bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive Evaluation of Primary Care Sports Medicine Fellowship Websites
Authors: Pagan-Rosado Robert , Hurdle Mark Friedrich , Jimenez Claudia , Cheville Andrea , Rosario-Concepcion Raul A 
Published: July 2021

Objective: To evaluate the comprehensiveness of primary care sports medicine fellowship websites and identify potential areas of improvement. Design: Cross-sectional analysis of fellowship program websites using quantitative and descriptive statistics. Setting: Internet. Participants: A total of 192 primary care sports medicine fellowship websites listed on the Electronic Residency Application Service (ERAS) website. Independent Variables: Program Specialty and Program Region. Main Outcome Measures: The presence or absence of 19 predetermined criteria on primary care sports medicine fellowship websites. Results: The average number of criteria that was included on each website was 9.8 (SD 3.5) (51.6%) of the possible 19. Programs had as few as 2 of the 19 (10.5%) criteria included on their website, and others had as many as 17 of the 19 (89.4%) criteria. Of the 192 primary care sports medicine fellowships, only 5 (2.6%) addressed at least 80% of the 19 different criteria. No primary care sports medicine fellowship website included all 19 criteria. Conclusions: Most primary care sports medicine fellowship websites do not offer comprehensive information about their programs for prospective applicants.
Continuous-infusion von Willebrand factor concentrate is effective for the management of acquired von Willebrand disease
Authors: Dane Kathryn E. , Lindsley John P. , Kickler Thomas , Streiff Michael B. , Moliterno Alison , Yui Jennifer , Naik Rakhi , Chaturvedi Shruti 
Published: July 2021

Abstract
Acquired von Willebrand disease (aVWD) is a rare disorder associated with a reduction in von Willebrand factor (VWF) activity, leading to increased bleeding risk. Monoclonal gammopathy of undetermined significance (MGUS) is the most common cause of lymphoproliferative disorder-associated aVWD and is caused by accelerated clearance of circulating VWF. Standard VWF replacement protocols for congenital VWD based on intermittent bolus dosing are typically less effective for aVWD because of antibody-mediated clearance. Intermittent bolus dosing of VWF concentrates often leads to inadequate peak response and profoundly shortened VWF half-life in aVWD. Intravenous immune globulin (IVIG) has demonstrated efficacy in aVWD; however, treatment effect is delayed up to 4 days, limiting its efficacy in acutely bleeding patients. We report the successful use of continuous-infusion VWF concentrate (with or without concomitant IVIG) in 3 patients with MGUS-associated aVWD who had demonstrated an inadequate response to bolus dosing. VWF concentrate doses required in this cohort were higher than typical doses for bleeding treatment in congenital VWD. This report illustrates that continuous-infusion VWF concentrate administration with or without intravenous immunoglobulin rapidly achieves target ristocetin cofactor activity and provides adequate hemostasis in aVWD associated with immunoglobulin G MGUS.
2-O, 3-O desulfated heparin (ODSH) increases bacterial clearance and attenuates lung injury in cystic fibrosis by restoring HMGB1-compromised macrophage function
Authors: Wang Mao , Gauthier Alex G. , Kennedy Thomas P. , Wang Haichao , Velagapudi Uday Kiran , Talele Tanaji T. , Lin Mosi , Wu Jiaqi , Daley LeeAnne , Yang Xiaojing , Patel Vivek , Mun Sung Soo , Ashby Charles R. , Mantell Lin L. 
Published: July 2021

Abstract
Background
High mobility group box 1 protein (HMGB1) is an alarmin following its release by immune cells upon cellular activation or stress. High levels of extracellular HMGB1 play a critical role in impairing the clearance of invading pulmonary pathogens and dying neutrophils in the injured lungs of cystic fibrosis (CF) and acute respiratory distress syndrome (ARDS). A heparin derivative, 2-O, 3-O desulfated heparin (ODSH), has been shown to inhibit HMGB1 release from a macrophage cell line and is efficacious in increasing bacterial clearance in a mouse model of pneumonia. Thus, we hypothesized that ODSH can attenuate the bacterial burden and inflammatory lung injury in CF and we conducted experiments to determine the underlying mechanisms.

Methods
We determined the effects of ODSH on lung injury produced by Pseudomonas aeruginosa (PA) infection in CF mice with the transmembrane conductance regulator gene knockout (CFTR−/−). Mice were given ODSH or normal saline intraperitoneally, followed by the determination of the bacterial load and lung injury in the airways and lung tissues. ODSH binding to HMGB1 was determined using surface plasmon resonance and in silico docking analysis of the interaction of the pentasaccharide form of ODSH with HMGB1.

Results
CF mice given 25 mg/kg i.p. of ODSH had significantly lower PA-induced lung injury compared to mice given vehicle alone. The CF mice infected with PA had decreased levels of nitric oxide (NO), increased levels of airway HMGB1 and HMGB1-impaired macrophage phagocytic function. ODSH partially attenuated the PA-induced alteration in the levels of NO and airway HMGB1 in CF mice. In addition, ODSH reversed HMGB1-impaired macrophage phagocytic function. These effects of ODSH subsequently decreased the bacterial burden in the CF lungs. In a surface plasmon resonance assay, ODSH interacted with HMGB1 with high affinity (KD = 3.89 × 10–8 M) and induced conformational changes that may decrease HMGB1’s binding to its membrane receptors, thus attenuating HMGB1-induced macrophage dysfunction.

Conclusions
The results suggest that ODSH can significantly decrease bacterial infection-induced lung injury in CF mice by decreasing both HMGB1-mediated impairment of macrophage function and the interaction of HMGB1 with membrane receptors. Thus, ODSH could represent a novel approach for treating CF and ARDS patients that have HMGB1-mediated lung injury.

Graphic abstract
A multi-country study using MALDI-TOF mass spectrometry for rapid identification of Burkholderia pseudomallei
Authors: Watthanaworawit Wanitda , Roberts Tamalee , Hopkins Jill , Gassiep Ian , Norton Robert , Robinson Matthew T. , Silisouk Joy , Sar Poda , Sao Sena , Amornchai Premjit , Limmathurotsakul Direk , Wuthiekanun Vanaporn , Nosten Francois , Simpson Andrew J. H. , Turner Paul , Ling Clare L. 
Published: July 2021

Abstract
Background
Burkholderia pseudomallei is the bacterial causative agent of melioidosis, a difficult disease to diagnose clinically with high mortality if not appropriately treated. Definitive diagnosis requires isolation and identification of the organism. With the increased adoption of MALDI-TOF MS for the identification of bacteria, we established a method for rapid identification of B. pseudomallei using the Vitek MS, a system that does not currently have B. pseudomallei in its in-vitro diagnostic database.

Results
A routine direct spotting method was employed to create spectra and SuperSpectra. An initial B. pseudomallei SuperSpectrum was created at Shoklo Malaria Research Unit (SMRU) from 17 reference isolates (46 spectra). When tested, this initial SMRU SuperSpectrum was able to identify 98.2 % (54/55) of Asian isolates, but just 46.7 % (35/75) of Australian isolates. Using spectra (430) from different reference and clinical isolates, two additional SMRU SuperSpectra were created. Using the combination of all SMRU SuperSpectra with seven existing SuperSpectra from Townsville, Australia 119 (100 %) Asian isolates and 31 (100 %) Australian isolates were correctly identified. In addition, no misidentifications were obtained when using these 11 SuperSpectra when tested with 34 isolates of other bacteria including the closely related species Burkholderia thailandensis and Burkholderia cepacia.

Conclusions
This study has established a method for identification of B. pseudomallei using Vitek MS, and highlights the impact of geographical differences between strains for identification using this technique.
Delivery of acetamiprid to tea leaves enabled by porous silica nanoparticles: efficiency, distribution and metabolism of acetamiprid in tea plants
Authors: Wang Xinyi , Yan Min , Zhou Jie , Song Wei , Xiao Yu , Cui Chuanjian , Gao Wanjun , Ke Fei , Zhu Jing , Gu Zi , Hou Ruyan 
Published: July 2021

Abstract
Background
Pesticide residue and its poor utilization remains problematic in agricultural development. To address the issue, a nano-pesticide has been developed by incorporating pesticide acetamiprid in porous silica nanoparticles.

Results
This nano-pesticide had an acetamiprid loading content of 354.01 mg g−1. Testing LC50 value against tea aphids of the commercial preparation was three times that of the nano-pesticide. In tea seedlings (Camellia sinensis L.), acetamiprid was transported upward from the stem to the young leaves. On day 30, the average retained concentrations in tea leaves treated with the commercial preparation were about 1.3 times of that in the nano-pesticide preparation. The residual concentrations of dimethyl-acetamiprid in leaves for plants treated with the commercial preparation were about 1.1 times of that in the nano-pesticide preparation. Untargeted metabolomics of by LC–MS on the young leaves of tea seedlings under nano-pesticide and commercial pesticide treatments showed significant numbers of differentially expressed metabolites (P < 0.05 and VIP > 1). Between the nano-pesticide treatment group and the commercial preparation treatment group there were 196 differentially expressed metabolites 2 h after treatment, 200 (7th day), 207 (21st day), and 201 (30th day) in negative ion mode, and 294 (2nd h), 356 (7th day), and 286 (30th day) in positive ion mode. Preliminary identification showed that the major differentially expressed metabolites were glutamic acid, salicylic acid, p-coumaric acid, ribonic acid, glutamine, naringenin diglucoside, sanguiin H4, PG (34:2) and epiafzelechin.

Conclusions
This work demonstrated that our nano-pesticide outperformed the conventional pesticide acetamiprid in terms of insecticidal activity and pesticide residue, and the absorption, transportation and metabolism of nano-pesticide in tea plant were different, which pave a new pathway for pest control in agricultural sector.

Graphical abstract
Proposal for the use of echocardiography in bloodstream infections due to different streptococcal species
Authors: Chamat-Hedemand Sandra , Bruun Niels Eske , Østergaard Lauge , Arpi Magnus , Fosbøl Emil , Boel Jonas , Oestergaard Louise Bruun , Lauridsen Trine K. , Gislason Gunnar , Torp-Pedersen Christian , Dahl Anders 
Published: July 2021

Abstract
Background
Infective endocarditis (IE) is diagnosed in 7–8% of streptococcal bloodstream infections (BSIs), yet it is unclear when to perform transthoracic (TTE) and transoesophageal echocardiography (TOE) according to different streptococcal species. The aim of this sub-study was to propose a flowchart for the use of echocardiography in streptococcal BSIs.

Methods
In a population-based setup, we investigated all patients admitted with streptococcal BSIs and crosslinked data with nationwide registries to identify comorbidities and concomitant hospitalization with IE. Streptococcal species were divided in four groups based on the crude risk of being diagnosed with IE (low-risk < 3%, moderate-risk 3–10%, high-risk 10–30% and very high-risk > 30%). Based on number of positive blood culture (BC) bottles and IE risk factors (prosthetic valve, previous IE, native valve disease, and cardiac device), we further stratified cases according to probability of concomitant IE diagnosis to create a flowchart suggesting TTE plus TOE (IE > 10%), TTE (IE 3–10%), or “wait & see” (IE < 3%).

Results
We included 6393 cases with streptococcal BSIs (mean age 68.1 years [SD 16.2], 52.8% men). BSIs with low-risk streptococci (S. pneumoniae, S. pyogenes, S. intermedius) are not initially recommended echocardiography, unless they have ≥3 positive BC bottles and an IE risk factor. Moderate-risk streptococci (S. agalactiae, S. anginosus, S. constellatus, S. dysgalactiae, S. salivarius, S. thermophilus) are guided to “wait & see” strategy if they neither have a risk factor nor ≥3 positive BC bottles, while a TTE is recommended if they have either ≥3 positive BC bottles or a risk factor. Further, a TTE and TOE are recommended if they present with both. High-risk streptococci (S. mitis/oralis, S. parasanguinis, G. adiacens) are directed to a TTE if they neither have a risk factor nor ≥3 positive BC bottles, but to TTE and TOE if they have either ≥3 positive BC bottles or a risk factor. Very high-risk streptococci (S. gordonii, S. gallolyticus, S. mutans, S. sanguinis) are guided directly to TTE and TOE due to a high baseline IE prevalence.

Conclusion
In addition to the clinical picture, this flowchart based on streptococcal species, number of positive blood culture bottles, and risk factors, can help guide the use of echocardiography in streptococcal bloodstream infections. Since echocardiography results are not available the findings should be confirmed prospectively with the use of systematic echocardiography.
Sonographic evaluation of spleen size in apparently healthy children in north-west Ethiopia, 2020: time to define splenomegaly
Authors: Tsehay Binalfew , Shitie Dessalegn , Afenigus Abebe , Essa Mustofa 
Published: July 2021

Abstract
Background
Assessment of spleen size is an important part of the clinical skills of medical students and physicians. Many diseases can affect the size of the aforementioned organ, ranging from infective processes to malignant disorders. However, to detect changes, prior knowledge of the actual normal size of these viscera is required in the population being studied. Establishing a customized chart and curve for a specific population of the same sociodemographic characteristics enables a better interpretation of sonographic assessments.

Methods
A hospital-based cross-sectional study design was conducted among 403 children in primary and referral hospitals of the east and west Gojjam zone. Data were collected using a structured questionnaire, physical examination, and ultrasound. The collected data were entered into Epi Data version 3.1 and exports to SPSS version 24 for analysis. Descriptive data were analyzed using descriptive statistics. A Pearson product-moment correlation was run to determine the relationship between age, anthropometric measurements of children, and ultrasound measurements of the spleen. Reference intervals were established using non-parametric reference limits (2.5th -97.5th ) and (5th – 97th ) percentiles by MedCalc software version 20.0.3.

Results
Four hundred three children aged from 7 to 15 years were included in this study. The mean sonographic longitudinal (length), anteroposterior(depth) and transverse (width) dimension of the spleen was, (8.24 ± 1.26 cm), (3.98 ± 0.57 cm), and (4.26 ± 0.59 cm) respectively. The mean volume of the spleen was 75.04 ± 23.92 cm3. The height and body surface area of children were best correlated with sonographic dimensions of the spleen. Reference intervals were established using height, age, and body surface area specific for clinically practical dimensions of the spleen.

Conclusions
According to this study, the children are considered as having enlarged longitudinal dimension of the spleen(splenomegaly) if he or she has a size above 97.5th percentile based on their respective height.
Programmed cell death protein-1 (PD-1) protects liver damage by suppressing IFN-γ expression in T cells in infants and neonatal mice
Authors: Guo Xuangjie , Xu Yiping , Luo Wei , Fang Rongli , Cai Li , Wang Ping , Zhang Yuxia , Wen Zhe , Xu Yanhui 
Published: July 2021

Abstract
Background
Biliary atresia (BA) is a severe cholangiopathy possibly resulting from virus-induced and immune-mediated injury of the biliary system. IFN-γ, secreted from CD4+ Th1 cells and CD8+ cytotoxic T cells, is a major mediator of liver pathology. Programmed death protein-1 (PD-1) signaling suppresses T cell function. However, how PD-1 modify T cell function in BA remains incompletely understood.

Methods
Frequencies of PD-1 expressing CD4+ and CD8+ T cells were analyzed in the liver and blood from BA and control subjects. Associations of PD-1+CD4+/CD8+T cell abundances with liver function indices were measured. Function of PD-1 was measured by administration of an anti-PD-1 antibody in a Rhesus Rotavirus (RRV)-induced BA model. Survival, histology, direct bilirubin, liver immune cell subsets and cytokine production were analyzed.

Results
PD-1 was significantly upregulated in CD4+ and CD8+ T cells in patients with BA compared with control subjects. PD-1 expression in T cells was negatively associated with IFN-γ concentration in liver (PD-1+CD4+T cells in liver vs. IFN-γ concentration, r = − 0.25, p = 0.05; PD-1+CD8+T cells in liver vs. IFN-γ concentration, r = − 0.39, p = 0.004). Blockade of PD-1 increased IFN-γ expression in CD4+ T and CD8+ T cells (RRV vs. anti-PD-1 treated RRV mice: 11.59 ± 3.43% vs. 21.26 ± 5.32% IFN-γ+ in hepatic CD4+T cells, p = 0.0003; 9.33 ± 4.03% vs. 22.55 ± 7.47% IFN-γ+ in hepatic CD8+T cells, p = 0.0001), suppressed bilirubin production (RRV vs. anti-PD-1 treated RRV mice: 285.4 ± 47.93 vs. 229.8 ± 45.86 μmol/L total bilirubin, p = 0.01) and exacerbated liver immunopathology.

Conclusions
PD-1 plays a protective role in infants with BA by suppressing IFN-γ production in T cells. Increasing PD-1 signaling may serve as a therapeutic strategy for BA.
Effect of long working hours and insomnia on depressive symptoms among employees of Chinese internet companies
Authors: Liu Xiaoman , Wang Chao , Wang Jin , Ji Yuqing , Li Shuang 
Published: July 2021

Abstract
Background
In China, long working hours and insomnia are relatively common among internet company employees. Considering that both can affect mental health, we examined their independent and interaction effects on these employees’ depressive symptoms (DS).

Methods
We analyzed data from the 2016 occupational health questionnaire survey conducted in 35 large-, medium-, and small-scale internet companies. Overall, 3589 full-time employees were recruited to evaluate the association among working hours, insomnia, and DS. The Patient Health Questionnaire (PHQ-9) was used to assess DS. The association of DS (PHQ-9 ≥ 10) with working hours (≤40, 41–50, 51–60, and > 60 h/week), insomnia (with or without), and interaction of both was estimated using multivariable logistic regression analysis.

Results
Compared with the group working for ≤40 h/week, the adjusted odds ratios (ORs) for DS among participants who worked for 41–50 h/week, 51–60 h/week, and > 60 h/week were 1.32 (1.11–1.56), 1.74 (1.35–2.24), and 2.54 (1.90–3.39), respectively. The ORs for DS among those with insomnia were 2.36 (2.04–2.74) after adjusting for general characteristics. The ORs for DS related to insomnia were similar [1.91 (1.46–2.50), 2.00 (1.61–2.50), respectively] in the participants who worked for < 50 h/week. However, among participants working for 51–60 h or > 60 h/week, the adjusted ORs for DS substantially increased to 4.62 (2.90–7.37) and 5.60 (3.36–9.33), respectively. Moreover, among the participants with insomnia, working overtime showed a greater association with DS.

Conclusions
We showed that long working hours and insomnia are independent factors associated with the prevalence of DS; furthermore, an interaction effect of long working hours and insomnia on DS was observed. For relieving DS in internet company employees, it is important to reduce insomnia.
Can Achilles tendon xanthoma be distinguished from Achilles tendinopathy using Dixon method MRI? A cross-sectional exploratory study
Authors: Zahradnik Thomas Michael , Cresswell Mark , Squier Kip , Waugh Charlotte , Brunham Liam , Screen Hazel , Scott Alex 
Published: July 2021

Abstract
Background
Familial hypercholesterolemia is a genetic condition characterized by life-long elevations of plasma low-density lipoprotein cholesterol. In addition to life-threatening cardiovascular complications, intratendinous cholesterol deposits (xanthomas) can lead to pain and tendon thickening, particularly in the Achilles. Clinical detection of xanthomas currently relies upon visual assessment and palpation, or ultrasound-based measures of tendon thickening or echotexture. Misdiagnosis of xanthoma can delay the commencement of potentially life-saving lipid-lowering therapy. Our primary purpose was to determine whether analysis of separated fat and water magnetic resonance images may be able to differentiate between xanthomatic and nonxanthomatic Achilles tendons through quantification of intratendinous fat content. The main hypothesis was that Achilles tendon xanthomas will demonstrate greater lipid content than Achilles tendinopathy or healthy control tendons.

Methods
Bilateral MRI scans of Achilles tendons from 30 participants (n = 10 Achilles tendon xanthoma, n = 10 Achilles overuse tendinopathy, n = 10 healthy controls) were analyzed for total lipid content using the Dixon method of fat and water signal separation. Secondary outcome measures included tendon water content, as well as ultrasound characterization of tendon tissue organization and thickness.

Results
Fat content was greater in Achilles tendon xanthomas compared to the tendinopathy (p < 0.0001) and control groups (p < 0.0001). Water content was also greater in Achilles tendon xanthomas compared to the tendinopathy (p < 0.0001) and control groups (p = 0.0002). Ultrasound tissue characterization revealed worse tissue organization in Achilles tendon xanthoma tendons compared to Achilles tendinopathy (p < 0.05) but demonstrated largely overlapping distributions. Achilles tendon xanthoma tendons were, on average, significantly thicker than the tendons of the other two groups (p < 0.01 and p < 0.001, respectively).

Conclusion
MRI-derived measures of Achilles tendon fat content may be able to distinguish xanthomas from control and tendinopathic tissue. Dixon method MRI warrants further evaluation in an adequately powered study to develop and test clinically relevant diagnostic thresholds.