bluuebunny/crossref_metadata_2025_split huggingface dataset:
The National Economic Burden of Rare Disease in United States in 2019
Authors: Yang Grace , Cintina Inna , Pariser Anne , Oehrlein Elisabeth , Sullivan Jamie , Kennedy Annie 
Published: November 2021

Abstract
Background: To provide a comprehensive assessment of the total economic burden of rare diseases (RD) in the U.S. in 2019.We followed a prevalence-based approach that combined the prevalence of 379 RDs with the per-capita direct medical and indirect costs, to derive the national economic burden by patient age and type of RD. To estimate prevalence and the direct medical cost of RD, we used claims data from three sources: Medicare 5% Standard Analytical File, Transformed Medicaid Statistical Information System, and Optum claims data for the privately insured. To estimate indirect and non-medical cost components, we worked with the rare disease community to design and implement a primary survey.Results: There were an estimated 15.5 million U.S. children (N=1,322,886) and adults (N=14,222,299) with any of the 379 RDs in 2019 with a total economic burden of $997 billion, including a direct medical cost of $449 billion (45%), $437 billion (44%) in indirect costs, and $111 billion (11%) in non-medical costs. The top drivers for excess medical costs associated with RD are hospital inpatient care and prescription medication; the top indirect cost categories are labor market productivity losses due to absenteeism, presenteeism, and forced early retirement.Conclusions: Our findings highlight the scale of the RD economic burden and call for immediate attention from the scientific communities, policy leaders, and other key stakeholders such as health care providers and employers, to think innovatively and collectively, to identify new ways to help improve the care, management, and treatment of these often-devastating diseases.
Prevalences of Antibiotic-Resistant and Multidrug Resistant Bacteria in Urine Cultures from Inpatients with Spinal Cord Injuries and Disorders: An 8-Year, Single-Center Experience
Authors: Šámal Vladimir , Paldus Vít , Fáčková Daniela , Mečl Jan , Šrám Jaroslav 
Published: November 2021

Abstract
Background
Patients, especially inpatients, with spinal cord lesions and disorders (SCI/D) have an elevated risk of recurrent urinary tract infections with multidrug resistant (MDR) bacteria. This study evaluated antimicrobial resistance and the prevalence of multidrug resistance and determined the risk factors for multidrug resistance.
Methods
In this retrospective cohort study, urine culture results were used to calculate the antimicrobial resistance rate and the incidence of infection with MDR bacteria in the SCI/D population. MDR was defined as acquired nonsusceptibility to at least one agent from three or more antimicrobial categories. The cohort included 402 inpatients from 2013 to 2020, with 1385 urine isolates. We included only the first isolate, and duplicate isolates, defined as positive cultures of the same strain within 14 days, were excluded from the evaluation.
Results
The most common MDR strains were Klebsiella spp. (29%) and Escherichia coli (24%). MDR isolates were detected in 50% of the samples and extended spectrum beta-lactamase (ESBL)-producing isolates in 26%, while carbapenem resistance was found in 0.1%. Significantly higher rates of infection with MDR bacteria were identified in the groups of patients with indwelling urethral/suprapubic catheters (p=0.003) and severity score C1-C4/AIS A-C (p=0.01). We identified age (OR: 0.99, 95% CI; 0.98-0.99, p=0.000), male sex (OR: 1.55, 95% CI; 1.16-2.06, p=0.003), management with urethral/suprapubic catheters (OR: 2.76, 95% CI; 2.04-3.74, p=0.000), and spontaneous voiding (OR: 1.84, 95% CI; 1.03-3.29, p=0.038) as independent predictors of multidrug resistance in our study population.
Conclusions
We identified a high antibiotic resistance rate and an increasing prevalence of infection with MDR bacteria in the SCI/D inpatient population. Particular attention should be given to bladder management, with an emphasis on minimizing the use of indwelling catheters.
Inhibition of hemozoin-induced neuroinflammation by medicinal plants used for the treatment of malaria in Southwest Nigeria: implications for cerebral malaria
Authors: Olajide Olumayokun , Iwuanyanwu Victoria 
Published: November 2021

Abstract
This study aimed to investigate some antimalarial plants for effects on neuroinflammation. Freeze-dried infusions of the plants were investigated for effects on hemozoin-induced neuroinflammation in BV-2 microglia and levels of inflammatory mediators measured. Alstonia boonei (stem bark), Anacardium occidentale (stem bark), Azadiractha indica (leaves), Enantia chlorantha (stem bark), Khaya senegalensis (stem bark), Mangifera indica (stem bark), and Nauclea latifolia (stem bark) produced significant (p<0.05) reduction in TNFα, IL-6, IL-1β, MCP-1, RANTES and iNOS/NO production in BV-2 microglia stimulated with a synthetic hemozoin (400 µg/mL). Further experiments showed that pre-treatment with 50 µg/mL of A. boonei, A. indica, A. occidentale, E. chlorantha and M. indica prior to hemozoin stimulation resulted in inhibition of NF-κB activation by >40%, while E. chlorantha, K. senegalensis and N. latifolia produced weak activities. Pretreatment with A. indica (50 µg/mL) produced the highest inhibition (58.6%) of hemozoin-induced increased NLRP3 protein expression, while A. occidentale (50 µg/mL), M. indica (50 µg/mL) and A. boonei (50 µg/mL) reduced expression by 54.1%, 49.2% and 47.1%, respectively. Hemozoin-induced increased caspase-1 activity was reduced by A. boonei, A. occidentale, A. indica, E. chlorantha, and M. indica. These results suggest that A. boonei, A. occidentale, A. indica and M. indica produced strong inhibition of hemozoin-induced neuroinflammation through mechanisms involving NFκB and NLRP3 inflammasome activation, while moderate activities were produced by E. chlorantha, K. senegalensis and N. latifolia. The outcome of the study provides pharmacological evidence for the potential benefits of the plants as herbal treatments of cerebral malaria symptoms.
A 500,000-Person Experiment Evaluating the Impact of Geographically-Targeted, High-Payoff Vaccine Lotteries
Authors: Milkman Katherine , Gandhi Linnea , Ellis Sean , Graci Heather , Gromet Dena , Mobarak Rayyan , Buttenheim Alison , Duckworth Angela , Pope Devin , Stanford Ala , Thaler Richard , Volpp Kevin 
Published: November 2021

Abstract
Lotteries have been shown to motivate behavior change in many settings. However, the value of large-scale, geographically-targeted lotteries as a policy tool for changing the behaviors of entire populations is a matter of heated debate. In mid-2021, we implemented a pre-registered, city-wide experiment in Philadelphia to test the effects of three, high-payoff (up to $50,000) geographically-targeted lotteries designed to motivate adult residents of Philadelphia to get vaccinated against COVID-19. All Philadelphia residents ages 18 and older were eligible for inclusion in each drawing but, if selected, could not accept a prize unless they had received at least one dose of a COVID-19 vaccine. In each drawing, residents of a randomly selected “treatment” zip code received half of the 12 lottery prizes (boosting their chances of a win to 50-100x those of other Philadelphians). This experimental design makes possible a causal estimate of the impact of vastly increasing people’s odds of winning a vaccine lottery. We estimate that the first treated zip code, which drew considerable media attention, may have experienced a small bump in vaccinations compared to control zip codes: vaccinations rose by an estimated 61 per 100,000 people (an 11% increase). Pooling results from all three zip codes treated over the course of our six-week experiment, however, we do not detect any overall benefits. This unsustained effect may be because media attention waned, salience of the lottery declined, or attitudes about vaccination became increasingly entrenched over time. Further, our 95% confidence interval provides an upper bound on the overall benefits of treatment in our study of 9%. Given that lotteries of this scale cost hundreds of thousands of dollars to implement, the lack of a substantial benefit from this experiment strengthens the policy case for other, more impactful ways to encourage health behavior change.
Treatment Goals for Achondroplasia: A Qualitative Study with Parents and Adults
Authors: McGraw Sarah A. , Henne Jeff , Nutter James , Larkin Adelpha Abrahamson , Chen Er 
Published: November 2021

Abstract
Background: Achondroplasia is characterized by disproportionate short stature accompanied by other changes to the musculoskeletal system. Individuals with this condition typically experience a variety of medical complications. Pharmacologic treatments are being developed for the treatment of achondroplasia. It is important to understand the goals for pharmacologic treatment among those affected by achondroplasia and factors that shape these views. Methods: This qualitative study is based on semi-structured interviews with 19 parents of children with achondroplasia and 5 adults with achondroplasia in the United States. We employed thematic analysis using an iterative process to identify themes across the interviews. Results:Participants had two goals for pharmacologic treatment of achondroplasia: ameliorating complications associated with the condition and increasing stature to overcome functional limitations and psychosocial challenges. Complications of particular concern were chronic pain and surgeries to repair spinal, ENT, and neurological sequelae. Increased height would enhance independence, fitting in socially, and avoiding social stigma. Despite many challenges, parents and adults with achondroplasia expressed that they found ways to adapt and emphasized satisfaction and the positive aspects of their lives. Concerns about medical treatment included fear of loss of their identity as a little person. Conclusions:This study offers evidence about how individuals affected by achondroplasia think about pharmacologic treatment of this condition, including both the benefits of ameliorating complications and increasing height. The findings can offer practical insights for parents of children considering treatment, treating physicians and decision makers evaluating coverage decisions for treatment of achondroplasia.
Clinico-Epidemiological Characteristics of Children with Cystic Fibrosis: A Tertiary Care Experience
Authors: Sarkar Probir Kumar , Akand Nabila , Tahura Sarabon , Kamruzzaman Md , Akter Johora , Zaman Khandakar Ashikur , Farhana Tanzila , Hossain Md Mosharaf , Alam Md Jahangir , Khan Md. Abdullah Saeed , Hasan Mohammad Jahid 
Published: November 2021

Abstract
Background: Cystic fibrosis (CF) is considered to be rare among individuals from Bangladesh. The objective of the study was to delineate the clinico-epidemiological characteristics of pediatric cystic fibrosis cases.Method: This observational study included pediatric patients (up to 14 years of age) with a clinical diagnosis of CF. Data were collected within the period from February 2021 and October 2021. Written informed consent was obtained from the accompanying parent. Clinical and epidemiological characteristics were analyzed on the basis of demographic data, medical history, laboratory tests, and outcome information. Data analysis was done with SPSS 26.Result: A total of 50 patients (66% male) with a mean age of 39.7 ±30.75 (SD) months were included. Twenty-eight patients (57.14%) had siblings with CF, and 41.67% of parents had a history of consanguineous marriage. The majority of them were stunted (86%) and underweight (86%), and half of them had wasting (54%). Median disease duration was 12 months (range: 2 – 72). Cough (100%) and purulent sputum (100%) were the predominant respiratory symptoms, while failure to thrive (98%) and bulky offensive stools (86%) were prime gastrointestinal symptoms. Among the signs, malnutrition (94%), short stature (72%), digital clubbing (64%), and bronchiectasis (40%) were most frequent. Pulmonary hypertension (48%, n=24) was the most common comorbidity identified in the study participants. In hospital, mortality was 16% (n=8). Digital clubbing, bronchiectasis, pancreatic insufficiency, and abnormal liver function tests were significantly higher in the patient who died.Conclusion: Children with cystic fibrosis most commonly present with undernutrition and respiratory symptoms. Failure to thrive was almost a global phenomenon. Pulmonary hypertension was the most common complication found in echocardiography.
Outcome of Life-Threatening Arrhythmias Among Patients Presenting in an Emergency Setting at a Tertiary Hospital in Accra-Ghana
Authors: Doku Alfred , Asare Bernard Yeboah-Asiamah , Osei Richard , Owoo Christian , Djagbletey Robert , Akamah Joseph , Aniteye Ernest , Ahadzi Dzifa 
Published: November 2021

Abstract
Background Management of life-threatening arrhythmia can be incredibly challenging in advanced health systems. In sub-Saharan Africa (SSA), this is likely more challenging because of weak pre-hospital and in-hospital critical care systems. Little is known about life-threatening arrhythmia, and their outcomes in SSA. The aim of this study was to examine the outcomes and types of arrhythmias among haemodynamically unstable patients presenting at a tertiary hospital in Accra-Ghana.Method This was a retrospective case series study conducted at the Korle-Bu Teaching Hospital (KBTH), Accra-Ghana. Medical records of patients who presented with or developed haemodynamically unstable arrhythmias within 24 hours of admission from January 2018 to December 2020 were reviewed. The demographic characteristics and clinical data including outcomes of patients were collected. Descriptive statistics was used, and results presented in frequency table.Results A total of 42 patients with life-threatening arrhythmias were included. Haemodynamically unstable tachyarrhythmias were the commonest arrhythmias found among the patients (70%). Approximately, 52.5% of patients had structural heart diseases (52.5%) whereas 27.5% had no apparent underlying cause or predisposing factor. Cardioversion (44.8%), commonly electrical (31.0%), and pacemaker implantation (34.5%) were the common initial interventions. Majority of the patients (88.1%) survived and were discharged home. Conclusion Tachyarrhythmias are the most common haemodynamically unstable arrhythmias seen among patients presenting emergently in a leading tertiary hospital in Ghana. The high survival rate observed was likely due to the presence of specialists on duty in our facility. This outcome cannot be extrapolated to other healthcare settings in sub-Saharan Africa with limited resources to manage these clinical entities.
Risk Factors of New Vertebral Compression Fracture After Percutaneous Kyphoplasty or Vertebroplasty: A Retrospective Study of 752 Patients
Authors: Zhang Bo-bo , Song Zhong-wei , Wang Ying , Ren Zhi-wei , Yang Wei-zhou , Yang Yi-min 
Published: November 2021

Abstract
Summary Irregularly postoperative anti-osteoporosis treatment (AOT), number of treated vertebrae (NTV) ≥ 2, bone mineral density (BMD) ≤－3.0 SDs, body mass index (BMI) <18.5kg/m2 or BMI ≥ 24kg/m2, vertebral height loss ratio (VHLR)＞20% were strong risk factors associated with new vertebral compression fractures (NVCF) after percutaneous vertebroplasty or kyphoplasty (PVP/PKP) in patients with osteoporotic vertebral compression fractures (OVCF). There was no difference between NVCF occurred adjacent or remote after PKP/PVP intervention.Introduction NVCF have been connected to PVP/PKP surgery for patients with VCF. There are some debates about whether new vertebral body fractures are simply a result of the natural progression of osteoporosis or whether they should be regarded as a consequence of augmentation. We tried to investigate and identify the risk factors which may be relevant to NVCF after PVP/PKP surgery in OVCF patients.Methods The authors retrospectively analyzed the occurrence of NVCF in 752 patients treated with PVP or PKP for OVCF. Possible risk factors, such as age, gender, refracture time (RT), AOT, NTV, BMD, BMI, and VHLR, were assessed.All methods are carried out in accordance with relevant guidelines and regulations.Results Significant differences (P<0.05) were found between the NVCF and control groups with regard to AOT, number of treated vertebrae, BMD, BMI, and VHLR by univariate analysis. And irregularly AOT, NTV ≥ 2, BMD ≤－3.0 SDs, BMI < 18.5 kg/m2 or BMI ≥ 24kg/m2, VHLR＞20% were found to be the significant factors in multivariate analysis. To evaluate a direct and more precise effect of the procedures on untreated vertebrae, the NVCF group was subdivided into adjacent and remote fracture groups. All of factors have no significant difference between two subgroups.Conclusion In the current study, the incidence of NVCF after PVP/PKP is 9.58%. Irregularly AOT, NTV ≥ 2, BMD ≤－3.0 SDs, BMI <18.5kg/m2 or BMI ≥ 24kg/m2, VHLR＞20% were strong risk factors associated with NVCF after PVP/PKP in patients with OVCF. There was no difference between NVCF occurred adjacent or remote after PKP/PVP intervention and that might be the result of the osteoporosis itself. All of those should be addressed during preoperative communication and postoperative management.
Renal Function Improvement Correlates with 3D Echocardiographic Findings: Effect of Surgical Mitral Valve Repair
Authors: Wang Chenchen , Yang Wenbo , Shi Zhongwei , Fang Yuehua 
Published: November 2021

Abstract

Purpose
The relationship between surgical treatment of mitral regurgitation (MR) and renal function is not well described. We sought to evaluate renal function before and after surgical mitral valve repair (SMVR) in degenerative significant MR.
Methods
Patients with primary severe ( 4+) MR and preserved left ventricular ejection fraction (LVEF) who underwent surgical mitral valve repair, evaluated by a cutting-edge 3-dimensional (3D) echocardiographic probe were included in this study. Three CKD-EPI equations were used to calculate estimated glomerular filtration rate (eGFR) before surgery and before patients discharge. Forty patients with baseline lower mean eGFR were studied.
Results
Measurements substantiated statistically remarkable improvements in eGFR (P<0.001), multivariable linear regression modeling demonstrated a strong association between increase of eGFR and reduction of MR (P=0.003), reduction of pulmonary arterial systolic pressure (PASP, P=0.018), as well as increase of forward stroke volume(FSV, P=0.02), regardless of the reduction of LVEF, left ventricular global longitudinal strain (GLS) and left atrial ejection fraction (LAEF).
Conclusion
Renal function improves after surgical mitral valve repair in patients with degenerative severe mitral regurgitation and preserved LVEF, despite of cardiac functional worsening.
Efficient Pressure Sensors Placement for Water Distribution Network Using Flow-Tracking Analysis
Authors: Huang Y.C. , Yang W.L. 
Published: November 2021

Abstract
This letter presents a novel approach for efficient deployment of top pressure sensors in water distribution network. Flow-Tracking analysis using head loss coverage ratio explores a least number of top sensors in network topologies. The following sequence of top sensor plans can be effortlessly determined by simple greedy algorithm. A regular hydraulic model with 33 sensor nodes is to validate the fast and effective feature of flow-tracking method. A top set of 5 sensor nodes selected by head loss coverage ratio Hcr in flow-tracking analysis agree exactly with top set of 5 sensitive nodes selected by objective function f(Xk) by means of Sensitivity Analysis. A linear relationship between objective function f(Xk) and heads loss coverage ratio Hcr of top sensor nodes reveals high accuracy mapping from flow-tracking method to Sensitivity Analysis. Time complexity of searching top sensors node set by flow-tracking analysis is O(m⋅n). Average pressure error can be expected as low as 0.08 m with top-two sensors in sensors layout. As top sensors in deployment plan are all used, minimum error of 0.04 m is achieved. Flow-Tracking analysis has the advantages of little time complexity and accurate top sensors strategy as a new efficient solution for pressure sensors deployment in associated flow network.
Plasma RIPK3 And HMGB1 Predict Severe COVID-19 Progression In ICU Patients: A Single-Center Cohort Study
Authors: Ruskowski Katharina , Neb Holger , Talbot Steven R , Choorapoikayil Suma , Adam Elisabeth H , von Knethen Andreas , Zacharowski Kai , Heinicke Ulrike 
Published: November 2021

Abstract
Background: Severe progression of coronavirus disease 2019 (COVID‑19) causes respiratory failure and critical illness. Recently, these pathologies have been associated with necroptosis, a receptor‑interacting serine/threonine‑protein kinase 3 (RIPK3) dependent regulated form of inflammatory cell death. Investigations of indicator necroptosis proteins like RIPK3, mixed lineage kinase domain‑like pseudokinase (MLKL), receptor‑interacting serine/threonine‑protein kinases 1 (RIPK1), and high‑mobility group box 1 (HMGB1) in clinical COVID‑19 manifestations are lacking.Methods: A prospective prolonged cohort study including 46 intensive care unit (ICU) patients classified with moderate and severe COVID‑19 was conducted with daily measured plasma levels of indicator necroptosis proteins like RIPK3, MLKL, RIPK1, and HMGB1 by enzyme‑linked immunosorbent assay (ELISA). On this basis, a multiple logistic (regression) classification for the prediction of severe COVID‑19 progression was performed. Results: We found significantly elevated RIPK3, MLKL, HMGB1, and RIPK1 levels in COVID‑19 patients admitted to the ICU compared to healthy controls throughout the ongoing disease, indicating necroptotic processes. Above all, with combined measurements of RIPK3 and HMGB1 plasma levels, we were able to time‑independently predict COVID‑19 severity with 84% accuracy, 90% sensitivity, and 76% specificity.Conclusion: We suggest that HMGB1 and RIPK3 are potential biomarkers to identify high‑risk COVID‑19 patients and developed a classifier for COVID‑19 severity.