bluuebunny/crossref_metadata_2025 huggingface dataset:
Future precipitation projections for Brazil and tropical South America from a convection-permitting climate simulation
Authors: Kahana Ron , Halladay Kate , Alves Lincoln Muniz , Chadwick Robin , Hartley Andrew J.
Published: November 2024

Understanding precipitation properties at regional scales and generating reliable future projections is crucial in providing actionable information for decision-makers, especially in regions with high vulnerability to climate change, where future changes impact ecosystem resilience, biodiversity, agriculture, water resources and human health. The South America Convection-Permitting Regional Climate Model experiment (SA-CPRCM) examines climate change effects in convection-permitting simulations at 4.5 km resolution, on climate time scales (10 year present-day and 10-year future RCP8.5 around 2100), over a domain covering most of South America, using the Met Office Unified Model (UM) convection-permitting RCM.

Under the RCP8.5 scenario, precipitation in the CPRCM decreases, becomes less frequent and more seasonal over the Eastern Amazon region. Dry spells lengthen, increasing the risk of drought. In the Western Amazon, precipitation increases in the wetter austral autumn (Apr. – Jun.) and decreases in the drier austral winter and spring (July – Oct.), leading to a more distinct dry season and imposing a greater risk of contraction of the tropical forest. Over South-eastern Brazil, future precipitation increases and becomes more frequent and more intense, increasing the risk of floods and landslides. A future increase in the intensity of precipitation and extremes is evident over all these regions, regardless of whether the mean precipitation is increasing or decreasing. The CPRCM and its driving GCM respond in a similar way to the future forcing. The models produce broadly similar large-scale spatial patterns of mean precipitation and comparable changes to frequency, intensity, and extremes, although the magnitude of change varies by region and season.
Student assistants as mentor-participants: a case study of distributing leadership in academic co-design education
Authors: Troost Ivar , van den Bosch Lio J. , Nederlof Niels , Nazar Shahin , Wijers Monica , Bakker Arthur , Pieters Toine
Published: November 2024

Student Assistants (SAs) are generally regarded as support to the instructor's teaching agency in a course. This case study assesses SAs taking on the more autonomous role of mentor-participants in student teams during an advanced bachelor's co-design course, advancing our understanding of distributing leadership within such open-ended educational contexts. We use semi-structured interviews and grounded theory analysis to understand how students, teachers and SAs experienced and responded to this shift in SA role. We conceptualize that SAs combined the qualities of both the instructor in creating and holding space for learning based on their personal experiences (i.e., mentoring) and the student in being a pro-active learner and contributor themselves (i.e., participant). Herein they acted as models for students, redistributing the traditional hierarchy of teaching (with a fixed object and subject of teaching) across course participants (i.e., instructors, SAs and students) and into more nuanced roles (i.e., teaching, coaching, mentoring and facilitating). Taking on this role as SA allowed students to take charge while being closely and safely supported. Moreover, this arrangement nurtured a sense of community: students reported experiencing an atmosphere of trust, informality and closeness. Instructors took a more distant role in this constellation, taking responsibility for formal assessment. We conclude that this rearrangement of roles facilitated students' personal leadership and development, authentic undergraduate research and challenge-based learning - and outline course design choices that likely contributed to this.
Somatic mutational landscape reveals mutational signatures and significantly mutated genes of cancer immunotherapeutic outcome and sex disparities
Authors: Li Yuting , Wang Qinghua , Gao Xiaopan , Zheng Jinyang , Zhang Wenjing , Ren Yanfeng , Shen Wei , Su Wei , Lu Ping
Published: November 2024

Background

Currently developed molecular markers can predict the effectiveness of cancer immunotherapy and screen beneficiaries to some extent, but they are not stable enough. Therefore, there is an urgent need for discovering novel biomarkers. At the same time, sex factor plays a vital role in the response to immunotherapy, so it is particularly important to identify sex-related molecular indicators.

Methods

We integrated a pan-cancer cohort consisting of 2348 cancer patients who received immune checkpoint inhibitors and targeted sequencing. Using somatic mutation profiles, we identified mutational signatures, molecular subtypes, and frequently mutated genes, and analyzed their relationships with immunotherapeutic outcomes. We also explored sex disparities of determined biomarkers in response to treatments.

Results

We found that male patients exhibited better immunotherapy outcomes and higher tumor mutational burden. A total of seven mutational signatures were identified, among which signatures 1 and 3 were associated with worse immunotherapy outcomes, while signatures 2 and 6 correlated with better outcomes. Gender-based analysis revealed that mutational signature 1 continued to show a worse immunotherapy outcome in female patients, whereas signature 6 demonstrated a better outcome in male patients. Based on mutational activities, we identified four potential molecular subtypes with gender differences and relevance to treatment outcomes. PI3K-AKT, RAS signaling pathways, and 68 significantly mutated genes were identified to be associated with immunotherapy outcomes, with nine genes (i.e., ATM, ATRX, DOT1L, EP300, EPHB1, NOTCH1, PBRM1, RBM10, and SETD2) exhibiting gender differences. Finally, we discovered co-mutated gene pairs and TP53 p.R282W mutations related to treatment outcomes, highlighting their gender-specific differences.

Conclusion

This study identified several molecular biomarkers related to cancer immunotherapy outcomes in terms of mutational signatures, molecular subtypes, and mutated genes, and explored their gender-relatedness in order to provide clues and basis for clinical treatment efficacy evaluation and patient selection.
Efficacy and safety analysis of neoadjuvant chemotherapy combined with immunotherapy in patients with muscle-invasive bladder cancer
Authors: Yu Yanhang , Zhang Chuanao , Chen Hao , Zhang Jianglei , Ouyang Jun , Zhang Zhiyu
Published: November 2024

Introduction

This study examined the efficacy and safety of neoadjuvant chemotherapy combined with immunotherapy in patients with muscle-invasive bladder cancer (MIBC).

Methods

This retrospective cohort study included patients diagnosed with MIBC at the First Affiliated Hospital of Soochow University between January 1, 2020, and December 31, 2023, assigned to either chemotherapy (gemcitabine with cisplatin) or combination (chemotherapy plus toripalimab or tislelizumab) groups based on the neoadjuvant treatment regimen. Key metrics, including pathological downstaging rate (PDR), pathological complete response rate (PCRR), and incidence and severity of adverse events (AEs), were compared between groups.

Results

This study included 53 patients (mean age: 67.21 years). In the combination group, 14 patients (51.85%) achieved pathological complete remission (ypT0), and seven (25.93%) achieved partial remission (ypT1), resulting in a PDR and PCRR of 77.78 and 51.85%, respectively. In the chemotherapy group, six patients (23.08%) achieved complete remission, and five (19.23%) achieved partial remission, resulting in a PDR and PCRR of 42.31 and 23.08%, respectively. Differences between groups were statistically significant (p < 0.05). There were no significant differences in pathological downstaging or complete remission rates among subgroups in the combination group (p > 0.05). No serious allergic reactions or fatal AEs were detected in either group, with no grade 4 AEs. Grade 3 AE rates were 22.22 and 20.83% in the combination and chemotherapy groups, respectively, although non-significant (p > 0.05).

Conclusion

Neoadjuvant chemotherapy combined with immunotherapy had enhanced efficacy and manageable safety in patients with MIBC, suggesting its potential for integration into clinical practice.
Behavioral response of Aedes aegypti (Diptera: Culicidae) to essential oils of Cymbopogon nardus (L.) Eucalyptus camaldulensis (Dehnh) and their blend in Y-maze olfactometer
Authors: Wangrawa Dimitri Wendgida , Chandrasegaran Karthikeyan , Upshur Forde , Borovsky Dov , Sharakhov Igor V. , Vinauger Clement , Badolo Athanase , Sanon Antoine , Lahondère Chloé
Published: November 2024

Background

Aedes aegypti vectors several important arboviruses including dengue and yellow fever. This vector mosquito is controlled mainly by using synthetic insecticides and repellents. Overusing these insecticides causes mosquito resistance, harms the environment, and affects human health. This report reevaluates the repellent activities of Cymbopogon nardus, Eucalyptus camaldulensis essential oils (EOs), and their mixtures against laboratory-reared adult Ae. aegypti.

Methods

The chemical composition of C. nardus, E. camaldulensis EOs, and their 1:1 combination was identified by gas chromatography-mass spectrometry (GC-MS). We evaluated the repellent activities of these oils against Ae. aegypti using a Y-maze olfactometer. The preference index (PI) was evaluated and compared with the binary data obtained from the olfactometer assay with samples that did not contain EOs (control) using an Exact Binomial test (α= 0.05)

Results

Several monoterpenes and sesquiterpene compounds were found in EOs and their mixture. The EOs of E. camaldulensis and the mixture of the two oils showed a repellent activity of 50%, whereas C. nardus was less active and attracted mosquitoes at 1 ppm.

Conclusion

We show that EOs from C. nardus and E. camaldulensis contain compounds that repel Ae. aegypti. Future studies will identify specific compounds with the highest repellent activities and use them to formulate in the future a potent repellent against Ae. aegypti for human protection.
The archaeal and bacterial community structure in composted cow manures is defined by the original populations: a shotgun metagenomic approach
Authors: Romero-Yahuitl Vanessa , Zarco-González Karla Estephanía , Toriz-Nava Ana Lilia , Hernández Mauricio , Velázquez-Fernández Jesús Bernardino , Navarro-Noya Yendi E. , Luna-Guido Marco , Dendooven Luc
Published: November 2024

Introduction

Organic wastes are composted to increase their plant nutritional value, but little is known about how this might alter the bacterial and archaeal community structure and their genes.

Methods

Cow manure was collected from three local small-scale farmers and composted under controlled conditions, while the bacterial and archaeal communities were determined using shotgun metagenomics at the onset and after 74 days of composting.

Results

The bacterial, archaeal, methanogen, methanotrophs, methylotroph, and nitrifying community structures and their genes were affected by composting for 74 days, but the original composition of these communities determined the changes. Most of these archaeal and bacterial groups showed considerable variation after composting and between the cow manures. However, the differences in the relative abundance of their genes were much smaller compared to those of the archaeal or bacterial groups.

Discussion

It was found that composting of different cow manures did not result in similar bacterial or archaeal communities, and the changes that were found after 74 days were defined by the original populations. However, more research is necessary to determine if other composting conditions will give the same results.
Fecal microbiota transplantation alleviates cognitive impairment by improving gut microbiome composition and barrier function in male rats of traumatic brain injury following gas explosion
Authors: Dong Xinwen , Su Yaguang , Luo Zheng , Li Cuiying , Gao Jie , Han Xiaofeng , Yao Sanqiao , Wu Weidong , Tian Linqiang , Bai Yichun , Wang Guizhi , Ren Wenjie
Published: November 2024

Background

Dysbiosis of gut microbiota (GM) is intricately linked with cognitive impairment and the incidence of traumatic brain injury (TBI) in both animal models and human subjects. However, there is limited understanding of the impact and mechanisms of fecal microbiota transplantation (FMT) on brain and gut barrier function in the treatment of TBI induced by gas explosion (GE).

Methods

We have employed FMT technology to establish models of gut microbiota dysbiosis in male rats, and subsequently conducted non-targeted metabolomics and microbiota diversity analysis to explore the bacteria with potential functional roles.

Results

Hematoxylin–eosin and transmission electron microscopy revealed that GE induced significant pathological damage and inflammation responses, as well as varying degrees of mitochondrial impairment in neuronal cells in the brains of rats, which was associated with cognitive decline. Furthermore, GE markedly elevated the levels of regulatory T cell (Tregs)-related factors interleukin-10, programmed death 1, and fork head box protein P3 in the brains of rats. Similar changes in these indicators were also observed in the colon; however, these alterations were reversed upon transfer of normal flora into the GE-exposed rats. Combined microbiome and metabolome analysis indicated up-regulation of Clostridium_T and Allobaculum, along with activation of fatty acid biosynthesis after FMT. Correlation network analysis indirectly suggested a causal relationship between FMT and alleviation of GE-induced TBI. FMT improved intestinal structure and up-regulated expression of tight junction proteins Claudin-1, Occludin, and ZO-1, potentially contributing to its protective effects on both brain and gut.

Conclusion

Transplantation of gut microbiota from healthy rats significantly enhanced cognitive function in male rats with traumatic brain injury caused by a gas explosion, through the modulation of gut microbiome composition and the improvement of both gut and brain barrier integrity via the gut-brain axis. These findings may offer a scientific foundation for potential clinical interventions targeting gas explosion-induced TBI using FMT.
Effects of the two-pore potassium channel subunit Task5 on neuronal function and signal processing in the auditory brainstem
Authors: Saber Mahshid Helia , Kaiser Michaela , Rüttiger Lukas , Körber Christoph
Published: November 2024

Processing of auditory signals critically depends on the neuron’s ability to fire brief, precisely timed action potentials (APs) at high frequencies and high fidelity for prolonged times. This requires the expression of specialized sets of ion channels to quickly repolarize neurons, prevent aberrant AP firing and tightly regulate neuronal excitability. Although critically important, the regulation of neuronal excitability has received little attention in the auditory system. Neuronal excitability is determined to a large extent by the resting membrane potential (RMP), which in turn depends on the kind and number of ion channels open at rest; mostly potassium channels. A large part of this resting potassium conductance is carried by two-pore potassium channels (K2P channels). Among the K2P channels, the subunit Task5 is expressed almost exclusively in the auditory brainstem, suggesting a specialized role in auditory processing. However, since it failed to form functional ion channels in heterologous expression systems, it was classified “non-functional” for a long time and its role in the auditory system remained elusive. Here, we generated Task5 knock-out (KO) mice. The loss of Task5 resulted in changes in neuronal excitability in bushy cells of the ventral cochlear nucleus (VCN) and principal neurons of the medial nucleus of the trapezoid body (MNTB). Moreover, auditory brainstem responses (ABRs) to loud sounds were altered in Tasko5-KO mice. Thus, our study provides evidence that Task5 is indeed a functional K2P subunit and contributes to sound processing in the auditory brainstem.
“Living with” CACNA1A-related hemiplegic migraine, a disease concept model
Authors: Schaare Donna , Allison Kendra , Skorge Kara , Fox Pangkong , Lusk Laina , Sarasua Sara M. , Helbig Ingo , Boccuto Luigi
Published: November 2024

Introduction

CACNA1A-related Hemiplegic Migraine (HM) is a rare neurological disorder distinguished by paroxysmal episodes of hemiparesis/hemiplegia with and without headache. Clinical features have been widely characterized, yet the impacts of the paroxysmal events on the patient and caregiver have not been thoroughly explored. Disease concept models are formal frameworks used to describe the lived experiences of patients and their families, offering a source for surrogate endpoints for clinical trials.

Methods

We completed 13 semi-structured interviews with caregivers of 12 individuals diagnosed with CACNA1A-related HM. We methodically coded themes, grouping concepts into three domains. We measured the occurrence of concepts throughout all interviews and subgroups stratified by age categories.

Results

Over 11 h of interviews yielded 2,018 references to 27 distinct concepts. Established symptoms such as seizures (87 references; including status epilepticus 27 references), hemiparesis/hemiplegia (24 references), and unconsciousness (17 references) were referenced, as well as previously underreported symptoms such as apneic episodes (32 references), lost ability to eat (13 references), and vascular access challenges (10 references). The symptom impacts were largely medical (294 references), followed by health (101 references), emotional (36 references), daily living (28 references), and social (26 references). Caregiver impacts were the most referenced domain (995 references), with the pivotal effects seen in caregiver requirements (355 references), emotional (245 references), HM treatments (179 references), daily living (148 references), and health support (135 references).

Discussion

CACNA1A-related HM is a complex disorder defined by serious paroxysmal events that affects a broad range of social and clinical domains. We systematically classified symptoms and impacts from HM episodes, creating a disease concept model to help develop surrogate endpoints for future clinical trials, and identified two opportunities to improve patient management, including a written emergency protocol and a transition plan for adolescents approaching adulthood.
Discriminative possibilistic clustering promoting cross-domain emotion recognition
Authors: Dan Yufang , Zhou Di , Wang Zhongheng
Published: November 2024

The affective Brain-Computer Interface (aBCI) systems strive to enhance prediction accuracy for individual subjects by leveraging data from multiple subjects. However, significant differences in EEG (Electroencephalogram) feature patterns among subjects often hinder these systems from achieving the desired outcomes. Although studies have attempted to address this challenge using subject-specific classifier strategies, the scarcity of labeled data remains a major hurdle. In light of this, Domain Adaptation (DA) technology has gradually emerged as a prominent approach in the field of EEG-based emotion recognition, attracting widespread research interest. The crux of DA learning lies in resolving the issue of distribution mismatch between training and testing datasets, which has become a focal point of academic attention. Currently, mainstream DA methods primarily focus on mitigating domain distribution discrepancies by minimizing the Maximum Mean Discrepancy (MMD) or its variants. Nevertheless, the presence of noisy samples in datasets can lead to pronounced shifts in domain means, thereby impairing the adaptive performance of DA methods based on MMD and its variants in practical applications to some extent. Research has revealed that the traditional MMD metric can be transformed into a 1-center clustering problem, and the possibility clustering model is adept at mitigating noise interference during the data clustering process. Consequently, the conventional MMD metric can be further relaxed into a possibilistic clustering model. Therefore, we construct a distributed distance measure with Discriminative Possibilistic Clustering criterion (DPC), which aims to achieve two objectives: (1) ensuring the discriminative effectiveness of domain distribution alignment by finding a shared subspace that minimizes the overall distribution distance between domains while maximizing the semantic distribution distance according to the principle of “sames attract and opposites repel”; and (2) enhancing the robustness of distribution distance measure by introducing a fuzzy entropy regularization term. Theoretical analysis confirms that the proposed DPC is an upper bound of the existing MMD metric under certain conditions. Therefore, the MMD objective can be effectively optimized by minimizing the DPC. Finally, we propose a domain adaptation in Emotion recognition based on DPC (EDPC) that introduces a graph Laplacian matrix to preserve the geometric structural consistency between data within the source and target domains, thereby enhancing label propagation performance. Simultaneously, by maximizing the use of source domain discriminative information to minimize domain discrimination errors, the generalization performance of the DA model is further improved. Comparative experiments on several representative domain adaptation learning methods using multiple EEG datasets (i.e., SEED and SEED-IV) show that, in most cases, the proposed method exhibits better or comparable consistent generalization performance.
VCAN in the extracellular matrix drives glioma recurrence by enhancing cell proliferation and migration
Authors: Wei Ruolun , Xie Haoyun , Zhou Yukun , Chen Xuhao , Zhang Liwei , Bui Brandon , Liu Xianzhi
Published: November 2024

Introduction

Gliomas are the most prevalent primary malignant intracranial tumors, characterized by high rates of therapy resistance, recurrence, and mortality. A major factor contributing to the poor prognosis of gliomas is their ability to diffusely infiltrate surrounding and even distant brain tissues, rendering complete total resection almost impossible and leading to frequent recurrences. The extracellular matrix (ECM) plays a key role in the tumor microenvironment and may significantly influence glioma progression, recurrence, and therapeutic response.

Methods

In this study, we first identified the ECM and the Versican (VCAN), a key ECM protein, as critical contributors to glioma recurrence through a comprehensive analysis of transcriptomic data comparing recurrent and primary gliomas. Using single-cell sequencing, we revealed heterogeneous distribution patterns and extensive intercellular communication among ECM components. External sequencing and immunohistochemical (IHC) staining further validated that VCAN is significantly upregulated in recurrent gliomas and is associated with poor patient outcomes.

Results

Functional assays conducted in glioma cell lines overexpressing VCAN demonstrated that VCAN promotes cell proliferation and migration via the PI3K/Akt/AP-1 signaling pathway. Furthermore, inhibiting the PI3K/Akt pathway effectively blocked VCAN-mediated glioma progression.

Conclusion

These findings provide valuable insights into the mechanisms underlying glioma recurrence and suggest that targeting both VCAN and the PI3K/Akt pathway could represent a promising therapeutic strategy for managing recurrent gliomas.
Waist-to-hip ratio and nonalcoholic fatty liver disease: a clinical observational and Mendelian randomization analysis
Authors: Xie Weining , Hong Yan , Chen Xinrong , Wang Shujuan , Zhang Fan , Chi Xiaoling
Published: November 2024

Background

Obesity often coincides with non-alcoholic fatty liver disease (NAFLD), yet a significant portion of NAFLD patients exhibit normal body mass index (BMI) but have abdominal obesity. Recognizing this discrepancy, we aimed to delve deeper into this phenomenon through observational studies coupled with two-sample Mendelian randomization (MR) analysis, with waist-to-hip ratio (WHR) serving as the indicator for abdominal obesity. Our objective was to ascertain whether WHR correlates with an increased risk of NAFLD development.

Methods

This study utilized data from the National Health and Nutrition Examination Survey (NHANES) 2017–2018 to examine the association between WHR and NAFLD through weighted multivariate logistic regression models. On this basis, subgroup analyses were performed to further explore the correlation between WHR and NAFLD. Subsequently, a two-sample MR analysis was conducted using genome-wide association studies (GWAS) data to investigate the potential causal relationship between WHR and NAFLD. Sensitivity analyses were also employed to ensure the robustness of our findings.

Results

A total of 3,732 eligible participants were included in the analysis. Weighted multivariable-adjusted logistic regression models revealed a positive association between WHR and the risk of NAFLD (Q2vsQ1: OR = 1.94 [95% CI: 1.55–2.44]; Q3vsQ1: OR = 2.08 [95% CI: 1.51–2.85]; Q4vsQ1: OR = 3.70 [95% CI: 2.13–6.43], p < 0.05). The results of the subgroup analysis suggested that there was an interaction in the correlation between WHR and NAFLD in normal weight, overweight, and obese populations (p < 0.05). The RCS curves indicated that there was a nonlinear relationship between WHR and NAFLD in populations with BMI in the normal versus obese categories. Furthermore, MR analysis provided additional support for the causal relationship between WHR and NAFLD. Using inverse variance weighting (IVW), the MR analysis yielded an OR of 2.062 (95% CI: 1.680–2.531, p<0.05). Consistent results were obtained with the other four MR methods, all supporting the same direction of causality. Sensitivity analyses were performed to assess the robustness of the findings (p > 0.5), further reinforcing the reliability of the observed associations.

Conclusion

WHR elevation heightens the susceptibility to NAFLD.
The impact of tumor burden score on prognosis in patients after radical resection of hepatocellular carcinoma: a single-center retrospective study
Authors: Huang Junzhang , Zhou Ying , Wei Suosu , Tang Yuntian , Zhang Qiuhuan , Tang Yi , Huang Wei , Mo Chongde , Dong Xiaofeng , Yang Jianrong
Published: November 2024

Purpose

This study examines the relationship between tumor burden score (TBS) and survival and recurrence following radical resection of hepatocellular carcinoma through a cohort study conducted in the Guangxi population of China.

Methods

This cohort study eventually recruited 576 HCC patients undergoing radical resection of HCC in the People’s Hospital of Guangxi Zhuang Autonomous Region during 2013–2022. After determining the best threshold TBS, all cases were grouped to evaluate the relationship between TBS versus overall survival (OS) and cumulative recurrence. Using X-Tile software, the best threshold TBS to judge patient prognostic outcome following radical resection of HCC was 10.77.

Results

Kaplan–Meier curve analysis revealed that patients with high TBS showed considerably decreased OS relative to the control group, accompanied by an increased recurrence rate. According to multivariate Cox proportional regression, the patients with high TBS were associated with poorer OS (HR = 2.56, 95% CI 1.64–3.99, P < 0.001) and recurrence-free survival (RFS) (HR = 1.55, 95% CI 1.02–2.35, P < 0.001).

Conclusion

In patients undergoing radical resection for HCC, higher TBS was significantly related to shorter OS and RFS.
Multidimensional immunotherapy for dry eye disease: current status and future directions
Authors: Huang Duliurui , Li Zhijie
Published: November 2024

Dry Eye Disease (DED) is a multifactorial condition driven by tear film hyperosmolarity, immune dysregulation, and neuro-immune interactions. The immune system plays a central role in its pathogenesis, influencing both inflammation and ocular surface damage. While traditional immunotherapies like anti-inflammatory agents and immunosuppressants offer symptom relief, their long-term use is limited by side effects. This review focuses on emerging immunotherapies, including biologics, stem cell therapy, gene therapy, nanotechnology, and exosome-based treatments, all of which hold promise in modulating immune responses and promoting tissue repair. The relationship between the ocular microbiome and DED is also explored, with an emphasis on personalized immunotherapy. Key challenges for future research include identifying novel therapeutic targets, optimizing clinical translation, and evaluating the long-term efficacy of these innovative treatments.
Contribution of fracture healing in paediatric DMP zone fracture patients using the pry lever technique
Authors: Zhang Jingyuan , Cao Hong
Published: November 2024

Background

This study describes the efficacy of applying the prying lever technique to distal radial metaphyseal symphysis diaphysis joining region (DMP) fractures in children, and reports that the technique has an ameliorative effect on the phenomenon of delayed healing and non-union that occurs after surgery for fractures in the DMP region.

Methods

The medical records of 72 children with fractures in the DMP region, treated between December 2017 and December 2023, were retrospectively analyzed. The patients were randomly assigned to either the cut-and-displace group (n = 36) or the pry-and-lever group (n = 36). Both groups were monitored for time to fracture healing, incidence of delayed or non-union, radiologic outcomes, complications, and functional assessments using the EQ-5D, DASH, and VAS scales.

Results

The follow-up period ranged from 3 to 5 years, with a mean of 26.5 months. After 6 months of follow-up, the incidence of delayed/non-union of fractures was 2.7% and 16.6% in the study and control groups, respectively, and the incidence of delayed healing was significant (P < 0.05) in both groups. Additional manipulations or complications caused by delayed healing or non-union were also significantly less in the study group than in the control group. The EQ-5D scale was used to compare the level of surgical satisfaction between the two groups, and the study group had a higher level of satisfaction. Carpal function was significantly improved in both groups compared to the preoperative period, scored using the DASH scale (P > 0.05). Postoperative pain level was scored using VAS (P < 0.05).

Conclusion

The prying lever technique has the advantages of low impact on periosteal blood supply, simple operation, and fast recovery, which makes it a worthwhile attempt of minimally invasive reduction of fractures in the DMP region in children.
Sex bias in prospective follow-up observational studies with drugs carried out in a southern region of Europe
Authors: Santomà Àlex , Jambrina Anna Maria , Perisé Adela , Armelles Mercè , Perisé Lluisa , Pareja Clara , Rams Neus , Rabanal Manel
Published: November 2024

Introduction

The impact of sex bias in medical research is a matter of significant relevance and importance especially in the modern age. Despite notable improvements in sex equity across various societal fields, disparities in sex representation persist within clinical and pharmacological research. The objective of this article is to investigate the sex bias within Prospective Follow-up Observational Studies with Drugs authorized by the Advisory Commission on Post-Authorization Studies with Medicines in Catalonia, a southern European region.

Methods

A retrospective study that analyses data from final reports of Prospective Follow-up Observational Studies with Drugs authorized by the Advisory Commission on Post-Authorization Studies with Medicines in Catalonia from 2015 to 2021. Disease categories and specific diseases, obtained from the Global Data Exchange, were evaluated for sex bias, comparing female participation to female prevalence.

Results

There were 1,06,399 participants, including 43,778 female participants (42.5%). A significant underrepresentation of females was observed across various disease categories. Notably, in 12 out of 19 categories (63.2%), a pronounced female underrepresentation (sex bias ≤ 0.05) was evident, particularly in the categories of HIV/AIDS and sexually transmitted infections (sex bias = −0.5659). Furthermore, 11 categories (57.9%) also demonstrated significant female underrepresentation, with the same notable categories, HIV/AIDS and sexually transmitted infections (sex bias = −0.4439). When examining specific diseases, significant female underrepresentation was observed in 13 out of 29 diseases (46.4%), especially in HIV (sex bias = −0.4781). The overall findings indicate that the degree of sex bias was notably less favorable for females in numerous disease categories and specific conditions.

Conclusion

Our study has demonstrated a significant sex bias within observational studies, mirroring patterns observed in clinical trials. Importantly, our findings highlight a pervasive underrepresentation of women across various disease categories and specific conditions. Despite efforts to promote both sexes inclusivity, our results emphasize the persistent challenges in achieving balanced sex representation in study populations. Furthermore, the absence of categorization of diseases based on male and female prevalence poses a significant challenge in accessing pertinent data, particularly concerning the sex distribution of specific diseases.
Allele frequencies and genotype distribution of three metformin transporter polymorphisms in Mexican population and their application in pharmacogenomics of type 2 diabetes
Authors: Chávez-Arreola Oscar I. , Lazalde Brissia , López-López Marisol , Ortega-Vázquez Alberto , Torres-Salazar Quitzia L.
Published: November 2024

Background

Metformin is the first-line antidiabetic therapy for type 2 diabetes in Mexico, despite recent recommendations highlighting alternatives like GLP-1 receptor agonists for individuals with obesity. Metformin elimination is reliant on liver and kidney function, and variants in transport proteins such as Multidrug and Toxin Extrusion Protein 1 (MATE1), MATE2, and Organic Cation Transporter 2 (OCT2) can influence its pharmacokinetics. Understanding these variants’ frequencies in the Mexican population is crucial for tailoring personalized treatment strategies.

Objective

This study aimed to determine the genotypic and allelic frequencies of key variants in metformin transporters within a Mexican population, addressing the interindividual variability in drug response.

Methodology

Genetic analysis was conducted on 101 healthy, unrelated Mexican subjects who were genotyped for the MATE1, MATE2, and OCT2 variants using allele-specific real-time PCR assays.

Results

The allele frequencies were 0.07 for OCT2, 0.23 for MATE1, and 0.67 for MATE2. The g.–66T→C variant was found only in wild-type and heterozygous forms. Comparative analysis indicated significant differences in allele frequencies between this Mexican population and other ethnic groups, highlighting potential implications for metformin efficacy and safety.

Conclusion

This study provides crucial insights into the genetic variability of metformin transporter genes in a Mexican population, offering a foundation for personalized therapeutic approaches in type 2 diabetes management.
Efficacy of different traditional Chinese medicine decoctions in the treatment of ischemic stroke: a network meta-analysis
Authors: Ning Baicheng , Zhu Xiaoting , Wu Xiaodong , Zhu Weiyao , Wang Runze , Qi Chang , Li Mingquan
Published: November 2024

Objective

Currently, traditional Chinese medicine (TCM) and its combinations are widely used in the treatment and rehabilitation of patients with ischemic stroke. However, current studies should mainly focus on the therapeutic effects of traditional Chinese medicines alone. This paper will employ a network meta-analysis to compare the efficacy of different TCM decoctions in the treatment of patients with ischemic stroke.

Methods

Chinese and English databases including PubMed, Embase, Cochrane Library, and Web of Science were searched to collect randomized controlled trials of TCM decoctions in the treatment of patients with ischemic stroke (IS), with a search time frame until April 2024. A library of references was created using EndNote 21. Quality assessment was performed using the Version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB 2). A Bayesian network meta-analysis of data was performed using R4.3.1 and STATA 15.0.

Results

A network meta-analysis was conducted on 119 randomized controlled trials including 12,137 IS patients. The following TCM decoctions were involved: Xinglou Chengqi Decoction (XLCQT), Shenqi Tongluo Decoction (SQTLF), Zhongfeng Jiuxian Decoction (ZFJXT), Yiqi Tongluo Decoction (YQTLT), Tongqiao Huoxue Tang (TQHXT), Tongluo Xifeng Decoction (TLXFT), Tongluo Fuzheng Decoction (TLFZT), Xuefu Zhuyu Decoction (XFZYT), Xiaoxuming Decoction (XXMT), Qufeng Xingxue Tongluo Formula (QFXXTLF), Banxia Baizhu Tianma Decoction (BXBZTMT), Buyang Huanwu Tang (BYHWT),Huatan Tongluo Decoction (HTTLT), Yiqi Huoxue Tongluo Decoction (YQHXTLT), Yiqi Huoxue Decoction (YQHXT), and Yiqi Huoxue Kaiqiao Prescription (YQHXKQP). Of them, XFZYT was most effective in reducing the NIHSS score; SQTLF was most effective in increasing the Barthel Index (BI) score; and HTTLT was most effective in improving activities of daily living (ADL).

Conclusion

This network meta-analysis provided data on the relative efficacy of different TCM decoctions. Of them, XFZYT was most effective in reducing the NIHSS score; SQTLF was most effective in increasing the BI score; and HTTLT was most effective in improving the ADL score. At the same time, overall, XFZYT ranked first with its best efficacy regarding all the three outcome measures above, and SQTLF came second with its impact on two of the outcome measures.
Targeting programmed cell death via active ingredients from natural plants: a promising approach to cancer therapy
Authors: Li Qian , Tong Yan , Chen Jianxiang , Xie Tian
Published: November 2024

Cancer is a serious public health problem in humans, and prevention and control strategies are still necessary. Therefore, the development of new therapeutic drugs is urgently needed. Targeting programmed cell death, particularly via the induction of cancer cell apoptosis, is one of the cancer treatment approaches employed. Recently, an increasing number of studies have shown that compounds from natural plants can target programmed cell death and kill cancer cells, laying the groundwork for use in future anticancer treatments. In this review, we focus on the latest research progress on the role and mechanism of natural plant active ingredients in different forms of programmed cell death, such as apoptosis, autophagy, necroptosis, ferroptosis, and pyroptosis, to provide a strong theoretical basis for the clinical development of antitumor drugs.
Modern broiler chickens exhibit a differential gastrointestinal immune and metabolic response to repeated CpG injection relative to a 1950s heritage broiler breed
Authors: Aylward Bridget A. , Johnson Casey N. , Perry Famatta , Whelan Rose , Arsenault Ryan J.
Published: November 2024

The Athens Canadian Random Bred (ACRB) heritage broiler breed, which has not been selectively bred since the 1950s, is a point of comparison to the modern-day broiler and could highlight potential genetic-derived differences in immune responses. To observe the modern and heritage birds’ immune responses in action, the innate immune ligand CpG oligonucleotides were administered at multiple time points through the birds’ lives from the day after hatch to day 35 post-hatch. This study allowed for the observation of changes in metabolic and immune signaling in response to repeated injections of a known Toll-like receptor (TLR) ligand, CpG. Jejunum and cecal tonsil samples at multiple time points during grow out were collected and used for kinome array analysis to measure kinase activity in immunometabolic signaling pathways in the gut tissue. In addition cytokine gene expression was measured in these tissues. The modern birds’ response to the treatment was more innate and showed evidence of metabolic energy shift. The heritage birds’ response to the treatment was adaptive, with metabolic changes indicative of a well-regulated response. Overall, the results from this study suggest that modern broiler chickens do not adequately balance resources between growth and immune responses during an immune challenge, and this deficit is most evident around the 2-week post-hatch time point. This is a critical time for these birds, as their muscle deposition continues to accelerate, and they are vulnerable to disease challenges. Ideally, future work can clarify the reason for this response discrepancy in the modern broiler and therapeutic interventions to rescue this phenotype could be elucidated.
Incidence of aphid-transmitted viruses in raspberry and raspberry aphids in Norway and experiments on aphid transmission of black raspberry necrosis virus
Authors: Sapkota Bijaya , Trandem Nina , Fránová Jana , Koloniuk Igor , Blystad Dag-Ragnar , Hamborg Zhibo
Published: November 2024

Raspberry (Rubus idaeus L.) is susceptible to aphid-borne viruses. We studied the incidence of four of them – black raspberry necrosis virus (BRNV), raspberry leaf mottle virus (RLMV), raspberry vein chlorosis virus (RVCV), and Rubus yellow net virus (RYNV) – in raspberry plants and aphids in and around Norwegian raspberry crops for three years (2019, 2021, and 2022). Most of the samples were from symptomatic plants. Applying RT-PCR, 274 leaf samples and 107 aphid samples were analyzed. All four viruses were found, but BRNV dominated: it was detected in 93% of the 178 leaf samples with virus and was the only virus that occurred more frequently as a single infection than in co-infections with the other viruses. The old cv. Veten had the highest virus incidence (97%) among the sampled plants, followed by uncultivated raspberry in the boundary vegetation (82%). All aphids identified were Amphorophora idaei and Aphis idaei. BRNV and/or RLMV was detected in 27% of the aphid samples. Notably, BRNV was detected in 30% of A. idaei samples, a species not known as a BRNV vector. In subsequent transmission experiments we found that although A. idaei can acquire BRNV within one hour, it did not transmit the virus to healthy raspberry plants. In contrast, Am. idaei, a known BRNV vector, was able to acquire the virus within one minute and transmit it within one hour of inoculation. Our study will improve the identification and management of BRNV.
Elucidation of pineapple softening based on cell wall polysaccharides degradation during storage
Authors: Li Fengjun , Xia Xingzhou , Li Lilang , Song Longlong , Ye Yuping , Jiang Yueming , Liu Hai
Published: November 2024

The degradation of cell wall polysaccharides in pineapple fruit during softening was investigated in the present study. Two pectin fractions and two hemicellulose fractions were extracted from the cell wall materials of ‘Comte de Paris’ pineapple fruit at five softening stages, and their compositional changes were subsequently analyzed. The process of softening of the fruit corresponded to an increase in the water-soluble pectin (WSP) and 1 M KOH-soluble hemicellulose (HC1) fractions, and a decrease in the acid-soluble pectin (ASP) fraction, which suggested the solubilization and conversion of cellular wall components. However, the content of 4 M KOH-soluble hemicellulose (HC2) decreased and then returned to the initial level. Furthermore, WSP, ASP, and HC1 showed an increment in the content of low molecular weight polymers while a decline in the high molecular weight polymers throughout softening, and not significant change in the contents of different molecular polymers of HC2 was observed. Moreover, the galacturonic acid (GalA) content in the main chain of WSP was maintained at a relatively constant level, but the major branch monosaccharide galactose (Gal) in WSP decreased. Different from WSP, the molar percentages of Gal and GalA in ASP decreased. The Gal or Arabinose (Ara) in HC1 exhibited a gradual decline while the molar percentages of xylose (Xyl) and glucose (Glu) in the main chain increased. These suggested that the main chain of ASP degraded while the branched chains of ASP, WSP and HC1 depolymerized during pineapple softening. Overall, fruit softening of ‘Comte de Paris’ pineapple was found to be the result of differential modification of pectin and hemicellulose.
Morally “loaded” labels in the built environment influence perceptions and social judgments
Authors: Haga Andreas
Published: November 2024

Products and artifacts with morally loaded labels (e.g., environmentally friendly) appear to influence people's perceptions and behaviors. Previous studies have shown that desktop lamps labeled “environmentally friendly” can enhance perceived color discrimination and improve certain reading activities compared to a physically identical lamp labeled “conventional.” This effect may occur because people tend to align their behavior with moral principles. The present study explored the generalizability and robustness of this label effect by asking participants to make trait judgments of photographed faces. In an experimental design, participants evaluated photos illuminated by a desktop lamp that was either labeled environmentally friendly or not labeled at all. The results revealed that participants assigned more positive traits to individuals in the photographs when the lamp was labeled “environmentally friendly,” particularly those with high altruistic values. The pattern was reversed for participants with low altruistic values. Moreover, participants rated the light from the lamp labeled “environmentally friendly” as more comfortable and claimed that the light increased (perceived) visibility. In conclusion, the source of the light—whether from an environmentally friendly or conventional lamp—affects both the evaluation of the light itself and the judgments made about other individuals. This study explores theoretical explanations for these label effects and discusses their potential implications for pro-environmental interventions.