bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of a circulating long non-coding RNA signature panel in plasma as a novel biomarker for the detection of acute/early-stage HIV-1 infection
Authors: Biswas Santanu , Nagarajan Namrata , Hewlett Indira , Devadas Krishnakumar 
Published: June 2024

Abstract
Background
Individuals with acute / early HIV-1 infection are often unaware that they are infected with HIV-1 and may be involved in high-risk behavior leading to transmission of HIV-1. Identifying individuals with acute / early HIV-1 infection is critical to prevent further HIV-1 transmission, as diagnosis can lead to several effective HIV-1 prevention strategies. Identification of disease-stage specific non-viral host biomarkers would be useful as surrogate markers to accurately identify new HIV-1 infections. The goal of this study was to identify a panel of host derived plasma long non-coding RNAs (lncRNAs) that could serve as prognostic and predictive biomarkers to detect early/acute HIV-1 infection.

Methods
A total of 84 lncRNAs were analyzed in sixteen plasma samples from HIV-1 infected individuals and four healthy controls using the lncRNA PCR-array. Twenty-one lncRNAs were selected and validated in 80 plasma samples from HIV-1 infected individuals [HIV-1 infected patients in the eclipse stage (n = 20), acute stage (n = 20), post-seroconversion p31 negative stage (n = 20), and post-seroconversion p31 positive stage (n = 20) of infection] and 20 healthy controls. The validation study results were used to develop a plasma lncRNA panel that was evaluated in the panel test phase to detect early/acute HIV-1 infection in 52 independent samples.

Results
We identified a lncRNA panel (Pmodel−I) containing eight lncRNAs (DISC2, H19, IPW, KRASP1, NEAT1, PRINS, WT1-AS and ZFAS1) that could distinguish HIV-1 infection from healthy controls with high AUC 0·990 (95% CI 0.972-1.000), sensitivity (98.75%), and specificity (95%). We also found that Pmodel−II and Pmodel−III demonstrates 100% sensitivity and specificity (AUC 1·00; 95%CI:1·00–1·00) and could distinguish eclipse stage and acute stage of HIV-1 infection from healthy controls respectively. Antiretroviral treatment (ART) cumulatively restored the levels of lncRNAs to healthy controls levels.

Conclusion
lncRNA expression changes significantly in response to HIV-1 infection. Our findings also highlight the potential of using circulating lncRNAs to detect both the eclipse and acute stages of HIV-1 infection, which may help to shorten the window period and facilitate early detection and treatment initiation. Initiating ART treatment at this stage would significantly reduce HIV-1 transmission. The differentially expressed lncRNAs identified in this study could serve as potential prognostic and diagnostic biomarkers of HIV-1 infection, as well as new therapeutic targets.
Not too old to rock: ESR and OSL dating reveal Quaternary activity of the Periadriatic Fault in the Alps
Authors: Prince Erick , Tsukamoto Sumiko , Grützner Christoph , Vrabec Marko , Ustaszewski Kamil 
Published: June 2024

AbstractThe Periadriatic Fault system (PAF) ranks among the largest post-collisional structures of the European Alps. Recent geodetic data suggest that a fraction of the Adria–Europe convergence is still being accommodated in the Eastern Alps. However, the historical seismicity records along the easternmost segment of the PAF are ambiguous, and instrumental records indicate that seismotectonic deformation is mostly concentrated in the adjacent Southern Alps and Dinarides. Both electron spin resonance (ESR) and optically stimulated luminescence (OSL) dating methods can be used to date coseismic slip (with a combined range covering a few decades to a couple of million years) in slowly deforming fault zones, such as the PAF. Since the saturation doses of the quartz ESR signals are larger than quartz and feldspar OSL, ESR enables establishing a maximum age of the last resetting event of the system, while OSL allows constraining their minimum age when the signal is in saturation. We collected fault gouge samples from three localities along the easternmost segment of the PAF. For ESR, we measured the signals from the Al center in quartz comparing the results from the single aliquot additive dose (SAAD) and single aliquot regenerative (SAR) dose protocols. For OSL, we recorded the infrared stimulated luminescence signal at 50°C (IR50) and post-infrared infrared-stimulated luminescence signal at 225 °C (pIRIR225). Our dating results indicate that the studied segment of the PAF system accommodated seismotectonic deformation during the Quaternary, with a maximum age for the last resetting event of the system ranging from 1075 ± 48 to 552 ± 26 ka (ESR SAR) and minimum ages in the range from 196 ± 12 to 281 ± 16 ka (saturation of pIRIR225). The obtained ages suggest that the studied segment of the PAF could be considered at least as a potentially active fault.
Graphical abstract
Prevalence of vitamin B 12 deficiency and associated factors among primary school children: North East Ethiopia: multicenter cross-sectional study
Authors: Melaku Ermiyas Endewunet , Urgie Besufekad Mulugeta , Tilahun Alemnesh Tesema , Assefa Hilina Ketema , Abebe Alemayehu Abera , Tefera Aklile Semu 
Published: June 2024

Abstract
Background
The prevalence of Vitamin B12 deficiency is common and is more frequent in low- and middle-income countries with a poor or inadequate diet of animal foods. In Ethiopia, researches related to the status of micronutrients in children are limited. Therefore, this study aimed to assess the prevalence of vitamin B12 deficiency and associated factors among primary school children.

Methods
A cross-sectional study design was conducted from January 10-February 30/2023. A total of 514 students were selected using a systematic random sampling technique. Face-to-face interviews using a structured questionnaire, document review, anthropometric measurement, and laboratory studies were implemented to collect data. Data was analyzed by STATA version 14 and summarized by using frequency tables and graphs. Logistic regression analysis was done to identify factors associated with vitamin B12 Deficiency.

Results
About 34% of the students were found to have vitamin B12 deficiency. Not Consuming animal products (AOR = 1.83, 95% CI:1.20–2.79) and low body mass index (AOR = 1.62, 95% CI:1.05–2.47) were associated with vitamin B12 deficiency.

Conclusions
The study revealed a notable high deficiency of vitamin B12 in primary school students. Consumption of animal products and BMI were identified as statically significant associated factors with serum concentration of vitamin B12.
Doppler ultrasound compared to shear wave elastography for assessment of liver cirrhosis
Authors: Ellaban Heba Said , Afify Sameh Abdel Mawgoud , Abdelgawad Mohamed Saied 
Published: June 2024

Abstract
Background
The progression of liver fibrosis to cirrhosis is a dynamic process necessitating non-invasive evaluation modalities. This study aims to evaluate the ability of Doppler ultrasound studies (DUS) in defining morphological and hemodynamic blood flow changes in the hepatic vasculature coinciding with advanced liver fibrosis.

Methods
A prospective study was conducted on 100 patients with liver cirrhosis (F4). All cases underwent liver stiffness (LS) measurement by shear wave elastography (SWE), along with DUS to evaluate the liver texture, splenic size, hepatic artery resistive index (HARI), portal and splenic vein diameters, portal vein velocity (PVV), and hepatic vein waveform (HVV). All measures were assessed concurrently with a highly qualified single operator.

Results
Patients aged 55.5 ± 10.2 years with male predominance (72%). A highly significant correlation was found between LS by SWE and hepatic parenchymal texture, splenic size, portal vein width, and HVV (monophasic and biphasic) (p < 0.001). There were also high significant positive correlations (p < 0.001) between LS and PVV. However, there was no definitive correlation between LS and HARI, as well as splenic vein diameter.

Conclusion
The widely available economic Doppler studies including portal vein velocity and hepatic vein waveform changes could be of substantial diagnostic value to liver cirrhosis.

Study design
Prospective cohort study, employing descriptive and analytical statistics.
Mechanical and Fatigue behavior of G22NiMoCr5-6 and G18NiMoCr3-6 used in heavy-duty crawler track plates
Authors: Elsabbagh Ahmed , El-Kashif Emad , Sayed Sahour 
Published: June 2024

AbstractG22NiMoCr5-6 and G18NiMoCr3-6 steels are commonly used in the manufacturing of crawler track plates of heavy-duty equipment due to their enhanced mechanical properties which allow them to be suitable for this particular application. This research aims to investigate the mechanical and fatigue behavior of both material grades to evaluate their performance in the manufacturing of heavy-duty crawler track plates. In the present work, experimental investigations were carried out including chemical composition, tensile, hardness, Charpy impact, and low-cycle fatigue tests. Also, metallographic examination was conducted to show the microstructure of both materials. Based on the experimental analysis results, the bainitic structure of G18NiMoCr3-6 was found to have longer fatigue life and higher toughness than the tempered-martensitic structure of G22NiMoCr5-6 which qualifies G18NiMoCr3-6 to be more suitable for manufacturing of heavy-duty crawler track plates than G22NiMoCr5-6 steel.
The impact of a zero-flaring system on gas plants, environment, and health
Authors: Taha Ayman , Abdelalim Galal , AboulFotouh Tarek 
Published: June 2024

AbstractContinuous natural gas flaring wastes significant energy resources and increases greenhouse gas emissions, contributing to global warming. Our work provides an overview of a technique to recover flare gas and reduce CO2 emissions to a minimum level. There are two methods to recover flare gas: the recovery of natural gas liquids and sales gas production by existing LPG unit and the production of liquid fuels by mini-GTL unit (gas to liquid). This study was conducted using real data from the field. All cases were simulated using Aspen HYSYS software. The mini-GTL unit is modeled using an autothermal reforming method. CO2 emissions will be reduced by 107.68 tonne/day in both methods. Economic analyses revealed that the NGL and sales gas product has a net present value (NPV) of 77.03 MMUSD, while the mini-GTL product has an NPV of 73.7 MMUSD. The study showed that we could extract natural gas liquids (NGLs), including propane, LPG, and sales gas, from the flare gas or convert it to liquid products, including gasoline and diesel. The expected internal rate of return (IRR) and payout time (POT) for NGL and sales gas method are 150.73% and 0.27 years, respectively. The mini-GTL method is recommended due to Egypt’s petroleum fuel shortage and the best solution without an entry point to the Egyptian national gas grid in the plant. However, the IRR and POT for the mini-GTL method are 30.09% and 1.19 years, respectively, and it needs more CAPEX than the NGL and sales gas method.
Graphical Abstract
Clinically significant variant classification resulting from the addition of RNA sequencing: Experience at high-volume cancer genetics center.
Authors: Rudowski Sydney , Gallant Alexis , Stupar Ana , Reeves Ashley , Campian Sarah , Zakalik Dana 
Published: June 2024

10603 Background: Germline cancer genetic testing plays an important role in prevention, early detection, and targeted therapy1. The increasing use of multi-gene panel testing (MGPT) underscores the importance of accurate variant classification. We report on the significant contribution of RNA analysis to variant classification with impact on clinical care. Methods: A total of 6343 patients who presented to the Nancy & James Grosfeld Cancer Genetics Center between 2019 to 2023 and underwent MGPT at a laboratory with RNA sequencing were evaluated. Patients underwent MGPT using standard DNA technology with added RNA sequencing. We analyzed these patients for clinically significant variant reclassification which includes upgrades from non-actionable variants of uncertain significance (VUS) to pathogenic/likely pathogenic (P/LP) or P/LP to VUS as a significant downgrade. Results: A total of 177 patients (2.8%) had a variant classification significantly impacted by RNA sequencing. Of those 177 patients 45 (25.4%) had clinically relevant change due to their reclassification which resulted in a change in medical or surgical management. The majority of these 45 patients were upgraded from a non-actionable result to P/LP and 14 were downgraded to non-actionable. The clinically significant upgrades included the following genes: BRCA1/2 (5), MSH2 (4), MSH6 (1), PMS2 (1), ATM (5), CHEK2 (5), RAD51C (5), CDH1 (2), and PALB2 (3), which lead to evidence-based early detection and prevention. The clinically significant downgrades included the following genes: BRCA2 (5), RAD50 (1), and RAD51D (8), which allowed for a reduction in medical burden. Of the 177 cases impacted by RNA sequencing, 61 uncertain variants (34.4%) were downgraded to benign polymorphisms, helping to reduce uncertainty regarding management. Conclusions: Our study demonstrates the importance and added benefit of RNA sequencing in variant classification for patients undergoing multigene panel testing for hereditary cancer. The addition of RNA sequencing improved identification of individuals at increased risk, while lowering the number of uncertain variants. This improved technology will allow for a more precise approach to cancer screening, treatment and prevention.
FURTHER: A global study to evaluate furmonertinib in patients with EGFR mutant NSCLC including uncommon EGFR mutations (FURMO-002).
Authors: Le Xiuning , Spira Alexander I. , Gadgeel Shirish M. , Riess Jonathan W. , Yu Yan , Zhao Yanqiu , Cheng Ying , Juan-Vidal Oscar , Gao Bo , Yoh Kiyotaka , Forster Martin , Kitazono Satoru , Hayashi Hidetoshi , Planchard David , Jiang Yong , Baio Nichole , Kowanetz Marcin , Leung William , Hsu Jerry Y. , Wang Jie 
Published: June 2024

TPS8666 Background: Furmonertinib (AST2818) is an oral, highly brain-penetrant, and broadly active mutation-selective epidermal growth factor receptor ( EGFR) inhibitor engineered for broad activity and selectivity across EGFRmutations (mts) (1). Furmonertinib is approved in China for first-line advanced NSCLC with EGFR Ex19del or L858R mts based on the progression-free survival benefit observed in the Phase 3 study versus gefitinib (FURLONG). Furmonertinib has also demonstrated promising interim efficacy and safety in patients (pts) with NSCLC harboring EGFR exon 20 insertion (ex20ins) mts with a confirmed overall response rate (ORR) of 78.6% (n=28) by blinded independent central review (BICR) and a preliminary median duration of response (DoR) of 15.2 months in the front-line setting (FAVOUR study; see Han et al., WCLC 2023). Furmonertinib recently obtained FDA Breakthrough Therapy Designation for the treatment of pts with advanced NSCLC with EGFR ex20ins mts. P-loop and αC-helix Compressing (PACC) mts represent another subset of uncommon EGFR mts (2) that are similar to ex20ins mts in narrowing the drug-binding pocket; including G719X, S768I, E709X, L747X, V774M. Preclinical data indicating that furmonertinib is potent in models harboring EGFR PACC mts Developing efficacious, well-tolerated, and CNS-penetrant medicines for NSCLC pts with EGFR ex20ins mts and PACC mts remains an unmet need. Methods: FURTHER (FURMO-002) is the first global trial evaluating furmonertinib in NSCLC pts with EGFR and HER2 mts in North America, Europe, and the Asia-Pacific. FURTHER is a phase 1b, open-label, multicenter study in which pts will be treated orally with furmonertinib daily. For Stage 1 dose-escalation, the primary endpoint is incidence and severity of adverse events, including dose limiting toxicities and has been completed. For Stage 2 dose expansion, approximately 120 pts will be enrolled across 4 expansion cohorts. Stage 2 Cohorts 1-3 dose expansion cohorts will enroll pts with previously treated, locally advanced or metastatic NSCLC pts with either EGFR ex20ins mts, HER2 ex20ins mts, or EGFR activating mts, respectively. Cohorts 1-3 allow enrollment of pts with prior EGFR or HER2-directed therapy. Stage 2 Cohort 4 will enroll EGFR TKI-naïve NSCLC pts with EGFR PACC mts. Key inclusion criteria include documented EGFR or HER2 mts by local testing and measurable disease per RECIST v1.1. Stage 2 primary endpoint is ORR using RECIST v1.1. Key secondary endpoints include progression-free survival and overall survival. Stage 2 enrollment is ongoing. 1. Musib et al., NACLC 2022. 2. Robichaux et al., 2021. Clinical trial information: NCT05364073 .
REZILIENT3: Phase 3 study of zipalertinib plus chemotherapy in patients with previously untreated, advanced nonsquamous non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) exon 20 insertions (ex20ins) mutations.
Authors: Yu Helena Alexandra , Besse Benjamin , Nishio Makoto , Cheng Ying , Wei Li , Wacheck Volker , Heymach John 
Published: June 2024

TPS8671 Background: Despite recent advances, tolerable and effective treatments for patients with NSCLC harboring EGFR ex20ins mutations are needed, particularly in the first-line setting, where platinum-based chemotherapy remains the standard of care. Zipalertinib (CLN-081/TAS6417), an oral tyrosine kinase inhibitor (TKI) of EGFR with broad activity against EGFR mutations, showed encouraging antitumor activity in heavily pretreated patients with EGFR ex20ins–mutant NSCLC, leading to ‘Breakthrough Therapy’ designation by the U.S. Food and Drug Administration in January 2022. Data suggest that combining EGFR TKIs with chemotherapy can improve antitumor efficacy versus chemotherapy or TKI treatment alone in patients with EGFR-mutated nonsquamous NSCLC. REZILIENT3 is a pivotal phase 3 study designed to compare the efficacy and safety of zipalertinib plus first-line standard-of-care platinum-based chemotherapy versus chemotherapy alone in previously untreated patients with nonsquamous NSCLC harboring EGFR ex20ins mutations. Methods: This randomized, controlled, open-label, phase 3 study (NCT05973773) will be conducted in two parts. Part A (safety lead-in) will confirm the safety of zipalertinib 100 mg twice daily as the recommended dose in combination with chemotherapy in patients with locally advanced or metastatic nonsquamous NSCLC harboring uncommon EGFRmutations. In Part B (randomized part), patients with EGFR ex20ins mutations and at least one measurable lesion (per Response Evaluation Criteria in Solid Tumours, version 1.1) will be randomized 1:1 to zipalertinib plus chemotherapy or chemotherapy alone, stratified by Eastern Cooperative Oncology Group performance status (0/1), brain metastases (yes/no), and geography (Asia/rest of world). Zipalertinib will be administered orally at a starting dose of 100 mg twice daily (pending confirmation in Part A). Chemotherapy (pemetrexed 500 mg/m² plus cisplatin 75 mg/m² or carboplatin area under the curve 5 mg/mL/min) will be administered intravenously on Day 1 of each cycle (carboplatin/cisplatin for four cycles). The primary objective in Part A is safety and tolerability. In Part B, the primary objective is efficacy; progression-free survival assessed by blinded independent central review is the primary endpoint. Secondary endpoints include overall survival, investigator-assessed progression-free survival, objective response rate, duration of response, disease control rate, safety, intracranial efficacy endpoints, and quality of life. Part A is anticipated to enroll between 6 and 12 patients, while Part B is estimated to enroll approximately 300 patients. Enrollment commenced in June 2023. Clinical trial information: NCT05973773 .
Novel RNA-nanoparticle vaccine for the treatment of early melanoma recurrence following adjuvant anti-PD-1 antibody therapy.
Authors: Doonan Bently Patrick , Shaw Christiana M. , Lee Ji-Hyun , Simon Manso Eugenio , Mendez-Gomez Hector , Von Roemeling Christina , Mitchell Duane Anthony , Sayour Elias , George Thomas J. 
Published: June 2024

TPS9609 Background: Melanoma is a major public health concern with an anticipated increase in prevalence and incidence in the coming years. Early detection and surgical management remain the mainstay of treatment of early-stage disease and use of adjuvant immunotherapy has improved outcomes for patients with more aggressive (IIB-IIC) local disease or those with lymph node involvement (IIIA-IIID). Based on the tolerability and efficacy across subjects with both BRAF mutated and wildtype melanoma anti-PD1 (aPD1) therapy with either nivolumab or pembrolizumab are considered first line treatment in this setting. Adjuvant aPD1 therapy has significant improvement in relapse free survival (RFS) yet 25-30% of subjects will have disease recurrence within 1 year of surgery. When disease recurs, the response rate to immunotherapy is significantly reduced, re-challenged with aPD1 therapy has shown an Objective Response Rate (ORR) of zero and a marginally better response to CTLA-4 blockade. Novel strategies are needed for this at-risk population with early aPD1 resistance. To address this need we have developed a novel multi-lamellar lipid-nanoparticle complexed with total-tumor derived mRNA administered intravenously to restore responsiveness to aPD1 through reprogramming the tumor microenvironment (TME) bridging an innate and adaptive immune response. We have designed a clinical trial in which patients who progress on while on aPD1 therapy or within 6 months of therapy will have tumor sampled and a personalized lipid-nanoparticle vaccine generated. This vaccine is then administered IV for a total of 3 doses spanning 6 weeks to reprogram the TME and restore response to aPD1 which will be resumed on completion of vaccine series. This phase I study will assess initial feasibility and safety of vaccine generation, utilize ctDNA surveillance as early detection of adjuvant failure, and provide essential biologic information on immunotherapy resistance to aPD1 therapy. Methods: We have designed a modified 3+3 phase I clinical trial that will enroll subjects who have evidence of progressive disease (PD) by ctDNA and/or RECIST 1.1 criteria while receiving adjuvant aPD1 therapy, or those who progress within 6 months of completion of treatment for stage IIB-IIID melanoma. The goal of this study is to assess safety, tolerability, and feasibility of tumor specific RNA-LPs. Important biological correlates will also be collected and analyzed including tumor tissue sampling at initial time of checkpoint resistance and following vaccination series to identify key changes to the TME and tumor induced by lipid-nanoparticle vaccine administration. Clinical trial information: NCT05264974 .