bluuebunny/crossref_metadata_2025 huggingface dataset:
Pemanfaatan pelepah pisang sebagai inovasi keripik sehat dan ramah lingkungan
Authors: Pido Rifaldo , Ilolu Jeremy Mohamad , Hamzah Elsa Risti , Hintalo Indrawati , Arapa Sri Nurhayati , Husain Mirlan
Published: February 2025

Utilizing banana stem waste into a snack known as "Upaso Sagi" is an innovation in the field of community empowerment in Buata Village, Atinggola District, North Gorontalo Regency. This activity aims to provide a solution to the problem of organic waste, as well as improve community welfare through training in making chips from banana stems. This training was attended by local residents, with a focus on techniques for processing banana stems into value-added products that are suitable for consumption. The results of this activity show an increase in community skills and knowledge in processing waste into marketable products, thereby providing a positive impact on the local economy. In addition, this program also contributes to reducing organic waste in the region. Thus, it is hoped that this initiative can become a model for environmental and economic-based community empowerment efforts in other regions.
Effectiveness of Back Massage Acupressure for Treating Dysmenorrhea
Authors: Purwanto Triana Septianti , Fatmayati Feby Angzila , Rahayu Tri Kurnia
Published: February 2025

Background: Back massage acupressure is a natural complementary technique that minimizes side effects and can be administered to teenage girls experiencing dysmenorrhea. This technique was performed during the menstrual cycle, specifically from the 1st to the 3rd day, administered once a day for approximately 30 minutes. The novelty of the study lies in the complementary combination of a back massage and acupressure to reduce menstrual pain. This study aimed to analyze the effectiveness of back massage acupressure in reducing the intensity of pain and the duration of dysmenorrhea. Methods: A quasi-experimental study with a pretest-posttest control group design was conducted on 60 teenage girls in the Magetan district. Systematic random sampling was used to select 30 respondents for both the intervention and control groups. Data were obtained from observations and interviews with respondents regarding the intensity of pain and duration of dysmenorrhea. Results: Back mass acupressure effectively reduces the intensity of dysmenorrhea pain from the 1st to 3rd day (p-value= 0.000) and shortens the duration of dysmenorrhea (p-value <0.05), thereby improving adolescent reproductive health. Conclusions: Back massage acupressure is a simple, cost-effective, and minimally invasive solution for managing dysmenorrhea. This innovative technique has been proven highly effective in reducing both the intensity of pain and the duration of dysmenorrhea. It is recommended for use among teenage girls to promote better reproductive health.
Reliable machine learning models in genomic medicine using conformal prediction
Authors: Papangelou Christina , Kyriakidis Konstantinos , Natsiavas Pantelis , Chouvarda Ioanna , Malousi Andigoni
Published: February 2025

Machine learning and genomic medicine are the mainstays of research in delivering personalized healthcare services for disease diagnosis, risk stratification, tailored treatment, and prediction of adverse effects. However, potential prediction errors in healthcare services can have life-threatening impact, raising reasonable skepticism about whether these applications have practical benefit in clinical settings. Conformal prediction offers a versatile framework for addressing these concerns by quantifying the uncertainty of predictive models. In this perspective review, we investigate potential applications of conformalized models in genomic medicine and discuss the challenges towards bridging genomic medicine applications with clinical practice. We also demonstrate the impact of a binary transductive model and a regression-based inductive model in predicting drug response as well as the performance of a multi-class inductive predictor in addressing distribution shifts in molecular subtyping. The main conclusion is that as machine learning and genomic medicine are increasingly infiltrating healthcare services, conformal prediction has the potential to overcome the safety limitations of current methods and could be effectively integrated into uncertainty-informed applications within clinical environments.
Computational evaluation of the biomechanical effects of position changes in the femoral neck system on Pauwels type III femoral neck fractures: an in silico study
Authors: Zhang Xiang , Zhang Shenghang , Zhong Zhou , Zhang Wen , Xiong Zhongwei
Published: February 2025

Introduction

Despite the biomechanical advantages of the Femoral Neck System (FNS), improvements in postoperative complication rates have not been significant. This study evaluated the effects of different FNS positions on the biomechanical stability of Pauwels type III femoral neck fractures (FNFs) using finite element analysis (FEA).

Methods

Pauwels type III FNF models fixed with different FNS positions were constructed using various bolt lengths, bolt positions, and axis–bolt angles. Biomechanical parameters, including stiffness, maximum implant von Mises stress (MIVS), maximum interfragmentary shear stress (MISS), and maximum interfragmentary gap (MIG), were analyzed by simulating early postoperative weight-bearing. Entropy scoring was used to rank the performance of different fixation positions to determine the optimal FNS implantation position.

Results

Compared with that of the standard model, the biomechanical stability changed when FNS positioning was altered. Among all the evaluated parameters, MIG had the highest weight (60.04%). In the lateral view, fracture fixation was most stable when the bolt was rotated 5° anteriorly relative to the femoral neck axis (composite score = 0.87). However, stability was poorer when the bolt was rotated 9° inward relative to the femoral neck axis (composite score = 0.13).

Discussion

The MIG is an important biomechanical parameter for assessing the stability of different FNS positions when treating FNFs. Shortening the distance between the bolt and the subchondral bone, upward movement, external rotation, and anterior rotation of the bolt can help improve the stability of the FNS in the treatment of Pauwels III FNFs.
Autophagy: regulating the seesaw of bone–fat balance
Authors: Zhang Boya , Cui Jing , Zhang Xu , Pan Ziyi , Du Liuyi , Ye RongRong , Wen Linlin , Zhai Wenhao , Huang Lei , Li Daowei , Sun Hongchen
Published: February 2025

The interrelationship between bone and fat can be described as a seesaw in bone homeostasis, in which both osteogenesis and adipogenesis occur in a delicate balance. Osteoblasts and adipocytes share a common origin and play key roles in osteogenesis and adipogenesis. Bone–fat balance indicates osteogenesis and adipogenesis keeps a balance for concordant distribution of trabecular bone and bone marrow adipose tissue in bone, thereby leading to the balance between bone metabolism and lipid metabolism. Bone–fat balance is crucial for metabolic health. When disrupted by various factors, this balance can lead to several bone-related metabolic diseases and systemic disorders, such as obesity, osteoporosis, and osteoarthritis. Recent research highlights the role of autophagy dysfunction in these metabolic conditions. Restoring autophagic function can help restore metabolic homeostasis and re-establish the bone–fat balance. The current review explores the factors that regulate bone–fat balance, the consequences of imbalance under pathological conditions, and the potential of autophagy modulation as a therapeutic approach. Overall, it can be concluded that targeting autophagy presents a promising strategy for treating metabolic disorders and restoring bone–fat balance.
Drug resistance mutations to integrase inhibitors, proteinase, and reverse transcriptase inhibitors in newly diagnosed HIV-1 infections in Hebei province, China, 2018–2022
Authors: Lu Xinli , Li Yan , Liu Meng , Wang Yingying , An Ning , Sun Dandan , Li Qi
Published: February 2025

Background

HIV-1 protease (PR)-reverse transcriptase (RT) inhibitors as national free antiretroviral drugs have been used for 20 years. Integrase strand transfer inhibitors (INSTIs) have been conditionally used as a component of HIV/AIDS treatment regimens in recent years. However, the systematic investigation on the changes in primary drug resistance (PDR) in Hebei province, China was limited.

Methods

A continuous cross-sectional investigation on HIV-1 PDR was conducted, integrating detection of drug resistance genotype, molecular network, and statistical analysis.

Results

The overall prevalence of PDR was 8.3%, with 77 of 925 samples showing different levels of resistance to INSTIs (1.9%), protease inhibitors (PIs, 0.2%), nucleoside reverse transcriptase inhibitors (NRTIs, 1.2%), and non-NRTIs (NNRTIs, 5.2%). In the PR-RT gene coding region, E138EK/G was the most common (1.6%), followed by K103N (1.4%), G190GE/A/S (0.6%), K101E (0.5%), A98G (0.4%), and T215I/TS (0.3%), associated with the low- to high-level resistance to doravirine (DOR), efavirenz (EFV), etravirine (ETR), nevirapine (NVP), rilpivirine (RPV), and zidovudine (AZT). In the INSTI gene coding region, six mutations were identified, namely, four major mutations (P145PS, Q148QH, Y143S, and T66A) and two accessory mutations (S153SF and G163GRS/EK). Of these mutations, the most frequent INSTI mutations were S153SF (0.6%) and G163GRS/EK (0.6%), followed by P145PS (0.2%), Y143S (0.2%), Q148QH (0.1%), and T66A (0.1%). G163GRS/EK, P145PS, Y143S, and T66A were associated with the resistance to elvitegravir (EVG) and raltegravir (RAL). S153SF and Q148QH were mainly related to the resistance to dolutegravir (DTG), bictegravir (BIC), and caboteravir (CAB). Furthermore, 30 resistant sequences were circulating in 16 transmission networks with HIV-1 DR mutations (DRMs), accounting for 62.5% of 77 total participants with DRMs. Multivariable analysis showed that those who had CRF07_BC had 1.79 times greater odds of PDR compared with participants with CRF01_AE. Compared to participants with volunteer blood donor, those with voluntary consultation and testing had 0.27 times greater odds of PDR.

Conclusions

The overall prevalence of HIV-1 PDR in Hebei is high, belonging to a moderate resistant level (5.0%–15.0%). It is necessary for us to strengthen the effective surveillance of PDR among treatment-naive patients, and we should adjust the treatment plan according to the results of PDR surveillance.
Case Report: A usual procedure in an unusual situation: a patient with a rare Ehlers Danlos/osteogenesis imperfecta overlap undergoing aortic valve replacement
Authors: Nunez-Ordonez Nicolas , Amado-Olivares Andrés F. , Jimenez-Ordonez Andrés F. , Obando Carlos , Chalela Tomas , Senosiain Julián , Sandoval Nestor , Camacho-Mackenzie Jaime , Villa-Hincapié Carlos
Published: February 2025

Connective tissue disorders are known to cause cardiac and vascular complications. We present the case of a 37-year-old female patient with a rare Ehlers Danlos/Osteogenesis Imperfecta Overlap Syndrome, referred to cardiac surgery with aortic valve regurgitation, who underwent a successful Biological Surgical Aortic Valve Replacement (SAVR). A multidisciplinary, patient-centered, heart-team approach is essential in managing patients with rare genetic disorders to optimize postoperative outcomes. Adult cardiac surgeons must become familiar with genetic syndromes and their implications for improving perioperative outcomes.
Intraprocedural activated clotting time and heparin dosage in pulsed field ablation of paroxysmal atrial fibrillation
Authors: Ma Chengming , Xiao Xianjie , Chen Qian , Li Wenwen , Wang Zhongzhen , Dai Shiyu , Sun Yuanjun , Xia Yunlong , Gao Lianjun , Yin Xiaomeng
Published: February 2025

Aims

Whether the intraprocedural anticoagulation regimen and activated clotting time (ACT) in pulsed field ablation (PFA) for atrial fibrillation (AF) are the same as those for radiofrequency catheter ablation (RFCA) is currently unknown.

Methods and results

Our retrospective study included 51 paroxysmal AF patients who underwent PFA (PFA group) and were matched with paroxysmal AF patients who underwent RFCA. Nearest-neighbor propensity score matching was performed at a 1:1 ratio (no tolerance to anticoagulant regimens and a tolerance of 0.02 on the CHA2DS2-VASc score, left atrial diameter, and left ventricular ejection fraction). Compared with the RFCA group, the PFA group had a significantly shorter procedure time but a longer fluoroscopy time. In both groups, an initial heparin dose of 110 U/kg was given. The 30-min ACT in the PFA group (240 ± 95.5 s) was shorter than that in the RFCA group (294.4 ± 82.3 s, P = 0.003). The 60-, 90-, and 120-min ACTs were significantly longer in the PFA group. The percentage of 30 min-ACTs in the therapeutic range in the RFCA group (33.3%) was greater than that in the PFA group (15.7%, P = 0.038). The time to achieve the target ACT was longer in the PFA group. There were no differences in the incidence of periprocedural thromboembolism or bleeding events between the two groups.

Conclusions

Compared with RFCA, PFA was associated with longer intraprocedural ACTs, shorter initial ACTs, fewer initial ACTs in the therapeutic range, and longer times to achieve the target ACT.
Late Holocene Indian summer monsoon evolution and centennial fluctuations inferred by grain-size sensitive component from Lake MangCo, southeastern Tibetan Plateau
Authors: Ning Dongliang , Sun Weiwei , Wan Dejun , Cheng Longjuan , Jiang Qingfeng
Published: February 2025

Identifying the late Holocene Indian summer monsoon (ISM) changes and their possible forcing mechanisms provides an important perspective for understanding the current monsoon shifts driven by anthropogenic climate change within a natural baseline. In this study, we present a well-dated, ca. 4.0 ka grain-size sensitive component record from Lake MangCo, located in the southeastern Tibetan Plateau. The record depicts late Holocene ISM evolution and centennial-scale precipitation events superimposed on millennial-scale climate changes. The results indicate that precipitation was relatively high during the first half of the late Holocene, likely before 2.0 cal ka BP, followed by a period of relatively reduced precipitation thereafter, which indicates that the Northern Hemisphere summer insolation (NHSI) has primarily controlled ISM intensity. A slight increasing trend in ISM strength since 1.1 cal ka BP was observed, which may correspond to the reported “2.0-kyr-shift” and could be related to warming tropical temperatures. Three low precipitation intervals, occurring at ∼1.1, 2.0, and 3.2 cal ka BP, align well with known centennial-scale ISM weakening events during the late Holocene, such as the Medieval Warm Period (MWP) and the “2.0-ka-dry-event.” Our findings further validate the climatic effects of tropical ocean–atmospheric interactions in the Pacific and Indian Ocean basins on ISM variabilities at centennial timescales.
Situating the “human” in forest landscape restoration
Authors: Mansourian Stephanie , Djenontin Ida N. S. , Elias Marlène , Oldekop Johan A. , Derkyi Mercy Afua Adutwumwaa , Kull Christian A. , Pacheco Pablo
Published: February 2025

Globally, forest landscape restoration (FLR) is gaining ground, alongside other forms of restoration under the UN Decade on Ecosystem Restoration. In most cases, projects and initiatives fail to consider human dimensions that influence the processes and outcomes of the restoration effort. These dimensions refer to how and why humans value natural resources; how humans want resources to be managed; and how humans affect or are affected by natural resource management decisions. Using the model of the forest transition curve that shows the trajectory from loss of forests to restored forests, we discuss how FLR intersects in different ways with this transition curve. We conclude that: 1) definitions and their implications are a fundamental challenge for FLR; 2) there is an intrinsic interdependence between people and forests that varies across spatial and temporal scales and that is mediated by institutions; 3) power differentials among stakeholders create imbalances in restoration; 4) conflicts around restoration result from differing interests, power and values. Equitable and durable restoration requires a much greater inclusion of human dimensions along all steps of the process.
First report of the emerging pathogenic yeast Candida palmioleophila in commercially relevant fish from southeastern Brazil
Authors: Oliveira Manoel M. E. , Lima Viviane Felix Moraes , Costa Gisela Lara da , Baptista Barbara de Oliveira , Augusto Julia Auad , Hauser-Davis Rachel Ann
Published: February 2025

The emerging fungal pathogen Candida palmioleophila (C. palmioleophila) has been increasingly detected in environmental and animal samples, although studies in this regard are still scarce, especially in fisheries contexts. This study reports the first-time detection of C. palmioleophila in a commercially relevant fish species belonging to the Sciaenidae family (Cynoscion sp.), indicating its potential emergence as a pathogen in Brazil. We applied CHROMagar Candida Plus medium identification associated to Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) for the identification of C. palmioleophila isolates. Although only one fish specimen was shown to be contaminated by C. palmioleophila, this study provides the first evidence of this yeast circulating in commercially relevant fish species in Brazil, highlighting the potential risks associated with this emerging pathogen.
Update on tocilizumab in rheumatoid arthritis: a narrative review
Authors: Parisi Simone , Ditto Maria Chiara , Ghellere Francesco , Panaro Salvatore , Piccione Francesca , Borrelli Richard , Fusaro Enrico
Published: February 2025

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint pain, swelling, and stiffness, affecting approximately 1% of the adult population. Tocilizumab (TCZ), a monoclonal antibody targeting the IL-6 receptor, has emerged as an effective treatment for RA. This narrative review provides an update on TCZ’s efficacy and safety based on data from randomized controlled trials (RCTs) and real-world evidence (RWE). TCZ, available in subcutaneous (SC) and intravenous (IV) formulations, has shown significant benefits in RA management. Key clinical trials, including SAMURAI, OPTION, RADIATE, and TOWARD, have demonstrated TCZ’s efficacy as monotherapy and in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), particularly in patients with inadequate responses to methotrexate or TNF inhibitors. Long-term studies, such as STREAM, have highlighted TCZ’s sustained efficacy and favorable safety profile over 5 years. The impact of TCZ on cardiovascular health, lipid profiles, and the risk of infections has been a focal point, with findings suggesting no significant increase in cardiovascular disease risk compared to other RA therapies. RWE further highlights the effectiveness of TCZ, identifying predictors of response, such as age, and emphasizes its suitability for biologic-naïve and overweight patients. Special considerations include TCZ use in RA-associated interstitial lung disease and amyloidosis. Overall, TCZ remains a pivotal option in RA treatment, with a well-established safety and efficacy profile supported by extensive clinical and real-world data.
Survival benefits of postoperative radiotherapy in esophageal cancer during the immunotherapy era:a retrospective cohort study based on the SEER database and a single-center registry in China
Authors: Zhang Qian , Zhang Tao , Gu Jiaqi , Zhang Xuemei , Mao Yuxin , Zhu Yingying , Zhang Jin , Wang Jingyi , Chen Shuyang , Cao Yang , Wang Muhong , Wang Chunbo
Published: February 2025

Purpose

The aim of this study was to investigate the survival benefits of postoperative radiotherapy (PORT) in patients with resectable esophageal cancer (EC) after neoadjuvant therapy in the Immunotherapy era.

Methods

The study was designed as a retrospective cohort study, which included a total of 733 patients with EC from the SEER database and a single-center cohort. We used propensity score matching (PSM) to equilibrate patient characteristics. The investigation incorporated Kaplan-Meier survival analysis and the Cox proportional risk regression model to assess outcomes.

Results

PORT did not significantly improve survival in the overall cohort, with a median overall survival of 38 months (p=0.56) in the SEER cohort and 39 months (p=0.75) in the Chinese cohort. However, in the immunotherapy subgroup, the Chinese cohort demonstrated that immunotherapy combined with PORT significantly improved survival (p=0.044).Multivariate Cox regression analysis demonstrated that patients aged 50-59 years (HR=5.93, 95% CI: 1.67-21.06) and those aged ≥70 years (HR=10.96, 95% CI:3.04-39.56) had increased survival risks compared to patients aged <50 years. Additionally, ypT3-4 stage patients exhibited a higher risk than those with ypT1-2 stage (HR=2.12, 95% CI: 1.14-3.93, p=0.017).Similar trends were observed in cT3-4 staging, R1/R2 and no immunotherapy. Lymph node metastasis also showed a progressive relationship with survival risk, with patients categorized as ypN1 (HR=1.90), ypN2 (HR=4.24), and ypN3 (HR=6.68) experiencing increasingly higher risks (p<0.05).

Conclusions

The collaborative effect of immunotherapy and PORT potentially enhances survival outcomes for patients with EC. However, further prospective research is essential to confirm our results.
Integrated multiomics analysis and machine learning refine neutrophil extracellular trap-related molecular subtypes and prognostic models for acute myeloid leukemia
Authors: Zhong Fangmin , Yao Fangyi , Wang Zihao , Liu Jing , Huang Bo , Wang Xiaozhong
Published: February 2025

Background

Neutrophil extracellular traps (NETs) play pivotal roles in various pathological processes. The formation of NETs is impaired in acute myeloid leukemia (AML), which can result in immunodeficiency and increased susceptibility to infection.

Methods

The gene set variation analysis (GSVA) algorithm was employed for the calculation of NET score, while the consensus clustering algorithm was utilized to identify molecular subtypes. Weighted gene coexpression network analysis (WGCNA) revealed potential genes and biological pathways associated with NETs, and a total of 10 machine learning algorithms were applied to construct the optimal prognostic model.

Results

Through the analysis of multiomics data, we identified two molecular subtypes with high and low NET scores. The low-NET score subgroup exhibited increased infiltration of immune effector cells. Conversely, the high-NET score subtype presented an abundance of monocytes and M2 macrophages, accompanied by elevated expression levels of immune checkpoint genes. These findings suggest that a pronounced immunosuppressive effect is associated with a significantly worse prognosis for this subtype. The optimal risk score model was selected by employing the C-index as the criterion on the basis of training 10 machine learning algorithms on 9 multicenter AML cohorts. Survival analysis confirmed that patients with high-risk scores had considerably poorer prognoses than those with lower scores. Receiver operating characteristic (ROC) curve and Cox regression analyses further validated the strong independent prognostic value of the risk score model. The nomogram, which was constructed by integrating the risk score model and clinicopathological factors, demonstrated high accuracy in predicting the overall survival of AML patients. Moreover, patients with refractory or chemotherapy-unresponsive AML had significantly higher risk scores. By analyzing drug therapy data from in vitro AML cells, we identified a subset of drugs that demonstrated increased sensitivity in the high-risk score group. Additionally, patients with a high risk score were also predicted to exhibit a favorable response to anti-PD-1 therapy, suggesting that these individuals may derive greater benefits from immunotherapy.

Conclusion

The NET-related signature, derived from a combination of diverse machine learning algorithms, has promising potential as a valuable tool for prognostic prediction, preventive measures, and personalized medicine in patients with AML.
Somatic mutations in Brazilian patients with paroxysmal nocturnal hemoglobinuria: a comprehensive analysis
Authors: Eiko Yamakawa Patricia , Perez Gomes Caio , Ribeiro Mendes Agatha , Cesar Justino de Oliveira Caio , Porto Freitas Florencio , Bettoni Fabiana , Xavier dos Santos Ernande , Campos de Molla Vinicius , Vescovi Gonçalves Matheus , Branquinho Jessica , Ribeiro Nogueira Beatriz , Bosco Pesquero Joao , Arrais-Rodrigues Celso
Published: February 2025

Background

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal hematopoietic stem cell disease characterized by acquired abnormalities in the phosphatidylinositol glycan class A (PIG-A) gene.

Methods

This study analyzed PIG-A gene using polymerase chain reaction (PCR) followed by Sanger sequencing of 31 Brazilian patients with PNH, including 23 with classical PNH and 8 with subclinical PNH (aplastic anemia and a PNH clone).

Results

A diverse spectrum of acquired PIG-A variants was identified, encompassing insertions, deletions, and single-base substitutions. The majority of variants identified (17 out of 29) were deemed likely pathogenic for paroxysmal nocturnal hemoglobinuria (PNH). Six variants have undetermined significance (VUS) and six variants are probably benign. Somatic variants exhibited variability in type and location among the patients, with a predominance of small deletions and simple base changes. Notably, 41% of the variants were frameshift and 35% were missense. Among the 23 patients with hemolytic PNH, 19 had at least one detectable pathogenic variant. Subclinical PNH cases were characterized solely by polymorphisms.

Conclusion

In conclusion, the somatic variants in Brazilian PNH patients displayed variability in both site distribution and type. Contrary to mutational hotspots observed in previous studies, none were identified in this cohort. No specific correlation between the clinical characteristics of hemolytic PNH patients and their variants was found, likely due to the extensive variety of mutations.
Development and validation of a dynamic nomogram for acute kidney injury prediction in ICU patients with acute heart failure
Authors: Feng Lu-Huai , Su Tingting , Huang Lina , Liao Tianbao , Lu Yang , Wu Lili
Published: February 2025

Objective

Developing and validating a simple and clinically useful dynamic nomogram for predicting early acute kidney injury (AKI) in patients with acute heart failure (AHF) admitted to the intensive care unit (ICU).

Methods

Clinical data from patients with AHF were obtained from the Medical Information Mart for Intensive Care IV database. The patients with AHF were randomly allocated into derivation and validation sets. The independent predictors for AKI development in AHF patients were identified through least absolute shrinkage and selection operator and multivariate logistic regression analyses. A nomogram was developed based on the results of the multivariable logistic regression to predict early AKI onset in AHF patients, which was subsequently implemented as a web-based calculator for clinical application. An evaluation of the nomogram was conducted using discrimination, calibration curves, and decision curve analyses (DCA).

Results

After strict screening, 1,338 patients with AHF were included in the derivation set, and 3,129 in the validation set. Sepsis, use of human albumin, age, mechanical ventilation, aminoglycoside administration, and serum creatinine levels were identified as predictive factors for AKI in patients with AHF. The discrimination of the nomogram in both the derivation and validation sets was 0.81 (95% confidence interval: 0.78–0.83) and 0.79 (95% confidence interval: 0.76–0.83). Additionally, the calibration curve demonstrated that the predicted outcomes aligned well with the actual observations. Ultimately, the DCA curves indicated that the nomogram exhibited favorable clinical applicability.

Conclusion

The nomogram that integrates clinical risk factors and enables the personalized prediction of AKI in patients with AHF upon admission to the ICU, which has the potential to assist in identifying AHF patients who would derive the greatest benefit from interventions aimed at preventing and treating AKI.
Robotic animals as new tools in rodent neuroscience research: proposed applications of zooinspired robots for mouse behavioral testing
Authors: d’Isa Raffaele
Published: February 2025

Bioinspired robots are machines which reproduce structural or functional features of a living organism. In particular, the bioinspired robots which reproduce features of animals can be more specifically defined as zooinspired robots. Currently, the applications of animal robots are various and range across different fields, such as, for instance, nature conservation, search and rescue of humans after natural or man-made disasters, exploration of extraterrestrial environments and robotic pets for elderly people under care for dementia. Several animal species have been imitated up to now, from lizards to butterflies, and from fish to dogs. Animal robots used to investigate the social behavior of an animal species through animal-robot interactions are called ethorobots. Intriguingly, ethorobots are able to reproduce in the laboratory behaviors that are generally produced spontaneously in nature and are difficult or impossible to evoke and modulate in captive animals, which makes these animal robots particularly useful tools for experimental ethology and ethological neuroscience. Rodents, primarily mice and rats, are the most common animal model in biomedical research. Coherently with the importance of these species for scientific research, robotic mice and rats have been attracting increasing efforts in bioinspired robotics over the course of the past five decades. The technological advancement of animal robots will make their employment for scientific research increasingly useful. However, clear experimental applications of animal robots should be identified in order to challenge engineers to design robots that can serve these experimental scopes. In the present work, we will describe possible practical applications of robotic animals for mouse behavioral testing across six different behavioral domains, namely courtship, parental care, antipredatory behavior, helping behavior, predation and territory defense-related aggression. In particular, we will outline how robotic animals could be employed to interact with living mice in a series of specific tests of social behavior. Finally, in the conclusion we will consider the ethical and epistemological advantages of the use of robotic animals in behavioral neuroscience. Indeed, robotic animals can benefit scientific research on social behaviors both in terms of optimized animal welfare of the tested subjects and of extended opportunities of experimental designing due to an unprecedented control over the independent variables.
The influence of circadian rhythm disruption during Ramadan on metabolic responses to physical activity: a pilot study
Authors: Anwardeen Najeha Rizwana , Naja Khaled , Almuraikhy Shamma , Sellami Maha , Al-Amri Hadaia Saleh , Philip Nebu , Tamimi Faleh , Agil Ahmed , Elrayess Mohamed A.
Published: February 2025

Background

Circadian rhythms and sleep patterns are important regulators of metabolic health. During Ramadan intermittent fasting (RIF), the sleep–wake cycles are often disrupted, which can affect physical activity (PA) and related metabolic responses. Limited knowledge is available on how sleep disruption influences PA in the general population during RIF. This pilot study aimed to examine the metabolic responses to moderate PA under normal and disrupted sleep patterns during RIF.

Methods

A pilot study was conducted on 12 participants comprising of individuals with normal (n = 5) and disrupted sleep patterns (n = 7). Blood samples were collected, and measurements of clinical traits, cytokines, homeostasis model assessment of insulin resistance (HOMA-IR) and metabolic profiles were performed before and after intervention. Orthogonal partial least square – discriminant analysis (OPLS-DA) and linear regressions were performed to assess metabolic responses to PA during RIF under different patterns.

Results and conclusion

Fasting participants with normal sleep patterns exhibited lower HOMA-IR (β = −0.416, p = 0.047) in response to PA compared to those with disrupted sleep. Additionally, they demonstrated more efficient lipid utilization during PA, characterized by reduced diacylglycerol levels, which could enhance insulin sensitivity and lower the risk of type 2 diabetes. In contrast, fasting participants with disrupted sleep patterns experienced metabolic stress, marked by significant depletion of polyunsaturated fatty acids (PUFAs), monounsaturated fatty acids (MUFAs), and plasmalogens in response to PA. These changes were associated with increased inflammation and oxidative stress, potentially leading to metabolic dysregulation.
Efficacy and safety of nanoparticle albumin-bound paclitaxel plus cisplatin or nedaplatin plus tegafur/gimeracil/oteracil as induction chemotherapy regimen for hypopharyngeal cancer
Authors: Jiang Cailing , Liu Yulan , Mo Yunyan , Xu Lieyin , Zhu Lin , Li Zhenya , Xu Shengyuan , Qin Xi , Wu Guangteng , Kang Mafei , He Xiaosong , Xue Feng
Published: February 2025

Background

Treatment of hypopharyngeal carcinoma involves surgery, radiotherapy, and chemotherapy. The combination of docetaxel, cisplatin, and 5-fluorouracil as a standard induction chemotherapy regimen allows enhanced laryngeal preservation after surgery. In this study, our objective was to retrospectively analyze the short-term efficacy and adverse events of nab-paclitaxel plus cisplatin or nedaplatin plus tegafur/gimeracil/oteracil as an induction chemotherapy regimen for hypopharyngeal cancer.

Methods

This retrospective study involved 19 patients who received nab-paclitaxel plus cisplatin/nedaplatin plus tegafur/gimeracil/oteracil every 21 days intervals for three cycles at the Affiliated Hospital of Guilin Medical University (December 2020 to February 2023). The primary endpoint was progression-free survival. Adverse events were assessed in all patients.

Results

Treatment response was evaluated after the second cycle. Clinical outcomes indicated that 2 (10.53%), 15 (78.94%), and 2 (10.53%) patients exhibited clinical complete response, partial response, and stable disease, respectively. The objective response and disease control rates were 89.47% (17/19) and 100%, respectively. The pathological complete response rate was 71.43% (5/7) among the seven patients who underwent surgery after three cycles. Following induction chemotherapy, 4 (21.05%), 2 (10.53%), and 2 (10.53%) patients received radiotherapy, chemotherapy, and chemotherapy plus immunotherapy, respectively, whereas 4 (21.05%) patients discontinued treatment. At the 17.43-month median follow-up, median progression-free survival was 17.6 months (95% confidence interval, 13.9-21.2). The most common grade 3 treatment-related adverse events were alopecia (36.8%), leukopenia (26.3%), and anemia (15.8%). No grade 4/5 treatment-emergent adverse events were observed.

Conclusions

The combination of nab-paclitaxel, cisplatin/nedaplatin, and tegafur/gimeracil/oteracil is a safe induction chemotherapy for treating hypopharyngeal cancer.
Parent-identified intrinsic and extrinsic factors that influence performance across developmental domains and participation in their communities
Authors: Bican Rachel , Shaffer Sydney , Kinkade Jayna , McAdams Quinn , Hughes Allyson S.
Published: February 2025

Children with neurodevelopmental disabilities living in rural and low-resourced regions within the United States, such as Appalachia, face gaps and barriers to accessing healthcare services due to a shortage of providers, specialists, hospitals, and clinics. Without access to specialized medical and rehabilitation services, their performance across developmental domains and participation within their communities is likely suboptimal. The purpose of this study was to identify both intrinsic and extrinsic factors using a mixed-methods approach to better understand factors that may impact performance across developmental domains and participation for children with disabilities living in Appalachia. Parents completed one study visit in which they completed a total of 4 surveys and a semi-structured interview. The surveys included a parent survey (demographic information, medical history for the child, and barriers to receiving healthcare for their child), health literacy screen, the F-Words Life Wheel, and the Pediatric Evaluation of Disability Inventory (PEDI-CAT). The semi-structured interview asked questions in five primary categories: (1) background, (2) understanding of their child's medical diagnosis and management of their disability, (3) insurance coverage, (4) barriers to receiving healthcare, and (5) social support. This cross-sectional study included n = 17 parents of n = 26 children with neurodevelopmental disabilities. Themes from the interviews were coded both inductively and deductively. Most of the children had delays in important developmental domains, indicating a need for rehabilitation services. Participants reported significant difficulty finding specialists due to the distance from their house to the specialist, they experienced long waitlists and delayed diagnoses, they had difficulties finding caregivers for their children, they frequently had multiple children with disabilities, and they experience sleep disruptions due to their child(ren) with neurodevelopmental disabilities. The authors provide clinical research recommendations and policy changes that may be considered to help mitigate barriers to healthcare for children with neurodevelopmental disabilities living in rural and low-resourced regions.
Progress of tanshinone IIA against respiratory diseases: therapeutic targets and potential mechanisms
Authors: Ding Zhaohui , Deng Youlin , Luo Huie , Liu Cuiwang , Yang Minjuan , Xue Hanrong , Chen Zhengtao
Published: February 2025

The respiratory system stands as one of the eight pivotal systems within the human body, responsible for a range of essential functions. Primarily, it facilitates the absorption of oxygen from the external environment and the expulsion of carbon dioxide, thereby playing a crucial role in regulating the body’s acid-base balance. Furthermore, it helps to maintain the stability of the internal environment, ensuring the smooth progression of normal metabolic processes and sustaining life activities. In the wake of the novel coronavirus pneumonia outbreak, respiratory diseases have continued to exhibit comparatively high morbidity and mortality rates, underscoring the urgent need for the discovery of novel therapeutic agents. Tanshinone IIA (Tan IIA), a bioactive chemical constituent derived from Salvia miltiorrhiza Bunge, has emerged as a promising candidate. As a significant fat-soluble compound, Tan IIA has traditionally been utilized in the treatment of cardiovascular diseases. As research on Tan IIA has progressed, its multifaceted therapeutic potential has been unveiled. Specifically, Tan IIA has demonstrated anti-inflammatory, anti-oxidative stress, anti-fibrosis, and anti-cancer effects. In recent years, a wealth of studies has concentrated on elucidating its impact on various respiratory diseases, including asthma, chronic obstructive pulmonary disease, pulmonary hypertension, pulmonary fibrosis, acute lung injury/acute respiratory distress syndrome, and lung cancer. These findings collectively suggest that Tan IIA holds considerable promise in the realm of anti-respiratory disease therapies. The present article undertakes a comprehensive review of the targets and potential mechanisms of Tan IIA against respiratory diseases, offering valuable insights that can serve as a reference for future research endeavors and clinical applications of Tan IIA in the treatment of respiratory ailments.
Cepharanthine hydrochloride: a novel ferroptosis-inducing agent for prostate cancer treatment
Authors: Guan Jing-Song , Jia Jing , Huang Ze-Xiu , Zhou Yu-Qing , Zheng Jing-Jie , Lin Qi-Man , Wang Yi-Fei , Fan Jiang-Lin , Wang Yao
Published: February 2025

Background

Ferroptosis is an intracellular iron-dependent cell death that is distinct from apoptosis, necrosis, and autophagy. Increasing evidence indicated that ferroptosis plays a crucial role in suppressing tumors, thus providing new opportunities for cancer therapy. The drug cepharanthine, commonly used to treat leukopenia, has been discovered to function as an anticancer agent to multiple types of cancer via diverse mechanisms. However, the effect of cepharanthine on prostate cancer remains unclear.

Methods

A semi-synthetic derivative of cepharanthine, cepharanthine hydrochloride (CH), is used in this study due to its better water solubility and bioavailability. The prostate cancer cell lines LNCaP, 22Rv1, PC3 and xenograft mouse models are used for detecting the anti-tumor effect of CH in vitro and in vivo. Types of cell death including ferroptosis are detected by flow cytometry using annexin V and total/lipid reactive oxygen species probes, drug combination of CH with ferroptosis inhibitor/ion chelator, and the appearance of mitochondria under a transmission electron microscopy. The mechanism is investigated by high-throughput transcriptome analysis and transcription factor function analysis of androgen receptor.

Results

CH inhibits cellular functions and trigger ferroptosis in prostate cancer cells. Mechanistic research revealed both common and distinct pharmacological mechanisms of CH-induced ferroptosis in different prostate cancer cells. High-throughput transcriptome analysis revealed that ferroptosis-related genes are significantly regulated in androgen receptor-dependent cells 22Rv1 and LNCaP, and less significantly in androgen receptor-independent cell PC3. Furthermore, CH was found to reduce the gene expressions and protein levels of GPX4 and FSP1 through modulating the activity of the androgen receptor signaling pathway, but not through its transcription factor activity. In addition, CH upregulated ACSL4 and downregulated DHODH, with the combined regulatory outcomes synergistically inducing ferroptosis. An in vivo experiment employing CH and ion chelator-treated nude mice validated the mechanism by which CH induces ferroptosis to combat prostate cancer.

Conclusion

This study has identified CH as a novel ferroptosis-inducing agent for the treatment of prostate cancer. The multiple mechanisms we found provides strong evidence for the eventual clinical application of the drug.
Gold complex QB1561 suppresses drug-resistant cancer cells by inhibiting TrxR and mitochondrial respiratory function
Authors: Gao Hai-Ling , Ding Wenwen , Shen Zhi-Xin , Cui Qingbin
Published: February 2025

Introduction

Multi-drug resistance (MDR) is one of the leading reasons that cause the failures of cancer treatment. Novel agents that may reverse MDR and neutralize drug-resistant cancer cells are highly desirable for clinical practice. The targeting of cellular redox homeostasis and/or mitochondria-mediated energy metabolism are promising strategies for the suppression of drug-resistant cancer cells. Based on the structure of mono-gold(I) complex auranofin (AF), a drug candidate under clinical trials for cancer, we synthesized a new dual-gold(I) complex QB1561 and tested if it can inhibit drug-resistant cancer cells overexpressing ATP-binding cassette (ABC) transporters. We also investigated if QB1561 could inhibit thioredoxin reductase (TrxR), a well-known target of AF and other gold complexes, and assessed its impact on mitochondrial respiration.

Methodology

Cell viability of drug-resistant cells upon QB1561 alone or combined with topotecan and mitoxantrone was determined by MTS assay. The expression of ABC sub-family G member 2 (ABCG2) in the lung cancer cell line NCI-H460/MX20 after treatment with QB1561 was assessed by Western blot. The Vi-sensitive ABCG2 ATPase activity in the membrane vesicles of High Five insect cells, TrxR activity, and ROS production were measured following QB1561 treatment. Colony formation was used to assess QB1561’s anticancer potential. SeaHorce Seahorse XF Analyzers were used to measure the oxygen consumption rate (OCR).

Results

QB1561 suppressed the proliferation of drug-resistant cancer cells overexpressing ABC transporters, with IC50 values ranging from 0.57 to 1.80 μM, which was more effective than AF. QB1561 was able to partially reverse the resistance of mitoxantrone and topotecan in lung cancer NCI-H460/MX20 cells which overexpressed ABCG2, without altering the expression levels of ABCG2. QB1561 suppressed the colony formation of NCI-H460/MX20 cells, probably via ROS induction due to TrxR inhibition. QB1561 also efficiently suppressed OCR, suggesting its inhibition on mitochondrial respiration.

Conclusion

QB1561 was effective for the treatment of MDR in drug-resistant cancer cells. Its further evaluation could be useful for the design and development of more gold-based anticancer drugs.
Validation of the Contextual Sensation-Seeking Questionnaire for skiing and snowboarding among Chinese adult skiers and its relationship with risk-taking behavior
Authors: Guo Zeyou , Gao Shenmao , Liu Yuanguo , Zhang Renfang , Dou Guangbo
Published: February 2025

Objective

To validate the reliability and validity of the Contextual Sensation-seeking Questionnaire for Skiing and Snowboarding (CSSQ-S) among Chinese adult skiers, and to explore the relationship between sensation seeking and risk-taking behavior.

Methods

Snowball sampling was employed to gather data from 515 individuals, aged between 18 and 40 years old, with at least one year of experience in skiing or snowboarding. Exploratory factor analysis (EFA), confirmatory factor analysis (CFA), and other statistical methods were utilized for data analysis.

Results

The CSSQ-S demonstrated strong factor validity, internal consistency, and construct validity. Sensation seeking was significantly positively correlated with injury frequency, and risk perception mediated this relationship.

Conclusion

The CSSQ-S can be regarded as a reliable and valid tool for measuring sensation-seeking levels and potential injury risks among Chinese adult skiers, providing a useful reference for ski safety management and training.
Evaluating attention deficit and hyperactivity disorder (ADHD): a review of current methods and issues
Authors: Musullulu Hande
Published: February 2025

Attention-deficit/hyperactivity disorder (ADHD) is a common and complex neurodevelopmental disorder that affects individuals across the lifespan. This review provides an overview of the DSM diagnostic criteria for ADHD and discusses recommended considerations for the diagnosis of ADHD in children, adolescents, and adults. Its complexity requires careful consideration in the diagnostic process due to heterogeneity in clinical presentation and symptom overlap with other conditions. Commonly used assessment tools, including clinical interviews, rating scales and continuous performance tasks are reviewed with a focus on their psychometric qualities. Limitations of current diagnostic techniques, including issues related to gender bias, comorbidities and the importance of differential diagnosis are also reviewed. Improvements in the consistency and accuracy of ADHD diagnosis may be achieved by addressing these factors and evaluating the practical application of diagnostic tools.