bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of an electronic medication management support system in patients with polypharmacy in general practice: study protocol of a quantitative process evaluation of the AdAM trial
Authors: Brünn Robin , Lemke Dorothea , Chapidi Kiran , Köberlein-Neu Juliane , Piotrowski Alexandra , Söling Sara , Greiner Wolfgang , Kellermann-Mühlhoff Petra , Timmesfeld Nina , van den Akker Marjan , Muth Christiane ,   AdAM study group
Published: January 2022

Background: Interventional studies on polypharmacy often fail to significantly improve patient-relevant outcomes, or confine themselves to measuring surrogate parameters. Interventions and settings are complex, with many factors affecting results. The AdAM study’s aim is to reduce hospitalization and death by requiring general practitioners (GPs) to use a computerized decision-support system (CDSS). The study will undergo a process evaluation to identify factors for successful implementation and to assess whether the intervention was implemented as intended. Objective: To evaluate our complex intervention, based on the Medical Research Council’s guideline dimensions. Research Questions: We will assess implementation (reach, fidelity, dose, tailoring) by asking: (1) Who took part in the intervention (proportion of GPs using the CDSS, proportion of patients enrolled in them)? Information on GPs’ and patients’ characteristics will also be collected. (2) How many and which medication alerts were dealt with? (3) Was the intervention implemented as intended? (4) On what days did GPs use the intervention tool? Methods: The process evaluation is part of a stepped-wedge cluster-randomized controlled trial. Characteristics of practices, GPs and patients using the CDSS will be compared with the non-participating population. CDSS log data will be analyzed to evaluate how the number of medication alerts changed between baseline and 2 months later, and to identify the kind of alerts that were dealt with. Comparison of enrolled patients on weekdays versus weekends will shed light on GPs’ use of the CDSS in the absence or presence of patients. Outcomes will be presented using descriptive statistics, and significance tests will be used to identify associations between them. We will conduct subgroup analyses, including time effects to account for software improvements. Discussion: This study protocol is the basis for conducting analyses of the quantitative process evaluation. By providing insight into how GPs conduct medication reviews, the evaluation will provide context to the trial results and support their interpretation. The evaluation relies on the proper documentation by GPs, potentially limiting its explanatory power.
Non-contrast-enhanced magnetic resonance imaging can be used to assess renal cortical and medullary volumes—A validation study
Authors: Liefke Jonas , Steding-Ehrenborg Katarina , Asgeirsson Daniel , Nordlund David , Kopic Sascha , Morsing Eva , Hedström Erik 
Published: January 2022

Background Magnetic resonance imaging (MRI) biomarkers can diagnose and prognosticate kidney disease. Renal volume validation studies are however scarce, and measurements are limited by use of contrast agent or advanced post-processing. Purpose To validate a widely available non-contrast-enhanced MRI method for quantification of renal cortical and medullary volumes in pigs; investigate observer variability of cortical and medullary volumes in humans; and present reference values for renal cortical and medullary volumes in adolescents. Materials and Methods Cortical and medullary volumes were quantified from transaxial in-vivo water-excited MR images in six pigs and 15 healthy adolescents (13–16years). Pig kidneys were excised, and renal cortex and medulla were separately quantified by the water displacement method. Both limits of agreement by the Bland-Altman method and reference ranges are presented as 2.5–97.5 percentiles. Results Agreement between MRI and ex-vivo quantification were -7 mL (-10–0 mL) for total parenchyma, -4 mL (-9–3 mL) for cortex, and -2 mL (-7–2 mL) for medulla. Intraobserver variability for pig and human kidneys were <5% for total parenchyma, cortex, and medulla. Interobserver variability for both pig and human kidneys were ≤4% for total parenchyma and cortex, and 6% and 12% for medulla. Reference ranges indexed for body surface area and sex were 54–103 mL/m2 (boys) and 56–103 mL/m2 (girls) for total parenchyma, 39–62 mL/m2 and 36–68 mL/m2 for cortex, and 16–45 mL/m2 and 17–42 mL/m2 for medulla. Conclusion The proposed widely available non-contrast-enhanced MRI method can quantify cortical and medullary renal volumes and can be directly implemented clinically.
Utilization of an Electronic Health Record Integrated Risk Score to Predict Hospitalization Among COVID-19 Patients
Authors: Nyman Mark A. , Jose Thulasee , Croghan Ivana T. , Parkulo Mark A. , Burger Charles D. , Schroeder Darrell R. , Hurt Ryan T. , O’Horo John C. 
Published: January 2022

Objective: To evaluate the performance of an Electronic Health Record (EHR) integrated risk score for COVID-19 positive outpatients to predict 30-day risk of hospitalization. Patients and Methods: A retrospective observational study of 67 470 patients with COVID-19 confirmed by polymerase chain reaction (PCR) test between March 12, 2020 and February 8, 2021. Risk scores were calculated based on data in the chart at the time of the incident infection. Results: The Mayo Clinic COVID-19 risk score consisted of 13 components included age, sex, chronic lung disease, congenital heart disease, congestive heart failure, coronary artery disease, diabetes mellitus, end stage liver disease, end stage renal disease, hypertension, immune compromised, nursing home resident, and pregnant. Univariate analysis showed all components, except pregnancy, have significant ( P < .001) association with admission. The Mayo Clinic COVID-19 risk score showed a Receiver Operating Characteristic Area Under Curve (AUC) of 0.837 for the prediction of admission for this large cohort of COVID-19 positive patients. Conclusion: The Mayo Clinic COVID-19 risk score is a simple score that is easily integrated into the EHR with excellent predictive performance for severe COVID-19. It can be leveraged to stratify risk for severe COVID-19 at initial contact, when considering therapeutics or in the allocation of vaccine supply.
Comparison of Physical Function and Pain Levels of Hallux Rigidus Patients before and after Synthetic Cartilage Implant vs Arthrodesis Surgery
Authors: Oh Irvin , Joo Peter , Baumhauer Judith F. , Houck Jeffrey , Kohring Jessica M. , Flemister Adolph S. , Ketz John P. , DiGiovanni Benedict F. 
Published: January 2022

Category: Bunion; Midfoot/Forefoot Introduction/Purpose: Hallux rigidus is a common and painful degenerative condition of the great toe limiting a patient's physical function and quality of life. The purpose of this study was to investigate pre- and postoperative physical function (PF) and pain interference (PI) levels of patients undergoing synthetic cartilage implant hemiarthroplasty (SCI) versus arthrodesis (AD) for treatment of hallux rigidus using the Patient Reported Outcome Measurement Information System (PROMIS). Methods: Pre- and postoperative PROMIS PF and PI t-scores were analyzed for patients who underwent either SCI or AD. Postoperative final PROMIS t-scores were obtained via phone survey. Linear mixed model analysis was used to assess differences in PF and PI at each follow up point. Final follow-up scores were analyzed using independent sample t-tests. Results: Total 181 (59 SCI, 122 AD) operatively managed patients were included for analysis of PROMIS scores. Final phone survey was performed at mean 33 (14-59) months postoperatively, with 101 patients (40 SCI, 61 AD) successfully contacted. Mean age of the SCI cohort was younger than the AD cohort (57.5 versus 61.5 years-old, p = 0.01). Average PF t-scores were higher in the SCI cohort compared to AD cohort at baseline (47.1 versus 43.9, respectively; p = 0.01) and at final follow up (51.4 versus 45.9, respectively; p < 0.01). A main effect of superior improvement in PF was detected in SCI group (+4.3) versus AD group (+2) across time intervals (p < 0.01). PI t-scores were similar between the two procedures across time points. Conclusion: The SCI cohort reported superior PF t-scores at all follow-up time points compared to the arthrodesis group. No differences were found for PI or complication rates between the two treatment groups during this study timeframe.
A Comparison of Portable Ultrasonography and the Fluoroscopy for Evaluating Medial Ankle Instability: A Cadaveric Study
Authors: Saengsin Jirawat , Sato Go , Sornsakrin Pongpanot , Lubberts Bart , Waryasz Gregory R. , Guss Daniel , DiGiovanni Christopher W. 
Published: January 2022

Category: Ankle; Trauma Introduction/Purpose: Diagnosis of destabilizing deltoid ligament injuries remains challenging and is best identified with dynamic imaging techniques. This study aims to assess and compare medial clear space (MCS) distances in various stages of sequentially created supination external rotation (SER) ankle injury model using portable ultrasound (P-US) and fluoroscopy. We hypothesize that there is a strong correlation between the P-US and fluoroscopic measurements for the assessment of medial ankle instability in SER type ankle injury during the gravity stress test (GST), weight-bearing, or external rotation stress test. Methods: Ten cadaveric specimens were used for assessing medial ankle instability. The assessment was performed with all structures intact, and later with sequential transection of the anterior inferior tibiofibular ligament (Stage I), fibular (Weber-B fracture) (Stage II), posterior inferior tibiofibular ligament (Stage III), superficial deltoid ligament (Stage IVa), and deep deltoid ligament (Stage IVb). In all scenarios, the GST, external rotation stress test(45N), and Simulated weight-bearing condition(750N) were performed. The P-US measurement of the MCS was assessed at the anteromedial and inferomedial aspect of the ankle joint. Three different MCS distances were measured, as demonstrated in Figure 1. The fluoroscopic MCS measurements were assessed on a true mortise ankle view achieved during each loading condition. Spearman rank correlation was used to investigate the relationship between the P-US and fluoroscopic measurements. The inter- and intra-observer agreement was assessed using the intraclass correlation coefficient (ICC) through a two-way mixed-effects model with absolute agreement. Results: The P-US and fluoroscopic assessed medial ankle instability values during the GST, weight-bearing, and the external rotation stress test increased as the SER ankle injury stage progressed. The P-US values measured during all stress tests demonstrated a moderate to strong positive correlation with those measured with the fluoroscopy (Spearman's rank correlation ranged from 0.61-0.93, p-values <0.001). Inter-rater (P-US: 0.97, 95%CI: 0.96-0.98) and intra-rater reliability (P-US, 0.95, 95%CI: 0.94-0.96) for the P-US measurements were all substantial. Conclusion: The use of dynamic P-US to measure the MCS appears to be a reliable and repeatable technique. The P-US MCS measurement values measured in the SER ankle injury model during the GST, weight-bearing and the external rotation stress test are well correlated with those values measured with fluoroscopy. Therefore, the dynamic P-US with stress examination of the ankle has the potential to quantify medial ankle instability in a radiation-free, non-invasive, low cost, and point of care setting.
Comparative transcriptomics and eQTL mapping of response to Melampsora americana in selected Salix purpurea F2 progeny
Authors: Wilkerson Dustin G. , Crowell Chase R. , Carlson Craig H. , McMullen Patrick W. , Smart Christine D. , Smart Lawrence B. 
Published: January 2022

Abstract
Background
Melampsora spp. rusts are the greatest pathogen threat to shrub willow (Salix spp.) bioenergy crops. Genetic resistance is key to limit the effects of these foliar diseases on host response and biomass yield, however, the genetic basis of host resistance has not been characterized. The addition of new genomic resources for Salix provides greater power to investigate the interaction between S. purpurea and M. americana, species commonly found in the Northeast US. Here, we utilize 3′ RNA-seq to investigate host-pathogen interactions following controlled inoculations of M. americana on resistant and susceptible F2S. purpurea genotypes identified in a recent QTL mapping study. Differential gene expression, network analysis, and eQTL mapping were used to contrast the response to inoculation and to identify associated candidate genes.

Results
Controlled inoculation in a replicated greenhouse study identified 19 and 105 differentially expressed genes between resistant and susceptible genotypes at 42 and 66 HPI, respectively. Defense response gene networks were activated in both resistant and susceptible genotypes and enriched for many of the same defense response genes, yet the hub genes of these common response modules showed greater mean expression among the resistant plants. Further, eight and six eQTL hotspots were identified at 42 and 66 HPI, respectively. The combined results of three analyses highlight 124 candidate genes in the host for further analysis while analysis of pathogen RNA showed differential expression of 22 genes, two of which are candidate pathogen effectors.

Conclusions
We identified two differentially expressed M. americana transcripts and 124 S. purpurea genes that are good candidates for future studies to confirm their role in conferring resistance.
Hyperosmotic stress-induced microtubule disassembly in Chlamydomonas reinhardtii
Authors: Ng Lee Mei , Komaki Shinichiro , Takahashi Hideyuki , Yamano Takashi , Fukuzawa Hideya , Hashimoto Takashi 
Published: January 2022

Abstract
Background
Land plants respond to drought and salinity by employing multitude of sophisticated mechanisms with physiological and developmental consequences. Abscisic acid-mediated signaling pathways have evolved as land plant ancestors explored their habitats toward terrestrial dry area, and now play major roles in hyperosmotic stress responses in flowering plants. Green algae living in fresh water habitat do not possess abscisic acid signaling pathways but need to cope with increasing salt concentrations or high osmolarity when challenged with adverse aquatic environment. Hyperosmotic stress responses in green algae are largely unexplored.

Results
In this study, we characterized hyperosmotic stress-induced cytoskeletal responses in Chlamydomonas reinhardtii, a fresh water green algae. The Chlamydomonas PROPYZAMIDE-HYPERSENSITEVE 1 (PHS1) tubulin kinase quickly and transiently phosphorylated a large proportion of cellular α-tubulin at Thr349 in G1 phase and during mitosis, which resulted in transient disassembly of microtubules, when challenged with > 0.2 M sorbitol or > 0.1 M NaCl. By using phs1 loss-of-function algal mutant cells, we demonstrated that transient microtubule destabilization by sorbitol did not affect cell growth in G1 phase but delayed mitotic cell cycle progression. Genome sequence analyses indicate that PHS1 genes evolved in ancestors of the Chlorophyta. Interestingly, PHS1 genes are present in all sequenced genomes of freshwater Chlorophyta green algae (including Chlamydomonas) but are absent in some marine algae of this phylum.

Conclusion
PHS1-mediated tubulin phosphorylation was found to be partly responsible for the efficient stress-responsive mitotic delay in Chlamydomonas cells. Ancient hyperosmotic stress-triggered cytoskeletal remodeling responses thus emerged when the PHS1 tubulin kinase gene evolved in freshwater green algae.
Potentially inappropriate medications in relation to length of nursing home stay among older adults
Authors: Sönnerstam Eva , Gustafsson Maria , Lövheim Hugo 
Published: January 2022

Abstract
Background
To investigate the use of potentially inappropriate medications and their relation to the length of nursing home stay among older adults.

Methods
Questionnaire surveys using the Multi-Dimensional Dementia Assessment scale were sent out to all nursing homes in Västerbotten county in northern Sweden in 2007 and 2013. In total, 3186 adults (1881 from 2007 and 1305 from 2013) ≥65 years old were included and 71.8% of those had cognitive impairment. Potentially inappropriate medications were identified using drug-specific quality indicators according to Swedish National Board of Health and Welfare.

Results
Potentially inappropriate medications were used by 48.0% of the 2007 study sample and by 28.4% of the 2013 study sample. The prevalence of glibenclamide use 2007 and antipsychotic drug use 2013 increased linearly (β = 0.534E− 3, 95% CI: 0.040E− 3-0.103E− 2, p = 0.034 and β = 0.155E− 2, 95% CI: 0.229E− 3-0.288E− 2, p = 0.022, respectively) with the length of nursing home stay. No significant association was found between the prevalence of propiomazine, codeine, long-acting benzodiazepines, anticholinergics, NSAIDs, tramadol or the total use of potentially inappropriate medications and the length of stay in nursing homes in 2007 or 2013. Antipsychotics were the most commonly prescribed of the drug classes investigated and used by 22.6% of the residents 2007 and by 16.0% of the residents 2013.

Conclusions
These results indicate that treatment with potentially inappropriate medications is common among older adults living in nursing homes, but it seems to be related to the length of nursing home stay only to a smaller extent. Drug treatment should regularly be reviewed and followed-up among nursing home residents regardless of their length of nursing home stay, in order to prevent unnecessary adverse events.
Low incidence of COVID-19 case severity and mortality in Africa; Could malaria co-infection provide the missing link?
Authors: Osei Silas Acheampong , Biney Robert Peter , Anning Alberta Serwah , Nortey Lydia Nkuah , Ghartey-Kwansah George 
Published: January 2022

Abstract
Background
Despite reports of malaria and coronavirus diseases 2019 (COVID-19) co-infection, malaria-endemic regions have so far recorded fewer cases of COVID-19 and deaths from COVID-19, indicating a probable protection from the poor outcome of COVID-19 by malaria. On the contrary, other evidence suggests that malaria might contribute to the death caused by COVID-19. Hence, this paper reviewed existing evidence hypothesizing poor outcome or protection of COVID-19 patients when co-infected with malaria.

Methods
PRISMA guidelines for systematic review were employed in this study. Published articles from December 2019 to May 2021on COVID-19 and malaria co-infection and outcome were systematically searched in relevant and accessible databases following a pre-defined strategy. Studies involving human, in vivo animal studies, and in vitro studies were included.

Results
Twenty three (23) studies were included in the review out of the 3866 records identified in the selected scientific databases. Nine (9) papers reported on co-infection of COVID-19 and malaria. Five (5) papers provided information about synergism of malaria and COVID-19 poor prognosis, 2 papers reported on syndemic of COVID-19 and malaria intervention, and 7 studies indicated that malaria protects individuals from COVID-19.

Conclusions
Low incidence of COVID-19 in malaria-endemic regions supports the hypothesis that COVID-19 poor prognosis is prevented by malaria. Although further studies are required to ascertain this hypothesis, cross-immunity and common immunodominant isotopes provide strong evidence to support this hypothesis. Also, increase in co-inhibitory receptors and atypical memory B cells indicate synergy between COVID-19 and malaria outcome, though, more studies are required to make a definite conclusion.
Prevalence and genotype distribution of hepatitis C virus within hemodialysis units in Thailand: role of HCV core antigen in the assessment of viremia
Authors: Chuaypen Natthaya , Khlaiphuengsin Apichaya , Prasoppokakorn Thaninee , Susantitaphong Paweena , Prasithsirikul Wisit , Avihingsanon Anchalee , Tangkijvanich Pisit , Praditpornsilpa Kearkiat 
Published: January 2022

Abstract
Background
Individuals with end-stage renal disease have a higher risk of hepatitis C virus (HCV) acquisition during long-term hemodialysis (HD). Our report was designed to investigate HCV prevalence and genotype, in addition to the clinical use of HCV core antigen (HCVcAg), within multiple HD facilities in Thailand.

Methods
This cross‐sectional report was investigated between January and June 2019. HCV infection was assessed by anti-HCV and confirmed active infection by measuring HCV RNA and HCVcAg. HCV genotype was determined by phylogenetic analysis using nucleotide sequences of NS5B region.

Results
Overall, 140 of 3,305 (4.2%) patients in 15 dialysis centers had anti-HCV positive. Among them, HCV RNA was further assessed in 93 patients and was detectable in 59 (63.4%) persons. Considering HCV viremia, HCVcAg measurement exhibited high accuracy (96.8%), sensitivity (94.9%) and specificity (100%) in comparison with HCV RNA testing. Moreover, individuals infected with HCV received a longer duration of dialysis vintage when compared to anti-HCV negative controls. The major sub-genotypes were 1a, 1b, 3a, 3b, 6f and 6n. Regarding phylogenetic analysis, there were 7 clusters of isolates with high sequence homology affecting 17 individuals, indicating possible HCV transmission within the same HD centers.

Conclusions
HCV frequency and common sub-genotypes in HD centers were different from those found in the Thai general population. HCVcAg might be an alternate testing for viremia within resource-limited countries. Enhanced preventive practices, dialyzer reuse policy and better access to antiviral therapy are crucial for HCV micro-elimination within HD facilities.
Cardiac valve calcification is associated with mortality in hemodialysis patients: a retrospective cohort study
Authors: Bai Jiuxu , Zhang Xiaoling , Zhang Aihong , Zhang Yanping , Ren Kaiming , Ren Zhuo , Zhao Chen , Wang Qian , Cao Ning 
Published: January 2022

Abstract
Background
Cardiac valve calcification (CVC) is common in end-stage renal disease (ESRD). We investigated the effect of CVC on all-cause and cardiovascular (CV) mortality in maintenance hemodialysis (MHD) patients.

Methods
A retrospective cohort study was conducted on 434 hemodialysis patients who underwent echocardiography for qualitative assessment of valve calcification with complete follow-up data from January 1, 2014, to April 30, 2021. The baseline data between the CVC and non-CVC groups were compared. The Kaplan–Meier method was used to analyse all-cause and cardiovascular mortality. The association of CVC with all-cause and cardiovascular mortality was evaluated using multivariate Cox regression analysis.

Results
Overall, 27.2% of patients had mitral valve calcification (MVC), and 31.8% had aortic valve calcification (AVC) on echocardiography. Patients with CVC showed significantly higher all-cause (log-rank P < 0.001) and cardiovascular (log-rank P < 0.001) mortality rates than patients without CVC. In multivariate regression analyses, MVC (HR: 1.517, P = 0.010) and AVC (HR: 1.433, P = 0.028) were significant factors associated with all-cause mortality. MVC (HR: 2.340, P < 0.001) and AVC (HR: 2.410, P < 0.001) were also significant factors associated with cardiovascular mortality.

Conclusions
MVC and AVC increased the risk of all-cause and cardiovascular mortality in MHD patients. Regular follow-up with echocardiography could be a useful method for risk stratification in MHD patients.