bluuebunny/crossref_metadata_2025 huggingface dataset:
Generalized local ansatz for scale-dependent primordial non-Gaussianities and future galaxy surveys
Authors: Yamauchi Daisuke , Yokoyama Shuichiro , Takahashi Tomo
Published: October 2021

We revisit a possible scale-dependence of local-type primordial non-Gaussianities induced by super-horizon evolution of scalar field perturbations. We develop the formulation based on δN formalism and derive the generalized form of the local-type bispectrum and also trispectrum which allows us to implement the scale-dependence and suitably compare model prediction with observational data. We propose simple but phenomenologically meaningful expressions, which encompass the information of a wide range of physically motivated models. We also formulate a large-scale power spectrum and bispectrum of biased objects in the presence of the scale-dependent primordial non-Gaussianities. We perform the Fisher analysis for future galaxy surveys and give the projected constraints on the parameters of the generalized local-form of primordial non-Gaussianities.
In Planta Cell Wall Engineering: From Mutants to Artificial Cell Walls
Authors: Yoshida Kouki , Sakamoto Shingo , Mitsuda Nobutaka
Published: October 2021

To mitigate the effects of global warming and to preserve the limited fossil fuel resources, an increased exploitation of plant-based materials and fuels is required, which would be one of the most important innovations related to sustainable development. Cell walls account for the majority of plant dry biomass and so is the target of such innovations. In this review, we discuss recent advances in in planta cell wall engineering through genetic manipulations, with a focus on wild-type-based and mutant-based approaches. The long history of using a wild-type-based approach has resulted in the development of many strategies for manipulating lignin, hemicellulose and pectin to decrease cell wall recalcitrance. In addition to enzyme-encoding genes, many transcription factor genes important for changing relevant cell wall characteristics have been identified. Although mutant-based cell wall engineering is relatively new, it has become feasible due to the rapid development of genome-editing technologies and systems biology–related research; we will soon enter an age of designed artificial wood production via complex genetic manipulations of many industrially important trees and crops.
miR169q and NUCLEAR FACTOR YA8 enhance salt tolerance by activating PEROXIDASE1 expression in response to ROS
Authors: Xing Lijuan , Zhu Ming , Luan Mingda , Zhang Min , Jin Lian , Liu Yueping , Zou Junjie , Wang Lei , Xu Miaoyun
Published: October 2021

Salt stress signiﬁcantly reduces the productivity of crop plants including maize (Zea mays). miRNAs are major regulators of plant growth and stress responses, but few studies have examined the potential impacts of miRNAs on salt stress responses in maize. Here, we show that ZmmiR169q is responsive to stress-induced ROS signals. After detecting that salt stress and exogenous H2O2 treatment reduced the accumulation of ZmmiR169q, stress assays with transgenic materials showed that depleting ZmmiR169q increased seedling salt tolerance whereas overexpressing ZmmiR169q decreased salt tolerance. Helping explain these observations, we found that ZmmiR169q repressed the transcript abundance of its target NUCLEAR FACTOR YA8 (ZmNF-YA8), and overexpression of ZmNF-YA8 in maize improved salt tolerance, specifically by transcriptionally activating the expression of the efficient antioxidant enzyme PEROXIDASE1. Our study reveals a direct functional link between salt stress and a miR169q-NF-YA8 regulatory module that plants use to manage ROS stress and strongly suggests that ZmNF-YA8 can be harnessed as a resource for developing salt-tolerant crop varieties.
Strigo-D2—a bio-sensor for monitoring spatio-temporal strigolactone signaling patterns in intact plants
Authors: Song Changzheng , Zhao Jiao , Guichard Marjorie , Shi Dongbo , Grossmann Guido , Schmitt Christian , Jouannet Virginie , Greb Thomas
Published: October 2021

Strigolactones (SLs) are a class of plant hormones that mediate biotic interactions and modulate developmental programs in response to endogenous and exogenous stimuli. However, a comprehensive view on the spatio-temporal pattern of SL signaling has not been established, and tools for a systematic in planta analysis do not exist. Here, we present Strigo-D2, a genetically encoded ratiometric SL signaling sensor that enables the examination of SL signaling distribution at cellular resolution and is capable of rapid response to altered SL levels in intact Arabidopsis (Arabidopsis thaliana) plants. By monitoring the abundance of a truncated and fluorescently labeled SUPPRESSOR OF MAX2 1-LIKE 6 (SMXL6) protein, a proteolytic target of the SL signaling machinery, we show that all cell types investigated have the capacity to respond to changes in SL levels but with very different dynamics. In particular, SL signaling is pronounced in vascular cells but low in guard cells and the meristematic region of the root. We also show that other hormones leave Strigo-D2 activity unchanged, indicating that initial SL signaling steps work in isolation from other hormonal signaling pathways. The specificity and spatio-temporal resolution of Strigo-D2 underline the value of the sensor for monitoring SL signaling in a broad range of biological contexts with highly instructive analytical depth.
Can Central Sensitization After Injury Persist as an Autonomous Pain Generator? A Comprehensive Search for Evidence
Authors: Brazenor Graeme A , Malham Gregory M , Teddy Peter J
Published: October 2021

Objective

To conduct a comprehensive search for evidence with regard to whether central sensitization after an injury can act as a persistent autonomous pain generator after the inducing injury has healed.

Methods

We searched Medline on PubMed and the Cochrane Library, screening 3,572 abstracts, from which 937 full-text articles were obtained, with 186 of these discarded as irrelevant to the question being posed. The remaining 751 articles were studied for evidence.

Results

Fourteen publications were judged to provide weak evidence for the hypothesis of central sensitization as a persisting autonomous pain generator, but none addressed the question directly. No strong evidence for the affirmative answer was found. Sixty-one publications were judged to provide weak evidence for a negative answer, and ten were judged to provide strong evidence. Unexpectedly, serious weaknesses were discovered in the literature underpinning the validity of the clinical diagnosis of central sensitization in humans: 1) inappropriate extrapolation, in many publications, of laboratory animal data to humans; 2) failure to demonstrate the absence of peripheral pain generators that might be perpetuating central sensitization; and 3) many factors now shown to confound what is being measured by quantitative sensory testing, conditioned pain modulation, and the Central Sensitization Inventory.

Conclusions

We found no evidence proving that central sensitization can persist as an autonomous pain generator after the initiating injury has healed. Our review has also shown that the evidential basis for the diagnosis of central sensitization in individual patients is seriously in question.
Tensor network approach to two-dimensional Yang–Mills theories
Authors: Fukuma Masafumi , Kadoh Daisuke , Matsumoto Nobuyuki
Published: October 2021

We propose a novel tensor network representation for two-dimensional Yang–Mills theories with arbitrary compact gauge groups. In this method, tensor indices are given directly by group elements with no direct use of the character expansion. We apply the tensor renormalization group method to this tensor network for SU(2) and SU(3), and find that the free energy density and the energy density are accurately evaluated. We also show that the singular value decomposition of a tensor has a group-theoretic structure and can be associated with the character expansion.
Evidence on Job Search Models from a Survey of Unemployed Workers in Germany
Authors: DellaVigna Stefano , Heining Jörg , Schmieder Johannes F , Trenkle Simon
Published: October 2021

The job-finding rate of unemployment insurance (UI) recipients declines in the initial months of unemployment and then exhibits a spike at the benefit exhaustion point. A range of theoretical explanations have been proposed, but those are hard to disentangle using data on job finding alone. To better understand the underlying mechanisms, we conducted a large text-message-based survey of unemployed workers in Germany. We surveyed 6,349 UI recipients twice a week for four months about their job search effort. The panel structure allows us to observe how search effort evolves in individuals over the unemployment spell. We provide three key facts: (i) search effort is flat early on in the UI spell, (ii) search effort exhibits an increase up to UI exhaustion and a decrease thereafter, (iii) UI recipients do not appear to time job start dates to coincide with the UI exhaustion point. A standard search model with unobserved heterogeneity struggles to explain the second fact, and a model of storable offers is not consistent with the third fact. The patterns are well captured by a model of reference-dependent job search or by a model with duration dependence in search cost.
Patent Screening, Innovation, and Welfare
Authors: Schankerman Mark , Schuett Florian
Published: October 2021

Critics claim that patent screening is ineffective, granting low-quality patents that impose unnecessary social costs. We develop an integrated framework, involving patent office examination, fees, and endogenous validity challenges in the courts, to study patent screening both theoretically and quantitatively. In our model, some inventions require the patent incentive while others do not, and asymmetric information creates a need for screening. We show that the endogeneity of challenges implies that courts, even if perfect, cannot solve the screening problem. Simulations of the model, calibrated on U.S. data, indicate that screening is highly imperfect, with almost half of all patents issued on inventions that do not require the patent incentive. While we find that the current patent system generates positive social value, intensifying examination would yield large welfare gains. The social value of the patent system would also be larger if complemented by antitrust limits on licensing.
Body composition in long-standing juvenile dermatomyositis: associations with disease activity, muscle strength and cardiometabolic measures
Authors: Witczak Birgit Nomeland , Bollerslev Jens , Godang Kristin , Schwartz Thomas , Flatø Berit , Molberg Øyvind , Sjaastad Ivar , Sanner Helga
Published: October 2021

Objective

To compare body composition parameters in patients with long-standing JDM and controls and to explore associations between body composition and disease activity/inflammation, muscle strength, health-related quality of life (HRQoL) and cardiometabolic measures.

Methods

We included 59 patients (median disease duration 16.7 y; median age 21.5 y) and 59 age- and sex-matched controls in a cross-sectional study. Active and inactive disease were defined by the PRINTO criteria. Body composition was assessed by total body DXA, inflammation by high-sensitivity CRP (hs-CRP) and cytokines, muscle strength by the eight-muscle manual muscle test, HRQoL by the 36-item Short Form Health Survey physical component score and cardiometabolic function by echocardiography (systolic and diastolic function) and serum lipids.

Results

DXA analyses revealed lower appendicular lean mass index (ALMI; reflecting limb skeletal muscle mass), higher body fat percentage (BF%) and a higher android fat:gynoid fat (A:G) ratio (reflecting central fat distribution) in patients than controls, despite similar BMI. Patients with active disease had lower ALMI and higher BF% than those with inactive disease; lower ALMI and higher BF% were associated with inflammation (elevated monocyte attractant protein-1 and hs-CRP). Lower ALMI was associated with reduced muscle strength, while higher BF% was associated with impaired HRQoL. Central fat distribution (higher A:G ratio) was associated with impaired cardiac function and unfavourable serum lipids.

Conclusion

Despite normal BMI, patients with JDM, especially those with active disease, had unfavourable body composition, which was associated with impaired HRQoL, muscle strength and cardiometabolic function. The association between central fat distribution and cardiometabolic alterations is a novel finding in JDM.
Mitochondrial DNA genetic variants are associated with systemic lupus erythematosus susceptibility, glucocorticoids efficacy and prognosis
Authors: Teng Ying , Yan Zi-Ye , Wang Lin-Lin , Wang Yu-Hua , Zhang Ting-Yu , Li Zhen , Liu Shuang , Cai Jing , Chen Yang-Fan , Li Mu , Liu Sheng-Xiu , Xu Zhou-Zhou , Huang Hai-Liang , Wang Fang , Pan Fa-Ming , Pan Hai-Feng , Su Hong , Zou Yan-Feng
Published: October 2021

Objective

To investigate the associations of mitochondrial DNA (mtDNA) genetic variants with SLE susceptibility, glucocorticoid (GC) efficacy and prognosis.

Methods

Our study was done in two stages. First, we performed whole mitochondrial genome sequencing in 100 patients and 100 controls to initially screen potential mtDNA variants associated with disease and GC efficacy. Then, we validated the results in an independent set of samples. In total, 605 SLE patients and 604 normal controls were included in our two-stage study. A two-stage efficacy study was conducted in 512 patients treated with GCs for 12 weeks. We also explored the association between mtDNA variants and SLE prognosis.

Results

In the combined sample, four mtDNA variants (A4833G, T5108C, G14569A, CA514-515-) were associated with SLE susceptibility (all PBH < 0.05). We confirmed that T16362C was related to efficacy of GCs (PBH = 0.014). Significant associations were detected between T16362C and T16519C and the efficacy of GCs in females with SLE (PBH < 0.05). In the prognosis study, variants A4833G (PBH = 0.003) and G14569A (PBH = 9.744 × 10−4) substantially increased SLE relapse risk. Female patients harbouring variants T5108C and T16362C were more prone to relapse (PBH < 0.05). Haplotype analysis showed that haplogroup G was linked with SLE susceptibility (PBH = 0.001) and prognosis (PBH = 0.013). Moreover, mtDNA variant–environment interactions were observed.

Conclusion

We identified novel mtDNA genetic variants that were associated with SLE susceptibility, GC efficacy, and prognosis. Interactions between mtDNA variants and environmental factors were related to SLE risk and GC efficacy. Our findings provide important information for future understanding of the occurrence and development of SLE.
Population-based incidence and time to classification of systemic lupus erythematosus by three different classification criteria: a Lupus Midwest Network (LUMEN) study
Authors: Duarte-García Alí , Hocaoglu Mehmet , Osei-Onomah Shirley-Ann , Dabit Jesse Y , Giblon Rachel E , Helmick Charles G , Crowson Cynthia S
Published: October 2021

Objective

To estimate the incidence and time-to-classification of SLE by the 1997 ACR (ACR97) criteria, the SLICC criteria, and the European Alliance of Associations for Rheumatology/ACR (EULAR/ACR) criteria.

Methods

We identified all incident SLE cases from 2000–2018 in the well-defined Olmsted County population. Clinical data included in the ACR97, SLICC and EULAR/ACR criteria were manually abstracted from medical records. All incident cases met at least one of the three classification criteria. Time-to-classification was estimated from the first documented lupus-attributable disease manifestation to the time of criteria fulfilment by each of the three definitions. Annual incidence rates were age or age/sex adjusted to the 2000 US population.

Results

Of 139 incident cases there were 126 cases by the EULAR/ACR criteria, corresponding to an age/sex-adjusted incidence of 4.5 per 100 000 population (95% CI: 3.7, 5.2). The age/sex-incidence was higher than that of the SLICC criteria (113 cases; 4.0 per 100 000 [95% CI: 3.3, 4.7], P = 0.020) and the ACR97 (92 cases; 3.3 per 100 000 [95% CI: 2.6, 3.9], P < 0.001). The median time from first disease manifestation to criteria fulfilment was shorter for the EULAR/ACR criteria (29.4 months) than the ACR97 criteria (47.0 months, P < 0.001) and similar to the SLICC criteria (30.6 months, P = 0.83).

Conclusion

The incidence of SLE was higher by the EULAR/ACR criteria compared with the ACR97 and the SLICC criteria, and the EULAR/ACR criteria classified patients earlier that the ACR97 criteria but similar to the SLICC criteria.
Sex differences in the behavioral inhibition system and ventromedial prefrontal cortex connectivity
Authors: Jung Wi Hoon , Lee Tae Young , Kim Minah , Lee Junhee , Oh Sanghoon , Lho Silvia Kyungjin , Moon Sun-Young , Kwon Jun Soo
Published: October 2021

The reinforcement sensitivity theory proposes brain–behavioral systems that underlie individual differences in sensitivity to punishment and reward. Such trait sensitivity is assessed using the behavioral inhibition/activation system (BIS/BAS) scales. Recent studies have reported sex-linked neuroanatomical correlates of the BIS/BAS, especially in the regions belonging to the valuation and salience networks that are associated with the representation of subjective value (SV), whereas less effort has been focused on investigating the neurofunctional aspects associated with sex differences in the BIS/BAS. We tested whether functional connectivity (FC) of the regions associated with the representation of SV mediates the relationship between sex and BIS sensitivity in healthy young adults by using resting-state functional magnetic resonance imaging data and self-reported BIS/BAS measures. Compared with males, females had heightened BIS sensitivity and increased FC between the ventromedial prefrontal cortex (vmPFC) seed and posterior parietal areas; this FC mediated the impact of sex on BIS sensitivity. Given that the observed vmPFC FC maps are considered part of the default-mode network, which is involved in ruminative processes, and that the BIS is associated with rumination and negative affect, our results may have implications for psychiatric disorders such as depression and anxiety, both of which have high incidence in females.
Using factorial mediation analysis to better understand the effects of interventions
Authors: Strayhorn Jillian C , Collins Linda M , Brick Timothy R , Marchese Sara H , Pfammatter Angela Fidler , Pellegrini Christine , Spring Bonnie
Published: October 2021

To improve understanding of how interventions work or why they do not work, there is need for methods of testing hypotheses about the causal mechanisms underlying the individual and combined effects of the components that make up interventions. Factorial mediation analysis, i.e., mediation analysis applied to data from a factorial optimization trial, enables testing such hypotheses. In this commentary, we demonstrate how factorial mediation analysis can contribute detailed information about an intervention’s causal mechanisms. We briefly review the multiphase optimization strategy (MOST) and the factorial experiment. We use an empirical example from a 25 factorial optimization trial to demonstrate how factorial mediation analysis opens possibilities for better understanding the individual and combined effects of intervention components. Factorial mediation analysis has important potential to advance theory about interventions and to inform intervention improvements.
EffectorP 3.0: Prediction of Apoplastic and Cytoplasmic Effectors in Fungi and Oomycetes
Authors: Sperschneider Jana , Dodds Peter N.
Published: October 2021

Many fungi and oomycete species are devasting plant pathogens. These eukaryotic filamentous pathogens secrete effector proteins to facilitate plant infection. Fungi and oomycete pathogens have diverse infection strategies and their effectors generally do not share sequence homology. However, they occupy similar host environments, either the plant apoplast or plant cytoplasm, and, therefore, may share some unifying properties based on the requirements of these host compartments. Here, we exploit these biological signals and present the first classifier (EffectorP 3.0) that uses two machine-learning models: one trained on apoplastic effectors and one trained on cytoplasmic effectors. EffectorP 3.0 accurately predicts known apoplastic and cytoplasmic effectors in fungal and oomycete secretomes with low estimated false-positive rates of 3 and 8%, respectively. Cytoplasmic effectors have a higher proportion of positively charged amino acids, whereas apoplastic effectors are enriched for cysteine residues. The combination of fungal and oomycete effectors in training leads to a higher number of predicted cytoplasmic effectors in biotrophic fungi. EffectorP 3.0 expands predicted effector repertoires beyond small, cysteine-rich secreted proteins in fungi and RxLR-motif containing secreted proteins in oomycetes. We show that signal peptide prediction is essential for accurate effector prediction, because EffectorP 3.0 recognizes a cytoplasmic signal also in intracellular, nonsecreted proteins.

[Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Coinfection of Tomato Plants withTomato yellow leaf curl virusandTomato chlorosis virusAffects the Interaction with Host and Whiteflies
Authors: Ontiveros Irene , López-Moya Juan José , Díaz-Pendón Juan Antonio
Published: October 2021

Susceptible plants infected by single or multiple viruses can differ in symptoms and other alterations influencing virus dissemination. Furthermore, behavior of viruliferous vectors may be altered in certain cases to favor acquisition and inoculation processes conductive to virus transmission. We explored single and mixed infections frequently occurring in tomato crops, caused by two viruses transmitted by the whitefly Bemisia tabaci: Tomato yellow leaf curl virus (TYLCV, Begomovirus, Geminiviridae) and Tomato chlorosis virus (ToCV, Crinivirus, Closteroviridae). Coinfection of both viruses in tomato plants showed more severe symptoms at late stages compared with single infections, although at earlier stages the interaction began with attenuation. This asymmetric synergism correlated with the dynamics of ToCV accumulation and expression of the salicylic acid responsive gene PR-P6. Visual and olfactory cues in whitefly preference were evaluated under controlled conditions in choice assays, testing viruliferous and nonviruliferous adult whiteflies. In experiments allowing both visual and olfactory cues, whiteflies preferred symptomatic leaflets from plants infected either with TYLCV alone or with TYLCV and ToCV, over those infected with ToCV alone or noninfected leaflets, suggesting that TYLCV drove host selection. Odor cues tested in Y-tube olfactometer assays showed neutral effects on whiteflies’ preference, and bioassays comparing the attractiveness of colored sticky cards confirmed preference for sectors colored to mimic TYLCV symptomatic leaves compared with asymptomatic leaves. Our results show that the presence of coinfecting viruses affect the host and could alter the behavior of insect vectors.
The acceptability of a novel procedure service run by PAs and NPs
Authors: Kim Nancy , Herbert Tara , Marranca Sheyla , Bergman Eric , Castillo Ronald , Romano Lindsey , Heacock Daniel , Cushing William
Published: October 2021

Background:

Hospitalist physicians are performing fewer procedures because of multiple reasons, including expanded responsibilities beyond their patient panel. A procedure service that offloads hospitalists could expedite these necessary services. An opportunity exists for physician assistants (PAs) and NPs to fill this gap.

Objective:

To describe the implementation of a PA- and NP-run procedure service at a large academic hospital.

Methods:

This is a retrospective cohort study of procedures by the procedure service at one institution from 2015 to 2019.

Results:

Over 5 years, 7,002 procedures were performed, with requests increasing over time. The most frequent procedures were venous access, lumbar puncture, paracentesis, and placement of nasogastric or nasojejunal tubes. Requesting services included hospitalists and residents from internal medicine, surgery, and neurology.

Conclusions:

A PA- and NP-run procedure service is well accepted at a large academic hospital despite the lack of involvement by attending physicians. Future directions are focused on augmenting coverage and procedures offered.
Financial analysis of PA lifetime earnings and debt
Authors: Bruza-Augatis Mirela , Hooker Roderick S. , Coombs Jennifer M.
Published: October 2021

This economic analysis of physician assistant/associate (PA) career earnings sought to assess the increasing effect of student debt, its potential effect on job selection, and whether such financial obligations may influence graduates to select higher-paying specialties. The model was a 30-year-old newly graduated PA who begins working in family medicine. A simulation included wages, student debt, national household expenditures, and real estate statistics. The scenario consisted of a high and middle cost of living in two geographic areas, a family of four, and an average life expectancy. Using a validated economic program, a series of calculations produced the financial effect on moderate-income levels and expenditures based on median PA earnings. On the deficit side is education debt, loan repayment, financing a house, college for children, retirement, and discretionary spending. Weighted variables were used to maximize the sensitivity effect of the simulation. A Monte Carlo probabilistic program predicted the likely outcome of income, expenses, inflation, and investments. Furthermore, the lifetime earnings of a PA who retires at age 67 years and lives to age 85 years falls in the 75th percentile of income of all Americans. The conclusion is that a full-time PA career in any clinical role is as economically rewarding as it is satisfying.
Extended High-frequency Hearing Impairment Despite a Normal Audiogram: Relation to Early Aging, Speech-in-noise Perception, Cochlear Function, and Routine Earphone Use
Authors: Mishra Srikanta K. , Saxena Udit , Rodrigo Hansapani
Published: October 2021

Objectives:

Humans can hear up to 20 kHz. Emerging evidence suggests that hearing in the extended high frequencies (EHFs; >8 kHz) contributes to speech perception in noise. The objective of the present study was to describe the features of EHF hearing impairment in young adults with normal standard audiograms (0.25–8 kHz). Specifically, the study goals were to: (1) characterize the EHF hearing impairment and identify potential risk factors; (2) elucidate the age-related changes in EHF hearing; (3) determine the effect of EHF hearing impairment on speech-in-noise recognition; and (4) examine the extent to which EHF hearing impairment influences cochlear functioning in the standard frequencies.

Design:

Hearing thresholds at standard frequencies and EHFs (10, 12.5, 14, and 16 kHz), and speech recognition thresholds (SRTs) using digit triplets in multi-talker babble were measured in both ears from 222 participants (19–38 years; n = 444 ears) with normal audiograms (≤20 dB HL at standard frequencies). Test–retest measurement of hearing thresholds was obtained in a subset of 50 participants (100 ears), and clinical distortion product otoacoustic emissions (f
2 frequency = 2, 3, 4, and 5 kHz) were recorded in 49 participants (98 ears).

Results:

Forty-two of 222 participants had EHF hearing impairment (>20 dB HL for at least one EHF in either ear). Only seven individuals with EHF impairment had significant case history and/or listening-in-noise complaints. A breakpoint in the threshold-age function was observed for the EHFs for males but not for females. Linear mixed models revealed a significant effect of age, pure-tone averages for speech frequencies (0.5, 1, 2, and 4 kHz), and EHFs and group (NH versus EHF hearing impairment) independent of each other on the SRTs. Individuals with EHF hearing impairment had less measurable emissions and when present, had a lower magnitude of otoacoustic emissions relative to NH controls. There was no difference in hearing thresholds, SRTs, or otoacoustic emissions between earphone users and nonusers.

Conclusions:

The hearing thresholds for the EHFs exhibit signs of early auditory aging. Age-related deterioration in auditory function can be observed in the third decade of human life. A breakpoint in the threshold-age function suggests that rapid aging processes are operational at a relatively younger age (21 years) for males. The audibility of EHFs contributes to speech-in-noise recognition. EHF hearing impairment independent of age and speech frequencies can affect speech-in-noise recognition. Reduced distortion product otoacoustic emissions in the standard frequencies may suggest preclinical cochlear degeneration in individuals with EHF hearing impairment.
Impact of the 2018 Society of Critical Care Medicine Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Guidelines on Nonopioid Analgesic Use and Related Outcomes in Critically Ill Adults After Major Surgery
Authors: Sutton Spencer , McCrobie Trevor R. , Kovacevic Mary R. , Dube Kevin M. , Szumita Paul M. , Herod Kyle , Bezio Aaron , Choi Hannah , Duprey Matthew S. , Zeballos Jose , Devlin John W.
Published: October 2021

We compared ICU nonopioid analgesic use, opioid use, and pain before and after Pain, Agitation/Sedation, Delirium, Immobility, and Sleep guideline publication at one academic center among critically ill adults receiving an opioid infusion and greater than or equal to 24 hours of mechanical ventilation after major surgery. The 2017 (n = 77) and 2019 (n = 57) groups were similar at baseline. The 2019 (vs 2017) patients were more likely to receive scheduled IV/oral acetaminophen (84% vs 69%; p = 0.05), less likely to receive a lidocaine patch (33% vs 50%; p = 0.05), and just as likely to receive ketamine (4% vs 3%; p = 1.0), an nonsteroidal anti-inflammatory drug (7% vs 3%; p = 0.26), or gabapentin/pregabalin (16% vs 9%; p = 0.23). Daily average opioid exposure (in IV morphine milligram equivalent) was not different (70 [42–99] [2017] vs 78 mg [49–109 mg]; p = 0.94). The 2019 (vs 2017) group spent more ICU days with severe pain (p = 0.04). At our center, Pain, Agitation/Sedation, Delirium, Immobility, and Sleep guideline publication had little effect on nonopioid analgesic or opioid prescribing practices in critically ill surgical adults.
Juvenile open angle glaucoma: current diagnosis and management
Authors: Ciociola Elizabeth C. , Klifto Meredith R.
Published: October 2021

Purpose of review

The aim of this article is to summarize up-to-date research on the diagnosis and management of juvenile open-angle glaucoma (JOAG).

Recent findings

JOAG can be subclassified into four clinical phenotypes, and faster myopic shift is a risk factor for disease progression. Vessel density is associated with structural damage and worsening visual acuity in JOAG and can be monitored with optical coherence tomography angiography. Genetic studies have revealed molecular causes of JOAG including variants in CPAMD8, MYOC, and CYP1B1. Tube shunt surgeries as well as gonioscopy-assisted transluminal trabeculotomy have been shown to be successful in JOAG.

Although genetic advances may improve future screening, intraocular pressure monitoring and fundoscopic exam remain the current mainstay of diagnosis. Medical treatment alone for JOAG is typically insufficient with patients requiring surgical management. Selective laser trabeculoplasty may delay or decrease the need for surgery. Trabeculectomy has traditionally been shown to be effective in JOAG, but tube shunt surgery and microinvasive glaucoma surgery are effective alternatives.
American Medical Society for Sports Medicine Position Statement: Principles for the Responsible Use of Regenerative Medicine in Sports Medicine
Authors: Finnoff Jonathan T. , Awan Tariq M. , Borg-Stein Joanne , Harmon Kimberly G. , Herman Daniel C. , Malanga Gerard A. , Master Zubin , Mautner Kenneth R. , Shapiro Shane A.
Published: October 2021

Many sports medicine physicians are currently considering introducing regenerative medicine into their practice. Regenerative medicine and the subclassification of orthobiologics are a complicated topic and have produced widely varying opinions. Although there is concern by government regulators, clinicians, scientists, patient advocacy organizations, and the media regarding the use of regenerative medicine products, there is also excitement about the potential benefits with growing evidence that certain regenerative medicine products are safe and potentially efficacious in treating musculoskeletal conditions. Sports medicine physicians would benefit from decision-making guidance about whether to introduce orthobiologics into their practice and how to do it responsibly. The purpose of this position statement is to provide sports medicine physicians with information regarding regenerative medicine terminology, a brief review of basic science and clinical studies within the subclassification of orthobiologics, regulatory considerations, and best practices for introducing regenerative medicine into clinical practice. This information will help sports medicine physicians make informed and responsible decisions about the role of regenerative medicine and orthobiologics in their practice.
Bulging of the Oval Window in Common Cavity Deformity: A Possible Predictor of Meningitis
Authors: Manara Renzo , Avato Irene , Uberti Andrea , Trevisi Patrizia , Bovo Roberto , Martini Alessandro , Brotto Davide ,   EU.COM Group, Berettini Stefano , Canzi Pietro , Ciorba Andrea , Cristofari Eliana , Cuda Domenico , Della Volpe Antonio , Frau Giuseppe Nicolò , Genovese Elisabetta , Marsella Pasquale , Murri Alessandra , Sorrentino Flavia , Vincenti Vincenzo , Zanetti Diego
Published: October 2021

Objective:

To investigate the prevalence-rate of oval window bulging in the common cavity and its association with bacterial meningitis.

Patients:

CT and clinical files of 29 children with preliminary diagnosis of common cavity deformity were collected from 13 Italian centers.

Intervention:

A retrospective case review study was conducted with a centralized evaluation of the temporal bone CT imaging was performed at Azienda Ospedale – Università Padova, Padova, Italy.

Main Outcome Measure:

Diagnosis of common cavity was reviewed; in addition, a fluid protrusion into the middle-ear cavity through the oval window at CT imaging was considered as oval window bulging. Its association with the history of bacterial meningitis was investigated.

Results:

Common cavity deformity was confirmed in 14/29 children (mean-age 11.4 ± 3.8; age-range 5–20; nine females) referred with this diagnosis. In 7/14 patients, the common cavity deformity was bilateral (i.e., 21 common cavities). Oval window bulging was found in 3/19 common cavities (concomitant middle-ear effusive otitis hampered the evaluation in two cases), while the internal acoustic meatus fundus was defective in 10/21 cases. History of bacterial meningitis was found in three children (21%) and two of them had oval window bulging at CT. In the case unrelated to oval window bulging, meningitis occurred late at the age of 12 during acute otitis contralateral to common cavity deformity (ipsilaterally to incomplete partition type 1).

Conclusion:

Patients harboring common cavity deformity have a high risk of meningitis in their first years of life. Oval window bulging seems to be associated with a higher risk of meningitis. This information might be important for appropriate surgical planning.
The potential of microbiome replacement therapies for Clostridium difficile infection
Authors: Buckley Anthony M. , Moura Ines B. , Wilcox Mark H.
Published: October 2021

Purpose of review

There is a paradox when treating Clostridium difficile infection (CDI); treatment antibiotics reduce C. difficile colonization but cause further microbiota disruption and can lead to recurrent disease. The success of faecal microbiota transplants (FMT) in treating CDI has become a new research area in microbiome restorative therapies but are they a viable long-term treatment option?

Recent findings

C. difficile displays metabolic flexibility to use different nutritional sources during CDI. Using microbiome therapies for the efficient restoration of bile homeostasis and to reduce the bioavailability of preferential nutrients will target the germination ability of C. difficile spores and the growth rate of vegetative cells. Several biotechnology companies have developed microbiome therapeutics for treating CDI, which are undergoing clinical trials.

There is confidence in using restorative microbiome therapies for treating CDI after the demonstrated efficacy of FMT, where several biotechnology companies are aiming to supply what would be a ‘first in class’ treatment option. Efficient removal of C. difficile from the different intestinal biogeographies should be considered in future microbiome therapies. With the gut microbiota implicated in different diseases, more work is needed to assess the long-term consequences of microbiome therapies.
Diverse functions of long noncoding RNAs in acute myeloid leukemia: emerging roles in pathophysiology, prognosis, and treatment resistance
Authors: Mishra Srishti , Liu Jun , Chai Li , Tenen Daniel G.
Published: October 2021

Purpose of review

Advancements in the next-generation sequencing technologies have identified rare transcripts of long noncoding RNAs (lncRNAs) in the genome of cancers, including in acute myeloid leukemia (AML). The purpose of this review is to highlight the contribution of lncRNAs in AML pathogenesis, prognosis, and chemoresistance.

Recent findings

Several studies have recently reported that deregulated lncRNAs are novel key players in the development of AML and are associated with AML pathophysiology and may serve as prognostic indicators. A few aberrantly expressed lncRNAs that correlated with the recurrent genetic mutations in AML such as NPM1 and RUNX1 have recently been characterized. Moreover, a few lncRNAs in MLL-rearranged leukemia have been described. Additionally, the involvement of lncRNAs in AML chemoresistance has been postulated.

Investigating the functional roles of the noncoding regions including lncRNAs, may provide novel insights into the pathophysiology, refine the prognostic schema, and provide novel therapeutic treatment strategies in AML.
Preprint servers in lipidology: current status and future role
Authors: Perera Shehan D. , Muleta Ayana D. , Vlasschaert Caitlyn , Hegele Robert A.
Published: October 2021

Purpose of review

Preprinting, or the sharing of non-peer reviewed, unpublished scholarly manuscripts, has exploded in all fields of science and medicine over the past 5 years. We searched the literature and evaluated the posting and uptake of preprint publications in the field of lipidology in bioRxiv and medRxiv servers. We also contacted the editorial offices of 20 journals that publish original research in lipidology to gauge their policies on preprints.

Recent findings

All 20 journals contacted indicated that they accepted preprints. As of 31 May 2021, 473 and 231 preprints in lipidology had been submitted to bioRxiv and medRxiv, respectively. About half of all lipidology preprints were related to cardiovascular, cardiometabolic, and/or metabolic diseases (CVMD) and their risk factors, but at least 12 other disease categories were also represented. 16.9% and 1.08% of medRxiv and bioRxiv preprints, respectively, were related to coronavirus disease 2019 (COVID-19).

All identified journals accept lipidology themed preprints for submission, removing any barriers authors may have had regarding preprinting. Based on growing experience with preprinting, this trend should encourage increased community feedback and facilitate higher quality lipidology research in the future.
Longer Time Intervals From Symptom Onset to Diagnosis Affect the Overall Survival in Children With Acute Lymphoblastic Leukemia
Authors: Dai Qingkai , Liu Rui , Wang Yuefang , Ye Lei , Peng Luyun , Shi Rui , Guo Siqi , He Jiajing , Yang Hao , Zhang Ge , Jiang Yongmei
Published: October 2021

Background:

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Early diagnosis and timely treatment are essential for effective cancer control and have been widely analyzed in childhood cancer. However, few studies have described the time to diagnosis and treatment in children with ALL. This study investigated delays in diagnosis and treatment initiation and their impact on survival.

Methods:

This retrospective cohort study included 419 patients 0 to 14 years old at a tertiary hospital between 2011 and 2015. The optimal cutoff values for delays were determined by X-tile software. The Kaplan-Meier method and Cox regression models were used to evaluate the impact of delays on survival.

Results:

The median diagnosis, treatment, and total delays were 21 (interquartile range [IQR]: 11-35), 4 (IQR: 2-7), and 26 (IQR: 16-43) days, respectively. The results of multivariate analyses showed that diagnosis delay, risk stratification, and minimal residual disease level were independent predictors for treatment outcome in childhood ALL.

Conclusions:

These findings suggested that a longer time to diagnosis negatively affected the clinical outcome of childhood ALL. Reducing the time to diagnosis could help to improve survival in these patients.
Poststroke Bipolar Disorder
Authors: Saraiva Rodrigo , Proença Filipa , Gonçalves Maria , Sereijo Carolina , Barandas Rita , Coentre Ricardo , Levy Pedro
Published: October 2021

Various diseases that impact different systems and organs in the body may trigger manic episodes. Strokes are often associated with psychiatric symptoms, particularly depressive and, more rarely, manic. We herein report a case of bipolar disorder secondary to cerebrovascular disease in a 67-year-old man with no personal or family history of psychiatric illness who, at the age of 64, had a bilateral ischemic stroke in the middle cerebral artery territory. About 20 days after this stroke, he experienced a manic episode. Three years later, he experienced a second manic episode, with another hospitalization in a psychiatric ward. With this case, we intend to emphasize that, although rare, the diagnosis of mania after stroke should not be forgotten, and most important, one should be aware of the recurrence of affective episodes just as in non–medical-caused bipolar disorder.
Too Young for Clear Cell Sarcoma of the Kidney? A Case Report With Review of Differential Considerations
Authors: Russell Daniel Hugh
Published: October 2021

Clear cell sarcoma of the kidney (CCSK) comprises 3% of all childhood renal cancers. Accurate diagnosis is vital for appropriate therapy, which results in a 70% to 90% overall survival rate in this previously lethal tumor. Renowned for its ability to mimic and be mimicked by every other pediatric renal tumor, and even some extrarenal retroperitoneal tumors, CCSK has a unique metastatic pattern and molecular aberrations, as well as a generally consistent clinical presentation which is of great utility in the differential. A case of CCSK in a 4-month-old boy is presented, only the fifth case reported in a patient younger than 6 months.
Composite Renal Cell Carcinoma and Angiomyolipoma: A Rare Case and Possible Diagnostic Pitfalls
Authors: Dehner Carina , Sehn Jennifer
Published: October 2021

Angiomyolipomas are benign renal neoplasms commonly associated with tuberous sclerosis complex (Semin Diagn Pathol 1998;15(1):21–40). However, angiomyolipoma with concurrent renal cell neoplasia is very uncommon, with fewer than 50 reported cases. Even less common is direct admixture of renal cell carcinoma (RCC) and angiomyolipoma within 1 tumor mass, with only rare possible cases reported in the literature. A multi-institutional study of 36 cases of synchronous renal cell neoplasm and angiomyolipoma found that clear cell RCC was the most common concurrent cancer in patients with sporadic or tuberous sclerosis-associated angiomyolipoma; angiomyolipoma in these cases was incidental (Mod Pathol 2001;14(3):157–163). Here, we report the exceptionally uncommon occurrence of a composite RCC and angiomyolipoma, occurring as an intimate admixture within a single tumor mass.
Uterine Sarcoma With a Novel WWOX-NTRK2 Fusion in a Postmenopausal Woman With Li-Fraumeni–Like Syndrome: A Case That Expands the Spectrum of NTRK-Rearranged Uterine Tumors
Authors: Moh Michelle , Johnson Colin M. , Geurts Jennifer , Bishop Erin
Published: October 2021

NTRK-rearranged tumors are being increasingly recognized and targeted with TRK inhibitor therapies. A novel NTRK2 fusion–positive uterine sarcoma arising in a patient with Li-Fraumeni–like syndrome is described in this article.
Perioperative Safety of Combined Augmentation-Mastopexy
Authors: Ali Barkat , Choi EunHo Eunice , Barlas Venus , Nuzzi Laura , Morrell Nathan T. , Labow Brian , Borah Gregory , Taghinia Amir
Published: October 2021

Introduction

The safety of combined augmentation-mastopexy is controversial. This study evaluates a national database to analyze the perioperative safety of combined augmentation-mastopexy to either augmentation or mastopexy alone.

Methods

The American College of Surgeons National Surgical Quality Improvement Program database was queried to identify patients undergoing augmentation mammaplasty and mastopexy from 2005 to 2018. The patients were divided into the following groups: group I, augmentation; group II, mastopexy; group III, combined augmentation-mastopexy. Baseline characteristics and outcomes were compared. Outcomes were 30-day complications, reoperation, and readmission.

Results

We found 5868 (74.2%) augmentation only, 1508 (19.1%) mastopexy only and 534 (6.6%) combined augmentation-mastopexy cases. Mean operative time was highest among the combined group at 129 minutes compared with 127 minutes for mastopexy alone and 66 minutes for augmentation alone (P < 0.01). Rates of any complications and readmission were different among groups (0.8% vs 2.5% vs 1.5% respectively, P < 0.01 and 0.7% vs 1.5% vs 1.5% respectively, P = 0.049), whereas reoperation was not statistically different (1.2% vs 1.4% vs 1.5%, P = 0.75). The incidence of dehiscence (0.6%; P < 0.01) was highest in the combined group. Multivariable logistic regression analysis did not reveal an increased odds of complications, reoperation, or readmission with combined augmentation-mastopexy.

Conclusions

An evaluation of the nationwide cohort suggests that combined augmentation-mastopexy is a safe procedure in the perioperative period.