bluuebunny/crossref_metadata_2025_split huggingface dataset:
BRAF and MEK inhibitor combinations induce potent molecular and immunological effects in NRAS‐mutant melanoma cells: Insights into mode of action and resistance mechanisms
Authors: Dinter Lisa , Karitzky Paula C. , Schulz Alexander , Wurm Alexander A. , Mehnert Marie‐Christin , Sergon Mildred , Tunger Antje , Lesche Mathias , Wehner Rebekka , Müller Anja , Käubler Theresa , Niessner Heike , Dahl Andreas , Beissert Stefan , Schmitz Marc , Meier Friedegund , Seliger Barbara , Westphal Dana 
Published: December 2023

AbstractAbout 25% of melanoma harbor activating NRAS mutations, which are associated with aggressive disease therefore requiring a rapid antitumor intervention. However, no efficient targeted therapy options are currently available for patients with NRAS‐mutant melanoma. MEK inhibitors (MEKi) appear to display a moderate antitumor activity and also immunological effects in NRAS‐mutant melanoma, providing an ideal backbone for combination treatments. In our study, the MEKi binimetinib, cobimetinib and trametinib combined with the BRAF inhibitors (BRAFi) encorafenib, vemurafenib and dabrafenib were investigated for their ability to inhibit proliferation, induce apoptosis and alter the expression of immune modulatory molecules in sensitive NRAS‐mutant melanoma cells using two‐ and three‐dimensional cell culture models as well as RNA sequencing analyses. Furthermore, NRAS‐mutant melanoma cells resistant to the three BRAFi/MEKi combinations were established to characterize the mechanisms contributing to their resistance. All BRAFi induced a stress response in the sensitive NRAS‐mutant melanoma cells thereby significantly enhancing the antiproliferative and proapoptotic activity of the MEKi analyzed. Furthermore, BRAFi/MEKi combinations upregulated immune relevant molecules, such as ICOS‐L, components of antigen‐presenting machinery and the “don't eat me signal” molecule CD47 in the melanoma cells. The BRAFi/MEKi‐resistant, NRAS‐mutant melanoma cells counteracted the molecular and immunological effects of BRAFi/MEKi by upregulating downstream mitogen‐activated protein kinase pathway molecules, inhibiting apoptosis and promoting immune escape mechanisms. Together, our study reveals potent molecular and immunological effects of BRAFi/MEKi in sensitive NRAS‐mutant melanoma cells that may be exploited in new combinational treatment strategies for patients with NRAS‐mutant melanoma.
Tongue microarchitecture and functional characterization of the lingual papillae in the desert hedgehog (Paraechinus aethiopicus)
Authors: Massoud Diaa , AbdRabou Mervat A. , Fouda Maged , Shaldoum Fayez , Alrashdi Barakat M. , Germoush Mousa O. , Alfassam Haifa E. , Al‐ Otaibi Aljohara M. , Soliman Soha A. , Abd‐Elhafeez Hanan H. , Hassan Mervat , Mahmoud Ayman M. 
Published: December 2023

AbstractThe present work attempted to provide a comprehensive description of the morphoanatomical, histological, and ultrastructural characteristics of the tongue in the desert hedgehog (Paraechinus aethiopicus), and to correlate lingual modifications to the feeding lifestyle. Five adult male hedgehogs were utilized in our investigation. The macroscopic observations revealed elongated, with a moderately pointed apex, tongue and the tongue dorsum lacks both lingual prominence and median sulcus. The main subdivisions of the tongue are radix linguae (root), corpus linguae (body), and apex linguae (apex). The tongue dorsum carries two types of mechanical (conical and filiform) and gustatory (fungiform and circumvallate) papillae. The lingual apex is characterized by the existence of a unique encapsulated muscular structure. Additionally, the lingual glands were interposed between the muscular strands and no lingual glands were detected on the lingual apex. The dorsal surface of the lingual apex exhibited the highest level of keratinization as revealed by histochemical staining while the root showed moderate staining. The topography of the tongue was investigated by scanning electron microscopy (SEM). The obtained results are important to provide basic knowledge that can contribute to better understanding of the nourishment, feeding habits and behavior in this species. Furthermore, the addition of the newly investigated species may help us to determine the evolutionary relationships among species.
[11C]CO2 BOP fixation with amines to access 11C‐labeled ureas for PET imaging
Authors: Bonnemaire Coralie M. , Windhorst Albert D. , Orru Romano , Ruijter Eelco , Vugts Danielle J. 
Published: December 2023

Carbon‐11 (11C) is a widely used radionuclide for positron emission tomography (PET) owing to the omnipresence of carbon atoms in organic molecules. While its half‐life of 20.4 min is ideal for imaging and dosimetry, it also limits the synthetic possibilities. As such, the development of fast and easy, high‐yielding synthesis methods is crucial for the application of 11C‐labeled tracers in humans.In this study, we present a novel and efficient method for the reaction of [11C]CO2 with amine precursors using benzotriazole‐1‐yl‐oxy‐tris‐(dimethylamino)‐phosphonium hexafluorophosphate (BOP) to access 11C‐labeled ureas. Our method is extremely fast as it only requires transfer of [11C]CO2 into a solution with precursor and BOP at room temperature, where it reacts momentary into the desired 11C‐labeled urea. This simple procedure makes it possible to radiolabel urea directly from [11C]CO2 without the need for advanced equipment, making the method applicable for all laboratories where [11C]CO2 is available. We synthesized a small series of aliphatic symmetrical and non‐symmetrical 11C‐labeled ureas using this method, and achieved good to excellent yields.The novelty of our study lies in the fact that peptide coupling reagent BOP is used for the first time in radiochemistry to activate [11C]CO2, facilitating its reaction with amines to obtain 11C‐labeled ureas.
Viral AMGs‐driven pentose phosphate pathway in natural wetland
Authors: Li Yanmei , Yu Hang , Xiong Lingling , Wei Yunlin , Li Haiyan , Ji Xiuling 
Published: December 2023

AbstractViruses exist anywhere on earth where there is life, and among them, virus‐encoded auxiliary metabolic genes (AMGs) can maintain ecosystem balance and play a major role in the global ecosystem. Although the function of AMGs has been widely reported, the genetic diversity of AMGs in natural ecosystems is still poorly understood. Exploring the genetic diversity of viral community‐wide AMGs is essential to gain insight into the complex interactions between viruses and hosts. In this article, we studied the phylogenetic tree, principal co‐ordinates analysis (PCoA), α diversity, and metabolic pathways of viral auxiliary metabolism genes involved in the pentose phosphate pathway (PPP) through metagenomics, and the changes of metabolites and genes of host bacteria were further studied by using Pseudomonas mandelii SW‐3 and its lytic phage based on metabolic flow and AMGs expression. We found that the viral AMGs in the Napahai plateau wetland were created by a combination of various external forces, which contributed to the rich genetic diversity, uniqueness, and differences of the virus, which promoted the reproduction of offspring and better adaptation to the environment. Overall, this study systematically describes the genetic diversity of AMGs associated with the PPP in plateau wetland ecosystems and further expands the understanding of phage–host unique interactions.
The recent evolution of the salt marsh ‘Pantano Grande’ (NE Sicily, Italy): interplay between natural and human activity over the last 3700 years
Authors: Palli Jordan , Monaco Lorenzo , Bini Monica , Cosma Emanuela , Giaccio Biagio , Izdebski Adam , Masi Alessia , Mensing Scott , Piovesan Gianluca , Rossi Veronica , Sadori Laura , Wagner Bernd , Zanchetta Giovanni 
Published: December 2023

AbstractCombined natural processes and human activities shaped the late Holocene landscape history in many Mediterranean regions. This is especially true with areas subjected to specific human interest, such as coastal areas morphologically suitable to the establishment of harbours. Here, we test the hypothesis on the location of the Roman harbour Portus Trajectus in Peloro Cape (NE Sicily, Italy) and describe the evolution of the area over the last 3700 years through lithostratigraphic, geochemical, meiofauna and microfossil analyses performed on a new sediment core recovered from the coastal salt marsh Pantano Grande (aka Lago di Ganzirri). The age–depth model was developed on radiocarbon dates and geochemical fingerprinting of two tephra layers. Results indicate that the area underwent dramatic changes ca. 650 bce. The anthropogenic impact of Greek colonies may have contributed to modifying the coastal environment of Peloro Cape due to their widespread impact on natural resources. This happened at many localities in the Mediterranean, indicating the magnitude of impact of the Greek colonies over the landscape. According to our results, it is unlikely that the current Pantano Grande basin was used as a harbour in Roman times, although the presence of a harbour in the nearby Pantano Piccolo marsh cannot be excluded. Pantano Grande had been isolated from the sea for more than 2000 years. Human intervention in the 19th century halted that isolation and provided the background for the ecological, economic and social functions the salt marsh performs today.
Minimally invasive interval cytoreductive surgery for advanced ovarian cancer
Authors: Melamed Alexander , Eisenhauer Eric L. 
Published: December 2023

AbstractWith the increasing use of neoadjuvant chemotherapy, it has also become apparent that some patients will require a less extensive interval cytoreductive surgery which could be performed as a minimally invasive procedure. This observation, and expertise with minimally invasive surgery for other indications in gynecologic oncology, has driven surgeons in the United States and other countries to perform an increasing portion of interval cytoreductive surgery using minimally invasive techniques. Further observational and trial data will continue to inform which patients are best suited for this approach.
The impact of sex on treatment and outcome in relation to histological subtype in patients with resectable gastric cancer: Results from the randomized CRITICS trial
Authors: Caspers Irene A. , Slagter Astrid E. , Lind Pehr , Sikorska Karolina , Wiklund Katja , Pontén Fredrik , Nordsmark Marianne , van de Velde Cornelis J. H. , Kranenbarg Elma Meershoek‐Klein , van Sandick Johanna W. , Jansen Edwin P. M. , van Laarhoven Hanneke W. M. , Verheij Marcel , van Grieken Nicole C. T. , Cats Annemieke 
Published: December 2023

AbstractBackground and ObjectiveThis study aims to investigate the impact of sex on outcome measures stratified by histological subtype in patients with resectable gastric cancer (GC).MethodsA post‐hoc analysis of the CRITICS‐trial, in which patients with resectable GC were treated with perioperative therapy, was performed. Histopathological characteristics and survival were evaluated for males and females stratified for histological subtype (intestinal/diffuse). Additionally, therapy‐related toxicity and compliance were compared.ResultsData from 781 patients (523 males) were available for analyses. Female sex was associated with a distal tumor localization in intestinal (p = 0.014) and diffuse tumors (p < 0.001), and younger age in diffuse GC (p = 0.035). In diffuse GC, tumor‐positive resection margins were also more common in females than males (21% vs. 10%; p = 0.020), specifically at the duodenal margin. During preoperative chemotherapy, severe toxicity occurred in 327 (63%) males and 184 (71%) females (p = 0.015). Notwithstanding this, relative dose intensities were not significantly different between sexes.ConclusionsPositive distal margin rates were higher in females with diffuse GC, predominantly at the duodenal site. Females also experience more toxicity, but this neither impacts dose intensities nor surgical resection rates. Clinicians should be aware of these different surgical outcomes when treating males and females with GC.
Seasonal and spatial variability of CO2 emissions in a large tropical mangrove‐dominated delta
Authors: Chielle Raisa S.A. , Marins Rozane V. , Cavalcante Mariany S. , Cotovicz Luiz C. 
Published: December 2023

AbstractThis study quantified the seasonal and spatial variability of partial pressure of CO2 (pCO2) and water‐atmosphere CO2 fluxes in the Parnaíba River Delta, the largest delta in the Americas. It is a pristine equatorial, mangrove‐dominated environment located in a transitional between humid and semi‐arid climates, with marked seasonality in rainfall and river discharge. Major channels and bays were sampled during dry and wet seasons, with continuous measurements of pCO2, temperature, salinity, and wind velocity. Subsurface water samples were collected in discrete stations for pH, total alkalinity (TA), dissolved inorganic carbon (DIC), dissolved oxygen and chlorophyll a quantification. A significant positive correlation between carbonate system parameters with salinity was found in both periods, with salinity significantly higher in the dry season. Strong deviations of pCO2, TA, and DIC from two endmembers conservative mixing were found, particularly in mangrove‐dominated waters, due to organic matter degradation. The Delta showed high spatial variability of pCO2, with the highest values in mangrove‐dominated waters, moderate in the river‐dominated regions, and lowest in the high salinity areas, suggesting that pCO2 variability is likely controlled by a combination of river‐ocean mixing and biological processes (respiration and photosynthesis). The Delta outgasses about 20 times less CO2 in the dry season (9.06 ± 11.09 mmol m−2.d−1) than in the rainy season (209.68 ± 250.87 mmol m−2 d−1). Our results indicate this large mangrove‐dominated tropical delta is an important source of CO2 to the atmosphere, but a sharp decrease was observed during dry periods.
Oral Troxerutin Alleviates Depression Symptoms in Mice by Modulating Gut Microbiota and Microbial Metabolism
Authors: Lan Zhi‐fang , Yao Wei , Xie Yi‐ci , Chen Wushisi , Zhu Yin‐ying , Chen Jia‐qi , Zhou Xing‐yi , Huang Jun‐qing , Wu Man‐si , Chen Jia‐xu 
Published: December 2023

ScopeA growing body of evidence suggests that the harmful gut microbiota in depression patients can play a role in the progression of depression. There is limited research on troxerutin's impact on the central nervous system (CNS), especially in depression. The study finds that troxerutin effectively alleviates depression and anxiety‐like behavior in mice by increasing the abundance of beneficial bacteria like Lactobacillus and Firmicutes while decreasing the abundance of harmful bacteria like Proteobacteria, Bacteroides, and Actinobacteria in the gut. Furthermore, the research reveals that troxerutin regulates various metabolic pathways in mice, including nucleotide metabolism, caffeine metabolism, purine metabolism, arginine biosynthesis, histidine metabolism, 2‐oxocarboxylic acid metabolism, biosynthesis of amino acids, glycine, serine and threonine metabolism, and Arginine and proline metabolism.ConclusionsIn conclusion, the study provides compelling evidence for the antidepressant efficacy of troxerutin. Through the investigation of the role of intestinal microorganisms and metabolites, the study identifies these factors as key players in troxerutin's ability to prevent depression. Troxerutin achieves its neuroprotective effects and effectively prevents depression and anxiety by modulating the abundance of gut microbiota, including Proteobacteria, Bacteroides, and Actinobacteria, as well as regulating metabolites such as creatine.
Microstrip‐line‐based K‐band isolator and Ku‐band phase shifter with barium hexa ferrite disc
Authors: Akkapanthula Sai Haranadh , Kagita Srujana , Voma U. K. 
Published: December 2023

AbstractThis article deals with the operational behavior of barium hexaferrite (BHF) disc when incorporated in microwave substrates for wireless applications. A microstrip line printed on a Rogers substrate (35 mm × 35 mm × 1.6 mm) has been used in the design to observe the effect of BHF material. A BHF circular‐shaped disc of radius 4.5 mm and thickness 1 mm is inserted in the middle of the microstrip line. The ferrite is biased using miniature lightweight neodymium magnets stacked one over the other to obtain desired magnetic field strength. The proposed microstrip line inserted with a BHF disc exhibits wide band isolation properties in the K‐band (15–21 GHz) with an average isolation of 20 dB and peak isolation of 51 dB centered at 18.5 GHz. It is observed that the same circuit is behaving as a phase shifter showing a 45° ± 3° phase shift in the band ranging from 12 to 14 GHz. The proposed compact microstrip‐line circuit can be used as both ferrite phase shifter and isolator in consecutive bands (Ku‐ and K‐bands) with ease of integration and biasing.
Treatment practices and response in kaposiform hemangioendothelioma: A multicenter cohort study
Authors: Borst Alexandra J. , Eng Whitney , Griffin Morgan , Ricci Kiersten W. , Engel Elissa , Adams Denise M. , Dayneka Jillian , Cohen‐Cutler Sally J. , Andreoli Steven M. , Wu Melinda D. , Wheeler Allison P. , Heym Kenneth M. , Crary Shelley E. , Nakano Taizo A. , Schulte Rachael R. , Setty Bhuvana A. , McLean Thomas W. , Pahl Kristy S. , Intzes Stefanos , Pateva Irina , Teitelbaum Max , Zong Zili , Li Yimei , Jeng Michael R. 
Published: December 2023

AbstractBackground and objectivesKaposiform hemangioendothelioma (KHE) and tufted angioma (TA) are rare vascular tumors in children historically associated with significant morbidity and mortality. This study was conducted to determine first‐line therapy in the absence of available prospective clinical trials.MethodsPatients from 17 institutions diagnosed with KHE/TA between 2005 and 2020 with more than 6 months of follow‐up were included. Response rates to sirolimus and vincristine were compared at 3 and 6 months. Durability of response and response to other treatment modalities were also evaluated.ResultsOf 159 unique KHE/TA subjects, Kasabach–Merritt phenomenon (KMP) was present in 64 (40.3%), and only two patients were deceased (1.3%). Over 60% (n = 96) demonstrated treatment response at 3 months, and more than 70% (n = 114) by 6 months (no significant difference across groups). The vincristine group had higher radiologic response at 3 months compared to sirolimus (72.7% vs. 20%, p = .03), but there were no differences between these groups at 6 months. There were no differences in rates of recurrent or progressive disease between vincristine and sirolimus.ConclusionsIn this large, multicenter cohort of 159 patients with KHE/TA, rates of KMP were consistent with historical literature, but the mortality rate (1.3%) was much lower. Overall treatment response rates were high (>70%), and there was no significant difference in treatment response or durability of disease comparing sirolimus to vincristine. Our results support individualized treatment decision plans depending on clinical scenario and patient/physician preferences. Response criteria and response rates reported here will be useful for guiding future treatment protocols for vascular tumors.
Hemostatic balance between pro‐ and anticoagulant is maintained during glucocorticoid treatment
Authors: Yamashita Atsuki , Nagae Chiai , Umezawa Yotaro , Mori Mika , Ashikaga Tomoko , Akita Mieko , Suzuki Noriko , Yamazaki Satoshi , Takayama Shigenobu , Taki Masashi 
Published: December 2023

AbstractBackgroundGlucocorticoids are associated with an increased risk of venous thrombosis. Glucocorticoid treatment increases coagulation factor and anticoagulant levels; however, its effect on hemostatic function remains unclear. This study aimed to investigate the changes in comprehensive coagulation profiles after glucocorticoid treatment in noninflammatory diseases to elucidate the direct contribution of glucocorticoids to hemostatic function.ProcedurePatients diagnosed with primary immune thrombocytopenia requiring glucocorticoid treatment were prospectively enrolled in this study. Changes in coagulation factors and anticoagulants during glucocorticoid treatment and changes in thrombin generation potential were determined in the absence and presence of soluble thrombomodulin (sTM).ResultsSeven treatment cases (four for steroid pulse therapy and three for oral glucocorticoid therapy) in six patients with immune thrombocytopenia were examined. After glucocorticoid treatment, activated partial thromboplastin time significantly shortened, and activities of factor VIII, IX, XI, and XII significantly increased, except for von Willebrand factor antigen. Moreover, antithrombin and protein C (PC) activities significantly increased after glucocorticoid treatment. Two major parameters of thrombin generation potential, endogenous thrombin potential (ETP) and peak thrombin (Peak), significantly increased in the absence of sTM after glucocorticoid treatment. However, no significant increases in either parameter were observed in the presence of sTM. ETP‐TM and Peak‐TM ratios, which represent resistance to the anticoagulant effect of the PC pathway, significantly decreased after glucocorticoid treatment, suggesting that anticoagulant function via the PC pathway is elevated after glucocorticoid treatment.ConclusionsAs glucocorticoids increase intrinsic coagulation factor and anticoagulant levels, hemostatic balance between pro‐ and anticoagulant functions is maintained.
Interpersonal psychotherapy for comorbid prolonged grief disorder and persistent depressive disorder in a Japanese patient: A case report
Authors: Okami Takuya , Toshishige Yuko , Kondo Masaki , Okazaki Junya , Mizushima Hiroko , Akechi Tatsuo 
Published: December 2023

AbstractBackgroundProlonged grief disorder (PGD) is a new diagnostic entity. However, treatment for PGD is not yet available. Interpersonal psychotherapy (IPT) may be effective for PGD.Case PresentationA single 27‐year‐old Japanese woman lost her brother to suicide. However, she did not express her grief to anyone or visit a psychiatric clinic. After experiencing strong depressive symptoms triggered by work stress, she visited a psychiatric clinic, where she was diagnosed with depression as well as PGD. Through pharmacotherapy, her depressive symptoms improved, but no improvement was noted in her PGD symptoms. She therefore began IPT for PGD at our hospital, 5 years after her brother's suicide and after 4 years of PGD symptoms. In the introductory phase of IPT, she was diagnosed with comorbid persistent depressive disorder (PDD). After this diagnosis, through psychoeducation on PDD, she could identify the symptoms that reflected her personality traits as “PDD symptoms.” Furthermore, she could affirm her positive and negative feelings and share them with others. Consequently, the grieving process was facilitated, and her interests and relationships were re‐established. Her PGD and PDD symptoms improved.ConclusionIPT may be effective for PGD comorbid with PDD among Japanese.