bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing Quality in Systematic Literature Reviews: A Study of Novice Rater Training
Authors: Acosta Sandra , Garza Tiberio , Hsu Hsien-Yuan , Goodson Patricia
Published: July 2020

This study investigated performance variability when graduate students critically appraised original studies from a systematic review. Fourteen doctoral students from different academic programs, with no systematic review experience, received training on the Methodological Quality Questionnaire (MQQ) rating scale. Participants were mostly male (71%) and non-native English speakers (79%). Each rater was randomly assigned one original study to independently assess using the MQQ. Their scores were compared to an expert rater. Statistical analysis comprised the following: percentage of agreement (POA), Kappa coefficient, and Kendall’s tau-b correlation. On the completed MQQ rating scale, 43% of the novice raters had a POA of 78% or higher with the expert rater. From this case study, a guide for improving training on methodological quality assessment was developed. Benefits include the following: (a) developing and supporting critical reasoning as well as problem-solving skills and (b) increasing research skills and competencies in the systematic review process.
Higher Paraspinal Muscle Density Effect on Outcomes After Anterior Cervical Discectomy and Fusion
Authors: Pinter Zachariah W. , Wagner Scott C. , Fredericks Donald R. , Xiong Ashley , Freedman Brett A. , Elder Benjamin D. , Nassr Ahmad , Bydon Mohamad , Kepler Christopher K. , Sebastian Arjun S.
Published: July 2020

Study Design:

Retrospective cohort study.

Objectives:

Studies in the lumbar spine suggest a correlation between sarcopenia and worse patient outcomes. The purpose of this study was to determine whether paraspinal Goutalier grade of fat degeneration is associated with patient-reported outcomes in patients undergoing anterior cervical discectomy and fusion (ACDF).

Methods:

We performed a retrospective review of a prospective cohort of patients undergoing 1- to 3-level ACDF at a single institution between the years 2011-2014. We utilized preoperative magnetic resonance images to classify patients into Goutalier grades. Patient-reported outcomes, including Neck Disability Index (NDI), RAND score, and EQ-5D score were collected and analyzed according to patients’ Goutalier grade.

Results:

We identified 69 patients for inclusion. A total of 29 patients were classified as Goutalier 0-1 (group 1), 29 were Goutalier 1.5-2 (group 2), and 11 were Goutalier 2.5-4.0 (group 3). All Goutalier groups experienced significant improvement in all 3 outcome scores. Average postoperative NDI scores were 25.3 in group 1, 13.9 in group 2, and 25.1 in group 3 ( P = .02). The percentage of patients in each group reporting worse disability after surgery was 17.2%, 3.3%, and 9.1%, respectively ( P = .05). No statistically significant difference was seen between groups in postoperative EQ-5D ( P = .07) or RAND scores ( P > .05).

Conclusions:

The present study is the first to assess the association between cervical paraspinal muscle Goutalier grade and patient-reported outcomes following ACDF. Based on our study, patients with worse cervical paraspinal degeneration may benefit from improved symptom relief in comparison to patients with a lesser degree of degeneration undergoing ACDF.
An Assessment of Nonoperative Management Strategies in a Herniated Lumbar Disc Population: Successes Versus Failures
Authors: Lilly Daniel T. , Davison Mark A. , Eldridge Cody M. , Singh Ravinderjit , Montgomery Eric Y. , Bagley Carlos , Adogwa Owoicho
Published: July 2020

Study Design:

Retrospective cohort study.

Objective:

To compare the utilization of conservative treatments in patients with lumbar intervertebral disc herniations who were successfully managed nonoperatively versus patients who failed conservative therapies and elected to undergo surgery (microdiscectomy).

Methods:

Clinical records from adult patients with an initial herniated lumbar disc between 2007 and 2017 were selected from a large insurance database. Patients were divided into 2 cohorts: patients treated successfully with nonoperative therapies and patients that failed conservative management and opted for microdiscectomy surgery. Nonoperative treatments utilized by the 2 groups were collected over a 2-year surveillance window. “Utilization” was defined by cost billed to patients, prescriptions written, and number of units disbursed.

Results:

A total of 277 941 patients with lumbar intervertebral disc herniations were included. Of these, 269 713 (97.0%) were successfully managed with nonoperative treatments, while 8228 (3.0%) failed maximal nonoperative therapy (MNT) and underwent a lumbar microdiscectomy. MNT failures occurred more frequently in males (3.7%), and patients with a history of lumbar epidural steroid injections (4.5%) or preoperative opioid use (3.6%). In a logistic multivariate regression analysis, male sex and utilization of opioids were independent predictors of conservative management failure. Furthermore, a cost analysis indicated that patients who failed nonoperative treatments billed for nearly double ($1718/patient) compared to patients who were successfully treated ($906/patient).

Conclusion:

Our results suggest that the majority of patients are successfully managed nonoperatively. However, in the subset of patients that fail conservative management, male sex and prior opioid use appear to be independent predictors of treatment failure.
Revisiting the Marginal Man: Bridging Immigration Scholarship and Mixed-Race Studies
Authors: Newman Alyssa M.
Published: July 2020

Immigrant and multiracial populations have both attracted attention for their significant impact on the demographic makeup of the United States. The anticipation of their continued growth raises important questions about how their increasing representation may alter the racial hierarchy. Although immigration scholarship frequently interprets intermarriage and multiracial identity as markers of assimilation, a large disconnect exists between the fields of immigration and mixed-race studies. This article bridges the gap between the two areas of scholarship by tracing their sociological origins to a shared theoretical progenitor: the marginal man. Through narrow interpretations of the resolution to experiences of marginality, the assimilation paradigm has largely failed to take into consideration the implications of multiracial identity, examining it only as transitive state assessed primarily through parental identification or within existing frameworks of immigrant identity. Based on interviews with 26 multiracial adults who have at least one immigrant parent, this study examines the meaning, content, and salience of multiracial identity for analyses of assimilation. Although much scholarship is concerned with the eroding and expanding boundaries of whiteness, this research analyzes how both part-white and nonwhite multiracial children of immigrant experiences contribute to understanding the role of multiraciality in blurring, crossing, or disrupting the boundaries that divide racial groups. The findings indicate that multiracial identity assertion was a mechanism for study participants to claim connection and belonging to multiple ethnoracial groups, rather than be rendered marginalized, distant, or partial with respect to their immigrant heritage(s).
What Can Donors Do? The Role of Donors in Advocating for Family and Community-Based Care in South Asia
Authors: Keshavarzian Ghazal , Borgström Joel
Published: July 2020

Elevate Children Funders Group (ECFG), a consortium of foundations dedicated to building strong families and a life free from violence for all children, strongly believes and supports the idea that children are best able to thrive and reach their full potential when they remain with their families and communities rather than living in residential care. Years of research has shown that orphanages often expose children to serious abuse, harm and neglect, can impact a child’s physical and psychological development and is often much more expensive than family or community-based care. However, despite this evidence, the number of residential care institutions has been steadily or even exponentially increasing. Donors continue to invest in orphanages—drawing more children into institutions and away from families. To this end, this article will make a case for investing in families and communities rather than orphanages by putting a spotlight on ECFG member investments in Asia. By drawing on recent ECFG funding research and foundation investments, this article will highlight how donors can do more to help deinstitutionalisation efforts across the region.
Cognitive, Behavioural and Emotional Benefits of Deinstitutionalisation for Children with Disabilities: A Comparative Study of the United Kingdom and India
Authors: Khetawat Devanshi
Published: July 2020

Research states that institutionalisation often results in negative outcomes for children’s mental, physical and emotional health and behaviour. Alternatively, deinstitutionalisation can buffer this negative impact across countries and cultures. However, these results have been inadequately replicated with children having disabilities, who are at heightened risk of negative psychosocial outcomes of institutionalisation. Owing to the large number of children with disabilities in institutional care and this seems unrepresentative and undesirable. In the current article, the cognitive, emotional, mental health, and behavioural benefits of deinstitutionalisation for children with varied disabilities in India and UK are discused. For this, the researcher’s compilation of observational data and personal reflections from 4.5 years of practical work with deinstitutionalised children with disabilities is used. Further, interview extracts and reflections from children and their adoptive/foster carers post deinstitutionalisation are included. With this, an attempt is made to advance how and why deinstitutionalisation is beneficial for children with disabilities.
First-Birth Timing and the Motherhood Wage Gap in 140 Occupations
Authors: Landivar Liana Christin
Published: July 2020

Is delayed fertility associated with a reduced motherhood wage gap in all occupations? Using multilevel models and data from the 2011–2015 American Community Survey, O*NET, and the Current Population Survey, I examine whether delayed fertility is associated with a reduced motherhood wage gap in 140 occupations. Delayed childbearing is one strategy women use to mitigate the motherhood wage penalty. Findings indicate that mothers in high-earning professional occupations experienced the largest wage penalties with early motherhood but also the largest premiums with delayed childbearing. Although delaying a first birth mitigated the motherhood wage penalty in high-wage occupations requiring extensive career preparation, the majority of women who worked in lower wage occupations with more limited human capital requirements experienced no economic benefit from older motherhood. These results challenge the broader narrative that most women can improve their long-term earnings and partly overcome the structural motherhood wage gap by delaying fertility.
Radiographic Outcomes after Flexible Flatfoot Reconstruction with and without Spring Ligament Reconstruction
Authors: Kohring Jessica M. , MacDonald Ashlee , Karnyski Steven , Oh Irvin , Baumhauer Judith F. , Ketz John P. , Flemister Adolph S.
Published: July 2020

Category:

Hindfoot

Introduction/Purpose:

The purpose of this study was to determine postoperative radiographic differences between patients who underwent flexible flatfoot reconstruction and spring ligament repair with a FiberTape suture device versus those who underwent spring ligament reconstruction with suture repair alone or those without reconstruction of the spring ligament for patients with Stage II adult acquired flatfoot deformity (AAFD).

Methods:

84 patients with Stage II AAFD met inclusion criteria with 18 undergoing flatfoot reconstruction and spring ligament (SL) repair with a FiberTape suture device (SL+FT), 12 with suture repair alone (SL+suture), and 54 without repair of the SL. Radiographic measurements were made on weight bearing radiographs pre- and postoperatively at an average of 90 ±108 weeks after surgery. The radiographic measurements included tibiotalar tilt (TT), talar-first metatarsal angle (T1M), talar-second metatarsal angle (T2M), talonavicular uncoverage angle (TN), Meary’s angle (MA), calcaneal pitch (CP), medial column height (MCH), and lateral column height (LCH). Statistical analysis was performed using two-way ANOVA.

Results:

There were no differences in preoperative radiographic measurements between the three groups. Postoperatively, the SL+FT and SL+suture groups had statistically significantly improved radiographic outcomes for T1M, T2M, TN, MA, CP, and LCH when compared to the no SL repair group (p<0.05). There were no differences in any radiographic outcomes between the SL+FT and SL+suture groups ( Figure 1 ).

Conclusion:

Spring ligament reconstruction with either a FiberTape construct or suture repair alone demonstrates significant improvements in postoperative radiographic outcomes after undergoing flexible flatfoot reconstruction at an average of 2 years after surgery as compared to patients that did not have SL repair. The results of our study support spring ligament repair or reconstruction for patients when performing flexible flatfoot surgery for Stage II AAFD.
G-DIF: A geospatial data integration framework to rapidly estimate post-earthquake damage
Authors: Loos Sabine , Lallemant David , Baker Jack , McCaughey Jamie , Yun Sang-Ho , Budhathoki Nama , Khan Feroz , Singh Ritika
Published: July 2020

While unprecedented amounts of building damage data are now produced after earthquakes, stakeholders do not have a systematic method to synthesize and evaluate damage information, thus leaving many datasets unused. We propose a Geospatial Data Integration Framework (G-DIF) that employs regression kriging to combine a sparse sample of accurate field surveys with spatially exhaustive, though uncertain, damage data from forecasts or remote sensing. The framework can be implemented after an earthquake to produce a spatially distributed estimate of damage and, importantly, its uncertainty. An example application with real data collected after the 2015 Nepal earthquake illustrates how regression kriging can combine a diversity of datasets—and downweight uninformative sources—reflecting its ability to accommodate context-specific variations in data type and quality. Through a sensitivity analysis on the number of field surveys, we demonstrate that with only a few surveys, this method can provide more accurate results than a standard engineering forecast.
Real-world data confirm the effectiveness of caplacizumab in acquired thrombotic thrombocytopenic purpura
Authors: Völker Linus A. , Kaufeld Jessica , Miesbach Wolfgang , Brähler Sebastian , Reinhardt Martin , Kühne Lucas , Mühlfeld Anja , Schreiber Adrian , Gaedeke Jens , Tölle Markus , Jabs Wolfram J. , Özcan Fedai , Markau Silke , Girndt Matthias , Bauer Frederic , Westhoff Timm H. , Felten Helmut , Hausberg Martin , Brand Marcus , Gerth Jens , Bieringer Markus , Bommer Martin , Zschiedrich Stefan , Schneider Johanna , Elitok Saban , Gawlik Alexander , Gäckler Anja , Kribben Andreas , Schwenger Vedat , Schoenermarck Ulf , Roeder Maximilian , Radermacher Jörg , Bramstedt Jörn , Morgner Anke , Herbst Regina , Harth Ana , Potthoff Sebastian A. , von Auer Charis , Wendt Ralph , Christ Hildegard , Brinkkoetter Paul T. , Menne Jan
Published: July 2020

Acquired thrombotic thrombocytopenic purpura (aTTP) is a rare but life-threatening condition. In 2018, the nanobody caplacizumab was approved for the treatment of adults experiencing an acute episode of aTTP, in conjunction with plasma exchange (PEX) and immunosuppression for a minimum of 30 days after stopping daily PEX. We performed a retrospective, observational analysis on the use of caplacizumab in 60 patients from 29 medical centers in Germany during acute disease management. Caplacizumab led to a rapid normalization of the platelet count (median, 3 days; mean 3.78 days). One patient died after late treatment initiation due to aTTP-associated complications. In 2 patients with initial disease presentation and in 4 additional patients with laboratory signs of an exacerbation or relapse after the initial therapy, PEX-free treatment regimens could be established with overall favorable outcome. Caplacizumab is efficacious in the treatment of aTTP independent of timing and ancillary treatment modalities. Based on this real-world experience and published literature, we propose to administer caplacizumab immediately to all patients with an acute episode of aTTP. Treatment decisions regarding the use of PEX should be based on the severity of the clinical presentation and known risk factors. PEX might be dispensable in some patients.
ADAMTS13 and VWF activities guide individualized caplacizumab treatment in patients with aTTP
Authors: Völker Linus A. , Kaufeld Jessica , Miesbach Wolfgang , Brähler Sebastian , Reinhardt Martin , Kühne Lucas , Mühlfeld Anja , Schreiber Adrian , Gaedeke Jens , Tölle Markus , Jabs Wolfram J. , Özcan Fedai , Markau Silke , Girndt Matthias , Bauer Frederic , Westhoff Timm H. , Felten Helmut , Hausberg Martin , Brand Marcus , Gerth Jens , Bieringer Markus , Bommer Martin , Zschiedrich Stefan , Schneider Johanna , Elitok Saban , Gawlik Alexander , Gäckler Anja , Kribben Andreas , Schwenger Vedat , Schoenermarck Ulf , Roeder Maximilian , Radermacher Jörg , Bramstedt Jörn , Morgner Anke , Herbst Regina , Harth Ana , Potthoff Sebastian A. , von Auer Charis , Wendt Ralph , Christ Hildegard , Brinkkoetter Paul T. , Menne Jan
Published: July 2020

Introduction of the nanobody caplacizumab was shown to be effective in the treatment of acquired thrombotic thrombocytopenic purpura (aTTP) in the acute setting. The official recommendations include plasma exchange (PEX), immunosuppression, and the use of caplacizumab for a minimum of 30 days after stopping daily PEX. This study was a retrospective, observational analysis of the use of caplacizumab in 60 patients from 29 medical centers in Germany. Immunosuppressive treatment led to a rapid normalization of ADAMTS13 activities (calculated median, 21 days). In 35 of 60 patients, ADAMTS13 activities started to normalize before day 30 after PEX; in 11 of 60 patients, the treatment was extended beyond day 30; and in 5 patients, it was extended even beyond day 58 due to persistent autoimmune activity. In 34 of 60 instances, caplacizumab was stopped before day 30 with a favorable outcome whenever ADAMTS13 activities were >10%. In contrast, 11 of 34 patients with ADAMTS13 activities <10% at the time of stopping caplacizumab treatment developed a nonfavorable outcome (disease exacerbation or relapse). In some cases, prolongation of the treatment interval to every other day was feasible and resulted in a sustained reduction of von Willebrand factor activity. ADAMTS13 activity measurements are central for a rapid diagnosis in the acute setting but also to tailor disease management. An ADAMTS13 activity–guided approach seems safe for identifying the individual time point when to stop caplacizumab to prevent overtreatment and undertreatment; this approach will result in significant cost savings without jeopardizing the well-being of patients. In addition, von Willebrand factor activity may serve as a biomarker for drug monitoring.
Decoding the differentiation of mesenchymal stem cells into mesangial cells at the transcriptomic level
Authors: Wong Chee-Yin , Chang Yao-Ming , Tsai Yu-Shuen , Ng Wailap Victor , Cheong Soon-Keng , Chang Ting-Yu , Chung I-Fang , Lim Yang-Mooi
Published: July 2020

Background

Mesangial cells play an important role in the glomerulus to provide mechanical support and maintaine efficient ultrafiltration of renal plasma. Loss of mesangial cells due to pathologic conditions may lead to impaired renal function. Mesenchymal stem cells (MSC) can differentiate into many cell types, including mesangial cells. However transcriptomic profiling during MSC differentiation into mesangial cells had not been studied yet. The aim of this study is to examine the pattern of transcriptomic changes during MSC differentiation into mesangial cells, to understand the involvement of transcription factor (TF) along the differentiation process, and finally to elucidate the relationship among TF-TF and TF-key gene or biomarkers during the differentiation of MSC into mesangial cells.

Results

Several ascending and descending monotonic key genes were identified by Monotonic Feature Selector. The identified descending monotonic key genes are related to stemness or regulation of cell cycle while ascending monotonic key genes are associated with the functions of mesangial cells. The TFs were arranged in a co-expression network in order of time by Time-Ordered Gene Co-expression Network (TO-GCN) analysis. TO-GCN analysis can classify the differentiation process into three stages: differentiation preparation, differentiation initiation and maturation. Furthermore, it can also explore TF-TF-key genes regulatory relationships in the muscle contraction process.

Conclusions

A systematic analysis for transcriptomic profiling of MSC differentiation into mesangial cells has been established. Key genes or biomarkers, TFs and pathways involved in differentiation of MSC-mesangial cells have been identified and the related biological implications have been discussed. Finally, we further elucidated for the first time the three main stages of mesangial cell differentiation, and the regulatory relationships between TF-TF-key genes involved in the muscle contraction process. Through this study, we have increased fundamental understanding of the gene transcripts during the differentiation of MSC into mesangial cells.
Identifying and exploring biohydrogenating rumen bacteria with emphasis on pathways including trans-10 intermediates
Authors: Dewanckele Lore , Jeyanathan Jeyamalar , Vlaeminck Bruno , Fievez Veerle
Published: July 2020

Background

Bacteria involved in ruminal formation of trans-10 intermediates are unclear. Therefore, this study aimed at identifying rumen bacteria that produce trans-10 intermediates from 18-carbon unsaturated fatty acids.

Results

Pure cultures of 28 rumen bacterial species were incubated individually in the presence of 40 μg/mL 18:3n-3, 18:2n-6 or trans-11 18:1 under control or lactate-enriched (200 mM Na lactate) conditions for 24 h. Of the 28 strains, Cutibacterium acnes (formerly Propionibacterium acnes) was the only bacterium found to produce trans-10 intermediates from 18:3n-3 and 18:2n-6, irrespective of the growth condition. To further assess the potential importance of this species in the trans-11 to trans-10 shift, different biomass ratios of Butyrivibrio fibrisolvens (as a trans-11 producer) and C. acnes were incubated in different growth media (control, low pH and 22:6n-3 enriched media) containing 40 μg/mL 18:2n-6. Under control conditions, a trans-10 shift, defined in the current study as trans-10/trans-11 ≥ 0.9, occurred when the biomass of C. acnes represented between 90 and 98% of the inoculum. A low pH or addition of 22:6n-3 inhibited cis-9, trans-11 CLA and trans-10, cis-12 CLA formation by B. fibrisolvens and C. acnes, respectively, whereby C. acnes seemed to be more tolerant. This resulted in a decreased biomass of C. acnes required at inoculation to induce a trans-10 shift to 50% (low pH) and 90% (22:6n-3 addition).

Conclusions

Among the bacterial species studied,C. acnes was the only bacterium that have the metabolic ability to produce trans-10 intermediates from 18:3n-3 and 18:2n-6. Nevertheless, this experiment revealed that it is unlikely that C. acnes is the only or predominant species involved in the trans-11 to trans-10 shift in vivo.
Quantitative genome-wide association analyses of receptive language in the Danish High Risk and Resilience Study
Authors: Nudel Ron , Christiani Camilla A. J. , Ohland Jessica , Uddin Md Jamal , Hemager Nicoline , Ellersgaard Ditte , Spang Katrine S. , Burton Birgitte K. , Greve Aja N. , Gantriis Ditte L. , Bybjerg-Grauholm Jonas , Jepsen Jens Richardt M. , Thorup Anne A. E. , Mors Ole , Werge Thomas , Nordentoft Merete
Published: July 2020

Background

One of the most basic human traits is language. Linguistic ability, and disability, have been shown to have a strong genetic component in family and twin studies, but molecular genetic studies of language phenotypes are scarce, relative to studies of other cognitive traits and neurodevelopmental phenotypes. Moreover, most genetic studies examining such phenotypes do not incorporate parent-of-origin effects, which could account for some of the heritability of the investigated trait. We performed a genome-wide association study of receptive language, examining both child genetic effects and parent-of-origin effects.

Results

Using a family-based cohort with 400 children with receptive language scores, we found a genome-wide significant paternal parent-of-origin effect with a SNP, rs11787922, on chromosome 9q21.31, whereby the T allele reduced the mean receptive language score by ~ 23, constituting a reduction of more than 1.5 times the population SD (P = 1.04 × 10−8). We further confirmed that this association was not driven by broader neurodevelopmental diagnoses in the child or a family history of psychiatric diagnoses by incorporating covariates for the above and repeating the analysis.

Conclusions

Our study reports a genome-wide significant association for receptive language skills; to our knowledge, this is the first documented genome-wide significant association for this phenotype. Furthermore, our study illustrates the importance of considering parent-of-origin effects in association studies, particularly in the case of cognitive or neurodevelopmental traits, in which parental genetic data are not always incorporated.
The natural alkaloid Jerantinine B has activity in acute myeloid leukemia cells through a mechanism involving c-Jun
Authors: Alhuthali Hayaa Moeed , Bradshaw Tracey D. , Lim Kuan-Hon , Kam Toh-Seok , Seedhouse Claire H.
Published: July 2020

Background

Acute myeloid leukemia (AML) is a heterogenous hematological malignancy with poor long-term survival. New drugs which improve the outcome of AML patients are urgently required. In this work, the activity and mechanism of action of the cytotoxic indole alkaloid Jerantinine B (JB), was examined in AML cells.

Methods

We used a combination of proliferation and apoptosis assays to assess the effect of JB on AML cell lines and patient samples, with BH3 profiling being performed to identify early effects of the drug (4 h). Phosphokinase arrays were adopted to identify potential driver proteins in the cellular response to JB, the results of which were confirmed and extended using western blotting and inhibitor assays and measuring levels of reactive oxygen species.

Results

AML cell growth was significantly impaired following JB exposure in a dose-dependent manner; potent colony inhibition of primary patient cells was also observed. An apoptotic mode of death was demonstrated using Annexin V and upregulation of apoptotic biomarkers (active caspase 3 and cleaved PARP). Using BH3 profiling, JB was shown to prime cells to apoptosis at an early time point (4 h) and phospho-kinase arrays demonstrated this to be associated with a strong upregulation and activation of both total and phosphorylated c-Jun (S63). The mechanism of c-Jun activation was probed and significant induction of reactive oxygen species (ROS) was demonstrated which resulted in an increase in the DNA damage response marker γH2AX. This was further verified by the loss of JB-induced C-Jun activation and maintenance of cell viability when using the ROS scavenger N-acetyl-L-cysteine (NAC).

Conclusions

This work provides the first evidence of cytotoxicity of JB against AML cells and identifies ROS-induced c-Jun activation as the major mechanism of action.
Treatment outcomes of severe acute malnutrition and predictors of recovery in under-five children treated within outpatient therapeutic programs in Ethiopia: a systematic review and meta-analysis
Authors: Bitew Zebenay Workneh , Alemu Ayinalem , Worku Teshager
Published: July 2020

Background

Severe acute malnutrition affects around 17 million under-five children in the world, of which the highest burden is accounted by Sub-Saharan Africa where Ethiopia is found. Though there are few individual, inconsistent and inconclusive studies, there is no nationally representative study on treatment outcomes of SAM in outpatient therapeutic feeding programs of Ethiopia. This study aimed at estimating the pooled treatment outcomes and predictors of recovery rate among under- five children with SAM in Ethiopia.

Methods

Electronic databases (PubMed, Medline (EBSCOhost), EMBASE (Elsevier), CINAHL (EBSCOhost), web of science, Scopus, Science Direct and Food Science and Technology Abstracts (FSTA)), and grey literature sources (Google scholar, Mednar, World Cat and google) were used to retrieve articles. The random effect model was used to estimate the pooled treatment outcomes. Hazard ratios were used to determine the predictors of recovery rate. Cochran’s Q, I2, and univariate Meta regression were done for heterogeneity. Begg’s & Egger’s tests were used for publication bias.

Results

Nineteen articles with a total number of 23,395 under-five children with SAM were used for this meta-analysis. The pooled recovery, death, defaulter and non-recovery rates were 70% (95% CI: 64, 76), 2% (95% CI: 1, 2), 10% (95%CI: 7, 12), 15% (95% CI: 10, 20), respectively. Diarrhea (HR = 0.8, 95% CI: 0.75, 0.94), no edema (HR = 0.41, 95% CI: 0.33, 0.50) and amoxicillin (HR = 1.81, 95% CI: 1.18, 2.44) were independent predictors of recovery rate of children with SAM in Ethiopia. Publication year was found to be the potential source of heterogeneity between included studies.

Conclusion

The treatment outcomes of children with SAM from outpatient therapeutic feeding programs of Ethiopia are lower than the sphere guidelines, WHO and national recommendations. Diarrhea and no edema antagonized the recovery rate of children, while amoxicillin enhanced the recovery rate of children from SAM. Community health workers need to be trained. Especial attention should be given while treating children with diarrhea and severe wasting. Community mobilization is also recommended to improve community awareness about the therapeutic foods.
Pressure Support Ventilation (PSV) versus Neurally Adjusted Ventilatory Assist (NAVA) in difficult to wean pediatric ARDS patients: a physiologic crossover study
Authors: Spinazzola Giorgia , Costa Roberta , De Luca Daniele , Chidini Giovanna , Ferrone Giuliano , Piastra Marco , Conti Giorgio
Published: July 2020

Background

Neurally adjusted ventilatory assist (NAVA) is an innovative mode for assisted ventilation that improves patient-ventilator interaction in children. The aim of this study was to assess the effects of patient-ventilator interaction comparing NAVA with pressure support ventilation (PSV) in patients difficult to wean from mechanical ventilation after moderate pediatric acute respiratory distress syndrome (PARDS).

Methods

In this physiological crossover study, 12 patients admitted in the Pediatric Intensive Care Unit (PICU) with moderate PARDS failing up to 3 spontaneous breathing trials in less than 7 days, were enrolled. Patients underwent three study conditions lasting 1 h each: PSV1, NAVA and PSV2.

Results

The Asynchrony Index (AI) was significantly reduced during the NAVA trial compared to both the PSV1 and PSV2 trials (p = 0.001). During the NAVA trial, the inspiratory and expiratory trigger delays were significantly shorter compared to those obtained during PSV1 and PSV2 trials (Delaytrinspp < 0.001, Delaytrexpp = 0.013). These results explain the significantly longer Timesync observed during the NAVA trial (p < 0.001). In terms of gas exchanges, PaO2 value significantly improved in the NAVA trial with respect to the PSV trials (p < 0.02). The PaO2/FiO2 ratio showed a significant improvement during the NAVA trial compared to both the PSV1 and PSV2 trials (p = 0.004).

Conclusions

In this specific PICU population, presenting difficulty in weaning after PARDS, NAVA was associated with a reduction of the AI and a significant improvement in oxygenation compared to PSV mode.

Trial registration

ClinicalTrial.gov Identifier: NCT04360590 “Retrospectively registered”.
Is all-inside with suspensory cortical button fixation a superior technique for anterior cruciate ligament reconstruction surgery? A systematic review and meta-analysis
Authors: Fu Chun-Wei , Chen Wei-Cheng , Lu Yung-Chang
Published: July 2020

Background

To compare the clinical results of all-inside anterior cruciate ligament reconstruction (ACLR) using suspensory cortical button fixation and full tibial tunnel drilling.

Methods

Systematic searches were conducted of published literature up to November 2019 on PubMed, Embase, and Cochrane for studies comparing all-inside ACLR using suspensory cortical button fixation and full tibial tunnel ACLR. Two reviewers independently determined eligibility, extracted the outcome data, and assessed the risk of bias of the eligible studies. The clinical outcome and graft reruptures were pooled by using random effects with mean differences and risk ratios for continuous and dichotomous variables, respectively.

Result

A total of nine studies (five randomized controlled trials and four comparative studies) involving 613 patients were included in the meta-analysis. The postoperative functional outcome, knee laxity measured with arthrometer, and graft reruptures were comparable between patients with all-inside ACLR using suspensory cortical button fixation and full tibial tunnel ACLR. However, a significantly greater thickness of autologous tendon was used and less change in drilling tunnel diameter was noted in patients with suspensory cortical button graft fixation.

Conclusions

All-inside ACLR with suspensory cortical button fixation was not clinically superior to full tibial tunnel ACLR with interference screw fixation in functional outcomes, knee laxity measured with arthrometer, or rerupture rate. However, the advantage of using suspensory cortical button fixation was that a thicker graft could be used for reconstruction, and brought less tibia tunnel widening compared with bioabsorbable interference screw fixation.
An evaluation of continuous subcutaneous infusions across seven NHS acute hospitals: is there potential for 48-hour infusions?
Authors: Baker J. , Dickman A. , Mason S. , Bickerstaff M. , Jackson R. , McArdle A. , Lawrence I. , Stephenson F. , Paton N. , Kirk J. , Waters B. , Ellershaw J.
Published: July 2020

Background

Continuous subcutaneous infusions (CSCIs) are commonly used in the United Kingdom as a way of administering medication to patients requiring symptom control when the oral route is compromised. These infusions are typically administered over 24 h due to currently available safety data. The ability to deliver prescribed medication by CSCI over 48 h may have numerous benefits in both patient care and health service resource utilisation. This service evaluation aims to identify the frequency at which CSCI prescriptions are altered at NHS Acute Hospitals.

Methods

Pharmacists or members of palliative care teams at seven acute NHS hospitals recorded anonymised prescription data relating to the drug combination(s), doses, diluent and compatibility of CSCIs containing two or more drugs on a daily basis for a minimum of 2 days, to a maximum of 7 days.

Results

A total of 1301 prescriptions from 288 patients were recorded across the seven sites, yielding 584 discrete drug combinations. Of the 584 combinations, 91% (n = 533) included an opioid. The 10 most-common CSCI drug combinations represented 37% of the combinations recorded. Median duration of an unchanged CSCI prescription across all sites was 2 days.

Conclusion

Data suggests medication delivered by CSCI over 48 h may be a viable option. Before a clinical feasibility study can be undertaken, a pharmacoeconomic assessment and robust chemical and microbiological stability data will be required, as will the assessment of the perceptions from clinical staff, patients and their families on the acceptability of such a change in practice.
Differential influences of social support on app use for diabetes self-management – a mixed methods approach
Authors: Brew-Sam Nicola , Chib Arul , Rossmann Constanze
Published: July 2020

Background

Recent studies increasingly examine social support for diabetes self-management delivered via mHealth. In contrast to previous studies examining social support as an outcome of technology use, or technology as a means for delivering social support, this paper argues that social support has an impact on the use of diabetes mHealth apps. Specifically, we postulate differences between the impact of healthcare professional versus non-professional (family/friends) support on mobile app use for diabetes self-management.

Methods

This research employed a triangulation of methods including exploratory semi-structured face-to-face interviews (N = 21, Study 1) and an online survey (N = 65, Study 2) with adult type 1 and type 2 diabetes patients. Thematic analysis (Study 1) was used to explore the relevance of social support (by professionals versus non-professionals) for diabetes app use. Binary logistic regression (Study 2) was applied to compare healthcare decision-making, healthcare-patient communication, and the support by the personal patient network as predictors of diabetes app use, complemented by other predictors from self-management and technology adoption theory.

Results

The interviews (Study 1) demonstrated that (technology-supported) shared decision-making and supportive communication by healthcare professionals depended on their medical specialty. The personal patient network was perceived as either facilitating or hindering the use of mHealth for self-management. Binary logistic regression (Study 2) showed that the physician specialty significantly predicted the use of diabetes apps, with supervision by diabetes specialists increasing the likelihood of app use (as opposed to general practitioners). Additionally, specialist care positively related to a higher chance of shared decision-making and better physician-patient communication. The support by the personal patient network predicted diabetes app use in the opposite direction, with less family/friend support increasing the likelihood of app use.

Conclusion

The results emphasize the relevance of support by healthcare professionals and by the patient network for diabetes app use and disclose differences from the existing literature. In particular, the use of diabetes apps may increase in the absence of social support by family or friends (e.g., compensation for lack of support), and may decrease when such support is high (e.g., no perceived need to use technology).
Exploring the acceptability of controlled human infection with SARSCoV2—a public consultation
Authors: Gbesemete D. , Barker M. , Lawrence W. T. , Watson D. , de Graaf H. , Read R. C.
Published: July 2020

Rapid development of an effective vaccine for SARSCoV2 is a global priority. A controlled human infection model (CHIM) would accelerate the efficacy assessment of candidate vaccines. This strategy would require deliberate exposure of volunteers to SARSCoV2 with no currently available treatment and a small but definite risk of serious illness or death. This raises complex questions about the social and ethical acceptability of risk to individuals, given the potential benefit to the wider population, and as such, a study cannot be done without public involvement. We conducted a structured public consultation with 57 individuals aged 20–40 years to understand public attitudes to a CHIM, and pre-requisites for enrolment. The overall response to this strategy was positive, and many would volunteer altruistically. Carefully controlled infection is viewed as safer than natural exposure to wild virus. The prolonged social isolation required for the proposed CHIM is considered an obstacle but not insurmountable, with reasonable compensation and supportive care. Given the significant level of public interest, a CHIM should be done as open science with regular, controlled dissemination of information into the public domain. Importantly, there was a strong view that the final decision whether to conduct a CHIM should be in the hands of qualified and experienced clinician-scientists and the authorities.
Preference of individuals in the treatment strategies of acute myocardial infarction in China: a discrete choice experiment
Authors: Dai Weiqian , Liu Chang , Liu Jiahe , Lin Yaduan , Cheng Yu , Ming Wai-kit
Published: July 2020

Background

Acute myocardial infarction (AMI) is a significant cause of mortality and morbidity worldwide. Today, with increasing life quality and social economy, people pay much attention to the cost-effectiveness of a treatment strategy. This study investigated the preferences of individuals who would be potential caregivers or patients for AMI treatment in order to provide liable and instructive information for cardiologists and other related physicians.

Methods

A discrete choice experiment was conducted among people to assess preferences for hypothetical AMI treatment scenarios characterized by the attributes of treatment method, mortality within 5 years, complication rate within 1 year, treatment duration and expense. A conditional logit regression model and latent class analysis were used to interpret the collected data systematically. The relative importance of each attribute and willingness to pay of people on the trade-offs between different treatment strategies were estimated.

Results

Participants valued mortality within 5 years most highly (average importance: 40.9, 95%CI 0.447–0.530). Three classes of participants were identified: Class 1 placed the most importance on treatment duration, class 2 corresponded with the overall result while expense was regarded as the most important attribute in class 3. Individuals favored an intermediate treatment duration of about 10 days instead of the shortest (95% CI 1.044–1.248, P < 0.001). People’s characteristics (sex, age, marriage, education and income) affected their preferences (P < 0.01).

Conclusion

People considered a mortality rate within 5 years as the most crucial attribute in the MI treatment and preferred an intermediate treatment duration of about 10 days. Furthermore, the findings estimated the trade-offs acceptable to patients and heterogeneity in preferences for AMI treatment.
Upregulation of fibronectin following loss of p53 function is a poor prognostic factor in ovarian carcinoma with a unique immunophenotype
Authors: Yokoi Ako , Matsumoto Toshihide , Oguri Yasuko , Hasegawa Yoshinori , Tochimoto Masataka , Nakagawa Mayu , Saegusa Makoto
Published: July 2020

Background

We previously demonstrated that ovarian high grade serous carcinomas (OHGSeCa) and ovarian clear cell carcinomas (OCCCa) with an HNF-1β+/p53+/ARID1A+ immunophenotype were associated with the worst unfavorable prognosis. To clarify the molecular mechanisms underlying this finding, we focused on alterations in the p53 signaling pathway in these tumors.

Methods

Changes in cell phenotype and function following knockdown of wild-type p53 (p53-KD) were assessed using OCCCa cells expressing endogenous HNF-1β and ARID1A. The prognostic significance of molecules that were deregulated following p53-KD was also examined using 129 OCCCa/OHGSeCa cases.

Results

p53-KD cells had increased expression of Snail, phospho-Akt (pAkt), and pGSK3β, and decreased E-cadherin expression, leading to epithelial-mesenchymal transition (EMT)/cancer stem cell (CSC) features. The cells also exhibited acceleration of cell motility and inhibition of cell proliferation and apoptosis. Next generation sequencing revealed that fibronectin (FN) expression was significantly increased in the p53 KD-cells, in line with our observation that wild-type p53 (but not mutant p53) repressed FN1 promoter activity. In addition, treatment of OCCCa cells with FN significantly increased cell migration capacity and decreased cell proliferation rate, independent of induction of EMT features. In clinical samples, FN/p53 scores were significantly higher in OCCCa/OHGSeCa with the HNF-1β+/p53+/ARID1A+ immunophenotype when compared to others. Moreover, high FN/high p53 expression was associated with the worst overall survival and progression-free survival in OCCCa/OHGSeCa patients.

Conclusion

These findings suggest that upregulation of FN following loss of p53 function may impact the biological behavior of OCCCa/OHGSeCa, particularly in tumors with an HNF-1β+/p53+/ARID1A+ immunophenotype, through alterations in cell mobility and cell proliferation. The accompanying induction of EMT/CSC properties and inhibition of apoptosis due to p53 abnormalities also contribute to the establishment and maintenance of tumor phenotypic characteristics.
Analysis of SARS-CoV-2 RNA-dependent RNA polymerase as a potential therapeutic drug target using a computational approach
Authors: Aftab Syed Ovais , Ghouri Muhammad Zubair , Masood Muhammad Umer , Haider Zeshan , Khan Zulqurnain , Ahmad Aftab , Munawar Nayla
Published: July 2020

Background

The Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) outbreak originating in Wuhan, China, has raised global health concerns and the pandemic has now been reported on all inhabited continents. Hitherto, no antiviral drug is available to combat this viral outbreak.

Methods

Keeping in mind the urgency of the situation, the current study was designed to devise new strategies for drug discovery and/or repositioning against SARS-CoV-2. In the current study, RNA-dependent RNA polymerase (RdRp), which regulates viral replication, is proposed as a potential therapeutic target to inhibit viral infection.

Results

Evolutionary studies of whole-genome sequences of SARS-CoV-2 represent high similarity (> 90%) with other SARS viruses. Targeting the RdRp active sites, ASP760 and ASP761, by antiviral drugs could be a potential therapeutic option for inhibition of coronavirus RdRp, and thus viral replication. Target-based virtual screening and molecular docking results show that the antiviral Galidesivir and its structurally similar compounds have shown promise against SARS-CoV-2.

Conclusions

The anti-polymerase drugs predicted here—CID123624208 and CID11687749—may be considered for in vitro and in vivo clinical trials.