influencing cellular function, development, and disease. Traditional loss-of-function methods for studying miRNA functions, such as miRNA inhibitors and sponges, present limitations in terms of specificity, transient effects, and off-target effects. Similarly, CRISPR/Cas9-based editing of miRNAs using single guide RNAs (sgRNAs) also has limitations in terms of design space for generating effective gRNAs. In this study, we introduce a novel approach that utilizes CRISPR/Cas9 with dual guide RNAs (dgRNAs) for the rapid and efficient generation of short deletions within miRNA genomic regions. Through the expression of dgRNAs through single-copy lentiviral integration, this approach achieves over a 90% downregulation of targeted miRNAs within a week. We conducted a comprehensive analysis of various parameters influencing efficient deletion formation. In addition, we employed doxycycline (Dox)-inducible expression of Cas9 from the AAVS1 locus, enabling homogeneous, temporal, and stage-specific editing during cellular differentiation. Compared to miRNA inhibitory methods, the dgRNA-based approach offers higher specificity, allowing for the deletion of individual miRNAs with similar seed sequences, without affecting other miRNAs. Due to the increased design space, the dgRNA-based approach provides greater flexibility in gRNA design compared to the sgRNA-based approach. We successfully applied this approach in two human cell lines, demonstrating its applicability for studying the mechanisms of human erythropoiesis and pluripotent stem cell (iPSC) biology and differentiation. Efficient deletion of miR-451 and miR-144 resulted in blockage of erythroid differentiation, and the deletion of miR-23a and miR-27a significantly affected iPSC survival. We have validated the highly efficient deletion of genomic regions by editing protein-coding genes, resulting in a significant impact on protein expression. This protocol has the potential to be extended to delete multiple miRNAs within miRNA clusters, allowing for future investigations into the cooperative effects of the cluster members on cellular functions. The protocol utilizing dgRNAs for miRNA deletion can be employed to generate efficient pooled libraries for high-throughput comprehensive analysis of miRNAs involved in different biological processes.
Plexin B3 guides axons to cross the midline in vivo
Authors: Liu Zhi-Zhi , Liu Ling-Yan , Zhu Lou-Yin , Zhu Jian , Luo Jia-Yu , Wang Ye-Fan , Xu Hong A.
Published: April 2024

During the development of neural circuits, axons are guided by a variety of molecular cues to navigate through the brain and establish precise connections with correct partners at the right time and place. Many axon guidance cues have been identified and they play pleiotropic roles in not only axon guidance but also axon fasciculation, axon pruning, and synaptogenesis as well as cell migration, angiogenesis, and bone formation. In search of receptors for Sema3E in axon guidance, we unexpectedly found that Plexin B3 is highly expressed in retinal ganglion cells of zebrafish embryos when retinal axons are crossing the midline to form the chiasm. Plexin B3 has been characterized to be related to neurodevelopmental disorders. However, the investigation of its pathological mechanisms is hampered by the lack of appropriate animal model. We provide evidence that Plexin B3 is critical for axon guidance in vivo. Plexin B3 might function as a receptor for Sema3E while Neuropilin1 could be a co-receptor. The intracellular domain of Plexin B3 is required for Semaphorin signaling transduction. Our data suggest that zebrafish could be an ideal animal model for investigating the role and mechanisms of Sema3E and Plexin B3 in vivo.
Dual effects of serum urate on stroke risk and prognosis: insights from Mendelian randomization
Authors: Chen Shixuan , Chen Zhenzhen , Xu Qingqing , Jiang Xia , Lin Chuyong , Ji Jing
Published: April 2024

Background

To investigate the causal associations of serum urate (SUA) with stroke risk and prognosis using Mendelian randomization (MR) and the potential mediating role of stroke risk factors in the causal pathways.

Methods

We used the random-effects inverse variance weighting (IVW) as our primary method. We initially performed two-sample univariable MR (UVMR) to identify the causal associations of SUA (n = 437,354) with any stroke (AS, FinnGen: n = 311,635; MEGASTROKE: n = 446,696), ischemic stroke (IS, FinnGen: n = 212,774; MEGASTROKE: n = 440,328), intracranial hemorrhage (ICH, FinnGen: n = 343,663; ISGC: n = 3,026), functional outcome after ischemic stroke at 90d (n = 4,363), and motor recovery within 24 months after stroke (n = 488), and then multivariable MR (MVMR) to estimate the direct causal effects of SUA on these outcomes, adjusting for potential confounders. Finally, we further conducted a two-step MR to investigate the potential mediating role of body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), and estimated glomerular filtration rate (eGFR) in the identified causal pathways.

Results

Genetically predicted elevated SUA levels were significantly associated with increased risk of AS (meta-analysis: OR = 1.09, 95% CI [1.04–1.13], p = 3.69e-05) and IS (meta-analysis: OR = 1.10, 95% CI [1.01–1.19], p = 0.021) and with improved poor functional outcome after ischemic stroke at 90d (OR = 0.81, 95% CI [0.72–0.90], p = 1.79e-04) and motor recovery within 24 months after stroke (OR = 1.42, 95% CI [1.23–1.64], p = 2.15e-06). In MVMR, SBP and DBP significantly attenuated the causal effects of SUA on AS, IS, and functional outcome after ischemic stroke at 90d and motor recovery within 24 months after stroke. Further mediation analyses showed that SBP mediated 52.4 and 34.5% of the effects of SUA on AS and IS, while DBP mediated 28.5 and 23.4% of the causal effects, respectively.

Conclusion

This study supports the dual role of genetically predicted SUA in increasing stroke risk, especially ischemic stroke risk, and in improving functional outcome and motor recovery. SBP and DBP are key mediators lying on the causal pathways of SUA with AS and IS.
The greatest loss of unpleasant smells may be related to the risk of more severe PD symptoms
Authors: Chiu Shih-Chi , Fang Ting-Chun , Lei Hsin-Bei , Lin Yu-Hsuan , Chang Ming-Hong , Guo Yi-Jen
Published: April 2024

Background

Limited research has explored the relationship between the valence of olfactory dysfunction and PD clinical symptoms. This study aimed to investigate correlations between the emotional valence of olfactory impairment and different domains of PD symptoms.

Methods

PD patients who fulfilled the clinically probable PD diagnostic criteria of the International Parkinson and Movement Disorder Society Clinical Diagnostic Criteria for Parkinson’s Disease were recruited from the Center for Parkinson and Movement Disorders at Taichung Veterans General Hospital between October 2016 and April 2022. Demographic data and serial clinical assessments were collected, including the traditional Chinese version of the University of Pennsylvania Smell Identification Test (UPSIT-TC) and Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). Thirty-five odors from the UPSIT-TC were classified into neutral, pleasant or unpleasant groups. Group comparisons, correlation analyses, and linear regression analyses were conducted to examine the relationship between olfactory impairment of UPSIT-TC odors, considering emotional valence, and MDS-UPDRS subscores across various domains.

Results

A total of 176 PD patients were recruited for analysis. Patients in the predominantly neutral/unpleasant odor impairment groups had higher MDS-UPDRS part III scores compared to those in the predominantly pleasant odor impairment group (pleasant vs. neutral vs. unpleasant odor impairment groups: 26.79 ± 13.59 vs. 35.33 ± 16.36 vs. 31.57 ± 12.37, p = 0.009). This trend was also noted in MDS-UPDRS rigidity, bradykinesia, and akinetic-rigid subscores (p = 0.003, p = 0.012, and p = 0.001, respectively). Correlation analysis revealed a weak but significant correlation between rigidity/akinetic-rigid subscores and misidentification numbers for neutral/unpleasant odors (all p < 0.05), with age, gender, LEDD, and disease duration as covariates. All significances were retained in the linear regression analysis.

Conclusion

Our results emphasize the link between olfactory impairment of specific emotional valence, neutral/unpleasant odors, and PD severity, particularly with respect to akinetic-rigid symptoms. A concise olfactory test that focuses on both neutral and unpleasant odors may offer deeper insights into PD symptoms.
Motivational context and neurocomputation of stop expectation moderate early attention responses supporting proactive inhibitory control
Authors: Gupta Resh S. , Simmons Alan N. , Dugas Nathalie N. , Stout Daniel M. , Harlé Katia M.
Published: April 2024

Alterations in attention to cues signaling the need for inhibitory control play a significant role in a wide range of psychopathology. However, the degree to which motivational and attentional factors shape the neurocomputations of proactive inhibitory control remains poorly understood. The present study investigated how variation in monetary incentive valence and stake modulate the neurocomputational signatures of proactive inhibitory control. Adults (N = 46) completed a Stop-Signal Task (SST) with concurrent EEG recording under four conditions associated with stop performance feedback: low and high punishment (following unsuccessful stops) and low and high reward (following successful stops). A Bayesian learning model was used to infer individual's probabilistic expectations of the need to stop on each trial: P(stop). Linear mixed effects models were used to examine whether interactions between motivational valence, stake, and P(stop) parameters predicted P1 and N1 attention-related event-related potentials (ERPs) time-locked to the go-onset stimulus. We found that P1 amplitudes increased at higher levels of P(stop) in punished but not rewarded conditions, although P1 amplitude differences between punished and rewarded blocks were maximal on trials when the need to inhibit was least expected. N1 amplitudes were positively related to P(stop) in the high punishment condition (low N1 amplitude), but negatively related to P(stop) in the high reward condition (high N1 amplitude). Critically, high P(stop)-related N1 amplitude to the go-stimulus predicted behavioral stop success during the high reward block, providing evidence for the role of motivationally relevant context and inhibitory control expectations in modulating the proactive allocation of attentional resources that affect inhibitory control. These findings provide novel insights into the neurocomputational mechanisms underlying proactive inhibitory control under valence-dependent motivational contexts, setting the stage for developing motivation-based interventions that boost inhibitory control.
Brain vital sign monitoring of sleep deprivation detects situational cognitive impairment
Authors: Jones Katherine B. , Frizzell Tory , Fickling Shaun , Pawlowski Gabriela , Brodie Sonia M. , Lakhani Bimal , Venter Jan , D’Arcy Ryan C. N.
Published: April 2024

Objective, rapid evaluation of cognitive function is critical for identifying situational impairment due to sleep deprivation. The present study used brain vital sign monitoring to evaluate acute changes in cognitive function for healthy adults. Thirty (30) participants were scanned using portable electroencephalography before and after either a night of regular sleep or a night of total sleep deprivation. Brain vital signs were extracted from three established event-related potential components: (1) the N100 (Auditory sensation); (2) the P300 (Basic attention); and (3) the N400 (Cognitive processing) for all time points. As predicted, the P300 amplitude was significantly reduced in the sleep deprivation group. The findings indicate that it is possible to detect situational cognitive impairment due to sleep deprivation using objective, rapid brain vital sign monitoring.
Mechanoreceptor sensory feedback is impaired by pressure induced cutaneous ischemia on the human foot sole and can predict cutaneous microvascular reactivity
Authors: Howe Erika E. , Apollinaro Michael , Bent Leah R.
Published: April 2024

Introduction

The foot sole endures high magnitudes of pressure for sustained periods which results in transient but habitual cutaneous ischemia. Upon unloading, microvascular reactivity in cutaneous capillaries generates an influx of blood flow (PORH: post-occlusive reactive hyperemia). Whether pressure induced cutaneous ischemia from loading the foot sole impacts mechanoreceptor sensitivity remains unknown.

Methods

Pressure induced ischemia was attained using a custom-built-loading device that applied load to the whole right foot sole at 2 magnitudes (15 or 50% body weight), for 2 durations (2 or 10 minutes) in thirteen seated participants. Mechanoreceptor sensitivity was assessed using Semmes-Weinstein monofilaments over the third metatarsal (3MT), medial arch (MA), and heel. Perceptual thresholds (PT) were determined for each site prior to loading and then applied repeatedly to a metronome to establish the time course to return to PT upon unload, defined as PT recovery time. Microvascular flux was recorded from an in-line laser speckle contrast imager (FLPI-2, Moor Instruments Inc.) to establish PORH peak and recovery rates at each site.

Results

PT recovery and PORH recovery rate were most influenced at the heel and by load duration rather than load magnitude. PT recovery time at the heel was significantly longer with 10 minutes of loading, regardless of magnitude. Heel PORH recovery rate was significantly slower with 10minutes of loading. The 3MT PT recovery time was only longer after 10 minutes of loading at 50% body weight. Microvascular reactivity or sensitivity was not influenced with loading at the MA. A simple linear regression found that PORH recovery rate could predict PT recovery time at the heel (R2=0.184, p<0.001).

Conclusion

In populations with degraded sensory feedback, such as diabetic neuropathy, the risk for ulcer development is heightened. Our work demonstrated that prolonged loading in healthy individuals can impair skin sensitivity, which highlights the risks of prolonged loading and is likely exacerbated in diabetes. Understanding the direct association between sensory function and microvascular reactivity in age and diabetes related nerve damage, could help detect early progressions of neuropathy and mitigate ulcer development.
Supplementation of Crataegi fructus alleviates functional dyspepsia and restores gut microbiota in mice
Authors: Hao Liyu , Yu Zeyue , Sun Jianhui , Li Zongyuan , Li Jianliang , Deng Yurong , Huang Hanhui , Huo Hairu , Li Hongmei , Huang Luqi
Published: April 2024

Introduction

Functional dyspepsia (FD), also known as non-ulcerative dyspepsia, is a common digestive system disorder.

Methods

In this study, an FD model was established using hunger and satiety disorders combined with an intraperitoneal injection of L-arginine. Indices used to evaluate the efficacy of hawthorn in FD mice include small intestinal propulsion rate, gastric residual rate, general condition, food intake, amount of drinking water, gastric histopathological examination, and serum nitric oxide (NO) and gastrin levels. Based on the intestinal flora and their metabolites, short-chain fatty acids (SCFAs), the mechanism of action of Crataegi Fructus (hawthorn) on FD was studied. The fecal microbiota transplantation test was used to verify whether hawthorn altered the structure of the intestinal flora.

Results

The results showed that hawthorn improved FD by significantly reducing the gastric residual rate, increasing the intestinal propulsion rate, the intake of food and drinking water, and the levels of gastrointestinal hormones. Simultaneously, hawthorn elevated substance P and 5-hydroxytryptamine expression in the duodenum, reduced serum NO levels, and increased vasoactive intestinal peptide expression in the duodenum. Notably, hawthorn increased the abundance of beneficial bacteria and SCFA-producing bacteria in the intestines of FD mice, decreased the abundance of conditional pathogenic bacteria, and significantly increased the SCFA content in feces.

Discussion

The mechanism by which hawthorn improves FD may be related to the regulation of intestinal flora structure and the production of SCFAs.
Adolescents’ use of online food delivery applications and perceptions of healthy food options and food safety: a cross-sectional study in the United Arab Emirates
Authors: Saleh Sheima T. , Osaili Tareq M. , Al-Jawaldeh Ayoub , Hasan Haydar A. , Hashim Mona , Mohamad Maysm N. , Qiyas Salma Abu , Al Sabbah Haleama , Al Daour Rameez , Al Rajaby Radhiya , Masuadi Emad , Stojanovska Lily , Papandreou Dimitrios , Zampelas Antonis , Al Dhaheri Ayesha S. , Kassem Hanin , Cheikh Ismail Leila
Published: April 2024

Introduction

This cross-sectional study aimed to assess Online food delivery applications (OFDA) usage trends among adolescent users in the United Arab Emirates (UAE), focusing on their perceptions of healthy food options and food safety (n = 532).

Methods

Sociodemographic information, frequency of OFDA use, factors affecting food choices, and perceptions of healthy food and food safety were investigated. A total perception score was calculated for each participant;

Results

Most participants used OFDAs weekly (65.4%), favoring fast food (85.7%). Factors like appearance and price drove food choices (65.0%), while taste and cost hindered healthy food orders (29.7 and 28.2%). Younger and frequent users had lower scores for perceiving healthy food, while seeking healthy options was associated with higher scores (p < 0.05). Females and those seeking healthy food showed higher food safety scores (p < 0.05).

Discussion

The study suggests tailored interventions to promote healthier choices and improve food safety perceptions among adolescents using OFDAs in the UAE.
Gastric paraganglioma: a case report and review of literature
Authors: Hu Chengyu , Luo Bixian , Hong Bo , Zhang Mingqi , Wu Zelai , Zhu Xiuliang , Luan Fengming , Huang Yi , Gong Weihua
Published: April 2024

Paragangliomas (PGLs) are rare neuroendocrine tumors which overproduce catecholamines (CAs). They are extra-adrenal, catecholamine-secreting tumors occurring outside the adrenal glands. Gastric PGLs originating from extra-adrenal paraganglia are exceptionally rare, and their presentation in geriatric patients further adds to the complexity of diagnosis and management. A 72-year-old male patient presented with enduring left upper abdominal pain and anemia persisting for over a year, and hypertension for six months. Physical examination revealed epigastric discomfort and pallor. Computed tomography scans revealed enlarged lymph nodes in the lesser curvature of the stomach and thickening of the gastric antrum wall with concavity. The patient underwent three cycles of neoadjuvant therapy before radical gastrectomy for gastric cancer. These imaging findings were confirmed during surgery and intraoperative blood pressure was in fluctuation. After the successful resection of the tumor, postoperative pathology confirmed paraganglioma. During postoperative examination, it was observed that the patient’s CAs and their metabolites had returned to within the normal range. Combined with the existing ten literatures, we retrospective report the clinical and pathological characteristics and treatment strategies of the rare gastric paraganglioma.
Advances in the study of tertiary lymphoid structures in the immunotherapy of breast cancer
Authors: Li Xin , Xu Han , Du Ziwei , Cao Qiang , Liu Xiaofei
Published: April 2024

Breast cancer, as one of the most common malignancies in women, exhibits complex and heterogeneous pathological characteristics across different subtypes. Triple-negative breast cancer (TNBC) and HER2-positive breast cancer are two common and highly invasive subtypes within breast cancer. The stability of the breast microbiota is closely intertwined with the immune environment, and immunotherapy is a common approach for treating breast cancer.Tertiary lymphoid structures (TLSs), recently discovered immune cell aggregates surrounding breast cancer, resemble secondary lymphoid organs (SLOs) and are associated with the prognosis and survival of some breast cancer patients, offering new avenues for immunotherapy. Machine learning, as a form of artificial intelligence, has increasingly been used for detecting biomarkers and constructing tumor prognosis models. This article systematically reviews the latest research progress on TLSs in breast cancer and the application of machine learning in the detection of TLSs and the study of breast cancer prognosis. The insights provided contribute valuable perspectives for further exploring the biological differences among different subtypes of breast cancer and formulating personalized treatment strategies.
Case Report: Novel compound heterozygous TPRKB variants cause Galloway-Mowat syndrome
Authors: Hiraide Takuya , Hayashi Taiju , Ito Yusuke , Urushibata Rei , Uchida Hiroshi , Kitagata Ryoichi , Ishigaki Hidetoshi , Ogata Tsutomu , Saitsu Hirotomo , Fukuda Tokiko
Published: April 2024

Background

Galloway-Mowat syndrome (GAMOS) is a rare genetic disease characterized by early-onset nephrotic syndrome and microcephaly with central nervous system abnormalities. Pathogenic variants in genes encoding kinase, endopeptidase, and other proteins of small size (KEOPS) complex subunits cause GAMOS. The subunit TPRKB (TP53RK binding protein) has been reported in only two patients with GAMOS with homozygous missense variants.

Clinical report

Herein, we described a three-year-old male with GAMOS. He exhibited developmental delay, developmental regression, microcephaly, distinctive facial features, skeletal abnormalities, and epilepsy. Brain magnetic resonance imaging revealed progressive brain atrophy, delayed myelination, T2-hypointense signals in the thalamus, and multiple intracranial abnormal signals on diffusion-weighted imaging. He presented with relapsing nephrotic proteinuria exacerbated by upper respiratory tract infections and progressive renal function decline. Exome sequencing identified compound heterozygous missense and frameshift variants in TPRKB: c.224dup, p.(Ser76IlefsTer3) and c.247C>T, p.(Leu83Phe).

Conclusions

Our study supports that pathogenic TPRKB variants cause KEOPS complex-related GAMOS.
The construction of a nomogram to predict the prognosis and recurrence risks of UPJO
Authors: Ma Wenyue , Gao Hongjie , Chang Mengmeng , Lu Zhiyi , Li Ding , Ding Chen , Bi Dan , Sun Fengyin
Published: April 2024

Objective

This study was conducted to explore the risk factors for the prognosis and recurrence of ureteropelvic junction obstruction (UPJO).

Methods

The correlation of these variables with the prognosis and recurrence risks was analyzed by binary and multivariate logistic regression. Besides, a nomogram was constructed based on the multivariate logistic regression calculation. After the model was verified by the C-statistic, the ROC curve was plotted to evaluate the sensitivity of the model. Finally, the decision curve analysis (DCA) was conducted to estimate the clinical benefits and losses of intervention measures under a series of risk thresholds.

Results

Preoperative automated peritoneal dialysis (APD), preoperative urinary tract infection (UTI), preoperative renal parenchymal thickness (RPT), Mayo adhesive probability (MAP) score, and surgeon proficiency were the high-risk factors for the prognosis and recurrence of UPJO. In addition, a nomogram was constructed based on the above 5 variables. The area under the curve (AUC) was 0.8831 after self cross-validation, which validated that the specificity of the model was favorable.

Conclusion

The column chart constructed by five factors has good predictive ability for the prognosis and recurrence of UPJO, which may provide more reasonable guidance for the clinical diagnosis and treatment of this disease.
Real-world evidence of the effects of sodium-glucose co-transporter 2 inhibitors on the dosing of diuretics in patients with heart failure: a retrospective cohort study
Authors: Alsalem Abdulaziz , Alsultan Mohammed M. , Alqarni Faisal , Almangour Abdullah , Alsharekh Lolwa , Alenazi Saleem , Alzahrani Saleh , Almanqour Raghad A. , Alazmi Abdullah , Alzahrani Abdullah
Published: April 2024

Background: Heart failure (HF) was estimated to impact approximately 64 million individuals worldwide in 2017 and is predicted to rise in the coming years. Therefore, the aim of our study was to evaluate the effects of sodium-glucose transport protein 2 (SGLT2) inhibitors on the dosing of diuretics among individuals diagnosed with HF.

Methods: A retrospective cohort study was conducted at Security Forces Hospital in Riyadh, Saudi Arabia, between January 2018 and August 2022. The study included adult patients who were diagnosed with heart failure and received dapagliflozin and/or diuretic. A descriptive analysis was conducted to identify significant differences between both groups by using the chi-square test for categorical variables and the Student’s t-test for continuous variables. A logistic regression model was also run to identify the odds of each event. Statistical significance was indicated by p values less than .05.

Results: Overall reduction in diuretics was reported in 68 patients in the SGLT2 inhibitors plus diuretic therapy group, while in the diuretic therapy group 25 patients reported overall reduction in diuretics (OR = 4.81, 95% [2.74–8.45]). The reduction of the loop dose level was reported by 58 patients in the SGLT2 inhibitors plus diuretic group and by 25 patients in the diuretic group (OR = 3.48, 95% [1.98–6.11]). The discontinuation of thiazide was reported by 16 patients in the SGLT2 inhibitors plus diuretic therapy group, but by only two patients in the diuretic group (OR = 9.04, 95% [2.03–40.19]). After 6 months, ejection fraction was increased by 2.74 in the SGLT2 inhibitors plus diuretic group (p = .0019) and decreased by 2.56 in the diuretic group (p = .0485), both of which were statistically significant. The mean dose changes were decreased by 14.52 in the SGLT2 inhibitors plus diuretic group (p < .0001), which was statistically significant.

Conclusion: Treatment with SGLT2 inhibitors plus diuretic significantly reduced the patients’ diuretic requirements. Therefore, our finding supports the theoretical concept of minimizing the level of diuretic upon the initiation of SGLT2 inhibitors.
Construction of Yemilab
Authors: Park K. S. , Kim Y. D. , Bang K. M. , Park H. K. , Lee M. H. , So J. , Kim S. H. , Jang J. H. , Kim J. H. , Kim S. B.
Published: April 2024

The Center for Underground Physics of the Institute for Basic Science (IBS) in Korea has been planning the construction of a deep underground laboratory since 2013 to search for extremely rare interactions such as dark matter and neutrinos. In September 2022, a new underground laboratory, Yemilab, was finally completed in Jeongseon, Gangwon Province, with a depth of 1,000 m and an exclusive experimental area spanning 3,000 m3. The tunnel is encased in limestone and accommodates 17 independent experimental spaces. Over 2 years, from 2023 to 2024, the Yangyang Underground Laboratory facilities will be relocated to Yemilab. Preparations are underway for the AMoRE-II, a neutrinoless double beta decay experiment, scheduled to begin in Q2 2024 at Yemilab. Additionally, Yemilab includes a cylindrical pit with a volume of approximately 6,300 m3, designed as a multipurpose laboratory for next-generation experiments involving neutrinos, dark matter, and related research. This article provides a focused overview of the construction and structure of Yemilab.
Microbial dysbiosis in roots and rhizosphere of grapevines experiencing decline is associated with active metabolic functions
Authors: Darriaut Romain , Marzari Tania , Lailheugue Vincent , Tran Joseph , Martins Guilherme , Marguerit Elisa , Masneuf-Pomarède Isabelle , Lauvergeat Virginie
Published: April 2024

When grapevine decline, characterized by a premature decrease in vigor and yield and sometimes plant death, cannot be explained by pathological or physiological diseases, one may inquire whether the microbiological status of the soil is responsible. Previous studies have shown that the composition and structure of bacterial and fungal microbial communities in inter-row soil are affected in areas displaying vine decline, compared to areas with non-declining vines within the same plot. A more comprehensive analysis was conducted in one such plot. Although soil chemical parameters could not directly explain these differences, the declining vines presented lower vigor, yield, berry quality, and petiole mineral content than those in non-declining vines. The bacterial and fungal microbiome of the root endosphere, rhizosphere, and different horizons of the bulk soil were explored through enzymatic, metabolic diversity, and metabarcoding analysis in both areas. Despite the lower microbial diversity and richness in symptomatic roots and soil, higher microbial activity and enrichment of potentially both beneficial bacteria and pathogenic fungi were found in the declining area. Path modeling analysis linked the root microbial activity to berry quality, suggesting a determinant role of root microbiome in the berry mineral content. Furthermore, certain fungal and bacterial taxa were correlated with predicted metabolic pathways and metabolic processes assessed with Eco-Plates. These results unexpectedly revealed active microbial profiles in the belowground compartments associated with stressed vines, highlighting the interest of exploring the functional microbiota of plants, and more specifically roots and rhizosphere, under stressed conditions.
Health consultations at a performing arts health centre among classical music students based on electronic health record data: a cross-sectional study
Authors: Steemers Suze , van Rijn Rogier M. , van Middelkoop Marienke , Bierma-Zeinstra Sita M. A. , Stubbe Janine H.
Published: April 2024

Physical and mental health problems in music students are usually identified using self-reported data. The use of an Electronic Health Record database can avoid biases to give an overview of the extent of health problems in this population. Therefore, the aim of this study is to gain insight into both physical and mental health related issues in classical music students using this type of data collection. An Electronic Health Record database including five years of data from a Performing Arts Health Centre (PAHC) of a university or the arts, was used to analyze the number and characteristics of health consultations in music students. The total number of students, health consultations and the average number of visits per health consultation were calculated over five years. Furthermore, numbers and percentages of both physical and mental health consultations were registered. Also, the number and percentage of health consultations per instrument group were compared to the proportion of each instrument group within the specific sample. Over a period of five years, 230 students visited the PAHC and 417 health consultations were reported. 43.5% of the students who visited a health professional indicated at least one physical health consultation, 29.1% at least one mental health consultation and 27.4% at least one in both categories. An injury was the most frequently registered physical health consultation (40.2%), followed by performance improvement (9.8%) and stress (9.6%). Voice students registered relatively most health consultations. As far as we know, this is the first cross-sectional study using Electronic Health Record data from a PAHC to gain insight into both physical and mental health related issues in a population of classical music students. Looking at the variety of health consultations registered in the database, a multidisciplinary team and multidisciplinary approach are necessary to meet the needs of the students in terms of physical and mental health support and performance improvement.
Examining the predictive validity of a managerial coaching scale: a longitudinal study
Authors: Stone Katie , Nimon Kim , Ellinger Andrea D.
Published: April 2024

Managerial coaching remains a widespread and popular organizational development intervention applied across numerous industries to enhance critical workplace outcomes and employee attitudes, yet no studies to date have evaluated the temporal precedence within these relationships. This study sought to assess the predictive validity of the widely used Employee Perceptions of Supervisor/Line Manager Coaching Behavior Measure managerial coaching scale (CBI), employing a longitudinal design and following the testing of the causal hypothesized relationship framework. Three hypotheses were evaluated using three commonly associated variables with managerial coaching (role clarity, job satisfaction, and organization commitment), using longitudinal data collected over two waves from full-time US employees (n = 313). The study followed a two-wave design, collecting data over two time points to test for longitudinal measurement invariance and three reciprocal cross-lagged models. Results detected statistically significant cross-lagged and reciprocal cross-lagged effects in the role clarity and organization commitment models, highlighting a reciprocal relationship between managerial coaching behaviors and the two variables. However, only the reciprocal cross-lagged effect was statistically significant in the job satisfaction model. Findings suggest the predictive validity of the CBI scale for role clarity and organization commitment. Moreover, results indicate employee attitudes influenced managerial coaching behaviors over time across all three models, emphasizing the potential impact of employee attitudes on leadership effectiveness. This study highlights the complex relationships between managerial coaching and workplace outcomes, offering nuanced insights for improved understanding.
Capturing differences in perception and aesthetic judgment of live or medially presented music: development of a self-report instrument
Authors: Meinel Larina Sue , Bullerjahn Claudia , Lindau Alexander , Wald-Fuhrmann Melanie
Published: April 2024

Nowadays there are multiple ways to perceive music, from attending concerts (live) to listening to recorded music through headphones (medial). In between there are many mixed modes, such as playback performances. In empirical music research, this plurality of performance forms has so far found little recognition. Until now no measuring instrument has existed that could adequately capture the differences in perception and aesthetic judgment. The purpose of our empirical investigation was to capture all dimensions relevant to such an assessment. Using 3D-simulations and dynamic binaural synthesis, various live and medial situations were simulated. A qualitative survey was conducted at the Department of Audio Communication of the Technical University of Berlin (TU Berlin). With the help of the repertory grid technique, a data pool of approximately 400 attribute pairs was created and individual rating data were collected. Our first study served to create a semantic differential. In a second study, this semantic differential was evaluated. The development of the semantic differential was carried out by first using a mixed-method approach to qualitative analysis according to grounded theory. Thereafter, a principal component analysis reduced the attribute pairs to 67 items in four components. The semantic differential consists of items concerning acoustic, visual and audio-visual interaction as well as items with an overarching assessment of the stimuli. The evaluation study, comprising 45 participants (23 male and 22 female, M = 42.56 years, SD = 17.16) who rated 12 stimuli each, reduced the items to 61 and resulted in 18 subscales and nine single items. Because the survey used simulations, the social component may be underrepresented. Nevertheless, the questionnaire we created enables the evaluation of music performances (especially for classical concerts) in a new scope, thus opening many opportunities for further research. For example, in a live concert context, we observed not only that seating position influences the judgment of sound quality but also that visual elements influence immersion and felt affect. In the future, the differential could be reviewed for a larger stimulus pool, extended or used modularly for different research questions.