bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Primary Healthcare Centers’ Service Availability and Readiness for Implementing Diabetes Care in Abuja, Nigeria: A Cross-Sectional, Formative Assessment
Authors: Orji Ikechukwu A. , Baldridge Abigail S. , Ikechukwu-Orji Mercy U. , Banigbe Bolanle , Eze Nelson C. , Chopra Aashima , Omitiran Kasarachi , Iyer Guhan , Odoh Deborah , Alex-Okoh Morenike , Reng Rifkatu , Hirschhorn Lisa R. , Huffman Mark D. , Ojji Dike B.
Published: March 2024

Introduction:
Noncommunicable diseases (NCDs) are associated with a high and rising burden of morbidity and mortality in sub-Saharan Africa, including Nigeria. Diabetes mellitus (DM) is among the leading causes of NCD-related deaths worldwide and is a foremost public health problem in Nigeria. As part of the National Multi-Sectoral Action Plan for the Prevention and Control of NCDs, Nigeria has committed to implementing the World Health Organization (WHO) Package of Essential NCD control interventions. Implementing the intervention requires the availability of essential elements, including guidelines, trained staff, health management information systems, equipment, and medications, in primary healthcare centers (PHCs). This study assessed the availability of the WHO package components and the readiness of PHCs to implement a DM screening, evaluation, and management program.
Methods
This cross-sectional formative assessment adapted the WHO Service Availability and Readiness Assessment (SARA) tool to survey 30 PHCs selected by multistage sampling for readiness to deliver DM diagnosis and care in Abuja, Nigeria, between August 2021 and October 2021. The service availability and readiness indicator scores were calculated based on the proportion of PHCs with available DM care services, minimum staff requirement, diagnostic tests, equipment, medications, and national guidelines/protocols for DM care within the defined SARA domain.
Results
All 30 PHCs reported the availability of at least two full-time staff (median [interquartile range] staff = 5 [4–9]), which were mostly community health extension workers (median [interquartile range]) = 3 [1–4]. At least one staff member was recently trained in DM care in only 11 (36%) of the PHCs. The study also reported high availability (100%) of paper-based health management information systems (HMIS) and DM screening services using a glucometer (87%), but low availability of DM treatment (23%), printed job aids (27%), and national guidelines/protocols (0%).
Conclusion
This systematic assessment of PHCs’ readiness to implement a DM screening, evaluation, and management program in Abuja demonstrated readiness to integrate DM care into PHCs in terms of equipment, paper-based HMIS, and nonphysician health workers' availability. However, strategies are needed to promote DM health workforce training, provide DM management guidelines, and ensure a reliable supply of essential DM medications.
Disentangling Mnemonic Metacognition from Confidence by Communication between the Precuneus and Hippocampus
Authors: Jiang Hongjie , pan kai , Guo Xinxia , Zheng Zhe , Zhu Zhoule , Wu Hemmings , Zhu Junming , Santos-Pata Diogo , zhang jianmin , Kwok Sze Chai
Published: March 2024

Metacognition, the ability to introspectively monitor confidence prior to decision-making, remains an area with unclear neural mechanisms, particularly concerning the intercommunication among various brain regions. Recently, the precuneus has emerged as a key player in mnemonic metacognitive tasks, while the hippocampus's involvement in memory function is well-established. Our study sought to examine the roles of the precuneus and hippocampus in mnemonic metacognition, employing intracranial electrode recordings from patients with intractable epilepsy to analyze the regulatory and correlational dynamics between these regions. We identified distinct communication patterns between the precuneus and hippocampus during metacognition and confidence generation. Furthermore, we conducted a quantitative assessment of the temporal dynamics involved in metacognition and the generation of confidence. Our observations reveal that introspective judgments typically occur subsequent to the generation of confidence. Our study sheds light on the neural underpinnings of metacognition and the genesis of confidence, focusing on the interplay between the hippocampus and the precuneus. This investigation lays the groundwork for deepening our comprehension of the nuances distinguishing confidence from metacognition.
Retrosynthesis prediction enhanced by in-silico reaction data augmentation
Authors: Yang Yi , Zhang Xu , Mo Yiming , Wang Wenguan
Published: March 2024

Recent advances in machine learning (ML) have expedited retrosynthesis research by assisting chemists to design experiments more efficiently. However, all ML-based methods consume substantial amounts of paired training data (i.e., chemical reaction: product-reactant(s) pair), which is costly to obtain. Moreover, companies view reaction data as a valuable asset and restrict the accessibility to researchers. These issues prevent the creation of more powerful retrosynthesis models due to their data-driven nature. As a response, we exploit easy-to-access unpaired data (i.e., one component of product-reactant(s) pair) for generating in-silico paired data to facilitate model training. Specifically, we present RetroWISE, a self-boosting framework that employs a base model inferred from real paired data to perform in-silico reaction generation and augmentation using unpaired data, ultimately leading to a superior model. On three benchmark datasets, RetroWISE achieves the best overall performance against state-of-the-art models (e.g., +8.6% top-1 accuracy on the USPTO-50K test dataset). Moreover, it consistently improves the prediction accuracy of rare transformations. These results show that RetroWISE overcomes the training bottleneck by in-silico reactions, thereby paving the way toward more effective ML-based retrosynthesis models.
Interformer: An Interaction-Aware Model for Protein-Ligand Docking and Affinity Prediction
Authors: Lai Houtim , Wang Longyue , Qian Ruiyuan , Ye Geyan , Huang Juhong , Wu Fandi , Wu Fang , Zeng Xiangxiang , Liu Wei
Published: March 2024

In recent years, there has been a growing interest in using deep learning models for protein-ligand docking and affinity prediction, both vital for structure based drug design. However, many of these models overlook the intricate modeling of interactions between ligand and protein atoms, thereby constraining their capabilities in generalization and interpretability. In this paper, we introduce \textsc{Interformer}, a unified model built upon the Graph-Transformer architecture, which specially crafted to capture non-covalent interactions through the interaction-aware mixture density network. Besides, we incorporated a new strategy that utilizes negative samples, effective interaction distribution correction for affinity prediction. Experimental results on widely-used and our in-house datasets demonstrate the effectiveness and universality of the proposed approach. Extensive analyses confirm our claim that our approach improves performance by modelling protein-ligand specific interactions. Encouragingly, our approach propels the SOTA performance docking tasks forward. We intend to make our code publicly available, hoping to facilitate future research in this field.
Characteristics of adult retroperitoneal lymphangioma: a single center Chinese cohort study of 15 cases
Authors: Liu Jie , Zhong Zhi-Han , Zheng Shu-Sen
Published: March 2024

Background
Lymphangioma is a rare cystic tumor that occurs across different locations. Retroperitoneal lymphangioma accounts for about 1% of all lymphangiomas. In this study, we report the clinicopathological features of retroperitoneal lymphangioma and describe our experience in treating this disease.
Methods
We collected clinical data from all patients who were pathologically diagnosed with retroperitoneal lymphangioma at Zhejiang Provincial People's Hospital, between June 2013 and August 2022.
Results
The 7 and 8 male and female patients analyzed herein had a mean age of 48.6 (SD 14.24) years at diagnosis. The mean duration of follow-up was 4.7 years. Among them, 66.67% were asymptomatic, with the rest manifesting abdominal pain, nausea, low back pain and elevated blood pressure as the main symptoms. Preoperative diagnosis and evaluation of cysts were mainly performed via Computed Tomography(CT)(n = 10, 66.67%) or magnetic resonance imaging༈MRI༉ (n = 8, 53.33%). All patients were completely resected following surgery. Immunohistochemical analysis, performed on 6 patients, revealed that they were positive for D2-40. A total of 4, 4 and 3 patients were positive for CD31, CD34 and SMA, respectively. Moreover, the study cohort had an average postoperative hospital stay of 6.6 days. Follow up, after the end of the study, revealed no relapse in any of the 15 patients.
Conclusions
Lymphangioma is a benign tumor of the lymphatic system. Although typical imaging features can be accurate for preoperative diagnosis, histological examination is crucial to final confirmation. Complete surgical resection is the best option to limit the risk of recurrence in cases with symptomatic lesions.
Correction of batch effects in high throughput proximity extension assays for proteomic studies using bridging controls: the BAMBOO method.
Authors: Smits H.M. , Delemarre E.M. , Pandit A. , Schoneveld A.H. , Oldenburg B. , Wijk F. van , Nierkens S. , Drylewicz J.
Published: March 2024

Background: The proximity extension assay (PEA) facilitates large-scale proteomic studies involving a large number of proteins and samples. However, inevitable discrepancies in day-to-day measurements may introduce the inherent risk of undesirable variation, known as batch effects, which may impact down-stream statistical analyses and increase the chances of false discoveries. The implementation of bridging controls on each plate has been suggested to mitigate this complication, but a clear method on how to use this strategy is still lacking. In this study, we characterized potential batch effects in proteomics using PEAs and generated guidelines to mitigate batch effects using bridging controls.
Results: This study characterized three distinct types of batch effects (protein-specific, sample-specific, and plate-wide) in PEA proteomic studies. We developed a new method, BAMBOO (Batch AdjustMents using Bridging cOntrOls), based on a robust regression model. In a simulation study, we compared BAMBOO with established batch correction techniques; median centering, median of the difference (MOD), and ComBat. We observed that median centering and ComBat were significantly impacted by outliers within the bridging controls, whereas BAMBOO and MOD were more robust when no plate-wide batch effects were introduced. Moreover, upon introduction of plate-wide batch effects, BAMBOO was performing better than MOD in terms of accuracy, true negative rate and true positive rate. Inclusion of 10-12 bridging controls was found to optimally correct for batch effects. Applying the different methods to experimental data showed that BAMBOO and MOD result in a reduced incidence of false discoveries compared to the alternative methods.
Conclusion: Our study underscores the prevalent existence of batch effects in PEA proteomic studies, which can be corrected using bridging controls using an innovative, robust and effective tool, BAMBOO. The use of BAMBOO may enhance the reliability of large-scale analyses in the proteomic field using PEA.
Causation Between the Gut Microbiota and Inguinal Hernia: A Two-Sample Double-Sided Mendelian Randomization Study
Authors: Wu Changyuan , Zhu Yujin , Xi Hongwei
Published: March 2024

Background
Inguinal hernias are the most common type of enterocele and are frequently caused by defects in the abdominal wall muscles in the groin area. Numerous animal models and human studies have shown that the gut microbiota is associated with skeletal muscle aging and loss. However, the causation between the gut microbiota and inguinal hernia remains unclear. To reveal the causal association between the gut microbiota and inguinal hernia, we conducted a two-sample double-sided Mendelian randomization analysis.
Methods
We used genome-wide association analysis (GWAS) summary statistics of the gut microbiota from the MiBioGen consortium and GWAS statistics of inguinal hernia from the FinnGen R10 database. The causation between the gut microbiota and inguinal hernia was explored through the inverse variance weighted (IVW) method, MR Egger regression method, weighted median method, weighted model method, and simple model method. Sensitivity analysis was used to test whether the Mendelian randomization analysis results were reliable. Reverse Mendelian randomization was used to conduct effect analysis and sensitivity analysis using the entire gut microbiota as the outcome.
Results
The IVW results indicated that Verrucomicrobia, Lactobacilliales, Clostridiaceae1, Butyricococcus, Categorybacter, Hungatella, Odoribacter, and Olsenella had a direct negative causation with the gut microbiota. The reverse Mendelian Randomization results showed that Eubacterium brachygroup, Eubacterium eligensgroup, Eubacterium xylanophilumgroup, Coprococcus3, Ruminococcus1, and Senegalimassilia were directly related to inguinal hernia. The bilateral sensitivity analysis revealed no heterogeneity or horizontal pleiotropy.
Conclusions
The results confirmed that 8 bacterial traits had a negative causation with inguinal hernia. Reverse MR analysis revealed a positive correlation between inguinal hernia and 6 bacterial traits. Modulating the diversity and components of the gut microbiota is envisaged to contribute to improving the incidence and prognosis of inguinal hernia.
Hidden RIP mutation – a ‘back-seat driver’ of effector diversity revealed by pan-genome analysis of the necrotroph Parastagonospora nodorum across the Western Australian wheat-belt region.
Authors: Hane James , Jones Darcy , Rybak Kasia , Hossain Mohitul , Bertazzoni Stefania , Williams Angela , Tan Kar-Chun , Phan Huyen
Published: March 2024

The fungal species Parastagonospora nodorum is an important pathogen of wheat and model necrotroph with significant genomic resources. In this study, population-level pan-genome data for 173 P. nodorum isolates - 156 from the Western Australian (WA) wheat-belt, and 17 internationally-sourced isolates – were examined for genomic diversity and pathogenicity effector gene content. A heterothallic core population was observed across all regions of WA, with asexually-reproducing clonal clusters in dryer northern regions. An abundant potential for SNP diversity –the majority in the form of repeat-induced point (RIP)-like C-T transitions - was evenly spread across the genome, however increases in non-synonymous mutations were concentrated around repeat-rich regions. Known effector genes and effector-like candidates were typically located around these and sub-telomeric regions. Protein isoform profiles of known effector loci (SnToxA, SnTox1, SnTox3, SnTox267, and SnTox5) indicated similarly low-level non-synonymous and high-level silent RIP-like mutations, and showed distinctive profiles across WA relative to international isolates. Prediction of novel effector genes across resulted in 186 candidate secreted predicted effector proteins (CSEPs), 69 with functional annotations that included 6 confirmed effectors. These new P. nodorum pan-genomic resources and diagnostic methods will support new approaches to region-specific surveillance and management of host-pathogen interactions in commercial crops.
Divergent antibody recognition profiles are generated by protective mRNA vaccines against Marburg and Ravn viruses.
Authors: Bukreyev Alexander , Meyer Michelle , Gunn Bronwyn , Pietzsch Colette , Subramani Chandru , Saphire Erica , Crowe James , Alter Galit , Himansu Sunny , Carfi Andrea
Published: March 2024

The first-ever recent Marburg virus (MARV) outbreak in Ghana, West Africa and Equatorial Guinea has refocused efforts towards the development of therapeutics since no vaccine or treatment has been approved. mRNA vaccines were proven successful in a pandemic-response to severe acute respiratory syndrome coronavirus-2, making it an appealing vaccine platform to target highly pathogenic emerging viruses. Here, 1-methyl-pseudouridine-modified mRNA vaccines formulated in lipid nanoparticles (LNP) were developed against MARV and the closely-related Ravn virus (RAVV), which were based on sequences of the glycoproteins (GP) of the two viruses. Vaccination of guinea pigs with both vaccines elicited robust binding and neutralizing antibodies and conferred complete protection against virus replication, disease and death. The study characterized antibody responses to identify disparities in the binding and functional profiles between the two viruses and regions in GP that are broadly reactive. For the first time, the glycan cap is highlighted as an immunoreactive site for marburgviruses, inducing both binding and neutralizing antibody responses that are dependent on the virus. Profiling the antibody responses against the two viruses provided an insight into how antigenic differences may affect the response towards conserved GP regions which would otherwise be predicted to be cross-reactive and has implications for the future design of broadly protective vaccines. The results support the use of mRNA-LNPs against pathogens of high consequence.
Effects of slag-based cementitious material on the mechanical behavior and microstructure evolution of copper-base cemented tailings backfill
Authors: Zhang Haina , Jiang Xinyue , Li Huan , Chen Shunman , Hu Wenhui , Kang Wenhan
Published: March 2024

A novel cementitious material (abbreviated as a cementitious powder (CP)) was developed by to achieve low-cost backfill mining. A comparative analysis of the strength test for cemented tailings backfill (CTB) was carried out to demonstrate the superiority of the CP over ordinary Portland cement (OPC). Furthermore, the deformation behavior and failure mode associated with the strength growth mechanism of the CTB assembled with CP were examined using uniaxial compression tests and micro-scanning observation. The findings indicate that CP has significant potential in replacing OPC; A higher mass concentration and longer curing age, as well as a lower tailing-to-cement ratio, have a favorable impact on the strength enhancement of the CTB; And the formation of C-S-H gel and ettringite cement the tailings particles and promote the densification of the cavity structure, thereby resulting in the high strength of CTB at the macro level. This work provides valuable insights into green mining.
Temporal Patterns of EEG Connectivity Unveil Parkinson's Disease Progression: Insights from Machine Learning Analysis
Authors: Alves Caroline L. , Sallum Loriz Francisco , Rodrigues Francisco Aparecido , Toutain Thaise G. L. de O. , Aguiar Patricia Maria de Carvalho , Moeckel Michael
Published: March 2024

Objectives: Parkinson’s disease is a multifactorial neurodegenerative disorder whose progression remains complex despiteextensive research. Our study presents an innovative approach to understanding PD progression through detailed analysis ofelectroencephalography signals. By segmenting patients based on disease duration, we uncover unique neural connectivitypatterns corresponding to different duration of PD development.
Methods: Employing advanced machine learning techniques,our methodology achieves exceptional accuracy rates in binary classification tasks compared to prior literature. Integrationof Shapley Additive Explanations values enhances model interpretability, revealing critical brain regions and connectivitypatterns implicated in PD pathophysiology.
Results: Coherence emerges as a crucial metric for capturing synchronizedsignal behaviors, aiding in discriminating PD patients from controls. Further, our analysis suggests a continuum of neuralconnectivity patterns across disease duration, with early-stage PD resembling healthy brain function and advanced durationexhibiting distinct features indicative of disease progression.
Conclusions: These findings deepen our understanding of PDpathogenesis, laying the groundwork for personalized diagnostic and therapeutic approaches tailored to different diseaseduration. Our study contributes significant insights into the complex interplay between neural dynamics, disease progression,and age-related changes in PD, offering potential for future research and clinical applications
A new day 4 embryo evaluation criteria to predict the formation of blastocyst
Authors: Dai Fangfang , Yasong Geng , Tao Linlin , Li Guozhen , Dai Haoyang , Wang Shusong , zheng Bo
Published: March 2024

Background
Currently, in vitro fertilization and embryo transfer (IVF-ET) typically involve transferring embryos on the third (D3) or fifth day (D5). However, a fresh cycle fourth day (D4) morula transfer offers a flexible and effective alternative. The compaction on the fourth day serves as a simple and reliable indicator to predict embryo implantation potential. The use of D4 transfer is gradually gaining popularity. Nevertheless, there is still a need for a comprehensive evaluation system for fourth day embryos.Thus, this study proposes to explore a day 4 embryo evaluation system based on the potential for the embryo to develop into a transferableblastocyst.
Methods We observed the outcome of blastocyst culture for 1235 embryos from 199 patients. We considered the developmental stage, fragmentation, whether it was in a stage-specific cleavage pattern, and normal fertilization on the fourth day. The fourth day embryo evaluation system was proposed by comparing them with the effect on blastocyst formation rate. The rates of blastocyst formation with different embryo grades were compared. The receiver operative characteristics(ROC) curve was used to compare the predictive abilities of four criteria for day 4 evaluation to develop into transferableblastocysts and high-quality blastocysts.
Results The developmental stage, fragmentation, normal fertilization and stage-specific cleavage pattern had the greatest impact on the formation of transferable blastocysts. There were significant differences in the formation rates of transferableblastocysts and high-quality blastocysts among different embryo grades. The areas under ROC curves of the day 4 embryo evaluation criteria constructed in this study was the highest in predicting formation of transferable or high-quality blastocyst, relative to the other three evaluation criteria. This study observed the presence of pseudo-compacted embryos similar to cleavage-stage embryos on the rate of blastocyst formation.
Conclusion The Day 4 embryo evaluation criteria constructed in this study can effectively predict the ability to develop into a blastocyst.
Enamel surface roughness following debonding resin clean up using high speed air-turbine and electric handpieces. In vitro study.
Authors: Yousry Tarek N. , Abolgheit salma , Kasssem Hassan E.
Published: March 2024

Background: High speed electric handpieces have been recently gaining popularity in the dental industry. Advantages include smoother surface preparation and increased cutting efficiency.
Aim: The primary objective was to compare the enamel surface roughness following post-debonding resin cleanup and polishing using highspeed air turbine and electric handpieces. The secondary objective was to record the time needed for resin-clean up.
Method: Forty de-identified freshly extracted human premolars were cleaned and sectioned. The crowns were imbedded in acrylic blocks. Roughness parameters of the enamel surface roughness were measured using a stylus profilometer recording (Ra, Rq, Rp and Rt). Brackets were bonded using a light cure orthodontic adhesive. Following bracket debonding, the specimens were randomly divided into 2 groups. Resin clean-up was carried out using a 12-fluted carbide bur mounted on a high-speed air turbine in the first group and an electric handpiece in the second group. Following resin cleanup, the enamel surfaces were polished using pumice and a rubber cup. Surface roughness parameters were recorded following resin clean up and after polishing. Time needed for resin clean-up was recorded. Comparison of surface roughness parameters and time will be compared between groups will be carried out using repeated measures ANOVA and independent samples t-test, respectively at P ≤ 0.05.
Results:
The electric handpiece groups showed significantly higher values for Ra, Rz and Rp both following resin cleanup and polishing. Time taken for resin cleanup was significantly longer for the electric handpiece group.
Conclusion
Considering both surface roughness and time, electric handpiece do not seem to add greater effectiveness or efficiency to resin cleanup following orthodontic bracket debonding.
Global, regional and national burdens of Nasopharynx cancer in the Adolescents and young adults from 1990 to 2019 and its predictions
Authors: Wang Yaojie , Huang Guoxin , Qin Bingqing , Zeng Jing , tan Huazhang , Zhang Dongdong , Wang Qiuyang
Published: March 2024

Purpose
To use data from the Global Burden of Disease (GBD) Study 2019 to report the global, regional and national rates and trends of deaths incidence, prevalence, disability-adjusted life years (DALYs) for Nasopharynx cancer (NPC) in adolescents and young adults (AYAs).
Methods
Data from the GBD 2019 were used to analyze deaths incidence, prevalence and DALYs due to NPC at global, regional, and national levels. Joinpoint regression analysis calculated the average annual percentage changes(AAPC). Then analyse the association between incidence, prevalence and DALYs and socioeconomic development using the GBD Socio-demographic Index (SDI). Finally, projections were made until 2030 and calculated in Nordpred.
Results
The deaths, incidence, prevalence and DALYs rates (95%UI) were 0.20 (0.19–0.22), 0.96 (0.85–1.09, 6.31 (5.54–7.20) and 12.23(11.27–13.29)in 2019, respectively. From 1990 to 2019, the deaths, incidence, prevalence, and DALYs rates AAPC (95%CI) were-1.64(-1.78 to -1.49), 1.79(1.03 to 2.55), 2.97(2.13 to 3.82)and-1.6(-1.75 to -1.4), respectively. Deaths and DALYs rates in South Asia, East Asia, North Africa and Middle East decreased with SDI. Incidence and prevalence rates in East Asia increased with SDI. At the national level, the incidence and prevalence rates are high in China, Taiwan(Province of China), Sinagapore, Malaysla, Brunel Darussaiam, Algeria, Tunisia, Libya and Malta. Meanwhile, the deaths and DALYs rates are still high in Malaysla, Brunel Darussaiam, Greenland and Taiwan(Province of China). The deaths and DALYs rates are low in Honduras, Finland and Norway. From the 2020 to 2030, ASIR、ASPR and ASDR in most regions are predicted to stable, but DALYs tends to decline.
Conclusion
NPC in AYAs is a significant global public problem. The incidence, prevalence, and DALYs rates vary widely by region and country. Therefore different regions and countries should be targeted to improve the disease burden of NPC.
Evaluating the bi-directional causal association between temporomandibular disorders and neurodegenerative diseases: a two-sample Mendelian randomisation study
Authors: Huang Xin , Li Jianing , Wang Rui , Tian Wenxin , Wang Yue
Published: March 2024

Background
Previous observational studies suggested that temporomandibular disorders (TMD) are associated with neurodegenerative diseases (NDs). This association may be mediated by confounding factors or reverse causation. Therefore, the objective of this study was to test the causal relationship between TMD and the four most common NDs [Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic Lateral Sclerosis (ALS) and Multiple Sclerosis (MS)].
Methods
Data on TMD (N = 134,280), AD (N = 63,926), PD (N = 482,730), ALS (N = 80,610), and MS (N = 115,803) were extracted from publicly available Genome-Wide Association Studies (GWAS). Single-nucleotide polymorphisms (SNPs) used as instrumental variables (IVs) were screened by setting the association strength and eliminating linkage disequilibrium. Inverse-variance weighting (IVW) method was employed as the primary analytical approach. However, weighted median, Mendelian randomization-Egger, and simple and weighted modes were used as complementary analysis methods to evaluate the causal effects. Tests for heterogeneity and pleiotropy were also performed. The results' stability was assessed using a leave-one-out analysis.
Results
Our findings revealed significant positive genetic correlations between TMD and PD (odds ratio = 1.223, 95% confidence interval = 1.064–1.406, P = 0.005). There was no significant association between TMD and AD, ALS, or MS. In the reverse Mendelian randomisation, no significant results supported the effect of NDs on TMD (all P > 0.05). The analyses did not reveal any evidence of heterogeneity or horizontal pleiotropy.
Conclusions
These results supply evidence of a potential causal relationship between TMD and PD, emphasising the importance of effectively managing TMD to prevent PD. However, it is imperative to conduct comprehensive studies to validate and elucidate the underlying mechanisms of this association.
RSR-YOLO: a real-time method for small target tomato detection based on improved YOLOv8 network
Authors: Yue Xiang , Qi Kai , Yang Fuhao , Na Xinyi , Liu Yanhua , Liu Cuihong
Published: March 2024

In tomato producing fields, automated large-area detection method is critical for fruit health monitoring and harvesting. However, due to the limited feature information included in tomatoes, large-area detection across long distances results in more missing or incorrect detections. To address this issue, this research proposes an improved YOLOv8 network, RSR-YOLO, for long-distance identification of tomato fruits. Firstly, this paper designs a partial group convolution (PgConv) and furthermore an innovative FasterNet (IFN) module for feature extraction, taking into account the impact of split operations on the computational complexity of the backbone network. The IFN module is lightweight and efficient, which improves the detection accuracy and real-time detection performance of the model. Secondly, this research combines the Gather and Distribute mechanism (GD) and redesigns the feature fusion module to implement the extraction and fusion of various levels of tomato features, given the critical significance that low-dimensional features play in small target recognition and localization. Finally, Repulsion Loss is used in this paper to examine the impact of fruit overlap and leaf occlusion on detection outcomes. RSR-YOLO achieves precision, recall, F1 score, and mean average precision (mAP@0.5) of 91.6%, 85.9%, 88.7%, and 90.7%, respectively, marking increases of 4.2%, 4%, 4.2%, and 3.6% compared to YOLOv8n. In addition, this paper designs a specialized Graphical User Interface (GUI) for the real-time detection task of tomatoes.
Asymptomatic malaria reservoirs in Honduras: a challenge for elimination
Authors: Banegas Sharon , Escobar Denis , Pinto Alejandra , Moncada Marcela , Matamoros Gabriela , Valdivia Hugo O. , Reyes Allan , Fontecha Gustavo
Published: March 2024

Background
Efforts on a global scale for combating malaria have achieved substantial progress over the past twenty years. Two Central American nations have accomplished their goal of eliminating malaria: El Salvador and Belize. Honduras has decreased the incidence of malaria and now reports fewer than 4,000 malaria cases annually, aspiring to reach elimination by 2030. To accomplish this goal, it is essential to assess the existing strategies employed for malaria control and to address the task of incorporating novel intervention strategies to identify asymptomatic reservoirs.
Methods
A survey for detecting asymptomatic cases was carried out in the community of Kaukira, in Gracias a Dios, Honduras, considered the focus of malaria transmission during 2023. Asymptomatic community members were recruited as participants, malaria screening was performed through a rapid diagnostic test in situ, and a blood sample was collected on filter paper. Highly sensitive molecular assays based on photo-induced electron transfer PCR (PET-PCR) were performed to detect the two species of Plasmodium circulating in Honduras, Plasmodium vivax and Plasmodium falciparum. In addition, the identification of the parasite species was verified by amplifying three genetic markers (Pvmsp3α, Pvmsp3ß, and Pfmsp1).
Results
A total of 138 participants were recruited, mostly adult women. All individuals tested negative on the rapid diagnostic test. Positive results for malaria were detected by PET-PCR in 17 samples (12.3%). Most samples were amplified with a Ct value between 37 and 42, indicating very low parasitaemias. Out of the 17 samples, 15 of them also showed amplification in the species assays. There were nine cases of P. falciparum infections and seven cases of P. vivax infections that were further confirmed by nested PCR (nPCR) of Pvmsp3 and Pfmsp1. Parasitaemias ranged from 100 p/µL to less than 0.25 p/µL. One sample showed mixed infection.
Conclusions
The existence of asymptomatic malaria reservoirs in Honduras can contribute to disease transmission and poses a challenge that may hinder elimination efforts, requiring public health authorities to modify surveillance strategies to identify the disease and treat this population accordingly.
Genesis of the Lakhshak orogenic Au–Sb deposit, SE Iran: insights from geology, microthermometry and stable isotope geochemistry
Authors: Rajabpour Shahrokh , Niroomand Shojaeddin , Dehkordi Nasim Heydarian , Tajeddin Hossein Ali , Nozaem Reza
Published: March 2024

The Lakhshak Au–Sb deposit in the SE Iran, is closely associated with Eocene calc–schist and quartz schist rocks intruded by Oligocene dikes and mylonitic granitoid. The main mineralization is characterized by a NE–SW shear zone structure and hydrothermal alterations have mainly developed in the contact zones of granitoid and calc–schist units. Quartz veins and veinlets are associated with Au and Sb–bearing minerals consisting of pyrite, arsenopyrite, stibnite, pyrrhotite, chalcopyrite, sphalerite, gold and electrum. The ore genesis, metallogenic processes, and the origin of ore fluids in the Lakhshak deposit are unknown, hence we report for the first time the geological, petrographic, microthermometry of fluid inclusions, Raman spectroscopy and sulfur and oxygen isotopes studies. In this study, four types of fluid inclusion assemblages were recognized in the mineralized quartz veins. The results of fluid inclusion microthermometric measurments yield homogenization temperatures of two–phase LV (type III) and ternary carbonic–aqueous phase (LCO2 + LH2 O + VCO2; type IV) fluid inclusions vary between 200 to 280°C and 300 to 330°C, whereas their salinity range from 9 to 11% and 8 to 13% wt. % NaCl, respectively. This implies that gold precipitation is derived from low–temperature and low–salinity ore fluids. The calculated δ18Ofluid values of quartz vary from 7.5 to 9.8‰, implying that the ore fluids may have a metamorphic origin that reacted repeatedly with the volcanic rocks along the conduits as well as the granitoid units adjacent to the ores and subsequently experienced sporadic equilibrium in oxygen fractionation during formation. Therefore, due to the significant oxygen isotopic exchange in the fluid–rock reaction, the metamorphic fluids show the isotopic properties of specific fluids of magmatic origin. Moreover, the δ34S values of pyrite (3.0 to 4.1‰) and stibnite (–0.9 to 0.8‰) from the main satge of mineralization show a magmatic origin for sulfur. Accordingly, it is suggested that the mixing and dilution of metamorphic fluids with meteoric water plausibly had a substantial effect on the evolution of ore–forming system at Lakhshak, similar to orogenic gold deposits worldwide.
In-silico analysis of SARS-CoV-2 N protein host interactors involved in Parkinson’s Disease and Dementia
Authors: Jain Priyanjal , Naithani Urshila , Prakash Vijeta , Gabrani Reema
Published: March 2024

Severe-acute-respiratory-syndrome-coronavirus-2 (SARS-CoV-2) is a highly pathogenic and contagious coronavirus that first surfaced in late 2019. The genome encodes four major structural proteins, non-structural proteins and accessory proteins. The nucleocapsid (N) protein of SARS-CoV-2 is an evolutionarily conserved RNA-binding protein that is abundant and plays a critical role in packaging the viral genome. Researchers have explored its potential as a target for therapeutic purposes. People with pre-existing neurological conditions like Parkinson’s disease (PD) and dementia have been recognised as a high-risk population for severe COVID-19 illness as SARS-CoV-2 has been reported to cause deterioration of the symptoms of these diseases. This study aims to identify the shared human interactors of SARS-CoV-2 N protein, PD and dementia. Proteins involved were retrieved from databases, and protein-protein interaction networks were created and visualized in Cytoscape. Individual intersection networks of SARS-CoV-2 N protein with PD and dementia resulted in 46 and 26 proteins, respectively, while intersection networks of SARS-CoV-2 N protein, PD and dementia resulted in 15 common proteins. Seed proteins were identified from network clusters and their Gene Ontology (GO) analysis revealed their involvement in several biological processes. Valosin-containing-protein (VCP) was found to be the only seed protein involved during the co-occurrence of SARS-CoV-2 N protein infection, PD and dementia and is mainly concerned with the regulation of the ubiquitin-proteasome system (UPS). Further, gene enrichment analysis of the identified 15 common proteins was conducted using the DAVID tool, followed by the identification of 7 druggable targets using the Therapeutic Target Database (TTD) and DrugBank. Studying the biological functions of the identified host-protein interactors is crucial for understanding the progression of the disease at a molecular level. Moreover, approved therapeutic compounds against the potential drug target proteins can also be utilized to develop effective treatments.
Directional output distance functions: A profit maximizing iterative method for choosing the optimal direction
Authors: Deng Zhongqi , Jiang Nan , Pang Ruizhi , Fan Xuecheng
Published: March 2024

Building upon the work established by Färe et al. (2013) and Divisia (1926), this study proposes an iterative method to tackle the issue of how to select an optimal direction in a directional output distance function analysis. The core idea behind this method is using shadow prices of outputs, which are estimated by iterating directional output distance functions with slacks-based measure, to replace their real prices. By projecting inefficient firms towards profit maximizing benchmarks, our direction selection is consistent with firms’ profit maximizing behavior. At the end, we provide an illustration that evaluates the health system efficiency of public hospitals in New Zealand during 2011–2017.
A mixture of experts regression model for functional response with functional covariates
Authors: TCHOMGUI Jean Steve TAMO , JACQUES Julien , FRAYSSE Guillaume , BARRIAC Vincent , CHRETIEN Stéphane
Published: March 2024

Due to the fast growth of data that are measured on a continuous scale, functional data analysis has undergone many developments in recent years. Regression models with a functional response involving functional covariates, also called "function-on-function", are thus becoming very common. Studying this type of model in the presence of heterogeneous data can be particularly useful in various practical situations. We mainly develop in this work a Function-on-Function Mixture of Experts (FFMoE) regression model. Like most of the inference approach for models on functional data, we use basis expansion (B-splines) both for covariates and parameters. A regularized inference approach is also proposed, it accurately smoothes functional parameters in order to provide interpretable estimators. Numerical studies on simulated data illustrate the good performance of FFMoE as compared with competitors. Usefullness of the proposed model is illustrated on two data sets: the reference Canadian weather data set, in which the precipitations are modeled according to the temperature, and a Cycling data set, in which the developed power is explained by the speed, the cyclist heart rate and the slope of the road.
Navigating the Multiverse: A Hitchhiker's Guide to Selecting Harmonisation Methods for Multimodal Biomedical Data
Authors: Saras Murali Aadhitya Magateshvaren , Mitra Mithun K. , Tyagi Sonika
Published: March 2024

Introduction: The application of machine learning (ML) techniques in classification and prediction tasks has greatly advanced our comprehension of biological systems. There is a notable shift in the trend towards integration methods that specifically target the simultaneous analysis of multiple modes or types of data, showcasing superior results compared to individual analyses. Despite the availability of diverse ML architectures for researchers interested in embracing a multimodal approach, the current literature lacks a comprehensive taxonomy that includes the pros and cons of these methods to guide the entire process. Closing this gap is imperative, necessitating the creation of a robust framework. This framework should not only categorise the diverse ML architectures suitable for multimodal analysis but also offer insights into their respective advantages and limitations. Additionally, such a framework can act as a guide for selecting an appropriate workflow for multimodal analysis. This comprehensive taxonomy would furnish a clear guidance and aid in informed decision-making within the progressively intricate realm of biomedical and clinical data analysis, and is imperative for advancing personalised medicine.
Objective: The aims of the work are to comprehensively study and describe the harmonisation processes that are performed and reported in the literature and present a working guide that would enable planning and selecting an appropriate integrative model.
Methods: A systematic review of publications that report the multimodal harmonisation of biomedical and clinical data has been performed.
Results: We present harmonisation as a dual process of representation and integration, each with multiple methods and categories. The taxonomy of the various representation and integration methods are classified into six broad categories and detailed with the advantages, disadvantages and examples. A guide flowchart that describes the step-by-step processes that are needed to adopt a multimodal approach is also presented along with examples and references.
Conclusions: This review provides a thorough taxonomy of methods for harmonising multimodal data and introduces a foundational 10-step guide for newcomers to implement a multimodal workflow.
Revisiting Termination of the Multi-Agent Pathfinding Algorithm CoDy
Authors: Schwarz Leon
Published: March 2024

This paper presents analyses and optimizations on the termination behavior of the Multi- Agent Pathfinding (MAPF) algorithm CoDy (Cooperative Dynamic). Its purpose is to address reliable path planning of autonomous Multi-Robot Systems. CoDy is the only MAPF algorithm of its kind that is especially designed for the path planning of fully equal and fully decentralized agents in a robust manner. Depending on the given task however, CoDy cannot find solutions reliable in an appropriate amount of time. Of all presented performance results, the task in which these reliability issues appear the most is the so called ”6vs6” task. This work examines the possibilities to enhance reliability for this task. An optimization that deals with a common group of strong termination delays is implemented. Simulations show that this optimization improves the termination rate under appropriate time immensely and can even increase the termination rate of other tasks.
Medicago sativa Extracts Enhance the Anticancer Efficacy of GEM in PANC-1 Cells through Apoptosis Induction and BAX/BCL-2/CASP3 Expression Modulation
Authors: Jamshidi Nazanin , Jamshidi Negar , Zaman Mohammad , Chehresaz Mahta , Roshanfarzad Farnaz , Chaleshi Vahid , Aghdaei Hamid Asadzadeh
Published: March 2024

Introduction
Pancreatic cancer (PC) has a poor prognosis and limited response to therapies. Combinatorial approaches, such as natural product-based therapies, can enhance anticancer efficacy while minimizing side effects. This study evaluated M. sativa’s anticancer properties and its potential as adjunctive therapy with GEM to sensitize PANC-1 cells to chemotherapy.
Methods
The antioxidant activity (AA) and total phenolic content (TPC) of M. sativa extracts (MeOH, EtOAc, and water) were assessed using the DPPH radical scavenging assay. Cytotoxic effects on PANC1 and HUVEC cells were also evaluated by utilizing the MTT assay. Then, apoptosis detection was performed by Annexin V/PI-flow cytometry (FC). Besides, the DNA fragmentation analysis was conducted utilizing agarose gel electrophoresis (AGE). BCL-2, BAX, and CASP3 expression levels in PANC-1 cells using western blot analysis and qRT-PCR.
Results
Herein, DPPH IC50 values for M. sativa extracts (water, MeOH, EtOH) were 76.21, 110.32, and 65.39 µg/ml, respectively. The water extract of M. sativa exhibited the highest TPC (4612.15 ± 119.4 mgGAE/g). The cytotoxicity IC50 values for EtOH M. sativa extract, GEM, and combined GEM with EtOH M. sativa on PANC1 cells were 68.74, 43.53, and 41.22 µg/ml M. sativa + 25 µg/ml GEM, respectively, with no toxicity observed in HUVEC cells. FC analysis revealed that Combining GEM and EtOH M. sativa yielded the highest apoptosis rate (25.6%). Expression changes in BCL-2, BAX, and CASP3, as well as morphological alterations and DNA fragmentation, indicated apoptotic cell death.
Conclusion
Our findings suggested that combining M.sativa EtOH extracts with GEM may represent a promising strategy for treating PC.
Bridging the Research Gap: Establishing a Rabbit Model for Perianal Fistula (Nassor-E Maqad) Study
Authors: Bukhari Syed Abdul Shakoor , Begum Zaibunnisa , Patil Pradeep B.
Published: March 2024

Fistula-in-ano, termed ‘Nassor-e-Maqad’in traditional Arabic medicine, presents a challenging perianal pathology necessitating a robust experimental framework for comprehensive inquiry. This investigation endeavors to establish an induced Fistula-in-ano model in New Zealand White (NZW) Rabbits (n=12) utilizing a protocol involving surgical suturing steel wire implantation for durations of 20 days (Group ‘A’) and 40 days (Group ‘B').
The principal aim of this research is to develop an induced Fistula-in-anomodel in NZW rabbits, with the objective of enhancing comprehension of perianal disease pathogenesis and exploring novel therapeutic modalities. Given the absence of universally efficacious and complication-free treatments, the development of innovative therapeutic approaches is imperative. Hence, the creation of an optimal animal model capable of simulating persistent anal fistulas with lesions resembling clinical manifestations is vital for preclinical investigations in this domain.
Upon imaging (X-ray and perianal ultrasonography) the patency of fistula was evaluated whereas histological evaluation exhibited that animals in Group ‘A’ (n=06) fistula has openings with modest epithelialization subsequent to the removal of the surgical steel suture ring, along with favorable diagnostic outcomes, 20 days post-surgery. Conversely, animals in Group ‘B’ (n=6), upon steel wire removal after 40 days, displayed notable changes in epithelization, indicative of further progression in the induced fistula model.
In summary, this study successfully establishes a preclinical rabbit model of perianal fistula devoid of chemical agents, relying solely on surgical induction via surgical suturing steel wire (SSSW). The considerable anatomical and histological parallels between rabbit and human perianal pathophysiology underscore the suitability of rabbits as an experimental model for advancing therapeutic strategies in proctology.