bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of genomic and phenomic prediction for application in apple breeding
Authors: Jung Michaela , Hodel Marius , Knauf Andrea , Kupper Daniela , Neuditschko Markus , Bühlmann-Schütz Simone , Studer Bruno , Patocchi Andrea , Broggini Giovanni AL
Published: January 2025

Background

Apple breeding schemes can be improved by using genomic prediction models to forecast the performance of breeding material. The predictive ability of these models depends on factors like trait genetic architecture, training set size, relatedness of the selected material to the training set, and the validation method used. Alternative genotyping methods such as RADseq and complementary data from near-infrared spectroscopy could help improve the cost-effectiveness of genomic prediction. However, the impact of these factors and alternative approaches on predictive ability beyond experimental populations still need to be investigated. In this study, we evaluated 137 prediction scenarios varying the described factors and alternative approaches, offering recommendations for implementing genomic selection in apple breeding.

Results

Our results show that extending the training set with germplasm related to the predicted breeding material can improve average predictive ability across eleven studied traits by up to 0.08. The study emphasizes the usefulness of leave-one-family-out cross-validation, reflecting the application of genomic prediction to a new family, although it reduced average predictive ability across traits by up to 0.24 compared to 10-fold cross-validation. Similar average predictive abilities across traits indicate that imputed RADseq data could be a suitable genotyping alternative to SNP array datasets. The best-performing scenario using near-infrared spectroscopy data for phenomic prediction showed a 0.35 decrease in average predictive ability across traits compared to conventional genomic prediction, suggesting that the tested phenomic prediction approach is impractical.

Conclusions

Extending the training set using germplasm related with the target breeding material is crucial to improve the predictive ability of genomic prediction in apple. RADseq is a viable alternative to SNP array genotyping, while phenomic prediction is impractical. These findings offer valuable guidance for applying genomic selection in apple breeding, ultimately leading to the development of breeding material with improved quality.
Framework for types of metainferences in mixed methods research
Authors: Younas Ahtisham , Fàbregues Sergi , Munce Sarah , Creswell John W
Published: January 2025

Background

The generation of metainferences is a core and significant feature of mixed methods research. In recent years, there has been some discussion in the literature about criteria for appraising the quality of metainferences, the processes for generating them, and the critical role that assessing the “fit” of quantitative and qualitative data and results plays in this generative process. However, little is known about the types of insights that emerge from generating metainferences. To address this gap, this paper conceptualize and present the types and forms of metainferences that can be generated in MMR studies for guiding future research projects.

Methods

A critical review of literature sources was conducted, including peer-reviewed articles, book chapters, and research reports. We performed a non-systematic literature search in the Scopus, Web of Science, Ovid, and Google Scholar databases using general phrases such as “inferences in research”, “metainferences in mixed methods”, “inferences in mixed methods research”, and “inference types”. Additional searches included key methodological journals, such as the Journal of Mixed Methods Research, International Journal of Multiple Research Approaches, Methodological Innovations, and the Sage Research Methods database, to locate books, chapters, and peer-reviewed articles that discussed inferences and metainferences.

Results

We propose two broad types of metainferences and five sub-types. The broad metainferences are global and specific, and the subtypes include relational, predictive, causal, comparative, and elaborative metainferences. Furthermore, we provide examples of each type of metainference from published mixed methods empirical studies.

Conclusions

This paper contributes to the field of mixed methods research by expanding the knowledge about metainferences and offering a practical framework of types of metainferences for mixed methods researchers and educators. The proposed framework offers an approach to identifying and recognizing types of metainferences in mixed methods research and serves as an opportunity for future discussion on the nature, insights, and characteristic features of metainferences within this methodology. By proposing a foundation for metainferences, our framework advances this critical area of mixed methods research.
A systemic review of the utility of antituberculosis therapy for presumed tuberculous uveitis
Authors: Taylor Jemma W. , Wright Ginevra E. L. , Lim Lyndell L. , Denholm Justin T.
Published: January 2025

Background

Uveitis presumed to be secondary to Mycobacterium tuberculosis is a rare but potentially blinding condition. Difficulty in making an accurate diagnosis and the low incidence of TB uveitis (TBU) contribute to the lack of evidence regarding the best management of this condition. This systematic review aims to analyse existing research to provide a summary of the literature regarding the utility of TB therapy for the management of TBU.

Methods

This systematic review was prospectively registered on PROSPERO (PROSPERO 2021 CRD42021273379). We searched Medline, Embase and Central databases, and the search was done on 20th June 2023 with an updated literature search.

Results

We included 55 studies and found that the heterogeneity in the methodology of these studies precluded metanalysis, and a narrative analysis was undertaken. Risk of bias analysis was undertaken using the Newcastle–Ottawa scale.

Conclusions

Key findings of this systematic review include multiple systemic biases in the available evidence, and general lack of control for confounding variables. This results in many unanswered questions regarding the utility of TB therapy for TBU and reinforces the need for more data in this area.
Increased aqueous humor levels of endothelin-1 in patients with open angle glaucoma
Authors: Hedberg-Buenz Adam , Boese Erin A. , Nyunt Angela W. , Sears Nathan C. , Pouw Andrew E. , Wang Kai , Fingert John H.
Published: January 2025

Background

Endothelin is a potent vasoconstrictor and contributes to the regulation of vascular perfusion. Aberrant endothelin-1 (ET-1) levels in aqueous humor have been reported across a variety of vascular diseases of the eye, including glaucoma. These findings suggest that dysregulation of ET-1 production may contribute to glaucoma pathophysiology. In this study, aqueous humor from patients undergoing ocular surgery was assayed for ET-1 abundance and related to the presence of glaucoma.

Patients

Open angle glaucoma patients (n=62 total) from the ophthalmology clinics of the University of Iowa Hospitals and Clinics were enrolled in this study and organized into three distinct cohorts based on their diagnostic criteria, including those with primary open angle glaucoma (POAG, n=25 patients), normal tension glaucoma (NTG, n=17 patients), exfoliation glaucoma (XFG, n=8 patients), and normal controls (n=12 patients).

Methods

Aqueous humor was collected intraoperatively from patients undergoing surgeries for glaucoma (including minimally invasive glaucoma surgeries, trabeculectomy, or glaucoma drainage device implantation) for samples in the glaucoma cohorts and cataract extraction for those in the control cohort. Aqueous humor was assayed by ELISA to measure and compare ET-1 abundance between the glaucoma cohorts and control cohort. ET-1 levels were also analyzed with linear regression to control for the covariates of age and sex.

Results

ET-1 was significantly elevated in the aqueous humor of patients in the POAG (mean ± SD: 7.8 ± 5.1 pg/mL; p = 0.002) and NTG cohorts (6.1 ± 3.0 pg/mL; p = 0.030) compared to the control (4.0 ± 1.9 pg/mL). No significant difference in aqueous ET-1 was detected in the XFG cohort (6.2 ± 4.5 pg/mL; p = 0.230) compared to the control. Significantly higher ET-1 levels were detected in a merged grouping of all glaucoma cohorts (POAG, NTG, XFG) relative to controls (p = 0.021). Analysis of covariance indicated neither age nor sex was associated with ET-1 level (p = 0.60 and p = 0.27), respectively. Controlling for age and sex had minimal influence on the comparison of ET-1 levels in the POAG versus control cohort (p = 0.018) and nominal influence on the comparisons between the NTG (p = 0.089) or XFG cohort (p = 0.15) relative to the control.

Conclusions

Elevated ET-1 in aqueous humor was associated with POAG and NTG compared to controls amongst cohorts of patients at the University of Iowa. These data suggest that dysregulation of vascular perfusion may have a role in the pathophysiology of POAG. The analyses of NTG and XFG samples were limited by the relatively small sample sizes.
The role of cyclooxygenase-2 (COX-2) and inflammatory markers in the progress of Alport syndrome in Egyptian children
Authors: Zaki Moushira , Orban Hisham A. , Shahba Mohamed A. , Moustafa Rehab S. I. , Adel Ahmed , Fadel Fatina I. , Selim Abeer , El-Bassyouni Hala T. , Youness Eman R.
Published: January 2025

Background

Chronic inflammation and its control are crucial to the responses of glomerular and renal tubular cells. This contributes to the pathogenic mechanisms and advancement of the disease in Alport syndrome. The study aimed to elucidate the role of cyclooxygenase-2, Interleukin 4, Plasminogen activating inhibitor 1, and Prostaglandin E2 in the development and course of Alport syndrome.

Methods

In our study inflammatory markers were evaluated in 26 Alport syndrome patients, 15 males and 11 females and 24 controls.

Results

Their age ranged from 4 to 16 years (mean ± SD was 8.50 ± 2.877) and 24 were normal controls matching age and sex. The serum levels of cyclooxygenase-2, Prostaglandin E2, Interleukin 4, and Plasminogen activating inhibitor 1 were evaluated in all patients. The serum level of cyclooxygenase-2, Prostaglandin E2, Interleukin 4, and Plasminogen activating inhibitor 1 were all increased significantly in the Alport syndrome patients compared to control (588.68 ± 73.08, 42.57 ± 4.18, 42.32 ± 3.49, and 846.47 ± 45.433, respectively versus controls (369.12 ± 50.28, 25.52 ± 4.98, 28.89 ± 3.19, and 312.79 ± 40.53 respectively).

Conclusion

The role of inflammatory markers cyclooxygenase-2, Prostaglandin E2, Interleukin 4, and Plasminogen activating inhibitor 1 in Alport syndrome that are causally connected and have a role in the development and course of Alport disease was delineated. This may highlight and speculate an innovative strategy for targeting the creation of safe and efficient anti-inflammatory treatments to inhibit disease progression in Alport syndrome.
Nurse management of minor problems in primary care emergencies: a non-randomized controlled trial
Authors: Estarlich-Corominas Jordi , Soler-Abril Neus , Casanellas-Chuecos Anna , Becerra-Corzo Sara , Bianco Andrea Sofia , Torán-Monserrat Pere , García-Sierra Rosa
Published: January 2025

Background

Health systems must implement strategies to adapt to the high demand in primary care caused by social changes. Since 2009, the Catalan Institute of Health has been expanding the Nurse Demand Management programme through which nursing autonomously addresses minor health problems. This study aims to analyse whether this programme is a factor in improving the efficiency and quality of care in a primary care emergency centre. The results come from a non-randomised controlled experimental study that tested the implementation of the programme applied to an experimental group treated by nurses versus a control group treated by doctors. The study was approved on 14 July 2022 by the Research Ethics Committee of the Jordi Gol University Institute following the guidelines of the TREND statement.

Results

A total of 312 patients were included in the study, all of whom came to the emergency centre with five types of minor problems. Exactly half (156) were seen by nurses and half were seen by doctors. The experimental group had an average waiting time of 15.1 min and the control group 33.25 min. There was no significant difference in the assessment of the quality of care received and there were no differences in the total number of consultations for the same problem. There were fewer prescriptions given out by nurses, with an average of 1.79 medicines per participant versus 2.26 medicines prescribed by doctors. The results of the study suggest that the Nurse Demand Management programme was a factor in improving the efficiency and in the emergency centre. Nurse resolution capacity, after applying algorithms, offered quality care, with fewer prescriptions and good patient satisfaction without increasing the total number of consultations due to the same problem.

Trial registration

The protocol for the current study was registered at Clinicaltrials.gov, with identification NCT06298240, retrospectively registered February 29, 2024.
In-home work environment for home care workers in Northern Sweden before and during the Covid-19 pandemic
Authors: Norström Fredrik , Bölenius Karin , Sahlén Klas-Göran , Zingmark Magnus , Pettersson-Strömbäck Anita
Published: January 2025

Background

The in-home work environment is the main work environment for home care workers, but it has only been sparsely studied. Our aim was to investigate the in-home work environment for home care workers by exploring challenges that arise regardless of a pandemic and by investigating Covid-19–specific challenges.

Methods

Two cross-sectional studies were conducted, one before (2017) and one during the pandemic (2021/2022) in three Swedish regions (Jämtland/Härjedalen, Västerbotten and Västernorrland), in which 1,154 (58%) out of 2,000 and 629 (33%) of 1,900 invited home care workers participated, respectively. Participants responded to a questionnaire asking about 10 problems associated with the in-home work environment as well as Covid-19–related challenges. Comparisons were conducted between regions and between study years using univariable analyses.

Results

Daily problems with the in-home work environment were common before the pandemic, and they increased statistically significantly during the pandemic for, among other things, non-ergonomic beds (29% vs. 37%), impractical bathrooms (40% vs. 50%), indoor smoking (24% vs. 31%), and pets (19% vs. 25%). There were major concerns about the risk of getting infected with Covid-19 for both staff (42%) and the home care recipients (50%). There were statistically significant differences between regions, e.g. many problems were more common in the Västerbotten region than in the other two regions during the pandemic, while challenges with protective equipment was most common in the Västernorrland region.

Conclusions

In-home work environment problems are common for home care workers and worsen in a more strained situation. Efforts are needed to strengthen the work environment for home care workers.
Social-structural barriers to primary care among sex workers: findings from a community-based cohort in Vancouver, Canada (2014–2021)
Authors: Harris Miriam T. H. , Shannon Kate , Krüsi Andrea , Zhou Haoxuan , Goldenberg Shira M.
Published: January 2025

Background

Due to social-structural marginalization, sex workers experience health inequities including a high prevalence of sexually transmitted and blood-borne infections, mental health disorders, trauma, and substance use, alongside a multitude of barriers to HIV and substance use services. Given limited evidence on sex workers’ broader primary healthcare access, we aimed to examine social-structural factors associated with primary care use among sex workers over 7 years.

Methods

Data were derived from An Evaluation of Sex Workers Health Access (AESHA), a community-based open prospective cohort of women (cis and trans) sex workers in Metro Vancouver, from 2014 to 2021. Descriptive statistics were used to summarize the proportion of primary care use in the past six months and to assess primary care trends over time from 2014–2021. We used multivariate logistic regression with generalized estimating equations (GEE) to identify social-structural factors associated with primary care access (seeing a family doctor in the last six months), after adjusting for confounders.

Results

Amongst the 646 participants, most (87.4%) accessed primary care at some point during the study period, and primary care use in the last 6 months was relatively stable (ranging from 60–78%) across each follow-up period. At first available observation, participants faced a high burden of sexually transmitted and blood-borne infections (STBBIs) (48.0%, 11.5%, and 10.4% were HCV, HIV, or STI seropositive, respectively), 56.8% were diagnosed with a mental health disorder, 8.1% had recently overdosed, and 14.7% were recently hospitalized. In multivariable GEE analysis, exposure to intimate partner violence was associated with reduced primary care use (Adjusted odds ratios (AOR) 0.63, 95% Confidence interval (CI): 0.49—0.82), and limited English fluency was marginally associated (AOR 0.76 CI: 0.51—1.14).

Conclusions

This study characterized primary care use and its social-structural determinants among sex workers over 7 years. Participants faced a high burden of STBBIs and other health disparities, and a proportion faced gaps in primary care utilization. Scale-up of trauma-informed, culturally and linguistically tailored, sex worker-friendly primary care models are needed, alongside structural interventions to decriminalize and destigmatize sex work and substance use.
Clinicopathological study and molecular subtyping of muscle-invasive bladder cancer (MIBC) using dual immunohistochemical (IHC) markers
Authors: Vaithegi R. , Pai Kanthilatha , Calicut Kini Rao Anuradha , Monappa Vidya , Prabhu Swathi , Suvarna Nischitha
Published: January 2025

Background

Muscle-invasive bladder carcinomas (MIBCs) exhibit significant heterogeneity, with diverse histopathological features associated with varied prognosis and therapeutic response. Although genomic profiling studies have identified several molecular subtypes of MIBC, two basic molecular subtypes are identified - luminal and basal, differing in biological behaviour and response to treatment. As molecular subtyping is complex, surrogate immunohistochemical (IHC) markers have been used to determine the molecular subtypes with good correlation to genomic profiling.

Methods

We analysed the clinicopathological features of 66 cases of MIBCs received over a 5-year study period. IHC expression was determined using GATA3 and CK5/6 to classify MIBC into luminal, basal and double-negative subtypes. The association between clinicopathologic variables and molecular subtypes were analysed using Chi-square test.

Results

The mean age at diagnosis of MIBC was 65.91 years with a male predominance. Based on IHC expression of GATA3 and CK5/6, MIBCs were classified into luminal, basal and double negative subtypes in 62.1%, 30.3% and 7.6% respectively. The luminal subtype occurred at an older age and showed predominantly conventional urothelial carcinoma with papillary morphology. Basal subtype occurred at earlier age, showed greater association with smoking and was more commonly associated with urothelial carcinoma with non -papillary morphology and exhibiting divergent differentiation as well as pure squamous cell carcinoma on histopathological examination. The double-negative subtype was found exclusively in males and exhibited a non-papillary morphology. Notably, all diagnosed neuroendocrine carcinomas were classified as double-negative type. While there was no statistically significant difference in tumour stage in cystectomy specimens between the molecular subtypes, lympho-vascular invasion and lymph node metastasis was more commonly associated with the basal type (p < 0.05) There was no significant difference in recurrence rates, metastasis and death between luminal and basal subtypes.

Conclusion

A simple two-antibody panel using GATA3 and CK5/6 could help in classifying MIBC into basic molecular subtypes of MIBC with distinctive histopathological features that can provide insights into the corresponding molecular subtype. Greater association of lymphovascular invasion and lymph nodal involvement in cystectomy specimens in basal type and distant metastasis in the double-negative subtype suggests a more aggressive clinical behaviour of these, necessitating more intensive treatment.
A simple new method to determine leaf specific heat capacity
Authors: Zhang Jiayu , Kaiser Elias , Zhang Hanyi , Marcelis Leo F. M. , Vialet-Chabrand Silvere
Published: January 2025

Background

Quantifying plant transpiration via thermal imaging is desirable for applications in agriculture, plant breeding, and plant science. However, thermal imaging under natural non-steady state conditions is currently limited by the difficulty of quantifying thermal properties of leaves, especially specific heat capacity (Cp). Existing literature offers only rough estimates of Cp and lacks simple and accurate methods to determine it.

Results

We developed a non-invasive method to quantify k (the product of leaf thickness (lt), leaf density(ρ), and Cp), by fitting a leaf energy balance model to a leaf temperature (Tleaf) transient during and after a ~ 10 s light pulse. Cp was then estimated by dividing k by lt*ρ. Using this method, we quantified Cp for 13 horticultural and tropical plant species, and explored the relationship between Cp and leaf water content, specific leaf area and Tleaf response rate during the light pulse. Values of Cp ranged between 3200–4000 J kg−1 K−1, and were positively correlated with leaf water content. In species with very thick leaves, such as Phalaenopsis amabilis, we found leaf thickness to be a major factor in the temperature response to a short light pulse.

Conclusions

Our method allows for easy determination of leaf Cp of different species, and may help pave the way to apply more accurate thermal imaging under natural non-steady state conditions.
Cinnamic acid alleviates endothelial dysfunction and oxidative stress by targeting PPARδ in obesity and diabetes
Authors: Bai Yizhen , Tan Dechao , Deng Qiaowen , Miao Lingchao , Wang Yuehan , Zhou Yan , Yang Yifan , Wang Shengpeng , Vong Chi Teng , Cheang Wai San
Published: January 2025

Objective

Cinnamic acid (CA) is a bioactive compound isolated from cinnamon. It has been demonstrated to ameliorate inflammation and metabolic diseases, which are associated with endothelial dysfunction. This study was aimed to study the potential protective effects of CA against diabetes-associated endothelial dysfunction and its underlying mechanisms.

Methods

High-fat diet (HFD) with 60 kcal% fat was used to induce obesity/diabetes in C57BL/6 mice for 12 weeks. These diet-induced obese (DIO) mice were orally administered with CA at 20 or 40 mg/kg/day, pioglitazone (PIO) at 20 mg/kg/day or same volume of vehicle during the last 4 weeks. Isolated mouse aortic segments and primary culture rat aortic endothelial cells (RAECs) were induced with high glucose (HG) to mimic hyperglycemia and co-treated with different concentrations of CA.

Results

In DIO mice, four-week administration of CA, particularly at 40 mg/kg/day, diminished the body weights, blood pressure, fasting blood glucose and plasma lipid levels, and ameliorated endothelium-dependent relaxations (EDRs) and oxidative stress in aortas. The beneficial effects of CA were comparable to the positive control group, PIO. Western blotting results indicated that CA treatment upregulated the expression of peroxisome proliferator-activated receptor delta (PPARδ), and activated nuclear factor erythroid 2-related factor 2 (Nrf2)/ heme oxygenase-1 (HO-1) and AMP-activated protein kinase (AMPK)/ protein kinase B (Akt)/ endothelial nitric oxide synthase (eNOS) signaling pathways in mouse aortas in vivo and ex vivo. HG stimulation impaired EDRs in mouse aortas and inhibited nitric oxide (NO) production but elevated reactive oxygen species (ROS) levels in RAECs. CA reversed these impairments. Importantly, PPARδ antagonist GSK0660 abolished the vasoprotective effects of CA. Molecular docking analysis suggested a high likelihood of mutual binding between CA and PPARδ.

Conclusion

CA protects against endothelial dysfunction and oxidative stress in diabetes and obesity by targeting PPARδ through Nrf2/HO-1 and Akt/eNOS signaling pathways.
What contributes to consumer price inflation? A novel decomposition framework with an application to Austria
Authors: Schneider Martin
Published: January 2025

This paper introduces a novel approach to decomposing consumer price inflation. Expanding upon the established decomposition method for the value-added deflator, our methodology combines the cost structure of the consumption expenditures from the input–output table with quarterly national accounts data. This enables a detailed breakdown of HICP inflation, including imports. Applying this method to Austria from Q1 2019 to Q1 2023, we identify energy and non-energy imports as major contributors to inflation in 2022. Profits began contributing to inflation from H2 2022, while wage pressures remained minimal. The results of the analysis show that the decomposition can provide valuable insights for the conduct of monetary policy.
Treatment of peri-implant mucositis using an Er:YAG laser or an ultrasonic device: a randomized, controlled clinical trial
Authors: Bengtsson Viveca Wallin , Aoki Akira , Mizutani Koji , Lindahl Christel , Renvert Stefan
Published: January 2025

Purpose

The study assessed the clinical outcomes following treatment of peri-implant mucositis using Er:YAG laser or an ultrasonic device over six months. Patients' experience of pain, aesthetics, and Quality of life were further assessed.

Methods

One dental implant, per included patient, diagnosed with peri-implant mucositis underwent treatment with an Er:YAG laser (test) or an ultrasonic scaler (control) randomly. Treatments were performed at baseline and months three and six. At each session, oral hygiene was instructed after plaque registration, and the patient was guided in proper cleaning technique using a toothbrush and interproximal aids as needed. Full mouth bleeding on probing (FMBoP), full mouth plaque score (FMPS), implant bleeding on probing (BoP), implant mean graded bleeding (mBI), implant probing pocket depts (PPD), implant suppuration and bone levels were assessed. Oral health-related Quality of life (OHQoL) and visual analog scales (VAS), which reflect aesthetic satisfaction and pain of the treatment, were also evaluated.

Results

Forty-six patients were included. FMBoP was significantly reduced from 30.1 to 21.5% (test) (p < 0.001) respectively from 35.0% to 30% (control) (p < 0.01). FMPS showed significant reduction from 61.5 to 32.7% (test) (p < 0.001) and from 58.7 to 39.1% (control) (p < 0.001). At the implant BoP reduced from 89.0 to 55.7% (test) (p < 0.001) respectively from 94.9 to 63.7% (control) (p < 0.001). mBI was reduced from 1.3 to 0.6 (test) (p < 0.01) and from 1.9 to 0.8 (control) (p < 0.001). Distribution of “no bleeding” increased from 13 to 61% (test) (p < 0.05) and from 0 to 35% (control) (p < 0.05). At month three, statistically significant intergroup differences were shown for PPD ≥ 4 mm with 43.5% (test) respectively 73.9% (control) (p < 0.05). At month six, statistically significant intergroup differences, were shown for FMBoP 21.5% (test) respectively 30% (control) (p < 0.05) and for plaque score at the implant 4.0% (test) respectively 26% (control) (p < 0.05). Less pain was reported in the laser group at three days 0.08 (test) respectively 0.2 (control) (p < 0.05).

Conclusions

Treatment of peri-implant mucositis was effective regardless of whether the treatment was performed with an Er:YAG laser or an ultrasonic scaler. Fewer diseased sites were diagnosed at six months following laser treatment.

Trial registration: Registered at www.clinicaltrials.gov: study no, NCT05772299.
Causal association among smoking, bitter beverage consumption, and risk of osteoporosis: a two-sample mendelian randomization-based study
Authors: Wu Yanqian , Chao Jianqian , Bao Min , Zhang Na , Wang Leixia
Published: January 2025

Objectives

Two-sample MR methods were employed to analyze the impact of smoking and bitter beverage consumption on the risk of osteoporosis and osteoporosis with pathological fractures, in order to assess the causal association.

Methods

Publicly available genome-wide association study summary data were analyzed using MR methods. The exposures investigated were smoking (smoking per day, smoking initiation, and lifetime smoking index) and bitter beverages (coffee, tea, bitter alcoholic beverages, bitter non-alcoholic beverages, and total bitter beverages). The outcomes examined were the risk of osteoporosis and osteoporosis with pathological fractures. The inverse-variance weighted (IVW) method was used as the main statistical model. The stability and reliability of the results were verified by the Cochran’s Q test, the Egger-intercept test, and the leave-one-out analysis.

Results

Smoking per day was causally associated with the risk of osteoporosis OR = 1.417, 95% CI = 1.119–1.794, P = 0.003), and lifetime smoking index had a possible genetic causal association with the risk of osteoporosis with pathological fractures (OR = 4.187, 95% CI = 1.909–9.184, P < 0.001). No genetic causal association was found between smoking initiation or lifetime smoking index and the risk of osteoporosis (P > 0.05). No genetic causal association was identified between smoking per day or smoking initiation and the risk of osteoporosis with pathological fractures (P > 0.05). Total and bitter non-alcoholic beverage consumption showed a potential effect on the risk of osteoporosis (OR = 3.687, 95% CI = 1.535–8.858, P = 0.003 and OR = 3.040, 95% CI = 1.466–6.304, P = 0.002, respectively).

Conclusions

This study found smoking raises the risk of osteoporosis and osteoporosis with pathological fractures based on genetics. Certain bitter beverages are linked to an increased osteoporosis risk.
Utility of the C-Peptide/Insulin Molar Ratio for Distinguishing Type A Insulin Resistance Syndrome From Type 2 Diabetes
Authors: Nishikage Seiji , Hirota Yushi , Takayoshi Tomofumi , Yoshimura Kai , Takeuchi Takehito , Hamaguchi Tetsushi , Ueda Mariko , Yamamoto Akane , Sakaguchi Kazuhiko , Ogawa Wataru
Published: January 2025

Objective

Type A insulin resistance syndrome (IRS), characterized by impaired insulin receptor function due to variants of the insulin receptor gene, manifests as severe insulin-resistant diabetes. Differentiation of type A IRS from type 2 diabetes on the basis of hyperinsulinemia can be challenging. Given the association between insulin receptor dysfunction and reduced insulin clearance, we evaluated the potential of the circulating C-peptide reactivity (CPR)/immunoreactive insulin (IRI) molar ratio, a marker of insulin clearance, for distinguishing type A IRS from type 2 diabetes.

Methods

We retrospectively analyzed CPR and IRI levels measured during a 75-g oral glucose tolerance test (OGTT) in 18 individuals with type A IRS and 126 with type 2 diabetes. Receiver operating characteristic (ROC) curve analysis was performed to determine the diagnostic performance of the CPR/IRI molar ratio and IRI levels.

Results

IRI levels were significantly higher and the CPR/IRI molar ratio significantly lower in individuals with type A IRS compared with those with type 2 diabetes. The area under the ROC curve for the CPR/IRI molar ratio at baseline, 1 hour, and 2 hours after OGTT initiation was 0.997 (sensitivity 100%, specificity 99.2%), 0.999 (sensitivity 100%, specificity 97.6%), and 0.997 (sensitivity 100%, specificity 95.1%), respectively. The CPR/IRI molar ratio demonstrated robust diagnostic performance regardless of body mass index or hyperinsulinemia severity.

Conclusion

The CPR/IRI molar ratio, both at baseline and during OGTT, exhibited higher sensitivity and specificity than IRI levels alone for distinguishing type A IRS from type 2 diabetes. This ratio may serve as a reliable clinical marker for early and accurate diagnosis of type A IRS.
Acute Myocardial Infarction With Nonobstructive Coronary Arteries Across Endocrine Disorders: A Case Series
Authors: Roy Ayan , Patel Deepika , Merugu Chandhana , Kamalanathan Sadishkumar , Sahoo Jayaprakash , Naik Dukhabandhu
Published: January 2025

The endocrine and cardiology interface is particularly interesting and important. This is a case series of 3 endocrine diseases presenting with acute myocardial infarction without obstructive coronary arterial diseases (MINOCA). The diagnosis was Cushing’s disease due to pituitary microadenoma, adrenal pheochromocytoma, and primary hyperaldosteronism due to unilateral adrenal hyperplasia. All patients were managed conservatively and improved considerably following the management of underlying endocrine and cardiovascular diseases. A spectrum of classical endocrine diseases can present with MINOCA, and the underlying diagnosis is often overlooked. Patients without traditional risk factors for MINOCA should undergo hormonal workup to reveal the underlying diagnosis.
The Ironies of National Allegory
Authors: Chandra Paresh
Published: January 2025

This article conceptualizes the relationship between the transitional aspect of third-world nationhood and its allegorical aspect. It argues that to say that the moment of national self-determinations is “transitional” is not to say that it is a necessary “stage” in the path to proletariat self-determination. Rather, “transition” designates a present nonidentical with itself, in which an undetermined contest for hegemony determines the politics of an anti-colonial movement. Given this nonidentity of such a movement with itself, its every document must be treated allegorically, that is, as necessarily contesting any totalizing representation of the movement as a “national” movement. This article takes as its occasion Fredric Jameson's controversial argument that all third-world texts project a “political dimension,” by rendering individual stories as “national allegories.” The author shows that the persistently undialectical dimension of Jameson's argument, which amounts to a “stagist” reduction of the aforesaid transitional aspect of nationhood, springs from his refusal to see how these very third-world texts invariably also flip the national-allegorical script by treating—as proposed above—the nation as allegory: as an inadequate form of appearance for diverse struggles for self-determination that needs to be read not with but against its own grain.
The Anthropocene Interregnum: Ecological Marxism and the Social Metabolism of the Present
Authors: Haines Christian
Published: January 2025

This essay argues for an understanding of the Anthropocene as both historical impasse and historical transition. It is an impasse insofar as there is a conceptual and practical gap between human history and planetary history, or politics and ecology. It is a transition insofar as it marks the passage from one geological epoch to another and from one dominant social formation (capitalism) and the possibility of another. The author makes the case that ecopoetry and ecological Marxism operate a dialectical reversal from historical impasse to transition by mediating between ecology and politics. The author reads a poem by Stephanie Burt, “Advice from Rock Creek Park,” as an instrument for sensing and conceptualizing the present as a complex coordination of contradictory social and ecological temporalities. The author then looks to ecological Marxism for how it historicizes capitalism as a transformation of human and nonhuman natures. Marxism and Karl Marx's writing contain insightful meditations on the historical realities of the human species, the social production of subsistence, and the metabolism between society and nature. Marxism offers a rich conceptual apparatus for historicizing the climate crisis as the transition to a new epoch—one that may yet hold a place for human civilization.
The Taviefe Massacre, 1888: Violence and Colonial Rule in British Ghana
Authors: Balakrishnan Sarah
Published: January 2025

Between June 18 and 24, 1888, the British colonial government of the Gold Coast killed an estimated eight hundred people on the small borderland town of Taviefe. This essay studies the massacre at Taviefe as a central event in the colonization of the Gold Coast. Although Taviefe existed on the margins of the colony—and in fact, it would soon be consigned to German rule—the massacre shocked Gold Coast communities everywhere, signaling that European rule had fundamentally changed. The concept of interregnum is studied as an analytical framework for colonization. This essay argues that the Taviefe Massacre initiated a period of interregnum on the Gold Coast, plunging communities into a state of morbid suspense, the old political order having clearly been abandoned but the new regime not yet established. Furthermore, the essay suggests that the reason the Taviefe Massacre has remained absent from histories of the Gold Coast and Ghana is because it occurred during this liminal period of transition, belonging neither fully to the precolonial nor colonial eras.
Pedagogy of Power
Authors: Rydel Courtney E.
Published: January 2025

Students in a first-year seminar gained a deeper understanding of Arthurian literature and its modern adaptations by studying the 2018 animated series She-Ra and the Princesses of Power in conversation with Chrétien de Troyes's twelfth-century story Perceval. She-Ra and Perceval share many motifs, symbols, and character elements due to their common heritage in medieval romance. Students analyzed how the inclusive, diverse She-Ra recuperates the themes of the Grail story from Perceval and extended its tradition of coming-of-age stories, which provides strategies for other teachers to use in bringing together historically and generically disparate texts. Studying She-Ra in the context of medieval literature enabled my students to deepen their understanding of both works and to think critically about how modern media transforms and transmits the stories and ideologies of the past.
Rites of Passage in the Atlanta Forest
Authors: Tycko Sasha
Published: January 2025

Through a combination of photography and text, this essay considers the activist occupation of the Atlanta Forest and the conflict over the city's plan to build a police training center known as Cop City in light of classical anthropological thought on rites of passage and liminal phenomena. It draws from nearly two years of ethnographic fieldwork and photography exploring time, memory, and history in the occupied forest between 2021 and 2023. Photography is here used to present, rather than represent, the forest as a liminal phenomenon, where norms are suspended and distinctions between city and nature, past and present, and politics and ecology blur.
Cdkn1c orchestrates a molecular network that regulates euploidy of male mouse germline stem cells
Authors: Kanatsu-Shinohara Mito , Yamamoto Takuya , Liu Tianjiao , Nakayama Keiichi I. , Shinohara Takashi
Published: January 2025

Karyotype instability in the germline leads to infertility. Unlike the female germline, the male germline continuously produces fertile sperm throughout life. Here, we present a molecular network responsible for maintaining karyotype stability in the male mouse germline. Loss of the cyclin-dependent kinase inhibitor Cdkn1c in undifferentiated spermatogonia induced degeneration of spermatogenesis prior to entry into the differentiating spermatogonia stage. In vitro analysis of mouse spermatogonial stem cells revealed that CDKN1C localized to spindle microtubules during metaphase, and that disrupted microtubule dynamics increased its phosphorylation. Cdkn1c deficiency activated the spindle assembly checkpoint and led to centrosome amplification, premature chromosome segregation, and loss of AURKB, and ultimately TRP53-dependent apoptosis. Trp53-deficient spermatogonial stem cells exhibited karyotype defects, but proliferated normally despite reduced CDKN1C and AURKB expression. In contrast, Aurkb depletion upregulated TRP53 and CDKN1C, suggesting a negative feedback loop to maintain euploidy. Thus, Cdkn1c regulates the male germline karyotype.
Patient-derived xenograft models of gastrointestinal stromal tumors provide a ready-to-use platform for translational research
Authors: Sutter Luna De , De Cock Lore , Wang Chao-Chi , Gorgels Daniël , Wyns Karo , Verbeeck Kimberly , Vanleeuw Ulla , Douchy Thomas , Hompes Daphne , Jaekers Joris , Van Raemdonck Dirk , Vanden Bempt Isabelle , Debiec-Rychter Maria , Sciot Raf , Wozniak Agnieszka , Schöffski Patrick
Published: January 2025

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal malignancy of the gastrointestinal tract. Most GISTs harbor mutations in oncogenes, such as KIT, and are treated with tyrosine kinase inhibitors (TKIs), such as imatinib. Most tumors develop secondary mutations, inducing drug resistance against the available TKIs, requiring novel therapies. We established a GIST patient-derived xenograft (PDX) platform of GIST that can be used for preclinical drug testing. Tumor tissue from consenting GIST patients was transplanted subcutaneously to NMRI nu/nu mice. Once tumor growth was observed, the tumor was re-transplanted to a next generation of mice. Tumors were characterized histopathologically and molecularly at every re-transplantation and compared with the original patient tumor. We transplanted 112 tumor samples from 99 GIST patients, resulting in 12 established and well-characterized GIST models with different mutations and TKI sensitivity. Three models harbor secondary KIT mutations. One model is characterized by a primary, imatinib-resistant PDGFRA exon 18 p.D842V mutation. Our established platform of well-characterized GIST PDX models, covering the most relevant driver mutations, serves as an excellent tool for preclinical drug testing and tumor biology studies.
Impact of non-alcoholic fatty liver disease and liver fibrosis on outcomes of acute ischemic stroke: A systematic review and meta-analysis
Authors: Yang Liting , Han Jian , Qin Chenghui , Song Feifeng
Published: January 2025

Objective: We reviewed the evidence on the impact of non-alcoholic fatty liver disease (NAFLD) and liver fibrosis on mortality, functional dependence, and recurrence after acute ischemic stroke (AIS).
Methods: This PROSPERO registered review searched PubMed, Embase, CENTRAL, and Web of Science databases from inception of databases to 30th July 2023 for studies comparing outcomes of AIS based on the presence of NAFLD and liver fibrosis. Adjusted data on mortality, functional dependence and risk of recurrent AIS was pooled to obtain odds ratio (OR) with 95% confidence intervals (CI) in a random-effects model
Results: Ten studies were included. Descriptive analysis showed conflicting effects of NAFLD on AIS outcomes with some studies showing better functional outcomes with the presence of NAFLD. Meta-analysis showed that the presence of liver fibrosis was associated with a significantly increased risk of mortality (OR: 2.22 95% CI: 1.02–4.86 I2=92%) and functional dependence (OR: 1.89 95% CI: 1.27–2.82 I2=53%) as compared to no fibrosis. Meta-analysis found that liver fibrosis did not increase the risk of recurrent AIS (OR: 1.32 95% CI: 0.74–2.37 I2=74%).
Conclusion: Scant evidence exists for the effect of NAFLD and liver fibrosis on AIS outcomes. A paradoxical effect of NAFLD on functional outcomes has been noted which needs confirmation by future studies. Liver fibrosis was found to increase the risk of mortality and functional dependence in AIS.
doi: https://doi.org/10.12669/pjms.41.2.10729
How to cite this: Yang L, Han J, Qin C, Song F. Impact of non-alcoholic fatty liver disease and liver fibrosis on outcomes of acute ischemic stroke: A systematic review and meta-analysis. Pak J Med Sci. 2025;41(2):630-636. doi: https://doi.org/10.12669/pjms.41.2.10729
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Correlation of shear wave elastography with liver biopsy in children with Chronic Liver disease
Authors: Imtiaz Mehwish , Khaqan Muhammad Umer , Mazhar Maryam , Seerat Iqtadar
Published: January 2025

Background & Objectives: Liver biopsy remains the gold standard for assessment of liver fibrosis; however, it is limited practically because of issues of sampling errors and invasiveness. This opens the way for other important non-invasive processes of diagnosis including the role and utilisation of Shear Wave Elastography in coming years for liver diseases. This post-hoc study will firstly aim to establish the correlation existing between the currently preferred gold standard liver biopsy and 2D-Shear Wave elastography’s diagnostic accuracy in paediatric patients presenting with suspected or confirmed liver disease.
Methods: This retrospective study was conducted in Pakistan Kidney and Liver Institute and Research Center in Lahore, Pakistan from August 2017 to January 2024. In this analysis, 37 Paediatric patients with various liver diseases who underwent liver biopsy for autoimmune hepatitis, Budd-Chiari syndrome, Wilson disease and other liver-related pathologies were included.
Results:  Thirty-seven patients with a mean age of 10 years (ranging from 4–14 years) were enrolled. According to this study, sixteen out of thirty seven (43%) cases of chronic liver disease were caused by autoimmune hepatitis. Patients’ average liver stiffness as determined by SWE was 12.14 ± 0.75 kPa. According to elastography, the average liver stiffness in individuals with F0–F1 fibrosis was 6 ± 0.01 kPa, 7.67 ± 0.29 in stage F2, 8.62 ± 0.20 in stage F3, and 14.05 ± 3.69 kPa in stage F4. We discovered that the mean level of hepatic stiffness varied significantly depending on the degree of fibrosis (p = 0.0001).
Conclusion: SWE gauges the liver tissue’s stiffness, which rises with fibrosis severity. Research has demonstrated that SWE, which is frequently equivalent to liver biopsy, has a high degree of accuracy in identifying and staging hepatic fibrosis.
doi: https://doi.org/10.12669/pjms.41.2.9886
How to cite this: Imtiaz M, Khaqan MU, Mazhar M, Seerat I. Correlation of shear wave elastography with liver biopsy in children with Chronic Liver disease. Pak J Med Sci. 2025;41(2):585-589. doi: https://doi.org/10.12669/pjms.41.2.9886
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.