bluuebunny/crossref_metadata_2025 huggingface dataset:
Simultaneous multi-target ultrasound neuromodulation in freely-moving mice based on a single-element ultrasound transducer
Authors: He Jiaru , Zhu Yiyue , Wu Canwen , Wu Junwei , Chen Yan , Yuan Maodan , Cheng Zhongwen , Zeng Lvming , Ji Xuanrong
Published: January 2023

Objective. Ultrasound neuromodulation has become an emerging method for the therapy of neurodegenerative and psychiatric diseases. The phased array ultrasonic transducer enables multi-target ultrasound neuromodulation in small animals, but the relatively large size and mass and the thick cables of the array limit the free movement of small animals. Furthermore, spatial interference may occur during multi-target ultrasound brain stimulation with multiple micro transducers. Approach. In this study, we developed a miniature power ultrasound transducer and used the virtual source time inversion method and 3D printing technology to design, optimize, and manufacture the acoustic holographic lens to construct a multi-target ultrasound neuromodulation system for free-moving mice. The feasibility of the system was verified by in vitro transcranial ultrasound field measurements, in vivo dual-target blood-brain barrier (BBB) opening experiments, and in vivo dual-target ultrasound neuromodulation experiments. Main results. The developed miniature transducer had a diameter of 4.0 mm, a center frequency of 1.1 MHz, and a weight of 1.25 g. The developed miniature acoustic holographic lens had a weight of 0.019 g to generate dual-focus transcranial ultrasound. The ultrasonic field measurements’ results showed that the bifocal’s horizontal distance was 3.0 mm, the −6 dB focal spot width in the x-direction was 2.5 and 2.25 mm, and 2.12 and 2.24 mm in the y-direction. Finally, the in vivo experimental results showed that the system could achieve dual-target BBB opening and ultrasound neuromodulation in freely-moving mice. Significance. The ultrasonic neuromodulation system based on a miniature single-element transducer and the miniature acoustic holographic lens could achieve dual-target neuromodulation in awake small animals, which is expected to be applied to the research of non-invasive dual-target ultrasonic treatment of brain diseases in awake small animals.
Stranded assets and early closures in global coal mining under 1.5∘C
Authors: Hauenstein Christian
Published: January 2023

With the Glasgow Climate Pact 2021, the global community has committed explicitly to phasing down coal consumption. Yet the coal supply sector continues to develop new capacities, despite the risk of asset stranding. This article presents the first assessment of the implications of 1.5∘C mitigation pathways for the coal mining industry. Based on open coal mine data and a new version of the open coal sector model COALMOD-World, the prospects for individual coal mining regions and their risk of early mine closures and asset stranding are analyzed. Results show that global cumulative production capacity from operating thermal coal mines exceed the remaining consumption values for 2020 through 2050 by more than 50%. This supply-consumption discrepancy would hit Russia and the USA especially hard, causing the stranding of around 80% of operating capacities in each case. But the early closure of operating coal mines would affect all of the world’s major thermal coal producing regions, with most regions seeing more than three-fourths of their mine capacity closing early by 2030. Stranded assets from operating coal mines would total some USD2015 120 to 150 billion until 2050, with an additional USD2015 100 billion should currently proposed new coal mining projects be realized. If demand declines in accordance with 1.5∘C pathways, new coal mines or mine extensions would be redundant in all coal regions. Although the stranded asset value of mines is relatively small compared to that of the coal power plant sector, early closures would especially affect workers and local communities. Thus, efforts are urgently needed to ensure a just transition in coal mining regions and to address excess operating and proposed coal supply capacities that continue to fuel global warming.
Corrigendum: Reinterpreting local wisdom of Rumah Kaki Seribu as sustainable architecture (IOP Conf. Series: Earth and Environmental Science 907 (2021) 012018)
Authors: Prabaswara B C , Hariyanto L , Arifin L S
Published: January 2023

Please see Article PDF for corrigendum text.
One-step generation of core–shell biomimetic microspheres encapsulating double-layer cells using microfluidics for hair regeneration
Authors: Huang Junfei , Fu Danlan , Wu Xiaoqi , Li Yue , Zheng BoWen , Liu Zhen , Zhou Yi , Gan Yuyang , Miao Yong , Hu Zhiqi
Published: January 2023

Tissue engineering of hair follicles (HFs) has enormous potential in the treatment of hair loss. HF morphogenesis is triggered by reciprocal interactions between HF germ epithelial and mesenchymal layers. Here, a microfluidic-assisted technology is developed for the preparation of double aqueous microdroplets that entrap double-layer cells and growth factors to ultimately be used for hair regeneration. Mouse mesenchymal cells (MSCs) and epidermal cells (EPCs) are encapsulated in gelatin methacrylate (GelMA) cores and photo-curable catechol-grafted hyaluronic acid (HAD) shells to fabricate GelMA-MSC/HAD-EPC (G/HAD) microspheres. The findings show that the G/HAD microspheres exhibit ultrafast gelation, aqueous phase separation, superior biocompatibility, and favorable wet adhesion properties. G/HAD microspheres can also support cell proliferation and sustain growth factor release. These composite cell microspheres are capable of efficient HF generation upon transplantation into the dorsal dermis of nude mice. This finding facilitates the large-scale preparation of approximately 80 double-layer cell spheres per min. This simple double-layer cell sphere preparation approach is a promising strategy for improving current hair-regenerative medicine techniques and can potentially be applied along with other organoid techniques for extended applications.
An insight to current collapse in GaN HEMT and suppressing techniques
Authors: Kharei Pichingla , Baidya Achinta , Maity Niladri Pratap , Maity Reshmi
Published: January 2023

High Electron Mobility Transistors (HEMT) made of aluminum gallium nitride/gallium nitride (AlGaN/GaN) have become a major focus for all electronic devices based on gallium nitride due to its excellent system characteristics. AlGaN/GaN HEMTs have severe problems that degrade their performance and the drain current collapse (CC) is one of them. During switching operations, the CC increases the on-resistance (RON) leading to an increase in device loss and temperature. This review features the basics related to the CC in HEMT and its significance in performance degradation. This paper is concerned with the various advancements reported in recent years to suppress CC in GaN HEMT. Various techniques such as passivation, illumination, free-standing GaN substrate, GaN cap layer including high resistivity GaN cap layer, device structure, surface treatment and deposition techniques, buffer design, and field plates (FP) have been introduced by various researchers to combat CC. This review analysis will help researchers to employ suitable techniques in their HEMT design for future development.
City-scale analysis of annual ambient PM2.5 source contributions with the InMAP reduced-complexity air quality model: a case study of Madison, Wisconsin
Authors: Jackson Clara M , Holloway Tracey , Tessum Christopher W
Published: January 2023

Air pollution is highly variable, such that source contributions to air pollution can vary even within a single city. However, few tools exist to support city-scale air quality analyses, including impacts of energy system changes. We present a methodology that utilizes regional ground-based monitor measurements to scale speciation data from the Intervention Model for Air Pollution (InMAP), a national-scale reduced-complexity model. InMAP, like all air quality models, has biases in its concentration estimates; these biases may be pronounced when examining a single city. We apply the bias correction methodology to Madison, Wisconsin and estimate the relative contributions of sources to annual-average fine particulate matter (PM2.5), as well as the impacts of coal power plant retirements and electric vehicle (EV) adoption. We find that the largest contributors to ambient PM2.5 concentrations in Madison are on-road transportation, contributing 21% of total PM2.5; non-point sources, 16%; and electricity generating units, 14%. State-wide coal power plant closures from 2014 to 2020 and planned closures through 2025 were modeled to assess air quality benefits. The largest relative reductions are seen in areas north of Milwaukee (up to 7%), though population-weighted PM2.5 was reduced by only 3.8% across the state. EV adoption scenarios lead to a relative reduction in PM2.5 over Madison of 0.5% to 13.7% or a 9.3% reduction in total PM2.5 from a total replacement of light-duty vehicles (LDVs) with EVs. Similar percent reductions are calculated for population-weighted concentrations over Madison. Replacing 100% of LDVs with EVs reduced CO2 emissions by over 50%, highlighting the potential benefits of EVs to both climate and air quality. This work illustrates the potential of combining data from models and monitors to inform city-scale air quality analyses, supporting local decision-makers working to reduce air pollution and improve public health.
Comparative analysis of prebiotic effects of four oligosaccharides usingin vitrogut model: digestibility, microbiome, and metabolome changes
Authors: Cheon Seongwon , Kim Geonhee , Bae Jae-Han , Lee Dong Hyeon , Seong Hyunbin , Kim Da Hye , Han Jung-Sook , Lim Su-Youn , Han Nam Soo
Published: January 2023

Fructooligosaccharides (FOS), Ad-fructooligosaccharides (Ad-FOS), resistant maltodextrin (RMD), and maltooligosaccharides (MOS) are commercially available prebiotic oligosaccharides. In this study, the effects of prebiotics on the human gut microbial ecosystem were evaluated using an in vitro gut model. FOS and Ad-FOS showed tolerance to digestion, whereas RMD and MOS showed moderate digestion by digestive enzymes. In in vitro fecal fermentation, Bifidobacterium spp. increased in the following order: FOS, Ad-FOS, MOS, and RMD, whereas Bacteroides spp. increased in RMD medium. Bacteroides xylanisolvens exhibited cross-feeding by enabling the growth of other beneficial bacteria during co-culture in RMD medium. In metabolome analysis, total short-chain fatty acids (SCFAs) were highly produced in the following order: RMD, FOS, MOS, and Ad-FOS; acetate in the order of FOS, MOS/RMD, and Ad-FOS; butyrate in the order of RMD, MOS, FOS, and Ad-FOS; and propionate only in RMD. In addition, the conversion of betaine to trimethylamine was rarely affected in the following order: MOS, RMD, FOS, and Ad-FOS. Lastly, the four oligosaccharides inhibited the adhesion of pathogenic Escherichia coli to human epithelial cells to a similar extent. The comparative analysis results obtained in this study will provide comprehensive information of these substances to manufacturers and customers.
Acute pain management after thoracoscopic lung resection: a systematic review and explorative meta-analysis
Authors: Spaans Louisa N , Bousema Jelle E , Meijer Patrick , Bouwman R A (Arthur) , van den Broek Renee , Mourisse Jo , Dijkgraaf Marcel G W , Verhagen Ad F T M , van den Broek Frank J C
Published: January 2023

OBJECTIVES

Pain after thoracoscopic surgery may increase the incidence of postoperative complications and impair recovery. Guidelines lack consensus regarding postoperative analgesia. We performed a systematic review and meta-analysis to determine the mean pain scores of different analgesic techniques (thoracic epidural analgesia, continuous or single-shot unilateral regional analgesia and only systemic analgesia) after thoracoscopic anatomical lung resection.

METHODS

Medline, Embase and Cochrane databases were searched until 1 October 2022. Patients undergoing at least >70% anatomical resections through thoracoscopy reporting postoperative pain scores were included. Due to a high inter-study variability an explorative meta-analysis next to an analytic meta-analysis was performed. The quality of evidence has been evaluated using the Grading of Recommendations Assessment, Development and Evaluation system.

RESULTS

A total of 51 studies comprising 5573 patients were included. Mean 24, 48 and 72 h pain scores with 95% confidence interval on a 0–10 scale were calculated. Length of hospital stay, postoperative nausea and vomiting, additional opioids and the use of rescue analgesia were analysed as secondary outcomes. A common-effect size was estimated with an extreme high heterogeneity for which pooling of the studies was not appropriate. An exploratory meta-analysis demonstrated acceptable mean pain scores of Numeric Rating Scale <4 for all analgesic techniques.

CONCLUSIONS

This extensive literature review and attempt to pool mean pain scores for meta-analysis demonstrates that unilateral regional analgesia is gaining popularity over thoracic epidural analgesia in thoracoscopic anatomical lung resection, despite great heterogeneity and limitations of current studies precluding such recommendations.

PROSPERO REGISTRATION

ID number 205311
Systematic review of time lag between antibiotic use and rise of resistant pathogens among hospitalized adults in Europe
Authors: Poku Edith , Cooper Katy , Cantrell Anna , Harnan Sue , Sin Muna Abu , Zanuzdana Arina , Hoffmann Alexandra
Published: January 2023

Background

Antimicrobial resistance (AMR) causes substantial health and economic burden to individuals, healthcare systems and societies globally. Understanding the temporal relationship between antibiotic consumption and antibiotic resistance in hospitalized patients can better inform antibiotic stewardship activities and the time frame for their evaluation.

Objectives

This systematic review examined the temporal relationship between antibiotic use and development of antibiotic resistance for 42 pre-defined antibiotic and pathogen combinations in hospitalized adults in Europe.

Methods

Searches in MEDLINE, Embase, Cochrane Library and NIHR Centre for Reviews and Dissemination were undertaken from 2000 to August 2021. Pathogens of interest were Escherichia coli, Klebsiella pneumoniae, Streptococcus pneumoniae, Staphylococcus aureus, Enterococcus faecium, CoNS, Pseudomonas aeruginosa and Acinetobacter baumannii complex.

Results

Twenty-eight ecological studies and one individual-level study were included. Ecological studies were predominantly retrospective in design (19 studies) and of reasonable (20 studies) to high (8 studies) methodological quality. Of the eight pathogens of interest, no relevant data were identified for S. pneumoniae and CoNS. Across all pathogens, the time-lag data from the 28 ecological studies showed a similar pattern, with the majority of studies reporting lags ranging from 0 to 6 months.

Conclusions

Development of antibiotic resistance for the investigated antibiotic/pathogen combinations tends to occur over 0 to 6 months following exposure within European hospitals. This information could inform planning of antibiotic stewardship activities in hospital settings.
CircAGK regulates high dihydrotestosterone‐induced apoptosis in DPCs through the miR‐3180‐5p/BAX axis
Authors: Wei Hanxiao , Yang Shuai , Yi Tian , Xu Xiaoyu , Liu Chang , Shen Caiqi , Guo Yanping , Li Qiang , Jin Peisheng
Published: January 2023

The incidence of androgen alopecia (AGA), also known as seborrheic alopecia, has surged in recent years, and onset is occurring at younger ages. Dermal papilla cells (DPCs) are key to maintaining hair cycling, and apoptosis‐driven processes in DPCs are closely related to hair follicle regeneration. Circular RNAs (circRNAs) are widely present in the human body and are closely related to the occurrence and development of many diseases. Currently, the biological functions of circRNAs in AGA are largely unknown. Whole‐transcriptome sequencing was used to screen differential circRNA expression profiles between AGA patients and non‐AGA patients. We found that hsa_circ_0002980 (circAGK) was significantly highly expressed in the AGA group. CircAGK promoted DPC apoptosis in the presence of high dihydrotestosterone (DHT) (15 nmol/L). By regulating the miR‐3180‐5p/BAX axis, circAGK promotes DPC apoptosis in a high DHT environment in vitro and inhibits hair growth in AGA mice in vivo, indicating that circAGK is a potential target for the clinical treatment of AGA.
The functional implication of ATF6α in castration‐resistant prostate cancer cells
Authors: Zhou Hongqing , Zhang Tingting , Chen Liang , Cui Fengzhen , Xu Chenxiang , Peng Jiaxi , Ma Weixiang , Huang Jirong , Sheng Xia , Liu Mingsheng , Zhao Faming
Published: January 2023

Stress in the endoplasmic reticulum (ER) may perturb proteostasis and activates the unfolded protein response (UPR). UPR activation is frequently observed in cancer cells and is believed to fuel cancer progression. Here, we report that one of the three UPR sensors, ATF6α, was associated with prostate cancer (PCa) development, while both genetic and pharmacological inhibition of ATF6α impaired the survival of castration‐resistance PCa (CRPC) cells. Transcriptomic analyses identified the molecular pathways deregulated upon ATF6α depletion, and also discovered considerable disparity in global gene expression between ATF6α knockdown and Ceapin‐A7 treatment. In addition, combined analyses of human CRPC bulk RNA‐seq and single‐cell RNA‐seq (scRNA‐seq) public datasets confirmed that CRPC tumors with higher ATF6α activity displayed higher androgen receptor (AR) activity, proliferative and neuroendocrine (NE) like phenotypes, as well as immunosuppressive features. Lastly, we identified a 14‐gene set as ATF6α NE gene signature with encouraging prognostic power. In conclusion, our results indicate that ATF6α is correlated with PCa progression and is functionally relevant to CRPC cell survival. Both specificity and efficacy of ATF6α inhibitors require further refinement and evaluation.
Sumoylation regulates functional properties of the oocyte transcription factors SOHLH1 and NOBOX
Authors: Patton Bethany K. , Madadi Surabhi , Briley Shawn M. , Ahmed Avery A. , Pangas Stephanie A.
Published: January 2023

SOHLH1 and NOBOX are oocyte‐expressed transcription factors with critical roles in ovary development and fertility. In mice, Sohlh1 and Nobox are essential for fertility through their regulation of the oocyte transcriptional network and cross‐talk to somatic cells. Sumoylation is a posttranslational modification that regulates transcription factor function, and we previously showed that mouse oocytes deficient for sumoylation had an altered transcriptional landscape that included significant changes in NOBOX target genes. Here, we show that mouse SOHLH1 is modified by SUMO2/3 at lysine 345 and mutation of this residue alters SOHLH1 nuclear to cytoplasmic localization. In NOBOX, we identify a non‐consensus SUMO site, K97, that eliminates NOBOX mono‐SUMO2/3 conjugation, while a point mutation at K125 had no effect on NOBOX sumoylation. However, NOBOXK97R/K125R double mutants showed loss of mono‐SUMO2/3 and altered higher molecular weight modifications, suggesting cooperation between these lysine's. NOBOXK97R and NOBOXK97R/K125R differentially regulated NOBOX promoter targets, with increased activity on the Gdf9 promoter, but no effect on the Pou5f1 promoter. These data implicate sumoylation as a novel regulatory mechanism for SOHLH1 and NOBOX, which may prove useful in refining their roles during oogenesis as well as their function during reprogramming to generate de novo germ cells.
Probability Distributions for Associations Between Cognitive Screening and Pure-tone Thresholds in Older Adults
Authors: Eberhard Jacqueline M. , Matthews Lois. J. , Vaden Kenneth I. , Dubno Judy R. , Eckert Mark A.
Published: January 2023

Objectives:

Lower general cognitive function is frequently reported in older adults with elevated pure-tone thresholds. Here, we examined reason(s) for this association, including whether this relationship is dependent on the frequency range or extent of hearing loss and cognitive screening performance.

Design:

Linear regression was used to examine associations between better-ear pure-tone thresholds and Mini-Mental Status Exam (MMSE) performance in a cross-sectional sample of relatively healthy older adults (N = 508; 68% women, 60–89+ years; M age = 72). Quantile regression was also used to identify the ranges of 0.5 and 4.0 kHz thresholds and MMSE scores where these variables exhibited significant associations.

Results:

MMSE scores and pure-tone thresholds exhibited small but significant associations, particularly for better-ear 0.5 kHz thresholds. This hearing threshold and cognitive screening association was present among participants with better hearing, including the oldest older adults. There was limited evidence for mediating health condition effects on this association. An item analysis of the MMSE revealed that the MMSE and pure-tone threshold associations were largely due to the delayed recall item of the MMSE.

Conclusions:

Together, the small effect results are consistent with the extant literature and suggest that there are multiple reasons for modest pure-tone threshold and cognitive screening performance associations.
Accelerated Cognitive Decline Associated With Hearing Loss and Bilateral Vestibulopathy: Insights From a Prospective Cross-Sectional Study Using the Repeatable Battery for the Assessment of Neuropsychological Status Adjusted for the Hearing Impaired in the DFNA9 Population
Authors: Gommeren Hanne , Bosmans Joyce , Moyaert Julie , Mertens Griet , Cras Patrick , Engelborghs Sebastiaan , Van Ombergen Angelique , Gilles Annick , Fransen Erik , van de Berg Raymond , JanssensdeVarebeke Sebastien , Van Rompaey Vincent
Published: January 2023

Background:

DeaFNess Autosomal dominant 9 (DFNA9) is a hereditary disorder known to affect both hearing and vestibular function in its carriers. Its phenotype is characterized by progressive sensorineural hearing loss (SNHL) and vestibular dysfunction evolving towards bilateral vestibulopathy (BV) by the 3rd to 5th life decade. Recent studies have identified the impact of hearing loss and vestibular dysfunction on cognitive functioning.

Objective:

The main objective of this study was to investigate how the cognitive functioning of carriers of the p.Pro51Ser variant in the COCH gene is affected by the disease and compare these results with a matched healthy control group.

Study design:

Forty-six carriers of the pathogenic p.Pro51Ser variant in the COCH gene were included in this study, of which 38 met the Bárány Society criteria and were thus diagnosed with BV. All subjects were between the age of 22 and 72 years old. Each control was individually matched based on age, gender, and education level. A cognitive, vestibular, and hearing assessment was performed in all subjects. All participants completed the Repeatable Battery for the Assessment of Neuropsychological Status, adjusted for the Hearing Impaired (RBANS-H), a cognitive test battery that includes subtests probing Immediate and Delayed Memory, Visuospatial/Constructional, Language, and Attention.

Results:

Overall, the DFNA9 patients demonstrated significantly lower scores on the Immediate Memory subscale and lower Total Scale scores than their healthy matched controls. The total sample was divided into two groups: age <55 years old and age ≥55 years old. The DFNA9 group aged ≥55 years old obtained significantly lower scores on the Attention subscale and lower Total Scale scores than their matched controls. Cognition of DFNA9 patients aged <55 years old no longer differed significantly from their matched controls.

Conclusion:

This cross-sectional study found that DFNA9 patients demonstrated cognitive deficits in comparison with their healthy matched controls. The DFNA9 group aged ≥ 55 years old obtained significantly lower scores on the Total Scale and Attention subscale. This finding; however, was not observed for the age group younger than 55 years old. Further research is needed on the individual trajectory of SNHL and vestibular function, and how hearing rehabilitation affects cognitive functioning.
The Cross-Sectional Association Between Tinnitus and Actigraphy-Estimated Sleep in a Population-Based Cohort of Middle-Aged and Elderly Persons
Authors: de Feijter Maud , Oosterloo Berthe C. , Goedegebure André , Luik Annemarie I.
Published: January 2023

Objectives:

Tinnitus is a common and burdensome disease, often accompanied by complaints of poor sleep. However, associations of tinnitus with objective estimates of sleep remain unclear, particularly in the general population. We assessed these associations in a population-based cohort of middle-aged and elderly persons.

Design:

This study included 1456 participants (mean age: 65.0 ± 7.1 years, 52% women) from the population-based Rotterdam Study. Tinnitus was self-reported and in those who reported tinnitus daily, symptom severity was assessed with the Tinnitus Handicap Inventory. We used actigraphy to estimate sleep and 24-hour activity rhythms objectively and sleep diaries to assess self-reported sleep. We estimated the difference in sleep and 24-hour activity rhythms first between those with and those without tinnitus and secondly with tinnitus severity.

Results:

Tinnitus, reported by 341 (23%) participants, and tinnitus severity, assessed in 194 participants with daily tinnitus, were not associated with actigraphy-estimated sleep or 24-hour activity rhythms, but were associated with a longer self-reported sleep onset latency (adjusted differencetinnitus = 2.36, 95% confidence interval [CI] = 0.95–3.78, adjusted differencetinnitus severity = 0.27, 95% CI = 0.013–0.54). After stratification for hearing loss, tinnitus was associated with longer self-reported sleep onset latency (adjusted difference = 2.26, 95% CI = 0.98–3.53) and less stable 24-hour activity rhythms (adjusted difference = −0.02, 95% CI = −0.04 to −0.00) in those with hearing loss. In those without hearing loss, tinnitus was associated with more stable rhythms (adjusted difference = 0.03, 95% CI = 0.01–0.05).

Conclusions:

Having tinnitus is associated with a longer self-reported sleep onset latency, but not with objective estimates of sleep, suggesting that the subjective experience of sleep may be particularly disturbed in those with tinnitus. In addition, hearing loss may modify the association of tinnitus and 24-hour activity rhythms.
Sex-Specific Interactions Between Hearing and Memory in Older Adults With Mild Cognitive Impairment: Findings From the COMPASS-ND Study
Authors: Al-Yawer Faisal , Pichora-Fuller M. Kathleen , Wittich Walter , Mick Paul , Giroud Nathalie , Rehan Sana , Phillips Natalie A.
Published: January 2023

Objectives:

Hearing loss (HL) in older adults is associated with a decline in performance on cognitive tasks and the risk of developing dementia. However, very few studies have investigated sex-related effects on these associations. A previous study of cognitively healthy older adults showed an association between HL and lower cognitive performance in females only. In the present study, we examined the effects of sex and hearing on cognition in individuals with mild cognitive impairment (MCI). We predicted that females with HL would be more likely to show poorer performance on the cognitive measures compared to females with normal hearing (NH), while cognitive performance in males would not depend on hearing. We further predicted that these auditory-cognitive associations would not depend on test modality, and would thus be observed in females for both auditory and visual tests.

Design:

Participants were 101 older adults with amnestic MCI (M = 71 years, 45% females) in the Canadian Consortium on Neurodegeneration in Aging (CCNA) COMPASS-ND study. Performance on the Montreal Cognitive Assessment (MoCA), Rey Auditory Verbal Learning (RAVLT), and Brief Visuospatial Memory Test-Revised (BVMT-R) was analyzed to investigate sex-related differences and/or hearing-related differences. Participants were categorized as having NH or HL using two different measures: pure-tone hearing screening results (normal based on a pure-tone threshold < 25 dB HL at 2000 Hz in the worse ear) and speech-in-noise speech reception thresholds (SRTs; normal < −10 dB SNR on the Canadian Digit Triplet Test [CDTT]).

Results:

Males and female groups did not differ in age, years of education, or other relevant covariates. Yet, females with better hearing on either pure-tone or speech-in-noise measures outperformed their worse hearing counterparts on the MoCA total score. Additionally, females with better hearing were more likely to recall several words on the MoCA delayed recall trial relative to those with worse hearing. Females with NH showed significant correlations between CDTT SRTs and both MoCA and RAVLT scores, while no correlations were observed in males. In contrast, males but not females showed an effect of hearing group on BVMT-R test status.

Conclusions:

There were sex-specific differences in auditory-cognitive associations in individuals with MCI. These associations were mostly observed in females and on auditory tests. Potential mechanisms and implications are discussed.
Prospective, Randomized Ponseti Treatment for Clubfoot: Orthopaedic Surgeons Versus Physical Therapists
Authors: Chen Stephanie N. , Ragsdale Tyler D. , Rhodes Leslie N. , Locke Lindsey L. , Moisan Alice , Kelly Derek M.
Published: January 2023

Background:

Clubfoot is a common congenital foot deformity in children. The Ponseti method of serial casting has become the standard of care in clubfoot treatment. Clubfoot casting is performed in many centers by both orthopaedic surgeons and physical therapists (PTs); however, direct comparison of outcomes and complications of this treatment between these providers is limited. This study prospectively compared the outcomes of patients with clubfoot treated by these 2 groups of specialists.

Methods:

Between January 2010 and December 2014, all patients under the age of 12 months with a diagnosis of clubfoot were included. Patients were randomized to an orthopaedic surgeon (MD) group or a PT group for weekly serial casting. Main outcome measures included the number of casts required to achieve correction, clinical recurrence of the deformity, and the need for additional surgical intervention.

Results:

One hundred twenty-six infants were included in the study. Patient demographics and characteristics (sex, race, family history of clubfoot, laterality, and severity of deformity) were similar between treatment groups, with the only significant difference being the mean age of entry into the study (5.2 weeks in the MD group and 9.2 weeks in the PT group, P=0.01). Mean length of follow-up was 2.6 years. The number of casts required trended to a lower number in the MD group. There was no significant difference in the rates of clinical recurrence or additional surgical intervention between groups.

Conclusions:

Ponseti casting for treatment of clubfoot performed by orthopaedic surgeons and PTs results in equivalent outcomes without any difference in complications. Although the number of casts required trended to a lower number in the MD group, this likely did not result in any clinical significance, as the difference in cast number equaled <1 week’s difference in the overall duration of serial casting.

Level of Evidence:

Level I—therapeutic.
The Ulnar Olecranon-Coronoid Notch Angle Affects Terminal Elbow Extension in Children and Adolescents
Authors: Abraham Edward , Lin Ye , Castillo Tafur Julio , Boroda Nickolas , Schwarzman Garrett
Published: January 2023

Background:

Limitations to terminal elbow extension (TEE) in pediatric populations have been commonly associated with the degree of ligamentous laxity and not bony factors. Ligamentous laxity, quantified through the Beighton score, is criticized for unreliably assessing joint mobility. This study aims to show that the olecranon-coronoid notch angle (OCNA) affects TEE in healthy children and adolescents.

Methods:

A retrospective study of 711 pediatric patients treated for upper extremity and shoulder injuries was cross-sectionally studied at 2 tertiary centers from 2014 to 2021. Radiographs were used to measure the OCNA, humerocondylar angle, proximal anterior ulnar angle, and the presence of secondary centers of ossification. A 2-axis goniometer measured clinical TEE to a firm endpoint. The statistical analysis studied the relationships between OCNA and TEE and the effect that age and sex have on these measurements.

Results:

Increased TEE was associated with increased OCNA (P<0.001) when accounting for age and sex. The average OCNA was 30.0 degrees (7.5 degrees), and the average TEE was 5.6 degrees (8.0 degrees). There was a difference in OCNA between subjects who had elbow hypoextension, normal TEE, and elbow hyperextension (P<0.001). The most common injuries were distal radius fractures (182, 26%), elbow sprains and contusions (111, 16%), distal both bone forearm fractures (95, 14%), single or both bone shaft fractures (77, 11%), and supracondylar fractures (74, 11%).

Conclusion:

These results show that the orientation of the opening of the olecranon-coronoid notch influences the arc of TEE motion in a healthy pediatric population. The notch restrains TEE by activating the bony block mechanism between the olecranon apophysis and the olecranon fossa. The measurement of the OCNA can serve as a reproducible and quantitative method to predict hypomobility to hypermobility of TEE motion.

Level of Evidence:

Prognostic study: Level II
Reliability of Preoperative Supine Versus Bending Radiographs in Estimating the Structural Nature of Curves in EOS
Authors: Skaggs Kira F. , Bainton Nicole M. , Boby Afrain Z. , Rymond Christina C. , Fields Michael W. , Roye Benjamin D. , Vitale Michael G.
Published: January 2023

Background:

The study sought to evaluate the utility of a single supine radiograph in determining curve flexibility in early-onset scoliosis (EOS) patients.

Methods:

EOS patients with upright (standing/seated), supine, and side-bending radiographs who underwent spinal deformity surgery were identified. Coronal parameters included: proximal thoracic (PT) curve, main thoracic (MT) curve, and thoracolumbar/lumbar (TL/L) curve. Each radiograph was measured twice by 2 different raters. Correlation coefficients were utilized to investigate associations between the different radiographs. Interrater Correlation Coefficient (ICC) assessed intrarater and interrater reliability.

Results:

Thirty-seven EOS patients were identified (age at diagnosis: 7.0±2.9 y, preoperative age: 13.0±2.9 y; 73% female; etiologies: 54% idiopathic, 30% syndromic, and 16% neuromuscular). Supine PT and MT curve measurements were highly associated with corresponding side-bending measurements (PT: r=0.75, P<0.001; MT: r=0.80, P<0.001), and TL/L curves were very highly associated (TL/L: r=0.92, P<0.001). The mean absolute differences between supine and side-bending measurements were PT: 11.3±7.8 degrees, MT: 14.8±8.3 degrees, and TL/L: 16.2±7.6 degrees, where the side-bending was on average smaller than the supine measurement. The intrarater reliabilities were excellent, with an ICC ranging from 0.93 to 0.96 for side-bending films and 0.94 to 0.97 for supine films. The interrater reliability was excellent with ICC value of 0.88 for side-bending films and 0.93 for supine films.

Conclusions:

A single, preoperative supine radiograph was highly predictive of side-bending radiographs in patients with EOS. Supine curves measured an average of 15 degrees larger than bending curves in the MT and TL/L region. A single supine film may eliminate the need for effort-related, dual side-bending radiographs.

Level of Evidence:

Level II—retrospective study.
Clinical Diagnosis of the Infantile Shoulder Subluxation in Residual Brachial Plexus Birth Injury and Its Correlation With Ultrasound Diagnosis
Authors: Shah Maulin , Shah Shalin , Sangole Chinmay , Bansal Sheenam , Naik Nischal , Patel Tejas
Published: January 2023

Introduction and aims of study:

Timely detection of shoulder subluxation in infants with brachial plexus birth injury (BPBI) is essential to prevent the progression of glenohumeral deformity. Shoulder ultrasonography (USG) is routinely used to detect an infantile subluxation/dislocation, but its use is limited because of the paucity of expert radiologists in developing countries. The aim of this study was to determine the clinical examination predictors to determine shoulder subluxation in patients with BPBI correlating with ultrasound confirmation.

Methods:

We prospectively studied children who presented to our hospital between 2017 and 2021 diagnosed as brachial plexus birth injury. In patients developing internal rotation contracture of the shoulder, we looked for 3 standard clinical signs: reduced passive external rotation <60 degrees, deep anterior crease (DAC) and relatively short arm segment. Shoulder subluxation was defined as USG measurement of alpha angle>30 degrees and ossific nuclei of the humerus lying behind the dorsal scapular line. Sensitivity and specificity were used to assess their efficacy in clinical diagnosis of shoulder subluxation in different groups. The predicted probability of shoulder subluxation from each prediction rule was compared with actual distributions based on USG confirmation.

Results:

Of the 58 BPBI infants who developed PER<60 degrees at the shoulder, 41 had USG confirmed shoulder subluxation. The 2 independent predictors of shoulder subluxation (PER<45 degrees and DAC) were identified in the current patient population based on data analysis. The presence of short arm segment is a very specific marker of shoulder subluxation but not sensitive. The predicted probability of shoulder subluxation from the prediction rule combining all the 3 markers were similar to the actual distributions in the current patient population.

Conclusions:

PER<45 degrees and presence of deep anterior crease are clinical markers indicating shoulder dislocation in patients with BPBI developing reduced external rotation at the shoulder. On the basis of the proposed clinical diagnosis algorithm, the above markers along with the selective use of USG can help in early detection and treatment of infantile shoulder dislocation.
A Predictive Model to Identify Treatment-related Risk Factors for Odontoid Fracture Nonunion Using Machine Learning
Authors: Leister Iris , Haider Thomas , Vogel Matthias , Vastmans Jan , Langthaler Patrick , Mattiassich Georg , Christ Alexandra , Etschmaier Martin , Eijkenboom Alexander , Burghuber Julia , Kindermann Harald , Mach Orpheus , Maier Doris , Högel Florian
Published: January 2023

Study Design.

Multicenter retrospective analysis of routinely collected data.

Objective.

The underlying aim of this study was to identify potential treatment-related risk factors for odontoid fracture nonunion while accounting for known patient- and injury-related risk factors.

Summary of Background Data.

Type II and III odontoid fractures represent the most common cervical spine fracture in elderly patients and are associated with a relatively high nonunion rate. The management of odontoid fractures is controversial and treatment strategies range from conservative treatment to extensive surgical stabilization and fusion.

Methods.

A total of 415 individuals who sustained odontoid fracture and were treated in either of four tertiary referral centers in Austria and Germany were included in the study. We included the following potential contributing factors for fracture nonunion in cross-validated extreme gradient boosted (XGBoost) and binary logistic regression models: age, gender, fracture displacement, mechanism of injury (high vs. low energy), fracture classification (Anderson II vs. III), presence of comorbidities (Charlson comorbidity index), and treatment (conservative, anterior screw fixation with one or two screws, posterior C1/C2 spondylodesis, cervico-occipital C0–C4 fusion).

Results.

In our cohort, 187 (45%) had radiologically confirmed odontoid nonunion six months postinjury. The odds for nonunion increase significantly with age, and are lower in type III compared to type II fractures. Also, odds for nonunion are significantly lower in posterior C1/C2 spondylodesis, and C0–C4 fusion compared to conservative treatment. Importantly, odds are not statistically significantly lower in the group treated with anterior screw fixation compared to conservative treatment. The factors gender, fracture displacement, mechanism of injury, and the presence of comorbidities did not produce significant odds.

Conclusion.

Higher age, type II fractures, and conservative treatment are the main risk factors for odontoid nonunion. Anterior screw fixation did not differ significantly from conservative treatment in terms of fracture union.

Level of Evidence.

3.
Immunocompromised Children With Acute Respiratory Distress Syndrome Possess a Distinct Circulating Inflammatory Profile
Authors: Nguyen John , Thompson Jill M. , Balcarcel Daniel R. , Alder Matthew N. , McKeone Daniel J. , Halstead E. Scott , Rowan Courtney M. , Lindell Robert B. , Yehya Nadir
Published: January 2023

IMPORTANCE:

Immunocompromised status, with and without stem cell transplant, confers a worse prognosis in pediatric acute respiratory distress syndrome. An improved understanding of the biochemical profile of immunocompromised children with acute respiratory distress syndrome would inform whether specific pathways are targetable, or merely bystanders, in order to improve outcomes in this high-risk subgroup.

OBJECTIVES:

We aimed to identify a biomarker profile of immunocompromised children, with and without stem cell transplant, independent of illness severity.

DESIGN, SETTINGS, AND PARTICIPANTS:

This was a secondary analysis of a prospective cohort study of intubated children with Berlin-defined acute respiratory distress syndrome with existing biomarker measurements conducted in a large academic PICU between 2014 and 2019.

MAIN OUTCOMES AND MEASURES:

Biomarker levels were compared between immunocompetent and immunocompromised children, with and without stem cell transplant, both prior to and after adjusting for severity of illness.

RESULTS:

In 333 children with acute respiratory distress syndrome, 84 were immunocompromised, of whom 39 had a stem cell transplant. Circulating neutrophil levels were strongly correlated with biomarkers, with 14 of 18 measured proteins differentially expressed in patients with versus without neutropenia. In order to identify biomarker levels independent of severity of illness, acute respiratory distress syndrome etiology, and neutrophil levels, we computed predicted (log-transformed) biomarker levels after adjusting for confounders using linear regression and then compared these severity-adjusted levels between immunocompetent and immunocompromised (with and without stem cell transplant) subjects using analyses of variance and post hoc Bonferroni. After multivariable adjustment, 11 biomarkers were higher in immunocompromised subjects without stem cell transplant, relative to immunocompetent, implicating endotheliopathy (angiopoietin-2), tissue damage (procollagen type III N-terminal peptide), and innate immunity. A single biomarker, C-C motif chemokine ligand 22, was lower in immunocompromised subjects with and without stem cell transplant.

CONCLUSIONS AND RELEVANCE:

Immunocompromised children with acute respiratory distress syndrome were characterized by elevations in pro-inflammatory and endothelial damage biomarkers. Our study provides insight into mechanisms underlying the molecular heterogeneity of this population and potentially identifies targetable pathways to mitigate their increased mortality risk.
Applications of Speech Analysis in Psychiatry
Authors: Dikaios Katerina , Rempel Sheri , Dumpala Sri Harsha , Oore Sageev , Kiefte Michael , Uher Rudolf
Published: January 2023

The need for objective measurement in psychiatry has stimulated interest in alternative indicators of the presence and severity of illness. Speech may offer a source of information that bridges the subjective and objective in the assessment of mental disorders. We systematically reviewed the literature for articles exploring speech analysis for psychiatric applications. The utility of speech analysis depends on how accurately speech features represent clinical symptoms within and across disorders. We identified four domains of the application of speech analysis in the literature: diagnostic classification, assessment of illness severity, prediction of onset of illness, and prognosis and treatment outcomes. We discuss the findings in each of these domains, with a focus on how types of speech features characterize different aspects of psychopathology. Models that bring together multiple speech features can distinguish speakers with psychiatric disorders from healthy controls with high accuracy. Differentiating between types of mental disorders and symptom dimensions are more complex problems that expose the transdiagnostic nature of speech features. Convergent progress in speech research and computer sciences opens avenues for implementing speech analysis to enhance objectivity of assessment in clinical practice. Application of speech analysis will need to address issues of ethics and equity, including the potential to perpetuate discriminatory bias through models that learn from clinical assessment data. Methods that mitigate bias are available and should play a key role in the implementation of speech analysis.
A double-blind phase II randomized controlled trial of an online cognitive bias modification for interpretation program with and without psychoeducation for people with chronic pain
Authors: Sharpe Louise , Jones Emma Blaisdale , Pradhan Poorva , Todd Jemma , Colagiuri Ben
Published: January 2023

Cognitive bias modification for interpretation (CBM-I) is an effective intervention for anxiety, but there is only a single trial in people with chronic pain. The aim of this randomized controlled trial was to test CBM-I with and without psychoeducation for people with chronic pain. We randomized 288 participants to 4 groups comprising treatment (CBM-I vs placebo) with or without psychoeducation. One hundred and eighty-three participants (64%) completed 4, 15-minute training sessions over 2 weeks. The coprimary outcomes were pain interference and pain intensity. We also measured interpretation bias, fear of movement, catastrophizing, depression, anxiety, and stress. Participants with more psychopathology at baseline were more likely to dropout, as were those allocated to psychoeducation. Intention-to-treat analyses using linear mixed models regression were conducted. Training effects of CBM-I were found on interpretation bias, but not a near-transfer task. Cognitive bias modification of interpretation improved both primary outcomes compared with placebo. For pain interference, there was also a main effect favoring psychoeducation. The CBM-I group improved significantly more than placebo for fear of movement, but not catastrophizing, depression, or anxiety. Cognitive bias modification of interpretation reduced stress but only for those who also received psychoeducation. This trial shows that CBM-I has promise in the management of pain, but there was limited evidence that psychoeducation improved the efficacy of CBM-I. Cognitive bias modification of interpretation was administered entirely remotely and is highly scalable, but future research should focus on paradigms that lead to better engagement of people with chronic pain with CBM-I.