bluuebunny/crossref_metadata_2025_split huggingface dataset:
Histopathological changes in tear-secreting tissues and cornea in a mouse model of autoimmune disease
Authors: Hiraishi Masaya , Masum Md Abdul , Namba Takashi , Otani Yuki , Elewa Yaser HA , Ichii Osamu , Kon Yasuhiro 
Published: May 2020

The tear film covers the cornea, and its abnormalities (including immunological) induce dry eye. Using autoimmune disease model mice, BXSB/MpJ- Yaa (BXSB-Yaa), histopathological changes in the eye and tear-secreting tissues were examined using histopathology, immunohistochemistry, and electron microscopy at 8, 20, and 28 weeks for early, middle, and late disease stages. Early and middle stage BXSB-Yaa showed increased serum autoantibody and spleen weight-to-body weight (S/B) ratio, respectively, and higher tear volume than controls, BXSB/MpJ (BXSB), at early stages, which decreased with ageing and negatively correlated with autoimmune disease indices. Smaller Meibomian gland acini, intraorbital lacrimal glands, and Harderian gland acinar cells were seen in late stage BXSB-Yaa than in BXSB; the latter two indices decreased with ageing and negatively correlated with the S/B ratio. Cell infiltration occurred in the middle stage BXSB-Yaa extraorbital lacrimal gland, and acinar cells were smaller than BXSB. The conjunctival goblet cells decreased from early to middle stages in both strains, but in BXSB-Yaa, they increased at late stages with a partial lack of microvilli on the cornea and were inversely altered with anterior epithelium thickness through ageing, suggesting that they compensated for anterior epithelium damage. In conclusion, the tear film was unstable due to an autoimmune disease condition in BXSB-Yaa. Impact statement Cornea, an outermost layer of mammalian eye, is protected by tear film and abnormalities of tear film causes dry eye. Dry eye injures the cornea which results lower vision in patients. Several factors cause dry eye, including altered systemic conditions, environment, and immunological abnormality of the patient in autoimmune disease like Sjögren’s syndrome (SS). However, the detailed pathology of autoimmune abnormality-mediated dry eye is unclear. Here we demonstrated that systemic autoimmune abnormality in BXSB-Yaa mice was associated with histological changes in the exocrine glands and cornea of the eyes. We also showed that BXSB-Yaa mice developed mild or early stage dry eye-like disease and explain the existence of a compensatory mechanism associated with the dysfunction of these tissues. Thus, BXSB-Yaa could be a model for SS-like disease-associated dry eye and these data would contribute to the understanding of the pathogenesis of autoimmune-related dry eye disease.
Association Between Physical Fitness and Bone Strength and Structure in 3- to 5-Year-Old Children
Authors: Gómez-Bruton Alejandro , Marín-Puyalto Jorge , Muñiz-Pardos Borja , Lozano-Berges Gabriel , Cadenas-Sanchez Cristina , Matute-Llorente Angel , Gómez-Cabello Alba , Moreno Luis A. , Gonzalez-Agüero Alex , Casajus Jose A. , Vicente-Rodríguez Germán 
Published: May 2020

Background: The positive association between physical fitness and bone structure has been widely investigated in children and adolescents, yet no studies have evaluated this influence in young children (ie, preschoolers). Hypothesis: Fit children will present improved bone variables when compared with unfit children, and no sex-based differences will emerge in the sample. Study Design: Cross-sectional study. Level of Evidence: Level 3. Methods: Handgrip strength, standing long jump (SLJ), speed/agility, balance, and cardiorespiratory fitness (CRF) were assessed using the Assessing FITness levels in PREschoolers (PREFIT) test battery in 92 children (50 boys; age range, 3-5 years). A peripheral quantitative computed tomography scan was performed at 38% of the length of the nondominant tibia. Cluster analysis from handgrip strength, SLJ, speed/agility, and CRF was developed to identify fitness groups. Bone variables were compared between sexes and between cluster groups. The association between individual physical fitness components and different bone variables was also tested. Results: Three cluster groups emerged: fit (high values on all included physical fitness variables), strong (high strength values and low speed/agility and CRF), and unfit (low strength, speed/agility, and CRF). The fit group presented higher values than the strong and unfit groups for total and cortical bone mineral content, cortical area, and polar strength strain index (all P < 0.05). The fit group also presented a higher cortical thickness when compared with the unfit group ( P < 0.05). Handgrip, SLJ, and speed/agility predicted all bone variables except for total and cortical volumetric bone mineral density. No differences were found for bone variables between sexes. Conclusion: The results suggest that global fitness in preschoolers is a key determinant for bone structure and strength but not volumetric bone mineral density. Clinical Relevance: Physical fitness is a determinant for tibial bone mineral content, structure, and strength in very young children. Performing physical fitness tests could provide useful information related to bone health in preschoolers.
From ER to OR: Results After Implementation of Multidisciplinary Pathway for Fragility Hip Fractures at a Level I Trauma Center
Authors: Anighoro Kenoma , Bridges Carla , Graf Alexander , Nielsen Alexander , Court Tannor , McKeon Jack , Schwab Joseph M. 
Published: May 2020

Introduction: Hip fractures are one of the most common indications for hospitalization and orthopedic intervention. Fragility hip fractures are frequently associated with multiple comorbidities and thus may benefit from a structured multidisciplinary approach for treatment. The purpose of this article was to retrospectively analyze patient outcomes after the implementation of a multidisciplinary hip fracture pathway at a level I trauma center. Materials and Methods: A retrospective review of 263 patients over the age of 65 with fragility hip fracture was performed. Time to surgery, hospital length of stay, Charlson Comorbidity Index (CCI), American Society of Anesthesiologists, complication rates, and other clinical outcomes were compared between patients treated in the year before and after implementation of a multidisciplinary hip fracture pathway. Results: Timing to OR, hospital length of stay, and complication rates did not differ between pre- and postpathway groups. The postpathway group had a greater CCI score (pre: 3.10 ± 3.11 and post: 3.80 ± 3.18). Fewer total blood products were administered in the postpathway group (pre: 1.5 ± 1.8 and post: 0.8 ± 1.5). Discussion: The maintenance of clinical outcomes in the postpathway cohort, while having a greater CCI, indicates the same quality of care was provided for a more medically complex patient population. With a decrease in total blood products in the postpathway group, this highlights the economic importance of perioperative optimization that can be obtained in a multidisciplinary pathway. Conclusion: Implementation of a multidisciplinary hip fracture pathway is an effective strategy for maintaining care standards for fragility hip fracture management, particularly in the setting of complex medical comorbidities.
Chromosome 1 abnormalities and survival of patients with multiple myeloma in the era of novel agents
Authors: Giri Smith , Huntington Scott F. , Wang Rong , Zeidan Amer M. , Podoltsev Nikolai , Gore Steven D. , Ma Xiaomei , Gross Cary P. , Davidoff Amy J. , Neparidze Natalia 
Published: May 2020

AbstractChromosome 1 abnormalities (C1As) are common genetic aberrations among patients with multiple myeloma (MM). We aimed to evaluate the significance of C1As among a contemporary cohort of patients with MM in the United States. We used electronic health records from the Flatiron Health database to select patients newly diagnosed with MM from January 2011 to March 2018 who were tested using fluorescence in situ hybridization within 90 days of diagnosis. We characterized patients as having documented C1As or other high-risk chromosomal abnormalities (HRCAs) as defined by the Revised-International Staging System (R-ISS) such as del(17p), t(14;16), and t(4;14). We used Kaplan-Meier methods to compare overall survival (OS) of patients with or without C1As and stratified log-rank tests (with the presence of HRCAs as a stratifying variable). We used Cox proportional hazards regression models to compare OS, adjusting for age, sex, stage, HRCAs, and type of first-line therapy. Of 3578 eligible patients, 844 (24%) had documented C1As. Compared with patients without C1As, patients with C1As were more likely to have higher stage (R-ISS stage III; 18% vs 12%), to have HRCAs (27% vs 14%), and to receive combinations of proteasome inhibitors and immunomodulatory agents (41% vs 34%). Median OS was lower for patients with C1As (46.6 vs 70.1 months; log-rank P &lt; .001). C1As were independently associated with worse OS (adjusted hazard ratio, 1.42; 95% confidence interval, 1.19-2.69; P &lt; .001), as were older age, higher R-ISS stage, HRCAs, and immunoglobulin A isotype. C1As were associated with inferior OS, independent of other HRCAs, despite greater use of novel therapies. Clinical trials testing newer therapies for high-risk MM should incorporate patients with C1As.
Adult cord blood transplant results in comparable overall survival and improved GRFS vs matched related transplant
Authors: Sharma Prashant , Purev Enkhtsetseg , Haverkos Bradley , Pollyea Daniel A. , Cherry Evan , Kamdar Manali , Mark Tomer , Forsberg Peter , Sherbenou Daniel , Hammes Andrew , Rabinovitch Rachel , Smith Clayton A. , Gutman Jonathan A. 
Published: May 2020

Abstract
We compared outcomes among adult matched related donor (MRD) patients undergoing peripheral blood stem cell transplantation and adult patients undergoing double unit cord blood transplantation (CBT) at our center between 2010 and 2017. A total of 190 CBT patients were compared with 123 MRD patients. Median follow-up was 896 days (range, 169-3350) among surviving CBT patients and 1262 days (range, 249-3327) among surviving MRD patients. Comparing all CBT with all MRD patients, overall survival (OS) was comparable (P = .61) and graft-versus-host disease (GVHD) relapse-free survival (GRFS) was significantly improved among CBT patients (P = .0056), primarily because of decreased moderate to severe chronic GVHD following CBT (P &lt; .0001; hazard ratio [HR], 3.99; 95% confidence interval [CI], 2.26-7.04). Among patients undergoing our most commonly used MRD and umbilical cord blood (CB) myeloablative regimens, OS was comparable (P = .136) and GRFS was significantly improved among CBT patients (P = .006). Cumulative incidence of relapse trended toward decreased in the CBT group (P = .075; HR, 1.85; CI 0.94-3.67), whereas transplant-related mortality (TRM) was comparable (P = .55; HR, 0.75; CI, 0.29-1.95). Among patients undergoing our most commonly used nonmyeloablative regimens, OS and GRFS were comparable (P = .158 and P = .697). Cumulative incidence of both relapse and TRM were comparable (P = .32; HR, 1.35; CI, 0.75-2.5 for relapse and P = .14; HR, 0.482; CI, 0.18-1.23 for TRM). Our outcomes support the efficacy of CBT and suggest that among patients able to tolerate more intensive conditioning regimens at high risk for relapse, CB may be the preferred donor source.
Parents’ experiences of accessing respite care for children with Autism Spectrum Disorder (ASD) at the acute and primary care interface: a systematic review
Authors: Cooke Emma , Smith Valerie , Brenner Maria 
Published: May 2020

Abstract
Background
Population prevalence estimates by the World Health Organisation suggest that 1 in 160 children worldwide has an Autism Spectrum Disorder (ASD). Accessing respite care services for children with an ASD can often be a daunting and exhaustive process, with parents sometimes forced to access acute hospital services as an initial point of contact for respite care or in a crisis situation. To gain an in-depth understanding of accessing respite care for children with an ASD, from the perspectives of parents, a systematic review of the evidence on parent’s experiences and views of respite care for children with an ASD at the acute and primary interface was undertaken.

Methods
Pubmed, Embase, CINAHL and PsycINFO were systematically searched. Studies identified as relevant based on predetermined eligibility criteria were selected for inclusion. The search strategy also targeted unpublished studies and grey literature. Qualitative data and qualitative components of mixed method studies that represented the experiences of parents accessing respite care for children with an ASD were eligible for inclusion. A meta-aggregative approach was used during data synthesis.

Results
Database searching elicited 430 records of which 291 studies remained after removal of duplicates. These 291 studies were screened for title and abstract by two reviewers resulting in 31 studies to be screened at full text and assessed for eligibility. Six studies met the inclusion criteria and a further additional study also met the inclusion criteria during a manual search. As a result, 7 studies were selected for the review as set out in Fig. 1.

Conclusion
In the absence of appropriate services and defined pathways to support services such as respite care, overwhelmed parents and community providers of mental health resources may not be in a position to meet the specific needs of children with an ASD and their families which may be contributing to a direct increase in hospitalizations. This systematic review identified a number of barriers to respite care, of which the findings can be used to inform future service development and further research. Knowledge of parental experiences in caring for a child with an ASD is vital in addressing the need and type of respite care required for children with an ASD.

Systematic review registration
PROSPERO CRD42018106629.
The SMA Clinical Trial Readiness Program: creation and evaluation of a program to enhance SMA trial readiness in the United States
Authors: Peterson Ilse , Cruz Rosángel , Sarr Fatou , Stanley Ann Marie , Jarecki Jill 
Published: May 2020

AbstractSpinal muscular atrophy (SMA) is a rare neuromuscular disease with a rapidly evolving treatment landscape. To better meet the needs of trial sponsors and the patient community in the United States (US) in this evolving context, Cure SMA established a clinical trial readiness program for new and prospective SMA clinical trial sites. Program development was informed by a review of the SMA clinical trial landscape, successful NMD trial and care networks, and factors important to effective trial conduct in SMA. The program was piloted in 2018 with a virtual site readiness evaluation, a trial readiness toolkit, and a readiness program for physical therapists and clinical evaluators. Nine US research hospitals participated in the pilot. Cure SMA evaluated the pilot program and resources through feedback surveys, which supported the program’s relevance and value. Since 2018, the program has been expanded with additional sites, new best practices toolkits, and workshops. In partnership with Cure SMA, SMA Europe is also extending programming to European countries. The program is significant as an example of a patient advocacy group working successfully with pharmaceutical companies, other patient advocacy organizations, and research hospitals to promote trial readiness, and may serve as a model for organizations in other regions and diseases.
Hagfish genome reveals parallel evolution of 7SL RNA-derived SINEs
Authors: Kojima Kenji K. 
Published: May 2020

Abstract
Background
Short interspersed elements (SINEs) are ubiquitous components of eukaryotic genomes. SINEs are composite transposable elements that are mobilized by non-long terminal repeat (non-LTR) retrotransposons, also called long interspersed elements (LINEs). The 3′ part of SINEs usually originated from that of counterpart non-LTR retrotransposons. The 5′ part of SINEs mostly originated from small RNA genes. SINE1 is a group of SINEs whose 5′ part originated from 7SL RNA, and is represented by primate Alu and murine B1. Well-defined SINE1 has been found only from Euarchontoglires, a group of mammals, in contrast to the wide distribution of SINE2, which has a tRNA-derived sequence, from animals to plants to protists. Both Alu and B1 are mobilized by L1-type non-LTR retrotransposons, which are the only lineage of autonomous non-LTR retrotransposons active in these mammalian lineages.

Results
Here a new lineage of SINE1 is characterized from the seashore hagfish Eptatretus burgeri genome. This SINE1 family, designated SINE1-1_EBu, is young, and is transposed by RTE-type non-LTR retrotransposon, not L1-type. Comparison with other SINE families from hagfish indicated the birth of SINE1-1_EBu through chimera formation of a 7SL RNA-derived sequence and an older tRNA-derived SINE family. It reveals parallel evolution of SINE1 in two vertebrate lineages with different autonomous non-LTR retrotransposon partners. The comparison between two SINE1 lineages supports that the RNA secondary structure of the Alu domain of 7SL RNA is required for the efficient retrotransposition.

Conclusions
The hagfish SINE1 is the first evident SINE1 family found outside of Euarchontoglires. Independent evolution of SINE1 with similar RNA secondary structure originated in 7SL RNA indicates the functional importance of 7SL RNA-derived sequence in the proliferation of SINEs.
Successful respiratory management of a Marshall-Smith syndrome patient with a tracheo-innominate artery fistula
Authors: Noguchi Satoko , Saito Junichi , Kawaguchi Jun , Kushikata Tetsuya , Hirota Kazuyoshi 
Published: May 2020

Abstract
Background
Tracheo-innominate artery fistula (TIF) is a life-threatening complication of tracheostomy. We describe perioperative management for innominate artery transection in a case with TIF.

Case presentation
A 4-year-old Japanese female with Marshal-Smith syndrome presented for management of TIF. She underwent tracheostomy at the age of 3 months and an uncuffed tracheostomy tube was inserted. One month before admission to our hospital, intermittent tracheal bleeding, suggesting TIF, occurred. Although we considered to change to a cuffed endotracheal tube, craniofacial abnormality suggested difficult oral intubation, and there was a possibility of rebleeding. Finally, innominate artery transection was performed under total intravenous anesthesia without changing the tracheostomy tube. Surgery completed uneventfully and she received mechanical ventilation under sedation for a day, followed by weaning without complications.

Conclusions
A cuffed tracheostomy tube should have been inserted before surgery for effective hemostasis against sudden bleeding from TIF even though conversion to oral intubation was difficult.
MicroRNA expression profiling in PBMCs of Indian water Buffalo (Bubalus bubalis) infected with Brucella and Johne’s disease
Authors: Singh Jasdeep , Dhanoa Jasdeep Kaur , Choudhary Ratan K , Singh Amarjit , Sethi Ram Saran , Kaur Simarjeet , Mukhopadhyay Chandra Sekhar 
Published: May 2020

Abstract
Background
MicroRNAs play key roles in host-pathogen-interactions and disease pathogenesis. Our aim was to characterize the differentially expressed miRNAs in the blood cells of diseased (Brucellosis-positive, Johne’s disease-positive) and healthy- water buffaloes. The pooled small-RNA samples of each group were sequenced on Ion Torrent Personal Genome Machine (PGM) sequencer and the data were analyzed for differential expression.

Results
Here we identified 274 known miRNAs with bovine homologs and 36 novel mature-star miRNAs from the sequnces of small RNA libraries. Overall 195 miRNAs were common to all the three groups. Certain miRNAs such as bta-miR-21-5p, −26a, −29a/b, −30d − 103, − 140, − 150, − 191, − 374, − 1434-5p,-1260b, − 2484 and let-7 members were abundantly expressed in diseased groups. Bta-miR-1434-5p, − 188, −200c were up-regulated (> 1.5 folds) while bta-miR-27a-5p, −34b and -2285x were down-regulated (> 100 folds) in Brucellosis group. In Johne’s Disease group, only 3 miRNAs (bta-miR-1434-5p, − 2340 and − 2484) were up-regulated (> 1.5 folds). The functional classification of miRNA target genes into gene ontology (GO) terms indicated their involvement in innate immunity and cellular process of disease pathogenesis. Expression profile of four differentially expressed miRNAs (bta-miR-9-5p, − 677, − 331-3p and − 2440) and eight predicted target-genes were validated through reverse transcriptase qPCR.

Conclusion
This study provides a valuable frame of reference for elucidation of regulatory roles of miRNAs associated with disease pathogenesis in water buffaloes as well as identification of miRNA biomarkers for disease diagnosis and treatment.
A Computational Study on the Intramolecular C4-C8′ Interflavan Bond Formations of Tethered Catechin Derivatives
Authors: Fukaya Keisuke , Saito Akiko , Nakajima Noriyuki , Urabe Daisuke 
Published: May 2020

Abstract
The procyanidin B series is a family of dimeric flavonoids composed of catechin(s) and/or epicatechin(s) with a C4-C8′ interflavan bond. We previously reported four TMSOTf-promoted couplings for C4-C8′ interflavan bond formations by using tethered catechin(s) and/or epicatechin(s). Although one of the reactions did not provide the coupling product, the other three reactions proceeded stereoselectively at the C4-position to provide stereochemically diversified products at C3 and C3′ positions toward the procyanidin B series. Here we report computer-assisted models of transition states for the C-C bond formations to explore origins of the stereoselectivity. A systematic search of the transition states using truncated compounds provided TS-Ad, TS-Ba or TS-Cd as the most energetically favorable transition state in each of the three reactions to reproduce the C4-stereoselectivity of the experiments. Exploration of origins of the stabilized energies of TS-Ad, TS-Ba, and TS-Cd by NCIPLOT demonstrated the importance of attractive non-covalent interactions.
The diagnostic and predictive accuracy of the PRISMA-7 screening tool for frailty in older adults: A systematic review protocol
Authors: Higginbotham Owen , O'Neill Aoife , Barry Louise , Leahy Aoife , Robinson Katie , O'Connor Margaret , Galvin Rose 
Published: May 2020

Background: Older adults are at risk of adverse outcomes due to frailty. A number of frailty screening instruments have been developed to identify older adults at increased risk of frailty. This systematic review and meta-analysis will look to examine the diagnostic accuracy of the Program of Research to Integrate the Services for the Maintenance of Autonomy 7 (PRISMA-7). Methods and analysis: A systematic literature search will be conducted from 2008-February 2020 in PubMed, EMBASE, CINAHL, EBSCO and the Cochrane Library to identify validation studies of the PRISMA-7 tool. A pre-specified PRISMA-7 score of ≥3 (maximum score 7 points) will be used to identify frailty in older adults. Prospective or retrospective cohort studies, cross-sectional studies and the control arm of randomised controlled trials will be included that attempt to validate the diagnostic accuracy of the PRISMA-7 screening tool in older adults across all healthcare settings when compared to a reference standard. The predictive accuracy of the PRISMA-7 tool will also be explored. Study quality will be assessed by the QUADAS-2 tool. A bivariate random effects model will be used to generate pooled estimates of sensitivity and specificity. Statistical heterogeneity will be explored using validated methods. Ethics and dissemination: Formal ethical approval is not required as primary data will not be collected. The results will be disseminated through a peer-reviewed publication, conference presentation and the popular press. Protocol registration: Awaiting registration with the International Prospective Register for Systematic Reviews (PROSPERO).