bluuebunny/crossref_metadata_2025 huggingface dataset:
The secreted host-cell protein clusterin interacts with PmpD and promotes Chlamydia trachomatis infection
Authors: Kocher Fabienne , Hegemann Johannes H.
Published: January 2025

Attachment and uptake into host cells are pivotal steps in the life cycle of the Chlamydiaceae, a family of obligate intracellular pathogens. Chlamydia trachomatis (Ctr) possesses a family of nine polymorphic membrane proteins (Pmps), which have been shown to be crucial for adhesion and internalization. However, the host-cell molecules involved have so far remained unknown. Here, we show that a fragment of Ctr PmpD, which forms high-molecular-weight oligomers in solution and adheres to epithelial cells, also binds to secreted clusterin (sCLU), a chaperone-like protein that is secreted into the extracellular space by the host cell, and forms part of the chaperone- and receptor-mediated extracellular protein degradation (CRED) pathway. Using in vitro assays, we demonstrate that sCLU interacts directly with soluble rPmpD. In infection experiments, depletion of sCLU from the culture medium leads to a significant decrease in Ctr infection. Thus, sCLU is the first host-cell interaction partner identified for a Ctr Pmp and the first case in which sCLU has been shown to be a vital component for the establishment of a bacterial infection.
Development and validation of a prediction model of hospital mortality for patients with cardiac arrest survived 24 hours after cardiopulmonary resuscitation
Authors: Zhang Renwei , Liu Zhenxing , Liu Yumin , Peng Li
Published: January 2025

Objective

Research on predictive models for hospital mortality in patients who have survived 24 h following cardiopulmonary resuscitation (CPR) is limited. We aim to explore the factors associated with hospital mortality in these patients and develop a predictive model to aid clinical decision-making and enhance the survival rates of patients post-resuscitation.

Methods

We sourced the data from a retrospective study within the Dryad dataset, dividing patients who suffered cardiac arrest following CPR into a training set and a validation set at a 7:3 ratio. We identified variables linked to hospital mortality in the training set using Least Absolute Shrinkage and Selection Operator (LASSO) regression, as well as univariate and multivariate logistic analyses. Utilizing these variables, we developed a prognostic nomogram for predicting mortality post-CPR. Calibration curves, the area under receiver operating curves (ROC), decision curve analysis (DCA), and clinical impact curve were used to assess the discriminability, accuracy, and clinical utility of the nomogram.

Results

The study population comprised 374 patients, with 262 allocated to the training group and 112 to the validation group. Of these, 213 patients were dead in the hospital. Multivariate logistic analysis revealed age (OR 1.05, 95% CI: 1.03–1.08), witnessed arrest (OR 0.28, 95% CI: 0.11–0.73), time to return of spontaneous circulation (ROSC) (OR 1.05, 95% CI: 1.02–1.08), non-shockable rhythm (OR 3.41, 95% CI: 1.61–7.18), alkaline phosphatase (OR 1.01, 95% CI: 1–1.01), and sequential organ failure assessment (SOFA) (OR 1.27, 95% CI: 1.15–1.4) were independent risk factors for hospital mortality for patients who survived 24 h after CPR. ROC of the nomogram showed the AUC in the training and validation group was 0.827 and 0.817, respectively. Calibration curves, DCA, and clinical impact curve demonstrated the nomogram with good accuracy and clinical utility.

Conclusion

Our prediction model had accurate predictive value for hospital mortality in patients who survived 24 h after CPR, which will be beneficial for assisting in identifying high-risk patients and intervention. Further confirmation of the model's accuracy required external validation data.
Insights from feature tracking of optical satellite data for studying rock glacier kinematics in the Northern Tien Shan
Authors: Wood Ella , Bolch Tobias , Streeter Richard
Published: January 2025

Rock glaciers are prevalent across the Tien Shan and exhibit complex, but poorly understood kinematics linked to climate and environmental fluctuations. This study employed a frequency domain cross-correlation method to investigate rock glacier velocities in the Northern Tien Shan. We compared different sources of satellite imagery, including 0.5m Pléiades, 3m Planet, 10m Sentinel-2 and 15m Landsat-8 data. Analysis of high-resolution Pléiades imagery in the Central Ile Alatau showed considerable spatial heterogeneity in flow. The highest median velocity of 0.65 m/yr was observed on Timofeyeva rock glacier, with an upper quartile value of 0.90 m/yr. Ordzhonikidze and Morennyi rock glaciers also exhibited high activity, with upper quartile values of 1.91 m/yr and 0.96 m/yr, respectively, despite considerably lower mean and median values than Timofeyeva. We observed bimodal velocity distributions on a number of rock glaciers, highlighting the limitations of using mean and median statistics for characterising rock glacier activity. Sentinel-2 data was capable of detecting kinematic patterns that closely reflected those identified by high-resolution Pléiades data. Velocities were derived from Sentinel-2 imagery for 672 rock glaciers across the Northern Tien Shan over a 7-year period (2016–2023). Many of the larger rock glaciers in the regional inventory exhibited active areas with velocities that exceeded 2 m per year. Topographic analysis in the Central Ile Alatau and visual inspection showed the fastest velocities to generally occur on lower, flatter areas near the rock glacier front. However, topography did not entirely explain the spatial flow heterogeneity. We interpret that these spatial patterns in activity are related to individual rock glacier’s internal structure.
Bridging the gap: community health workers as a vital link in humanitarian medical responses
Authors: Nally Cora P. , Van de Voorde Patrick , Temmerman Marleen , Koroma Adama , Mitchell Monique , Adam Mary B.
Published: January 2025

Community Health Workers (CHWs) have proven essential in improving health outcomes and building community trust and their role in humanitarian emergency medical responses warrants further study. We illustrate this point with two case studies, the integration of community health workers into Mobile Medical Teams [MMTs] in both The Bahamas and Sierra Leone. CHWs in these examples came to the forefront of addressing community mistrust for external medical teams, health communication efforts and patient follow-up care. In Sierra Leone, this program resulted in a 32% rise in referrals to established health services. By exploring these contexts, the paper provides a new framework for enhancing humanitarian responses through CHWs, outlining the strategic, logistical, and cultural benefits of such an approach. This research suggests that integrating CHWs with MMT's can bolster health outcomes, especially in communities affected by political instability, natural disasters, and resource limitations. The paper ends by providing policy implications and recommendations for further research on the use of CHWs during a range of emergency contexts.
Transcriptome analysis reveals effects of ethynylestradiol and bisphenol A on multiple endocrine and metabolic pathways in the pituitary and liver of female Atlantic cod (Gadus morhua)
Authors: Yadetie Fekadu , Zhang Xiaokang , Reboa Anna , Noally Gwenaëlle Samantha Chloe , Eilertsen Mariann , Fleming Mitchell Stewart , Helvik Jon Vidar , Jonassen Inge , Goksøyr Anders , Karlsen Odd André
Published: January 2025

Introduction

The pituitary and liver are among the main sites of action of estrogens in fish. Years of research has shown that xenoestrogens can interfere with functions of estrogens. There is however incomplete understanding of xenoestrogen targets genes, their molecular mechanisms and potential effects in some of the target organs, particularly the pituitary.

Methods

We performed a comprehensive analysis of pituitary and liver transcriptome 72 h after injection of ethynylestradiol (EE2: 10, 50 or 250 nmol/kg body weight/bw) and bisphenol A (BPA: 8, 40 or 200 μmol/kg bw) in juvenile female Atlantic cod (Gadus morhua).

Results

A broad range of reproductive and metabolic pathways were affected in both organs by BPA and EE2. In the pituitary, effects on the expression of many genes associated with reproduction-related hormonal pathways including the gonadotropin system, as well as genes in processes such as cell differentiation and metabolic homeostasis were observed. In the liver, in addition to upregulation of well-known estrogen marker genes, effects on metabolic pathways, in particular, a coordinated downregulation of genes in the triglyceride synthesis pathways were observed.

Discussion

The results suggest that estrogenic compounds affect a broad range of reproductive and metabolic processes in the pituitary. The alterations in the liver unravel the transcriptional changes underlying metabolic remodeling during estrogen induced vitellogenesis. This study provides new insights into mechanisms of endocrine and metabolic interactions that can be potential targets of environmental estrogens in fish. The study also identifies potential gene expression biomarkers for pituitary and liver effects of xenoestrogens.
The correlation between high-sensitivity cardiac troponin levels in diabetic patients’ serum and lower limb lesions: based on NHANES data
Authors: Li Lin , Jiao Linxi , Yang Danyang , Zhao Jingxia , Li Ping
Published: January 2025

Objective

To evaluate the association of hypersensitive cardiac troponin (hs-cTnT), a biomarker of myocardial injury, with diabetic lower extremity disease in American adults.

Methods

We conducted a cross-sectional study (unweighted N=1,196) of diabetic patients aged 40 years or older who participated in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2004. Logistic regression was used to assess the association of hs-cTnT with lower extremity disease, including peripheral neuropathy (as assessed by monofilament test), peripheral artery disease (as assessed by ankle-brachial index), history of foot ulcers, or amputation. All analyses are weighted.

Results

The prevalence rate of diabetic lower extremity disease was 41.6%. Adjusted hs-cTnT was significantly associated with lower limb disease in adults with diabetes. There is interaction between chronic kidney disease and hs-cTnT, which strongly interferes with the correlation between hs-cTnT and lower extremity lesions in diabetic patients.

Conclusions

Our study suggests the usefulness of hs-cTnT as a biomarker for lower extremity lesions in adults with diabetes and highlights the potential direct interaction of hs-cTnT with chronic kidney disease.
The role of SPINK5 mutation distribution in phenotypes of Netherton syndrome
Authors: Xu Min , Shi Yujie , Lin Li , Wang Liang , Zhu Xianzhong , Xiong Jinglin , Yin Jiawen , Qi Qing , Yang Wenlin
Published: January 2025

Objective

Netherton syndrome (NS) is a rare hereditary dermatosis, and the correlation between genotype and phenotype in this disease warrants further investigation. This study aimed to explore the genotype-phenotype correlation in NS.

Methods

We collect cases from our clinic and relevant literature. After rigorous screening, we included 162 patients with NS-associated symptoms and SPINK5 mutations. We characterized the distribution and mutation types of allele variants. Logistic regression was employed to analyze the correlation between the location of these variants and phenotypes. Additionally, the association between the homozygous condition of variants and death during infancy was analyzed using the Chi-square test.

Results

Among 162 patients, we identified 324 allele variants, comprising 75 different mutations. Of these, 73 patients carried heterozygous variants, while 89 patients had homozygous variants. We observed that patients with variants or homozygous variants located in the 5′ half of the gene were more likely to experience failure to thrive (P < 0.05). Similarly, variants or homozygous variants located outside DomainR-5 were also associated with an increased risk of failure to thrive (P < 0.05). Furthermore, variants in domain regions were significantly correlated with the presence of ichthyosis linearis circumflexa (P < 0.01). Patients with homozygous fatal variants (c.153delT, c.1431-12G>A, c.1111C>T, c. 1887 + 1G>A, and c. 995delT) had a higher likelihood of mortality during infancy (P < 0.001).

Conclusion

Our study provides valuable insights into the genotype-phenotype correlation in Netherton syndrome, enhancing our understanding of the disease and potentially informing the development of future therapeutic approaches.
Tangible consumption data landscapes of teenagers
Authors: Ağça Ayşe Özge
Published: January 2025

Teenagers are increasingly concerned about clean energy and play a crucial role in driving energy transition. In this study, I investigate how teenagers understand energy consumption, how tangible data mapping through anthropological theories may increase their awareness, and what ideas they may have about how to change habits. I present an approach for designing new data physicalizations, shaping how to facilitate data interaction sessions, and analyzing data physicalization and interactions based on Ingoldian concepts such as the Life of Lines and Imagining for Real. The empirical material includes 1-h sessions in two secondary education schools with 30 teenagers and video-recorded explanations about their consumption habits. The teenagers completed a questionnaire, drew a layout drawing of their home, and built a physical model of their home with products and rooms representing their energy consumption. The data landscapes encouraged participants to explore the perceptual integrity of energy-consuming habits and identify ways to change them. The self-expressive sessions demonstrate that the three data-mapping techniques enable teenagers to recount their daily consumption patterns. In particular, the tangible mapping of Consumption Data Landscapes can open avenues for engagement to increase their awareness of energy consumption and spawn responsibility for a change of habits.
Immune microenvironment features underlying the superior efficacy of neoadjuvant immunochemotherapy over chemotherapy in local advanced gastric cancer
Authors: Zhang Ning , Li Chunyu , Zhao Zehua , Jiang Biying , Wang Wentao , Sun Fujing , Zhang Yong , Zhu Yanmei
Published: January 2025

Background

The therapeutic efficacy of neoadjuvant immunotherapy combined with chemotherapy (Io+Chemo) is superior than chemotherapy alone (Chemo). However, the mechanism of Io+Chemo superiority remains to be further elucidated.

Methods

The study included 128 patients with resectable stage II-III gastric cancer, in which 63 were given neoadjuvant Io+Chemo, and 65 Chemo alone. Patients given Io+Chemo were treated with 2-4 cycles of PD-(L)1 inhibitor (Pembrolizumab, Sintililimab or Nivolumab) with S-1 and oxaliplatin (SOX) or capecitabine and oxaliplatin (XELOX) before surgical resection. Patients given Chemo were treated with 2-4 cycles of SOX or XELOX before surgical resection. Tumor tissues were evaluated for tumor-infiltrating immune cells (TIICs) using immunohistochemistry and QuPath software quantitative analysis, for detecting T, B, NK, plasma cells, and macrophages. The relationship between TIICs and different neoadjuvant treatment regimens and pathological responses was also explored.

Results

Compared with Chemo, Io+Chemo induced higher rates of pathological complete response (33.3 vs. 9.2%, p=0.001) and major pathological response (MPR) (49.2 vs. 30.8%, p=0.033). Compared with Chemo group, density of CD4+(1904.8 vs. 1530), CD8+(1982.9 vs. 1124.4), CD20+(1115.6 vs. 574), CD38+(1580.4 vs. 1128), CD138+(1237.2 vs. 496.4), and CD56+ (596.8 vs. 159) cells was increased 24.5%, 76.4%, 94.4%, 40.1%, and 149.2% respectively, whereas CD163+ macrophages (994.4 vs. 1706) was decreased 41.7% in Io+Chemo group.

Conclusions

Our study favors neoadjuvant Io+Chemo over Chemo and reveals Io+Chemo can induce the formation of an immune-activated microenvironment that make Io+Chemo superior to Chemo.
T cell receptors specific for an imatinib-induced mutation in BCR-ABL for adoptive T cell therapy
Authors: Hsu Meng-Tung , Willimsky Gerald , Hansmann Leo , Blankenstein Thomas
Published: January 2025

BCR-ABL kinase is the major oncogenic driver of chronic myeloid leukemia (CML). Tyrosine kinase inhibitors (TKIs), which are highly potent in targeting BCR-ABL, are currently used as first-line treatment. Although TKIs are effective, drug resistance caused by the emergence of drug-selected secondary mutations in BCR-ABL remains a major problem for relapse, especially in patients with compound mutations. In this study, we aimed to investigate potential neoepitopes derived from mutated BCR-ABL and to generate neoepitope-specific TCRs for adoptive T cell therapy. Two candidate peptides derived from the E255V and the T315I mutation (designated ABL-E255V and ABL-T315I) were selected for study based on their in silico predicted binding affinity to HLA-A2. By immunizing transgenic mice that express a diverse human T cell receptor (TCR) repertoire restricted to HLA-A2, we detected CD8+ T cell responses against the ABL-E255V, but not the ABL-T315I peptide. From immune responding mice, two E255V-specific TCRs were isolated. Human CD8+ T cells were engineered to express the specific TCRs for characterization, in which one TCR was identified as a therapeutic candidate due to its superior avidity and lack of detectable off-target reactivity. Importantly, we demonstrated that the ABL-E255V neoepitope was naturally processed and presented. In summary, our results demonstrate that HLA-A2+ CML cells harboring the E255V mutation can be targeted by specific TCRs, which may benefit patients who are highly resistant to available TKIs due to compound mutations.
The rise of aerial additive manufacturing in construction: a review of material advancements
Authors: Dams Barrie , Chen Binling , Kaya Yusuf Furkan , Shepherd Paul , Kovac Mirko , Ball Richard J.
Published: January 2025

The construction industry has recently increased the adoption of additive manufacturing (AM, also known as 3D-printing) technologies. This review paper presents the state of the art of ground-based AM systems in construction, focusing comprehensively on developments in the material aspect towards using unmanned aerial vehicles (UAV), commonly referred to as “drones”. AM itself is introduced, and an overview of the history of AM is provided. Key projects developing both ground-based cementitious and polymeric AM applications for construction purposes are reviewed along with material constituents, AM deposition methods and reinforcement techniques to mitigate against crack propagation. The review details a cutting-edge Aerial Additive Manufacturing (AAM) system developed to utilise untethered, self-powered UAV platforms extruding material during autonomous flight, which is designed to bring multi-agent aerial mobility to AM in the construction industry. An overview of the history of UAV development is presented, as well as the current use of UAV platforms combined with material deposition devices for construction and considerations for developing suitable materials and future research.
Qualitative evaluation of kerf taper angle of conventionally drilled holes in glass fiber epoxy composite
Authors: Patil Dipak S. , Bhoomkar Manmohan M. , Sunheriya Neeraj , Giri Jayant , Kulkarni Atul , Patil Lalit N. , Toke Lalit K. , Sathish Thanikodi , Kanan Mohammad
Published: January 2025

This study analyses the impact of process parameters on Glass Fiber Reinforced Polymer (GFRP) components produced through conventional drilling on a CNC drilling machine (VMC). GFRP’s challenging machinability is due to its high strength-to-weight ratio, durability, and customizable mechanical properties. The study aims to minimize kerf angles in drilled holes, identifying optimal parameter combinations based on Signal-to-Noise ratios. The best combination of parameters that used to reduce the value of the kerf angle was considered at 2,800 RPM spindle speed and 1,200 mm/rev feed rate. The experimental work reveals that the spindle speed significantly affects the kerf angle, while the feed rate and spindle speed both influence the variation in the kerf angle and show the best results at the ideal values of the two parameters. The study details an analysis of the process parameters of drilled holes on kerf angle in multiple holes in the specimen, applying Taguchi’s design of experiments and analysis of variance. Comparison of findings was made with existing literature on determination of the importance of spindle speed and feed rate for the determination of kerf angle. The best results were obtained when all these parameters set to the ideal values, where the minimum angular kerf of 0.1145° was observed.
Case report: Dupilumab-induced linear psoriasis: a rare presentation
Authors: Sun Wen , Wang Kexin , Ren Yuekang , Yuan Huajie , Lang Xiaoqing , Guo Shuping , Liu Hongye
Published: January 2025

A 42 year-old male with prurigo nodularis treated with dupilumab showed a case of linear psoriasis, highlighting the potential of dupilumab to induce immune shift and chimeric gene expression.
Challenges and ongoing initiatives towards better integrated EU scientific advice
Authors: Gravanis Iordanis , Berntgen Michael , Vamvakas Spiros , Demolis Pierre , Foggi Paolo
Published: January 2025

Scientific advice is the main avenue for clarification of EU regulators’ scientific evidence requirements during medicines development. There are multiple avenues for seeking scientific advice in the EU with partially overlapping scope which creates room for divergence and contradictions; simplification and better integration among them could help harmonize EU regulators’ requirements. Interaction with other decision makers providing advice along the lifecycle of medicines and other healthcare solutions reduces development uncertainties. The proposal for a new EU pharmaceutical legislation solidifies existing advice mechanisms and creates new avenues for enhanced integration of development support.
Chronic osteomyelitis with pathological fracture induced by Mycoplasma hominis infection: a case report and review of the literature
Authors: Zhu Ling-Na , Shen Wen-Bin , Zou Xiao-Yan , Zuo Jiang-Cheng , Xiao Ning
Published: January 2025

Mycoplasma hominis, commonly residing in the genitourinary tract, can cause rare extragenital infections, especially in immunocompromised individuals. This report details a case of chronic osteomyelitis with a pathological femur fracture in a 79-year-old woman. Despite a history of bone tuberculosis, the infection was identified as Mycoplasma hominis through culture and mass spectrometry, highlighting the diagnostic challenges due to the organism’s lack of a cell wall. This case underscores the necessity for advanced diagnostic methods and awareness of Mycoplasma hominis in non-urogenital infections.
Genome sequence and evaluation of safety and probiotic potential of Lacticaseibacillus paracasei LC86 and Lacticaseibacillus casei LC89
Authors: Chen Ting , Zhao Yunjiao , Fan Yixuan , Dong Yao , Gai Zhonghui
Published: January 2025

Aim

A comprehensive safety assessment of potential probiotic strains was essential for their application in the food industry. This article systematically evaluated the probiotic characteristics, whole-genome sequence analysis and safety of Lacticaseibacillus paracasei LC86 and Lacticaseibacillus casei LC89.

Methods

Firstly, the two strains of lactic acid bacteria selected were identified. Secondly, whole-genome sequencing was performed on LC86 and LC89, and their antibiotic resistance, pathogenicity, and virulence genes were analyzed. We tested various properties of the two strains, included tolerance, cell adhesion, hemolytic activity, catalase activity, gelatin hydrolysis, arginine hydrolysis ability, bile salt hydrolysis capacity, mucin degradation, bioamine, D-/L-lactic acid production and antibiotic susceptibility, to confirm the safety of LC86 and LC89 both in vitro and in vivo. Additionally, we studied the acute toxicity of LC86 and LC89 in mice through a 14-day oral gavage experiment.

Results

The two strains selected were identified as Lacticaseibacillus paracasei and Lacticaseibacillus casei. The genomes of both LC86 and LC89 were devoid of virulence, antibiotic resistance and pathogenicity genes. LC86 and LC89 exhibited good tolerance to temperature, artificial gastric fluid and artificial intestinal fluid; they were non-hemolytic, their catalase activity, gelatin hydrolysis, arginine hydrolysis and bile salt hydrolysis were all negative. They exhibited the capability to break down proteins and demonstrated sensitivity to a range of antibiotics. The oral LD50 for both LC86 and LC89 in mice was >2 × 1010 CFU/kg.

Conclusion

The experimental results above demonstrated the probiotic characteristics and safety of LC86 and LC89, indicating their potential as candidates for probiotics for human and animal applications.
Mixed fungal strains challenge host resistance: insights into Magnaporthiopsis maydis pathogenicity in maize
Authors: Shofman Galia , Degani Ofir
Published: January 2025

Maize late wilt disease, caused by the fungus Magnaporthiopsis maydis, poses a significant threat to susceptible crops. Despite efforts to control it through resistant maize varieties, virulent fungal strains might overcome immunity. This study assessed Israeli M. maydis strains with weak, moderate, and highly pathogenic degrees in two open-air pot trials. Even weak pathogenic strains harmed susceptible cultivars (17% growth suppression and 33% death). In contrast, resistant cultivars were minimally affected, except when exposed to a highly aggressive isolate, resulting in a 5% growth suppression and 11% mortality at harvest. Unexpectedly, in a susceptible cultivar during sprouting, a mixed inoculum with the two more virulent isolates resulted in reduced disease (15%) compared to the highly aggressive strain alone (33%). At harvest (day 84), this pattern was reversed, and adding a weak virulent strain to this combination led to more severe growth (33%) and health (71%) disruption, accompanied by a higher level of M. maydis infection (371% compared to the aggressive strain alone). Similar interactions were found in other strain groups tested. Additionally, some subspecies groups specialize in growth suppression, while others in wilting, suggesting biotrophic/necrotrophic variations. The study revealed complex interactions in mixed populations, emphasizing the destructive potential of the pathogen to resistant cultivars. Understanding the role of maize age-related immunity in disease generation uncovers risks associated with this pathogen.
The double-edged sword of statins in intracerebral hemorrhage patients: a systematic review and meta-analysis
Authors: Li Zheng , Xu Wen-qi , Wang Jiao-qi , Yang Jia-hui , Shi Xiao-hua , Wang Cheng-bing , Xu Zhong-xin , Jiang Jin-lan
Published: January 2025

Background

This meta-analysis aimed to investigate the effect of statins on the prognosis of patients with intracerebral hemorrhage (ICH).

Methods

We conducted a systematic search using the keywords “statin” and “intracerebral hemorrhage” across four electronic databases (PubMed, Cochrane Library, Web of Science, and Embase) from their inception to October 31, 2023, to identify studies comparing the effects of statins on the prognosis of patients with ICH. The primary outcome was total mortality after ICH. This meta-analysis was registered online (PROSPERO ID: CRD42023493063).

Results

Our initial search identified 5,543 studies. After applying inclusion criteria, 30 studies with a total of 42,298 patients were included in the final analysis. Our meta-analysis showed that statins significantly reduced overall mortality in patients with ICH (OR: 0.61; 95% CI: 0.51–0.73; I2 = 87%; p < 0.01). Subgroup analyses further demonstrated lower mortality in ICH patients treated with statins compared to those not treated, including in the propensity score matching (PSM) group (OR: 0.59; 95% CI: 0.48–0.74; I2 = 90%; p < 0.01), the prospective cohort study (PCS) group (OR: 0.56; 95% CI: 0.40–0.77; I2 = 89%, p < 0.01), and the retrospective cohort study (RCS) group (OR: 0.64; 95% CI: 0.51–0.81; I2 = 87%, p < 0.01).

Conclusion

Our meta-analysis of 30 studies suggests that statin use may be associated with improved mortality and functional outcomes in patients with intracerebral hemorrhage (ICH).

Systematic Review Registration

https://www.crd.york.ac.uk/PROSPERO/, CRD42023493063.
Joint effect of modifiable risk factors on Parkinson’s disease: a large-scale longitudinal study
Authors: Li Panlong , Zhu Xirui , Liu Min , Wang Yanfeng , Huang Chun , Sun Junwei , Tian Shan , Li Yuna , Qiao Yuan , Yang Junting , Cao Shanshan , Cong Chaohua , Zhao Lei , Su Jingjing , Tian Dandan
Published: January 2025

Introduction

Previous researches have often underestimated the diversity and combined effects of risk factors for Parkinson’s disease (PD). This study aimed to identify how multiple modifiable risk factors collectively impact PD.

Methods

The study included 452,492 participants from the UK Biobank, utilizing genetic data and 255 phenotypic variables. A broad exposure association study was conducted across seven domains: socioeconomic status, medical history, psychosocial factors, physical measures, early life, local environment, and lifestyle. Risk scores of each domain for each participant were generated. The joint effects of modifiable and genetic risks assessed using Cox proportional hazards model. Population attributable fraction (PAF) was estimated to quantify contribution ratio of risk factors in different domains to the occurrence of PD.

Results

Multiple risk factors significantly (p < 1.96 × 10−4) associated with PD was observed. The top 5 factors were hand grip strength (hazard ratio (HR) = 0.98, p = 1.59 × 10−24), long-standing illness (HR = 1.38, p = 3.63 × 10−20), self-reported nervousness (HR = 1.56, p = 5.9 × 10−20), ever suffered from mental health concerns (HR = 1.42, p = 5.48 × 10−18) and chest pain (HR = 1.42, p = 1.43 × 10−18). Individuals with unfavorable medical history, psychosocial factors, physical measures, and lifestyle had an increased risk of PD by 33 to 51% compared to those with favorable factors (p < 0.001).

Discussion

Results indicated that addressing modifiable risk factors, especially in physical measures and psychological factors, could potentially prevent up to 33.87% of PD cases. In formulating prevention strategies, it is recommended to prioritize domains such as physical measures, psychosocial factors, lifestyle, and medical history.
Prevalence of overweight/obesity and its association with fast food consumption among adolescents in Southern Ethiopia, 2022: a community-based cross-sectional study
Authors: Elias Chernet , Abraham Awoke , Asrat Chernet , Yakob Tagese , Girma Daniel
Published: January 2025

Overweight and obesity are body mass index (BMI) for age Z-score > +1SD and > +2SD, respectively. Despite its largest contribution to overweight/obesity, there is little attention in our country about fast-food consumption. Hence, this study aimed to assess the prevalence of overweight/obesity and its association with fast-food consumption among adolescents in Southern Ethiopia. From 14 June 2022 to 15 July 2022, a cross-sectional study design was conducted using a structured questionnaire and anthropometric measurements, with a sample size of 563. The data were coded, cleaned, and imported into EPI-INF version 7.2 before being exported to SPSS version 25 for analysis. All variables with p-values less than or equal to 0.25 in bivariate logistic regression were candidate variables for multivariable logistic regression. The response rate of this study was 97%. Based on BMI, the combined prevalence of overweight/obesity was 6.0% (95% CI: 4.2–8.4%). Adolescents who are female, come from high-income families, and eat fast-food frequently are more likely to be overweight or obese. Future health initiatives aimed at lowering the prevalence of overweight and obesity in adolescents should pay special attention to female adolescents and those from high-income families.
Screening potential antileukemia ingredients from sweet potato: integration of metabolomics analysis, network pharmacology, and experimental validation
Authors: Xu Lianling , Zeng Kaixuan , Duan Zuoyue , Liu Jing , Zeng Yan , Zhang Miao , Yang You , Guo Qulian , Jin Yanling , Liu Wenjun , Guo Ling
Published: January 2025

Background

Active dietary flavonoids are a promising resource for novel drug discovery. Sweet potato, a widely cultivated functional crop, is abundant in flavonoids. However, the active ingredients associated with acute myeloid leukemia (AML) treatment and their underlying mechanisms have not been reported to date.

Objective

This study aims to identify novel drugs against AML from sweet potato by integrating metabolomics analysis, network pharmacology, and experimental validation.

Methods

Firstly, ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was employed to analyze the major constituents in sweet potato. Then, nine active ingredients were selected for validation of their anti-leukemia effects. Subsequently, three of them underwent network pharmacology analyses and in vitro experimental verification. Finally, the anti-leukemia effect of cynaroside was further confirmed through in vivo experimental validation.

Results

Firstly, the flavonoid content of stem, leaves, flesh, and peel from 13 sweet potato cultivars was examined. The leaves of Nanshu 017 exhibited the highest flavonoid content of 2.27% dry weight (DW). Then, an extract derived from these leaves was employed for in vitro experiments, demonstrating significant inhibition of AML cell growth. Subsequently, based on the results of metabolomics analysis and network pharmacology, cynaroside, nepitrin, and yuanhuanin were identified as potential antileukemia agents present in sweet potato for the first time; while CASP3, KDR, EGFR, and SRC were recognized as pivotal targets of these three monomers against AML. Finally, the antileukemia effects of cynaroside, nepitrin, and yuanhuanin were confirmed through in vitro and in vivo experimental validation.

Conclusion

In summary, sweet potato leaves extract possesses an antileukemic effect while cynaroside, nepitrin, and yuanhuanin demonstrate potential as treatments for AML.
Harnessing the power of proteins in modulation of miRNAs for targeting Iron deficiency Anemia: Opinion for future implications and strategies
Authors: Wagiu Basrowi Ray , Sundjaya Tonny , Pratiwi Dessy , Amalia Nurlinah , Tandi Yosi Yohanes Putra , Syafa’atulloh Muhammad Yasir , Utomo Garuda Nusantara Putra , Albarok Muhammad Abdir Rahman , Nurkolis Fahrul
Published: January 2025

Iron Deficiency Anemia (IDA) remains a pervasive global health challenge, disproportionately affecting vulnerable populations such as women and children. This review explores the cutting-edge interplay between microRNAs (miRNAs) and proteins in erythropoiesis, highlighting novel therapeutic strategies for IDA. Emerging evidence underscores the pivotal role of miRNAs—such as miR-15a, miR-24, miR-150, and miR-223—in regulating erythropoiesis, with dysregulation linked to hematologic and systemic diseases. Proteins, acting as modulators of miRNA activity, present innovative pathways for intervention by influencing erythropoiesis at multiple stages, from stem cell proliferation to red blood cell maturation. Our synthesis highlights key molecular mechanisms: miR-15a suppresses erythropoiesis by inhibiting c-Myb, miR-24 impairs heme biosynthesis through ALK4 regulation, while miR-150 and miR-223 modulate critical hematopoietic pathways affecting cell differentiation and apoptosis. These miRNA-protein interactions suggest targeted therapies such as protein-based miRNA modulators could optimize erythropoiesis, advancing IDA management. Additionally, the review emphasizes the potential of leveraging protein-miRNA interactions for precision medicine, especially in resource-limited settings where anemia’s burden is profound. By bridging current knowledge gaps, our proposed strategies offer personalized and scalable therapeutic solutions. This comprehensive perspective lays the groundwork for future interventions addressing one of the world’s most widespread public health crises.
An MRI radiomics model for predicting a prostate-specific antigen response following abiraterone treatment in patients with metastatic castration-resistant prostate cancer
Authors: Wu Yi , Liu Xiang , Chen Shaoxian , Fang Fen , Shi Feng , Xia Yuwei , Yang Zehong , Lin Daiying
Published: January 2025

Objective

To establish a combined radiomics-clinical model for the early prediction of a prostate-specific antigen(PSA) response in patients with metastatic castration-resistant prostate cancer(mCRPC) after treatment with abiraterone acetate(AA).

Methods

The data of a total of 60 mCRPC patients from two hospitals were retrospectively analyzed and randomized into a training group(n=48) or a validation group(n=12). By extracting features from biparametric MRI, including T2-weighted imaging(T2WI), diffusion-weighted imaging(DWI), and apparent diffusion coefficient(ADC) maps, radiomics features from the training dataset were selected using least absolute shrinkage and selection operator(LASSO) regression. Four predictive models were developed to assess the efficacy of abiraterone in treating patients with mCRPC. The primary outcome variable was the PSA response following AA treatment. The performance of each model was evaluated using the area under the receiver operating characteristic curve(AUC). Univariate and multivariate analyses were performed using Cox regression to identify significant predictors of the efficacy of abiraterone treatment in patients with mCRPC.

Results

The integrated model was constructed from seven radiomics features extracted from the T2WI, DWI, and ADC sequence images of the training data. This model demonstrated the highest AUC in both the training and validation cohorts, with values of 0.889 (95% CI, 0.764-0.961) and 0.875 (95% CI, 0.564-0.991). The Rad-score served as an independent predictor of the response to abiraterone treatment in patients with mCRPC (HR: 2.21, 95% CI: 1.01-4.44).

Conclusion

The biparametric MRI-based radiomics model has the potential to predict the PSA response in patients with mCRPC following abiraterone treatment.

Clinical relevance statement

The MRI-based radiomics model could be used to noninvasively identify the AA response in mCRPC patients, which is helpful for early clinical decision-making.
Artificial intelligence in high-dose-rate brachytherapy treatment planning for cervical cancer: a review
Authors: Shi Junyue , Chen Jun , He Gaokui , Peng Qinghe
Published: January 2025

Cervical cancer remains a significant global health concern, characterized by high morbidity and mortality rates. High-dose-rate brachytherapy (HDR-BT) is a critical component of cervical cancer treatment, requiring precise and efficient treatment planning. However, the process is labor-intensive, heavily reliant on operator expertise, and prone to variability due to factors such as applicator shifts and organ filling changes. Recent advancements in artificial intelligence (AI), particularly in medical image processing, offer significant potential for automating and standardizing treatment planning in HDR-BT. This review examines the progress and challenge of AI applications in HDR-BT treatment planning, focusing on automatic segmentation, applicator reconstruction, dose calculation, and plan optimization. By addressing current limitations and exploring future directions, this paper aims to guide the integration of AI into clinical practice, ultimately improving treatment accuracy, reducing preparation time, and enhancing patient outcomes.
Supraclavicular lymph node metastasis in esophageal carcinoma: a topic of ongoing controversy
Authors: Zhang Bowen , Zhang Huan , Chen Yu , Xia Wanli , Wang Yichun
Published: January 2025

Lymph node metastasis is an important prognostic factor in esophageal carcinoma (EC). Currently, there are no consensus-based staging methods for EC with supraclavicular lymph node (SCLN) metastasis. In this review, we present a summary of several classification methods of the SCLNs and highlight their differences in anatomic definitions. Then, we analyze the lymphatic drainage of the SCLNs from esophagus and the distribution patterns of the SCLNs metastasis from EC. Moreover, we discuss the prognostic influence and different staging methods of the SCLN metastasis. In summary, the variations in different classification methods make the SCLNs confusing for clinical application. A standardized and precise definition of the SCLNs should be established urgently for EC. SCLNs can drain lymphatics at various levels of the esophagus, even from the intramural esophagus directly. Therefore, the SCLNs can be metastatic in superficial EC and even become sentinel nodes. Metastatic SCLNs are usually located on the surface of the scalenus anterior muscle and near the venous angle. Increasing pieces of evidence have shown that patients with SCLN metastasis have similar survival than those with regional lymph node metastasis and better survival than those with organ metastasis, which bring challenges to current staging methods.
Following intravenous thrombolysis, the outcome of diabetes mellitus associated with acute ischemic stroke was predicted via machine learning
Authors: Liu Xiaoqing , Wang Miaoran , Wen Rui , Zhu Haoyue , Xiao Ying , He Qian , Shi Yangdi , Hong Zhe , Xu Bing
Published: January 2025

This cohort study aimed to evaluate the prognostic outcomes of patients with acute ischemic stroke (AIS) and diabetes mellitus following intravenous thrombolysis, utilizing machine learning techniques. The analysis was conducted using data from Shenyang First People’s Hospital, involving 3,478 AIS patients with diabetes who received thrombolytic therapy from January 2018 to December 2023, ultimately focusing on 1,314 patients after screening. The primary outcome measured was the 90-day Modified Rankin Scale (MRS). An 80/20 train-test split was implemented for model development and validation, employing various machine learning classifiers, including artificial neural networks (ANN), random forest (RF), XGBoost (XGB), and LASSO regression. Results indicated that the average accuracy of the XGB model was 0.7355 (±0.0307), outperforming the other models. Key predictors for prognosis post-thrombolysis included the National Institutes of Health Stroke Scale (NIHSS) and blood platelet count. The findings underscore the effectiveness of machine learning algorithms, particularly XGB, in predicting functional outcomes in diabetic AIS patients, providing clinicians with a valuable tool for treatment planning and improving patient outcome predictions based on receiver operating characteristic (ROC) analysis and accuracy assessments.
Inhibition of high glucose-induced cardiac fibroblast activation: an effective treatment for diabetic cardiomyopathy using Chinese herbal medicine
Authors: Wan Bin , Hu Jing , Luo Yue , Han Yutong , Zhang Yaowen , Huang Qinchuan , Leng Yulin , Xie Chunguang
Published: January 2025

Diabetic cardiomyopathy (DCM) is one of the common diabetic microangiopathy in clinical practice. In the early stage of the disease, there are no obvious clinical symptoms. In the middle and late stages, MF, arrhythmia, and even heart failure may occur, affecting the life and health of patients. MF, as one of the pathological features of DCM at the end stage, is the key factor of poor prognosis leading to ventricular wall stiffness and heart failure, which affects the clinical process and outcome of patients. The development of MF in a high glucose environment involves multiple complex fibrogenic pathways that work together to activate fibroblasts, thereby promoting MF. Indeed, aberrant activation of cardiac fibroblasts (CFs) is a key factor in MF. Therefore, inhibiting the activation of CFs may become a new strategy for the treatment of DCM. Previous studies have shown that Chinese herbal medicine (CHM) has potential in the treatment of DCM. In this review, we first introduced the physiology and function of CFs and discussed the conditions for the pathological activation of CFs in the process of diabetes, and then systematically summarized the effects of CHM on the activation of CFs by controlling the production of advanced glycosylation end products, oxidative stress and inflammation. This review will illustrate the potential of CHM to inhibit the activation of CFs and provide new ideas for the treatment of DCM.
The mutation atlas of giant kelp (Macrocystis pyrifera): a mutation database resource for natural knockouts
Authors: Diesel Jose Francisco , Molano Gary , Nuzhdin Sergey V.
Published: January 2025

Giant kelp (Macrocystis pyrifera) is a paramount species of immense ecological and economic importance. It forms dense underwater forests, providing crucial habitat and serving as a foundation species for diverse marine ecosystems. Understanding the genetics of giant kelp is essential for conservation and sustainable farming, safeguarding these valuable ecosystems and their benefits. By analyzing mutations based on their impact, we can gain insights into the potential functional consequences and implications for the organism, helping to identify critical genes or regions that may play a significant role in adaptation, development, and environmental response. To achieve this, we annotated the effects and impact of spontaneous mutations in 559 giant kelp individuals from four different populations. We found over 15.9 million mutations in genes of giant kelp, and classified them into modifier, low, moderate, and high impact depending on their predicted effects. The creation of this mutation effect database, attached to the seedbank of these individuals, offers several applications, including enhancing breeding programs, aiding genetic engineering with naturally occurring mutations, and developing strategies to mitigate the impact of environmental changes.
Interaction between arbuscular mycorrhizal fungi and dark septate endophytes in the root systems of Populus euphratica and Haloxylon ammodendron under different drought conditions in Xinjiang, China
Authors: Wang Huimei , Wang Hengfang , Wei Shengtao , Sun Li , Cheng Linlin
Published: January 2025

Background and Aims

Arbuscular mycorrhizal fungi (AMF) and dark septate endophytes (DSE) are known to enhance the tolerance of host plants to biotic and abiotic stresses, but the mechanism of their interaction under natural conditions has not been extensively studied.

Methods

We analyzed the endophytic fungal diversity and colonization characteristics in the typical desert plants Populus euphratica and Haloxylon ammodendron and the relationship between them and environmental factors.

Results

Except for DSE in the roots of H. ammodendron, the colonization rates of AMF and DSE were significantly positively correlated with drought severity. The abundance of AMF and DSE under medium and mild drought conditions was greater than that under severe drought conditions. The root colonization rate and abundance of AMF were lower than those of DSE under the same drought conditions. The species diversity and abundance of AMF and DSE in P. euphratica were greater than those in H. ammodendron. AMF were more susceptible to soil factors such as soil water content, soil nitrogen and phosphorus content, and urease, whereas DSE were more affected by pH.

Conclusion

Drought stress has different effects on AMF and DSE in the roots of P. euphratica and H. ammodendron. DSE have a greater advantage in extremely arid environments. This study demonstrates the interaction between AMF and DSE with the host plants P. euphratica and H. ammodendron as well as their effects on the adaptation of host plants to the desert environment, which can provide a basis for strengthening desert vegetation management.