bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rehabilitation healthcare professionals’ competence and confidence in differentially diagnosing deafblindness from autism spectrum disorders: a cross-sectional survey in South Africa
Authors: Moroe Nomfundo , Masuku Khetsiwe , Shirame Lebogang 
Published: March 2022

AbstractBackgroundEarly diagnosis and management of children who are deafblind is important to alleviate the effects of deafblindness on the development of the child who is deafblind and their families. However, children who are deafblind are often misdiagnosed or diagnosed late. The misdiagnosis or late diagnosis has been attributed to many factors, one of which is the competence and confidence of healthcare professionals in differentially diagnosing deafblindness from other conditions, in most cases, autism spectrum disorder (ASD). The study therefore aimed to establish the competence and confidence of rehabilitation healthcare professionals in differentially diagnosing deafblindness from ASD in the South African context.MethodsA cross-sectional survey design was employed for the study. An online questionnaire was distributed to rehabilitation healthcare professionals (N = 78) via Survey Monkey. Data were analyzed using descriptive and inferential statistics. Ethical clearance and permission were obtained from relevant stakeholders prior to the commencement of the study.ResultsRegarding the rehabilitation healthcare professionals in this study, 54% were competent in diagnosing ASD, while only 35% could correctly diagnose deafblindness. In some instances, symptoms were classified as associated with both ASD and deafblindness, when they were just those of deafblindness. Of all the rehabilitation healthcare professionals in this study, speech language therapists displayed the most knowledge of deafblindness. Furthermore, healthcare professionals who had between one and nine years of working experience had more knowledge of deafblindness than other professionals with more or less experience.ConclusionDeafblindness is often underdiagnosed or misdiagnosed as ASD. This is due to the lack of competence and confidence of rehabilitation healthcare professionals in diagnosing it. The findings therefore highlight the need for training of rehabilitation healthcare professionals. Training on deafblindness could be included as part of the curriculum in the various undergraduate programs. Deafblindness could also form part of the Continuous Professional Development (CPD) training programs at various healthcare facilities. A team approach to the training would be ideal as it would facilitate peer learning and support. More research is required as it would inform evidence-based assessment, and management and support strategies for children who are deafblind and their families.
GATD3A, a mitochondrial deglycase with evolutionary origins from gammaproteobacteria, restricts the formation of advanced glycation end products
Authors: Smith Andrew J. , Advani Jayshree , Brock Daniel C. , Nellissery Jacob , Gumerson Jessica , Dong Lijin , Aravind L. , Kennedy Breandán , Swaroop Anand 
Published: March 2022

Abstract
Background
Functional complexity of the eukaryotic mitochondrial proteome is augmented by independent gene acquisition from bacteria since its endosymbiotic origins. Mammalian homologs of many ancestral mitochondrial proteins have uncharacterized catalytic activities. Recent forward genetic approaches attributed functions to proteins in established metabolic pathways, thereby limiting the possibility of identifying novel biology relevant to human disease. We undertook a bottom-up biochemistry approach to discern evolutionarily conserved mitochondrial proteins with catalytic potential.

Results
Here, we identify a Parkinson-associated DJ-1/PARK7-like protein—glutamine amidotransferase-like class 1 domain-containing 3A (GATD3A), with bacterial evolutionary affinities although not from alphaproteobacteria. We demonstrate that GATD3A localizes to the mitochondrial matrix and functions as a deglycase. Through its amidolysis domain, GATD3A removes non-enzymatic chemical modifications produced during the Maillard reaction between dicarbonyls and amines of nucleotides and amino acids. GATD3A interacts with factors involved in mitochondrial mRNA processing and translation, suggestive of a role in maintaining integrity of important biomolecules through its deglycase activity. The loss of GATD3A in mice is associated with accumulation of advanced glycation end products (AGEs) and altered mitochondrial dynamics.

Conclusions
An evolutionary perspective helped us prioritize a previously uncharacterized but predicted mitochondrial protein GATD3A, which mediates the removal of early glycation intermediates. GATD3A restricts the formation of AGEs in mitochondria and is a relevant target for diseases where AGE deposition is a pathological hallmark.
Ezetimibe combination therapy with statin for non-alcoholic fatty liver disease: an open-label randomized controlled trial (ESSENTIAL study)
Authors: Cho Yongin , Rhee Hyungjin , Kim Young-eun , Lee Minyoung , Lee Byung-Wan , Kang Eun Seok , Cha Bong-Soo , Choi Jin-Young , Lee Yong-ho 
Published: March 2022

Abstract
Background
The effect of ezetimibe, Niemann-Pick C1-like 1 inhibitor, on liver fat is not clearly elucidated. Our primary objective was to evaluate the efficacy of ezetimibe plus rosuvastatin versus rosuvastatin monotherapy to reduce liver fat using magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) in patients with non-alcoholic fatty liver disease (NAFLD).

Methods
A randomized controlled, open-label trial of 70 participants with NAFLD confirmed by ultrasound who were assigned to receive either ezetimibe 10 mg plus rosuvastatin 5 mg daily or rosuvastatin 5 mg for up to 24 weeks. The liver fat change was measured as average values in each of nine liver segments by MRI-PDFF. Magnetic resonance elastography (MRE) was used to measure liver fibrosis change.

Results
Combination therapy significantly reduced liver fat compared with monotherapy by MRI-PDFF (mean difference: 3.2%; p = 0.020). There were significant reductions from baseline to study completion by MRI-PDFF for both the combination and monotherapy groups, respectively (18.1 to 12.3%; p < 0.001 and 15.0 to 12.4%; p = 0.003). Individuals with higher body mass index, type 2 diabetes, insulin resistance, and severe liver fibrosis were likely to be good responders to treatment with ezetimibe. MRE-derived change in liver fibrosis was not significantly different (both groups, p > 0.05). Controlled attenuation parameter (CAP) by transient elastography was significantly reduced in the combination group (321 to 287 dB/m; p = 0.018), but not in the monotherapy group (323 to 311 dB/m; p = 0.104).

Conclusions
Ezetimibe and rosuvastatin were found to be safe to treat participants with NAFLD. Furthermore, ezetimibe combined with rosuvastatin significantly reduced liver fat in this population.

Trial registration
The trial was registered at ClinicalTrials.gov (registration number: NCT03434613).
One-year pulmonary impairment after severe COVID-19: a prospective, multicenter follow-up study
Authors: Faverio Paola , Luppi Fabrizio , Rebora Paola , D’Andrea Gabriele , Stainer Anna , Busnelli Sara , Catalano Martina , Modafferi Giuseppe , Franco Giovanni , Monzani Anna , Galimberti Stefania , Scarpazza Paolo , Oggionni Elisa , Betti Monia , Oggionni Tiberio , De Giacomi Federica , Bini Francesco , Bodini Bruno Dino , Parati Mara , Bilucaglia Luca , Ceruti Paolo , Modina Denise , Harari Sergio , Caminati Antonella , Intotero Marcello , Sergio Pietro , Monzillo Giuseppe , Leati Giovanni , Borghesi Andrea , Zompatori Maurizio , Corso Rocco , Valsecchi Maria Grazia , Bellani Giacomo , Foti Giuseppe , Pesci Alberto 
Published: March 2022

Abstract
Background
Long-term pulmonary sequelae following hospitalization for SARS-CoV-2 pneumonia is largely unclear. The aim of this study was to identify and characterise pulmonary sequelae caused by SARS-CoV-2 pneumonia at 12-month from discharge.

Methods
In this multicentre, prospective, observational study, patients hospitalised for SARS-CoV-2 pneumonia and without prior diagnosis of structural lung diseases were stratified by maximum ventilatory support (“oxygen only”, “continuous positive airway pressure (CPAP)” and “invasive mechanical ventilation (IMV)”) and followed up at 12 months from discharge. Pulmonary function tests and diffusion capacity for carbon monoxide (DLCO), 6 min walking test, high resolution CT (HRCT) scan, and modified Medical Research Council (mMRC) dyspnea scale were collected.

Results
Out of 287 patients hospitalized with SARS-CoV-2 pneumonia and followed up at 1 year, DLCO impairment, mainly of mild entity and improved with respect to the 6-month follow-up, was observed more frequently in the “oxygen only” and “IMV” group (53% and 49% of patients, respectively), compared to 29% in the “CPAP” group. Abnormalities at chest HRCT were found in 46%, 65% and 80% of cases in the “oxygen only”, “CPAP” and “IMV” group, respectively. Non-fibrotic interstitial lung abnormalities, in particular reticulations and ground-glass attenuation, were the main finding, while honeycombing was found only in 1% of cases. Older patients and those requiring IMV were at higher risk of developing radiological pulmonary sequelae. Dyspnea evaluated through mMRC scale was reported by 35% of patients with no differences between groups, compared to 29% at 6-month follow-up.

Conclusion
DLCO alteration and non-fibrotic interstitial lung abnormalities are common after 1 year from hospitalization due to SARS-CoV-2 pneumonia, particularly in older patients requiring higher ventilatory support. Studies with longer follow-ups are needed.
High fibrinogen-to-albumin ratio with type 2 diabetes mellitus is associated with poor prognosis in patients undergoing percutaneous coronary intervention: 5-year findings from a large cohort
Authors: Wang Peizhi , Yuan Deshan , Zhang Ce , Zhu Pei , Jia Sida , Song Ying , Tang Xiaofang , Xu Jingjing , Li Tianyu , Zeng Guyu , Zhao Xueyan , Yang Yuejin , Xu Bo , Gao Runlin , Yuan Jinqing 
Published: March 2022

Abstract
Background
Inflammation plays a crucial role in coronary atherosclerosis progression, and growing evidence has demonstrated that the fibrinogen-to-albumin ratio (FAR), as a novel inflammation biomarker, is associated with the severity of coronary artery disease (CAD). However, the long-term risk of cardiovascular events remains indistinct in patients with different level of FAR and different glycemic metabolism status. This study was to assess 5-year clinical outcomes of diabetic and non-diabetic patients who underwent percutaneous coronary intervention (PCI) with different level of FAR.

Methods
We consecutively enrolled 10,724 patients with CAD hospitalized for PCI and followed up for the major adverse cardiac and cerebrovascular events (MACCE) covering all-cause mortality, cardiac mortality, non-fatal myocardial infarction, non-fatal ischemic stroke, and unplanned coronary revascularization. FAR was computed using the following formula: Fibrinogen (g/L)/Albumin (g/L). According to the optimal cut-off value of FAR for MACCE prediction, patients were divided into higher level of FAR (FAR-H) and lower level of FAR (FAR-L) subgroups, and were further categorized into four groups as FAR-H with DM and non-DM, and FAR-L with DM and non-DM.

Results
5298 patients (58.36 ± 10.36 years, 77.7% male) were ultimately enrolled in the present study. A total of 1099 (20.7%) MACCEs were documented during the 5-year follow-up. The optimal cut-off value of FAR was 0.0783 by the surv_cutpoint function. Compared to ones with FAR-H and DM, patients with FAR-L and non-DM, FAR-H and non-DM, FAR-L and DM had decreased risk of MACCEs [adjusted hazard ratio (HR): 0.75, 95% confidence interval (CI) 0.64–0.89, P = 0.001; HR: 0.78, 95% CI 0.66–0.93, P = 0.006; HR: 0.81, 95% CI 0.68–0.97, P = 0.019; respectively]. Notably, non-diabetic patients with lower level of FAR also had lower all-cause mortality and cardiac mortality risk than those in the FAR-H/DM group (HR: 0.41, 95% CI 0.27–0.63, P < 0.001; HR: 0.30, 95% CI 0.17–0.53, P < 0.001; respectively). Multivariate Cox proportional hazards regression analysis also indicated the highest risk of MACCEs in patients with FAR-H and DM than others (P for trend = 0.005). In addition, post-hoc analysis revealed consistent effects on 5-year MACCE across various subgroups.

Conclusion
In this real-world cohort study, higher level of FAR combined with DM was associated with worse 5-year outcomes among patients with CAD undergoing PCI. The level of FAR may help to identify high-risk individuals in this specific population, where more precise risk assessment should be performed.
Antimicrobial activity of ceftazidime-avibactam and comparators against levofloxacin-resistant Escherichia coli collected from four geographic regions, 2012–2018
Authors: Stone Gregory G. , Hackel Meredith A. 
Published: March 2022

Abstract
Background
Increases in resistance to fluoroquinolones have been correlated with the use of levofloxacin in the treatment of infections caused by Escherichia coli. The analysis presents the in vitro activity of ceftazidime-avibactam and comparator agents against 10,840 levofloxacin-resistant E. coli isolates collected from four geographic regions (Africa/Middle East, Europe, Asia/South Pacific, Latin America) between 2012 and 2018.

Methods
Non-duplicate clinical isolates of E. coli were collected from participating centres and shipped to IHMA, Inc., (Schaumburg, IL, USA). Susceptibility testing was performed with frozen broth microdilution panels manufactured by IHMA, according to CLSI guidelines. Levofloxacin-resistance was defined at a minimum inhibitory concentration of ≥ 2 mg/L. Isolates collected between 2012 and 2015 were tested for extended-spectrum β-lactamase (ESBL) activity by determining susceptibility to cefotaxime, cefotaxime-clavulanate, ceftazidime, and ceftazidime-clavulanate as recommended by CLSI guidelines. Isolates collected between 2016 and 2018 were identified as ESBL-positive by genotype using multiplex polymerase chain reaction assays.

Results
A total of 74.8% of levofloxacin-resistant E. coli isolates in the analysis were from three culture sources: urinary tract infections (N = 3229; 29.8%), skin and skin structure infections (N = 2564; 23.7%) and intra-abdominal infections (N = 2313; 21.3%). Susceptibility rates to ceftazidime-avibactam were consistently high in all regions against both ESBL-positive (97.0% in Asia/South Pacific to 99.7% in Africa/Middle East and Latin America) and ESBL-negative isolates (99.4% in Asia/South Pacific to 100% in Latin America). Susceptibility was also high in each region among ESBL-positive and ESBL-negative isolates to colistin (≥ 98.5%), imipenem (≥ 96.5%), meropenem (≥ 96.5%) and tigecycline (≥ 94.1%).

Conclusions
Antimicrobial susceptibility to ceftazidime-avibactam among levofloxacin-resistant E. coli isolates, including ESBL-positive isolates, collected from four geographical regions between 2012 and 2018 was consistently high. Susceptibility to the comparator agents colistin, tigecycline, imipenem and meropenem was also high.
A clinician’s handbook for using ctDNA throughout the patient journey
Authors: Hasenleithner Samantha O. , Speicher Michael R. 
Published: March 2022

Abstract
Background
The promise of precision cancer medicine presently centers around the genomic sequence of a patient’s tumor being translated into timely, actionable information to inform clinical care. The analysis of cell-free DNA from liquid biopsy, which contains circulating tumor DNA (ctDNA) in patients with cancer, has proven to be amenable to various settings in oncology. However, open questions surrounding the clinical validity and utility of plasma-based analyses have hindered widespread clinical adoption.

Main body
Owing to the rapid evolution of the field, studies supporting the use of ctDNA as a biomarker throughout a patient’s journey with cancer have accumulated in the last few years, warranting a review of the latest status for clinicians who may employ ctDNA in their precision oncology programs. In this work, we take a step back from the intricate coverage of detection approaches described extensively elsewhere and cover basic concepts around the practical implementation of next generation sequencing (NGS)-guided liquid biopsy. We compare relevant targeted and untargeted approaches to plasma DNA analysis, describe the latest evidence for clinical validity and utility, and highlight the value of genome-wide ctDNA analysis, particularly as it relates to early detection strategies and discovery applications harnessing the non-coding genome.

Conclusions
The maturation of liquid biopsy for clinical application will require interdisciplinary efforts to address current challenges. However, patients and clinicians alike may greatly benefit in the future from its incorporation into routine oncology care.
Comparative analyses in transcriptome of human granulosa cells and follicular fluid micro-environment between poor ovarian responders with conventional controlled ovarian or mild ovarian stimulations
Authors: Liu Xiaoping , Mai Huisi , Chen Panyu , Zhang Zhiqiang , Wu Taibao , Chen Jianhui , Sun Peng , Zhou Chuanchuan , Liang Xiaoyan , Huang Rui 
Published: March 2022

Abstract
Background
Both mild and conventional controlled ovarian stimulation are the frequently used protocols for poor ovarian responders. However, there are some debates about which treatment is better. Moreover, little is known about the follicular physiology after the two ovarian stimulation protocols. This study was intended to investigate the features in granulosa cells and follicular fluid micro-environment after the two different ovarian stimulation protocols in poor responders.

Methods
Granulosa cells RNA were sequenced using Illumina Hiseq technology. Specific differently expressed genes and proteins were verified by real-time quantitative PCR and Western blot analysis. Moreover, hormone and cytokine concentrations in the follicular fluid were measured by electrochemiluminescence immunoassay and enzyme-linked immunoabsorbent assay. The correlation between the results of molecular experiments and the laboratory outcomes were analyzed by Spearman correlation analysis.

Results
The differentially expressed genes between the two groups were involved in 4 signaling pathways related to the follicular development; three proteins pertinent to the TGF-β signaling pathway were expressed differently in granulosa cells between the two, and the constituents in the follicular fluid were also different. Further, a correlation between the TGF-β signaling pathway and the good-quality embryo was observed.

Conclusions
The present study made a comparison for the first time in the transcriptome of human granulosa cells and the follicular fluid micro-environment between poor responders with the conventional controlled ovarian stimulation or the mild ovarian stimulation, showing that the TGF-β signaling pathway may correlate with the good-quality of embryos in the mild group, which may be instrumental to the choice of optimal management for IVF patients.
The innate immune receptor Nlrp12 suppresses autoimmunity to the retina
Authors: Lee Ellen J. , Napier Ruth J. , Vance Emily E. , Lashley Sydney J. , Truax Agnieszka D. , Ting Jenny P. , Rosenzweig Holly L. 
Published: March 2022

Abstract
Background
Nod-like receptors (NLRs) are critical to innate immune activation and induction of adaptive T cell responses. Yet, their role in autoinflammatory diseases of the central nervous system (CNS) remains incompletely defined. The NLR, Nlrp12, has been reported to both inhibit and promote neuroinflammation in an animal model of multiple sclerosis (experimental autoimmune encephalomyelitis, EAE), where its T cell-specific role has been investigated. Uveitis resulting from autoimmunity of the neuroretina, an extension of the CNS, involves a breach in immune privilege and entry of T cells into the eye. Here, we examined the contribution of Nlrp12 in a T cell-mediated model of uveitis, experimental autoimmune uveitis (EAU).

Methods
Mice were immunized with interphotoreceptor retinoid-binding protein peptide 1–20 (IRBP1–20) emulsified in Complete Freund’s adjuvant, CFA. Uveitis was evaluated by clinical and histopathological scoring, and comparisons were made in WT vs. Nlrp12−/− mice, lymphopenic Rag1−/− mice reconstituted with WT vs. Nlrp12−/− CD4+ T cells, or among bone marrow (BM) chimeric mice. Antigen-specific Th-effector responses were evaluated by ELISA and intracellular cytokine staining. Cellular composition of uveitic eyes from WT or Nlrp12−/− mice was compared using flow cytometry. Expression of Nlrp12 and of cytokines/chemokines within the neuroretina was evaluated by immunoblotting and quantitative PCR.

Results
Nlrp12−/− mice developed exacerbated uveitis characterized by extensive vasculitis, chorioretinal infiltrates and photoreceptor damage. Nlrp12 was dispensable for T cell priming and differentiation of peripheral Th1 or Th17 cells, and uveitis in immunodeficient mice reconstituted with either Nlrp12−/− or WT T cells was similar. Collectively, this ruled out T cells as the source of Nlrp12-mediated protection to EAU. Uveitic Nlrp12−/− eyes had more pronounced myeloid cell accumulation than uveitic WT eyes. Transplantation of Nlrp12−/− BM resulted in increased susceptibility to EAU regardless of host genotype, but interestingly, a non-hematopoietic origin for Nlrp12 function was also observed. Indeed, Nlrp12 was found to be constitutively expressed in the neuroretina, where it suppressed chemokine/cytokine induction.

Conclusions
Our data identify a combinatorial role for Nlrp12 in dampening autoimmunity of the neuroretina. These findings could provide a pathway for development of therapies for uveitis and potentially other autoinflammatory/autoimmune diseases of the CNS.