bluuebunny/crossref_metadata_2025_split huggingface dataset:
Linaclotide for The Treatment of Refractory Lower Bowel Manifestations of Systemic Sclerosis
Authors: Dein Eric , Wigley Fredrick M. , McMahan Zsuzsanna H. 
Published: October 2020

Abstract
Objective: Lower gastrointestinal tract involvement can affect up to 50% of SSc patients, and may result in malabsorption, pseudo-obstruction, hospitalization, and death. We report our experience with linaclotide, a selective agonist of guanylate cyclase C, for SSc patients with refractory lower GI disease.Methods: We performed a analysis of patients seen at the Johns Hopkins Scleroderma Center and identified patients prescribed linaclotide for refractory lower GI manifestations. Patients had clinical data prospectively collected in our longitudinal database. Linaclotide responders were on medication for at least 12 months with documented effectiveness by the treating physician. Results: Thirty-one patients with SSc were treated with linaclotide. Twenty-three of these patients (74%) had severe GI disease on initiation of linaclotide (Medsger GI score ≥3), as defined by recurrent pseudo-obstruction, malabsorption, and/or need for artificial nutrition. The majority of patients (90.3%; 28/31) had a treatment response, while only three patients (9.7%) reported ineffectiveness or intolerable side effects. Low-dose linaclotide (≤ 145 mcg daily) was used in 18 patients and was effective in 94%. High-dose therapy (>145 mcg daily) was effective in 11 of 13 patients (85%). Common side effects were diarrhea, cramping, or bloating (11/31, 35%). Ineffectiveness, cost, and abdominal pain were complaints cited among those who discontinued therapy. Conclusion: Linaclotide is a well-tolerated and efficacious pro-secretory and pro-motility agent that can be used to manage refractory lower GI manifestations in SSc. We found that low-dose linaclotide is an effective option and may be better tolerated, though a subset of patients may require high dose regimens.
Living on the Edge of the Community: Factors Associated with Discontinuation of Community Living Among People with Cognitive Impairment
Authors: Ura Chiaki , Okamura Tsuyoshi , Sugiyama Mika , Miyamae Fumiko , Yamashita Mari , Nakayama Riko , Edahiro Ayako , Taga Tsutomu , Inagaki Hiroki , Ogawa Madoka , Awata Shuichi 
Published: October 2020

Abstract
BackgroundThe experiences of people with cognitive impairment in the real world have not been fully explored because of methodological difficulties. This study re-accessed people with cognitive impairment identified in a previous epidemiological survey to explore their current situation and the risk factors associated with all-cause discontinuation of community living.MethodsIn 2016, a three-step survey was conducted of 7,614 older residents. In the last step of the survey, a research team visited the homes of 198 participants with a Mini-Mental State Examination score <24. In 2019, we re-accessed these people. We ran a community space in the study area for 3 years to build partnerships with community residents and community workers, and were able to re-access the participants using multiple methods.ResultsWe found that 126 (63.6%) participants had continued living in the same community, but 58 (29.3%) had discontinued community living. Of these, 18 (9.1%) had died, 18 (9.1%) were institutionalized, 9 (4.5%) were hospitalized, and 13 (6.6%) had moved out of the community. A multiple logistic regression analysis identified the following risk factors associated with discontinuation of community living: being certified under long-term insurance, needing housing support, and needing rights protection.ConclusionsThree years after the baseline survey, 29.3% people with cognitive impairment had discontinued community living. Despite having dementia or living alone, older people could continue to live in the community if their needs for housing support and rights protection were met. Both social interventions and medical interventions are important to build age-friendly communities.Trial registration﻿UMIN, UMIN000038189,　Registered 3 October 2019, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000043521
Diagnostic Delays in Vasculitis and Factors Associated With Time to Diagnosis
Authors: Sr Antoine , Cronin Keri , Shaw Dianne , Young Kalen , Burroughs Cristina , Kullman Joyce , Machireddy Kirthi , McAlear Carol , Merkel Peter 
Published: October 2020

Abstract
Background: Patients with vasculitis, a set of rare diseases, encounter delays in obtaining an accurate diagnosis which can lead to substantial morbidity and increased mortality. This study sought to describe the diagnostic journey of patients with vasculitis and identify factors associated with time to diagnosis. Methods: Patients with vasculitis enrolled in an online registry completed a two-stage study: Stage 1: Survey of open-ended questions about patients’ diagnostic journeys and perceived factors associated with rapid or delayed diagnosis; Stage 2: Survey with specific questions based on data from Stage 1 and additional investigator-identified factors. Results: 375 patients with vasculitis participated in Stage 1; 456 patients participated in Stage 2. 85% of patients were seen by a healthcare provider within 3 months of the onset of symptoms. The median time to diagnosis of vasculitis was 7 months. 313/456 (73%) of patients were misdiagnosed initially. 40% of diagnoses were made in a hospital setting; 2% of diagnoses were made at a specialized vasculitis center. 60% of patients had at least 1 visit to an emergency room prior to diagnosis. Unemployment, time to travel to a medical center > 1 hour, initial misdiagnosis, and delays in seeing a specialist were all associated with longer times to diagnosis. 373/456 (82%) of patients reported that a delayed diagnosis had negative consequences on their health.Conclusion: Patients with vasculitis encounter substantial delays in achieving an accurate diagnosis and these delays are associated with negative health consequences. Both patient-related factors and healthcare-related factors are associated with diagnostic delays.
Juvenile Idiopathic Arthritis in South Australia
Authors: Min Ming , Edwards Suzanne , Gibson Catherine , Crotti Tania , Boros Christina 
Published: October 2020

Abstract
Background: Juvenile Idiopathic Arthritis (JIA) is a chronic rheumatic disease that shows variation in subtype distribution by geographic regions. The aim of this study was to create a JIA registry, which could describe the epidemiology and characteristics of JIA patients in South Australia (SA).Methods: Prospectively collected data from JIA patients at the Women’s and Children’s Hospital in Adelaide, between August 2019 and March 2020 were reported. All children and young people diagnosed with JIA according to the International League of Associations for Rheumatology (ILAR) classification criteria were eligible for inclusion. Data including demographics, complications/comorbidities, medications, disease activity as well as patient-reported data using Childhood Health Assessment Questionnaire (CHAQ) were documented. Non-identified data were extracted from this registry and utilised in descriptive analysis and comparative studies.Results: There are currently n=112 JIA patients in this registry, including n=11 incident cases (9.8%), with a predominance of female (n=75, 67.0%). The median disease duration was 3.6 years (interquartile range 1.3-7.6). The most common subtype was persistent oligoarthritis (n=35/112, 31.3%), followed by rheumatoid factor-negative polyarthritis (n=32/112, 28.6%), extended oligoarthritis (n=23/112, 20.5%), enthesitis-related arthritis (ERA; n=12/112, 10.7%), systemic onset arthritis (n=5/112, 4.5%), rheumatoid factor-positive polyarthritis (n=3/112, 2.7%) and psoriatic arthritis (n=2/112, 1.8%). Complications were documented in n=40/112 (35.7%) patients, with n=21/94 (22.3%) observed to have uveitis, and musculoskeletal complications observed in n=10/112 (8.9%). Methotrexate intolerance was present in n=10/79 (12.7%) patients. Forty-nine out of 112 (43.8%) patients had at least one comorbidity, with anxiety/depression (n=5/112, 4.5%) and asthma (n=5/112, 4.5%) being the most common. Around half of patients (n=52/112, 46.4%) had clinically inactive disease at enrolment and most (n=85/112, 75.9%) reported no to low functional disability. Non-steroidal anti-inflammatory drugs have been almost universally used (n=100/112, 89.3%), and n=26/112 (23.2%) have received treatment with biologics.Conclusions: In this JIA registry study, we found that the JIA cohort in SA is female-dominated with persistent oligoarthritis as the most common subtype, consistent with other studies. Most patients have good disease control and report no or mild disability. Further longitudinal work will add to the current description of our JIA cohort and assist improvement of clinical care.
Profiling Basal Forebrain Cholinergic Neurons Reveals a Molecular Basis for Vulnerability Within the Ts65Dn&nbsp;Model of Down Syndrome and Alzheimer’s Disease
Authors: Alldred Melissa J. , Penikalapati Sai C. , Lee Sang Han , Heguy Adriana , Roussos Panos , Ginsberg Stephen 
Published: October 2020

Abstract
Background: Basal forebrain cholinergic neuron (BFCN) degeneration is a hallmark of Down syndrome (DS) and Alzheimer’s disease (AD). Current therapeutics have been unsuccessful in slowing disease progression, likely due to complex pathological interactions and dysregulated pathways that are poorly understood. The Ts65Dn trisomic mouse model recapitulates both cognitive and morphological deficits of DS and AD, including BFCN degeneration. Methods: We utilized Ts65Dn mice to understand mechanisms underlying BFCN degeneration to identify novel targets for therapeutic intervention. We performed high-throughput, single population RNA sequencing (RNA-seq) to interrogate transcriptomic changes within medial septal nucleus (MSN) BFCNs, using laser capture microdissection to individually isolate ~500 choline acetyltransferase-immunopositive neurons in Ts65Dn and normal disomic (2N) mice at 6 months of age (MO). Results: Ts65Dn mice had unique MSN BFCNs transcriptomic profiles at ~6 MO clearly differentiating them from 2N mice. Leveraging Ingenuity Pathway Analysis and KEGG analysis, we linked differentially expressed gene (DEG) changes within MSN BFCNs to several canonical pathways and aberrant physiological functions. The dysregulated transcriptomic profile of trisomic BFCNs provides key information underscoring selective vulnerability within the septohippocampal circuit. Conclusions: We propose both expected and novel therapeutic targets for DS and AD, including specific DEGs within cholinergic, glutamate, GABAergic, and neurotrophin pathways, as well as select targets for repairing oxidative phosphorylation status in neurons. We demonstrate and validate an interrogative quantitative bioinformatic analysis of a key dysregulated neuronal population linking single population transcript changes to an established pathological hallmark associated with cognitive decline for therapeutic development in human DS and AD.
Call to Action – Closing the Gap to Make Patient Blood Management the New Norm(al) as Viewed by Implementors in Diverse Countries
Authors: Hofmann Axel , Spahn Donat R. , Holtorf Anke-Peggy 
Published: October 2020

Abstract
BackgroundMillions of hospitalized patients are anemic. However, anemia is an independent risk factor for adverse outcomes including morbidity and mortality. In combination with blood loss, anemia is the main driver for transfusion, thus adding risk for adverse outcomes. Patient Blood Management (PBM) is a concept to identify and correct anemia and to minimize blood loss. Evidence demonstrates that PBM significantly improves outcomes and safety while reducing cost by macroeconomic magnitudes. Despite its huge potential to improve healthcare systems, PBM is not yet adopted broadly. By gathering the experiences of a diverse group of PBM implementors across countries with different healthcare contexts, we aimed to identify the drivers, barriers, measures, and stakeholders regarding the implementation of PBM. The synthesis of this information should provide a matrix of complementary measures, allowing PBM stakeholders from diverse professional backgrounds to initiate and orchestrate PBM implementation.MethodsSemi-structured interviews were conducted with 1-4 PBM implementors from 12 countries in Asia, Latin America, Australia, Central and Eastern Europe, the Middle East, and Africa. Responses were summarized per country, and key observations extracted. By defining the levels of intervention for PBM implementation and applying the Donabedian Quality Framework, we created and populated a matrix of key measures and outcomes as identified from the interviews.ResultsWe were able to extract a set of structural and procedural PBM implementation measures from interviews with the implementors. We created a matrix addressing six levels of implementation including government, healthcare providers (HCP), funding, research, training/education and patients and identified structural and procedural measures on each level. ConclusionThis matrix helps to decompose the complexity of PBM implementation into concrete measures on each implementation level. It provides guidance for diverse stakeholders to independently initiate and develop strategies to make PBM a national standard of care, thus closing current practice gaps and matching this unmet public health need.
Definition of Acute Respiratory Distress Syndrome in Plateau of Xining,Qinghai: Verification of Berlin Definition Plateau Criteria
Authors: Liu Xiaoqin , Pan Chun , Si Li-Ning , Tong Shijun , Niu Yi , Qiu Haibo , Gan Guifen 
Published: October 2020

Abstract
Background Acute respiratory distress syndrome（ARDS） is a common respiratory critical illness. The high altitude hypoxic environment has a great influence on its occurrence and development. Now we lack clear diagnostic definition of high altitude acute respiratory distress syndrome.To verify the application value of Berlin Definition plateau criteria of Acute Respiratory Distress Syndrome in Xining , Qinghai ( 2261m).Methods Retrospective analysis of the clinical data of ARDS patients admitted to the Department of Critical Care Medicine of the Affiliated Hospital of Qinghai University from January 2018 to December 2018. The severity was divided according to the Berlin definition, the plateau standard, and the Zhang standard, and the differences of three standards were compared.Results In this study, 512 patients with mechanical ventilation were selected. 229 patients who met the criteria of Berlin Definition plateau criteria , including 107 patients with mild ARDS (46.72%), 84 moderate patients (36.68%) and 38 severe ARDS patients (16.59%). Among 253 meet Berlin definition patients , 49(19.77%) were mild,148(58.50%) were moderate,and 56 (22.13%) were severe ARDS. There are 204 patients that meet Zhang criteria, among the 204 enrolled patients, 87(42.65%) were ALI and 117(57.35%) were ARDS. The AUROC of the Berlin Definition, the Plateau criteria and Zhang criteria were 0.6675 (95% CI 0.5866-0.7484), 0.6216 (95%CI 0.5317-0.7116) and 0.6050 (95% CI 0.5084-0.7016).Conclusion For Xining, Qinghai, the Berlin Definition Plateau oxygenation index correction criteria can distinguish the severity of ARDS , but it needs to be enlarged and confirmed by multicenter clinical studies.
Use of Patient Reported Outcome Measures (PROMs) by Orthopedic Surgeons in Saudi Arabia
Authors: Alshehri Fayez , Alarabi Abdulaziz , Alharthi Mohammed , Alanazi Thamer , Alohali Ahmed , Alsaleem Mohammed 
Published: October 2020

Abstract
Background There is increasing literature on the usefulness of patient-reported outcome measures (PROMs), but far fewer studies to determine their use by orthopedic surgeons and the barriers they face in applying PROMs in their daily clinical activity.Methods Cross-sectional study using a questionnaire that was distributed in both soft and hard copy formats to a sample of 262 orthopedic surgeons. Participants included orthopedic surgeons who are employed by the Ministry of Health (MOH) in Riyadh and the Eastern Province, Saudi Arabia. The questionnaire was distributed through onsite visitations to orthopedic departments in MOH hospitals as well as through online correspondence by email, WhatsApp, and social media.Results The study sample included 262 orthopedic surgeons (13.7% females and 86.3% males). Surgeons aged < 34, 35 – 44, and 45 - 54 years old represented 28.66%, 38.9%, and 20.2% of the study sample, respectively. The majority of the included surgeons did not use PROMs (69.1%) and some (17.2%) used it for research purposes. Only 5% used it regularly in daily clinical work.Conclusion The clinical use of PROMs among orthopedic surgeons was negligible, even though an overwhelming majority were interested in using PROMs. The reasons provided included a lack of knowledge on how to use PROMs and the perception that it is too time-consuming to add to regular clinical routine. There should be more effort towards training surgeons on how to use PROMs, whereas increasing compatibility with existing software tools used by MOH hospitals may help offset time-related reservations.
Mid-term Subsidence and Periprosthetic Radiolucency of the AMIStem: A 5-year EBRA-FCA Analysis
Authors: Hasler Julian , Flury Andreas , Dimitriou Dimitris , Holweg Iris , Helmy Naeder , Finsterwald Michael 
Published: October 2020

Abstract
Background: There has been an evolution in cementless total hip arthroplasty (THA) with newer short stem designs aim to preserve metaphyseal bone stock and facilitate implantation through minimally invasive approaches. While early subsidence has been correlated to aseptic loosening in conventional stems, there is a paucity of data regarding short stems. The current study aims to report on stem subsidence and midterm clinical outcomes of a cementless, metaphyseal-anchored short femoral stem, specifically designed for the direct anterior approach (DAA).Methods: 94 consecutive patients (100 hips) with a minimum follow-up of 5 years following cementless THA were included in this single-center retrospective study. Subsidence was evaluated using the “Ein-Bild-Roentgen-Analyse” (EBRA). Periprosthetic radiolucency allocated to the Zones of Charnley and Gruen was assessed. Additionally, demographic and implant-related factors potentially associated with increased subsidence and clinical outcomes were evaluated.Results: At the last follow-up, the average stem subsidence was 1.98 ± 1.20 mm, with 48% of the implants demonstrating subsidence of > 2 mm. Periprosthetic radiolucency of > 2 mm was found in 26% of the implants in Zone 1, and in 9% in Zone 7, respectively. Neither the amount of subsidence nor proximal periprosthetic radiolucency was associated with aseptic loosening or worse clinical outcomes. Conclusions: Comparable to other proximally-fixed short stem designs, the highest subsidence was observed within the first 3 months following implantation. No demographic or implant-related factors were found to have a statistically significant influence on stem subsidence. Periprosthetic radiolucency and subsidence of the AMISstem is not correlated with worse clinical outcomes at 5-years follow-up.
A Prospective and Nutrition-Related Nomogram Model for Prognosis in Colorectal Cancer Survival: A Multicenter Cohort Study in China
Authors: Ruan Guo-Tian , Zhang Kang-Ping , Zhang Qi , Zhang Xi , Tang Meng , Song Meng-Meng , Zhang Xiao-Wei , Ge Yi-Zhong , Yang Ming , Song Chun-Hua , Cong Ming-Hua , Guo Zeng-Qing , Zhu Li-Chen , Braga Marco , Cederholm Tommy E , Xu Hong-Xia , Li Wei , Xiao Chun-Yun , shi hanping 
Published: October 2020

Abstract
BackgroundColorectal cancer (CRC) is a common malignancy with high incidence of malnutrition. Increasing evidence showed that nutritional status could be a prognostic indicator of cancer survival. However, there were few prognostic models involving nutrition-related indicators in CRC. This study aimed to develop a nutrition-related prognostic model for CRC survival.MethodsThis multicenter retrospectively primary cohort data included 1,373 CRC patients, and the external validation cohort enrolled other 108 CRC patients. LASSO and multivariate regression analyses were used to select prognostic indicators and develop the nomogram. We performed C-index, calibration curves, and DCA to assess the discrimination, calibration, and applicability. Finally, the indicators of the nomogram model were used as adjustment factors. Multivariate Cox survival analyses were performed to investigate the benefit of the Patient-Generated Subjective Global Assessment (PG-SGA) and Global Leadership Initiative on Malnutrition (GLIM) malnutrition criteria to CRC prognosis.ResultsFive prognostic indicators (TNM stage, radical resection, reduced food intake, activities and function decline, and low albumin) were chosen to develop the nomogram. C-index of the nomogram was 0.74 (95% CI 0.72-0.77) and 0.72 (95% CI 0.62-0.81) in the primary cohort and validation cohort, which were higher than other models. Calibration plots and DCA showed that the nomogram model has a good consistency and clinical benefit in predicting CRC survival. Multivariate Cox survival analysis suggested moderate (P<0.05, HR 1.32, 95% CI 1.002-1.75) and severe malnutrition (P<0.001, HR 1.69, 95% CI 1.27-2.25) were associated with worse overall survival (OS) in CRC using the PG-SGA criteria. However, there was no prognostic significance in GLIM criteria (all P>0.05). Finally, stratified analysis suggested that malnourished CRC patients with low albumin synergistically increased the death risk of CRC OS both in PG-SGA and GLIM. (P for interaction = 0.007 and 0.004, respectively)ConclusionThis study established a prospective model to predict the OS in CRC patients using nutrition-related indicators. Moreover, we also found that PG-SGA had a better prognostic and predictive efficiency in CRC than GLIM. These findings grant further verification.
Identification of Lipidomic Profiles Associated with Drug-Resistant Prostate Cancer Cells
Authors: Ingram Lishann M. , Mansoura Maryam , Chou Chau-wen , Cummings Brian S. 
Published: October 2020

Abstract
BackgroundThe association of circulating lipids with clinical outcomes of drug-resistant castration-resistant prostate cancer (CRPC) is not fully understood. While it is known that increases in select lipids correlates to decreased survival, neither the mechanisms mediating these alterations nor the correlation of resistance to drug treatments are well characterized.MethodsWe addressed this gap-in-knowledge using in vitro models of non-cancerous, hormone-sensitive, CRPC and drug-resistant cell lines combined with quantitative LC-ESI-Orbitrap-MS lipidomic analysis and subsequent analysis such as Metaboanalyst and Lipid Pathway Enrichment (LIPEA).ResultsThis approach identified several lipid regulatory pathways associated with Docetaxel resistance in PCa. These included those controlling glycerophospholipid metabolism, sphingolipid signaling pathways and ferroptosis. In total, 7,460 features were identified as being dysregulated between the cell lines studied, and 21 lipid species were significantly altered in drug-resistant cell lines as compared to nonresistant cell lines. Docetaxel resistance cells (PC3-Rx and DU145-DR) and had higher levels of phosphatidylcholine (PC), oxidized lipid species, phosphatidylethanolamine (PE), and sphingomyelin (SM) as compared to parent control cells (PC-3 and DU-145). These cells also had higher levels of ceramides release into the media.ConclusionThese data identify lipids whose levels may correlate to Docetaxel sensitivity and progression of prostate cancer.