bluuebunny/crossref_metadata_2025 huggingface dataset:
Directional presplit blasting in an innovative no-pillar mining approach
Authors: Hu Jinzhu , Zhang Xingyu , Gao Yubing , Ma Zimin , Xu Xinzeng , Zhang Xiuping
Published: August 2019

Directional presplit blasting (DPB) technology for an innovative no-pillar mining approach is introduced. First, a mechanical model is established to analyze crack initiation and coalescence using the new technology. The explosion pressure formula containing tress concentration factor explains the relationship between the quantity of explosives and the crack initiation and coalescence. Subsequently, a dynamic finite element simulation method is used to study the stress and damage evolution process of the blasthole wall in ordinary explosion and DPB. The simulation results indicate that the stress concentration factor is approximately 4c10 for the same quantity of explosives. Finally, a field test was conducted in the Fucheng coal mine of China. Based on the field test, the concept of cracking ability is proposed, the relationship between the quantity of explosives and cracking ability is determined, and the quantity of explosives is divided into four stages that are compatible with the roof rock strength. The results can provide some clinical guidance for application of DPB in other projects of the gob-side entry retaining by roof cutting.
Cementless bipolar hemiarthroplasty in a patient with PMF: a case report
Authors: Alturki Abdullah A , Alshammari Nayf A , Alsebayel Firas M , Alhandi Ali A
Published: August 2019

Myelofibrosis is a myeloproliferative disease that falls under a group of bone marrow malignancies known as myeloproliferative neoplasms. It manifests with splenomegaly, anemia, leukocytosis and, less commonly, bone pain. Ruxolitinib, Janus kinase inhibitor, has been shown to increase survival, to improve symptoms and has the potential to decrease osteosclerotic changes. Herein, we present a case of primary myelofibrosis (PMF) in a 60-year-old female who presented with 8-month history of progressive left hip pain and later was diagnosed with pathological neck of femur fracture that was treated with cementless hemiarthroplasty. In conclusion, the use of cementless implants in hip arthroplasty in the presence of PMF has shown to be an effective and safe choice.
Properties of the post-inspiral common envelope ejecta – I. Dynamical and thermal evolution
Authors: Iaconi Roberto , Maeda Keiichi , De Marco Orsola , Nozawa Takaya , Reichardt Thomas
Published: August 2019

We investigate the common envelope binary interaction, that leads to the formation of compact binaries, such as the progenitors of Type Ia supernovae or of mergers that emit detectable gravitational waves. In this work, we diverge from the classic numerical approach that models the dynamic inspiral. We focus instead on the asymptotic behaviour of the common envelope expansion after the dynamic inspiral terminates. We use the SPH code phantom to simulate one of the set-ups from Passy et al., with a 0.88 M⊙, 83 R⊙ RGB primary and a 0.6 M⊙ companion, then we follow the ejecta expansion for 50 yr. Additionally, we utilize a tabulated equation of state including the envelope recombination energy in the simulation (Reichardt et al.), achieving a full unbinding. We show that, as time passes, the envelope’s radial velocities dominate over the tangential ones, hence allowing us to apply an homologous expansion kinematic model to the ejecta. The external layers of the envelope become homologous as soon as they are ejected, but it takes 5000 d (14 yr) for the bulk of the unbound gas to achieve the homologously expanding regime. We observe that the complex distribution generated by the dynamic inspiral evolves into a more ordered, shell-like shaped one in the asymptotic regime. We show that the thermodynamics of the expanding envelope are in very good agreement with those expected for an adiabatically expanding sphere under the homologous condition and give a prediction for the location and temperature of the photosphere assuming dust to be the main source of opacity. This technique ploughs the way to determining the long-term light behaviour of common envelope transients.
Elemental abundances in the centre of the Galactic nuclear disc
Authors: Kovtyukh V V , Andrievsky S M , Martin R P , Korotin S A , Lepine J R D , Maciel W J , Keir L E , Panko E A
Published: August 2019

We have made the first attempt to derive the chemical properties of the Galactic disc at its very central part using high-resolution infrared spectroscopic observations of four classical Cepheids. These stars are located at Galactocentric distances smaller than 1 kpc. All investigated stars show near-to-solar elemental abundances. By combining these new data with our previous studies, our results suggest that the radial distribution of iron abundance on a logarithmic scale gradually increases from the outskirts of the Galactic disc to Galactocentric distances of about 2–4 kpc. There, it reaches a maximal value of about +0.4 dex, and then declines sharply to about the solar value at the Galactic Centre.
Queer Music Theory
Authors: Lee Gavin
Published: August 2019

Queer musical phenomenology refers to the practice of disorientation away from established music theories, including one’s own. In Lewin’s “Phenomenology” article, queering can be understood as his intentional, self-critical, conceptual disorientations—first departing from Schenkerian theory, and then moving toward and finally away from the perception-model. Through a close reading of Lewin in combination with Sara Ahmed’s Queer Phenomenology, which offers a theory of embodied lives marginalized by pathways of normativity, I examine the generalizable application of theories such as queer phenomenology to another domain beyond gender and sexual embodiment: music theory at large. Lewin’s practice models a form of music theory that I regard as phenomenologically queer.
Emerging Therapeutic Targets in Chordomas: A Review of the Literature in the Genomic Era
Authors: Gill Corey M , Fowkes Mary , Shrivastava Raj K
Published: August 2019

Chordomas are rare primary malignant tumors of the bones that occur along the skull base, spine, and sacrum. Long-term survival and neurological outcome continue to be challenging with continued low percentages of long-term survival. Recent studies have used genome, exome, transcriptome, and proteome sequencing to assess the mutational profile of chordomas. Most notably, Brachyury, or T-protein, has been shown to be an early mutational event in chordoma evolution. Clinically actionable mutations, including in the PI3K pathway, were identified. Preliminary evidence suggests that there may be mutational differences associated with primary tumor location. In this study, we review the therapeutic landscape of chordomas and discuss emerging targets in the genomic era.
Prediction of recurrent glioblastoma after laser interstitial thermal therapy: The role of diffusion imaging
Authors: Mahammedi Abdelkader , Bachir Suha , Escott Edward J , Barnett Gene H , Mohammadi Alireza M , Larvie Mykol
Published: August 2019

Background

Evaluate the utility of diffusion-weighted imaging (DWI) for the assessment of local recurrence of glioblastoma (GBM) on imaging performed 24 h following MRI-guided laser interstitial thermal therapy (LITT). We hypothesize that microscopic peritumoral infiltration correlates with early subtle variations on DWI images and apparent diffusion coefficient (ADC) maps.

Methods

Of 64 patients with GBM treated with LITT, 39 had MRI scans within 24 h after undergoing LITT. Patterns on DWI images and ADC maps 24 h following LITT were correlated with areas of future GBM recurrence identified through coregistration of subsequent MRI examinations. In the areas of suspected recurrence within the periphery of post-LITT lesions, signal intensity values on ADC maps were recorded and compared with the remaining peritumoral ring.

Results

Thirty-nine patients with GBM met the inclusion criteria. For predicting recurrent GBM, areas of decreased DWI signal and increased signal on ADC maps within the expected peritumoral ring of restricted diffusion identified 24 h following LITT showed 86.1% sensitivity, 75.2% specificity, and high correlation (r = 0.53) with future areas of GBM recurrence (P < .01). Areas of future recurrence demonstrated a 37% increase in the ADC value (P < .001), compared with findings in the surrounding treated peritumoral region. A significantly greater area under the receiver operating characteristics curve was determined for ADC values (P < .01).

Conclusions

DWI obtained 24 h following LITT can help predict the location of GBM recurrence months before the development of abnormal enhancement. This may alter future treatment planning, perhaps suggesting areas that may be targeted for additional therapy.
Expansion of effector and memory T cells is associated with increased survival in recurrent glioblastomas treated with dendritic cell immunotherapy
Authors: Eoli Marica , Corbetta Cristina , Anghileri Elena , Di Ianni Natalia , Milani Micaela , Cuccarini Valeria , Musio Silvia , Paterra Rosina , Frigerio Simona , Nava Sara , Lisini Daniela , Pessina Sara , Maddaloni Luisa , Lombardi Raffaella , Tardini Maria , Ferroli Paolo , DiMeco Francesco , Bruzzone Maria Grazia , Antozzi Carlo , Pollo Bianca , Finocchiaro Gaetano , Pellegatta Serena
Published: August 2019

Background

The efficacy of dendritic cell (DC) immunotherapy as a single therapeutic modality for the treatment of glioblastoma (GBM) patients remains limited. In this study, we evaluated in patients with GBM recurrence the immune-mediated effects of DC loaded with autologous tumor lysate combined with temozolomide (TMZ) or tetanus toxoid (TT).

Methods

In the phase I-II clinical study DENDR2, 12 patients were treated with 5 DC vaccinations combined with dose-dense TMZ. Subsequently, in eight patients, here defined as Variant (V)-DENDR2, the vaccine site was preconditioned with TT 24 hours before DC vaccination and TMZ was avoided. As a survival endpoint for these studies, we considered overall survival 9 months (OS9) after second surgery. Patients were analyzed for the generation of effector, memory, and T helper immune response.

Results

Four of 12 DENDR2 patients reached OS9, but all failed to show an immunological response. Five of eight V-DENDR2 patients (62%) reached OS9, and one patient is still alive (OS >30 months). A robust CD8+ T-cell activation and memory T-cell formation were observed in V-DENDR2 OS>9. Only in these patients, the vaccine-specific CD4+ T-cell activation (CD38+/HLA-DR+) was paralleled by an increase in TT-induced CD4+/CD38low/CD127high memory T cells. Only V-DENDR2 patients showed the formation of a nodule at the DC injection site infiltrated by CCL3-expressing CD4+ T cells.

Conclusions

TT preconditioning of the vaccine site and lack of TMZ could contribute to the efficacy of DC immunotherapy by inducing an effector response, memory, and helper T-cell generation.
Controlling the Uncontrollable: Perceptions of Balance in People With Parkinson Disease
Authors: Johansson Hanna , Franzén Erika , Skavberg Roaldsen Kirsti , Hagströmer Maria , Leavy Breiffni
Published: August 2019

Background

Exercise improves balance in Parkinson disease (PD), yet the majority of people with the diagnosis are physically inactive. Insights gained from understanding how people with PD (PwPD) make sense of their symptoms and their ability to control them may inform the communication strategies and motivational approaches adopted by physical therapists. To our knowledge, no previous study has qualitatively explored how PwPD perceive the concept of balance and the beliefs they hold concerning their ability to affect balance.

Objective

This study aimed to explore the meaning of balance for PwPD and the beliefs they hold regarding their ability to influence their balance in everyday life.

Design

The design was a qualitative study with an inductive approach.

Methods

In-depth interviews were conducted with 18 participants with PD (age range 46–83 years, Hoehn and Yahr range 1–4), and transcripts were analyzed using qualitative content analysis.

Results

Five main themes emerged from the analysis: remaining in control over the body, adapting behavior to deal with uncertainty, directing focus to stay 1 step ahead, resilience as a defense, and exercise beliefs and reservations. Interpretation of the underlying patterns in the main themes yielded the overarching theme of focus and determination to regain control over shifting balance.

Conclusions

The concept of balance was perceived as both bodily equilibrium and mind-body interplay and was described in the context of remaining in control over one’s body and everyday life. Cognitive resources were utilized to direct focus and attention during balance-challenging situations in a process involving internal dialogue. Even participants who did not express beliefs in their ability to affect balance through exercise used psychological resilience to counter the challenges of impaired balance.
Solving the jigsaw of conflict-related environmental damage: Utilizing open-source analysis to improve research into environmental health risks
Authors: Zwijnenburg Wim , Hochhauser David , Dewachi Omar , Sullivan Richard , Nguyen Vinh-Kim
Published: August 2019

Investigation of the environmental impacts of armed conflict has been made easier in recent years with the development of new and improved methods for documenting and monitoring environmental damage and pollution. For decades, research into conflict-linked environmental damage and its links to human health have been overlooked and research underfunded, hindering a complete humanitarian response and effective post-conflict reconstruction. Recent developments in the field of open-source investigation have shown promising results due to the increased use of mobile phones, access to the internet and freely available methods for remote observation by satellite. Utilizing and analysing these sources of data can help us to understand how conflicts are associated with environmental damage, pollution and their negative impacts upon public health. Further research and development in this field will help to inform more effective humanitarian responses, mitigate risks to health and identify priorities for post-conflict reconstruction programs. Data-driven open-source research can also strengthen international discussions on state accountability for military activities and build a case for the responsibility of warring parties to protect the environment as well as the people who depend on it.
Treatment guidelines in psoriatic arthritis
Authors: Ogdie Alexis , Coates Laura C , Gladman Dafna D
Published: August 2019

Psoriatic arthritis (PsA) is a complex inflammatory musculoskeletal and skin disease. The treatment of PsA has changed substantially over the past 10 years. Clinical practice guidelines are developed to help busy clinicians rapidly integrate evolving knowledge of therapeutic management into practice. In this review, we compare PsA treatment recommendations or guidelines developed by one national organization [ACR and National Psoriasis Foundation (NPF) in 2018], one regional organization (EULAR in 2015), and one international organization (the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis in 2015). We examine the development of guidelines in PsA more broadly and examine similarities and differences in the three sets of recommendations.
Trends of venous thromboembolism risk before and after diagnosis of gout: a general population-based study
Authors: Li Lingyi , McCormick Natalie , Sayre Eric C , Esdaile John M , Lacaille Diane , Xie Hui , Choi Hyon K , Aviña-Zubieta J Antonio
Published: August 2019

Objective

To estimate the overall risk and the temporal trend of venous thromboembolism (VTE), deep vein thrombosis (DVT), and pulmonary embolism (PE) before and after gout diagnosis in an incident gout cohort compared with the general population.

Methods

We conducted a matched cohort study using a province-wide population-based administrative health database in Canada. We calculated incidence rates (IRs) and multivariable adjusted hazard ratios (HRs) for the risk of VTE, DVT and PE before and after gout diagnosis.

Results

Among 130 708 incident individuals with gout (64% male, mean age 59 years), 2071 developed VTE, 1377 developed DVT and 1012 developed PE. IRs per 1000 person-years for gout were 2.63, 1.74 and 1.28 compared with 2.03, 1.28 and 1.06 for non-gout, respectively. The fully adjusted HRs (95% CI) for VTE, DVT and PE were 1.22 (1.13, 1.32), 1.28 (1.17, 1.41) and 1.16 (1.05, 1.29). For the pre-gout period, the fully adjusted HRs (95% CI) were 1.51 (1.38, 1.64), 1.55 (1.40, 1.72) and 1.47 (1.31, 1.66) for VTE, DVT and PE. During the third, second and first years preceding gout, the fully adjusted HRs for VTE were 1.44, 1.56 and 1.62. During the first, second, third, fourth and fifth years after gout, the fully adjusted HRs were 1.63, 1.29, 1.33, 1.28 and 1.22. Similar trends were also seen for DVT and PE.

Conclusion

Increased risks of VTE, DVT and PE were found both before and after gout diagnosis. The risk increased gradually before gout, peaking in the year prior to diagnosis, and then progressively declined. Gout-associated inflammation may contribute to venous thrombosis risk.
Detection of Prompt Gamma Radiation Near the LVR-15 Research Reactor
Authors: Viererbl Ladislav , Klupák Vít , Kolros Antonín , Assmann Vratislavská Hana , Lahodová Zdena
Published: August 2019

The paper describes a method of pulse height spectrum measurement in a wide energy range. The LVR‑15 research reactor building was chosen to demonstrate this method. Pulse height spectra were measured on the third floor of the reactor building. Two types of scintillation detectors, NaI (Tl) and a plastic scintillator, were used. The detectors were placed for about 25 m from the reactor core, thus, separated from the primary circuit water in the reactor pool, biological shielding, building wall and other constructional materials. Spectra were measured in a wide energy range from 30 keV to 1000 MeV, in which signals were recorded from natural and man-made radionuclides, prompt gamma radiation and cosmic radiation. Experimental data were collected both while the reactor was in operation and while it was out of operation. This study confirms that differences in these spectra can be detected remotely over relatively large distances from the reactor core by adequately simple detection means.
Do Family Privileges Bring Gender Equality? Instrumentalism and (De) Stereotyping of STEM Career Aspiration among Chinese Adolescents
Authors: Liu Ran
Published: August 2019

When studying the persistent underrepresentation of a women in science, engineering, technology, and mathematics (STEM) fields across different countries, some evidence shows a paradox of affluence: gender differences in STEM aspirations and outcomes are found to be more pronounced in more developed, postindustrial countries and among students from more affluent families. The argument of “indulging gendered selves” provides an explanation: students in more affluent settings are less compelled to pursue lucrative STEM careers and more encouraged to indulge gendered passions as a form of self-expression. Extending this argument, this paper uses nationally representative data from China to examine the effect of family privileges on adolescents’ STEM aspirations. Two distinct mechanisms are identified: instrumentalism, which considers the instrumental calculation of material security and economic returns in developing career aspirations, and (de) stereotyping, which considers whether family privileges cultivate or alleviate gender stereotypes. Findings show that less privileged girls such as ethnic minorities and those having rural hukou tend to have higher instrumental motivation to learn math, indicating an instrumentalism mechanism; on the other hand, girls with privileges such as higher parental education and more books at home enjoy more gender-egalitarian values, indicating a de-stereotyping mechanism. Moreover, Internet access at home as a privilege can foster gender stereotypes and decrease students’ motivation to learn math, and the latter association is stronger for girls than boys. Results suggest the importance of distinguishing the instrumentalism and (de) stereotyping mechanisms and the need for educational programs to refute gender stereotypes.
Evaluating Sufficient Similarity of Botanical Dietary Supplements: Combining Chemical and In Vitro Biological Data
Authors: Ryan Kristen R , Huang Madelyn C , Ferguson Stephen S , Waidyanatha Suramya , Ramaiahgari Sreenivasa , Rice Julie R , Dunlap Paul E , Auerbach Scott S , Mutlu Esra , Cristy Tim , Peirfelice Jessica , DeVito Michael J , Smith-Roe Stephanie L , Rider Cynthia V
Published: August 2019

Botanical dietary supplements are complex mixtures with numerous potential sources of variation along the supply chain from raw plant material to the market. Approaches for determining sufficient similarity (ie, complex mixture read-across) may be required to extrapolate efficacy or safety data from a tested sample to other products containing the botanical ingredient(s) of interest. In this work, screening-level approaches for generating both chemical and biological-response profiles were used to evaluate the similarity of black cohosh (Actaea racemosa) and Echinacea purpurea samples to well-characterized National Toxicology Program (NTP) test articles. Data from nontargeted chemical analyses and gene expression of toxicologically important hepatic receptor pathways (aryl hydrocarbon receptor [AhR], constitutive androstane receptor [CAR], pregnane X receptor [PXR], farnesoid X receptor [FXR], and peroxisome proliferator-activated receptor alpha [PPARα]) in primary human hepatocyte cultures were used to determine similarity through hierarchical clustering. Although there were differences in chemical profiles across black cohosh samples, these differences were not reflected in the biological-response profiles. These findings highlight the complexity of biological-response dynamics that may not be reflected in chemical composition profiles. Thus, biological-response data could be used as the primary basis for determining similarity among black cohosh samples. Samples of E. purpurea displayed better correlation in similarity across chemical and biological-response measures. The general approaches described herein can be applied to complex mixtures with unidentified active constituents to determine when data from a tested mixture (eg, NTP test article) can be used for hazard identification of sufficiently similar mixtures, with the knowledge of toxicological targets informing assay selection when possible.
Youthfuls, Matures, and Veterans: Subtyping Subjective Age in Late-Career Employees
Authors: Nagy Noemi , Fasbender Ulrike , North Michael S
Published: August 2019

Subjective age research is on the rise, and the term has become an overarching way of describing how individuals idiosyncratically experience the aging process (“How old one feels”). Furthermore, the theory of aged heterogeneity posits that interindividual variability of similarly aged adults increases over time, suggesting that subjective age may become more variable in later life. Subjective aging has usually been investigated in a variable-centered manner—which over-assumes homogeneity among people’s aging experience—producing mixed evidence regarding the utility of single subjective age constructs in different populations. Person-centered approaches, in contrast, acknowledge interindividual heterogeneity in the aging experience, providing an alternative angle of investigation, and enable insights into how variables operate conjointly within persons. Therefore, the current research uses a latent profile analysis to investigate various conceptualizations of subjective age among late-career employees. Using a time-lagged design with a sample of 229 older workers (aged 50–66 years), we uncover three distinct subjective age profiles: Youthfuls, Matures, and Veterans. Moreover, we investigate how person-related correlates of subjective aging differ between the uncovered profiles, and how, in turn, these profiles are related to work engagement and organizational citizenship behavior. Through a person-centered approach, we receive valuable insights on the concurrent interplay of various subjective age concepts in a highly heterogeneous population and provide a better understanding of subjective age in late career.
Genetic structure of the Chagas disease vector Triatoma infestans (Hemiptera: Reduviidae) based on nuclear and mitochondrial DNA sequences
Authors: Fernández Cintia J , González-Ittig Raúl E , García Beatriz A
Published: August 2019

In the present study, we analysed the genetic structure of Triatoma infestans populations with a phylogeographical approach using sequences of the mitochondrial NADH dehydrogenase subunit 5 (ND5) and the nuclear elongation factor-1 alpha (EF-1α) genes of bugs obtained from Argentina and Bolivia. Spatially circumscribed haplogroups were distinguished from the ND5 gene sequences, one distributed exclusively to the south of the studied area and, in agreement with the results from the EF-1α gene, one haplogroup limited to Bolivia and another to Morajú located in the Chaco region of Argentina. In both the ND5 and EF-1α networks, the most widespread haplogroup or allele group showed a star-like topology, which is compatible with a recent demographic expansion. The asymmetric historical gene flow detected from a population of the Chaco region towards Bolivia and the spatiotemporal phylogeographical reconstruction of lineage dispersal would support the hypothesis that postulates the Chaco biogeographical region as the area of origin for the species. However, additional studies with a broader sampling in the Andean region are needed to define with certainty whether the origin of T. infestans is Chacoan or Andean.
A randomized pilot study to investigate the effect of opioids on immunomarkers using gene expression profiling during surgery
Authors: Wodehouse Theresa , Demopoulos Mary , Petty Robert , Miraki-Moud Farideh , Belhaj Alla , Husband Michael , Fulton Laura , Randive Nilesh , Oksche Alexander , Mehta Vivek , Gribben John , Langford Richard
Published: August 2019

Endogenous opioid peptides and exogenous opioids modulate immune function, and animal and human studies have shown that some have a depressant immunomodulatory effect. This is potentially of high clinical significance, eg, in cancer patients and surgery. The primary objective of this pilot study was to evaluate the effect of morphine and oxycodone on immune pathways associated with immunosuppression in gynecological laparotomy patients. Gene expression was analyzed in CD4+, CD8+, and natural killer (NK) cells using the 3′ Affymetrix microarray. Patients were randomized to receive morphine, oxycodone, or nonopioid “control” analgesia during and after surgery. Genes demonstrating differential expression were those with a ≥±2-fold difference and P-value ≤0.05 after analysis of variance. Cytometric bead array and NK cell degranulation assay were used to investigate changes in serum cytokine concentration and in NK cell cytotoxicity, respectively. Forty patients had satisfactory RNA which was hybridized to gene chips. Genes were identified (Partek Genomics Suite 6.6) at baseline, 2, 6, and 24 hours and were either ≥2-fold upregulated or downregulated from baseline. At 2 hours, a large number of genes were downregulated with morphine but not with control analgesia or oxycodone. Statistically significant increases in IL-6 concentrations were induced by morphine only; NK cell activity was suppressed with morphine, but maintained with oxycodone and epidural analgesia. Gene expression profiles suggest that at 2 hours, post incision morphine appeared to be immunosuppressive as compared to oxycodone and nonopioid control analgesia.
Mortality Risk of Atypical Antipsychotics for Behavioral and Psychological Symptoms of Dementia
Authors: Yeh Ta-Chuan , Tzeng Nian-Sheng , Li Juo-Chi , Huang Yu-Chieh , Hsieh Huai-Te , Chu Che-Sheng , Liang Chih-Sung
Published: August 2019

Background

Evidence suggests that atypical antipsychotics (AAPs) exert a short-term mortality risk in people with dementia. We assessed whether additional randomized clinical trials influence the current evidence and the potential effect modifiers.

Methods

Electronic databases were systematically searched for randomized controlled trials from their inception through March 2018. A random-effects model was used for analysis. Potential effect modifiers were examined through meta-regression. Trial sequential analysis was performed to quantify the statistical reliability of data in the cumulative meta-analysis with adjustment of significance levels for sparse data and repetitive testing on accumulating data. Certainty of evidence and risk of bias were also evaluated.

Results

We found that compared with placebos, AAPs may increase the risk of mortality (odds ratio [OR], 1.536; 95% confidence intervals [CIs], 1.028–2.296; P = 0.036, high certainty). In the subgroup analysis, the estimated ORs were the highest for olanzapine (1.919; P = 0.232), followed by those for quetiapine (1.663; P = 0.506), aripiprazole (1.649; P = 0.297), and risperidone (1.354; P = 0.277); however, the mortality risk presented by individual AAPs did not exhibit between-group differences. The meta-regression did not identify any effect modifiers, including the chlorpromazine equivalent dose, trial duration, and cognitive status. The trial sequential analysis revealed that future similar trials are unlikely to alter our findings.

Conclusions

Atypical antipsychotics are associated with increased short-term mortality risk, although a disease-drug interaction may contribute to such risk in people with dementia. Patients with dementia may still benefit by AAPs after appropriate assessment of the disease severity as well as the dosage of AAPs, treatment duration, and monitoring of AAPs.
Extracellular matrix-based hydrogels obtained from human tissues: a work still in progress
Authors: Gazia Carlo , Tamburrini Riccardo , Asthana Amish , Chaimov Deborah , Muir Sean M. , Marino Domenica I. , Delbono Luciano , Villani Valentina , Perin Laura , Di Nardo Paolo , Robertson John , Orlando Giuseppe
Published: August 2019

Purpose of review

The current review summarizes contemporary decellularization and hydrogel manufacturing strategies in the field of tissue engineering and regenerative medicine.

Recent findings

Decellularized extracellular matrix (ECM) bioscaffolds are a valuable biomaterial that can be purposed into various forms of synthetic tissues such as hydrogels. ECM-based hydrogels can be of animal or human origin. The use of human tissues as a source for ECM hydrogels in the clinical setting is still in its infancy and current literature is scant and anecdotal, resulting in inconclusive results.

Thus far the methods used to obtain hydrogels from human tissues remains a work in progress. Gelation, the most complex technique in obtaining hydrogels, is challenging due to remarkable heterogeneity of the tissues secondary to interindividual variability. Age, sex, ethnicity, and preexisting conditions are factors that dramatically undermine the technical feasibility of the gelation process. This is contrasted with animals whose well defined anatomical and histological characteristics have been selectively bred for the goal of manufacturing hydrogels.
Terminal Ileitis Presenting With a Spontaneously Reduced Ileocolic Intussusception Diagnosed by Point-of-Care Ultrasonography
Authors: Riera Antonio , Langhan Melissa , Silva Cicero Torres
Published: August 2019

Point-of-care ultrasound can be used in the initial workup of ileocolic (IC) intussusception. In general, these lesions require immediate attention and reduction to prevent ischemic bowel injury. We discuss the case of a 27-month-old boy whose IC intussusception was found to spontaneously reduce before a radiology performed ultrasound and the planned air enema reduction procedure. Radiology ultrasound revealed significant inflammatory changes of the terminal ileum. The incidence of spontaneous reduction of IC intussusception is not definitively known. It is important to be familiar with the possibility of spontaneous reduction as children are often referred to academic centers for radiological or surgical reduction. This may also impact the sensitivity of studies that evaluate test characteristics of point-of-care ultrasound compared with radiology performed ultrasound for the diagnosis of IC intussusception. We review the diagnostic technique for IC intussusception and the importance of a prereduction ultrasound immediately before image-guided pressure reduction attempt.
Low-grade Appendiceal Mucinous Neoplasm and Endometriosis: Incidental Coincident Pathologies at Cesarean Section
Authors: Yohannes Nathaniel , Watkins Jaclyn C. , Weeks Amy G. , Osmundson Sarah S. , Shi Chanjuan , Kovach Alexandra E.
Published: August 2019

Incidental pathologic findings at the time of Cesarean section are exceedingly uncommon. Similarly, occult low-grade appendiceal mucinous neoplasms and other noninflammatory, non-neoplastic appendiceal pathologies are rare, although appendiceal neoplasia, most commonly well-differentiated neuroendocrine tumors, may be found during evaluation of acute appendicitis. Here we report the first case of incidental coincident low-grade appendiceal mucinous tumor and endometriosis involving the appendix at the time of Cesarean section. We highlight pitfalls in the histopathologic evaluation of these processes, particularly given the setting of decidualization of ectopic endometrial stroma, as well as the prognostic implications of low-grade appendiceal mucinous tumors to emphasize the importance of clinicopathologic correlation and careful intraoperative examination of the appendix and other visible structures during Cesarean section.
Cytological Abnormalities and its relation to CD4 count among HIV seropositive women living in Ahvaz, southwest of Iran
Authors: Darvishi Amene , Alavi Seyed Mohammad , Khafaie Morteza Abdullatif , Sokooti Alireza , Molavi Shahla , Salmanzadeh Shokralleh
Published: August 2019

Introduction

Human immunodeficiency virus (HIV) infection is a known risk factor for abnormal cervical cytology and cervical cancer. The aim of this study was to investigate cervical cytological abnormalities and its relation with CD4 (T4 Lymphocyte) count among HIV seropositive women.

Methods

We conducted a study on 58 HIV positive women referred to Ahvaz Counseling Center for Behavioral Disease, southwest of Iran between 2016 and 2017. Pap smear was performed for all participants from the cervix and endocervix. Patient’s’ characteristics including age, duration of disease, treatment with anti-retroviral treatment (ART), marital status, number of children, and contraception method were also recorded. Cervical cytological abnormalities reported as Bethesda system (TBS). A regular blood sample was taken from all the patients to evaluate the CD4 cells counts. Logistic regression models were used to obtain OR of presences of cytological abnormalities related to CD4 counts, controlling for important factors.

Results

Out of 58 patients only 5 were not under ART. We demonstrated that 29.3 % of patients had squamous cell abnormalities and these abnormalities, was more prevalent among 30-40 years old patients (70.6%). The prevalence of ASC-US (Atypical Squamous Cells of Undetermined Significance), LSIL (Low-Grade Squamous Intraepithelial Lesions) and HSIL (High-Grade Squamous Intraepithelial Lesions) were 19.0%, 3.4%, and 6.9% respectively. Overall 9 patients need to repeat Pap smear test. Presence of cervical cytological abnormalities was not associated with the CD4 count, even after adjusting for the variable such age, duration of disease and ART.

Conclusion

We found a high prevalence of ASC-US in HIV-infected women which was independent of age, duration of diseases and history of ART. Though cervical cancer screening in this population might have a substantial public health benefit.

Summary box

- More than 70% of cervical cancers incidences associated with Genital HPV infections

- Prevalent of Squamous cell abnormalities among HIV-infected women was about sex time more than general population

- We demonstrated that squamous cell abnormalities are more prevalent in middle age women (30 to 40 years)

- The high prevalence of Squamous cell abnormalities in HIV-infected women warrants the need for regular Pap smear screening
Triage-based care of people with Back Pain: STarT Back or Start diagnosing? An observational study.
Authors: Germon Tim , Jack Alex , Hobart Jeremy
Published: August 2019

Objectives
Back pain is a massive public health problem. The STarT Back Screening Tool (SBST) was developed for use in primary care to triage people with lumbar pain, classifying them as low, medium or high risk of prolonged symptoms. This classification guides non-surgical interventions including manual treatments, exercise and cognitive behavioural therapy. Claims suggest SBST brings generic health and cost benefits. National guidance recommends STarT Back is used at the first primary care consultation but can be used at any stage. For SBST to be an effective triage tool it should distinguish structural from non-structural pain. We tested this requirement in consecutive people referred to a single triage practitioner, hypothesising it was not possible conceptually.
Design
An observational study of the relationship between routine, prospectively collected triage data and diagnosis.
Setting
A secondary care spinal triage service based in a teaching hospital.
Participants
We studied consecutive referrals with lumbar pain triaged by a single extended scope practitioner (ESP) over 22 months (Nov 2015-Sept 2017).
Main Outcome Measures
SBST and pain visual analogue scores (VAS: 0-10) were collected at the initial consultation. We compared data for people with and without surgically remedial lesions.
Results
1041 people were seen (61% female, mean age 53), n=234 (28%) had surgically amenable explanations for pain. People with surgical lesions were older (58 v 51yrs), more likely male (48 v 35%) and had higher VAS scores (6.8 v 6.1). Surgery and non-surgery subgroups had similar SBST total and domain score distribution profiles. The surgery subgroup had less low risk (9%v21%) and more high risk (37% v 30%) classified people.
Conclusion
SBST scores did not differentiate surgical from non-surgical pathologies. It seems unlikely that symptom questionnaires can estimate prognosis accurately unless everyone has the same diagnosis, not just the same symptom. Diagnosis, rather than questionnaire scores, should guide treatment and inform prognosis.
Prevalence and clinical importance of titin truncating variants in adults without known congestive heart failure
Authors: Pirruccello James P. , Bick Alexander , Friedman Samuel , Chaffin Mark , Aragam Krishna G. , Choi Seung Hoan , Lubitz Steven A. , Ho Carolyn Y. , Ng Kenney , Philippakis Anthony , Ellinor Patrick T. , Kathiresan Sekar , Khera Amit V.
Published: August 2019

Background

Cross-sectional studies of various forms of dilated cardiomyopathy have noted a truncating mutation in the gene encoding titin (‘TTNtv’) in 7-30% of patients, but the clinical importance of identifying a TTNtv in an asymptomatic adult is largely unknown. In contrast to cross-sectional studies, prospective cohort studies allow for unbiased estimates of the disease risks associated with a genotype exposure.

Objectives

To determine the prevalence of cardiac imaging abnormalities and risk of incident disease among middle-aged TTNtv carriers without known congestive heart failure.

Methods

We analyze exome sequencing data of 45,747 participants of the UK Biobank without known congestive heart failure to identify TTNtv carriers. Among 10,552 with cardiac magnetic resonance imaging (MRI), we determine the relationship between TTNtv carrier status and left ventricular ejection fraction. In this prospective cohort, we quantify the absolute and relative risks of incident disease in TTNtv carriers versus noncarriers.

Results

Among 45,747 middle-aged participants without known congestive heart failure, 196 (0.43%) harbored a TTNtv. The average ejection fraction was 61% in TTNtv carriers versus 65% in noncarriers (P = 1.8 × 10−8), with a 9.3-fold increase (95% CI 3.9 – 22.2) in odds of subnormal ejection fraction (P = 5.7 × 10−5). Over a median follow-up of 6.9 years, a composite endpoint of incident dilated cardiomyopathy, congestive heart failure, or all-cause mortality was observed in 6.6% of TTNtv carriers versus 2.9% of non-carriers (adjusted hazard ratio 2.5; 95% CI 1.4 – 4.3; p = 1.1 × 10−3).

Conclusions

Approximately 1 in 230 middle-aged adults without known congestive heart failure harbored a TTNtv. These carriers had a substantially increased relative risk—but modest absolute risk—of having a subnormal ejection fraction or manifesting clinical disease during prospective follow-up.

Condensed Abstract

Cross-sectional studies of dilated cardiomyopathy have noted a truncating mutation in the gene encoding titin (‘TTNtv’) in up to 30% of patients—but the clinical importance of TTNtv in asymptomatic adults is largely unknown. Here, we observe a TTNtv in 0.43% of 45,747 middle-aged adults. Average ejection fraction was 61% in TTNtv carriers versus 65% in non-carriers (p<0.001). Over a median follow-up of 7 years, incident congestive heart failure or mortality was observed in 6.6% of TTTtv carriers versus 2.9% of non-carriers (hazard ratio 2.5; p = 0.001).
An Analysis for Key Indicators of Reproducibility in Radiology
Authors: Wright Bryan D. , Vo Nam , Nolan Johnny , Johnson Austin L. , Braaten Tyler , Tritz Daniel , Vassar Matt
Published: August 2019

Background

Given the central role of radiology in patient care, it is important that radiological research is grounded in reproducible science. It remains unexamined whether there is a lack of reproducibility or transparency in radiologic research.

Purpose

The purpose of this study was to analyze published radiology literature for the presence or absence of key indicators of reproducibility.

Methods

This cross-sectional, retrospective study was performed by conducting a search of the National Library of Medicine to identify publications contained within journals in the field of Radiology. Journals that were not written in English or MEDLINE indexed were excluded from the analysis. Studies published from January 1, 2014 to December 31, 2018 were used to generate a random list of 300 publications for this meta-analysis. A pilot-tested, Google form was used to evaluate key indicators of reproducibility in the queried publications.

Results

Our initial search returned 295,543 records, from which 300 were randomly selected for analysis. Of these 300 records, 294 met the inclusion criteria. Among the empirical publications, 5.6% contained a data availability statement (11/195, 95% CI: 3.0-8.3), 0.51% provided clearly documented raw data (1/195), 12.0% provided a materials availability statement (23/191, 8.4-15.7), none provided analysis scripts, 4.1% provided a preregistration statement (8/195, 1.9-6.3), 2.1% provided a protocol statement (4/195, 0.4-3.7), and 3.6% were preregistered (7/195, 1.5-5.7).

Conclusion

Our findings demonstrate that key indicators of reproducibility are missing in the field of radiology. Thus, the ability to reproduce radiological studies may be problematic and may have potential clinical implications.
Coverage profile correction of shallow-depth circulating cell-free DNA sequencing via multi-distance learning
Authors: Larson Nicholas B. , Larson Melissa C. , Na Jie , Sosa Carlos , Wang Chen , Kocher Jean-Pierre , Rowsey Ross
Published: August 2019

Shallow-depth whole-genome sequencing (WGS) of circulating cell-free DNA (ccfDNA) is a popular approach for non-invasive genomic screening assays, including liquid biopsy for early detection of invasive tumors as well as non-invasive prenatal screening (NIPS) for common fetal trisomies. In contrast to nuclear DNA WGS, ccfDNA WGS exhibits extensive inter- and intra-sample coverage variability that is not fully explained by typical sources of variation in WGS, such as GC content. This variability may inflate false positive and false negative screening rates of copy-number alterations and aneuploidy, particularly if these features are present at a relatively low proportion of total sequenced content. Herein, we propose an empirically-driven coverage correction strategy that leverages prior annotation information in a multi-distance learning context to improve within-sample coverage profile correction. Specifically, we train a weighted k-nearest neighbors-style method on non-pregnant female donor ccfDNA WGS samples, and apply it to NIPS samples to evaluate coverage profile variability reduction. We additionally characterize improvement in the discrimination of positive fetal trisomy cases relative to normal controls, and compare our results against a more traditional regression-based approach to profile coverage correction based on GC content and mappability. Under cross-validation, performance measures indicated benefit to combining the two feature sets relative to either in isolation. We also observed substantial improvement in coverage profile variability reduction in leave-out clinical NIPS samples, with variability reduced by 26.5-53.5% relative to the standard regression-based method as quantified by median absolute deviation. Finally, we observed improvement discrimination for screening positive trisomy cases reducing ccfDNA WGS coverage variability while additionally improving NIPS trisomy screening assay performance. Overall, our results indicate that machine learning approaches can substantially improve ccfDNA WGS coverage profile correction and downstream analyses.
Forensics and DNA Barcodes – Do Identification Errors Arise in the Lab or in the Sequence Libraries?
Authors: Pentinsaari Mikko , Ratnasingham Sujeevan , Miller Scott E. , Hebert Paul D. N.
Published: August 2019

Forensic studies often require the determination of biological materials to a species level. As such, DNA-based approaches to identification, particularly DNA barcoding, are attracting increased interest. The capacity of DNA barcodes to assign newly encountered specimens to a species relies upon access to informatics platforms, such as BOLD and GenBank, which host libraries of reference sequences and support the comparison of new sequences to them. As parameterization of these libraries expands, DNA barcoding has the potential to make valuable contributions in diverse forensic contexts. However, a recent publication called for caution after finding that both platforms performed poorly in identifying specimens of 17 common insect species. This study follows up on this concern by asking if the misidentifications reflected problems in the reference libraries or in the query sequences used to test them. Because this reanalysis revealed that missteps in acquiring and analyzing the query sequences were responsible for the misidentifications, a workflow is described to minimize such errors in future investigations. The present study also revealed the limitations imposed by the lack of a polished species-level taxonomy for many groups. In such cases, forensic applications can be strengthened by mapping the geographic distributions of sequence-based species proxies rather than waiting for the maturation of formal taxonomic systems based on morphology.