bluuebunny/crossref_metadata_2025_split huggingface dataset:
Study protocol of the PIMPI-project, a cohort study on acceptance, tolerability and immunogenicity of second trimester maternal pertussis immunization in relation to term and preterm infants
Authors: Immink Maarten M. , Bekker Mireille N. , de Melker Hester E. , Rots Nynke Y. , Sanders Elisabeth A. M. , van der Maas Nicoline A. T. 
Published: September 2021

Abstract
Background
Maternal immunization confers passive immunity to the fetus by transplacental antibody transfer. Infants may be better protected against pertussis if the mother received a diphtheriae, tetanus and acellular pertussis (Tdap) vaccination in the second trimester of pregnancy compared to the third trimester. This study evaluates IgG antibody concentrations in term and preterm infants at birth and 2 months after birth after maternal Tdap-vaccination between 200 and 240 w of gestation vs third trimester Tdap-vaccination. Further aims are assessing the determinants that underlie acceptance of second trimester maternal Tdap-vaccination as well as the tolerability of vaccination.

Methods
This prospective cohort study consists of two parts. In the acceptance part, pregnant women complete a questionnaire on determinants that underlie acceptance of a second trimester Tdap-vaccination, which is offered subsequently between 200 and 240 w of gestation. Vaccinated women complete an additional questionnaire on vaccination tolerability. Vaccinated women may also participate in the immunogenicity part, in which blood is drawn from mother at delivery and from infant at birth and 2 months after birth. Women are also eligible for the immunogenicity part if they received a Tdap-vaccination between 200 and 240 w of gestation via the national immunization program and get hospitalized for an imminent preterm delivery. Blood sampling continues until 60 term and 60 preterm mother-infant-pairs have been included. Pertussis-specific IgG antibody concentrations are determined in serum using a fluorescent bead-based multiplex immunoassay. For term infants, non-inferiority in IgG antibody concentrations against pertussis toxin (anti-PT) will be assessed referred to a historical control group in which mothers were Tdap-vaccinated between 300 and 320 w of gestation. For preterm infants, non-inferiority of anti-PT IgG concentrations is referred to as 85% of infants having ≥ 20 international units/mL at 2 months after birth.

Discussion
This study investigates acceptance, tolerability and immunogenicity regarding maternal Tdap-immunization between 200 and 240 w of gestation. Its results provide insight into the effects of second trimester Tdap-vaccination on IgG antibody concentrations in term and preterm infants before primary infant vaccinations. Results on acceptance and tolerability guide antenatal care providers in communication with pregnant women and maintain the safety of second trimester Tdap-vaccination.
Trial registration: EU Clinical Trials Register, 2018-002976-41, retrospectively registered 24 July 2019, https://www.clinicaltrialsregister.eu/ctr-search/search?query=2018-002976-41.
COVID-19: a fatal case of acute liver failure associated with SARS-CoV-2 infection in pre-existing liver cirrhosis
Authors: Ihlow Jana , Seelhoff Alexander , Corman Victor M. , Gruber Achim D. , Dökel Simon , Meinhardt Jenny , Radbruch Helena , Späth-Schwalbe Ernst , Elezkurtaj Sefer , Horst David , Herbst Hermann 
Published: September 2021

Abstract
Background
The detection of severe acute respiratory syndrome coronavirus (SARS-CoV-2) is challenging, particularly in post-mortem human tissues. However, there is increasing evidence for viral SARS-CoV-2 manifestation in non-respiratory tissues. In this context, it is a current matter of debate, whether SARS-CoV-2 shows hepatotropism.

Case presentation
Here, we report a case of an 88-year-old women with massive SARS-CoV-2 viremia, severe jaundice and clinical signs of an acute hepatitis, who died within a few days from an acute liver failure without showing any clinical signs of pneumonia. Autopsy revealed a severe chronic and acute liver damage with bile duct infestation by SARS-CoV-2 that was accompanied by higher expressions of angiotensin-converting enzyme-2 (ACE2), Cathepsin L and transmembrane serine protease 2 (TMPRSS2).

Conclusion
Our findings indicate an enhanced biliary susceptibility to viral infection with SARS-CoV-2, that might have resulted from pre-existing severe liver damage. Furthermore, our findings emphasize the differential diagnosis of coronavirus disease 2019 (COVID-19)-associated liver failure in the clinical setting of an inexplicable jaundice.
Outcome evaluation of COVID-19 infected patients by disease symptoms: a cross-sectional study in Ilam Province, Iran
Authors: Sadeghifar Jamil , Jalilian Habib , Momeni Khalil , Delam Hamed , Sheleme Tadesse , Rashidi Ayoub , Hemmati Fariba , Falahi Shahab , Arab-Zozani Morteza 
Published: September 2021

AbstractBackgroundNovel coronavirus disease-19 (COVID-19) was declared as a global pandemic in 2020. With the spread of the disease, a better understanding of patient outcomes associated with their symptoms in diverse geographic levels is vital. This study aimed to evaluate clinical outcomes of COVID-19 patients by disease symptoms in Ilam province, Iran.MethodsThis was a cross-sectional study. Data were collected from integrated health system records for all hospitals affiliated with the Ilam University of Medical Sciences between 26-Jan-2020 and 02-May-2020. All patients with a confirmed positive test were included in this study. Descriptive analyses, chi-square test, and binary logistic regression model were performed by using SPSS version 22.ResultsThe mean age of participants was 46.47 ± 18.24 years. Of the 3608 patients, 3477 (96.1%) were discharged, and 129 (3.9%) died. 54.2% of the patients were male and were in the age group of 30–40 years. Cough, sore throat, shortness of breath or difficulty breathing, and fever or chills were the most common symptoms. Patients with symptoms of shortness of breath, abnormal radiographic findings of the chest, and chest pain and pressure were relatively more likely to die. According to binary logistic regression results, the probability of death in patients with shortness of breath, abnormal chest radiographic findings, and chest pain was 1.34, 1.24, and 1.32 times higher, respectively, than for those without.ConclusionOur study provides evidence that the presentation of some symptoms significantly impacts outcomes of patients infected with SARS-CoV-2. Early detection of symptoms and proper management of outcomes can reduce mortality in patients with COVID-19.
The correlation between serum selenium, zinc, and COVID-19 severity: an observational study
Authors: Razeghi Jahromi Soodeh , Moradi Tabriz Hedieh , Togha Mansoureh , Ariyanfar Shadi , Ghorbani Zeinab , Naeeni Sima , Haghighi Samaneh , Jazayeri Aboozar , Montazeri Mahnaz , Talebpour Mohammad , Ashraf Haleh , Ebrahimi Mehdi , Hekmatdoost Azita , Jafari Elham 
Published: September 2021

Abstract
Background
Without an adequate immune response, SARS-CoV2 virus can simply spread throughout the body of the host. Two of the well-known immunonutrients are selenium (Se) and zinc (Zn). Se and Zn deficiency might lead to inflammation, oxidative stress, and viral entry into the cells by decreasing ACE-2 expression; three factors that are proposed to be involved in COVID-19 pathogenesis. Thus, in the current study we aimed at evaluating the correlation between serum Se and Zn status and COVID-19 severity.

Methods
Eighty-four COVID-19 patients were enrolled in this observational study. Patients were diagnosed based on an infectious disease specialist diagnosis, using WHO interim guidance and the recommendations of the Iranian National Committee of Covid-19. The patients with acute respiratory tract infection symptoms were checked for compatibility of chest computed tomography (CT) scan results with that of Covid-19 and Real-time polymerase chain reaction (RT-PCR) for corona virus infection. The severity of Covid-19 was categorized into three groups (mild, moderate, and severe) using CDC criteria. Serum Zn and Se level of all subjects was measured. The severity of the disease was determined only once at the onset of disease.

Results
According to the results of linear regression test, there was a significant association between Zn and Se level and COVID-19 severity (β = − 0.28, P-value = 0.01 for Se; β = − 0.26, P-value = 0.02). However the significance disappeared after adjusting for confounding factors. Spearman correlation analysis showed a significant negative association between serum Zn, Se and CRP level (r = − 0.35, P-value = 0.001 for Se; r = − 0.41, P-value < 0.001 for Zn).

Conclusion
Results suggest that increasing levels of Se and Zn were accompanied by a decrease in serum CRP level. However, the significant association between Se, Zn, and disease severity was lost after adjusting for confounding factors.
Case report: Osteomalacia due to bisphosphonate treatment in a patient on hemodialysis
Authors: Hatano Masaki , Kitajima Izuru , Yamamoto Seizo , Nakamura Masaki , Isawa Kazuya , Hirota Yutaka , Hoshino Junichi , Sawa Naoki , Ubara Yoshifumi 
Published: September 2021

Abstract
Background
No publications have reported on osteomalacia in patients receiving intermittent cyclical therapy with etidronate (a bisphosphonate) and undergoing long-term hemodialysis (HD).

Case presentation
We report on a 46-year-old Japanese man admitted to our hospital for further examination of left forearm pain. Maintenance HD was started at age 24 years, and the man had been on HD since then. At age 38 years, surgical parathyroidectomy was performed for secondary hyperparathyroidism; iliac crest bone biopsy performed at the same time showed osteitis fibrosa. The active vitamin D3 preparation calcitriol was started, and intermittent cyclical etidronate therapy was introduced 2 years later for osteoporosis. At age 45 years, the patient stopped taking calcitriol because of hypercalcemia but continued with etidronate. At age 46 years, a pseudofracture with a Looser zone occurred in the left ulna, and left femur bone biopsy revealed osteomalacia. Etidronate was discontinued, and calcitriol was restarted; open reduction and internal fixation with an angular stability plate were performed. Union of the bone was achieved 10 months after the operation. At age 49 years, a lumber bone biopsy confirmed improved bone morphometry.

Conclusions
We believe that intermittent cyclical etidronate therapy without administration of active vitamin D3 during long-term HD might have induced osteomalacia, resulting in the ulna insufficiency fracture. Therefore, we propose that administration of active vitamin D3 is essential to prevent osteomalacia in patients on long-term HD who are receiving bisphosphonates and have potential vitamin D3 deficiency.
Impairment of the visuospatial working memory in the patients with Parkinson’s Disease: an fMRI study
Authors: Kawashima Shoji , Shimizu Yoko , Ueki Yoshino , Matsukawa Noriyuki 
Published: September 2021

Abstract
Background
Mild cognitive impairment (MCI) is a common symptom in the patients with Parkinson’s disease (PD). The characteristics of cognitive impairment in PD are executive function (including working memory) and visuo-perceptual processing. The visuospatial n-back test has the merit of minimizing the influence of educational biases involved in the verbal n-back test. Furthermore, it can assess both visuospatial recognition and working memory in a single test.

Methods
We aimed to clarify the advantage of the visuospatial n-back test as a tool for detecting impairments of working memory in PD. We enrolled 28 right-handed patients with PD (18 males, 10 females) and 12 age-matched healthy controls (HC; 7 males, 5 females). Thirteen patients were classified as MCI (PD-MCI), and 15 as cognitively normal PD (PD-CN). Using functional MRI (fMRI), we explored the specific brain regions associated with the performance of the n-back test in the PD-MCI, PD-CN, and HC groups. The 0-back test assesses visuospatial recognition, while the 1-back and 2-back tests assess visuospatial working memory. Group comparisons were performed for three loads of this test.

Results
Patients with PD performed significantly worse in terms of the correct answer rates of all n-back tests compared with HC. fMRI analyses performed during the 2-back test revealed reduced activation in the bilateral dorsolateral prefrontal cortex, middle frontal gyrus (MFG), and parietal lobule in the PD group compared with the HC group. In contrast, the fMRI result during the 0-back test showed only a marginal difference in the frontal lobe. On comparisons of task performance between the PD-MCI and PD-CN groups, we found that the correct answer rate in the 2-back test was lower in the PD-MCI group than in the PD-CN group. However, scores of the 0-back and 1-back tests were not significantly different between the two groups. The fMRI findings revealed that activations within the middle frontal gyrus (MFG) and inferior parietal lobule (IPL) during the 2-back test were reduced in the patients with PD-MCI when compared to those with PD-CN.

Conclusions
This study reports reduced activation of the MFG and IPL in patients with PD-MCI. These regions may be associated with the pathophysiology of working memory impairment in patients with PD, which involves fronto-striatal network dysfunction.
Higher BMI predicts liver fibrosis among obese children and adolescents with NAFLD - an interventional pilot study
Authors: Moran-Lev Hadar , Cohen Shlomi , Webb Muriel , Yerushalmy-Feler Anat , Amir Achiya , Gal Dana L. , Lubetzky Ronit 
Published: September 2021

Abstract
Background
Non-alcoholic fatty liver disease (NAFLD) can range from simple steatosis to steatohepatitis with or without fibrosis. The predictors for liver fibrosis and the effect of nutritional intervention on hepatic fibrosis in pediatric population are not well established. We aimed to investigate the predictors for liver fibrosis and the effects of short-term nutritional intervention on steatosis and fibrosis among obese adolescents with NAFLD.

Methods
Cross-sectional study among obese adolescents. Sociodemographic and clinical data were collected. Liver fibrosis was estimated by Shearwave elastography. All participants were recommended to consume a low carbohydrate diet and were followed biweekly. Blood tests and elastography were performed upon admission and repeated after 3 months.

Results
Fifty-seven pediatric patients were recruited (35 males, mean age 13.5±2.9 years, mean body mass index [BMI] 38.8±9.7). Liver fibrosis was diagnosed in 34 (60%) subjects, which was moderate/severe (F≥2) in 24 (70%). A higher BMI Z score and moderate/severe steatosis correlated with moderate/severe fibrosis (P < 0.05). Seventeen patients completed 3 months of follow-up and displayed a decrease in BMI Z score (from BMI Z score 2.6±0.5 before intervention to 2.4±0.5 after intervention), with a significant decrease in liver fibrosis (P = 0.001).

Conclusion
Pediatric patients with high BMIs and severe liver steatosis are at risk for severe liver fibrosis. Nutritional intervention with minimal weight loss may improves hepatic fibrosis among the pediatric population.

Trial registration
TRN NCT04561804 (9/17/2020)
Factors associated with bone health status of Malaysian pre-adolescent children in the PREBONE-Kids Study
Authors: Chang Chung Yuan , Arasu Kanimolli , Wong Soon Yee , Ong Shu Hwa , Yang Wai Yew , Chong Megan Hueh Zan , Mavinkurve Meenal , Khoo Erwin Jiayuan , Chinna Karuthan , Weaver Connie Marie , Chee Winnie Siew Swee 
Published: September 2021

Abstract
Background
Modifiable lifestyle factors and body composition can affect the attainment of peak bone mass during childhood. This study performed a cross-sectional analysis of the determinants of bone health among pre-adolescent (N = 243) Malaysian children with habitually low calcium intakes and vitamin D status in Kuala Lumpur (PREBONE-Kids Study).

Methods
Body composition, bone mineral density (BMD), and bone mineral content (BMC) at the lumbar spine (LS) and total body (TB) were assessed using dual-energy X-ray absorptiometry (DXA). Calcium intake was assessed using 1-week diet history, MET (metabolic equivalent of task) score using cPAQ physical activity questionnaire, and serum 25(OH) vitamin D using LC-MS/MS.

Results
The mean calcium intake was 349 ± 180 mg/day and mean serum 25(OH)D level was 43.9 ± 14.5 nmol/L. In boys, lean mass (LM) was a significant predictor of LSBMC (β = 0.539, p < 0.001), LSBMD (β = 0.607, p < 0.001), TBBMC (β = 0.675, p < 0.001) and TBBMD (β = 0.481, p < 0.01). Height was a significant predictor of LSBMC (β = 0.346, p < 0.001) and TBBMC (β = 0.282, p < 0.001) while fat mass (FM) (β = 0.261, p = 0.034) and physical activity measured as MET scores (β = 0.163, p = 0.026) were significant predictors of TBBMD in boys. Among girls, LM was also a significant predictor of LSBMC (β = 0.620, p < 0.001), LSBMD (β = 0.700, p < 0.001), TBBMC (β = 0.542, p < 0.001) and TBBMD (β = 0.747, p < 0.001). Calcium intake was a significant predictor of LSBMC (β = 0.102, p = 0.034), TBBMC (β = 0.122, p < 0.001) and TBBMD (β = 0.196, p = 0.002) in girls.

Conclusions
LM was the major determinant of BMC and BMD among pre-adolescent Malaysian children alongside other modifiable lifestyle factors such as physical activity and calcium intake.
Characteristics and surgical outcomes of cleft palate in kabuki syndrome: a case series of 11 patients
Authors: Kim Jong-Ho , Kang Jiwon , Oh Joon Seok , Ahn Taeseon , Kim Baek-kyu , Baek Rong-Min 
Published: September 2021

Abstract
Objective
A significant number of patients with KS have cleft palate (CP) or submucous cleft palate (SMCP) and show delayed speech development. However, few reports have discussed the characteristics of CP in KS and the outcomes of postoperative speech development. The purpose of this study was to investigate the characteristics and surgical outcomes of CP in patients with KS, and to discuss the importance of the diagnosis of CP or SMCP.

Methods
We conducted a retrospective study on patients with clinically diagnosed KS who underwent palatoplasty. Clinical and surgical data were collected from patients’ medical records, and velopharyngeal function was evaluated using nasopharyngoscopy and speech analysis.

Results
In 11 cases, 5 patients had CP (45.5%) and 6 had SMCP (54.5%). Four patients who were genetically tested had a pathogenic variant of KMT2D. Seven of nine patients (77.8%) who underwent conventional palatoplasty showed velopharyngeal insufficiency and hypernasality. All patients who underwent pharyngeal flap surgery achieved velopharyngeal competency. Statistical analysis revealed a statistically significant difference in postoperative results between non-syndromic and KS patients.

Conclusion
Patients with SMCP may be more common than previously reported. The results showed that it is difficult to produce optimal results with conventional palatoplasty; therefore, pharyngeal flap surgery should be considered as a treatment to obtain favorable results. Pharyngeal flap surgery in patients with KS should be carefully designed based on speech evaluation and nasopharyngoscopic findings.
Vitamin D, pregnancy and caries in children in the INMA-Asturias birth cohort
Authors: Suárez-Calleja Claudia , Aza-Morera Jaime , Iglesias-Cabo Tania , Tardón Adonina 
Published: September 2021

Abstract
Background
Vitamin D is traditionally associated with the metabolism of calcium and phosphorus, a process essential for the mineralization of hard tissue such as bone or tooth. Deficiency of this vitamin is a problem worldwide, however. Given the possibly significant role of Vitamin D in odontogenesis in children, the objective of our study was to determine the influence of vitamin D levels in the blood on dental anomalies in children between 6 and 10 years of age, by means of 25-hydroxy vitamin D tests performed during pregnancy and the first years of life.

Methods
The data analyzed were sourced from data belonging to the INMA-Asturias birth cohort, a prospective cohort study initiated in 2004 as part of the INMA Project. The 25-hydroxy vitamin D (25(OH)D) test was performed with samples from 188 children in the INMA-Asturias birth cohort with a dental examination performed between 6 and 10 years of age. The samples were taken at three stages: in the mother at 12 weeks of gestation, and subsequently in the child at 4 and 8 years of age. Diet, nutritional and oro-dental hygiene habits were also analyzed by means of questionnaires.

Results
The results indicate a significant association between caries and correct or incorrect brushing technique. With incorrect brushing technique, the prevalence of caries was 48.89%, but this dropped to 22.38% with correct brushing technique. An association was also found between tooth decay and frequency of sugar intake. The prevalence of caries was 24.54% with occasional sugar intake, but this rose to 56% with regular sugar intake. On the other hand, levels < 20 ng/ml in both mother and child at 8 years of age would also be risk factors (ORgest = 2.51(1.01–6.36) and OR8years = 3.45(1.14–11.01)) for the presence of caries in children. The risk of caries practically tripled where 25(OH) D values were < 20 ng/ml.

Conclusions
Although incorrect brushing technique and regular sugar consumption was found to be the main cause of caries in the children, the low concentrations of vitamin D in the blood of the pregnant mothers may have magnified this correlation, indicating that the monitoring of vitamin D levels during pregnancy should be included in antenatal programmes. It is particularly striking that 50% of the children were deficient in vitamin D at the age of 4, and that dental floss was practically absent from regular cleaning routines.