bluuebunny/crossref_metadata_2025 huggingface dataset:
TOURMALINE: A phase 3b study of durvalumab with gemcitabine-based chemotherapy regimens in advanced biliary tract cancer.
Authors: Vogel Arndt , He Aiwu Ruth , Oh Do-Youn , Macarulla Teresa , Dane Aaron , Nguyen Binh , Wetherill Graham , Baur Boris , Ikeda Masafumi
Published: July 2024

TPS4188

Background: In the Phase 3 TOPAZ-1 study (NCT03875235), durvalumab plus gemcitabine + cisplatin (GC) significantly improved overall survival (OS) versus placebo + GC in participants with advanced biliary tract cancer (aBTC) with a manageable safety profile. To expand on TOPAZ-1, there is a need to further assess the safety and efficacy of durvalumab in combination with other gemcitabine (G)-based chemotherapy regimens used in aBTC, and in a more diverse population to reflect real-world clinical practice. Methods: TOURMALINE (NCT05771480) is a Phase 3b, single-arm, multicenter, international study. Approximately 140 adults with aBTC (intra- or extra-hepatic cholangiocarcinoma, gallbladder or ampulla of Vater carcinoma) will be enrolled. Key inclusion criteria include unresectable disease (advanced, metastatic), WHO/ECOG PS of 0–2, and no prior systemic therapy. Key exclusion criteria include any prior immune-mediated therapy and history of another primary malignancy. Participants will receive durvalumab 1500 mg IV plus an investigator-selected, G-based background chemotherapy; durvalumab will be administered Q3W when combined with a G-based chemotherapy Q3W (8 cycles of durvalumab) except for when combined with GC + S-1 Q2W, in which case durvalumab will be administered Q4W (4 cycles of durvalumab/8 cycles of chemotherapy). G-based chemotherapy will consist of G monotherapy, GC (for WHO/ECOG PS 2 participants only), G + oxaliplatin, G + carboplatin, GC + S-1, G + S-1, and GC + albumin-bound paclitaxel. Following the treatment period, durvalumab Q4W +/- chemotherapy (except for paclitaxel) may continue, at the investigator’s discretion, until discontinuation criteria are met. The primary endpoint is the incidence of Grade 3 or 4 adverse events, assessed by the investigator to be possibly related to any study treatment within 6 months after initiation of durvalumab. Secondary endpoints include OS, objective response rate, progression-free survival, and duration of response. Enrollment is ongoing and planned in France, Germany, United States, Spain, Italy, Japan, South Korea, and Singapore. Clinical trial information: NCT05771480 .
A phase 1/2, safety lead-in and dose expansion, open-label, multicenter trial investigating the safety, tolerability, and preliminary activity of ivosidenib in combination with nivolumab and ipilimumab in previously treated subjects with IDH1-mutated nonresectable or metastatic cholangiocarcinoma.
Authors: Kelley Robin Kate , Cleary James M. , Sahai Vaibhav , Baretti Marina , Bridgewater John A , Hua Zhaowei , Gliser Camelia , Bian Ying , Abou-Alfa Ghassan K.
Published: July 2024

TPS4197

Background: Cholangiocarcinoma (CCA) is a rare cancer with limited therapeutic options, though molecularly targeted therapies have demonstrated anti-tumor activity in certain subsets. Approximately 15% of patients with intrahepatic CCA harbor activating mutations in isocitrate dehydrogenase-1 (mIDH1), and treatment with the mIDH1 inhibitor, ivosidenib (IVO) improved progression-free survival in the phase 3 ClarIDHy trial. mIDH1 is associated with an immune-excluded tumor microenvironment, and anti-CTLA4 immune checkpoint inhibition (ICI) augments anti-tumor activity when combined with IVO in preclinical models. Preliminary anti-tumor activity of dual immune checkpoint inhibitors (IPI, NIVO) has been reported in biliary tract cancers. Methods: This is a phase 1/2, non-comparative, multicenter, open-label study of IVO, IPI, NIVO, in subjects with unresectable or metastatic CCA with mIDH1. Key eligibility criteria include: a histopathological diagnosis; tumor mIDH1 based on local testing; progression on and/or intolerance to 1-2 prior lines of systemic therapy, at least one of which contained either gemcitabine and/or 5-fluorouracil; prior anti-PD-(L)1 therapy is allowed in the safety lead in; Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1; at least 1 measurable lesion as defined by RECIST version 1.1. The study has a safety lead-in phase and an expansion phase with 2 different expansion cohorts: cohort 1, ICI-naive; cohort 2, prior ICI allowed. The primary objective is to evaluate the safety and tolerability of IVO in combination with IPI plus NIVO and determine the recommended combination dose (RCD). This phase will enroll ~6 to 12 dose-limiting toxicity (DLT)–evaluable patients. The first 6 patients enrolled will receive IVO 500 mg orally once daily in combination with IPI 1 mg/kg IV infusion and NIVO 3 mg/kg IV infusion concurrently once every 3 weeks for 4 doses followed by NIVO at 480 mg IV once every 4 weeks until progression or unacceptable toxicity (up to a maximum of 24 months of NIVO). DLTs will be evaluated during the first 2 cycles of treatment. An additional 6 patients may be enrolled to assess an alternative dose of ivosidenib 250 mg once daily. Upon determination of the RCD, the two expansion cohorts will be initiated to assess the clinical activity of the triplet combination in patients with and without prior ICI. First patient in occurred in November 2023. Clinical trial information: NCT05921760 .
REPLACE: A phase III, randomized, open-label trial to evaluate the safety and efficacy of regorafenib and pembrolizumab versus locoregional therapy (LRT) with transarterial chemoembolization (TACE) or transarterial radioembolization (TARE), for the first-line treatment of intermediate-stage hepatocellular carcinoma (HCC) with beyond up-to-7 criteria.
Authors: Galle Peter Robert , Kudo Masatoshi , Llovet Josep M , Cheng Ann-Lii , Lencioni Riccardo , Oviedo Yanina , Desai Kalpna , Monier Amandine , Finn Richard S.
Published: July 2024

TPS4200

Background: Intermediate-stage HCC represents a heterogeneous population, posing unique challenges for therapeutic management. With the advent of effective systemic therapies for unresectable HCC, the treatment landscape for intermediate-stage extends beyond LRT, particularly in patients with high tumor burden. The growing evidence about the benefit of systemic therapy in intermediate-stage HCC led to the inclusion in some recent guidelines of systemic therapy as the first choice of treatment in TACE-unsuitable patients with intermediate-stage HCC. Despite these recommendations, no randomized clinical trial has been published comparing LRT with TACE/TARE versus systemic therapy in patients with intermediate-stage HCC and high tumor burden. Methods: REPLACE is a phase III, multicenter, randomized, open-label trial that will compare the efficacy and safety of LRT with TACE/TARE versus systemic therapy, for the first-line treatment of intermediate-stage HCC with beyond up-to-7 criteria. Eligible participants will be randomized 1:1 to receive regorafenib (90 mg orally q.d. on days 1 to 21 of a 4-week cycle), and pembrolizumab (400 mg i.v. on day 1 of a 6-week cycle) or LRT with TACE or TARE, and will be stratified according to geographic region (Asia vs. non-Asia), ECOG Performance Status (0 vs 1) and Albumin-Bilirubin (ALBI) grade (1 vs 2). Patients must have intermediate-stage HCC with beyond up-to-seven criteria (Up-to-7 criteria = largest tumor diameter (cm) + number of tumors ≤7), measurable disease per RECIST 1.1, disease not amenable to curative treatment but amenable to LRT with TACE or TARE, no prior systemic or LRT for HCC, except for successful resection and/or ablation completed ≥ 6 months prior to randomization. Patients will be treated until progressive disease, unacceptable toxicity, or other treatment discontinuation criteria is met. The primary endpoint is progression free survival (PFS), assessed locally by the Investigator using mRECIST for HCC. Secondary endpoints include PFS assessed locally by the Investigator using RECIST 1.1; PFS centrally assessed using mRECIST and RECIST 1.1; overall survival; overall response rate according to RECIST v.1.1 and mRECIST based on the Investigator’s and central assessment; time to unTACEable progression; duration of response; safety and tolerability of the trial treatments, and patient reported outcomes for health-related quality of life. The estimated enrollment is 496 patients from approximately 14 countries. Recruitment started in October 2023 and is currently ongoing. Clinical trial information: NCT04777851 .
Repurposing atovaquone as a STAT3 inhibitor for the treatment of platinum resistant ovarian cancer.
Authors: Wood Sarah Jeanne , Frank David , Haas Elizabeth Brannan , Wang Weiyuan , Meisel Jane Lowe , Khanna Namita
Published: July 2024

TPS5631

Background: Despite advances, ovarian cancer (OC) is the most lethal gynecologic cancer with 5-year survival rates for stage III and IV disease 41% and 21%, respectively. After initial treatment with cytoreductive surgery and chemotherapy, 70% of patients (pts) will relapse. Treatment of relapsed OC is dependent on the amount of time between completion of platinum-based therapy and relapse, known as the platinum-free interval (PFI). Pts with PFI of less than six months are deemed platinum-resistant with low response to further chemotherapy and median progression-free survival (PFS) of 3.6 months. Additional treatment options are needed. Oncogenic signal transduction pathways are a critical component of cancer pathogenesis. In a variety of cancer types, including OC, the transcription factor STAT3 (Signal Transducer and Activator of Transcription 3) has emerged as a key promoter of cellular proliferation and resistance to therapeutic drugs. In OC cells, STAT3 is constitutively activated in over 70% of cells, resulting in enhanced cell survival, angiogenesis, and metastasis. STAT3 also controls innate and adaptive immune response by driving myeloid-derived suppressor cells and regulatory T cells, while hampering CD8+ T cell cytotoxicity. Using the Connectivity Map database to identify drugs that induce gene expression changes contrary to the STAT3 signature, the FDA-approved antimicrobial atovaquone (ATO) was identified as the most active. ATO, a well-tolerated, readily available drug inhibits STAT3 tyrosine phosphorylation by downregulating the cell surface expression of glycoprotein 130, which is necessary for signaling of IL-6 and Janus Kinase, and subsequent phosphorylation of STAT3. Given that the STAT3 pathway is constitutively activated in OC, we hypothesize that ATO, a potent inhibitor of STAT3, could be a repurposed therapeutic agent in OC. Methods: A Phase II, single-arm, investigator-initiated clinical trial is in process at our institution where we are evaluating ATO as targeted therapy in pts with platinum resistant OC whose tumors have progressed despite standard therapies. To date, we have currently enrolled 2 of an anticipated 28 pts. The primary endpoint is PFS, with clinical secondary endpoints to include clinical benefit rate and overall survival. In addition, to confirm the STAT inhibitory effect on OC cells, pre and on-treatment tissue sampling is being obtained to assess changes in STAT3 dependent gene expression via RT-PCR and quantitate changes to the immune profile via flow cytometry. We hypothesize targeting inappropriate activation of STAT3 could be a novel and promising treatment approach in OC. This is the first clinical trial evaluating the clinical efficacy of ATO in OC and could have wide implications on treatment options in the future. Clinical trial information: NCT05998135 .
Neoadjuvant adebrelimab plus dalpiciclib in HPV-negative locally advanced head and neck squamous cell carcinoma: A phase II clinical trial.
Authors: Liu Lei , Li Yi , Chen Fei , Li Chunjie , Xie Huixu , Zhang Zhuoyuan , Xz Xiang , Zeng Yuanyuan , Wang Jun , Zhang Bowen , Tan Chenfeng , Dai Zelei
Published: July 2024

TPS6129

Background: The efficacy and safety of neoadjuvant immunotherapy (NAI) for treating resectable locally advanced head and neck squamous cell carcinoma (LAHNSCC) remain uncertain, and the comprehensive protocol of NAI needs further explored. The tumor suppressor gene CDKN2A plays a pivotal role in cell cycle regulation by modulating cyclin-dependent kinase (CDK) activity. Mutations in CDKN2A lead to continuous activation of CDK4/6, resulting in uncontrolled cell proliferation and tumor growth. Approximately 35.7% of HNSCC patients exhibit CDKN2A mutations, with the incidence rising to 58% among HPV-negative LAHNSCC patients. Studies have shown that combining immunotherapy with a CDK4/6 inhibitor produces a synergistic anti-tumor effect. This study aims to assess the efficacy and safety of combining anti-PD-L1 (adebrelimab) with a CDK4/6 inhibitor (dalpiciclib) as NAI in resectable LAHNSCC patients. Methods: This open-label, single-arm, prospective phase II trial will enroll LAHNSCC patients eligible for surgery. Inclusion criteria include: being 18 to 75 years old at study entry; pathologically confirmed HPV-negative HNSCC (oral, laryngeal, hypopharyngeal, and HPV-negative oropharyngeal carcinoma), determined via p16 immunohistochemistry or HPV DNA tests; with CDKN2A mutation; resectable LAHNSCC, staged III-IVB according to the UICC/AJCC 8th edition TNM system; an ECOG Performance Status score of 0 or 1; no prior relevant anti-tumor treatments; intent for curative treatment; and adequate organ function. Key exclusion criteria are active autoimmune diseases, use of immunosuppressive drugs, or systemic corticosteroids. Eligible patients receive 3 cycles of adebrelimab (1200 mg intravenously every 3 weeks, Day 1, 22 and 43) and 2 cycles of dalpiciclib (150 mg, po, every 4 weeks, day 1-21 and 29-49) before surgery. Dose adjustments are allowed based on toxicity. Surgery will follow 2-4 weeks post-NAI, with subsequent adjuvant radiotherapy or chemoradiotherapy based on risk factors after surgery. The primary endpoints are 1-year disease-free survival (defined as the time from surgical resection to local recurrence) and major pathological response (MPR, defined as ≤10% residual viable tumor cells), with secondary endpoints focusing on safety and predictive biomarkers. Clinical trial information: NCT06199271 .
Preparation and Evaluation of Berberine-Excipient Complexes in Enhancing the Dissolution Rate of Berberine Incorporated into Pellet Formulations
Authors: Abbaspour Mohammadreza , Faeznia Faezeh , Zanjanian Parisa , Ruzbehi Milad , Shourgashti Kamran , Ziaee Amirhosseinn , Sardou Hossein Shahdadi , Nokhodchi Ali
Published: July 2024

Berberine is used in the treatment of metabolic syndrome and its low solubility and very poor oral bioavailability of berberine was one of the primary hurdles for its market approval. This study aimed to improve the solubility and bioavailability of berberine by preparing pellet formulations containing drug-excipient complex (obtained by solid dispersion). Berberine-excipient solid dispersion complexes were obtained with different ratios by the solvent evaporation method. The maximum saturation solubility test was performed as a key factor for choosing the optimal complex for the drug-excipient. The properties of these complexes were investigated by FTIR, DSC, XRD and dissolution tests. The obtained pellets were evaluated and compared in terms of pelletization efficiency, particle size, mechanical strength, sphericity and drug release profile in simulated media of gastric and intestine. Solid-state analysis showed complex formation between the drug and excipients used in solid dispersion. The optimal berberine-phospholipid complex showed a 2-fold increase and the optimal berberine-gelucire and berberine-citric acid complexes showed more than a 3-fold increase in the solubility of berberine compared to pure berberine powder. The evaluation of pellets from each of the optimal complexes showed that the rate and amount of drug released from all pellet formulations in the simulated gastric medium were significantly lower than in the intestine medium. The results of this study showed that the use of berberine-citric acid or berberine-gelucire complex could be considered a promising technique to increase the saturation solubility and improve the release characteristics of berberine from the pellet formulation.

Graphical Abstract
The stationary Klein-Gordon equation with a delta-like source: A generalized function approach
Authors: Ferreira J. P. , Barone F. E. , Barone F. A.
Published: July 2024

This work aims to initiate a discussion on finding solutions to non-homogeneous differential equations in terms of generalized functions. For simplicity, we conduct the analysis within the specific context of the stationary Klein-Gordon equation with a point-like source, identifying a generalized function that solves such an equation and aligns with the solution obtained through the Fourier approach with dimensional regularization. In addition to being regular at the source singularity, a notable advantage of our solution is its presentation as a single expression, eliminating the need for piecewise definitions. The arguments presented here are applicable to a broader range of situations, offering a novel approach to addressing divergences in field theories using generalized functions. Moreover, we anticipate that the approach introduced in this work could provide a new method for handling Green functions regularized at coincident points, thereby simplifying the renormalization process in a wide range of theories.
Exploring the reciprocity between pioneer factors and development
Authors: Freund Meghan M. , Harrison Melissa M. , Torres-Zelada Eliana F.
Published: July 2024

Development is regulated by coordinated changes in gene expression. Control of these changes in expression is largely governed by the binding of transcription factors to specific regulatory elements. However, the packaging of DNA into chromatin prevents the binding of many transcription factors. Pioneer factors overcome this barrier owing to unique properties that enable them to bind closed chromatin, promote accessibility and, in so doing, mediate binding of additional factors that activate gene expression. Because of these properties, pioneer factors act at the top of gene-regulatory networks and drive developmental transitions. Despite the ability to bind target motifs in closed chromatin, pioneer factors have cell type-specific chromatin occupancy and activity. Thus, developmental context clearly shapes pioneer-factor function. Here, we discuss this reciprocal interplay between pioneer factors and development: how pioneer factors control changes in cell fate and how cellular environment influences pioneer-factor binding and activity.
Complexity, Reality and Ontological Insecurity: On Mistakes and Navigational Skills
Authors: Uribe-Lopera Lucas , González Sebastián
Published: July 2024

This article explores the concept of reality and the transformation concerning the complex approach to the modes of existence based on the interrelation between diverse actants that make up our world. Considering recent ontological debates and critiques of modernity, the article argues for a shift away from ready-made suppositions about reality and the desire for simplified answers. We propose a radical idea of an actant interaction perspective grounded in Bruno Latour’s and Hartmut Rosa’s ideas of exploring an ontology embracing curiosity, imagination, and the importance of making mistakes as necessary attitudes in navigating the uncontrollable nature of reality. The article emphasizes the importance of embracing a sense of liberty when comprehending and interacting with the world. It encourages us to concentrate on the strengths and connections of living organisms.
The German-American physician and philologist Achilles Rose (1839-1916), the grand Philhellene
Authors: Tsoucalas Gregory , Vladimiros Lazaros
Published: July 2024

Achilles Rose, a German-American physician of the late 19th century, became famous for his persistent global struggle to promote the Hellenic language as the official language in medicine and science in general. Having studied in Zurich, Jena, and New York, he became a general practice physician. His most well-known medical treatise was “The Carbonic Acid in Medicine”, and he was the author of various works celebrating the Greeks and their vivid language. The Medical Society of Athens elected him as a member of a committee for such a purpose. Although Latin appeared to have won this linguistic battle, Hellenic terms eventually conquered international nomenclature. Greece must not forget this valiant Philhellene.
Life expectancy from Prehistoric times to the 21st Century
Authors: Yfantopoulos John
Published: July 2024

The purpose of this article is to investigate the factors contributing to significant improvements in longevity from the pre-historic times to the 21st century. Examining historical data, we witness an improvement in life expectancy from 20 years in prehistoric times to around 85 years in 2023. Several socio-economic and medical factors have contributed to this improvement, including living conditions, sanitation, housing, nutrition, education, disease prevention, medical advancements, environment, and economic growth. Analysing historical trends we can distinguish seven periods. In prehistoric times, primitive sanitary and living conditions, limited access to basic resources, high rates of accidents and infectious diseases resulted in short human longevity, ranging between 20 to 30 years. During ancient times, several historical sources from Egypt, Greece and Rome estimate life expectancy also at 20 to 35 years. Warfare, infectious diseases, malnutrition, and high rates of infant mortality are recorded as the main factors for this short life span. In the Middle Ages (500–1500 AD), the great killers like the Plagues (Black Death) had a significant impact on the reduction of population. Life expectancy fluctuated around 30 to 40 years. The Early Modern Period (1500–1800 AD) is marked by the advent of the agricultural revolution, enhancements in diet, and better sanitary conditions. Despite these advancements, life expectancy remained relatively unchanged, hovering between 30 and 40 years. With the Industrial Revolution (18th–19th centuries), life expectancy increased to 40-50 years. Advancements in the Twentieth Century, including medical care, sanitation, living conditions, nutrition, reforms in health systems for improved access to health services, and technological innovations, significantly increased life expectancy. These developments, predominantly in developed regions, led to life expectancy surpassing 70 years. The 21st Century is characterised by ongoing improvements in life expectancy, which has reached 85 years. However, significant health disparities persist between nations, regions, and socioeconomic groups. In 2022, the disparity in life expectancy among nations was as large as 33.5 years, with figures ranging from 52.5 years in Chad, Nigeria, and Central African Republic to 86 years in Monaco, Hong Kong, and Japan.
Luigi Taborelli (2022), Stamped Medicine Flasks nei ‘Virginia R. Grace Papers’ e i pogressi della ricerca, Roma: Edizioni Quasar, [2022]
Authors: Totelin Laurence
Published: July 2024

Luigi Taborelli is the world expert on microcontainers produced in the Hellenistic period and stamped with the word ‘lukion’, referring to a medicinal preparation. In the book reviewed, Taborelli examines the archives of the famous American archaeologist Virginia Grace on the matter of these microcontainers. Examining archival material allows scholars to identify exemplars of these microcontainers which remain unexamined. As more examples of these microcontainers come to light, scholars will be able to better understand the trade in medicinal substances in the Hellenistic world.
The Influence of Teacher Professionalism and School Culture on Education Quality at Private Vocational High Schools in Indramayu
Authors: Satria Nugraha Rizki , Dekawati Ipong
Published: July 2024

Education is essential in enhancing life quality. It fosters societal benefits and prosperity. The necessity of education extends its significance to individuals, societies, and even nations. Multiple elements contribute to enhancing education quality, encompassing teacher professionalism and school culture. Hence, this study assesses the impact of teacher professionalism and school culture on education quality, individually and collectively. The research utilizes a descriptive and verificative methodology, employing Likert scale questionnaires to gather data from 59 teachers. Regression analysis techniques process the data, and significance is assessed via F-tests. The findings indicate: (1) Teacher professionalism significantly and positively affects education quality; (2) School culture similarly exerts a positive and significant influence; (3) Simultaneously, teacher professionalism and school culture significantly enhance education quality. In light of these outcomes, the author proposes (1) Enhancing teacher professionalism through self-growth, academic participation, and adherence to ethical standards, further enriched by engaging in educational activities and community collaborations facilitated by school committees. (2) For improved education quality, emphasize the underrepresented dimension of norms within school culture, integrate various educational norms into school life and social interactions, and foster alignment with internal school policies and government regulations
Pengelolaan Kelas Pada Pembelajaran Matematika di Bimbingan Belajar
Authors: Muna Khozainul , Suparni Suparni
Published: July 2024

Pendidikan formal tidak cukup untuk mempersiapkan siswa dalam, menghadapi berbagai ujian, termasuk ujian nasional sehingga banyak dari mereka yang menenpuh pendidikan non-formal di luar jam sekolah di lembaga bimbingan belajar. Lembaga bimbingan belajar di luar sekolah menjadi alternatif para siswa untuk memperoleh pelajarann yang belum diajarkan disekolah. Matematika merupakan pelajaran yang dianggap sulit. Sebagia besar siswa kurang memahami pelajaran matematika yang hanya diajarkan di sekolah, dikarenakan terbatasnya waktu. Dalam kelas segala aspek pembelajaran berkumpul dan berproses, sehingga guru harus memiliki kemampuan pengeloaan kelas yang efektif. Pengelolaan kelas adalah upaya yang dilakukan guru untuk mewujudkan lingkungan belajar yang efektif dan menyenangkan serta dapat memotivasi siswa untuk belajar dengan baik sesuai kemampuan. Pengelolaan kelas yang efektif adalah persyaratan mutlak untuk membangun kegiatan belajar mengajar yang efektif. Tujuan dari penelitian ini adalah untuk mendeskripsikan pengelolaan kelas pada pembelajaran matematika di bimbingan belajar non formal. Penelitian ini menggunakan metode penlitian deskriptif dengan teknik pengumpulan data berupa wawancara dan observasi. Sampel dari penelitian adalah tentor matematika dari Bimbel CITAR. Dari hasil penelitian dapat disimpulkan bahwa pengelolaan kelas pada pembelajaran matematika di Bimbel CITAR sudah baik. Teknik pengelolaan kelas yang dilakukan tentor matematika di dalam kelas meliputi pengelolaan peserta didik, pengeloaan fasilitas, dan pengloaan pembelajaran.
Transforming Educational Environments: A Comprehensive Study on the Acceptance and Social Attitudes Towards LGBTQIA+ Students within Higher Education
Authors: Tomas Mary Jane L.
Published: July 2024

This study investigates the social attitudes and acceptance levels towards Lesbian, Gay, Bisexual, Transgender, Queer or Questioning, Intersex, Asexual, and other sexualities and gender identities, collectively referred to as LGBTQIA+, among students within the College of Education at Nueva Ecija University of Science and Technology. Employing a descriptive correlational research design, the research utilized surveys and interviews to collect data from a diverse student body, analyzing their perspectives on LGBTQIA+ inclusion and the impact of educational environments on their acceptance levels. Results indicate a generally positive attitude and high acceptance of LGBTQIA+ students, with significant relationships identified between students' acceptance levels and their gender and year level, while no significant correlations were found with their course and religion. The study emphasizes the critical role of educational settings in fostering an inclusive atmosphere that supports LGBTQIA+ students, highlighting the importance of promoting understanding and acceptance to enhance the educational experience for all students. By shedding light on current attitudes and acceptance levels, this research contributes valuable insights into the efforts required to create more inclusive educational environments for LGBTQIA+ individuals. The findings are of particular relevance to educators, policymakers, and educational researchers interested in advancing LGBTQIA+ inclusion within educational settings.
Prognosis of Covid-19 on its 1st Anniversary: Global v/s indian Scenario
Authors: Biradar S M. , Kohima B. , Mulimani M S. , Nayak Vishwanath , Warad Vijayakumar , Jugati Avinash , Hunasagi B S. , Pathi Indu , M Chetankumar , Awasthi Santhosh R. , V Basavaraj , Hawaldar yoti
Published: July 2024

Corona virus disease 2019 (Covid-19) is an acute respiratory illness caused by the Corona virus. Corona virus 2 (SARS-CoV-2) is a continuing global health crisis that has harmed the physiological and psychological health of people in over 200 countries worldwide. The current study performed a narrative review of its origin, epidemiology, transmission, clinical parameters, effects on mental health, management, vaccines and their trails, and future perspectives. The ease with which humans may transmit information to one another is unnoticeable in the early stages, making COVID-19 both terrifying and remarkable, but as time progresses, it can be managed successfully with the available therapies to some extent. Based on the condition and co-morbidities, therapeutic management is used in the pandemic situation, which includes drugs like antivirals, chloroquine and hydroxychloroquine, convalescent plasma therapy, Azithromycin, Corticosteroids, Cytokine’s, and oxygen therapy. Strategies such as self-quarantine, social isolation, and 70-day nationwide and state-by-state lockdowns in India aided in slowing the virus's spread, which may have been catastrophic otherwise. However, there are no clinically approved safer vaccines until the end of 2020. Several businesses have taken the lead in producing COVID-19 vaccines and came up with vaccines like Pfizer, Moderna from the US and UK, Covaxin, and Covishield from India, and vaccination programs began in India for targeting more than 300 million people.
Formulation and Characterization of Nanoparticle-Protein Sirtuin 1 (NPS1) by Nanoprecipitation Technique
Authors: Wihastuti Titin Andri , Chomsy Indah Nur , Cesa Fibe Yulinda , Sujuti Hidayat , Nurwidyaningtyas Wiwit , Kumboyono Kumboyono
Published: July 2024

Atherosclerosis is a cardiovascular disease caused by endothelial dysfunction. This situation will trigger the bone marrow to immediately replace it with new endothelial progenitor cells (EPC) cells. However, some studies suggest that EPC can experience premature senescence. Sirtuin-1 (SIRT1) is a cellular post-translational protein that has the task of repairing dysfunctional EPC cells. Studies have tried to develop SIRT1 activation, but currently, there are no studies that have attempted to increase SIRT1 levels in cells. Nanoparticles (NPS) are one of the methods in nanomedicine, which has the advantage of being a drug carrier. So, further research is needed on adding exogenous SIRT1 levels, NPS, which can improve the quality of EPC cells and prevent premature senescence. This study aims to report the formulation and characterization stages of nanoparticles carrying SIRT1 (NPS1) with different solvents, such as ethanol and aquadest. The method used in this formulation uses nanoprecipitation. The characterization of nanoparticles at this stage included organoleptic tests, pH tests, and quantifying using Nanodrops in determining the presence of adsorbed proteins. The pH and organoleptic test showed that the NPS1 formulation was acidic (K1 = 5.412 ± 0.73; K2 = 3.624 ± 0.45; F1 = 5.418 ± 0.55; F2 = 4.182 ± 0.07), yellow in color, and had a characteristic odor. Thus, the formulation and characteristics of NPS1 can be used as a method in drug development for anti-senescence therapy in EPC cells in further research, both in vitro, in vivo, and evaluation of preparations that are still very possible to be developed.
Exploring Genetic and Phenotypic Factors Contributing to Urethral Catheter Biofilm Formation in Hospitalised Patients in Jordan
Authors: Abu-Shoura Esra’a Jebreel Ibrahim , Hudu Shuaibu Abdullahi , AL- Quadan Tasneem Farouq
Published: July 2024

Background The biofilm phenomenon represents a prevalent mode of microbial life in nature which is characterized by cells irreversibly attaching to surfaces or each other and getting embedded in a matrix of extracellular polymeric substances. Object This study aimed to identify and characterize the genes associated with the common bacterial species responsible for biofilm formation in the catheters of hospitalized patients. Method Different bacterial strains were collected from catheterised patients at three local Jordanian hospitals for biofilm formation. The isolates were identified using Gram stain and Remel Rapid test. Biofilm formation was detected using the Tube method and tissue culture plate method. Result The presence of fimA and csgD genes was detected by polymerase chain reaction (PCR). Gram-negative bacteria species were isolated on the urethral catheters and the result shows the majority of the isolates were E. coli (40%), followed by K. pneumonia (27%). In comparison, the least was Citrobacter sp (2.6%). Similarly, some Gram-positive bacteria were also identified such as Staphylococcus aureus (4%) and Staphylococcus epidermidis (2.6%). K. pneumonia is strongly associated with biofilm formation (45%) followed by E. coli (33%). Conclusion Biofilm-associated genes, fimA and csgD were detected in all biofilm-positive samples containing the F plasmid, while csgD was detected in all biofilm-negative samples. Biofilm formation tends to be a prevalent process in patients included in this study and may cause dangerous complications in the patients especially in the elderly due to prolonged catheterization periods.
Role of Endoscopic Ultrasound in Diagnosis of Submucosal Lesions of Gastrointestinal Tract
Authors: Fathy Youssry , Sadek Ahmed , Wafy Wafaa , Elansary Mahmoud , Ragab Khaled , Ali Ahmed , Kamal Elwy , Gawad Amira Mohamed Abdel , Ahmed Hend M. , Shahba Mohamed A. , Youness Eman R.
Published: July 2024

The study aimed to understand the magnitude of submucosal lesions as part of the referral to the endoscopic ultrasound (EUS) unit in one year and know the percent of the different types and sites of submucosal lesions of GIT in Theodore Bilharz Research Institute as tertiary referral center draining Egyptian community. Within one year, all patients referred to the EUS unit at Theodore Bilharz Research Institute (TBRI) for assessment to assess the percent of submucosal lesions cases as part of the total referral and know the different types seen and their common sites as compared to the international literature. Patients diagnosed to have submucosal lesion will be subjected to; full clinical history, thorough physical examination, laboratory investigations, BUS for more characterization (site, size, location, echo pattern, etc.) and BUS-guided ﬁne-needle aspiration (FNA) for histopathological examination. The work comprised 36 patients; 16 females and 20 males. Their ages ranged from 21 to 75 years. All patients had preliminary upper endoscopy or colonoscopy. According to the indication of upper preliminary endoscopy or colonoscopy, 12 (33.3%) were complaining of melena, 5 (13.8%) hematemesis, 1 (2.7%) bleeding per rectum, 7 (19.4%) upper abdominal pain, 2 (5.5%) dysphagia, finally, 8 (22.2%) vomiting. According to the site of the submucosal lesion, 24 (66.6%) were gastric, 6 (16.6%) esophageal, 4 (11.1%) duodenal, 1 gastro-esophageal (2.8%), and 1 (2.8%) rectal. 34 cases (94%) were covered by normal overlying mucosa while 2 cases (6%) had superficial ulcerations. It was concluded that EUS criteria, can be used without FNA and histopathologic examination to reduce the cost of differentiation between malignant and benign lesions. All homogenous lesions were benign. Lesion size of 4.5 cm is a cut off; > 4.5 cm were malignant whereas < 4.5 cm were benign. All submucosal lesions without areas of breakdown were benign. Those infiltrating all layers are malignant. EUS guided fine needle aspiration (FNA) and histopathological examination should be done for some submucosal masses to put a definite diagnosis. EUS with colored Doppler is necessary in differentiating cystic from vascular lesions.
Diabetes Prediction Using Machine Learning and Flask
Authors: Raju N Kushal Kumar , Krishnamurthy Keshav , Bhagavath Bhuvanagiri Prahal , Shankar Nathan , Janani M. , Avinash N
Published: July 2024

Diabetes is one of the costliest chronic diseases, it is a metabolic disorder in which a patient has excessive blood sugar levels due to the body's inability to create enough insulin, and it can also cause long-term harm to the heart, blood vessels, eyes, kidneys, and nerves. Adults with diabetes are twice as likely as non-diabetics to have a heart attack or stroke. Despite its massive impact on the global population, no kind of diabetes has a cure. Although most medications help patients manage their symptoms to some extent, diabetics nevertheless suffer several long-term health concerns. So, if we are able to predict diabetes early, we could control it and it can be done by using Machine learning techniques. Our work aim is to predict if the patient has diabetes using Machine learning techniques and the ensemble method. We will be using four algorithms which are SVM, KNN, Logistic Regression, and Random Forest classifier and we would also compare all four models to check which model is giving the best accuracy and link our best model to a web app that could predict if the patient has any chances of having diabetes.
Factors influencing patient decision-making to undergo shoulder arthroplasty
Authors: Davies Andrew R. , Sabharwal Sanjeeve , Reilly Peter , Sankey R. A. , Griffiths Dylan , Archer Stephanie
Published: July 2024

Aims

Shoulder arthroplasty is effective in the management of end-stage glenohumeral joint arthritis. However, it is major surgery and patients must balance multiple factors when considering the procedure. An understanding of patients’ decision-making processes may facilitate greater support of those considering shoulder arthroplasty and inform the outcomes of future research.

Methods

Participants were recruited from waiting lists of three consultant upper limb surgeons across two NHS hospitals. Semi-structured interviews were conducted with 12 participants who were awaiting elective shoulder arthroplasty. Transcribed interviews were analyzed using a grounded theory approach. Systematic coding was performed; initial codes were categorized and further developed into summary narratives through a process of discussion and refinement. Data collection and analyses continued until thematic saturation was reached.

Results

Two overall categories emerged: the motivations to consider surgery, and the information participants used to inform their decision-making. Motivations were, broadly, the relief of pain and the opportunity to get on with life and regain independence. When participants’ symptoms and restrictions prevented them enjoying life to a sufficient extent, this provided the motivation to proceed with surgery. Younger participants tended to focus on maintaining employment and recreational activities, and older patients were eager to make the most of their remaining lifetime. Participants gathered information from a range of sources and were keen to optimize their recovery where possible. An important factor for participants was whether they trusted their surgeon and were prepared to delegate responsibility for elements of their care.

Conclusion

Relief of pain and the opportunity to get on with life were the primary reasons to undergo shoulder arthroplasty. Participants highlighted the importance of the patient-surgeon relationship and the need for accurate information in an accessible format which is relevant to people of different ages and functional demands.

Cite this article: Bone Jt Open 2024;5(7):543–549.
Influence of Laminate Twist and Clamping Pressure on Bonding Performance of Low-Grade Lumber in Cross-Laminated Timber
Authors: Adeniran Abiola Teslim , Englund Karl , Li Hui , Silva do Carmo Dalisson Peterson
Published: July 2024

The geometric variations of low-grade lumber raise concerns about bond strength of cross-laminated timber (CLT) produced from such lumber. This study seeks to investigate the effect of low clamping pressure and geometric variations of laminates on the bond strength of CLT. CLT panels were manufactured from low-grade grand fir (Abies grandis). Block shear tests and cyclic delamination tests were conducted on specimens randomly taken at specific points that correspond to a wide range of twist magnitude. Twist distribution in the lumber used as laminates in the CLT ranges from 0 to 160 mm. Results showed that twist magnitude and clamping pressure have significant effect on bond performance, with twist magnitude having an overriding effect on pressure.
Sound Presentation of the Silent History: Orature in Yvonne Vera’s The Stone Virgins
Authors: Duan Jing
Published: July 2024

Abstract: In her novel The Stone Virgins , Zimbabwean author Yvonne Vera provides a model of orature writing by using sound in the interaction between literature and history as well as literature and politics. This essay will principally draw on the ideas of Kenyan author Ngugi Wa Thiong’o as well as Roland Barthes’ ideas about listening to analyze this effect. As a medium of oral tradition that carries traditional aesthetic and cultural values throughout the text, sound and its spatiotemporal framework establish an interpretative community among the author, the character, and the reader. In this community, silence—an extreme state of sound—and distorted sound highlight the individual memories of the suppressed people and form a contrast with the collective national memory that is put under the framework of the history of patriotism by official nationalist discourse. To reconstruct the suppressed history of the common people, Vera adopts the performance mechanism of orature by sound and thereby presents the inner monologue of the characters, which helps restore the subjectivity of the oppressed and sends out a call to the reader to participate in the reconstruction of a new history with the people as subjects. Vera’s sound presentation of the silenced Zimbabwean history is an important example of orature writing, showcasing a strong sense of historical responsibility among Zimbabwean writers and contributing to the formation of originality of African Europhone literature.
Deep-learning approach to measuring the refractive index of transparent liquids
Authors: Wang Chuanqi , Gu Xiaoming , Zhong Zhenguo , Feng Guoying
Published: July 2024

A deep-learning approach is introduced to determine the refractive index of transparent liquids based on variations in the displacement of ultra-smooth interference fringes. The phase characteristics of these fringe variations captured in video data were analyzed and modeled using group-phase fitting. A neural network model, integrating a dense convolutional network with a long short-term memory network, was then developed and trained for high-precision liquid refractive index measurements. Experiments demonstrated an R2 accuracy of 99.70% and a mean squared error of 0.0003. This methodology has been confirmed to be temperature-dependent, considerably stable against external disturbances, highly accurate, and capable of real-time processing.
Geometrical misalignment-induced nonlinear error in homodyne interferometers
Authors: Lin Zichao , Feng Jingtong , Wu Yize , Zhu Hongyu , Deng Xiao , Dun Xiong , Cheng Xinbin , Duan Lifeng , Li Tongbao
Published: July 2024

This paper discusses the generation of a novel periodic nonlinear error in homodyne interferometers due to geometric misalignments. These misalignments arise from cumulative assembly errors among the sensor head interior, target mirror, test platform, and detector, leading to dynamic misplacement of the measurement beam on the detector's surface. A physical model was developed to explain this error, focusing on the interference field produced by Gaussian beams under conditions of beam separation and inclined interference. Observations from misaligned setups revealed a strong correlation between the modulation of the interference signal by an envelope curve and the distorted, complex patterns of Lissajous figures, with the movement of the target mirror. Numerical simulations and experimental results demonstrated that segmented elliptical fitting effectively calibrates vortex trajectories and substantially reduces periodic nonlinear errors. However, numerical simulations also uncovered previously undetected picometer-scale second-order nonlinear errors due to the geometric misalignments. This research highlights the physical mechanisms behind new nonlinear errors, emphasizing their importance in advancing homodyne interferometers toward picometer-level accuracy.
1283–1460 nm continuously tunable, watt-level bismuth-doped phosphosilicate fiber laser and its frequency doubling to a visible laser
Authors: Wang Hang , Song Luming , Chen Tingting , Huang Lu , Han Fengbo , Chen Huaixi , Dong Zhipeng , Bu Yikun , Melkumov Mikhail , Firstov Sergei , Lobanov Alexey , Luo Zhengqian
Published: July 2024

We report, to the best of our knowledge, the first demonstration of an O + E-band tunable watt-level bismuth-doped phosphosilicate fiber laser and its frequency doubling to tunable red laser. Benefiting from the two types of bismuth active centers associated with silicon and phosphorus introduced in one fiber, an ultrabroad gain is available in the designed low-water-peak bismuth-doped phosphosilicate fiber (Bi-PSF) pumped by a self-made 1239 nm Raman fiber laser. The high-efficiency tunable lasing is achieved with a maximum output power of 1.705 W around 1320 nm and a slope efficiency of 33.0%. The wavelength can be continuously tuned from 1283 to 1460 nm over a 177 nm spectral range, almost covering the whole O+E-bands. We further employ a polarization beam splitter in the cavity to output an O + E-band linear-polarization laser for second-harmonic generation by a designed multi-period MgO2:PPLN crystal, and a 650–690-nm tunable visible laser is correspondingly obtained. Such an O+E-wideband tunable high-power laser and the SHG red laser may have great potential in the all-band optical communications, biophotonics, and spectroscopy.
Sea surface Fresnel reflections difference driven de-glint algorithm for airborne optical images
Authors: Wang Mingxiu , Wang LiFeng , Jiao JunNan , Song QingJun , Ma ChaoFei , Yang Sheng , Ju WeiMin , Tian LiQiao , Lu YingCheng
Published: July 2024

This paper presents a glint correction algorithm for high spatial resolution optical remote sensing imagery captured by the ER-2 Airborne Visual Infrared Imaging Spectrometer (AVIRIS). The algorithm employs linear and differential techniques to mitigate sun glint and sky glint effects, encompassing statistical glint reflections resulting from variations in imaging angles within strips and inter-strip variations due to Fresnel reflectance disparities. It aims to diminish Fresnel reflectance diversity on water surfaces and mitigate the distortions induced by glint reflectance during spectral and ocean color inversion. A comparative analysis of spectral and ocean color information in AVIRIS images before and after correction reveals enhanced accuracy following the glint correction. By systematically addressing multiple glint reflections and their ramifications, this method offers a valuable framework for correcting water surface glint in diverse high spatial resolution optical imagery.