bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations Between Nonclinical Services and Patient-Experience Outcomes in US Acute Care Hospitals
Authors: Schiaffino Melody K , Suzuki Yukari , Ho Tarryn , Finlayson Tracy L , Harman Jeffrey S
Published: December 2019

Background:

Patient experience is an important measure of hospital quality and performance. Since the passage of the Affordable Care Act, patient experiences with their care encounters are embedded into the framework of payment incentives. However, drivers of patient experience in the context of the supportive, nonclinical, services that relate to patient care have not been as well understood.

Aims:

To assess the role of organizational factors on patient experience.

Methods:

This cross-sectional analysis integrates hospital patient-experience scores from Hospital Consumer Assessment of Healthcare Providers and Systems, and Centers for Medicaid and Medicare Service data from 2013 to 2015 (N = 3392). Based on hospitals with “top-box” responses, the aggregate proportion of hospital patients responding “always” on a Likert scale represented a top-box hospital. Domains were split at the mean for analysis (above average = 1). Multivariable logistic regression models for each domain were analyzed against hospital factors and services, including offering a patient education center, patient-enabling services, and language services.

Results:

Most hospitals reported a full-time hospitalist (64.4%) and a patient education center (60.4%), while fewer provided enabling/support services (33.7%). In multivariable models, small and medium hospitals performed better compared to the largest hospitals (300+ beds; P < .0001). Structurally, medium and small hospitals reported significantly greater odds of top-box patient-experience versus large hospitals. Across all domains, only hospitals with patient education centers returned better performance (adjusted odds ratio: 1.27-1.64; P = .0002-.0166).

Discussion/Conclusion:

Patient education centers provide relevant information at the point of service and may improve overall patient experience of care. Given the growing reliance on accountable care delivery models, opportunities to partner with community health education partners may be profitable.
The difference in sleep, sedentary behaviour, and physical activity between older adults with ‘healthy’ and ‘unhealthy’ cardiometabolic profiles: a cross-sectional compositional data analysis approach
Authors: Ryan Declan John , Wullems Jorgen Antonin , Stebbings Georgina Kate , Morse Christopher Ian , Stewart Claire Elizabeth , Onambele-Pearson Gladys Leopoldine
Published: December 2019

Background

Studies have seldom used Compositional Data Analysis (CoDA) to map the effects of sleep, sedentary behaviour, and physical activity on older adults’ cardio-metabolic profiles. This study therefore aimed to illustrate how sleep, sedentary behaviour, and physical activity profiles differ between older adult groups (60–89 years), with ‘low’ compared to those with ‘high’ concentrations of endocrine cardio-metabolic disease risk markers, using CoDA.

Method

Ninety-three participants (55% female) wore a thigh-mounted triaxial accelerometer for seven consecutive free-living days. Accelerometer estimates of daily average hours of engagement in sedentary behaviour (SB), standing, light-intensity physical activity (LIPA), sporadic moderate-vigorous physical activity (sMVPA, accumulated with bouts between 1 and 10 min), 10-min moderate-vigorous physical activity (10MVPA, accumulated with bouts ≥10 min), in addition to self-reported sleeping hours were reported. Fasted whole blood concentrations of total cholesterol, triglyceride, glucose, and glycated haemoglobin, and serum lipoprotein lipase (LPL), interleukin-6 (IL-6), and procollagen III N-terminal propeptide were determined.

Results

Triglyceride concentration appeared to be highly dependent on 10MVPA engagement as the ‘low’ and ‘high’ concentration groups engaged in 48% more and 32% less 10MVPA, respectively, relative to the geometric mean of the entire study sample. Time-use composition of the ‘low’ LPL group’s engagement in 10MVPA was 26% less, while the ‘high’ LPL group was 7.9% more, than the entire study sample. Time-use composition of the ‘high’ glucose and glycated haemoglobin groups appeared to be similar as both engaged in more Sleep and SB, and less 10MVPA compared to the study sample. Participants with a ‘low’ IL-6 concentration engaged in 4.8% more Sleep and 2.7% less 10MVPA than the entire study sample. Time-use composition of the Total Cholesterol groups was mixed with the ‘low’ concentration group engaging in more Standing and 10MVPA but less Sleep, SB, LIPA, and sMVPA than the entire study sample.

Conclusion

Older adults should aim to increase 10MVPA engagement to improve lipid profile and decrease SB engagement to improve glucose profile.
A comparison between the combined effect of calcium carbonate with sucroferric oxyhydroxide and other phosphate binders: an in vitro and in vivo experimental study
Authors: Yaguchi Atsushi , Akahane Kenji , Tsuchioka Kumi , Yonekubo Saori , Yamamoto Shota , Tamai Yasuaki , Tatemichi Satoshi , Takeda Hiroo
Published: December 2019

Background

Approximately 30% of patients on dialysis received combination therapy for their phosphate binder prescription; however, few studies for combined effects of phosphate binders are reported. For the purpose of evaluating the efficacy of combination therapy, we compared the efficacy of sucroferric oxyhydroxide (PA21) combined with calcium carbonate with that of lanthanum carbonate hydrate, sevelamer hydrochloride, and ferric citrate hydrate combined with calcium carbonate.

Methods

For in vitro studies, calcium carbonate and the other phosphate binders alone or in combination were stirred in phosphate solution at pH 2–8 for 2 h. After centrifuging the suspension, the phosphorus level in the supernatant was determined. For in vivo studies, rats were orally administered calcium carbonate and the other phosphate binders (except for sevelamer hydrochloride) alone or in combination, followed by oral administration of phosphate solution adjusted to pH 2 or 7. Serum samples were collected from the rats at predetermined timepoints and the serum phosphorus levels were determined and analyzed using a two-way analysis of variance.

Results

In the in vitro study, the measured phosphate-binding capacity of combining sevelamer hydrochloride, PA21, and lanthanum carbonate hydrate with calcium carbonate was approximately equal to or greater than the theoretical values under most conditions. Furthermore, these combined effects were insensitive to pH in that order. The measured phosphate-binding capacity of ferric citrate hydrate combined with calcium carbonate was smaller than the theoretical values, and the combination did not exhibit efficacy under any of the tested conditions. In the in vivo study, the combined effect of PA21 and calcium carbonate at both pH values and that of lanthanum carbonate hydrate and calcium carbonate at pH 2 were additive. In contrast, the combined effect of lanthanum carbonate hydrate and calcium carbonate at pH 7 and that of ferric citrate hydrate and calcium carbonate at pH 2 were antagonistic.

Conclusions

These results suggest that coadministration of PA21 and calcium carbonate showed good and relatively stable efficacy throughout the range of the gastrointestinal pH and that combining lanthanum carbonate hydrate and ferric citrate hydrate with calcium carbonate may not produce the expected efficacy under certain conditions.
Employing a sequential multiple assignment randomized trial (SMART) to evaluate the impact of brief risk and protective factor prevention interventions for American Indian Youth Suicide
Authors:   The Celebrating Life Team, O’Keefe Victoria M. , Haroz Emily E. , Goklish Novalene , Ivanich Jerreed , Cwik Mary F. , Barlow Allison
Published: December 2019

Background

This study is built on a long-standing research partnership between the Johns Hopkins Center for American Indian Health and the White Mountain Apache Tribe to identify effective interventions to prevent suicide and promote resilience among American Indian (AI) youth. The work is founded on a tribally-mandated, community-based suicide surveillance system with case management by local community mental health specialists (CMHSs) who strive to connect at-risk youth to treatment and brief, adjunctive interventions piloted in past research.

Methods

Our primary aim is to evaluate which brief interventions, alone or in combination, have the greater effect on suicide ideation (primary outcome) and resilience (secondary outcome) among AI youth ages 10–24 ascertained for suicide-related behaviors by the tribal surveillance system. We are using a Sequential Multiple Assignment Randomized Trial with stratified assignment based on age and suicidal-behavior type, and randomizing N = 304 youth. Brief interventions are delivered by AI CMHSs, or by Elders with CMHS support, and include: 1) New Hope, an evidence-based intervention to reduce immediate suicide risk through safety planning, emotion regulation skills, and facilitated care connections; and 2) Elders’ Resilience, a culturally-grounded intervention to promote resilience through connectedness, self-esteem and cultural identity/values. The control condition is Optimized Case Management, which all study participants receive. We hypothesize that youth who receive: a) New Hope vs. Optimized Case Management will have significant reductions in suicide ideation; b) Elders’ Resilience vs. Optimized Case Management will have significant gains in resilience; c) New Hope followed by Elders’ Resilience will have the largest improvements on suicide ideation and resilience; and d) Optimized Case Management will have the weakest effects of all groups. Our secondary aim will examine mediators and moderators of treatment effectiveness and sequencing.

Discussion

Due to heterogeneity of suicide risk/protective factors among AI youth, not all youth require the same types of interventions. Generating evidence for what works, when it works, and for whom is paramount to AI youth suicide prevention efforts, where rates are currently high and resources are limited. Employing Native paraprofessionals is a means of task-shifting psychoeducation, culturally competent patient support and continuity of care.

Trial registration

Clinical Trials NCT03543865, June 1, 2018.
Joint pain and osteoarthritis in former recreational and elite cricketers
Authors: Cai He , Bullock Garrett S. , Sanchez-Santos Maria T. , Peirce Nicholas , Arden Nigel K. , Filbay Stephanie R.
Published: December 2019

Background

Sport participants are at increased risk of joint pain and osteoarthritis. A better understanding of factors associated with joint pain and osteoarthritis in this population could inform the development of strategies to optimise their long-term joint health. The purpose of the study was to describe the prevalence of joint pain and osteoarthritis in former cricketers, and determine whether playing position, playing standard (i.e. elite or recreational standard) and length-of-play are associated with region-specific joint pain.

Methods

The data were from the Cricket Health and Wellbeing Study (CHWS), a cohort of 2294 current and former cricketers (played ≥1 season) in England and Wales. For this study, eligible individuals had to be aged ≥30 years and be a former cricket participant. Joint pain was defined as region-specific (hip/knee/ankle/shoulder/hand/back) pain on most days of the last month. Osteoarthritis was defined as joint-specific doctor-diagnosed osteoarthritis. Logistic regression was used to calculate unadjusted and adjusted (for history of joint injury resulting in > 4 weeks of reduced activity +/− age) odds ratios (ORs) and 95% confidence intervals (95% CIs).

Results

846 individuals from the CHWS were former cricketers aged ≥30 years (3% female, aged median 62(IQR 54–69) years, 62% played cricket recreationally, median 33(IQR 21–41) cricket seasons). One-in-two (48%) reported joint pain and 38% had been diagnosed with osteoarthritis. Joint pain and OA were most common in the knee (23% pain, 22% osteoarthritis), followed by the back (14% pain, 10% osteoarthritis) and hand (12% pain, 6% osteoarthritis). After adjusting for injury, bowlers had greater odds of shoulder pain (OR (95% CI) 3.1(1.3, 7.4)) and back pain (3.6(1.8, 7.4)), and all-rounders had greater odds of knee (1.7(1.0, 2.7)) and back pain (2.1(1.0, 4.2)), compared to batters. Former elite cricketers had greater odds of hand pain (1.6(1.0, 2.5)) than former recreational cricketers. Playing standard was not related to pain at other sites, and length-of-play was not associated with joint pain in former cricketers.

Conclusions

Every second former cricketer experienced joint pain on most days of the last month, and more than one in three had been diagnosed with osteoarthritis. Compared with batters, bowlers had higher odds of shoulder and back pain and all-rounders had higher odds of back and knee pain. Elite cricket participation was only related to higher odds of hand pain compared with recreational cricket participation.
“Whatever happens, happens” challenges of end-of-life communication from the perspective of older adults and family caregivers: a Qualitative study
Authors: Im Jennifer , Mak Susanna , Upshur Ross , Steinberg Leah , Kuluski Kerry
Published: December 2019

Background

Effective communication is integral to the delivery of goal-concordant care for older adults and their family caregivers, and yet, it is uncommon in people with serious illness. This study explores the challenges of integrating end-of-life communication into heart failure management from the perspectives of older adults and family caregivers.

Methods

In a qualitative study of older adults with heart failure and their family caregivers, fourteen semi-structured interviews were conducted with 19 participants in Ontario, Canada. The interviews were transcribed verbatim and thematic analysis was applied to analyze the data.

Results

Four themes were identified in the context of participants’ understanding of illness: 1) trivializing illness-related challenges, 2) positivity in late life, 3) discomfort in having end-of-life conversations, and 4) reluctant to engage despite need. These challenges often intertwine with one another. Most participants had not engaged in end-of-life discussions with their clinicians or family members.

Conclusion

The findings provide insights that can inform approaches to integrate end-of-life communication for older adults with serious illness and caregivers. The identified challenges highlight a need for end-of-life communication to occur earlier in illness to be able to support individuals throughout the period of decline. In addition, end-of-life communication should be introduced iteratively for those who may not be ready to engage. Alternative approaches to communication are needed to elicit the challenges that patients and caregivers experience throughout the progression of illness to improve care for people nearing the end of life.
Experiences from Decentralised Radiological Services in Norway – a rural case study
Authors: Myklebust Aud Mette , Eide Hilde , Ellis Brian , Beattie Rona
Published: December 2019

Background

Implementation of the Norwegian government’s Coordination Reform (2012) aims to decentralise health care services from centralised hospitals to local communities. Radiological services in Norway are mainly organised in hospitals, because of the significant financial and human resource demands engendered by the need for advanced technological equipment, and specialised staff. Some selected conventional x-ray services have been decentralised into rural communities. The purpose of this single case study was to highlight experiences from different stakeholders’ of organising decentralised radiological services in a rural area in Norway.

Methods

A qualitative single case study design was adopted, collected data using focus groups with healthcare professionals and managers to obtain stakeholder’s experiences of the radiological services in this rural area. The key emergent themes from the literature, decentralisation, quality, professional roles, organisation and economic consequences were discussed with each focus group. Thematic analysis was used for analyzing the primary data collected.

Results

Four main themes emerged from the focus groups: 1) organisation, 2) quality and safety, 3) funding of radiological services and 4) cooperation between health care professions and health care levels. It was found that the organisation of decentralised radiological services to rural areas is challenging because of the way health services are structured in Norway. The quality of service was found to be inadequate in some areas because of the superficial level of training given to non-radiographic staff. The experience is that the Norwegian funding system hinders an efficient decentralised health care service. Effective cooperation and responsibility between health care professions and levels was challenging. There needs to be improved co-working by clearly defining roles and responsibilities.

Conclusions

A key recommendation for the organisation of rural radiological service was the development of a satellite link with an acute hospital. Quality of the service could be improved and should be given priority. Structural change to the financial system whereby money follows patients, might also facilitate more patientcentred services across healthcare levels. Improved mutual understanding between rural radiological services and hospital specialists and managers is important for a high quality and consistent radiological service to be delivered across Norway.
Analysis of disease comorbidity patterns in a large-scale China population
Authors: Guo Mengfei , Yu Yanan , Wen Tiancai , Zhang Xiaoping , Liu Baoyan , Zhang Jin , Zhang Runshun , Zhang Yanning , Zhou Xuezhong
Published: December 2019

Background

Disease comorbidity is popular and has significant indications for disease progress and management. We aim to detect the general disease comorbidity patterns in Chinese populations using a large-scale clinical data set.

Methods

We extracted the diseases from a large-scale anonymized data set derived from 8,572,137 inpatients in 453 hospitals across China. We built a Disease Comorbidity Network (DCN) using correlation analysis and detected the topological patterns of disease comorbidity using both complex network and data mining methods. The comorbidity patterns were further validated by shared molecular mechanisms using disease-gene associations and pathways. To predict the disease occurrence during the whole disease progressions, we applied four machine learning methods to model the disease trajectories of patients.

Results

We obtained the DCN with 5702 nodes and 258,535 edges, which shows a power law distribution of the degree and weight. It further indicated that there exists high heterogeneity of comorbidities for different diseases and we found that the DCN is a hierarchical modular network with community structures, which have both homogeneous and heterogeneous disease categories. Furthermore, adhering to the previous work from US and Europe populations, we found that the disease comorbidities have their shared underlying molecular mechanisms. Furthermore, take hypertension and psychiatric disease as instance, we used four classification methods to predicte the disease occurrence using the comorbid disease trajectories and obtained acceptable performance, in which in particular, random forest obtained an overall best performance (with F1-score 0.6689 for hypertension and 0.6802 for psychiatric disease).

Conclusions

Our study indicates that disease comorbidity is significant and valuable to understand the disease incidences and their interactions in real-world populations, which will provide important insights for detection of the patterns of disease classification, diagnosis and prognosis.
ClC transporter activity modulates histidine catabolism in Lactobacillus reuteri by altering intracellular pH and membrane potential
Authors: Hall Anne E. , Engevik Melinda A. , Oezguen Numan , Haag Anthony , Versalovic James
Published: December 2019

Background

Histamine is a key mediator of the anti-inflammatory activity conferred by the probiotic organism Lactobacillus reuteri ATCC PTA 6475 in animal models of colitis and colorectal cancer. In L. reuteri, histamine synthesis and secretion requires l-histidine decarboxylase and a l-histidine/histamine exchanger. Chloride channel (ClC)-family proton/chloride antiporters have been proposed to act as electrochemical shunts in conjunction with amino acid decarboxylase systems, correcting ion imbalances generated by decarboxylation through fixed ratio exchange of two chloride ions for one proton. This family is unique among transporters by facilitating ion flux in either direction. Here we examine the histidine decarboxylase system in relation to ClC antiporters in the probiotic organism Lactobacillus reuteri.

Results

In silico analyses reveal that L. reuteri possesses two ClC transporters, EriC and EriC2, as well as a complete histidine decarboxylase gene cluster (HDC) for the synthesis and export of histamine. When the transport activity of either proton/chloride antiporter is disrupted by genetic manipulation, bacterial histamine output is reduced. Using fluorescent reporter assays, we further show that ClC transporters affect histamine output by altering intracellular pH and membrane potential. ClC transport also alters the expression and activity of two key HDC genes: the histidine decarboxylase (hdcA) and the histidine/histamine exchanger (hdcP).

Conclusions

Histamine production is a potentially beneficial feature for intestinal microbes by promoting long-term colonization and suppression of inflammation and host immune responses. ClC transporters may serve as tunable modulators for histamine production by L. reuteri and other gut microbes.
Improving pregnant women’s knowledge on danger signs and birth preparedness practices using an interactive mobile messaging alert system in Dodoma region, Tanzania: a controlled quasi experimental study
Authors: Masoi Theresia J. , Kibusi Stephen M.
Published: December 2019

Background

Unacceptably high maternal and perinatal mortality remain a major challenge in many low income countries. Early detection and management of danger signs through improved access to maternal services is highly needed for better maternal and infant outcomes. The aim of this study was to test the effectiveness of an interactive mobile messaging alert system on improving knowledge on danger signs, birth preparedness and complication readiness practices among pregnant women in Dodoma region, Tanzania.

Methods

A controlled quasi experimental study of 450 randomly selected pregnant women attending antenatal care was carried in Dodoma municipal. Participants were recruited at less than 20 weeks of gestation during the first visit where 150 were assigned to the intervention and 300 to the control group. The intervention groups was enrolled in an interactive mobile messaging system and received health education messages and were also able to send and receive individualized responses on a need basis. The control group continued receiving usual antenatal care services offered at the ANC centers. Pregnant women were followed from their initial visit to the point of delivery. Level of knowledge on danger signs and birth preparedness were assessed at baseline and a post test was again given after delivery for both groups. Analyses of covariance, linear regression were employed to test the effectiveness of the intervention.

Results

The mean age of participants was 25.6 years ranging from 16 to 48 years. There was significant mean scores differences for both knowleadge and birth preparedness between the intervention and the control group after the intervention (p < .001). The mean knowleadge score was (M = 9.531,SD = 2.666 in the intervention compared to M = 6.518,SD = 4.304 in the control, equivalent to an effect size of 85% of the intervention. Meanwhile, the mean score for IBPACR was M = 4.165,SD = 1.365 for the intervention compared to M = 2.631,SD = 1.775 in the control group with an effect size of 90% A multivariate linear regression showed a positive association between the intervention (p < 0.001) and level of knowledge (B = 2.910,95%CI = 2.199–3.621) and birth preparediness (B = 1.463,95%CI = 1.185–1.740).

Conclusion

The Interactive mobile messaging alert system demonstrated to be effective in increasing women’s knowledge on danger signs and improving their birth preparedness practices.
Trauma in the Kashmir Valley and the mediating effect of stressors of daily life on symptoms of posttraumatic stress disorder, depression and anxiety
Authors: Housen Tambri , Lenglet Annick , Shah Showkat , Sha Helal , Ara Shabnum , Pintaldi Giovanni , Richardson Alice
Published: December 2019

Background

The negative psychological impact of living in a setting of protracted conflict has been well studied, however there is a recognized need to understand the role that non-conflict related factors have on mediating exposure to trauma and signs of psychological distress.

Methods

We used data from the 2015 Kashmir Mental Health Survey and conducted mediation analysis to assess the extent to which daily stressors mediated the effect of traumatic experiences on poor mental health outcomes. Outcomes of interest were probable diagnosis of anxiety, depression, or PTSD; measured using the pre-validated Hopkins Symptoms Checklist (HSCL-25) and the Harvard Trauma Questionnaire (HTQ).

Results

Total effect mediated were statistically significant but the proportions of effect mediated were found to be small in practical terms. Financial stress mediated 6.8% [95% Confidence Interval (CI) 6∙0–8∙4], 6.7% [CI 6.2–7∙7] and 3.6% [CI 3∙4–4∙0] of the effect of experiencing multiple traumaticogenic events on symptoms of anxiety, depression and PTSD, respectively. Family stress mediated 11.3% [CI 10.3–13.8], 10.3% [CI 9.5–11.9] and 6.1% [CI 5.7–6.7] of the effect of experiencing multiple traumatogenic events on symptoms of anxiety, depression and PTSD, respectively. Poor physical health mediated 10.0% [CI 9.1–12∙0], 7.2% [CI 6.6–8.2] and 4.0% [CI 3.8,4.4] of the effect of experiencing more than seven traumatic events on symptoms of anxiety, depression and PTSD, respectively.

Conclusion

Our findings highlight that not only do we need to move beyond a trauma-focussed approach to addressing psychological distress in populations affected by protracted conflict but we must also move beyond focussing on daily stressors as explanatory mediators.
The clinical outcome of Dienogest treatment followed by in vitro fertilization and embryo transfer in infertile women with endometriosis
Authors: Tamura Hiroshi , Yoshida Hiroaki , Kikuchi Hiroyuki , Josaki Mai , Mihara Yumiko , Shirafuta Yuichro , Shinagawa Masahiro , Tamura Isao , Taketani Toshiaki , Takasaki Akihisa , Sugino Norihiro
Published: December 2019

Background

Endometriosis is considered to be the most intractable cause of female infertility. Administering any type of treatment for endometriosis before in vitro fertilization and embryo transfer (IVF-ET) is an important strategy for improving the IVF-ET outcomes for infertile women with endometriosis. In fact, treatment with a gonadotropin-releasing hormone (GnRH) agonist just before IVF-ET has been reported to improve the clinical outcome in endometriosis patients. However, the benefit of Dienogest (DNG), a synthetic progestin, treatment just before IVF-ET remains unclear.

Methods

Sixty-eight infertile women with Stage III or IV endometriosis (ovarian endometrial cyst < 4 cm) were recruited for this study. The subjects were divided into 2 groups: a DNG group (n = 33) and a control group (n = 35). DNG was administered orally every day for 12 weeks prior to the conventional IVF-ET cycle in the DNG group. Standard controlled ovarian hyperstimulation with the GnRH agonist long protocol was performed in the control group. The numbers of mature follicles and retrieved oocytes, fertilization rates, implantation rates, and clinical pregnancy rate were compared between the two groups. In addition, the concentrations of inflammatory cytokines, oxidative stress markers, and antioxidants in follicular fluids were also measured.

Results

The numbers of growing follicles, retrieved oocytes, fertilized oocytes, and blastocysts were significantly lower in the DNG group than in the control group. The fertilization and blastocyst rates were also lower in the DNG group than in the control group. Although there was no significant difference in the implantation rate between the groups, the cumulative pregnancy rate and live birth rate were lower in the DNG group than in the control group. There was no significant difference in the abortion rate. Our results failed to show that DNG reduces the inflammatory cytokine levels and oxidative stress in follicular fluids.

Conclusions

Administering DNG treatment just before IVF-ET did not provide any benefits to improve the clinical outcomes for infertile women with endometriosis.
scPred: accurate supervised method for cell-type classification from single-cell RNA-seq data
Authors: Alquicira-Hernandez Jose , Sathe Anuja , Ji Hanlee P. , Nguyen Quan , Powell Joseph E.
Published: December 2019

Single-cell RNA sequencing has enabled the characterization of highly specific cell types in many tissues, as well as both primary and stem cell-derived cell lines. An important facet of these studies is the ability to identify the transcriptional signatures that define a cell type or state. In theory, this information can be used to classify an individual cell based on its transcriptional profile. Here, we presentscPred, a new generalizable method that is able to provide highly accurate classification of single cells, using a combination of unbiased feature selection from a reduced-dimension space, and machine-learning probability-based prediction method. We applyscPredto scRNA-seq data from pancreatic tissue, mononuclear cells, colorectal tumor biopsies, and circulating dendritic cells and show thatscPredis able to classify individual cells with high accuracy. The generalized method is available athttps://github.com/powellgenomicslab/scPred/.
Promotion of osteoclastogenesis by IL-26 in rheumatoid arthritis
Authors: Lee Kyung-Ann , Kim Kyoung-Woon , Kim Bo-Mi , Won Ji-Yeon , Min Hong Ki , Lee Dhong Won , Kim Hae-Rim , Lee Sang-Heon
Published: December 2019

Background

The inflammatory cascade in the rheumatoid arthritis (RA) synovium is modulated by a variety of cytokine and chemokine networks; however, the roles of IL-26, in RA pathogenesis, are poorly defined. Here, we investigated the functional role of interleukin-26 (IL)-26 in osteoclastogenesis in RA.

Methods

We analyzed levels of IL-20 receptor subunit A (IL-20RA), CD55, and receptor activator of nuclear factor kappaB (NF-κB) ligand (RANKL) in RA fibroblast-like synoviocytes (FLSs) using confocal microscopy. Recombinant human IL-26-induced RANKL expression in RA-FLSs was examined using real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). Human peripheral blood monocytes were cultured with macrophage colony-stimulating factor (M-CSF) and IL-26, after which osteoclastogenesis was evaluated by counting the number of tartrate-resistant acid phosphatase-positive multinucleated cells. Additionally, osteoclastogenesis was evaluated by monocytes co-cultured with IL-26-prestimulated FLSs.

Results

The expression of IL-20RA in RA-FLSs was higher than that in osteoarthritis-FLSs. Additionally, in IL-26-pretreated RA-FLSs, the expression of IL-20RA (but not IL-10 receptor subunit B) and RANKL increased in a dose-dependent manner, with IL-26-induced RANKL expression reduced by IL-20RA knockdown. Moreover, IL-26-induced RANKL expression was significantly downregulated by inhibition of signal transducer and activator of transcription 1, mitogen-activated protein kinase, and NF-κB signaling. Furthermore, IL-26 promoted osteoclast differentiation from peripheral blood monocytes in the presence of low dose of RANKL, with IL-26 exerting an additive effect. Furthermore, co-culture of IL-26-pretreated RA-FLSs with peripheral blood monocytes also increased osteoclast differentiation in the absence of addition of RANKL.

Conclusions

IL-26 regulated osteoclastogenesis in RA through increased RANKL expression in FLSs and direct stimulation of osteoclast differentiation. These results suggest the IL-26/IL-20RA/RANKL axis as a potential therapeutic target for addressing RA-related joint damage.
Evaluation of serum iron overload, AST:ALT ratio and log10ferritin:AST ratio among schizophrenia patients in the Kumasi Metropolis, Ghana: a case–control study
Authors: Owiredu W. K. B. A. , Brenya Peter Kojo , Osei Yaw , Laing Edwin Ferguson , Okrah Clement Opoku , Obirikorang Christian , Anto Enoch Odame , Acheampong Emmanuel , Donkor Sampson
Published: December 2019

Objective

The association between unbalanced iron indices and the conditions of schizophrenia are not well understood. Liver dysfunction which has been linked to iron metabolism might be a contributing factor. This case–control study evaluated serum iron indices and liver function in treatment-naïve schizophrenia patients and those already on treatment at the Psychiatric Department of the Komfo Anokye Teaching Hospital (KATH), Kumasi-Ghana.

Results

The mean age of the respondents was 39.6 ± 0.8 years. Increased levels of serum iron, TS, AST, ALT and AST:ALT ratio and lower levels of UIBC, TIBC, Transferrin, and log Ferritin:AST ratio levels were observed among the treatment-naïve group compared to the control. The treatment-naïve and treatment groups showed significantly higher serum AST:ALT ratio, and lower log10ferrtin:AST ratio than the healthy controls. There was a significant correlation between log10ferritin and AST, and log10ferritin and GGT in both treatments (r = 0.343; p = 0.003, and r = 0.502; p = 0.001 respectively) and treatment-naïve groups (r = 0.348; p = 0.002, and r = 0.614; p < 0.001 respectively). Percentage transferrin saturation correlated significantly with GGT only, in the treatment-naïve group (r = 0.667; p < 0.001), and ALT and GGT in the treatment group (r = 0.252; p = 0.030 and r = 0.646; p = 0.014 respectively).
HHV-6A infection induces amyloid-beta expression and activation of microglial cells
Authors: Bortolotti Daria , Gentili Valentina , Rotola Antonella , Caselli Elisabetta , Rizzo Roberta
Published: December 2019

Background

The control of viral infections in the brain involves the activation of microglial cells, the macrophages of the brain that are constantly surveying the central nervous system, and the production of amyloid-beta (Aβ) as an anti-microbial molecule. Recent findings suggest a possible implication of HHV-6A in AD. We evaluated the effect of HHV-6A infection on microglial cell expression Aβ and the activation status, determined by TREM2, ApoE, cytokines, and tau expression.

Methods

We have infected microglial cells (HMC3, ATCC®CRL-3304), in monolayer and human peripheral blood monocyte-derived microglia (PBM-microglia) spheroid 3D model, with HHV-6A (strain U1102) cell-free virus inocula with 100 genome equivalents per 1 cell. We collected the cells 1, 3, 7, and 14 days post-infection (d.p.i.) and analyzed them for viral DNA and RNA, ApoE, Aβ (1-40, 1-42), tau, and phospho-tau (Threonine 181) by real-time immunofluorescence and cytokines by immunoenzymatic assay.

Results

We observed a productive infection by HHV-6A. The expression of Aβ 1-42 increased from 3 d.p.i., while no significant induction was observed for Aβ 1-40. The HHV-6A infection induced the activation (TREM2, IL-1beta, ApoE) and migration of microglial cells. The secretion of tau started from 7 d.p.i., with an increasing percentage of the phosphorylated form.

Conclusions

In conclusion, microglial cells are permissive to HHV-6A infection that induces the expression of Aβ and an activation status. Meanwhile, we hypothesize a paracrine effect of HHV-6A infection that activates and induces microglia migration to the site of infection.
EphA4 loss improves social memory performance and alters dendritic spine morphology without changes in amyloid pathology in a mouse model of Alzheimer’s disease
Authors: Poppe Lindsay , Rué Laura , Timmers Mieke , Lenaerts Annette , Storm Annet , Callaerts-Vegh Zsuzsanna , Courtand Gilles , de Boer Antina , Smolders Silke , Van Damme Philip , Van Den Bosch Ludo , D’Hooge Rudi , De Strooper Bart , Robberecht Wim , Lemmens Robin
Published: December 2019

Background

EphA4 is a receptor of the ephrin system regulating spine morphology and plasticity in the brain. These processes are pivotal in the pathophysiology of Alzheimer’s disease (AD), characterized by synapse dysfunction and loss, and the progressive loss of memory and other cognitive functions. Reduced EphA4 signaling has been shown to rescue beta-amyloid-induced dendritic spine loss and long-term potentiation (LTP) deficits in cultured hippocampal slices and primary hippocampal cultures. In this study, we investigated whether EphA4 ablation might preserve synapse function and ameliorate cognitive performance in the APPPS1 transgenic mouse model of AD.

Methods

A postnatal genetic ablation of EphA4 in the forebrain was established in the APPPS1 mouse model of AD, followed by a battery of cognitive tests at 9 months of age to investigate cognitive function upon EphA4 loss. A Golgi-Cox staining was used to explore alterations in dendritic spine density and morphology in the CA1 region of the hippocampus.

Results

Upon EphA4 loss in APPPS1 mice, we observed improved social memory in the preference for social novelty test without affecting other cognitive functions. Dendritic spine analysis revealed altered synapse morphology as characterized by increased dendritic spine length and head width. These modifications were independent of hippocampal plaque load and beta-amyloid peptide levels since these were similar in mice with normal versus reduced levels of EphA4.

Conclusion

Loss of EphA4 improved social memory in a mouse model of Alzheimer’s disease in association with alterations in spine morphology.
Familiality of behavioral flexibility and response inhibition deficits in autism spectrum disorder (ASD)
Authors: Schmitt Lauren M. , Bojanek Erin , White Stormi P. , Ragozzino Michael E. , Cook Edwin H. , Sweeney John A. , Mosconi Matthew W.
Published: December 2019

Background

Diminished cognitive control, including reduced behavioral flexibility and behavioral response inhibition, has been repeatedly documented in autism spectrum disorder (ASD). We evaluated behavioral flexibility and response inhibition in probands and their parents using a family trio design to determine the extent to which these cognitive control impairments represent familial traits associated with ASD.

Methods

We examined 66 individuals with ASD (probands), 135 unaffected biological parents, and 76 typically developing controls. Participants completed a probabilistic reversal learning task (PRL) and a stop-signal task (SST) to assess behavioral flexibility and response inhibition respectively. Rates of PRL and SST errors were examined across groups, within families, and in relation to clinical and subclinical traits of ASD. Based on prior findings that subclinical broader autism phenotypic (BAP) traits may co-segregate within families and reflect heritable risk factors, we also examined whether cognitive control deficits were more prominent in families in which parents showed BAP features (BAP+).

Results

Probands and parents each showed increased rates of PRL and SST errors relative to controls. Error rates across tasks were not related. SST error rates inter-correlated among probands and their parents. PRL errors were more severe in BAP+ parents and their children relative to BAP− parents and their children. For probands of BAP+ parents, PRL and SST error rates were associated with more severe social-communication abnormalities and repetitive behaviors, respectively.

Conclusion

Reduced behavioral flexibility and response inhibition are present among probands and their unaffected parents, but represent unique familial deficits associated with ASD that track with separate clinical issues. Specifically, behavioral response inhibition impairments are familial in ASD and manifest independently from parental subclinical features. In contrast, behavioral flexibility deficits are selectively present in families with BAP characteristics, suggesting they co-segregate in families with parental subclinical social, communication, and rigid personality traits. Together, these findings provide evidence that behavioral flexibility and response inhibition impairments track differentially with ASD risk mechanisms and related behavioral traits.
Assessment of brain delivery of a model ABCB1/ABCG2 substrate in patients with non-contrast-enhancing brain tumors with positron emission tomography
Authors: Wulkersdorfer Beatrix , Bauer Martin , Karch Rudolf , Stefanits Harald , Philippe Cécile , Weber Maria , Czech Thomas , Menet Marie-Claude , Declèves Xavier , Hainfellner Johannes A. , Preusser Matthias , Hacker Marcus , Zeitlinger Markus , Müller Markus , Langer Oliver
Published: December 2019

Background

P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) are two efflux transporters expressed at the blood–brain barrier which effectively restrict the brain distribution of the majority of currently known anticancer drugs. High-grade brain tumors often possess a disrupted blood–brain tumor barrier (BBTB) leading to enhanced accumulation of magnetic resonance imaging contrast agents, and possibly anticancer drugs, as compared to normal brain. In contrast to high-grade brain tumors, considerably less information is available with respect to BBTB integrity in lower grade brain tumors.

Materials and methods

We performed positron emission tomography imaging with the radiolabeled ABCB1 inhibitor [11C]tariquidar, a prototypical ABCB1/ABCG2 substrate, in seven patients with non-contrast -enhancing brain tumors (WHO grades I–III). In addition, ABCB1 and ABCG2 levels were determined in surgically resected tumor tissue of four patients using quantitative targeted absolute proteomics.

Results

Brain distribution of [11C]tariquidar was found to be very low across the whole brain and not significantly different between tumor and tumor-free brain tissue. Only one patient showed a small area of enhanced [11C]tariquidar uptake within the brain tumor. ABCG2/ABCB1 ratios in surgically resected tumor tissue (1.4 ± 0.2) were comparable to previously reported ABCG2/ABCB1 ratios in isolated human micro-vessels (1.3), which suggested that no overexpression of ABCB1 or ABCG2 occurred in the investigated tumors.

Conclusions

Our data suggest that the investigated brain tumors had an intact BBTB, which is impermeable to anticancer drugs, which are dual ABCB1/ABCG2 substrates. Therefore, effective drugs for antitumor treatment should have high passive permeability and lack ABCB1/ABCG2 substrate affinity.

Trial registration

European Union Drug Regulating Authorities Clinical Trials Database (EUDRACT), 2011-004189-13. Registered on 23 February 2012, https://www.clinicaltrialsregister.eu/ctr-search/search?query=2011-004189-13.
Patient-reported data informing early benefit assessment of rare diseases in Germany: A systematic review
Authors: Babac Ana , Damm Kathrin , Graf von der Schulenburg J.-Matthias
Published: December 2019

Background

Since the implementation of the Regulation on Patient Integration (2003), the Act on the Reorganization of the Pharmaceutical Market (2011), and the Patient Rights Law (2013), the inclusion of patient perspectives has been further anchored in the German early benefit assessment process. During the assessment of rare disease interventions, patient perspectives are particularly important, as clinical studies are often designed acknowledging small samples and patients suffering from severe symptoms and the chronic course of the disease. Therefore, our research question is whether patient perspectives are considered as part of early benefit assessments for rare diseases. We also strive to examine how patient perspectives are methodologically elicited and presented.

Methods

Our empirical evidence comes from a systematic review of orphan drug value dossiers submitted to the German Federal Joint Committee as well as the corresponding evaluations conducted between January 1, 2011 and March 1, 2019 (n = 81). Data on patient perspective integration were extracted using the following patient-reported outcome subcategories: clinical patient-reported outcomes, health-related quality of life, patient preferences, and patient satisfaction.

Results

The analysis demonstrates the specific relevance of patient-reported outcomes raised as part of the medical data set and presented during the early benefit assessment process. They are predominantly presented in the form of health-related quality of life data (n = 75%) and clinical outcomes (n = 49%). Preferences (n = 2%) and satisfaction (n = 1%) are still rarely presented, although the heated methodological discussion in Germany would suggest otherwise. While various methodologies for the integration of clinical outcomes and quality of life data were found, presenting data on satisfaction and preferences still lacks methodological rigor. The German Federal Joint Committee has not yet integrated these data in their decision text. Clinical outcomes and quality of life have been included in 46% and 73% of the cases, respectively.

Conclusions

The underlying analysis demonstrates that there is still a relative high potential for the regular and systematic inclusion of patient perspectives within the early benefit assessment process for rare diseases. In particular, patient preferences and patient satisfaction are still rarely included suggesting the need for a clear-cut methodological foundation and incentives.
Periodic solutions for second order damped boundary value problem with nonnegative Green’s functions
Authors: Jiang Yongxin
Published: December 2019

In this article, we study the existence of positive periodic solutions of second order damped boundary value problem$u'' + p(t)u'+q(t)u = g(t,u,u')$u″+p(t)u′+q(t)u=g(t,u,u′),$u(0) = u(T )$u(0)=u(T),$u'(0) = u'(T )$u′(0)=u′(T). The main tools are the nonlinear alternative principle of Leray–Schauder and Schauder’s fixed point theorem. We emphasize that the damped term and nonnegative Green’s functions are the key points. We also apply the results to examples for testing. Some recent results in the literature are improved and generalized.
A fourth order non-polynomial quintic spline collocation technique for solving time fractional superdiffusion equations
Authors: Amin Muhammad , Abbas Muhammad , Iqbal Muhammad Kashif , Ismail Ahmad Izani Md. , Baleanu Dumitru
Published: December 2019

The purpose of this article is to present a technique for the numerical solution of Caputo time fractional superdiffusion equation. The central difference approximation is used to discretize the time derivative, while non-polynomial quintic spline is employed as an interpolating function in the spatial direction. The proposed method is shown to be unconditionally stable and$O(h^{4}+\Delta t^{2})$O(h4+Δt2)accurate. In order to check the feasibility of the proposed technique, some test examples have been considered and the simulation results are compared with those available in the existing literature.