bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of Immune Cells in Mediating the Causal Effect of Gut
Microbiota on Type 2 Diabetes
Authors: Ruifang Liu , Ruiting Chai , Zhaoyang Yang , Candong Li 
Published: February 2025

Background:
Previous studies have suggested that gut microbiota and
immune system regulation have potential links with type 2 diabetes (T2D). However,
the causal association between gut microbiota and T2D and whether immune cells
mediate this interaction is unclear.

Methods:
A two-sample, two-step Mendelian randomization (MR) study utilizing an
initial inverse-variance weighted (IVW) method was performed to explore the causal
impact of gut microbiota on T2D and the intermediary role of immune cells.

Results:
The MR analysis assigned 4 gut microbiota and metabolic pathways that
increase the risk of T2D (G_Prevotella, g_Anaerotruncus, g_Streptococcus.s_
Streptococcus_parasanguinis, and the pathway of PANTO-PWY) and 4 other gut
microbiota and metabolic pathways that have a protective effect against T2D (PWY5667, PWY-6892, PWY-7221, and the bacterial g_Paraprevotella.s_Paraprevotella_
clara). Furthermore, 17 immune cell traits have been identified as associated with T2D.
The finding from mediation MR analysis revealed that PANTO-PWY increases T2D
risk via CD3 on HLA DR+ CD4+, whereas PWY-7221 reduces T2D risk through CD4
on CD4 Treg.

Conclusion:
The research reveals a mediated causal link between the gut microbiota
and T2D via immune cells.
Synthesis of Novel 3-spirocephalosporins and Evaluation of their
Antibacterial Activity
Authors: Zwayyer Noor H. , Muhsen Usama A. , Faraj Rawah , Abebe Woubit 
Published: February 2025

Background and Objective:
Despite the well-known antibacterial activity of
cephalosporins, their analogous spirocyclic derivatives have not been adequately evaluated.
Thus, this work aimed to prepare a series of novel 3-spirocephalosporins and evaluate their
antibacterial activity.

Materials and Methods:
Novel 3-spirocephalosporins were prepared through a one-pot thioalkylation of chloromethyl cephalosporin GCLE with a range of 1,2,4-triazolidine-3-
thiones, followed by intramolecular Michael addition to the generated dihydrothiazine ring.
The reaction was performed at room temperature under basic conditions (K2CO3, acetone,
H2O). The antibacterial activities of the synthesized compounds were evaluated against a
panel of Gram-positive and Gram-negative bacteria

Results:
Most targets were obtained in moderate yield, and their structures were confirmed
by 1H and 13C NMR spectral techniques. All the tested compounds exhibited antibacterial
activity against methicillin-resistant S. aureus

Conclusion:
Seven novel thiazolidine-bearing 3-spirocephalosporins were prepared, and
most of them were potent against Gram-positive bacteria. Likely, the replacement of 1,2,4-
triazolidine-3-thiones with other heterocycles containing bidentate nucleophiles in advantageous positions could lead to different biologically active spirocephalosporins.
A Systematic Review and Meta-analysis on the Safety and Efficacy of CAR T Cell Therapy Targeting GPRC5D in Patients with Multiple Myeloma: A New Insight in Cancer Immunotherapy
Authors: Robat-Jazi Behrouz , Mahalleh Mehrdad , Dashti Mohsen , Nejati Negar , Ahmadpour Mahsa , Alinejad Erfan , Mohammadi Shiva , Lorestani Parsa , Hamidieh Amir Ali , Habibi Mohammad Amin , Jadidi-Niaragh Farhad 
Published: February 2025

Background:
Despite ongoing advances and introducing innovative therapeutic approaches for the
treatment of multiple myeloma (MM), relapses are common, with low overall survival rates. G protein–coupled
receptor, class C, group 5, and member D (GPRC5D) has been expressed in several myeloma cell lines and has
demonstrated encouraging outcomes results in in-vitro studies as a potential target for immunotherapies.

Objective:
We aimed to investigate the safety and efficacy of GPRC5D-targeted CAR T cell therapies in MM
patients.

Methods:
On August 24, 2023, the databases of PubMed, Scopus, Embase, and Web of Science were systematically
searched for pertinent studies. After completing a two‐step title/abstract and full-text screening process, the
eligible studies were included.

Results:
Following the screening of 107 articles, four studies of 130 multiple myeloma patients treated with
GPRC5D-targeted CAR T-cell therapy were included. The meta-analyses showed an ORR of 87% (95% CI [81-
93%]), with 74% (95% CI [65-73%]) for those with prior BCMA-targeted therapy and 88% (95% CI [78-99%])
for those without. PR was 25%, VGPR 33%, and CR/sCR 48%, with 65% achieving MRD-negativity. In terms of
safety, hematologic AEs were common, with anemia reported in 86% of patients. Non-hematologic common AEs
included CRS (83%, 5% grade ≥3) and hypocalcemia (63%, 10% grade ≥3). No significant publication bias was
detected.

Conclusion:
GPRC5D is an active and safe target that shows promising results in the treatment of relapsed and/or
refractory (R/R) MM and heavily pretreated patients.
Evaluation of Toxoplasma gondii Perforin-like Proteins (PLPs) to Find the
Potential Epitopes for Immunization through in silico Approach
Authors: Hosseini Seyyed Amir , Safari Mohamad Hosein , Siamian Davood , Majidiani Hamidreza , Basati Gholam , Asghari Ali 
Published: February 2025

Background:
Toxoplasma gondii (T. gondii) is a widespread apicomplexan parasite
that affects approximately one-third of the global population, posing particular risks to pregnant
women and individuals with weakened immune systems. Despite its significant impact, there is
currently no vaccine available for humans.

Objective:
This study employs computational methods (in silico) to investigate the physicochemical, antigenic, and structural properties of Perforin-like proteins (PLPs) from T. gondii, as well as
to identify immunogenic epitopes within these antigens.

Methods:
For this aim, amino acid sequences of TgPLP1 and TgPLP2 were retrieved and submitted to the ProtParam (physicochemical), VaxiJen v2.0 (antigenicity), NetSurfP-6.0 (2D structure),
Robetta (3D structure) web servers, along with the IEDB server to decipher the immunogenic epitopes. Subcellular characteristics such as signal peptide, transmembrane domain, post-translational modifications (PTMs), and cellular localization were also predicted.

Results:
Both proteins had a high MW of 125.50 and 92.21, respectively, with an alkaline pI, a 30
hours half-life in mammalian reticulocytes, good thermotolerance (high aliphatic index), and hydrophilicity properties (negative GRAVY). They also showed good antigenicity (0.7021 [PLP1]
vs 0.5701 [PLP2]), while they were non-allergenic. Both proteins were extracellular with numerous post-translational modification sites (phosphorylation, glycosylation, and acetylation), and a
transmembrane domain was only present in TgPLP1, with no signal peptide in both. Furthermore,
numerous immunogenic B- and T-cell epitopes were identified within the TgPLPs sequences,
suggesting their potential for inclusion in multi-epitope vaccine designs.

Conclusion:
Further studies are needed to confirm these findings and assess the efficacy of the
proposed vaccine constructs.
Status quo del paciente simulado y su empleo en telesimulación
Authors: Sánchez Herrera Irving Omar , Hermosillo Carrillo Jesús 
Published: February 2025

Simulated patients (SP) are protagonists of realistic scenarios with important emotional load for the health area. The COVID-19 pandemic limited in-person education using clinical simulation. This systematic review identified primary sources of information with the use of SP in telesimulation scenarios through a search ofthe terms “telesimulation”, “patient simulation”, “simulated patient”, “standardized patient”, on the platforms PubMed, ClinicalKey, Ebsco and OvidSP and “telesimulación”, “paciente simulado” and “paciente estandarizado” in Scielo and Medigraphic. Systematic and narrative reviews, meta-analyses, randomized controlled trials and clinical trials published between January 2020 and June 2023 aimed at the use of SP in telesimulation scenarios were selected. As a result, 242 potential articleswere found, 81.81% in English and 18.18% in Spanish, reviewing 48 full text and 12 articles for qualitative synthesis of which, 4 were included manually.COVID-19 triggered the use of video conferencing platforms as alternative for health education. The evidence provided during the pandemic period demonstrates that telesimulation SP has advantages associated with the cost of design, implementationand development of complex scenarios, as well as the improvement of soft and cognitive skills such as obtaining clinical records, interpreting diagnostic studies and medical prescription. However, its low realism, impossibility of performing face-to-faceprocedures with the patient and dependence on a stable internet prevent it from replacing simulation with the use of in-person SP.
Assessment of hemo- and cerebrospinal fluid dynamics disorders in idiopathic normal pressure hydrocephalus according to MRI data: a prospective study
Authors: Bogomyakova O. B. , Valova G. S. , Stankevich Yu. A. , Cherevko A. A. , Tulupov A. A. 
Published: February 2025

INTRODUCTION: Idiopathic normal pressure hydrocephalus (NPH) is a condition characterized by enlargement of the cerebral ventricles and an isolated disturbance of cerebrospinal fluid dynamics, the etiology and pathogenesis of which are still not fully determined.OBJECTIVE: To evaluate changes in hemo- and cerebrospinal fluid dynamics in idiopathic normal pressure hydrocephalus according to phase-contrast MRI data.MATERIALS AND METHODS: Three groups of subjects were formed: patients with NPH (12 people), elderly volunteers with atrophic ventriculomegaly (15 people), a group of healthy volunteers (15 people). For each subject, the data from a routine MRI study, the volumes of gray, white matter and cerebrospinal fluid were assessed, and the volume-velocity characteristics of CSF and blood flows at several levels were calculated.Statistics: For quantitative indicators of cerebrospinal fluid dynamics, the median (Me), 25% and 75% percentiles, and interquartile range were calculated. An intergroup assessment of the significance of differences was carried out using the Mann-Whitney U test and nonparametric multivariate analysis of variance MANOVA.RESULTS: Individual neuroimaging markers of IGT were determined, as well as an increase in the volume-velocity characteristics of CSF flow at the level of the cerebral aqueduct (p<0.01, with a predominance of the retrograde component) in comparison with the control group and patients with atrophic ventriculomegaly. Multidirectional changes in the volume of intracranial venous outflow were revealed in the study groups: in patients with IGT – a decrease in outflow along the straight sinus by 1.4 times (p<0.01), in patients with atrophic ventriculomegaly – a decrease in outflow along the superior sagittal sinus by 1.3 times (p<0.05).DISCUSSION: The data obtained show a significant impairment of cerebrospinal fluid dynamics in patients with NPH, in contrast to elderly volunteers with age-related atrophy and replacement expansion of the cerebrospinal fluid spaces at the level of the brain aqueduct, and also indicates the importance of the venous link in maintaining intracranial volumetric interactions.CONCLUSION: The combined use of a routine protocol and phase-contrast MRI techniques made it possible to identify a number of neuroimaging, hemo- and CSF dynamic changes in patients with NPH in comparison with healthy volunteers, and also, most importantly, with patients of comparable age with the presence of replacement ventriculomegaly against the background of atrophy.
Toxic effect of methanol: radiation and pathomorphological parallels
Authors: Antonova A. M. , Lodygin A. N. , Batotsyrenov B. V. , Kuznetsov S. V. , Klimanov D. V. , Shakhurin Yu. V. 
Published: February 2025

INTRODUCTION: Acute chemical poisoning with alcohol-containing products represents a pressing and socially significant health issue.OBJECTIVE: To analyze changes in the brain associated methanol poisoning and lung complications using to CT and traditional X-ray examination, observe how these changed evolve over time, and compare them with the pathomorphological findings.MATERIALS AND METHODS: Between 2017 and 2024, 80 patients aged 23 to 77 years (mean age: 44.2 years; men – 68; women – 12), were admitted to the Center for Acute Poisoning at the State Budgetary Institution «Research Institute of Emergency Medicine named after. I. I. Dzhanelidze» with signs of acute methanol poisoning. Of these, 45 patients died, and 35 were discharged. CT imaging of the brain was not performed in 13 deceased patients due to their extremely severe condition, as death occurrent within 2–3 hours to 24 hours of admission. CT was not conducted due to their stable condition, where no indications were present.RESULTS: CT was performed in 50 patients (in 62.5% of cases). Of these, 22 patients (44%) exhibited normal brain structures and parameters with no pathological changes; while 28 patients (56%) demonstrated pathological changes. These included diffuse edema in 17 (60.7%) and hemorrhagic complications in 9 (32.14%).CONCLUSION: In this study, diffuse brain edema, various types of hemorrhagic changes, and combination of hemorrhagic complications with diffuse edema. These radiological changes corresponded with the pathological findings observed during the forensic medical examination (FME). The data obtained can contribute to the refinement of diagnostic algorithms and the enhancement of medical care for methanol poisoning.
Health-Related Quality of Life and Health Utility After Metabolic/Bariatric Surgery Versus Medical/Lifestyle Intervention in Individuals With Type 2 Diabetes and Obesity: The ARMMS-T2D Study
Authors: Simonson Donald C. , Gourash William F. , Arterburn David E. , Hu Bo , Kashyap Sangeeta R. , Cummings David E. , Patti Mary-Elizabeth , Courcoulas Anita P. , Vernon Ashley H. , Jakicic John M. , Kirschling Sarah , Aminian Ali , Schauer Philip R. , Kirwan John P. 
Published: February 2025

OBJECTIVE
Type 2 diabetes and obesity are associated with reduced health-related quality of life (HRQoL) and health utility (HU), but long-term effects of metabolic/bariatric surgery (MBS) compared with those of medical/lifestyle intervention (MLI) on these outcomes are unclear.

RESEARCH DESIGN AND METHODS
We studied 228 individuals with type 2 diabetes and obesity randomly assigned to MBS (Roux-en-Y gastric bypass, sleeve gastrectomy, or gastric band; n = 152) or MLI (n = 76) in the ARMMS-T2D study. HRQoL (36-Item Short-Form Health Survey [SF-36], including Physical Component Score [PCS] and Mental Component Score [MCS]) and HU (Short Form 6 Dimensions [SF-6D]) were measured annually up to 12 years.

RESULTS
At baseline, participants’ mean ± SD age was 49.2 ± 8.0 years, 68.4% were female, BMI was 36.3 ± 3.4 kg/m2, and HbA1c was 8.7 ± 1.6%. PCS improved significantly more in the MBS versus MLI group over 12 years (+2.37 ± 0.53 vs. −0.95 ± 0.73; difference 3.32 ± 0.85; P &lt; 0.001). MBS was associated with better general health (P &lt; 0.001), physical functioning (P = 0.001), and vitality (P = 0.003). Reduction in BMI was greater after MBS versus MLI (P &lt; 0.001) and correlated with improved PCS (r = −0.43; P &lt; 0.001). Change in PCS was not associated with change in HbA1c. MCS changed minimally from baseline and was similar between MBS and MLI groups during follow-up (−0.21 ± 0.61 vs. −0.89 ± 0.84; difference 0.68 ± 0.97; P = 0.48). Improvements in HU were greater in the MBS versus MLI group over 12 years (+0.02 ± 0.01 vs. −0.01 ± 0.01; difference 0.03 ± 0.01; P = 0.003).

CONCLUSIONS
Metabolic surgery produces sustained weight loss and improves PCS, general health, physical functioning, vitality, and HU in individuals with type 2 diabetes and obesity compared with medical therapy up to 12 years after intervention.
Aspek Ekologi dan Sosial Budaya untuk Keberlanjutan Usaha Budidaya Rumput Laut di Nusa Lembongan
Authors: Manurung Elina , Arthana I Wayan , Kumbara A A Ngurah Anom 
Published: February 2025

Nusa Lembongan merupakan salah satu sentra penghasil rumput laut, namun padatahun 2017 produksinya mengalami penurunan sebesar akibat penyakit ice-ice, bibit yang kurang baik, harga jual rendah, dan peralihan profesi petani ke pariwisata. Selama pariwisata di Pulau Bali menurun akibat pandemi Covid-19,masyarakat kembali menggeluti budidaya rumput laut sebagai mata pencarian.. Penelitian ini bertujuan untuk melihat keterkaitan aspek ekologi dan sosial budaya usaha rumput laut agar berkelanjutan. Penelitian dilakukan di Nusa Lembongan, Kawasan Konservasi Perairan (KKP) Nusa Penida, Provinsi Bali, dengan metode kuantitatif dan kualitatif. Data yang diamati adalah laju pertumbuhan dan parameter kualitas air yaitu suhu, pH, salinitas, oksigen terlarut, kedalaman dan kecepatan arus serta data sosial budaya melalui wawancara dan observasi. Penelitian dimulai November 2022-Januari 2023. Hasil yang didapat rata-rata laju pertumbuhan mutlak rumput laut tertinggi 173 gram dan yang terendah sebesar 106 gram, produksi rumput laut tertinggi sebesar 1.376 gr/m dan rata-rata laju pertumbuhan harian spesifik berkisar antara 1,98-4,53% perhari. Parameter kualitas air suhu sebesar 29-31,4 °C; untuk pH 7,5-8,3; salinitas berkisar 29-31,5 ppt - oksigen terlarut 6,47-7,45 mg/L; kedalaman 0,2-0,9 m; dan kecepatan arus 0,1-0,3 m/s. Responden 20 orang pelaku pembudidaya, pendapatan dalam 1 kali budidaya berkisar antara Rp 5.000.000,00–15.000.000,00. Perairan Nusa Lembongan secara ekologi memenuhi syarat untuk usaha budidaya rumput laut berkelanjutan sebagai mata pencarian utama masyarakat Nusa Lembongan, dengan kearifan lokal Nyepi Segara. Budidaya rumput laut di Nusa Lembongan merupakan warisan budaya dan tradisi yang diwariskan dari satu generasi ke generasi dari tahap persiapan lokasi, penanaman, perawatan dan panen.
Portuguese Investor’s Perception of Investing in Companies With ESG Practices
Authors: Dias Henrique Amaral , Matos Fátima Regina Ney , Baptista Júlio de Albuquerque , Alves Ivo Daniel Mendes 
Published: February 2025

Objective: The objective of this study is to identify the perceptions of Portuguese investors regarding ESG (Environmental, Social and Governance) factors. It also aims to identify the criteria that lead investors to consider, or not, ESG criteria in their decisions.

Theoretical Framework: The concept of ESG (Environmental, Social, and Governance) has emerged as a fundamental framework for assessing the sustainability and ethical impact of companies. Its three dimensions – environmental, social, and governance – address different aspects of business operations and are increasingly considered in investment decisions and in the integration of their practices in companiesIn this topic, the main concepts and theories that underpin the research are presented.

Method: Based on a quantitative approach, 118 questionnaires were collected from Portuguese individuals, with the aim of deepening the understanding of this phenomenon and obtaining empirical data that can contribute to the academic and practical debate on the impact of these criteria in the business context.

Results and Discussion: The results obtained revealed [synthesize the main results of the research]. In the discussion section, these results are contextualized in light of the theoretical framework, highlighting the implications and relationships identified. Possible discrepancies and limitations of the study are also considered in this section.

Research Implications: The results of this study highlight the complexity of investment decisions in the ESG context and the diversity of factors that influence investor behavior. Familiarity with these factors emerges as a key variable, while other demographic factors such as age, education and location have a less evident influence.

Originality/Value: This research contributes to the field of socially responsible investing by identifying the variables that influence the adoption of ESG-aligned investment practices. However, further research is needed to understand how psychological, institutional and cultural factors may interact and influence investors’ perceptions of ESG practices, thus creating a broader field for future research.
Bioeconomy in the Amazon: Challenges, Opportunities, and Trends for Regional Development
Authors: Silva Júlio César Klipel , Soliani Rodrigo Duarte , Ferreira-Júnior Genildo Cavalcante , Freitas Renata Gomes de Abreu , Lobão Mario Sérgio Pedroza 
Published: February 2025

Objective: To analyze the challenges, opportunities, and trends related to the commercialization of bioeconomy products in the Amazon, highlighting their potential to promote sustainable development through the valorization of regional biodiversity.

Theoretical Framework: The bioeconomy, based on the sustainable use of biological resources, integrates traditional knowledge and technological innovations, standing out as a strategy for sustainable development in the Amazon. Challenges such as inadequate infrastructure and regulatory barriers hinder the entry of products into global markets, while sustainable practices and inclusive public policies emerge as solutions to strengthen value chains and integrate local communities.

Method: The study employed a Systematic Literature Review (SLR) of texts published between 2014 and 2024, including scientific articles and technical documents. The selection focused on the commercialization of Amazonian products, emphasizing sustainability and the inclusion of small producers. The SLR enabled the mapping of knowledge gaps and the identification of trends and opportunities, providing insights to enhance the competitiveness of the Amazonian bioeconomy.

Results and Discussion: The findings indicate that the Amazonian bioeconomy has the potential to meet the growing demand for sustainable products, such as food, cosmetics, and herbal medicines. However, it faces obstacles, including inadequate infrastructure, challenges in obtaining certifications, and limited access to credit. Trends highlight the increased value placed on sustainable practices, such as the domestication of native species and the use of innovative technologies to add value to products. Identified strategic guidelines include the integration of public and private policies, investments in science and technology, and the promotion of partnerships that ensure the inclusion of local communities, strengthening the region's global competitiveness.

Research Implications: The study contributes to the planning of actions that foster sustainable development in the Amazon, proposing incentives for technological innovation, the strengthening of value chains, and greater integration of communities into global value chains.

Originality/Value: By providing a detailed analysis of the challenges and trends of the Amazonian bioeconomy, the study offers practical guidelines to overcome structural barriers and promote environmental conservation alongside regional development, positioning the Amazon as a significant player in the global market for sustainable products.