bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined effect of dietary calcium consumption and physical activity on dental caries in children and adolescents: a study of the NHANES database
Authors: Zhang Qian , Bai Xiaofan , Jin Huan , Dong Ning 
Published: February 2024

AbstractBackgroundCalcium (Ca) is a nutritional factor that associated with dental caries. A recent study showed that in the case of adequate Ca intake, a higher level of physical activity may contribute to bone mass accumulation. However, the combined effect between Ca intake and physical activity on caries experience is unclear. Herein, we aimed to explore the above combined effect on dental caries in children and adolescents.MethodsData of 5,917 children and adolescents were extracted from the National Health and Nutrition Examination Surveys (NHANES) database in 2015–2020 in this cross-sectional study. The NHANES assessed the dietary Ca intake through the 24-hour dietary recalls, and the physical activity level was self-reported using the questionnaires. Also, the dental caries was diagnosed according to the Decayed, Missing and Filled Teeth/Surfaces (DMFT/S) index. Weighted univariate and multivariate logistic regression analyses were utilized to screen the covariates and to investigate the associations of dietary Ca intake and physical activity with dental caries, respectively, and assess the combined effect between dietary Ca intake and physical activity on dental caries. The evaluation indexes were odd ratios (ORs) and 95% confidence intervals (CIs). Subgroup analyses of age, obesity, and total sugar intake were also performed.ResultsAmong the eligible participants, 2,687 had caries experience. After adjusting for the covariates, we found that children and adolescents who not reach the recommendation level of Ca intake combined with physical activity less than 7 time in 1 week seemed to have higher odds of dental caries [OR = 1.77, 95%CI: (1.38–2.27)], compared with those who reached the standards. In addition, this potential combined effect was also found in age < 12 years old [OR = 1.62, 95%CI: (1.23–2.14)], non-obesity [OR = 1.88, 95%CI: (1.49–2.35)], and total sugar intake (allP < 0.05) subgroups.ConclusionsCa intake and physical activity had a potential combined effect on dental caries in children and adolescents, but the causal relationships between them needed further clarification.
Glutathione S-transferase M1, T1, and P1 polymorphisms and periodontitis in a Caucasian population: a case-control study
Authors: Izakovicova Pavla , Fassmann Antonin , Dusek Ladislav , Izakovicova Holla Lydie 
Published: February 2024

Abstract
Background
Glutathione S-transferases (GSTs) play important roles in protecting cells against oxidative stress and toxic chemicals. This study aimed to investigate the distribution of GSTM1, GSTT1, and GSTP1 variants and their roles in periodontitis susceptibility in a Caucasian population.

Methods
We analyzed 406 participants, including 204 healthy controls and 203 periodontitis patients. A multiplex polymerase chain reaction (PCR) approach was used to analyze GSTM1 and GSTT1 loci. GSTP1 variants were detected by PCR-haplotyping method in a subgroup of participants (N = 350). Chi-square or Fisher´s exact tests were used to compare genotypic and allelic differences. The Bonferroni method was applied to correct for multiple comparisons (pcorr).

Results
The GSTM1 genotype distribution did not differ significantly between controls and periodontitis patients (p = 0.44). Additionally, the wild/null genotypes of GSTT1, Ile105Val and Ala114Val frequencies of GSTP1 were not significantly different between the two groups after correction for multiple comparisons (p = 0.05, p = 0.55, p = 0.02, pcorr>0.05, respectively). The GSTM1 and GSTP1 Ile105Val gene variants were similarly distributed between non-smokers and smokers in both groups (p = 0.38, p = 0.20, and p = 0.14, p = 0.35, respectively). However, the wild genotype of the GSTT1 and Ala114Ala variant of the GSTP1 genes were present more frequently in non-smoking periodontitis patients than in non-smoking controls (p = 0.03, pcorr>0.05, and p = 0.009, pcorr>0.05, respectively) although their frequencies did not differ between smoking periodontitis patients and smoking controls (p = 0.23, p = 0.68, respectively).

Conclusions
This study in a Czech Caucasian population did not confirm a highly significant association between GST gene variants and susceptibility to periodontitis, as previously reported by Arshad and colleagues in Pakistanis. However, a weak relationship between GSTT1 and GSTP1 rs1138272 polymorphisms and periodontitis in non-smokers was observed.
Using formalin fixed paraffin embedded tissue to characterize the microbiota in p16-positive and p16-negative tongue squamous cell carcinoma: a pilot study
Authors: Yuanbo Zhan , Tianyi Liu , Xuejing Song , Xinpeng Liu , Jianqun Wang , Wenxia Xu , Jingshu Geng 
Published: February 2024

Abstract
Background
Tongue squamous cell carcinoma (TSCC) is the most common oral cavity cancer, and p16 immunohistochemistry is an exact and available tool in the prognostic and predictive characterization of squamous cell cancers in the head and neck. Microorganisms have a close relationship with the development of TSCC. However, the association between oral bacteria and p16 status has not been well defined in the case of TSCC. Compared with traditional clinical microbial collection methods, formalin-fixed paraffin-embedded (FFPE) tissue samples have several advantages.

Methods
To compare the microbiota compositions between p16-positive and p16-negative patients with TSCC, we performed a small pilot study of microbiological studies of TSCC by paraffin tissue. DNA from FFPE tissue blocks were extracted and microbiomes were profiled by sequencing the 16 S-rRNA-encoding gene (V1–V2/V3-V4/V4 regions). Alterations in the functional potential of the microbiome were predicted using PICRUSt, Tax4Fun, and BugBase.

Results
A total of 60 patients with TSCC were enrolled in the study, however, some challenges associated with DNA damage in FFPE tissues existed, and only 27 (15 p16-positive and 12 p16-negative) passed DNA quality control. Nevertheless, we have tentatively found some meaningful results. The p16 status is associated with microbiota diversity, which is significantly increased in p16-positive patients compared with p16-negative patients. Desulfobacteria, Limnochordia, Phycisphaerae, Anaerolineae, Saccharimonadia and Kapabacteria had higher abundances among participants with p16-positive. Moreover, functional prediction revealed that the increase of these bacteria may enhance viral carcinogenesis in p16-positive TSCC.

Conclusions
Bacterial profiles showed a significant difference between p16-positive TSCC and p16-negative TSCC. These findings may provide insights into the relationship between p16 status and the microbial taxa in TSCC, and these bacteria may provide new clues for developing therapeutic targets for TSCC.
Irreversible pulpitis in mature permanent teeth: a cost-effectiveness analysis of pulpotomy versus root canal treatment
Authors: Naved Nighat , Umer Fahad , Khowaja Asif R. 
Published: February 2024

Abstract
Introduction
Evidence-based dentistry suggests pulpotomy as a potential alternative to root canal treatment in mature permanent teeth with irreversible pulpitis. However, the evidence surrounding the cost-valuation and cost-efficacy of this treatment modality is not yet established. In this context, we adopted an economic modeling approach to assess the cost-effectiveness of pulpotomy versus root canal treatment, as this could aid in effective clinical decision-making.

Methods
A Markov model was constructed following a mature permanent tooth with irreversible pulpitis in an 18-year-old patient over a lifetime using TreeAge Pro Healthcare 2022. Transition probabilities were estimated based on existing literature. Costs were estimated based on the United States healthcare following a private-payer perspective and parameter uncertainties were addressed using Monte-Carlo simulations. The model was validated internally by sensitivity analyses, and face validation was performed by an experienced endodontist and health economist.

Results
In the base case scenario, root canal treatment was associated with additional health benefit but at an increased cost (1.08 more years with an incremental cost of 311.20 USD) over a period of an individual’s lifetime. The probabilistic sensitivity analysis revealed pulpotomy to be cost-effective at lower Willingness-To-Pay (WTP) values (99.9% acceptable at 50 USD) whereas increasing the values of WTP threshold root canal treatment was a cost-effective treatment (99.9% acceptable at 550 USD).

Conclusion
Based on current evidence, pulpotomy was a cost-effective treatment option at lower WTP values for the management of irreversible pulpitis in mature permanent teeth. However, by increasing the WTP threshold, root canal treatment became a more cost-effective treatment option over a period of lifetime of an individual.
“The great escape”: how an incident of elopement gave rise to trauma informed palliative care for a patient experiencing multiple disadvantage
Authors: Quinn Sam , Ferguson Libby , Read Derek , Richards Naomi 
Published: February 2024

Abstract
Background
This case report from Scotland, UK illustrates how unresolved traumatic experiences across the life course can affect a patient’s engagement with palliative care and offers insights into the flexibility and adaptations necessary for taking a trauma informed approach to care for an individual experiencing multiple disadvantage. Trauma informed care is a cornerstone in the pursuit of equitable palliative care, particularly for those facing multiple disadvantage, as it acknowledges the impact of past traumas on current healthcare experiences, and fosters an environment of understanding, acceptance, and tailored support to alleviate suffering in the final stages of life.

Case presentation
“M” was a veteran with a history of homelessness, living with end stage anal cancer and symptoms consistent with post-traumatic stress disorder, although he never received a formal diagnosis. M exhibited complex behaviours perceived to be related to his history of trauma, including his decision to elope from the hospice, reluctance to accept personal care from nurses, and unpredictability. These behaviours posed a significant challenge to his palliative care team, both in the hospice and at home. An individualised and flexible approach to care delivery was eventually adopted, which included a ‘safety-netting’ approach and care delivery outside of the hospice. M was ultimately supported to remain at home until a week before he died.

Conclusion
M’s case underscores the necessity of adopting a trauma informed approach to palliative care, particularly for patients with a history of trauma and multiple disadvantage. The case highlights the importance of understanding and respecting a patient’s past traumas, promoting safety and autonomy, and ensuring flexibility in care delivery.
Development and validation of the adolescent behavioural change Counselling Assessment Tool in Indonesia
Authors: Agung Fransisca Handy , Sekartini Rini , Sudarsono Nani Cahyani , Hendarto Aryono , Werdhani Retno Asti , Pudjiati Sri Retno , Hanum Lathifah , Naufal Affan , Sawyer Susan M 
Published: February 2024

Abstract
Background
Primary care provides an important context to engage adolescents and their families in healthy lifestyles with the goal of reducing future behaviour-related health problems. Developing a valid tool to assess health professionals’ skills in behavioural change counselling is integral to improving the quality of clinical care provided to adolescents in Indonesia.

Methods
This work was nested within a project to develop a training program to enhance the behaviour-change counselling of adolescents and their parents by Indonesian primary care professionals. Initial item development was based on the content of the training module and the domain structure of the Behavioral Change Counselling Index (BECCI), a commonly used tool to assess counselling quality in healthcare settings. Expert panels were used to test content validity, while face validity was assessed by a group of trained psychologists. Inter-rater agreement was calculated prior to tests of construct validity and reliability, which involved psychologists rating 125 audio-taped counselling sessions between the health professional and adolescent patients, together with a parent.

Results
An initial 13-item tool was developed using a 1–5 Likert scale. Validity and reliability testing resulted in the decision to use a 14-item tool with a 0–3 Likert scale. The scale was found to have a Cronbach’s α coefficient of 0.839 (internal consistency), and there was strong inter-rater agreement (0.931).

Conclusion
The assessment tool known as the Adolescent Behavioural Change Counselling Assessment Tool, is a valid and reliable instrument to measure Indonesian health professionals’ behavioural-change counselling skills with adolescent patients. The tool provides an evaluation framework for future interventions that aim to improve health professionals’ skills in addressing adolescent behaviour-related health problems.
Integration of transcription regulation and functional genomic data reveals lncRNA SNHG6’s role in hematopoietic differentiation and leukemia
Authors: Hazan Joshua M. , Amador Raziel , Ali-Nasser Tahleel , Lahav Tamar , Shotan Stav Roni , Steinberg Miryam , Cohen Ziv , Aran Dvir , Meiri David , Assaraf Yehuda G. , Guigó Roderic , Bester Assaf C. 
Published: February 2024

Abstract
Background
Long non-coding RNAs (lncRNAs) are pivotal players in cellular processes, and their unique cell-type specific expression patterns render them attractive biomarkers and therapeutic targets. Yet, the functional roles of most lncRNAs remain enigmatic. To address the need to identify new druggable lncRNAs, we developed a comprehensive approach integrating transcription factor binding data with other genetic features to generate a machine learning model, which we have called INFLAMeR (Identifying Novel Functional LncRNAs with Advanced Machine Learning Resources).

Methods
INFLAMeR was trained on high-throughput CRISPR interference (CRISPRi) screens across seven cell lines, and the algorithm was based on 71 genetic features. To validate the predictions, we selected candidate lncRNAs in the human K562 leukemia cell line and determined the impact of their knockdown (KD) on cell proliferation and chemotherapeutic drug response. We further performed transcriptomic analysis for candidate genes. Based on these findings, we assessed the lncRNA small nucleolar RNA host gene 6 (SNHG6) for its role in myeloid differentiation. Finally, we established a mouse K562 leukemia xenograft model to determine whether SNHG6 KD attenuates tumor growth in vivo.

Results
The INFLAMeR model successfully reconstituted CRISPRi screening data and predicted functional lncRNAs that were previously overlooked. Intensive cell-based and transcriptomic validation of nearly fifty genes in K562 revealed cell type-specific functionality for 85% of the predicted lncRNAs. In this respect, our cell-based and transcriptomic analyses predicted a role for SNHG6 in hematopoiesis and leukemia. Consistent with its predicted role in hematopoietic differentiation, SNHG6 transcription is regulated by hematopoiesis-associated transcription factors. SNHG6 KD reduced the proliferation of leukemia cells and sensitized them to differentiation. Treatment of K562 leukemic cells with hemin and PMA, respectively, demonstrated that SNHG6 inhibits red blood cell differentiation but strongly promotes megakaryocyte differentiation. Using a xenograft mouse model, we demonstrate that SNHG6 KD attenuated tumor growth in vivo.

Conclusions
Our approach not only improved the identification and characterization of functional lncRNAs through genomic approaches in a cell type-specific manner, but also identified new lncRNAs with roles in hematopoiesis and leukemia. Such approaches can be readily applied to identify novel targets for precision medicine.
Immunomodulatory and clinical effects of receptor-interacting protein kinase 1 (RIPK1) inhibitor eclitasertib (SAR443122) in patients with severe COVID-19: a phase 1b, randomized, double-blinded, placebo-controlled study
Authors: Clot Pierre-Francois , Farenc Christine , Suratt Benjamin T. , Krahnke Tillmann , Tardat Agnes , Florian Peter , Pomponio Robert , Patel Naimish , Wiekowski Maria , Lin Yong , Terrier Benjamin , Staudinger Heribert 
Published: February 2024

Abstract
Background
Targeting receptor-interacting serine/threonine protein kinase 1 could mitigate the devastating sequelae of the hyperinflammatory state observed in severe cases of COVID-19. This study explored the immunomodulatory and clinical effects of the receptor-interacting serine/threonine protein kinase 1 inhibitor SAR443122 (eclitasertib) in patients with severe COVID-19.

Methods
In this Phase 1b, double-blinded, placebo-controlled study (NCT04469621) a total of 82 patients were screened, of whom 68 patients were eligible and randomized (2:1) to receive eclitasertib 600 mg (300 mg twice daily) or placebo up to 14 days. Primary outcome was relative change in C-reactive protein from baseline to Day 7. Time to clinical improvement using 7-point ordinal scale, ventilator/respiratory failure-free days, change in SpO2/FiO2 ratio, and biomarkers of severe COVID-19 were explored.

Results
Geometric mean ratio (point estimate [90% confidence interval]) of the relative change from baseline in C-reactive protein with eclitasertib vs. placebo on Day 7 was 0.85 (0.49–1.45; p = 0.30). Median time to 50% decrease in C-reactive protein from baseline was 3 days vs. 5 days (p = 0.056) with eclitasertib vs. placebo. Median time to ≥ 2-point improvement on 7-point clinical symptoms scale was 8 days vs. 10 days with eclitasertib vs. placebo (p = 0.38). Mean ventilator/respiratory failure-free days, change in baseline-adjusted SpO2/FiO2 ratio, and clinical biomarkers showed consistent numerical improvements with eclitasertib vs. placebo. The most frequently reported treatment-emergent adverse events were gastrointestinal disorders and condition aggravated/worsened COVID-19 pneumonia.

Conclusions
Eclitasertib was well tolerated with consistent trends toward more rapid resolution of inflammatory biomarkers and clinical improvement in severe COVID-19 patients than placebo.

ClinicalTrials.gov identifier
NCT04469621, first posted on clinicaltrials.gov on July 14, 2020.
Association between body fat decrease during the first year after diagnosis and the prognosis of idiopathic pulmonary fibrosis: CT-based body composition analysis
Authors: Lee Ji Young , Yoon Soon Ho , Goo Jin Mo , Park Jimyung , Lee Jong Hyuk 
Published: February 2024

Abstract
Background
The prognostic role of changes in body fat in patients with idiopathic pulmonary fibrosis (IPF) remains underexplored. We investigated the association between changes in body fat during the first year post-diagnosis and outcomes in patients with IPF.

Methods
This single-center, retrospective study included IPF patients with chest CT scan and pulmonary function test (PFT) at diagnosis and a one-year follow-up between January 2010 and December 2020. The fat area (cm2, sum of subcutaneous and visceral fat) and muscle area (cm2) at the T12-L1 level were obtained from chest CT images using a fully automatic deep learning-based software. Changes in the body composition were dichotomized using thresholds dividing the lowest quartile and others, respectively (fat area: -52.3 cm2, muscle area: -7.4 cm2). Multivariable Cox regression analyses adjusted for PFT result and IPF extent on CT images and the log-rank test were performed to assess the association between the fat area change during the first year post-diagnosis and the composite outcome of death or lung transplantation.

Results
In total, 307 IPF patients (69.3 ± 8.1 years; 238 men) were included. During the first year post-diagnosis, fat area, muscle area, and body mass index (BMI) changed by -15.4 cm2, -1 cm2, and − 0.4 kg/m2, respectively. During a median follow-up of 47 months, 146 patients had the composite outcome (47.6%). In Cox regression analyses, a change in the fat area < -52.3 cm2 was associated with composite outcome incidence in models adjusted with baseline clinical variables (hazard ratio [HR], 1.566, P = .022; HR, 1.503, P = .036 in a model including gender, age, and physiology [GAP] index). This prognostic value was consistent when adjusted with one-year changes in clinical variables (HR, 1.495; P = .030). However, the change in BMI during the first year was not a significant prognostic factor (P = .941). Patients with a change in fat area exceeding this threshold experienced the composite outcome more frequently than their counterparts (58.4% vs. 43.9%; P = .007).

Conclusion
A ≥ 52.3 cm2 decrease in fat area, automatically measured using deep learning technique, at T12-L1 in one year post-diagnosis was an independent poor prognostic factor in IPF patients.
Fatty liver index is an independent risk factor for all-cause mortality and major cardiovascular events in type 1 diabetes: an 11-year observational study
Authors: Garofolo Monia , Lucchesi Daniela , Giambalvo Massimo , Aragona Michele , Bertolotto Alessandra , Campi Fabrizio , Bianchi Cristina , Francesconi Paolo , Marchetti Piero , Del Prato Stefano , Penno Giuseppe 
Published: February 2024

Abstract
Background
Non-alcoholic fatty liver disease (NAFLD), identified by the Fatty Liver Index (FLI), is associated with increased mortality and cardiovascular (CV) outcomes. Whether this also applies to type 1 diabetes (T1D) has not been yet reported.

Methods
We prospectively observed 774 subjects with type 1 diabetes (males 52%, 30.3 ± 11.1 years old, diabetes duration (DD) 18.5 ± 11.6 years, HbA1c 7.8 ± 1.2%) to assess the associations between FLI (based on BMI, waist circumference, gamma-glutamyl transferase and triglycerides) and all-cause death and first CV events.

Results
Over a median 11-year follow-up, 57 subjects died (7.4%) and 49 CV events (6.7%) occurred among 736 individuals with retrievable incidence data. At baseline, FLI was < 30 in 515 subjects (66.5%), 30–59 in 169 (21.8%), and ≥ 60 in 90 (11.6%). Mortality increased steeply with FLI: 3.9, 10.1, 22.2% (p < 0.0001). In unadjusted Cox analysis, compared to FLI < 30, risk of death increased in FLI 30–59 (HR 2.85, 95% CI 1.49–5.45, p = 0.002) and FLI ≥ 60 (6.07, 3.27–11.29, p < 0.0001). Adjusting for Steno Type 1 Risk Engine (ST1-RE; based on age, sex, DD, systolic BP, LDL cholesterol, HbA1c, albuminuria, eGFR, smoking and exercise), HR was 1.52 (0.78–2.97) for FLI 30–59 and 3.04 (1.59–5.82, p = 0.001) for FLI ≥ 60. Inclusion of prior CV events slightly modified HRs. FLI impact was confirmed upon adjustment for EURODIAB Risk Engine (EURO-RE; based on age, HbA1c, waist-to-hip ratio, albuminuria and HDL cholesterol): FLI 30–59: HR 1.24, 0.62–2.48; FLI ≥ 60: 2.54, 1.30–4.95, p = 0.007), even after inclusion of prior CVD. CV events incidence increased with FLI: 3.5, 10.5, 17.2% (p < 0.0001). In unadjusted Cox, HR was 3.24 (1.65–6.34, p = 0.001) for FLI 30–59 and 5.41 (2.70–10.83, p < 0.0001) for FLI ≥ 60. After adjustment for ST1-RE or EURO-RE, FLI ≥ 60 remained statistically associated with risk of incident CV events, with trivial modification with prior CVD inclusion.

Conclusions
This observational prospective study shows that FLI is associated with higher all-cause mortality and increased risk of incident CV events in type 1 diabetes.