bluuebunny/crossref_metadata_2025 huggingface dataset:
IMBUHAN DALAM BAHASA DAWAN (KAJIAN MORFOLOGI)
Authors: Liunokas Emanti , Adam Lenny N. , Lelo Lein Adeline
Published: August 2024

Tujuan penelitian ini adalah untuk mendeskripsikan bentuk kata yang berimbuhan dalam Alkitab Bahasa Dawan. Jenis penelitian ini merupakan penelitian kualitatif dengan metode deskripstif. Objek dalam penelitian ini adalah bentuk imbuhan bahasa dawan dalam Alkitab bahasa Dawan. Sumber data dalam penelitian ini adalah Alkitab bahasa dawan. Teknik pengumpulan data dalam penelitian ini adalah studi pustaka,  dan teknik catat. Hasil penelitian terdapat 48 imbuhan bahasa dawan dengan rincian sebagai berikut  yang terdiri dari 32 bentuk prefiks, 15 bentuk konfiks, dan 1 bentuk sufiks.
MENUMBUHKAN NILAI-NILAI BUDAYA MELALUI MODEL PEMBELAJARAN BAHASA INDONESIA BERBASIS KEARIFAN LOKAL
Authors: Kharisma Giri Indra , Talan Maria Rosalinda
Published: August 2024

Penelitian ini bertujuan menjelaskan penerapan pembelajaran bahasa Indonesia berbasis nilai-nilai kearifan lokal. Penelitian ini menggunakan metode studi pustaka yang bertujuan memaparkan hasil kajian dari berbagai sumber pustaka yang memuat informasi tentang teori pendidikan, pembelajaran bahasa Indonesia, dan kearifan lokal. Pembelajaran Bahasa Indonesia berbasis kearifan lokal merupakan model pembelajaran bahasa Indonesia yang digunakan untuk mendeskripsikan, menafsirkan, dan merespons budaya lokal. Pembelajaran tersebut diintegrasikan dengan kearifan lokal. Bentuk integrasi tersebut dapat berupa metode, media, strategi maupun materi pembelajaran Bahasa Indonesia.
Edema pulmonar en paciente gestante, un reto diagnóstico y terapéutico para el anestesiólogo: reporte de caso
Authors: Zuluaga Gil Adolfo , Gallego González Daniel , De la Peña Ancizar
Published: August 2024

Introducción:
los cambios fisiológicos del embarazo aumentan el riesgo de desarrollar edema pulmonar, especialmente en casos relacionados con trastornos hipertensivos asociados al embarazo (THAE) o en cardiomiopatías periparto. El edema agudo de pulmón (EAP) se define como la acumulación de líquido en el espacio alveolo intersticial y aumenta la morbimortalidad materno perinatal especialmente cuando ocurre en el periparto, por lo que se debe monitorizar de manera adecuada y tratar oportunamente para evitar desenlaces adversos. Caso clínico: se presenta el caso clínico de una paciente de 25 años, con embarazo de 33 semanas y 6 días, atendida en un centro de referencia de ginecobstetricia de la ciudad de Medellín - Colombia, inicialmente por cuadro de pielonefritis con posterior desarrollo de sepsis, quien tras manejo con líquidos intravenosos desarrolló un cuadro de dificultad respiratoria. Durante la evaluación preanestésica para la analgesia epidural se realizó el diagnóstico de preeclampsia grave por cifras tensionales y edema pulmonar concomitante, que respondió satisfactoriamente al manejo con diurético de asa, restricción hídrica y ventilación mecánica no invasiva durante la inducción del trabajo de parto. Conclusión: Las pacientes gestantes son más proclives a complicaciones por sobrecarga hídrica que impacta en la morbimortalidad, un adecuado manejo médico basado en la ecografía y monitoria mínimamente invasiva a la cabecera de la paciente permite un manejo guiado por metas y seguimiento en tiempo real de su estado hemodinámico lo que facilita un adecuado tratamiento.
HEADACHES AFTER SPINAL ANESTHESIA AND THEIR LINK WITH RELATED FACTORS IN CANDIDATES FOR CESAREAN
Authors: Abdi Kamel , Abdullahzadeh Mehrdad , Gholamveisi Behzad , Aghabakpour Hatam , Karimian Aram
Published: August 2024

Background: During a cesarean section, spinal anesthesia can result in post-dural puncture headaches.
Objective: A group of female candidates for cesarean was studied to explore the link between post-spinal anesthesia headaches and factors, including age, BMI, blood pressure, fasting blood sugar, duration of immobilization in the supine position after spinal anesthesia, and history of prior spinal anesthesia and post-dural puncture headache. The needle size, type, and technique used for spinal anesthesia remained constant throughout the study.
Methods: A cohort study was conducted on 80 women who were scheduled to undergo cesarean sections at a hospital in Iran. Researchers used the numeric pain rating scale to assess the severity of the women's headaches following spinal anesthesia. Through t-tests and chi-square tests, the potential link between headaches and related factors was analyzed.
Result: The researchers found no significant association between headaches and factors such as age, BMI, blood pressure, fasting blood sugar, duration of immobilization in the supine position after spinal anesthesia, and history of prior spinal anesthesia and post-dural puncture headache (P > 0.5).
Conclusion: When performing cesarean sections, anesthesia providers should consider all possible factors that could cause headaches in women who have undergone spinal anesthesia, regardless of age, BMI, blood sugar levels, blood pressure, immobilization time, or prior history of headaches.
THE NURSE'S ROLE IN COMMUNICATION WITH THE PATIENT/CLIENT
Authors: Tushe Mirela
Published: August 2024

The nurse plays a vital role in communication with the patient/ client. She/he is the person who spends the most time with the patient and constantly takes care of him/ her.
From the first moments of presentation, reception and companionship of the patient, a relationship of interaction is created between each other.
The nurse is the health professional who in the communication process is the information provider and the patient/client are the receiver, still these roles are sometimes exchanged depending on the situation.
The way we communicate, the ethics we use, the behavior and attitude we maintain, the values ​​we present, show and highlight the figure and model of the professional nurse.
IDENTITAS GARAP MUSIK JOMBANGAN PADA KESENIAN JARANAN DOR DI KABUPATEN KEDIRI
Authors: Nugraha Andre Prasetya , Salim Muhammad Nur
Published: August 2024

This study aims to analyze the identity of Jombangan music garap and its forming factors in the art of Jaranan Dor art group "Karya Budaya" in Kediri Regency. The problem is analyzed using theories put forward by several figures. In the process of analyzing identity in garap music, Jaranan Dor uses the theory offered by George M. Head and Rahayu Supanggah, and to describe the factors of identity formation using the theory proposed by Stuart Hall. This research uses qualitative methods, with stages of data collection, data analysis, and data presentation. The data collection phase includes interviews, observation, documentation, and transcription. The data analysis stage includes data reduction, data presentation, and conclusions. The data presentation stage is carried out after obtaining the results of the data analysis stage and then presented in a scientific writing work. The identity formed through the elements of music garap in the Jaranan Dor art group "Karya Budaya" is Jombangan. Jombangan identity can be formed due to several factors, including geographical location, cultural conditions of the community, and history.
Monitoring of CO2 emission fluxes and organic C balance in limed sod-podzolic soil in winter rapeseed field
Authors: Polovyi V. , Yashchenko L. , Rovna H. , Huk B.
Published: August 2024

Management of carbon sequestration processes is one of the main issues in overcoming soil organic matter degradation in the Polissya zone, especially taking into account climate changes. There is a need to research and develop measures to reduce unproductive losses of CO2 from the soil, which will contribute to the stabilization of the organic carbon content in the soil under intensive agriculture. The goal of the research was to establish the peculiarities of CO2 emission fluxes formation and the balance of organic carbon in sod-podzolic soil on average over the cultivation years of winter rapeseed in short crop rotation at different doses of ameliorants and fertilizers. Research methods: field experiment, laboratory, computational and statistical analysis. According to the research results it was found that during the spring- summer period of cultivation of winter rapeseed cultivation in crop rotation the highest unproductive losses of CO2 from the soil can be traced in the variant without fertilizers. Significant reductions in the average daily emission fluxes of CO2 from the soil and unproductive losses of carbon dioxide were noted with the application of 1.5 doses of CaMg(CO3 )2 against the background of N120P90K120 to 218.5 kg/ha and 3.64 kg/ ha/h, respectively. Improvement of growing conditions in this variant contributes to increased accumulation of CO2 22% in the biomass of winter rapeseed and, accordingly, an increase in the share of crop residues when they are plowed into the soil to 62.8% of the total carbon dioxide emissions into the atmosphere. Taking into account the share of fertilizers and dolomite flour, the share of humus mineralization decreased to 22.6%. It was found that the application of 1.5 doses of CaMg(- CO3 ) 2 against the background of the recommended dose of fertilizer with the incorporation of by-products into the soil stabilizes the organic carbon balance at the level of 0.05 t/ha.
Key words: winter rapeseed, CO2 emissions, chemical reclamation, fertilization, organic carbon balance.
The influence of biological preparations on the formation of quantitative indicators of spring barley variety «Bravyi» under different nutritional backgrounds
Authors: Vyskub R. , Sknypa N.
Published: August 2024

Goal of research was to study of the effect of microbiological preparations on biometric indicators formation of spring barley plants (Hordeum vulgare L.) under mineral and organic fertilization systems (spring barley variety «Bravyi»). The research was carried out in the field crop rotation of the Donetsk State Agricultural Science Station of the National Academy of Agrarian Sciences of Ukraine in 2021-2023 on two nutritional backgrounds: mineral (N30P30) and organic (biohumus – 1000 kg/ha). As a result of quantitative analysis the highest tillering coefficient of spring barley at the end of the tillering phase on a mineral nutrition background was when using «Microhumin» and «Baikal» preparations for seed treatment (1.9); on an organic nutrition background all options for using microbiological preparations for seed treatment contributed to the formation of the number of shoots at the level of 1.5-1.6 pcs. The largest number of nodal roots on a spring barley plant on a mineral background (2.3) made it possible to form variants where seeds and crops were treated with biological preparations. On an organic background, an average of 0.1 pcs there were fewer nodal roots than on the mineral background. During plants analysis in the phase of full maturity, it was established that with a mineral nutrition background the highest coefficients of general tillering were in the variants with inoculation of seeds with «Microhumin» and spraying of crops with «Baikal» (1,9). «Baikal» (spraying of crops in tilling phase) and «Baikal» (seed processing) + «Biorhythm» (spraying of crops in tilling phase) variants had the highest coefficients of productive tillering (1.8 and 1.7 respectively). When using an organic nutritional background the best indicator of general tillering coefficient was obtained when inoculating seeds with the drug «Mikrohumin» (spraying of crops in tilling phase) –1.6, the coefficients of productive tillering ranged from 1.2 to 1.3. The use of Microbiological preparations application for seed treatment contributed to an increase in the tillering coefficient and secondary roots formation in spring barley plants regardless of the nutritional background. The number of total and productive stems was greater on the mineral nutrition background in all experimental variants.
Key words: spring barley, mineral and organic fertilizing system, microbiological preparations, tillering phase, phase of full ripeness, biometric indicators.
Peculiarities of root system and aerial part formation in evergreen boxwood cuttings with twoyear-old and one-year-old wood
Authors: Koval S. , Vitenko V. , Adamenko S. , Bayura O. , Kurka S. , Didenko I.
Published: August 2024

The study results of the peculiarities of evergreen boxwood rooting (Buxus sempervirens L.) cuttings with two-year wood were presented, regeneration processes in which are insufficiently studied. Also the cuttings with one-year wood, as well as analysis and comparison of biometric indicators of cutting seedlings obtained from the cuttings of both types are presented. The formation and formation of the root system and the growth of the above-ground part of boxwood cuttings were studied at the Uman National University of Horticulture in a greenhouse equipped with a device for finely dispersed moistening. It was investigated that the most effective for stimulating regeneration processes in boxwood cuttings with two-year wood is a solution of β-indolylbutyric acid (β-IMK) with a concentration of 60 mg/l. In cuttings with one-year wood these processes are most effectively stimulated by β-IMK solution with a concentration of 40 mg/l. It was found that cuttings of the first type form more roots compared to cuttings of the second type, they also develop a longer and branched root system. In the optimal version, the cuttings of the first type regenerated 71.3 pieces of main roots, while the cuttings of the second type of roots formed 44.5 pieces. Evergreen boxwood cuttings of the first type form the longest root system – 365.6 cm, while cuttings with one-year wood – 159.7 cm on average for the 2019-2021 research years. Treatment of boxwood cuttings with both two-year-old and one-year-old wood with β-IMK solutions also revealed a significant positive effect on the height of their above-ground part, which in the optimal version exceeded the control version by 1.3 times or by 5.8 cm, and by 1.2 times or by 3.5 cm on average during the research period. The best indicators of economic efficiency are the following: the highest level of profitability – 126.17%, the largest profit – 3246.76 UAH. for the lowest cost of a seedling – UAH 13.26. in terms of 1 m2 of a greenhouse with equipment for fine-dispersed humidification, obtained after growing rooted boxwood cuttings of the first type in the variant using β-IMK with a concentration of 60 mg/l. Thus, the study of the effect of a growth-regulatory substance on the formation of root system and the above-ground part in both types of evergreen boxwood cuttings and the improvement of technological measures for growing seedlings is currently an urgent problem, the solution of which will be provided by the development of scientifically based recommendations for producers of high-quality planting material of this valuable decorative plant.
Key words: grafting, number and length of roots, rooting, growing, seedling.
Chất lượng vốn nhân lực và lựa chọn nghề nghiệp của người lao động ở Việt Nam
Authors: Bùi Quang Tuyến , Mai Thanh Lan
Published: August 2024

Nghiên cứu này phân tích tác động của vốn nhân lực, được đo bằng trình độ giáo dục tới lựa chọn nghề của người lao động ở Việt Nam. Sử dụng dữ liệu điều tra lao động việc làm năm 2022 và mô hình hồi quy logit đa thức, kết quả nghiên cứu cho thấy các cá nhân có nhiều năm năm đi học thường có khả năng cao hơn làm công việc chủ cơ sở kinh doanh so với lao động tự làm. Tuy nhiên, người lao động có trình độ cao đẳng/đại học lại có khả năng cao hơn chọn làm công ăn lương so với làm chủ cơ sở kinh doanh. Kết quả này cũng được tìm ở nhóm lao động nữ. Bên cạnh đó, kết quả cho thấy bằng cấp cao đẳng/đại học không ảnh hưởng tới khả năng lựa chọn công việc làm chủ cơ sở kinh doanh hay làm công ăn lương cho nhóm lao động nam. Phát hiện này hàm ý rằng chất lượng vốn nhân lực có vai trò quan trọng trong lựa chọn nghề nghiệp của người lao động ở Việt Nam.
Network-based food availability affects the keystoneness of predators and functional diversity of the marine food web
Authors: Xu Y , Jordán F
Published: August 2024

Marine predators play an important role in food webs, and their food availability affects the structure and function of marine ecosystems. In this research, we calculated 6 network-level topological indices and the keystone index for predator nodes. We also quantified the functional homogenization degree of the food web by using a measure of functional diversity. We simulated food availability variation by adding or deleting a link to each predator node and recalculating the above indicators in turn when generating a new network. We found that increased food availability can increase the topological complexity in food webs, yet top predators show less plasticity in network structure than lower predators. The resulting variability in average path length may be related to the threshold at which omnivory affects food web stability. When food availability ranges from 0.3 to 0.6, predators at higher trophic levels may have a positive impact on the stability of the food web, as an interplay between bottom-up and top-down mechanisms. In addition, high food availability may lead to functional homogenization, particularly in predators with lower trophic levels. For top predators, reduced food availability is more conducive to the resilience of network functional diversity. Finally, increasing food availability increases the relative positional importance of predator nodes in the network. Especially for top predators, this amplifies their top-down effects on lower levels in the food web. This research reveals the mechanistic basis of the homogenization of marine food webs and contributes a theoretical basis for the effective management of marine ecosystems.
Isolation and characterization of plant growth-promoting rhizobacteria (PGPR) from eelgrass Zostera marina rhizosphere: implications for bioremediation
Authors: Sun J , Zhang YH , Zhao X , Yan WJ , Li WT , Zhang PD
Published: August 2024

Plant growth-promoting rhizobacteria (PGPR) play a crucial role in enhancing plant growth. However, investigations into the presence and function of PGPR in seagrass rhizospheres remain relatively limited. In this study, we isolated 45 strains of PGPR from Zostera marina rhizospheres and assessed their functional attributes. Additionally, we evaluated the performance of these candidate strains under varying environmental conditions, such as temperature, salinity, and pH. Out of the 45 analyzed strains, 6 were found to possess the nifH gene; some strains also exhibited the ability to solubilize inorganic phosphorus, with dissolved phosphorus content ranging widely from 14.6 to 393.9 mg l-1. Eleven strains demonstrated indole-3-acetic acid production, with yields spanning from 16.3 to 42.8 mg l-1. Siderophores and ammoniated proteins were produced by 32 and 20 strains, respectively. Notably, 5 PGPR strains (F65, G84, G85, G86, and I109) displayed multiple growth-promoting properties along with strong adaptability to a wide range of physicochemical conditions. This study highlights the potential reservoir of PGPR in the eelgrass rhizosphere and provides significant implications for utilizing these bacteria to enhance the success rate of restoring degraded seagrass meadows.
Optimalisasi Penerapan Sistem Informasi Pemerintahan Daerah Dalam Meningkatkan Kualitas Laporan Keuangan di Kabupaten Gianyar
Authors: Wahyudi Kadek Prawira , Johannes Ayu Widowati , Sinurat Marja , Romarina Arina
Published: August 2024

ABSTRACT
This research aims to determine the optimization of the implementation of the Regional Government Information System (SIPD) in improving the quality of regional government financial reports in increasing the use of SIPD so that it can improve the quality of regional government financial reporting in Gianyar Regency. This research design is qualitative research using descriptive methods. Data collection techniques use three methods, namely observation, interviews and documentation. The data that has been collected is analyzed according to the Miles and Huberman analysis model, which includes data reduction techniques, data presentation, and drawing conclusions. The theoretical basis that researchers use in this research is to use the theory according to DeLone and McLean with six key elements. System quality, information quality, service quality, intensity of use, user satisfaction and net benefits.
Keywords: Information System, Report Quality, Regional Government Financial Reports
ABSTRAK
Penelitian ini bertujuan untuk mengetahui optimalisasi penerapan Sistem Informasi Pemerintahan Daerah (SIPD) dalam meningkatkan kualitas laporan keuangan pemerintah daerah dalam meningkatkan pemanfaatan SIPD sehingga dapat meningkatkan kualitas pelaporan keuangan pemerintah daerah di Kabupaten Gianyar. Desain penelitian ini adalah penelitian kualitatif dengan menggunakan metode deskriptif. Teknik pengumpulan data menggunakan tiga cara yaitu observasi, wawancara, dan dokumentasi. Data-data yang telah terkumpul dianalisis sesuai model analisis Miles dan Huberman, yang mencakup teknik reduksi data, penyajian data, dan pengambilan kesimpulan. Landasan teori yang peneliti gunakan dalam penelitian ini adalah dengan menggunakan teori menurut DeLone dan McLean dengan enam elemen kunci. Kualitas sistem (system quality), kualitas informasi (information quality), kualitas layanan (service quality), intensitas penggunaan (intention to use), kepuasan pengguna (user satisfaction), serta manfaat bersih (benefit).
Kata Kunci: Sistem Informasi, Kualitas Laporan, Laporan Keuangan Pemerintah Daerah
Analisis Pendapatan Asli Daerah Dalam Meningkatkan Kemandirian Daerah Kabupaten Sarolangun Provinsi Jambi
Authors: Hafiz Mahfuz Al , Sari Agni Grandita Permata
Published: August 2024

Otonomi daerah, yang ditetapkan melalui Peraturan Perundang-Undangan Nomor 22 tahun 1999 tentang Pemerintahan Daerah, memberikan kewenangan kepada daerah otonom untuk mengurus dan mengatur kepentingan masyarakat setempat. Namun, ketergantungan pada dana transfer dari pemerintah pusat masih menjadi kenyataan, yang menghasilkan ketergantungan fiskal.Penelitian ini bertujuan untuk memahami kontribusi pendapatan asli  daerah Kabupaten Sarolangun dalam meningkatkan kemandirian daerah, tantangan yang dihadapi, dan upaya yang dilakukan pemerintah daerah dalam mewujudkan otonomi daerah. Metode penelitian kualitatif digunakan untuk mendapatkan informasi yang akurat dan lengkap dari informan yang dipilih melalui purposive sampling. Hasil penelitian menunjukkan bahwa data yang diperoleh dari tahun 2020-2022, berdasarkan beberapa kategori rasio yang diantaranya yaitu kemandirian tidak bisa dikatakan mandiri. Rasio keefektifan hanya mendapatkan katergori kurang efektif. Rasio efisiensi dapat dikatan sangat efisien. Rasio ketergantungan dibilang sangat bergantung. Rasio desentralisasi memiliki tingkat desentralisasi yang tinggi. Efisensi pajak mendaptkan hasil yang tidak efisien. Efektivitas  pajak yang tiap taunnya mengalami peningkatan. Derajat Kontribusi BMD masih rendah.  Rasio Hutang terhadap pendapatan terjadi fluktuatif. Rasio kemampuan mengembalikan pinjaman masih dibawah angka 2,5. Tantangan dalam meningkatkan kemandirian daerah mencakup faktor internal yaitu rendahnya kualifikasi sumber daya manusia, ketergantungan pada sumber pendapatan tertentu, pemungutan pajak yang tidak optimal serta faktor eksternal yaitu infrastruktur terbatas, ketidakpastian kondisi ekonomi dan pasar, serta rendahnya investasi dan inovasi. Upaya yang dilakukan oleh pemerintah Kabupaten Sarolangun dalam meningkatkan kemandirian daerah yaitu melakukan Diversifikasi Sumber Pendapatan, Peningkatan Kualifikasi Sumber Daya Manusia, serta Optimalisasi Pemungutan Pajak.
Kata Kunci : Jumlah kata kunci antara 3-5 kata yang ditulis berdasarkan alfabetis.
From stress fiber to focal adhesion: a role of actin crosslinkers in force transmission
Authors: Katsuta Hiroki , Sokabe Masahiro , Hirata Hiroaki
Published: August 2024

The contractile apparatus, stress fiber (SF), is connected to the cell adhesion machinery, focal adhesion (FA), at the termini of SF. The SF-FA complex is essential for various mechanical activities of cells, including cell adhesion to the extracellular matrix (ECM), ECM rigidity sensing, and cell migration. This mini-review highlights the importance of SF mechanics in these cellular activities. Actin-crosslinking proteins solidify SFs by attenuating myosin-driven flows of actin and myosin filaments within the SF. In the solidified SFs, viscous slippage between actin filaments in SFs and between the filaments and the surrounding cytosol is reduced, leading to efficient transmission of myosin-generated contractile force along the SFs. Hence, SF solidification via actin crosslinking ensures exertion of a large force to FAs, enabling FA maturation, ECM rigidity sensing and cell migration. We further discuss intracellular mechanisms for tuning crosslinker-modulated SF mechanics and the potential relationship between the aberrance of SF mechanics and pathology including cancer.
Network medicine analysis for dissecting the therapeutic mechanism of consensus TCM formulae in treating hepatocellular carcinoma with different TCM syndromes
Authors: Gao Kai , Cao WanChen , He ZiHao , Liu Liu , Guo JinCheng , Dong Lei , Song Jini , Wu Yang , Zhao Yi
Published: August 2024

Introduction

Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality worldwide. Traditional Chinese Medicine (TCM) is widely utilized as an adjunct therapy, improving patient survival and quality of life. TCM categorizes HCC into five distinct syndromes, each treated with specific herbal formulae. However, the molecular mechanisms underlying these treatments remain unclear.

Methods

We employed a network medicine approach to explore the therapeutic mechanisms of TCM in HCC. By constructing a protein-protein interaction (PPI) network, we integrated genes associated with TCM syndromes and their corresponding herbal formulae. This allowed for a quantitative analysis of the topological and functional relationships between TCM syndromes, HCC, and the specific formulae used for treatment.

Results

Our findings revealed that genes related to the five TCM syndromes were closely associated with HCC-related genes within the PPI network. The gene sets corresponding to the five TCM formulae exhibited significant proximity to HCC and its related syndromes, suggesting the efficacy of TCM syndrome differentiation and treatment. Additionally, through a random walk algorithm applied to a heterogeneous network, we prioritized active herbal ingredients, with results confirmed by literature.

Discussion

The identification of these key compounds underscores the potential of network medicine to unravel the complex pharmacological actions of TCM. This study provides a molecular basis for TCM’s therapeutic strategies in HCC and highlights specific herbal ingredients as potential leads for drug development and precision medicine.
First step results from a phase II study of a dendritic cell vaccine in glioblastoma patients (CombiG-vax)
Authors: Ridolfi Laura , Gurrieri Lorena , Riva Nada , Bulgarelli Jenny , De Rosa Francesco , Guidoboni Massimo , Fausti Valentina , Ranallo Nicoletta , Calpona Sebastiano , Tazzari Marcella , Petrini Massimiliano , Granato Anna Maria , Pancisi Elena , Foca Flavia , Dall’Agata Monia , Bondi Isabella , Amadori Elena , Cortesi Pietro , Zani Chiara , Ancarani Valentina , Gamboni Alessandro , Polselli Antonio , Pasini Giuseppe , Bartolini Daniela , Maimone Giuseppe , Arpa Donatella , Tosatto Luigino
Published: August 2024

Background

Glioblastoma (GBM) is a poor prognosis grade 4 glioma. After surgical resection, the standard therapy consists of concurrent radiotherapy (RT) and temozolomide (TMZ) followed by TMZ alone. Our previous data on melanoma patients showed that Dendritic Cell vaccination (DCvax) could increase the amount of intratumoral-activated cytotoxic T lymphocytes

Methods

This is a single-arm, monocentric, phase II trial in two steps according to Simon’s design. The trial aims to evaluate progression-free survival (PFS) at three months and the safety of a DCvax integrated with standard therapy in resected GBM patients. DCvax administration begins after completion of RT-CTwith weekly administrations for 4 weeks, then is alternated monthly with TMZ cycles. The primary endpoints are PFS at three months and safety. One of the secondary objectives is to evaluate the immune response both in vitro and in vivo (DTH skin test).

Results

By December 2022, the first pre-planned step of the study was concluded with the enrollment, treatment and follow up of 9 evaluable patients. Two patients had progressed within three months after leukapheresis, but none had experienced DCvax-related G3-4 toxicities Five patients experienced a positive DTH test towards KLH and one of these also towards autologous tumor homogenate. The median PFS from leukapheresis was 11.3 months and 12.2 months from surgery.

Conclusions

This combination therapy is well-tolerated, and the two endpoints required for the first step have been achieved. Therefore, the study will proceed to enroll the remaining 19 patients. (Eudract number: 2020-003755-15 https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-003755-15/IT)
Acute T-cell lymphoblastic leukemia: chimeric antigen receptor technology may offer a new hope
Authors: Jing Jiajie , Ma Yuan , Xie Ziwen , Wang Bingyan , Chen Yueming , Chi Enjie , Wang Jiadong , Zhang Kejin , Wang Zhujun , Li Sisi
Published: August 2024

Acute lymphoblastic leukemia (ALL) is a prevalent malignancy affecting the hematopoietic system, encompassing both B-cell ALL (B-ALL) and T-cell ALL (T-ALL). T-ALL, characterized by the proliferation of T-cell progenitors in the bone marrow, presents significant treatment challenges, with patients often experiencing high relapse rates and poor long-term survival despite advances in chemotherapy and hematopoietic stem cell transplantation (HSCT). This review explores the pathogenesis and traditional treatment strategies of T-ALL, emphasizing the promising potential of chimeric antigen receptor (CAR) technology in overcoming current therapeutic limitations. CAR therapy, leveraging genetically modified immune cells to target leukemia-specific antigens, offers a novel and precise approach to T-ALL treatment. The review critically analyzes recent developments in CAR-T and CAR-NK cell therapies, their common targets, optimization strategies, clinical outcomes, and the associated challenges, providing a comprehensive overview of their clinical prospects in T-ALL treatment.
Aryl hydrocarbon receptor: current perspectives on key signaling partners and immunoregulatory role in inflammatory diseases
Authors: Bahman Fatemah , Choudhry Khubaib , Al-Rashed Fatema , Al-Mulla Fahd , Sindhu Sardar , Ahmad Rasheed
Published: August 2024

The aryl hydrocarbon receptor (AhR) is a versatile environmental sensor and transcription factor found throughout the body, responding to a wide range of small molecules originating from the environment, our diets, host microbiomes, and internal metabolic processes. Increasing evidence highlights AhR’s role as a critical regulator of numerous biological functions, such as cellular differentiation, immune response, metabolism, and even tumor formation. Typically located in the cytoplasm, AhR moves to the nucleus upon activation by an agonist where it partners with either the aryl hydrocarbon receptor nuclear translocator (ARNT) or hypoxia-inducible factor 1β (HIF-1β). This complex then interacts with xenobiotic response elements (XREs) to control the expression of key genes. AhR is notably present in various crucial immune cells, and recent research underscores its significant impact on both innate and adaptive immunity. This review delves into the latest insights on AhR’s structure, activating ligands, and its multifaceted roles. We explore the sophisticated molecular pathways through which AhR influences immune and lymphoid cells, emphasizing its emerging importance in managing inflammatory diseases. Furthermore, we discuss the exciting potential of developing targeted therapies that modulate AhR activity, opening new avenues for medical intervention in immune-related conditions.
Stiffness regulates dendritic cell and macrophage subtype development and increased stiffness induces a tumor–associated macrophage phenotype in cancer co–cultures
Authors: Guenther Carla
Published: August 2024

Mechanical properties of tissues including their stiffness change throughout our lives, during both healthy development but also during chronic diseases like cancer. How changes to stiffness, occurring during cancer progression, impact leukocytes is unknown. To address this, myeloid phenotypes resulting from mono- and cancer co-cultures of primary murine and human myeloid cells on 2D and 3D hydrogels with varying stiffnesses were analyzed. On soft hydrogels, conventional DCs (cDCs) developed, whereas on stiff hydrogels plasmacytoid DCs (pDCs) developed. Soft substrates promoted T cell proliferation and activation, while phagocytosis was increased on stiffer substrates. Cell populations expressing macrophage markers CD14, Ly6C, and CD16 also increased on stiff hydrogels. In cancer co–cultures, CD86+ populations decreased on higher stiffnesses across four different cancer types. High stiffness also led to increased vascular endothelial growth factor A (VEGFA), matrix metalloproteinases (MMP) and CD206 expression; ‘M2’ markers expressed by tumor–associated macrophages (TAMs). Indeed, the majority of CD11c+ cells expressed CD206 across human cancer models. Targeting the PI3K/Akt pathway led to a decrease in CD206+ cells in murine cultures only, while human CD86+ cells increased. Increased stiffness in cancer could, thus, lead to the dysregulation of infiltrating myeloid cells and shift their phenotypes towards a M2–like TAM phenotype, thereby actively enabling tumor progression. Additionally, stiffness–dependent intracellular signaling appears extremely cell context–dependent, potentially contributing to the high failure rate of clinical trials.
Effect of glycerol on properties of chitosan/chlorhexidine membranes and antibacterial activity against Streptococcus mutans
Authors: Hachity-Ortega José Alberto , Jerezano-Domínguez Alberto V. , Pazos-Rojas Laura Abisai , Flores-Ledesma Abigailt , Pazos-Guarneros Diana del C. , Parra-Solar Karla Aimée , Reyes-Cervantes Eric , Juárez-Díaz Ismael , Medina Manuel E. , González-Martínez Mayra , Castillo-Silva Brenda Eréndida , Ávila-Curiel Beatriz Xochitl , Hernández-Juárez Jesús , Rivera-Urbalejo América , Gordillo-Guerra Paola G. , Casillas-Santana Miguel Angel
Published: August 2024

Introduction

Chitosan membranes with glycerol can function as an effective dispersing agent for different antibiotics or active ingredients that can be used in the treatment of diseases present in the oral cavity.

Methods

The effects of the addition of glycerol on the mechanical, water absorption, swelling, pH, thickness, disintegration, rugosity, and antibacterial properties of chitosan-chlorhexidine- glycerol membranes were investigated in this study.

Results and discussion

Mechanical results indicated that chitosan membranes' rugosity, strength, flexion, and thickness differed at loading 1, 3, 5, 10, 15, and 20% of glycerol (p < 0.05). The chitosan membranes' rugosity, dissolution, strength, and pH results were significantly enhanced by the presence of glycerol at 3, 5, and 10% concentrations. In this investigation, the antimicrobial activity model used was the inhibition of Streptococcus mutans CDBB-B-1455 by chitosan-chlorhexidine membranes. It was observed that there was no change in inhibition with different concentrations of glycerol. The results suggest that chitosan-glycerol-chlorhexidine membranes may be a potential candidate for topical antiseptic application in buccal-dental disorders caused by S. mutans, such as caries, periodontal diseases, and oral squamous cell carcinoma, helping to prevent the development of serious conditions that can compromise human health.
Multi-omics analysis of gut microbiota and metabolites reveals contrasting profiles in domestic pigs and wild boars across urban environments
Authors: Ding Jingjing , Cui Xinyuan , Wang Xuan , Zhai Feifei , Wang Lei , Zhu Lifeng
Published: August 2024

The gut microbiota plays a crucial role in host health and metabolism. This study explores the differences in gut microbiota and metabolites between domestic pigs (DP) and wild boars (WB) in urban environments. We analyzed gut microbial composition, metabolic profiles, virome composition, antibiotic resistance genes (ARGs), and human pathogenic bacteria (HPB) in both DP and WB. Our results revealed that DP exhibited a higher Firmicutes/Bacteroidetes ratio and were enriched in bacterial genera associated with domestication and modern feeding practices. Metabolomic analysis showed distinct profiles, with WB significantly enriched in the Pantothenate and CoA biosynthesis pathway, highlighting dietary and environmental influences on host metabolism. Additionally, DP had a distinct gut virome composition, particularly enriched in lytic phages of the Chaseviridae family. ARG analysis indicated a higher abundance of tetracycline resistance genes in DP, likely due to antibiotic use in pig farms. Furthermore, variations in HPB composition underscored potential health risks associated with contact with pig feces. These findings provide valuable insights into the microbial ecology of domestic pigs and wild boars, emphasizing the importance of these comparisons in identifying zoonotic pathogen transmission pathways and managing antibiotic resistance. Continued research in this area is essential for developing effective strategies to mitigate public health risks and promote sustainable livestock management practices.
Efficacy and safety of deep brain stimulation in mesencephalic locomotor region for motor function in patients with post-stroke hemiplegia: a study protocol for a multi-center double-blind crossover randomized controlled trial
Authors: Xu Junpeng , Liu Bin , Liu Shuzhen , Feng Zhebin , Zhang Yanyang , Liu Di , Chang Qing , Yang Haonan , Chen Yuhan , Yu Xinguang , Mao Zhiqi
Published: August 2024

Background

Deep brain stimulation (DBS) is a potential treatment for improving movement disorder. However, few large-sample studies can reveal its efficacy and safety. This study aims to initially explore the efficacy and safety of DBS in the mesencephalic locomotor region (MLR) on motor function in patients with post-stroke hemiplegia.

Methods/design

This multicenter, prospective, double-blind, randomized crossover clinical trial aims to assess the safety and effectiveness of Deep Brain Stimulation (DBS) in the mesencephalic locomotor region (MLR) for patients with moderate to severe post-stroke hemiplegia. Sixty-two patients with stable disease after a year of conservative treatment will be enrolled and implanted with deep brain electrodes. Post-surgery, patients will be randomly assigned to either the DBS group or the control group, with 31 patients in each. The DBS group will receive electrical stimulation 1 month later, while the control group will undergo sham stimulation. Stimulation will be discontinued after 3 and 6 months, followed by a 2-week washout period. Subsequently, the control group will receive electrical stimulation, while the DBS group will undergo sham stimulation. Both groups will resume electrical stimulation at the 9th and 12th-month follow-ups. Post-12-month follow-up, motor-related scores will be collected for analysis, with the Fugl-Meyer Assessment Upper Extremity Scale (FMA-UE) as the primary metric. Secondary outcomes include balance function, neuropsychiatric behavior, fall risk, daily living activities, and quality of life. This study aims to provide insights into the therapeutic benefits of DBS for post-stroke hemiplegia patients.

Result/conclusion

We proposed this study for the first time to comprehensively explore the effectiveness and safety of DBS in improving motor function for post-stroke hemiplegia, and provide evidence for DBS in the treatment of post-stroke hemiplegia. Study limitations are related to the small sample size and short study period.

Clinical Trial Registration

Clinicaltrials.gov, identifier NCT05968248.
Neurologic manifestations of Long COVID in Colombia: a comparative analysis of post-hospitalization vs. non-hospitalized patients
Authors: Hurtado Carolina , Rojas-Gualdrón Diego Fernando , Pérez Giraldo Gina S. , Villegas Arbelaez Esteban , Mantilla Salvador Ernesto Medina , Campuzano-Sierra Mariana , Ospina-Patino Santiago , Arroyave-Bustamante Mariana , Uribe-Vizcarra Valeria , Restrepo-Arbelaez Daniel , Cardona Paul , Llano-Piedrahita Julián , Vásquez-Builes Santiago , Agudelo-Quintero Esteban , Vélez-Arroyave Juliana , Menges Sebastián , Jimenez Millenia , Miller Janet , Quique Yina M. , Koralnik Igor J.
Published: August 2024

Objective

To analyze patient-reported outcomes, cognitive function, and persistent symptoms in patients with neurologic post-acute sequelae of SARS-CoV-2 infection (Neuro-PASC) in Colombia.

Methods

We recruited patients with laboratory-confirmed COVID-19 and PASC symptoms lasting more than 6 weeks at the CES University and CES Clinic (Medellín, Colombia). We included 50 post-hospitalization Neuro-PASC (PNP) and 50 non-hospitalized Neuro-PASC (NNP) patients. Long-COVID symptoms, cognitive (NIH Toolbox v2.1-Spanish for 18+), patient-reported (PROMIS) outcomes, and relevant medical history were evaluated. Statistical analyses were performed via generalized linear models.

Results

Overall, brain fog (60%), myalgia (42%), and numbness or tingling (41%) were the most common neurological symptoms, while fatigue (74%), sleep problems (46%), and anxiety (44%) were the most common non-neurological symptoms. Compared to NNP, PNP patients showed a higher frequency of abnormal neurological exam findings (64% vs. 42%, p = 0.028). Both groups had impaired quality of life (QoL) in domains of cognition, fatigue, anxiety depression and sleep disturbance, and performed worse on processing speed and attention than a normative population. In addition, NNP patients performed worse on executive function than PNP patients (T-score 42.6 vs. 48.5, p = 0.012). PASC symptoms of anxiety and depression were associated with worse QoL and cognitive outcomes. Brain fog and fatigue remained persistent symptoms across all durations of Long COVID.

Conclusion

Our findings highlight the high incidence and heterogeneity of the neurologic symptoms and impacts of Long COVID even more than 2 years from disease onset. Early detection, emotional support and targeted management of Neuro-PASC patients are warranted.
I like the way you move: how animate motion affects visual attention in early human infancy
Authors: Lunghi Marco , Di Giorgio Elisa
Published: August 2024

The ability to detect animates (as compared with inanimates) rapidly is advantageous for human survival. Due to its relevance, not only the adult human brain has evolved specific neural mechanisms to discriminate animates, but it has been proposed that selection finely tuned the human visual attention system to prioritize visual cues that signal the presence of living things. Among them, animate motion—i.e., the motion of animate entities -, is one of the most powerful cues that triggers humans’ attention. From a developmental point of view, whether such specialization is inborn or acquired through experience is a fascinating research topic. This mini-review aims to summarize and discuss recent behavioral and electrophysiological research that suggests that animate motion has an attentional advantage in the first year of life starting from birth. Specifically, the rationale underlying this paper concerns how attention deployment is affected by animate motion conveyed both by the movement of a single dot and, also, when the single dot is embedded in a complex array, named biological motion. Overall, it will highlight the importance of both inborn predispositions to pay attention preferentially to animate motion, mainly supported by subcortical structures, and the exposure to certain experiences, shortly after birth, to drive the cortical attentional visual system to become the way it is in adults.
Factors associated with elevated SARS-CoV-2 immune response in children and adolescents
Authors: Messiah Sarah E. , Abbas Rhiana , Bergqvist Emma , Kohl Harold W. , Swartz Michael D. , Talebi Yashar , Sabharwal Rachit , Han Haoting , Valerio-Shewmaker Melissa A. , DeSantis Stacia M. , Yaseen Ashraf , Gandhi Henal A. , Amavisca Ximena Flandes , Ross Jessica A. , Padilla Lindsay N. , Gonzalez Michael O. , Wu Leqing , Silberman Mark A. , Lakey David , Shuford Jennifer A. , Pont Stephen J. , Boerwinkle Eric
Published: August 2024

Background

Understanding the distinct immunologic responses to SARS-CoV-2 infection among pediatric populations is pivotal in navigating the COVID-19 pandemic and informing future public health strategies. This study aimed to identify factors associated with heightened antibody responses in children and adolescents to identify potential unique immune dynamics in this population.

Methods

Data collected between July and December 2023 from the Texas Coronavirus Antibody REsponse Survey (Texas CARES), a statewide prospective population-based antibody survey among 1-to-19-year-old participants, were analyzed. Each participant had the following data available for analysis: (1) Roche Elecsys® Anti-SARS-CoV-2 Immunoassay for Nucleocapsid protein antibodies (Roche N-test), (2) qualitative and semi-quantitative detection of antibodies to the SARS CoV-2 spike protein receptor binding domain (Roche S-test), and (3) self-reported antigen/PCR COVID-19 test results, vaccination, and health status. Statistical analysis identified associations between participant characteristics and spike antibody quartile group.

Results

The analytical sample consisted of 411 participants (mean age 12.2 years, 50.6% female). Spike antibody values ranged from a low of 6.3 U/ml in the lowest quartile to a maximum of 203,132.0 U/ml in the highest quartile in the aggregate sample. Older age at test date (OR = 1.22, 95% CI: 1.12, 1.35, p < .001) and vaccination status (primary series/partially vaccinated, one or multiple boosters) showed significantly higher odds of being in the highest spike antibody quartile compared to younger age and unvaccinated status. Conversely, fewer days since the last immunity challenge showed decreased odds (OR = 0.98, 95% CI: 0.96, 0.99, p = 0.002) of being in the highest spike antibody quartile vs. more days since last immunity challenge. Additionally, one out of every three COVID-19 infections were asymptomatic.

Conclusions

Older age, duration since the last immunity challenge (vaccine or infection), and vaccination status were associated with heightened spike antibody responses, highlighting the nuanced immune dynamics in the pediatric population. A significant proportion of children/adolescents continue to have asymptomatic infection, which has important public health implications.