bluuebunny/crossref_metadata_2025_split huggingface dataset:
Whole genome analysis of rare deleterious variants adds further evidence to BRSK2 and other risk genes in Autism Spectrum Disorder
Authors: Bacchelli Elena , Viggiano Marta , Ceroni Fabiola , Visconti Paola , Posar Annio , Scaduto Maria , Sandoni Laura , Baravelli Irene , Cameli Cinzia , Rochat Magali , Maresca Alessandra , Vaisfeld Alessandro , Gentilini Davide , Calzari Luciano , Carelli Valerio , Zody Michael , Maestrini Elena 
Published: October 2023

Abstract
Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with a strong genetic component in which rare variants contribute significantly to risk. We have performed whole genome and/or exome sequencing (WGS and WES) and SNP-array analysis to identify both rare sequence and copy number variants (SNVs and CNVs) in 435 individuals from 116 ASD families. We identified 37 rare potentially damaging de novo SNVs (pdSNVs) in cases (n = 144). Interestingly, two of them (one stop-gain and one missense variant) occurred in the same gene, BRSK2. Moreover, the identification of 9 severe de novo pdSNVs in genes not previously implicated in ASD (RASAL2, RAP1A, IRX5, SLC9A1, AGPAT3, MGAT3, RAB8B, MGAT5B, YME1L1), highlighted novel candidates. Potentially damaging CNVs (pdCNVs) provided support to the involvement of inherited variants in PHF3, NEGR1, TIAM1 and HOMER1 in neurodevelopmental disorders (NDD), although mostly acting as susceptibility factors with incomplete penetrance. Interpretation of identified pdSNVs/pdCNVs according to the ACMG guidelines led to a molecular diagnosis in 19/144 cases, but this figure represents a lower limit and is expected to increase thanks to further clarification of the role of likely pathogenic variants in new ASD/NDD candidates. In conclusion, our study strengthens the role of BRSK2 and other neurodevelopmental genes in ASD risk, highlights novel candidates and contributes to characterize the allelic diversity, mode of inheritance and phenotypic impact of de novo and inherited risk variants in ASD/NDD genes.
Unraveling the effects of the Ebola experience on behaviour choices during COVID-19 in Liberia: A mixed methods study across successive outbreaks
Authors: Skrip Laura , Weller Malcolm , Dukuly Sheikh , Candy Neima , Harmon-Gray Wahdae-Mai , Clarke Adolphus , Dahn Bernice T. 
Published: October 2023

Abstract
Background
The burden of the COVID-19 pandemic in terms of morbidity and mortality differentially affected populations. Between and within populations, behaviour change was likewise heterogeneous. Factors influencing precautionary behaviour adoption during COVID-19 have been associated with multi-dimensional aspects of risk perception; however, the influence of lived experiences during other recent outbreaks on behaviour change during COVID-19 has been less studied.
Methods
To consider how the direct disease experience (‘near misses’) and behaviour change during the 2014–2016 Ebola virus disease (EVD) outbreak may have impacted behaviour change during the early waves of the COVID-19 outbreak in West Africa, we analyzed data from a mixed-methods study that included a phone-based survey and in-depth interviews among vaccinated Liberian adults. Logistic regression via generalized estimating equations with QIC-based model selection was conducted to evaluate influence of the interaction between and individual effects of outbreak (EVD and COVID-19) and ‘near miss’ experience on adoption of individual precautionary behaviours. Thematic analysis of interview transcripts explored reasons for differential behaviour adoption between the two outbreaks.
Results
At the population level, being a ‘near miss’ was not associated with significantly different behavior during COVID-19 versus Ebola; however, overall, people had lower odds of adopting precautionary behaviors during COVID-19 relative to during Ebola. Qualitatively, participants often reflected on themes around more proximal and personal experiences with Ebola than with COVID-19; they also commented on how EVD led to better preparedness at the systems level and within communities for how to behave during an outbreak, despite such awareness not necessarily translating into action during COVID-19.
Conclusion
The results suggest that perceived proximity and intensity to disease threats in space and time affects behavioural decisions. For successive disease threats, comparisons of the present outbreak to past outbreaks compound those effects, regardless of whether individuals had directly been impacted via a ‘near miss’ experience. Measures, such as risk communication and community engagement efforts, that gauge and reflect comparisons with previous outbreaks should be considered within response strategies to enhance precautionary behaviour adoption.
Knowledge and practice of Doctors on the biomarker score in determining the risk of heart failure in GOMA
Authors: Ng’ekieb Ferdinand , Nkodila Aliocha Natuhoyila , Kipela Augustin Mpwo , Kalala Cedric Mbala , Situakibanza Hippolyte Nani tuma , Mukadi-Bamuleka Daniel , Mihanda Richard Bitwe , Wembomyama Stannislas Okitotsho , Tsongo Zacharie Kibendelwa 
Published: October 2023

Abstract
Background : Heart failure (HF) is a common condition, long considered a symptomatic disease. Today the burden linked to HF has pushed researchers to implement means of early detection such as the biomarker score.
Methods : This was a transverse and analytical study that included 135 doctors from the public and private sectors. The snowball method was used to identify doctors. Sociodemographic and knowledge characteristics were studied.
Results : a total of 135 Doctors were interviewed, The majority of Doctors had poor knowledge (35.6%). After adjustment in multivariate analysis, provision in the West block (aOR 3.62 95% CI: 1.74-5.93), training in a public university (aOR 2.64 95% CI: 1.27-3.96), the specialty in Internal Medicine (aOR 2.73 95% CI: 1.44-3.91) and service in a tertiary hospital (aOR 3.43 95% CI: 1.52-5.91) had emerged as independent determinants of good knowledge on biomarker score in heart failure determination.
Conclusion : Doctors' knowledge of this topic is low; following difficulties in the means of sharing knowledge.
The correlation between antioxidant, anti-inflammatory activity and the composition of free and bound phenolics in Chinese olive cultivars
Authors: He Fangqing , Du Yixuan , Pan Zhuangguang , Zeng Huize , Luo Haolin , Wang Junyi , Sun Yuanming , Li Meiying 
Published: October 2023

Abstract
As the food of homologous of medicine and food in China, the Chinese olive (Canarium album L.) is a natural phenolic antioxidant and anti-inflammatory agent. However, the disparity of anti-inflammatory activity in different cultivars and existing forms may be due to peculiar phenolic compounds that are not yet well-explored in the literature. In this study, 44 phenolic compounds were found in three species of free phenolics (FP) and bound phenolics (BP) and 17 phenolic compounds including syringic acid, caffeic acid, esculetin and so on were first reported in Chinese olive. Among cultivars, ‘Tan xiang’ and ‘Na zhong’ showed the best antioxidant and inhibition (LPS-induced NO and TNF-α production) activities in FP and BP separately. Furthermore, clustering correlation analysis showed that gallic acid, catechin, syringic acid and nobiletin contribute similarly, galloyl-bis-HHDP-glucose, epigallocatechin, dihydrokaempferol, genistein, galloylquinic acid, 4-hydroxycinnamic acid, and methyl ellagic acid pentoside may cause discrepancies to inflammatory effects in FP and BP. Collectively, our study uncovered the relationship between the constitution of phenolic compounds and bioactivities in cultivars of Chinese olives.
FBXO11 Variants are Associated with Intellectual Disability and Variable Clinical Manifestation in Chinese Patients
Authors: Pan Xin , Liu Li , Zhang Xu , Tang Xianglan , Qian Guanhua , Qiu Hao , Lin Shuhong , Yao Hong , Dong Xiaojing , Tan Bo 
Published: October 2023

Abstract

F-box protein 11 (FBXO11) is a member of F-Box protein family, which has recently been proved to be associated with intellectual developmental disorder with dysmorphic facies and behavioral abnormalities (IDDFBA, OMIM: 618089). In this study, 12 intellectual disability patients from 5 Chinese ID families were collected, and whole exome sequencing (WES), sanger sequencing, and RNA sequencing (RNA-seq) were conducted. Almost all the patients presented with mild to severe intellectual disability (12/12), global developmental delay (10/12), speech and language development delay (8/12) associated with a range of alternate features including increased body weight (7/12), short stature (6/12), seizures (3/12), reduced visual acuity (4/12), hypotonia (1/12), and auditory hallucinations and hallucinations (1/12). Distinguishingly, malformation was not observed in all the patients. WES analysis showed 5 novel FBXO11 variants, which include an inframe deletion variant, a missense variant, two frameshift variants, and a partial deletion of FBXO11 (exon 22-23). RNA-seq indicated that exon 22-23 deletion of FBXO11 results in a new mRNA structure. Conservation and protein structure prediction demonstrated deleterious effect of these variants. The DEGs analysis revealed 488 differentially expressed genes shared among 6 patients, which were associate with genes of immune system, metabolism, protein binding, cytosol, and nucleoplasm. Among them, 272 genes were down-regulated and 216 were up-regulated. Our research is the first report of FBXO11-associated IDDFBA in Chinese patients, which expands the genetic and clinical spectrum of this newly identified NDD/ID syndrome and advances understanding of molecular pathogenesis of FBXO11.
Differences in sarcopenia status and mortality according to physical activity: Results from the Korean Longitudinal Study on Health and Aging (KLoSHA)
Authors: Shim Ga Yang , Jang Hak Chul , Kim Ki-Woong , Lim Jae-young 
Published: October 2023

Abstract
Purpose: There is increasing evidence that promoting physical activity (PA) can prevent sarcopenia. However, PA decreases with age, and the impact of PA intensity on health is unclear. This study investigated the relationship between the level of PA and sarcopenia, and the association between PA levels and mortality in patients with and without sarcopenia.
Methods: Data were derived from the Korean Longitudinal Study on Health and Aging. PA was classified as sedentary behavior (SB), light physical activity (LPA), or moderate-to-vigorous physical activity (MVPA). Each PA level was subdivided based on the median time spent engaged in that activity, yielding eight PA profiles. Logistic regression and Cox proportional hazard models were used to investigate the association between PA level and sarcopenia, and between PA profiles and mortality.
Results: This study included 620 participants. During follow-up, 264 (42.6%) participants died. Overall, sarcopenic participants were less physically active than non-sarcopenic participants. After multivariate adjustment, more SB and less MVPA were associated with sarcopenia and all related variables, except muscle mass. Compared with the reference, non-sarcopenic participants with lower SB and concomitantly higher MVPA had significantly lower hazard ratios for mortality, while higher LPA reduced mortality in sarcopenic participants regardless of time spent engaged in SB or MVPA.
Conclusions: PA, especially SB and MVPA, was associated with sarcopenia and related variables, but the level of PA that prevented death differed according to sarcopenia status. Our findings may help determine the optimal intensity and amount of PA.
The male-to-female ratio in late-onset multiple acyl-CoA dehydrogenase deficiency: a systematic review and meta-analysis
Authors: Ma Jing , Zhang Huiqiu , Liang Feng , Li Guanxi , Pang Xiaomin , Zhao Rongjuan , Wang Juan , Chang Xueli , Guo Junhong , Zhang Wei 
Published: October 2023

Abstract
Background: Late-onset multiple acyl-CoA dehydrogenase deficiency (MADD) is the most common lipid storage myopathy. There are sex differences in fat metabolism and it is not known whether late-onset MADD affects men and women equally.
Methods: In this systematic review and meta-analysis, the PubMed, Embase, Web of Science, CNKI, CBM, and Wanfang databases were searched until 01/08/2023. Studies reporting sex distribution in patients with late-onset MADD were included. Two authors independently screened studies for eligibility, extracted data, and assessed risk of bias. Pre-specified outcomes of interest were the male-to-female ratio (MFR) of patients with late-onset MADD, the differences of clinical characteristics between the sexes, and factors influencing the MFR.
Results: Of 3379 identified studies, 34 met inclusion criteria, yielding a total of 609 late-onset MADD patients. The overall pooled percentage of males was 58% (95% CI, 54%-63%) with low heterogeneity between studies (I2 = 2.99%; P = 0.42). The mean onset ages, diagnostic delay, and serum creatine kinase (CK), and allelic frequencies of 3 hotspot variants in ETFDH gene were similar between male and female patients (P > 0.05). Meta-regressions revealed that ethnic group was associated with the MFR in late-onset MADD, and subgroup meta-analyses demonstrated that East-Asian patients had a higher percentage of male, lower CK, and higher proportion of hotspot variants in ETFDH gene than non-East-Asian patients (P < 0.05).
Conclusions: Male patients with late-onset MADD were more common than female patients. Ethnic was proved to be a factor influencing the MFR in late-onset MADD. These findings have implications for that male sex may be a risk factor for the disease.
Determinants of Malaria treatment seeking time for under five years children in Uganda. A Case Study of Apac District
Authors: Nabulya Olivia , Mbaka Paul , Walekhwa Abel Wilson , Ordur Bernard 
Published: October 2023

Abstract
Background
Malaria is a public health threat in sub–Saharan Africa and endemic in Uganda with Apac one of high burden districts. Malaria is known to be leading cause of morbidity and mortality among children under five years old in Uganda. However, little is known about the community management of malaria and treatment-seeking patterns. We aimed to assess determinants of malaria treatment-seeking behaviour for children under-five years by their caretakers in Apac district.
Methods
A cross sectional descriptive study was designed with quantitative data collection methods. Simple random sampling technique was used in identifying the caretakers as study participants for this study. Structured questionnaires were administered to caregivers in 240 households. Survival analysis was done to investigate the socio-economic, demographic, and behavioural factors that affect time to seek malaria treatment for children by their caretakers/parents using R.
Results
We had 100% response rate. All caregivers sought treatment for their children and out of the 240 caregivers, (70%) are female. Our results showed that education level, employment status, marital status, household wealth index, choice of the hospital and reason for delayed treatment were significantly associated with malaria treatment seeking time among caretakers of children under five years.
Conclusion
Timely drug supply to the main hospital and to households by the Village Health Teams to effectively ensure early treatment-seeking behaviours for malaria and sensitization of caregivers on early malaria treatment attendance of their ill children. The government should expand education financing for basic, intermediate, and university institutions, as well as adult education initiatives. Non-governmental organizations (NGOs) should be encouraged to play a role in educating caregivers, particularly on treatment-seeking behaviours for malaria-infected children under the age of five. Early malaria treatment in children under the age of five requires efficient medicine supply to primary hospitals and families by Village Health Teams (VHTs). It is also critical to educate caregivers on early treatment and suitable healthcare options for fever.
Trial registration
Not applicable
Reduction of Sulfur in Fuel oil Using Fe2O3 Hybrid Nanoadsorbent by Solvent Deasphalting and Optimization of Operational Parameters with CCD
Authors: Malek Mohammadreza , Samipourgiri Mohammad , Rashidi Alimorad , Majidian Nasrolah 
Published: October 2023

Abstract
The present study investigated and tested the effect of adding three types of nanoadsorbents (multi-walled carbon nanotubes (MWCNT)) in pure form, multi-walled carbon nanotubes with Fe2O3 particles (MWCNT-Fe2O3) hybrid, and Silanated-Fe2O3 hybrid to heavy fuel oil to reduce sulfur using a deasphalting process with solvent. First, all three types of nanoadsorbents were synthesized. Then, the Central Composite Design (CCD) method was used to identify the parameters effective in deasphalting, such as the type of nanoadsorbent, the weight percentage of nanoadsorbent, and the solvent-to-fuel ratio, and to obtain their optimal values. Based on the optimization result, under laboratory temperature and pressure conditions, the highest percentage of sulfur reduction in deasphalted fuel (DAO) was obtained by adding 2.5% by weight of silanated-Fe2O3 nano-adsorbent and with a solvent-to-fuel ratio of 7.7 (The weight percentage of sulfur in DAO increased from 3.5% by weight to 2.46%, indicating a decrease of 30%). Additionally, by increasing the temperature to 70°C, in optimal conditions, the results revealed that the remaining sulfur percentage in DAO decreased to 2.13% by weight, indicating a decrease of 40%. Synthesized nanoadsorbents and asphaltene particles adsorbed on the surfaces of nanoadsorbents were evaluated by XRD, FTIR, FESEM, and TEM techniques.
Comparative functional aspects of 3T3 fibroblasts in 2D and 3D cell- culture environment
Authors: Chaturvedi Madhusudan , Chugh Rishi Man , Raisuddin Sheikh , Yerneni Lakshmana Kumar 
Published: October 2023

Abstract
Tissue engineering is a multipurpose and valuable tool extensively employed for tissue architecture, and the evaluation of drug efficacy, with other applications. Its particular focus on techniques aimed at restoring or replacing part or entire tissues of replaceable organs. The development of in-vitro bioengineered skin models holds significant potential for clinical utilization. Most existing skin bioengineering methods primarily rely on two-dimensional (2D) cell cultures, which, however, possess notable limitations, particularly in the context of assessing the safety and effectiveness of topical pharmaceutical agents’ due absence of dermal-epidermal interaction. In contrast, three-dimensional (3D) skin bioengineering model enabling the epidermal keratinocytes culture in combination with fibroblasts embedded within 3D matrices. In this study, we have designed a comprehensive experimental approach to investigate the role of Swiss 3T3 cells and their variants pre-exposed to a single pulse of varying doses of Mitomycin C collagen-embedded in supporting the growth of keratinocytes. We examined the proliferation and viability of 3T3 cells to assess their ability to provide growth of epidermal cells in an embedded niche. Additionally, we analysed the levels of Keratinocyte Growth Factor, paracrine secretion by fibroblasts in both 2D and 3D cell culture condition. Furthermore, we conducted a histological comparison of the epidermal layers constructed under 2D and 3D cell culture conditions, evaluating the expression of various epidermal markers to gain insights into their structural and functional differences. This study sheds light on the pivotal role of 2D and 3D skin bioengineering models and their potential applications in dermatological research and pharmaceutical development.
Cost-Effectiveness Analysis of talazoparib Maintenance Treatment for patients with germline BRCA1/2 mutated HER2-negative advanced breast cancer in China and the US
Authors: Xu Qiaoping , Pan Junjie , Ren Ning , Ren Lanqi , Yang YiBei , Wang Gang 
Published: October 2023

Abstract
Objective: Breast cancer is one of the tumors with the highest prevalence rate among women in the world, and its BRCA1/2 gene is a common mutation site. Talazoparib, as a targeted PARP inhibitor, can effectively control the occurrence and development of breast cancer with BRCA1/2 gene mutation, and play a therapeutic role. Based on the phase III EMBRACE trial (NCT01945775 clinical trial), this paper aims to use Talazoparib's scheme to treat HER2-negative advanced breast cancer and obtain the economic cost-effectiveness of Talazoparib. This article conducts a cost-benefit analysis of the treatment regimen for Talazoparib from the perspectives of Chinese and American patients.
Methods: To evaluate the cost-effectiveness of Talazoparib more scientifically and provide clinicians with chemotherapy options, this paper developed a Markov model based on the EMBRACA clinical trial (clinical Trails.gov No., NCT01945775) to simulate the survival events of breast cancer patients in the Talazoparib group and the standard treatment group. The state transition probability and clinical data of breast cancer patients during treatment were extracted from the phase III EMBRACA clinical trial. The cost data generated during the treatment process comes from local hospital pricing, other references, and expert consultation. This article uses US dollars to calculate the treatment cost and incremental cost-effectiveness ratio. Health outcomes are expressed in Quality Adjusted Life Years (QALYs). In addition, Outcomes were measured in quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio, which robustness was evaluated by deterministic and probabilistic sensitivity analyses.
Results: This article establishes a Markov model for single-item sensitivity analysis. The results show that the economic benefits of using Talazoparib as a new treatment strategy in both China and the United States are higher than other drugs, and it is cost-effective. Compared to the control group, the incremental cost incurred by the Talazoparib treatment group in China was $2484.48/QALY, with an incremental QALY of 1.5. However, Talazoparib in the United States holds a dominant position, saving costs of $10223.43 and increasing QALYs by 1.5.
Conclusion: Through pharmacoeconomic analysis, this paper found that when the QALY thresholds in China and the United States were 3185 US dollars/month and 19100 US dollars/month respectively, the maintenance treatment of Talazoparib for HER2 negative advanced breast cancer patients with BRCA1/2 gene mutation was more cost-effective than that of Eribulin, Gemcitabine and Capecitabine. So, Talazoparib is expected to become a new treatment option.