bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic challenges and burden of idiopathic hypersomnia: a systematic literature review
Authors: Boulanger Talia , Pigeon Pascale , Crawford Stephen
Published: August 2024

Idiopathic hypersomnia (IH) is a rare neurological sleep disorder, characterized by excessive daytime sleepiness despite normal sleep duration, that can significantly impact patient’s lives. The burden of IH goes beyond excessive daytime sleepiness, pervading all aspects of everyday life. Characteristic and burdensome symptoms of IH include sleep inertia/drunkenness, long sleep duration, and daytime cognitive dysfunction. This systematic review assessed current knowledge regarding IH diagnostic challenges and burden of illness. Literature searches for original epidemiological, clinical, humanistic, or economic research relevant to IH published between 2012 and 2022 in MEDLINE, Embase, Cochrane, gray literature (diagnostic criteria and treatment guidelines), conferences (2019–2022), and clinical trial databases yielded 97 articles. Findings indicate that IH remains a poorly defined diagnosis of exclusion that is difficult to distinguish from narcolepsy type 2 because of symptom overlap and inadequacies of objective testing. Consequently, individuals with IH endure diagnostic delays of up to 9 years. The economic burden of IH has not been characterized to any appreciable extent. Pharmacological treatment options can improve symptoms and functional status, but rarely restores normal levels of functioning. These findings highlight the need to reclassify central disorders of hypersomnolence. Further collaboration is now required between research groups to identify and validate objective markers to help redefine diagnostic criteria for IH. This would move IH into a position that could benefit from future targeted therapeutic interventions. The study was funded by Takeda Development Center Americas, Inc.
A Diazeniumdiolate Signal in Pseudomonas syringae Upregulates Virulence Factors and Promotes Survival in Plants
Authors: Guo Qiang , Vitro Caitlin N. , Crawford Drake M. , Li Bo
Published: August 2024

Pseudomonas syringae infects a wide variety of crops. The mangotoxin-generating operon ( mgo) is conserved across many P. syringae strains and is responsible for producing an extracellular chemical signal, leudiazen. Disruption of the mgoA gene in P. syringae pv. syringae ( Pss) UMAF0158 alleviated tomato chlorosis caused by this bacterium. We showed that deletion of the entire mgo reduced Pss UMAF0158 population in tomato leaflets. Leudiazen restored the signaling activity of the deletion mutant at a concentration as low as 10 nM. Both the diazeniumdiolate and isobutyl groups of leudiazen are critical for this potent signaling activity. Transcriptional analysis showed that mgo and leudiazen induce the expression of mangotoxin biosynthetic operon as well as an uncharacterized gene cluster, RS17235–RS17245. We found that this cluster enhances the survival of Pss UMAF0158 in planta and is widely distributed in P. syringae strains. Our results demonstrate that mgo plays prominent roles in the virulence and growth of P. syringae. The mgo and mgo-like signaling systems in different bacteria likely regulate diverse microbe-host interactions.

[Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
Ralstonia solanacearum Species Complex in Australia
Authors: Ray Jane D. , Vala Bhuwaneshwariba , Mintoff Sharl , Pathania Nandita , Bellgard Stanley E.
Published: August 2024

The Ralstonia solanacearum species complex (RSSC) causes vascular wilt of many crops and is considered one of the most destructive plant pathogenic bacteria worldwide. The species complex was recently resolved into a stable taxonomy of three species aligning with the previously determined phylotypes, namely R. solanacearum (phylotype II), R. pseudosolanacearum (phylotype I and III), and R. syzygii (phylotype IV). Knowing which Ralstonia species and subspecies are established in Australia is important to Australia’s biosecurity and market access. The goal of this study was to analyze Australia’s Ralstonia culture collections and to assign the isolates to the modern taxonomic groups. The results shed light on the identity, distribution, and pathogenicity of the Ralstonia strains in Australia. Ralstonia solanacearum, R. pseudosolanacearum phylotype I, and R. syzygii phylotype IV-11 are present in Australia but have limited geographic ranges. We identified two aberrant RSSC strains that have genetic similarity to R. syzygii based on sequevar analysis, but do not yield a phylotype IV multiplex PCR band, similar to the known aberrant strain ACH732. The aberrant strains may represent a novel species. Three new sequevars were determined, 72, 73, and 74. Several Ralstonia lineages remain undetected in Australia, providing evidence that they are absent. These include R. pseudosolanacearum phylotype III and the phylotype I mulberry infecting strains; R. solanacearum strains IIC and the Moko causing strains; and R. syzygii subsp. celebesensis, and R. syzygii subsp. syzygii. This study fulfilled Koch’s postulates for the Australian strains, R. solanacearum wilted potato plants, and R. pseudosolanacearum wilted blueberry plants, the hosts from which they were initially isolated. The data supports the hypothesis that Australia has native and introduced strains of Ralstonia.
Genomic Analysis of ‘Candidatus Liberibacter africanus’ Strain from Zimbabwe Reveals Unique Virulence and Prophage Characteristics Compared with ‘Ca. L. asiaticus’
Authors: Zheng Yongqin , Huang Wenxia , Josiah Runyanga Tinashe , Clemence Tauya , Vernon Shumbayaonda Chiyedzo , Enklebert Takawira , Deng Xiaoling , Zheng Zheng
Published: August 2024

Citrus Huanglongbing (HLB) is caused by the phloem-limited α-proteobacterium ‘Candidatus Liberibacter spp.’, among which ‘Ca. L. africanus’ (CLaf) has posed a significant threat to citrus production in Africa for nearly a century. CLaf is closely related to the globally prevalent ‘Ca. L. asiaticus’ (CLas), whereas little is known about the virulence of CLaf, primarily because of limited genome resources. In this study, we completed the whole-genome assembly and annotation of the CLaf strain Zim (from Zimbabwe). Compared with CLas, a total of 102 CLaf unique genes were identified, including 14 potential Sec-dependent effector (SDE) genes, 29 phage-associated genes, and 59 genes with hypothetical function. Among 14 SDEs, V9J15_03810 was able to induce a significant hypersensitive response in Nicotiana benthamiana, indicating its potential as a virulence factor for CLaf. Genome analysis showed that the CLaf strain Zim genome harbored a complete prophage region (named P-Zim-1, 42,208 bp). P-Zim-1 retained two immunosuppressive peroxidase genes (V9J15_02125 and V9J15_02130) homologous to CLas prophage SC1/SC2, whereas the lysogen-associated genes encoding integrase (V9J15_01970) and repressor (V9J15_02080) were homologous to the prophage of ‘Ca. L. solanacearum’, the causal agent of potato zebra chip disease. In addition, P-Zim-1 carried a novel CRISPR/Cas system, including a CRISPR array (located within V9J15_02040, ranging from 443,643 to 443,897) and five CRISPR-related Cas proteins (V9J15_02005, V9J15_02010, V9J15_02015, V9J15_02025, and V9J15_02035). This study first characterized the unique genomic feature of CLaf related to virulence and prophage, which will facilitate future research on CLaf biology and African HLB management.
Visualized Detection of Tobacco Anthracnose by a Recombinase Polymerase Amplification–Lateral Flow Dipstick Assay
Authors: Li Tao , Feng Ji , Chen Yangyin , Zhang Yu , Wang Hancheng , Zhang Chuanqing
Published: August 2024

Anthracnose caused by Colletotrichum spp. is a widespread fungal disease that is detrimental to tobacco growth and inflicts economic damage of up to 100 million in tobacco-growing regions in China. An early diagnostic tool is vital for the accurate determination and management of anthracnose in the field. This study investigated the diversity of Colletotrichum spp. on tobacco leaves with anthracnose and developed a recombinase polymerase amplification–lateral flow dipstick (RPA-LFD) diagnostic method for the rapid and equipment-independent detection of the main Colletotrichum spp. causing tobacco anthracnose. This assay targeted the chitin synthase gene (chs1) and could be performed in a few minutes (6 to 10 min). All isolates of C. karstii, C. fructicola, and C. gloeosporioides yielded positive results in the RPA-LFD assay, and no cross-reaction occurred with other fungal species from tobacco or other hosts. The detection threshold was 1 pg of genomic DNA under optimal reaction conditions. The entire RPA-LFD assay enabled the detection of pathogen visualization within 30 min without specialized equipment by combining a polyethylene glycol-KOH method for extracting gDNA rapidly from tobacco leaves infected with C. karstii, C. fructicola, and C. gloeosporioides. Based on these results, the RPA-LFD assay is easy to operate, rapid, and equipment-independent and is promising for development as a kit to diagnose tobacco anthracnose in resource-limited settings at point-of-care.
The Role of Oxalic Acid in Clarireedia jacksonii Virulence and Development on Creeping Bentgrass
Authors: Huo Daowen , Westrick Nathaniel M. , Nelson Ashley , Kabbage Mehdi , Koch Paul
Published: August 2024

Dollar spot is a destructive foliar disease of amenity turfgrass caused by Clarireedia spp. fungi, mainly C. jacksonii, on the Northern United States region's cool-season grass. Oxalic acid (OA) is an important pathogenicity factor in related fungal plant pathogens such as Sclerotinia sclerotiorum; however, the role of OA in the pathogenic development of C. jacksonii remains unclear due to its recalcitrance to genetic manipulation. To overcome these challenges, a CRISPR/Cas9-mediated homologous recombination approach was developed. Using this novel approach, the oxaloacetate acetylhydrolase ( oah) gene that is required for the biosynthesis of OA was deleted from a C. jacksonii wild-type (WT) strain. Two independent knockout mutants, Δ Cjoah-1 and Δ Cjoah-2, were generated and inoculated on potted creeping bentgrass along with a WT isolate and a genome sequenced isolate LWC-10. After 12 days, bentgrass inoculated with the mutants Δ Cjoah-1 and Δ Cjoah-2 exhibited 59.41% lower dollar spot severity compared with the WT and LWC-10 isolates. OA production and environmental acidification were significantly reduced in both mutants when compared with the WT and LWC-10. Surprisingly, stromal formation was also severely undermined in the mutants in vitro, suggesting a critical developmental role of OA independent of plant infection. These results demonstrate that OA plays a significant role in C. jacksonii virulence and provide novel directions for future management of dollar spot.

[Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
The Effect of Valacyclovir on Secondary Prevention of Congenital Cytomegalovirus Infection, Following Primary Maternal Infection Acquired Periconceptionally or in the First Trimester of Pregnancy: An Individual Patient Data Meta-analysis
Authors: Chatzakis Christos , Shahar-Nissan Karen , Faure-Bardon Valentine , Picone Olivier , Hadar Eran , Amir Jacob , Egloff Charles , Vivanti Alexandre , Sotiriadis Alexandros , Leruez-Ville Marianne , Ville Yves
Published: August 2024

(Abstracted from Am J Obstet Gynecol 2024;230(2):109–117

The incidence rate for congenital cytomegalovirus (cCMV) infection ranges from 0.2% to 2.2%. CMV is the most common cause of congenital hearing loss and accounts for about a third of cases.
Germline and Somatic Testing for Ovarian Cancer: An SGO Clinical Practice Statement
Authors: Gressel G. M. , Frey M. K. , Norquist B. , Senter L. , Blank S. V. , Urban R. R.
Published: August 2024

(Abstracted from Gynecol Oncol 2024;181:170–178

Identification of germline and somatic pathogenic variants as well as homologous recombination deficiency (HRD) can contribute to the prediction of treatment response, prognostic outcome, and suitability for targeted agents. Germline genetic testing can also serve to inform risk for other malignancies and prompt risk management for at-risk relatives.
Two years in a post-Dobbs world: clinical, social and professional consequences
Authors: Beshar Isabel , Corn Megan , Blumenthal Paul D.
Published: August 2024

Purpose of review

Dobbs v Jackson Women's Health Organization revoked the decades-old precedent that pregnancy termination is a constitutional right. This review article explores the research landscape describing the consequences of overturning Roe v Wade for patients and providers.

Recent findings

To date, fourteen states have enforced total bans on abortion, with seven more restricting abortion access to levels not seen since before Roe. Dobbs has had immediate and swift consequences from clinical, social and professional perspectives, with increases in maternal mortality and demand for long-acting and permanent contraception, matched by declines in both access to methotrexate and applications to Obstetrics & Gynecology training programs.

Eighteen million patients now live in states where abortion access is highly if not completely inaccessible. Abortion restrictions have profound implications beyond those desiring pregnancy termination; future research should continue to explore the ways Dobbs has affected clinical care, public health and social practices.
Abortion in entertainment media, 2019–2024
Authors: Herold Stephanie
Published: August 2024

Purpose of review

Entertainment media contribute to how people understand and make sense of health issues, especially stigmatized ones such as abortion. This paper reviews the peer-reviewed literature published between 2019 and 2024 on how abortion is depicted in scripted television and film available for viewing in the United States.

Recent findings

The majority of recent studies focus on qualitative content analysis of a composite of television shows, documenting the myriad ways that these programs reflect and are distinct from the reality of abortion access in the United States. The quantitative studies find small but significant increases in abortion knowledge related to exposure to television abortion plotlines, but no increases in support for abortion postexposure. No studies track the impact of exposure to multiple abortion plotlines at multiple points in time. Only one study included a sample of entertainment content creators to understand their motivations for creating abortion plotlines.

Media depictions of abortion are often rife with misinformation, and may influence the U.S. public's general knowledge and beliefs about abortion. More research is needed to understand possible relationships between television and film abortion content and its impact on viewers.
Adolescent reproductive health in a post-Dobbs landscape: a review
Authors: Doyle Alexis A. , Liu Serena M. , Tyson Nichole A.
Published: August 2024

Purpose of review

To summarize notable recent research in adolescent reproductive health, particularly with respect to a rapidly changing legal landscape surrounding health services that significantly impact adolescent health.

Recent findings

Approval of the first over-the-counter contraceptive pill represented a major advance in adolescent reproductive health, which relied on research regarding its safety, efficacy, and potential to increase access for vulnerable groups. Despite this approval, disparities persist in equitable contraceptive access for adolescents of color and those from sexual and gender identity minorities. Legal changes in access to abortion care and parental involvement in reproductive health decision-making have presented significant challenges for young people across the U.S. Recent research points to the promise of telehealth abortion care and parental acceptance of confidentiality in adolescent reproductive healthcare. Misinformation remains a barrier to advancing adolescent reproductive health and points to continued opportunities for providers to create evidence-based online content.

In this review, we discuss recent research regarding adolescent reproductive health and laws impacting the reproductive health of adolescents. As the legal landscape evolves, further research surrounding the effect of policy changes that both expand and restrict access to adolescent reproductive health services will be critical to advancing adolescent health.
A Biologic With Otologic Consequences: Analysis of Hearing Loss and Teprotumumab Using the FDA Adverse Event Reporting System
Authors: Huynh Pauline P. , Saba Elias , Rivero Alexander , Peralta Robert , Liang Jonathan
Published: August 2024

Objectives

To evaluate otologic adverse reactions (OARs), including hearing loss (OARs-HL) among patients taking teprotumumab, a new biologic approved for the treatment of active thyroid eye disease, using publicly available pharmacovigilance reporting data.

Study Design

Retrospective database review

Methods

The Food and Drug Administration Adverse Events Reporting System (FAERS) was queried for cases involving teprotumumab from 2020Q1 to 2023Q1. Patient demographics and adverse reactions (OAR and OAR-HL) were evaluated. Logistic regression was used to predict OAR and OAR-HL, and disproportionality analysis was performed using OpenVigil.

Results

A total of 2,109 teprotumumab-AR cases were reported, of which 296 (14.05%; mean age 55.46 yr) were OARs. Of these, 149 (7.06%) reported OAR-HL and 194 (9.20%) reported other OAR (e.g., tinnitus, ear discomfort, vertigo), with 47 (2.23%) reporting both. Disproportionality analysis showed a reported odds ratio (ROR) for OARs-HL of 44.33 (95% confidence interval [CI], 37.40–52.55; p < 0.001). Age was associated with RORs of 1.02 (95% CI, 1.01–1.04) and 1.04 (95% CI, 1.02–1.07) for developing OARs and specifically OARs-HL, respectively (p < 0.01). Age 50 and 65 years and older were associated with RORs of 2.54 (95% CI, 1.16–6.38) and 3.36 (95% CI, 1.75–6.53), respectively, for OARs-HL (p < 0.05).

Conclusion

This study using FAERS data suggests an increased risk of OARs, specifically hearing loss, associated with teprotumumab. Increasing age was a significant predictor of OARs. Audiometric counseling and evaluation should be considered with teprotumumab therapy in Graves' orbitopathy patients, especially in older patients.
Impact of Migraine on the Tinnitus-Specific Health-Related Quality of Life and Psychiatric Comorbidities in Patients with Tinnitus
Authors: Kabaya Kayoko , Takahashi Mariko , Esaki Shinichi , Minakata Toshiya , Iwasaki Shinichi
Published: August 2024

Objective

To investigate the impact of migraine on the tinnitus-specific health-related quality of life (HRQOL) and psychiatric comorbidities in patients with tinnitus.

Methods

This cross-sectional study included 227 consecutive patients with tinnitus as their primary complaint. Patients who were diagnosed as having comorbid migraine were asked whether their tinnitus exacerbated during attacks of migraine. All the patients completed three questionnaires: the Tinnitus Handicap Inventory (THI), the Hearing Handicap Inventory for Adults (HHIA) or its counterpart for the Elderly (HHIE), and the Hospital Anxiety and Depression Scale (HADS).

Results

Among the 227 tinnitus patients, 60 (26.4%) had comorbid migraine. There were no significant differences in the THI or HHIA/HHIE scores between patients with migraine and those without migraine (both p > 0.05). The HADS score was significantly higher in patients with migraine than those without migraine (p < 0.05).

Out of the 60 tinnitus patients with comorbid migraine, 27 (45.0%) experienced exacerbation of tinnitus during migraine attacks. Patients whose tinnitus exacerbated during migraine attacks had significantly higher scores in THI, HHIA/HHIE, and HADS compared to those whose tinnitus did not change during migraine attacks (p < 0.05 for THI and HADS, p < 0.01 for HHIA/HHIE).

Conclusion

The presence of migraine did not affect the tinnitus-specific HRQOL in tinnitus patients but had significant impacts on their psychiatric comorbidities. However, in patients who experienced exacerbation of tinnitus during migraine attacks, the presence of migraine had a significant impact on the tinnitus-specific HRQOL, hearing handicap, and psychiatric comorbidities.
Feasibility and Outcomes of an Active Osseointegrated Bone Conduction Implant in Children as Young as 5 Years of Age
Authors: Cushing Sharon L. , Goh Samantha , Treble Alexander , Papsin Blake C. , Gordon Karen A.
Published: August 2024

Introduction

This study reviews the feasibility of implanting active osseointegrated bone conduction devices in young children, below the prior age for FDA indication (<12 years), which has recently been reduced to 5 years. Outcomes included differences in adverse event rates and operative time between two groups (<12 and 12 years or older).

Materials and Methods

This study is a retrospective review of children receiving active osseointegrated bone conduction devices at a tertiary referral center academic hospital. One hundred and twenty-four children received 135 active osseointegrated bone conduction devices (May 2018–March 2024).

Results

Of 135 devices, 77 (57%) were in children <12 years (mean age (SD) = 7.9 (2.0) years, range = 4.9–11.9 years) and 58 (43%) were in 12 years or older (mean age (SD) = 15.1 (1.7) years, range = 12–18 years). Adverse events were significantly higher in the older group, occurring in 8 (10%) of 77 devices in children <12 years and 15 (26%) of 58 devices in children 12 years and older (26%) (Fisher’s exact test = 0.0217 at p < 0.05). Major adverse events occurred in 5/124 (4%) patients, with 2 in patients <12 years (2/73, 3%) and 3 in children 12 and older (3/51, 6%). The proportion of major events between groups was not significantly different (Fisher’s exact test = 0.4, p < 0.05). Mean surgical time was significantly less (t = −2.8799, df = 120.26, p = 0.005) in the children <12 years (mean (SD) = 66.5 (22.4) min) compared to those 12 and over (mean (SD) = 78.32 (23.1) min).

Conclusions

Implantation of active osseointegrated bone conduction devices is feasible in children as young as 5 years and demonstrates low rates of complication. Further miniaturization may allow even earlier safe intervention.
Sound Localization in Active Transcutaneous Bone Conduction Implant Users with Single-Sided Deafness
Authors: Epperson Madison V. , Jones Gerilyn , Abdulrazzak Obada , Anidi Chioma , Ibrahim Nadine , Banakis Hartl Renee
Published: August 2024

Objective

Evaluate sound localization accuracy of subjects with single-sided deafness (SSD) with active transcutaneous bone conduction implants (atBCIs).

Study Design

Prospective case–control study.

Setting

Tertiary referral center.

Patients

Ten SSD patients (with ATBCIS) and 10 controls.

Interventions

Localization was assessed in a semianechoic chamber using a 24-speaker array. Stimuli included broadband noise (BBN) and narrowband noise (NBN). Perceived stimulus angle was recorded and compared with presented location. Statistical analyses were performed using ANOVA and Wilcoxon rank sum tests.

Main Outcome Measures

The primary outcome measures were as follows: 1) mean angular error (MAE) error (°) and regression slope and 2) subjective benefit assessment (Speech Spatial Qualities questionnaire).

Results

Subjects with SSD demonstrated worse localization by MAE and regression slope compared with controls for both broadband noise (p < 0.0001) and narrowband noise at 500 Hz and 1000 kHz (p < 0.0001). There was no statistically significant difference (p = 0.1090) in slope between all groups at 4000 Hz. There was no significant difference in slope or MAE aided compared with unaided. Localization ability varied widely within the SSD cohort, with some individuals showing some ability in the unaided condition, best at 4000 Hz. Although SSQ confirmed particular difficulty in the spatial hearing domain, all domains improved with device use.

Conclusions

Localization ability for individuals with SSD falls into a somewhat bimodal distribution. Some have fair localization, particularly at high frequencies, that is preserved but not improved with the atBCI. Others have minimal to no localization ability at any frequency, with no apparent device benefit.
Influence of Anatomy-Based Fitting in Cochlear Implant Users on Music Perception Using the Montreal Battery of Evaluation of Amusia
Authors: Heitkötter Felix S. , Krämer Bianca A. , Beule Achim G. , Rudack Claudia
Published: August 2024

Objectives

The aim is to investigate the influence of the anatomy-based fitting (ABF) in cochlear implants (CI) on the perception of specific musical features.

Design

The Montreal Battery of Evaluation of Amusia (MBEA) test battery was performed with a collective of 16 CI users with and without an anatomy-based fitting and 9 normal hearing subjects. The insertion angles of the intracochlear electrode arrays were calculated using Otoplan® (MED-EL, Innsbruck, Austria) software.

Results

CI users with an anatomy-based fitting achieve better results in the MBEA in all categories, especially in rhythm, meter, and memory. There is no effect of insertion depth alone on the ability to perceive musical features, even after anatomy-based fitting.

Conclusions

The results of the CI users in comparison to normal hearing people confirm previous studies. Apart from better speech understanding in CI users, which has been demonstrated in other studies, the anatomy-based fitting also contributes to a better perception of musical features. Currently, there are no comparable studies on this relationship. Investigations with further parameters with the help of the MBEA are pending.

Significance

Our results show that anatomy-based fitting of cochlear implants significantly improves the perception of specific musical attributes and thus leads to an increased enjoyment of music.
Cochlear implantation in children with single-sided deafness under the age of 5 years: a review of current literature
Authors: Mammen Luke , Zlatopolsky Aaron , Tu Nathan
Published: August 2024

Purpose of review

Here we explore the current literature on cochlear implantation of pediatric patients under the age of 5 years with single-sided deafness (SSD).

Recent findings

Single-sided deafness has been noted to cause developmental delays in speech, language, and cognition because of loss of binaural hearing. Currently, cochlear implantation is the only intervention capable of restoring binaural hearing for pediatric patients with SSD. Young children have been shown to have the greatest neuroplasticity of the auditory cortex before 4 years of age. Currently, only children over the age of 5 years are approved by the United States Food and Drug Administration (FDA) to undergo cochlear implantation for SSD. Cochlear implantation for SSD in patients under the age of 5 years has been performed on a limited basis and has been shown to have excellent results.

Cochlear implantation is a well tolerated and effective treatment for pediatric patients under the age of 5 years with SSD. Receiving cochlear implantation under the age of 5 years is critical for child development as neuroplasticity decreases after this age.
Autoimmune dysphagia
Authors: Tai Vicky , Suppiah Ravi
Published: August 2024

Purpose of review

Dysphagia is a complication of several autoimmune rheumatic diseases and otorhinolaryngologists are likely to be involved in the assessment and management of patients with such conditions. This review provides an update on rheumatic diseases that may cause swallowing impairment, with particular focus on the epidemiology, pathophysiology and management of dysphagia in these conditions.

Recent findings

Dysphagia is a common complication of the following rheumatic diseases: idiopathic inflammatory myopathies, systemic sclerosis, Sjogren's syndrome, systemic lupus erythematosus and rheumatoid arthritis. It may also be a complication of rarer autoimmune conditions such as Bechet's syndrome, sarcoidosis and granulomatosis with polyangiitis. All three stages of swallowing (oral, pharyngeal and oesophageal) may be impaired in these conditions. Both medical therapy and surgical intervention play an important role in the management of autoimmune dysphagia.

The investigation and management of autoimmune dysphagia requires close collaboration between rheumatologists and otorhinolaryngologists. There is a need for further research to establish standardised guidelines on the assessment and management of autoimmune dysphagia.
Exoscope-assisted surgery in otology and neurotology
Authors: Di Bari Matteo , Colombo Giovanni
Published: August 2024

Purpose of review

This review addresses the pressing need for an updated understanding of high-definition 3D exoscope role in contemporary otologic and neurotologic practice. With technological advancements driving innovations in surgical visualization, it is crucial to evaluate the efficacy of exoscope-assisted surgery compared to traditional microscopic approaches. By synthesizing recent literature, this review offers insights into the current state of exoscopic ear and lateral skull base surgery and its implications for clinical practice and research.

Recent findings

Recent literature has focused on several key themes. Firstly, studies have demonstrated the feasibility and safety of exoscopic approaches for various otologic and neurotologic procedures. Secondly, comparative studies have highlighted similar outcomes with exoscopic techniques compared to conventional microscopic surgery, particularly in terms of operative time and complication rates. Thirdly, the exoscope can be a valuable tool for the education and training of surgeons.

The findings from recent literature underscore the growing significance of exoscope-assisted surgery in otology and lateral skull base practice. However, challenges such as high magnification image quality and learning curve must be addressed to optimize its widespread adoption. Overall, this review highlights the importance of continued research and innovation in this rapidly evolving field.
Experiences of Care, Racism, and Communication of Postpartum Black Women Readmitted After Delivery
Authors: Burdick Micki , Oshewa Oluwadamilola , Janevic Teresa , Wang-Koehler Eileen , Zeitlin Jennifer , Howell Elizabeth A.
Published: August 2024

OBJECTIVE:

To explore the contribution of psychosocial factors, perceived barriers to care, structural racism, and experiences of care to disparities in postpartum outcomes for Black patients, as measured by emergency department (ED) visits and postpartum readmissions.

METHODS:

We conducted semi-structured interviews with women of color who were readmitted or had an ED visit related to perinatal outcomes within 30 days of delivery hospitalization. We created an interview guide based on patient, community, and health system factors, asking questions about care and lived experience through delivery, discharge, coming home, and ED visits or readmission during the postpartum period. Patients were identified through the electronic medical record system. Interviews ranged from 30 to 60 minutes and were transcribed, and medical charts were reviewed for delivery and postpartum outcomes. We coded interviews through deductive engagement with the interview guide, which was validated through double-comparative coding between researchers, and used content analysis to delineate themes surrounding barriers to and lack of quality postpartum care for birthing people of color.

RESULTS:

Principal themes that emerged from the interviews with participants were: perceived lack of communication about the complications they experienced; structural racism described through examples of not being listened to or believed; a perceived lack of respect for Black women's bodies by doctors and nurses, which became embedded in inappropriate verbal and nonverbal communication practices by clinicians and staff; and mismatches in care for participants were noted from the care provided and chart documentation compared with what patients understood to be happening with their health.

CONCLUSION:

To counter the increasing rates of morbidity and mortality among postpartum Black patients, stronger efforts are required to address the needs of Black patients during the postpartum period through documenting and acknowledging patients' lived experiences, addressing communication needs, and understanding the consequences of structural racism.
Review of Hard Palate Lipoma and Retrospective Clinicopathological Analysis of Patients With Oral Lipomas
Authors: Zhao Guile , Wang Guanru , Paka Lubamba Grace , Bao Mingzhe , Li Chunjie , Gao Ning
Published: August 2024

Lipomas occurring in the hard palate are extremely rare, and treating lipomas in this area presents challenges due to the thinness of soft tissue and the risk of postoperative bony surface exposure. We present a case of hard palate lipoma that was successfully removed using the partial thickness flap dissection technique. In addition, we reviewed the clinicopathological features of 20 reported cases of hard palate lipomas worldwide and retrospectively analyzed the clinical characteristics and pathological types of 68 oral lipomas in China. The use of a partial thickness flap demonstrates potential effectiveness in excising benign masses located in the hard palate. Regarding 68 patients with oral lipomas, the most commonly affected sites were the buccal region, tongue, and floor of the mouth. Histologically, simple lipomas and fibrolipomas were the predominant types observed.
MicroRNA-32-5p inhibits metastasis by directly targeting VPS4B and increases sensitivity to dihydroartemisinin in neuroblastoma
Authors: Chen Lina , Liu Hui , Zheng Zhongyuan , Qu Shuiqing , Zhang Yu , Deng Shuoqiu , Shen Shuo , Liu Tuo , Dai Yue , Li Yu , Cui Honghua , Li Yujie
Published: August 2024

Background

Neuroblastoma (NB) is a malignant pediatric tumor requiring new therapies. Accumulating evidence has confirmed that microRNAs play critical roles in NB metastasis. Dihydroartemisinin (DHA) is capable of inhibiting the growth of NB cells. The primary objective of the current investigation was to characterize a newly discovered microRNA, miR-32-5p, in terms of the functional role, underlying mechanism of action, and potential synergistic therapeutic impact in the context of NB metastasis.

Materials and methods

Real-time quantitative polymerase chain reaction and Western blotting were employed to assess the expression levels of miR-32-5p and its target, vacuolar protein sorting 4B (VPS4B). Furthermore, Transwell assay was utilized to evaluate in vitro cell migration and invasion, whereas a metastasis xenograft model was established in nude mice via caudal vein injections.

Results

Gene Expression Omnibus database and real-time quantitative polymerase chain reaction analysis showed that miR-32-5p was downregulated in human NB samples and NB cell lines, in comparison with the normal tissue and cell lines. Inhibiting miR-32-5p induced the migration and invasion of NB cells, whereas overexpression of miR-32-5p prevented the migration and invasion in NB cell lines. Furthermore, VPS4B was identified as the direct target of miR-32-5p and the miR-32-5p reduction associated with NB metastasis upregulated the expression of VPS4B. Conversely, overexpression of VPS4B reversed the suppressive effects of miR-32-5p on NB cells. Moreover, miR-32-5p increased the sensitivity to DHA both in NB cells and in the metastasis xenograft model of nude mice.

Conclusions

The downregulation of miR-32-5p in NB regulates NB metastasis by targeting VPS4B. Moreover, miR-32-5b can improve the sensitivity of DHA in the xenograft mouse model. Our findings have important implications for the combined application of miR-32-5p and DHA in the treatment of NB.
Transcriptomic signatures of mouse ovarian aging and estropausal transition at single cell resolution
Authors: Wang Xifan , Yang Jiping , Jin Chen , Wang Xizhe , Contreras Daniela , Devos Melody , Suh Yousin
Published: August 2024

Female reproductive aging affects fertility and overall health. Functional decline in mouse ovary during reproductive aging is accompanied by estrous cycle prolongation and cessation. However, the molecular mechanism underlying reproductive aging concomitant with such cycle changes remains unclear. Using single-cell transcriptomics, we characterized aging signatures in mouse ovaries across the reproductive lifespan ranging from reproductively young (regular cycle) through peri-estropause (regular vs. irregular cycles) to post-estropause age (acyclic). Reproductive aging significantly remodeled cell compositions and increased transcriptional heterogeneity, with more pronounced changes post-estropause, exhibiting coordinated alterations across cell types in the ovary. Genes undergoing monotonic changes during reproductive aging across cell types were consistently enriched in the conserved pathways of aging, including oxidative phosphorylation, stress responses, and proteostasis. Additionally, cell type-specific changes were identified including dysregulation of hormone synthesis in granulosa cells, alterations in collagen and hyaluronan metabolism in stromal and early theca cells, and functional decline of a unique phagocytosis-associated macrophage. Aging also led to a significant decrease in cell-cell communications, particularly between stromal and granulosa cells, and an increase in extracellular vesicle secretion. Furthermore, we found increased expression of the senescence marker Cdkn1a and senescence-associated secretory phenotype (SASP) factors during ovarian aging, especially in granulosa cells. Notably, most of these aging-associated changes were more pronounced in irregular cycling ovaries compared to the regular cycling counterparts at the same age during the peri-estropause stage, suggesting that aging-related molecular changes in the ovary drive the estropausal transition in mice.
The effect of microsaccades in the primary visual cortex: a two-phase modulation in the absence of visual stimulation
Authors: Nativ Yarden , Bouhnik Tomer , Slovin Hamutal
Published: August 2024

Our eyes are never still. Even when we attempt to fixate, the visual gaze is never motionless, as we continuously perform miniature oculomotor movements termed as fixational eye movements. The fastest eye movements during the fixation epochs are termed microsaccades (MSs), that are leading to continual motion of the visual input, affecting mainly neurons in the fovea. Yet our vision appears to be stable. To explain this gap, previous studies suggested the existence of an extra-retinal input (ERI) into the visual cortex that can account for the motion and produce visual stability. Here, we investigated the existence of an ERI to V1 fovea in behaving monkeys while they performed spontaneous MSs, during fixation. We used voltage-sensitive dye imaging (VSDI) to measure and characterize at high spatio-temporal resolution the influence of MSs on neural population activity, in the foveal region of the primary visual cortex (V1). In the absence of a visual stimulus, MSs induced a two-phase response modulation: an early suppression transient followed by an enhancement transient. A correlation analysis revealed an increase in neural synchronization around ∼100 ms after MS onset. Next, we investigated the MS effects in the presence of a small visual stimulus, and found that this modulation was different from the non-stimulated condition yet both modulations co-existed in the fovea. Finally, the VSD response to an external motion of the fixation point could not explain the MS modulation. These results support an ERI that may be involved in visual stabilization already at the level of V1.
Identification of In Vivo Internalizing Cardiac-Specific RNA Aptamers
Authors: Narayan Chandan , Lin Li-Hsien , Barros Maya N. , Gilbert Trent C. , Brown Caroline R. , Reddin Dominic , London Barry , Chen Yani , Wilson Mary E. , Streeter Jennifer , Thiel William H.
Published: August 2024

Background

The pursuit of selective therapeutic delivery to target tissue types represents a key goal in the treatment of a range of adverse health issues, including diseases afflicting the heart. The development of new cardiac-specific ligands is a crucial step towards effectively targeting therapeutics to the heart.

Methods

Utilizing anex vivoandin vivoSELEX approaches, we enriched a library of 2’-fluoro modified aptamers for ventricular cardiomyocyte specificity. Lead candidates were identified from this library, and their binding and internalization into cardiomyocytes was evaluated in bothex vivoandin vivomouse studies.

Results

Theex vivoandin vivoSELEX processes generated an aptamer library with significant cardiac specificity over non-cardiac tissues such as liver and skeletal muscle. Our lead candidate aptamer from this library, CA1, demonstrates selectivein vivotargeting and delivery of a fluorophore cargo to ventricular cardiomyocytes within the murine heart, while minimizing off-target localization to non-cardiac tissues, including the liver. By employing a novel RNase-based assay to evaluate aptamer interactions with cardiomyocytes, we discovered that CA1 predominantly internalizes into ventricular cardiomyocytes; conversely, another candidate CA41 primarily binds to the cardiomyocyte cell surface.

Conclusions

These findings suggest that CA1 and CA41 have the potential to be promising candidates for targeted drug delivery and imaging applications in cardiac diseases.
Long-term non-trophic effects of large herbivores on plant diversity are underestimated
Authors: Chen Qingqing , Bakker Jan P. , Alberti Juan , Bakker Elisabeth S. , Smit Christian , Olff Han
Published: August 2024

The positive effects of large herbivores on plant diversity in grasslands have so far been mainly attributed to increased light availability or suppressed dominance, and thus to the consequences of aboveground biomass consumption (trophic effects). However, these insights are mainly derived from short-term experiments. Using a 46-year experiment in a salt marsh, comparing cattle grazing, mowing (as a proxy of aboveground consumption) and the ungrazed control, we found that the non-trophic effects (e.g. trampling, deposition of urine and dung) of large herbivores on plant diversity increased over time, exceeding that of the trophic effects after 23 years. This long-term accumulation of non-trophic effects through slow ecosystem-level feedback highlights the sustainability of using low to moderate densities of large herbivores to conserve plant diversity. Our results emphasize the need for the conservation and re-introduction of large herbivores, domestic or wild, to sustain long-term grassland plant diversity.
Submolecular-scale Hairpin DNA Folding Dynamics Studied by High-Speed AFM with Optical Tweezers
Authors: Umeda Kenichi , Yamanaka Shin’nosuke , Imamura Motonori , Nagae Fritz , Fukuda Shingo , Watanabe Hiroki , Uchihashi Takayuki , Takada Shoji , Ando Toshio
Published: August 2024

Optical tweezers have contributed to elucidate the folding mechanisms associated with biomolecules. By combining single-molecule or super-resolution techniques, imaging can also be performed while measuring or inducing force coupling with biochemical reactions; however, they cannot capture structural information beyond the fluorophore spatial resolution. To overcome this problem, here, we developed a technique that combines optical tweezers with high-speed atomic force microscopy (AFM). To solve the problem of incompatible instrumental configurations, we developed a unique optical tweezers measurement system that is specialized for high-speed AFM. Upon applying an external force to a synthesized DNA secondary structure, we successfully visualized the dissociation of the duplex structure. Furthermore, we succeeded in observing spontaneous reannealing of the duplex structure upon releasing the force, which demonstrates that the folding reaction can be reversibly controlled. We also reveal that along with duplex unfolding, a metastable secondary structure is generated and its topology changes transiently over time. The results indicate that this technique provides structural insights that cannot be obtained by conventional fluorescence techniques.
Dysregulated Airway Host Defense in Hyper IgE Syndrome due to STAT3 Mutations
Authors: Sun Ling , Walls Samantha A. , Dang Hong , Quinney Nancy L. , Sears Patrick R. , Sadritabrizi Taraneh , Hasegawa Koichi , Okuda Kenichi , Asakura Takanori , Chang Xiuya , Zheng Meiqi , Mikami Yu , Dizmond Felicia U. , Danilova Daniela , Zhou Lynn , Deshmukh Anshulika , Cholon Deborah M. , Radicioni Giorgia , Rogers Troy D. , Kissner William J. , Markovetz Matthew R. , Guhr Lee Tara N. , Gutay Mark I. , Esther Charles R. , Chua Michael , Grubb Barbara R. , Ehre Camille , Kesimer Mehmet , Hill David B. , Ostrowski Lawrence E. , Button Brian , Gentzsch Martina , Robinson Chevalia , Olivier Kenneth N. , Freeman Alexandra F. , Randell Scott H. , O’Neal Wanda K. , Boucher Richard C. , Chen Gang
Published: August 2024

Rationale

Hyper IgE syndrome (STAT3-HIES), also known as Job’s syndrome, is a rare immunodeficiency disease typically caused by dominant-negative STAT3 mutations. STAT3-HIES syndrome is characterized by chronic pulmonary infection and inflammation, suggesting impairment of pulmonary innate host defense.

Objectives

To identify airway epithelial host defense defects consequent to STAT3 mutations that, in addition to reported mutant STAT3 immunologic abnormalities, produce pulmonary infection.

Methods

STAT3-HIES sputum was evaluated for biochemical/biophysical properties. STAT3-HIES excised lungs were harvested for histology; bronchial brush samples were collected for RNA sequencing and in vitro culture. A STAT3-HIES-specific mutation (R382W), expressed by lentiviruses, and a STAT3 knockout, generated by CRISPR/Cas9, were maintained in normal human bronchial epithelia under basal or inflammatory (IL1β) conditions. Effects of STAT3 deficiency on transcriptomics, and epithelial ion channel, secretory, antimicrobial, and ciliary functions were assessed.

Measurements and Main Results

Mucus concentrations and viscoelasticity were increased in STAT3-HIES sputum. STAT3-HIES excised lungs exhibited mucus obstruction and elevated IL1β expression. STAT3 deficiency impaired CFTR-dependent fluid and mucin secretion, inhibited expression of antimicrobial peptides, cytokines, and chemokines, and acidified airway surface liquid at baseline and post-IL1β exposure in vitro. Notably, mutant STAT3 suppressed IL1R1 expression. STAT3 mutations also inhibited ciliogenesis in vivo and impaired mucociliary transport in vitro, a process mediated via HES6 suppression. Administration of a γ-secretase inhibitor increased HES6 expression and improved ciliogenesis in STAT3 R382W mutant cells.

Conclusions

STAT3 dysfunction leads to multi-component defects in airway epithelial innate defense, which, in conjunction with STAT3-HIES immune deficiency, contributes to chronic pulmonary infection.