bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chronic Disseminated Candidiasis in Children and the Role of Corticosteroids Therapy
Authors: Al Yazidi Laila S. , Elsidig Nagi , Wali Yasser , Nazir Hanan 
Published: February 2023

Background:
Little is known about chronic disseminated candidiasis (CDC) in children. This study was done to describe the epidemiology, risk factors and outcome of CDC in children managed at Sultan Qaboos University Hospital (SQUH), Oman, and to describe the role of corticosteroids in the management of immune reconstitution inflammatory syndrome (IRIS) complicating CDC.

Methods:
We retrospectively reported demographic, clinical and laboratory data of all children managed in our center for CDC between January 2013 and December 2021. In addition, we discuss the available literature on the role of corticosteroids for management of CDC-related IRIS in children since 2005.

Results:
Between January 2013 and December 2021, 36 immunocompromised children were diagnosed with invasive fungal infection at our center, of whom 6 had CDC (all with acute leukemia). Their median age was 5.75 years. Prolonged fever despite broad-spectrum antibiotics (6/6) followed by skin rash (4/6) were the most common clinical features of CDC. Four children grew Candida tropicalis from blood or skin. CDC-related IRIS was documented in 5 children (83%) and 2 received corticosteroids. Our literature review revealed that 28 children were managed with corticosteroids for CDC-related IRIS since 2005. The majority of these children had defervescence of fever within 48 hours. Prednisolone of 1–2 mg/kg/day for 2–6 weeks was the most common regimen used. No major side effects reported in these patients.

Conclusion:
CDC is more common in children with acute leukemia and CDC-related IRIS is not uncommon. Corticosteroid therapy looks effective and safe as adjunctive therapy for CDC-related IRIS.
Antidepressant Poisoning Trends in Pediatric Intensive Care
Authors: Gurbanov Anar , Kandemir Hande , Gurbanova Lala , Gün Emrah , Botan Edin , Balaban Burak , Kahveci Fevzi , Özen Hasan , Uçmak Hacer , Özdemir İhsan , Havan Merve , Tekin Deniz , Kendirli Tanil 
Published: February 2023

Abstract

Purpose/Background
This study aimed to compare the frequency, clinical findings, treatment practices, and outcomes of toxicity to old-generation (OG) and new-generation (NG) antidepressants in our pediatric intensive care unit (PICU) by year-to-year.

Methods/Procedures
The study included patients hospitalized for antidepressant poisoning during the 11-year period of January 2010 through December 2020. Antidepressants were classified as OG and NG. The groups were compared in terms of patient demographic characteristics, type of poisoning (accidental/suicidal), clinical findings, supportive and extracorporeal treatments received, and outcomes.

Findings/Results
The study included 58 patients (NG, n = 30; OG, n = 28). The median age of the patients was 178 months (range, 13.6–215 months) and 47 patients (81%) were female. Patients admitted for only antidepressant poisoning constituted 13.3% of all poisoning cases (58/436). Of these, 22 cases (37.9%) were accidental and 36 (62.3%) were suicidal. The most common cause of poisoning was amitriptyline (24/28) in the OG group and sertraline (13/30) in the NG group. Neurological symptoms were significantly more common in the OG group (76.2% vs 23.8%), while gastrointestinal involvement was more common in the NG group (82% vs 18%; P = 0.001 and P = 0.026, respectively). Old-generation antidepressant poisoning was associated with more frequent intubation (4 vs 0 patients, P = 0.048) and longer length of PICU stay (median, 1 day [range, 1–8] vs 1 day [range, 1–4], P = 0.019). Rates of therapeutic plasma exchange and intravenous lipid emulsion therapy did not differ (P = 0.483 and P = 0.229, respectively).

Implications/Conclusions
In poisoned patients, proper evaluation and management of patients requiring PICU admission are vital for favorable patient outcomes.
Peripheral Artery Bypass Graft for the Treatment of Ischemic Ulcer or Severe Pain of Hand in Connective Tissue Diseases
Authors: Kim Jong-Ho , Kim Yumin , Eun Seokchan 
Published: February 2023

Abstract
Chronic ischemia of the hands and feet is a rare medical condition that requires surgical revascularization. In particular, digital ischemia resulting from connective tissue diseases (CTDs) is among the most important manifestations that negatively affect patients' quality of life. Here, we describe a bypass graft technique for treating digital ischemia. This study aimed to share the considerable benefits of surgical intervention for CTD and present a treatment algorithm. From 2009 to 2020, bypass graft surgery was performed on 10 patients with CTD to relieve their ischemic symptoms or ulceration. Preoperative angiography was performed, and blood distribution patterns were analyzed in detail. Based on the angiographic 4-level analysis, bypass graft surgeries were performed accordingly. The postoperative follow-up was 15 to 72 months. Pain in the hands that underwent the bypass graft surgery improved immediately after surgery. All ulcerations healed and the mean time recorded for ulceration healing was 45.7 days. Here, we propose an appropriate surgical treatment algorithm for managing CTD using arterial bypass graft surgery, and its positive long-term results demonstrate that it is an appropriate option for treating digital ischemia. In conclusion, strict measures with precise preoperative planning can provide satisfactory long-term results in patients with CTD.
Reverse Abdominoplasty for Mastectomy Defect Closure in Advanced Breast Cancer
Authors: Whalen Kristen , Liu Langfeier , Rejano Courtney Johns , Mhaskar Rahul , Khakpour Nazanin , Dayicioglu Deniz 
Published: February 2023

BackgroundBreast cancer patients with locally advanced breast cancer who require radical mastectomy are left with large chest wall defects. This poses a significant reconstructive challenge as many high-risk patients require timely postmastectomy adjuvant therapy. While the reverse abdominoplasty technique is commonly used for aesthetic improvement of the anterior trunk, it can be also be effectively used for closure of extensive mastectomy defects in this patient population.MethodsWe conducted a retrospective cohort study of all consecutive patients who underwent an extensive radical mastectomy followed by immediate closure with the reverse abdominoplasty technique at a single tertiary cancer center from June 2017 to July 2022. Patients who had concurrent skin grafting or breast mound flap reconstruction were excluded. Demographic, medical, oncologic, and reconstructive data were collected.ResultsSix patients were treated with reverse abdominoplasty for 9 chest wall defects after surgical excision of locally advanced breast cancer. The median tumor size was 10.7 cm (range, 6.7–10 cm) and the median mastectomy weight was 865.7 g (range, 356.4–1247.7 g). On average, the operation length was 191 minutes (range, 86–257 minutes) and the postoperative length of stay was 2.2 days (range, 1–5 days). All patients underwent systemic adjuvant therapy and the median time from surgery to initiation of therapy was 44.5 days (range, 32–75 days).ConclusionsReverse abdominoplasty is a simple and safe technique to reliably close large defects after locally advanced breast cancer excision. It has a short operative time, hospital stay, and turnaround time to initiation of adjuvant therapy.
Ensemble learning for higher diagnostic precision in schizophrenia using peripheral blood gene expression profile
Authors: Wagh Vipul Vilas , Agrawal Suchita , Purohit Shruti , Pachpor Tejaswini , Narlikar Leelavati , Paralikar Vasudeo , Khare Satyajeet 
Published: February 2023

AbstractThe need for molecular biomarkers for schizophrenia has been well recognized. Peripheral blood gene expression profiling and machine learning (ML) tools have recently become popular for biomarker discovery. The stigmatization associated with schizophrenia advocates the need for diagnostic models with higher precision. In this study, we propose a strategy to develop higher-precision ML models using ensemble learning. We performed a meta-analysis using peripheral blood expression microarray data. The ML models, support vector machines (SVM), and prediction analysis for microarrays (PAM) were developed using differentially expressed genes as features. The ensemble of SVM-radial and PAM predicted test samples with a precision of 81.33% (SD: 0.078). The precision of the ensemble model was significantly higher than SVM-radial (63.83%, SD: 0.081) and PAM (66.89%, SD: 0.097). The feature genes identified were enriched for biological processes such as response to stress, response to stimulus, regulation of the immune system, and metabolism of organic nitrogen compounds. The network analysis of feature genes identifiedPRF1, GZMB, IL2RB, ITGAL, andIL2RGas hub genes. Additionally, the ensemble model developed using microarray data classified the RNA-Sequencing samples with moderately high precision (72.00%, SD: 0.08). The pipeline developed in this study allows the prediction of a single microarray and RNA-Sequencing sample. In summary, this study developed robust models for clinical application and suggested ensemble learning for higher diagnostic precision in psychiatric disorders.Research highlightsEnsemble learning of Support Vector Machines (SVM) and Prediction Analysis for Microarrays (PAM) algorithms classified schizophrenia samples with higher precision.The pipeline developed in this analysis produced robust models with the ability to classify single microarray sample.Cross-platform validation of ensemble model using RNA-Sequencing data resulted in high precision.Graphical abstractBlood based SCZ diagnosis using ensemble learning for higher precision
Efficacy and safety of bempedoic acid in women with hypercholesterolemia: Pooled analyses from phase 3 trials
Authors: Goldberg Anne C. , Banach Maciej , Catapano Alberico L. , Duell P. Barton , Leiter Lawrence A. , Hanselman Jeffrey C. , Lei Lei , Mancini G.B. John 
Published: February 2023

AbstractBackground and aimsSex-specific differences in the response to lipid-lowering therapies have been reported. Here, we assessed the effect of bempedoic acid in women and men using pooled, patient-level data from four phase 3 clinical trials of bempedoic acid.MethodsPatients were grouped into two pools: atherosclerotic cardiovascular disease (ASCVD) and/or heterozygous familial hypercholesterolemia (HeFH) “on statins”, and “low-dose or no statin”. Percent changes from baseline to at least week 12 in low-density lipoprotein-cholesterol (LDL-C), non–high-density lipoprotein-cholesterol (non–HDL-C), total cholesterol (TC), apolipoprotein B (Apo B), and high-sensitivity C-reactive protein (hsCRP), as well as safety, were analyzed by statin pool and sex.ResultsOverall, 3623 patients were included (bempedoic acid, 2425; placebo, 1198). Significant reductions in lipid parameters and hsCRP were observed with bempedoic acidvs. placebo in both sexes in the ASCVD and/or HeFH on statins (n = 3009) and the low-dose or no statin (n = 614) pools (p≤0.002). Compared with men, women had significantly greater placebo-corrected reductions in LDL-C (−21.2%vs. −17.4%;p=0.044), non–HDL-C (−17.3%vs. −12.1%;p=0.003), TC (−13.8%vs. −10.5%;p=0.012), and Apo B (−16.0%vs. −11.3%;p=0.004) in the ASCVD and/or HeFH on statins pool. Women had numerically greater reductions than men in lipid parameters in the low-dose or no statin pool and hsCRP in both pools. The safety of bempedoic acid was comparable between sexes.ConclusionsIn this pooled analysis, women experienced significant improvements in levels of LDL-C and other lipid parameters with bempedoic acid.
Clinically relevant gene signatures provide independent prognostic information in older breast cancer patients
Authors: Castresana-Aguirre Miguel , Johansson Annelie , Matikas Alexios , Foukakis Theodoros , Lindström Linda S. , Tobin Nicholas P. 
Published: February 2023

ABSTRACTPurposeGene signatures have been shown to add prognostic information beyond that of routine clinico-pathological factors, however their utility in older breast cancer patients remains unclear. As such, the aim of this study was to determine if gene signatures can provide prognostic information that may aid treatment decisions for older breast cancer patients.Experimental designResearch versions of the genomic grade index (GGI), 70-gene recurrence score (RS), cell cycle score (CCS), PAM50 Risk of Recurrence score - Proliferation (ROR-P), and PAM50 signatures were applied to 39 breast cancer datasets totalling 9583 patients. After filtering based on age ≥ 70 years, the presence of Estrogen Receptor (ER) and survival information availability 871 patients remained. The prognostic capacity of signatures was tested in all (n=871), ER-positive/lymph node-positive (ER+/LN+, n=335) and ER-positive/lymph node-negative (ER+/LN-, n=374) patients using Kaplan-Meier and multivariable Cox proportional hazard modeling.ResultsAll gene signatures were statistically significant in Kaplan-Meier analysis of all and ER+/LN+ patients (Log-rankP< 0.001). This significance remained in multivariable analysis (Cox proportional hazards,P≤ 0.05). In ER+/LN-patients the GGI, 70-gene, CCS, ROR-P, and PAM50 signatures were significant in Kaplan-Meier analysis (Log-rankP≤ 0.05) but only the 70-gene, CCS, ROR-P, and PAM50 signatures remained so in multivariable analysis (Cox proportional hazards,P≤ 0.05).ConclusionsIn general, we found that gene signatures provide prognostic information in survival analyses of all, ER+/LN+ and ER+/LN-older (≥70 years) breast cancer patients, suggesting a potential role in aiding treatment decision in older patients.Translational RelevanceThe utility of gene expression signatures in breast cancer patients has been most clearly demonstrated in the TAILORx, RxPONDER and MINDACT randomised clinical trials. However, few older patients (≥70 years) were included in these trials meaning that signature utility in this patient group remains unclear. As such, we performed the first comprehensive study comparing the prognostic performance of multiple clinically relevant gene expression signatures in a single older breast cancer patient cohort. We show that in general gene signatures provide independent prognostic information in All, ER+/LN+ and ER+/LN-patients who are over the age of 70 years. These results support a potential role for signatures in aiding treatment decisions in older breast cancer patients and indicate that further investigation is warranted in prospective clinical study to elucidate their treatment predictive value.
Prebiotic activity of lactulose optimizes gut metabolites and prevents systemic infection in liver disease patients
Authors: Odenwald Matthew A. , Lin Huaiying , Lehmann Christopher , Dylla Nicholas P. , Ramanswamy Ramanujam , Moran Angelica , Hutchison Alan L. , Stutz Matthew R. , Cruz Mark Dela , Adler Emerald , Boissiere Jaye , Khalid Maryam , Cantoral Jackelyn , Haro Fidel , Oliveira Rita A. , Waligurski Emily , Cotter Thomas G. , Light Samuel H. , Beavis Kathleen G. , Sundararajan Anitha , Sidebottom Ashley M. , Reddy K. Gautham , Paul Sonali , Pilliai Anjana , Te Helen S. , Rinella Mary E. , Charlton Michael R. , Pamer Eric G. , Aronsohn Andrew I. 
Published: February 2023

ABSTRACTProgression of chronic liver diseases is precipitated by hepatocyte loss, inflammation and fibrosis. This process results in the loss of critical hepatic functions, increasing morbidity and the risk of infection. Medical interventions that treat complications of hepatic failure, including antibiotic administration for systemic infections, impact gut microbiome composition and metabolite production. Using a multi-omics approach on 850 fecal samples from 263 patients with acute or chronic liver disease, we demonstrate that patients hospitalized for liver disease have reduced microbiome diversity and a paucity of bioactive metabolites. We find that patients treated with the orally administered but non-absorbable disaccharide lactulose have increased densities of intestinalBifidobacteriaand reduced incidence of systemic infections and mortality.Bifidobacteriametabolize lactulose, produce high concentrations of acetate and acidify the gut lumen, which, in combination, can reduce the growth of antibiotic-resistant pathobionts such as Vancomycin-resistantEnterococcus faecium. Our studies suggest that lactulose andBifidobacteriaserve as a synbiotic to reduce rates of infection in patients with severe liver disease.
Generative Molecular Design and Experimental Validation of Selective Histamine H1 Inhibitors
Authors: McLoughlin Kevin S. , Shi Da , Mast Jeffrey E. , Bucci John , Williams John P. , Jones W. Derek , Miyao Derrick , Nam Luke , Osswald Heather L. , Zegelman Lev , Allen Jonathan , Bennion Brian J. , Paulson Amanda K. , Abagyan Ruben , Head Martha S. , Brase James M. 
Published: February 2023

ABSTRACTGenerative molecular design (GMD) is an increasingly popular strategy for drug discovery, using machine learning models to propose, evaluate and optimize chemical structures against a set of target design criteria. We present the ATOM-GMD platform, a scalable multiprocessing framework to optimize many parameters simultaneously over large populations of proposed molecules. ATOM-GMD uses a junction tree variational autoencoder mapping structures to latent vectors, along with a genetic algorithm operating on latent vector elements, to search a diverse molecular space for compounds that meet the design criteria. We used the ATOM-GMD framework in a lead optimization case study to develop potent and selective histamine H1 receptor antagonists. We synthesized 103 of the top scoring compounds and measured their properties experimentally. Six of the tested compounds bind H1 withKi’s between 10 and 100 nM and are at least 100-fold selective relative to muscarinic M2 receptors, validating the effectiveness of our GMD approach.
Enhanced protein secretion in reduced genome strains ofStreptomyces lividans
Authors: Hamed M. B. , Busche T. , Simoens K. , Carpentier S. , Kormanec J. , Van Mellaert L. , Anné J. , Kalinowski J. , Bernaerts K. , Karamanou S. , Economou A. 
Published: February 2023

AbstractS. lividansTK24 is a popular host for the production of small molecules and for the secretion of heterologous proteins. TK24 has a large genome with at least 29 secondary metabolite gene clusters that are non-essential for viability and undergo complex regulation. To optimize heterologous protein secretion, we previously constructed ten chassis strains that are devoid of several secondary metabolite gene clusters. Genome reduction was aimed at reducing carbon flow to secondary metabolites and pigmentation in the spent growth medium and improving colony morphology. Strains RG1.0-RG1.10 contain various deletion combinations of the blue actinorhodin cluster (act), the calcium-dependent antibiotic (cda), the undecylprodigiosin (red) and coelimycin A (cpk) clusters, the melanin cluster (mel), thematAB genes that affect mycelial aggregation and the non-essential sigma factorhrdD that controls the transcription of Act and Red regulatory proteins. Two derivative strains, RG1.5 and 1.9, showed a ∼15% reduction in growth rate, >2-fold increase in the total mass yield of their native secretome and altered abundance of several specific proteins compared with TK24. Metabolomics and RNAseq analysis revealed that genome reduction led to rapid cessation of growth due to aminoacid depletion and caused both redox and cell envelope stresses, upregulation of the Sec-pathway componentssecDFand chaperones and a cell envelope two component regulator. RG1.9 maintained elevated heterologous secretion of mRFP and mTNFα by 12-70%. An integrated model is presented linking genome reduction and enhanced secretion.
Quality in Clinical Research: An Observational Study of Randomisation Techniques in Urological and General Surgical Studies
Authors: Raison Nicholas , Giona Simone , Brunckhorst Oliver , Cohen Alexander , Muir Gordon 
Published: February 2023

ABSTRACTObjectivesTo quantitatively test the quality of randomised controlled trials reported to international scientific meetings through a critical analysis of randomisation outcomes.Design and Main Outcome MeasuresAll randomised controlled trials presented at international surgical and urological congresses using simple randomisation were identified. Primary analysis of randomisation technique was performed by comparing the observed and expected numbers of trials with equal numbers of participants in each arm. Sensitivity analyses compared study design, type of study and presence of external sponsorship. All abstracts were assessed according to the CONSORT for reporting randomised trials in journal and conference abstracts checklist.Results345 studies met the inclusion criteria. 148 studies reported simple randomisation to allocate 26,510 patients. Randomisation technique could not be identified in 104 studies. Primary and all secondary analyses demonstrated a probability of p<0.0001 that simple randomisation was used for participant allocation in all studies. Mean consort score was 9.4ConclusionsIt is extremely unlikely that simple randomisation was performed as reported in a significant proportion of the 148 RCTs in this study. These results raise concerning questions of the veracity and reliability of current medical research. There needs to be a greater awareness of the potential for methodological inaccuracy and error.
CCR5 deficiency: decreased neuronal resilience to oxidative stress and increased risk of vascular dementia
Authors: Tournier Benjamin B. , Sorce Silvia , Marteyn Antoine , Ghidoni Roberta , Benussi Luisa , Binetti Giuliano , Herrmann François R , Krause Karl-Heinz , Zekry Dina 
Published: February 2023

AbstractIntroductionAs the chemokine receptor5 (CCR5) may play a role in ischemia, we studied the links between CCR5 deficiency, the sensitivity of neurons to oxidative stress, and the development of dementia.MethodsLogistic regression models with CCR5 and ApoE polymorphisms were applied to 205 cognitively normal and 189 dementia patients included in Geneva. The impact of oxidative stress onCcr5expression and cell death was assessed in mice neurons.ResultsCCR5-Δ32 allele synergized with ApoEε4 as risk factor for dementia and specifically for dementia with a vascular component. We confirmed these results in an independent cohort from Italy (157 cognitively normal and 620 dementia). Carriers of the ApoEε4/CCR5-Δ32 genotype aged ≥80 years have an eleven-fold greater risk of vascular and mixed dementia. Oxidative stress induced cell death inCcr5-/-mice neurons.DiscussionWe propose the vulnerability of CCR5-deficient neurons in response to oxidative stress as possible mechanisms contributing to dementia.