bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing stroke severity using electronic health record data: a machine learning approach
Authors: Kogan Emily , Twyman Kathryn , Heap Jesse , Milentijevic Dejan , Lin Jennifer H. , Alberts Mark
Published: January 2020

Background

Stroke severity is an important predictor of patient outcomes and is commonly measured with the National Institutes of Health Stroke Scale (NIHSS) scores. Because these scores are often recorded as free text in physician reports, structured real-world evidence databases seldom include the severity. The aim of this study was to use machine learning models to impute NIHSS scores for all patients with newly diagnosed stroke from multi-institution electronic health record (EHR) data.

Methods

NIHSS scores available in the Optum© de-identified Integrated Claims-Clinical dataset were extracted from physician notes by applying natural language processing (NLP) methods. The cohort analyzed in the study consists of the 7149 patients with an inpatient or emergency room diagnosis of ischemic stroke, hemorrhagic stroke, or transient ischemic attack and a corresponding NLP-extracted NIHSS score. A subset of these patients (n = 1033, 14%) were held out for independent validation of model performance and the remaining patients (n = 6116, 86%) were used for training the model. Several machine learning models were evaluated, and parameters optimized using cross-validation on the training set. The model with optimal performance, a random forest model, was ultimately evaluated on the holdout set.

Results

Leveraging machine learning we identified the main factors in electronic health record data for assessing stroke severity, including death within the same month as stroke occurrence, length of hospital stay following stroke occurrence, aphagia/dysphagia diagnosis, hemiplegia diagnosis, and whether a patient was discharged to home or self-care. Comparing the imputed NIHSS scores to the NLP-extracted NIHSS scores on the holdout data set yielded an R2 (coefficient of determination) of 0.57, an R (Pearson correlation coefficient) of 0.76, and a root-mean-squared error of 4.5.

Conclusions

Machine learning models built on EHR data can be used to determine proxies for stroke severity. This enables severity to be incorporated in studies of stroke patient outcomes using administrative and EHR databases.
Qualitative evaluation of a community health representative program on patient experiences in Navajo Nation
Authors: Lalla Amber , Salt Shine , Schrier Elizabeth , Brown Christian , Curley Cameron , Muskett Olivia , Begay Mae-Gilene , Shirley Lenora , Clark Clarina , Singer Judy , Shin Sonya , Nelson Adrianne Katrina
Published: January 2020

Background

Community Health Representatives (CHRs) overcome health disparities in Native communities by delivering home care, health education, and community health promotion. The Navajo CHR Program partners with the non-profit Community Outreach and Patient Empowerment (COPE), to provide home-based outreach to Navajo clients living with diabetes. COPE has created an intervention (COPE intervention) focusing on multiple levels of improved care including trainings for CHRs on Motivational Interviewing and providing CHRs with culturally-appropriate education materials. The objective of this research is to understand the participant perspective of the CHR-COPE collaborative outreach through exploring patient-reported outcomes (PROs) of clients who consent to receiving the COPE intervention (COPE clients) using a qualitative methods evaluation.

Methods

Seven COPE clients were selected to participate in semi-structured interviews one year after finishing COPE to explore their perspective and experiences. Qualitative interviews were recorded, transcribed, and coded to identify themes.

Results

Clients revealed that health education delivered by CHRs facilitated lifestyle changes by helping them understand key health indicators and setting achievable goals through the use of accessible material and encouragement. Clients felt comfortable with CHRs who respected traditional practices and made regular visits. Clients also appreciated when CHRs educated their family members, who in turn were better able to support the client in their health management. Finally, CHRs who implemented the COPE intervention helped patients who were unable to regularly see a primary care doctor for critical care and support in their disease management.

Conclusion

The COPE-CHR collaboration facilitated trusting client-CHR relationships and allowed clients to better understand their diagnoses. Further investment in materials that respect traditional practices and aim to educate clients’ families may foster these relationships and improve health outcomes.

Trial registration

clinicaltrials.gov: NCT03326206. Registered 9/26/2017 (retrospectively registered).
Long live the king: chromosome-level assembly of the lion (Panthera leo) using linked-read, Hi-C, and long-read data
Authors: Armstrong Ellie E. , Taylor Ryan W. , Miller Danny E. , Kaelin Christopher B. , Barsh Gregory S. , Hadly Elizabeth A. , Petrov Dmitri
Published: January 2020

Background

The lion (Panthera leo) is one of the most popular and iconic feline species on the planet, yet in spite of its popularity, the last century has seen massive declines for lion populations worldwide. Genomic resources for endangered species represent an important way forward for the field of conservation, enabling high-resolution studies of demography, disease, and population dynamics. Here, we present a chromosome-level assembly from a captive African lion from the Exotic Feline Rescue Center (Center Point, IN) as a resource for current and subsequent genetic work of the sole social species of the Panthera clade.

Results

Our assembly is composed of 10x Genomics Chromium data, Dovetail Hi-C, and Oxford Nanopore long-read data. Synteny is highly conserved between the lion, other Panthera genomes, and the domestic cat. We find variability in the length of runs of homozygosity across lion genomes, indicating contrasting histories of recent and possibly intense inbreeding and bottleneck events. Demographic analyses reveal similar ancient histories across all individuals during the Pleistocene except the Asiatic lion, which shows a more rapid decline in population size. We show a substantial influence on the reference genome choice in the inference of demographic history and heterozygosity.

Conclusions

We demonstrate that the choice of reference genome is important when comparing heterozygosity estimates across species and those inferred from different references should not be compared to each other. In addition, estimates of heterozygosity or the amount or length of runs of homozygosity should not be taken as reflective of a species, as these can differ substantially among individuals. This high-quality genome will greatly aid in the continuing research and conservation efforts for the lion, which is rapidly moving towards becoming a species in danger of extinction.
Prevalence, antibiotic susceptibility and virulence factors of Enterococcus species in racing pigeons (Columba livia f. domestica)
Authors: Dolka Beata , Czopowicz Michał , Chrobak-Chmiel Dorota , Ledwoń Aleksandra , Szeleszczuk Piotr
Published: January 2020

Background

This study was aimed to investigate the intestinal microbiota in racing pigeons with regard to Enterococcus species distribution, virulence factors and antibiotic susceptibility. Three methods (API, Multiplex sodA-PCR, 16S rRNA sequencing) were compared for Enterococcus species identification. Cloacal samples from 179 apparently healthy pigeons of 13 different flocks were tested.

Results

Multiplex sodA-PCR and 16S rRNA gene sequencing showed almost perfect agreement in Enterococcus species identification. Isolates were identified as Enterococcus columbae (34.5%), Enterococcus hirae (20.7%), Enterococcus faecalis (11.7%), Enterococcus faecium (11.7%), Enterococcus gallinarum (9%), Enterococcus mundtii (4.8%), Enterococcus casseliflavus (3.4%), Enterococcus cecorum (2.1%), Enterococcus durans (2.1%). More Enterococcus species were found after the race season than before. The study showed differences between Enterococcus species in relation to 68.8% (22/32) biochemical parameters. Six out of seven virulence genes were detected: gelE (43.5%), asa1 (42.1%), efaA (30.3%), ace (30.3%), cylA (27.6%), and esp (9%). None of the isolates harboured hyl gene. Overall 15.2% of Enterococcus isolates produced gelatinase, but 66.7% gelE genes were silent. Enterococcus faecalis showed the most often efaA, ace and gelatinase activity than other enterococcal species. Nearly all isolates (93.1%) were resistant to at least one antibiotic. The most frequent resistance was to enrofloxacin (80%), doxycycline with teicoplanin (73.1%), erythromycin (49.7%). The study revealed significant differences between some enterococcal species in the antibiotic susceptibility to different antibiotics. Enterococcus columbae and E. cecorum showed significantly more frequent resistance to chloramphenicol than other enterococci. The presence of VRE (19.3%), HLGR (2.8%) and no LRE were found. Overall 30.3% of isolates were positive for vancomycin resistance genes, where vanC1 (E. gallinarum), vanC2-C3 (E. hirae, E. casseliflavus), vanB (E. columbae) predominated.

Conclusions

We conclude, that intestinal microbiota in racing pigeons is composed by 9 different Enterococcus species. Given that racing pigeons are kept in close contact with humans and backyard animals, combined with their long-distance flight abilities, they can serve as potential source of virulent and antibiotic resistant Enterococcus spp. in the environment.
Climate factors driven typhus group rickettsiosis incidence dynamics in Xishuangbanna Dai autonomous prefecture of Yunnan province in China, 2005–2017
Authors: Gao Yuan , Niu Yanlin , Sun Wanwan , Liu Keke , Liu Xiaobo , Zhao Ning , Yue Yujuan , Wu Haixia , Meng Fengxia , Wang Jun , Wang Xueshuang , Liu Qiyong
Published: January 2020

Background

Typhus group rickettsiosis (TGR), which is a neglected vector-borne infectious disease, including epidemic typhus and endemic typhus. We explored the lag effects and nonlinear association between meteorological factors and TGR incidence in Xishuangbanna Dai autonomous prefecture from 2005 to 2017, China.

Methods

A Poisson regression with a distributed lag nonlinear model (DLNM) was utilized to analyze TGR cases data and the contemporaneous meteorological data.

Results

A J-shaped nonlinear association between weekly mean temperature and TGR incidence was found. The cumulative exposure to weekly mean temperature indicated that the RR increased with the increment of temperature. Taking the median value as the reference, lower temperatures could decrease the risk of TGR incidence, while higher temperatures could increase the risk of TGR incidence and last for 21 weeks. We also found a reversed U-shaped nonlinear association between weekly mean precipitation and TGR incidence. Precipitation between 5 mm and 13 mm could increase the risk of TGR incidence. Taking the median value as the reference, no precipitation and lower precipitation could decrease the risk of TGR incidence, while higher precipitation could increase the risk of TGR incidence and last for 18 weeks.

Conclusions

The prevention and control measures of TGR should be implemented according to climatic conditions by the local government and health departments in order to improve the efficiency.
Reducing Harm, Supporting Recovery: a partnership and evidence-informed approach to developing the new Irish health led, National Drug Strategy
Authors: Comiskey Catherine
Published: January 2020

Background

Policy development by partnership is difficult, however, ‘Reducing Harm, Supporting Recovery- A health led response to drug and alcohol use in Ireland 2017-2025’ hailed a new era. This policy was based on an agreed philosophy and core values across a 21-member partnership and has stated a common commitment to a health-led response.

Methods

To drive strategy development, a cross-discipline committee with an independent Chair was created by the Minister. Members came from statutory, voluntary, community, research and service-user organisations. A consensus-based, partnership approach was taken to developing the policy and the action plan. Over 18 months of debate, a public consultation, focus groups, evidence reviews and an external expert review were conducted. Evidence was reviewed by the committee and following a very robust debate, a set of priority actions and responsible organisations were established.

Results

Nineteen meetings were held. Epidemiological indicators illustrated that cannabis use, young people, chronic opiate use, mortality and geography were a priority. Almost 3000 individuals/organisations responded to the public consultation and themes arising were, supply-reduction, prevention, treatment, rehabilitation and research. The evidence review found that evidence was weak or lacking. The focus groups addressed priorities in supply, education, prevention, continuum of care, evidence and best practice. Finally, the expert review examined structures. Significant contentious debate arose around the initial terms of reference and the authority of a member to agree to an action on behalf of a ministry. While not all members were fully satisfied with the strategy, all welcomed the commitment to the health-led approach. An implementation committee was established, a tender for the first medically supervised injecting facility was issued and a sub-committee to explore decriminalisation was formed.

Conclusion

A key recommendation from the process was to ensure that all voices had an equal opportunity to be heard and to ensure that priority actions identified from the wider sources of evidence were not lost during the extended process. The breath of the partnership aided this. While we have succeeded in developing a sound strategy, success will depend on continuing support from the partnership and appropriate resourcing from the ministries.
Phagocytosis of full-length Tau oligomers by Actin-remodeling of activated microglia
Authors: Das Rashmi , Balmik Abhishek Ankur , Chinnathambi Subashchandrabose
Published: January 2020

Background

Alzheimer’s disease is associated with the accumulation of intracellular Tau tangles within neurons and extracellular amyloid-β plaques in the brain parenchyma, which altogether results in synaptic loss and neurodegeneration. Extracellular concentrations of oligomers and aggregated proteins initiate microglial activation and convert their state of synaptic surveillance into a destructive inflammatory state. Although Tau oligomers have fleeting nature, they were shown to mediate neurotoxicity and microglial pro-inflammation. Due to the instability of oligomers, in vitro experiments become challenging, and hence, the stability of the full-length Tau oligomers is a major concern.

Methods

In this study, we have prepared and stabilized hTau40WToligomers, which were purified by size-exclusion chromatography. The formation of the oligomers was confirmed by western blot, thioflavin-S, 8-anilinonaphthaalene-1-sulfonic acid fluorescence, and circular dichroism spectroscopy, which determine the intermolecular cross-β sheet structure and hydrophobicity. The efficiency of N9 microglial cells to phagocytose hTau40WToligomer and subsequent microglial activation was studied by immunofluorescence microscopy with apotome. The one-way ANOVA was performed for the statistical analysis of fluorometric assay and microscopic analysis.

Results

Full-length Tau oligomers were detected in heterogeneous globular structures ranging from 5 to 50 nm as observed by high-resolution transmission electron microscopy, which was further characterized by oligomer-specific A11 antibody. Immunocytochemistry studies for oligomer treatment were evidenced with A11+Iba1highmicroglia, suggesting that the phagocytosis of extracellular Tau oligomers leads to microglial activation. Also, the microglia were observed with remodeled filopodia-like actin structures upon the exposure of oligomers and aggregated Tau.

Conclusion

The peri-membrane polymerization of actin filament and co-localization of Iba1 relate to the microglial movements for phagocytosis. Here, these findings suggest that microglia modified actin cytoskeleton for phagocytosis and rapid clearance of Tau oligomers in Alzheimer’s disease condition.
Can sexual health interventions make community-based health systems more responsive to adolescents? A realist informed study in rural Zambia
Authors: Mulubwa Chama , Hurtig Anna-Karin , Zulu Joseph Mumba , Michelo Charles , Sandøy Ingvild Fossgard , Goicolea Isabel
Published: January 2020

Introduction

Community-based sexual reproductive interventions are key in attaining universal health coverage for all by 2030, yet adolescents in many countries still lack health services that are responsive to their sexual reproductive health and rights’ needs. As the first step of realist evaluation, this study provides a programme theory that explains how, why and under what circumstances community-based sexual reproductive health interventions can transform (or not) ‘ordinary’ community-based health systems (CBHSs) into systems that are responsive to the sexual reproductive health of adolescents.

Methods

This realist approach adopted a case study design. We nested the study in the full intervention arm of the Research Initiative to Support the Empowerment of Girls trial in Zambia. Sixteen in-depth interviews were conducted with stakeholders involved in the development and/or implementation of the trial. All the interviews were recorded and analysed using NVIVO version 12.0. Thematic analysis was used guided by realist evaluation concepts. The findings were later synthesized using the Intervention−Context−Actors−Mechanism−Outcomes conceptualization tool. Using the retroduction approach, we summarized the findings into two programme theories.

Results

We identified two initial testable programme theories. The first theory presumes that adolescent sexual reproductive health and rights (SRHR) interventions that are supported by contextual factors, such as existing policies and guidelines related to SRHR, socio-cultural norms and CBHS structures are more likely to trigger mechanisms among the different actors that can encourage uptake of the interventions, and thus contribute to making the CBHS responsive to the SRHR needs of adolescents. The second and alternative theory suggests that SRHR interventions, if not supported by contextual factors, are less likely to transform the CBHSs in which they are implemented. At individual level the mechanisms, awareness and knowledge were expected to lead to value clarification’, which was also expected would lead to individuals developing a ‘supportive attitude towards adolescent SRHR. It was anticipated that these individual mechanisms would in turn trigger the collective mechanisms, communication, cohesion, social connection and linkages.

Conclusion

The two alternative programme theories describe how, why and under what circumstances SRHR interventions that target adolescents can transform ‘ordinary’ community-based health systems into systems that are responsive to adolescents.
Giant unruptured sinus of Valsalva aneurysm successfully managed with valve-sparing procedure – a case report
Authors: Pólos Miklós , Șulea Cristina-Maria , Benke Kálmán , Ágg Bence , Kovács Attila , Hartyánszky István , Merkely Béla , Schäfers Hans-Joachim , Szabolcs Zoltán
Published: January 2020

Background

Sinus of Valsalva aneurysm (SVA) is an uncommon cardiac anomaly, with an incidence of less than 1% of open heart surgery cases. Its evolution is most frequently silent, being found incidentally or discovered in the event of its acute rupture. Non-ruptured giant SVAs may cause unusual clinical manifestations, as a consequence of their protrusion into the heart chambers or compression of the coronary vessels and are frequently associated with aortic insufficiency of various degrees of severity. The gold standard treatment for SVAs consists of complete replacement of the aortic root and valve. However, in certain cases, valve-sparing procedures may prove to be a more suitable alternative.

Case presentation

A 68-year-old male patient presented with dyspnea as symptom caused by a large (> 5 cm) right sinus of Valsalva aneurysm. The aneurysm was occupying most of the right ventricle and was associated with severe aortic regurgitation. The surgical treatment of the condition involved valve-sparing root reconstruction procedure (remodeling technique), completed with external stabilization of the aortic valve annulus via running suture annuloplasty. Following the uneventful intervention, the patient did well and his status improved. The follow-up transthoracic echocardiography obtained 1 month after surgery showed a fully competent aortic valve with no regurgitation.

Conclusions

Despite complete aortic root and valve replacement being considered the safest approach to large SVAs complicated with aortic insufficiency, valve-sparing procedures should not be overlooked in case of a dilated aortic root with uncalcified aortic valve. Performing valve-sparing by applying a remodeling technique operation completed with annuloplasty reduces aortic valve insufficiency, avoiding side-effects related to implanted valves.
Transcatheter and intraoperative device closure of atrial septal defect in infants under three years of age
Authors: Han Yangyang , Zhang Xiquan , Zhang Fengwei
Published: January 2020

Background

Transcatheter and intraoperative device closures have been widely used in the treatment of secundum atrial septal defect (ASD). However, for young infants with ASD, device closure remains controversial, and such treatment features limited data. We compared the clinical data and follow-up results of percutaneous and intraoperative device closure for ASD to evaluate the feasibility, safety, and efficacy of both treatments in infants under 3 years of age.

Methods

From September 2010 to September 2018, 186 children under 3 years of age with significant secundum ASD were included in this study. A total of 88 and 98 patients were divided into groups A (transcatheter device closure) and B (intraoperative device closure), respectively. The clinical data and follow-up results of the two groups were analyzed retrospectively.

Result

The mean age and weight of patients in group A were significantly higher than those in group B. The proportion of complex ASDs (multiples or rims deficiency) and the device/weight ratio in group B were significantly higher than those in group A. Successful closure was obtained in 86 (97.7%) and 96 (98.0%) infants in groups A and B, respectively, with two failed cases in each group (2.3% vs 2%). The rate of periprocedural complications reached 13.6 and 26.5% for groups A and B (P = 0.058), respectively. The durations of the procedure and postoperative hospital stay in group A were significantly shorter than those in group B (P < 0.05). Excellent follow-up results were observed in both groups. At present, no death nor major complications have occurred. Symptoms either resolved completely or improved significantly for all symptomatic infants. No residual shunts at the 6th month of follow-up evaluation were observed. Patients with failure to thrive gained weight appropriately for age, and the structure and hemodynamic parameters significantly improved during follow-up.

Conclusion

Transcatheter and intraoperative device closure are feasible, effective, and safe methods for the treatment of ASDs in infants under 3 years of age. Considering improved cosmetic effect and the short duration of the procedure and postoperative hospital stay, transcatheter is preferred for patients with appropriate conditions. Intraoperative device closure can be performed as an alternative to percutaneous closure, particularly for infants with large, complex ASDs, young age, or low-body weight.
The PROMOTE study (High-protein and resistance-training combination in overweight and obesity) for short-term weight loss and long-term weight maintenance for Chinese people: a protocol for a pilot randomized controlled trial
Authors: Xu Shaoyong , Zhang Juan , Dong Yuxiang , Chen Ruikun , Xu Wenlei , Tan Zhijun , Gao Ling , Shang Lei
Published: January 2020

Background

It is very important for clinicians and dieticians to explore reasonable weight management strategies for obese people that address both short-term weight loss and subsequent weight maintenance. We hypothesized that resistance training combined with a high-protein diet would result in similar short-term weight loss but better long-term weight maintenance than either a conventional low-fat diet control or a high-protein diet alone.

Methods/design

This is an 8-week randomized parallel controlled trial followed by a 24-week observational follow-up study. A 48-week supplementary follow-up study will be carried out if necessary. The study will be conducted between June 2019 and October 2020. The 90 overweight or obese participants will be randomly assigned to the conventional low-fat diet group, the high-protein diet group and the high-protein diet and resistance training combination group. Primary outcomes are body weight change at week 8 and week 24 compared with the baseline level.

Discussion

High-quality research on the effect of a high-protein diet combined resistance training on weight loss and weight maintenance is limited in the Chinese population. Our study will provide a basis for obesity management in China and will promote the development of exercise- and diet-related studies.

Trial registration

Chinese Clinical Trial Registry, ChiCTR1900023841. Registered on 14 June 2019.
Impact of point-of-care ultrasound on the hospital length of stay for internal medicine inpatients with cardiopulmonary diagnosis at admission: study protocol of a randomized controlled trial—the IMFCU-1 (Internal Medicine Focused Clinical Ultrasound) study
Authors: Cid Ximena , Canty David , Royse Alistair , Maier Andrea B. , Johnson Douglas , El-Ansary Doa , Clarke-Errey Sandy , Fazio Timothy , Royse Colin
Published: January 2020

Background

Point-of-care ultrasound (POCUS) is emerging as a reliable and valid clinical tool that impacts diagnosis and clinical decision-making as well as timely intervention for optimal patient management. This makes its utility in patients admitted to internal medicine wards attractive. However, there is still an evidence gap in all the medical setting of how its use affects clinical variables such as length of stay, morbidity, and mortality.

Methods/design

A prospective randomized controlled trial assessing the effect of a surface POCUS of the heart, lungs, and femoral and popliteal veins performed by an internal medicine physician during the first 24 h of patient admission to the unit with a presumptive cardiopulmonary diagnosis. The University of Melbourne iHeartScan, iLungScan, and two-point venous compression protocols are followed to identify left and right ventricular function, significant valvular heart disease, pericardial and pleural effusion, consolidation, pulmonary edema, pneumothorax, and proximal deep venous thrombosis. Patient management is not commanded by the protocol and is at the discretion of the treating team. A total of 250 patients will be recruited at one tertiary hospital. Participants are randomized to receive POCUS or no POCUS. The primary outcome measured will be hospital length of stay. Secondary outcomes include the change in diagnosis and management, 30-day hospital readmission, and healthcare costs.

Discussion

This study will evaluate the clinical impact of multi-organ POCUS in internal medicine patients admitted with cardiopulmonary diagnosis on the hospital length of stay. Recruitment of participants commenced in September 2018 and is estimated to be completed by March 2020.

Trial registration

Australian and New Zealand Clinical Trial Registry,
ACTRN12618001442291. Registered on 28 August 2018.
Feasibility of cardiac output measurements in critically ill patients by medical students
Authors: Koster Geert , Kaufmann Thomas , Hiemstra Bart , Wiersema Renske , Vos Madelon E. , Dijkhuizen Devon , Wong Adrian , Scheeren Thomas W. L. , Hummel Yoran M. , Keus Frederik , van der Horst Iwan C. C.
Published: January 2020

Background

Critical care ultrasonography (CCUS) is increasingly applied also in the intensive care unit (ICU) and performed by non-experts, including even medical students. There is limited data on the training efforts necessary for novices to attain images of sufficient quality. There is no data on medical students performing CCUS for the measurement of cardiac output (CO), a hemodynamic variable of importance for daily critical care.

Objective

The aim of this study was to explore the agreement of cardiac output measurements as well as the quality of images obtained by medical students in critically ill patients compared to the measurements obtained by experts in these images.

Methods

In a prospective observational cohort study, all acutely admitted adults with an expected ICU stay over 24 h were included. CCUS was performed by students within 24 h of admission. CCUS included the images required to measure the CO, i.e., the left ventricular outflow tract (LVOT) diameter and the velocity time integral (VTI) in the LVOT. Echocardiography experts were involved in the evaluation of the quality of images obtained and the quality of the CO measurements.

Results

There was an opportunity for a CCUS attempt in 1155 of the 1212 eligible patients (95%) and in 1075 of the 1212 patients (89%) CCUS examination was performed by medical students. In 871 out of 1075 patients (81%) medical students measured CO. Experts measured CO in 783 patients (73%). In 760 patients (71%) CO was measured by both which allowed for comparison; bias of CO was 0.0 L min−1 with limits of agreement of − 2.6 L min−1 to 2.7 L min−1. The percentage error was 50%, reflecting poor agreement of the CO measurement by students compared with the experts CO measurement.

Conclusions

Medical students seem capable of obtaining sufficient quality CCUS images for CO measurement in the majority of critically ill patients. Measurements of CO by medical students, however, had poor agreement with expert measurements. Experts remain indispensable for reliable CO measurements.

Trial registration Clinicaltrials.gov; http://www.clinicaltrials.gov; registration number NCT02912624
Establishment of long-term serum-free culture for lacrimal gland stem cells aiming at lacrimal gland repair
Authors: Xiao Sa , Zhang Yan
Published: January 2020

Background

Aqueous-deficient dry eye disease (ADDED) resulting from dysfunction of the lacrimal gland (LG) is currently incurable. Although LG stem/progenitor cell-based therapy is considered to be a promising strategy for ADDED patients, the lack of a reliable serum-free culture method to obtain enough lacrimal gland stem cells (LGSCs) and the basic standard of LGSC transplantation are obstacles for further research.

Methods

Adult mouse LGSCs were cultured in Matrigel-based 3D culture under serum-free culture condition, which contained EGF, FGF10, Wnt3A, and Y-27632. LGSCs were continuously passaged over 40 times every 7 days, and the morphology and cell numbers were recorded. LGSCs were induced to differentiate to ductal cells by reducing Matrigel rigidity, while fetal bovine serum was used for the induction of acinar cells. RT-PCR or qRT-PCR analysis, RNA-sequence analysis, H&E staining, and immunofluorescence were used for characterization and examining the differentiation of LGSCs. LGSCs were allotransplanted into diseased LGs to examine the ability of repairing the damage. The condition of eye orbits was recorded using a camera, the tear production was measured using phenol red-impregnated cotton threads, and the engraftments of LGSCs were examined by immunohistochemistry.

Results

We established an efficient 3D serum-free culture for adult mouse LGSCs, in which LGSCs could be continuously passaged for long-term expansion. LGSCs cultured from both the healthy and ADDED mouse LGs expressed stem/progenitor cell markers Krt14, Krt5, P63, and nestin, had the potential to differentiate into acinar or ductal-like cells in vitro and could engraft into diseased LGs and relieve symptoms of ADDED after orthotopic injection of LGSCs.

Conclusion

We successfully established an efficient serum-free culture for adult mouse LGSCs aiming at LG repair for the first time. Our approach provides an excellent theoretical and technical reference for future clinical research for ADDED stem cell therapy.
Mol-CycleGAN: a generative model for molecular optimization
Authors: Maziarka Łukasz , Pocha Agnieszka , Kaczmarczyk Jan , Rataj Krzysztof , Danel Tomasz , Warchoł Michał
Published: January 2020

Designing a molecule with desired properties is one of the biggest challenges in drug development, as it requires optimization of chemical compound structures with respect to many complex properties. To improve the compound design process, we introduce Mol-CycleGAN—a CycleGAN-based model that generates optimized compounds with high structural similarity to the original ones. Namely, given a molecule our model generates a structurally similar one with an optimized value of the considered property. We evaluate the performance of the model on selected optimization objectives related to structural properties (presence of halogen groups, number of aromatic rings) and to a physicochemical property (penalized logP). In the task of optimization of penalized logP of drug-like molecules our model significantly outperforms previous results.
LOX family and ZFPM2 as novel diagnostic biomarkers for malignant pleural mesothelioma
Authors: Kim Min-Kyu , Kim Hyun-won , Jang Mirae , Oh Sung Soo , Yong Suk-Joong , Jeong Yangsik , Jung Soon-Hee , Choi Jong-Whan
Published: January 2020

Background

Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer that develops in the pleural and outer layer of tissues surrounding the lungs. MPM is primarily caused by occupational exposure to asbestos and results in a poor prognosis. Effective therapeutics as well as early diagnostics for the MPM are still lacking. To identify potential diagnostic biomarkers for MPM, we performed bioinformatics analysis of public database.

Methods

Utilizing databases from Cancer Cell Line Encyclopedia (CCLE) and Gene Expression Omnibus (GEO), we identified several potential candidates that could act as MPM biomarkers. We carried out additional molecular analyses of these potential markers using MPM patient tissue samples via quantitative polymerase chain reaction.

Results

We identified Lysyl oxidase (LOX), Lysyl oxidase homologs 1&2 (LOXL1& LOXL2) Zinc Finger Protein, FOG Family Member 2 (ZFPM2) as potential diagnostic biomarkers for MPM. In this study, we found that the LOX family and ZFPM2 showed comparable diagnostic ability to Fibulin-3 or mesothelin (MSLN) and would be better potential biomarkers than Sulfatase 1 (SULF1), Thrombospondin 2 (THBS2) and Cadherin 11 (CDH11).

Conclusions

LOX family and ZPFM2 were identified as novel MPM diagnostic biomarkers which could strengthen MPM clinical diagnostic capabilities.
Correction to: Comprehensive gene expression meta-analysis identifies signature genes that distinguish microglia from peripheral monocytes/macrophages in health and glioma
Authors: Haage Verena , Semtner Marcus , Vidal Ramon Oliveira , Hernandez Daniel Perez , Pong Winnie W. , Chen Zhihong , Hambardzumyan Dolores , Magrini Vincent , Ly Amy , Walker Jason , Mardis Elaine , Mertins Philipp , Sauer Sascha , Kettenmann Helmut , Gutmann David H.
Published: January 2020

The original publication of this article [1] contained 3 minor errors in Figs. 1, 3 and 5. In this correction article the updated figures are published. The figure captions describe the updated information in these figures.
Innate signaling within the central nervous system recruits protective neutrophils
Authors: Khorooshi Reza , Marczynska Joanna , Dieu Ruthe Storgaard , Wais Vian , Hansen Christian Rønn , Kavan Stephanie , Thomassen Mads , Burton Mark , Kruse Torben , Webster Gill A. , Owens Trevor
Published: January 2020

There is great interest in understanding how the central nervous system (CNS) communicates with the immune system for recruitment of protective responses. Infiltrating phagocytic monocytes and granulocytes are implicated in neuroinflammation in multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE). To investigate how CNS endogenous signals can be harnessed to promote anti-inflammatory programs, we have used a particulate Toll-like receptor 9 and nucleotide-oligomerization domain 2 bispecific innate ligand (MIS416), to address whether its phagocytosis within the CNS recruits protective myeloid cells. We find that MIS416 injected intrathecally into the cerebrospinal fluid via the cisterna magna induced a local chemokine response that recruited blood-derived monocytes and neutrophils to the CNS. These cells phagocytosed MIS416. The increase in EAE severity normally seen from time of onset did not occur in mice receiving MIS416. This suppression of disease symptoms was dependent on expression of the type I interferon receptor (IFNAR). Transfer of intrathecal MIS416-induced neutrophils suppressed EAE in recipient mice, while monocytes did not transfer protection. MIS416-induced neutrophils showed increased IL-10 expression that was IFNAR1-driven. In contrast to intrathecal administration, intravenous administration of MIS416 led to monocyte but not neutrophil infiltration to the CNS. We thus identify a CNS-intrinsic and -specific phagocytosis-induced recruitment of anti-inflammatory neutrophils that contribute to CNS homeostasis and may have therapeutic potential.
Health economic evaluations of sepsis interventions in critically ill adult patients: a systematic review
Authors: Higgins Alisa M. , Brooker Joanne E. , Mackie Michael , Cooper D. Jamie , Harris Anthony H.
Published: January 2020

Background

Sepsis is a global health priority. Interventions to reduce the burden of sepsis need to be both effective and cost-effective. We performed a systematic review of the literature on health economic evaluations of sepsis treatments in critically ill adult patients and summarised the evidence for cost-effectiveness.

Methods

We systematically searched MEDLINE, Embase, and the Cochrane Library using thesaurus (e.g. MeSH) and free-text terms related to sepsis and economic evaluations. We included all articles that reported, in any language, an economic evaluation of an intervention for the management of sepsis in critically ill adult patients. Data extracted included study details, intervention details, economic evaluation methodology, and outcomes. Included studies were appraised for reporting quality using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist.

Results

We identified 50 records representing 46 economic evaluations for a variety of interventions including antibiotics (n = 5), fluid therapy (n = 2), early goal-directed therapy and other resuscitation protocols (n = 8), immunoglobulins (n = 2), and interventions no longer in clinical use such as monoclonal antibodies (n = 7) and drotrecogin alfa (n = 13). Twelve (26%) evaluations were of excellent reporting quality. Incremental cost-effectiveness ratios (ICERs) ranged from dominant (lower costs and higher effectiveness) for early goal-directed therapy, albumin, and a multifaceted sepsis education program to dominated (higher costs and lower effectiveness) for polymerase chain reaction assays (LightCycler SeptiFast testing MGRADE®, SepsiTest™, and IRIDICA BAC BSI assay). ICERs varied widely across evaluations, particularly in subgroup analyses.

Conclusions

There is wide variation in the cost-effectiveness of sepsis interventions. There remain important gaps in the literature, with no economic evaluations identified for several interventions routinely used in sepsis. Given the high economic and social burden of sepsis, high-quality economic evaluations are needed to increase our understanding of the cost-effectiveness of these interventions in routine clinical practice and to inform decision makers.

Trial registration

PROSPERO CRD42018095980
Hypomagnesaemia induced recurrent cerebellar ataxia: an interesting case with successful management
Authors: Kumar Singh Saraj , Khushbu Goel , Dev Mukherji Joy
Published: January 2020

Purpose

Severe Hypomagnesaemia is a rare biochemical findings utilized for identifying the etiology of cerebellar ataxia. It requires a high degree of suspicion to diagnose. MRI findings are often nonspecific.

Methods

The author presents a case of 38 yrs. old male patient presented with vomiting, gait imabalance and nystagmus. Biochemical investigations lead to severe hypomagnesaemia. Also MRI findings were matched suggesting of hyperintesity in left cerebellar hemisphere.

Results

Patient was treated with magnesium infusion which leads to recovery of patient. Again the same symptomology was repeated after 3 months and disappearance after same treatment. Offending cause was diagnosed and proton pump inhibitors stopped.

Conclusion

Severe Hypomagnesaemia is a rare but treatable cause if diagnosed at right time. It requires a high degree of suspicion to diagnose it. Measurement of serum magnesium levels should always be kept in back of mind if definite management of cerebellar symptoms has to be done.
Torsion of vermiform appendix: case report and review of the literature
Authors: Endo Kosuke , Sato Masahito , Saga Kenichi , Higashio Atsushi , Yuba Yoshiaki , Morotomi Yoshiki
Published: January 2020

Background

Torsion of the vermiform appendix is a rare disease with symptoms very similar to those of acute appendicitis. We herein report a case of torsion of the vermiform appendix diagnosed by intraoperative findings.

Case presentation

A 4-year-old boy presented to our hospital because of abdominal pain and vomiting. Laboratory data revealed a C-reactive protein level of 0.08 mg/dL and white blood cell count of 19,300/μL (neutrophils, 88.9%). Abdominal ultrasound showed a target sign-like finding in the ileocecal region. A computed tomography scan showed swelling of the appendix. We performed an emergency operation under suspicion of acute appendicitis. Laparoscopic examination showed that the appendix had twisted 720° in the clockwise direction. Appendectomy was performed, and the postoperative course was uneventful.

Conclusions

Although torsion of the vermiform appendix is a very rare disease and difficult to differentiate from appendicitis, an inappropriate treatment plan could lead to necrosis and perforation of the appendix. It is important to consider this disease as a differential diagnosis in patients with right lower abdominal pain.
On the accuracy of macroscopic equations for linearized rarefied gas flows
Authors: Wu Lei , Gu Xiao-Jun
Published: January 2020

Many macroscopic equations are proposed to describe the rarefied gas dynamics beyond the Navier-Stokes level, either from the mesoscopic Boltzmann equation or some physical arguments, including (i) Burnett, Woods, super-Burnett, augmented Burnett equations derived from the Chapman-Enskog expansion of the Boltzmann equation, (ii) Grad 13, regularized 13/26 moment equations, rational extended thermodynamics equations, and generalized hydrodynamic equations, where the velocity distribution function is expressed in terms of low-order moments and Hermite polynomials, and (iii) bi-velocity equations and “thermo-mechanically consistent" Burnett equations based on the argument of “volume diffusion”. This paper is dedicated to assess the accuracy of these macroscopic equations. We first consider the Rayleigh-Brillouin scattering, where light is scattered by the density fluctuation in gas. In this specific problem macroscopic equations can be linearized and solutions can always be obtained, no matter whether they are stable or not. Moreover, the accuracy assessment is not contaminated by the gas-wall boundary condition in this periodic problem. Rayleigh-Brillouin spectra of the scattered light are calculated by solving the linearized macroscopic equations and compared to those from the linearized Boltzmann equation. We find that (i) the accuracy of Chapman-Enskog expansion does not always increase with the order of expansion, (ii) for the moment method, the more moments are included, the more accurate the results are, and (iii) macroscopic equations based on “volume diffusion" do not work well even when the Knudsen number is very small. Therefore, among about a dozen tested equations, the regularized 26 moment equations are the most accurate. However, for moderate and highly rarefied gas flows, huge number of moments should be included, as the convergence to true solutions is rather slow. The same conclusion is drawn from the problem of sound propagation between the transducer and receiver. This slow convergence of moment equations is due to the incapability of Hermite polynomials in the capturing of large discontinuities and rapid variations of the velocity distribution function. This study sheds some light on how to choose/develop macroscopic equations for rarefied gas dynamics.
Two-incision laparoscopic cholecystectomy performed via the “marionette” technique versus conventional laparoscopic cholecystectomy in pediatrics
Authors: Shehata Mohamed A. , Ebeid Abdelmotaleb E. , El Attar Ashraf A.
Published: January 2020

Background

Laparoscopic cholecystectomy (LC) has considered the gold standard for the treatment of symptomatic gallstones. The “marionette” technique is a surgical technique for performing a safe, two-incision laparoscopic cholecystectomy without the use of an additional port or any new access devices. This study aimed to compare between the cost and outcome of two incisions LC performed via the marionette technique and the standard LC in pediatrics.

Results

All 32 children with symptomatic cholecystolithiasis were discharged from the hospital in the first postoperative day with no statistically significant difference within days to return to normal work (p = 0.607). The operative time in the group (A) which included 16 children who underwent 2 incisions marionette style LC technique was non-significantly longer time (p = 0.184) than the group (B) which included 16 children who underwent conventional 4 incisions LC technique. Visual analog scores for pain showed a significant difference between both groups at 6 h and 12 h postoperative (p = 0.000 and 0.003, respectively). Overall patient in marionette group was very satisfied by fewer incision and better cosmesis.

Conclusion

Marionette technique performed by an experienced surgeon among pediatric shows a statistically significant cost benefit while maintaining good operative time, less postoperative pain, and more patient’s satisfaction and provides excellent aesthetic results.