bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of internet use on health among older adults in China: a nationally representative study
Authors: Zhou Yanyan , Bai Yang , Wang Jun
Published: April 2024

Background and objectives

Aging poses a significant challenge worldwide, with China’s aging status becoming particularly severe. What is the impact of Internet use on the health of the elderly? Existing studies have drawn conflicting conclusions that Internet use improves or harms health. The purpose of this study was to explore how Internet use affects the health of older adults, and the mechanisms and heterogeneity of these effects.

Research design and methods

Based on Grossman’s theory, this paper constructs a health production function model. Using the data of China Family Panel Studies (CFPS) from 2014 to 2020, we investigated the impact of Internet use on the health of older adults using fixed effect model and instrumental variable method. We also examined the mediating role of health information acquisition, lifestyle, and social interaction in these associations.

Results

Internet use is positively associated with self-rated health and negatively associated with psychological sub-health level. Internet use promotes the health of older adults by facilitating access to health information, healthy lifestyles, and enhancing social interaction. And the impacts are heterogeneous at the individual and regional levels.

Discussion and implications

We should progressively enhance the level of internet accessibility for older adults, while concurrently addressing and narrowing the ‘digital divide’. By generating an abundance of superior health-related information, we can significantly improve health education tailored for the elderly. Additionally, it is crucial to offer extensive training opportunities designed to equip older adults with the necessary skills to proficiently navigate the internet.
Clinical phenotypes of comorbidities in end-stage knee osteoarthritis: a cluster analysis
Authors: Ma Jun , Zhang Kai , Ma Xilong , Wang Hao , Ma Chao , Zhang Yahui , Liu Ruiyu
Published: April 2024

Objectives

Comorbidities, as components of these heterogeneous features, often coexist with knee osteoarthritis, and are particularly prevalent in end-stage knee osteoarthritis. Here, we attempted to identify the different clinical phenotypes of comorbidities in patients with end-stage knee osteoarthritis by cluster analysis.

Methods

A total of 421 inpatients diagnosed with end-stage knee osteoarthritis who underwent inpatient surgery were included in this cross-sectional study. 23 demographic, comorbidity, inflammatory immune and evaluation scale variables were collected. Systematic clustering after factor analysis and separate two-step cluster analysis were performed for individual comorbidity variables and all variables, respectively, to objectively identify the different clinical phenotypes of the study patients.

Results

Four clusters were finally identified. Cluster 1 had the largest proportion of obese patients (93.8%) and hypertension was common (71.2%). Almost all patients in cluster 2 were depressed (95.8%) and anxiety disorders (94.7%). Cluster 3 combined patients with isolated end-stage knee osteoarthritis and a few comorbidities. Cluster 4 had the highest proportion of patients with rheumatoid arthritis (58.8%).

Conclusions

Patients with end-stage knee osteoarthritis may be classified into four different clinical phenotypes: "isolated end-stage knee osteoarthritis"; "obesity + hypertension"; "depression + anxiety"; and "rheumatoid arthritis", which may help guide individualized patient care and treatment strategies.
An anthocyanin-rich extract from Zea mays L. var. ceratina alleviates neuronal cell death caused by hydrogen peroxide-induced cytotoxicity in SH-SY5Y cells
Authors: Mairuae Nootchanat , Palachai Nut , Noisa Parinya
Published: April 2024

The incidence of dementia is rising, with neuronal cell death from oxidative stress and apoptosis recognized as a significant contributor to its development. However, effective strategies to combat this condition are lacking, necessitating further investigation. This study aimed to assess the potential of an anthocyanin-rich extract from Zea mays L. var. ceratina (AZC) in alleviating neuronal cell death.

Neurotoxicity was induced in SH-SY5Y cells using hydrogen peroxide (H2O2) at a concentration of 200 µM. Cells were pretreated with varying doses (31.25 and 62.5 µg/mL) of AZC. Cell viability was assessed using the MTT assay, and molecular mechanisms including reactive oxygen species (ROS) levels, antioxidant enzyme activities (catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px)), malondialdehyde (MDA) levels for oxidative stress, and the activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2), cAMP response element-binding protein (CREB), and apoptotic factors (B-cell lymphoma 2 (Bcl-2), caspase 3) were explored.

Results showed that AZC significantly improved cell viability, reduced ROS production and MDA levels, and downregulated caspase 3 expression. It enhanced CAT, SOD, and GSH-Px activities, activated ERK1/2 and CREB, and upregulated Bcl-2 expression. These findings support the neuroprotective effects of AZC, suggesting it activates ERK1/2, leading to CREB activation and subsequent upregulation of Bcl-2 expression while suppressing caspase 3. AZC may mitigate neuronal cell death by reducing ROS levels through enhanced scavenging enzyme activities.

In conclusion, this study underscores the potential of AZC as a neuroprotective agent against neuronal cell death. However, further investigations including toxicity assessments, in vivo studies, and clinical trials are necessary to validate its benefits in neuroprotection.
Lipid metabolic reprogramming mediated by circulating Nrg4 alleviates metabolic dysfunction-associated steatotic liver disease during the early recovery phase after sleeve gastrectomy
Authors: Yang Chengcan , Zhu Dongzi , Liu Chaofan , Wang Wenyue , He Yining , Wang Bing , Li Meiyi
Published: April 2024

Background

The metabolic benefits of bariatric surgery that contribute to the alleviation of metabolic dysfunction-associated steatotic liver disease (MASLD) have been reported. However, the processes and mechanisms underlying the contribution of lipid metabolic reprogramming after bariatric surgery to attenuating MASLD remain elusive.

Methods

A case–control study was designed to evaluate the impact of three of the most common adipokines (Nrg4, leptin, and adiponectin) on hepatic steatosis in the early recovery phase following sleeve gastrectomy (SG). A series of rodent and cell line experiments were subsequently used to determine the role and mechanism of secreted adipokines following SG in the alleviation of MASLD.

Results

In morbidly obese patients, an increase in circulating Nrg4 levels is associated with the alleviation of hepatic steatosis in the early recovery phase following SG before remarkable weight loss. The temporal parameters of the mice confirmed that an increase in circulating Nrg4 levels was initially stimulated by SG and contributed to the beneficial effect of SG on hepatic lipid deposition. Moreover, this occurred early following bariatric surgery. Mechanistically, gain- and loss-of-function studies in mice or cell lines revealed that circulating Nrg4 activates ErbB4, which could positively regulate fatty acid oxidation in hepatocytes to reduce intracellular lipid deposition.

Conclusions

This study demonstrated that the rapid effect of SG on hepatic lipid metabolic reprogramming mediated by circulating Nrg4 alleviates MASLD.
Adherence to the Mediterranean diet can beneficially affect the gut microbiota composition: a systematic review
Authors: Khavandegar Armin , Heidarzadeh Ali , Angoorani Pooneh , Hasani-Ranjbar Shirin , Ejtahed Hanieh-Sadat , Larijani Bagher , Qorbani Mostafa
Published: April 2024

Aim

Dietary patterns could have a notable role in shaping gut microbiota composition. Evidence confirms the positive impact of the Mediterranean diet (MD), as one of the most studied healthy dietary patterns, on the gut microbiota profile. We conducted this systematic review to investigate the results of observational studies and clinical trials regarding the possible changes in the gut microbiota composition, metabolites, and clinical outcomes following adherence to MD in healthy cases or patients suffering from metabolic disorders.

Methods

A systematic literature search was conducted on PubMed, Web of Science, and Scopus databases until October 2023. Two researchers separately screened the titles, abstracts, and then full-text of the articles and selected the relevant studies. Quality assessment of observational and interventional studies was performed by Newcastle-Ottawa and Cochrane checklists, respectively.

Results

A total of 1637 articles were obtained during the initial search. Ultimately, 37 articles, including 17 observational and 20 interventional studies, were included in this systematic review. Ten observational and 14 interventional studies reported a correlation between MD adherence and microbiota diversity. Faecalibacterium and Prevotella were the most frequent bacterial genera with increased abundance in both observational and interventional studies; an Increment of Bacteroides genus was also reported in observational studies. Better glycemic control, lowering fat mass, better bowel movement, decreased bloating, inflammation, and hospitalization risk were the reported clinical outcomes.

Conclusion

Adherence to the MD is associated with significant beneficial changes in the gut microbiota diversity, composition, and functions and major clinical improvements in most populations.
A tempo-spatial controllable microfluidic shear-stress generator for in-vitro mimicking of the thrombus
Authors: Yu Zhihang , Chen Yiqun , Li Jingjing , Chen Chang , Lu Huaxiu , Chen Siyuan , Zhang Tingting , Guo Tianruo , Zhu Yonggang , Jin Jing , Yan Sheng , Chen Huaying
Published: April 2024

Pathological conditions linked to shear stress have been identified in hematological diseases, cardiovascular diseases, and cancer. These conditions often exhibit significantly elevated shear stress levels, surpassing 1000 dyn/cm2 in severely stenotic arteries. Heightened shear stress can induce mechanical harm to endothelial cells, potentially leading to bleeding and fatal consequences. However, current technology still grapples with limitations, including inadequate flexibility in simulating bodily shear stress environments, limited range of shear stress generation, and spatial and temporal adaptability. Consequently, a comprehensive understanding of the mechanisms underlying the impact of shear stress on physiological and pathological conditions, like thrombosis, remains inadequate. To address these limitations, this study presents a microfluidic-based shear stress generation chip as a proposed solution. The chip achieves a substantial 929-fold variation in shear stress solely by adjusting the degree of constriction in branch channels after PDMS fabrication. Experiments demonstrated that a rapid increase in shear stress up to 1000 dyn/cm2 significantly detached 88.2% cells from the substrate. Long-term exposure (24 h) to shear stress levels below 8.3 dyn/cm2 did not significantly impact cell growth. Furthermore, cells exposed to shear stress levels equal to or greater than 8.3 dyn/cm2 exhibited significant alterations in aspect ratio and orientation, following a normal distribution. This microfluidic chip provides a reliable tool for investigating cellular responses to the wide-ranging shear stress existing in both physiological and pathological flow conditions.

Graphical Abstract
DNA-based molecular classifiers for the profiling of gene expression signatures
Authors: Zhang Li , Liu Qian , Guo Yongcan , Tian Luyao , Chen Kena , Bai Dan , Yu Hongyan , Han Xiaole , Luo Wang , Feng Tong , Deng Shixiong , Xie Guoming
Published: April 2024

Although gene expression signatures offer tremendous potential in diseases diagnostic and prognostic, but massive gene expression signatures caused challenges for experimental detection and computational analysis in clinical setting. Here, we introduce a universal DNA-based molecular classifier for profiling gene expression signatures and generating immediate diagnostic outcomes. The molecular classifier begins with feature transformation, a modular and programmable strategy was used to capture relative relationships of low-concentration RNAs and convert them to general coding inputs. Then, competitive inhibition of the DNA catalytic reaction enables strict weight assignment for different inputs according to their importance, followed by summation, annihilation and reporting to accurately implement the mathematical model of the classifier. We validated the entire workflow by utilizing miRNA expression levels for the diagnosis of hepatocellular carcinoma (HCC) in clinical samples with an accuracy 85.7%. The results demonstrate the molecular classifier provides a universal solution to explore the correlation between gene expression patterns and disease diagnostics, monitoring, and prognosis, and supports personalized healthcare in primary care.
Landscapes of gut bacterial and fecal metabolic signatures and their relationship in severe preeclampsia
Authors: Liu Xianxian , Zeng Xiaoming , Li Xing , Xin Siming , Zhang Feng , Liu Faying , Zeng Yang , Wu Jilin , Zou Yang , Xiong Xinwei
Published: April 2024

Background

Preeclampsia is a pregnancy-specific disease leading to maternal and perinatal morbidity. Hypertension and inflammation are the main characteristics of preeclampsia. Many factors can lead to hypertension and inflammation, including gut microbiota which plays an important role in hypertension and inflammation in humans. However, alterations to the gut microbiome and fecal metabolome, and their relationships in severe preeclampsia are not well known. This study aims to identify biomarkers significantly associated with severe preeclampsia and provide a knowledge base for treatments regulating the gut microbiome.

Methods

In this study, fecal samples were collected from individuals with severe preeclampsia and healthy controls for shotgun metagenomic sequencing to evaluate changes in gut microbiota composition. Quantitative polymerase chain reaction analysis was used to validate the reliability of our shotgun metagenomic sequencing results. Additionally, untargeted metabolomics analysis was performed to measure fecal metabolome concentrations.

Results

We identified several Lactobacillaceae that were significantly enriched in the gut of healthy controls, including Limosilactobacillus fermentum, the key biomarker distinguishing severe preeclampsia from healthy controls. Limosilactobacillus fermentum was significantly associated with shifts in KEGG Orthology (KO) genes and KEGG pathways of the gut microbiome in severe preeclampsia, such as flagellar assembly. Untargeted fecal metabolome analysis found that severe preeclampsia had higher concentrations of Phenylpropanoate and Agmatine. Increased concentrations of Phenylpropanoate and Agmatine were associated with the abundance of Limosilactobacillus fermentum. Furthermore, all metabolites with higher abundances in healthy controls were enriched in the arginine and proline metabolism pathway.

Conclusion

Our research indicates that changes in metabolites, possibly due to the gut microbe Limosilactobacillus fermentum, can contribute to the development of severe preeclampsia. This study provides insights into the interaction between gut microbiome and fecal metabolites and offers a basis for improving severe preeclampsia by modulating the gut microbiome.
IL-33 regulates adipogenesis via Wnt/β-catenin/PPAR-γ signaling pathway in preadipocytes
Authors: Xu Danning , Zhuang Siqi , Chen Hongzhi , Jiang Mengjie , Jiang Ping , Wang Qian , Wang Xuemei , Chen Ruohong , Tang Haoneng , Tang Lingli
Published: April 2024

Interleukin-33 (IL-33), an emerging cytokine within the IL-1 family, assumes a pivotal function in the control of obesity. However, the specific mechanism of its regulation of obesity formation remains unclear. In this study, we found that the expression level of IL-33 increased in visceral adipose tissue in mice fed with a high-fat diet (HFD) compared with that in mice fed with a normal diet (ND). In vitro, we also found the expression level of IL-33 was upregulated during the adipogenesis of 3T3-L1 cells. Functional test results showed that knockdown of IL-33 in 3T3-L1 cells differentiation could promote the accumulation of lipid droplets, the content of triglyceride and the expression of adipogenic–related genes (i.e. PPAR-γ, C/EBPα, FABP4, LPL, Adipoq and CD36). In contrast, overexpression of IL-33 inhibits adipogenic differentiation. Meanwhile, the above tests were repeated after over-differentiation of 3T3-L1 cells induced by oleic acid, and the results showed that IL-33 played a more significant role in the regulation of adipogenesis. To explore the mechanism, transcriptome sequencing was performed and results showed that IL-33 regulated the PPAR signaling pathway in 3T3-L1 cells. Further, Western blot and confocal microscopy showed that the inhibition of IL-33 could promote PPAR-γ expression by inhibiting the Wnt/β-catenin signal in 3T3-L1 cells. This study demonstrated that IL-33 was an important regulator of preadipocyte differentiation and inhibited adipogenesis by regulating the Wnt/β-catenin/PPAR-γ signaling pathway, which provided a new insight for further research on IL-33 as a new intervention target for metabolic disorders.
Tumor immune dysfunction and exclusion subtypes in bladder cancer and pan-cancer: a novel molecular subtyping strategy and immunotherapeutic prediction model
Authors: Zheng Kun , Hai Youlong , Chen Hongqi , Zhang Yukun , Hu Xiaoyong , Ni Kai
Published: April 2024

Background

Molecular subtyping is expected to enable precise treatment. However, reliable subtyping strategies for clinical application remains defective and controversial. Given the significance of tumor immune dysfunction and exclusion (TIDE), we aimed to develop a novel TIDE-based subtyping strategy to guide personalized immunotherapy in the bladder cancer (BC).

Methods

Transcriptome data of BC was used to evaluate the heterogeneity and the status of TIDE patterns. Subsequently, consensus clustering was applied to classify BC patients based on TIDE marker-genes. Patients’ clinicopathological, molecular features and signaling pathways of the different TIDE subtypes were well characterized. We also utilize the deconvolution algorithms to analyze the tumor microenvironment, and further explore the sensitivity and mechanisms of each subtype to immunotherapy. Furthermore, BC patient clinical information, real-world BC samples and urine samples were collected for the validation of our findings, which were used for RNA-seq analysis, H&E staining, immunohistochemistry and immunofluorescence staining, and enzyme-linked immunosorbent assay. Finally, we also explored the conservation of our novel TIDE subtypes in pan-cancers.

Results

We identified 69 TIDE biomarker genes and classified BC samples into three subtypes using consensus clustering. Subtype I showed the lowest TIDE status and malignancy with the best prognosis and highest sensitivity to immune checkpoint blockade (ICB) treatment, which was enriched of metabolic related signaling pathways. Subtype III represented the highest TIDE status and malignancy with the poorest prognosis and resistance to ICB treatment, resulting from its inhibitory immune microenvironment and T cell terminal exhaustion. Subtype II was in a transitional state with intermediate TIDE level, malignancy, and prognosis. We further confirmed the existence and characteristics of our novel TIDE subtypes using real-world BC samples and collected patient clinical data. This subtyping method was proved to be more efficient than previous known methods in identifying non-responders to immunotherapy. We also propose that combining our TIDE subtypes with known biomarkers can potentially improve the sensitivity and specificity of these biomarkers. Moreover, besides guiding ICB treatment, this classification approach can assist in selecting the frontline or recommended drugs. Finally, we confirmed that the TIDE subtypes are conserved across the pan-tumors.

Conclusions

Our novel TIDE-based subtyping method can serve as a powerful clinical tool for BC and pan-cancer patients, and potentially guiding personalized therapy decisions for selecting potential beneficiaries and excluding resistant patients of ICB therapy.
An early-onset specific polygenic risk score optimizes age-based risk estimate and stratification of prostate cancer: population-based cohort study
Authors: Cheng Yifei , Wu Lang , Xin Junyi , Ben Shuai , Chen Silu , Li Huiqin , Zhao Lingyan , Wang Meilin , Cheng Gong , Du Mulong
Published: April 2024

Background

Early-onset prostate cancer (EOPC, ≤ 55 years) has a unique clinical entity harboring high genetic risk, but the majority of EOPC patients still substantial opportunity to be early-detected thus suffering an unfavorable prognosis. A refined understanding of age-based polygenic risk score (PRS) for prostate cancer (PCa) would be essential for personalized risk stratification.

Methods

We included 167,517 male participants [4882 cases including 205 EOPC and 4677 late-onset PCa (LOPC)] from UK Biobank. A General-, an EOPC- and an LOPC-PRS were derived from age-specific genome-wide association studies. Weighted Cox proportional hazard models were applied to estimate the risk of PCa associated with PRSs. The discriminatory capability of PRSs were validated using time-dependent receiver operating characteristic (ROC) curves with additional 4238 males from PLCO and TCGA. Phenome-wide association studies underlying Mendelian Randomization were conducted to discover EOPC linking phenotypes.

Results

The 269-PRS calculated via well-established risk variants was more strongly associated with risk of EOPC [hazard ratio (HR) = 2.35, 95% confidence interval (CI) 1.99–2.78] than LOPC (HR = 1.95, 95% CI 1.89–2.01; I2 = 79%). EOPC-PRS was dramatically related to EOPC risk (HR = 4.70, 95% CI 3.98–5.54) but not to LOPC (HR = 0.98, 95% CI 0.96–1.01), while LOPC-PRS had similar risk estimates for EOPC and LOPC (I2 = 0%). Particularly, EOPC-PRS performed optimal discriminatory capability for EOPC (area under the ROC = 0.613). Among the phenomic factors to PCa deposited in the platform of ProAP (Prostate cancerAge-basedPheWAS; https://mulongdu.shinyapps.io/proap), EOPC was preferentially associated with PCa family history while LOPC was prone to environmental and lifestyles exposures.

Conclusions

This study comprehensively profiled the distinct genetic and phenotypic architecture of EOPC. The EOPC-PRS may optimize risk estimate of PCa in young males, particularly those without family history, thus providing guidance for precision population stratification.
Complement propagates visual system pathology following traumatic brain injury
Authors: Borucki Davis M. , Rohrer Baerbel , Tomlinson Stephen
Published: April 2024

Background

Traumatic brain injury (TBI) is associated with the development of visual system disorders. Visual deficits can present with delay and worsen over time, and may be associated with an ongoing neuroinflammatory response that is known to occur after TBI. Complement system activation is strongly associated with the neuroinflammatory response after TBI, but whether it contributes to vision loss after TBI is unexplored.

Methods

Acute and chronic neuroinflammatory changes within the dorsal lateral geniculate nucleus (dLGN) and retina were investigated subsequent to a moderate to severe murine unilateral controlled cortical impact. Neuroinflammatory and histopathological outcomes were interpreted in the context of behavioral and visual function data. To investigate the role of complement, cohorts were treated after TBI with the complement inhibitor, CR2-Crry.

Results

At 3 days after TBI, complement component C3 was deposited on retinogeniculate synapses in the dLGN both ipsilateral and contralateral to the lesion, which was reduced in CR2-Crry treated animals. This was associated with microglia morphological changes in both the ipsilateral and contralateral dLGN, with a less ramified phenotype in vehicle compared to CR2-Crry treated animals. Microglia in vehicle treated animals also had a greater internalized VGlut2 + synaptic volume after TBI compared to CR2-Crry treated animals. Microglia morphological changes seen acutely persisted for at least 49 days after injury. Complement inhibition also reduced microglial synaptic internalization in the contralateral dLGN and increased the association between VGLUT2 and PSD95 puncta, indicating preservation of intact synapses. Unexpectedly, there were no changes in the thickness of the inner retina, retinal nerve fiber layer or retinal ganglion layer. Neuropathological changes in the dLGN were accompanied by reduced visual acuity at subacute and chronic time points after TBI, with improvement seen in CR2-Crry treated animals.

Conclusion

TBI induces complement activation within the dLGN and promotes microglial activation and synaptic internalization. Complement inhibition after TBI in a clinically relevant paradigm reduces complement activation, maintains a more surveillance-like microglia phenotype, and preserves synaptic density within the dLGN. Together, the data indicate that complement plays a key role in the development of visual deficits after TBI via complement-dependent microglial phagocytosis of synapses within the dLGN.
A comprehensive tool in recycling plant-waste of Gossypium barbadense L agricultural and industrial waste extracts containing gossypin and gossypol: hepatoprotective, anti-inflammatory and antioxidant effects
Authors: Mohammed Mona A. , Amer Nagat M. , Abdallah Heba M. I. , Saleh Mai S.
Published: April 2024

Improper management of agricultural and industrial cotton wastes causes environmental pollution and worsens the climate change challenge. Green recycling of cotton could contribute to a circular economy. One of the economic values of cotton wastes lies in their bioactive components. Two types of cotton wastes—agricultural and industrial—of the species Gossypium barbadense L. Giza 95 were targeted in the current study, aiming to maximize their medicinal value and investigate the anti-inflammatory, hepatoprotective, and antioxidant activities of their phytochemical extracts. Phytochemical extraction was performed using different solvents extraction. An anti-inflammatory effect was tested in carrageenan-induced acute edema in a rat paw model. A carbon tetrachloride chronic model of liver injury was used for the assessment of hepatoprotective potential. Liver enzymes (AST and ALT), oxidative stress markers (MDA and GSH), inflammatory biomarkers (C-reactive protein), and histopathological features were investigated. As a result, ethyl acetate proved to be the solvent of best choice to extract the gossypin polyphenolics, where the extracted amount reached 14,826.2 µg/g, followed by butanol (8751.4 µg/g extract). The chloroform (CHCL3) fraction showed the highest amounts of gossypol (190.7 µg/g extract), followed by petroleum ether. Cotton waste’s composition analysis showed a wide range of components, including 33 metabolites such as gossypetin, polyphenolics, and other metabolites that possess therapeutic effects. Both chloroform extract and industrial waste extracts showed superior anti-inflammatory and hepatoprotective effects in comparison to other extracts. All tested extracts (ethyl acetate, chloroform, and industrial waste) showed proper antioxidant activities.

Graphical Abstract
Comment on Ombashi, van der Goes, Versnel, Khonsari, van der Molen: guidance to develop a multidisciplinary, international, pediatric registry: a systematic review, Orphanet Journal of Rare diseases, 2023
Authors: Klintö Kristina , Becker Magnus
Published: April 2024

Recently, Ombashi et al. published a systematic review aiming to identify the pitfalls in the development and implementation as well as factors influencing long-term success of a multidisciplinary, international registry for cleft care on a global scale. The purpose of this letter to the editor is to highlight that the review failed to include the Swedish quality registry for patients born with cleft lip and palate, which fulfils the inclusion criteria. The Swedish cleft lip and palate registry is multidisciplinary, has a high coverage and reporting degree, and most outcome measures have been checked for reliability and validity. It is regularly used for open comparisons between treatment centers. Several research studies have been published based on the Swedish cleft lip and palate registry, and more are ongoing. The information we provide about the Swedish cleft lip and palate registry complements and expands the information of the results reported by Ombashi et al. in their research.
Prediction of pure tone thresholds using the speech reception threshold and age in elderly individuals with hearing loss
Authors: Dindamrongkul Ramida , Liabsuetrakul Tippawan , Pitathawatchai Pittayapon
Published: April 2024

Objective

Early detection and effective management of hearing loss constitute the key to improving the quality of life of individuals with hearing loss. However, in standardized pure tone audiometry, it is sometimes difficult for elderly patients to understand and follow all instructions. Audiologists also require time, expertise, and patience to ensure that an elderly can identify the faintest levels of stimuli during a hearing test. Therefore, this study aimed to devise and validate a formula to predict the pure tone threshold at each frequency across 0.5–4 kHz (PTTs) using speech reception threshold.

Methods

The 1226 audiograms of hearing-impaired individuals aged 60–90 years were reviewed. The random sample function randomly assigned 613 participants to the training and testing sets each. A linear model was created to predict the PTT value at each frequency based on variables significant at all frequencies across 0.5–4 kHz. The adjusted-R2 value was considered to indicate the performance of the predictive model. Pearson’s correlation coefficient was used to describe the relationship between the actual and predicted PTT at 0.5, 1, 2, and 4 kHz among the testing set to measure the performance of the proposed model.

Results

The predictive model was devised using variables based on the speech recognition threshold (SRT) after adjusting with age in the training set. The overall prediction accuracy demonstrated a higher adjusted-R2 ranging from 0.74 to 0.89 at frequencies of 0.5, 1, and 2 kHz, whereas a low percentage of explained variance was observed at 4 kHz (adjusted-R2 = 0.41). This predictive model can serve as an adjunctive clinical tool for guiding determination of the PTTs. Moreover, the predicted PTTs can be applied in the hearing aid programming software to set appropriate hearing aid gain using standard prescriptive formulas.
Microglia and macrophage metabolism: a regulator of cerebral gliomas
Authors: Deng Yue , Chen Qinyan , Wan Chao , Sun Yajie , Huang Fang , Hu Yan , Yang Kunyu
Published: April 2024

Reciprocal interactions between the tumor microenvironment (TME) and cancer cells play important roles in tumorigenesis and progression of glioma. Glioma-associated macrophages (GAMs), either of peripheral origin or representing brain-intrinsic microglia, are the majority population of infiltrating immune cells in glioma. GAMs, usually classified into M1 and M2 phenotypes, have remarkable plasticity and regulate tumor progression through different metabolic pathways. Recently, research efforts have increasingly focused on GAMs metabolism as potential targets for glioma therapy. This review aims to delineate the metabolic characteristics of GAMs within the TME and provide a summary of current therapeutic strategies targeting GAMs metabolism in glioma. The goal is to provide novel insights and therapeutic pathways for glioma by highlighting the significance of GAMs metabolism.
Optimizing waste management for green shipping: industry commitment through participatory processes in Cyprus
Authors: Loizidou X. I. , Loizides M. I. , Orthodoxou D. L. , Petsa D.
Published: April 2024

Every year, up to 0.3 million tonnes of waste from the European shipping industry is not properly delivered at ports. Most of the waste produced by the shipping industry is plastic waste, putting plastics at the forefront of the shipping industry’s waste management efforts. In an increasingly connected global economy, concerted actions that encourage and incentivise waste minimisation and waste management optimisation are essential for the reduction of marine litter and the achievement of a circular economy within the shipping industry. Cyprus, an important flag state, can take a leadership role towards this direction. This article presents the results of the implementation of the DeCyDe-4-Shipping decision-support participatory method in Cyprus, which allowed effective multi-stakeholder interactions and resulted in the identification of actions for waste minimisation and waste management optimization that are relevant, effective, implementable, and stem from stakeholder consensus. The method resulted in the definition of yearly action plans with prioritized actions and provided the tools through which to monitor the industry’s annual progress. As the shipping industry is dependent on a global supply chain, DeCyDe-4-Shipping could be replicated at a wider geographic scale, starting with Mediterranean ports, to ensure consistent industry progress towards waste minimization and waste management optimization.
Automated radiolabelling of [68Ga]Ga-PSMA-11 (gallium (68Ga)-gozetotide) using the Locametz® kit and two generators
Authors: van Brandwijk Elke A. , Aalbersberg Else A. , Hosseini Arman S. , Huitema Alwin D. R. , Hendrikx Jeroen J. M. A.
Published: April 2024

Background

Steps have been taken by pharmaceutical companies to obtain marketing authorisation of PSMA ligands in the European Union. Since December 2022, Locametz® (PSMA-11, gozetotide) is licensed as kit for manual radiolabelling with gallium-68 and commercially available since mid-2023. The Summary of Product Characteristic (SmPC) describes manual radiolabelling with a maximum activity after radiolabelling of 1369 MBq. We aimed for radiolabelling with a higher activity to increase production efficiency, and thus, automated radiolabelling is strongly preferred over manual radiolabelling to reduce radiation exposure to personnel. The aim of this study was to develop and validate a method for automated radiolabelling of the Locametz® kit using ~ 2000 MBq of gallium-68 eluate for radiolabelling.

Results

Automated radiolabelling of [68Ga]Ga-PSMA-11 using the Locametz® kit provided a product which complies to the Ph. Eur., had a shelf-life of 6 h at room temperature, and theoretically reduced radiation exposure 5.7 times. Radiolabelling with one and two generator(s) resulted in a radiochemical yield of 91–102% and 96–101% after preparation, respectively. The radiochemical purity ranged from 98.0 to 99.6% for radiolabelling with one generator and ranged from 98.4 to 99.3% for radiolabelling with two generators with similar stability. The activity of the final product was much higher when using two generators, 1961–2035 MBq compared to 740–1260 MBq, which leads to ~ 1.5 times more patient syringes available per preparation.

Conclusion

Automated radiolabelling of [68Ga]Ga-PSMA-11 using the Locametz® kit with higher gallium-68 activity than specified in the SmPC results in a product that is in compliance with the Ph. Eur. monograph and has a shelf-life of 6 h at room temperature. Radiolabelling with two generators proved possible and resulted in a product with similar quality but with much higher efficiency.
Unravelling protein corona formation on pristine and leached microplastics
Authors: Dawson Amanda Louise , Bose Utpal , Ni Dongdong , Nelis Joost Laurus Dinant
Published: April 2024

Upon entering the environment, the surface properties of pristine plastics are rapidly altered due to interactions with exogenous biomolecules, contaminants, and even microbiota, which ultimately alter their ecological impacts. When present in biological fluids or high protein environments, micro(nano)plastics bind with proteins, which form a protein corona around the particle. Although a significant body of literature exists on protein corona formation on nanomaterials, less is known about how the physiochemical properties of microplastics may influence protein corona formation. This study utilises quantitative proteomics to quantify protein binding to pristine and leached microplastics. Pristine polyethylene (PE) beads (50 and 500 μm), polyamide (PA) fibres (100 μm), polyethylene terephthalate fibres (500 μm), and fragments (< 300 μm), as well as pristine and leached textile microfibres comprised of PET, recycled PET, PA or cotton were incubated for 24 h in bovine serum albumin solution (2 mg mL−1) to form a protein corona. Protein adsorption to microplastics was dependant on particle surface area to volume ratio but only when additives were absent. For environmentally relevant textile microfibres, cotton microfibres adsorbed significantly more protein than synthetic microfibres. Fourteen-day aqueous leaching increased the zeta potential of all microfibres. However, only PA fibres adsorbed significantly higher protein on the leached fibres compared to their pristine counterparts. Overall, the presence of chemical additives in microplastics strongly influenced protein corona formation, and this phenomenon should be incorporated into routine microplastic toxicity assessment.

Graphical Abstract
Integration of Telemedicine Consultation Into a Tertiary Radiation Oncology Department: Predictors of Use, Treatment Yield, and Effects on Patient Population
Authors: Sharifzadeh Yasamin , Breen William G. , Harmsen William S. , Amundson Adam C. , Garda Allison E. , Routman David M. , Waddle Mark R. , Merrell Kenneth W. , Hallemeier Christopher L. , Laack Nadia N. , Kollengode Anantha , Corbin Kimberly S.
Published: April 2024

PURPOSE

The COVID-19 pandemic led to rapid expansion of telemedicine. The implications of telemedicine have not been rigorously studied in radiation oncology, a procedural specialty. This study aimed to evaluate the characteristics of in-person patients (IPPs) and virtual patients (VPs) who presented to a large cancer center before and during the pandemic and to understand variables affecting likelihood of receiving radiotherapy (yield) at our institution.

METHODS

A total of 17,915 patients presenting for new consultation between 2019 and 2021 were included, stratified by prepandemic and pandemic periods starting March 24, 2020. Telemedicine visits included video and telephone calls. Area deprivation indices (ADIs) were also compared.

RESULTS

The overall population was 56% male and 93% White with mean age of 63 years. During the pandemic, VPs accounted for 21% of visits, were on average younger than their in-person (IP) counterparts (63.3 years IP v 62.4 VP), and lived further away from clinic (215 miles IP v 402 VP). Among treated VPs, living closer to clinic was associated with higher yield (odds ratio [OR], 0.95; P < .001). This was also seen among IPPs who received treatment (OR, 0.96; P < .001); however, the average distance from clinic was significantly lower for IPPs than VPs (205 miles IP v 349 VP). Specialized radiotherapy (proton and brachytherapy) was used more in VPs. IPPs had higher ADI than VPs. Among VPs, those treated had higher ADI ( P < .001).

CONCLUSION

Patient characteristics and yield were significantly different between IPPs and VPs. Telemedicine increased reach to patients further away from clinic, including from rural or health care–deprived areas, allowing access to specialized radiation oncology care. Telemedicine has the potential to increase the reach of other technical and procedural specialties.
Group-by-Treatment Interaction Effects in Comparative Bioavailability Studies
Authors: Schütz Helmut , Burger Divan A. , Cobo Erik , Dubins David D. , Farkás Tibor , Labes Detlew , Lang Benjamin , Ocaña Jordi , Ring Arne , Shitova Anastasia , Stus Volodymyr , Tomashevskiy Michael
Published: April 2024

Comparative bioavailability studies often involve multiple groups of subjects for a variety of reasons, such as clinical capacity limitations. This raises questions about the validity of pooling data from these groups in the statistical analysis and whether a group-by-treatment interaction should be evaluated. We investigated the presence or absence of group-by-treatment interactions through both simulation techniques and a meta-study of well-controlled trials. Our findings reveal that the test falsely detects an interaction when no true group-by-treatment interaction exists. Conversely, when a true group-by-treatment interaction does exist, it often goes undetected. In our meta-study, the detected group-by-treatment interactions were observed at approximately the level of the test and, thus, can be considered false positives. Testing for a group-by-treatment interaction is both misleading and uninformative. It often falsely identifies an interaction when none exists and fails to detect a real one. This occurs because the test is performed between subjects in crossover designs, and studies are powered to compare treatments within subjects. This work demonstrates a lack of utility for including a group-by-treatment interaction in the model when assessing single-site comparative bioavailability studies, and the clinical trial study structure is divided into groups.

Graphical Abstract
Genital Surgery Outcomes Using an Individualized Algorithm for Hormone Management in Transfeminine Individuals
Authors: Herndon Justine , Gupta Nidhi , Davidge-Pitts Caroline , Imhof Nicole , Gonzalez Cesar , Carlson Sara , Will Marissa , Martinez-Jorge Jorys , Fahradyan Vahe , Tamire Lily , Lin Anna , Nippoldt Todd B , Chang Alice Y
Published: April 2024

Context

Transgender and gender diverse (TGD) individuals have greater access to genital surgery (GS) with improved insurance coverage and access to trained surgeons and interdisciplinary gender-affirming providers.

Objective

To determine perioperative medical and behavioral health outcomes in transfeminine (TF) individuals undergoing GS, with use of a specific gender-affirming hormone therapy (GAHT) algorithm based on individualized risk factor assessment.

Methods

In this retrospective observational cohort study, we collected preoperative and postoperative data from 183 TF individuals at a single tertiary referral center from 2017 to 2022, grouping patients by those who continued estradiol (Group 1) vs those who had temporarily discontinued estradiol for 2 to 6 weeks preoperatively (Group 2). Data included clinical and biochemical assessment, GAHT regimens, validated behavioral health measures, and postoperative complications. Main outcomes included venous thromboembolism (VTE) incidence, non-VTE postoperative complication incidence, and change in behavioral health assessments.

Results

The majority of individuals continued estradiol perioperatively (Group 1; 138 [75.4%]). Individuals who temporarily held estradiol preoperatively (Group 2; 45 [24.6%]) were statistically older (P < .01), had higher incidence of cardiometabolic comorbidities (P < .01), and higher Caprini scores (P < .01). Group 1 was statistically more likely to use oral estradiol (P < .01). One episode (0.05%) of VTE occurred (Group 1). There was no significant difference in postoperative complications or behavioral health measures between groups.

Conclusion

An individualized algorithm for preoperative hormone management for TF GS resulted in perioperative continuation of GAHT for the majority of individuals without significantly increasing the risk for postoperative surgical complications, while maintaining stable behavioral health measures perioperatively.
The Ethnographer's Way
Authors: Peterson Kristin , Olson Valerie
Published: April 2024

The Ethnographer’s Way guides researchers through the exciting process of turning an initial idea into an in-depth research project. Kristin Peterson and Valerie Olson introduce “multidimensioning,” a method for planning projects that invites scholars to examine their research interests from all angles. Researchers learn to integrate seemingly disparate groups, processes, sites, and things into a unified conceptual framework. The handbook’s ten modules walk readers step-by-step, from the initial lightbulb moment to constructing research descriptions, planning data gathering, writing grant and dissertation proposals, and preparing for fieldwork. Designed for ethnographers and those working across disciplines, these modules provide examples of multidimensional research projects with exercises readers can utilize to formulate their own projects. The authors incorporate group work into each module to break the isolation common in academic project design. In so doing, Peterson and Olson’s handbook provides essential support and guidance for researchers working at all levels and stages of a project.
The First Year of Successful Execution & Examination of Integrated Modular Curriculum 2k23 by UHS Pakistan
Authors: Naseem Nadia
Published: April 2024

doi: https://doi.org/10.12669/pjms.40.5.9951

How to cite this: Naseem N. The First Year of Successful Execution and Examination of Integrated Modular Curriculum 2k23 by UHS Pakistan. Pak J Med Sci. 2024;40(5):1047. doi: https://doi.org/10.12669/pjms.40.5.9951
Evolution of informed consent in research: From the Hippocratic Oath to the tailored consent
Authors: Fons-Martinez Jaime , Murciano-Gamborino Carlos , Diez-Domingo Javier
Published: April 2024

Background Informed consent (IC) is essential in defending the autonomy of potential participants in clinical research. Despite the advances in research ethics, particularly in IC, the different guidelines and codes have not been fully implemented. Several studies have presented consent deficiencies that have resulted in unethical practices or poor understanding of the IC. Main body This article reviews the evolution of IC, from its philosophical origins and initial use in the Ottoman Empire (16th century) to its use in clinical research today. It also presents the vision of the European project i-CONSENT (Grant Agreement number: 741856), whose main purpose is to improve the understanding of ICs in research and identifies the key components of a new paradigm to develop patient-centred ICs. Conclusions In many cases, the IC has served to protect the investigator or sponsor from complaints. Different ethical guidelines have sought to make the IC a more useful tool, with little success. Today’s IC is mainly a bureaucratic and legal process that fails to consider the patient’s point of view. In this context, the Guidelines for Tailoring the Informed Consent Process in Clinical Studies provide alternatives to the current IC process, focusing on the patient’s opinions and making them part of the process, thereby improving clinical research quality.