bluuebunny/crossref_metadata_2025 huggingface dataset:
FTO inhibition mitigates high-fat diet-induced metabolic disturbances and cognitive decline in SAMP8 mice
Authors: Irisarri Alba , Corral Ana , Perez-Salvador Núria , Bellver-Sanchis Aina , Ribalta-Vilella Marta , Bentanachs Roger , Alegret Marta , Laguna Juan Carlos , Barroso Emma , Palomer Xavier , Ortuño-Sahagún Daniel , Vázquez-Carrera Manuel , Pallàs Mercè , Herrero Laura , Griñán-Ferré Christian
Published: February 2025

This study investigated the effects of fat mass and obesity-associated (FTO) inhibition on cognitive function and metabolic parameters of senescence-accelerated mouse prone 8 (SAMP8) mice fed a high-fat diet (HFD). SAMP8 mice fed an HFD exhibited increased body weight, impaired glucose tolerance, and elevated serum leptin levels. In epididymal white adipose tissue (eWAT), pharmacological treatment with FB23, a well-established FTO inhibitor, increased leptin production and modulated genes involved in lipid metabolism (Cpt1a, Atgl
,
Hsl
,
Fas), oxidative stress (OS) (Bip
,
Edem), and inflammation (Mcp1, Tnfα). Expression of hepatic genes related to lipid metabolism (Cpt1a, Atgl
,
Mgl, Dgat2, Srebp
,
Plin2) and OS (catalase, Edem) were modulated by FB23, although hepatic steatosis remained unchanged. Remarkably, FB23 treatment increased m6A RNA methylation in the brain, accompanied by changes in N6-methyladenosine (m6A)-regulatory enzymes and modulation of neuroinflammatory markers (Il6, Mcp1, iNOS). FTO inhibition reduced the activity of matrix metalloproteases (Mmp2, Mmp9) and altered IGF1 signaling (Igf1, Pten). Notably, enhanced leptin signaling was observed through increased expression of immediate early genes (Arc, Fos) and the transcription factor Stat3. Improved synaptic plasticity was evident, as shown by increased levels of neurotrophic factors (Bdnf
,
Ngf) and restored neurite length and spine density. Consistent with these findings, behavioral tests demonstrated that FB23 treatment effectively rescued cognitive impairments in SAMP8 HFD mice. The novel object recognition test (NORT) and object location test (OLT) revealed that treated mice exhibited enhanced short- and long-term memory and spatial memory compared to the HFD control group. Additionally, the open field test showed a reduction in anxiety-like behavior after treatment with FB23. In conclusion, pharmacological FTO inhibition ameliorated HFD-induced metabolic disturbances and cognitive decline in SAMP8 mice. These results suggest that targeting FTO may be a promising therapeutic approach to counteract obesity-induced cognitive impairment and age-related neurodegeneration.
Validation of loci and genes associated with fertility in Holstein cows using gene-set enrichment analysis-SNP and genotype-by-sequencing
Authors: Kiser Jennifer N. , Seabury Christopher M. , Neupane Mahesh , Moraes Joao G. N. , Herrick Allison L. , Dalton Joseph , Burns Gregory W. , Spencer Thomas E. , Neibergs Holly L.
Published: February 2025

Background

The financial strain fertility issues cause the dairy cattle industry is substantial, with over $7 billion in lost revenue accrued annually due to a relatively low cow conception rate (CCR; 30–43%) for US dairy cows. While CCR has been improving through genomic selection, identification of causal mutations would help improve the rate of genetic progress with genomic selection and provide a better understanding of infertility. The objectives of this study were to: (1) identify genes and gene-sets associated with CCR to the first breeding (CCR1) and the number of breedings required to conceive (TBRD) in Holstein cows and (2) identify putative functional variants associated with CCR1 and TBRD through a custom genotype-by-sequencing array. The study consisted of 1,032 cows (494 pregnant to first breeding, 472 pregnant to subsequent [2–20] services, and 66 that never conceived). Cows were artificially inseminated, and pregnancy was determined 35d later by rectal palpation of uterine contents. Gene-set enrichment analyses with SNP data (GSEA-SNP) were conducted for CCR1 and TBRD with a normalized enrichment score (NES) ≥ 3.0 required for significance. Leading edge genes (LEG) and positional candidate genes from this and 26 additional studies were used to validate 100 loci associated (P < 1 × 10− 5) with cow fertility using a custom sequencing genotyping array of putative functional variants (exons, promoters, splice sites, and conserved regions).

Results

GSEA-SNP identified 95 gene-sets (1,473 LEG) enriched for CCR1 and 67 gene sets enriched (1,438 LEG) for TBRD (NES ≥ 3). Thirty-four gene-sets were shared between CCR1 and TBRD along with 788 LEG. The association analysis for TBRD identified three loci: BTA1 at 83 Mb, BTA1 at 145 Mb, and BTA 20 at 46 Mb (P < 1 × 10− 5). The loci associated with TBRD contained candidate genes with functions relating to implantation and uterine receptivity. No loci were associated with CCR1, however a single locus on BTA1 at 146 Mb trended toward significance with an FDR of 0.04.

Conclusions

The validation of three loci associated with CCR and TBRD in Holsteins can be used to improve fertility through genomic selection and provide insight into understanding infertility.
Comprehensive implementations of multiple imputation using retrieved dropouts for continuous endpoints
Authors: Wang Shuai , Schwartz Pamela F. , Mancuso James P.
Published: February 2025

Background

In the metabolic disease area, there has been a long-time debate against using mixed models for repeated measures (MMRM) as the primary analysis of longitudinal continuous endpoints. As missing data arising from missing not at random assumptions are not addressed in MMRM, multiple imputation based on specific assumptions has been brought into play. Among many missing not at random assumptions with varying degrees of conservativeness, multiple imputation based on retrieved dropouts (MIRD) has been accepted by regulatory agencies in several type 2 diabetes and chronic weight management products in recent years, marking the beginning of a new standard for analysis of longitudinal data in this disease area.

Methods

On top of the established MIRD approach of which the imputation is based on last on-treatment data of retrieved dropout (RD)s, we propose a new class of MIRD approaches utilizing all available data from RDs. The imputation implementation can be one-step Markov Chain Monte Carlo (MCMC) or two-step (creating monotone missingness, followed by regression approach). ANCOVA can be applied to the complete dataset post imputation and Rubin’s rule can be used to combine all estimates into a single estimate. Simulation studies in a wide range of scenarios are conducted to understand the type-I error and power rates of the new class versus the established MIRD approach and other reference statistical methods such as MMRM.

Results

Overall, the new class has very similar performance compared to the established MIRD approach based on last on-treatment data. What’s more interesting is the one-step MCMC approach has better controlled type-I error and is more powerful than the established MIRD approach in certain scenarios with the difference gradually diminishing with larger sample size. The data analyses based on two real phase 3 datasets further manifest the power conclusions, with the results based on the new class applied to the larger of the two datasets almost identical to that of on-study MMRM.

Conclusions

We have presented comprehensive implementations of the MIRD approach for continuous endpoints in a longitudinal setting that fully fit within the strategy of treatment policy. The proposed new class based on all observed data of RDs is proved to be as powerful as the established MIRD approach based on last on-treatment visit in most scenarios. The one-step MCMC approach is more powerful than the established MIRD approach in certain scenarios. Since the new class involves less programming derivation of additional flags, it’s anticipated to be more easily implemented in clinical trial reporting.
Treating neuromuscular diseases: unveiling gene therapy breakthroughs and pioneering future applications
Authors: Wu Yu-Fu , Chen Jun-An , Jong Yuh-Jyh
Published: February 2025

In this review, we highlight recent advancements in adeno-associated virus (AAV)-based gene therapy for genetic neuromuscular diseases (NMDs), focusing on spinal muscular atrophy (SMA) and Duchenne muscular dystrophy (DMD). We discuss the current FDA-approved gene therapies for NMDs and provide updates on preclinical studies that demonstrate the potential of various AAV-based gene therapies to reduce SMA severity and serve as effective treatments for DMD. Additionally, we explore the transformative impact of CRISPR/Cas9 technology on the future of gene therapy for NMDs. Despite these encouraging developments, further research is required to identify robust biomarkers that can guide treatment decisions and predict outcomes. Overall, these pioneering advancements in AAV-based gene therapy lay the groundwork for future efforts aimed at curing genetic NMDs and offer a roadmap for developing gene therapies for other neurodegenerative diseases.
Deficiency in nucleoside diphosphate kinase B leads to endothelial activation of the hexosamine biosynthesis pathway and cardiac dysfunction
Authors: Shao Feng , Wieland Johanna , Wang Yixin , Keles Merve , Meng Zenghui , Lomada Santosh , Qin Miao , Leiss Veronika , Martin-Garrido Abel , Fuhrmann Manuela , Qiu Yi , Felix Trogisch , Vettel Christiane , Heineke Joerg , Feng Yuxi
Published: February 2025

Background

Nucleoside diphosphate kinase B (NDPKB) deficiency in endothelial cells (ECs) promotes the activation of the hexosamine biosynthesis pathway (HBP), leading to vascular damage in the retina. The aim of this study was to investigate the consequences of NDPKB deficiency in the mouse heart.

Methods

NDPKB deficient mice were used in the study. Echocardiography was employed to assess cardiac function in vivo. Characterization of contractility in hiPSC-derived cardiomyocytes (hiPSC-CMs) was measured with the IonOptix contractility system. Immunoblotting and immunofluorescence were carried out to analyze the expression and localization of proteins in cultured cells and left ventricles (LVs).

Results

NDPKB deficient mice displayed impaired glucose tolerance and increased heart weight compared to controls. Echocardiographic analysis revealed an increase in the diastolic diameter of the left ventricular posterior wall (LVPW), a decrease in the early diastolic mitral valve E and E′ wave, and in the ratios of E/A and E′/A′ in NDPKB deficient hearts, suggesting cardiac hypertrophy and diastolic dysfunction. In line with cardiac dysfunction, the phosphorylation of myocardial phospholamban (PLN) and the expression of sarcoplasmic/endoplasmic reticulum Ca2+-ATPase 2 (SERCA2) in the NDPKB deficient LVs were significantly reduced. Moreover, the accumulation of collagen, fibronectin as well as the upregulation of transforming growth factor β (TGF-β), were detected in NDPKB deficient LVs. In addition, activation of the HBP and its downstream O-GlcNAc cycle was observed in the LVs and cardiac ECs (CECs) isolated from the NDPKB−/− mice. Furthermore, a bipolar O-GlcNAc regulation was identified in CMs. O-GlcNAc was decreased in NDPKB-depleted CMs, while conditioned medium from NDPKB-depleted ECs significantly increased O-GlcNAc levels, along with contractile and relaxation dysfunction of the hiPSC-CMs, which was attenuated by inhibiting endothelial HBP activation.

Conclusions

Deficiency in NDPKB leads to endothelial activation of the HBP and cardiac dysfunction. Our findings may highlight the crucial role of proper endothelial HBP in maintaining cardiovascular homeostasis.
Post-traumatic growth and influencing factors of parents with children with Duchenne muscular dystrophy: a cross-sectional survey study
Authors: Xu Li , Liu Meili , Chen Yuewei , Wu Liwen , Gan Siyi , Xie Jianhui , Latour Jos M.
Published: February 2025

Background

The aim of the study was to identify the post-traumatic growth status and influencing factors of parents with children with Duchenne muscular dystrophy (DMD).

Methods

We adopted a cross-section survey study. Between February and December 2022, 181 parents responded to the survey including a participants’ characteristics section, post-traumatic growth assessment scale, caregiver burden scale, and social support assessment scale. Multiple linear regression analysis was used to investigate influencing factors of post-traumatic growth.

Results

The mean score of post-traumatic growth of parents was 56.66 (SD ± 18.67). Post-traumatic growth was positively correlated with social support (r = 0.452, P < 0.01) and negatively correlated with care burden (r = -0.207, P < 0.01). Multiple linear regression showed that the child’s age, course of disease, self-care ability, parent’s working condition, residence, education, number of children, and health status were the main influencing factors for the post-traumatic growth of parents (P < 0.001).

Conclusion

The post-traumatic growth of parents with children with DMD was at a moderate level. Healthcare professionals should pay attention to the psychological state of parents with children with this rare disease and promote post-traumatic growth through psychological mindfulness interventions, strengthening family and social support, and providing care knowledge and skills.
De novo familial adenomatous polyposis with germline double heterozygosity of APC/BRCA2: a case report and literature review
Authors: Zhang Tian-Qi , Cai Ji-Dong , Li Cong , Xu Yun , Xu Ye
Published: February 2025

Background

The widespread application of colonoscopy screening and genetic testing in colorectal cancer (CRC) treatment has led to the identification of a subset of familial adenomatous polyposis (FAP) patients who lack a family history of the disease but harbor germline gene mutations. Moreover, distinct genotypes may be associated with varied clinical presentations and therapeutic options. This case report describes a male patient with de novo FAP who harbored germline double heterozygosity (GDH) for APC and BRCA2 mutations. The patient underwent total colectomy, and genetic testing enabled personalized surveillance and management strategies for his family members.

Case presentation

A 43-year-old male with no family history of cancer presented to the outpatient clinic of the Colorectal Surgery Department with complaints of constipation and hematochezia. Colonoscopy revealed hundreds of polyps throughout the colon and a rectal adenocarcinoma located 5 cm from the anal verge. Gastroduodenal endoscopy did not detect any upper gastrointestinal adenomas. The patient underwent laparoscopic total colectomy with abdominoperineal resection of the rectum and end ileostomy. With the consent of the patient and his family, genetic testing was performed. The index patient was found to carry an APC splicing site mutation (exon 15: c.1744-1G > A) and a BRCA2 missense mutation (exon 17: c.7976G > A: p.R2659K). His daughter was found to have inherited the same germline BRCA2 variant. Additionally, the rectal cancer exhibited proficient DNA mismatch repair (pMMR) status, ERBB2 copy number amplification, and a missense mutation, while the KRAS, NRAS, and BRAF genes were wild-type. Based on the genetic testing results and clinical manifestations, the index patient was diagnosed with familial adenomatous polyposis (FAP) and rectal cancer. Personalized surveillance and management strategies were implemented for the patient and his family, focusing on the risks of extra-colonic diseases and potential malignancies in the prostate, pancreas, breast, and ovaries.

Conclusion

De novo FAP with double germline mutations in APC and BRCA2, along with somatic ERBB2 mutations, is exceptionally rare among hereditary cancer cases. With the rapid advancements in genomics, the detection of multiple gene variants in individuals or families has become increasingly common. Additionally, the application of artificial intelligence (AI) in medical research may provide powerful tools for genetic analysis and clinical decision-making. Consequently, a comprehensive evaluation of family history, a deep understanding of hereditary cancer syndromes, and precise interpretation of genetic mutations are essential for personalized clinical management in the era of precision medicine. However, these tasks pose significant challenges for clinicians and genetic counselors alike.
Awareness and perception of antimicrobial stewardship program among healthcare professionals in the hospitals of ministry of health and population, Egypt: antimicrobial stewardship toolkit survey
Authors: Abd El Azeem Khalaf Yara Mohsen , Gad Zahira Metwally , Arafa Mostafa Ahmed , Abdou Marwa Shawky
Published: February 2025

Background

Antimicrobial resistance (AMR) has been recognized by international policymakers as a serious threat due to its current and projected influence on global population health, healthcare expenditures and gross domestic product (GDP). The present work aimed to assess the awareness, perceptions, and practices of healthcare professionals regarding the implementation of the Antimicrobial Stewardship program (ASP).

Methods

A cross-sectional study was conducted among 310 health care professionals. A self-administered questionnaire based on Antimicrobial Stewardship Toolkit for Acute and Long-Term Care Facilities; Greater New York Hospital Association (GNYAHA) was used to assess perceptions and knowledge about AMR and automatic selective perception.

Results

A total of 310 healthcare professionals participated in the study, of which 60.6% were females, with a mean age of 37.32 ± 8.71, mean years of working of 6.0 ± 5.95 and mean years of experience of 7.97 ± 7.14. The mean scores for AMR awareness, antibiotic (AB) prescribing practices, ASP perception, and intervention beliefs were 73.05 ± 11.21, 32.97 ± 8.22, 52.85 ± 13.99, and 18.24 ± 2.71, respectively. Bivariate analysis showed that profession, primary work unit, staff position significantly affect the AMR awareness and ASP perception, while only staff position affect intervention beliefs. The Multivariate linear regression showed that working in pharmacy, ABs prescribing practice and ASP perception were independent predictors of AMR awareness. Years of work in hospital, AMR awareness and ASP perception were the independent predictors of ABs prescribing practice. AMR awareness, ABs prescribing practice and intervention beliefs were independent predictors of ASP perception while ASP perception was the only independent predictors of intervention beliefs.

Conclusions

The study found a high level of awareness and practice regarding AMR and ASP among healthcare professionals. Pharmacists had higher levels of AMR awareness and ASP perception than physician in different specialities. Levels of AMR awareness, ABs prescribing practice, ASP perception and intervention beliefs affect each other in different ways. Linear regression supported our findings that pharmacists had a higher level of AMR awareness, while years of work in hospital had a significant effect on ABs prescribing practice.
Snail control as a crucial approach to schistosomiasis elimination: evidence from the People’s Republic of China
Authors: Lv Shan , Xu Jing , Li Yin-Long , Bao Zi-Ping , Zhang Li-Juan , Yang Kun , Lin Dan-Dan , Liu Jian-Bing , Wang Tian-Ping , Ren Guang-Hui , Zhong Bo , Dong Yi , Cai Li , Wen Li-Yong , Jiang Zhi-Hua , Deng Zhuo-Hui , Xie Han-Guo , Li Shi-Zhu , Bergquist Robert , Utzinger Jürg , Zhou Xiao-Nong
Published: February 2025

Background

Asian schistosomiasis is projected to be eliminated by 2030 according to World Health Organization road map for neglected tropical diseases 2021–2030. Snail control is an important measure but has not yet been systematically evaluated at a country scale. Here, we report the findings from a nationwide survey to demonstrate the dynamics of Oncomelania and its potential role in transmission interruption of schistisomiasis in the People’s Republic of China (P.R. China).

Methods

Between March 2016 and December 2017, we conducted a nationwide census on Oncomelania snail habitats in P.R. China. All historically recorded snail habitats were identified and reviewed. Information on habitat attributes, including the infestation of snails, was collected. The shape of habitats was determined using global positioning system and geographical information system technologies. The relationship between snail control and schistosomiasis elimination was established in 378 endemic counties. The comparison of accumulated snail-infested range (ASR) and the median ratio of eliminated ASR between the transmission-interrupted and endemic counties was tested by a non-parametric test (Mann–Whitney) with a significance level of 0.05.

Results

Overall, 15,377.7 million m2 of potential snail habitats with a total of 356,550 snail habitats were identified in P.R. China. The ASR amounted to 86.0% of the total area. Most of the ASR (94.9%) and habitats (68.5%) were distributed in the middle and lower reaches of the Yangtze River. Snail habitats were found up to an altitude of 2859 m above the mean sea level. By 2017, 85.1% of habitats (73.0% of the ASR) had been eliminated with almost half of them eliminated between 1965 and 1982. The elimination of snail habitats promoted transmission interruption of schistosomiasis, but showed variable patterns in different landscapes. The ratio of eliminated ASR was 99.6 and 91.4% in water network and hilly areas, respectively, while it was only 64.8% in marshland areas, particularly in Hunan and Jiangxi where the two largest freshwater lakes of P.R. China are located. Marshland habitats were seen as the most difficult for transmission interruption, which calls for additional control measures in these settings.

Conclusions

Our results support recent recommendations by the World Health Organization to implement snail control and demonstrate that schistosomiasis elimination can be achieved. The nationwide, high-resolution map of Oncomelania snail habitats in P.R. China will support further efforts to eliminate schistosomiasis.

Graphical Abstract
Comparison of the flocking behavior of Katahdin and Rambouillet sheep breeds in an extensive range environment using GPS technology
Authors: Wilson Carrie S. , Taylor J. Bret , Spiess Jonathan W. , Wilmer Hailey
Published: February 2025

Background

There is considerable interest in the suitability of the farm-flock Katahdin hair sheep breed for large-scale extensive range sheep production systems. Flocking behavior or “flockability”, a measure of gregariousness, is critical for sheep to produce in extensive, herded management systems. An evaluation of the Katahdin breed in a Western U.S. range environment compared to the traditional range-adapted Rambouillet breed is underway. The objective was to compare the flockability of range-reared Katahdin ewes to Rambouillet ewes during the summer grazing season using GPS collars. Flockability was measured by how far a ewe was dispersed from the centroid of the study flock and the total daily distance traveled compared to the study flock.

Results

Complete GPS coordinates were available from 23 Rambouillet and 29 Katahdin ewes in 2023 and five Rambouillet and five Katahdin ewes in 2024. Study groups were managed in bands of 800–1,000 ewes with lambs. During the day, the Katahdin breed had a farther dispersion from the study flock centroid for one of the study groups (P < 0.05), the Rambouillet breed was more dispersed for one study group (P < 0.05), and the breeds did not differ for one study group (P > 0.05). The effect size, measured using Cohen’s d, was small for all groups. The daily distance traveled was farther for the Rambouillet breed in two study groups (P < 0.05) when compared to the Katahdin breed, but did not differ for the other study group (P > 0.05). The effect size was low regardless of significance. When individual ewes were compared, both breeds had ewes that were either closer or farther away from the flock centroid (P < 0.05) or ewes that traveled farther or shorter daily distance (P < 0.05).

Conclusions

The Katahdin breed was similar in flockability to the traditional, range-adapted Rambouillet breed, indicating that the Katahdin breed is well suited for grazing in an extensive range environment. This study indicates the Katahdin breed exhibits favorable behavioral characteristics to flock well in large-scale extensive range systems and provides an opportunity for Western U.S. producers interested in incorporating this breed into their flock.
A machine learning-based recommendation framework for material extrusion fabricated triply periodic minimal surface lattice structures
Authors: Hussain Sajjad , Lee Carman Ka Man , Tsang Yung Po , Waqar Saad
Published: February 2025

Lattice structures (LS) have been utilized in various fields, from engineering to biomedical sciences. In the lattice structures, the triply periodic minimal surface (TPMS) LS attains benefits in terms of higher productivity and less material usage, a step towards greener 3D printing. However, no automated system exists that can effectively recommend LS parameters to reduce material waste, which is often neglected in traditional methods. To overcome these challenges, this study presents a machine learning (ML) and Deep Learning (DL) based framework recommending TPMS LS according to specific requirements. Initially, a dataset of 144 samples was created using the Material Extrusion (ME) technique. The four TPMS LS were chosen (Split-P, Gyroid, Diamond, and Schwarz) and manufactured with Polylactic acid (PLA). This dataset was used to train both ML and DL algorithms. ML algorithms included Bayesian regression (BR), K-nearest neighbors (KNN), Random Forest (RF), Decision Tree (DT), and DL algorithm convolutional neural network (CNN). These models were used to predict the key parameters of TPMS LS, including wall thickness, unit cell type, loading direction, and unit cell size. Extensive testing was performed to evaluate the performance of the algorithms, employing R-squared values and root mean square error (RMSE). The results showed that the machine learning models, specifically the RF and DT algorithms, performed the best, achieving R-squared scores of 0.993 and 1.0 and RMSE scores of 0.1180 and 0.0795, respectively. The deep learning model, CNN, achieved an RMSE value of 0.46 and an R-squared score of 97%. This study not only contributes to a better understanding of automated TPMS lattice structures but also has significant implications for sustainable design and innovation, particularly in enhancing efficient and environmentally friendly 3D printing technologies.
Narrative visualizations: Depicting accumulating risks and increasing trust in data
Authors: Fansher Madison , Walls Logan , Hao Chenxu , Subramonyam Hari , Boduroglu Aysecan , Shah Priti , Witt Jessica K.
Published: February 2025

In contexts where people lack prior knowledge and risk awareness—such as the COVID-19 pandemic—even truthful visualizations of data can seem surprising. This can lead people to mistrust the veracity of the data and to discount it, leading to poor risk decisions. In this work, we illustrate how narrative visualizations can achieve a balance between the benefits of three common risk communication mediums (static visualizations, interactive simulations, and affect-laden anecdotes). We demonstrate empirically that viewing a narrative visualization mitigates the reduced concern induced by a static visualization when communicating COVID-19 transmission risk (Study 1). Through mediation analysis, we show that narrative visualizations are more effective than static visualizations at increasing concern about large risks because they increase one’s perceived understanding and trust in data (Study 2). We argue that narrative visualizations deserve attention as a distinct class of visualizations that have the potential to be powerful tools for scientific communication (especially in contexts where data are surprising, and empiricism is important).
Comparative content analysis of national health policies, strategies and plans before and after COVID-19 among OECD and BRICS countries
Authors: Song Jialu , Zhu Ziqi , Li Qi , Chen Ying , Wang Zhebin , Zhou Shuduo , Xu Ming , Zheng Zhi-Jie
Published: February 2025

Background

The COVID-19 pandemic exposed significant limitations in health systems worldwide and emphasized the need for updated National Health Policies, Strategies, and Plans (NHPSPs). This study aimed to evaluate the NHPSPs of Organization for Economic Cooperation and Development (OECD) and BRICS (Brazil, Russia, India, China, and South Africa) countries before and after the COVID-19 pandemic. Specifically, it explored each country’s commitment to strengthening health systems to address health threats and analyzed the specific changes made.

Methods

NHPSP documents from the WHO document repository and official governmental websites were systematically searched. Data were extracted using a standardized template. A coding framework was inductively developed to sort qualitative texts into categories, with frequencies calculated and weighting evaluated, followed by organizing underlying content into subthemes.

Results

Out of 154 documents initially identified, 36 met the screening criteria, covering 14 OECD and 3 BRICS countries. The most predominant theme was prevention (88.9% pre-pandemic, 99.4% post-pandemic), which was addressed as a primary theme in 26 included NHPSPs. After the COVID-19 pandemic, 6 out of 14 analyzed themes saw higher occurrences, among which infection prevention and control (22.2–50.0%) and resilience to health crisis (22.2–44.4%) increased most significantly. Themes mainstreamed in post-pandemic NHPSPs included prevention (94.4%), health research and technology (61.1%), and One Health (66.7%). Primary healthcare emerged as the most concerned subtheme under prevention. Notably, OECD countries displayed more increased occurrences of themes (13 out of 14) or increased emphasis on themes with similar occurrences before and after COVID-19, while BRICS countries only differed in infection control. Additionally, OECD and BRICS countries varied in their subthemes and specific actions under similar primary themes.

Conclusions

COVID-19 exposed vulnerabilities in many countries' health systems, highlighting the need to build resilient health infrastructures through the optimization of NHPSPs. However, only about half of the OECD and BRICS countries have implemented new NHPSPs since the pandemic. Our findings highlight the critical need for global health system reforms and offer actionable recommendations for other countries in formulating their NHPSPs.
Endophytic Bacillus spp. of coffee plants (Coffea arabica L.) and its potential in the biocontrol of phytopathogenic fungi and Lepidoptera larvae
Authors: de Castro Marcelo Tavares , de Lima Ferreira Antônia Débora Camila , do Nascimento Izabela Nunes , Rocha Gabriela Teodoro , Celestino Matheus Felipe , Freire Ítalo Alves , Moreira Isabela Cardoso Farias , Gomes Giovana Cidade , dos Reis Cunha Breno Beda , Montalvão Sandro Coelho Linhares , Moreira Flávia Melo , Monnerat Rose Gomes
Published: February 2025

Background

Research with coffee (Coffea arabica L., Rubiaceae) endophytic microorganisms demonstrates that there is a rich microbiota that has diverse abilities to protect plants and act against phytopathogens. Therefore, the isolation and knowledge of endophytic microorganisms are important for future explorations aimed at using promising strains in controlling pests and diseases and promoting plant growth. The present work aimed to: (i) isolate and identify endophytic Bacillus strains from leaves of C. arabica plants; (ii) carry out the morphological and molecular characterization; (iii) evaluate the mycelial inhibition capacity of soil phytopathogens in vitro; (iv) and evaluate the pathogenicity of the strains against the tested lepidopteran insect pests.

Results

As a result, three species of Bacillus were isolated: B. mycoides, B. thuringiensis and B. velezensis. B. thuringiensis was virulent to Spodoptera frugiperda, Helicoverpa armigera, Chrysodeixis includens and Diatraea saccharalis and showed 100% pest mortality, and the lethal concentration (LC50 values) was estimated: 6.78 × 103 spores/ml to S. frugiperda; 6.23 × 102 spores/ml to H. armigera; 9.28 × 102 spores/ml to C. includens; and 5.81 × 101 spores/ml to D. saccharalis. In total, seven genes related to pathogenicity in insects were found in B. thuringiensis based on genome: cry1Ab24, cry1Bd2, cry2Aa9, cry2Ab41, cry1Ea7, cry1Ia37 and Spp1Aa1. Furthermore, B. velezensis was able to inhibit the growth of phytopathogens: Fusarium oxysporum (49%), Rhizoctonia solani (72%) and Macrophomina phaseolina (65%) and provided above 50% mortality on S. frugiperda and C. includens. Regarding B. mycoides, it was not efficient in inhibiting the growth of pathogens and causing pest mortality.

Conclusion

Two (B. thuringiensis and B. velezensis) of three endophytic bacteria isolated from coffee leaves showed potential to use in biological control of important pests and phytopathogens of agriculture, with high mortality of lepidopteran larvae in laboratory with B. thurigiensis and high mycelial inhibition with B. velezensis. More studies with these two strains must be carried out in greenhouse and in field to prove its beneficial properties.
Measuring energy expenditure in Göttingen Minipigs using indirect calorimetry: validation and methodological considerations
Authors: Bredum Simon K. , Jacobsen Julie , Cirera Susanna , Christoffersen Berit Ø.
Published: February 2025

Background

Obesity affects nearly a billion people globally and is associated with various health consequences. Current anti-obesity medications primarily target appetite, but drug candidates that modulate energy expenditure (EE) and substrate utilization based on respiratory exchange ratio (RER) are also essential to continuously improve the treatment modalities for people living with obesity. Selecting appropriate animal models and methods is crucial to improving translational value in preclinical research. While pig obesity models provide a relevant alternative to rodent models due to their similarities to humans, little is known about the assessment and translatability of EE in pigs. The aim of this study was to evaluate the translatability of minipigs for assessing the effect of EE-modulating drugs using indirect calorimetry and three positive control compounds that have known effects on EE and/or RER in humans. The study consisted of five sub-studies: Sub-study 1 assessed EE and RER based on sex (male/female) and diet (chow/high-fat diet) with and without correction for body composition; Sub-studies 2–4 evaluated changes in EE and RER after treatment with three positive control compounds: 2,4-dinitrophenol, DNP; a glucagon receptor agonist, GCG-RA; and a melanocortin receptor 4 agonist, MC4-RA; and sub-study 5 established three predictive equations for resting metabolic rate.

Results

Sub-study 1 resulted in detectable differences in EE and RER based on diet/body sizes (P-value < 0.0001), while EE adjusted for body composition resulted in differences based on sex (P-value < 0.0001). Sub-studies 2–4 revealed that the three pharmacological interventions known to affect EE in humans, DNP, GCG-RA, and MC4-RA, showed similar effects in the Göttingen Minipigs by significantly increasing EE by 26.1% (P-value: 0.0014), 21.3% (P-value: 0.0491), and 25.4% (P-value: 0.0013), respectively, emphasizing the translational value of the model. In sub-study 5, three predictive equations were established for RMR based on body composition, demographic and anthropometric measurements, and the most accurate equation based on all variables. All three equations demonstrated acceptable accuracy (adjusted R2: 0.73–0.85).

Conclusions

The present study qualifies the use of Göttingen Minipigs for investigating EE in preclinical research and provides a framework for conducting such research.
Obstructed infracardiac total anomalous pulmonary venous connection with patent ductus venosus: possibility of emergency palliation
Authors: Singh Damandeep , Pandey Niraj Nirmal , Thomas Joseph , Gupta Saurabh Kumar , Jagia Priya
Published: February 2025

Background

Patients with obstructed infra-cardiac total anomalous pulmonary venous connection (TAPVC) require urgent intervention to relieve the obstruction, with or without restoration of anatomical continuity between the pulmonary veins and the left atrium. In cases of infra-cardiac TAPVC draining into the inferior vena cava (IVC) or hepatic vein, the obstructed channel can be accessed via the systemic venous approach for endovascular palliation. However, in cases of infra-cardiac TAPVC draining into the portal venous system, an endovascular approach to the obstructed channel is not possible via the transfemoral route and may require direct percutaneous puncture of the splenoportal axis.

Case presentation

A 45-day-old boy presented with acute respiratory distress and cyanosis. CT angiography demonstrated infra-cardiac TAPVC with a focal critical stenosis in the descending channel, just proximal to its confluence with the portal vein. Incidentally, a vascular channel connecting the left branch of the main portal vein and the intra-hepatic IVC suggestive of a patent ductus venosus was noted. The patent ductus venosus would allow access to the site of obstruction (transfemoral venous approach → IVC → patent ductus venosus → left portal vein → main portal vein → obstructed descending common channel) to achieve emergency palliation by dilating the obstructed segment and subsequently, stenting the ductus venosus to circumvent the distal obstruction at the portal venous sinusoids.

Conclusion

The present case highlights the role of CT angiography in delineating cardiovascular anatomy and demonstrating alternate vascular pathways that may be utilized for performing palliative endovascular procedures.
A type-5 metabotropic glutamate receptor-perineuronal net axis shapes the function of cortical GABAergic interneurons in chronic pain
Authors: Mascio Giada , Nicoletti Ferdinando , Battaglia Giuseppe , Notartomaso Serena
Published: February 2025

Parvalbumin-positive (PV+) interneurons (basket and chandelier cells) regulate the firing rate of pyramidal neurons in the cerebral cortex and play a key role in the generation of network oscillations in the cerebral cortex. A growing body of evidence suggest that cortical PV+ interneurons become overactive in chronic pain and contribute to nociceptive sensitization by inhibiting a top-down analgesic pathway. Here, we provide further support to this hypothesis showing that intracortical infusion of the GABA

A

receptor antagonist, bicuculline, caused analgesia in a mouse model of chronic inflammatory pain, although it reduced pain thresholds in healthy mice. We propose that mGlu5 metabotropic glutamate receptors and perineuronal nets (PNNs) shape the activity of PV+ interneurons in chronic pain, generating a form of maladaptive plasticity that enhances behavioural pain responses. mGlu5 receptors might be locally targeted by drugs activated by light delivered in cortical regions of the pain matrix, whereas the density of PNNs enwrapping PV+ interneurons might be reduced by local activation of PNN-degrading enzyme, such as type-9 matrix metalloproteinase. These strategies, which may require invasive treatments, might be beneficial in the management of severe pain which is refractory to conventional pharmacological and non-pharmacological interventions.
Routes to stratified turbulence and temporal intermittency revealed by a cluster-based network model of experimental data
Authors: Lefauve Adrien , Cheung Yui Hin Marvil , Jiang Xianyang , Couchman Miles M. P.
Published: February 2025

Modelling fluid turbulence using a 'skeleton' of coherent structures has traditionally progressed by focusing on a few canonical laboratory experiments such as pipe flow and Taylor-Couette flow. We here consider the stratified inclined duct, a sustained shear flow whose density stratification allows for the exploration of a wealth of new coherent and intermittent states at significantly higher Reynolds numbers than in unstratified flows. We automatically identify the underlying turbulent skeleton of this experiment with a data-driven method combining dimensionality reduction and unsupervised clustering of shadowgraph visualisations. We demonstrate the existence of multiple types of turbulence across parameter space and intermittent cycling between them, revealing distinct transition pathways. With a cluster-based network model of intermittency we uncover patterns in the transition probabilities and residence times under increasing levels of turbulent dissipation. Our method and results pave the way for new reduced-order models of multi-physics turbulence.
After Revolutionary Alliance: Jazz and Langston Hughes’s Midcentury Internationalism
Authors: Liu Wei
Published: February 2025

While studies of Langston Hughes’s transnationality don’t often prioritize his involvement with the international Left, this essay takes up the question of how his global imaginary and his radicalism inform one other, examining specifically the fate of Hughes’s early radicalism—his early understanding of African American liberation struggles as aligned with anti-capitalist and anti-imperialist movements abroad—in his post-WWII writing. Against McCarthyism and the United States’ militant Cold War nationalism, Hughes develops a jazz poetics that salvages a margin of his ideal of revolutionary alliance—a poetics courting plausible yet indeterminable comparisons between the communality jazz enables across races and nationalities and a leftist international coalition. Hughes’s post-WWII deployment of jazz constitutes a “midcentury internationalism” that reckons with the diminishing possibilities of asserting solidarity among oppressed peoples. Hughes’s midcentury internationalism should be understood less as valorizing irreconcilable otherness and unpredictable encounters than as offering a complex imaginary that might maintain some sense of those possibilities.
An investigation of Y-TZP surface characteristics and adhesive properties following treatment with Tri-biochemical Silica Coating, Femtosecond Laser, and Nano-hydroxyapatite: A scanning electron microscopy evaluation
Authors: Alkhudhairy Fahad , Nourah N. Shono
Published: February 2025

Objectives: To examine how advanced surface pretreatment techniques - Tribochemical silica coating (TBC), Femtosecond laser (FS), and Nano-hydroxyapatite (HA) coating - affect the surface roughness (Ra) and shear bond strength (SBS) between resin luting cement and Yttria-stabilized tetragonal zirconia polycrystals (Y-TZP)
Methods: The lab-based comparative study was approved by the ethical committee of King Saud University under IRB number F98-971X9 and was completed in three months (June to September, 2024). Eighty-four YTZP zirconia discs were created and sorted into four groups based on different conditioning agents: Group-I (APA) as the control, Group-II (TBC), Group-III (FS laser), and Group-IV (Nano-HA coating). Ra was measured on five discs from each group using a profilometer, while surface topography was examined through SEM analysis. Ten specimens per group were bonded with luting cement, followed by SBS testing and fracture mode analysis using a universal testing machine and stereomicroscope, respectively. One-way ANOVA with post hoc Tukey tests (p<0.05) was used for statistical analysis of Ra and SBS means across the groups.
Results: Group-IV (Nano-HA coating) exhibited the highest Ra and SBS values. Conversely, Group II (TBC) displayed the lowest Ra and weakest bond strength.
Conclusion: Nano-HA coating and FS laser can be employed as viable alternatives to APA without compromising the physical and mechanical properties of zirconia ceramic.
doi: https://doi.org/10.12669/pjms.41.3.11302
How to cite this: Alkhudhairy F, Shono NN. An investigation of Y-TZP surface characteristics and adhesive properties following treatment with Tri-biochemical Silica Coating, Femtosecond Laser, and Nano-hydroxyapatite: A scanning electron microscopy evaluation. Pak J Med Sci. 2025;41(3):758-762. doi: https://doi.org/10.12669/pjms.41.3.11302
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.
Construction and validation of nomogram model for chronic postsurgical pain in patients after total knee arthroplasty: A retrospective study
Authors: Zhao Shenghao , Hu Ying , Li Ye , Tang Jie
Published: February 2025

Objective: Chronic postsurgical pain (CPSP) after total knee arthroplasty (TKA) is the most common postoperative complication in orthopedics. This study aims to explore the risk factors for CPSP after TKA and construct a nomogram model.
Methods: This retrospective study included clinical records of 430 patients who received TKA treatment at Wuhan Fourth Hospital between January 2020 to January 2024. Patients were randomly divided into a training cohort (n=301) and a validation cohort (n=129) in a 7:3 ratios. The Least Absolute Shrinkage and Selection Operator (LASSO) algorithm and logistic regression analysis were used to identify the independent risk factors, and a predictive nomogram model was established based on the identified risk factors. The concordance index (C-index), calibration curve, receiver operating characteristic (ROC) curve and decision curve analysis were used to assess the predictive accuracy and clinical application value of the nomogram model.
Results: Six risk factors for predicting CPSP were identified, including preoperative anxiety, preoperative depression, preoperative pain, duration of tourniquet use, pain upon discharge, and postoperative C-reactive protein levels. The nomogram model demonstrated sufficient predictive accuracy, with the area under the curve (AUC) values of 0.761 (95% CI: 0.689-0.833) and 0.806 (95% CI: 0.700-0.911) in the training cohort and validation cohort, respectively. The C-index of the training cohort and validation cohort were 0.733 and 0.761, respectively. The calibration curve shows good consistency between the predicted risk of the model and the actual risk of CPSP. Decision curve analysis (DCA) demonstrated the clinical applicability of the model.
Conclusions: The nomogram model established in this study for predicting CPSP after TKA has good predictive value and may be used in clinical practice to identify patients at high risk of developing CPSP after TKA.
doi: https://doi.org/10.12669/pjms.41.3.11525
How to cite this: Zhao S, Hu Y, Li Y, Tang J. Construction and validation of nomogram model for chronic postsurgical pain in patients after total knee arthroplasty: A retrospective study. Pak J Med Sci. 2025;41(3):780-787. doi: https://doi.org/10.12669/pjms.41.3.11525
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.