bluuebunny/crossref_metadata_2025 huggingface dataset:
Turtle ants harbor metabolically versatile microbiomes with conserved functions across development and phylogeny
Authors: Béchade Benoît , Hu Yi , Sanders Jon G , Cabuslay Christian S , Łukasik Piotr , Williams Bethany R , Fiers Valerie J , Lu Richard , Wertz John T , Russell Jacob A
Published: June 2022

Gut bacterial symbionts can support animal nutrition by facilitating digestion and providing valuable metabolites. However, changes in symbiotic roles between immature and adult stages are not well documented, especially in ants. Here, we explored the metabolic capabilities of microbiomes sampled from herbivorous turtle ant (Cephalotes sp.) larvae and adult workers through (meta)genomic screening and in vitro metabolic assays. We reveal that larval guts harbor bacterial symbionts with impressive metabolic capabilities, including catabolism of plant and fungal recalcitrant dietary fibers and energy-generating fermentation. Additionally, several members of the specialized adult gut microbiome, sampled downstream of an anatomical barrier that dams large food particles, show a conserved potential to depolymerize many dietary fibers. Symbionts from both life stages have the genomic capacity to recycle nitrogen and synthesize amino acids and B-vitamins. With help of their gut symbionts, including several bacteria likely acquired from the environment, turtle ant larvae may aid colony digestion and contribute to colony-wide nitrogen, B-vitamin and energy budgets. In addition, the conserved nature of the digestive capacities among adult-associated symbionts suggests that nutritional ecology of turtle ant colonies has long been shaped by specialized, behaviorally-transferred gut bacteria with over 45 million years of residency.
Chromosome-scale assembly with a phased sex-determining region resolves features of early Z and W chromosome differentiation in a wild octoploid strawberry
Authors: Cauret Caroline M S , Mortimer Sebastian M E , Roberti Marcelina C , Ashman Tia-Lynn , Liston Aaron
Published: June 2022

When sex chromosomes stop recombining, they start to accumulate differences. The sex-limited chromosome (Y or W) especially is expected to degenerate via the loss of nucleotide sequence and the accumulation of repetitive sequences. However, how early signs of degeneration can be detected in a new sex chromosome is still unclear. The sex-determining region of the octoploid strawberries is young, small, and dynamic. Using PacBio HiFi reads, we obtained a chromosome-scale assembly of a female (ZW) Fragaria chiloensis plant carrying the youngest and largest of the known sex-determining region on the W in strawberries. We fully characterized the previously incomplete sex-determining region, confirming its gene content, genomic location, and evolutionary history. Resolution of gaps in the previous characterization of the sex-determining region added 10 kb of sequence including a noncanonical long terminal repeat-retrotransposon; whereas the Z sequence revealed a Harbinger transposable element adjoining the sex-determining region insertion site. Limited genetic differentiation of the sex chromosomes coupled with structural variation may indicate an early stage of W degeneration. The sex chromosomes have a similar percentage of repeats but differ in their repeat distribution. Differences in the pattern of repeats (transposable element polymorphism) apparently precede sex chromosome differentiation, thus potentially contributing to recombination cessation as opposed to being a consequence of it.
Integrative analysis and prediction of human R-loop binding proteins
Authors: Kumar Arun , Fournier Louis-Alexandre , Stirling Peter C
Published: June 2022

In the past decade, there has been a growing appreciation for R-loop structures as important regulators of the epigenome, telomere maintenance, DNA repair, and replication. Given these numerous functions, dozens, or potentially hundreds, of proteins could serve as direct or indirect regulators of R-loop writing, reading, and erasing. In order to understand common properties shared amongst potential R-loop binding proteins, we mined published proteomic studies and distilled 10 features that were enriched in R-loop binding proteins compared with the rest of the proteome. Applying an easy-ensemble machine learning approach, we used these R-loop binding protein-specific features along with their amino acid composition to create random forest classifiers that predict the likelihood of a protein to bind to R-loops. Known R-loop regulating pathways such as splicing, DNA damage repair and chromatin remodeling are highly enriched in our datasets, and we validate 2 new R-loop binding proteins LIG1 and FXR1 in human cells. Together these datasets provide a reference to pursue analyses of novel R-loop regulatory proteins.
Loss of BAF (mSWI/SNF) chromatin-remodeling ATPase Brg1 causes multiple malformations of cortical development in mice
Authors: Jin Yecheng , Gao Xiaotong , Lu Miaoqing , Chen Ge , Yang Xiaofan , Ren Naixia , Song Yuning , Hou Congzhe , Li Jiangxia , Liu Qiji , Gao Jiangang
Published: June 2022

Mutations in genes encoding subunits of the BAF (BRG1/BRM-associated factor) complex cause various neurodevelopmental diseases. However, the underlying pathophysiology remains largely unknown. Here, we analyzed the function of Brahma-related gene 1 (Brg1), a core ATPase of BAF complexes, in the developing cerebral cortex. Loss of Brg1 causes several morphological defects resembling human malformations of cortical developments (MCDs), including microcephaly, cortical dysplasia, cobblestone lissencephaly and periventricular heterotopia. We demonstrated that neural progenitor cell renewal, neuronal differentiation, neuronal migration, apoptotic cell death, pial basement membrane and apical junctional complexes, which are associated with MCD formation, were impaired after Brg1 deletion. Furthermore, transcriptome profiling indicated that a large number of genes were deregulated. The deregulated genes were closely related to MCD formation, and most of these genes were bound by Brg1. Cumulatively, our study indicates an essential role of Brg1 in cortical development and provides a new possible pathogenesis underlying Brg1-based BAF complex-related neurodevelopmental disorders.
The Squamate Clitoris: A Review and Directions for Future Research
Authors: Folwell Megan , Sanders Kate , Crowe-Riddell Jenna
Published: June 2022

The clitoris is a part of the genitalia of female amniotes that typically functions to stimulate sensory arousal. It usually consists of a small organ that is dimorphic and homologous to the penis. The developing amniote embryo forms a genital tubule, then sex hormones initiate a developmental cascade to form either a penis or clitoris. In squamates (lizards and snakes), the genital tubule develops into a paired hemiphallus structure called the “hemiclitores” in the female and the “hemipenes” in the male. The complex evolution of squamate hemipenes has been extensively researched since early discoveries in the 1800s and this has uncovered a huge diversity in hemipenis size, shape, and ornamentation (e.g., protrusions of spines, hooks, chalices, and cups). In contrast, the squamate hemiclitoris has been conspicuously under-investigated, and the studies that describe this anatomy are fraught with inconsistences. This paper aims to clarify the current state of knowledge of the squamate hemiclitoris, providing a foundation for further research on its morphology and functional role. We show that while several studies have described the gross anatomy of hemiclitores in lizards, comparative information is entirely lacking for snakes. Several papers cite earlier authors as having reported discoveries of the snake hemiclitores in vipers and colubrid snakes. However, our examination of this reveals only erroneous reports of hemiclitores in snakes and shows that these stem from misinterpretations of the true anatomy or species involved. An especially problematic source of confusion is the presence of intersex individuals in some snake populations; these form reproductively functional ovaries and a single hemipenis, with the latter sometimes mistaken for a hemiclitoris. (The intersex hemipenis is usually smaller and less spinous than the male hemipenis.) Further research is recommended to identify the defining anatomical features of the squamate hemiclitores. Such studies will form a vital basis of future comparative analyzes of variation in female genitalia in squamates and other amniotes.
Evaluation of the Salmonella CANARY® Zephyr Assay for the Detection of Salmonella enterica on Environmental Surfaces: AOAC Performance Tested MethodSM 042201
Authors: Wang Yangyang , Wright Samantha , Rodriguez Maria , Young Deevyne , Maltbie Alexandra , Lehett J J , Flannery Andrew R
Published: June 2022

Background

The Salmonella CANARY® Zephyr assay is designed to provide rapid and reliable detection of Salmonella enterica from various types of environmental surfaces, including stainless steel, silicone rubber, high-density polyethylene (HDPE), and glazed ceramic. The assay is using cell- and immuno-based CANARY technology and tested on Smiths Detection’s Zephyr platform.

Objective

The objective of this validation study was to evaluate the Salmonella CANARY Zephyr assay for its inclusivity/exclusivity, matrix study for 4 claimed environmental surfaces, consistency/stability, and robustness.

Methods

The Salmonella CANARY Zephyr assay was compared to the U.S. Food and Drug Administration Bacteriological Analytical Manual (BAM) Chapter 5 “Salmonella” using an unpaired study design for environmental surfaces including stainless steel, silicone rubber, HDPE, and glazed ceramic (1” × 1” test area).

Results

For the inclusivity and exclusivity evaluation, the Salmonella CANARY Zephyr assay correctly identified 101 out of 102 target organism isolates (with one strain of S. enterica subsp. indica not detected) and excluded all 33 non-target strains that were analyzed. For the matrix study, the Salmonella CANARY Zephyr assay demonstrated no statistically significant differences between presumptive and confirmed results or between candidate and reference method results. Probability of detection analysis of the Salmonella CANARY Zephyr method on robustness and product consistency/stability (lot-to-lot) study demonstrated no statistically significant differences.

Conclusion

The Salmonella CANARY Zephyr assay is an effective method for the detection of Salmonella enterica from various environmental surfaces including stainless steel, silicone rubber, HDPE, and glazed ceramic.

Highlight

The Salmonella CANARY Zephyr assay allows for rapid and sensitive detection of Salmonella enterica on environmental surfaces. It only takes less than 5 min to prepare the sample and 1 min for instrument running/reading.
Analysis of Bovine Lactoferrin in Infant Formula and Adult Nutritional Products by Optical Biosensor Immunoassay: First Action 2021.07
Authors: Gill Brendon D , Kobayashi Tadashi , Wood Jackie E , Indyk Harvey E
Published: June 2022

Background

Bovine lactoferrin is increasingly being used as an ingredient in infant formula manufacture to enhance nutritional efficacy through the provision of immunoprotective, growth, and antimicrobial factors to the neonate.

Objective

To evaluate the analytical performance of an optical biosensor immunoassay for compliance with the method performance requirements described in SMPR 2020.005.

Method

Following dilution of the sample in buffer, an automated, label-free, real-time optical biosensor immunoassay was used in a direct assay format to quantitate bovine lactoferrin by its interaction with an immobilized anti-lactoferrin antibody. Quantitation was accomplished by the external standard technique with interpolation from a 4-parameter calibration regression.

Results

The analytical range (0–200 mg/hg), method detection limit (0.8 mg/hg), recovery (96.1–109.2%), and repeatability (1.0–5.3%) complied with the requirements given in the lactoferrin SMPR. The method was shown to be specific for native, intact lactoferrin; thermally denatured lactoferrin generated no measurable binding response.

Conclusion

The method described is suitable for the quantification of intact, undenatured lactoferrin in milk products, infant formulas (bovine milk protein-based, soy protein-based, and amino acid-based), and adult nutritionals and has been demonstrated to meet the performance requirements defined in SMPR 2020.005.

Highlights

A single-laboratory validation (SLV) of an automated biosensor immunoassay for the determination of intact, undenatured lactoferrin is described.
Burns During Coronavirus Disease 19 Lockdown: a Multi-Center Retrospective Study in Israel
Authors: Kruchevsky Dani , Levanon Shir , Givon Adi , Bodas Moran ,   Israeli Trauma Group, Acker Asaf , Aviran Nimrod , Bahouth Hany , Bar Alon , Becker Alexander , Braslavsky Alexander , Fadeev Dmitry , Goldstein Adam Lee , Grevtsev Ilia , Jeroukhimov Igor , Kedar Asaf , Korin Alexander , Qarawany Milad , Schwarz Alon , Shomar Wael , Soffer Dror , Stein Michael , Venturero Moris , Weiss Michael , Yaslowitz Ori , Zoarets Itay , Ramon Yitzchak , Ullmann Yehuda , Zeltzer Assaf A
Published: June 2022

The coronavirus disease 2019 (COVID-19) pandemic forced many countries into lockdowns to limit the spread of infection. Israel’s containment measures included school closures, mobility restrictions, and workforce reductions. Our study evaluated the effect of COVID-19 on the occurrence and patterns of burn injuries. The study data was obtained via retrospective chart review of burn patients treated between March 15, 2020 and April 30, 2020, namely the period of strict national lockdown. This data was compared against data from paralleling periods between 2017 and 2019. A total of 686 patients were treated for burn injuries in the two study periods. Age group analysis revealed an increased ratio of pediatric patients aged 0–3 years during the lockdown (55.91% vs 40.79%, P = .002). In contrast, there were fewer patients presenting with burn injuries in the 7–16 and 17–29 age groups (9.66% vs 3.15%, P = .017; 16.46% vs 7.09%, P = .007, respectively). During both study periods, scald injuries were the most common burn etiology and burn injuries occurred most often at home. This predominance was further pronounced during the lockdown (71.65% vs 58.68%, P = .007; 90.55% vs 74.60%, P = .0001, respectively). The lockdown period underlined the danger faced by pediatric patients in their household environment. This danger was possibly compounded by an improper level of adult supervision as parents transitioned to remote work. These findings can educate us about factors that render burn injuries more likely not only during lockdowns, but also during regular times, thus shaping the development of burn prevention practices.
Sensitivity Training for Mothers With Premature Infants: A Randomized Controlled Trial
Authors: Yu Nicky Ka Ki , Shum Kathy Kar-man , Lam Yuen Yu , Kwan Queenie Kwok Loi , Ng Sylvia Yin Ping , Chan Natalie Tsz Ting
Published: June 2022

Objective

This single-blind parallel design randomized controlled trial evaluated the feasibility and effectiveness of a modified version of the Mother–Infant Transaction Program (MITP) in enhancing Chinese mothers’ sensitivity towards their premature infants’ physiological and social cues.

Methods

Sixty mothers of hospitalized premature infants (mean gestational age = 32.1 weeks; SD = 2.8) were randomly assigned to either the MITP group or the treatment-as-usual control group. The intervention group (n = 30) received four sessions of parental sensitivity training adapted from the MITP, delivered by clinical psychologists before the infants were discharged. The control group (n = 30) received standard care provided by the hospitals. Each dyad was assessed at baseline (Time 1), immediately after intervention (Time 2), and when the infants were at the gestation-corrected ages of 3, 6, 9, and 12 months (Times 3–6). Maternal sensitivity, mother–infant interaction quality, parenting stress, postpartum depression, and mother’s perception of infant’s temperament were measured at Times 1–4, whereas infants’ weight gain and developmental performance were assessed at Times 3–6.

Results

The MITP group showed significantly higher maternal sensitivity and better mother–infant interaction quality after completing the training. They also reported less parenting stress and postnatal depression than the control group at Time 2 and subsequent follow-ups. The intervention significantly predicted better weight gain and developmental outcomes in infants across Times 3–6, mediated by maternal wellbeing and interaction quality.

Conclusion

 Our results demonstrated the feasibility and effectiveness of this adapted sensitivity training among Chinese mothers with premature infants. [ClinicalTrials.gov NCT04383340]
Handlebar hernia–unusual complication from blunt trauma
Authors: Vieira Bruno , Melo Ana , Gomes Carina , Lajut Leandro , Ribeiro Artur , Fernandes Urânia , Guidi Gonçalo , Leal Clara , Pinto-de-Sousa João
Published: June 2022

Handlebar hernia is a rare entity, mainly resulting from blunt abdominal trauma with a sudden deceleration mechanism. Diagnosis of handlebar at admission may be difficult because the rupture of abdominal wall layers often is not clinically recognized in the emergency department, which requires a high degree of suspicion to identify theses lesions. It is very important to rule out the presence of intra-abdominal injuries, and in adults, surgical repair is needed. Herein, the case of an adult man who presented to the emergency department with blunt abdominal trauma caused by a motorcycle handlebar is described.
Interactions Between Natural Selection and Recombination Shape the Genomic Landscape of Introgression
Authors: Duranton Maud , Pool John E
Published: June 2022

Hybridization between lineages that have not reached complete reproductive isolation appears more and more like a common phenomenon. Indeed, speciation genomic studies have now extensively shown that many species’ genomes have hybrid ancestry. However, genomic patterns of introgression are often heterogeneous across the genome. In many organisms, a positive correlation between introgression levels and recombination rate has been observed. It is usually explained by the purging of deleterious introgressed material due to incompatibilities. However, the opposite relationship was observed in a North American population of Drosophila melanogaster with admixed European and African ancestry. In order to explore how directional and epistatic selection can impact the relationship between introgression and recombination, we performed forward simulations of whole D. melanogaster genomes reflecting the North American population’s history. Our results revealed that the simplest models of positive selection often yield negative correlations between introgression and recombination such as the one observed in D. melanogaster. We also confirmed that incompatibilities tend to produce positive introgression–recombination correlations. And yet, we identify parameter space under each model where the predicted correlation is reversed. These findings deepen our understanding of the evolutionary forces that may shape patterns of ancestry across genomes, and they strengthen the foundation for future studies aimed at estimating genome-wide parameters of selection in admixed populations.
Identification of Streptomyces spp. in a Clinical Sample: Always Contamination? Results of a French Retrospective Study
Authors: Gras Emmanuelle , Bergeron Emmanuelle , Puges Mathilde , Ducours Maïlys , Leleux Charlotte , Amoureux Lucie , Jean Baptiste , Bendjelloul Imane , Camelena François , Chenouard Rachel , Mahieu Rafael , Lemenand Olivier , Toro Alexandre , Lecoustumier Alain , Lortholary Olivier , Rodriguez Nava Véronica , Lebeaux David ,   for the French Streptomyces Study Group
Published: June 2022

Background

Streptomyces are environmental gram-positive bacilli that can cause ubiquitous mycetoma and, more rarely, invasive infections. We describe the clinical relevance of Streptomyces spp. identified in human samples and characteristics of patients with invasive Streptomyces infections.

Methods

We conducted a retrospective (2006–2017) study of Streptomyces isolates identified in clinical samples in French microbiology laboratories. Streptomyces genus was confirmed by a specific 16S rRNA polymerase chain reaction, and antibiotic susceptibility testing was performed by disk diffusion and trimethoprim-sulfamethoxazole minimum inhibitory concentration (E-test) if resistance was suspected. Patient characteristics, treatments, and outcomes were collected. Invasive infection was defined as a positive culture from a sterile site with signs of infection but without cutaneous inoculation.

Results

Of 137 Streptomyces isolates, all were susceptible to amikacin (113/113) and linezolid (112/112), and 92.9% to imipenem (105/113). Using disk diffusion, 50.9% (57/112) of isolates were susceptible to trimethoprim-sulfamethoxazole, but most of the apparently resistant isolates (25/36, 69.4%) tested by E-test were ultimately classified as susceptible. Clinical data were obtained for 63/137 (45.9%) isolates: 30 (47.6%) invasive infections, 8 (12.7%) primary cutaneous infections, 22 (34.9%) contaminations, 3 (4.7%) respiratory colonization. Patients with invasive infection were more frequently receiving corticosteroids than patients without invasive infection (11/30, 36.7%, vs 2/25, 8.0%; P = .03), and at 6-month follow-up, 14 of them were cured, 3 had relapsed, 4 were dead, and 9 were lost to follow-up.

Conclusions

Half of the clinical samples that grew Streptomyces were from patients with invasive infection. In that case, antimicrobial therapy should include 1 or 2 antibiotics among linezolid, amikacin, or imipenem.
Temporal changes in coronary artery function and flow velocity reserve in mice exposed to chronic intermittent hypoxia
Authors: Badran Mohammad , Bender Shawn B , Khalyfa Abdelnaby , Padilla Jaume , Martinez-Lemus Luis A , Gozal David
Published: June 2022

Study Objectives

Obstructive sleep apnea (OSA) is a chronic condition characterized by intermittent hypoxia (IH) that is implicated in an increased risk of cardiovascular disease (i.e., coronary heart disease, CHD) and associated with increased overall and cardiac-specific mortality. Accordingly, we tested the hypothesis that experimental IH progressively impairs coronary vascular function and in vivo coronary flow reserve.

Methods

Male C57BL/6J mice (8-week-old) were exposed to IH (FiO2 21% 90 s–6% 90 s) or room air (RA; 21%) 12 h/day during the light cycle for 2, 6, 16, and 28 weeks. Coronary artery flow velocity reserve (CFVR) was measured at each time point using a Doppler system. After euthanasia, coronary arteries were micro-dissected and mounted on wire myograph to assess reactivity to acetylcholine (ACh) and sodium nitroprusside (SNP).

Results

Endothelium-dependent coronary relaxation to ACh was preserved after 2 weeks of IH (80.6 ± 7.8%) compared to RA (87.8 ± 7.8%, p = 0.23), but was significantly impaired after 6 weeks of IH (58.7 ± 16.2%, p = 0.02). Compared to ACh responses at 6 weeks, endothelial dysfunction was more pronounced in mice exposed to 16 weeks (48.2 ± 5.3%) but did not worsen following 28 weeks of IH (44.8 ± 11.6%). A 2-week normoxic recovery after a 6-week IH exposure reversed the ACh abnormalities. CFVR was significantly reduced after 6 (p = 0.0006) and 28 weeks (p < 0.0001) of IH when compared to controls.

Conclusion

Chronic IH emulating the hypoxia-re-oxygenation cycles of moderate-to-severe OSA promotes coronary artery endothelial dysfunction and CFVR reductions in mice, which progressively worsen until reaching asymptote between 16 and 28 weeks. Normoxic recovery after 6 weeks exposure reverses the vascular abnormalities.
The space-time profiles of sleep spindles and their coordination with slow oscillations on the electrode manifold
Authors: Malerba Paola , Whitehurst Lauren , Mednick Sara C
Published: June 2022

Sleep spindles are important for sleep quality and cognitive functions, with their coordination with slow oscillations (SOs) potentially organizing cross-region reactivation of memory traces. Here, we describe the organization of spindles on the electrode manifold and their relation to SOs. We analyzed the sleep night EEG of 34 subjects and detected spindles and SOs separately at each electrode. We compared spindle properties (frequency, duration, and amplitude) in slow wave sleep (SWS) and Stage 2 sleep (S2); and in spindles that coordinate with SOs or are uncoupled. We identified different topographical spindle types using clustering analysis that grouped together spindles co-detected across electrodes within a short delay (±300 ms). We then analyzed the properties of spindles of each type, and coordination to SOs. We found that SWS spindles are shorter than S2 spindles, and spindles at frontal electrodes have higher frequencies in S2 compared to SWS. Furthermore, S2 spindles closely following an SO (about 10% of all spindles) show faster frequency, shorter duration, and larger amplitude than uncoupled ones. Clustering identified Global, Local, Posterior, Frontal-Right and Left spindle types. At centro-parietal locations, Posterior spindles show faster frequencies compared to other types. Furthermore, the infrequent SO-spindle complexes are preferentially recruiting Global SO waves coupled with fast Posterior spindles. Our results suggest a non-uniform participation of spindles to complexes, especially evident in S2. This suggests the possibility that different mechanisms could initiate an SO-spindle complex compared to SOs and spindles separately. This has implications for understanding the role of SOs-spindle complexes in memory reactivation.
Economic assessments from experimental research trials of feedlot cattle health and performance: a scoping review
Authors: Dixon Andrea L , Hanthorn Christy J , Pendell Dustin L , Cernicchiaro Natalia , Renter David G
Published: June 2022

Animal husbandry decisions for feedlot cattle may be based on economic or financial impacts reported from livestock research trials comparing interventions such as health practices or performance technologies. Despite the importance of economic assessments to production management decisions, there are no consensus guidelines for their methods or reporting. Thus, we hypothesized that methods and reporting of economic assessments in the scientific literature are inconsistent. This scoping review describes the types of economic assessments used to evaluate the costs and benefits of interventions in feedlot trials, how measured health and performance outcomes are utilized in economic evaluations, and the completeness of reporting. A structured search was used to retrieve peer-reviewed articles (published in English) on experimental trials performed in Australia, North America, or South Africa, which reported feedlot cattle health, performance, or carcass characteristics and included an economic outcome. A total of 7,086 articles were screened for eligibility; 91 articles (comprising 113 trials) met the inclusion criteria. Trial characteristics, methods, and reporting data were extracted. A primary outcome was stated in only 36% (41/113) of the trials. Of these 41 trials, an economic outcome was reported as a primary outcome in 18 (44%). Methodology for the economic assessment was reported for 54 trials (48%), the type of economic assessment was explicitly stated for 21 trials (19%), and both the type of economic assessment and methodology used were reported for 29 trials (26%); neither were reported for nine trials (8%). Eight types of economic assessments were explicitly reported: cost-effectiveness, cost–benefit analysis, enterprise analysis, partial budget, break-even analysis, profitability, decision analysis, and economic advantage. From the trials that did not report an assessment type, three were identified: partial budget, enterprise analysis, and gross margin analysis. Overall, only 32 trials (28%) reported economics as an outcome of interest, the methodology used or the type of assessment, and values, sources, and dates for at least some of the price data used in the analysis. Given the variability in methods and inconsistent reporting for feedlot trials identified by this scoping review, a guideline to facilitate consistency on appropriate methods and reporting is warranted.
Inhibition of Rho‐associated protein kinase activity enhances oxidative phosphorylation to support corneal endothelial cell migration
Authors: Ho Wei‐Ting , Chang Jung‐Shen , Chen Tsan‐Chi , Wang Jia‐Kang , Chang Shu‐Wen , Yang Muh‐Hwa , Jou Tzuu‐Shuh , Wang I‐Jong
Published: June 2022

Corneal endothelial cell (CEC) dysfunction causes corneal edema and severe visual impairment that require transplantation to restore vision. To address the unmet need of organ shortage, descemetorhexis without endothelial keratoplasty has been specifically employed to treat early stage Fuchs endothelial corneal dystrophy, which is pathophysiologically related to oxidative stress and exhibits centrally located corneal guttae. After stripping off central Descemet's membrane, rho‐associated protein kinase (ROCK) inhibitor has been found to facilitate CEC migration, an energy‐demanding task, thereby achieving wound closure. However, the correlation between ROCK inhibition and the change in bioenergetic status of CECs remained to be elucidated. Through transcriptomic profiling, we found that the inhibition of ROCK activity by the selective inhibitor, ripasudil or Y27632, promoted enrichment of oxidative phosphorylation (OXPHOS) gene set in bovine CECs (BCECs). Functional analysis revealed that ripasudil, a clinically approved anti‐glaucoma agent, enhanced mitochondrial respiration, increased spare respiratory capacity, and induced overexpression of electron transport chain components through upregulation of AMP‐activated protein kinase (AMPK) pathway. Accelerated BCEC migration and in vitro wound healing by ripasudil were diminished by OXPHOS and AMPK inhibition, but not by glycolysis inhibition. Correspondingly, lamellipodial protrusion and actin assembly that were augmented by ripasudil became reduced with additional OXPHOS or AMPK inhibition. These results indicate that ROCK inhibition induces metabolic reprogramming toward OXPHOS to support migration of CECs.
Random Forest Classification to Predict Response to High-Definition Transcranial Direct Current Stimulation for Tinnitus Relief: A Preliminary Feasibility Study
Authors: Cardon Emilie , Jacquemin Laure , Schecklmann Martin , Langguth Berthold , Mertens Griet , Vanderveken Olivier M. , Lammers Marc , Van de Heyning Paul , Van Rompaey Vincent , Gilles Annick
Published: June 2022

Objectives:

Transcranial direct current stimulation (tDCS) of the right dorsolateral prefrontal cortex has been hypothesized to reduce tinnitus severity by modifying cortical activity in brain regions associated with the perception of tinnitus. However, individual response to tDCS has proven to be variable. We investigated the feasibility of using random forest classification to predict the response to high-definition (HD) tDCS for tinnitus relief.

Design:

A retrospective analysis was performed on a dataset consisting of 99 patients with subjective tinnitus receiving six consecutive sessions of HD-tDCS at the Antwerp University Hospital. A baseline assessment consisted of pure-tone audiometry and a set of questionnaires including the Tinnitus Functional Index (TFI), Hospital Anxiety and Depression Scale, and Edinburgh Handedness Inventory. Random forest classification was applied to predict, based on baseline questionnaire scores and hearing levels, whether each individual responded positively to the treatment (defined as a decrease of at least 13 points on the TFI). Further testing of the model was performed on an independent cohort of 32 patients obtained from the tinnitus center at the University of Regensburg.

Results:

Twenty-four participants responded positively to the HD-tDCS treatment. The random forest classifier predicted treatment response with an accuracy of 85.71% (100% sensitivity, 81.48% specificity), significantly outperforming a more traditional logistic regression approach. Performance of the classifier on an independent cohort was slightly but not significantly above chance level (71.88% accuracy, 66.67% sensitivity, 73.08% specificity). Feature importance analyses revealed that baseline tinnitus severity, co-occurrence of depressive symptoms and handedness were the most important predictors of treatment response. Baseline TFI scores were significantly higher in responders than in nonresponders.

Conclusions:

The proposed random forest classifier predicted treatment response with a high accuracy, significantly outperforming a more traditional statistical approach. Machine learning methods to predict treatment response might ultimately be used in a clinical setting to guide targeted treatment recommendations for individual tinnitus patients.
Inclisiran: Small Interfering Ribonucleic Acid Injectable for the Treatment of Hyperlipidemia
Authors: Hughes-Hubley Frances , Iskander Mina , Cheng-Lai Angela , Frishman William H. , Nawarskas James
Published: June 2022

Elevated plasma lipid levels, especially low-density lipoprotein, are correlated with atherosclerotic cardiovascular disease (ASCVD) and increased risk of ischemic heart disease and stroke. Statins are first-line agents for reducing low-density lipoprotein cholesterol (LDL-C) and the risk of major cardiovascular events, but patients with a genetic susceptibility or established ASCVD oftentimes remain subtherapeutic on statin therapy alone. Biotechnological advancements in medication therapy have led to the development of inclisiran, a recently approved twice-yearly injectable agent to help patients with heterozygous familial hypercholesterolemia and clinical ASCVD on a maximally tolerated statin to reach LDL-C targets. Inclisiran has demonstrated robust LDL-C reduction in clinical trials in combination with a favorable safety profile; however, the effect on cardiovascular clinical outcomes still remains under evaluation.
Dapagliflozin Attenuates Contrast-induced Acute Kidney Injury by Regulating the HIF-1α/HE4/NF-κB Pathway
Authors: Huang Xu , Guo Xiaoxu , Yan Gaoliang , Zhang Yang , Yao Yuyu , Qiao Yong , Wang Dong , Chen Gecai , Zhang Weiwei , Tang Chengchun , Cao Feng
Published: June 2022

Contrast-induced acute kidney injury (CI-AKI) causes clinically acquired nephropathy in patients who undergo coronary interventions. Hypoxic injury to proximal tubular epithelial cells is a pathological mechanism of CI-AKI. Previous studies have shown that hypoxia activates HIF-1α/HE4/NF-κB to enhance renal fibrosis, and the SGLT-2 inhibitor luseogliflozin inhibits hypoxia-inducible factor (HIF)-1α expression to reduce the progression of diabetic nephropathy. However, the therapeutic effects and mechanisms of SGLT-2 inhibitors on CI-AKI are unclear. We explored the role of the HIF-1α/HE4/NF-κB pathway in CI-AKI and how dapagliflozin effectively treats CI-AKI by inhibiting this pathway. In vitro, cells were divided into the control, hypoxia, hypoxia + dapagliflozin, and hypoxia + pSilencer-HIF-1α groups. Cellular hypoxia, apoptosis, and related protein expression were evaluated by immunofluorescence, western blotting, and flow cytometry, respectively. Dapagliflozin significantly decreased oxygen consumption, HIF-1α, human epididymis protein 4 (HE4), NF-κB expression, and apoptotic cells compared with the control (P < 0.01). In vivo, rats were divided into the control (C), diabetes (D), diabetes + contrast media, and diabetes + contrast media + dapagliflozin groups. Rats in the latter 2 groups were treated with dapagliflozin for 2 days. CI-AKI was induced by intravenously injecting indomethacin, N-nitro-l-arginine methyl ester, and iohexol. The effects of dapagliflozin on CI-AKI rats were elucidated by assessing renal function, H&E staining, and immunohistochemistry. Serum creatinine, urea nitrogen, TUNEL-positive tubular cells, HIF-1α, HE4, NF-κB expression, and histopathological scores were increased in diabetes + contrast media rats compared with C, D, and diabetes + dapagliflozin + contrast media rats (P < 0.01). Thus, dapagliflozin may ameliorate CI-AKI through suppression of HIF-1α/HE4/NF-κB signaling in vitro and in vivo.
EXTREME MACULAR SCHISIS–SIMULATING RETINAL DETACHMENT IN EYES WITH PATHOLOGIC MYOPIA
Authors: Uramoto Kengo , Azuma Takeshi , Watanabe Takashi , Takahashi Hiroyuki , Igarashi-Yokoi Tae , Shimada Noriaki , Ohno-Matsui Kyoko
Published: June 2022

Purpose:

To determine the clinical and imaging characteristics, natural course, and surgical outcomes of pathologic myopic eyes with an extreme macular schisis simulating a retinal detachment (EMSSRD).

Methods:

The data of 617 highly myopic eyes with myopic traction maculopathy were studied. The diagnosis of EMSSRD in the optical coherence tomography images was made based on a high elevation of the retina (>500 µm), less obvious columnar structures, and the presence of thin remnants of outer retinal tissues above the retinal pigment epithelium.

Results:

Among 617 eyes, 25 eyes had an EMSSRD. All of the eyes with an EMSSRD had macular atrophy caused by myopic macular neovascularization. In the five eyes they had progressed to MHRD, the retinal detachment started away from the macular atrophy. Among the 10 eyes which required surgery, there was no significant difference in the presurgical and postsurgical best-corrected visual acuity between the eyes operated because of a worsening of the EMSSRD and the eyes operated because of a progression to MHRD.

Conclusion:

In severely myopic eyes with macular neovascularization–related macular atrophy, a novel condition termed EMSSRD can be present. The optical coherence tomography images resemble those of a MHRD except the presence of thin remnants of the retina remaining on the retinal pigment epithelium.
CLINICAL OUTCOMES OF PATIENTS WITH ENDOPHTHALMITIS AFTER DEXAMETHASONE INTRAVITREAL IMPLANT
Authors: Samuelson Annika G. , Nahar Ankur , Patel Samir N. , Mahmoudzadeh Raziyeh , Salabati Mirataollah , Yu-Chuan Kang Eugene , Hinkle John W. , Soares Rebecca R. , Kuriyan Ajay E. , Garg Sunir J.
Published: June 2022

Purpose:

To report a case series of endophthalmitis associated with intravitreal dexamethasone injections in a single practice and to discuss the clinical findings and visual outcomes of each case.

Methods:

All endophthalmitis cases following intravitreal dexamethasone injections performed from January 1, 2014 to October 20, 2020 were identified using Wills Eye/MidAtlantic billing records. The diagnosis, clinical information, and microbiology were confirmed for each case. Data were analyzed using Excel (Microsoft Excel, Redmond, WA).

Results:

Four cases of endophthalmitis were identified from 3,925 intravitreal dexamethasone injections in a single practice and one case was referred from an outside institution, resulting in an incidence of 0.102% (1 in 981 injections). Mean age was 82.3 years (range, 63–88 years) with a mean of 11.3 intravitreal dexamethasone injections performed (range, 2–30 injections) before endophthalmitis. Cases presented with endophthalmitis a mean (SD) of 3.6 (1.64) days after causative injection. Three cases grew gram-positive organisms. All patients responded to intravitreal antibiotics. Mean logarithm of the minimal angle of resolution visual acuity at causative injection, endophthalmitis presentation, 3 months, and last follow-up was 0.44 (20/55), 2.22 (20/3,319), 1.18 (20/303), and 1.46 (20/577), respectively.

Conclusion:

Endophthalmitis following intravitreal steroid injections may occur more frequently than other intravitreal injections. Dexamethasone-attributed endophthalmitis remains uncommon, and prompt intravitreal antibiotic treatment seems to be effective in this series.
High-Dose Vancomycin in the Treatment of Clostridioides difficile Infection
Authors: Bader Mazen S. , Mertz Dominik , Hawboldt John , Farrell Alison , Alajmi Abdulaziz , Maleki-Yazdi Keon
Published: June 2022

Background

There is significant variability in guideline recommendations regarding the dosing of vancomycin in treating Clostridioides difficile infection (CDI). The aim of this systematic review and meta-analysis was to investigate the efficacy of high-dose vancomycin compared with other current standard of care and other CDI treatment regimens.

Methods

We conducted a comprehensive literature search in PubMed, the Cochrane Library, Embase, and Web of Science for publications that studied the comparative effectiveness of high-dose vancomycin to other CDI treatment regimens for the period up to July 2020.

Results

A total of 14 studies, 6 randomized controlled trials (372 participants) and 8 observational controlled studies (952 participants), with a total of 1324 patients were included in the final analysis. There was no statistically significant effect between high-dose vancomycin and other treatment options of CDI on clinical cure/response (odd ratio [OR], 0.70; 95% confidence interval [CI], 0.34 to 1.43; I
2 = 59%), clinical relapse and recurrence (OR, 1.01; 95% CI, 0.72–1.42; I
2 = 61%), and mortality (OR, 1.03; 95% CI, 0.37–2.84; I
2 = 44%).

Conclusions

High-dose oral vancomycin was not superior to other treatment regimens for the outcomes of clinical response and cure, recurrence, and mortality of CDI.
Multisystem Inflammatory Syndrome in Adults Presenting as Retropharyngeal Phlegmon
Authors: Sy Hendrik , Humphreys Sarah , Shapiro Janet M. , Stavropoulos Christine F.
Published: June 2022

Multisystem inflammatory syndrome in adults presents with extrapulmonary organ dysfunction in patients with a recent COVID-19 infection. A 22-year-old man with a history of ataxia with vitamin E deficiency and recent asymptomatic COVID-19 infection presented with retropharyngeal edema treated as phlegmon. He developed cardiac dysfunction and required vasopressor support with evidence of high inflammatory markers. Multisystem inflammatory syndrome in adults was diagnosed, and he rapidly improved with intravenous (IV) corticosteroids. Multisystem inflammatory syndrome in adults can rarely present with retropharyngeal phlegmon. We identified 2 reported cases in adults and 5 in children with an age range of 4 to 51 years. COVID-19 infection was established in all cases but was often previously unknown. All patients recovered with IV corticosteroids with or without IV immunoglobulin. In conclusion, multisystem inflammatory syndrome in adults can present with retropharyngeal edema, and previous COVID-19 infection may not be apparent.
Cochlear implant mapping strategy to solve difficulty in speech recognition
Authors: Chang Chan-Jung , Sun Chuan-Hung , Hsu Chuan-Jen , Chiu Ting , Yu Szu-Hui , Wu Hung-Pin
Published: June 2022

Background:

Cochlear implants (CIs) are viable treatment options in patients with severe to profound hearing loss. Speech recognition difficulties were reported in some CI recipients even with a good-aided hearing threshold. The aim of this study was to report a mapping strategy based on different target-aided hearing thresholds to achieve optimal speech recognition and maximize functional outcomes. The safety and efficacy of the mapping strategy were also inspected in the article.

Methods:

This prospective repeated measures study enrolled 20 adult CI recipients with postlingual deafness using the MED-EL CI system. Word and sentence discrimination assessment and administration of a questionnaire pertaining to comfort level were conducted at the end of each session. The electrophysiological features of the CI mapping were recorded.

Results:

The correlation between audiometry results and word and sentence recognition was not high. CIs performed best at an audiometry threshold between 25 and 35 dB.

Conclusion:

CI performance with the best perception relies on a balance between minimizing the hearing threshold and maximizing the dynamic range while maintaining an appropriate comfort level, which was achieved when the target hearing threshold was set at 25–35 dB in this study.
Potentiality of impulse oscillometry to evaluate bronchodilator reversibility in untreated adult patients with newly diagnosed asthma
Authors: Hsiao Yi-Han , Lin Yu-Jung , Jeng Tien-Hsin , Su Kang-Cheng , Ko Hsin-Kuo , Yang Sheau-Ning , Perng Diahn-Warng , Kou Yu Ru
Published: June 2022

Background:

Identifying positive bronchodilator reversibility (BDR) helps the diagnosis of asthma. However, not all patients can adequately perform the forced expiration during the spirometry test. An alternative test is required. Impulse oscillometry (IOS) is an effort-independent technique that enables the measurement of lung mechanics during quiet tidal breathing. We investigated the potentiality of IOS to evaluate BDR in untreated adult patients with newly diagnosed asthma (UAPNDS).

Methods:

All UAPNDS (aged 20–80 years) who never smoke and underwent IOS and spirometry before and after salbutamol inhalation at their initial visit to the hospital from March 22, 2017, to December 31, 2019, were identified. A total of 323 patients were enrolled. Data from the medical record, including demographic characteristics, laboratory examination, spirometric data, and IOS parameters, were retrospectively reviewed. The associations of parameters with the positive BDR and the performance of parameters in predicting the positive BDR were evaluated by statistical methods.

Results:

Patients (n = 323) had a median age of 64 years and were mostly female (67.5%). Several variables, including serum total immunoglobulin level, blood eosinophil counts, blood eosinophil percentage (%), and two IOS parameters, were found to be different between the positive (n = 93) and negative BDR (n = 230) groups. Multivariate logistic regression analyses after adjustment by cofactors revealed that the percentage change of the area under the reactance curve between 5 Hz and resonant frequency [ΔAx (%)] after salbutamol inhalation was the only independent factor for the positive BDR. The area under the receiver operating characteristic curve of ΔAx (%) in predicting the positive BDR was 0.614 (p = 0.0013), and its optimal cutoff value was −53.8% (sensitivity, 39.78% and specificity, 80.43%).

Conclusion:

In addition to spirometry, ΔAx (%), an IOS parameter, may serve as a novel indicator to evaluate BDR in UAPNDS.