bluuebunny/crossref_metadata_2025 huggingface dataset:
ANALISA KELAYAKAN INVESTASI SISTEM INFORMASI MANAJEMEN RUMAH SAKIT (SIMRS) MENGGUNAKAN METODE INFORMATION ECONOMICS (IE)
Authors: Pratama Yudha Herlambang Cahya , Supriyanto Heri , Supriyanto Heri
Published: August 2023

Perkembangan teknologi dan bisnis yang begitu cepat, menuntut perusahan untuk terus berkembang seperti pada fasilitas Kesehatan yaitu rumah sakit. Salah satu upaya yang dilakukan guna menjawab tuntutan pelayanan kesehatan yang baik adalah dengan melakukan investasi di bidang teknologi. Penelitian ini bertujuan untuk melakukan analisis terhadap investasi yang dilakukan oleh sebuah rumah sakit. Metode yang akan digunakan untuk menganalisis kelayakan investasi TI yaitu dilakukan menggunakan metode Information Economic (IE). Berdasarkan hasil analisis non finansial manfaat yang diperoleh yaitu adanya penghematan biaya kertas untuk laporan dan pengurangan tenaga SDM (operator), menghemat biaya penggajian karyawan, dan membantu mencapai tujuan strategis perusahaan. Selanjutnya berdasarkan hasil analisis finansial, Nilai ROI sebesar 1,00% yang menunjukan keuntungan dari investasi mencapai 1 kali lipat dari total investasi 5 tahun. Nilai NPV sebesar Rp. 9.477.162 yang menunjukan nilainya lebih dari 0 (>0) dan Nilai PP sebesar 1 bulan.  Berdasarkan Dampak ekonomis dan kelayakan investasi menunjukan bahwa penghematan langsung biaya operasional selama 5 tahun sebesar Rp. 131.762.250. Sedangkan skor akhir proyek sebesar 75,01 dengan skor minimal -20 dan skor maksimal 100, sehingga menghasilkan justifikasi kategori Layak.
Identifikasi Jenis Daun Tanaman Obat Menggunakan Metode Convolutional Neural Network (CNN) Dengan Model VGG16
Authors: ALBAKIA SRI ADININGSI ERNI , Saputra Rizal Adi
Published: August 2023

Tanaman obat memiliki peran penting dalam pengobatan alami dan pengembangan obat-obatan baru. Klasifikasi jenis daun tanaman obat menjadi langkah penting dalam penelitian ini. Saya mengusulkan metode klasifikasi menggunakan Convolutional Neural Network (CNN) dengan model VGG16 untuk mengenali jenis daun tanaman obat secara otomatis. Model VGG16 yang telah dilatih sebelumnya digunakan sebagai arsitektur dasar, dengan penyesuaian lapisan kustom yang sesuai. Pra-pemrosesan data dilakukan melalui augmentasi data, termasuk rotasi, pergeseran, dan pemotongan citra, untuk meningkatkan variasi data pelatihan. Dataset yang digunakan terdiri dari 10 jenis daun tanaman obat yang dikumpulkan secara eksklusif. Dari percobaan ini mendapatkan training akurasi 81,61% dan validasi akurasinya 90,74%. Pada uji data 50 citra daun mendapatkan hasil akurasi 92% dengan 46 data yang terklasifikasi dan 4 data citra yang salah terklasifikasi. Temuan ini menunjukkan adanya potensi penggunaan CNN dengan model VGG16 dalam identifikasi dan pemilihan tanaman obat secara efisien dalam bidang medis dan farmasi. Penelitian ini memberikan landasan untuk pengembangan lebih lanjut dalam penelitian tentang tanaman obat dan pemanfaatan teknologi pengenalan pola untuk tujuan pengobatan dan farmasi.
SISTEM PENDUKUNG KEPUTUSAN PEMILIHAN SITUS LOWONGAN KERJA MENGGUNAKAN METODE MOORA
Authors: Agustin Fajriyah Mayzura , Wijaya Indra Dharma , Harijanto Budi
Published: August 2023

Indonesia merupakan urutan ke-10 negara yang durasi penggunaan media sosial tersering menurut (DataIndonesia.id, 2022), dengan menggunakan media sosial dapat menemukan banyak hal yang berguna seperti iklan online yang dapat menjadi sarana yang lebih efektif dalam mencari kerja. Namun terdapat juga dampak negatif bagi pencari kerja hal tersebut dibuktikan masih banyak yang mengalami penipuan lowongan kerja dalam platform yang tidak resmi sehingga tidak terjamin informasi dan keamanannya. Hal tersebut membuat para pencari kerja kuwalahan dalam memilih papan iklan (board job) lowongan kerja yang terpercaya. Berdasarkan dari permasalahan tersebut dibutuhkan sebuah Sistem Pendukung Keputusan yang dapat membantu menentukan platform resmi untuk mencari lowongan kerja bagi pencari kerja. Pada penelitian milik (Kurnianty, Ekojono, & Rohadi, 2023) tentang pendukung keputusan menggunakan metode MOORA menghasilkan akurasi sebesar 100%, dimana penggunaan metode MOORA memiliki tingkat selektifitas yang baik sehingga dapat digunakan pada penelitian ini. Metode yang digunakan yakni metode Multi-Objective Optimization On The Basis Of Ratio Analysis (MOORA) dikarenakan kriteria yang dibutuhkan terdapat beberapa kriteria yang bertentangan. Hasil yang didapatkan dengan menggunakan metode ini yakni hasil yang sesuai. Hasil Pengujian dengan membandingkan perhitungan secara manual dengan sistem menggunakan Confusion Matrix mendapatkan hasil akurasi sebesar 100%, kemudian pengujian kepada responden mendapat hasil akhir rata-rata kepuasan sebesar  89.28%, hal tersebut dapat disimpulkan bahwa sistem ini dapat memenuhi kebutuhan dan dapat membantu pencari kerja dalam memilih situs lowongan kerja.
Control de síntomas al final de la vida con Dexmedetomidina
Authors: Miñarcaja Mirian , Estrella Adriana , Vallejo Martínez Mariana
Published: August 2023

Introducción: El manejo de los síntomas refractarios con dexmetomidina (DXM) es una alternativa en pacientes oncológicos en la atención al final de la vida (AFV) lo que puede convertirse en un gran desafío, ante la necesidad de iniciar sedación paliativa. El objetivo del presente estudio es determinar el efecto de la DXM comparado con el midazolam (MDZ) en el control de síntomas refractarios en pacientes con cáncer avanzado AFV, como parte de una estrategia asistencial de sedación paliativa.
Metodología: Estudio observacional, longitudinal, se revisaron los informes médicos en las historias clínicas de pacientes hospitalizados con diagnóstico de cáncer avanzado terminal y síntomas refractarios (dolor, disnea y delirio), que recibieron sedación paliativa con DXM o MDZ. Se utilizaron los registros de Escala de Evaluación de Síntomas de Edmonton - revisada (ESAS-r) para intensidad de síntomas y la Escala de Sedación/Agitación de Richmond (RASS) para respuesta a la sedación.
Resultados: Un total de 35 pacientes recibieron DXM y 18 MDZ. El dolor (32 %) y delirio (30 %) fueron los síntomas refractarios más identificados. Dolor intenso en 89.3 % antes del inicio de DXM. A las 72 horas, el grupo DXM presentó disminución de la intensidad del delirio a leve y moderado, mientras que la mayoría de los pacientes del grupo MDZ fallecieron antes de las 72 horas.
Conclusiones: El uso clínico de la DXM permite un enfoque multimodal, ampliando su utilidad en la atención al final de la vida para el manejo del dolor y delirio, ya que permite un estado de respuesta para la interacción con los miembros de la familia, función relevante en cuidados paliativos.
Evaluation of a static mixer as a new microfluidic method for liposome formulation
Authors: Ota Aoba , Mochizuki Ayaka , Sou Keitaro , Takeoka Shinji
Published: August 2023

Introduction: Microfluidic formulation of liposomes has been extensively studied as a potential replacement for batch methods, which struggle with problems in scalability and difficulty in modulating conditions. Although microfluidic devices are considered to be able to combat these issues, an adequate replacement method has yet to be established.

Methods: This paper examines the potential of a static mixer (SM) by comparing the encapsulation efficiency, loading, lamellarity, and user-friendliness with a commonly used microfluidic device, a staggered herringbone micromixer (SHM).

Results: In both devices, it was found that as the initial lipid concentration increased, the particle size increased; however, the overall particle size was seen to be significantly larger in the liposomes prepared with SM. PDI remained significantly smaller in SM, however, signifying that better control of the particle size was accomplished in SM. In addition, the encapsulation efficiency was slightly smaller in SM compared to SHM, and in both devices, the values increased as the initial lipid concentration increased. The increase in encapsulation efficiencies was significantly smaller than that of the theoretical encapsulation efficiency, and this was found to be due to the increase in lamellarity as the initial lipid concentration increased.

Discussion: In terms of user-friendliness, SM demonstrated significant advantages. The mixing elements could be taken out from the device, allowing for thorough cleaning of the element and device before and after experiments and ensuring experiments are conducted at virgin state in every round. Consequently, it was found that SM not only can produce uniformly distributed liposomes but has the potential to become a more practical method for liposome formulation with modifications in the mixing elements.
4-Dimensional printing: exploring current and future capabilities in biomedical and healthcare systems—a Concise review
Authors: Agarwal Neha , Solanki Vijendra Singh , Ameta Keshav Lalit , Yadav Virendra Kumar , Gupta Premlata , Wanale Shivraj Gangadhar , Shrivastava Ruchi , Soni Anjali , Sahoo Dipak Kumar , Patel Ashish
Published: August 2023

4-Dimensional Printing (4DP) is the latest concept in the pharmacy and biomedical segment with enormous potential in dosage from personalization and medication designing, which adopts time as the fourth dimension, giving printed structures the flexibility to modify their morphology. It can be defined as the fabrication in morphology with the help of smart/intelligent materials like polymers that permit the final object to alter its properties, shape, or function in response to external stimuli such as heat, light, pH, and moisture. The applications of 4DP in biomedicines and healthcare are explored with a focus on tissue engineering, artificial organs, drug delivery, pharmaceutical and biomedical field, etc. In the medical treatments and pharmaceutical field 4DP is paving the way with unlimited potential applications; however, its mainstream use in healthcare and medical treatments is highly dependent on future developments and thorough research findings. Therefore, previous innovations with smart materials are likely to act as precursors of 4DP in many industries. This review highlights the most recent applications of 4DP technology and smart materials in biomedical and healthcare fields which can show a better perspective of 4DP applications in the future. However, in view of the existing limitations, major challenges of this technology must be addressed along with some suggestions for future research. We believe that the application of proper regulatory constraints with 4DP technology would pave the way for the next technological revolution in the biomedical and healthcare sectors.
Case report: Sodium-glucose cotransporter 2 inhibitors induce left ventricular reverse remodeling in anthracycline-related cardiac dysfunction—a case series
Authors: Giangiacomi Francesco , Faggiano Andrea , Cardinale Daniela , Rossi Francesca Gaia , Pollina Alberto , Gherbesi Elisa , Gnan Eleonora , Carugo Stefano , Vicenzi Marco
Published: August 2023

Purpose

To describe the efficacy and safety of sodium-glucose cotransporter 2 inhibitors as a specific treatment for anthracycline-related cardiac dysfunction in a small real-world population.

Methods

Seven patients with anthracycline-related cardiac dysfunction were clinically and echocardiographically evaluated before and after the introduction of sodium-glucose cotransporter 2 inhibitors.

Results

After a median period of 24 weeks with uninterrupted sodium-glucose cotransporter 2 inhibitors treatment, a significant clinical improvement was observed with at least one New York Heart Association Functional Class (NHYA FC) improvement in all patients (median NYHA FC: I vs. III, p < 0.010). A noteworthy left ventricular reserve remodeling (median left ventricular end diastolic volume indexed: 53 vs. 82.5 ml/m2, p = 0.018; median left ventricular ejection fraction: 50% vs. 40%, p = 0.17) was also observed. Sodium-glucose cotransporter 2 inhibitors therapy was well tolerated by every patients; no cases of discontinuation or relevant side effects were observed.

Conclusion

Sodium-glucose cotransporter 2 inhibitors induce a significant clinical improvement and left ventricular reserve remodeling in patients affected by anthracycline-related cardiac dysfunction.
Adopting a multi-systems approach: examining the academic belongingness of first-generation college students with multiple stigmatized identities in STEM
Authors: Google Angela N. , Sekaya Grace , McMullen Zachery , Henning Jeremiah A.
Published: August 2023

First-generation college students often experience greater social alienation and marginalization due to a mismatch of their cultural values compared to those of their university and often report lower academic satisfaction and sense of belonging. The effects on sense of belonging and satisfaction are intensified when first-generation college students have identities that intersect with other stigmatized social and cultural identities, like low socioeconomic status, Black or Latinx racial identities or religious identities, specifically for STEM majors. Students’ holistic health and well-being, including their sense of belonging, is highly correlated to their academic achievement, persistence, and overall student success, especially for underrepresented minority groups. However, there has been limited consideration for the nuanced experiences of first-generation college students with multiple stigmatized identities, and for how the academic STEM environment shapes student’s perceptions of inclusivity considering their social identities. To address these concerns, we used the Bioecological Systems theory to contextualize drivers of sense of belonging for students with stigmatized social and cultural identities by allowing space to explicitly consider institutional, departmental, classroom and societal-level phenomena that may operate to erode or fortify belonging for some individuals over others. Findings were organized contextually first, revealing how broader societal and familial values shaped their perceptions of their first-generation identity. Next, we reported how various forms of engagement and interactions with institutional agents impacted their perceptions of support at the institutional level. We then documented behavioral patterns within STEM departments that culminated to reveal how first-generation college students’ sense of belonging was impacted by perceived departmental culture. Last, we revealed interactions within STEM classrooms that signaled inclusivity through humanizing and intentional pedagogical practices. Infused throughout all findings are instances where student experiences were mediated through their multiple identities and were shaped by dual global pandemics of 2020, that being COVID-19 and the racial unrest resurfaced by the murder of George Floyd. Implications for this work have the potential to restructure how institutions provide support for first-generation college students given the salience of their intersecting stigmatized identities in shaping their institutional, disciplinary, and classroom belonging.
Association between dietary glycemic index and non-alcoholic fatty liver disease in patients with type 2 diabetes mellitus
Authors: Salavatizadeh Marieh , Soltanieh Samira , Ataei Kachouei Amirhossein , Abdollahi Fallahi Zahra , Kord-Varkaneh Hamed , Poustchi Hossein , Mansour Asieh , Khamseh Mohammad E. , Alaei-Shahmiri Fariba , Santos Heitor O. , Hekmatdoost Azita
Published: August 2023

Objective

Managing dietary glycemic index (GI) deserves further attention in the interplay between non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM). This study aimed to evaluate the relationship between dietary GI and the odds of NAFLD in patients with T2DM.

Methods

A cross-sectional study was carried out between April 2021 and February 2022, including 200 participants with T2DM aged 18-70 years, of which 133 had NAFLD and 67 were in the non-NAFLD group. Cardiometabolic parameters were analyzed using standard biochemical kits and dietary intake was assessed using a validated food frequency questionnaire. Binary logistic regression was applied to explore odds ratios (ORs) and 95% confidence intervals (CIs) for NAFLD according to tertiles of dietary GI.

Results

Highest vs. lowest tertile (< 57 vs. > 60.89) of energy-adjusted GI was not associated with the odds of having NAFLD (OR 1.25, 95% CI = 0.6-2.57; P-trend = 0.54) in the crude model. However, there was an OR of 3.24 (95% CI = 1.03-10.15) accompanied by a significant trend (P-trend = 0.04) after full control for potential confounders (age, gender, smoking status, duration of diabetes, physical activity, waist circumference, HbA1c, triglycerides, total cholesterol, dietary intake of total carbohydrates, simple carbohydrates, fat, and protein).

Conclusion

High dietary GI is associated with increased odds of NAFLD in subjects with T2DM. However, interventional and longitudinal cohort studies are required to confirm these findings.
Regulation of the renin-angiotensin-aldosterone system by cyclic nucleotides and phosphodiesterases
Authors: Gambaryan Stepan , Mohagaonkar Sanika , Nikolaev Viacheslav O.
Published: August 2023

The renin-angiotensin-aldosterone system (RAAS) is one of the key players in the regulation of blood volume and blood pressure. Dysfunction of this system is connected with cardiovascular and renal diseases. Regulation of RAAS is under the control of multiple intracellular mechanisms. Cyclic nucleotides and phosphodiesterases are the major regulators of this system since they control expression and activity of renin and aldosterone. In this review, we summarize known mechanisms by which cyclic nucleotides and phosphodiesterases regulate renin gene expression, secretion of renin granules from juxtaglomerular cells and aldosterone production from zona glomerulosa cells of adrenal gland. We also discuss several open questions which deserve future attention.
Identification and classification of digital green innovation based on interaction Maclaurin symmetric mean operators by using T-spherical fuzzy information
Authors: Hou Xiaona , Naseem Areeba , Ullah Kifayat , Naeem Muhammad , Akram Maria , Yin Shi
Published: August 2023

The digital green concept refers to the devotion to digital technology, i.e., techniques of procedures in the area of ecological or sustainable conservation. It contains leveraging digital techniques, procedures, and new tools to evaluate environmental problems and promote sustainable development. The major influence of this article is to evaluate the selection of the best digital green technology. For this, we aim to propose the idea of Maclaurin symmetric mean (MSM) operators based on interaction operational laws for T-spherical fuzzy (TSF) information, such as TSF interaction weighted averaging (TSFIWA), generalized TSF interaction weighted averaging (GTSFIWA), TSF interaction weighted geometric averaging (TSFIWGA), TSF interaction MSM (TSFIMSM), TSF interaction Bonferroni mean (TSFIBM), and TSF interaction weighted Maclaurin symmetric mean (TSFIWMSM) operators. Some dominant and reliable properties are also invented for evaluation. Moreover, to address the best digital green innovation (DGI) among the top five DGIs, we illustrate the procedure of the multi-attribute decision-making (MADM) technique under the presence of the derived operators. Finally, we demonstrate a numerical example for evaluating the comparative study between the proposed and existing or prevailing operators to enhance the worth of the derived theory.
Micro- and nanoplastics current status: legislation, gaps, limitations and socio-economic prospects for future
Authors: Osuna-Laveaga Daryl Rafael , Ojeda-Castillo Valeria , Flores-Payán Valentín , Gutiérrez-Becerra Alberto , Moreno-Medrano Edgar David
Published: August 2023

The pollution caused by micro- (MP) and nanoplastics (NP) in the planet’s ecosystems has gained significant interest in recent years due to their environmental impact and effects on the health of living organisms. Given this, it is necessary to conduct a comprehensive analysis of the actions required to mitigate their impacts. This paper analyzes existing legislation across different countries and regions, including Europe, North America, China, Russia, India, Brazil, Mexico, and the global initiatives undertaken by the United Nations. Furthermore, it highlights the need for additional measures to mitigate the impact of MP/NP in future years, such as the development of technologies for the separation or degradation of these particles in water intended for human consumption and in wastewater treatment plant effluents, studying plastic particulate material in the air considering meteorological parameters, MP/NP detection protocols in human fluid samples, creating truly biodegradable polymers for use as bioplastics, and establishing institutions responsible for the management of plastic waste. The study also shows the current state of abundance (characterization and quantification) of MP/NP in different environmental matrices based on reports from recent years, and identifies key research opportunities and actions required to evaluate the risks and toxicity associated with MP/NP. Socio-economic aspects are considered, including the impact of MP/NP on different regions, by associating economic and human wellness parameters to plastic waste generation by using available data from 148 countries. As result of this analysis, both the most populated and developed countries contribute to MP/NP generation, however, they have different capacities to address this problem due to social circumstances. The solution to this problem requires efforts from authorities, industry, the scientific community, and the active participation of the population, then, resolving social, political, and economic issues between countries and regions of the world is necessary.
Mesozoic Notocupes revealed as the sister group of Cupedidae (Coleoptera: Archostemata)
Authors: Li Yan-Da , Tihelka Erik , Yamamoto Shûhei , Newton Alfred F. , Xia Fang-Yuan , Liu Ye , Huang Di-Ying , Cai Chen-Yang
Published: August 2023

Despite encompassing only about 50 extant species, beetles of the suborder Archostemata have a rich fossil history, being known from the Permian and dominating coleopteran assemblages in the Mesozoic before declining in richness towards the Late Cretaceous. Given the limited diversity of extant archostematans, fossils provide a valuable line of evidence for reconstructing the relationships among its constituent families. Here we re-evaluate the phylogenetic position of the Triassic–Cretaceous genus Notocupes, the most species-rich archostematan taxon in the fossil record. Exquisitely preserved fossils from the Middle Jurassic Haifanggou Formation (Daohugou; ~165 Ma) and mid-Cretaceous amber (~99 Ma) reveal critical differences from Ommatidae in the presence of separated procoxae and overlapping abdominal ventrites. Our analyses confirm that Notocupes is not a member of Ommatidae, but is closely related to Cupedidae. Our fossils reveal that Notocupes possessed unique adaptations for protecting their appendages, such as unusual dorsal pronotal grooves for the reception of antennae and epipleural grooves for the reception of legs, shedding light on ecological interactions in Mesozoic saproxylic habitats. The high similarity between Jurassic and Cretaceous Notocupes provides an exceptional example of long-term morphological stasis, suggesting a consistent microhabitat for the group.
Bone whistle modeling method based on robust scan point tracking
Authors: Khysru Kuntharrgyal , Wei Jianguo
Published: August 2023

Several excavations at the Hemudu site in Zhejiang Province have led to the discovery of more than 100 pieces of bird bones that were likely used to create a kind of musical instrument. However, in contrast to the Jiahu bone flute, it is not clear for what the Hemudu bone whistle was used, although it was probably used for musical purposes. In this paper, the 7000-year-old Hemudu bone whistle is reproduced with 3D scanning and printing technology. Therefore, we propose a robust scan point detection and tracking method that includes three main stages. First, we conducted robust point detection and selection where noise and irrelevant points were removed. Then, we propose to track the key points and conduct 3D model optimization. With the above efforts, we obtained the 3D model of the bone whistle, and the audio of the bone whistle is replicated. The purpose of the bone whistles is inferred and evaluated through audio analyses. The experimental results show that the method is feasible.
Indirect effects of urbanization: consequences of increased aggression in an urban male songbird for mates and offspring
Authors: Lane Samuel J. , VanDiest Isaac J. , Brewer Valerie N. , Linkous Courtney R. , Fossett Taylor E. , Goodchild Christopher G. , Sewall Kendra B.
Published: August 2023

Behavioral traits are often the first response to changing environmental conditions, including human induced rapid environmental change. For example, animals living in urban areas are often more aggressive than rural animals. This is especially evident in songbirds; males of several species display elevated aggression in urban habitats. Increased male aggression has been associated with reduced parental care, but the consequences of this trade-off for males, social partners, and offspring in the context of urbanization remains unclear. We explored the effects of increased urban male aggression on the life history traits, parental care, and offspring outcomes of song sparrows (Melospiza melodia). We predicted that urban males would reduce paternal investment and result in urban females providing greater nestling care or reduced fledging success in urban habitats compared to rural. Contrary to our prediction, aggressive urban males did not decrease care but visited the nest more often compared to rural males. Additionally, urban birds had higher nest and fledging success compared to rural, though this was largely due to higher nest predation in rural habitats. Our study is among the first to evaluate trade-offs associated with elevated aggression expressed by urban animals and adds to a growing body of evidence that urban habitats provide benefits to some species.
Mycobacterium tuberculosis PE/PPE proteins enhance the production of reactive oxygen species and formation of neutrophil extracellular traps
Authors: García-Bengoa María , Meurer Marita , Stehr Matthias , Elamin Ayssar A. , Singh Mahavir , Oehlmann Wulf , Mörgelin Matthias , von Köckritz-Blickwede Maren
Published: August 2023

Introduction

Neutrophil granulocytes predominate in the lungs of patients infected with Mycobacterium tuberculosis (Mtb) in earlier stages of the disease. During infection, neutrophils release neutrophil extracellular traps (NETs), an antimicrobial mechanism by which a DNA-backbone spiked with antimicrobial components traps the mycobacteria. However, the specific mycobacterial factors driving NET formation remain unclear. Proteins from the proline-glutamic acid (PE)/proline-proline-glutamic acid (PPE) family are critical to Mtb pathophysiology and virulence.

Methods

Here, we investigated NET induction by PE18, PPE26, and PE31 in primary human blood-derived neutrophils. Neutrophils were stimulated with the respective proteins for 3h, and NET formation was subsequently assessed using confocal fluorescence microscopy. Intracellular ROS levels and cell necrosis were estimated by flow cytometry. Additionally, the influence of phorbol-12-myristate-13-acetate (PMA), a known NADPH oxidase enhancer, on NET formation was examined. Neutrophil integrity following incubation with the PE/PPE proteins was evaluated using transmission electron microscopy.

Results

For the first time, we report that stimulation of primary human blood-derived neutrophils with Mtb proteins PE18, PPE26, and PE31 resulted in the formation of NETs, which correlated with an increase in intracellular ROS levels. Notably, the presence of PMA further amplified this effect. Following incubation with the PE/PPE proteins, neutrophils were found to remain viable and structurally intact, as verified through transmission electron microscopy, indicating the occurrence of vital NET formation.

Discussion

These findings offer valuable insights that contribute to a better understanding of host-pathogen interactions during Mtb infection. Moreover, they underscore the significance of these particular Mtb antigens in triggering NET formation, representing a distinctive and previously unrecognized function of PE/PPE antigens.
Crosstalk between autophagy and metabolic regulation of (CAR) T cells: therapeutic implications
Authors: Panahi Meymandi Ahmad Reza , Akbari Behnia , Soltantoyeh Tahereh , Hadjati Jamshid , Klionsky Daniel J. , Badie Behnam , Mirzaei Hamid Reza
Published: August 2023

Despite chimeric antigen receptor (CAR) T cell therapy’s extraordinary success in subsets of B-cell lymphoma and leukemia, various barriers restrict its application in solid tumors. This has prompted investigating new approaches for producing CAR T cells with superior therapeutic potential. Emerging insights into the barriers to CAR T cell clinical success indicate that autophagy shapes the immune response via reprogramming cellular metabolism and vice versa. Autophagy, a self-cannibalization process that includes destroying and recycling intracellular components in the lysosome, influences T cell biology, including development, survival, memory formation, and cellular metabolism. In this review, we will emphasize the critical role of autophagy in regulating and rewiring metabolic circuits in CAR T cells, as well as how the metabolic status of CAR T cells and the tumor microenvironment (TME) alter autophagy regulation in CAR T cells to restore functional competence in CAR Ts traversing solid TMEs.
Use of Epivolve phage display to generate a monoclonal antibody with opsonic activity directed against a subdominant epitope on extracellular loop 4 of Treponema pallidum BamA (TP0326)
Authors: Ferguson Mary R. , Delgado Kristina N. , McBride Shannon , Orbe Isabel C. , La Vake Carson J. , Caimano Melissa J. , Mendez Qiana , Moraes Trevor F. , Schryvers Anthony B. , Moody M. Anthony , Radolf Justin D. , Weiner Michael P. , Hawley Kelly L.
Published: August 2023

Introduction

Syphilis, a sexually transmitted infection caused by the spirochete Treponema pallidum (Tp), is resurging globally. Tp’s repertoire of outer membrane proteins (OMPs) includes BamA (β-barrel assembly machinery subunit A/TP0326), a bipartite protein consisting of a 16-stranded β-barrel with nine extracellular loops (ECLs) and five periplasmic POTRA (polypeptide transport-associated) domains. BamA ECL4 antisera promotes internalization of Tp by rabbit peritoneal macrophages.

Methods

Three overlapping BamA ECL4 peptides and a two-stage, phage display strategy, termed “Epivolve” (for epitope evolution) were employed to generate single-chain variable fragments (scFvs). Additionally, antisera generated by immunizing mice and rabbits with BamA ECL4 displayed by a Pyrococcus furiosus thioredoxin scaffold (PfTrxBamA/ECL4). MAbs and antisera reactivities were evaluated by immunoblotting and ELISA. A comparison of murine and rabbit opsonophagocytosis assays was conducted to evaluate the functional ability of the Abs (e.g., opsonization) and validate the mouse assay. Sera from Tp-infected mice (MSS) and rabbits (IRS) were evaluated for ECL4-specific Abs using PfTrxBamA/ECL4 and overlapping ECL4 peptides in immunoblotting and ELISA assays.

Results

Each of the five mAbs demonstrated reactivity by immunoblotting and ELISA to nanogram amounts of PfTrxBamA/ECL4. One mAb, containing a unique amino acid sequence in both the light and heavy chains, showed activity in the murine opsonophagocytosis assay. Mice and rabbits hyperimmunized with PfTrxBamA/ECL4 produced opsonic antisera that strongly recognized the ECL presented in a heterologous scaffold and overlapping ECL4 peptides, including S2. In contrast, Abs generated during Tp infection of mice and rabbits poorly recognized the peptides, indicating that S2 contains a subdominant epitope.

Discussion

Epivolve produced mAbs target subdominant opsonic epitopes in BamA ECL4, a top syphilis vaccine candidate. The murine opsonophagocytosis assay can serve as an alternative model to investigate the opsonic potential of vaccinogens. Detailed characterization of BamA ECL4-specific Abs provided a means to dissect Ab responses elicited by Tp infection.
KLRC1 knockout overcomes HLA-E-mediated inhibition and improves NK cell antitumor activity against solid tumors
Authors: Mac Donald Alice , Guipouy Delphine , Lemieux William , Harvey Mario , Bordeleau Louis-Jean , Guay David , Roméro Hugo , Li Yuanyi , Dion Renaud , Béland Kathie , Haddad Elie
Published: August 2023

Introduction

Natural Killer (NK) cells hold the potential to shift cell therapy from a complex autologous option to a universal off-the-shelf one. Although NK cells have demonstrated efficacy and safety in the treatment of leukemia, the limited efficacy of NK cell-based immunotherapies against solid tumors still represents a major hurdle. In the immunosuppressive tumor microenvironment (TME), inhibitory interactions between cancer and immune cells impair antitumoral immunity. KLRC1 gene encodes the NK cell inhibitory receptor NKG2A, which is a potent NK cell immune checkpoint. NKG2A specifically binds HLA-E, a non-classical HLA class I molecule frequently overexpressed in tumors, leading to the transmission of inhibitory signals that strongly impair NK cell function.

Methods

To restore NK cell cytotoxicity against HLA-E+ tumors, we have targeted the NKG2A/HLA-E immune checkpoint by using a CRISPR-mediated KLRC1 gene editing.

Results

KLRC1 knockout resulted in a reduction of 81% of NKG2A+ cell frequency in ex vivo expanded human NK cells post-cell sorting. In vitro, the overexpression of HLA-E by tumor cells significantly inhibited wild-type (WT) NK cell cytotoxicity with p-values ranging from 0.0071 to 0.0473 depending on tumor cell lines. In contrast, KLRC1KO NK cells exhibited significantly higher cytotoxicity when compared to WT NK cells against four different HLA-E+ solid tumor cell lines, with p-values ranging from<0.0001 to 0.0154. Interestingly, a proportion of 43.5% to 60.2% of NKG2A− NK cells within the edited NK cell population was sufficient to reverse at its maximum the HLA-E-mediated inhibition of NK cell cytotoxicity. The expression of the activating receptor NKG2C was increased in KLRC1KO NK cells and contributed to the improved NK cell cytotoxicity against HLA-E+ tumors. In vivo, the adoptive transfer of human KLRC1KO NK cells significantly delayed tumor progression and increased survival in a xenogeneic mouse model of HLA-E+ metastatic breast cancer, as compared to WT NK cells (p = 0.0015).

Conclusions

Our results demonstrate that KLRC1 knockout is an effective strategy to improve NK cell antitumor activity against HLA-E+ tumors and could be applied in the development of NK cell therapy for solid tumors.
Comparison of clinical outcomes in critical patients undergoing different mechanical ventilation modes: a systematic review and network meta-analysis
Authors: Wu Mengyu , Zhang Xiaohong , Jiang Yu , Guo Yun , Zhang Wenjing , He Hong , Yin Yanhua
Published: August 2023

Purpose

To evaluate the effects of different mechanical ventilation modes on critical patients.

Methods

PubMed, Embase, Web of science, and Cochrane Library databases were searched from their inception to November 15, 2022 for randomized controlled trials on the application of different mechanical ventilation modes in critical patients. Two researchers independently screened the literature, extracted data, and assessed the risk of bias in the included studies. R4.2.1 was used for this network meta-analysis.

Results

Twenty-eight RCTs involving 3,189 patients were included. The interventions in these RCTs included NAVA (neurally adjusted ventilatory assist), PAV (proportional assist ventilation), ASV (adaptive support ventilation), Smartcare/PS (Smartcare/pressure support), PSV (pressure support ventilation), PSV_ATC (pressure support ventilation_automatic tube compensation), and SIMV (synchronized intermittent mandatory ventilation). The network meta-analysis showed that, compared with the PSV group, there was no significant difference in duration of mechanical ventilation, duration of ICU stay, and hospital stay between NAVA, SIMV, AVS, PAV, Smartcare/PS, and PSV_ATC groups. Compared with PSV, PAV improved the success rate of withdrawal of ventilator [OR = 3.07, 95%CI (1.21, 8.52)]. Compared with PSV and PAV, NAVA reduced mortality in the ICU [OR = 0.63, 95%CI (0.43, 0.93); OR = 0.45, 95%CI (0.21, 0.97)].

Conclusion

NAVA can reduce mortality in ICU, and PAV may increase the risk of withdrawal of the ventilator. There was no significant difference between PSV and other mechanical ventilation modes (NAVA, SIMV, AVS, PAV, Smartcare/PS, and PSV_ATC) in the duration of mechanical ventilation, duration of ICU stay, or hospital stay. Due to the limitations, more high-quality studies are needed to verify these findings.
Minimizing blood loss in laparoscopic myomectomy with temporary occlusion of the hypogastric artery
Authors: Balulescu Ligia , Nistor Samuel , Lungeanu Diana , Brasoveanu Simona , Pirtea Marilena , Secosan Cristina , Grigoras Dorin , Caprariu Radu , Pasquini Andrea , Pirtea Laurentiu
Published: August 2023

Introduction

Uterine leiomyomas are common benign pelvic tumors. Currently, laparoscopic myomectomy (LM) is the preferred treatment option for women in the fertile age group with symptomatic myomas. The authors hypothesize that combining LM with a bilateral temporary occlusion of the hypogastric artery (TOHA) using vascular clips minimizes uterine blood flow during surgery and can significantly reduce surgery-associated blood loss.

Materials and methods

This single-center, prospective randomized study was conducted at the Department of Obstetrics and Gynecology, Municipal Emergency Clinical Hospital Timisoara, Romania. Patients aged between 18 and 49 who preferred laparoscopic myomectomy and wished to preserve fertility were included, provided they had intramural uterine leiomyomas larger than 4 cm in diameter that deformed the uterine cavity. The study analyzed data from 60 laparoscopic myomectomies performed by a single surgeon between January 2018 and December 2020. Patients were randomly assigned to either: “LM + TOHA” group (29 patients), and “LM” group (31 patients). The study’s main objective was to evaluate the impact of TOHA on perioperative blood loss, expressed as mean differences in Hb (delta Hb).

Results

Delta Hb was statistically lower in the “LM + TOHA” group compared to “LM” group, with mean ± standard (min–max): 1.68 ± 0.67 (0.39–3.99) vs. 2.63 ± 1.06 (0.83–4.92) g/dL, respectively (p < 0.001). There was a statistically significant higher need for postoperative iron perfusion in the “LM” group, specifically 0 vs. 12 patients (p < 0.001), and lower postoperative anemia in “LM + TOHA” group (p < 0.001). Necessary artery clipping time was 10.62 ± 2.47 (7–15) minutes, with no significant impact on overall operative time: 110.2 ± 13.65 vs. 106.3 ± 16.48 (p = 0.21). There was no difference in the length of hospitalization or 12-month post-intervention fertility.

Discussion

Performing bilateral TOHA prior to laparoscopic myomectomy has proven to be a valuable technique in reducing surgery-associated blood loss, while minimizing complications during surgery, with no significant increase in the overall operative time.

Clinical trial registration

ISRCTN registry, (www.isrctn.com), identifier ISRCTN66897343.
Transition to remote/hybrid learning during the COVID-19 pandemic among Saudi students of the College of Applied Medical Sciences: a cross-sectional study
Authors: Alshamrani Khalid M. , Ghulam Enas M. , Alattas Maryam , Aljaddani Haneen , Alhakami Montaha , Al Nufaiei Ziyad F. , Althaqafy Majid S.
Published: August 2023

Background

The novel Coronavirus Disease 2019 (COVID-19) pandemic has presented unparalleled and unique stressors and challenges to the field of applied health sciences education. This study explored how the College of Applied Medical Sciences (COAMS) Saudi students perceive the transition to remote/ hybrid learning during the COVID-19 pandemic.

Methods

A cross-sectional exploratory investigation was carried out during the months of February and March in the year 2023 among 196- COAMS Saudi students, using the 48-item previously developed and validated questionnaire, and with a non-probability convenient sampling technique. Descriptive statistics were generated for participants’ demographics, and for each questionnaire item and statistical analysis was performed using chi-square test.

Results

Out of the 283 undergraduates who have enrolled in COAMS, a total of 196 students have agreed to participate in the study with an overall response rate of 69.3%. Over 70% of COAMS students were satisfied and engaged in their on-site coursework. Nevertheless, questionnaire data indicates that their satisfaction and level of engagement diminished following the shift to remote learning. More than 62% of COAMS students were satisfied with their instructors’ instructional and assessment strategies during on-site coursework, but such perceptions have decreased with remote instruction. Hybrid learning can be beneficial and effective in improving the performance and learning experience of COAMS students. As compared to female students, COAMS male students were more satisfied with remote learning because it met their needs (p = 0.017).

Conclusion

Remote classrooms have lower attendance and interest than on-site classes. Despite lower satisfaction levels in online courses, hybrid learning was viewed favourably by COAMS students. Higher educational institutions should develop plans to increase student involvement, improve academic integrity, and assess the effect of the pandemic on undergraduate education on a regular basis. By incorporating these measures, educational institutions can enhance and support the remote learning experience for their students.
Phenotypic and genomic characterization of Bathyarchaeum tardum gen. nov., sp. nov., a cultivated representative of the archaeal class Bathyarchaeia
Authors: Khomyakova Maria A. , Merkel Alexander Y. , Mamiy Dana D. , Klyukina Alexandra A. , Slobodkin Alexander I.
Published: August 2023

Bathyarchaeia are widespread in various anoxic ecosystems and are considered one of the most abundant microbial groups on the earth. There are only a few reports of laboratory cultivation of Bathyarchaeia, and none of the representatives of this class has been isolated in pure culture. Here, we report a sustainable cultivation of the Bathyarchaeia archaeon (strain M17CTs) enriched from anaerobic sediment of a coastal lake. The cells of strain M17CTs were small non-motile cocci, 0.4–0.7 μm in diameter. The cytoplasmic membrane was surrounded by an S-layer and covered with an outermost electron-dense sheath. Strain M17CTs is strictly anaerobic mesophile. It grows at 10–45°C (optimum 37°C), at pH 6.0–10.0 (optimum 8.0), and at NaCl concentrations of 0–60 g l−1 (optimum 20 g l−1). Growth occurred in the presence of methoxylated aromatic compounds (3,4-dimethoxybenzoate and vanillate) together with complex proteinaceous substrates. Dimethyl sulfoxide and nitrate stimulated growth. The phylogenomic analysis placed strain M17CTs to BIN-L-1 genus-level lineage from the BA1 family-level lineage and B26-1 order-level lineage (former subgroup-8) within the class Bathyarchaeia. The complete genome of strain M17CTs had a size of 2.15 Mb with a DNA G + C content of 38.1%. Based on phylogenomic position and phenotypic and genomic properties, we propose to assign strain M17CTs to a new species of a novel genus Bathyarchaeum tardum gen. nov., sp. nov. within the class Bathyarchaeia. This is the first sustainably cultivated representative of Bathyarchaeia. We propose under SeqCode the complete genome sequence of strain M17CTs (CP122380) as a nomenclatural type of Bathyarchaeum tardum, which should be considered as a type for the genus Bathyarchaeum, which is proposed as a type for the family Bathyarchaeaceae, order Bathyarchaeales, and of the class Bathyarchaeia.
MV-CVIB: a microbiome-based multi-view convolutional variational information bottleneck for predicting metastatic colorectal cancer
Authors: Cui Zhen , Wu Yan , Zhang Qin-Hu , Wang Si-Guo , He Ying , Huang De-Shuang
Published: August 2023

Introduction

Imbalances in gut microbes have been implied in many human diseases, including colorectal cancer (CRC), inflammatory bowel disease, type 2 diabetes, obesity, autism, and Alzheimer's disease. Compared with other human diseases, CRC is a gastrointestinal malignancy with high mortality and a high probability of metastasis. However, current studies mainly focus on the prediction of colorectal cancer while neglecting the more serious malignancy of metastatic colorectal cancer (mCRC). In addition, high dimensionality and small samples lead to the complexity of gut microbial data, which increases the difficulty of traditional machine learning models.

Methods

To address these challenges, we collected and processed 16S rRNA data and calculated abundance data from patients with non-metastatic colorectal cancer (non-mCRC) and mCRC. Different from the traditional health-disease classification strategy, we adopted a novel disease-disease classification strategy and proposed a microbiome-based multi-view convolutional variational information bottleneck (MV-CVIB).

Results

The experimental results show that MV-CVIB can effectively predict mCRC. This model can achieve AUC values above 0.9 compared to other state-of-the-art models. Not only that, MV-CVIB also achieved satisfactory predictive performance on multiple published CRC gut microbiome datasets.

Discussion

Finally, multiple gut microbiota analyses were used to elucidate communities and differences between mCRC and non-mCRC, and the metastatic properties of CRC were assessed by patient age and microbiota expression.
16S rRNA gene-based microbiota profiles from diverse avian faeces are largely independent of DNA preservation and extraction method
Authors: Edwards Johnson , Hoffbeck Carmen , West Annie G. , Pas An , Taylor Michael W.
Published: August 2023

The avian gut microbiota has been the subject of considerable recent attention, with potential implications for diverse fields such as the poultry industry, microbial ecology, and conservation. Faecal microbiotas are frequently used as a non-invasive proxy for the gut microbiota, however the extraction of high-quality microbial DNA from avian faeces has often proven challenging. Here we aimed to evaluate the performance of two DNA preservation methods (95% ethanol and RNAlater) and five extraction approaches (IndiSpin Pathogen Kit, QIAamp PowerFecal Pro DNA Kit, MicroGEM PrepGEM Bacteria Kit, ZymoBIOMICS DNA Miniprep Kit, and an in-house phase separation-based method) for studying the avian gut microbiota. Systematic testing of the efficacy of these approaches on faecal samples from an initial three avian species (chicken, ostrich, and the flightless parrot kākāpō) revealed substantial differences in the quality, quantity and integrity of extracted DNA, but negligible influence of applied method on 16S rRNA gene-based microbiota profiles. Subsequent testing with a selected combination of preservation and extraction method on 10 further phylogenetically and ecologically diverse avian species reiterated the efficacy of the chosen approach, with bacterial community structure clustering strongly by technical replicates for a given avian species. Our finding that marked differences in extraction efficacy do not appear to influence 16S rRNA gene-based bacterial community profiles provides an important foundation for ongoing research on the avian gut microbiota.