bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of knee resizing illusions on pain and swelling in symptomatic knee osteoarthritis: a case report
Authors: MacIntyre Erin , Sigerseth Maja , Pulling Brian W. , Newport Roger , Stanton Tasha R.
Published: November 2019

Introduction:

Resizing illusions that manipulate perceived body size are analgesic in some chronic pain conditions. Little is known whether such illusions may also alter other physiological features, such as swelling.

Objectives:

To determine the effects of a knee resizing illusion on knee pain and swelling in symptomatic osteoarthritis.

Methods:

This case study was extracted from a larger study evaluating the analgesic effects of resizing illusions in people with knee osteoarthritis. A mediated reality system (alters real-time video) was used to provide resizing “stretch” and “shrink” illusions of the knee. Knee pain intensity (0–100 numerical rating scale) was measured before and after illusion and after sustained (3 minutes) and repeated (n = 10) illusions. In this case study, knee swelling (leg circumference below, at, and above the knee) was also measured.

Results:

The 55-year-old male participant reported a long history of episodic knee pain and swelling that was subsequently diagnosed as severe osteoarthritis in 2013. In the first testing session, the participant experienced an increase in pain with the shrink illusion and a decrease in pain with stretch illusion. A noticeable increase in knee swelling was also observed. Thus, in sessions 2/3, swelling was also assessed. The stretch illusion decreased pain to the largest extent, but resulted in increased knee swelling. Repeated and sustained stretch illusions had cumulative analgesic effects but resulted in cumulative increases in swelling. While the shrink illusion increased pain, sustained (∼10 minutes) visual minification of the entire knee and leg reduced both pain and swelling.

Conclusion:

Our case report suggests that both pain and swelling may be modifiable by altering body-relevant sensory input in symptomatic knee osteoarthritis.
Surgical Approach and Periprocedural Outcomes by Race and Ethnicity of Children Undergoing Craniosynostosis Surgery
Authors: Wallace Erin R. , Birgfeld Craig , Speltz Matthew L. , Starr Jacqueline R. , Collett Brent R.
Published: November 2019

Background:

Surgical repair for craniosynostosis varies depending on the infant’s age, location of suture fusion, and approach (e.g., open versus endoscopic). Existing data suggest possible racial and ethnic disparities in timely access to surgical care for craniosynostosis that may, in turn, be associated with surgical approach and perioperative outcomes. This study examined racial and ethnic variation in craniosynostosis operations by surgical approach and perioperative outcomes.

Methods:

Data were collected by the 2013 to 2015 Pediatric National Surgical Quality Improvement Program. Patients aged younger than 24 months with diagnoses and procedure codes consistent with surgery for craniosynostosis were identified. Periprocedural characteristics and surgical approach (open, endoscopic/minimally invasive, or both) were examined descriptively, overall, and separately by race and ethnicity.

Results:

The authors identified 1982 admissions. Mean age at surgery was 7.8 ± 4.7 months. Ninety-one percent of procedures were classified as open operations, 5.8 percent were endoscopic, and 3.4 percent were both open and endoscopic. Relative to white/non-Hispanic patients, Hispanic and nonwhite patients underwent surgery at older ages, experienced longer operative and anesthesia times, and were hospitalized longer. Hispanic patients had the highest rates of open operations.

Conclusions:

These data suggest that Hispanic and nonwhite patients tend to undergo craniosynostosis repair at older ages and to have lengthier operations than white/non-Hispanic patients. Although we were unable to examine the root cause(s) of these differences, delayed diagnosis is one factor that might result in surgery at an older age and more complex operations requiring open surgery. Prospective studies examining racial/ethnic disparities are needed to inform a comparison of outcomes associated with surgical approach.
Analysis of the Visual Perception of Female Breast Aesthetics and Symmetry: An Eye-Tracking Study
Authors: Pietruski Piotr , Paskal Wiktor , Paskal Adriana M. , Jaworowski Janusz , Paluch Łukasz , Noszczyk Bartłomiej
Published: November 2019

Background:

Because of its subjective character, the term “breast attractiveness” is poorly defined and thus its reliable standardized assessment can be particularly challenging. Because of objective analysis of the observer’s gaze pattern, eye-tracking technology may provide a better insight into the visual perception of breast aesthetics and symmetry.

Methods:

One hundred observers, 50 women and 50 men, assessed the aesthetics and symmetry of eight types of female breasts displayed as digital images on frontal, lateral, and oblique projections. The gaze pattern of each observer was recorded using eye-tracking technology, and gaze data were subsequently analyzed.

Results:

Although sex and breast type exerted an effect on attention capturing by some areas of interest, key characteristics of gaze patterns in female and male observers were essentially the same. Irrespective of observers’ sex, the longest fixation duration and the highest fixation number were recorded for lower breast regions, in particular, for the nipple-areola complex. Mean fixation duration in this area corresponded to 58 and 57 percent of overall observation time for female and male observers, respectively, during the assessment of breast aesthetics; and to 56 and 52 percent of overall observation time for female and male observers, respectively, during the assessment of breast symmetry.

Conclusions:

Nipple-areola complex and lower breast are key focus areas for the assessment of breast aesthetics and symmetry. Gaze data collected during this study may constitute a valuable source of reference values for future eye-tracking research on various patient groups’ visual perception of breast attractiveness and deformities.
Prioritizing Patient Safety Efforts in Office Practice Settings
Authors: Kravet Steven , Bhatnagar Melissa , Dwyer Marian , Kjaer Klaus , Evanko John , Singh Hardeep
Published: November 2019

Objectives

Outpatient care settings face unique risks of adverse events and medico-legal liability, often worsened by inconsistent processes and fragmented care. Health systems are increasingly providing integrated care that includes outpatient care, but models of how to systematically target medico-legal risk in office practices are largely absent. Innovative and scalable efforts are needed to guide large health systems in their approach to outpatient safety.

Methods

A malpractice consortium consisting of five large health care delivery systems identified that its ambulatory care cases (including office practices, outpatient hospital settings, and emergency departments) account for 30% to 35% of annual medical malpractice costs, and missed or delayed diagnoses account for approximately 50% of office practice liability risk. To further understand risks and opportunities in office-based practices, a team of patient safety and loss prevention professionals conducted site visits to seven outpatient-affiliated sites of the five health systems from January to March 2016 and interviewed several key informant members of physician, nursing, and administrative leadership.

Results

We identified eight common patient safety risk domains based on analysis of eight sets of group interviews. Risk domains were then prioritized by members of the consortium leadership using scoring criteria that we developed based on existing risk assessment and prioritization approaches. The method helped identify communication and follow-up of diagnostic test results in the outpatient setting as the single most important risk area to target improvement efforts.

Conclusions

A targeted approach to identify a single high-risk area led to development of dedicated teams to conduct local patient safety improvement projects at the affiliated health systems and for sharing lessons learned. Similar efforts elsewhere could lead to safety improvements in office practices at other large health systems.
Eligibility for differentiated models of HIV treatment service delivery: an estimate from Malawi and Zambia
Authors: Hoffman Risa M. , Balakasi Kelvin , Bardon Ashley R. , Siwale Zumbe , Hubbard Julie , Kakwesa Gift , Haambokoma Mwiza , Kalua Thoko , Pisa Pedro , Moyo Crispin , Dovel Kathryn , Xulu Thembi , Sanne Ian , Fox Matt , Rosen Sydney
Published: November 2019

Background:

Little is known about the proportion of HIV-positive clients on antiretroviral therapy (ART) who meet stability criteria for differentiated service delivery (DSD) models. We report the proportion of ART clients meeting stability criteria as part of screening for a randomized trial of multimonth dispensing in Malawi and Zambia.

Methods:

For a DSD trial now underway, we screened HIV-positive clients aged at least 18 years presenting for HIV treatment in 30 adult ART clinics in Malawi and Zambia to determine eligibility for DSD. Stability was defined as on first-line ART (efavirenz/tenofovir/lamivudine) for at least 6 months, no ART side effects, no toxicity or infectious complications, no noncommunicable diseases being treated in ART clinic, no lapses in ART adherence in the prior 6 months (>30 days without taking ART), and if female, not pregnant or breastfeeding.

Results:

In total, 3465 adult ART clients were approached between 10 May 2017 and 30 April 2018 (Malawi: 1680; Zambia: 1785). Of the 2938 who answered screening questions (Malawi: 1527; Zambia: 1411), 2173 (73.5%) met criteria for DSD eligibility (Malawi: 72.8%; Zambia: 74.3%). The most common reasons for ineligibility were being on ART less than 6 months (9.6%) and a regimen other than standard first-line (7.9%).

Conclusion:

Approximately three-quarters of all adult clients presenting at ART clinics in Malawi and Zambia were eligible for DSD using a typical definition of stability. High uptake of DSD models by eligible clients would have a major impact on the infrastructure and the allocation of HIV treatment resources.
HIV postexposure prophylaxis-in-pocket: long-term follow-up of individuals with low-frequency, high-risk HIV exposures
Authors: Alghamdi Amenah , Hempel Amanda , Heendeniya Amila , Clifford-Rashotte Matthew , Tan Darrell H.S. , Bogoch Isaac I.
Published: November 2019

Background:

HIV preexposure prophylaxis and postexposure prophylaxis are two major biomedical HIV prevention modalities. The utility of these prevention tools for individuals with infrequent high-risk HIV exposures remains uncertain. HIV postexposure prophylaxis-in-pocket (’PIP’) may be an effective HIV prevention tool in such situations. Here, we present long-term follow-up of a cohort of patients initiated on PIP for HIV prevention.

Methods:

We retrospectively evaluated clinical characteristics of patients initiated on PIP as a primary HIV prevention tool between 1 January 2016 to 31 May 2019 at the Toronto General Hospital HIV Prevention Clinic and St. Michael's Hospital HIV Clinic, both in Toronto, Canada. Patients were referred for consideration of a biomedical HIV prevention modality. Individuals with a low frequency of high-risk exposures to HIV were initiated on PIP after counselling, and were followed at regular intervals. Demographic and clinical data was collected with a standardized form.

Results:

In total, 79 patients were initiated on PIP as a primary HIV prevention modality and followed for a mean duration of 14.8 months combining for a total of 97.3 patient-years. Twenty-one (26.6%) patients used their PIP, and 32 courses of PIP were taken during the study period. Transitions between HIV prevention modalities included 13 (16.5%) patients who transitioned from PrEP to PIP, and 22 (27.8%) patients who transitioned from PIP to PrEP. No HIV seroconversions were detected during the course of this study.

Conclusion:

PIP is helpful HIV prevention modality for individuals with a low frequency of high-risk HIV exposures.
Bridging the Efficacy–Effectiveness Gap in HIV Programs: Lessons From Economics
Authors: Bor Jacob , Thirumurthy Harsha
Published: November 2019

Background:

Bridging the efficacy–effectiveness gap in HIV prevention and treatment requires policies that account for human behavior.

Setting:

Worldwide.

Methods:

We conducted a narrative review of the literature on HIV in the field of economics, identified common themes within the literature, and identified lessons for implementation science.

Results:

The reviewed studies illustrate how behaviors are shaped by perceived costs and benefits across a wide range of health and nonhealth domains, how structural constraints shape decision-making, how information interventions can still be effective in the epidemic's fourth decade, and how lessons from behavioral economics can be used to improve intervention effectiveness.

Conclusion:

Economics provides theoretical insights and empirical methods that can guide HIV implementation science.
Human-Centered Design Lessons for Implementation Science: Improving the Implementation of a Patient-Centered Care Intervention
Authors: Beres Laura K. , Simbeza Sandra , Holmes Charles B. , Mwamba Chanda , Mukamba Njekwa , Sharma Anjali , Munamunungu Virginia , Mwachande Monica , Sikombe Kombatende , Bolton Moore Carolyn , Mody Aaloke , Koyuncu Aybüke , Christopoulous Katerina , Jere Lazarus , Pry Jake , Ehrenkranz Peter D. , Budden Ashwin , Geng Elvin , Sikazwe Izukanji
Published: November 2019

Background:

Evidence-based HIV interventions often fail to reach anticipated impact due to insufficient utilization in real-world health systems. Human-centered design (HCD) represents a novel approach in tailoring innovations to fit end-users, narrowing the gap between efficacious interventions and impact at scale.

Methods:

We combined a narrative literature review of HCD in HIV programs with our experience using HCD to redesign an intervention promoting patient-centered care (PCC) practices among health care workers (HCW) in Zambia. We summarize the use and results of HCD in the global HIV response and share case study insights to advance conceptualization of HCD applications.

Results:

The literature review identified 13 articles (representing 7 studies) on the use of HCD in HIV. All studies featured HCD hallmarks including empathy development, user-driven inquiry, ideation, and iterative refinement. HCD was applied to mHealth design, a management intervention and pre-exposure prophylaxis delivery. Our HCD application addressed a behavioral service delivery target: changing HCW patient-centered beliefs, attitudes, and practices. Through in-depth developer–user interaction, our HCD approach revealed specific HCW support for and resistance to PCC, suggesting intervention revisions to improve feasibility and acceptability and PCC considerations that could inform implementation in transferable settings.

Conclusions:

As both a research and implementation tool, HCD has potential to improve effective implementation of the HIV response, particularly for product development; new intervention introduction; and complex system interventions. Further research on HCD application strengths and limitations is needed. Those promoting PCC may improve implementation success by seeking out resonance and anticipating the challenges our HCD process identified.
Integrating Economic Evaluation and Implementation Science to Advance the Global HIV Response
Authors: Salomon Joshua A.
Published: November 2019

Background:

Numerous cost-effectiveness analyses have indicated good value for money from a wide array of interventions for treatment and prevention of HIV/AIDS. There is limited evidence, however, regarding how cost-effectiveness information contributes to better decision-making around investment and action in the global HIV response.

Methods:

We review challenges for economic evaluation relevant to the global HIV response and consider how the practice of cost-effectiveness analysis could integrate approaches and insights from implementation science to enhance the impact and efficiency of HIV investments.

Results:

In light of signals that cost-effectiveness analyses may be vulnerable to systematic bias toward overly optimistic conclusions, we emphasize two priorities for advancing the field of economic evaluation in HIV/AIDS and more broadly in global health: (1) systematic reevaluation of the cost-effectiveness literature with reference to ex-post empirical evidence on costs and effects in real-world programs and (2) development and adoption of good-practice guidelines for incorporating implementation and delivery aspects into economic evaluations. Toward the latter aim, we propose an integrative approach that focuses on comparative evaluation of strategies, which specify both technologies/interventions as well as the delivery platforms, complementary interventions, and actions needed to increase coverage, quality, and uptake of those technologies/interventions. Specific recommendations draw on several existing implementation science models that provide systematic frameworks for understanding implementation barriers and enablers, designing and choosing specific implementation and policy actions, and evaluating outcomes.

Discussion:

These preliminary steps aimed at bridging the divide between economic evaluation and implementation science can help to advance the practice of economic evaluation toward a science of comparative strategy evaluation.
Role of Implementation Science: Linking Fundamental Discovery Science and Innovation Science to Ending the HIV Epidemic at the Community Level
Authors: Eisinger Robert W. , Dieffenbach Carl W. , Fauci Anthony S.
Published: November 2019

Background:

During the past 4 decades, substantial progress has been made in the development of strategies for HIV prevention, treatment, and care resulting from observational science, discovery and innovation science, and implementation science. Building on these fundamental discoveries, innovation science has led to novel, safe, and effective modalities for HIV treatment and prevention, including combination antiretroviral therapy and treatment as prevention and pre-exposure prophylaxis, respectively.

Setting:

In the United States and globally, there remains a major challenge in the optimal implementation of the strategies that we already have in the areas of HIV prevention, diagnosis, treatment, and care.

Methods:

Implementation science will be essential to the successful achievement of ending the global HIV epidemic by translating evidence-based interventions, resulting from discovery and innovation science, into real-world practice. Strategies are needed that integrate and implement the biomedical tools currently available within the social and structural contexts and across all stages of the HIV prevention and care continuum. Several of the latest methodologies and analytical approaches that are being actively pursued, as well as the research challenges and opportunities to conducting implementation science in the context of both the global and domestic responses to HIV, are the focus of this special supplement to the Journal of AIDS.

Conclusions:

Knowledge resulting from implementation science will be critical to define and refine the approaches to successfully bring HIV prevention and treatment interventions to scale and achieve the goal of ending the HIV epidemic in the United States and worldwide.
Applying the Chinese Wood Joinery Mortise-and-Tenon Principle to Repair Widening Surface Scars
Authors: Wang Di , Ma Ning , Wang Weixin , Chen Wen
Published: November 2019

We applied the classical Chinese wood joinery mortise-and-tenon principle to repair widening surface scars caused by incision tension. Along the outer margin of surface scars, the top half of the scar tissue was cut and removed. The authors designed serial tenon structures on the retained dermal surface of the scar and a series of corresponding mortise structures in the dermal tissue on the opposite side of the incision. Finally, the mortise and tenon structures were integrated and sutured, resulting in tensionless closure. Thirty-two surface scars were repaired with this method. The follow-up time ranged from 6 to 24 months. The incisions healed in the form of fine linear scars. No widening scars were observed in this series. The proposed mortise-and-tenon scar repair technique can effectively reduce incision tension and thus reduce scar formation at the incision site. The authors recommend this technique as an alternative effective method for revising widening surface scars.
Application of tpsDig2 Software in Nasal Angle Measurements
Authors: Kaur Tej , Krishan Kewal , Kaur Paramjit , Sharma Suresh K. , Kumar Adarsh
Published: November 2019

Introduction and objectives:

Nose is considered to be a conspicuous feature of human face. Its different parameters like shape, size, nasal angles etc may indicate one's gender, age, race, adapted climatic conditions, and the environment to which one belongs to. Furthermore, it is an important component and determinant of an individual's physical outlook and appearance. The current study provides a new approach for the assistance of anthropologists and forensic experts in human identification and sex determination from the nasal angles.

Methodology:

The study was performed on a total of 500 subjects (250 males and 250 females) belonging to north India (Mandi, Himachal Pradesh State). In comparison to the classical and manual methods for nasal angle measurements, an automated approach was followed in the present study. A Windows-based software called tpsDig2 was used for nasal angle measurements by utilization of the landmarks (nasion, pronasale, subnasale, and alare). Three nasal angles (nasal prominence angle, inter-alar angle, and nasal tip angle) were measured in all the subjects and each measurement was repeated thrice to reduce the measurement error and increase the specificity and efficiency of the results. Discriminant function statistics was used for determination of sex from different nasal angles.

Results and Conclusion:

The results of the statistical analysis (ANOVA) performed using SPSS reveal the significant difference between males and females in all the 3 repeated measurements of nasal angles. The final discriminant classification statistics show that 64% of original grouped cases have been correctly classified and the designed statistical model can be used in several forensic scenarios for the sex determination on the basis of the available nasal angles. The study may be further useful in the identification cases pertaining to facial reconstruction. The investigation may also be helpful in providing specific correlation of the nasal angles with the other parts of the face in the cases of remodelling and reformation of craniofacial alterations and reconstructions in plastic surgery and aesthetics.
Comparison of Endoscope-Assisted Coblation Adenoidectomy to Conventional Curettage Adenoidectomy in Terms of Postoperative Eustachian Tube Function
Authors: Gülşen Secaattin , Çikrikçi Sercan
Published: November 2019

Introduction:

Adenoidectomy is one of the most common surgical procedures performed in children in otorhinolaryngology practice. This study aims to compare the conventional curettage adenoidectomy (CCA) and the endoscope-assisted coblation adenoidectomy (EACA) in terms of the postoperative Eustachian tube function and the surgical outcomes.

Methods:

A prospective, randomized, controlled study was carried out at a tertiary referral center and private hospital. Seventy-two adenoid hypertrophy patients without middle ear disease were randomly assigned to 2 groups to be operated via CCA and EACA techniques prior to surgery. Parameters including middle ear pressure values (MEPV), operative time, intraoperative hemorrhage, postoperative residual adenoid tissue, and postoperative pain were compared between groups.

Results:

In the CCA group for both ears, there was a statistically significant difference between preoperative mean MEPV and mean MEPV of postoperative day 1, while MEPV returned to normal ranges at the postoperative day 7. No statistically significant differences were observed in mean MEPV on preoperatively and 1st and 7th postoperative days in the EACA group for both right and left ears. Mean operative time was significantly higher in the EACA group compared to the CCA group (P < 0.001). Eight (22.2%) out of 36 patients who underwent CCA had a residual adenoid tissue postoperatively, while there was no residual adenoid tissue in any patients who operated via the EACA technique. Mean pain score on postoperative day 1 and 2 and blood loss were significantly less in the EACA group than the CCA group.

Conclusion:

Endoscope-assisted coblation adenoidectomy may serve a reasonable alternative to conventional curettage adenoidectomy because it provides Eustachian tube functions preserved, decreased intraoperative hemorrhage, complete resection of the adenoid tissue, and lower pain score.
Prognosis of Pediatric Patients With Mucoepidermoid Carcinoma of the Parotid Gland
Authors: Li Mo-Zi , Mao Ming-Hui , Feng Zhi-En , Li Jin-Zhong , Li Hua , Qin Li-Zheng , Li Jian-Hua , Huang Xin , Xing Ru-Dong , Han Zheng-Xue
Published: November 2019

Objective:

To summarize the prognosis of pediatric patients with mucoepidermoid carcinoma (MEC) of the parotid gland.

Methods:

Pediatric patients with MEC of parotid gland who were surgically treated at the Capital Medical University School of Stomatology from 2000 to 2014 were retrospectively analyzed. Clinical characteristics, pathology reports, and operation records were reviewed and analyzed.

Results:

In total, 33 patients with an average age of 13.2 years were enrolled. The 5-year overall survival and disease-free survival were 95.8% and 84.4%, respectively. The disease-free survival and overall survival rates were lower in the under-10 age group (75.0 versus 87.7% and 83.3% versus 100%), though no statistically significant difference was found (P = 0.279 and P = 0.075). The patients who underwent complete resection all had a good prognosis without any recurrence or death regardless of whether the cut margin was 1.0 cm, 0.5 cm, or only extracapsular. One patient experienced 3 recurrences within 18 months and eventually died of disease.

Conclusion:

Good outcomes were achieved in pediatric patients with MEC of the parotid gland. Radical resection ensured a good prognosis regardless of the extent of resection. Frequent recurrence in a short period was associated with a poor prognosis.

Trial registration: None.
Removal of Circulating Neutrophil Extracellular Trap Components With an Immobilized Polymyxin B Filter: A Preliminary Study
Authors: Gocho Takayoshi , Mori Hisatake , Islam Md. Monirul , Maruchi Yuki , Takenaka Nobuyoshi , Tomino Atsutoshi , Tsuda Masanobu , Kano Hideki , Takeyama Naoshi
Published: November 2019

Components of neutrophil extracellular traps (NETs) are released into the circulation by neutrophils and contribute to microcirculatory disturbance in sepsis. Removing NET components (DNA, histones, and proteases) from the circulation could be a new strategy for counteracting NET-dependent tissue damage. We evaluated the effect of hemoperfusion with a polymyxin B (PMX) cartridge, which was originally developed for treating gram-negative infection, on circulating NET components in patients with septic shock, as well as the effect on phorbol myristate acetate (PMA)-stimulated neutrophils obtained from healthy volunteers. Ex vivo closed loop hemoperfusion was performed through PMX filters in a laboratory circuit. Whole blood from healthy volunteers (incubated with or without PMA) or from septic shock patients was perfused through the circuit. For in vivo experiment blood samples were collected before and immediately after hemoperfusion with PMX to measure the plasma levels of cell-free NETs. The level of cell-free NETs was assessed by measuring myeloperoxidase-associated DNA (MPO-DNA), neutrophil elastase-associated DNA (NE-DNA), and cell-free DNA (cf-DNA). Plasma levels of MPO-DNA, NE-DNA, and cf-DNA were significantly increased after 2 h of PMA stimulation. When the circuit was perfused with blood from septic shock patients or PMA-stimulated neutrophils from healthy volunteers, circulating levels of MPO-DNA, NE-DNA, and cf-DNA were significantly reduced after 1 and 2 h of perfusion with a PMX filter compared with perfusion without a PMX filter. In 10 patients with sepsis, direct hemoperfusion through filters with immobilized PMX significantly reduced plasma levels of MPO-DNA and NE-DNA. These ex vivo and in vivo findings demonstrated that hemoperfusion with PMX removes circulating NET components. Selective removal of circulating NET components from the blood could be effective for prevention/treatment of NET-related inappropriate inflammation and thrombogenesis in patients with sepsis.
Presenilin 1 intronic polymorphism in sporadic Alzheimer’s disease in a Northern Chinese population
Authors: Fan Chunqiu , Huang Xiaoqin , Song Haiqing , Jia Jianping
Published: November 2019

Background:

Two types of alleles exist within intron 3′ and exon 8 in the presenilin 1 (PS1) gene at nucleotide 16: allele 1 (A at site 16) and allele 2 (C at site 16), and three genotypes (1/1, 1/2, and 2/2) are formed with a combination of these alleles. The present study aims to investigate the association between the intronic polymorphism of PS1 gene and the occurrence of sporadic Alzheimer’s disease in a northern Chinese population.

Materials and methods:

The genotype and allele frequencies of PS1 gene were compared for 90 sporadic Alzheimer’s disease patients and 90 healthy controls. The intronic polymorphism of the PS1 gene was determined by the PCR-restriction fragment length polymorphism method.

Result:

PS1 alleles (allele 1 [A at site 16] and allele 2 [C at site 16]) and genotypes (1/1, 1/2, and 2/2) were in Hardy-Weinberg equilibrium for both Alzheimer’s disease and control subjects. The frequencies of PS1 intronic genotype 1/1 and allele 1 in the sporadic Alzheimer’s disease group were significantly higher than those in the control group (P < 0.005). The genotype 2/2 was significantly lower among the patients with sporadic Alzheimer’s disease compared with the controls. The onset of sporadic Alzheimer’s disease was positively associated with PS1 intronic allele 1 (odds ratio = 2.14) and negatively associated with PS1 intronic allele 2 (odds ratio = 0.48).

Conclusions:

A polymorphism of the PS1 gene is associated with sporadic Alzheimer’s disease risk in a northern Chinese population. PS1 intronic allele 1 is a risk factor, and PS1 intronic allele 2 is a protective factor for sporadic Alzheimer’s disease.
Immunopotentiator thymosin alpha-1 attenuates inflammatory pain by modulating the Wnt3a/β-catenin pathway in spinal cord
Authors: Huang Jiahua , Jiang Huaqing , Pan Meijun , Jiang Yanjun , Xie Lijin
Published: November 2019

The mechanism of inflammatory pain involves the central nervous system (CNS) and the immune system. It is reported that immunopotentiator thymosin alpha-1 (Tα1) can reduce inflammation, protect neurons and strengthen the immune function. However, the roles of Tα1 in inflammatory pain still remain unclear. In this study, we found Tα1 can attenuate the complete Freund’s adjuvant (CFA)-induced mechanical allodynia and heat hyperalgesia. Meanwhile, it reduced the upregulation of CFA-induced inflammatory mediators (interferon (IFN)-γ, tumor necrosis factor-α and brain-derived neurotrophic factor). In addition, we found the Wnt3a/β-catenin pathway was activated in spinal cord after the injection of CFA, paralleling with pain hypersensitivity. However, Tα1 reversed this status. In summary, Tα1 could attenuate inflammatory pain by modulating the Wnt3a/β-catenin pathway. It might be related to the downregulation of inflammatory mediators.
Differential expression of circular RNAs in the proximal and distal segments of the sciatic nerve after injury
Authors: Sohn Eun Jung , Park Hwan Tae
Published: November 2019

To investigate the functions of circular RNAs (circRNAs) in axonal regeneration and degeneration after injury, circRNA expression profiles in the injured peripheral nerves were determined using a circRNA-based microarray. The results showed that 281 upregulated and 261 downregulated circRNAs were found in the proximal stump of the sciatic nerve after injury. In the distal stump after injury, 217 circRNAs were upregulated and 224 circRNAs were downregulated. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment and gene ontology (GO) analysis of circRNAs after injury were associated with axon regeneration pathways, including thyroid hormone, Ras signaling, endocytosis, and the ErbB signaling pathway, as well as with Schwann cell differentiation and proliferation, including the axon guidance, focal adhesion, Glutamatergic synapse, and MAPK signaling pathway. To verify the microarray results, among the regulated circRNAs, the upregulation of circRNA 012142 in both proximal and distal segments was validated using quantitative PCR analysis. The biological function of the circRNA 012412/microRNA/mRNA network based on GO analysis and KEGG pathway was identified in cell differentiation, phosphorylation, intracellular signaling transduction, and focal adhesion, the Rap1 signaling pathway. Thus, circRNAs after nerve injury may be involved in these biological functions during nerve regeneration and degeneration.
Discrete scattering by a pair of parallel defects
Authors: Sharma Basant Lal , Maurya Gaurav
Published: November 2019

Scattering of a time-harmonic anti-plane shear wave due to either a pair of crack tips or a pair of rigid constraint tips on square lattice is considered. The two problems correspond to the so-called zero-offset case of scattering due to a pair of identical Sommerfeld screens. The peculiar structural symmetry allows the reduction of coupled equations to two scalar Wiener–Hopf equations and a total of four geometrically reduced problems on lattice half-plane. Exact solution of each problem for incidence from the bulk lattice, as well as from an associated lattice waveguide, is constructed. A suitable superposition of the four expressions is used to construct the solution of the main problem. The discrete paradigm involving the wave mode incident from the waveguide is relevant for modern applications where an investigation of mechanisms of electronic and thermal transport at nanoscale remains an interesting problem.

This article is part of the theme issue ‘Modelling of dynamic phenomena and localization in structured media (part 2)’.
Supersonic kinks and solitons in active solids
Authors: Gorbushin N. , Truskinovsky L.
Published: November 2019

To show that steadily propagating nonlinear waves in active matter can be driven internally, we develop a prototypical model of a topological kink moving with a constant supersonic speed. We use a model of a bi-stable mass-spring (Fermi–Pasta–Ulam) chain capable of generating active stress. In contrast to subsonic kinks in passive bi-stable chains that are necessarily dissipative, the obtained supersonic solutions are purely anti-dissipative. Our numerical experiments point towards the stability of the obtained kink-type solutions and the possibility of propagating kink-anti-kink bundles reminiscent of solitons. We show that even the simplest quasi-continuum approximation of the discrete model captures the most important features of the predicted active phenomena.

This article is part of the theme issue ‘Modelling of dynamic phenomena and localization in structured media (part 2)’.
On the universality of the frequency spectrum and band-gap optimization of quasicrystalline-generated structured rods
Authors: Morini Lorenzo , Gokay Tetik Zafar , Shmuel Gal , Gei Massimiliano
Published: November 2019

The dynamical properties of periodic two-component phononic rods, whose elementary cells are generated adopting the Fibonacci substitution rules, are studied through the recently introduced method of the toroidal manifold. The method allows all band gaps and pass bands featuring the frequency spectrum to be represented in a compact form with a frequency-dependent flow line on the surface describing their ordered sequence. The flow lines on the torus can be either closed or open: in the former case, (i) the frequency spectrum is periodic and the elementary cell corresponds to a canonical configuration, (ii) the band gap density depends on the lengths of the two phases; in the latter, the flow lines cover ergodically the torus and the band gap density is independent of those lengths. It is then shown how the proposed compact description of the spectrum can be exploited (i) to find the widest band gap for a given configuration and (ii) to optimize the layout of the elementary cell in order to maximize the low-frequency band gap. The scaling property of the frequency spectrum, that is a distinctive feature of quasicrystalline-generated phononic media, is also confirmed by inspecting band-gap/pass-band regions on the torus for the elementary cells of different Fibonacci orders.

This article is part of the theme issue ‘Modelling of dynamic phenomena and localization in structured media (part 2)’.
Influenza forecasting for the French regions by using EHR, web and climatic data sources with an ensemble approach ARGONet
Authors: Poirier Canelle , Hswen Yulin , Bouzillé Guillaume , Cuggia Marc , Lavenu Audrey , Brownstein John S , Brewer Thomas , Santillana Mauricio
Published: November 2019

Effective and timely disease surveillance systems have the potential to help public health officials design interventions to mitigate the effects of disease outbreaks. Currently, healthcare-based disease monitoring systems in France offer influenza activity information that lags real-time by 1 to 3 weeks. This temporal data gap introduces uncertainty that prevents public health officials from having a timely perspective on the population-level disease activity. Here, we present a machine-learning modeling approach that produces real-time estimates and short-term forecasts of influenza activity for the 12 continental regions of France by leveraging multiple disparate data sources that include, Google search activity, real-time and local weather information, flu-related Twitter micro-blogs, electronic health records data, and historical disease activity synchronicities across regions. Our results show that all data sources contribute to improving influenza surveillance and that machine-learning ensembles that combine all data sources lead to accurate and timely predictions.

Author summary

The role of public health is to protect the health of populations by providing the right intervention to the right population at the right time. In France and all around the world, Influenza is a major public health problem. Traditional surveillance systems produce estimates of influenza-like illness (ILI) incidence rates, but with one-to three-week delay. Accurate real-time monitoring systems of influenza outbreaks could be useful for public health decisions. By combining different data sources and different statistical models, we propose an accurate and timely forecasting platform to track the flu in France at a spatial resolution that, to our knowledge, has not been explored before.
Detection of parasite-derived transrenal DNA for the diagnosis of chronic Trypanosoma cruzi infection
Authors: Madrigal Ana G. , Marcus Rachel , Gilman Robert , Scott Alan L. , Shiff Clive
Published: November 2019

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is a potentially life-threatening infection endemic to Latin America that has emerged as a global public health issue due to globalization and emigration patterns. Diagnosis of T. cruzi infection is complex, especially for the chronic phase of the disease that is characterized by a low to moderate burden of the difficult to detect, tissue-dwelling, intracellular form of the parasite. Diagnosis relies on a multistep indirect serological detection approach that requires positive results in at least two independent anti-T. cruzi antibody tests. With no gold standard diagnostic method for chronic T. cruzi, new approaches are needed that can more directly test for the presence of the parasite. Here, we report on of the potential utility of a noninvasive diagnostic approach that specifically detects T. cruzi-derived cell-free repeat DNA in the urine of patients who are both serologically positive and negative.
Diversified RACE Sampling on Data Streams Applied to Metagenomic Sequence Analysis
Authors: Coleman Benjamin , Geordie Benito , Chou Li , Elworth R. A. Leo , Treangen Todd J. , Shrivastava Anshumali
Published: November 2019

The rise of whole-genome shotgun sequencing (WGS) has enabled numerous breakthroughs in large-scale comparative genomics research. However, the size of genomic datasets has grown exponentially over the last few years, leading to new challenges for traditional streaming algorithms. Modern petabyte-sized genomic datasets are difficult to process because they are delivered by high-throughput data streams and are difficult to store. As a result, many traditional streaming problems are becoming increasingly relevant. One such problem is the task of constructing a maximally diverse sample over a data stream. In this regime, complex sampling procedures are not possible due to the overwhelming data generation rate. In theory, the best diversity sampling methods are based on a simple greedy algorithm that compares the current sequence with a large pool of sampled sequences and decides whether to accept or reject the sequence. While these methods are elegant and optimal, they are largely confined to the theoretical realm because the greedy procedure is too slow in practice. While there are many methods to identify common elements in data streams efficiently, fast and memory-efficient diversity sampling remains a challenging and fundamental data streaming problem with few satisfactory solutions. In this work, we bridge the gap with RACE sampling, an online algorithm for diversified sampling. Unlike random sampling, which samples uniformly, RACE selectively accepts samples from streams that lead to higher sequence diversity. At the same time, RACE is as computationally efficient as random sampling and avoids pairwise similarity comparisons between sequences. At the heart of RACE lies an efficient lookup array constructed using locality-sensitive hashing (LSH). Our theory indicates that an accept/reject procedure based on LSH lookups is sufficient to obtain a highly diverse subsample. We provide rigorous theoretical guarantees for well-known biodiversity indices and show that RACE can nearly double the Shannon and Simpson indices of a genetic sample in practice, all while using the same resources as random sampling. We also compare RACE against Diginorm and coreset-based diversity sampling methods and find that RACE is faster and more memory efficient. Our algorithm is straightforward to implement, easy to parallelize, and fast enough to keep pace with the overwhelming data generation rates. We expect that as DNA sequence data streams become more mainstream and faster, RACE will become an essential component for many applications.1
Comprehensive gene expression analysis detects global reduction of proteasome subunits in schizophrenia
Authors: Hertzberg Libi , Maggio Nicola , Muler Inna , Yitzhaky Assif , Majer Michael , Haroutunian Vahram , Katsel Pavel , Domany Eytan , Weiser Mark
Published: November 2019

OBJECTIVE

A main challenge in the study of schizophrenia is its high heterogeneity. While it is generally accepted that there exist several biological mechanisms that may define distinct schizophrenia subtypes, they haven’t been identified yet. We applied comprehensive gene expression analysis, searching for molecular signals that differentiate patients with schizophrenia from healthy controls, and examined whether the identified signal characterizes a particular subgroup of the patients.

METHODS

We performed transcriptome sequencing of 14 superior temporal gyrus (STG) samples of relatively young (mean age: 44) subjects with schizophrenia and 15 matched controls from the Stanley Medical Research Institute. Analyses of differential expression and pathway enrichment were applied and the results were compared with those obtained from an independent cohort of elderly (mean age: 74) patients. Replicability was then tested on six additional independent datasets of various brain regions.

RESULTS

The two STG cohorts of relatively young and elderly subjects showed high replicability. Pathway enrichment analysis of the down-regulated genes pointed to proteasome-related pathways. Meta-analysis of differential expression identified down-regulation of 12 of 39 proteasome subunits in schizophrenia. Down-regulation of multiple proteasome subunits was replicated in six additional datasets (overall 8 cohorts, with 267 schizophrenia and 266 control samples, from 5 brain regions, were studied). This signal was concentrated in a subgroup of the patients.

CONCLUSIONS

We detect global down-regulation of proteasome subunits in a subgroup of the patients with schizophrenia. The proteasome is a major intracellular protein degradation system, where ubiquitinated proteins (proteins bound by the small protein called ubiquitin) are targeted for degradation. We hypothesize that the down-regulation we detect leads to proteasome dysfunction that causes accumulation of ubiquitinated proteins. Such accumulation has recently been identified, also in a subgroup of the studied patients with schizophrenia. Thus, down-regulation of proteasome subunits might define a biological subtype of schizophrenia.
A versatile high throughput screening platform for plant metabolic engineering highlights the major role of ABI3 in lipid metabolism regulation
Authors: Pouvreau Benjamin , Blundell Cheryl , Vohra Harpreet , Zwart Alexander B. , Arndell Taj , Singh Surinder , Vanhercke Thomas
Published: November 2019

Traditional functional genetic studies in crops are time-consuming, complicated and cannot be readily scaled up. The reason is that mutant or transformed crops need to be generated to study the effect of gene modifications on specific traits of interest. However, many crop species have a complex genome and a long generation time. As a result, it usually takes several months to over a year to obtain desired mutants or transgenic plants, which represents a significant bottleneck in the development of new crop varieties.

To overcome this major issue, we are currently establishing a versatile plant genetic screening platform, amenable to high throughput screening in almost any crop species, with a unique workflow. This platform combines protoplast transformation and fluorescence-activated cell sorting.

Here we show that tobacco protoplasts can accumulate high levels of lipids if transiently transformed with genes involved in lipid biosynthesis and can be sorted based on lipid content. Hence, protoplasts can be used as a predictive tool for plant lipid engineering. Using this newly established strategy, we demonstrate the major role of ABI3 in plant lipid accumulation.

We anticipate that this workflow can be applied to numerous highly valuable metabolic traits other than storage lipid accumulation. This new strategy represents a significant step towards screening complex genetic libraries, in a single experiment and in a matter of days, as opposed to years by conventional means.