bluuebunny/crossref_metadata_2025_split huggingface dataset:
Postintravitreal Injection Endophthalmitis: An Infection Control Investigation and Case–Control Analysis of Risk Factors
Authors: Halsey James , Tischendorf Jessica , Anderson Laura , Pop-Vicas Aurora , Osman Fauzia , Safdar Nasia 
Published: November 2020

Background: Intravitreal injection of vascular endothelial growth factor inhibitors with or without steroids is a well-established, effective therapy for several ocular disorders. The expected rate of complications from these injections is low, with meta-analyses reporting 5–6 occurrences of infectious endophthalmitis per 10,000 injections. Through October 2019, our health system observed 8 cases of endophthalmitis among 7,693 injections (10.4 per 10,000 injections), compared to 1 case in 2018. This unusually high rate prompted an infection control investigation and a case control study to examine risk factors for the development of postintravitreal injection endophthalmitis. Methods: Infection control providers performed direct observation of several ophthalmologists performing intravitreal injections on 3 separate occasions to determine points of intervention to prevent infection. To define risk factors for postintravitreal injection endophthalmitis, we conducted a retrospective case-control study of the 8 affected patients. Four control patients were selected per case, matched by clinic location, drug injected, and date of injection (total subjects, N = 40). We extracted patient-level risk factors from medical records; documentation was not sufficient to compare procedure-level factors. We conducted unadjusted univariate Poisson regression and Mantel–Cox method rate ratios to identify significant risk predictors of endophthalmitis. Results: Direct observation yielded variable practice in use of masks, gloves, sterile lid speculum, and the duration of povidone-iodine contact on the ocular surface prior to injection. The location of alcohol hand gel relative to the procedure field was suboptimal. Due to patient volume, there were significant delays between procedure and patient prep and injection time. The mean age was 76 years among cases and 74.1 years among controls; 35% of patients were men. Age-related macular degeneration was the most common indication for injection (55%). Only 10% of injections were bilateral. Although not statistically significant, patients with coronary artery disease had a higher rate of infection than those without coronary artery disease (165.3 vs 16.3 per 10,000 person years; IRR = 3.0; 95% CI, 0.60–14.8; P = .18); current smokers were also at higher risk (86.9 per 10,000; IRR, 3.2; 95% CI, 0.33–30.4; P = .32). Conclusions: Coronary artery disease and smoking were risk factors for the development of postintravitreal injection endophthalmitis in a 2019 cluster of cases in our organization. We are continuing to work with our ophthalmologists to optimize infection prevention in the injection environment, including strict use of gloves, appropriate use of povidone-iodine, and routinely wearing a mask and encouraging a no-talking policy during injections.Funding: NoneDisclosures: None
Prevalence, Distribution, and Antibiotic Susceptibilities of Nosocomial Infections at a Tertiary Hospital in Port Harcourt, Nigeria
Authors: Stanley Catherine Nonyelum , Ekada Inimuvie 
Published: November 2020

Background: Previously, many infections could be treated effectively based on the clinician’s past clinical experience. The development of resistance to essentially all of the antimicrobial agents currently in use in clinical practice has made this scenario more of the exception than the norm. Selecting an appropriate antimicrobial agent has become increasingly more challenging; the clinician has to navigate through the variety of available agents in the face of increasing antimicrobial resistance. The diagnostic laboratory now plays very important role in clinical practice. To ensure safe and effective empirical treatment, a surveillance study of the susceptibility pattern of common pathogens and appropriate use of antibiotics is imperative. Objective: We report on the prevalence, distribution, and antibiotic susceptibility patterns of nosocomial pathogens isolated at the University of Port Harcourt Teaching Hospital (UPTH) and the effectiveness of the antibiotics commonly prescribed at the hospital in treating these infections. Methods: A retrospective cross-sectional study of specimens received at the microbiology laboratory was conducted over a 6-month period, from October 2015 to March 2016, using urine, blood, and semen specimens. In total, 5,160 samples received and analyzed at the laboratory within the study period were assessed. Results: Of the 5,160 specimens analyzed, 881(17.07%) were positive for bacteria: 691(78.43%) from urine, 86 (9.76%) from blood, and 104 (11. 81%) from semen. Escherichia coli (35.74%), Klebsiella pneumoniae (52.33%), and Staphylococcus aureus (65.4%) were the most frequently isolated pathogens from urine, blood, and semen, respectively. Widespread multidrug resistance was observed among the organisms. Klebsiella pneumoniae, S. aureus, and E. coli isolated from urine were resistant to amoxicillin/clavulanate, cefuroxime, ceftazidime, ciprofloxacin, ampicillin, gentamycin, and ceftriaxone. A review of the pattern of prescribing antibiotics revealed that in the emergency unit, ceftriaxone (34.09%) and metronidazole (30.09%) were most frequently prescribed, whereas in the general outpatient department, metronidazole (19.09%), amoxicillin (16.61%), amoxicillin/clavulanate (9.39%), and ofloxacin (9.39%) were often prescribed. S. aureus was susceptible to only ceftriaxone, whereas K. pneumoniae and E. coli were susceptible only to ofloxacin. Conclusions: Most of the isolated pathogens were not susceptible to the frequently prescribed antibiotics. Empirical prescribing of antibiotics without current epidemiological data of pathogens in the hospital can only further exacerbate the problem of antimicrobial resistance. The need for periodic epidemiological surveillance and rational use of antibiotics anchored on a good antibiotic stewardship program is therefore strongly recommended.Funding: NoneDisclosures: None
Reduced Length of Stay Using Clinical Decision Support Tool (ASAP) for Empiric Antibiotic Selection
Authors: Acree Mary , Singh Kamaljit , Ravichandran Urmila , Grant Jennifer , Fleming Gary , Hadsell Bryce , Shah Nirav 
Published: November 2020

Background: Empiric antibiotic selection is challenging and requires knowledge of the local antibiogram, national guidelines and patient-specific factors, such as drug allergy and recent antibiotic exposure. Clinical decision support for empiric antibiotic selection has the potential to improve adherence to guidelines and improve patient outcomes. Methods: At NorthShore University HealthSystem, a 4-hospital, 789 bed system, an automated point-of-care decision support tool referred to as Antimicrobial Stewardship Assistance Program (ASAP) was created for empiric antibiotic selection for 4 infectious syndromes: pneumonia, skin and soft-tissue infections, urinary tract infection, and intra-abdominal infection. The tool input data from the electronic health record, which can be modified by any user. Using an algorithm created with electronic health record data, antibiogram data, and national guidelines, the tool produces an antibiotic recommendation that can be ordered via a link to order entry. If the tool identifies a patient with a high likelihood for a multidrug-resistant infection, a consultation by an infectious diseases specialist is recommended. Utilization of the tool and associated outcomes were evaluated from July 2018 to May 2019. Results: The ASAP tool was executed by 140 unique, noninfectious diseases providers 790 times. The tool was utilized most often for pneumonia (194 tool uses), followed by urinary tract infection (166 tool uses). The most common provider type to use the tool was an internal medicine hospitalist. The tool increased adherence to the recommended antibiotic regimen for each condition. Antibiotic appropriateness was assessed by an infectious diseases physician. Antibiotics were considered appropriate when they were similar to the antibiotic regimen recommended by the ASAP. Inappropriate antibiotics were classified as broad or narrow. When antibiotic coverage was appropriate, hospital length of stay was statistically significantly shorter (4.8 days vs 6.8 days for broad antibiotics vs 7.4 days for narrow antibiotics; P < .01). No significant differences were identified in mortality or readmission. Conclusions: A clinical decision support tool in the electronic health record can improve adherence to recommended empiric antibiotic therapy. Use of appropriate antibiotics recommended by such a tool can reduce hospital length of stay.Funding: NoneDisclosures: None
Malaria Exposure in Ann Township, Myanmar, as a Function of Land Cover and Land Use: Combining Satellite Earth Observations and Field Surveys
Authors: Hoffman‐Hall Amanda , Puett Robin , Silva Julie A. , Chen Dong , Baer Allison , Han Kay Thwe , Han Zay Yar , Thi Aung , Htay Thura , Thein Zaw Win , Aung Poe Poe , Plowe Christopher V. , Nyunt Myaing Myaing , Loboda Tatiana V. 
Published: November 2020

AbstractDespite progress toward malaria elimination in the Greater Mekong Subregion, challenges remain owing to the emergence of drug resistance and the persistence of focal transmission reservoirs. Malaria transmission foci in Myanmar are heterogeneous and complex, and many remaining infections are clinically silent, rendering them invisible to routine monitoring. The goal of this research is to define criteria for easy‐to‐implement methodologies, not reliant on routine monitoring, that can increase the efficiency of targeted malaria elimination strategies. Studies have shown relationships between malaria risk and land cover and land use (LCLU), which can be mapped using remote sensing methodologies. Here we aim to explain malaria risk as a function of LCLU for five rural villages in Myanmar's Rakhine State. Malaria prevalence and incidence data were analyzed through logistic regression with a land use survey of ~1,000 participants and a 30‐m land cover map. Malaria prevalence per village ranged from 5% to 20% with the overwhelming majority of cases being subclinical. Villages with high forest cover were associated with increased risk of malaria, even for villagers who did not report visits to forests. Villagers living near croplands experienced decreased malaria risk unless they were directly engaged in farm work. Finally, land cover change (specifically, natural forest loss) appeared to be a substantial contributor to malaria risk in the region, although this was not confirmed through sensitivity analyses. Overall, this study demonstrates that remotely sensed data contextualized with field survey data can be used to inform critical targeting strategies in support of malaria elimination.
Hybrid gold/DNA nanowire circuit with sub-10 nm nanostructure arrays
Authors: Choi Jong Seob , Park Hye Bin , Tsui Jonathan H. , Hong Byungyou , Kim Deok-Ho , Kim Hyung Jin 
Published: November 2020

AbstractWe report on a simple and efficient method for the selective positioning of Au/DNA hybrid nanocircuits using a sequential combination of electron-beam lithography (EBL), plasma ashing, and a molecular patterning process. The nanostructures produced by the EBL and ashing process could be uniformly formed over a 12.6 in2 substrate with sub-10 nm patterning with good pattern fidelity. In addition, DNA molecules were immobilized on the selectively nanopatterned regions by alternating surface coating procedures of 3-(aminopropyl)triethoxysilane (APS) and diamond like carbon (DLC), followed by deposition of DNA molecules into a well-defined single DNA nanowire. These single DNA nanowires were used not only for fabricating Au/DNA hybrid nanowires by the conjugation of Au nanoparticles with DNA, but also for the formation of Au/DNA hybrid nanocircuits. These nanocircuits prepared from Au/DNA hybrid nanowires demonstrate conductivities of up to 4.3 × 105 S/m in stable electrical performance. This selective and precise positioning method capable of controlling the size of nanostructures may find application in making sub-10 nm DNA wires and metal/DNA hybrid nanocircuits.
Microneedle-based skin patch for blood-free rapid diagnostic testing
Authors: Jiang Xue , Lillehoj Peter B. 
Published: November 2020

AbstractRapid diagnostic tests are one of the most commonly used tests to detect and screen for infectious diseases in the developing world. While these tests are simple, inexpensive, and readily available, they rely on finger-prick blood sampling, which requires trained medical personnel, poses risks of infection, and can complicate cooperation in young children, asymptomatic individuals, and communities with blood taboos. Here, we report a novel microneedle-based skin patch for the rapid detection of protein biomarkers in dermal interstitial fluid. Sample collection is facilitated by a hydrophilic hollow microneedle array that autonomously extracts and transports interstitial fluid to an antibody-based lateral flow test strip via surface tension for colorimetric antigen detection. We employ a simple gold enhancement treatment to enhance the detection sensitivity of this colloidal gold-based lateral flow assay and elucidate the underlying mechanism of this enhancement mechanism through experimental investigation. For proof-of-concept, this device was used to detect Plasmodium falciparum histidine-rich protein 2, a biomarker for malaria infection, which could be detected at concentrations as low as 8 ng/mL. Each test can be completed in <20 min and requires no equipment. To the best of our knowledge, this work is the first demonstration of a microneedle-based lateral flow assay for rapid protein detection in dermal interstitial fluid. In addition to its simplicity, minimally invasive nature, and low cost, this diagnostic device can be readily adapted to detect other protein biomarkers in interstitial fluid, making it a promising tool for point-of-care testing.
Cognitive deficits and white matter abnormalities in never-treated first-episode schizophrenia
Authors: Yang Mi , Gao Shan , Zhang Xiangyang 
Published: November 2020

AbstractCognitive impairment is viewed as a core symptom of schizophrenia (SCZ), but its pathophysiological mechanism remains unclear. White matter (WM) disruption is considered to be a central abnormality that may contribute to cognitive impairment in SCZ patients. However, few studies have addressed the association between cognition and WM integrity in never-treated first-episode (NTFE) patients with SCZ. In this study, we used the MATRICS Consensus Cognitive Battery (MCCB) to evaluate cognitive function in NTFE patients (n = 39) and healthy controls (n = 30), and associated it with whole-brain fractional anisotropy (FA) values obtained via voxel-based diffusion tensor imaging. We found that FA was lower in five brain areas of SCZ patients, including the cingulate gyrus, internal capsule, corpus callosum, cerebellum, and brainstem. Compared with the healthy control group, the MCCB’s total score and 8 out of 10 subscores were significantly lower in NTFE patients (allp < 0.001). Moreover, in patients but not healthy controls, the performance in the Trail Making Test was negatively correlated with the FA value in the left cingulate. Our findings provide evidence that WM disconnection is involved in some cognitive impairment in the early course of SCZ.
The role of emotion regulation as a mediator between early life stress and posttraumatic stress disorder, depression and anxiety in Syrian refugees
Authors: Demir Zaynab , Böge Kerem , Fan Yan , Hartling Corinna , Harb Mazen R. , Hahn Eric , Seybold Joachim , Bajbouj Malek 
Published: November 2020

AbstractEarly life stress is an important factor in later psychopathology, including symptoms of posttraumatic stress disorder (PTSD), depression, and anxiety. The purpose of the present study was to investigate the effect of early life stress on psychiatric symptoms within a sample of Syrian refugees. In this model, the use of cognitive emotion regulation strategies was assessed as a potential mediator of the relationship between early life stress and current symptoms of PTSD, depression, and anxiety. Bootstrap analyses were generated to test the indirect effect of emotion regulation (Cognitive Emotion Regulation Questionnaire) on the relationship between early life stress (Childhood Trauma Questionnaire), PTSD (Harvard Trauma Questionnaire), depressive (PHQ-9) and anxiety (GAD-7) symptoms in eighty-nine Syrian refugees resided in Germany (n = 49) and Jordan (n = 40). The indirect effect of maladaptive strategies was significant between early life stress and psychopathology, whereas the mediation effect of adaptive strategies was not significant. The findings provide an evidence that emotional dysregulation is an underlying factor affecting psychological symptoms in refugees with adverse childhood experiences. These results suggest targeting cognitive emotion regulation in prospective prevention and treatment strategies.
Emotional face processing across neurodevelopmental disorders: a dynamic faces study in children with autism spectrum disorder, attention deficit hyperactivity disorder and obsessive-compulsive disorder
Authors: Vandewouw Marlee M. , Choi EunJung , Hammill Christopher , Arnold Paul , Schachar Russell , Lerch Jason P. , Anagnostou Evdokia , Taylor Margot J. 
Published: November 2020

AbstractAutism spectrum disorder (ASD) is classically associated with poor face processing skills, yet evidence suggests that those with obsessive-compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD) also have difficulties understanding emotions. We determined the neural underpinnings of dynamic emotional face processing across these three clinical paediatric groups, including developmental trajectories, compared with typically developing (TD) controls. We studied 279 children, 5–19 years of age but 57 were excluded due to excessive motion in fMRI, leaving 222: 87 ASD, 44 ADHD, 42 OCD and 49 TD. Groups were sex- and age-matched. Dynamic faces (happy, angry) and dynamic flowers were presented in 18 pseudo-randomized blocks while fMRI data were collected with a 3T MRI. Group-by-age interactions and group difference contrasts were analysed for the faces vs. flowers and between happy and angry faces. TD children demonstrated different activity patterns across the four contrasts; these patterns were more limited and distinct for the NDDs. Processing happy and angry faces compared to flowers yielded similar activation in occipital regions in the NDDs compared to TDs. Processing happy compared to angry faces showed an age by group interaction in the superior frontal gyrus, increasing with age for ASD and OCD, decreasing for TDs. Children with ASD, ADHD and OCD differentiated less between dynamic faces and dynamic flowers, with most of the effects seen in the occipital and temporal regions, suggesting that emotional difficulties shared in NDDs may be partly attributed to shared atypical visual information processing.
Nimodipine improves cortical efficiency during working memory in healthy subjects
Authors: Zink Caroline F. , Giegerich Mellissa , Prettyman Greer E. , Carta Kayla E. , van Ginkel Marcus , O’Rourke Molly P. , Singh Eesha , Fuchs Edward J. , Hendrix Craig W. , Zimmerman Eric , Breakey Jennifer , Marzinke Mark A. , Hummert Pamela , Pillai Jay J. , Weinberger Daniel R. , Bigos Kristin L. 
Published: November 2020

AbstractThe L-type calcium channel gene, CACNA1C, is a validated risk gene for schizophrenia and the target of calcium channel blockers. Carriers of the risk-associated genotype (rs1006737 A allele) have increased frontal cortical activity during working memory and higher CACNA1C mRNA expression in the prefrontal cortex. The aim of this study was to determine how the brain-penetrant calcium channel blocker, nimodipine, changes brain activity during working memory and other cognitive and emotional processes. We conducted a double-blind randomized cross-over pharmacoMRI study of a single 60 mg dose of oral nimodipine solution and matching placebo in healthy men, prospectively genotyped for rs1006737. With performance unchanged, nimodipine significantly decreased frontal cortical activity by 39.1% and parietal cortical activity by 42.8% during the N-back task (2-back > 0-back contrast; PFWE < 0.05; n = 28). Higher peripheral nimodipine concentrations were correlated with a greater decrease in activation in the frontal cortex. Carriers of the risk-associated allele, A (n = 14), had a greater decrease in frontal cortical activation during working memory compared to non-risk allele carriers. No differences in brain activation were found between nimodipine and placebo for other tasks. Future studies should be conducted to test if the decreased cortical brain activity after nimodipine is associated with improved working memory performance in patients with schizophrenia, particularly those who carry the risk-associated genotype. Furthermore, changes in cortical activity during working memory may be a useful biomarker in future trials of L-type calcium channel blockers.
Copanlisib promotes growth inhibition and apoptosis by modulating the AKT/FoxO3a/PUMA axis in colorectal cancer
Authors: Yan Ji , Yang Shida , Tian Hong , Zhang Yang , Zhao Hongmei 
Published: November 2020

AbstractColorectal cancer (CRC) is the type of cancer with the third highest incidence and is associated with high mortality and low 5-year survival rates. We observed that copanlisib, an inhibitor of PI3K (pan-class I phosphoinositide 3-kinase) that preferentially inhibits PI3Kδ and PI3Kα, impedes the growth of CRC cells by inducing apoptosis via PUMA. There was a marked increase in the expression of PUMA independent of p53 after treatment with copanlisib. The response of CRC cells to copanlisib could be predicted by PUMA expression. Copanlisib was found to induce PUMA expression through FoxO3a by directly binding to the PUMA promoter after inhibiting AKT signaling. PUMA deficiency mitigated the apoptosis induced by copanlisib. Caspase activation and mitochondrial dysfunction led to copanlisib resistance, as observed through a clonogenic assay, whereas enhanced expression of PUMA increased the copanlisib-induced susceptibility to apoptosis. Moreover, the antitumor effects of copanlisib were suppressed by a deficiency of PUMA in a xenograft model, and caspase activation and reduced apoptosis were also observed in vivo. Copanlisib-mediated chemosensitization seemed to involve the concurrent induction of PUMA expression via mechanisms that were both dependent and independent of p53. These observations indicate that apoptosis mediated by PUMA is crucial for the anticancer effects of copanlisib and that manipulation of PUMA may aid in enhancing anticancer activities.