bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractThe 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

AbstractStress 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

AbstractSOHLH1 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.