bluuebunny/crossref_metadata_2025 huggingface dataset:
The methodology of quantitative risk assessment studies
Authors: Rigaud Maxime , Buekers Jurgen , Bessems Jos , Basagaña Xavier , Mathy Sandrine , Nieuwenhuijsen Mark , Slama Rémy
Published: January 2024

Once an external factor has been deemed likely to influence human health and a dose response function is available, an assessment of its health impact or that of policies aimed at influencing this and possibly other factors in a specific population can be obtained through a quantitative risk assessment, or health impact assessment (HIA) study. The health impact is usually expressed as a number of disease cases or disability-adjusted life-years (DALYs) attributable to or expected from the exposure or policy. We review the methodology of quantitative risk assessment studies based on human data. The main steps of such studies include definition of counterfactual scenarios related to the exposure or policy, exposure(s) assessment, quantification of risks (usually relying on literature-based dose response functions), possibly economic assessment, followed by uncertainty analyses. We discuss issues and make recommendations relative to the accuracy and geographic scale at which factors are assessed, which can strongly influence the study results. If several factors are considered simultaneously, then correlation, mutual influences and possibly synergy between them should be taken into account. Gaps or issues in the methodology of quantitative risk assessment studies include 1) proposing a formal approach to the quantitative handling of the level of evidence regarding each exposure-health pair (essential to consider emerging factors); 2) contrasting risk assessment based on human dose–response functions with that relying on toxicological data; 3) clarification of terminology of health impact assessment and human-based risk assessment studies, which are actually very similar, and 4) other technical issues related to the simultaneous consideration of several factors, in particular when they are causally linked.
Recent progress of non-linear topological structure polymers: synthesis, and gene delivery
Authors: Wang Chenfei , He Wei , Wang Feifei , Yong Haiyang , Bo Tao , Yao Dingjin , Zhao Yitong , Pan Chaolan , Cao Qiaoyu , Zhang Si , Li Ming
Published: January 2024

Currently, many types of non-linear topological structure polymers, such as brush-shaped, star, branched and dendritic structures, have captured much attention in the field of gene delivery and nanomedicine. Compared with linear polymers, non-linear topological structural polymers offer many advantages, including multiple terminal groups, broad and complicated spatial architecture and multi-functionality sites to enhance gene delivery efficiency and targeting capabilities. Nevertheless, the complexity of their synthesis process severely hampers the development and applications of nonlinear topological polymers. This review aims to highlight various synthetic approaches of non-linear topological architecture polymers, including reversible-deactivation radical polymerization (RDRP) including atom-transfer radical polymerization (ATRP), nitroxide-mediated polymerization (NMP), reversible addition-fragmentation chain transfer (RAFT) polymerization, click chemistry reactions and Michael addition, and thoroughly discuss their advantages and disadvantages, as well as analyze their further application potential. Finally, we comprehensively discuss and summarize different non-linear topological structure polymers for genetic materials delivering performance both in vitro and in vivo, which indicated that topological effects and nonlinear topologies play a crucial role in enhancing the transfection performance of polymeric vectors. This review offered a promising guideline for the design and development of novel nonlinear polymers and facilitated the development of a new generation of polymer-based gene vectors.
Association of a novel frameshift variant and a known deleterious variant in MMR genes with Lynch syndrome in Chinese families
Authors: Li Juyi , Ni Haichun , Wang Xiufang , Cheng Wenzhuo , Li Li , Cheng Yong , Liu Chao , Li Yuanyuan , Deng Aiping
Published: January 2024

Background

Lynch syndrome (LS) is the most common hereditary colorectal cancer (CRC) syndrome. This condition is characterized by germline variants in DNA mismatch repair (MMR) genes, including MLH1, MSH2, MSH6, and PMS2. In this study, we analyzed the molecular defects and clinical manifestations of two families affected with CRC and proposed appropriate individual preventive strategies for all carriers of the variant.

Methods

We recruited two families diagnosed with CRC and combined their family history and immunohistochemical results to analyze the variants of probands and those of other family members by using whole exome sequencing. Subsequently, gene variants in each family were screened by comparing them with the variants available in the public database. Sanger sequencing was performed to verify the variant sites. An online platform (https://www.uniprot.org) was used to analyze the functional domains of mutant proteins.

Results

A novel frameshift variant (NM_001281492, c.1129_1130del, p.R377fs) in MSH6 and a known deleterious variant (NM_000249.4:c.1731G > A, p.S577S) in MLH1 were identified in the two families with CRC. Using bioinformatics tools, we noted that the frameshift variant reduced the number of amino acids in the MSH6 protein from 1230 to 383, thereby leading to no MSH6 protein expression. The silent variant caused splicing defects and was strongly associated with LS. 5-Fluorouracil-based adjuvant chemotherapy is not recommended for patients with LS.

Conclusions

The novel frameshift variant (MSH6, c.1129_1130del, p.R377fs) is likely pathogenic to LS, and the variant (MLH1, c.1731G > A, p.S577S) has been further confirmed to be pathogenic to LS. Our findings underscore the significance of genetic testing for LS and recommend that genetic consultation and regular follow-ups be conducted to guide individualized treatment for cancer-afflicted families, especially those with a deficiency in MMR expression.
Single-nucleus transcriptomic analysis reveals the relationship between gene expression in oligodendrocyte lineage and major depressive disorder
Authors: Xie Yinping , Chen Lijuan , Wang Leimin , Liu Tongou , Zheng Yage , Si Lujia , Ge Hailong , Xu Hong , Xiao Ling , Wang Gaohua
Published: January 2024

Background

Major depressive disorder (MDD) is a common mental illness that affects millions of people worldwide and imposes a heavy burden on individuals, families and society. Previous studies on MDD predominantly focused on neurons and employed bulk homogenates of brain tissues. This paper aims to decipher the relationship between oligodendrocyte lineage (OL) development and MDD at the single-cell resolution level.

Methods

Here, we present the use of a guided regularized random forest (GRRF) algorithm to explore single-nucleus RNA sequencing profiles (GSE144136) of the OL at four developmental stages, which contains dorsolateral prefrontal cortex of 17 healthy controls (HC) and 17 MDD cases, generated by Nagy C et al. We prioritized and ordered differentially expressed genes (DEGs) based on Nagy et al., which could predominantly discriminate cells in the four developmental stages and two adjacent developmental stages of the OL. We further screened top-ranked genes that distinguished between HC and MDD in four developmental stages. Moreover, we estimated the performance of the GRRF model via the area under the curve value. Additionally, we validated the pivotal candidate gene Malat1 in animal models.

Results

We found that, among the four developmental stages, the onset development of OL (OPC2) possesses the best predictive power for distinguishing HC and MDD, and long noncoding RNA MALAT1 has top-ranked importance value in candidate genes of four developmental stages. In addition, results of fluorescence in situ hybridization assay showed that Malat1 plays a critical role in the occurrence of depression.

Conclusions

Our work elucidates the mechanism of MDD from the perspective of OL development at the single-cell resolution level and provides novel insight into the occurrence of depression.
Combination of mutations in genes controlling DNA repair and high mutational load plays a prognostic role in pancreatic ductal adenocarcinoma (PDAC): a retrospective real-life study in Sardinian population
Authors: Sini Maria Cristina , Doro Maria Grazia , Frogheri Laura , Zinellu Angelo , Paliogiannis Panagiotis , Porcu Alberto , Scognamillo Fabrizio , Delogu Daniele , Santeufemia Davide Adriano , Persico Ivana , Palomba Grazia , Maestrale Giovanni Battista , Cossu Antonio , Palmieri Giuseppe
Published: January 2024

Background

Patients with pancreatic ductal adenocarcinoma (PDCA) carrying impaired mismatch repair mechanisms seem to have an outcome advantage under treatment with conventional chemotherapy, whereas the role for the tumor mutation burden on prognosis is controversial. In this study, we evaluated the prognostic role of the mutated genes involved in genome damage repair in a real-life series of PDAC patients in a hospital-based manner from the main Institution deputed to surgically treat such a disease in North Sardinia.

Methods

A cohort of fifty-five consecutive PDAC patients with potentially resectable/border line resectable PDAC (stage IIB-III) or oligometastatic disease (stage IV) and tumor tissue availability underwent next-generation sequencing (NGS)-based analysis using a panel containing driver oncogenes and tumor suppressor genes as well as genes controlling DNA repair mechanisms.

Results

Genes involved in the both genome damage repair (DR) and DNA mismatch repair (MMR) were found mutated in 17 (31%) and 15 (27%) cases, respectively. One fourth of PDAC cases (14/55; 25.5%) carried tumors presenting a combination of mutations in repair genes (DR and MMR) and the highest mutation load rates (MLR-H). After correction for confounders (surgery, adjuvant therapy, stage T, and metastasis), multivariate Cox regression analysis indicated that mutations in DR genes (HR = 3.0126, 95% CI 1.0707 to 8.4764, p = 0.0367) and the MLR (HR = 1.0018, 95%CI 1.0005 to 1.0032, p = 0.009) were significantly related to worse survival.

Conclusions

The combination of mutated repair genes and MLR-H, which is associated with a worse survival in our series of PDAC patients treated with conventional chemotherapy protocols, might become a predictive biomarker of response to immunotherapy in addition to its prognostic role in predicting survival.
Evaluation of three-dimensional reconstructed palatal morphology in skeletal class III subjects with different vertical patterns using cone beam computed tomography
Authors: Huang Xiaoyi , Huang Wenbin , Pei Tao , Zhao Yijiao , Wang Yong , Gu Yan , Bai Xueqin
Published: January 2024

Background

This study aims to evaluate the difference of three-dimensional (3D) reconstructed palatal morphology between subjects with skeletal Class III and skeletal Class I in different vertical patterns using cone beam computed tomography (CBCT).

Methods

In this study, 89 subjects with skeletal Class III (49 females, 40 males; 25.45 ± 3.81 years) and 85 subjects with skeletal Class I (45 females, 40 males; 23.95 ± 4.45 years) were collected retrospectively and divided into hyperdivergent, normodivergent and hypodivergent groups. Dolphin software was used to reorient the CBCT images of these subjects. After segmenting 3D object of maxilla from the 3D skull by ProPlan software, Geomagic Studio was used to reconstruct 3D palatal morphology and establish an average 3D palatal morphology for each group. The differences of 3D palatal morphology between different groups were compared by deviation patterns on 3D colored map analysis.

Results

3D colored map analysis showed the posterior part of male’s palate was higher and wider than that of female’s palate in skeletal Class III subjects. In skeletal Class III subjects, males with hyperdivergent pattern had a higher and narrower palate compared with hypodivergent subjects, while females with hyperdivergent had a higher but not obviously narrower palate compared with hypodivergent subjects. In the similar vertical patterns, skeletal Class III subjects had a flatter but not narrower palate compared with skeletal Class I subjects, along with a smaller palate volume.

Conclusions

This method allows more intuitive between-group comparisons of the differences of 3D palatal morphology. In skeletal Class III subjects, as the vertical dimension increased, the palate tends to be higher and narrower. Therefore, the influence of vertical patterns on the palatal morphology should be fully considered in the orthodontic and orthognathic treatment of skeletal Class III subjects.
Co-linear chaining on pangenome graphs
Authors: Rajput Jyotshna , Chandra Ghanshyam , Jain Chirag
Published: January 2024

Pangenome reference graphs are useful in genomics because they compactly represent the genetic diversity within a species, a capability that linear references lack. However, efficiently aligning sequences to these graphs with complex topology and cycles can be challenging. The seed-chain-extend based alignment algorithms use co-linear chaining as a standard technique to identify a good cluster of exact seed matches that can be combined to form an alignment. Recent works show how the co-linear chaining problem can be efficiently solved for acyclic pangenome graphs by exploiting their small width and how incorporating gap cost in the scoring function improves alignment accuracy. However, it remains open on how to effectively generalize these techniques for general pangenome graphs which contain cycles. Here we present the first practical formulation and an exact algorithm for co-linear chaining on cyclic pangenome graphs. We rigorously prove the correctness and computational complexity of the proposed algorithm. We evaluate the empirical performance of our algorithm by aligning simulated long reads from the human genome to a cyclic pangenome graph constructed from 95 publicly available haplotype-resolved human genome assemblies. While the existing heuristic-based algorithms are faster, the proposed algorithm provides a significant advantage in terms of accuracy.

Implementation (https://github.com/at-cg/PanAligner).
Targeting cancer stem cell OXPHOS with tailored ruthenium complexes as a new anti-cancer strategy
Authors: Alcalá Sonia , Villarino Lara , Ruiz-Cañas Laura , Couceiro José R. , Martínez-Calvo Miguel , Palencia-Campos Adrián , Navarro Diego , Cabezas-Sainz Pablo , Rodriguez-Arabaolaza Iker , Cordero-Barreal Alfonso , Trilla-Fuertes Lucia , Rubiolo Juan A. , Batres-Ramos Sandra , Vallespinos Mireia , González-Páramos Cristina , Rodríguez Jéssica , Gámez-Pozo Angelo , Vara Juan Ángel Fresno , Fernández Sara Fra , Berlinches Amparo Benito , Moreno-Mata Nicolás , Redondo Ana María Torres , Carrato Alfredo , Hermann Patrick C. , Sánchez Laura , Torrente Susana , Fernández-Moreno Miguel Ángel , Mascareñas José L. , Sainz Bruno
Published: January 2024

Background

Previous studies by our group have shown that oxidative phosphorylation (OXPHOS) is the main pathway by which pancreatic cancer stem cells (CSCs) meet their energetic requirements; therefore, OXPHOS represents an Achille’s heel of these highly tumorigenic cells. Unfortunately, therapies that target OXPHOS in CSCs are lacking.

Methods

The safety and anti-CSC activity of a ruthenium complex featuring bipyridine and terpyridine ligands and one coordination labile position (Ru1) were evaluated across primary pancreatic cancer cultures and in vivo, using 8 patient-derived xenografts (PDXs). RNAseq analysis followed by mitochondria-specific molecular assays were used to determine the mechanism of action.

Results

We show that Ru1 is capable of inhibiting CSC OXPHOS function in vitro, and more importantly, it presents excellent anti-cancer activity, with low toxicity, across a large panel of human pancreatic PDXs, as well as in colorectal cancer and osteosarcoma PDXs. Mechanistic studies suggest that this activity stems from Ru1 binding to the D-loop region of the mitochondrial DNA of CSCs, inhibiting OXPHOS complex-associated transcription, leading to reduced mitochondrial oxygen consumption, membrane potential, and ATP production, all of which are necessary for CSCs, which heavily depend on mitochondrial respiration.

Conclusions

Overall, the coordination complex Ru1 represents not only an exciting new anti-cancer agent, but also a molecular tool to dissect the role of OXPHOS in CSCs. Results indicating that the compound is safe, non-toxic and highly effective in vivo are extremely exciting, and have allowed us to uncover unprecedented mechanistic possibilities to fight different cancer types based on targeting CSC OXPHOS.
Effect of remimazolam vs propofol in high-risk patients undergoing upper gastrointestinal endoscopy: a non-inferiority randomized controlled trial
Authors: Li Zhi , Yuan Daming , Yu Yu , Xu Jie , Yang Weili , Chen Li , Luo Nanbo
Published: January 2024

Background

Procedural sedation is essential for optimizing upper gastrointestinal endoscopy, particularly in high-risk patients with multiple underlying diseases. Respiratory and circulatory complications present significant challenges for procedural sedation in this population. This non-inferiority randomized controlled trial aims to investigate the safety and comfort of remimazolam compared to propofol for procedural sedation during upper gastrointestinal endoscopy in high-risk patients.

Methods

A total of 576 high-risk patients scheduled to undergo upper gastrointestinal endoscopy are planned to be enrolled in this study and randomly allocated to either the remimazolam or propofol group. The primary outcome measure is a composite endpoint, which includes (1) achieving a Modified Observer’s Alertness/Sedation scale (MOAA/S) score ≤ 3 before endoscope insertion, (2) successful completion of the endoscopic procedure, (3) the absence of significant respiratory instability during the endoscopy and treatment, and (4) the absence of significant circulatory instability during the examination. The noninferiority margin was 10%. Any adverse events (AEs) that occur will be reported.

Discussion

This trial aims to determine whether remimazolam is non-inferior to propofol for procedural sedation during upper gastrointestinal endoscopy in high-risk patients, regarding success rate, complication incidence, patient comfort, and satisfaction.

Trial registration {2a and 2b}

Chinese Clinical Trial Registry ClinicalTrials.gov ChiCTR2200066527. Registered on 7 December 2022.
Changes in saliva protein profile throughout Rhipicephalus microplus blood feeding
Authors: da Silva Vaz Junior Itabajara , Lu Stephen , Pinto Antônio F. M. , Diedrich Jolene K. , Yates John R. , Mulenga Albert , Termignoni Carlos , Ribeiro José Marcos , Tirloni Lucas
Published: January 2024

Background

When feeding on a vertebrate host, ticks secrete saliva, which is a complex mixture of proteins, lipids, and other molecules. Tick saliva assists the vector in modulating host hemostasis, immunity, and tissue repair mechanisms. While helping the vector to feed, its saliva modifies the site where pathogens are inoculated and often facilitates the infection process. The objective of this study is to uncover the variation in protein composition of Rhipicephalus microplus saliva during blood feeding.

Methods

Ticks were fed on calves, and adult females were collected, weighed, and divided in nine weight groups, representing the slow and rapid feeding phases of blood feeding. Tick saliva was collected, and mass spectrometry analyses were used to identify differentially secreted proteins. Bioinformatic tools were employed to predict the structural and functional features of the salivary proteins. Reciprocal best hit analyses were used to identify conserved families of salivary proteins secreted by other tick species.

Results

Changes in the protein secretion profiles of R. microplus adult female saliva during the blood feeding were observed, characterizing the phenomenon known as “sialome switching.” This observation validates the idea that the switch in protein expression may serve as a mechanism for evading host responses against tick feeding. Cattle tick saliva is predominantly rich in heme-binding proteins, secreted conserved proteins, lipocalins, and protease inhibitors, many of which are conserved and present in the saliva of other tick species. Additionally, another remarkable observation was the identification of host-derived proteins as a component of tick saliva.

Conclusions

Overall, this study brings new insights to understanding the dynamics of the proteomic profile of tick saliva, which is an important component of tick feeding biology. The results presented here, along with the disclosed sequences, contribute to our understanding of tick feeding biology and might aid in the identification of new targets for the development of novel anti-tick methods.

Graphical Abstract
An evaluation of the Invisalign® Aligner Technique and consideration of the force system: a systematic review
Authors: Caruso Silvia , De Felice Maria Elena , Valenti Chiara , Pagano Stefano , Caruso Sara , Gatto Roberto , Lombardo Guido
Published: January 2024

Objective

Since its introduction 25 years ago, the Invisalign® system has undergone multiple digital and biomechanical evolutions and its effectiveness is often compared to traditional systems without considering the many differences which characterize them. The main aim of this systematic review is to look at the literature dealing with studies on teeth movements using the Invisalign® system and the management of these movements through digital planning and artificial intelligence.

Materials and methods

The following electronic databases were searched: MEDLINE, Embase, the Cochrane Oral Health Group’s Trials Register, and CENTRAL. Unpublished studies were searched on ClinicalTrials.gov, the National Research Register, and Pro-Quest Dissertation Abstracts and Thesis database.

Results

Twenty-four studies (15 retrospective, 5 prospective, 2 pilot, and 2 case–control) were included. The results of the analysis carried out on the available literature show that the Invisalign® system is recognized to be a valid alternative to conventional orthodontic treatment in no-extraction cases. The results are influenced by the methods for assessing the effectiveness of this technique and by the comparison bias of the traditional system with the innovative digital system.

Conclusions

Since the introduction of SmartForce and SmartTrack material, the efficacy of the treatment has improved. There is still a shortage of high-quality evidence concerning the treatment modality. In order to make the treatment with the aligners more efficient, a correct management of the ClinCheck® software and a proper use of the biomechanics are necessary. The aligned force-driven system should be taken into account when developing the digital planning.
No causal association between allergic rhinitis and migraine: a Mendelian randomization study
Authors: Lv Hao , Liu Kunyu , Xie Yulie , Wang Yunfei , Chen Siyuan , Liu Peiqiang , Guan Mengting , Cong Jianchao , Xu Yu
Published: January 2024

Purpose

Allergic rhinitis (AR) and migraine are among the most common public health problems worldwide. Observational studies on the correlation between AR and migraine have reported inconsistent results. This study aimed to investigate the causal relationship of AR with migraine and its subtypes, including migraine with aura (MA) and migraine without aura (MO).

Methods

Bidirectional two-sample Mendelian randomization (MR) analysis was performed with publicly available summary-level statistics of large genome-wide association studies to estimate the possible causal effects. The inverse variance-weighted method was selected for primary analysis and was supplemented with the weighted median, weighted mode, and MR-Egger methods. The causal analysis using summary effect estimates (CAUSE) were further performed to verify the causality. Several sensitivity tests, including the leave-one-out, Cochran’s Q, MR-Egger intercept, and MR-PRESSO tests, were performed to assess the robustness of the results.

Results

AR did not exhibit a significant causal correlation with the elevated risk of any migraine (odd ratio (OR), 0.816; 95% confidence interval (CI), 0.511–1.302; P = 0.394), MA (OR, 0.690; 95% CI 0.298–1.593; P = 0.384), or MO (OR, 1.022; 95% CI 0.490–2.131; P = 0.954). Consistently, reverse MR analysis did not reveal causal effects of any migraine or its subtypes on AR. Almost all sensitivity analyses supported the robustness of the results.

Conclusions

This MR study did not reveal a clear causal association between AR and migraine risk. More research is warranted to reveal the complex association between AR and migraine.
MDM4 was associated with poor prognosis and tumor-immune infiltration of cancers
Authors: Liu Jie , Yang Jie , Pan Qilong , Wang Xiangyu , Wang Xinyin , Chen Han , Zheng Xiaoling , Huang Qingling
Published: January 2024

MDM4 is one of the MDM protein family and is generally recognized as the key negative regulator of p53. As a cancer-promoting factor, it plays a non-negligible role in tumorigenesis and development. In this article, we analyzed the expression levels of MDM4 in pan-cancer through multiple databases. We also investigated the correlations between MDM4 expression and prognostic value, immune features, genetic mutation, and tumor-related pathways. We found that MDM4 overexpression is often accompanied by adverse clinical features, poor prognosis, oncogenic mutations, tumor-immune infiltration and aberrant activation of oncogenic signaling pathways. We also conducted transcriptomic sequencing to investigate the effect of MDM4 on transcript levels in colon cancer and performed qPCR to verify this. Finally, we carried out some in vitro experiments including colony formation assay, chemoresistance and senescence-associated β-galactosidase activity assay to study the anti-tumor treatment effect of small molecule MDM4 inhibitor, NSC146109. Our research confirmed that MDM4 is a prognostic biomarker and potential therapeutic target for a variety of malignancies.
Lotus (Nelumbo nucifera): a multidisciplinary review of its cultural, ecological, and nutraceutical significance
Authors: Yang Hang , He Simai , Feng Qi , Liu Zisen , Xia Shibin , Zhou Qiaohong , Wu Zhenbin , Zhang Yi
Published: January 2024

This comprehensive review systematically examines the multifarious aspects of Nelumbo nucifera, elucidating its ecological, nutritional, medicinal, and biomimetic significance. Renowned both culturally and scientifically, Nelumbo nucifera manifests remarkable adaptability, characterized by its extensive distribution across varied climatic regions, underpinned by its robust rhizome system and prolific reproductive strategies. Ecologically, this species plays a crucial role in aquatic ecosystems, primarily through biofiltration, thereby enhancing habitat biodiversity. The rhizomes and seeds of Nelumbo nucifera are nutritionally significant, being rich sources of dietary fiber, essential vitamins, and minerals, and have found extensive culinary applications. From a medicinal perspective, diverse constituents of Nelumbo nucifera exhibit therapeutic potential, including anti-inflammatory, antioxidant, and anti-cancer properties. Recent advancements in preservation technology and culinary innovation have further underscored its role in the food industry, highlighting its nutritional versatility. In biomimetics, the unique "lotus effect" is leveraged for the development of self-cleaning materials. Additionally, the transformation of Nelumbo nucifera into biochar is being explored for its potential in sustainable environmental practices. This review emphasizes the critical need for targeted conservation strategies to protect Nelumbo nucifera against the threats posed by climate change and habitat loss, advocating for its sustainable utilization as a species of significant value.

Graphical Abstract
Multimorbidity and its associated risk factors among adults in northern Sudan: a community-based cross-sectional study
Authors: Musa Imad R. , Hassan Ahmed Ali , Adam Ishag
Published: January 2024

Background

Multimorbidity (having two or more coexisting long-term conditions) is a growing global challenge. However, data on multimorbidity among adults in Africa, including Sudan, are scarce. Thus, this study aimed to investigate the prevalence of multimorbidity and its associated risk factors among adults in Sudan.

Methods

A community-based cross-sectional study was conducted in northern Sudan from March 2022 to May 2022. Participants’ sociodemographic characteristics were assessed using a questionnaire. Multimorbidity was defined as having two or more coexisting long-term conditions, including diabetes mellitus (DM), hypertension, obesity, anaemia and depression-anxiety. Multivariate logistic regression analyses were performed to determine the associated factors.

Results

The participants included 250 adults: 119 (47.6%) males and 131(52.4%) females. The median interquartile range (IQR) of the enrolled adults of the age was 43.0 (30.0‒55.0) years. Of the 250 adults, 82(32.8%), 17(6.8%), 84(33.6%), and 67(26.8%) were normal weight, underweight, overweight, and obese, respectively; 148(59.2%), 72(28.8%), 63(25.2%), 67(26.8%), and 98(39.2%) had hypertension, DM, anaemia, obesity, and depression-anxiety, respectively. A total of 154 adults (61.6%) had multimorbidity: 97(38.8%), 49(19.6%), and 8(3.2%) had two, three, and four morbidities, respectively. The remaining 21 (8.4%), and 75 (30.0%) adults had no morbidity, and one morbidity, respectively.

In amultivariate logistic regression analysis, increasing age (adjusted odd ratio [AOR] = 1.03, 95% CI = 1.01‒1.05), and female sex (AOR = 2.17, 95% CI = 1.16‒4.06) were associated with multimorbidity.

Conclusions

The high prevalence of multimorbidity revealed in this study uncovers a major public health problem among Sudanese adults. Our results show that increasing age and female sex are associated with multimorbidity. Additional extensive studies are necessary to evaluate the magnitude of multimorbidity for improved future planning and establishing effective health systems.
A balancing act: radicality and capture in institutionalising reflexive governance for urban sustainability transitions
Authors: de Geus Tessa , Wittmayer Julia M. , Silvestri Giorgia
Published: January 2024

Over the past two decades, urban actors have sought to foster long-lasting change towards sustainability through reflexive governance. Related activities, including transition labs, arenas, experiments, and roadmaps, have been problematised for disparities between using a discourse of transformation and radicality while failing to materialise radical action and succumbing to ‘projectification’ – meaning that the impact of an intervention tends to evaporate after the initial experiment impulse. Enabling a transformative legacy of such interventions requires institutionalising reflexive governance arrangements, i.e. a process of integrating these arrangements as part of the existing institutional set-ups while maintaining ‘radical’ elements. Particularly as the focus in certain urban transitions shifts from emerging and supporting niche practices towards institutionalising new ways of working and breaking down regime structures, it becomes paramount to better understand such processes. Based on a comparative empirical analysis of six European cities, we explore how these cities attempt to institutionalise reflexive governance and take stock of the tensions encountered, particularly to what extent cities manage to safeguard their radical ambitions, or whether these become ‘captured’ in the process. Other highlighted tensions are a focus on internal dynamics, a struggle around voluntary structures and accountability, and a challenge of keeping momentum with new actor constellations while trying to address complexity and uncertainty. We conclude by putting forward three recommendations for how reflexive governance processes may increase their impact: through prioritising institutional embeddedness in and outside of the local authority; creating transparency around how governance arrangements are adjusted and modified throughout the process for accountability; and renewing commitment periodically to ensure continuity and commitment from actors involved.
Beverage Consumption, Genetic Predisposition, and Risk of Cardiovascular Disease Among Adults With Type 2 Diabetes
Authors: Zhu Kai , Geng Tingting , Qiu Zixin , Li Rui , Li Lin , Li Ruyi , Chen Xue , Pan An , Manson JoAnn E , Liu Gang
Published: January 2024

Background

The evidence regarding the relationship between different types of beverages and cardiovascular health in individuals with type 2 diabetes (T2D) is scarce.

Aims

To prospectively examine the associations between individual beverage consumption, genetic predisposition, and risk of incident cardiovascular disease (CVD) among adults with T2D.

Methods

We analyzed the associations of individual beverage intake with risks of CVD and ischemic heart disease (IHD) in 7315 participants with T2D, overall or stratified by genetic risk to CVD, using data from the UK Biobank study.

Results

During a median follow-up of 6.1 years, 878 incident CVD cases were identified, including 517 IHD cases. Higher intakes of sugar-sweetened beverages (SSBs), artificially sweetened beverages (ASBs), and natural juices were each linearly associated with a higher CVD (Pnonlinearity > .05). Comparing the highest to lowest groups of beverage consumption, the multivariable-adjusted hazard ratios (95% confidence intervals) of CVD were 1.54 (1.14, 2.07) for SSBs, 1.34 (1.07, 1.69) for ASBs, and 1.33 (1.01, 1.76) for natural juices. Similar results were observed for incident IHD. Moreover, no significant interactions between these beverages and the CVD genetic risk score were observed. Replacing half-unit/day of SSBs or natural juices with coffee, tea, or yogurt, but not ASBs, was associated with a 20% to 46% lower risk of CVD and IHD.

Interpretation

Higher intakes of SSBs, ASBs, and natural juices were each linearly associated with an increased risk of CVD among individuals with T2D, regardless of genetic predisposition. Our findings highlight the importance of selecting healthy beverage options to improve cardiovascular health in patients with T2D.
Maternal High-Fat Diet Affects the Contents of Eggs and Causes Abnormal Development in the Medaka Fish
Authors: Inoue Yusuke , Fukushima Manatsu , Hirasawa Go , Furukawa Fumiya , Takeda Hiroyuki , Umatani Chie
Published: January 2024

Maternal nutritional status can affect development and metabolic phenotypes of progeny in animals. The effects of maternal diet are thought to be mediated mainly by changes inside oocytes such as organelles, maternal RNAs, and metabolites. However, to what extent each factor contributes to offspring phenotypes remains uncertain, especially in viviparous mammalian systems, where factors other than oocytes, such as placenta and milk, need to be considered. Here, using the medaka fish as an oviparous vertebrate model, we examined whether maternal high-fat diet (mHFD) feeding affects offspring development and what kind of changes occur in the contents of mature eggs. We found that mHFD caused the high frequency of embryonic deformities of offspring, accompanied by downregulation of transcription- and translation-related genes and zygotic transcripts at the blastula stage. Transcriptomic and metabolomic analyses of mature eggs suggested decreased catabolism of amino acids and glycogen, moderate upregulation of endoplasmic reticulum stress-related genes, and elevated lipid levels in mHFD eggs. Furthermore, high-fat diet females showed a higher incidence of oocyte atresia and downregulation of egg protein genes in the liver. These data suggest that attenuated amino acid catabolism triggered by decreased yolk protein load/processing, as well as elevated lipid levels inside eggs, are the prime candidates that account for the higher incidence of embryonic deformities in mHFD offspring. Our study presents a comprehensive data on the changes inside eggs in a mHFD model of nonmammalian vertebrates and provides insights into the mechanisms of parental nutritional effects on offspring.
Second Malignancy Masquerading as Recurrence of Neuroendocrine Tumor
Authors: Chakraborty Ananda Mohan , Bhardwaj Neha , Rastogi Ashu , Bhadada Sanjay Kumar
Published: January 2024

Neuroendocrine tumors (NETs) may mimic many endocrine syndromes, including Cushing syndrome (CS) secondary to ectopic ACTH secretion. Radiotherapy (RT) is often used as adjuvant therapy for such persistent or recurrent NETs. However, RT may predispose a susceptible person to a second malignancy. Here, we reported the story of a 37-year-old male, who presented with progressive weight loss, bone pain, and shortness of breath in the emergency department. He was diagnosed with CS secondary to a carcinoid tumor in the bronchopulmonary tree a decade previous and underwent total bilateral adrenalectomy. He also underwent lobectomy, and subsequent RT for a primary NET and was in clinical remission. His presenting symptoms were considered a recurrence of pulmonary NETs. However, the biopsy suggested high-grade mucoepidermoid carcinoma (MEC). MEC of the lung is a rare tumor with a prevalence of <1% of all lung malignancies. MEC of the lung after RT for bronchial NET-causing ectopic CS has not yet been reported in the literature. The present patient did not survive despite achieving remission of CS and primary tumor because of the aggressive second malignancy attributed to RT, which was given for the primary tumor.
Long-term Treatment of Pediatric Metastatic Papillary Thyroid Cancer With Lenvatinib
Authors: Donner Julia R , DeNardo Bradley , Topor Lisa Swartz
Published: January 2024

Papillary thyroid carcinoma (PTC) is the most common pediatric thyroid malignancy and incidence is increasing. Standard treatment for PTC in pediatric patients includes surgical intervention, suppression of TSH with levothyroxine, and radioactive iodine therapy (RAI) in select patients. In the setting of metastatic PTC or PTC refractory to RAI therapy, tyrosine kinase inhibitors (TKIs), such as lenvatinib, may be used. Until recently, experience with these targeted agents were largely limited to adult patients with progressive or refractory PTC. More recently, increased experience with TKI therapy has been reported in the pediatric population, with case reports and small series describing short-term TKI use. We report the case of a 15-year-old girl with RAI-refractory metastatic PTC who achieved stable disease with long-term lenvatinib treatment for more than 5.5 years. Prospective, longitudinal studies of TKIs in RAI-refractory pediatric PTC are needed.
Unraveling the Whipple Triad: Non–Islet Cell Tumor–Induced Hypoglycemia
Authors: Mohamed Farzahna , Raal Frederick J
Published: January 2024

Tumor-induced hypoglycemia (TIH) is a rare paraneoplastic phenomenon resulting from several tumor types and mechanisms. Insulinomas are the most common cause of TIH. However, non–islet cell tumors can also trigger hypoglycemia by releasing insulin-like growth factor 2 (IGF-II) or its precursor. We present a case of a 56-year-old woman experiencing spontaneous hypoglycemia due to a pleural-based solitary fibrous tumor. Diagnostic evaluations revealed diminished C-peptide levels, increased IGF-II, and a 4-fold increase in the IGF-II: IGF-I ratio, indicative of non–islet cell tumor hypoglycemia. Localization imaging identified a left pleural mass, confirming the diagnosis. Preoperatively, the patient received intravenous dextrose and corticosteroids, but surgical resection was essential for the resolution of symptoms. The identified tumor, a benign solitary fibrous tumor, was successfully removed, leading to an immediate postoperative cessation of hypoglycemia. Six years post resection, the patient remains symptom free. Managing TIH necessitates an early diagnosis aiming for complete tumor resection, with alternative approaches considered when complete resection is not possible. This case highlights the importance of a systematic diagnostic and management approach for TIH, emphasizing the need to identify the underlying cause, particularly in people without diabetes.
C-Reactive Protein/Albumin Ratio Is an Independent Risk Factor for Recurrence and Survival Following Curative Resection of Stage I–III Colorectal Cancer in Older Patients
Authors: Bekki Tomoaki , Shimomura Manabu , Hattori Minoru , Sato Saki , Watanabe Atsuhiro , Ishikawa Sho , Imaoka Kouki , Ono Kosuke , Matsubara Keiso , Mochizuki Tetsuya , Akabane Shintaro , Yano Takuya , Ohdan Hideki
Published: January 2024

Background

The number of older patients with cancer has increased, and colorectal cancer is expected to be affected by this trend. This study aimed to compare prognostic factors, including nutritional and inflammation-based indices, between patients aged ≥ 70 and < 70 years following curative resection of stage I–III colorectal cancer.

Patients and Methods

This study included 560 patients with stage I–III colorectal cancer who underwent curative resection between May 2010 and June 2018. A retrospective analysis was performed to identify prognosis-associated variables in patients aged ≥ 70 and < 70 years.

Results

Preoperative low body mass index, high C-reactive protein/albumin ratio, and comorbidities were mainly associated with poor prognosis in patients aged ≥ 70 years. Tumor factors were associated with a poor prognosis in patients aged < 70 years. The C-reactive protein/albumin ratio was independently associated with poor overall survival and recurrence-free survival in those aged ≥ 70 years. The time-dependent area under the curve for the C-reactive protein/albumin ratio was superior to those of other nutritional and inflammation-based indices in most postoperative observation periods in patients aged ≥ 70 years.

Conclusions

Tumor factors were associated with a poor prognosis in patients aged < 70 years. In addition to lymph node metastasis, preoperative statuses were associated with poor prognosis in patients aged ≥ 70 years. Specifically, the preoperative C-reactive protein/albumin ratio was independently associated with long-term prognosis in patients aged ≥ 70 years with stage I–III colorectal cancer after curative resection.
Critical Analysis of the Efficacy and Limitations of GLP-1 Pharmaceuticals in Obesity Management: A Comprehensive Literature Review
Authors: Gierlach Katarzyna , Nowak Karolina , Nowak Karolina , Olejarz Zuzanna , Słowik Magdalena , Drygała Zuzanna , Wyrwał Julia , Zielińska Zuzanna , Nieć Maria , Krasuska Martyna
Published: January 2024

Introduction and purpose

Obesity, a pervasive global pandemic intricately linked to various comorbidities, necessitates a comprehensive and nuanced approach. This article delves into the intricate realm of obesity guidelines, underscoring the significance of lifestyle modifications, preventive measures for childhood obesity, population-based strategies, clinical management protocols, and vigilant monitoring.

GLP-1 drugs, originally designed for type 2 diabetes management, exhibit multifaceted effects beyond glycemic control. They influence appetite regulation, gastric emptying dynamics, and potentially contribute to cardiovascular health improvements. However, the commendable effects come with a caveat - potential side effects necessitating careful consideration in clinical decision-making. Despite gaining popularity through celebrity endorsements, this article firmly underscores the need to view GLP-1 pharmacotherapy as a recommended intervention rather than a miraculous solution.

A brief description of the state of knowledge

Integral to the obesity discourse is the imperative to address weight stigma, demanding evidence-based approaches in both clinical and public health domains. The narrative extends into the future landscape of obesity pharmacotherapy, contemplating the potential role of probiotics. Emphasizing the necessity for long-term studies and randomized trials, it positions probiotics as a low-risk alternative with significant potential in mitigating obesity while simultaneously addressing concerns related to antibiotic resistance.

Summary

The pursuit of a balanced and effective approach to obesity management necessitates a nuanced understanding of medical interventions, consideration of societal perceptions, and exploration of innovative possibilities within the evolving landscape of healthcare.
Association between deficient levels of vitamin D and the occurrence of selected retinal diseases
Authors: Żmijewska Aleksandra , Maleszewska Monika , Sztybór Mateusz , Nowak Gabriela , Kapica Marcin , Piątkiewicz Julia , Krzyżanowska Maria , Momot Karol , Wojtas Mikołaj , Głogowska Karen
Published: January 2024

Introduction and Purpose:

Vision originates in the eye's retina, a complex structure essential for processing visual information. The connection between nutritional inadequacy, particularly vitamin deficiencies, and overall health, including ocular health, has long been acknowledged. Recent studies highlight the potential impact of vitamin D, a crucial nutrient, on retinal health. The aim is to investigate the association between low levels of vitamin D and retinal diseases like age-related macular degeneration (AMD) and diabetic retinopathy (DR), and to evaluate the potential benefits of vitamin D supplementation or lifestyle changes for at-risk patients.

Description of the State of Knowledge:

AMD, a significant cause of blindness in the elderly, involves factors like oxidative stress and inflammation. Various stages of AMD require different treatments, with limited options for advanced stages. DR, a complication of diabetes, leads to conditions such as retinal ischemia and neovascularization. Both conditions are potentially influenced by vitamin D levels. Studies show mixed results regarding the impact of vitamin D on these diseases. Some suggest lower levels may increase risk, while others report no significant effect or even contradictory findings.

Conclusions:

While some studies indicate a potential association between low vitamin D levels and the occurrence of retinal diseases, discrepancies exist in the findings. Lower vitamin D concentrations may be linked to a higher frequency of AMD and DR, but the evidence is not consistent across all studies. Therefore, a more in-depth exploration of this subject is warranted to draw conclusive insights. It is crucial to consider supplementation or dietary changes in cases of vitamin D deficiency, given its potential impact on systemic health.