bluuebunny/crossref_metadata_2025_split huggingface dataset:
Post-intravitreal injection endophthalmitis secondary to Turicella otitidis: a case report
Authors: Mammo Danny A. , Watson Daniel , Armbrust Karen R. 
Published: April 2020

Abstract
Background
Endophthalmitis is a rare but potentially devastating complication of intravitreal injection. The causative organism plays an important role in prognosis following endophthalmitis. Here we present the first reported case of Turicella otitidis endophthalmitis, which is notable for a delayed presentation.

Case presentation
A 71 year old male who was receiving intravitreal aflibercept injections for neovascular age-related macular degeneration presented 4 weeks after his most recent intravitreal injection and was found to have endophthalmitis. Polymerase chain reaction (PCR) testing of aqueous fluid was positive for Turicella otitidis. The endophthalmitis responded well to treatment with intravitreal antibiotics.

Conclusions
Coryneform bacteria are a rare cause of endophthalmitis, and this is the first reported case of endophthalmitis caused by the corynebacterium species Turicella otitidis. As in this case, post-intravitreal injection endophthalmitis may have a bacterial etiology even with delayed presentation. The relatively indolent disease course and excellent response to intravitreal antibiotics is consistent with previous ophthalmic reports regarding other corynebacteria, as well as with otolaryngology and hematology oncology reports addressing Turicella otitidis specifically. This case supports the growing body of evidence for pathogenicity of Turicella otitidis and demonstrates the utility of PCR for diagnosis in small volume aqueous specimens.
Effect of Gallic acid and Myricetin on ovarian cancer models: a possible alternative antitumoral treatment
Authors: Varela-Rodríguez Luis , Sánchez-Ramírez Blanca , Hernández-Ramírez Verónica Ivonne , Varela-Rodríguez Hugo , Castellanos-Mijangos Rodrigo Daniel , González-Horta Carmen , Chávez-Munguía Bibiana , Talamás-Rohana Patricia 
Published: April 2020

Abstract
Background
Ovarian cancer is the leading cause of mortality among malignant gynecological tumors. Surgical resection and chemotherapy with intravenous platinum/taxanes drugs are the treatments of choice, with little effectiveness in later stages and severe toxicological effects. Therefore, this study aimed to evaluate the antineoplastic activity of gallic acid (GA) and myricetin (Myr) administrated peritumorally in Nu/Nu mice xenotransplanted with SKOV-3 cells.

Methods
Biological activity of GA and MYR was evaluated in SKOV-3 and OVCAR-3 cells (ovarian adenocarcinomas) by confocal/transmission electron microscopy, PI-flow cytometry, H2-DCF-DA stain, MTT, and Annexin V/PI assays. Molecular targets of compounds were determined with ACD/I-Labs and SEA. Antineoplastic activity was performed in SKOV-3 cells subcutaneously xenotransplanted into female Nu/Nu mice treated peritumorally with 50 mg/kg of each compound (2 alternate days/week) for 28 days. Controls used were paclitaxel (5 mg/kg) and 20 μL of vehicle (0.5% DMSO in 1X PBS). Tumor lesions, organs and sera were evaluated with NMR, USG, histopathological, and paraclinical studies.

Results
In vitro studies showed a decrease of cell viability with GA and Myr in SKOV-3 (50 and 166 μg/mL) and OVCAR-3 (43 and 94 μg/mL) cells respectively, as well as morphological changes, cell cycle arrest, and apoptosis induction due to ROS generation (p ≤ 0.05, ANOVA). In silico studies suggest that GA and MYR could interact with carbonic anhydrase IX and PI3K, respectively. In vivo studies revealed inhibitory effects on tumor lesions development with GA and MYR up to 50% (p ≤ 0.05, ANOVA), with decreased vascularity, necrotic/fibrotic areas, neoplastic stroma retraction and apoptosis. However, toxicological effects were observed with GA treatment, such as leukocyte infiltrate and hepatic parenchyma loss, hypertransaminasemia (ALT: 150.7 ± 25.60 U/L), and hypoazotemia (urea: 33.4 ± 7.4 mg/dL), due to the development of chronic hepatitis (p ≤ 0.05, ANOVA).

Conclusion
GA and Myr (50 mg/kg) administered by peritumoral route, inhibit ovarian tumor lesions development in rodents with some toxicological effects. Additional studies will be necessary to find the appropriate therapeutic dose for GA. Therefore, GA and Myr could be considered as a starting point for the development of novel anticancer agents.
Characteristics, service use and mortality of clusters of multimorbid patients in England: a population-based study
Authors: Zhu Yajing , Edwards Duncan , Mant Jonathan , Payne Rupert A. , Kiddle Steven 
Published: April 2020

Abstract
Background
Multimorbidity is associated with mortality and service use, with specific types of multimorbidity having differential effects. Additionally, multimorbidity is often negatively associated with participation in research cohorts. Therefore, we set out to identify clusters of multimorbidity patients and how they are differentially associated with mortality and service use across age groups in a population-representative sample.

Methods
Linked primary and secondary care electronic health records contributed by 382 general practices in England to the Clinical Practice Research Datalink (CPRD) were used. The study included a representative set of multimorbid adults (18 years old or more, N = 113,211) with two or more long-term conditions (a total of 38 conditions were included). A random set of 80% of the multimorbid patients (N = 90,571) were stratified by age groups and clustered using latent class analysis. Consistency between obtained multimorbidity phenotypes, classification quality and associations with demographic characteristics and primary outcomes (GP consultations, hospitalisations, regular medications and mortality) was validated in the remaining 20% of multimorbid patients (N = 22,640).

Results
We identified 20 patient clusters across four age strata. The clusters with the highest mortality comprised psychoactive substance and alcohol misuse (aged 18–64); coronary heart disease, depression and pain (aged 65–84); and coronary heart disease, heart failure and atrial fibrillation (aged 85+). The clusters with the highest service use coincided with those with the highest mortality for people aged over 65. For people aged 18–64, the cluster with the highest service use comprised depression, anxiety and pain. The majority of 85+-year-old multimorbid patients belonged to the cluster with the lowest service use and mortality for that age range. Pain featured in 13 clusters.

Conclusions
This work has highlighted patterns of multimorbidity that have implications for health services. These include the importance of psychoactive substance and alcohol misuse in people under the age of 65, of co-morbid depression and coronary heart disease in people aged 65–84 and of cardiovascular disease in people aged 85+.
MicroRNA-196b-5p promotes malignant progression of colorectal cancer by targeting ING5
Authors: Xin He , Wang Chuanzhuo , Chi Yuan , Liu Zhaoyu 
Published: April 2020

Abstract
Background
miR-196b-5p expression is deregulated in many malignant tumors. Although miR-196b-5p has been implicated in the malignant transformation of colorectal cancer, its role in this specific type of cancer has not been fully explored. Thus, the present study was aimed to examine the cellular function of miR-196b-5p and its role in malignant biological behavior in colorectal cancer.

Methods
miR-196b-5p expression was measured in colorectal cancer tissues and cell lines using quantitative real-time PCR. Cell counting kit-8 (CCK-8) assay and Transwell assay were used to detect proliferation, migration, and invasion in cell lines, whereas flow cytometry was applied to study apoptosis. Western blot analysis was performed to measure the protein levels. Dual luciferase reporter assay was used to investigate the interaction between miR-196b-5p and ING5. Tumor formation was evaluated in mice.

Results
MiR-196b-5p was abundantly expressed in colorectal cancer tissues and cell lines, whereas ING5 was expressed at low levels. MiR-196b-5p was successfully overexpressed or knocked down in colorectal cancer cells. We found that miR-196b-5p overexpression significantly accelerated the proliferation, cell cycle, migration and invasion, while inhibited cell apoptosis in colorectal cancer cells. However, miR-196b-5p inhibitor showed the opposite effects. Moreover, ING5 overexpression or knockdown was successfully performed in colorectal cancer cells. ING5 overexpression suppressed proliferation, migration, invasion, the phosphorylation of PI3K, Akt as well as MEK, and promoted cell apoptosis, which could be reversed by ING5 knockdown. Additionally, ING5 was identified as a target of miR-196b-5p through bioinformatics analysis and a luciferase activity assay. Furthermore, ING5 knockdown could attenuate the decrease in proliferation, migration, invasion, and the protein levels of p-PI3K, p-Akt, and p-MEK, which were induced by miRNA-196b-5p inhibitor. Besides, miR-196b-5p knockdown inhibited tumor growth, whereas ING5 knockdown elevated it in vivo.

Conclusions
In conclusion, miR-196b-5p promotes cell proliferation, migration, invasion, and inhibits apoptosis in colorectal cancer by targeting ING5.
Moving beyond the mousetrap: current and emerging humanized mouse and rat models for investigating prevention and cure strategies against HIV infection and associated pathologies
Authors: Agarwal Yash , Beatty Cole , Biradar Shivkumar , Castronova Isabella , Ho Sara , Melody Kevin , Bility Moses Turkle 
Published: April 2020

AbstractThe development of safe and effective combination antiretroviral therapies for human immunodeficiency virus (HIV) infection over the past several decades has significantly reduced HIV-associated morbidity and mortality. Additionally, antiretroviral drugs have provided an effective means of protection against HIV transmission. Despite these advances, significant limitations exist; namely, the inability to eliminate HIV reservoirs, the inability to reverse lymphoid tissues damage, and the lack of an effective vaccine for preventing HIV transmission. Evaluation of the safety and efficacy of therapeutics and vaccines for eliminating HIV reservoirs and preventing HIV transmission requires robust in vivo models. Since HIV is a human-specific pathogen, that targets hematopoietic lineage cells and lymphoid tissues, in vivo animal models for HIV-host interactions require incorporation of human hematopoietic lineage cells and lymphoid tissues. In this review, we will discuss the construction of mouse models with human lymphoid tissues and/or hematopoietic lineage cells, termed, human immune system (HIS)-humanized mice. These HIS-humanized mouse models can support the development of functional human innate and adaptive immune cells, along with primary (thymus) and secondary (spleen) lymphoid tissues. We will discuss applications of HIS-humanized mouse models in evaluating the safety and efficacy of therapeutics against HIV reservoirs and associated immunopathology, and delineate the human immune response elicited by candidate HIV vaccines. In addition to focusing on how these HIS-humanized mouse models have already furthered our understanding of HIV and contributed to HIV therapeutics development, we discuss how emerging HIS-humanized rat models could address the limitations of HIS-mouse models.
Sum of phase-shifted sinusoids stimulation prolongs paralyzed muscle output
Authors: Gelenitis Kristen , Freeberg Max , Triolo Ronald 
Published: April 2020

AbstractNeuroprostheses that activate musculature of the lower extremities can enable standing and movement after paralysis. Current systems are functionally limited by rapid muscle fatigue induced by conventional, non-varying stimulus waveforms. Previous work has shown that sum of phase-shifted sinusoids (SOPS) stimulation, which selectively modulates activation of individual motor unit pools (MUPs) to lower the duty cycle of each while maintaining a high net muscle output, improves joint moment maintenance but introduces greater instability over conventional stimulation. In this case study, implementation of SOPS stimulation with a real-time feedback controller successfully decreased joint moment instability and further prolonged joint moment output with increased stimulation efficiency over open-loop approaches in one participant with spinal cord injury. These findings demonstrate the potential for closed-loop SOPS to improve functionality of neuroprosthetic systems.
Prevalence and factors associated with exclusive breastfeeding among rural mothers of infants less than six months of age in Southern Nations, Nationalities, Peoples (SNNP) and Tigray regions, Ethiopia: a cross-sectional study
Authors: Hagos Dawit , Tadesse Amare Worku 
Published: April 2020

Abstract
Background
Exclusive breastfeeding (EBF) is the global recommended nutrition for infants less than 6 months of age. The prevalence of exclusive breastfeeding in Ethiopia is much lower than the recommendations of World Health Organization (WHO). This study aimed to assess the prevalence and associated factors of EBF among rural mothers of infants less than 6 months of age in two regions, Southern Nations, Nationalities and Peoples (SNNP) and Tigray Regions, of Ethiopia.

Methods
The research was based on the secondary data analysis of community-based cross-sectional study conducted in 56 rural woredas (districts) in two regions of Ethiopia for impact evaluation of Alive & Thrive multi-year project. The 24-h recall dietary data were collected from 600 mother-infant dyads where the infant was less than 6 month of age, using multistage cluster sampling technique and 584 dyads were found eligible for analysis. Bivariate and multivariable logistic regressions were applied to identify the associated factors of exclusive breastfeeding.

Results
The prevalence of EBF of infants less than 6 months of age was 88.0% (95% CI 84.9, 90.4%). The odds of practicing EBF were significantly higher among infants less than 2 months of age (AOR 4.47, 95% CI 2.41, 8.27), married mothers (AOR 4.35, 95% CI 1.50, 12.67), mothers who gave birth in health facilities (AOR 2.07, 95% CI 1.15, 3.73) and mothers who received breastfeeding counseling during pregnancy (AOR 2.23, 95% CI 1.26, 3.96).

Conclusions
The prevalence of EBF was relatively high when compared with previous studies in Ethiopia but close to the WHO recommendations of 90 %. Infant age, marital status of mothers, delivery place and breastfeeding counseling during pregnancy were identified as factors associated with EBF practices in 24 h preceding the survey. Devising appropriate strategies on breastfeeding messaging/counseling and support in addressing poor breastfeeding practices through existing government-led health intervention packages are recommended.
Natural history of lung function in spinal muscular atrophy
Authors: Wijngaarde Camiel A. , Veldhoen Esther S. , van Eijk Ruben P. A. , Stam Marloes , Otto Louise A. M. , Asselman Fay-Lynn , Wösten-van Asperen Roelie M. , Hulzebos Erik H. J. , Verweij-van den Oudenrijn Laura P. , Bartels Bart , Cuppen Inge , Wadman Renske I. , van den Berg Leonard H. , van der Ent Cornelis K. , van der Pol W. Ludo 
Published: April 2020

Abstract
Background
Respiratory muscle weakness is an important feature of spinal muscular atrophy (SMA). Progressive lung function decline is the most important cause of mortality and morbidity in patients. The natural history of lung function in SMA has, however, not been studied in much detail.

Results
We analysed 2098 measurements of lung function from 170 treatment-naïve patients with SMA types 1c–4, aged 4–74 years. All patients are participating in an ongoing population-based prevalence cohort study. We measured Forced Expiratory Volume in 1 s (FEV1), Forced Vital Capacity (FVC), and Vital Capacity (VC). Longitudinal patterns of lung function were analysed using linear mixed-effects and non-linear models. Additionally, we also assessed postural effects on results of FEV1 and FVC tests. In early-onset SMA types (1c–3a), we observed a progressive decline of lung function at younger ages with relative stabilisation during adulthood. Estimated baseline values were significantly lower in more severely affected patients: %FEV1 ranged from 42% in SMA type 1c to 100% in type 3b, %FVC 50 to 109%, and %VC 44 to 96%. Average annual decline rates also differed significantly between SMA types, ranging from − 0.1% to − 1.4% for FEV1, − 0.2% to − 1.4% for FVC, and + 0.2% to − 1.7% for VC. In contrast to SMA types 1c–3a, we found normal values for all outcomes in later-onset SMA types 3b and 4 throughout life, although with some exceptions and based on limited available data. Finally, we found no important differences in FVC or FEV1 values measured in either sitting or supine position.

Conclusions
Our data illustrate the longitudinal course of lung function in patients with SMA, which is characterised by a progressive decline in childhood and stabilisation in early adulthood. The data do not support an additional benefit of measuring FEV1 or FVC in both sitting and supine position. These data may serve as a reference to assess longer-term outcomes in clinical trials.
Dynamic changes of CSF sTREM2 in preclinical Alzheimer’s disease: the CABLE study
Authors: Ma Ling-Zhi , Tan Lan , Bi Yan-Lin , Shen Xue-Ning , Xu Wei , Ma Ya-Hui , Li Hong-Qi , Dong Qiang , Yu Jin-Tai 
Published: April 2020

Abstract
Background
Loss of function of triggering receptor expressed on myeloid cell 2 (TREM2), a key receptor selectively expressed by microglia in the brain, contributes to the development of Alzheimer’s disease (AD). Whether TREM2 levels are pathologically altered during the preclinical phase, and whether cerebrospinal fluid (CSF) soluble TREM2 protein (sTREM2) has a relationship with major pathological processes including Aβ and tau deposition are still unclear.

Methods
According to the NIA-AA criteria, 659 cognitively normal participants from the Chinese Alzheimer’s Biomarker and LifestylE (CABLE) cohort were divided into four groups, stage 0 (normal Aβ1–42, T-tau and P-tau), stage 1 (low Aβ1–42, normal T-tau and P-tau), stage 2 (low Aβ1–42 and high T-tau or P-tau), and suspected non-AD pathology (SNAP) (normal Aβ1–42 and high T-tau or P-tau), to examine changes of CSF sTREM2 in the preclinical AD. Biomarker cut-off was based on the assumption that one-third of adults with normal cognition have AD pathology.

Results
The level of CSF sTREM2 in the stage 1 decreased compared with the stage 0 (P < 0.001), and then increased in the stage 2 (P = 0.008). SNAP individuals also had significantly increased CSF sTREM2 (P < 0.001). Results of multiple linear regressions also showed positive correlations of CSF sTREM2 with Aβ1–42 (β = 0.192, P < 0.001), T-tau (β = 0.215, P < 0.001) and P-tau (β = 0.123, P < 0.001).

Conclusion
CSF sTREM2 levels are dynamic in preclinical AD. Aβ pathology is associated with a decrease in CSF sTREM2 in the absence of tau deposition and neurodegeneration. However, tau pathology and neurodegeneration are associated with an increase in CSF sTREM2.
Alternatively activated macrophages are associated with the α2AP production that occurs with the development of dermal fibrosis
Authors: Kanno Yosuke , Shu En , Niwa Hirofumi , Kanoh Hiroyuki , Seishima Mariko 
Published: April 2020

AbstractBackgroundFibrotic diseases are characterized by tissue overgrowth, hardening, and/or scarring because of the excessive production, deposition, and contraction of the extracellular matrix (ECM). However, the detailed mechanisms underlying these disorders remain unclear. It was recently reported that α2-antiplasmin (α2AP) is elevated in fibrotic tissue and that it is associated with the development of fibrosis. In the present study, we examined the mechanism underlying the production of α2AP on the development of fibrosis.MethodsTo clarify the mechanism underlying the production of α2AP on the development of fibrosis, we focused on high-mobility group box 1 (HMGB1), which is associated with the development of fibrosis. The mouse model of bleomycin-induced fibrosis was used to evaluate the production of α2AP on the development of fibrosis.ResultsWe found that HMGB1 induced the production of α2AP through receptor for advanced glycation end products (RAGE) in fibroblasts. Next, we showed that macrophage reduction by a macrophage-depleting agent, clodronate, attenuated the progression of fibrosis and the production of α2AP and HMGB1 in the bleomycin-induced mice. We also showed that IL-4-stimulated alternatively activated macrophages induced the production of HMGB1, that IL-4-stimulated alternatively activated macrophage conditioned media (CM) induced pro-fibrotic changes and α2AP production, and that the inhibition of HMGB1 and RAGE attenuated these effects in fibroblasts. Furthermore, the blockade of IL-4 signaling by IL-4Rα neutralizing antibodies attenuated the progression of fibrosis and the production of α2AP and HMGB1 in the bleomycin-induced mice.ConclusionThese findings suggest that alternatively activated macrophage-derived HMGB1 induced the production of α2AP through RAGE and that these effects are associated with the development of fibrosis. Our findings may provide a clinical strategy for managing fibrotic disorders.
Metformin rescues rapamycin-induced mitochondrial dysfunction and attenuates rheumatoid arthritis with metabolic syndrome
Authors: Kim Eun Kyung , Min Hong Ki , Lee Seon-Yeong , Kim Da-Som , Ryu Jun-Geol , Na Hyun Sik , Jung Kyoung Ah , Choi Jeong Won , Park Sung-Hwan , Cho Mi-La 
Published: April 2020

Abstract
Background
Rapamycin, an inhibitor of the serine/threonine protein kinase mTOR, is an immunosuppressant used to treat renal transplant recipients, but it can cause endothelial and mitochondrial dysfunction. Metformin is used for the treatment of type 2 diabetes and was reported to exert therapeutic effects against rheumatoid arthritis and obesity by improving mitochondrial dysfunction via the activation of fibroblast growth factor 21. We investigated the therapeutic effects of rapamycin–metformin combination therapy in obese mice with collagen-induced arthritis (CIA).

Methods
Mouse embryonic fibroblasts were treated with rapamycin, metformin, or rapamycin–metformin, and their respiratory level and mitochondrial gene expression were assayed. Mice were fed a high-fat diet, immunized with type II collagen, and subsequently treated with rapamycin–metformin daily for 10 weeks.

Results
Rapamycin-treated cells exhibited dysfunction of mitochondrial respiration and decreased mitochondrial gene expression compared with rapamycin–metformin-treated cells. Moreover, rapamycin–metformin reduced the clinical arthritis score and the extent of histological inflammation and improved the metabolic profile in obese mice with CIA. Rapamycin–metformin enhanced the balance between T helper 17 and regulatory T cells in vitro and in vivo.

Conclusions
These results suggest that rapamycin–metformin is a potential therapeutic option for autoimmune arthritis.