bluuebunny/crossref_metadata_2025_split huggingface dataset:
Can upfront DPYD extended variant testing reduce toxicity and associated hospital costs of fluoropyrimidine chemotherapy? A propensity score matched analysis of 2022 UK patients
Authors: Tsiachristas Apostolos , Vallance Grant , Koleva-Kolarova Rositsa , Taylor Harriet , Solomons Luke , Rizzo Giovanni , Chaytor Catherine , Miah Junel , Wordsworth Sarah , Hassan A. Bassim 
Published: April 2022

Abstract
Aim
To independently assess the impact of mandatory testing using an extended DPYD variant panel (ToxNav®) and consequent dose adjustment of Capecitabine/5-FU on recorded quantitative toxicity, symptoms of depression, and hospital costs.

Methods
We used propensity score matching (PSM) to match 466 patients tested with ToxNav® with 1556 patients from a historical cohort, and performed regression analysis to estimate the impact of ToxNav®on toxicity, depression, and hospital costs.

Results
ToxNav® appeared to reduce the likelihood of experiencing moderate (OR: 0.59; 95%CI: 0.45–0.77) and severe anaemia (OR: 0.55; 95%CI: 0.33–0.90), and experience of pain for more than 4 days a week (OR: 0.50; 95%CI: 0.30–0.83), while it increased the likelihood of mild neutropenia (OR: 1.73; 95%CI: 1.27–2.35). It also reduced the cost of chemotherapy by 12% (95%CI: 3–31) or £9765, the cost of non-elective hospitalisation by 23% (95%CI: 8–36) or £2331, and the cost of critical care by 21% (95%CI: 2–36) or £1219 per patient. For the DPYD variant associated with critical risk of toxicity (rs3918290), the improved non-elective hospital costs were > £20,000, whereas variants associated with hand-foot syndrome toxicity had no detectable cost improvement.

Conclusion
Upfront testing of DPYD variants appears to reduce the toxicity burden of Capecitabine and 5-FU in cancer patients and can lead to substantial hospital cost savings, only if the dose management of the drugs in response to variants detected is standardised and regulated.
Optical coherence tomography biomarkers in patients with macular edema secondary to retinal vein occlusion treated with dexamethasone implant
Authors: Castro-Navarro Verónica , Monferrer-Adsuara Clara , Navarro-Palop Catalina , Montero-Hernández Javier , Cervera-Taulet Enrique 
Published: April 2022

AbstractPurposeTo evaluate the impact of optical coherence tomography (OCT) biomarkers on intravitreal dexamethasone (DEX) implant clinical outcomes in patients with macular edema secondary to retinal vein occlusion (RVO-ME).MethodsRetrospective study conducted on a cohort of patients with RVO-ME, either naïve or previously treated, who underwent treatment with DEX implant and had a follow-up of 6 months. Anatomic success was defined as a central retinal thickness (CRT) < 250 μm or a relative reduction of CRT ≥10% from baseline. The primary endpoint was the mean change in CRT from baseline to month-6. Secondary end-points included changes in BCVA, the impact of baseline OCT biomarkers on functional and anatomic outcomes; and the impact of treatment on the different OCT biomarkers. OCT biomarkers associated with functional and anatomic outcomes were estimated using a logistic regression model.ResultsFifty-seven eyes were included in the study. Baseline CRT was significantly decreased from 567.6 ± 226.2 μm to 326.9 ± 141.0 μm at month-6 (p < 0.0001). Baseline BCVA was significantly lower in the eyes with disrupted external limiting membrane (ELM) (mean 40.3 ± 21.3 letters) than in those with non-disrupted (mean 68.6 ± 10.7 letters) or partially-disrupted ELM (mean 59.6 ± 13.2 letters),p = 0.0001 andp = 0.0011, respectively. Baseline BCVA was significantly lower in eyes with > 20 hyperreflective foci (HRF) than in those with < 10 HRF (p = 0.0388). The eyes with disorganization of the retinal inner layers (DRIL) had lower baseline BCVA than those without DRIL (Hodges-Lehmann median difference: − 12.0 letters, 95% CI: − 25.0 to − 5.0 letters,p = 0.0042). At month-6, 26 (45.6%); 24 (42.1%), and 20 (35.1%) eyes achieved a BCVA improvement ≥5, ≥10, and ≥ 15 letters respectively. Forty (70.2%) eyes were classified as anatomic success at month-6. Logistic regression analysis found none factor significantly associated with success in the multivariate analysis.ConclusionsThe results of this study suggested a positive impact of DEX on CRT and BCVA in eyes with RVO-ME. No OCT-biomarkers were identified as predictors of clinical-outcomes. Additionally, presence of DRIL, presence of HRF (> 20), or disrupted ELM were significantly associated with worse baseline BCVA.
Bone quality effect on short implants in the edentulous mandible: a finite element study
Authors: Liu Chaowei , Xing Yifeng , Li Yan , Lin Yanjun , Xu Jianghan , Wu Dong 
Published: April 2022

Abstract
Introduction
The aim of this study was to verify whether the use of short implants could optimize stress distribution of bone surrounding implants in atrophic mandibles with different bone qualities.

Methods
A three-dimensional model of the atrophic mandible with three levels of bone quality was made using computer software. Short implants (6 mm) and standard implants (10 mm) were used in four designs: Design 1 "All-On four", Design 2 "All-On-four" with two short implants, Design 3 four vertical implants with two short implants, and Design 4 six short implants. The distal short implants were placed at the first molar position. All twelve models were imported into finite element analysis software, and 110 N oblique force was loaded on the left second premolar. Maximum principal stress values of peri-implant bone and the volumes of bone with over 3000 microstrians (overload)were analyzed.

Result
Stress values and volumes of overload bone increased in all four groups with the decline of bone quality. The highest stress values were found in the cortical bone surrounding the Design 1 inclined implant in two lower bone quality mandibles, and the lowest in Design 3. However, Design 1 had less overload bone tissue than all three designs with short implants.

Conclusion
Short implants placed posteriorly helped decrease stress values in peri-implant bone, while bone surrounding short implants had a high resorption risk in low bone quality mandible.
Knowledge, attitudes and professional practices of ortho-periodontal care of adults: a cross-sectional survey in France
Authors: Saloux Apolline , Couatarmanach Antoine , Chauvel Brice , Jeanne Sylvie , Brezulier Damien 
Published: April 2022

AbstractBackgroundDue to increasing numbers of adult patients, orthodontists are being confronted more and more with periodontal problems. Coordination amongst orthodontists, periodontists and general dentists is useful in preventing and stopping periodontal disease. The main objectives of this survey were to evaluate the technical knowledge, techniques and attitudes employed by French orthodontists, periodontists and general dentists in adult dental care.MethodsA cross-sectional online survey was distributed to French dentists. The questionnaire, consisting of 30 questions, was divided into six sections covering treatment programs and the forensic environment.ResultsOne thousand one hundred twenty-two complete answers were recorded. Adults undergoing orthodontic treatment represented 19.9% of the orthodontists' patients, but only 2.67% of the general dentists' patients. Communication between clinicians was rated as good, greater than 3 out of 5. Before treatment, orthodontists were less alarmed than generalists regarding bleeding, recessions, increased probing depths, halitosis and hyperplasia. During treatment, orthodontists never or only occasionally performed palpation or probing in 54.2% and 84.6% of cases. Gingivitis and recessions were the main reasons for consultations for 22.0% and 20.1% of general dentists and periodontists after orthodontic treatment. Of the practitioners surveyed, 43% felt that they experienced a setback in the ortho-periodontal treatment.ConclusionsThis study revealed discrepancies in the knowledge and attitudes of practitioners. Therapeutic management remains one of the major challenges of multidisciplinary treatments. Continuing education needs to be further developed in this field.
Effect of aqueous environment on wear resistance of dental glass–ceramics
Authors: Zhang Zhenzhen , Wang Qi , Wang Fu , Li Ding , Meng Meng , Zhang Yaming , Zhang Shaofeng 
Published: April 2022

Abstract
Background
Wear resistance affects dental ceramics longevity and the functions of the opposing teeth. However, data for the effect of aqueous environment on wear resistance of dental ceramics are lacking. This study evaluated the effect of aqueous environment on wear resistance of typical dental glass–ceramics.

Methods
Disk specimens were prepared from lithium disilicate glass–ceramics (LD) and leucite reinforced glass–ceramics (LEU). The disk specimens paired with steatite antagonists were tested in a pin-on-disk tribometer under both wet and dry conditions with 10 N up to 500,000 wear cycles. The wear analysis of glass–ceramics was performed using a 3D profilometer after 100,000, 300,000 and 500,000 wear cycles. Wear morphologies were analyzed by employing scanning electron microscopy (SEM). The crystalline compositions of specimens stored in a dry environment and subsequently immersed in distilled water for 40 h were separately determined using X-ray diffraction (XRD). The chemical states of the wear surfaces for LD were analyzed by X-ray photoelectron spectroscopy (XPS). The data analysis and multiple pair-wise comparisons of means were performed by using one-way analysis of variance (ANOVA) and Tukey’s post-hoc test.

Results
LEU in a wet environment exhibited less wear volume loss than that in a dry environment (p < 0.05). The volume loss of LD in a wet environment was higher than that in a dry environment (p < 0.05). The wear volumes of steatite antagonists paired with two glass–ceramics under dry conditions were higher than under wet conditions.

Conclusions
XPS spectra of LD under wet conditions indicated that high wear loss might result from the effect of stress corrosion by water and reaction of water with the ionic-covalent bonds at the crack tip. XPS spectra and SEM images of LD under dry conditions showed a possible formation of tribofilm. Within the limitations of this in vitro study, water was wear-friendly to LEU and all opposing steatites but aggravated wear for LD.
Foot-related diabetes complications: care pathways, patient profiles and costs
Authors: Kurkela Olli , Nevalainen Jaakko , Arffman Martti , Lahtela Jorma , Forma Leena 
Published: April 2022

AbstractBackgroundFoot-related diabetes complications reduce individual well-being, increase mortality and results in increased healthcare costs. Despite their notable stress on health services, studies examining the foot complication care pathways, especially from the viewpoint of health services, are limited. We aimed to identify the most typical care pathways following an initial foot-related diabetes complication, to characterize the patients on each pathway and calculate the related healthcare costs.MethodsThe identification of pathways was based on population-wide register-based data including all persons diagnosed with diabetes in Finland from 1964 to 2017. For each patient, initial foot-related complication from 2011–2016 was identified using the ICD-10 codes and related healthcare episodes were followed for two years until the end of 2017 or death. A sequence analysis was conducted on care episodes resulting in groups of typical care pathways, as well as their patient profiles. The costs of pathways resulting from the care episodes were calculated based on the data and the reported national unit costs and analyzed using linear models.ResultsWe identified six groups of typical pathways each comprising mainly single type of care episodes. Three of the groups comprised over 10 000 patients while the remaining groups ranged from a few hundred to a few thousand. Majority of pathways consisted only single care episode. However, among the rest of the care pathways variability in length of care pathways was observed between and within group of pathways. On average, the patients were over 65 years of age and were diagnosed with diabetes for over a decade. The pathways resulted in an annual cost of EUR 13 million. The mean costs were nearly 20-fold higher in the group with the highest costs (EUR 11 917) compared to the group with the lowest costs (EUR 609).ConclusionsWe identified groups of typical care pathways for diabetic foot and discovered notable heterogeneity in the resource use within the groups. This information is valuable in guiding the development of diabetes care to meet the growing need. Nevertheless, reasons underlying the observed heterogeneity requires further examination. Since foot complications are largely preventable, substantial savings could be achieved using cost-effective technologies and more efficient organization of care.
A proof of concept for continuous, non-invasive, free-living vital signs monitoring to predict readmission following an acute exacerbation of COPD: a prospective cohort study
Authors: Hawthorne Grace , Richardson Matthew , Greening Neil J. , Esliger Dale , Briggs-Price Samuel , Chaplin Emma J. , Clinch Lisa , Steiner Michael C. , Singh Sally J. , Orme Mark W. 
Published: April 2022

Abstract
Background
The use of vital signs monitoring in the early recognition of an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) post-hospital discharge is limited. This study investigated whether continuous vital signs monitoring could predict an AECOPD and readmission.

Methods
35 people were recruited at discharge following hospitalisation for an AECOPD. Participants were asked to wear an Equivital LifeMonitor during waking hours for 6 weeks and to complete the Exacerbations of Chronic Pulmonary Disease Tool (EXACT), a 14-item symptom diary, daily. The Equivital LifeMonitor recorded respiratory rate (RR), heart rate (HR), skin temperature (ST) and physical activity (PA) every 15-s. An AECOPD was classified as mild (by EXACT score), moderate (prescribed oral steroids/antibiotics) or severe (hospitalisation).

Results
Over the 6-week period, 31 participants provided vital signs and symptom data and 14 participants experienced an exacerbation, of which, 11 had sufficient data to predict an AECOPD. HR and PA were associated with EXACT score (p < 0.001). Three days prior to an exacerbation, RR increased by mean ± SD 2.0 ± 0.2 breaths/min for seven out of 11 exacerbations and HR increased by 8.1 ± 0.7 bpm for nine of these 11 exacerbations.

Conclusions
Increased heart rate and reduced physical activity were associated with worsening symptoms. Even with high-resolution data, the variation in vital signs data remains a challenge for predicting AECOPDs. Respiratory rate and heart rate should be further explored as potential predictors of an impending AECOPD.
Trial registration: ISRCTN registry; ISRCTN12855961. Registered 07 November 2018—Retrospectively registered, https://www.isrctn.com/ISRCTN12855961
Successful use of dalbavancin in the treatment of gram positive blood stream infections: a case series
Authors: Evins Connor , Lancaster Harrison , Schnee Amanda E. 
Published: April 2022

Abstract
Background
Dalbavancin is a semisynthetic antibiotic used as an alternative to vancomycin for skin infections and osteomyelitis. Its long half-life decreases length of hospitalizations. This study analyzes the effectiveness of Dalbavancin for bacteremia and infective endocarditis.

Methods
The authors performed a retrospective chart analysis on patients who received Dalbavancin due to being poor candidates for PICC placement, poor candidates for prolonged hospitalization, or who were leaving against medical advice. Their hospitalizations were analyzed and results were compiled using descriptive statistics.

Results
Our cohort had 22 patients treated with Dalbavancin for bacteremia and 1 for endocarditis. They were treated with IV antibiotics, typically a regimen of at least vancomycin and a cephalosporin, for a median of 6.5 days prior to receiving Dalbavancin. 20 received one dose, while three received two doses. 22 had confirmed culture clearance and one denied repeat culture. There were no reported side effects from the medication, no readmissions for worsened infection, and no deaths from the infection. 15 patients had follow-up visits within 90 days.

Conclusions
Overall, patients responded well. The lack of readmission to the hospital indicates possible outpatient treatment. This would help decrease cost and comorbidities of long-term hospital stays. These positive results are limited by small sample size and treatment of other antibiotics prior to receiving Dalbavancin. Further research is required to accurately estimate the efficacy of Dalbavancin on bloodstream infections and endocarditis, but these results are promising especially for patients who are not candidates for long term hospitalization or outpatient IV access.
Knowledge and experience of Kazakhstan athletes in anti-doping and the impact of past educational intervention
Authors: Zhumabayeva Galiya , Kapanova Gulnara , Vinnikov Denis , Bakasheva Maira , Abdulla Venera , Grjibovski Andrej 
Published: April 2022

Abstract
Background
Although Kazakhstan National Anti-Doping Organization (KazNADO) exists since 2013, but little is yet known about anti-doping (AD) knowledge of Kazakhstan athletes. The aim of this study was to assess the AD education knowledge level and experience among Kazakhstan athletes, as well as the impact of any past AD educational program on them.

Methods
Altogether, 590 athletes (the median was age 17 years (interquartile range 8)), representing various sports, participated in the web-based study and completed the questionnaire, which consisted of socio-demographic part and ALPHA test. We assessed the association of any past AD education and experience with anti-doping knowledge using adjusted regression models.

Results
A total of 54.6% participants underwent doping control and 82,7% of athletes received AD education at least once. More than 300 participants (50.8%) provided correct answers for 10 questions. Age and years in sports (competition duration) were significantly associated with the ALPHA scores of athletes. Athletes who received AD education more than once in the past had significantly higher ALPHA scores than non-AD educated athletes in most questions.

Conclusion
AD education was associated with AD knowledge. Further research is needed to identify the adherence to anti-doping knowledge.
Large-scale discovery of novel neurodevelopmental disorder-related genes through a unified analysis of single-nucleotide and copy number variants
Authors: Hamanaka Kohei , Miyake Noriko , Mizuguchi Takeshi , Miyatake Satoko , Uchiyama Yuri , Tsuchida Naomi , Sekiguchi Futoshi , Mitsuhashi Satomi , Tsurusaki Yoshinori , Nakashima Mitsuko , Saitsu Hirotomo , Yamada Kohei , Sakamoto Masamune , Fukuda Hiromi , Ohori Sachiko , Saida Ken , Itai Toshiyuki , Azuma Yoshiteru , Koshimizu Eriko , Fujita Atsushi , Erturk Biray , Hiraki Yoko , Ch’ng Gaik-Siew , Kato Mitsuhiro , Okamoto Nobuhiko , Takata Atsushi , Matsumoto Naomichi 
Published: April 2022

Abstract
Background
Previous large-scale studies of de novo variants identified a number of genes associated with neurodevelopmental disorders (NDDs); however, it was also predicted that many NDD-associated genes await discovery. Such genes can be discovered by integrating copy number variants (CNVs), which have not been fully considered in previous studies, and increasing the sample size.

Methods
We first constructed a model estimating the rates of de novo CNVs per gene from several factors such as gene length and number of exons. Second, we compiled a comprehensive list of de novo single-nucleotide variants (SNVs) in 41,165 individuals and de novo CNVs in 3675 individuals with NDDs by aggregating our own and publicly available datasets, including denovo-db and the Deciphering Developmental Disorders study data. Third, summing up the de novo CNV rates that we estimated and SNV rates previously established, gene-based enrichment of de novo deleterious SNVs and CNVs were assessed in the 41,165 cases. Significantly enriched genes were further prioritized according to their similarity to known NDD genes using a deep learning model that considers functional characteristics (e.g., gene ontology and expression patterns).

Results
We identified a total of 380 genes achieving statistical significance (5% false discovery rate), including 31 genes affected by de novo CNVs. Of the 380 genes, 52 have not previously been reported as NDD genes, and the data of de novo CNVs contributed to the significance of three genes (GLTSCR1, MARK2, and UBR3). Among the 52 genes, we reasonably excluded 18 genes [a number almost identical to the theoretically expected false positives (i.e., 380 × 0.05 = 19)] given their constraints against deleterious variants and extracted 34 “plausible” candidate genes. Their validity as NDD genes was consistently supported by their similarity in function and gene expression patterns to known NDD genes. Quantifying the overall similarity using deep learning, we identified 11 high-confidence (> 90% true-positive probabilities) candidate genes: HDAC2, SUPT16H, HECTD4, CHD5, XPO1, GSK3B, NLGN2, ADGRB1, CTR9, BRD3, and MARK2.

Conclusions
We identified dozens of new candidates for NDD genes. Both the methods and the resources developed here will contribute to the further identification of novel NDD-associated genes.
Virulence and phylogenetic groups of Escherichia coli cultured from raw sewage in Kuwait
Authors: Redha Mahdi A. , Al Sweih Noura , Albert M. John 
Published: April 2022

AbstractIn Kuwait, some untreated sewage is discharged into the sea which poses health risks. Therefore, we determined the virulence traits and the phylogenetic groups of E. coli cultured from raw sewage. Sewage was collected once every month for 12 months with culturing of a total of 140 E. coli isolates. E. coli was typed by the methods of Clermont. The five pathotypes of diarrheagenic E. coli (DEC), and extra-intestinal pathogenic E. coli (ExPEC) were detected by specific PCR assays. Four virulence genes which correlate with pathogenicity in animal models, were used for the first time for detection of ExPEC—vat (vacuolating auto-transporter toxin), fyuA (yersiniabactin receptor), chuA (heme-binding protein), and yfcV (major subunit of putative chaperon-usher fimbria). Most E. coli belonged to phylogenetic groups A (65[45%]) and B1 (34[24.3%]). Three (2.1%) isolates were DEC, while 14 (10%) isolates were ExPEC mostly in group B2 (57.1%). A relatively high prevalence of ExPEC in sewage has public health implications.