bluuebunny/crossref_metadata_2025_split huggingface dataset:
PANOVA-4 (EF-39): Pilot study of tumor treating fields (TTFields) therapy with atezolizumab, gemcitabine (GEM), and nab-paclitaxel (NabP) as first-line (1L) treatment for metastatic pancreatic ductal adenocarcinoma (mPDAC).
Authors: Seufferlein Thomas , Cubillo Gracian Antonio , Kueng Marc 
Published: January 2024

TPS718 Background: TTFields are electric fields that exert physical forces to disrupt cellular processes critical for cancer cell viability and tumor progression. TTFields therapy is noninvasive, locoregional, and is delivered via a portable electric field generator and skin-placed arrays. TTFields therapy has low risk of systemic toxicity and is approved for glioblastoma (and grade 4 glioma in Europe), and pleural mesothelioma. In vitro, TTFields (150 kHz) application decreased pancreatic cancer cell proliferation and clonogenicity; in vivo, TTFields concomitant with chemotherapy (chemo) had greater antitumor effect than chemo alone in orthotopic pancreatic tumors. Co-application of TTFields with immune checkpoint inhibitors (ICIs) significantly decreased tumor volume, increased tumor infiltration and IFN-γ production, and did not impede ICI-induced effector memory T-cell production versus in vivo controls. The pilot (phase 2) PANOVA clinical study (NCT01971281) showed safety and feasibility with TTFields therapy plus NabP and GEM in metastatic and locally advanced pancreatic adenocarcinoma (LAPC). The randomized, pivotal (phase 3) PANOVA-3 clinical study (NCT03377491), evaluating TTFields therapy with GEM and NabP in LAPC, is ongoing. Methods: PANOVA-4 (pilot, single-arm clinical study) assesses the safety and efficacy of TTFields therapy (NovoTTF-200T device) concomitant with atezolizumab, GEM, and NabP as 1L treatment for mPDAC. Eligible patients (pts) are ≥18 years of age and have a new mPDAC diagnosis, measurable abdominal disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, Eastern Cooperative Oncology Group performance status (ECOG PS) 0–1, and no prior systemic PDAC therapy. Atezolizumab (1680 mg, IV infusion) is given before chemo on day 1 of each 28-d cycle, with NabP (125 mg/m2 IV) and GEM (1000 mg/m2 IV) given on days 1, 8, and 15. TTFields therapy (150 kHz) is delivered for ≥18 h/d until disease progression per RECIST v1.1 or loss of clinical benefit. Clinical follow-up occurs every 4 weeks (q4w) with CT scans q8w. Survival is assessed every 3 mo post last on-site visit. The primary endpoint is disease control rate (DCR). Secondary endpoints include overall survival (OS), progression-free survival (PFS), 1-year OS rate, objective response rate, PFS at 6 mo, duration of response, and safety. 76 pts are required to achieve 80% power (1-sided α level 0.05) to detect a 63% DCR vs historical 48% DCR in pts with mPDAC receiving 1L GEM and NabP. Clinical trial information: EUCTR2022-003157-55 .
Cemiplimab for Kidney Transplant Recipients With Advanced Cutaneous Squamous Cell Carcinoma
Authors: Hanna Glenn J. , Dharanesswaran Harita , Giobbie-Hurder Anita , Harran John J. , Liao Zixi , Pai Lori , Tchekmedyian Vatche , Ruiz Emily S. , Waldman Abigail H. , Schmults Chrysalyne D. , Riella Leonardo V. , Lizotte Patrick , Paweletz Cloud P. , Chandraker Anil K. , Murakami Naoka , Silk Ann W. 
Published: January 2024

PURPOSE Cemiplimab is approved for treating locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC). Solid organ transplant recipients have been excluded from immunotherapy trials, given concern for allograft rejection despite their increased risk of skin cancers. Chronic immunosuppression is necessary to prevent organ rejection but may attenuate antitumor response with PD-1 inhibitors. METHODS We report a phase I study of cemiplimab for kidney transplant recipients (KTRs) with advanced CSCC. After cross-taper to a mammalian target of rapamycin (mTOR) inhibitor and pulsed dose corticosteroids (prednisone 40 mg once daily, the day before and on days 1-3 of each cycle, followed by 20 mg once daily on days 4-6, then 10 mg once daily until the day before each subsequent cycle), patients received cemiplimab 350 mg intravenously once every 3 weeks for up to 2 years and were assessed for response every 8 weeks. The primary end point was the rate of kidney rejection, with key secondary end points including rate and duration of response, and survival. RESULTS Twelve patients were treated. No kidney rejection or loss was observed. A response to cemiplimab was observed in five of 11 evaluable patients (46%; 90% CI, 22 to 73), including two with durable responses beyond a year. Median follow-up was 6.8 months (range, 0.7-29.8). Treatment-related grade 3 or greater adverse events occurred in five patients (42%), including diarrhea, infection, and metabolic disturbances. One patient died of angioedema and anaphylaxis attributed to mTOR inhibitor cross-taper. CONCLUSION mTOR inhibitor and corticosteroids represent a favorable immunosuppressive regimen for KTRs with advanced CSCC receiving immunotherapy. This combination resulted in durable antitumor responses with no kidney rejection events (funded by Regeneron Pharmaceuticals [ClinicalTrials.gov identifier: NCT04339062 ]).
Tirzepatide Improved Markers of Islet Cell Function and Insulin Sensitivity in People With T2D (SURPASS-2)
Authors: Frias Juan P , De Block Christophe , Brown Katelyn , Wang Hui , Thomas Melissa K , Zeytinoglu Meltem , Maldonado Juan M 
Published: January 2024

Abstract

Context
In previous SURPASS studies tirzepatide reduced hemoglobin glycated A1c (HbA1c) and body weight and improved markers of insulin sensitivity and β-cell function to a greater extent than comparators.

Objective
Explore changes in biomarkers of β-cell function and insulin sensitivity and in efficacy profiles in baseline biomarker quartile analyses with tirzepatide compared to semaglutide.

Design
Post hoc analysis of SURPASS-2 phase 3 trial (participants randomly assigned to receive weekly subcutaneous tirzepatide or semaglutide for 40 weeks).

Setting
Post hoc analysis of 128 sites in 8 countries.

Participants
A total of 1879 participants with type 2 diabetes.

Interventions
Once-weekly tirzepatide (5, 10, 15 mg) or semaglutide 1 mg.

Main outcomes measures
Change in homeostatic model assessment indices for pancreatic β-cell function (HOMA2-B) and for insulin resistance (HOMA2-IR), fasting glucagon, fasting C-peptide, and fasting insulin.

Results
At week 40, a greater increase in HOMA2-B was seen with tirzepatide (5, 10, 15 mg) doses (96.9-120.4%) than with semaglutide 1 mg (84.0%) (P &lt; .05). There was a greater reduction in HOMA2-IR with all doses of tirzepatide (15.5%-24.0%) than with semaglutide 1 mg (5.1%) (P &lt; .05). Tirzepatide 10 and 15 mg resulted in a significant reduction in both fasting C-peptide (5.2%-6.0%) and fasting glucagon (53.0%-55.3%) compared with an increase of C–peptide (3.3%) and a reduction of glucagon (47.7%) with semaglutide 1 mg (P &lt; .05). HbA1c and body weight reductions were greater with all tirzepatide doses than semaglutide within each HOMA2-B and HOMA2-IR baseline quartile.

Conclusion
In this post hoc analysis, improvements in HbA1c and weight loss were consistent and significantly higher with tirzepatide, regardless of baseline β-cell function and insulin resistance, compared with semaglutide.
ASCL2 is a key regulator of the proliferation–differentiation equilibrium in the esophageal epithelium
Authors: Hamilton Maude , Mars Zoéline , Sedeuil Molly , Rolland Marjorie , Jean Dominique , Boudreau François , Giroux Véronique 
Published: January 2024

ABSTRACT
The esophagus is protected from the hostile environment by a stratified epithelium, which renews rapidly. Homeostasis of this epithelium is ensured by a rare population of stem cells in the basal layer: Keratin 15+ (Krt15+) cells. However, little is known about the molecular mechanisms regulating their distinct features, namely self-renewal, potency and epithelial regeneration. Achaete-scute family BHLH transcription factor 2 (ASCL2) is strongly upregulated in Krt15+ stem cells and is known to contribute to stem cell maintenance in other tissues. Herein, we investigated the role of ASCL2 in maintaining homeostasis under normal and stress conditions in the esophageal epithelium. ASCL2 overexpression severely dysregulated cell differentiation and cell fate. Proliferation was also reduced due potentially to a blockage in the G1 phase of the cell cycle or an induction of quiescence. Mass spectrometry analysis confirmed alterations in several proteins associated with differentiation and the cell cycle. In addition, overexpression of ASCL2 enhanced resistance to radiation and chemotherapeutic drugs. Overall, these results denote the role of ASCL2 as a key regulator of the proliferation-differentiation equilibrium in the esophageal epithelium.
Prevalence of Abomasum Nematode infection in Sheep from North of Iran
Authors: Hamzehali Tehrani M , Shemshadi B , Shayan P , Shirali S , Panahi N 
Published: January 2024

Abstract
In many countries, small ruminants provide the primary source of human protein and play an important role in livestock production. Parasitic infections, especially gastrointestinal parasites, cause economic losses such as reduced fertility and milk production, damage to the leather industry, weight loss, treatment costs, and losses in severe infections. Thus, identifying and classifying these parasites, including the above cases, is essential for scientific research in any country. This study aimed to Prevalence of Abomasum Nematode infection in Sheep from North of Iran. In the present cross-sectional descriptive study, we have studied the prevalence of infection with abomasum nematodes in sheep in northern Iran from April 2020 to September 2021 in 2400 abomasum sheep slaughtered in industrial slaughterhouses in Gilan and Mazandaran provinces (1200 sheep from each province). With three age groups of below two years, two to four years, and above four years and gender segregation of hosts, after necropsy and preparation of sheep abomasal mucosa chip and isolation and segregation of samples, we studied the morphologic and morphometric characteristics of the samples. The actions were performed according to the taxonomic keys and using SPSS software V.16 and Paired Sample T-Test statistical test to determine the level of significance of the data (p <0.05) to classify and compare the obtained data and examine the ratio. The sex of the host was determined by the age of the animal and the prevalence of the parasite at the mentioned ages. The present study results and comparison of the prevalence of infection in Gilan and Mazandaran provinces showed that Marshallagia marshalli had the highest prevalence of 94.6% and 91.9% in Mazandaran and Gilan province, respectively. The prevalence of Ostertagia circumcincta was 87.2% and 77.2% in Gilan and Mazandaran provinces. The prevalence of Ostertagia occidentalis was 86.9% in Gilan province and 78% in Mazandaran province, while the prevalence of Parabronema skrjabini was 86.6% in Gilan province and 61.2% in Mazandaran province. The prevalence of Haemonchus contortus was 66.8% and 60.5% in Gilan and Mazandaran, the lowest prevalence in these two provinces. The present study results showed the importance of combating the spread of parasitic infections with strategic treatment methods and biological control of these parasites. Also, various reports of drug resistance in abomasal nematodes should be emphasized more and more by competent bodies.
Keywords: Abomasum, Nematodes, North of Iran, Parasitic infections, Sheep.
Presumptive injection-site sarcoma in a white tiger (Panthera tigris tigris): A case report
Authors: Moosavian H , Esmaeilzadeh H , Fazli M , Thompson CA , Farajzadeh A 
Published: January 2024

A 6-year-old female White Tiger (Panthera Tigris Tigris) was presented with a history of a recurrent ulcerating mass on the right lumbar wall which initially, was removed by surgery one year before presentation. Cytological and histological findings were consistent with a cutaneous injection site sarcomas. Immunohistochemistry results revealed that the neoplastic cells were strongly positive for vimentin and weakly positive for alpha-smooth muscle actin (SMA), but negative for Cytokeratin AE1/AE3, s100, and Desmin. Positive staining for vimentin and SMA is consistent with myofibroblast reactivity and reflects a continuous inflammatory response seen in feline injection-site sarcomas. Feline injection-site sarcomas are the most serious adverse effect following injection of the vaccine or some other pharmaceutical substances and should be considered in the differential diagnosis of skin swelling in injection sites in the Felidae family. Limited data are available for these tumors in animals outside of domesticated cats. To the best of our knowledge, there exists no available published information on the injection-site sarcoma in tigers. Similar to domestic felids, this case highlights the importance of considerations and management options in vaccination schedules for the reduction of sarcoma risk in wild felids.
Variants of changes in blood pressure during its three consecutive registrations
Authors: Popovych Igor , Kozyavkina Nataliya , Barylyak Liliya , Vovchyna Yuliya , Voronych-Semchenko Nataliya , Zukow Walery , Tsymbryla Volodymyr 
Published: January 2024

Introduction and aim. Earlier we noted that the patterns of blood pressure (BP) parameters recorded three times in a row deserve special attention. The aim of this article is to classify variants of changes in systolic and diastolic BP during its three consecutive registrations.
Material and methods. The object of observation were 20 volunteers: ten women and ten men aged 33-76 years with maladaptation. Systolic (Ps) and diastolic (Pd) BP was measured in a sitting position three times in a row without pause. Each patient was tested twice with a 7-day interval.
Results. We confirmed the diversity of Ps2/Ps1, Ps3/Ps1, Pd2/Pd1 and Pd3/Pd1 patterns identified earlier. 5 clusters were identified. The most characteristic feature of clusters are the changes in Pd during the second registration. Instead, the contribution of changes in Ps during the second registration is minimal. It was found that in 18 members of the most numerous cluster No1, Pd is practically stable, while Ps consistently falls with each subsequent measurement. In 8 members of cluster No.4, Pd slightly but consistently decreases, and Ps slightly but consistently increases. In 4 members of cluster No.5, Pd significantly decreases at the second measurement and remains at this level at the third measurement; Ps reacts to measurements similarly, but less noticeably. In 7 members of cluster No.3, Pd significantly increases in the second measurement, but in the next one it only slightly exceeds the initial level, while Ps is practically stable. In 3 members of cluster No2, Pd increases even more during the second measurement and remains significantly higher than the initial one thereafter, while Ps steadily decreases.
Conclusion. In the process of successive three-time measurement of blood pressure, changes in its values, which differ in severity and direction, were found, grouped into 5 patterns. The following article will show that each pattern is characterized by a specific constellation of parameters of the neuroendocrine-immune complex and metabolism, which determines a certain reaction to the occlusion of the brachial arteries by the factors of vasoconstriction, vasodilatation and inotropism.
Low Gamma-Glutamyl Transferase Cholestasis in a Patient With X-Linked Myotubular Myopathy and Crohn's Disease
Authors: Abi Radi Abou Jaoudeh Rasha , McCleary Brendan , Radhakrishnan Kadakkal 
Published: January 2024

ABSTRACT
X-linked myotubular myopathy (XLMTM) is a neuromuscular disorder manifesting at birth with hypotonia and respiratory distress. We describe the XLMTM case presenting at birth who developed normal gamma-glutamyl transferase cholestasis at 1 year of age. He was also diagnosed with Crohn's disease 4 years later. His cholestasis could be attributed to progressive familial intrahepatic cholestasis (PFIC) or primary sclerosing cholangitis in the setting of Crohn's disease. However, genetic testing ruled-out PFIC, and his radiographic and liver biopsy findings were not suggestive of primary sclerosing cholangitis. We believe that this cholestasis is related to XLMTM leading to a PFIC-like state.
Sevelamer-Induced Gastrointestinal Disease in 12 Patients with End-Stage Renal Disease: A Case Series
Authors: Todd James , Saboori Shadab , Zeidan Joseph , Ahrens William , Jacobs Carl , Moshiree Baha 
Published: January 2024

INTRODUCTION:
Isolated case reports and case series have linked the use of sevelamer to severe gastrointestinal (GI) inflammation and perforation among patients with end-stage renal disease.

METHODS:
In this study, we identified 12 cases of biopsy-proven sevelamer-induced gastrointestinal disease from a large urban community hospital over the course of 5 years. We described baseline characteristics, sites and types of injury, histological findings, timing and dosing of sevelamer initiation compared with symptom onset, and in a smaller subset, endoscopic resolution post drug cessation. We also reviewed preexisting conditions to identify trends in populations at risk.

RESULTS:
Several of the patients reviewed had preexisting conditions of decreased motility and/or impaired mucosal integrity. The presentation of disease was broad and included both upper-GI and lower-GI pathologies and in varying severity.

DISCUSSION:
There is a broad phenotypic range of sevelamer-induced gastrointestinal disease. As this becomes a more frequently recognized pathology, clinicians should be aware of how it may present and which populations may be more susceptible.
Reflexões sobre a memória de Joaquim Pinto de Oliveira, o Tebas (1733-1811)
Authors: Reis Luis Gustavo 
Published: January 2024

Este artigo tem como objetivo refletir sobre alguns aspectos da memória de Joaquim Pinto de Oliveira (1733-1811), popularmente conhecido como Tebas. Desde as primeiras décadas do século XX, cerca de 130 anos após seu sepultamento, Tebas tem despertado o interesse de diferentes estudiosos. Nos últimos três anos, especialmente, sua trajetória ganhou ainda mais força, quando o personagem passou a estampar manchetes de jornais, foi tema de livro, dissertação de mestrado, ganhou outorga de arquiteto, estátua na região central de São Paulo e pessoas interessadas em sua história.
Nascido de ventre escravizado, na cidade Santos, Tebas migrou para São Paulo em um período em que a cidade passava por mudanças administrativas, políticas, econômicas e arquitetônicas que impactaram decisivamente sua vida. Tebas dominava a técnica de construir edifícios aplicando pedras de cantaria, material que as igrejas em São Paulo começaram a usar em seus frontispícios a partir da segunda metade do século XVIII. Reconhecido por suas habilidades, o mestre de obras trabalhou na torre da antiga Catedral da Sé, reformou o Mosteiro de São Bento, a igreja da Ordem Terceira do Carmo e deixou marcas na paisagem urbana da cidade visíveis até os dias atuais.
Design and Implementation of a Problem-Based Learning Module in a Clinical Radiography Course to Foster Image Critique Skills: An Evaluative Case Study
Authors: Balac Vesna , Ozogul Gamze 
Published: January 2024

Numerous studies have been conducted to examine the effectiveness of problem-based learning (PBL) in higher education programs that prepare health professionals for their clinical careers, such as undergraduate nursing programs. Even though undergraduate nursing education and radiography education have similarities, studies that focus on the effectiveness of PBL in radiography have not been documented in the literature. While the nature of the nursing and radiography disciplines may lead radiography educators to believe that PBL use in radiography education may be appropriate, based on existing research in nursing, its effectiveness and student attitudes need to be researched before curriculum-wide PBL implementation is planned. A mixed methods evaluative case study was conducted to investigate if a PBL module had an effect on radiography students’ image critique skills and their perceptions. Quantitative data collection instruments consisted of a pretest and a posttest to assess students’ image critique skills before and after PBL. Qualitative data collection instruments included a pre- and post-PBL survey, as well as structured reflections after the PBL module. The results showed a statistically significant difference between the pretest and the posttest, suggesting that the PBL module improved image critique skills in radiography students. In addition, students reported to feel significantly better prepared for image critique after PBL, and perceived working in a group as a good way to practice critiquing images. Difficulties reported were related to working in a group and transitioning to PBL, most likely due to being accustomed to lecture-based instruction.
Volodymyr Zelensky’s Presidential Rhetoric as a Strategic Resource
Authors: Hordecki Bartosz , Nosova Bogdana 
Published: January 2024

The article exposes Volodymyr Zelenskyy’s presidential rhetoric as a strategic resource in Ukraine’s confrontation with the Russian aggressor after 24.02.2022. By grasping varied aspects of political communication exercised by the Ukrainian president, we try to explain how and why the Ukrainian state is capable of creating an effective communication campaign in times of being invaded by its powerful neighbor. According to our assumptions, it is particularly a matter of 1. clarity and relevance of goals that the head of Ukraine wants to achieve through his rhetoric, 2. inclusiveness of the formula that Zelenskyy uses to demonstrate the essence of being Ukrainian and contributing to Ukrainian culture; 3. his artistic proficiency which helps him in identifying the proper means of persuading broad audiences to his narrative and agenda.
To verify the accuracy of the hypotheses, we employed theoretical concepts of logos, ethos, and pathos in the course of analysing chosen speeches delivered by the Ukrainian president. Moreover, the notions of “facilitating leadership” proposed by George C. Edwards III, and the “Medici Effect” coined by Frans Johansson are involved.
The outcomes of the work confirmed our expectations. The high quality and strategic meaning of Zelenskyy’s statements after 24.02.2022 come from three main sources, i.e., 1. transparent and justified message; 2. the unifying qualities of the speaker; 3. his persuasive skilfulness.
“The Ukrainian Issue” at the G7 Summits in Conditions of the Russian-Ukrainian Conflict 2014–2022
Authors: Nemych Olena 
Published: January 2024

This article is aimed to provide an in-depth analysis of the G7 policy towards Ukraine in the context of Russian invasion 2014–2022. The hypothesis formed and verified in this paper is that since the beginning of Russian expansion on Ukraine in 2014 the G7 members have called for a negotiated process and a political solution to the conflict, but it was hardly possible to quickly adopt and implement timely and adequately decisions to resolve the crisis in the region through the bonding of global and regional security mechanisms. Thus, a comfortable field for prolonging the conflict, which has developed into a full-scale war, was formed. The research methodology is based on systemic, historical, structural and political approaches to the study of the problem. Research methods are comparative analysis, content analysis, chronological and classification methods.
This study allows us to distinguish the stages of the G7 involvement in the “Ukrainian issue” in the period of 2014–2022. During these years, the group’s policy underwent three shifts in course, influenced in large part not only by the activities of Russia, but also by policy course changes of individual G7 members. The example of the nine-year unresolved local Russian-Ukrainian conflict shows that such crisis may pose a threat not only to regional, but also to global stability and there is a strong correlation between them.