bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypovitaminosis D in persons with Down syndrome and autism spectrum disorder
Authors: Boyd Natalie K. , Nguyen Julia , Khoshnood Mellad M. , Jiang Timothy , Nguyen Lina , Mendez Lorena , Spinazzi Noemi A. , Manning Melanie A. , Rafii Michael S. , Santoro Jonathan D. 
Published: October 2023

Abstract
Background
Plasma levels of vitamin D have been reported to be low in persons with Down syndrome (DS) and existing data is limited to small and homogenous cohorts. This is of particular importance in persons with DS given the high rates of autoimmune disease in this population and the known relationship between vitamin D and immune function. This study sought to investigate vitamin D status in a multi-center cohort of individuals with DS and compare them to individuals with autism spectrum disorder (ASD) and neurotypical (NT) controls.

Methods
A retrospective, multi-center review was performed. The three sites were located at latitudes of 42.361145, 37.44466, and 34.05349. Patients were identified by the International Classification of Diseases (ICD)-9 or ICD-10 codes for DS, ASD, or well-child check visits for NT individuals. The first vitamin D 25-OH level recorded in the electronic medical record (EMR) was used in this study as it was felt to be the most reflective of a natural and non-supplemented state. Vitamin D 25-OH levels below 30 ng/mL were considered deficient.

Results
In total, 1624 individuals with DS, 5208 with ASD, and 30,775 NT controls were identified. Individuals with DS had the lowest mean level of vitamin D 25-OH at 20.67 ng/mL, compared to those with ASD (23.48 ng/mL) and NT controls (29.20 ng/mL) (p < 0.001, 95% CI: −8.97 to −6.44). A total of 399 (24.6%) individuals with DS were considered vitamin D deficient compared to 1472 (28.3%) with ASD and 12,397 (40.3%) NT controls (p < 0.001, 95% CI: −5.43 to −2.36). Individuals with DS with higher body mass index (BMI) were found to be more likely to have lower levels of vitamin D (p < 0.001, 95% CI: −0.3849 to −0.1509). Additionally, having both DS and a neurologic diagnosis increased the likelihood of having lower vitamin D levels (p < 0.001, 95% CI: −5.02 to −1.28). Individuals with DS and autoimmune disease were much more likely to have lower vitamin D levels (p < 0.001, 95% CI: −6.22 to −1.55). Similarly, a history of autoimmunity in a first-degree relative also increased the likelihood of having lower levels of vitamin D in persons with DS (p = 0.01, 95% CI: −2.45 to −0.63).

Conclusions
Individuals with DS were noted to have hypovitaminosis D in comparison to individuals with ASD and NT controls. Associations between vitamin D deficiency and high BMI, personal autoimmunity, and familial autoimmunity were present in individuals with DS.
The impact of the COVID-19 pandemic on primary health care practices and patient management in the Republic of Moldova - results from the PRICOV-19 survey
Authors: Delvento Giulia , Curteanu Ala , Rotaru Cristina , Van Poel Esther , Willems Sara , Prytherch Helen , Curocichin Ghenadie 
Published: October 2023

Abstract
Background
The COVID-19 pandemic has had an enormous impact on health systems in Europe and has generated unprecedented challenges for tertiary care. Less is known about the effects on the activities of local family doctors (FDs), who have shifted tasks and adapted their practice to accommodate the new services brought by the pandemic. The PRICOV-19 study was a multi-country survey aiming to understand the challenges posed by the pandemic in primary health care (PHC) practices around Europe. Within the framework of this study, we assessed the impact of the pandemic on PHC facilities in urban, rural, and mixed urban/rural areas in the Republic of Moldova.

Methods
We present the results from the PRICOV-19 questionnaire designed at Ghent University (Belgium) and distributed between January and March 2021 to PHC facilities from the 35 districts of the Republic of Moldova. This analysis presents descriptive data on limitations to service delivery, staff role changes, implementation and acceptance of COVID-19 guidelines, and incidents reported on staff and patient safety during the pandemic.

Results
Results highlighted the differences between facilities located in urban, rural, and mixed areas in several dimensions of PHC. Nearly half of the surveyed facilities experienced limitations in the building or infrastructure when delivering services during the pandemic. 95% of respondents reported an increase in time spent giving information to patients by phone, and 88% reported an increase in responsibilities. Few practices reported errors in clinical assessments, though a slightly higher number of incidents were reported in urban areas. Half of the respondents reported difficulties delivering routine care to patients with chronic conditions and a delay in treatment-seeking.

Conclusions
During the pandemic, the workload of PHC staff saw a significant increase, and practices met important structural and organizational limitations. Consequently, these limitations may have also affected care delivery for vulnerable patients with chronic conditions. Adjustments and bottlenecks need to be addressed, considering the different needs of PHC facilities in urban, rural, and mixed areas.
The role of geriatric syndromes in predicting unplanned hospitalizations: a population-based study using Minimum Data Set for Home Care
Authors: Rönneikkö Jukka , Huhtala Heini , Finne-Soveri Harriet , Valvanne Jaakko , Jämsen Esa 
Published: October 2023

Abstract
Background
The predictive accuracies of screening instruments for identifying home-dwelling old people at risk of hospitalization have ranged from poor to moderate, particularly among the oldest persons. This study aimed to identify variables that could improve the accuracy of a Minimum Data Set for Home Care (MDS-HC) based algorithm, the Detection of Indicators and Vulnerabilities for Emergency Room Trips (DIVERT) Scale, in classifying home care clients’ risk for unplanned hospitalization.

Methods
In this register-based retrospective study, factors associated with hospitalization among home care clients aged ≥ 80 years in the City of Tampere, Finland, were analyzed by linking MDS-HC assessments with hospital discharge records. MDS-HC determinants associated with hospitalization within 180 days after the assessment were analyzed for clients at low (DIVERT 1), moderate (DIVERT 2–3) and high (DIVERT 4–6) risk of hospitalization. Then, two new variables were selected to supplement the DIVERT algorithm. Finally, area under curve (AUC) values of the original and modified DIVERT scales were determined using the data of MDS-HC assessments of all home care clients in the City of Tampere to examine if addition of the variables related to the oldest age groups improved the accuracy of DIVERT.

Results
Of home care clients aged ≥ 80 years, 1,291 (65.4%) were hospitalized at least once during the two-year study period. Unplanned hospitalization occurred following 15.9%, 22.8%, and 33.9% MDS-HC assessments with DIVERT group 1, 2–3 and 4–6, respectively. Infectious diseases were the most common diagnosis within each DIVERT groups.
Many MDS-HC variables not included in the DIVERT algorithm were associated with hospitalization, including e.g. poor self-rated health and old fracture (other than hip fracture) (p 0.001) in DIVERT 1; impaired cognition and decision-making, urinary incontinence, unstable walking and fear of falling (p < 0.001) in DIVERT 2–3; and urinary incontinence, poor self-rated health (p < 0.001), and decreased social interaction (p 0.001) in DIVERT 4–6. Adding impaired cognition and urinary incontinence to the DIVERT algorithm improved sensitivity but not accuracy (AUC 0.64 (95% CI 0.62–0.65) vs. 0.62 (0.60–0.64) of the original DIVERT). More admissions occurred among the clients with higher scores in the modified than in the original DIVERT scale.

Conclusions
Certain geriatric syndromes and diagnosis groups were associated with unplanned hospitalization among home care clients at low or moderate risk level of hospitalization. However, the predictive accuracy of the DIVERT could not be improved. In a complex clinical context of home care clients, more important than existence of a set of risk factors related to an algorithm may be the various individual combinations of risk factors.
Comparative study of biomarkers for the early identification of Epstein–Barr virus-associated hemophagocytic lymphohistiocytosis in infectious mononucleosis
Authors: Cai Lisha , Xing Yuan , Xia Yahong , Zhang Zihan , Luo Zebin , Tang Yongmin , Chen Yan , Xu Xiaojun 
Published: October 2023

Abstract
Background and aim
Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) and infectious mononucleosis (EBV-IM) share mimic symptoms in the early stages of childhood development. We aimed to examine the clinical features and laboratory indices of these two diseases in children and uncover unique indicators to assist pediatricians in identifying these diseases early.

Methods
We collected clinical data from 791 pediatric patients diagnosed with EBV-IM or EBV-HLH, compared the clinical traits and laboratory biomarkers presented in the two groups, and constructed predictive models based on them.

Results
Patients with EBV-IM had greater ratios of cervical lymphadenopathy, eyelid edema, and tonsillitis, whereas individuals with EBV-HLH were more likely to have hepatomegaly and splenomegaly. When using the criteria of interleukin (IL)-10 > 89.6 pg/mL, interferon (IFN)-γ > 45.6 pg/mL, ferritin > 429 μg/L, D-dimer > 3.15 mg/L and triglycerides > 2.1 mmol/L, the sensitivity was 87.9%, 90.7%, 98.1%, 91.1% and 81.5% to predict EBV-HLH, while the specificity was 98.4%, 96.3%, 96.5%, 94.1% and 80.6%, respectively. A logistic regression model based on four parameters (IL-10, ferritin, D-dimer, and triglycerides) was established to distinguish EBV-HLH patients from EBV-IM patients, with a sensitivity of 98.0% and a specificity of 98.2%.

Conclusions
IL-10, IFN-γ, ferritin and D-dimer levels are significantly different between EBV-HLH and EBV-IM. Predictive models based on clinical signs and laboratory findings provide simple tools to distinguish the two situations.
Identification of microorganisms by a rapid PCR panel from positive blood cultures leads to faster optimal antimicrobial therapy – a before-after study
Authors: Agnetti Jessica , Büchler Andrea C. , Osthoff Michael , Helfenstein Fabrice , Weisser Maja , Siegemund Martin , Bassetti Stefano , Bingisser Roland , Schaefer Dirk J. , Clauss Martin , Hinic Vladimira , Tschudin-Sutter Sarah , Bättig Veronika , Khanna Nina , Egli Adrian 
Published: October 2023

Abstract
Background
The BioFire® FilmArray® Blood Culture Identification Panel 1 (BF-FA-BCIP) detects microorganisms with high accuracy in positive blood cultures (BC) – a key step in the management of patients with suspected bacteraemia. We aimed to compare the time to optimal antimicrobial therapy (OAT) for the BF-FA-BCIP vs. standard culture-based identification.

Methods
In this retrospective single-centre study with a before-after design, 386 positive BC cases with identification by BF-FA-BCIP were compared to 414 controls with culture-based identification. The primary endpoint was the time from BC sampling to OAT. Secondary endpoints were time to effective therapy, length of stay, (re-)admission to ICU, in-hospital and 30-day mortality. Outcomes were assessed using Cox proportional hazard models and logistic regressions.

Results
Baseline characteristics of included adult inpatients were comparable. Main sources of bacteraemia were urinary tract and intra-abdominal infection (19.2% vs. 22.0% and 16.8% vs. 15.7%, for cases and controls, respectively). Median (95%CI) time to OAT was 25.5 (21.0–31.2) hours with BF-FA-BCIP compared to 45.7 (37.7–51.4) hours with culture-based identification. We observed no significant difference for secondary outcomes.

Conclusions
Rapid microorganism identification by BF-FA-BCIP was associated with a median 20-h earlier initiation of OAT in patients with positive BC. No impact on length of stay and mortality was noted.

Trial registration
Clinicaltrials.gov, NCT04156633, registered on November 5, 2019.
Alterations of the expression of TET2 and DNA 5-hmC predict poor prognosis in Myelodysplastic Neoplasms
Authors: Seethy Ashikh A. , Pethusamy Karthikeyan , Kushwaha Tushar , Kumar Gaurav , Talukdar Joyeeta , Chaubey Rekha , Sundaram Udayakumar Dharmalingam , Mahapatra Manoranjan , Saxena Renu , Dhar Ruby , Inampudi Krishna K. , Karmakar Subhradip 
Published: October 2023

Abstract
Background
Myelodysplastic Neoplasms (MDS) are clonal stem cell disorders characterized by ineffective hematopoiesis and progression to acute myeloid leukemia, myelodysplasia-related (AML-MR). A major mechanism of pathogenesis of MDS is the aberration of the epigenetic landscape of the hematopoietic stem cells and/or progenitor cells, especially DNA cytosine methylation, and demethylation. Data on TET2, the predominant DNA demethylator of the hematopoietic system, is limited, particularly in the MDS patients from India, whose biology may differ since these patients present at a relatively younger age. We studied the expression and the variants of TET2 in Indian MDS and AML-MR patients and their effects on 5-hydroxymethyl cytosine (5-hmC, a product of TET2 catalysis) and on the prognosis of MDS patients.

Results
Of the 42 MDS patients, cytogenetics was available for 31 sub-categorized according to the Revised International Prognostic Scoring System (IPSS-R). Their age resembled that of the previous studies from India. Bone marrow nucleated cells (BMNCs) were also obtained from 13 patients with AML-MR, 26 patients with de-novo AML, and 11 subjects with morphologically normal bone marrow. The patients had a significantly lower TET2 expression which was more pronounced in AML-MR and the IPSS-R higher-risk MDS categories. The 5-hmC levels in higher-risk MDS and AML-MR correlated with TET2 expression, suggesting a possible mechanistic role in the loss of TET2 expression. The findings on TET2 and 5-hmC were also confirmed at the tissue level using immunohistochemistry. Pathogenic variants of TET2 were found in 7 of 24 patient samples (29%), spanning across the IPSS-R prognostic categories. One of the variants – H1778R – was found to affect local and global TET2 structure when studied using structural predictions and molecular dynamics simulations. Thus, it is plausible that some pathogenic variants in TET2 can compromise the structure of TET2 and hence in the formation of 5-hmC.

Conclusions
IPSS-R higher-risk MDS categories and AML-MR showed a reduction in TET2 expression, which was not apparent in lower-risk MDS. DNA 5-hmC levels followed a similar pattern. Overall, a decreased TET2 expression and a low DNA 5-hmC level are predictors of advanced disease and adverse outcome in MDS in the population studied, i.e., MDS patients from India.
Proteomic study of aqueous humour in diabetic patients with cataracts by TMT combined with HPLC-MS/MS
Authors: Xu Weihai , Liang Ya , Zhu Yunxia , Sun Tong , Yuan Zhilan , Han Xiao 
Published: October 2023

AbstractBackgroundThe purpose of this study is to identify the proteomic differences between the aqueous humour of diabetes patients with cataracts and that of non-diabetic sufferers of cataracts in a clinical setting.MethodsPatients were divided into the diabetic experimental group and the non-diabetic control group. Aqueous humour specimens were obtained via cataract surgery. Sample proteins were treated with a TMT reagent, separated using a cation chromatography column, and analysed using a C18 desalting column. Proteins were identified using HPLC-MS/MS. The differential proteins were identified using both a p value of < 0.05 and a fold change of > 1.2. GO classification enrichment analysis, KEGG pathway enrichment analysis, protein interaction network analysis, and ingenuity pathway analysis were all carried out. The expression level of four differential proteins were verified by Western blot, and GC and TTR expressions were further examined using an expanded sample pool.ResultsThe postprandial glucose levels between the experimental group (9.40 ± 1.35 mmol/L) and the control group (6.56 ± 0.81 mmol/L) were significantly different, with a p value of 1.16E-06. It is important to note, however, that the baseline levels of the parameters showed no statistical differences. In total, 397 aqueous humour proteins were identified; of these, 137 showed significant differences, with 63 upregulated ones and 74 down-regulated ones. The differential proteins play important roles in numerous biological processes and pathways, such as complement and coagulation cascades (p = 1.71E-09). Some of these differential proteins are associated with diabetic retinal degeneration and other diabetic complications. Differential proteins, such as HP, GC, and TTR, have high node degree in the protein interaction network. Western blot results further confirmed that GC were down-regulated while TTR was up-regulated in aqueous humour under diabetic condition.ConclusionA list of differential proteins in the human aqueous humour of diabetic patients was established. Proteins with high interaction scores as per protein interaction analysis, such as GC and TTR, were further verified and could potentially be used as early diagnostic markers for diabetic eye complications in clinical practice.
Impact of early-onset fetal growth restriction on the neurodevelopmental outcome of very preterm infants at 24 months: a retrospective cohort study
Authors: Cortez Ferreira Mariana , Mafra Joana , Dias Ana , Santos Silva Isabel , Taborda Adelaide 
Published: October 2023

Abstract
Background
The association between fetal growth restriction (FGR) and childhood neurodevelopmental delay is unclear and the evidence available to the present date shows conflicting results. Our aim was to analyse the impact of early-onset FGR on the neurodevelopmental outcome at 24 months of corrected age in very preterm infants.

Methods
Retrospective cohort study of very preterm infants (≤ 32 weeks’ gestation) admitted to a neonatal intensive care unit between 1 January 2013–31 December 2019. The control group comprised appropriate for gestational age (AGA) newborns. Griffiths III Mental Development Scale was performed at 24 months of corrected age.

Results
132 infants were included: 44 FGR and 88 AGA. Mean Global Development Quotient (GDQ) was lower for FGR infants (p = 0.004) even after adjusting for maternal and perinatal factors (βadjusted -16.703; p = 0.009). The average scores for the neurodevelopmental domains were highest for personal-social-emotional skills (107.02 ± 16.34), followed by eye/hand coordination (105.61 ± 14.20) and foundation of learning skills (102.23 ± 13.74) and were lowest for gross motor (97.90 ± 11.88) and language/communication skills (96.39 ± 18.88). FGR had a significant negative impact on all domains except for gross motor skills. After adjustment, FGR continued to have a significant adverse impact on language/communication (βadjusted -21.924; p = 0.013), eye/hand coordination (βadjusted -15.446; p = 0.015) and foundation of learning skills (βadjusted -15.211; p = 0.013).

Conclusions
In very preterm infants, FGR was associated with a significantly increased risk of poor neurodevelopmental outcome at 24 months of corrected age compared to age-matched AGA infants.
The impact of COVID-19 on the lives of Canadians with and without non-communicable chronic diseases: results from the iCARE Study
Authors: Deslauriers Frédérique , Gosselin-Boucher Vincent , Léger Camille , Vieira Ariany Marques , Bacon Simon L. , Lavoie Kim L. 
Published: October 2023

Abstract
Background
The COVID-19 pandemic and its prevention policies have taken a toll on Canadians, and certain subgroups may have been disproportionately affected, including those with non-communicable diseases (NCDs; e.g., heart and lung disease) due to their risk of COVID-19 complications and women due to excess domestic workload associated with traditional caregiver roles during the pandemic.

Aims/Objectives
We investigated the impacts of COVID-19 on mental health, lifestyle habits, and access to healthcare among Canadians with NCDs compared to those without, and the extent to which women with NCDs were disproportionately affected.

Methods
As part of the iCARE study (www.icarestudy.com), data from eight cross-sectional Canadian representative samples (total n = 24,028) was collected via online surveys between June 4, 2020 to February 2, 2022 and analyzed using general linear models.

Results
A total of 45.6% (n = 10,570) of survey respondents indicated having at least one physician-diagnosed NCD, the most common of which were hypertension (24.3%), chronic lung disease (13.3%) and diabetes (12.0%). In fully adjusted models, those with NCDs were 1.18–1.24 times more likely to report feeling lonely, irritable/frustrated, and angry ‘to a great extent’ compared to those without (p’s < 0.001). Similarly, those with NCDs were 1.22–1.24 times more likely to report worse eating and drinking habits and cancelling medical appointments/avoiding the emergency department compared to those without (p’s < 0.001). Moreover, although there were no sex differences in access to medical care, women with NCDs were more likely to report feeling anxious and depressed, and report drinking less alcohol, compared to men with NCDs (p’s < 0.01).

Conclusion
Results suggest that people with NCDs in general and women in general have been disproportionately more impacted by the pandemic, and that women with NCDs have suffered greater psychological distress (i.e., feeling anxious, depressed) compared to men, and men with NCDs reported having increased their alcohol consumption more since the start of COVID-19 compared to women. Findings point to potential intervention targets among people with NCDs (e.g., prioritizing access to medical care during a pandemic, increasing social support for this population and mental health support).
Automatic classification of 3D positional relationship between mandibular third molar and inferior alveolar canal using a distance-aware network
Authors: Chun So-Young , Kang Yun-Hui , Yang Su , Kang Se-Ryong , Lee Sang-Jeong , Kim Jun-Min , Kim Jo-Eun , Huh Kyung-Hoe , Lee Sam-Sun , Heo Min-Suk , Yi Won-Jin 
Published: October 2023

AbstractThe purpose of this study was to automatically classify the three-dimensional (3D) positional relationship between an impacted mandibular third molar (M3) and the inferior alveolar canal (MC) using a distance-aware network in cone-beam CT (CBCT) images. We developed a network consisting of cascaded stages of segmentation and classification for the buccal-lingual relationship between the M3 and the MC. The M3 and the MC were simultaneously segmented using Dense121 U-Net in the segmentation stage, and their buccal-lingual relationship was automatically classified using a 3D distance-aware network with the multichannel inputs of the original CBCT image and the signed distance map (SDM) generated from the segmentation in the classification stage. The Dense121 U-Net achieved the highest average precision of 0.87, 0.96, and 0.94 in the segmentation of the M3, the MC, and both together, respectively. The 3D distance-aware classification network of the Dense121 U-Net with the input of both the CBCT image and the SDM showed the highest performance of accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve, each of which had a value of 1.00. The SDM generated from the segmentation mask significantly contributed to increasing the accuracy of the classification network. The proposed distance-aware network demonstrated high accuracy in the automatic classification of the 3D positional relationship between the M3 and the MC by learning anatomical and geometrical information from the CBCT images.