bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive analysis of the Ppatg3 mutant reveals that autophagy plays important roles in gametophore senescence in Physcomitrella patens
Authors: Chen Zexi , Wang Wenbo , Pu Xiaojun , Dong Xiumei , Gao Bei , Li Ping , Jia Yanxia , Liu Aizhong , Liu Li 
Published: September 2020

Abstract
Background
Autophagy is an evolutionarily conserved system for the degradation of intracellular components in eukaryotic organisms. Autophagy plays essential roles in preventing premature senescence and extending the longevity of vascular plants. However, the mechanisms and physiological roles of autophagy in preventing senescence in basal land plants are still obscure.

Results
Here, we investigated the functional roles of the autophagy-related gene PpATG3 from Physcomitrella patens and demonstrated that its deletion prevents autophagy. In addition, Ppatg3 mutant showed premature gametophore senescence and reduced protonema formation compared to wild-type (WT) plants under normal growth conditions. The abundance of nitrogen (N) but not carbon (C) differed significantly between Ppatg3 mutant and WT plants, as did relative fatty acid levels. In vivo protein localization indicated that PpATG3 localizes to the cytoplasm, and in vitro Y2H assays confirmed that PpATG3 interacts with PpATG7 and PpATG12. Plastoglobuli (PGs) accumulated in Ppatg3, indicating that the process that degrades damaged chloroplasts in senescent gametophore cells was impaired in this mutant. RNA-Seq uncovered a detailed, comprehensive set of regulatory pathways that were affected by the autophagy mutation.

Conclusions
The autophagy-related gene PpATG3 is essential for autophagosome formation in P. patens. Our findings provide evidence that autophagy functions in N utilization, fatty acid metabolism and damaged chloroplast degradation under non-stress conditions. We identified differentially expressed genes in Ppatg3 involved in numerous biosynthetic and metabolic pathways, such as chlorophyll biosynthesis, lipid metabolism, reactive oxygen species removal and the recycling of unnecessary proteins that might have led to the premature senescence of this mutant due to defective autophagy. Our study provides new insights into the role of autophagy in preventing senescence to increase longevity in basal land plants.
Outcomes of Cardiac Resynchronization Therapy in Patients with Hypothyroidism and Heart Failure
Authors: Yang Mei , Li Xuping , Morris John C. , Liang Jinjun , Deshmukh Abhishek J. , Hodge David , Li Yigang , Cha Yong-Mei 
Published: September 2020

Abstract
Background
Hypothyroidism is known to be associated with adverse clinical outcomes in heart failure. The association between hypothyroidism and cardiac resynchronization therapy outcomes in patients with severe heart failure is not clear.

Methods
The study included 1316 patients who received cardiac resynchronization therapy between 2002 and 2015. Baseline demographics and cardiac resynchronization therapy outcomes, including left ventricular ejection fraction, New York Heart Association class, appropriate implantable cardioverter-defibrillator therapy, and all-cause mortality, were collected from the electronic health record.

Results
Of the study cohort, 350 patients (26.6%) were classified as the hypothyroidism group. The median duration of follow-up was 3.6 years (interquartile range, 1.7–6.2 years). Hypothyroidism was not associated with a higher risk of all-cause mortality in patients receiving CRT for heart failure. The risk of appropriate implantable cardioverter-defibrillator therapy significantly increased in association with increased baseline thyroid-stimulating hormone level in the entire cohort (hazard ratio, 1.23 per 5mIU/L increase; 95% CI, 1.01–1.5; P = 0.04) as well as in the hypothyroid group (hazard ratio, 1.44 per 5mIU/L increase; 95% CI, 1.13–1.84; P = 0.004).

Conclusions
CRT improves cardiac function in hypothyroid patients. The ventricular arrhythmic events requiring ICD therapies are associated with baseline TSH level, which might be considered as an important biomarker to stratify the risk of sudden death for patients with heart failure and hypothyroidism.
Avoiding misdiagnosis: expert consensus recommendations for the suspicion and diagnosis of transthyretin amyloidosis for the general practitioner
Authors: Gertz Morie , Adams David , Ando Yukio , Beirão João Melo , Bokhari Sabahat , Coelho Teresa , Comenzo Raymond L. , Damy Thibaud , Dorbala Sharmila , Drachman Brian M. , Fontana Marianna , Gillmore Julian D. , Grogan Martha , Hawkins Philip N. , Lousada Isabelle , Kristen Arnt V. , Ruberg Frederick L. , Suhr Ole B. , Maurer Mathew S. , Nativi-Nicolau Jose , Quarta Candida Cristina , Rapezzi Claudio , Witteles Ronald , Merlini Giampaolo 
Published: September 2020

Abstract
Background
Transthyretin amyloidosis (also known as ATTR amyloidosis) is a systemic, life-threatening disease characterized by transthyretin (TTR) fibril deposition in organs and tissue. A definitive diagnosis of ATTR amyloidosis is often a challenge, in large part because of its heterogeneous presentation. Although ATTR amyloidosis was previously considered untreatable, disease-modifying therapies for the treatment of this disease have recently become available. This article aims to raise awareness of the initial symptoms of ATTR amyloidosis among general practitioners to facilitate identification of a patient with suspicious signs and symptoms.

Methods
These consensus recommendations for the suspicion and diagnosis of ATTR amyloidosis were developed through a series of development and review cycles by an international working group comprising key amyloidosis specialists. This working group met to discuss the barriers to early and accurate diagnosis of ATTR amyloidosis and develop a consensus recommendation through a thorough search of the literature performed using PubMed Central.

Results
The cardiac and peripheral nervous systems are most frequently involved in ATTR amyloidosis; however, many patients often also experience gastrointestinal and other systemic manifestations. Given the multisystemic nature of symptoms, ATTR amyloidosis is often misdiagnosed as a more common disorder, leading to significant delays in the initiation of treatment. Although histologic evaluation has been the gold standard to confirm ATTR amyloidosis, a range of tools are available that can facilitate early and accurate diagnosis. Of importance, genetic testing should be considered early in the evaluation of a patient with unexplained peripheral neuropathy.

Conclusions
A diagnostic algorithm based on initial red flag symptoms and manifestations of cardiac or neurologic involvement will facilitate identification by the general practitioner of a patient with clinically suspicious symptoms, enabling subsequent referral of the patient to a multidisciplinary specialized medical center.
Role of sex hormones and their receptors on gastric Nrf2 and neuronal nitric oxide synthase function in an experimental hyperglycemia model
Authors: Sprouse Jeremy , Sampath Chethan , Gangula Pandu R. 
Published: September 2020

Abstract
Background
Gastroparesis, a condition of abnormal gastric emptying, is most commonly observed in diabetic women. To date, the role of ovarian hormones and/or gastric hormone receptors on regulating nitrergic-mediated gastric motility remains inconclusive.

Aim
The purpose of this study is to investigate whether sex hormones/their receptors can attenuate altered Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), neuronal Nitric Oxide Synthase (nNOS) expression and nitrergic relaxation in gastric neuromuscular tissues exposed to in-vitro hyperglycemia (HG).

Methods
Gastric neuromuscular sections from adult female C57BL/6 J mice were incubated in normoglycemic (NG, 5 mM) or hyperglycemic (30 mM or 50 mM) conditions in the presence or absence of selective estrogen receptor (ER) agonists (ERα /PPT or ERβ: DPN); or non-selective sex hormone receptor antagonists (ER/ICI 182,780, or progesterone receptor (PR)/ RU486) for 48 h. mRNA, protein expression and nitrergic relaxation of circular gastric neuromuscular strips were assessed.

Results
Our findings in HG, compared to NG, demonstrate a significant reduction in ER, Nrf2, and nNOS expression in gastric specimens. In addition, in-vitro treatment with sex hormones and/or their agonists significantly (*p < 0.05) restored Nrf2/nNOSα expression and total nitrite production. Conversely, ER, but not PR, antagonist significantly reduced Nrf2/nNOSα expression and nitrergic relaxation.

Conclusions
Our data suggest that ER’s can regulate nitrergic function by improving Nrf2/nNOS expression in experimental hyperglycemia.
Effects of proton pump inhibitor use on the esophageal microbial community
Authors: Tasnim Sadia , Miller Aaron L. , Jupiter Daniel C. , Hamilton Catherine F. , Reep Gabriel L. , Krill Timothy S. , Pyles Richard B. , Okereke Ikenna C. 
Published: September 2020

Abstract
Background
Changes in the esophageal microbiome correlate with esophageal disease, but the effects of proton pump inhibitor (PPI) drugs are incompletely characterized. Our objective was to identify the effects of PPI use on the microbial community of the esophagus.

Methods
Mucosal biopsies of the distal esophagus were analyzed using a customized esophageal microbiome qPCR panel array (EMB). Patient demographics, use of PPIs, duration of use and dose were recorded.

Results
Fifty-eight patients were included. Mean age was 60.5 years. Ninety percent (52/58) of patients were on PPIs. Mean dose was 42.7 mg. Mean duration of use was 2.5 years. The use of PPIs led to a significant difference in absolute levels of only one organism, Actinomyces, in the entire array (p < 0.01). Among patients who used proton pump inhibitors, there was no significant association between dose and absolute levels of any organism. Similarly, there was no association between duration of use and absolute levels of any organism.

Conclusions
PPI use does not seem to cause significant changes in the distal esophageal microbial community. Future studies with larger sample sizes and esophageal pH testing should be performed to determine the level of acidity and its relationship to the microbial community.
Symptom-burden in people living with frailty and chronic kidney disease
Authors: Nixon A. C. , Wilkinson T. J. , Young H.M.L. , Taal M. W. , Pendleton N. , Mitra S. , Brady M. E. , Dhaygude A. P. , Smith A. C. 
Published: September 2020

Abstract
Background
Frailty is independently associated with worse health-related quality of life (HRQOL) in chronic kidney disease (CKD). However, the relationship between frailty and symptom experience is not well described in people living with CKD. This study’s aim was to evaluate the relationship between frailty and symptom-burden in CKD.

Methods
This study is a secondary analysis of a cross-sectional observational study, the QCKD study (ISRCTN87066351), in which participants completed physical activity, cardiopulmonary fitness, symptom-burden and HRQOL questionnaires. A modified version of the Frailty Phenotype, comprising 3 self-report components, was created to assess frailty status. Multiple linear regression was performed to assess the association between symptom-burden/HRQOL and frailty. Logistic regression was performed to assess the association between experiencing symptoms frequently and frailty. Principal Component Analysis was used to assess the experienced symptom clusters.

Results
A total of 353 patients with CKD were recruited with 225 (64%) participants categorised as frail. Frail participants reported more symptoms, had higher symptom scores and worse HRQOL scores. Frailty was independently associated with higher total symptom score and lower HRQOL scores. Frailty was also independently associated with higher odds of frequently experiencing 9 out of 12 reported symptoms. Finally, frail participants experienced an additional symptom cluster that included loss of appetite, tiredness, feeling cold and poor concentration.

Conclusions
Frailty is independently associated with high symptom-burden and poor HRQOL in CKD. Moreover, people living with frailty and CKD have a distinctive symptom experience. Proactive interventions are needed that can effectively identify and address problematic symptoms to mitigate their impact on HRQOL.
Concurrent minimal change nephrotic syndrome and type 1 diabetes mellitus in an adult Japanese woman: a case report
Authors: Nishizono Ryuzoh , Kogou Hiroki , Ishizaki Yuri , Minakawa Akihiro , Kikuchi Masao , Inagaki Hiroko , Sato Yuji , Fujimoto Shouichi 
Published: September 2020

Abstract
Background
Concurrent type 1 diabetes mellitus (T1DM) and idiopathic nephrotic syndrome is rare, and most previously reported cases were in children. We report the case of an adult woman who developed T1DM and minimal change nephrotic syndrome (MCNS) nearly simultaneously.

Case presentation
A 24-year-old woman had first presented to another hospital with nausea, vomiting, and fatigue. She was diagnosed with diabetic ketoacidosis and T1DM on the basis of her hyperglycemia, ketoacidosis, and positive anti-glutamic acid decarboxylase antibody test result. Rapid infusion of normal saline and insulin administration alleviated hyperglycemia and ketoacidosis. Two weeks after admission, however, she developed nephrotic syndrome (NS) with rapidly decreasing urine volume. She was referred to our hospital with a diagnosis of acute kidney injury. Although she temporarily required dialysis and high doses of insulin, within 1 month NS and acute kidney injury had been alleviated by oral prednisolone and low-density lipoprotein apheresis. Renal biopsy showed minor glomerular abnormalities without diabetic nephropathy, so we diagnosed her with MCNS. Seven weeks after the discharge, NS relapsed, and cyclosporine was added to prednisolone. However, NS relapsed twice within the next 4 months, so we started her on rituximab. At 6 months after initiating rituximab therapy, she remained in complete remission.
Her mother also had T1DM but not MCNS. The patient had HLA-DRB1*09:01/09:01, DQB1*03:03/03:03, and her mother had HLA-DRB1*04:05/09:01, DQB1*03:03/04:01.

Conclusions
Concurrent T1DM and MCNS is rare and their coexistence might be coincidental. Alternatively, they might have been caused by an underlying, unidentified genetic predisposition. Previous reports and our patient’s findings suggest that specific HLA alleles and haplotypes or a Th1/Th2 imbalance might be associated with T1DM and MCNS that occurred nearly simultaneously.
Chronic kidney disease in Cameroon: a scoping review
Authors: Aseneh Jerry Brown , Kemah Ben-Lawrence A. , Mabouna Stephane , Njang Mbeng Emmanuel , Ekane Domin Sone Majunda , Agbor Valirie Ndip 
Published: September 2020

Abstract
Objectives
This scoping review sought to summarize available data on the prevalence, associated factors, etiology, comorbidities, treatment, cost and mortality of chronic kidney disease (CKD) in Cameroon.

Methods
We searched PubMed, Scopus and African Journals Online from database inception to 31 March, 2020 to identify all studies published on the prevalence, associated factors, etiology, comorbidities, treatment, cost and mortality of CKD in Cameroon.

Results
Thirty studies were included. The prevalence of CKD varied from 3 to 14.1 and 10.0%–14.2% in rural and urban areas, respectively. The prevalence of CKD in patients with hypertension, diabetes mellitus, and human immunodeficiency virus was 12.4–50.0, 18.5%, and 3.0–47.2%, respectively. Hypertension (22.3–59.1%), chronic glomerulonephritis (15.8–56.2%), and diabetes mellitus (15.8–56.2%) were the most common causes of CKD. The cause was unknown in 13.5–17.0% of the cases. Advanced age, hypertension, diabetes mellitus, and obesity were frequent associated factors. Hemodialysis was the main treatment modality in patients with End Stage Renal Disease (ESRD). The monthly cost of management of non-dialyzed CKD was 163 US dollars. The one-year mortality rate of ESRD was 26.8–38.6%.

Conclusion
Chronic kidney disease affects about one in 10 adults in the general population in Cameroon. Patients with hypertension, diabetes mellitus, and human immunodeficiency virus bear the greatest burden of CKD in Cameroon. Advanced age, hypertension, diabetes mellitus, and obesity are major factors associated with CKD. Chronic kidney disease in Cameroon is associated with high morbidity and mortality and huge economic cost on the patient.
Neuronal intranuclear inclusion disease with mental abnormality: a case report
Authors: Chi Xiaosa , Li Man , Huang Ting , Tong Kangyong , Xing Hongyi , Chen Jixiang 
Published: September 2020

Abstract
Background
Neuronal intranuclear inclusion disease (NIID) is a chronic progressive neurodegenerative disease that is characterized by the discovery of eosinophilic hyaline intranuclear inclusions in the central and peripheral nervous systems and visceral organs. In this paper, we report a case of an adult-onset neuronal intranuclear inclusion disease presenting with mental abnormality in China.

Case presentation
A 62-year-old woman presented with mental abnormality and forgetfulness for 3 months before she was admitted to our hospital. There were prodromal symptoms of fever before she had the mental disorder. Encephalitis was first suspected, and the patient underwent lumbar puncture and brain magnetic resonance imaging (MRI). A cerebrospinal fluid (CSF) examination indicated normal pressure, a normal white blood cell count, and slightly elevated protein and glucose levels. Coxsackie B virus, enterovirus, and cytomegalovirus tests showed normal results. Bacterial culture and Cryptococcus neoformans test results were negative. The contrast-enhanced MRI of the brain was normal. The brain diffusion-weighted imaging (DWI) showed a symmetrically distributed strip-shaped hyperintensity signal of the corticomedullary junction in the bilateral frontal, parietal, and temporal lobes. We considered the diagnosis of the NIID, and therefore, skin biopsy was performed. The electron microscopy revealed that intranuclear inclusions in the nucleus of fibrocytes existed and were composed of filaments.

Conclusions
NIID is a rare neurodegenerative disease with diverse clinical manifestations. In clinical work, when a patient presents with abnormal mental behavior and exhibits hyperintensity signals on DWI images of the corticomedullary junction, it is crucial to consider the diagnosis of NIID.
GLUT-1 as a predictor of worse prognosis in pancreatic adenocarcinoma: immunohistochemistry study showing the correlation between expression and survival
Authors: Achalandabaso Boira Mar , Di Martino Marcello , Gordillo Carlos , Adrados Magdalena , Martín-Pérez Elena 
Published: September 2020

Abstract
Background
Various parameters have been considered for predicting survival in pancreatic ductal adenocarcinoma. Information about western population is missing. The aim of this study is to assess the association between Glucose transporter type 1 (GLUT-1) expression and prognosis for patients with PDAC submitted for surgical resection in a European cohort.

Methods
Retrospective analysis of PDAC specimens after pancreatoduodenectomy assessing GLUT-1 expression according to intensity (weak vs strong) and extension (low if < 80% cells were stained, high if > 80%) was performed. Statistical analysis was performed using the exact Fisher test, Student t test or the Mann-Whitney U test. Survival was analysed using the Kaplan-Meier method and compared with the Log-rank test. The differences were considered significant at a two-sided p value of < 0.05. All statistical analyses were performed using SPSS® 23.0 for Windows (SPSS Inc., Chicago, IL, USA).

Results
Our study consisted of 39 patients of which 58.9% presented with weak and 41.1% with strong intensity. The median extension was 90%: 28.2% cases presented with a low extension and 71.8% with a high extension. No significant differences related to intensity were found. The high-extension group showed a higher percentage of T3 PDAC (92.9% vs 63.6%, p = 0.042) and LNR20 (35.7% vs 0%, p = 0.037) as well as shorter disease-free survival (17.58 vs 54.46 months; p = 0.048).

Conclusions
Our findings suggest that GLUT-1 could be related to higher aggressivity in PDAC and could be used as a prognostic marker, identifying patients with a worse response to current therapies who could benefit from more aggressive treatments.
Clinical presentation and prognostic analysis of adult patients with Langerhans cell histiocytosis with pulmonary involvement
Authors: Miao Hui-lei , Zhao Ai-lin , Duan Ming-hui , Zhou Dao-bin , Cao Xin-xin , Li Jian 
Published: September 2020

Abstract
Background
The study aimed to investigate the clinical features and prognosis factors of adult patients with Langerhans cell histiocytosis (LCH) with pulmonary involvement, especially multisystem (MS) LCH with pulmonary involvement.

Methods
We retrospectively analyzed the demographic materials, clinical features and treatment outcomes of 119 adult LCH patients with pulmonary involvement at our center from January 1990 to November 2019.

Results
Among 119 patients, 13 (10.9%) had single-system (SS) LCH, and 106 (89.1%) had MS-LCH with pulmonary involvement. SS-LCH patients had higher smoking rate (84.6% vs 52.8%, P = 0.026) and smoking index (300 vs 200, P = 0.019) than MS-LCH patients. The percentage of respiratory symptoms of SS-LCH patients was higher than MS-LCH patients (84.6% vs 53.8%, P = 0.034). Pulmonary function was impaired in 83.8% of the patients, and DLCO was the parameter most frequently impaired, accounting for 81.1%. The median DLCO was 65.1% predicted. Patients with pneumothorax had significantly worse DLCO (P = 0.022), FEV1 (P = 0.000) and FEV1/FVC (P = 0.000) than those without pneumothorax. During the follow-up, 72.4% of the patients had stable pulmonary function, and 13.8% showed improvements after chemotherapy. The estimated 3-year OS and EFS were 89.7 and 58.3%, respectively. Patients with a baseline FEV1 ≤ 55% predicted had worse OS. A history of pneumothorax indicated worse EFS and cytarabine based therapy predicted better EFS.

Conclusions
An FEV1 ≤ 55% predicted and a history of pneumothorax at diagnosis indicated a poor prognosis. Cytarabine based regimen may arrest the decline in pulmonary function in LCH patients with pulmonary involvement and improve EFS.
Multiple retinal astrocytic hamartomas in siblings with lebers congenital amaurosis: a case series and review of literature
Authors: Paul Lagan , Kumar Sumit , Singh Shalini , Jain Tanya 
Published: September 2020

Abstract
Background
Leber’s congenital amaurosis (LCA) is a known inherited retinal disease (IRD) associated with severe visual loss, nystagmus, amaurotic pupils, oculo-digital sign and markedly reduced or absent electroretinograms (ERG). Retinal astrocytic hamartomas (RAH) is a benign vascularized glial tumor of the retina. There is no known association of these two entities, more so in siblings.

Case presentation
A pair of siblings diagnosed as LCA who presented with RAH with no extraocular symptoms or signs of phakomatosis were imaged. Multimodal imaging was performed and are elaborately described in this article.

Conclusion
LCA in siblings with multiple RAHs is an extremely rare association. Recent advances in retinal imaging tools have aided in diagnosing even subtle and early RAH with high sensitivity using Infrared imaging (IRI) and Optical coherence tomography (OCT).