bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnostic potential of endothelin-1 in peri-implant diseases: a cross-sectional study
Authors: Saito Yoshiki , Nodai Tomotaka , Munemasa Takashi , Mukaibo Taro , Kondo Yusuke , Masaki Chihiro , Hosokawa Ryuji 
Published: June 2024

Abstract
Purpose
This study aimed to evaluate the potential of Endothelin-1 (ET-1), a peptide derived from vascular endothelial cells, as a biomarker for diagnosing peri-implant diseases.

Methods
A cohort of 29 patients with a total of 76 implants was included in this study and subsequently divided into three groups based on peri-implant clinical parameters and radiographic examination: healthy (peri-implant health) (n = 29), mucositis (n = 22), and peri-implantitis (n = 25) groups. The levels of ET-1 (ρg/site) and interleukin (IL)-1β (ρg/site) in peri-implant sulcus fluid (PISF) samples were determined using enzyme immunoassay. Statistical analyses were conducted using Kruskal–Wallis and Steel–Dwass tests. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed to evaluate the diagnostic performance of the biomarkers.

Results
ET-1 levels were significantly elevated in the peri-implantitis group compared to those in the healthy group, and were highest in the peri-implant mucositis group. Additionally, IL-1β levels were significantly higher in the peri-implantitis group than those in the healthy group. ROC curve analysis indicated that ET-1 exhibited superior area under the curve values, sensitivity, and specificity compared to those of IL-1β.

Conclusions
Our findings suggest that the presence of ET-1 in PISF plays a role in peri-implant diseases. Its significantly increased expression in peri-implant mucositis indicates its potential for enabling earlier and more accurate assessments of peri-implant inflammation when combined with conventional examination methods.
Gaining competitive advantage through integrated talent development and engagement practices in the telecommunication sector; the mediating role of corporate image
Authors: Boakye Kwame Owusu , Adu Isaac Nyarko , Kyei-Frimpong Michael , Twumasi Evelyn 
Published: June 2024

AbstractThe aim of the study is to investigate the influence of training in multiple functions, communication of strategy, and feedback on performance on competitive advantage while assessing the mediating role of corporate image. A cross-sectional survey design was used in this study. Three hundred and one permanent employees working in different organizations in the Ghanaian telecommunication service sector were sampled for this study. The respondents' responses were analyzed using descriptive and inferential statistics (structural equation modeling partial least squares) with the aid of IBM SPSS Statistics (Version 26.0) and Smart PLS (Version 4.0). The results revealed that training in multiple functions, communication of strategies, and feedback on performance does not significantly relate to competitive advantage. Further, the results established that corporate image mediated the relationship between both communication of strategy and training in multiple functions and competitive advantage. However, corporate image did not mediate the link between feedback on performance and competitive advantage. These results imply that human resource managers should devise strategies to rapidly respond to situations in this current, competitive and ever-changing business environment. To the best of our knowledge, studies that have explored the mediating role of corporate image in the relationship between training in multiple functions, communication of strategy, and feedback on performance and competitive advantage in the telecommunication service sector are rare.
Assessment of vitamin d status among egyptian covid-19 patients
Authors: Ahmed Marwa Ahmed Salah , Atta Mohamed Nabil Soliman , Aboul-Seoud Mona Abdel-Latif , Tahoun Mona Moustafa , Allah Sarah Abd El Rahim Rady Abd 
Published: June 2024

Abstract
Background
The COVID-19 outbreak has increased awareness of vitamin D's (Vit-D) potential advantages for both prevention and treatment. Adequate vitamin D levels are necessary for health of the immune system, which can help with cellular response and protection against the severity of microbial infection.

Purpose
To evaluate Vit-D levels and their association with illness severity in Egyptian COVID-19-infected individuals.

Methods
This case–control investigation was performed at the Alexandria Main University Hospital on 80 subjects divided into 2 groups: 40 COVID-19 patients and 40 healthy persons to measure the Vit-D levels of the Egyptian cohort.

Results
There was a statistically insignificant difference in the Vit-D serum levels of the studied groups (P = 1.000). The age of the Vit-D insufficient patients was significantly higher than that of Vit-D sufficient patients (P = 0.006). There was a statistically insignificant rise in the CRP level in the Vit-D insufficient patients (P = 0.862) compared to patients with sufficient Vit-D. Also, the D-dimer levels in Vit-D-insufficient patients were considerably higher (P = 0.015). Patients with sufficient Vit-D exhibited significantly lower levels of IL-6 than Vit-D insufficient patients. (P = 0.037). Patients in the Vit-D-insufficient subgroup needed substantially more breathing support than those in the Vit-D-sufficient group (P = 0.020).

Conclusion
Although there was no association between both levels of Vit-D and the COVID-19 infection risk, insufficiency of Vit-D was related to more severe infection.
Ckip-1 3’UTR alleviates prolonged sleep deprivation induced cardiac dysfunction by activating CaMKK2/AMPK/cTNI pathway
Authors: Dong Beilei , Xue Rui , Li Jianwei , Ling Shukuan , Xing Wenjuan , Liu Zizhong , Yuan Xinxin , Pan Junjie , Du Ruikai , Shen Xinming , Zhang Jingwen , Zhang Youzhi , Li Yingxian , Zhong Guohui 
Published: June 2024

AbstractSleep deprivation (SD) has emerged as a critical concern impacting human health, leading to significant damage to the cardiovascular system. However, the underlying mechanisms are still unclear, and the development of targeted drugs is lagging. Here, we used mice to explore the effects of prolonged SD on cardiac structure and function. Echocardiography analysis revealed that cardiac function was significantly decreased in mice after five weeks of SD. Real-time quantitative PCR (RT-q-PCR) and Masson staining analysis showed that cardiac remodeling marker gene Anp (atrial natriuretic peptide) and fibrosis were increased, Elisa assay of serum showed that the levels of creatine kinase (CK), creatine kinase-MB (CK-MB), ANP, brain natriuretic peptide (BNP) and cardiac troponin T (cTn-T) were increased after SD, suggesting that cardiac remodeling and injury occurred. Transcript sequencing analysis indicated that genes involved in the regulation of calcium signaling pathway, dilated cardiomyopathy, and cardiac muscle contraction were changed after SD. Accordingly, Western blotting analysis demonstrated that the cardiac-contraction associated CaMKK2/AMPK/cTNI pathway was inhibited. Since our preliminary research has confirmed the vital role of Casein Kinase-2 -Interacting Protein-1 (CKIP-1, also known as PLEKHO1) in cardiac remodeling regulation. Here, we found the levels of the 3’ untranslated region of Ckip-1 (Ckip-1 3’UTR) decreased, while the coding sequence of Ckip-1 (Ckip-1 CDS) remained unchanged after SD. Significantly, adenovirus-mediated overexpression of Ckip-1 3’UTR alleviated SD-induced cardiac dysfunction and remodeling by activating CaMKK2/AMPK/cTNI pathway, which proposed the therapeutic potential of Ckip-1 3’UTR in treating SD-induced heart disease.
Quasicrystal metasurface for dual functionality of holography and diffraction generation
Authors: Xu Chi , Zhao Ruizhe , Zhang Xue , Zhang Shifei , Li Xin , Geng Guangzhou , Li Junjie , Li Xiaowei , Wang Yongtian , Huang Lingling 
Published: June 2024

AbstractQuasicrystal has attracted lots of attention since its discovery because of the mathematically non-periodic arrangement and physically unique diffraction patterns. By combining the quasi-periodic features of quasicrystal and the special rotational symmetry with metasurface, many novel phenomena and applications are proposed such as optical spin-Hall effect, non-linear far-field radiation control, and broadband polarization conversion. However, the additional functions and effects brought by phase and amplitude modulation on quasicrystal arrangement still lack research. Here, we design and fabricate a dielectric quasicrystal metasurface which can simultaneously reconstruct holographic images and exhibit diffraction patterns by assembling the nanostructures in a quasi-periodic array. Most importantly, we combine the global arrangement of metasurfaces with the local responses (phase and amplitude) of meta-atoms for achieving the dual functionality. Furthermore, we also suppress the zero diffraction order in the far-field based on the quasi-momentum matching rule. The proposed method has great mathematical importance and explores new possibilities for multifunctional meta-devices for holographic display, optical switching and anti-counterfeiting.
Nano-structured metamaterial absorber based on a plus-shaped resonator for optical wavelength applications
Authors: Islam Istiaq Mohammad Tanvirul , Islam Sikder Sunbeam , Islam Md. Rashedul , Karim Abu Naser Md. Rezaul , Azim Rezaul 
Published: June 2024

AbstractMetamaterial absorbers have sparked widespread interest due to their remarkable electromagnetic properties, which enable a wide range of applications in light absorption and manipulation. This study introduces a new three-layer nanomaterial absorber (NMA) unit cell composed of nickel (Ni), silicon dioxide (SiO2), and nickel (Ni) designed to operate across the entire visible spectrum (390–780 nm). We demonstrate the NMA’s exceptional absorption characteristics through rigorous numerical simulations using industry-standard software, achieving a mean absorption rate of 97.17% and a maximum absorption peak of 99.99% at 694.89 nm under standard angles. Furthermore, the NMA unit cell has good impedance matching, efficient coupling between capacitors and inductors, and significant plasmonic resonance properties. Fabrication feasibility and potential applications in solar energy harvesting, optical sensing, and light detection.
Advances in research on the efficacy of traditional Chinese herbal medicine in combating African swine fever
Authors: Yang Yuwei , Zhao Ya , Zhang Qiang , Jin Meilin 
Published: June 2024

AbstractAfrican swine fever (ASF) is a highly contagious disease of domestic and wild pigs caused by African swine fever virus (ASFV). The mortality rate associated with ASF is remarkably high, almost approaching 100%. Since the introduction of ASF into China in 2018, its rapid spread has caused marked economic losses in the country’s swine industry. To date, there are no safe and effective commercial vaccines or antiviral drugs against ASF; thus, there is an urgent need to develop novel prevention and control strategies. Traditional Chinese medicine (TCM), which comprises various herbs that are abundant in various potential functional components, holds great promise for the prevention and control of ASF. Here, we provide a comprehensive review of the advancements in TCM and the effects of its compound formulas against ASF, including the antiviral abilities, immunoregulatory activities, and practical application of these formulas for the prevention and control of ASF. We specifically examined the potential and constraints of natural product-derived extracts and TCM formulas in combating ASFV. This review aims to offer insights and ideas for the holistic management and containment of ASF.
Phase I/II trial of gabapentin plus intranasal ketamine for the prevention and treatment of pain in patients undergoing radiotherapy for head and neck cancer.
Authors: Lockney Natalie A , Smith Derek , Mundy Lindsay , Kilpatrick Phyllis , Butler Taylor , Kohutek Zachary , Cmelak Anthony , All Sean , Whitaker Ryan , Murphy Barbara A. 
Published: June 2024

12123 Background: Pain is ubiquitous in head and neck cancer (HNC) patients undergoing radiotherapy (RT) with up to 40% developing chronic pain. Gabapentin initiated concurrently with RT reduces pain intensity, opioid use, and dysphagia; however, gabapentin may not fully control pain, and dose escalation may be limited by toxicity. Novel non-opioid analgesic combinations administered concurrent with RT may address these limitations. Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist. The NMDA receptor modulates mood and pain and is involved in central sensitization. Blocking the NMDA receptor may decrease the development and severity of neuropathic pain and decrease/prevent central sensitization. In combination with other analgesics, ketamine may enhance acute and chronic pain control at lower doses thus avoiding dose-limited toxicities. We report results from the dose-finding phase I study of gabapentin plus intranasal (NAS) ketamine in HNC patients undergoing RT; phase II is ongoing. Methods: Eligibility: locally advanced non-metastatic HNC planned for primary or adjuvant RT with or without concurrent chemotherapy. Primary objective of phase I was to determine the maximum tolerated dose (MTD) or maximum planned dose (MPD) for NAS ketamine combined with gabapentin (300mg TID). Planned dose levels (DL) were DL1: 10 mg TID, DL2: 20 mg TID, DL3: 30 mg TID and DL 4: 40 mg TID. A phase II expansion was planned at the MTD/MPD to confirm safety and feasibility. Results: Eleven patients were enrolled during phase I, which has been completed. No dose limiting toxicities (DLTs) were noted at DL1, DL2 or DL3. Two DLTs were reported at DL4: grade 2 dizziness and grade 2 sedation. The MTD was ketamine 30 mg NAS TID. Six patients are enrolled on the phase II trial at the MTD which is ongoing. Conclusions: The MTD of NAS ketamine was 30mg TID combined with gabapentin 300mg. The Phase II expansion is ongoing. Clinical trial information: NCT05156060 .
Identification of pharmaceutics with selective activity against melanoma-associated leptomeningeal disease using patient-derived circulating tumor cells.
Authors: Law Vincent , Bayle Simon , Duckett Derek R. , Forsyth Peter A. J. 
Published: June 2024

2032 Background: Patients with advanced stage of melanoma may develop leptomeningeal disease (LMD), a rare form metastasis in the meninges. Unfortunately, there are currently no rationally designed treatments for melanoma-associated LMD (M-LMD) and the prognosis is dismal; with survival measured in weeks. A major barrier to developing effective therapies for this disease is the absence of model systems, such as patient-derived cerebral spinal fluid-circulating tumor cell (PD-CSF-CTC) models to identify and assess novel therapeutics. Added to this challenge is the difficulty of collecting and analyzing M-LMD specimens in the clinic and at autopsy. To address these hurdles, we have made considerable progress recently in overcoming these barriers via CSF and tissue collection (in clinic and rapid autopsy) and successfully propagating CSF-CTCs from M-LMD patients in vitro and in xenograft mouse models. These valuable resources have allowed us to perform proteomic and transcriptomic analyses of CSF and PD-CSF-CTCs, respectively. By comparing M-LMD -omics data against those from normal brain and extracranial disease, we have found unique LMD-specific biological pathways. In this study, we identified clinical compounds that could target these biological pathways and have efficacy against PD-CSF-CTCs in vitro and in vivo. Methods: PD-CSF-CTCs were propagated from individual M-LMD patients. Next, we have developed a 384-well high throughput cell-based assay and performed a pilot screening of more than 1,400 FDA-approved small molecule compound library using Echo to identify pharmaceutics that inhibit cell proliferation. Clinical compounds with the highest sensitivity were selected for validation of efficacy in vivo via intrathecal (IT) delivery of patient-derived cell lines to establish M-LMD xenografts. Results: Of the 1,436 FDA-approved small molecule compounds, 57 (~3.9%) exerted 95% proliferation inhibition and 20 (~1.4%) had 100% killing effect in PD-CSF-CTCs and murine melanoma cell lines. The compounds with the highest sensitivity include ponatinib (EC50: 1.85 – 4.06e-06), sorafenib (EC50: 9.57 – 9.77e-06), ceritinib (EC50: 1.84 – 2.05e-06) and homoharringtonine (HHT) (3.63 – 4.11e-08). In a randomized murine M-LMD preclinical trial, we selected HHT, since it is a cephalotaxine ester compound that can penetrate the brain. Our results show that HHT was well-tolerated in vivogiven systemically or IT via a murine Ommaya. We found M-LMD mice that received 14.5ng HHT (g.d. IT) showed significant prolonged median survival (control vs. HHT, P value: 0.0006; Mantel Cox test). Conclusions: This is the first demonstration of an approach that allows for the rational development of therapeutics in M-LMD. Results will provide crucial new insights into biology and will identify drug candidates that may be suitable for future clinical trials.
Detection of immune-related adverse events among hospitalized patients using large language models.
Authors: Sun Virginia H. , Heemelaar Julius C. , Hadzic Ibrahim , Raghu Vineet K. , Wu Chia-Yun , Zubiri Leyre , Suero-Abreu Giselle Alexandra , Ghamari Azin , Wu Jessica , Villani Alexandra-Chloé , Ho Jor Sam , Mooradian Megan J. , Sise Meghan E. , Zlotoff Daniel A. , Blum Steven Michael , Dougan Michael L. , Sullivan Ryan J. , Neilan Tomas G. , Reynolds Kerry Lynn , Thomas Molly Fisher ,   MGH Severe Immunotherapy Complications Service
Published: June 2024

2638 Background: Immune checkpoint inhibitor (ICI)-induced colitis, hepatitis, and pneumonitis are common immune-related adverse events (irAEs); however, the true incidence for these irAEs remains incompletely understood. Chart review is the gold standard for their detection but is time-consuming and cannot be implemented in large cohorts. The use of ICD codes is limited in sensitivity and specificity. Large language models (LLMs) are a scalable method of answering queries from human-generated text, though there is no data on the use of LLM for the identification of irAEs. Therefore, we investigated the application of a LLM to identify ICI-colitis, hepatitis, and pneumonitis among hospitalized patients, comparing its performance to manual chart review and ICD codes. Methods: Hospital admissions of patients on ICI therapy from February 5th, 2011, to November 3rd, 2021, were manually reviewed by a multidisciplinary immunotoxicity team using established published definitions for the presence of ICI colitis, hepatitis, and pneumonitis. Standard ICD codes and a LLM pipeline with retrieval-augmented generation (RAG) were used to detect irAEs. Performance was measured via sensitivity, specificity, and model runtime. The LLM was validated with a second dataset of inpatients with ICI colitis, hepatitis, and pneumonitis admitted from November 4th, 2021, to September 5th, 2023. Results: Among 5,677 hospitalized patients on ICI therapy in the initial cohort, there were 132 cases adjudicated with ICI colitis, 57 with ICI hepatitis, and 47 with ICI pneumonitis. The LLM was more sensitive in detecting all three irAEs compared to ICD codes (94.2% vs. 71.8%), achieving significance for ICI hepatitis (p<0.001) and pneumonitis (p=0.006), while having similar specificities (92.5% vs 91.1%, Table 1). The LLM approach was also efficient, spending an average of 9.42s per chart, compared to an estimated 15 minutes per chart for individual chart review. The mean sensitivity and specificity of the LLM on the validation dataset for adjudicated ICI colitis (n=20), hepatitis (n=24), and pneumonitis (n=6) were 96.9% and 93.2%, respectively. Conclusions: LLMs serve as a useful tool for the detection of ICI colitis, hepatitis, and pneumonitis, significantly outperforming ICD-codes in accuracy and manual chart review in efficiency.[Table: see text]
Phase II dose optimization with EZH2/EZH1 inhibitor tulmimetostat in patients (pts) with advanced solid tumors or hematologic malignancies.
Authors: Oaknin Ana , Banda Kalyan , Drescher Charles , Ribrag Vincent , Kindler Hedy L. , Walter Harriet S. , Tewari Alok , Pons-Tostivint Elvire , Lakhani Nehal J. , Harvey R. Donald , Sullivan Ryan J. , Zinzani Pier Luigi , Gonzalez Martin Antonio , Eberst Lauriane , Manso Sánchez Luis , Thakur Anjali , Kann Lennart , Reddy Archana , Faulhaber Nicola , Duska Linda 
Published: June 2024

3097 Background: Phase I dose-finding recommended a Phase II dose of 350 mg for the investigational oral, next-generation, dual EZH2/EZH1 inhibitor tulmimetostat (1), with preliminary Phase II results previously reported (2). To find an optimal dose, design of the ongoing Phase II part was later updated under the FDA’s dose-optimization paradigm (NCT04104776). Here we report updated preliminary findings including dose expansions. Methods: Phase II is evaluating tulmimetostat ≤350 mg once daily (QD) in 28-day cycles in 6 disease-based cohorts. The dose-optimization design randomizes further pts with ovarian clear cell carcinoma (OCCC; M2)/endometrial carcinoma (EC; M3) to 200/300 mg tulmimetostat QD. Primary endpoint is objective response rate (complete response [CR]/partial response [PR]); secondary objectives include pharmacokinetics/pharmacodynamics and safety. Results: As of Oct 15, 2023, 117 pts received ≥1 dose (safety set); 111 had ≥1 post-baseline tumor assessment or discontinued prior to it (efficacy set). Median time since diagnosis was 2.8 years (0–19.6); 86.3% of pts had ≥2 prior lines of therapy. At cut-off, best responses of ≥1 CR/PR were seen in 5 cohorts (Table). 74.4% had dose modifications due to treatment-emergent adverse events (TEAEs), 41.9% had ≥1 serious TEAE, and 9.4% discontinued therapy due to TEAEs. Most frequent TEAEs (≥35% of pts; any grade/Grade ≥3) considered possibly related to treatment were diarrhea (49.6%/10.3%), thrombocytopenia (48.7%/24.8%), anemia (39.3%/16.2%), and nausea (35.9%/2.6%). Phase I/II data showed a direct correlation between increasing doses (50–375 mg) or exposure (area under the curve 0–24 hours or maximum concentration) and larger changes in gene expression, which plateau at higher doses (≥225–≤375 mg). Conclusions: The evolving Phase II data, including early data from lower doses, continue to show signs of antitumor activity/disease stabilization. The safety profile is consistent with EZH2 inhibition. These preliminary findings in heavily pretreated pts with multiple tumor types and evolving dose-optimization data support ongoing investigation of tulmimetostat. 1. Lakhani et al. ASCO 2021. 2. Drescher et al. ASCO 2023. Clinical trial information: NCT04104776 . [Table: see text]