bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inflammatory neuronal loss in the substantia nigra induced by systemic lipopolysaccharide is prevented by knockout of the P2Y6 receptor in mice
Authors: Milde Stefan , van Tartwijk Francesca W. , Vilalta Anna , Hornik Tamara C. , Dundee Jacob M. , Puigdellívol Mar , Brown Guy C. 
Published: October 2021

AbstractInflammation may contribute to multiple brain pathologies. One cause of inflammation is lipopolysaccharide/endotoxin (LPS), the levels of which are elevated in blood and/or brain during bacterial infections, gut dysfunction and neurodegenerative diseases, such as Parkinson’s disease. How inflammation causes neuronal loss is unclear, but one potential mechanism is microglial phagocytosis of neurons, which is dependent on the microglial P2Y6receptor. We investigated here whether the P2Y6receptor was required for inflammatory neuronal loss. Intraperitoneal injection of LPS on 4 successive days resulted in specific loss of dopaminergic neurons (measured as cells staining with tyrosine hydroxylase or NeuN) in thesubstantia nigraof wild-type mice, but no neuronal loss in cortex or hippocampus. This supports the hypothesis that neuronal loss in Parkinson’s disease may be driven by peripheral LPS. By contrast, there was no LPS-induced neuronal loss in P2Y6receptor knockout mice. In vitro, LPS-induced microglial phagocytosis of cells was prevented by inhibition of the P2Y6receptor, and LPS-induced neuronal loss was reduced in mixed glial–neuronal cultures from P2Y6receptor knockout mice. This supports the hypothesis that microglial phagocytosis contributes to inflammatory neuronal loss, and can be prevented by blocking the P2Y6receptor, suggesting that P2Y6receptor antagonists might be used to prevent inflammatory neuronal loss in Parkinson’s disease and other brain pathologies involving inflammatory neuronal loss.
Long-term effectiveness of carglumic acid in patients with propionic acidemia (PA) and methylmalonic acidemia (MMA): a randomized clinical trial
Authors: Alfadhel Majid , Nashabat Marwan , Saleh Mohammed , Elamin Mohammed , Alfares Ahmed , Al Othaim Ali , Umair Muhammad , Ahmed Hind , Ababneh Faroug , Al Mutairi Fuad , Eyaid Wafaa , Alswaid Abdulrahman , Alohali Lina , Faqeih Eissa , Almannai Mohammed , Aljeraisy Majed , Albdah Bayan , Hussein Mohamed A. , Rahbeeni Zuhair , Alasmari Ali 
Published: October 2021

Abstract
Background
Propionic acidemia (PA) and methylmalonic acidemia (MMA) are rare, autosomal recessive inborn errors of metabolism that require life-long medical treatment. The trial aimed to evaluate the effectiveness of the administration of carglumic acid with the standard treatment compared to the standard treatment alone in the management of these organic acidemias.

Methods
The study was a prospective, multicenter, randomized, parallel-group, open-label, controlled clinical trial. Patients aged ≤ 15 years with confirmed PA and MMA were included in the study. Patients were followed up for two years. The primary outcome was the number of emergency room (ER) admissions because of hyperammonemia. Secondary outcomes included plasma ammonia levels over time, time to the first episode of hyperammonemia, biomarkers, and differences in the duration of hospital stay.

Results
Thirty-eight patients were included in the study. On the primary efficacy endpoint, a mean of 6.31 ER admissions was observed for the carglumic acid arm, compared with 12.76 for standard treatment, with a significant difference between the groups (p = 0.0095). Of the secondary outcomes, the only significant differences were in glycine and free carnitine levels.

Conclusion
Using carglumic acid in addition to standard treatment over the long term significantly reduces the number of ER admissions because of hyperammonemia in patients with PA and MMA.
Clipper: p-value-free FDR control on high-throughput data from two conditions
Authors: Ge Xinzhou , Chen Yiling Elaine , Song Dongyuan , McDermott MeiLu , Woyshner Kyla , Manousopoulou Antigoni , Wang Ning , Li Wei , Wang Leo D. , Li Jingyi Jessica 
Published: October 2021

AbstractHigh-throughput biological data analysis commonly involves identifying features such as genes, genomic regions, and proteins, whose values differ between two conditions, from numerous features measured simultaneously. The most widely used criterion to ensure the analysis reliability is the false discovery rate (FDR), which is primarily controlled based onp-values. However, obtaining validp-values relies on either reasonable assumptions of data distribution or large numbers of replicates under both conditions. Clipper is a general statistical framework for FDR control without relying onp-values or specific data distributions. Clipper outperforms existing methods for a broad range of applications in high-throughput data analysis.
Catastrophic adult-onset Still’s disease as a distinct life-threatening clinical subset: case–control study with dimension reduction analysis
Authors: Wahbi Anaïs , Tessoulin Benoît , Bretonnière Cédric , Boileau Julien , Carpentier Dorothée , Decaux Olivier , Fardet Laurence , Geri Guillaume , Godmer Pascal , Goujard Cécile , Maisonneuve Hervé , Mari Arnaud , Pouchot Jacques , Ziza Jean-Marc , Georgin-Lavialle Sophie , Hamidou Mohamed , Néel Antoine 
Published: October 2021

Abstract
Objectives
Adult-onset Still’s disease (AOSD) is a rare systemic inflammatory disorder. Diagnosing AOSD can be challenging, as disease presentation and clinical course are highly heterogeneous. For unclear reasons, a few patients develop life-threatening complications. Our objective was to determine whether these cases resulted from therapeutic delay or could represent a peculiar AOSD subset.

Methods
We conducted a multicentre retrospective study of 20 AOSD patients with organ failure requiring intensive care unit admission and 41 control AOSD patients without organ failure. Clinico-biological data at hospital admission were explored using supervised analyses and unsupervised dimension reduction analysis (factor analysis of mixed data, FAMD).

Results
Disease duration before admission was shorter in patients with life-threatening AOSD (median, 10 vs 20 days, p = 0.007). Disease duration before AOSD therapy initiation also tended to be shorter (median, 24 vs 32 days, p = 0.068). Despite this shorter disease duration, FAMD, hierarchical clustering and univariate analyses showed that these patients exhibited distinctive characteristics at first presentation, including younger age; higher frequency of splenomegaly, liver, cardiac and/or lung involvement; less frequent arthralgia; and higher ferritin level. In multivariate analysis, 3 parameters predicted life-threatening complications: lack of arthralgia, younger age and shorter time between fever onset and hospitalisation.

Conclusion
This study suggests that life-threatening complications of AOSD occur very early, in a peculiar subset, which we propose to name catastrophic adult-onset Still’s disease (CAOSD). Its exact burden may be underestimated and remains to be clarified through large multicentre cohorts. Further studies are needed to identify red flags and define the optimal therapeutic strategy.
Brain Health Services: organization, structure, and challenges for implementation. A user manual for Brain Health Services—part 1 of 6
Authors: Altomare Daniele , Molinuevo José Luis , Ritchie Craig , Ribaldi Federica , Carrera Emmanuel , Dubois Bruno , Jessen Frank , McWhirter Laura , Scheltens Philip , van der Flier Wiesje M. , Vellas Bruno , Démonet Jean-François , Frisoni Giovanni B. ,   on behalf of the European Task Force for Brain Health Services, Abramowicz Marc , Altomare Daniele , Barkhof Frederik , Berthier Marcelo , Bieler Melanie , Blennow Kaj , Brayne Carol , Brioschi Andrea , Carrera Emmanuel , Chételat Gael , Csajka Chantal , Demonet Jean-François , Dodich Alessandra , Dubois Bruno , Frisoni Giovanni B. , Garibotto Valentina , Georges Jean , Hurst Samia , Jessen Frank , Kivipelto Miia , Llewellyn David , McWhirter Laura , Milne Richard , Minguillón Carolina , Miniussi Carlo , Molinuevo José Luis , Nilsson Peter M. , Ranson Janice , Ribaldi Federica , Ritchie Craig , Scheltens Philip , Solomon Alina , van Der Flier Wiesje , van Duijn Cornelia , Vellas Bruno , Visser Leonie 
Published: October 2021

AbstractDementia has a devastating impact on the quality of life of patients and families and comes with a huge cost to society. Dementia prevention is considered a public health priority by the World Health Organization. Delaying the onset of dementia by treating associated risk factors will bring huge individual and societal benefit. Empirical evidence suggests that, in higher-income countries, dementia incidence is decreasing as a result of healthier lifestyles. This observation supports the notion that preventing dementia is possible and that a certain degree of prevention is already in action. Further reduction of dementia incidence through deliberate prevention plans is needed to counteract its growing prevalence due to increasing life expectancy.An increasing number of individuals with normal cognitive performance seek help in the current memory clinics asking an evaluation of their dementia risk, preventive interventions, or interventions to ameliorate their cognitive performance. Consistent evidence suggests that some of these individuals are indeed at increased risk of dementia. This new health demand asks for a shift of target population, from patients with cognitive impairment to worried but cognitively unimpaired individuals. However, current memory clinics do not have the programs and protocols in place to deal with this new population.We envision the development of new services, henceforth called Brain Health Services, devoted to respond to demands from cognitively unimpaired individuals concerned about their risk of dementia. The missions of Brain Health Services will be (i) dementia risk profiling, (ii) dementia risk communication, (iii) dementia risk reduction, and (iv) cognitive enhancement. In this paper, we present the organizational and structural challenges associated with the set-up of Brain Health Services.
Protocols for cognitive enhancement. A user manual for Brain Health Services—part 5 of 6
Authors: Brioschi Guevara Andrea , Bieler Melanie , Altomare Daniele , Berthier Marcelo , Csajka Chantal , Dautricourt Sophie , Démonet Jean-François , Dodich Alessandra , Frisoni Giovanni B. , Miniussi Carlo , Molinuevo José Luis , Ribaldi Federica , Scheltens Philip , Chételat Gael 
Published: October 2021

AbstractCognitive complaints in the absence of objective cognitive impairment, observed in patients with subjective cognitive decline (SCD), are common in old age. The first step to postpone cognitive decline is to use techniques known to improve cognition, i.e., cognitive enhancement techniques.We aimed to provide clinical recommendations to improve cognitive performance in cognitively unimpaired individuals, by using cognitive, mental, or physical training (CMPT), non-invasive brain stimulations (NIBS), drugs, or nutrients. We made a systematic review of CMPT studies based on the GRADE method rating the strength of evidence.CMPT have clinically relevant effects on cognitive and non-cognitive outcomes. The quality of evidence supporting the improvement of outcomes following a CMPT was high for metamemory; moderate for executive functions, attention, global cognition, and generalization in daily life; and low for objective memory, subjective memory, motivation, mood, and quality of life, as well as a transfer to other cognitive functions. Regarding specific interventions, CMPT based on repeated practice (e.g., video games or mindfulness, but not physical training) improved attention and executive functions significantly, while CMPT based on strategic learning significantly improved objective memory.We found encouraging evidence supporting the potential effect of NIBS in improving memory performance, and reducing the perception of self-perceived memory decline in SCD. Yet, the high heterogeneity of stimulation protocols in the different studies prevent the issuing of clear-cut recommendations for implementation in a clinical setting. No conclusive argument was found to recommend any of the main pharmacological cognitive enhancement drugs (“smart drugs”, acetylcholinesterase inhibitors, memantine, antidepressant) or herbal extracts (Panax ginseng, Gingko biloba, and Bacopa monnieri) in people without cognitive impairment.Altogether, this systematic review provides evidence for CMPT to improve cognition, encouraging results for NIBS although more studies are needed, while it does not support the use of drugs or nutrients.
X-linked SCID with a rare mutation
Authors: Mahdavi Fatemeh Sadat , Keramatipour Mohammad , Ansari Sarina , Sharafian Samin , Karamzade Arezou , Tavakol Marzieh 
Published: October 2021

Abstract
Background
Severe combined immunodeficiency (SCID) is a group of relatively rare primary immunodeficiency disorders (PIDs), characterized by disturbed development of T cells and B cells, caused by several genetic mutations that bring on different clinical presentations. SCID may be inherited as an autosomal recessive or an X-linked genetic trait.

Case presentation
A 6-year-old male presented with a history of food allergy, productive coughs, and recurrent purulent rhinitis, poor weight gain and hypothyroidism. The total count of CD4+ T lymphocytes, along with their naïve and central memory subpopulations, as well as central memory CD8+ T cells were decreased in flow cytometry. A nucleotide substitution in exon one of interleukin 2 receptor gamma chain (IL-2RG) gene (c.115 G>A, p.D39N, ChrX: 70,331,275) was reported, based on which the diagnosis of X-liked SCID was confirmed. Antiviral and antibiotic prophylaxis, along with monthly IVIG (intravenous immunoglobulin) was started and the patient was subsequently referred for hematopoietic stem cell transplantation.

Conclusion
PIDs should be considered as the differential diagnosis in any patient with unexplained and bizarre symptoms associated with recurrent infections, allergic and autoimmune manifestations. Clinicians should also bear X-SCID in mind in case of approach to any patient with poor weight gain, unusual allergic or endocrine manifestations, even in the case of a normal or increased level of serum immunoglobulins or T and B cells numbers.
Median 10 years follow-up of patients with covert Cushing’s syndrome: a case series
Authors: Najafipour Farzad , Bahrami Amir , Niafar Mitra , Houshyar Jalil , Halimi Monireh , Sadra Vahideh 
Published: October 2021

Abstract
Background
Ectopic adrenocorticotropic hormone secretion syndrome occurs in 10% of all patients with adrenocorticotropic-hormone-dependent hypercortisolism. It is usually associated with overt malignancies or with occult and indolent tumors. This study aims to confirm the source of ectopic adrenocorticotropic hormone in four patients with ectopic Cushing’s syndrome over time.

Case presentation
A 38-year-old Iranian man with Cushing’s syndrome underwent bilateral adrenalectomy since the source of ectopic adrenocorticotropic hormone secretion was not localized and pituitary imaging was normal. A whole-body scan revealed a right-lung tumoral mass with mediastinal lymph node metastasis. The mass was assumed a lung carcinoid tumor with mediastinal adenopathy. Right-lung mid-zone lobectomy and mediastinal lymphadenectomy were done. In a 47-year-old Iranian man with Cushing’s syndrome, whole-body computed tomography scan revealed a pulmonary nodule in the posterior segment of the left lower lobe of the lung. The third case was a 25-year-old Iranian man who presented with symptoms and signs of Cushing’s syndrome. Pituitary magnetic resonance imaging revealed a microadenoma 5 × 9 mm. Whole-body scan showed abnormal focal somatostatin receptors analog avid lesion in the posterior aspect of inferior third of right lung, highly suggestive of ectopic adrenocorticotropic-hormone-producing tumor. The last case was a 43-year-old Iranian woman with Marfan syndrome with a history of mitral and aortic valve replacement and chronic dissection of the aorta, who presented with symptoms and signs of Cushing’s syndrome. She underwent bilateral adrenalectomy 1 year later owing to failure to locate ectopic adrenocorticotropic hormone syndrome. Whole-body scan showed abnormally increased radiotracer uptake in the midline of the skull base and posterior aspect of the middle zone of left hemithorax and bed of left lobe of thyroid.

Conclusion
The clinical spectrum of ectopic adrenocorticotropic hormone secretion syndrome is wide, and distinguishing Cushing’s disease from ectopic adrenocorticotropic hormone secretion syndrome is difficult. Initial failure to identify a tumor is common. Pulmonary carcinoid or occult source of ectopic adrenocorticotropic hormone secretion syndrome is usually the cause. In occult cases of ectopic adrenocorticotropic hormone in which the tumor cannot be localized, serial follow-up with serial computed tomography, magnetic resonance imaging, or scintigraphy is recommended for several years until the tumor can be localized and treated.
The generalized projection methods in countably normed spaces
Authors: Tawfeek Sarah , Faried Nashat , El-Sharkawy H. A. 
Published: October 2021

AbstractLet E be a Banach space with dual space $E^{*}$

E
∗

, and let K be a nonempty, closed, and convex subset of E. We generalize the concept of generalized projection operator “$\Pi _{K}: E \rightarrow K$

Π
K

:
E
→
K
” from uniformly convex uniformly smooth Banach spaces to uniformly convex uniformly smooth countably normed spaces and study its properties. We show the relation between J-orthogonality and generalized projection operator $\Pi _{K}$

Π
K

and give examples to clarify this relation. We introduce a comparison between the metric projection operator $P_{K}$

P
K

and the generalized projection operator $\Pi _{K}$

Π
K

in uniformly convex uniformly smooth complete countably normed spaces, and we give an example explaining how to evaluate the metric projection $P_{K}$

P
K

and the generalized projection $\Pi _{K}$

Π
K

in some cases of countably normed spaces, and this example illustrates that the generalized projection operator $\Pi _{K}$

Π
K

in general is a set-valued mapping. Also we generalize the generalized projection operator “$\pi _{K}: E^{*} \rightarrow K$

π
K

:

E
∗

→
K
” from reflexive Banach spaces to uniformly convex uniformly smooth countably normed spaces and study its properties in these spaces.
The impact of methamphetamine/amphetamine use on receipt and outcomes of medications for opioid use disorder: a systematic review
Authors: Frost Madeline C. , Lampert Hannah , Tsui Judith I. , Iles-Shih Matthew D. , Williams Emily C. 
Published: October 2021

Abstract
Background
Methamphetamine/amphetamine use has sharply increased among people with opioid use disorder (OUD). It is therefore important to understand whether and how use of these substances may impact receipt of, and outcomes associated with, medications for OUD (MOUD). This systematic review identified studies that examined associations between methamphetamine/amphetamine use or use disorder and 3 classes of outcomes: (1) receipt of MOUD, (2) retention in MOUD, and (3) opioid abstinence during MOUD.

Methods
We searched 3 databases (PubMed/MEDLINE, PsycINFO, CINAHL Complete) from 1/1/2000 to 7/28/2020 using key words and subject headings, and hand-searched reference lists of included articles. English-language studies of people with documented OUD/opioid use that reported a quantitative association between methamphetamine/amphetamine use or use disorder and an outcome of interest were included. Study data were extracted using a standardized template, and risk of bias was assessed for each study. Screening, inclusion, data extraction and bias assessment were conducted independently by 2 authors. Study characteristics and findings were summarized for each class of outcomes.

Results
Thirty-nine studies met inclusion criteria. Studies generally found that methamphetamine/amphetamine use or use disorder was negatively associated with receiving methadone and buprenorphine; 2 studies suggested positive associations with receiving naltrexone. Studies generally found negative associations with retention; most studies finding no association had small samples, and these studies tended to examine shorter retention timeframes and describe provision of adjunctive services to address substance use. Studies generally found negative associations with opioid abstinence during treatment among patients receiving methadone or sustained-release naltrexone implants, though observed associations may have been confounded by other polysubstance use. Most studies examining opioid abstinence during other types of MOUD treatment had small samples.

Conclusions
Overall, existing research suggests people who use methamphetamine/amphetamines may have lower receipt of MOUD, retention in MOUD, and opioid abstinence during MOUD. Future research should examine how specific policies and treatment models impact MOUD outcomes for these patients, and seek to understand the perspectives of MOUD providers and people who use both opioids and methamphetamine/amphetamines. Efforts to improve MOUD care and overdose prevention strategies are needed for this population.
Rate of malignancy for thyroid nodules with AUS/FLUS cytopathology in a tertiary care center – a retrospective cohort study
Authors: Hathi Kalpesh , Rahmeh Tarek , Munro Vicki , Northrup Victoria , Sherazi Ali , Chin Christopher J. 
Published: October 2021

Background Thyroid nodules are stratified through fine-needle aspiration (FNA) and are often categorized using The Bethesda System for Reporting Thyroid Cytopathology, which estimates the risk of malignancy for six cytopathological categories. The atypia of undetermined significance (AUS) and follicular lesion of undetermined significance (FLUS) categories have varying malignancy rates reported in the literature which can range from 6 to 72.9%. Due to this heterogeneity, we assessed the malignancy rate and effectiveness of repeat FNA (rFNA) for AUS/FLUS thyroid cytopathology at our institution. Methods Electronic health records of patients with AUS/FLUS thyroid cytopathology on FNA at our center since the implementation of the Bethesda System on May 1, 2014–December 31, 2019 were retrospectively reviewed. Patient demographics, treatment pathway, and pathology results were collected. The treatment pathway of the nodules, the rFNA results, and the malignant histopathology results were reported. Malignancy rates were calculated as an upper and lower limit estimate. Results This study described 182 AUS/FLUS thyroid nodules from 177 patients. In total, 24 thyroid nodules were deemed malignant upon histopathology, yielding a final malignancy rate of 13.2–25.3%. All of the malignancies were variants of papillary thyroid carcinoma. The malignancy rate of the nodules which underwent resection without rFNA (21.5%) was lower than the malignancy rate of the nodules which underwent resection after rFNA (43.8%). 45.5% of the rFNA results were re-classified into more definitive categories. Conclusion The malignancy rate of AUS/FLUS thyroid cytopathology at our center is in line with the risk of malignancy stated by the 2017 Bethesda System. However, our malignancy rate is lower than some other Canadian centers and approximately half of our rFNAs were re-classified, highlighting the importance of establishing center-specific malignancy and rFNA re-classification rates to guide treatment decisions.