bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hubungan Status Pekerjaan Ibu dengan Perkembangan Anak Toddler di Wilayah Kerja Puskesmas Talise
Authors: Farhana Ririn , Lenny Lenny , Patompo Fadli Dg. , Nurmalisa Baiq Emy 
Published: January 2024

Pertumbuhan dan perkembangan mengalami peningkatan yang pesat saat anak berusia 0-5 tahun yang biasa disebut sebagai fase “Golden Age”. Peran ibu diperlukan dalam memenuhi kebutuhan dasar untuk tumbuh kembang anaknya, mengingat hubungan keeratan emosional antara ibu dan anak sangat dekat. Tujuan penelitian ini adalah diketahuinya hubungan antara status pekerjaan ibu dengan perkembangan anak toddler di Wilayah Kerja Puskesmas Talise.
Penelitian ini merupakan metode penelitian analitik observasional dengan pendekatan cross sectional. Sampel penelitian berjumlah 43 anak toddler dengan umur 12-14 bulan dengan teknik pengambilan sampel yaitu purposive sampling. Data dikumpulkan dengan menggunakan kuesioner dan Formulir Kuesioner Pra Skrining Perkembangan (KPSP). Analisis bivariat dengan uji Chi-Square.
Hasil penelitian menunjukkan mayoritas anak adalah dengan perkembangan sesuai dengan tahap perkembangannya sebanyak 32 anak (74,4%) dan mayoritas ibu dari responden tidak bekerja yaitu sebanyak 23 orang (53,5%). Hasil uji chi-square diperoleh p value yaitu 0,257 (p > 0,05) artinya tidak ada hubungan yang signifikan antara status pekerjaan ibu dengan perkembangan pada anak toddler di Wilayah Kerja Puskesmas Talise. Saran penelitian ini Puskesmas Talise agar meningkatkan pelayanan kesehatan anak tentang perkembangan anak terutama dalam pengembangan program SDIDTK (Stimulasi, Deteksi dan Intervensi Dini Tumbuh Kembang Anak).
Mendelian randomization analysis to investigate the gut microbiome in oral and oropharyngeal cancer
Authors: Zhang Qihe , Wang Huanhuan , Tian Yuan , Li Jinjie , Xin Ying , Jiang Xin 
Published: January 2024

BackgroundEvidence supports an observational association between the gut microbiome and susceptibility to extraintestinal cancers, but the causal relationship of this association remains unclear.MethodsTo identify the specific causal gut microbiota of oral and oropharyngeal cancer, we performed two-sample Mendelian randomization (MR) analysis of gut microbiota on oral and oropharyngeal cancer using a fixed-effects inverse-variance-weighted model. Gut microbiota across five different taxonomical levels from the MiBioGen genome-wide association study (GWAS) were used as exposures. Oral cancer, oropharyngeal cancer and a combination of the two cancers defined from three separate data sources were used as the outcomes. Odds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher abundance of microbiome.Results &amp; ConclusionsThere was little evidence for a causal effect of gut microbiota on oral and oropharyngeal cancer when using a genome-wide p-value threshold for selecting instruments. Secondary analyses using a more lenient p-value threshold indicated that there were 90 causal relationships between 58 different microbial features but that sensitivity analyses suggested that these were possibly affected by violations of MR assumptions and were not consistent across MR methodologies or data sources and therefore are also to unlikely reflect causation. These findings provide new insights into gut microbiota-mediated oral and oropharyngeal cancers and warrant further investigation.
Spatial profiling of the placental chorioamniotic membranes reveals upregulation of immune checkpoint proteins during Group B Streptococcus infection in a nonhuman primate model
Authors: Manuel Gygeria , Coleman Michelle , Orvis Austyn S. , Munson Jeff , Li Amanda , Kapur Raj P. , Li Miranda , Li Edmunda , Armistead Blair , Rajagopal Lakshmi , Adams Waldorf Kristina M. 
Published: January 2024

BackgroundPreterm birth is a leading cause of neonatal mortality, which is often complicated by intrauterine infection and inflammation. We have established a nonhuman primate model of Group B Streptococcus (GBS, Streptococcus agalactiae) infection-associated preterm birth. Immune checkpoints are modulators of the immune response by activating or suppressing leukocyte function and are understudied in preterm birth. The objective of this study was to spatially profile changes in immune protein expression at the maternal-fetal interface during a GBS infection with a focus on immune checkpoints.MethodsTwelve nonhuman primates (pigtail macaques, Macaca nemestrina) received a choriodecidual inoculation of either: 1) 1-5 X 108 colony forming units (CFU) of hyperhemolytic/hypervirulent GBS (GBSΔcovR, N=4); 2) an isogenic/nonpigmented strain (GBS ΔcovRΔcylE, N=4); or, 3) saline (N=4). A Cesarean section was performed at preterm labor or 3 days after GBS infection or 7 days after saline inoculation. Nanostring GeoMx® Digital Spatial Profiling technology was used to segment protein expression within the amnion, chorion, and maternal decidua at the inoculation site using an immuno-oncology panel targeting 56 immunoproteins enriched in stimulatory and inhibitory immune checkpoint proteins or their protein ligands. Statistical analysis included R studio, Kruskal-Wallis, Pearson and Spearman tests.ResultsBoth inhibitory and stimulatory immune checkpoint proteins were significantly upregulated within the chorioamniotic membranes and decidua (VISTA, LAG3, PD-1, CD40, GITR), as well as their ligands (PD-L1, PD-L2, CD40L; all p&lt;0.05). Immunostaining for VISTA revealed positive (VISTA+) cells, predominantly in the chorion and decidua. There were strong correlations between VISTA and amniotic fluid concentrations of IL-1β, IL-6, IL-8, and TNF-α (all p&lt;0.05), as well as maternal placental histopathology scores (p&lt;0.05).ConclusionDifferential regulation of multiple immune checkpoint proteins in the decidua at the site of a GBS infection indicates a major perturbation in immunologic homeostasis that could benefit the host by restricting immune-driven pathologies or the pathogen by limiting immune surveillance. Protein expression of VISTA, an inhibitory immune checkpoint, was upregulated in the chorion and decidua after GBS infection. Investigating the impact of innate immune cell expression of inhibitory immune checkpoints may reveal new insights into placental host-pathogen interactions at the maternal-fetal interface.
Regulatory role of Mss11 in Candida glabrata virulence: adhesion and biofilm formation
Authors: Wang Lu-Ling , Huang Si-Jia , Zhao Jun-Tao , Liu Jin-Yan , Xiang Ming-Jie 
Published: January 2024

IntroductionCandida glabrata has emerged as a fungal pathogen with high infection and mortality rates, and its primary virulence factors are related to adhesion and biofilm formation. These virulence factors in C.glabrata are primarily mediated by epithelial adhesins (Epas), most of which are encoded in subtelomeric regions and regulated by subtelomeric silencing mechanisms. The transcription factor Mss11, known for its regulatory role in adhesion, biofilm formation, and filamentous growth in Saccharomyces cerevisiae and Candida albicans, has also been implicated in the expression of EPA6, suggesting its potential influence on C.glabrata virulence. The present study aims to determine the regulatory role of Mss11 in the virulence of C. glabrata.MethodsIn this work, a Δmss11 null mutant and its complemented strain were constructed from a C.glabrata standard strain. The impact of the transcription factor Mss11 on the virulence of C.glabrata was investigated through a series of phenotypic experiments, including the microbial adhesion to hydrocarbons (MATH) test, adherence assay, biofilm assay, scanning electron microscopy and Galleria mellonella virulence assay. Furthermore, transcriptome sequencing, quantitative reverse transcription polymerase chain reaction (RT-qPCR), and chromatin immunoprecipitation sequencing (ChIP-seq) were employed to investigate the molecular mechanisms behind the regulation of Mss11.ResultsIn C.glabrata, the loss of MSS11 led to a significant reduction in several virulence factors including cell surface hydrophobicity, epithelial cell adhesion, and biofilm formation. These observations were consistent with the decreased virulence of the Δmss11 mutant observed in the Galleria mellonella infection model. Further exploration demonstrated that Mss11 modulates C. glabrata virulence by regulating EPA1 and EPA6 expression. It binds to the upstream regions of EPA1 and EPA6, as well as the promoter regions of the subtelomeric silencing-related genes SIR4, RIF1, and RAP1, indicating the dual regulatory role of Mss11.ConclusionMss11 plays a crucial role in C. glabrata adhesion and biofilm formation, and thus has a broad influence on virulence. This regulation is achieved by regulating the expression of EPA1 and EPA6 through both promoter-specific regulation and subtelomeric silencing.
Investigating shared decision-making during the use of a digital health tool for physical activity planning in cardiac rehabilitation
Authors: Wurhofer Daniela , Neunteufel Julia , Strumegger Eva-Maria , Höppchen Isabel , Mayr Barbara , Egger Andreas , Sareban Mahdi , Reich Bernhard , Neudorfer Michael , Niebauer Josef , Smeddinck Jan David , Kulnik Stefan Tino 
Published: January 2024

BackgroundShared decision making (SDM) between healthcare professionals and persons with CVD can have a positive impact on motivation, adherence, or sustainability regarding long-term goals and integration of cardiovascular disease (CVD) rehabilitation in the everyday lives of persons with CVD. SDM can foster the transition between regular heart-healthy activity at rehabilitation facilities and more independent activity at home, but it is often challenging to implement SDM given limited time and resources, e.g., in the daily practice of rehabilitation. Digital tools can help but must be appropriately tailored for situated use and user needs.ObjectiveWe aimed to (1) describe in how far SDM is manifested in the situated context when using a digital tool developed by our group, and, based on that, (2) reflect on how digital health tools can be designed to facilitate and improve the SDM process.MethodsIn the context of a field study, we investigated how SDM is already naturally applied and manifested when using a digital tool for joint physical activity planning in cardiac rehabilitation in clinical practice. In a two-week qualitative study, we collected data on expectations, experiences and interactions during the use of a digital health tool by seven persons with CVD and five healthcare professionals. Data was collected by means of observations, interviews, questionnaires and a self-reported diary, and analysed with a particular focus on episodes related to SDM.ResultsWe found that SDM was manifested in the situated context to limited extent. For example, we identified high improvement potential for more structured goal-setting and more explicit consideration of preferences and routines. Based on mapping our findings to temporal phases where SDM can be adopted, we highlight implications for design to further support SDM in clinical practice. We consider this as “SDM supportive design in digital health apps,” suggesting for example step-by-step guidance to be used during the actual consultation.ConclusionThis study contributes to further understanding and integration of SDM in digital health tools with a focus on rehabilitation, to empower and support both persons with CVD and healthcare professionals.
Predicting the survival probability of functional neuroendocrine tumors treated with peptide receptor radionuclide therapy: Serbian experience
Authors: Vukomanovic Vladimir , Nedic Katarina Vuleta , Radojevic Marija Zivkovic , Dagovic Aleksandar , Milosavljevic Neda , Markovic Marina , Ignjatovic Vladimir , Simic Vukomanovic Ivana , Djukic Svetlana , Sreckovic Marijana , Backovic Milena , Vuleta Marko , Djukic Aleksandar , Vukicevic Verica , Ignjatovic Vesna 
Published: January 2024

IntroductionPeptide receptor radionuclide therapy (PRRT) is a treatment option for well-differentiated, somatostatin receptor positive, unresectable or/and metastatic neuroendocrine tumors (NETs). Although high disease control rates seen with PRRT a significant number NET patients have a short progression-free interval, and currently, there is a deficiency of effective biomarkers to pre-identify these patients. This study is aimed at determining the prognostic significance of biomarkers on survival of patients with NETs in initial PRRT treatment.MethodologyWe retrospectively analyzed 51 patients with NETs treated with PRRT at the Department for nuclear medicine, University Clinical Center Kragujevac, Serbia, with a five-year follow-up. Eligible patients with confirmed inoperable NETs, were retrospectively evaluated hematological, blood-based inflammatory markers, biochemical markers and clinical characteristics on disease progression. In accordance with the progression og the disease, the patients were divided into two groups: progression group (n=18) and a non-progression group (n=33). Clinical data were compared between the two groups.ResultsA total of 51 patients (Md=60, age 25-75 years) were treated with PRRT, of whom 29 (56.86%) demonstrated stable disease, 4 (7.84%) demonstrated a partial response, and 14 (27.46%) demonstrated progressive disease and death was recorded in 4 (7.84%) patients. The mean PFS was a 36.22 months (95% CI 30.14-42.29) and the mean OS was 44.68 months (95% CI 37.40-51.97). Univariate logistic regression analysis displayed that age (p&lt;0.05), functional tumors (p&lt;0.05), absolute neutrophil count (p&lt;0.05), neutrophil-lymphocyte ratio-NLR (p&lt;0.05), C-reactive protein-CRP (p&lt;0.05), CRP/Albumin (p&lt;0.05), alanine aminotransferase-ALT (p&lt;0.05), were risk factors for disease progression. Multivariate logistic regression analysis exhibited that functional tumors (p&lt;0.001), age (p&lt;0.05), CRP (p&lt;0.05), and ALT (p&lt;0.05), were independent risk factors for the disease progression in patients with NETs. Tumor functionality was the most powerful prognostic factor. The median PFS (11.86 ± 1.41 vs. 43.38 ± 3.16 months; p=0.001) and OS (21.81 ± 2.70 vs 53.86 ± 3.70, p=0.001) were significantly shorter in patients with functional than non-functional NETs respectively.ConclusionThe study’s results suggest that tumor functionality, and certain biomarkers may serve as prognostic survival indicators for patients with NETs undergoing PRRT. The findings can potentially help to identify patients who are at higher risk of disease progression and tailor treatment strategies accordingly.
Association between neutrophil-to-lymphocyte ratio and diabetic kidney disease in type 2 diabetes mellitus patients: a cross-sectional study
Authors: Li Xiaowan , Wang Lanyu , Liu Min , Zhou Hongyi , Xu Hongyang 
Published: January 2024

AimsThis investigation examined the possibility of a relationship between neutrophil-to-lymphocyte ratio (NLR) and diabetic kidney disease (DKD) in type 2 diabetes mellitus (T2DM) patients.MethodsAdults with T2DM who were included in the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2020 were the subjects of the current cross-sectional investigation. Low estimated glomerular filtration rate (eGFR) (&lt; 60 mL/min/1.73 m2) or albuminuria (urinary albumin-to-creatinine ratio (ACR) ≥ 30 mg/g) in T2DM patients were the diagnostic criteria for DKD. Weighted multivariable logistic regression models and generalized additive models were used to investigate the independent relationships between NLR levels with DKD, albuminuria, and low-eGFR. Additionally, we examined the relationships between DKD, albuminuria, and low-eGFR with other inflammatory markers, such as the aggregate index of systemic inflammation (AISI), systemic immune-inflammation index (SII), system inflammation response index (SIRI), and platelet-to-lymphocyte ratio (PLR) and monocyte-to-lymphocyte ratio (MLR). Their diagnostic capabilities were evaluated and contrasted using receiver operating characteristic (ROC) curves.Results44.65% of the 7,153 participants who were recruited for this study were males. DKD, albuminuria, and low-eGFR were prevalent in 31.76%, 23.08%, and 14.55% of cases, respectively. Positive correlations were seen between the NLR with the prevalences of DKD, albuminuria, and low-eGFR. Subgroup analysis and interaction tests revealed that the associations of NLR with DKD, albuminuria, and low-eGFR were not significantly different across populations. In addition, MLR, SII and SIRI showed positive associations with the prevalence of DKD. ROC analysis discovered that when compared to other inflammatory markers (MLR, PLR, SII, SIRI, and AISI), NLR may demonstrate more discriminatory power and accuracy in assessing the risk of DKD, albuminuria, and low-eGFR.ConclusionCompared to other inflammatory markers (MLR, PLR, SII, SIRI, and AISI), NLR may serve as the more effective potential inflammatory marker for identifying the risk of DKD, albuminuria, and low-eGFR in US T2DM patients. T2DM patients with elevated levels of NLR, MLR, SII, and SIRI should be closely monitored for their potential risk to renal function.
Carbon emission scenario prediction for highway construction projects
Authors: Wu Qixian , Chen Yun , Li Congying , Shi Xiaoya 
Published: January 2024

In order to carry out the research on the measurement and prediction of carbon emissions from highway projects, the prediction index system is constructed by selecting seven influencing factors, namely, urbanization rate, industrial structure, energy intensity, energy structure, key low-carbon technologies, highway construction planning, and green financial support. The carbon emission coefficient method is used to measure the carbon emissions of highway projects from the perspective of energy consumption, and finally, a carbon emission scenario prediction model based on the scenario analysis method and the LSTM algorithm of the recurrent neural network is constructed to put forward a new way of predicting the carbon emissions of highway projects. Taking Hunan province as a case study object, the carbon emission trends in the next 15 years are predicted under three scenarios: low carbon, baseline, and high carbon. The results show that the highway project in Hunan province is expected to peak in 2031 under the low-carbon scenario, in 2037 under the baseline scenario, and around 2044 under the high-carbon scenario. It is also found that energy saving and emission reduction measures have a certain lag in the emission reduction effect of highway projects. Finally, based on this, suggestions and countermeasures for carbon emission reduction of highway development in Hunan province are proposed.
“A very big challenge”: a qualitative study to explore the early barriers and enablers to implementing a national genomic medicine service in England
Authors: Friedrich Bettina , Vindrola-Padros Cecilia , Lucassen Anneke M. , Patch Chris , Clarke Angus , Lakhanpaul Monica , Lewis Celine 
Published: January 2024

Background: The Genomic Medicine Service (GMS) was launched in 2018 in England to create a step-change in the use of genomics in the NHS, including offering whole genome sequencing (WGS) as part of routine care. In this qualitative study on pediatric rare disease diagnosis, we used an implementation science framework to identify enablers and barriers which have influenced rollout.Methods: Semi-structured interviews were conducted with seven participants tasked with designing the GMS and 14 tasked with leading the implementation across the seven Genomic Medicine Service Alliances (GMSAs) and/or Genomic Laboratory Hubs (GLHs) between October 2021 and February 2022.Results: Overall, those involved in delivering the service strongly support its aims and ambitions. Challenges include: 1) concerns around the lack of trained and available workforce (clinicians and scientists) to seek consent from patients, interpret findings and communicate results; 2) the lack of a digital, coordinated infrastructure in place to support and standardize delivery with knock-on effects including onerous administrative aspects required to consent patients and order WGS tests; 3) that the “mainstreaming agenda”, whilst considered important, encountered reluctance to become engaged from those who did not see it as a priority or viewed it as being politically rather than clinically driven; 4) the timelines and targets set for the GMS were perceived by some as too ambitious. Interviewees discussed local adaptations and strategies employed to address the various challenges they had encountered, including 1) capacity-building, 2) employing genomic associates and other support staff to support the consent and test ordering process, 3) having “genomic champions” embedded in mainstream services to impart knowledge and best practice, 4) enhancing collaboration between genetic and mainstream specialties, 5) building evaluation into the service and 6) co-creating services with patients and the public.Conclusion: Our findings highlight the challenges of implementing system-wide change within a complex healthcare system. Local as well as national solutions can undoubtedly address many of these barriers over time.
Integration of multi-omics technologies for molecular diagnosis in ataxia patients
Authors: Audet Sebastien , Triassi Valerie , Gelinas Myriam , Legault-Cadieux Nab , Ferraro Vincent , Duquette Antoine , Tetreault Martine 
Published: January 2024

Background: Episodic ataxias are rare neurological disorders characterized by recurring episodes of imbalance and coordination difficulties. Obtaining definitive molecular diagnoses poses challenges, as clinical presentation is highly heterogeneous, and literature on the underlying genetics is limited. While the advent of high-throughput sequencing technologies has significantly contributed to Mendelian disorders genetics, interpretation of variants of uncertain significance and other limitations inherent to individual methods still leaves many patients undiagnosed. This study aimed to investigate the utility of multi-omics for the identification and validation of molecular candidates in a cohort of complex cases of ataxia with episodic presentation.Methods: Eight patients lacking molecular diagnosis despite extensive clinical examination were recruited following standard genetic testing. Whole genome and RNA sequencing were performed on samples isolated from peripheral blood mononuclear cells. Integration of expression and splicing data facilitated genomic variants prioritization. Subsequently, long-read sequencing played a crucial role in the validation of those candidate variants.Results: Whole genome sequencing uncovered pathogenic variants in four genes (SPG7, ATXN2, ELOVL4, PMPCB). A missense and a nonsense variant, both previously reported as likely pathogenic, configured in trans in individual #1 (SPG7: c.2228T&gt;C/p.I743T, c.1861C&gt;T/p.Q621*). An ATXN2 microsatellite expansion (CAG32) in another late-onset case. In two separate individuals, intronic variants near splice sites (ELOVL4: c.541 + 5G&gt;A; PMPCB: c.1154 + 5G&gt;C) were predicted to induce loss-of-function splicing, but had never been reported as disease-causing. Long-read sequencing confirmed the compound heterozygous variants configuration, repeat expansion length, as well as splicing landscape for those pathogenic variants. A potential genetic modifier of the ATXN2 expansion was discovered in ZFYVE26 (c.3022C&gt;T/p.R1008*).Conclusion: Despite failure to identify pathogenic variants through clinical genetic testing, the multi-omics approach enabled the molecular diagnosis in 50% of patients, also giving valuable insights for variant prioritization in remaining cases. The findings demonstrate the value of long-read sequencing for the validation of candidate variants in various scenarios. Our study demonstrates the effectiveness of leveraging complementary omics technologies to unravel the underlying genetics in patients with unresolved rare diseases such as ataxia. Molecular diagnoses not only hold significant promise in improving patient care management, but also alleviates the burden of diagnostic odysseys, more broadly enhancing quality of life.