bluuebunny/crossref_metadata_2025 huggingface dataset:
Salvage carbon ion radiotherapy for recurrent solitary fibrous tumor: A case report and literature review
Authors: Murata Kazuma , Endo Kenji , Aihara Takato , Matsuoka Yuji , Nishimura Hirosuke , Suzuki Hidekazu , Sawaji Yasunobu , Yamamoto Kengo , Fukami Shinjiro , Tanigawa Maki , Matsubayashi Jun , Nagao Toshitaka , Imai Reiko
Published: February 2020

Background:

Malignant solitary fibrous tumor (MSFT) arising from the spinal cord is extremely rare and poorly understood mesenchymal neoplasms: only a few MSFT in the spinal canal has been described. We describe the clinical course of the patient with MSFT arising from the thoracic spinal cord.

Case report:

We describe the clinical course of the patient and the radiological and pathological findings of the tumor. The tumor had been resected by microscopic posterior approach and video-assisted thoracic surgery, but local recurrence was observed by MRI at 1-year follow-up period. No metastatic lesion was confirmed. Then, carbon ion radiotherapy (CIRT) was administered to the recurrent lesion. Local suppression has been observed for 40 months after irradiation.

Conclusion:

Dumbbell-shaped MSFT arising from thoracic spinal cord is a highly unusual presentation. CIRT might be effective for treatment of recurrent tumors.
Reverse Migration to Mexico Led to US Undocumented Population Decline: 2010 to 2018
Authors: Warren Robert
Published: February 2020

Executive Summary

This report presents estimates of the undocumented population residing in the United States in 2018, highlighting demographic changes since 2010. The Center for Migration Studies of New York (CMS) compiled these estimates based primarily on information collected in the US Census Bureau’s American Community Survey (ACS). The annual CMS estimates of undocumented residents for 2010 to 2018 include all the detailed characteristics collected in the ACS. 1 A summary of the CMS estimation procedures, as well as a discussion of the plausibility of the estimates, is provided in the Appendix .

The total undocumented population in the United States continued to decline in 2018, primarily because large numbers of undocumented residents returned to Mexico. From 2010 to 2018, a total of 2.6 million Mexican nationals left the US undocumented population; 2 about 1.1 million, or 45 percent of them, returned to Mexico voluntarily. The decline in the US undocumented population from Mexico since 2010 contributed to declines in the undocumented population in many states. Major findings include the following: The total US undocumented population was 10.6 million in 2018, a decline of about 80,000 from 2017, and a drop of 1.2 million, or 10 percent, since 2010. Since 2010, about two-thirds of new arrivals have overstayed temporary visas and one-third entered illegally across the border. The undocumented population from Mexico fell from 6.6 million in 2010 to 5.1 million in 2018, a decline of 1.5 million, or 23 percent. Total arrivals in the US undocumented population from El Salvador, Guatemala, and Honduras — despite high numbers of Border Patrol apprehensions of these populations in recent years — remained at about the same level in 2018 as in the previous four years. 3 The total undocumented population in California was 2.3 million in 2018, a decline of about 600,000 compared to 2.9 million in 2010. The number from Mexico residing in the state dropped by 605,000 from 2010 to 2018. The undocumented population in New York State fell by 230,000, or 25 percent, from 2010 to 2018. Declines were largest for Jamaica (−51 percent), Trinidad and Tobago (−50 percent), Ecuador (−44 percent), and Mexico (−34 percent). The results shown here reinforce the view that improving social and economic conditions in sending countries would not only reduce pressure at the border but also likely cause a large decline in the undocumented population. Two countries had especially large population changes — in different directions — in the 2010 to 2018 period. The population from Poland dropped steadily, from 93,000 to 39,000, while the population from Venezuela increased from 65,000 to 172,000. Almost all the increase from Venezuela occurred after 2014.
Hippocampal Volume in Psychiatric Diagnoses: Should Psychiatry Biomarker Research Account for Comorbidities?
Authors: Gosnell Savannah N. , Meyer Matthew J. , Jennings Cassandra , Ramirez Danna , Schmidt Jake , Oldham John , Salas Ramiro
Published: February 2020

Background

Many research papers claim that patients with specific psychiatric disorders (major depressive disorder, posttraumatic stress disorder, borderline personality disorder, alcohol use disorder, and others) have smaller hippocampi, but most of those reports compared patients to healthy controls. We hypothesized that if psychiatrically matched controls (psychiatric control, matched for demographics and psychiatric comorbidities) were used, much of the biomarker literature in psychiatric research would not replicate. We used hippocampus and amygdala volume only as examples, as these are very commonly replicated results in psychiatry biomarker research. We propose that psychiatry biomarker research could benefit from using psychiatric controls, as the use of healthy controls results in data that are not disorder-specific.

Method

Hippocampus/amygdala volumes were compared between major depressive disorder, sex-/age-/race-matched healthy control, and psychiatric control (N = 126/group). Similar comparisons were performed for posttraumatic stress disorder (N = 67), borderline personality disorder (N = 111), and alcohol use disorder (N = 136).

Results

Major depressive disorder patients had smaller left (p = 8.79 × 10−3) and right (p = 3.13 × 10−3) hippocampal volumes than healthy control. Posttraumatic stress disorder had smaller left (p = 0.018) and right (p = 8.64 × 10−4) hippocampi than healthy control. Borderline personality disorder had smaller right hippocampus (p = 7.90 × 10−3) and amygdala (p = 1.49 × 10−3) than healthy control. Alcohol use disorder had smaller right hippocampus (p = 0.034) and amygdala (p = .024) than healthy control. No differences were found between any of the four diagnostic groups and psychiatric control.

Conclusion

When psychiatric controls were used, there was no difference in hippocampal or amygdalar volume between any of the diagnoses studied and controls. This strategy (keeping all possible relevant variables matched between experimental groups) has been used to advance science for hundreds of years, and we propose should also be used in biomarker psychiatry research.
Plywood adhesives using PF resin with fibrillated bark slurry from radiata pine (Pinus radiata D. Don): utilization of flavonoid compounds from bark and wood. IV
Authors: Horito Masayoshi , Kurushima Naoko , Ono Keiko , Yazaki Yoshikazu
Published: February 2020

In 2003, the first adhesives into which considerable amounts of bark particles (< 63 μm) were incorporated were developed using radiata pine bark. The quality of bark containing adhesives has now been substantially improved by fibrillating the bark. The finely ground bark (< 63 µm) was fibrillated using a disk mill and formulated into plywood adhesives. The adhesives contained different ratios of fibrillated bark, phenol–formaldehyde (PF) resin and water. The gluability of the fibrillated bark adhesives was evaluated according to the Japanese Agricultural Standard (JAS) for Plywood and was found to be excellent with the proportion of PF resin to bark being 6 to 4 and 5 to 5 on a solid basis. The bark was fibrillated with water (in the ratio 1 to 10), freeze-dried and used for the adhesive formulations. The freeze-drying process is extremely expensive and was considered inappropriate for the production of wood adhesives. However, it was found that when the ground bark (< 1 mm) was fibrillated with a bark to water ratio of 1 to 3, the resulting bark slurry was able to be directly incorporated into a PF resin to produce high performance plywood adhesives. This improved process is more economic because it requires neither further fractionation of the ground bark nor freeze-drying of the fibrillated bark slurry. The fibrillated bark slurry adhesives are able to produce a high quality of bonding in plywood samples from not only radiata pine, but also hinoki and karamatsu veneers.
Estimating linkage disequilibrium from genotypes under Hardy-Weinberg equilibrium
Authors: Hui Tin-Yu J. , Burt Austin
Published: February 2020

Background

Measures of linkage disequilibrium (LD) play a key role in a wide range of applications from disease association to demographic history estimation. The true population LD cannot be measured directly and instead can only be inferred from genetic samples, which are unavoidably subject to measurement error. Previous studies ofr2(a measure of LD), such as the bias due to finite sample size and its variance, were based on the special case that the true population-wise LD is zero. These results generally do not hold for non-zero$$ {r}_{true}^2 $$rtrue2values, which are more common in real genetic data.

Results

This work generalises the estimation ofr2to all levels of LD, and for both phased and unphased data. First, we provide new formulae for the effect of finite sample size on the observedr2values. Second, we find a new empirical formula for the variance of the observedr2, equals to 2E[r2](1 − E[r2])/n, wherenis the diploid sample size. Third, we propose a new routine, Constrained ML, a likelihood-based method to directly estimate haplotype frequencies andr2from diploid genotypes under Hardy-Weinberg Equilibrium. While serving the same purpose as the pre-existing Expectation-Maximisation algorithm, the new routine can have better convergence and is simpler to use. A new likelihood-ratio test is also introduced to test for the absence of a particular haplotype. Extensive simulations are run to support these findings.

Conclusion

Most inferences on LD will benefit from our new findings, from point and interval estimation to hypothesis testing. Genetic analyses utilisingr2information will become more accurate as a result.
Monitoring of anesthetic depth and EEG band power using phase lag entropy during propofol anesthesia
Authors: Shin Hye Won , Kim Hyun Jung , Jang Yoo Kyung , You Hae Sun , Huh Hyub , Choi Yoon Ji , Choi Seung Uk , Hong Ji Su
Published: February 2020

Background

Phase lag entropy (PLE) is a novel anesthetic depth indicator that uses four-channel electroencephalography (EEG) to measure the temporal pattern diversity in the phase relationship of frequency signals in the brain. The purpose of the study was to evaluate the anesthetic depth monitoring using PLE and to evaluate the correlation between PLE and bispectral index (BIS) values during propofol anesthesia.

Methods

In thirty-five adult patients undergoing elective surgery, anesthesia was induced with propofol using target-controlled infusion (the Schneider model). We recorded the PLE value, raw EEG, BIS value, and hemodynamic data when the target effect-site concentration (Ce) of propofol reached 2, 3, 4, 5, and 6 μg/ml before intubation and 6, 5, 4, 3, 2 μg/ml after intubation and injection of muscle relaxant. We analyzed whether PLE and raw EEG data from the PLE monitor reflected the anesthetic depth as the Ce of propofol changed, and whether PLE values were comparable to BIS values.

Results

PLE values were inversely correlated to changes in propofol Ce (propofol Ce from 0 to 6.0 μg/ml, r2 = − 0.83; propofol Ce from 6.0 to 2.0 μg/ml, r2 = − 0.46). In the spectral analysis of EEG acquired from the PLE monitor, the persistence spectrogram revealed a wide distribution of power at loss of consciousness (LOC) and recovery of consciousness (ROC), with a narrow distribution during unconsciousness. The power spectrogram showed the typical pattern seen in propofol anesthesia with slow alpha frequency band oscillation. The PLE value demonstrated a strong correlation with the BIS value during the change in propofol Ce from 0 to 6.0 μg/ml (r2 = 0.84). PLE and BIS values were similar at LOC (62.3 vs. 61.8) (P > 0.05), but PLE values were smaller than BIS values at ROC (64.4 vs 75.7) (P < 0.05).

Conclusions

The PLE value is a useful anesthetic depth indicator, similar to the BIS value, during propofol anesthesia. Spectral analysis of EEG acquired from the PLE monitor demonstrated the typical patterns seen in propofol anesthesia.

Trial registration

This clinical trial was retrospectively registered at ClinicalTrials.gov at October 2017 (NCT03299621).
No radiographic index predicts difficult intubation using the Optiscope™ in cervical spine surgery patients: a retrospective study
Authors: Oh Hyongmin , Kim Hansol , Yoon Hyun-Kyu , Lee Hyung-Chul , Park Hee-Pyoung
Published: February 2020

Background

The Optiscope™ can be used for intubation with minimal neck motion. We retrospectively investigated radiographic predictors of difficult intubation using the Optiscope™ by analyzing preoperative radiographic images.

Methods

One hundred eighty-four patients who were intubated with the Optiscope™ under manual in-line cervical stabilization for cervical spine surgery were enrolled. Radiographic indices were measured on preoperative cervical spine lateral X-ray and magnetic resonance imaging images. Difficult intubation was defined as failure or time consumption more than 90 s on the first attempt. To identify significant predictors of difficult intubation using the Optiscope™ and evaluate their diagnostic value, multivariable logistic regression and receiver operating characteristic analyses were used.

Results

Fourty-seven patients showed difficult intubation. There was no significant difference in radiographic indices between the difficult and easy intubation groups, but higher body mass index (BMI) (26.5 [3.0] vs. 24.6 [3.5] kg/m2, P = 0.001), shorter sternomental distance (SMD) (122.0 [104.0 to 150.0] vs. 150.0 [130.0 to 170.0] mm, P = 0.001), shorter interincisor gap (40.0 [35.0 to 45.0] vs. 43.0 [40.0 to 50.0] mm, P = 0.006), and higher incidence of excessive oral secretions (10.6% vs. 2.9%, P = 0.049) were observed in patients with difficult intubation. In multivariable analysis, BMI (odds ratio [95% confidence interval]; 1.15 [1.03 to 1.28], P = 0.011) and SMD (odds ratio [95% confidence interval]; 0.98 [0.97 to 1.00], P = 0.008) were associated with difficult intubation with the Optiscope™. In receiver operating characterstic analysis, the area under the curve for body mass index was 0.68 (95% confidence interval; 0.60 to 0.77, P < 0.001) and that for sternomental distance was 0.66 (95% confience interval; 0.57 to 0.75, P = 0.001).

Conclusions

The incidence of difficult intubation using the Optiscope™ under manual in-line cervical stabilization was 25.5% in cervical spine surgery patients. No significant predictor of difficult intubation with the Optiscope™ was identified among the measured radiographic indices. Although high BMI and short SMD were predictive of difficult intubation with the Optiscope™, their discrimination power was weak.
Elevated circulating metalloproteinase 7 predicts recurrent cardiovascular events in patients with carotid stenosis: a prospective cohort study
Authors: Moreno-Ajona David , Irimia Pablo , Rodríguez José Antonio , García-Velloso María José , López-Fidalgo Jesús , Fernández-Alonso Leopoldo , Grochowitz Lukasz , Muñoz Roberto , Domínguez Pablo , Gállego-Culleré Jaime , Martínez-Vila Eduardo
Published: February 2020

Background

Major adverse cardiovascular events are the main cause of morbidity and mortality over the long term in patients undergoing carotid endarterectomy. There are few reports assessing the prognostic value of markers of inflammation in relation to the risk of cardiovascular disease after carotid endarterectomy. Here, we aimed to determine whether matrix metalloproteinases (MMP-1, MMP-2, MMP-7, MMP-9 and MMP-10), tissue inhibitor of MMPs (TIMP-1) and in vivo inflammation studied by 18F-FDG-PET/CT predict recurrent cardiovascular events in patients with carotid stenosis who underwent endarterectomy.

Methods

This prospective cohort study was carried out on 31 consecutive patients with symptomatic (23/31) or asymptomatic (8/31) severe (> 70%) carotid stenosis who were scheduled for carotid endarterectomy between July 2013 and March 2016. In addition, 26 healthy controls were included in the study. Plasma and serum samples were collected 2 days prior to surgery and tested for MMP-1, MMP-2, MMP-7, MMP-9, MMP-10, TIMP-1, high-density lipoprotein, low-density lipoprotein, high-sensitivity C-reactive protein and erythrocyte sedimentation rate. 18F-FDG-PET/CT focusing on several territories’ vascular wall metabolism was performed on 29 of the patients because of no presurgical availability in 2 symptomatic patients. Histological and immunohistochemical studies were performed with antibodies targeting MMP-10, MMP-9, TIMP-1 and CD68.

Results

The patients with carotid stenosis had significantly more circulating MMP-1, MMP-7 and MMP-10 than the healthy controls. Intraplaque TIMP-1 was correlated with its plasma level (r = 0.42 P = .02) and with 18F-FDG uptake (r = 0.38 P = .05). We did not find any correlation between circulating MMPs and in vivo carotid plaque metabolism assessed by 18F-FDG-PET. After a median follow-up of 1077 days, 4 cerebrovascular, 7 cardiovascular and 11 peripheral vascular events requiring hospitalization were registered. Circulating MMP-7 was capable of predicting events over and above the traditional risk factors (HR = 1.15 P = .006). When the model was associated with the variables of interest, the risk predicted by 18F-FDG-PET was not significant.

Conclusions

Circulating MMP-7 may represent a novel marker for recurrent cardiovascular events in patients with moderate to severe carotid stenosis. MMP-7 may reflect the atherosclerotic burden but not plaque inflammation in this specific vascular territory.
Effect of a polyphenol-rich dietary pattern on intestinal permeability and gut and blood microbiomics in older subjects: study protocol of the MaPLE randomised controlled trial
Authors: Guglielmetti Simone , Bernardi Stefano , Del Bo’ Cristian , Cherubini Antonio , Porrini Marisa , Gargari Giorgio , Hidalgo-Liberona Nicole , Gonzalez-Dominguez Raul , Peron Gregorio , Zamora-Ros Raul , Winterbone Mark S. , Kirkup Benjamin , Kroon Paul A. , Andres-Lacueva Cristina , Riso Patrizia
Published: February 2020

Background

During aging, alterations of the intestinal microbial ecosystem can occur contributing to immunosenescence, inflamm-aging and impairment of intestinal barrier function (increased intestinal permeability; IP). In the context of a diet-microbiota-IP axis in older subjects, food bioactives such as polyphenols may play a beneficial modulatory role.

Methods

MaPLE is a project centered on a randomized, controlled cross-over dietary intervention trial [polyphenol-rich diet (PR-diet) versus control diet (C-diet)] targeted to older people (≥ 60 y) living in a well-controlled setting (i.e. nursing home). The 8-week interventions are separated by an 8-week wash-out period. Three small portions per day of selected polyphenol-rich foods are consumed during intervention in substitution of other comparable products within the C-diet. Biological samples are collected before and after each treatment period to evaluate markers related to IP, inflammation, vascular function, oxidative stress, gut and blood microbiomics, metabolomics. A sample size of 50 subjects was defined based on IP as primary outcome.

Discussion

Evidence that increasing the consumption of polyphenol-rich food products can positively affect intestinal microbial ecosystem resulting in reduced IP and decreased translocation of inflammogenic bacterial factors into the bloodstream will be provided. The integration of data from gut and blood microbiomics, metabolomics and other IP-related markers will improve the understanding of the beneficial effect of the intervention in the context of polyphenols−microbiota−IP interactions. Finally, findings obtained will provide a proof of concept of the reliability of the dietary intervention, also contributing to future implementations of dietary guidelines directed to IP management in the older and other at risk subjects.

Trial registration

The trial is registered at (ISRCTN10214981); April 28, 2017.
Natural polymorphisms in HIV-1 CRF01_AE strain and profile of acquired drug resistance mutations in a long-term combination treatment cohort in northeastern China
Authors: Sun Zesong , Ouyang Jinming , Zhao Bin , An Minghui , Wang Lin , Ding Haibo , Han Xiaoxu
Published: February 2020

Background

The impacts of genetic polymorphisms on drug resistance mutations (DRMs) among various HIV-1 subtypes have long been debated. In this study, we aimed to analyze the natural polymorphisms and acquired DRM profile in HIV-1 CRF01_AE-infected patients in a large first-line antiretroviral therapy (ART) cohort in northeastern China.

Methods

The natural polymorphisms of CRF01_AE were analyzed in 2034 patients from a long-term ART cohort in northeastern China. The polymorphisms in 105 treatment failure (TF) patients were compared with those in 1148 treatment success (TS) patients. The acquired DRM profile of 42 patients who experienced TF with tenofovir/lamivudine/efavirenz (TDF/3TC/EFV) treatment was analyzed by comparing the mutations at TF time point to those at baseline. The Stanford HIVdb algorithm was used to interpret the DRMs. Binomial distribution, McNemar test, Wilcoxon test and CorMut package were used to analyze the mutation rates and co-variation. Deep sequencing was used to analyze the evolutionary dynamics of co-variation.

Results

Before ART, there were significantly more natural polymorphisms of 31 sites on reverse transcriptase (RT) in CRF01_AE than subtype B HIV-1 (|Z value| ≥ 3), including five known drug resistance-associated sites (238, 118, 179, 103, and 40). However, only the polymorphism at site 75 was associated with TF (|Z value| ≥ 3). The mutation rate at 14 sites increased significantly at TF time point compared to baseline, with the most common DRMs comprising G190S/C, K65R, K101E/N/Q, M184 V/I, and V179D/I/A/T/E, ranging from 66.7 to 45.2%. Moreover, two unknown mutations (V75 L and L228R) increased by 19.0 and 11.9% respectively, and they were under positive selection (Ka/Ks > 1, log odds ratio [LOD] > 2) and were associated with several other DRMs (cKa/Ks > 1, LOD > 2). Deep sequencing of longitudinal plasma samples showed that L228R occurred simultaneously or followed the appearance of Y181C.

Conclusion

The high levels of natural polymorphisms in CRF01_AE had little impact on treatment outcomes. The findings regarding potential new CRF01_AE-specific minor DRMs indicate the need for more studies on the drug resistance phenotype of CRF01_AE.
Longitudinal impacts of an online safety and health intervention for women experiencing intimate partner violence: randomized controlled trial
Authors: Ford-Gilboe Marilyn , Varcoe Colleen , Scott-Storey Kelly , Perrin Nancy , Wuest Judith , Wathen C. Nadine , Case James , Glass Nancy
Published: February 2020

Background

Responding to intimate partner violence (IPV) and its consequences is made complex by women’s diverse needs, priorities and contexts. Tailored online IPV interventions that account for differences among women have potential to reduce barriers to support and improve key outcomes.

Methods

Double blind randomized controlled trial of 462 Canadian adult women who experienced recent IPV randomly were assigned to receive either atailored, interactive online safety and health intervention (iCAN Plan 4 Safety) or a static,non-tailoredversion of this tool. Primary (depressive symptoms, PTSD symptoms) and secondary (helpfulness of safety actions, confidence in safety planning, mastery, social support, experiences of coercive control, and decisional conflict) outcomes were measured at baseline and 3, 6, and 12 months later via online surveys. Generalized Estimating Equations were used to test for differences in outcomes by study arm. Differential effects of the tailored intervention for 4 strata of women were examined using effect sizes. Exit survey process evaluation data were analyzed using descriptive statistics, t-tests and conventional content analysis.

Results

Women in both tailored and non-tailored groups improved over time on primary outcomes of depression (p < .001) and PTSD (p < .001) and on all secondary outcomes. Changes over time did not differ by study arm. Women in both groups reported high levels of benefit, safety and accessibility of the online interventions, with low risk of harm, although those completing the tailored intervention were more positive about fit and helpfulness. Importantly, thetailoredintervention had greater positive effects for 4 groups of women, those: with children under 18 living at home; reporting more severe violence; living in medium-sized and large urban centers; and not living with a partner.

Conclusion

This trial extends evidence about the effectiveness of online safety and health interventions for women experiencing IPV to Canadian women and provides a contextualized understanding about intervention processes and effects useful for future refinement and scale up. The differential effects of the tailored intervention found for specific subgroups support the importance of attending to diverse contexts and needs.iCANis a promising intervention that can complement resources available to Canadian women experiencing IPV.

Trial registration

Clinicaltrials.gov IDNCT02258841(Prospectively Registered on Oct 2, 2014).
Effect of project-based experiential learning on the health service delivery indicators: a quasi-experiment study
Authors: Chelagat T. , Kokwaro G. , Onyango J. , Rice J.
Published: February 2020

Background

Kenya’s new constitution passed in 2010 recognizes the right of quality care resulting in the devolution of health service delivery to the sub-national units called counties in 2013. However, the health system performance continues to be poor. The main identified challenge is poor health systems leadership. Evidence shows that addressing health system leadership challenges using different leadership intervention models has the potential to improve health outcomes. The purpose of this study is to report findings on the effect of project-based experiential learning on the health service delivery indicators addressed by 15 health management teams from 13 counties in Kenya, as compared to the non-trained managers.

Methods

A quasi-experimental design without a random sample was used to evaluate the effectiveness of the leadership program. The health managers from the 13 Counties and 15 health facilities had previously undergone a 9-month leadership training, complimented with facility-based team coaching based on 15 priority institutional service improvement projects at the Strathmore University Business School. Pre-test and post-test data were collected in three-point periods (beginning, end of the training, and 24-to-60 months post-training). The control group comprised 14 other health institutions within the same counties.

Results

Leadership training and coaching built around priority institutional health service improvement projects in the intervention institutions showed: a) skilled birth attendance increased, on average, by 71%; b) full immunization of children, increased by 52%; c) utilization of in and out-patient services, which on average, increased by 90%; d) out-patient turn-around time reduced on average by 65% and; e) quality and customer satisfaction increased by 38.8% (in all the intervention facilities). These improvements were sustained for 60 months after the leadership training. In contrast, there were minimal improvements in service delivery indicators in the comparison institution over the same period of time. Ninety-three percent of the respondents attributed team-coaching built around priority institutional health service improvement projects as a key enabler to their success.

Conclusions

The study provides support that an intervention underpinned by challenge driven learning and team coaching can improve a range of health service delivery outcome variables.
Ca2+ mobilization-dependent reduction of the endoplasmic reticulum lumen is due to influx of cytosolic glutathione
Authors: Lizák Beáta , Birk Julia , Zana Melinda , Kosztyi Gergely , Kratschmar Denise V. , Odermatt Alex , Zimmermann Richard , Geiszt Miklós , Appenzeller-Herzog Christian , Bánhegyi Gábor
Published: February 2020

Background

The lumen of the endoplasmic reticulum (ER) acts as a cellular Ca2+ store and a site for oxidative protein folding, which is controlled by the reduced glutathione (GSH) and glutathione-disulfide (GSSG) redox pair. Although depletion of luminal Ca2+ from the ER provokes a rapid and reversible shift towards a more reducing poise in the ER, the underlying molecular basis remains unclear.

Results

We found that Ca2+ mobilization-dependent ER luminal reduction was sensitive to inhibition of GSH synthesis or dilution of cytosolic GSH by selective permeabilization of the plasma membrane. A glutathione-centered mechanism was further indicated by increased ER luminal glutathione levels in response to Ca2+ efflux. Inducible reduction of the ER lumen by GSH flux was independent of the Ca2+-binding chaperone calreticulin, which has previously been implicated in this process. However, opening the translocon channel by puromycin or addition of cyclosporine A mimicked the GSH-related effect of Ca2+ mobilization. While the action of puromycin was ascribable to Ca2+ leakage from the ER, the mechanism of cyclosporine A-induced GSH flux was independent of calcineurin and cyclophilins A and B and remained unclear.

Conclusions

Our data strongly suggest that ER influx of cytosolic GSH, rather than inhibition of local oxidoreductases, is responsible for the reductive shift upon Ca2+ mobilization. We postulate the existence of a Ca2+- and cyclosporine A-sensitive GSH transporter in the ER membrane. These findings have important implications for ER redox homeostasis under normal physiology and ER stress.
Is quality of YouTube content on Bankart lesion and its surgical treatment adequate?
Authors: Akpolat Ahmet Onur , Kurdal Demet Pepele
Published: February 2020

Background

The Internet has developed into a fast and easy to access source of information. The second most popular social media network is YouTube. We aimed to evaluate the accuracy and quality of videos uploaded to YouTube about Bankart lesion without diagnostic or treatment-related criteria.

Methods

Various keywords were searched for on YouTube. Videos were evaluated with the DISCERN and JAMA Benchmark scoring systems by two independent reviewers.

Results

A total of 48 videos were taken into evaluation as a result of the search. The mean view count was 28909.68 ± 30264.3. Mean length of the videos was 313,06 ± 344.65. The average DISCERN score of both reviewers was 2.35 ± 0.91. The average JAMA Benchmark score of both reviewers was 2.11 ± 0.77.

Conclusion

We concluded that the accuracy and reliability of the videos obtained from YouTube by searching for the words Bankart and labrum lesion/injury/treatment are low.
Allosteric inhibition of CRISPR-Cas9 by bacteriophage-derived peptides
Authors: Cui Yan-ru , Wang Shao-jie , Chen Jun , Li Jie , Chen Wenzhang , Wang Shuyue , Meng Bing , Zhu Wei , Zhang Zhuhong , Yang Bei , Jiang Biao , Yang Guang , Ma Peixiang , Liu Jia
Published: February 2020

Background

CRISPR-Cas9 has been developed as a therapeutic agent for various infectious and genetic diseases. In many clinically relevant applications, constitutively active CRISPR-Cas9 is delivered into human cells without a temporal control system. Excessive and prolonged expression of CRISPR-Cas9 can lead to elevated off-target cleavage. The need for modulating CRISPR-Cas9 activity over time and dose has created the demand of developing CRISPR-Cas off switches. Protein and small molecule-based CRISPR-Cas inhibitors have been reported in previous studies.

Results

We report the discovery of Cas9-inhibiting peptides from inoviridae bacteriophages. These peptides, derived from the periplasmic domain of phage major coat protein G8P (G8PPD), can inhibit the in vitro activity of Streptococcus pyogenes Cas9 (SpCas9) proteins in an allosteric manner. Importantly, the inhibitory activity of G8PPD on SpCas9 is dependent on the order of guide RNA addition. Ectopic expression of full-length G8P (G8PFL) or G8PPD in human cells can inactivate the genome-editing activity of SpyCas9 with minimum alterations of the mutation patterns. Furthermore, unlike the anti-CRISPR protein AcrII4A that completely abolishes the cellular activity of CRISPR-Cas9, G8P co-transfection can reduce the off-target activity of co-transfected SpCas9 while retaining its on-target activity.

Conclusion

G8Ps discovered in the current study represent the first anti-CRISPR peptides that can allosterically inactivate CRISPR-Cas9. This finding may provide insights into developing next-generation CRISPR-Cas inhibitors for precision genome engineering.
Biochar-mediated enhanced ethanol fermentation (BMEEF) in Zymomonas mobilis under furfural and acetic acid stress
Authors: Wang Wei-ting , Dai Li-chun , Wu Bo , Qi Bu-fan , Huang Tian-fang , Hu Guo-quan , He Ming-xiong
Published: February 2020

Background

Pretreatment of lignocellulosic biomass generates different types of inhibitors (e.g., furfural and acetic acid), which could remarkably inhibit subsequent ethanol fermentation. Here, biochar as an additive in the fermentation broth was first applied to enhance ethanol production by Z. mobilis wild-type strain ZM4 in the presence of typical inhibitors.

Results

This study showed that the biochar-mediated tolerance to furfural and acetic acid for the strain Z. mobilis ZM4 was the highest reported level, resulting in much higher ethanol productivity under stress conditions than that in non-treated conditions. Further analysis showed that adsorptive detoxification was not the controlling factor for enhanced ethanol production under stress conditions, attributed to its low removal of furfural (< 20%) and incapability of acetic acid removal. When biochar was filtered from the biochar-treated inhibitor-containing broth, it still showed enhanced ethanol production. Furthermore, Z. mobilis immobilized on biochar was also observed. Thus, biochar extracts in the fermentation broth and cell immobilization on biochar might be the controlling factors for enhanced ethanol production under stress conditions.

Conclusions

These results indicate that biochar-mediated enhanced ethanol fermentation (BMEEF) might be a promising strategy for ethanol production from lignocellulosic biomass.
Improvement of the catalytic activity and thermostability of a hyperthermostable endoglucanase by optimizing N-glycosylation sites
Authors: Han Chao , Wang Qunqing , Sun Yanxu , Yang Ruirui , Liu Mengyu , Wang Siqi , Liu Yifan , Zhou Lifan , Li Duochuan
Published: February 2020

Background

Endoglucanase has been extensively employed in industrial processes as a key biocatalyst for lignocellulosic biomass degradation. Thermostable endoglucanases with high catalytic activity at elevated temperatures are preferred in industrial use. To improve the activity and thermostability, site-directed mutagenesis was conducted to modify the N-glycosylation sites of the thermostable β-1,4-endoglucanase CTendo45 from Chaetomium thermophilum.

Results

In this study, structure-based rational design was performed based on the modification of N-glycosylation sites in CTendo45. Eight single mutants and one double mutant were constructed and successfully expressed in Pichia pastoris. When the unique N-glycosylation site of N88 was eliminated, a T90A variant was active, and its specific activity towards CMC-Na and β-d-glucan was increased 1.85- and 1.64-fold, respectively. The mutant R67S with an additional N-glycosylation site of N65 showed a distinct enhancement in catalytic efficiency. Moreover, T90A and R67S were endowed with extraordinary heat endurance after 200 min of incubation at different temperatures ranging from 30 to 90 °C. Likewise, the half-lives (t1/2) indicated that T90A and R67S exhibited improved enzyme thermostability at 80 °C and 90 °C. Notably, the double-mutant T90A/R67S possessed better hydrolysis activity and thermal stability than its single-mutant counterparts and the wild type.

Conclusions

This study provides initial insight into the biochemical function of N-glycosylation in thermostable endoglucanases. Moreover, the design approach to the optimization of N-glycosylation sites presents an effective and feasible strategy to improve enzymatic activity and thermostability.
Feasibility study of on-site solid-state enzyme production by Aspergillus oryzae
Authors: Shinkawa Satoru , Mitsuzawa Shigenobu
Published: February 2020

Background

The development of biorefinery systems that use lignocellulosic biomass as a renewable carbon source to produce fuels and chemicals is attracting increasing attention. The process cost of enzymatic saccharification of biomass is a major challenge for commercialization. To decrease this cost, researchers have proposed on-site solid-state fermentation (SSF). This study investigated the feasibility of usingAspergillus oryzaeas a host microorganism for SSF recombinant enzyme production with ammonia-treated rice straw as model biomass. EightA. oryzaestrains were tested, all of which are used in the food industry. We evaluated the effects of acetic acid, a fermentation inhibitor. We also developed a platform strain for targeted recombinant enzyme production by gene engineering technologies.

Results

The SSF validation test showed variation in the visibility of mycelium growth and secreted protein in all eightA. oryzaestrains. The strains used to produceshoyuandmisogrew better under test conditions. The ammonia-treated rice straw contained noticeable amounts of acetic acid. This acetic acid enhanced the protein production byA. oryzaein a liquid-state fermentation test. The newly developed platform strain successfully secreted three foreign saccharifying enzymes.

Conclusions

A. oryzaeis a promising candidate as a host microorganism for on-site SSF recombinant enzyme production, which bodes well for the future development of a more cost-efficient saccharifying enzyme production system.
Development of a system for efficient content-based retrieval to analyze large volumes of climate data
Authors: Nakagawa Yujin , Onoue Yosuke , Kawahara Shitnaro , Araki Fumiaki , Koyamada Koji , Matsuoka Daisuke , Ishikawa Yoichi , Fujita Mikiko , Sugimoto Shiori , Okada Yasuko , Kawazoe Sho , Watanabe Shingo , Ishii Masayoshi , Mizuta Ryo , Murata Akihiko , Kawase Hiroaki
Published: February 2020

Analyses of large ensemble data on future climate are significantly useful for the probabilistic future projection of climate change in various interdisciplinary fields. However, the data volume of the Database for Policy Decision making for Future climate change or d4PDF, which is a mega-ensemble dataset, exceeds ∼ 3 PB, which is too large to download to local computers. To allow users for retrieve and downloading necessary data, we developed a user-friendly system called “System for Efficient content-based retrieval to Analyze Large volume climate data” (SEAL) under the Social Implementation Program on Climate Change Adaptation Technology (SI-CAT). Conventional web-based retrieval systems allow retrievals using metadata associated with a data file itself. In contrast, SEAL allows the users to retrieve the necessary data by using metadata associated with contents, such as physical values, of a data file. We confirmed that SEAL can reduce data sizes and total time required for obtaining necessary data to less than 0.5% and 1%, respectively, compared to conventional web-based retrieval systems.
Study protocol for evaluating Six Building Blocks for opioid management implementation in primary care practices
Authors: Shoemaker-Hunt Sarah J. , Evans Leigh , Swan Holly , Bacon Olivia , Ike Brooke , Baldwin Laura-Mae , Parchman Michael L.
Published: February 2020

Background

The Six Building Blocks for improving opioid management (6BBs) is a program for improving the management of patients in primary care practices who are on long-term opioid therapy for chronic pain. The 6BBs include building leadership and consensus; aligning policies, patient agreements, and workflows; tracking and monitoring patient care; conducting planned, patient-centered visits; tailoring care for complex patients; and measuring success. The Agency for Healthcare Research and Quality funded the development of a 6BBs implementation guide: a step-by-step approach for independently implementing the 6BBs in a practice. This mixed-method study seeks to assess practices’ use of the implementation guide to implement the 6BBs and the effectiveness of 6BBs implementation on opioid management processes of care among practices using the implementation guide.

Methods

Data collection is guided by the Consolidated Framework for Implementation Research, Proctor’s taxonomy of implementation outcomes, and the Centers for Disease Control and Prevention’s Guideline for Prescribing Opioids for Chronic Pain. A diverse group of health care organizations with primary care clinics across the USA will participate in the study over 15 months. Qualitative data collection will include semi-structured interviews with stakeholders at each organization at two time points, notes from routine check-in calls, and document review. These data will be used to understand practices’ motivation for participation, history with opioid management efforts, barriers and facilitators to implementation, and implementation progress. Quantitative data collection will consist of a provider and staff survey, an implementation milestones assessment, and quarterly opioid prescribing quality measures. These data will supplement our understanding of implementation progress and will allow us to assess changes over time in providers’ opioid prescribing practices, prescribing self-efficacy, challenges to providing guideline-driven care, and practices’ opioid prescribing quality measures. Qualitative data will be coded and analyzed for emergent themes. Quantitative data will be analyzed using descriptive statistics and clustered multivariate regression.

Discussion

This study contributes to the knowledge of the implementation and effectiveness of a team-based approach to opioid management in primary care practices. Information gleaned from this study can be used to inform efforts to curtail opioid prescribing and assist primary care practices considering implementing the 6BBs.
Clinical Outcomes in Patients With Colon Cancer With Microsatellite Instability of Sporadic or Familial Origin Treated With Adjuvant FOLFOX With or Without Cetuximab: A Pooled Analysis of the PETACC8 and N0147 Trials
Authors: Zaanan Aziz , Shi Qian , Taieb Julien , Alberts Steven R. , Meyers Jeffrey P. , Smyrk Thomas C. , Julie Catherine , Zawadi Ayman , Tabernero Josep , Mini Enrico , Goldberg Richard M. , Folprecht Gunnar , Van Laethem Jean Luc , Le Malicot Karine , Sargent Daniel J. , Laurent-Puig Pierre , Sinicrope Frank A.
Published: February 2020

PURPOSE

The microsatellite instability (MSI) or deficient mismatch repair (dMMR) phenotype is usually regarded as a single biologic entity, given the absence of comparative analyses regarding prognosis and response to chemotherapy between sporadic and familial dMMR cancers.

PATIENTS AND METHODS

Patients with stage III colon cancers were randomly assigned to FOLFOX (leucovorin, fluorouracil, and oxaliplatin) with or without cetuximab in 2 large adjuvant phase III trials (N = 5,577). Among patients with MSI and KRAS exon 2 wild-type (WT) tumors, the prognostic and predictive impacts of sporadic versus familial dMMR cancers and BRAF V600E mutational status were determined. Multivariable Cox proportional hazards models were used to assess disease-free survival (DFS) by treatment arm, adjusting for age, sex, tumor grade, Eastern Cooperative Oncology Group performance status, pT/pN stage, and primary tumor location.

RESULTS

Among patients with MSI status with complete data for dMMR mechanism analysis (n = 354), 255 (72%) had sporadic ( BRAF mutation and/or MLH1 methylation) and 99 (28%) had familial tumors ( BRAF WT and unmethylated MLH1 or loss of MSH2/MSH6/PMS2 protein expression). A large proportion of dMMR sporadic tumors were mutated for BRAF (n = 200). In patients treated with FOLFOX, DFS did not differ statistically by dMMR mechanism, whereas in patients treated with FOLFOX plus cetuximab, those with sporadic tumors had worse DFS than those with familial cancers (multivariable hazard ratio, 2.69; 95% CI, 1.02 to 7.08; P = .04). Considering the predictive utility, the interaction between treatment and dMMR mechanism was significant ( P = .03). Furthermore, a nonsignificant trend toward a deleterious effect of adding cetuximab to FOLFOX was observed in patients with BRAF-mutant but not BRAF WT tumors.

CONCLUSION

The addition of cetuximab to adjuvant FOLFOX was associated with shorter DFS in patients with sporadic dMMR colon cancer. Additional studies are needed to validate these results in metastatic disease.
Mapping the Steroid Response to Major Trauma From Injury to Recovery: A Prospective Cohort Study
Authors: Foster Mark A , Taylor Angela E , Hill Neil E , Bentley Conor , Bishop Jon , Gilligan Lorna C , Shaheen Fozia , Bion Julian F , Fallowfield Joanne L , Woods David R , Bancos Irina , Midwinter Mark M , Lord Janet M , Arlt Wiebke
Published: February 2020

Context

Survival rates after severe injury are improving, but complication rates and outcomes are variable.

Objective

This cohort study addressed the lack of longitudinal data on the steroid response to major trauma and during recovery.

Design

We undertook a prospective, observational cohort study from time of injury to 6 months postinjury at a major UK trauma centre and a military rehabilitation unit, studying patients within 24 hours of major trauma (estimated New Injury Severity Score (NISS) > 15).

Main outcome measures

We measured adrenal and gonadal steroids in serum and 24-hour urine by mass spectrometry, assessed muscle loss by ultrasound and nitrogen excretion, and recorded clinical outcomes (ventilator days, length of hospital stay, opioid use, incidence of organ dysfunction, and sepsis); results were analyzed by generalized mixed-effect linear models.

Findings

We screened 996 multiple injured adults, approached 106, and recruited 95 eligible patients; 87 survived. We analyzed all male survivors <50 years not treated with steroids (N = 60; median age 27 [interquartile range 24–31] years; median NISS 34 [29–44]). Urinary nitrogen excretion and muscle loss peaked after 1 and 6 weeks, respectively. Serum testosterone, dehydroepiandrosterone, and dehydroepiandrosterone sulfate decreased immediately after trauma and took 2, 4, and more than 6 months, respectively, to recover; opioid treatment delayed dehydroepiandrosterone recovery in a dose-dependent fashion. Androgens and precursors correlated with SOFA score and probability of sepsis.

Conclusion

The catabolic response to severe injury was accompanied by acute and sustained androgen suppression. Whether androgen supplementation improves health outcomes after major trauma requires further investigation.