bluuebunny/crossref_metadata_2025 huggingface dataset:
Performing a physiologically relevant test for cladribine tablets
Authors: Losenkova P. A. , Gvozdev D. D. , Suvorova A. V. , Medvedev Yu. V. , Shcherbakova V. S. , Kazaishvili Yu. G. , Zaslavskaya K. Ya. , Poluyanov A. M. , Shohin I. E.
Published: August 2024

Introduction. The introduction of devices – analogues of GIS (hereinafter–- Gastro-intestinal simulator) is one of the current ways to develop in-vitro assessment of the quality of solid dosage forms. Testing on a physiologically relevant test device (hereinafter referred to as PRT) makes it possible to predict pharmacokinetic profiles due to more relevant conditions, including the use of biorelevant dissolution media, physiological volumes of the gastrointestinal tract, as well as transit between them.

Aim. Conduct a study of cladribine tablets on a physiologically relevant tester in order to predict the behavior of the drug in the human gastrointestinal tract.

Materials and methods. The objects of the study are "Mavenclad®, tablets, 10 mg" (series 2200754, expiration date until 04.2025, NERPHARMA, S.r.L., Italy) and "Cladribine, tablets, 10 mg" of domestic production with valid expiration date. During the study, the reagents necessary for the preparation of biorelevant dissolution media and quantitative determination by HPLC. Physiologically relevant test were carried out using an apparatus of our own production, consisting of a DT-6 dissolution tester (ERWEKA GmbH, Germany), a water bath equipped with a Thermomix WB-4 heating element (B. Braun, Germany), and peristaltic pumps (Kamoer, China). The quantitative content of released cladribine was assessed using a highly efficient liquid chromatograph "Khromatek-Kristall HPLC 2014" (ZAO SKB "Khromatek", Russia) using a validated method at a wavelength of 252 nm, analysis time – 7 min, column – Grace HPLC Column Platinum C18-EPS, 250 × 4.6 mm, 5 mm (Grace, USA), temperature – 35 °C, elution mode – isocratic (A : B 80 : 20), mobile phase A – 0.1 % H3PO4 solution, phase B – acetonitrile.

Results and discussion. Profiles were obtained to assess the dynamics and degree of release of the studied drugs in various parts of the human gastrointestinal tract. Despite the expected degradation of cladribine in an acidic environment (pH1.2), under physiologically relevant conditions, the drug reached the third section (small intestine model) without degradation. Complete release of cladribine from the test and reference dosage forms was observed. Also, in the future, based on the data obtained, it is possible to predict pharmacokinetic profiles using physiologically based pharmacokinetic modeling approaches.

Conclusion. A PSF study was conducted for the drugs "Mavenclad®, tablets, 10 mg" and "Cladribine, tablets, 10 mg". Quantitative determination was carried out by HPLC-UV method. The test results showed complete release of both drugs and reaching the intestinal tract, indicating the absence of degradation of cladribine in the region simulating the stomach.
Pelatihan Penerapan Metode Pencocokan Kartu Indeks untuk Meningkatkan Keterampilan Mendengar Bahasa Inggris Siswa Sekolah Menengah Atas
Authors: Sudewi Putu Wahyu , Putri Andi Mega Januarti , Amrang Amrang
Published: August 2024

This community engagement activity aims to enhance high school students' English listening skills through the application of the index card matching method. The implementation method of this service involved training that includes preparation, implementation, practice, and evaluation stages. The participants of this training were 34 students from class XII in SMAN 1 Wonomulyo, Polewali Mandar Regency. The evaluation instrument for this activity used a pre-test and post-test with quantitative data analysis. The results of this community service activity showed an improvement in students' listening skills after applying the index card matching method. The average student score increased by 34 points from the initial test average score of 46.00 to 80.00 on the final test. During the community service process, students showed interest and a positive response, and actively participated in the learning process with high enthusiasm and interaction.
Pemberdayaan Perempuan Melalui Pelatihan Life Skills Berbasis Agrobisnis di Desa Gapura Kabupaten Lombok Tengah NTB
Authors: Fajri Siti Rabiatul , Hajiriah Titi Laily , Fajri Nurul , Sarnita Fitria , Wibowo Sarwo Edi , Armiani Sucika , Sutajaya I Made
Published: August 2024

This service activity aims to improve women's life skills in processing the potential of the village, namely watermelon into an agribusiness product that has a high economic selling value. The method of implementing this service uses training with target partners, namely housewives, and women of productive age in Gapura village, Central Lombok Regency, NTB. The results of this service show that this activity could improve the ability and skills of the people of Gapura Village to process watermelon into products with more selling value, namely watermelon peel and jelly candy. In addition, this activity could increase the knowledge of Gapura Village women to process agricultural products based on agribusiness. Based on the results of the evaluation, most of the partners responded that this training was very useful in improving life skills by obtaining a percentage of 55%.
Avusturya Ve Macaristan Devlet Arşivlerinde Erken Cumhuriyet Dönemi’ne İlişkin Kataloglar
Authors: Saral Emre
Published: August 2024

Birinci Dünya Savaşı’nda müttefik olarak çarpışan Osmanlı Devleti ile Avusturya-Macaristan arasındaki siyasi ve diplomatik ilişkiler 30 Ekim 1918’de imzalanan Mondros Mütarekesi uyarınca kesilmiştir. Her iki ülkeyle de diplomatik ilişkiler 1924 yılı itibarıyla yeniden başlamıştır. Bu çalışmada 1920-1945 yıllarını kapsayan ve Avusturya ve Macaristan’ın Türkiye Cumhuriyeti ile ilişki kurarak bunu geliştirmeye gayret gösterdikleri dönemde dış temsilciliklerinde ürettikleri evrak üzerine katalog esaslı olarak okuyucuya bilgi verilmeye çalışılmıştır.
Türkiye’de Erken Cumhuriyet Dönemi çalışmalarında nadir olarak başvurulan iki birincil kaynak durumundaki bahsi geçen her iki ülkenin de Devlet Arşivlerinde yer alan evrakın araştırmacılar için ciddi bir potansiyel taşıdığı düşünülmektedir. Avusturya’nın Türkiye’deki temsilciliklerinden gönderilmiş olan belgeler Dış Meseleler (Auswärtige Angelegenheiten) başlıklı tasnifin altında yer alan Bundeskanzleramt, Auswärtige Angelegenheiten (Başbakanlık, Dış Meseleler) fonunda bulunabilecek Yeni Siyasi Arşiv (1918-1938) (Neues Politisches Archiv (1918-1938)) başlıklı fonda tasnif edilmiştir. Yine aynı döneme ait Macaristan Elçiliği belgeleri ise Macar Millî Arşivi Devlet Arşivi Dışişleri Bakanlığı Arşivi altında tasnif edilmiştir. Makalede her iki arşivde Türkiye ile ilgili döneme ilişkin inceleme yapmak isteyen araştırmacıların bakmaları gereken katalogların tanıtımının yanı sıra ülkenin ilgili arşivlerine ve kullanıcıların dikkat etmeleri gerekenlere dair temel bilgiler de okuyuculara sunulmuştur. Genel değerlendirme kısmında ise yeni araştırmalara ufuk açacak konular üzerine kısa bir değerlendirme yapılmıştır.
EKSPLORASI ETNOMATEMATIKA PADA KAIN TENUN UIS KABUPATEN KARO SUMATERA UTARA
Authors: Nasution Nirleka , Maysarah Siti
Published: August 2024

Etnomatematika adalah salah satu cara belajar matematika yang menghubungkan aktivitas kehidupan sehari-hari dengan konsep-konsep pembelajaran matematika. Penelitian ini bertujuan untuk mengeksplorasi konsep geometri pada motif-motif seni kain tenun Uis Karo di Masyarakat Kelurahan Mencirim Kecamatan Binjai Timur Kabupaten Kota Binjai Sumatera Utara. Penelitian ini menggunakan metode kualitatif dengan pendekatan etnografi. Teknik pengambilan data yang dilakukan yaitu observasi, wawancara dan dokumentasi. Analisis yang digunakan yaitu analisis deskriptif supaya dapat menyajikan informasi keterkaitan ilmu matematika dengan budaya. Hasil penelitian yang dilakukan pada Masyarakat Kelurahan Mencirim Kecamatan Binjai Timur Kabupaten Kota Binjai Sumatera Utara peneliti menemukan bahwa terdapat unsur-unsur matematika yang terkandung dalam proses pembuatan motif kain tenun Uis.
Movilidades académicas internacionales y estudiantes migrantes en la Universidad Nacional de Córdoba (Argentina)
Authors: Jiménez Zunino Cecilia , Florencia Maggi María
Published: August 2024

En este artículo se indagan las desigualdades en los itinerarios internacionales de entradas y salidas en el sistema universitario vinculando las migraciones con la educación y las movilidades académicas. A partir de un análisis cuantitativo de fuentes primarias y secundarias, se explora la presencia de estudiantes migrantes y de intercambio de grado y posgrado en la Universidad Nacional de Córdoba (UNC), así como las movilidades desde esta institución hacia diversos destinos del mundo. Entre los principales hallazgos destaca la identificación de espacios relativamente jerarquizados y un perfil selectivo de estudiantes en las movilidades que se encuadran en las políticas de internacionalización. Sobresale una mayor heterogeneidad de perfiles entre estudiantes de la UNC nacidos en el extranjero. El principal aporte del artículo es que se analizan simultáneamente movilidades que suelen observarse por separado, lo que permite vislumbrar los diversos recorridos de los estudiantes signados por el origen de la clase social.
Optimalisasi Penatausahaan Aset Tetap Berupa Tanah Dalam Meningkatkan Akuntabilitas Laporan Keuangan Di Kabupaten Jayawijaya
Authors: Tumija Tumija , Kogoya Yanechson Gwarry , Agustina Ika
Published: August 2024

Papua is an area where problems often arise regarding land ownership rights. One of them is in Jayawijaya Regency, where there are still frequent cases of land disputes, especially land owned by the Jayawijaya Regency Government. This issue regarding the legality of land belonging to the Jayawijaya Regency government will greatly influence the administration of land assets, because the assets recorded must have strong evidence of legality such as land certificates. Therefore, the Jayawijaya Regency Government must optimize the administration of fixed assets in Jayawijaya Regency, especially land assets. The aim of this research is to determine the optimization of the administration of fixed assets in the form of land in increasing the accountability of financial reports carried out by the Regional Financial and Asset Management Agency of Jayawijaya Regency. The research method used is descriptive qualitative. Researchers used observation, interview and documentation techniques. The data that has been collected is then analyzed by collecting data, analyzing the data, and drawing conclusions. The research results obtained show that the administration of land assets is not optimal, namely because there are still problems in securing assets and human resources within the Jayawijaya Regency BPKAD environment. In this case, the steps taken by BPKAD Jayawijaya Regency are to increase asset security and improve the quality of human resources through providing training and technical guidance
Influence of landscape on the presence of Batrachochytrium dendrobatidis and Ranavirus in tadpoles in the southern Atlantic Forest of Brazil
Authors: Santos Roseli Coelho dos , Dalmolin Diego Anderson , Ruggeri Joice , Brum Diego , Veronez Mauricio Roberto , Lucas Elaine Maria , Tozetti Alexandro Marques
Published: August 2024

Introduction

Habitat loss, as well as infectious diseases, have been suggested as the main causes for the worldwide decline of amphibian populations. Thus, the search for biotic indicators is a useful tool for mapping priority demands in disease management.

Aims

Here we analyzed the prevalence of two pathogens, Batrachochytrium dendrobatidis (Bd) and Ranavirus (Rv), in anuran communities in southern Brazil. We explored the relationship between the prevalence of Bd and landscape class and used an indicator-species and indicator-community approach to identify which species and communities have the potential to indicate the presence of Bd.

Methods

We used histological analyses to access Bd and PCR for Rv in tadpole communities.

Key results

Our data, based on 26 anuran communities, revealed high Bd prevalence but absence of Rv. Three species, of the 26 communities studied, were found to be Bd indicators, including endemic species from southern Brazil and Argentina. Additionally, the analysis with an indicator-community approach revealed that communities from larger forest areas are Bd indicators.

Conclusions

Analyses at the community level, which relate landscape to pathogens, provide unprecedented and highly relevant information for fragmented Atlantic Forest landscapes. Based on our results, we argue that even communities in larger forest patches (apparently well-preserved) are susceptible to Bd and deserve attention regarding the possibility of incidence of chytridiomycosis. Implications. From our results, we consider that the use of Bd-indicator species and Bd-indicator communities is a useful approach for conservation and could be used to evaluate the threatened status of species and for proposals for landscape management.
Comparison of two viscoelastic testing devices in a porcine model of surgery, hemorrhage and resuscitation
Authors: Gruneberg Daniel , Dietrich Maximilian , Studier-Fischer Alexander , Petersen Clara , von der Forst Maik , Özdemir Berkin , Schöchl Herbert , Nickel Felix , Weigand Markus A. , Schmitt Felix C. F.
Published: August 2024

Introduction

Viscoelastic hemostatic assays (VHA) are integral in contemporary hemostatic resuscitation, offering insights into clot formation, firmness, and lysis for rapid diagnosis and targeted therapy. Large animal models, particularly swine, provide anatomical and physiological analogies for coagulation research. Despite the growing use of VHAs, the ClotPro® device’s applicability in porcine models remains unexplored. This study investigates ClotPro® in a porcine model of abdominal surgery, severe hemorrhage, and resuscitation, comparing it with the established ROTEM® delta system.

Methods

Twenty-seven healthy pigs underwent abdominal surgery, hemorrhage and resuscitation. ClotPro® and ROTEM® were used to assess viscoelastic hemostatic properties at baseline, after surgery, 60 min after shock induction, 60 and 120 min after resuscitation.

Results

Clotting times in extrinsically and intrinsically stimulated assays exhibited fair to moderate correlation. Clot firmness in extrinsically stimulated tests could be used interchangeably while fibrin polymerization assays revealed significant differences between the devices. Fibrin polymerization assays in ClotPro® consistently yielded higher values than ROTEM®. Furthermore, the study evaluated the ClotPro® TPA-test’s applicability in porcine blood, revealing failure of lysis induction in porcine blood samples.

Conclusion

This research contributes valuable insights into the use of ClotPro® in porcine models of hemorrhage and coagulopathy, highlighting both its applicability and limitations in comparison to ROTEM® delta. The observed differences, especially in fibrin polymerization assays, emphasize the importance of understanding device-specific characteristics when interpreting results. Due to its inapplicability, TPA-test should not be used in porcine blood to evaluate fibrinolytic potential. The study provides a foundation for future investigations into the use of different viscoelastic hemostatic assays in porcine animal models.
Nanoscale pore structure in anthracite coals and its effect on methane adsorption capacity
Authors: Xu Qiang , Wang Ruyue , Wang Zebin , Zhao Yue , Miao Quanyun , Zhang Zhengguang , Bai Xiujia , Xinxin Feng
Published: August 2024

Although significant amounts of methane are present in anthracite coal seams, coalbed methane resources cannot be extracted effectively and quickly. This study mainly focused on investigating the pore system and methane adsorption capacity to clarify the storage of coalbed methane. Anthracite coal samples from the Anzenan coalbed methane block in China were collected, and pore characterization methods (low-pressure N2 adsorption, mercury injection experiments, and scanning electron microscopy (SEM) observations) and methane isothermal adsorption experiments were conducted. The results showed that few mesopores and nanoscale macropores were present in the anthracite coal samples. The volume of the 2–300 nm pores in these coal samples obtained from the N2 adsorption experiment was lower than 0.01 cm3/g. SEM observations also revealed that only a small number of mesopores and nanoscale macropores could be seen, and most of these pores were isolated. In terms of the methane isothermal adsorption data, it was found these anthracite coals have a large methane adsorption capacity, and the Langmuir volume ranges from 19.5 to 28.4 cm3/g, with an average of 22.2 cm3/g. With increasing ash yield, the Langmuir volume decreased linearly, indicating that methane molecules were mainly adsorbed in the organic matter of coal. As methane is mainly adsorbed in the micropores of coal organic matter and there are few mesopores and nanoscale macropores in the organic pores in coal, there are not enough tunnels to transport the adsorbed methane molecules to the outside. Thus, it is difficult to extract coalbed methane from anthracite. This study reveals the impact of pore system limitations on the storage and extraction of coalbed methane in anthracite coal. The findings can be applied to the extraction of coalbed methane from anthracite coal seams worldwide.
Robustness of characteristics of the Matuyama-Brunhes geomagnetic field reversal found in global models
Authors: Mahgoub Ahmed Nasser , Korte Monika , Panovska Sanja , Schanner Maximilian
Published: August 2024

Paleomagnetic data enables the global reconstruction of the geomagnetic field, allowing the investigation of significant events like polarity reversals and excursions. When compared to prior polarity reversals, the most recent one, the Matuyama-Brunhes (MB), is the best recorded reversal in terms of number of available paleomagnetic data. Nevertheless, several of these data have poor age control, and they are not distributed equally worldwide. Few global models have been presented for the MB; the most recent is the GGFMB (Global Geomagnetic Field Model for the MB reversal). Limitations imposed by input data and subjective assumptions about the data that are made in modelling restrict the resolution and reliability of these models. This study presents a suite of eight additional global models that reconstruct the magnetic field during the interval 700–900 ka ago, including the MB reversal and Kamikatsura (KKT) excursion. Through model comparisons, the robustness of the models in resolving MB reversal characteristics is assessed. The majority of models indicate that the reversal was mainly driven by the axial dipole field contribution gradually decreasing, while non-dipole parts slightly increased. At the core-mantle boundary, two high-latitude reverse flux patches appear at the beginning of the reversal, and it seems like a few precursors in the form of regionally seen transitional field occurred, related to variations in the decaying dipole moment. The main global polarity change occurred close to 778 ka, with the axial dipole quickly strengthening in the opposite direction in the following, completing the full polarity transition. All the models confirm the previously reported asymmetry of slow dipole decay and fast recovery, and indicate that the dipole moment was clearly lower in the late Matuyama than the early Brunhes. The whole reversal process occurred on average between 800 and 770 ka, with a duration of approximately 30 kyr. Out of four apparent excursions discovered in some of the models between 900 and 800 ka, the KKT excursion (890–884 ka), can be confirmed as a robust magnetic field feature. Additional, well dated paleomagnetic records in particular from the southern hemisphere are required to confirm several details suggested by the models that should only be interpreted with caution so far.
Incorporating core concepts into an undergraduate neuroscience program in a resource-restricted environment
Authors: Stocker Adam M. , Duncan Chad S.
Published: August 2024

Recently, community-derived core concepts for neuroscience higher education were developed and published. These core concepts can serve as a valuable resource to ensure that a neuroscience-based educational program is not only concept-focused but also addresses the call for reform of higher education, as noted in the vision and change report. The number of undergraduate neuroscience programs is expanding throughout the nation, but unfortunately, the existing blueprints to design and launch such programs do not incorporate these core concepts. Furthermore, unpacking these core concepts in a resource-limited setting is logistically challenging. We reflected on the coverage of these core concepts within our existing neuroscience minor at a medium-sized, primarily residential, high undergraduate, public 4-year institution. In addition to assessing the number of community-derived core concepts addressed in our courses, our reflection discusses strategies for addressing challenges associated with (1) a departmental home for the program, (2) a meaningful student experience with limited resources, and (3) growing and developing the program into a minor, or from a minor into a major. These strategies may provide a roadmap for other institutions to launch or grow their own neuroscience program.
Research progress of ultrasound in accurate evaluation of cartilage injury in osteoarthritis
Authors: Zhang Huili , Ning Eryu , Lu Lingfeng , Zhou Jing , Shao Zhiqiang , Yang Xing , Hao Yuefeng
Published: August 2024

Osteoarthritis (OA) is a prevalent cause of joint algesia, loss of function, and disability in adults, with cartilage injury being its core pathological manifestation. Since cartilage damage is non-renewable, the treatment outcome in the middle and late stages of OA is unsatisfactory, which can be minimized by changing lifestyle and other treatment modalities if diagnosed and managed in the early stages, indicating the importance of early diagnosis and monitoring of cartilage injury. Ultrasound technology has been used for timely diagnosis and even cartilage injury treatment, which is convenient and safe for the patient owing to no radiation exposure. Studies have demonstrated the effectiveness of ultrasound and its various quantitative ultrasound parameters, like ultrasound roughness index (URI), reflection coefficient (R), apparent integrated backscatter (AIB), thickness, and ultrasound elastography, in the early and accurate assessment of OA cartilage pathological changes, including surface and internal tissue, hardness, and thickness. Although many challenges are faced in the clinical application of this technology in diagnosis, ultrasound and ultrasound-assisted techniques offer a lot of promise for detecting early cartilage damage in OA. In this review, we have discussed the evaluation of ultrasonic cartilage quantitative parameters for early pathological cartilage changes.
Study on thermodynamic equivalent performance of fully ceramic microencapsulated fuel based on representative volume element model
Authors: Yin Chunyu , Xiao Zhong , Zhang Kun , Cao Peng , Tang Changbing , He Liang , Liu Shichao
Published: August 2024

Fully ceramic microencapsulated (FCM) fuel is a five-layer intercalation system material consisting of a UO2 core, a sparse pyrolytic carbon layer (Buffer), an inner dense pyrolytic carbon layer (IPyC), an outer dense pyrolytic carbon layer (OPyC), and a silicon carbide matrix (SiC). At first, this paper researched the thermodynamic models of the materials, including heat conduction coefficient, Young’s modulus, thermal expansion coefficient, etc. Then DIGIMAT, the finite element software, was used to establish the equivalent volume element (RVE) for the equivalent analysis of the thermodynamic properties of the FCM fuel pellet. Finally, the thermodynamic equivalent performance model of FCM fuel was obtained by multi-factor fitting analysis. The results show that among these thermodynamic properties of FCM fuel pellets, the Young’s modulus, thermal expansion coefficient and plastic performance are mainly affected by temperature, fast neutron fluence, and UO2 volume fraction; the specific heat capacity is mainly affected by UO2 volume fraction and temperature; the heat conduction coefficient is mainly affected by temperature and UO2 volume fraction. The thermal conductivity is mainly affected by temperature, burnup and UO2 volume fraction. In this study, the equivalent models obtained through the fitting analysis of RVE model parameters can well describe the thermodynamic behavior of FCM fuel particles.
Causal associations between severe COVID-19 and diseases of seven organs: a proteome-wide mendelian randomization study
Authors: Shen Yunhan , Zhang Yi , Xu Ye-yang , Li Xinyi , Wu Jiachen , Pei Hao , Wang Linyan , Zhu Tiansheng
Published: August 2024

The coronavirus disease 2019 (COVID-19) pandemic poses an enormous threat to public health worldwide. Many retrospective studies and case reports to date have shown associations between severe COVID-19 and diseases of multi-organs. However, the research on the causal mechanisms behind this phenomenon is neither extensive nor comprehensive. We conducted a proteome-wide Mendelian randomization (MR) study using summary statistics from a Genome-Wide Association Studies (GWAS) of severe COVID-19 and diseases related to seven organs: lung, spleen, liver, heart, kidney, testis, and thyroid, based on the European ancestry. The primary analytical method used is the radial inverse variance-weighted (radial IVW) method, supplemented with the inverse variance-weighted (IVW), weighted-median (WM), MR-Egger methods. Our findings have confirmed the association between severe COVID-19 and multiple organ-related diseases, such as Hypothyroidism, strict autoimmune (HTCBSA), Thyroid disorders (TD), and Graves’ disease (GD). And we have also identified certain proteins that are associated with organ-related diseases, such as Superoxide Dismutase 2 (SOD2) and TEK Receptor Tyrosine Kinase (TEK), which are also considered potential drug targets. Phenotype scanning and sensitivity analyses were implemented to consolidate the results for Mendelian randomization. This study provides a compelling foundation for investigating COVID-19 caused diseases in future studies.
Glioblastoma-derived exosomes promote lipid accumulation and induce ferroptosis in dendritic cells via the NRF2/GPX4 pathway
Authors: Yang Jian , Zhang Mingqi , Zhang Xuying , Zhou Yue , Ma Tingting , Liang Jia , Zhang Jinyi
Published: August 2024

Glioblastoma-derived exosomes (GDEs), containing nucleic acids, proteins, fatty acids and other substances, perform multiple important functions in glioblastoma microenvironment. Tumor-derived exosomes serve as carriers of fatty acids and induce a shift in metabolism towards oxidative phosphorylation, thus driving immune dysfunction of dendritic cells (DCs). Lipid peroxidation is an important characteristic of ferroptosis. Nevertheless, it remains unclear whether GDEs can induce lipid accumulation and lipid oxidation to trigger ferroptosis in DCs. In our study, we investigate the impact of GDEs on lipid accumulation and oxidation in DCs by inhibiting GDEs secretion through knocking down the expression of Rab27a using a rat orthotopic glioblastoma model. The results show that inhibiting the secretion of GDEs can reduce lipid accumulation in infiltrating DCs in the brain and decrease mature dendritic cells (mDCs) lipid peroxidation levels, thereby suppressing glioblastoma growth. Mechanistically, we employed in vitro treatments of bone marrow-derived dendritic cells (BMDCs) with GDEs. The results indicate that GDEs decrease the viability of mDCs compared to immature dendritic cells (imDCs) and trigger ferroptosis in mDCs via the NRF2/GPX4 pathway. Overall, these findings provide new insights into the development of immune-suppressive glioblastoma microenvironment through the interaction of GDEs with DCs.
The diagnostic value of 68Ga-NOTA-MAL-Cys-MZHER2:342 PET/CT imaging for HER2-positive lung adenocarcinoma
Authors: Li Shu , Wang Ke , Zhu Xue , Pan Donghui , Wang Ling , Guo Xu , Gao Xiaomin , Luo Qing , Wang Xun
Published: August 2024

Background

The human epidermal growth factor receptor 2 gene (HER2) has been identified as a potential therapeutic target in lung adenocarcinoma (LUAD). Non-invasive positron emission tomography (PET) imaging provides a reliable strategy for in vivo determination of HER2 expression through whole-body detection of abnormalities. The PET tracer 68Ga-NOTA-MAL-Cys-MZHER2:342 has shown promising results for HER2-positive breast and gastric cancers. This study aims to evaluate the performance of 68Ga-NOTA-MAL-Cys-MZHER2:342in vitro and in vivo models and in clinical patients with HER2-positive LUAD.

Methods

NOTA-MAL-Cys-MZHER2:342 was synthesized and labeled with 68Ga. Cell uptake, cell binding ability, and stability studies of 68Ga-NOTA-MAL-Cys-MZHER2:342 were assessed both in the Calu-3 lung cancer (LC) cell line and normal mice. In vivo assessment in tumor-bearing mice was conducted using microPET imaging and biodistribution experiments. Additionally, preliminary PET/CT imaging analysis was performed on HER2-positive LC patients.

Results

68Ga-NOTA-MAL-Cys-MZHER2:342 was prepared with a radiochemical purity (RCP) exceeding 95%. The tracer demonstrated high cell uptake in HER2-overexpressing Calu-3 cells, with an IC50 of 158.9, an adequate 1.73 nM. Good stability was exhibited both in vitro and in vivo. MicroPET imaging of Calu-3-bearing mice revealed high tumor uptake and notable tumor-to-background ratios. Positive outcomes were also observed in two HER2-positive LUAD patients.

Conclusion

68Ga-NOTA-MAL-Cys-MZHER2:342 demonstrated satisfactory stability, sensitivity, and specificity. These findings suggest that 68Ga-NOTA-MAL-Cys-MZHER2:342 PET/CT imaging provides a novel tool for non-invasive visual assessment of HER2 expression in LUAD patients.
A novel lytic phage infecting MDR Salmonella enterica and its application as effective food biocontrol
Authors: Jaglan Anu Bala , Verma Ravikant , Vashisth Medhavi , Virmani Nitin , Bera B. C. , Vaid R. K. , Anand Taruna
Published: August 2024

Salmonella enterica is a foodborne pathogen associated with both typhoid and non-typhoid illness in humans and animals. This problem is further exacerbated by the emergence of antibiotic-resistant strains of Salmonella enterica. Therefore, to meet public health and safety, there is a need for an alternative strategy to tackle antibiotic-resistant bacteria. Bacteriophages or (bacterial viruses), due to their specificity, self-dosing, and antibiofilm activity, serve as a better approach to fighting against drug-resistant bacteria. In the current study, a broad-host range lytic phage phiSalP219 was isolated against multidrug-resistant Salmonella enterica serotypes Paratyphi from a pond water sample. Salmonella phage phiSalP219 was able to lyse 28/30 tested strains of Salmonella enterica. Salmonella phage phiSalP219 exhibits activity in acidic environments (pH3) and high temperatures (70°C). Electron microscopy and genome analysis revealed that phage phiSalP219 is a member of class Caudoviricetes. The genome of Salmonella phage phiSalP219 is 146Kb in size with 44.5% GC content. A total of 250 Coding Sequence (CDS) and 25 tRNAs were predicted in its genome. Predicted open reading frames (ORFs) were divided into five groups based on their annotation results: (1) nucleotide metabolism, (2) DNA replication and transcription, (3) structural proteins, (4) lysis protein, and (5) other proteins. The absence of lysogeny-related genes in their genome indicates that Salmonella phage phiSalP219 is lytic in nature. Phage phiSalP219 was also found to be microbiologically safe (due to the absence of toxin or virulence-related genes) in the control of Salmonella enterica serovar Typhimurium infections in the ready-to-eat meat and also able to eradicate biofilm formed by the same bacterium on the borosilicate glass surface.
Occlusal effects on text reading: an eye-tracker study
Authors: Tramonti Fantozzi Maria Paola , De Cicco Vincenzo , Bazzani Andrea , Cataldo Enrico , Bruschini Luca , De Cicco Davide , d’Ascanio Paola , Faraguna Ugo , Manzoni Diego
Published: August 2024

Introduction

Asymmetric electromyographic (EMG) activity during teeth clenching has been linked to cognitive impairment, as evaluated by the Spinnler-Tognoni matrices test, and to asymmetric pupil size (anisocoria). Anisocoria indicates an asymmetric Locus Coeruleus activity, leading to an asymmetric hemispheric excitability worsening cognitive performance. Bite splint wearing corrects EMG asymmetry, reduces anisocoria and improves cognitive performance. This study explores the possible effect of EMG asymmetry on oculomotor behavior during text reading.

Methods

In subjects showing different degrees of EMG asymmetry during clenching, the number and duration of fixation periods during a reading task, performed under two different occlusal conditions were analyzed. The first lecture was executed with a dental impression (imprint) interposed between the dental arches (corrected condition) and the second one with the arches in direct contact (habitual condition), without clenching effort. The imprint reduced the EMG asymmetries during clenching.

Results

In both occlusal conditions, total reading time correlated with duration of fixations, but not with their number. An inverse relation was observed between the number of fixations and their duration across individuals. Fixation frequency and duration were positively and negatively correlated with the amplitude of EMG asymmetry, respectively. Differently, total reading time was not related to the EMG asymmetry. When switching from the corrected to the habitual condition, an increase in the number of fixations and a reduction in their duration was observed, while total reading time could be either increased or decreased. An increased fixation frequency was observed in most of the subjects, while a reduced duration only among individuals with shorter reading times in habitual condition.

Discussion

In the habitual condition, EMG asymmetry influences reading patterns (more saccades/shorter fixations, less saccades/longer fixations) in our sample. The changes in text reading behavior elicited by occlusal correction can be explained by assuming that occlusal disharmony negatively interferes with the reading task by increasing the number of saccades necessary for text scanning. This finding may also indicate an increased difficulty in processing of visual information. The potential involvement of trigeminal pathways in the relation between occlusal factors and oculomotor control is discussed.
External validation of a novel nomogram for diagnosis of Protein Energy Wasting in adult hemodialysis patients
Authors: Yan Danying , Wang Yi , Hu Jing , Lu Renhua , Ye Chaoyang , Liu Nanmei , Chen Dongping , Liang Weiwei , Zheng Liang , Liu Wenrui , Lan Tianying , Lan Naiying , Shao Qing , Zhuang Shougang , Ma Xiaoyan , Liu Na
Published: August 2024

Background

Protein Energy Wasting (PEW) has high incidence in adult hemodialysis patients and refers to a state of decreased protein and energy substance. It has been demonstrated that PEW highly affects the quality of survival and increases the risk of death. Nevertheless, its diagnostic criteria are complex in clinic. To simplify the diagnosis method of PEW in adult hemodialysis patients, we previously established a novel clinical prediction model that was well-validated internally using bootstrapping. In this multicenter cross-sectional study, we aimed to externally validate this nomogram in a new cohort of adult hemodialysis patients.

Methods

The novel prediction model was built by combining four independent variables with part of the International Society of Renal Nutrition and Metabolism (ISRNM) diagnostic criteria including albumin, total cholesterol, and body mass index (BMI). We evaluated the performance of the new model using discrimination (Concordance Index), calibration plots, and Clinical Impact Curve to assess its predictive utility.

Results

From September 1st, 2022 to August 31st, 2023, 1,158 patients were screened in five medical centers in Shanghai. 622 (53.7%) hemodialysis patients were included for analysis. The PEW predictive model was acceptable discrimination with the area under the curve of 0.777 (95% CI 0.741–0.814). Additionally, the model revealed well-fitted calibration curves. The McNemar test showed the novel model had similar diagnostic efficacy with the gold standard diagnostic method (p > 0.05).

Conclusion

Our results from this cross-sectional external validation study further demonstrate that the novel model is a valid tool to identify PEW in adult hemodialysis patients effectively.
Development of an algorithm to identify small cell lung cancer patients in claims databases
Authors: Danese Mark D. , Balasubramanian Akhila , Bebb D. Gwyn , Pundole Xerxes
Published: August 2024

Introduction

The treatment landscape of small cell lung cancer (SCLC) is evolving. Evidence generated from administrative claims is needed to characterize real-world SCLC patients. However, the current ICD-10 coding system cannot distinguish SCLC from non-small cell lung cancer (NSCLC). We developed and estimated the accuracy of an algorithm to identify SCLC in claims-only databases.

Methods

We performed a cross-sectional study of lung cancer patients diagnosed from 2016-2017 using the Surveillance, Epidemiology and End Results (SEER), linked with Medicare database. The analysis included two phases – data exploration (utilizing a 25% random sample) and data validation (remaining 75% sample). The SEER definition of SCLC and NSCLC were used as the gold standard. Claims-based algorithms were identified and evaluated for their sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).

Results

The eligible cohort included 31,912 lung cancer patients. The mean age was 76.3 years, 44.6% were male, with 9.4% having SCLC and 90.6% identified as NSCLC using SEER. The exploration analysis identified potential algorithms based on treatment data. In the validation analysis of 7,438 lung cancer patients who received systemic treatment in the outpatient setting, an etoposide-based algorithm (etoposide use in 180 days following lung cancer diagnosis) to identify SCLC showed: sensitivity 95%, specificity 95%, PPV 82% and NPV 99%.

Discussion

An etoposide treatment-based algorithm showed good accuracy in identifying SCLC patients. Such algorithms can facilitate analyses of treatment patterns, outcomes, healthcare resource and costs among treated SCLC patients, thereby bolstering the evidence-base for best patient care.
Association of the rs1042522 SNP with prostate cancer risk: a study of cancer tissues, primary tumor cultures, and serum samples from a Spanish Caucasian population
Authors: Toscano-Guerra Emily , Maggio Valentina , García Javier , Semidey Maria Eugenia , Celma Ana , Morote Juan , de Torres Inés , Giralt Marina , Ferrer-Costa Roser , Paciucci Rosanna
Published: August 2024

Background

Prostate cancer (PCa) is a leading cause of cancer-related deaths in European men, emphasizing the urgent need for effective risk assessment strategies. The TP53 gene, a tumor suppressor gene frequently mutated in cancer, commonly harbors the rs1042522 single nucleotide polymorphism (SNP), known as the P72R SNP, which may influence PCa susceptibility. This study investigated the prevalence of the P72R SNP in European Caucasian PCa samples and its association with PCa risk.

Methods

Genotyping was conducted on 12 hormone-naïve aggressive PCa cultures (hnPCs) from untreated patients (Gleason ≥8), 11 radical prostatectomies (RP), and 94 serum samples using DNA Sanger sequencing and melting curve analysis. Comparative analysis utilized data from the GnomAD database’s European Caucasian non-cancer population.

Results

Our results demonstrate a significantly higher frequency of the P72R SNP in PCa samples and serums compared to the general European non-cancer population. A robust and statistically significant association (p < 0.0001) between the SNP and prostate cancer risk was identified, with an odds ratio of 7.937 (95% CI 5.37-11.00). Notably, the G allele (R72) showed a pronounced prevalence in high Gleason score (≥8) patients, although statistical significance was not reached. These results highlight a potential association with undifferentiated and malignant PCa lesions.

Conclusion

The compelling association between the P72R SNP and prostate cancer risk underscores the potential utility of this marker for the early identification of patients at risk of aggressive metastatic prostate cancer. This insight could empower further research to intervene at an early stage by offering enhanced opportunities for timely and targeted interventions.
Primary intestinal diffuse large B-cell lymphoma: novel insights and clinical perception
Authors: Chen Xiaojun , Wang Jing , Liu Yanquan , Lin Suxia , Shen Jianzhen , Yin Yue , Wang Yili
Published: August 2024

Background

Extranodal Non-Hodgkin lymphoma (NHL) is more prevalent in the gastrointestinal (GI) tract than in other sites. This study aimed to explore the clinical features and prognostic factors of primary intestinal diffuse large B-cell lymphoma (PI-DLBCL), in order to provide new references for basic research and clinical diagnosis and treatment of the rare extranodal malignant lymphoma.

Methods

The clinical data of 88 patients with PI-DLBCL admitted to Fujian Medical University Union Hospital from June 2011 to June 2022 were retrospectively studied, the clinical and pathological features, diagnosis and treatment process and prognosis of PI-DLBCL were analyzed, and univariate and multivariate analysis of prognostic factors was carried out. The Kaplan-Meier method was used for survival analysis. Meanwhile, the latest literature from PubMed was retrieved to systematically discuss the research progress in the diagnosis and treatment of PI-DLBCL.

Results

Among the 88 patients with PI-DLBCL included in this study, 60 cases were males (68.18%), 28 cases were females (31.82%), and 62 patients (70.45%) were complaining of abdominal pain, and the second most common clinical manifestation was changes in bowel habits in 16 (18.18%), with a median age of onset of 57 (17–82) years. The first-line treatment regimen was surgery combined with R-CHOP chemotherapy (56.82%). The median follow-up time was 72 (1–148) months, 51 (57.95%) of 88 patients with PI-DLBCL survived, 30 patients (34.09%) died, 7 patients (7.95%) were lost to follow-up, and the PFS rates of 1-year, 3-year and 5-year were 57.95%, 29.55% and 15.91%, and the OS rates of 1-year, 3-year and 5-year were 79.55%, 45.45% and 28.41%, respectively. The results of univariate Cox regression analysis showed that ECOG score, Lugano stage, B symptoms, IPI score, white blood cells, serum LDH, albumin, β2 microglobulin were the influencing factors of OS in PI-DLBCL patients, and ECOG score, Lugano stage, B symptoms, IPI score, white blood cells, serum LDH, albumin, β2 microglobulin were all the influencing factors of PFS in PI-DLBCL patients. The results of multivariate Cox analysis showed that Lugano stage may be an independent prognostic factor affecting OS and PFS in PI-DLBCL patients.

Conclusion

PI-DLBCL is more common in middle-aged and elderly men, clinical manifestations lack specificity, first-line treatment is mainly surgery combined with standard chemotherapy regimens. The Lugano stage may be an independent prognostic factor affecting OS and PFS in PI-DLBCL patients.
Efficacy and challenges of anti-PD1 in MSI-H mCRC: a case report on concurrent infections and ir-AIHA
Authors: Pei Xiaxia , Zhao Jun , Luo Ruiying , Da Lijun , Li Enxi , Zhu Hao , Li Yanhong , Luo Yaoting , Tian Kun , Wang Zhiping , Song Feixue
Published: August 2024

Anti-programmed cell death protein 1 (PD-1) therapy has demonstrated notable efficacy in treating patients with deficient mismatch repair/high microsatellite instability (dMMR/MSI-H) metastatic colorectal cancer (mCRC). However, its clinical application is fraught with challenges and can lead to significant immune-related adverse events (ir-AEs). In this report, we present a complicated case of an mCRC patient with MSI-H and mutations in β2M and LRP1B proteins, complicated by concurrent bacteremia and liver fluke infection, who received first-line anti-PD1 therapy. The patient exhibited a positive response to anti-PD1 treatment, even in the presence of concomitant antibiotic and anti-parasitic interventions. Additionally, the patient experienced immunotherapy-related autoimmune hemolytic anemia (ir-AIHA), a rare hematological ir-AE, which was effectively treated later on. Immunotherapy represents a pivotal and highly effective approach to tumor treatment. Baseline assessment of the MMR and MSI status is a crucial step before initiating immunotherapy, and regular ongoing assessments during the treatment course can facilitate early recognition of any secondary complications, enabling prompt intervention and ensuring optimal therapeutic outcomes. Overall, a multidisciplinary diagnostic and therapeutic algorithm can help maximize the therapeutic benefits of immunotherapy.
Suppression of NLRP3 inflammasome orchestrates the protective efficacy of tiron against isoprenaline-induced myocardial injury
Authors: Abdelrahaman Doaa , Habotta Ola A. , Taher Ehab S. , El-Ashry Eman S. , Ibrahim Iman , Abdeen Ahmed , Ibrahim Ateya M. , Ibrahim Reham M. , Anwer Hala , Mihaela Ostan , Olga Rada , Alwutayed Khairiah M. , Al-Serwi Rasha H. , El-Sherbiny Mohamed , Sorour Safwa M. , El-Kashef Dalia H.
Published: August 2024

The major contribution of myocardial damage to global mortalities raises debate regarding the exploration of new therapeutic strategies for its treatment. Therefore, our study investigated the counteracting effect of tiron against isoprenaline (ISO)-mediated cardiac infarction in mice. Tiron was administered to mice for 7 days prior to two consecutive injections of ISO on days 8 and 9 of the treatment protocol. Tiron significantly reduced the levels of CK-MB, LDH, and AST in serum samples of ISO-challenged mice. A considerable increase in the cardiac antioxidant response was observed in tiron-treated mice, as indicated by depletion of MDA and enhancement of antioxidant activities. Furthermore, tiron induced a marked decrease in NLRP3, ASC, and caspase-1 levels accompanied by weak immune reactions of IL-1β, NF-κB, TLR4, and iNOS in the infarct cardiac tissues. Histopathological screening validated these variations observed in the cardiac specimens. Thus, tiron clearly mitigated the oxidative and inflammatory stress by repressing the NLRP3 inflammasome and the TLR4/NF-κB/iNOS signaling cascade.