bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immediately sequential bilateral cataract surgery: an academic teaching center's experience
Authors: Qi Susan Ruyu , Arsenault Roxanne , Hébert Mélanie , You Eunice , Légaré Marie Eve , Arshinoff Steve A. , Mercier Mathieu 
Published: July 2021

Purpose:
To evaluate the safety and outcomes of immediately sequential bilateral cataract surgery (ISBCS) at a Canadian academic teaching center.

Setting:
Tertiary university teaching hospital of Laval University, Quebec City, Canada.

Design:
Retrospective cohort study.

Methods:
2003 consecutive patients (4006 eyes) who underwent ISBCS under topical anesthesia from January 2019 to December 2019 were included. All charts were retrospectively reviewed. Outcome measures included intraoperative and postoperative complications, postoperative uncorrected distance (UCVA) and pinhole (PHVA) visual acuities, and autorefraction measurements.

Results:
4006 eyes from 1218 (60.8%) female and 785 (39.2%) male patients with a mean age of 74 ± 8 years had a mean preoperative visual acuity of 0.503 logMAR (Snellen 20/63). The mean axial length was 23.53 ± 1.37 mm. Most eyes had monofocal intraocular lenses (IOLs) implanted (n = 3738, 93.3%) followed by toric (n = 226, 5.6%), multifocal (n = 25, 0.6%), and multifocal toric (n = 17, 0.4%) IOLs. Intraoperative complications included 14 (0.3%) posterior capsule ruptures with 5 (0.1%) requiring sulcus IOL placement, and 7 (0.2%) partial zonulysis, with 3 requiring capsular tension rings (0.07%). There were no cases of endophthalmitis or toxic anterior segment syndrome. Mean 5-week postoperative UCVA was 0.223 (Snellen 20/33), PHVA was 0.153 (Snellen 20/28) with a mean spherical equivalent of −0.21 diopters.

Conclusions:
ISBCS performed following International Society of Bilateral Cataract Surgeons recommended guidelines is a safe procedure. This cohort of 4006 eyes had very few complications, with none attributable to the surgery being done bilaterally. The UCVA, PHVA, and refractive outcomes were good.
Is There a Role for Intraoperative Navigation During Cochlear Implantation in Patients With Aural Atresia?
Authors: Wong Kevin , Kaul Vivian F. , Fan Caleb J. , Schwam Zachary G. , Cosetti Maura K. 
Published: July 2021

Objective:
Concurrent bilateral congenital aural atresia (CAA) and profound sensorineural hearing loss are rare. While not a contraindication, temporal bone and cochleovestibular abnormalities are an important consideration for cochlear implantation (CI) candidacy. Intraoperative image-guided surgical navigation may play a role during CI surgery in patients with complex anatomy, such as CAA.

Patient:
One patient with bilateral CAA, cochlear dysplasia, speech delay, and profound sensorineural hearing loss underwent candidacy evaluation for cochlear implantation.

Interventions:
Cochlear implantation using intraoperative image-guided navigation.

Main Outcome Measures:
(1) Registration accuracy, (2) surgical outcomes, (3) audiometry.

Results:
A four-year-old girl with complete bilateral CAA and profound sensorineural hearing loss successfully underwent a right transmastoid approach for CI using intraoperative image-guided navigation with sticker fiducials. Bony landmarks included the mastoid tip, tympanomastoid suture line, helical root, zygomatic root, and lateral brow. A registration accuracy of 0.9 mm was achieved. There were no intraoperative or immediate postoperative complications. Postoperatively, Neural Response Imaging was confirmed on 9 electrodes and behavioral testing demonstrated Ling-6 access at 30 dB. On most recent follow-up, she has demonstrated gains in language development, vocalizations, and uses total communication in a hearing-impaired educational environment.

Conclusions:
Children with CAA and profound sensorineural hearing loss may be candidates for cochlear implantation, with successful outcomes in the setting of complex anatomy. Surgical navigation may play a role corroborating intraoperative landmarks.
Remission of Mucosal Melanoma of the Middle Ear and Petrous Temporal Bone and Reversal of Cranial Nerve Paresis Following Radiation and Single Agent Nivolumab: Clinical Capsule and Review of the Literature
Authors: Carlson Kevin J. , Volsky Peter G. 
Published: July 2021

Objective:
We report disease remission and recovery of fifth and seventh nerve paresis in a case of primary mucosal melanoma of the middle ear and petrous temporal bone.

Patient:
A 74-year-old man developed sudden, profound, right sided sensorineural hearing loss, disequilibrium, otalgia, and cranial nerve V and VII dysfunction. Imaging demonstrated an unresectable, osteolytic lesion involving the middle ear and anterior petrous apex. Melanoma was diagnosed via in-office biopsy; whole-body metabolic imaging revealed no other primary site.

Intervention:
Multidisciplinary management included radiation therapy (30 Gy, 10 fractions) followed by induction (five cycles, q2w) and maintenance nivolumab (six cycles, q3w).

Main Outcome Measure:
Complete metabolic response of primary site and metastases on imaging, recovery of cranial neuropathies.

Results:
Following palliative radiation therapy and induction nivolumab, cranial neuropathies resolved. With maintenance-dose nivolumab, primary site and metastases exhibited a complete response. Therapy was stopped at 16 months post-diagnosis. Complete remission was maintained until 22 months after diagnosis. The patient developed a solitary cerebral metastasis which was refractory to radiosurgery and biopsy confirmed melanoma. He expired 2 years, 8 months post-diagnosis.

Conclusions:
Mucosal melanoma of the middle ear and petrous temporal bone is exceedingly rare. Management is individualized and surgery is undertaken when possible. Key observations in this case are the complete metabolic response and reversal of cranial nerve neuropathies following radiation and anti-programed cell death receptor ligand 1 therapy. Non-surgical treatment is worthy of study as initial management for similar lesions.
Heritability analysis of liver stiffness detected by ultrasound shear wave elastography: a twin study
Authors: Fekete Marton , Piroska Marton , Szily Marcell , Erdei Mercedesz , Jokkel Zsofia , Szabo Helga , Littvay Levente , Baffy Gyorgy , Tarnoki Adam Domonkos , Tarnoki David Laszlo 
Published: July 2021

Objectives of the study
Nonalcoholic fatty liver disease (NAFLD) is a common condition with a subset of individuals developing liver fibrosis as a major risk factor for advanced liver disease. The contribution of genetic factors to this progression remains incompletely understood. Our aim was to analyze heritability in the development of liver fibrosis estimated by ultrasound shear wave elastography (SWE) in an asymptomatic adult twin cohort.

Methods
In total 172 adult Hungarian twins (51 monozygotic and 36 dizygotic pairs; 63% women; mean age 54.9 ± 15.1 years) underwent B-mode ultrasonography to assess steatosis and SWE to determine Young’s modulus as a noninvasive marker or liver fibrosis.

Results
We identified 99 subjects with steatosis, which was mild in 46 subjects (46%), moderate in 52 subjects (52%) and severe in a single subject (1%). Mean Young’s modulus was 7.58 ± 3.53 kPa in this slightly overweight study cohort (BMI: 25.7 ± 4.6 kg/m2). Univariate analysis adjusted for age, sex and BMI indicated no discernible role for genetic components in the presence of liver stiffness, whereas shared and unshared environmental effects accounted for 38.3% (95% confidence interval (CI), 17–56.1%) and 61.7% (95% CI, 43.9–83%).

Conclusions
Our findings do not support the heritability of liver stiffness in an asymptomatic, twin cohort with slight overweight and variable degree of steatosis, underscoring the importance of environmental factors in the development of NAFLD and liver fibrosis.
Chlorhexidine Mouthwash Fails to Eradicate Oropharyngeal Gonorrhea in a Clinical Pilot Trial (MoNg)
Authors: Van Dijck Christophe , Tsoumanis Achilleas , De Hondt Annelies , Cuylaerts Vicky , Laumen Jolein , Van Herrewege Yven , Florence Eric , De Baetselier Irith , Kenyon Chris 
Published: July 2021

Abstract
This single-arm open-label pilot trial in Antwerp, Belgium, was ended early in accordance with the protocol because twice-daily gargling with chlorhexidine 0.2% for 6 days failed to eradicate Neisseria gonorrhoeae from the oropharynx of asymptomatic men who have sex with men (n = 3; efficacy of 0%; 95% confidence interval, 0%–56.1%).
HER2 Testing: Insights From Pathologists’ Perspective on Technically Challenging HER2 FISH Cases
Authors: Grimm Erin V. , Allison Kimberly H. , Hicks David G. , Swenson Karen K. , Krueger Janet , Yaziji Hadi , Downs-Kelly Erinn , Rendi Mara H. , Susnik Barbara , Tsai Michaela L. , Lillemoe Tamera J. 
Published: July 2021

Objective:
College of American Pathologists and the American Society of Clinical Oncology guidelines provide straightforward criteria for HER2 interpretation in breast carcinomas; however, a subset of cases present unusual diagnostic dilemmas.

Materials and Methods:
Ten challenging HER2 fluorescence in situ hybridization (FISH) cases were selected for analysis. The study included a variety of problematic cases such as those with discordant immunohistochemistry (IHC) and FISH results, cases with high intratumoral variability in HER2 copy number, a case with a highly amplified clone in 5% to 10% of the tumor sample, and a case with tumor cells containing tightly clumped HER2 signals. Six high volume HER2 FISH laboratories performed and interpreted HER2 FISH (adding HER2 IHC if necessary). Interpretation strategies were discussed.

Results:
There was 100% concordance between laboratories in 4/10 cases. Tumors with increased intratumoral variability (tumors with high variability in HER2 copy number per cell but which otherwise do not fulfill College of American Pathologists and the American Society of Clinical Oncology criteria for heterogeneity) exhibited 100% concordance in 3/4 cases, but 1 case had only 50% agreement. Low positive HER2 cases (group 1 cases with <6 average HER2 copies/cell) had 1 laboratory disagreeing with the majority in 4/4 cases, and this was the only category with discordance between IHC and FISH methodologies. All laboratories identified the case with heterogeneity and interpreted it as positive. Five of the 6 laboratories interpreted the case with tightly clustered HER2 signals as positive.

Conclusions:
This study offers specific observations and interpretation strategies that laboratories can use when confronted with difficult HER 2 cases. It then highlights communication strategies a laboratory may use to discuss these unusual HER2 results with the clinical team.
The limitations of hospital and law enforcement databases in characterizing the epidemiology of firearm injury
Authors: Miller Keith R. , Egger Michael E. , Pike Annabelle , Burden Jennifer , Bozeman Matthew C. , Franklin Glen A. , Nash Nicholas A. , Smith Jason W. , Harbrecht Brian G. , Benns Matthew V. 
Published: July 2021

BACKGROUND
Current data on the epidemiology of firearm injury in the United States are incomplete. Common sources include hospital, law enforcement, consumer, and public health databases, but each database has limitations that exclude injury subgroups. By integrating hospital (inpatient and outpatient) and law enforcement databases, we hypothesized that a more accurate depiction of the totality of firearm injury in our region could be achieved.

METHODS
We constructed a collaborative firearm injury database consisting of all patients admitted as inpatients to the regional level 1 trauma hospital (inpatient registry), patients treated and released from the emergency department (ED), and subjects encountering local law enforcement as a result of firearm injury in Jefferson County, Kentucky. Injuries recorded from January 1, 2016, to December 31, 2020, were analyzed. Outcomes, demographics, and injury detection rates from individual databases were compared with those of the combined collaborative database and compared using χ2 testing across databases.

RESULTS
The inpatient registry (n = 1,441) and ED database (n = 1,109) were combined, resulting in 2,550 incidents in the hospital database. The law enforcement database consisted of 2,665 patient incidents, with 2,008 incidents in common with the hospital database and 657 unique incidents. The merged collaborative database consisted of 3,207 incidents. In comparison with the collaborative database, the inpatient, total hospital (inpatient and ED), and law enforcement databases failed to include 55%, 20%, and 17% of all injuries, respectively. The hospital captured nearly 94% of survivors but less than 40% of nonsurvivors. Law enforcement captured 93% of nonsurvivors but missed 20% of survivors. Mortality (11–26%) and injury incidence were markedly different across the databases.

DISCUSSION
The utilization of trauma registry or law enforcement databases alone do not accurately reflect the epidemiology of firearm injury and may misrepresent areas in need of greater injury prevention efforts.

LEVEL OF EVIDENCE
Epidemiological, level IV.
Combined Metabolic Activators Improves Cognitive Functions in Alzheimer’s Disease
Authors: Yulug Burak , Altay Ozlem , Li Xiangyu , Hanoglu Lutfu , Cankaya Seyda , Lam Simon , Yang Hong , Coskun Ebru , İdil Ezgi , Nogaylar Rahim , Bayram Cemil , Bolat Ismail , Öner Sena , Tozlu Özlem Özdemir , Arslan Mehmet Enes , Hacımuftuoglu Ahmet , Yıldırım Serkan , Arif Muhammad , Shoaie Saeed , Zhang Cheng , Nielsen Jens , Turkez Hasan , Borén Jan , Uhlén Mathias , Mardinoglu Adil 
Published: July 2021

ABSTRACTAlzheimer’s disease (AD) is associated with metabolic abnormalities linked to critical elements of neurodegeneration. Here, we analysed the brain transcriptomics data of more than 600 AD patients using genome-scale metabolic models and provided supporting evidence of mitochondrial dysfunction related to the pathophysiologic mechanisms of AD progression. Subsequently, we investigated, in a rat model of AD, the oral administration of Combined Metabolic Activators (CMAs), consisting of NAD+ and glutathione precursors, to explore the effect for improvement of biological functions in AD. CMAs includes L-serine, nicotinamide riboside, N-acetyl-L-cysteine, and L-carnitine tartrate, salt form of L-carnitine. The study revealed that supplementation of the CMAs improved the AD-associated histological parameters in the animals. Finally, we designed a randomized, double-blinded, placebo-controlled human phase 2 clinical trial and showed that the administration of CMAs improves cognitive functions in AD patients. As decreased AD Assessment Scale-cognitive subscale (ADAS-Cog) score is the indicator of the improved cognitive function in AD patients, we observed a significant decrease of ADAS-Cog scores on Day 84 vs Day 0 (Log2FC= -0.37, (29% improvement), p-value=0.00001) in the CMA group. We also observed a significant decrease in the placebo group on Day 84 vs Day 0 (Log2FC= -0.19, (14% improvement), p-value=0.001) due to the recommendations of exercise and Mediterranean diet to all AD patients participated in the trial. A comprehensive analysis of the human plasma metabolome and proteome revealed that plasma levels of proteins and metabolites associated with redox metabolism are significantly improved after treatment. In conclusion, our results show that treating AD patients with CMAs leads to enhanced cognitive functions, suggesting a role for such a therapeutic regime in treating AD and other neurodegenerative diseases.HIGHLIGHTS•Brain transcriptomics data of more than 600 AD patients is analysed.•Performed anin vivostudy using Combined Metabolic Activators (CMAs) in AD rat models.•We performed a randomized, double-blinded, placebo-controlled human phase 2 clinical trial.•We showed that cognitive functions in AD patients is improved 29% in the CMA group whereas 14% in the placebo group.
Association between telecommuting environment and low back pain among Japanese telecommuting workers: A cross-sectional study
Authors: Matsugaki Ryutaro , Muramatsu Keiji , Tateishi Seiichiro , Nagata Tomohisa , Tsuji Mayumi , Hino Ayako , Ikegami Kazunori , Fujino Yoshihisa , Matsuda Shinya 
Published: July 2021

AbstractObjectivesWe evaluated the relationship between telecommuting environment and low back pain (LBP) among desk-based workers in Japan.MethodsThis cross-sectional study included 3,663 desk-based, telecommuting workers. LBP was assessed using a 0–10 numerical rating scale. The telecommuting environment was evaluated using subjective questions. Mixed-effects logistic regression analysis was used to evaluate this association.ResultsThe results of mixed-effects logistic model revealed that not having a place or room to concentrate on work, desk not well-lit enough for work, lack of space on the desk to work, not having enough legroom, and uncomfortable temperature and humidity conditions in the workspace were significantly associated with higher odds of LBP.ConclusionsOur findings suggest that telecommuting environment is associated with the prevalence of LBP.
Real-time genomic surveillance during the 2021 re-emergence of the yellow fever virus in Rio Grande do Sul State, Brazil
Authors: Andrade M.S. , Campos F.S. , Campos A.A.S. , Abreu F.V.S. , Melo F.L. , Cardoso J.C. , Santos E. , Born L.C. , Silva C.M.D. , Müller N.F.D. , Oliveira C.H. , Silva A.J.J. , Simonini-Teixeira D. , Bernal-Valle S. , Mares-Guia M.A. , Albuquerque G.R. , Sevá A.P. , Romano A.P.M. , Franco A.C. , Ribeiro B.M. , Roehe P.M. , Almeida M.A.B. 
Published: July 2021

AbstractThe yellow fever virus (YFV) re-emergence in Rio Grande do Sul, Brazil, raised big concerns and led the state to declare a Public Health Emergency of State Importance. Here, we generated near-complete genomes from the ongoing outbreak in Southern Brazil, aiming to better understand the phylogenetic aspects and also spatio-temporal dynamics of the virus. Our findings highlight the path and dispersion in Rio Grande do Sul and that YFV was reintroduced from São Paulo to the Rio Grande do Sul state through Paraná and Santa Catarina states, at the end of 2020.
Genomic epidemiology and strain taxonomy ofCorynebacterium diphtheriae
Authors: Guglielmini Julien , Hennart Melanie , Badell Edgar , Toubiana Julie , Criscuolo Alexis , Brisse Sylvain 
Published: July 2021

AbstractBackgroundCorynebacterium diphtheriaeis highly transmissible and can cause large diphtheria outbreaks where vaccination coverage is insufficient. Sporadic cases or small clusters are observed in high-vaccination settings. The phylogeography and short timescale evolution ofC. diphtheriaeare not well understood, in part due to a lack of harmonized analytical approaches of genomic surveillance and strain tracking.MethodsWe combined 1,305 genes with highly reproducible allele calls into a core genome multilocus sequence typing (cgMLST) scheme. We analyzed cgMLST genes diversity among 602 isolates from sporadic clinical cases, small clusters or large outbreaks. We defined sublineages based on the phylogenetic structure withinC. diphtheriaeand strains based on the highest number of cgMLST mismatches within documented outbreaks. We performed time-scaled phylogenetic analyses of major sublineages.ResultsThe cgMLST scheme showed high allele call rate inC. diphtheriaeand the closely related speciesC. belfantiiandC. rouxii. We demonstrate its utility to delineate epidemiological case clusters and outbreaks using a 25 mismatches threshold, and reveal a number of cryptic transmission chains, most of which are geographically restricted to one or a few adjacent countries. Subcultures of the vaccine strain PW8 differed by up to 20 cgMLST mismatches. Phylogenetic analyses revealed short timescale evolutionary gain or loss of the diphtheria toxin and biovar-associated genes. We devised a genomic taxonomy of strains and deeper sublineages (defined using a 500 cgMLST mismatches threshold), currently comprising 151 sublineages, only a few of which are geographically widespread based on current sampling. The cgMLST genotyping tool and nomenclature was made publicly accessible athttps://bigsdb.pasteur.fr/diphtheria.ConclusionsStandardized genome-scale strain genotyping will help tracing transmission and geographic spread ofC. diphtheriae. The unified genomic taxonomy ofC. diphtheriaestrains provides a common language for studies into the ecology, evolution and virulence heterogeneity amongC. diphtheriaesublineages.
Differential stimulation of pluripotent stem cell-derived human microglia leads to exosomal proteomic changes affecting neurons
Authors: Mallach Anna , Gobom Johan , Arber Charles , Piers Thomas M , Hardy John , Wray Selina , Zetterberg Henrik , Pocock Jennifer 
Published: July 2021

AbstractMicroglial exosomes are an emerging communication pathway, implicated in fulfilling homeostatic microglial functions and transmitting neurodegenerative signals. Gene variants of the triggering receptor expressed myeloid cells-2 (TREM2) are associated with an increased risk of developing dementia. We investigated the influence of the TREM2 Alzheimer’s disease risk variant, R47Hhet, on the microglial exosomal proteome consisting of 3019 proteins secreted from human iPS-derived microglia (iPS-Mg). Exosomal protein content changed according to how iPS-Mg were stimulated. Thus lipopolysaccharide (LPS) induced microglial exosomes to contain more inflammatory signals, whilst stimulation with the TREM2 ligand phosphatidylserine (PS+) increased metabolic signals within the microglial exosomes. We tested the effect of these exosomes on neurons and found that the exosomal protein changes were functionally relevant and influenced downstream functions in both neurons and microglia. Exosomes from R47Hhet iPS-Mg contained disease-associated microglial (DAM) signature proteins, and were less able to promote outgrowth of neuronal processes and increase mitochondrial metabolism in neurons compared with exosomes from TREM2 common variant iPS-Mg. Taken together these data highlight the importance of microglial exosomes in fulfilling microglial functions. Additionally, variations in the exosomal proteome influenced by the R47HhetTREM2 variant may underlie the increased risk of Alzheimer’s disease associated with this variant.Graphical Abstract