bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combating Antimicrobial Resistance by Resensitising Bacteria to Antibiotics Using CRISPR: A Narrative Review
Authors: Nair Harihara Sujit 
Published: October 2024

Background: Antimicrobial resistance (AMR) remains a formidable global health threat. Conventional strategy of developing new antibiotics is costly and unsustainable. Thus, innovative approaches for resensitising bacteria using clustered regularly inter-spaced short palindromic repeats (CRISPR) technology are sought. Aims and Objectives: The aim of this study was to review existing technologies and approaches with the aim to identify the most feasible and practical approach to solve AMR globally. Methods: It is a narrative review of CRISPR research to identify a practical medical solution for combating AMR. By considering biological, social and pharmaceutical factors, feasible solutions and their limitations were identified. Next, CRISPR solutions were examined, then filtered based on strict medical expectations. A suitable cargo type and delivery mechanism will be established. Finally, the feasibility from a practical and economic perspective is considered. Results: Among the Cas effector modules examined, Cas12k was identified as the most promising candidate. Notably, Cas12k possesses a small protein size and lacks trans-cleavage activity, enhancing its specificity for targeted bacterial strains. Additionally, its naturally inactivated endonuclease domain further contributes to its precision. In line with this investigation, DNA plasmid was identified as the optimal cargo storage, while lipid nanoparticles were identified as the optimal delivery method. Conclusion: This is the first time an end-to-end consideration to AMR was considered for CRISPR-based strategies. This review offers valuable insights into a promising solution to addressing the AMR crisis. Such knowledge is essential to guide the development of novel AMR solutions.
Effects of a combination of dyslipidemia and hypertension on the glycemic control of patients with type 2 diabetes mellitus: a cross-sectional study
Authors: Lou Heqing , Jiang Yixue , Xu Chunrong , Dong Zong-Mei , Liu De , Qiao Cheng , Zhang Pan 
Published: October 2024

Objectives: Both dyslipidemia and hypertension contribute to poor glycemic control in patients with type 2 diabetes mellitus, but the combined effect of dyslipidemia and hypertension on glycemic control in patients with type 2 diabetes mellitus has not been evaluated. The aim of this study was to analyze the interaction effect between dyslipidemia and hypertension on glycemic control in patients with type 2 diabetes mellitus. Methods: A total of 2485 patients with type 2 diabetes mellitus were selected from the Xuzhou community of China by multi-stage cluster random sampling for a cross-sectional survey. Their glycated hemoglobin, dyslipidemia, and hypertension were assessed, and the interaction effects between dyslipidemia and hypertension on glycemic control were analyzed using relative excess risk due to the interaction, the synergy index, and the attributable proportion of the additive interaction. Results: Of the participants, 62.13% (1544/2485) had dyslipidemia and 55.01% (1367/2485) had hypertension. Of the participants, 76.66% (1905/2485) who had both dyslipidemia and hypertension also had poor glycemic control. The prevalence of poor glycemic control was higher in those with both dyslipidemia and hypertension (odds ratio 2.735, 95% confidence interval 2.117–3.532; p < 0.001) compared with those who had normal blood lipids and without hypertension, after adjustment for confounders. The relative excess risk due to the interaction, the attributable proportion, and the synergy index were 1.077 (95% confidence interval 0.558–1.596), 2.637 (95% confidence interval 1.268–4.006), and 0.394 (95% confidence interval 0.230–0.558), respectively, for the interaction between dyslipidemia and hypertension. Conclusions: Dyslipidemia and hypertension have an additive interaction on poor glycemic control in patients with type 2 diabetes mellitus.
GLP-1 Agonism for Kidney Transplant Recipients: A Narrative Review of Current Evidence and Future Directions Across the Research Spectrum
Authors: Riehl-Tonn Victoria J. , Medak Kyle D. , Rampersad Christie , MacPhee Anne , Harrison Tyrone G. 
Published: October 2024

Purpose of Review: Diabetes is the most common cause of kidney disease in individuals that receive a kidney transplant, and those without pre-existing diabetes are at greater risk of developing diabetes following kidney transplant. A class of diabetes treatment medications called glucagon-like peptide-1 receptor agonists (GLP-1RA) has seen recent widespread use for people with diabetes or obesity, with efficacy for improved glycemic control, weight loss, and reduced risk of cardiovascular events. Given these benefits, and indications for use that often co-occur in kidney transplant recipients, use of GLP-1RAs warrants consideration in this population. Therefore, we sought to review the current literature to better understand the mechanisms of action, clinical application, and person-centred considerations of GLP-1RAs in kidney transplant recipients. Sources of Information: Original articles were identified between December 2023 and July 2024 from electronic databases including the Ovid MEDLINE database, PubMed, and Google Scholar using terms “kidney transplant,” “GLP-1,” “glucagon-like peptide-1 receptor agonist,” and “diabetes.” Methods: A comprehensive review of the literature was conducted to explore the relationship between GLP-1RAs and kidney transplant recipients. We reviewed the current state of evidence across the research disciplines of basic or fundamental science, clinical and health services research, and person-centred equity science, and highlighted important knowledge gaps that offer opportunities for future research. Key Findings: Numerous clinical studies have demonstrated the benefit of GLP-1RAs in people with and without diabetic kidney disease, including decreased risk of cardiovascular events. However, there is a paucity of high-quality randomized controlled trials and observational studies analyzing use of GLP-1RAs in kidney transplant recipients. Evidence of benefit in this population is therefore limited to small studies or inferred from research conducted in nontransplant populations. Growing evidence from preclinical and clinical studies may elucidate renoprotective mechanisms of GLP-1RAs and remove barriers to application of these drugs in the transplant recipient population. Individuals who are female, non-white, have lower socioeconomic status, and live in rural communities are at greater risk of diabetes and have lower uptake of GLP-1RAs. There is a need for clinical trials across diverse kidney transplant populations to estimate the efficacy of GLP-1RAs on important health outcomes. Limitations: The search strategy for this narrative review may not have been sensitive to identify all relevant articles. Our search was limited to English language articles.
Protocol for a double-blind crossover randomised controlled trial to investigate inhalation CHallenge to assess Inducible Laryngeal Obstruction (CH-ILO)
Authors: Haines Jemma , Belvisi Maria G , Dubuis Eric C , Dockry Rachel J , Holt Kimberley J , Hull James H , Yorke Janelle , Fowler Stephen J , Ann Smith Jaclyn 
Published: October 2024

Current ILO diagnosis is dependent on an individual being symptomatic. If results prove citric acid inhalation challenge agent provokes ILO it will provide new insights into neuronal mechanisms and support development of a standardised diagnostic test.IntroductionInducible laryngeal obstruction (ILO) remains a poorly understood condition in part due to lack of understanding about the underlying neuronal mechanisms. Many suffer delayed confirmed diagnosis as no standardised assessment exists. Based on previous work, we propose citric acid (CA) is the most appropriate inhalation agent for inducing upper airway reflex responses, with a view to developing an inhalation challenge test for ILO.Methods and analysisA single-centre, double-blind crossover study. The primary objective is to identify if CA inhalation challenge provokes laryngeal obstruction in patients with confirmed ILO. We will recruit: 10 participants with ILO, 10 with refractory chronic cough (RCC), 10 healthy controls. Each will undergo two inhalation challenges during laryngoscopy, with ascending concentrations of citric acid or saline control; participants will be randomised sequentially by a computer-generated schedule to determine order of delivery. Follow up is a telephone consultation. Randomisation and preparation of challenge agents will be by an unblinded study team member, not involved in data analysis. Challenge agents will only be unblinded on study completion. Log10concentration of CA evoking ILO will be compared between patient groups using a one-way ANOVA, comparing participants with ILO and participants with RCC to healthy controls.ConclusionThis will be the first randomised controlled trial to investigate the role of inhalation challenge as an assessment tool to evoke laryngeal obstruction in patients with confirmed ILO. If results prove citric acid inhalation challenge agent provokes ILO it will provide new insights into neuronal mechanisms and support development of a standardised diagnostic test.
Carotid plaque thickness predicts cardiovascular events and death in patients with chronic kidney disease
Authors: Bjergfelt Sasha S. , Sørensen Ida M. H. , Urbak Laerke , Kofoed Klaus F. , Lange Theis , Feldt-Rasmussen Bo , Sillesen Henrik , Christoffersen Christina , Bro Susanne 
Published: October 2024

Abstract
Background
Classical risk scoring systems underestimate the risk of cardiovascular disease in chronic kidney disease (CKD). Coronary artery calcium score (CACS) has improved prediction of cardiovascular events in patients with CKD. The maximal carotid plaque thickness (cPTmax) measured in ultrasound scans of the carotid arteries has demonstrated similar predictive value as CACS in the general population. This is the first study to investigate whether cPTmax can predict cardiovascular events in CKD and to compare the predictive value of cPTmax and CACS in CKD.

Method
Two hundred patients with CKD stage 3 from the Copenhagen CKD Cohort underwent ultrasound scanning of the carotid arteries. The assessment consisted of locating plaque and measuring the thickest part of the plaque, cPTmax. Based on the distribution of cPTmax, the participants were divided into 3 groups: No plaques, cPTmax 1.0–1.9 mm and cPTmax > 1.9 mm (median cPTmax = 1.9 mm among patients with plaques). To measure CACS, 175 of the patients underwent a non-contrast CT scan of the coronary arteries. The follow-up time spanned between the ultrasound scan and a predefined end-date or the time of first event, defined as a composite of major cardiovascular events or death of any cause (MACE).

Results
The median follow-up time was 5.4 years during which 45 patients (22.5%) developed MACE. In a Cox-regression adjusted for classical cardiovascular risk factors, patients with cPTmax > 1.9 mm had a significantly increased hazard ratio of MACE (HR 3.2, CI: 1.1–9.3), p = 0.031) compared to patients without plaques. C-statistics was used to evaluate models for predicting MACE. The improvement in C-statistics was similar for the two models including classical cardiovascular risk factors plus cPTmax (0.247, CI: 0.181–0.312) and CACS (0.243, CI: 0.172–0.315), respectively, when compared to a model only controlled for time since baseline (a Cox model with no covariates).

Conclusion
Our results indicate that cPTmax may be useful for predicting MACE in CKD. cPTmax and CACS showed similar ability to predict MACE.
Copper homeostasis and copper-induced cell death in tumor immunity: implications for therapeutic strategies in cancer immunotherapy
Authors: Zhang Suhang , Huang Qibo , Ji Tuo , Li Qilin , Hu Chuanyu 
Published: October 2024

AbstractCopper is an important trace element for maintaining key biological functions such as cellular respiration, nerve conduction, and antioxidant defense. Maintaining copper homeostasis is critical for human health, and its imbalance has been linked to various diseases, especially cancer. Cuproptosis, a novel mechanism of copper-induced cell death, provides new therapeutic opportunities for metal ion regulation to interact with cell fate. This review provides insights into the complex mechanisms of copper metabolism, the molecular basis of cuproptosis, and its association with cancer development. We assess the role of cuproptosis-related genes (CRGs) associated with tumorigenesis, their importance as prognostic indicators and therapeutic targets, and the impact of copper homeostasis on the tumor microenvironment (TME) and immune response. Ultimately, this review highlights the complex interplay between copper, cuproptosis, and cancer immunotherapy.
Cocoa production in the 2020s: challenges and solutions
Authors: Kongor John Edem , Owusu Margaret , Oduro-Yeboah Charlotte 
Published: October 2024

Abstract

Background

Cocoa (
Theobroma cacao
L.) is a crop of huge economic significance worldwide and is grown mainly in tropical and subtropical countries. Currently, West Africa produces most of the world's cocoa. The crop provides economic support to cocoa-growing countries, smallholder farmers, and the chocolate confectionery industries. Cocoa is also valued for its appealing flavours and the health-promoting properties of the bioactive phytochemicals in the beans, which have received increased global attention in recent years.

Main body
The cocoa industry is divided into two sectors: upstream (cocoa bean production and marketing), which is dominated by cocoa-producing countries, and downstream (cocoa bean processing activities to produce semi-finished and finished products). Pests and diseases, climate change, low soil fertility, high soil cadmium levels, and the ongoing Russian-Ukrainian conflict threaten the crop's long-term production. In addition to these challenges, cocoa cultivation also contributes to environmental and biodiversity degradation.

Conclusion
To address these challenges and ensure a sustainable supply of high-quality cocoa beans to meet the rising global demand, sustainable intensification of its production in producing countries is deemed critical. These include breeding varieties that are resistant to yield-limiting factors, the use of integrated management strategies to improve soil fertility and control pests, diseases, and heavy metals like Cd, the implementation of agroforestry systems, increased farm gate prices, and the provision of social interventions such as alternative livelihoods for farmers to increase cocoa production on existing farmlands. Standardized and harmonized farm management and postharvest strategies are also required for the consistent production of high-quality beans each season.
Single-cell transcriptomic analysis reveals the commonality of immune response upon H1N1 influenza virus infection in mice and humans
Authors: Chen Yu , Cai Huaiyuan , Zhang Qian , Cao Gang , Zhang Jiahao , Yang Bing , Dai Jinxia 
Published: October 2024

AbstractSeasonal influenza A virus (IAV), particularly the H1N1 subtype, poses a significant public health threat because of its substantial morbidity and mortality rates worldwide. Understanding the immune response to H1N1 is crucial for developing effective treatments and vaccines. In this study, we deciphered the single-cell transcriptomic landscape of peripheral blood mononuclear cells (PBMCs) from H1N1-infected humans and lung tissue samples from H1N1-infected mice by mining HIN1-related single-cell RNA sequencing data from the GEO database. We observed similar changes in immune cell composition following H1N1 infection, with an increase in macrophages but a decrease in T cells in both species. Moreover, significant transcriptional changes in bystander immune cells upon H1N1 infection were identified, with the upregulation of the chemokine CCL2 in human PBMCs and increased expression of interferon-stimulated genes such as Ifit3, Ifit1 and Isg15 in mouse pulmonary immune cells. Intercellular cross-talk analysis highlighted enhanced interactions among bystander immune cells during H1N1 infection, with neutrophils in humans and macrophages in mice showing the most remarkable increases in interaction intensity. Transcription factor analysis revealed the conserved upregulation of key antiviral regulons, including STAT1 and IRF7, in T cells across both species, highlighting their pivotal roles in antiviral defense. These results suggest that humans and mice exhibit common immune responses to H1N1 infection, underscoring the similarity of vital immune mechanisms across species. The conserved immune mechanisms identified in this study provide potential therapeutic targets for enhancing antiviral immunity. Our research underscores the importance of understanding species-specific and conserved immune responses to H1N1 and offers insights that could inform the development of novel antiviral therapies and improve clinical outcomes for individuals affected by influenza.
Survival Risk Score for Invasive Nonmetastatic Breast Cancer: A Real-World Analysis
Authors: Mangone Lucia , Morabito Fortunato , Tripepi Giovanni , D'Arrigo Graziella , Romeo Santina Maria Grazia , Bisceglia Isabella , Braghiroli Maria Barbara , Marinelli Francesco , Bisagni Giancarlo , Neri Antonino , Pinto Carmine 
Published: October 2024

PURPOSE

This study aimed to develop a multivariable, weighted overall survival (OS) risk score (SRS) for nonmetastatic (M0) invasive breast cancer (M0-BC, SRS
M0-BC
).

MATERIALS AND METHODS
This study included a training (1,890 patients) and a validation cohort (850 patients) from the Reggio Emilia Cancer Registry (RE-CR). Ten traditional prognostic variables were evaluated.

RESULTS

In the training set, all the variables but the human epidermal growth factor receptor were significantly associated with OS at univariable analysis. A multivariable model identified an increased death risk for estrogen receptor (hazard ratio [HR], 2.0 [95% CI, 1.1 to 3.1];
P
= .021), tumor stages T2-T3 (HR, 2.4 [95% CI, 1.3 to 4.7];
P
= .009) and T4 (HR, 5.1 [95% CI, 2.0 to 13.0];
P
< .001), and age >74 years (HR, 5.7 [95% CI, 4.0 to 8.2];
P
< .001). By assigning scores according to HRs, four risk categories were generated (
P
for trend <.001). The HRs of death in the high- (282 patients, 15.6%), intermediate-high (275 patients, 15.2%), and intermediate-risk (349 patients, 19.2%) categories patients were, respectively, 27.3, 12.9, and 3.5 times higher, compared with the low-risk (909 patients, 50%) group. Harrell'C index was 81.1%, and the explained variation in mortality was 66.6. Internal cross-validation performed on the accrual index dates yielded a Harrell’C index ranging from 79.5% to 82.3% and an explained variation in mortality ranging from 60.3% to 69.4%. In the validation set, the same risk categories (
P
for trend <.001) were devised. The Harrell’C index and the explained variation in mortality were 76.1% and 53.7%, respectively, in the whole cohort, maintaining an elevated percentage according to the two accrual index dates.

CONCLUSION

SRS
M0-BC
using the real-world RE-CR data set may represent a low-cost, accessible, globally applicable model in daily clinical practice, helping to prognostically stratify patients with invasive M0-BC.
Uptake of Risk-Reducing Surgeries in an International Real-World Cohort of Hispanic Women
Authors: Chavarri-Guerra Yanin , Ferrigno-Guajardo Ana , Villarreal-Garza Cynthia , Martinez-Cannon Bertha Alejandra , Abugattas-Saba Julio , Fontaine Annette C. , Horcasitas Darling J. , Mora-Alferez Pamela , Unzeitig Gary W. , Brown Sandra , Mohar-Betancourt Alejandro , Nehoray Bita , Del Toro-Valero Azucena , Daneri-Navarro Adrian , Ganschow Pamela , Komenaka Ian , Rodriguez Yenni , Gutierrez Seymour Gubidxa , Valdez Leonora , Blazer Kathleen R. , Ellis Shellie , Weitzel Jeffrey N. 
Published: October 2024

PURPOSE
Women with pathogenic variants (PVs) in breast cancer (BC) and ovarian cancer (OC) associated genes are candidates for cancer risk-reducing strategies. Limited information is available regarding risk-reducing surgeries (RRS) among Hispanics. The aim of this study was to describe the uptake of RRS in an international real-world experience of Hispanic women referred for genetic cancer risk assessment (GCRA) and to identify factors affecting uptake.

METHODS
Between July 1997 and December 2019, Hispanic women, living in the United States or in Latin America, enrolled in the Clinical Cancer Genomics Community Research Network registry were prospectively included. Demographic characteristics and data regarding RRS were obtained from chart reviews and patient-reported follow-up questionnaires. Median follow-up was 41 months.

RESULTS

Among 1,736 Hispanic women referred for GCRA, 27.2% women underwent risk-reducing mastectomy (RRM), 25.5% risk-reducing salpingo-oophorectomy (RRSO) and, 10.7% both surgeries. Among
BRCA
carriers, rates of RRM and RRSO were 47.6% and 56.7%, respectively. In the multivariate analyses, being a carrier of a BC susceptibility gene (odds ratio [OR], 3.44), personal history of BC (OR, 6.22), living in the US (OR, 3.90), age ≤50 years (OR, 1.68) and, family history of BC (OR, 1.56) were associated with a higher likelihood of undergoing RRM. Carrying an OC susceptibility gene (OR, 6.72) was associated with a higher likelihood of undergoing RRSO.

CONCLUSION
The rate of RRS among Hispanic women is suboptimal. PV carriers, women with personal history of cancer, and those with a family history of cancer were more likely to have RRS, with less uptake outside the US. Understanding personal and systemic factors influencing uptake may enable interventions to increase risk appropriate uptake of RRS.
Respiratory syncytial virus: Understanding the patient journey and healthcare burden
Authors: Carroll Will , Adams Elizabeth , Evans Kath , Holmes Steve , Carreno Mariana 
Published: October 2024

Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis in infants in the United Kingdom (UK), contributing to a significant burden of disease for the healthcare system and healthcare professionals (HCPs). To understand how an infant with RSV can impact the various levels of the healthcare system, we explore the patients' and caregivers' experiences through the system using available literature, which was supplemented through interviews with two separate caregivers of infants with a previous diagnosis of RSV disease. In the UK, most infants (~60%) will have experienced an RSV infection by their first birthday. Of these, some will require multiple healthcare encounters, including hospitalisations and admission to paediatric intensive care units. The burden of RSV disease extends beyond the healthcare system, with a substantial impact on the caregivers of affected infants.