bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unlocking the potential: exploring the impact of dolutegravir treatment on body mass index improvement in underweight adults with HIV in Malawi
Authors: Maphosa Thulani , Dunga Shalom , Makonokaya Lucky , Woelk Godfrey , Maida Alice , Wang Alice , Ahimbisibwe Allan , Chamanga Rachel K. , Zimba Suzgo B. , Kayira Dumbani , Machekano Rhoderick 
Published: May 2024

Abstract
Background
The introduction of dolutegravir (DTG) in treating HIV has shown enhanced efficacy and tolerability. This study examined changes in weight gain and body mass index (BMI) at 6- and 12-months after post-initiating antiretroviral therapy (ART), comparing people living with HIV (PLHIV) on DTG-based regimens with those on non-DTG-based regimens in Malawi.

Methods
Retrospective cohort data from 40 public health facilities in Malawi were used, including adult ART patients (aged ≥ 15 years) from January 2017 to March 2020. The primary outcomes were BMI changes/transitions, with secondary outcomes focused on estimating the proportion of mean weight gain > 10% post-ART initiation and BMI category transitions. Descriptive statistics and binomial regression were used to estimate the unadjusted and adjusted relative risks (RR) of weight gain of more than ( >) 10%.

Results
The study included 3,520 adult ART patients with baseline weight after ART initiation, predominantly female (62.7%) and aged 25–49 (61.1%), with a median age of 33 years (interquartile range (IQR), 23–42 years). These findings highlight the influence of age, ART history, and current regimen on weight gain. After 12months follow up, compared to those aged 15–24 years, individuals aged 25–49 had an Adjusted RR (ARR) of 0.5 (95% Confidence Interval (CI): 0.35–0.70), suggesting a 50% reduced likelihood of > 10% weight gain after post-ART initiation. Similarly, those aged 50 + had an ARR of 0.33 (95% CI: 0.20–0.58), indicating a 67% decreased likelihood compared to the youngest age group 15–24 years. This study highlights the positive impact of DTG-based regimens, revealing significant transitions from underweight to normal BMI categories at 6- and 12-months post-initiation.

Conclusion
This study provides insights into weight gain patterns in patients on DTG-based regimens compared with those on non-DTG regimens. Younger individuals (15–24 years) exhibited higher odds of weight gain, suggesting a need for increased surveillance in this age group. These findings contribute to the understanding DTG's potential effects on weight gain, aiding clinical decision making. Further research is required to comprehensively understand the underlying mechanisms and long-term implications of weight gain in patients receiving DTG-based regimens.
No genetic causal associations between periodontitis and brain atrophy or cognitive impairment: evidence from a comprehensive bidirectional Mendelian randomization study
Authors: Deng Zhixing , Li Jiaming , Zhang Yuhao , Zhang Yinian 
Published: May 2024

Abstract
Background
Observational studies have explored the relationships of periodontitis with brain atrophy and cognitive impairment, but these findings are limited by reverse causation, confounders and have reported conflicting results. Our study aimed to investigate the causal associations of periodontitis with brain atrophy and cognitive impairment through a comprehensive bidirectional Mendelian randomization (MR) research.

Methods
We incorporated two distinct genome-wide association study (GWAS) summary datasets as an exploration cohort and a replication cohort for periodontitis. Four and eight metrics were selected for the insightful evaluation of brain atrophy and cognitive impairment, respectively. The former involved cortical thickness and surface area, left and right hippocampal volumes, with the latter covering assessments of cognitive performance, fluid intelligence scores, prospective memory, and reaction time for mild cognitive impairment to Alzheimer's disease (AD), Lewy body dementia, vascular dementia and frontotemporal dementia for severe situations. Furthermore, supplementary analyses were conducted to examine the associations between the longitudinal rates of change in brain atrophy and cognitive function metrics with periodontitis. The main analysis utilized the inverse variance weighting (IVW) method and evaluated the robustness of the results through a series of sensitivity analyses. For multiple tests, associations with p-values < 0.0021 were considered statistically significant, while p-values ≥ 0.0021 and < 0.05 were regarded as suggestive of significance.

Results
In the exploration cohort, forward and reverse MR results revealed no causal associations between periodontitis and brain atrophy or cognitive impairment, and only a potential causal association was found between AD and periodontitis (IVW: OR = 0.917, 95% CI from 0.845 to 0.995, P = 0.038). Results from the replication cohort similarly corroborated the absence of a causal relationship. In the supplementary analyses, the longitudinal rates of change in brain atrophy and cognitive function were also not found to have causal relationships with periodontitis.

Conclusions
The MR analyses indicated a lack of substantial evidence for a causal connection between periodontitis and both brain atrophy and cognitive impairment.
Non-technical skills training for Nigerian interprofessional surgical teams: a cross-sectional survey
Authors: Alayande Barnabas Tobi , Forbes Callum , Kingpriest Paul , Adejumo Adeyinka , Williams Wendy , Wina Felix , Agbo Christian Agbo , Omolabake Bamidele , Bekele Abebe , Ismaila Bashiru O , Kerray Fiona , Sule Augustine , Abahuje Egide , Robertson Jamie M. ,   The Non-technical Skills for Surgery Nigeria Group, Abah Tosin , Shattah Akims , Homoweto Linus Hapiyati , Onyeji John , Okoko Joseph , Sule Joshua , Yule Steven , Riviello Robert , Isichei Mercy 
Published: May 2024

Abstract
Introduction
Non-technical skills (NTS) including communication, teamwork, leadership, situational awareness, and decision making, are essential for enhancing surgical safety. Often perceived as tangential soft skills, NTS are many times not included in formal medical education curricula or continuing medical professional development. We aimed to explore exposure of interprofessional teams in North-Central Nigeria to NTS and ascertain perceived facilitators and barriers to interprofessional training in these skills to enhance surgical safety and inform design of a relevant contextualized curriculum.

Methods
Six health facilities characterised by high surgical volumes in Nigeria’s North-Central geopolitical zone were purposively identified. Federal, state, and private university teaching hospitals, non-teaching public and private hospitals, and a not-for-profit health facility were included. A nineteen-item, web-based, cross-sectional survey was distributed to 71 surgical providers, operating room nurses, and anaesthesia providers by snowball sampling through interprofessional surgical team leads from August to November 2021. Data were analysed using Fisher’s exact test, proportions, and constant comparative methods for free text responses.

Results
Respondents included 17 anaesthesia providers, 21 perioperative nurses, and 29 surgeons and surgical trainees, with a 95.7% survey completion rate. Over 96% had never heard of any NTS for surgery framework useful for variable resource contexts and only 8% had ever received any form of NTS training. Interprofessional teams identified communication and teamwork as the most deficient personal skills (38, 57%), and as the most needed for surgical team improvement (45, 67%). There was a very high demand for NTS training by all surgical team members (64, 96%). The main motivations for training were expectations of resultant improved patient safety and improved interprofessional team dynamics. Week-long, hybrid training courses (with combined in-person and online components) were the preferred format for delivery of NTS education. Factors that would facilitate attendance included a desire for patient safety and self-improvement, while barriers to attendance were conflicts of time, and training costs.

Conclusions
Interprofessional surgical teams in the Nigerian context have a high degree of interest in NTS training, and believe it can improve team dynamics, personal performance, and ultimately patient safety. Implementation of NTS training programs should emphasize interprofessional communication and teamworking.
Ethical considerations and concerns in the implementation of AI in pharmacy practice: a cross-sectional study
Authors: Hasan Hisham E. , Jaber Deema , Khabour Omar F. , Alzoubi Karem H. 
Published: May 2024

Abstract
Background
Integrating artificial intelligence (AI) into healthcare has raised significant ethical concerns. In pharmacy practice, AI offers promising advances but also poses ethical challenges.

Methods
A cross-sectional study was conducted in countries from the Middle East and North Africa (MENA) region on 501 pharmacy professionals. A 12-item online questionnaire assessed ethical concerns related to the adoption of AI in pharmacy practice. Demographic factors associated with ethical concerns were analyzed via SPSS v.27 software using appropriate statistical tests.

Results
Participants expressed concerns about patient data privacy (58.9%), cybersecurity threats (58.9%), potential job displacement (62.9%), and lack of legal regulation (67.0%). Tech-savviness and basic AI understanding were correlated with higher concern scores (p < 0.001). Ethical implications include the need for informed consent, beneficence, justice, and transparency in the use of AI.

Conclusion
The findings emphasize the importance of ethical guidelines, education, and patient autonomy in adopting AI. Collaboration, data privacy, and equitable access are crucial to the responsible use of AI in pharmacy practice.
Single-cell and spatial transcriptomics reveal metastasis mechanism and microenvironment remodeling of lymph node in osteosarcoma
Authors: Liu Yun , He Mingwei , Tang Haijun , Xie Tianyu , Lin Yunhua , Liu Shangyu , Liang Jiming , Li Feicui , Luo Kai , Yang Mingxiu , Teng Hongcai , Luo Xiaoting , He Juliang , Liao Shijie , Huang Qian , Feng Wenyu , Zhan Xinli , Wei Qingjun 
Published: May 2024

Abstract
Background
Osteosarcoma (OS) is the most common primary malignant bone tumor and is highly prone to metastasis. OS can metastasize to the lymph node (LN) through the lymphatics, and the metastasis of tumor cells reestablishes the immune landscape of the LN, which is conducive to the growth of tumor cells. However, the mechanism of LN metastasis of osteosarcoma and remodeling of the metastatic lymph node (MLN) microenvironment is not clear.

Methods
Single-cell RNA sequencing of 18 samples from paracancerous, primary tumor, and lymph nodes was performed. Then, new signaling axes closely related to metastasis were identified using bioinformatics, in vitro experiments, and immunohistochemistry. The mechanism of remodeling of the LN microenvironment in tumor cells was investigated by integrating single-cell and spatial transcriptomics.

Results
From 18 single-cell sequencing samples, we obtained 117,964 cells. The pseudotime analysis revealed that osteoblast(OB) cells may follow a differentiation path from paracancerous tissue (PC) → primary tumor (PT) → MLN or from PC → PT, during the process of LN metastasis. Next, in combination of bioinformatics, in vitro and in vivo experiments, and immunohistochemistry, we determined that ETS2/IBSP, a new signal axis, might promote LN metastasis. Finally, single-cell and spatial dissection uncovered that OS cells could reshape the microenvironment of LN by interacting with various cell components, such as myeloid, cancer-associated fibroblasts (CAFs), and NK/T cells.

Conclusions
Collectively, our research revealed a new molecular mechanism of LN metastasis and clarified how OS cells influenced the LN microenvironment, which might provide new insight for blocking LN metastasis.
Expansion of artemisinin partial resistance mutations and lack of histidine rich protein-2 and -3 deletions in Plasmodium falciparum infections from Rukara, Rwanda
Authors: Schreidah Cecile , Giesbrecht David , Gashema Pierre , Young Neeva Wernsman , Munyaneza Tharcisse , Muvunyi Claude Mambo , Thwai Kyaw , Mazarati Jean-Baptiste , Bailey Jeffrey A. , Juliano Jonathan J. , Karema Corine 
Published: May 2024

Abstract
Background
Emerging artemisinin partial resistance and diagnostic resistance are a threat to malaria control in Africa. Plasmodium falciparum kelch13 (k13) propeller-domain mutations that confer artemisinin partial resistance have emerged in Africa. k13-561H was initially described at a frequency of 7.4% from Masaka in 2014–2015, but not present in nearby Rukara. By 2018, 19.6% of isolates in Masaka and 22% of isolates in Rukara contained the mutation. Longitudinal monitoring is essential to inform control efforts. In Rukara, an assessment was conducted to evaluate recent k13-561H prevalence changes, as well as other key mutations. Prevalence of hrp2/3 deletions was also assessed.

Methods
Samples collected in Rukara in 2021 were genotyped for key artemisinin and partner drug resistance mutations using molecular inversion probe assays and for hrp2/3 deletions using qPCR.

Results
Clinically validated k13 artemisinin partial resistance mutations continue to increase in prevalence with the overall level of mutant infections reaching 32% in Rwanda. The increase appears to be due to the rapid emergence of k13-675V (6.4%, 6/94 infections), previously not observed, rather than continued expansion of 561H (23.5% 20/85). Mutations to partner drugs and other anti-malarials were variable, with high levels of multidrug resistance 1 (mdr1) N86 (95.5%) associated with lumefantrine decreased susceptibility and dihydrofolate reductase (dhfr) 164L (24.7%) associated with a high level of antifolate resistance, but low levels of amodiaquine resistance polymorphisms with chloroquine resistance transporter (crt) 76T: at 6.1% prevalence. No hrp2 or hrp3 gene deletions associated with diagnostic resistance were found.

Conclusions
Increasing prevalence of artemisinin partial resistance due to k13-561H and the rapid expansion of k13-675V is concerning for the longevity of artemisinin effectiveness in the region. False negative RDT results do not appear to be an issue with no hrp2 or hpr3 deletions detected. Continued molecular surveillance in this region and surrounding areas is needed to follow artemisinin partial resistance and provide early detection of partner drug resistance, which would likely compromise control and increase malaria morbidity and mortality in East Africa.
NEMO/NF-κB signaling functions as a double-edged sword in PanIN formation versus progression to pancreatic cancer
Authors: Tsesmelis Miltiadis , Büttner Ulrike F. G. , Gerstenlauer Melanie , Manfras Uta , Tsesmelis Konstantinos , Du Ziwei , Sperb Nadine , Weissinger Stephanie Ellen , Möller Peter , Barth Thomas F. E. , Maier Harald J. , Chan Lap Kwan , Wirth Thomas 
Published: May 2024

Abstract
Background
Pancreatic ductal adenocarcinoma (PDAC) is marked by a dismal survival rate, lacking effective therapeutics due to its aggressive growth, late-stage diagnosis, and chemotherapy resistance. Despite debates on NF-κB targeting for PDAC treatment, no successful approach has emerged.

Methods
To elucidate the role of NF-κB, we ablated NF-κB essential modulator (NEMO), critical for conventional NF-κB signaling, in the pancreata of mice that develop precancerous lesions (KC mouse model). Secretagogue-induced pancreatitis by cerulein injections was utilized to promote inflammation and accelerate PDAC development.

Results
NEMO deletion reduced fibrosis and inflammation in young KC mice, resulting in fewer pancreatic intraepithelial neoplasias (PanINs) at later stages. Paradoxically, however, NEMO deletion accelerated the progression of these fewer PanINs to PDAC and reduced median lifespan. Further, analysis of tissue microarrays from human PDAC sections highlighted the correlation between reduced NEMO expression in neoplastic cells and poorer prognosis, supporting our observation in mice. Mechanistically, NEMO deletion impeded oncogene-induced senescence (OIS), which is normally active in low-grade PanINs. This blockage resulted in fewer senescence-associated secretory phenotype (SASP) factors, reducing inflammation. However, blocked OIS fostered replication stress and DNA damage accumulation which accelerated PanIN progression to PDAC. Finally, treatment with the DNA damage-inducing reagent etoposide resulted in elevated cell death in NEMO-ablated PDAC cells compared to their NEMO-competent counterparts, indicative of a synthetic lethality paradigm.

Conclusions
NEMO exhibited both oncogenic and tumor-suppressive properties during PDAC development. Caution is suggested in therapeutic interventions targeting NF-κB, which may be detrimental during PanIN progression but beneficial post-PDAC development.

Graphical Abstract
Synergistic activity of gold nanoparticles with amphotericin B on persister cells of Candida tropicalis biofilms
Authors: Dasilva M. A. , Andrada K. F. Crespo , Torales M. Maldonado , Hughes I. Manrrique , Pez P. , García-Martínez J. C. , Paraje María Gabriela 
Published: May 2024

Abstract
Aim
The antifungal activity was studied on sessile and persister cells (PCs) of Candida tropicalis biofilms of gold nanoparticles (AuNPs) stabilized with cetyltrimethylammonium bromide (CTAB-AuNPs) and those conjugated with cysteine, in combination with Amphotericin B (AmB).

Materials/methods
The PC model was used and synergistic activity was tested by the checkerboard assay. Biofilms were studied by crystal violet and scanning electron microscopy.

Results/Conclusions
After the combination of both AuNPs and AmB the biofilm biomass was reduced, with significant differences in architecture being observed with a reduced biofilm matrix. In addition, the CTAB-AuNPs-AmB combination significantly reduced PCs. Understanding how these AuNPs aid in the fight against biofilms and the development of new approaches to eradicate PCs has relevance for chronic infection treatment.
Natural products in the management of neurodegenerative diseases
Authors: Goyal Rajat , Mittal Pooja , Gautam Rupesh K. , Kamal Mohammad Amjad , Perveen Asma , Garg Vandana , Alexiou Athanasios , Saboor Muhammad , Haque Shafiul , Farhana Aisha , Papadakis Marios , Ashraf Ghulam Md 
Published: May 2024

AbstractNeurodegenerative diseases represent one of the utmost imperative well-being health issues and apprehensions due to their escalating incidence of mortality. Natural derivatives are more efficacious in various preclinical models of neurodegenerative illnesses. These natural compounds include phytoconstituents in herbs, vegetables, fruits, nuts, and marine and freshwater flora, with remarkable efficacy in mitigating neurodegeneration and enhancing cognitive abilities in preclinical models. According to the latest research, the therapeutic activity of natural substances can be increased by adding phytoconstituents in nanocarriers such as nanoparticles, nanogels, and nanostructured lipid carriers. They can enhance the stability and specificity of the bioactive compounds to a more considerable extent. Nanotechnology can also provide targeting, enhancing their specificity to the respective site of action. In light of these findings, this article discusses the biological and therapeutic potential of natural products and their bioactive derivatives to exert neuroprotective effects and some clinical studies assessing their translational potential to treat neurodegenerative disorders.
Graphical Abstract
Common mechanisms, therapeutic targets, and molecular pathogenesis of neurodegeneration. It is focused on the biological and therapeutic potential of natural products and their bioactive derivatives to exert a neuroprotective effect on the pathologies of neurodegenerative diseases.
A novel MT-ATP6 variant associated with complicated ataxia in two unrelated Italian patients: case report and functional studies
Authors: Sala Daniele , Marchet Silvia , Nanetti Lorenzo , Legati Andrea , Mariotti Caterina , Lamantea Eleonora , Ghezzi Daniele , Catania Alessia , Lamperti Costanza 
Published: May 2024

Abstract
Background
MT-ATP6 is a mitochondrial gene which encodes for the intramembrane subunit 6 (or A) of the mitochondrial ATP synthase, also known asl complex V, which is involved in the last step of oxidative phosphorylation to produce cellular ATP through aerobic metabolism. Although classically associated with the NARP syndrome, recent evidence highlights an important role of MT-ATP6 pathogenic variants in complicated adult-onset ataxias.

Methods
We describe two unrelated patients with adult-onset cerebellar ataxia associated with severe optic atrophy and mild cognitive impairment. Whole mitochondrial DNA sequencing was performed in both patients. We employed patients’ primary fibroblasts and cytoplasmic hybrids (cybrids), generated from patients-derived cells, to assess the activity of respiratory chain complexes, oxygen consumption rate (OCR), ATP production and mitochondrial membrane potential.

Results
In both patients, we identified the same novel m.8777 T > C variant in MT-ATP6 with variable heteroplasmy level in different tissues. We identifed an additional heteroplasmic novel variant in MT-ATP6, m.8879G > T, in the patients with the most severe phenotype. A significant reduction in complex V activity, OCR and ATP production was observed in cybrid clones homoplasmic for the m.8777 T > C variant, while no functional defect was detected in m.8879G > T homoplasmic clones. In addition, fibroblasts with high heteroplasmic levelsof m.8777 T > C variant showed hyperpolarization of mitochondrial membranes.

Conclusions
We describe a novel pathogenic mtDNA variant in MT-ATP6 associated with adult-onset ataxia, reinforcing the value of mtDNA screening within the diagnostic workflow of selected patients with late onset ataxias.
3D molecular structural modeling and characterization of indium phosphide via irregularity topological indices
Authors: Salman Muhammad , Ullah Asad , Zaman Shahid , Mahmoud Emad E. , Belay Melaku Berhe 
Published: May 2024

AbstractIndium phosphide (InP) is a binary semiconductor composed of indium and phosphorus. It has a zinc blende crystal structure, which is a type of cubic lattice structure. This lattice is composed of indium and phosphorus atoms arranged in a lattice of cube-shaped cells, with each cell containing four indium atoms and four phosphorus atoms. This lattice structure is the same for all materials with a zinc blende crystal structure and is the most common type of lattice structure in semiconductors. Indium phosphide (InP) has several chemical applications. It is commonly used as a dopant in the production of semiconductors, where it helps control the electrical properties of the material. InP is also utilized in the synthesis various indium-containing compounds, which can have applications in catalysts and chemical reactions. Additionally, InP nanoparticles have been investigated for their potential use in biomedical imaging and drug delivery systems. The topological characterization of 3D molecular structures can be performed via graph theory. In graph theory, the connections between atoms are represented as edges and the atoms themselves are represented as nodes. Furthermore, graph theory can be used to calculate the topological descriptors of the molecule such as the degree-based and reverse degree-based irregularity toplogical indices. These descriptors can be used to compare the topology of different molecules. This paper deals with the modeling and topological characterization of indium phosphide $$({\text{InP}})$$

(
InP
)

via degree-based and reverse irregularity indices. The 3D crystal structure of the InP is topologically modeled via partition of the edges, and derived closed form expressions for its irregularity indices. Our obtained results will be surely be helpful in investigating the QSPR/QSAR analysis as well as understanding the deep irregular behavior of the indium phosphide $$({\text{InP}})$$

(
InP
)

.