bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcomes of Cyclosporine Ophthalmic Emulsion 0.05% Use in Pediatric Blepharokeratoconjunctivitis
Authors: Salini Raul Plasencia , Ma Elise L. , Huang Tiffany L. , Dallalzadeh Liane O. , Fung Simon S. M.
Published: September 2024

Purpose:

Pediatric blepharokeratoconjunctivitis (BKC) is a chronic ocular surface inflammatory disease. In this article, we report our experience using low-dose topical cyclosporine (CsA) 0.05% for the treatment of pediatric BKC.

Methods:

A retrospective review was conducted on pediatric patients treated with topical CsA 0.05% for BKC between 2018 and 2022 at a single academic institution. Patients with less than 6 weeks of follow-up, a history of ocular infectious disease, or previous usage of topical/systemic immunomodulators (except corticosteroids) were excluded. The primary outcome was the change in the number of episodes of disease reactivation (flare) before and after the use of CsA 0.05%. Secondary outcomes included the number of clinic visits per year, success rate in corticosteroid tapering, and usage of rescue topical corticosteroid.

Results:

A total of 21 patients (13 male patients and 8 female patients) treated with CsA 0.05% twice daily were included in this study. The mean age of patients was 9.7 ± 4.2 years, and the mean follow-up period was 62.2 ± 62.5 weeks. The median number of flares per year was 5.6 (95% CI, 3.9–7.3) before treatment with CsA 0.05%, which reduced to 0.0 (95% CI, 0.0–0.9) while on CsA 0.05% (P = 0.01). The median number of clinic visits significantly reduced from 9.5 (95% CI, 7.3–11.7) to 4.5 (95% CI, 3.7–6.8) visits per year (P < 0.0001). After 3.5 ± 2.7 weeks, 90.4% of patients using topical CSs concomitantly with topical CsA 0.05% could be successfully tapered off their topical CSs. Of the patients who tapered off their topical CSs, 3 patients (15%) later required rescue topical CSs despite ongoing CsA 0.05% treatment because of acute flare episodes. No adverse effects were reported with CsA use.

Conclusions:

This study demonstrates the efficacy of low-dose topical CsA 0.05% in reducing the frequency of acute flares and clinic visits per year in pediatric BKC.
INTIMASY-TBI Guideline: Optimization of INTIMAcy, SexualitY, and Relationships Among Adults With Traumatic Brain Injury
Authors: Patsakos Eleni M. , Backhaus Samantha , Farris Kathryn , King Marisa , Moreno Jhon Alexander , Neumann Dawn , Sander Angelle , Bayley Mark T.
Published: September 2024

Introduction:

Traumatic brain injury (TBI) can negatively impact intimacy, relationships, and sexual functioning through changes in physical, endocrine, cognitive, behavioral, and emotional function. Without intervention, diminished intimacy and/or sexual functioning in individuals with TBI may persist. Although most health care professionals agree that sexuality and intimacy in relationships are significant concerns and should be addressed in rehabilitation, these concerns are not typically discussed during rehabilitation and discharge planning for people with TBI. To address this gap, an expert panel of North American clinicians and researchers convened to develop evidence-informed recommendations to assist clinicians in providing a framework and guidance on how clinicians can support individuals after TBI.

Methods:

A systematic search of multiple databases was conducted to identify relevant evidence published from 2010 to 2023. The INTIMASY-TBI Expert Panel developed recommendations for optimizing discussions and interventions related to intimacy and sexuality for people with TBI in rehabilitation and community-based programs. For each recommendation, the experts evaluated the evidence by examining the study design and quality to determine the level of evidence.

Results:

A total of 12 recommendations were developed that address the following topic areas: (1) interprofessional team training, (2) early education on the effects of TBI on intimacy, relationships, and sexuality, (3) creating individualized interventions, (4) education, assessment, and management of the causes of sexual dysfunction, and (5) providing written materials and relationship coaching to persons with TBI and their partners. Two recommendations were supported by Level A evidence, 1 was supported by Level B evidence, and 9 were supported by Level C (consensus of the INTIMASY-TBI Expert Panel) evidence. A decision algorithm was developed to assist clinicians in navigating through the recommendations.

Conclusion:

The INTIMASY-TBI Guideline is one of the first comprehensive clinical practice guidelines to offer strategies to trained clinicians to discuss the physical, psychosocial, behavioral, and emotional aspects of intimacy and sexuality with persons with TBI.
The Predictive Value of Preoperative Measurements of Cochlear Nerve Diameters From MRT and Postoperative Speech Perception in Adult Patients With Cochlear Implant
Authors: Zhang Lichun , Schmidt Florian Herrmann , Cantré Daniel , Brenzel Robert , Ehrt Karsten , Großmann Wilma , Langner Sönke , Mlynski Robert
Published: September 2024

Objective

The current study aims to investigate whether objective measurements of the cochlear nerve (CN), derived from preoperative MRI images, correlate with postoperative speech perception in CI patients.

Study Design

Retrospective cohort study.

Setting

University Medical Center, tertiary academic referral center.

Patients

Patients undergoing a cochlear implant surgery including MED-EL (Synchrony 2, FLEX electrode series; MED-EL, Innsbruck, Austria) Cochlear (slim straight electrodes; Cochlear Ltd., Sydney, Australia), Advanced Bionics (HiRes Ultra 3D CI, HiFocus SlimJ electrodes; Sonova, Zürich, Switzerland), and Oticon (Neuro Zti EVO; Oticon A/S, Smørum, Denmark) between 2020 and 2023.

Intervention

Preoperative MRI images were utilized to measure the volume of the modiolus (VM), the cross-sectional areas of the CN (ACN), and for normalization, the area of the facial nerve (AFN) and the area of the internal ear canal (AIEC). Postoperative speech perceptions were assessed through word recognition scores (WRS) at several stages following the first fitting (FF) of the CI processor: immediately after FF, 1 month, 3 months, and 6 months after FF.

Main Outcome Measures

Sixty-eight patients were enrolled in this study. A statistically significant positive correlation between the ratio between ACN and AFN (ACN/AFN) and WRSFF was identified (R = 0.36, p < 0.003). However, this correlation disappeared in subsequent follow-up tests. Moreover, upon grouping patients based on their degree of asymmetrical hearing loss, it was observed that the correlation was primarily driven by patients with moderate to severe asymmetrical hearing loss (AHLm) on the contralateral side (R = 0.62, p = 0.0003).

Conclusion

The present results suggest that assessing the size of the CN through MRI has limited predictive utility for postoperative speech perceptions during CI consultations. This limitation seems to be particularly relevant for AHLm patients and is confined to the initial activation period.
A Selection Protocol to Identify Therapeutics to Target NLRP3-Associated Sensory Hearing Loss
Authors: Schiel Viktoria , Eftekharian Kourosh , Xia Anping , Bekale Laurent A. , Bhattacharya Ritwija , Santa Maria Peter L.
Published: September 2024

Objective

We propose a selection process to identify a small molecule inhibitor to treat NLRP3-associated sensory hearing loss.

Background

The NLRP3 inflammasome is an innate immune sensor and present in monocytes and macrophages. Once the inflammasome is activated, a cleavage cascade is initiated leading to the release of proinflammatory cytokines IL-1β and IL-18. The NLRP3 inflammasome has been implicated in many causes of hearing loss, including autoimmune disease, tumors, and chronic suppurative otitis media. Although the target has been identified, there is a lack of available therapeutics to treat NLRP3-associated hearing loss.

Methods

We created a target product profile with specific characteristics that are required for a compound to treat sensory hearing loss. We then looked at available small molecule NLRP3 inhibitors at different stages of development and selected compounds that fit that profile best. Those compounds were then tested for cell toxicity in MTT assays to determine the dosage to be used for efficacy testing. We tested efficacy of a known NLRP3 inhibitor, MCC950, in a proof-of-concept screen on reporter monocytes.

Results

Six compounds were selected that fulfilled our selection criteria for further testing. We found the maximum tolerated dose for each of those compounds that will be used for further efficacy testing. The proof-of-concept efficacy screen on reporter monocytes confirmed that those cells can be used for further efficacy testing.

Conclusion

Our selection process and preliminary results provide a promising concept to develop small molecule NLRP3 inhibitors to treat sensory hearing loss.
Validation of TMB-2285-BT wrist blood pressure monitor in general population according to the ISO 81060-2:2018 + Amd.1:2020 Protocol
Authors: Xie Zijian , Peng Bin , Hu Jia , Wang Xinda , Du Xiaoqin , Li Chaoya , Liang Jiahui
Published: September 2024

The objective of this study is to evaluate the accuracy of the wrist blood pressure (BP) monitor (TMB-2285-BT) in general population according to international standard of ISO 81060-2:2018+Amd.1:2020. The TMB-2285-BT BP monitor is an oscillometric device measuring BP from wrist. A single cuff for wrist sizes of 13.5–21.5 cm was used for the test device. The study was performed according to the ‘International Standard (ISO 81060-2:2018 + Amd.1:2020) protocol’ using the same-arm sequential BP measurement method. Subjects (n ≥ 85) fulfilling the age, gender, BP, and cuff distribution criteria of the protocol were enrolled. For criterion 1, the mean difference of SBP and DBP between the test device and the reference device was −0.27 mmHg and −0.80 mmHg, respectively. For criterion 2, the SD of the averaged paired determinations of SBP and DBP for the test device and the reference device was 2.60 and 2.06 mmHg, respectively, both of which were less than 6.95 and 6.89 mmHg. The accuracy of the test device fulfilled the requirements of the criterion 1 and 2 of ISO 81060-2:2018 + Amd.1:2020. The TMB-2285-BT wrist BP monitor can be recommended for home BP measurement for general population.
Education differences in blood pressure trajectories by sex through midlife: Findings from the National Health and Nutrition Examination Survey, 1999–2018
Authors: Calixte Rose , Besson Ayanna , Chahal Kunika , Kaplan Mark S.
Published: September 2024

Objective

Although it has long been established that age and sex play a role in blood pressure levels across the lifespan, the extent to which educational attainment moderates these relationships has been understudied. Thus, the purpose of this study was to assess educational differences in SBP, DBP, and pulse pressure (PP) trajectories among men and women through the midlife years.

Method

We conducted an analysis of pooled data from the 1999 to 2018 National Health and Nutrition Examination Survey to assess whether education moderates blood pressure measurements among men and women over the midlife years. Statistical analyses were performed using survey-weighted linear and quadratic regressions to assess these trajectories.

Results

During midlife, women with at least a college degree maintained the lowest average level of SBP compared to men at all education levels and women with a high school diploma or less. They also maintained the lowest level of PP, though not different from men with at least a college degree and women with less than a college degree. However, no educational differences were observed in DBP between men and women during the midlife years.

Conclusion

Our study shows clear delineation in the trajectories of PP and SBP by education such that a 4-year education is more protective than some college and a high school degree, particularly among women. These results highlight the need to consider upstream policy interventions (education policy initiatives) that could reduce population-wide elevated blood pressure.
Unattended versus conventional blood pressure measurements in hospitalized hypertensive patients
Authors: Hu Zhe , Chu Rui , Gao Yang , Chen Xin , Sheng Chang-Sheng
Published: September 2024

Background

This study aims to compare the differences between unattended and conventional blood pressure measurements in hospitalized hypertensive patients.

Methods

In fall of 2019, hypertensive patients at Ruijin Hospital underwent two rounds of unattended and conventional (nurse-monitored) blood pressure measurement. Both rounds used the same electronic blood pressure monitor with measurements taken three times, 30 s apart. Comparison was made using intra-class correlation coefficients, Bland–Altman plots, paired t-tests, etc.

Results

Among the 92 subjects in the study, the median age was 50 years old, with women accounting for 33.7%. Among the subjects, the median duration of hypertension was 8.0 years. The prevalence of diabetes, coronary heart disease, and stroke were 26.1%, 5.4%, and 6.5%, respectively. Whether unattended or conventional measurements were taken first, the average blood pressure measured first was slightly higher than the one measured later, but the difference was within 1–2 mmHg. Except that the average DBP during the round of conventional blood pressure measurements was significantly reduced by 1.6 mmHg compared to the conventional DBP, there were no other significant differences. Subgroup analysis by age, gender, BMI, and diabetes showed no significant difference in blood pressure measurement results between unattended and conventional methods.

Conclusion

No significant difference was observed between unattended and conventional methods of blood pressure measurement in hospitalized hypertensive patients. Unattended blood pressure measurement can be adopted as the current standard for blood pressure management in hospitalized patients.
Using Patient Experience Surveys to Identify Potential Diagnostic Safety Breakdowns: A Mixed Methods Study
Authors: Baker Kelley M. , Brahier Mark , Penne Mara , Hill Mary A. , Davis Siara , Gallagher William J. , Miller Kristen E. , Smith Kelly M.
Published: September 2024

Objectives

One in 20 outpatients in the United States experiences a diagnostic error each year, but there are no validated methods for collecting feedback from patients on diagnostic safety. We examined patient experience surveys to determine whether patients’ free text comments indicated diagnostic breakdowns. Our objective was to evaluate associations between patient-perceived diagnostic breakdowns reported in free text comments and patients’ responses to structured survey questions.

Methods

We conducted an exploratory mixed methods study using data from patient experience surveys collected from adult ambulatory care patients March 2020 to June 2020 in a large U.S. health system. Data analysis included content analysis of qualitative data and statistical analysis of quantitative data.

Results

In 2525 surveys with negative comments, 619 patients (24.5%) identified diagnostic breakdowns, including issues with accuracy (n = 282, 46%), timeliness (n = 243, 39%), or communication (n = 290, 47%); some patients (n = 181) reported breakdowns in multiple categories. Patients who gave a low average score (50 or less on a 100-point scale) on provider questions were almost seven times more likely to perceive a diagnostic breakdown than patients who scored their provider higher. Similarly, patients who gave a low average score on practice-related questions were twice as likely to perceive a diagnostic breakdown.

Conclusions

Patient feedback in routinely collected patient experience surveys is a valuable and actionable information source on diagnostic breakdowns in the ambulatory setting. The more easily monitored structured survey data provide a screening method to identify encounters that may have included a patient-perceived diagnostic breakdown and therefore require further examination.
Proteinuria and albuminuria among a global primary cardiovascular disease prevention cohort of people with HIV
Authors: Overton Edgar T. , Kantor Amy , Fitch Kathleen V. , Mosepele Mosepele , Aberg Judith A. , Fichtenbaum Carl J. , McComsey Grace A. , Malvestutto Carlos , Lu Michael T. , Negredo Eugenia , Bernardino Jose , Hickman Aubri B. , Douglas Pamela S. , Grinspoon Steven K. , Zanni Markella , Ribaudo Heather , Wyatt Christina ,   for the REPRIEVE Trial Investigators
Published: September 2024

Objective(s):

To determine baseline prevalence of proteinuria and albuminuria among participants from the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) and evaluate associated risk factors.

Design:

Cross sectional analysis of a baseline sample of participants from the REPRIEVE Trial.

Methods:

REPRIEVE is an international primary cardiovascular prevention randomized controlled trial (RCT) of pitavastatin calcium vs. placebo among people with HIV (PWH) on antiretroviral therapy (ART). A representative subset (2791 participants) had urine collected at study entry. Urine protein to creatinine ratios (uPCR) and albumin to creatinine ratios (uACR) were classified as normal, moderately increased and severely increased. These were dichotomized to Normal or Abnormal for log-binomial regression analysis. Demographic, cardiometabolic, and HIV-specific data were compared among those with normal versus abnormal results.

Results:

Overall, median age 49 years, 41% female sex, 47% black or African American race, 36% had estimated glomerular filtration rate (eGFR) less than 90 ml/min/1.73 mm2. For uPCR, 27% had moderately or severely increased values. For uACR, 9% had moderately or severely increased values. In the fully adjusted model for proteinuria, female sex, older age, residence in sub-Saharan Africa or East Asia, lower BMI, lower CD4+ cell count, and use of tenofovir disoproxil fumarate (TDF) were associated with abnormal values. In the fully adjusted model for albuminuria, a diagnosis of hypertension (HTN) was associated with abnormal values.

Conclusion:

Abnormal proteinuria and albuminuria remain common (27 and 9%) despite controlled HIV. Lower current CD4+ count and TDF use were strongly associated with proteinuria. Certain modifiable comorbidities, including HTN and smoking, were associated with abnormal values. In PWH with preserved eGFR, urine measures identify subclinical kidney disease and afford the opportunity for intervention.
CSF Susceptibility Variation in Patient With Intracranial Hemorrhage: Implications for Quantitative Susceptibility Mapping Reference Selection
Authors: Wang Shutao , Spincemaille Pascal , Selim Magdy , Hasan David , Thomas Ajith J. , Filippidis Aristotelis , Wen Yan , Wang Yi , Soman Salil
Published: September 2024

Background

Quantitative susceptibility mapping (QSM) is an emerging MRI technique with multiple clinical applications. As tissue susceptibility cannot be directly measured using MRI, QSM imaging techniques must indirectly compute susceptibility values, requiring regularization methods. CSF is a popular choice for regularization due to its near water susceptibility in healthy controls. However, the impact of pus, elevated protein, or blood dissolved in CSF on QSM regularization is not well defined.

Objective

This study aimed to investigate the effects of intracranial hemorrhage (ICH) on selecting CSF as reference for QSM imaging.

Materials and Methods

A total of 87 subjects, 53 with ICH (5 intraventricular, 19 subarachnoid, 27 both, and 2 intraparenchymal only) and 37 without hemorrhage (27 with MS, 10 without MS), were included in this study. Imaging was performed using 3D multiecho gradient echo, FLAIR, and multiecho complex total field inversion (mcTFI) at 3 T. McTFI with and without CSF zero-referencing regularization was generated from the 3DMEGRE data and reviewed with FLAIR images. Regions of hemorrhagic (H+) and nonhemorrhagic (H−) CSF were manually selected in reference to head CT and FLAIR images by a PGY III diagnostic radiology resident and Certificate of Added Qualification–certified neuroradiologist with 10 years' experience. Paired Student t test and one-way ANOVA were used with post hoc multicomparisons. A P value <0.05 was considered statistically significant.

Results

Areas of H− CSF were noted to have higher regularized QSM values in subjects with ICH relative to subjects without. Unregularized H− QSM values were also noted to have a systematically higher value in ICH subjects relative to subjects without blood. Subjects with MS and without ICH did not show significant difference in H− CSF regularized or unregularized QSM values.

Conclusions

QSM values of areas suggested to not have hemorrhage on other imaging showed significantly higher QSM values in ICH subjects relative to subjects without ICH. Additionally, areas of hemorrhage did not show significant QSM value difference between regularized and unregularized QSM images. These findings suggest that, in subjects with any area of ICH, QSM values for no-hemorrhagic areas may be significantly altered using CSF regularization relative to subjects without ICH, with implications for intra- and intersubject QSM value analysis.
Assessing Bronchiectasis Progression in Low-dose Screening for Lung Cancer
Authors: Cai Qiang , Triphuridet Natthaya , Zhu Yeqing , Yip Rowena , Yankelevitz David F. , Metersky Mark , Henschke Claudia I.
Published: September 2024

Purpose:

Bronchiectasis is associated with loss of lung function, substantial use of health care resources, and increased morbidity and mortality in people with cardiopulmonary diseases. We assessed the frequency of progression or new development of bronchiectasis and predictors of progression in participants in low-dose computed tomography (CT) screening programs.

Materials and Methods:

We reviewed our prospectively enrolled screening cohort in the Early Lung and Cardiac Action Program cohort of smokers, aged 40 to 90, between 2010 and 2019, and medical records to assess the progression of bronchiectasis after five or more years of follow-up after baseline low-dose CT. Logistic and multivariate-analysis-of-covariance regression analyses were used to examine factors associated with bronchiectasis progression.

Results:

Among 2182 baseline screening participants, we identified 534 (mean age: 65±9 y; 53.6% women) with follow-up screening of 5+ years (median follow-up: 103.2 mo). Of the 534 participants, 34 (6.4%) participants had progressed (25/126, 19.8%) or newly developed (9/408, 2.2%) bronchiectasis. Significant predictors of progression (progressed+newly developed) were: age (P=0.03), pack-years of smoking (P=0.004), baseline components of the ELCAP Bronchiectasis Score, including the severity of bronchial dilatation (P=0.01), its extent (P=0.01), bronchial wall thickening (P=0.04), and mucoid impaction (P<0.001).

Conclusions:

Assuming similar progression rates, ~136 out of 2182 participants are expected to progress on follow-up screening. This study sheds light on bronchiectasis progression and its significant predictors in a low-dose CT screening program. We recommend reporting bronchiectasis as participants who have smoked are at increased risk, and continued assessment over the entire period of participation in the low-dose CT screening program would allow for the identification of possible causes, early warning, and even early treatment.
Cerebral, Splanchnic, and Renal Transit Time Measurement and Blood Volume Estimation Using Contrast-Enhanced Ultrasonography
Authors: Monahan Ken , Kerrigan Deborah , Shibao Cyndya , Fissell William , Perri Roman , Planz Virginia
Published: September 2024

We aimed to measure cerebral, splanchnic, and renal transit times and the associated blood volumes using contrast ultrasound. In healthy individuals, regional transit times were calculated from time-intensity curves generated as ultrasound contrast passed through the associated inflow and outflow vessels. These included the internal carotid artery and internal jugular vein (brain), the superior mesenteric artery and portal vein (intestines), and the renal artery and renal vein (kidney). An organ's blood volume relative to the stroke volume delivered to that organ with each cardiac cycle was calculated from the product of heart rate and transit time of contrast passage through the associated vascular bed. The fraction of systemic stroke volume received by each organ was calculated from the respective velocity-time integral and inflow vessel cross-sectional area and used to estimate absolute organ blood volume. The cohort consisted of 16 participants (age: 42 ± 13 years; 5 female) without known cerebrovascular, gastrointestinal, or renal disease. Cerebral, splanchnic, and renal transit times were obtained for 15, 14, and 8 individuals, respectively. Anatomic variability of the renal vessels confounded the acquisition of renal transit times. For all organs, transit times were reproducible and the associated blood volumes were generally comparable to reference values. Cerebral, gastrointestinal, and renal transit times/blood volumes can be reasonably acquired from contrast ultrasound, although the latter is less reliably available. Assessment of the impact on regional blood volumes of pharmacologic or other interventions is a next step toward clinical application of this technique.
The Effect of NPWT on Odontogenic Cervical Necrotizing Fasciitis
Authors: Wang Qian , Yang Xiaolan , Wei Zhiyi , Lin Tianlai , Wang Longfeng
Published: September 2024

Objective:

To investigate the clinical efficacy of negative pressure wound therapy (NPWT) in the treatment of odontogenic cervical Necrotizing fasciitis (CNF).

Methods:

Sixteen cases of odontogenic cervical necrotizing fasciitis were randomly divided into observation group and control group after routine debridement and disinfection. The patients in the control group were treated with drainage tube and regular dressing changes, while those in the observation group were treated with NPWT. The therapeutic effects of the 2 groups were compared.

Results:

The frequency of operation, treatment length, and cost of treatment in the observation group were significantly less than those in the control group (P<0.05). During the treatment, the VAS (visual analog scale of pain) in the observation group was significantly lower than that in the control group (P<0.05). The levels of WBC, CRP, PCT, IL-6, and TNF-α in the observation group were lower than those in the control group (P<0.05). The levels of Il-10 and VEGF in the observation group were higher than those in the control group (P<0.05), the difference was statistically significant.

Conclusions:

The condition of odontogenic cervical necrotizing fasciitis progresses rapidly. Compared with conventional drainage and dressing change, NPWT can control infection in a short time, reduce operation frequency and treatment cost, and promote wound healing, shorten the treatment time, ease the pain of patients, improve the quality of life. The therapeutic scheme is safe, effective, and suitable for clinical application.
Clinical and Surgical Results of Treatment Modalities in Orbital Roof Fractures: Single-Center Experience
Authors: Tekeli Barut Irmak , Karataş Derya , Uygur Saygi , Yildirim Yakup , Doruk Efekan , Dağtekin Ahmet , Avci Emel
Published: September 2024

Orbital roof fractures are uncommon craniofacial fractures. Due to the location of the fracture and the mechanism of trauma, it is often associated with neuroophthalmological injuries. The authors aimed to evaluate the results of conservative and surgical treatments of patients with orbital roof fractures and present our clinical experiences regarding optimal treatment planning, especially in cases of moderate or severe head trauma. The authors retrospectively identified 145 patients who were treated for orbital roof fractures. Three colored silicone-injected cadaver samples and a dry skull were used to show the panoramic view of the anatomy of the orbital region. In this study, orbital roof fractures were classified under 4 types. The most common fracture type was type 1 (42%). Intracranial hemorrhage was observed in 60% of all cases and was most common in type 3 fractures (68%). Neuro-ophthalmological deficits were detected in 16% of all patients and were most common in Type 4 fractures (47%). Third cranial nerve deficit was the most common deficit (39%). Neuroophthalmological deficits were detected in 9.5 % of patients with mild head trauma and 32.5% in patients with moderate or severe head trauma. Moderate or severe head trauma was detected in 28% of the cases. Moderate or severe head trauma makes it difficult to detect neuro-ophthalmological complications, which are critical in determining the need for acute surgery. In patients with moderate or severe brain injury, treatment should be individualized according to the nature of the displacement and the relationship between concomitant fractures and intracranial hemorrhage.
Acute Vision Impairment Caused by Internal Carotid Artery Plaque Hemorrhage Combined With Thrombosis
Authors: Wang Shiqiang , Xing Hongshun , Xie Yingliang
Published: September 2024

Atherosclerosis (As) is an important pathologic basis for ischemic cerebrovascular disease and easily causes stenosis of the origin of the internal carotid artery (ICA). As the main source of intracranial blood supply, the ICA accounts for 70% to 80% of blood flow. This stenosis can cause various ocular symptoms in patients. In the existing literature, it is rare to report cases with only acute vision loss caused by ICA plaque hemorrhage combined with thrombosis. The authors report a case of acute vision impairment caused by ICA plaque hemorrhage. The clinical manifestations, imaging characteristics, differential diagnosis, and treatment methods were discussed based on relevant literature, and the diagnosis and differentiation of the disease were considered to deepen the understanding of the disease.
IDENTIFYING POTENTIAL KEY FERROPTOSIS-RELATED GENES AND THERAPEUTIC DRUGS IN SEPSIS-INDUCED ARDS BY BIOINFORMATICS AND EXPERIMENTAL VERIFICATION
Authors: Li Man , Ren Xiaojing , Lu Futai , Pang Shenyue , Ding Ling , Wang Lei , Xie Shuhua , Geng Licheng , Xu Jiangang , Yang Tao
Published: September 2024

Background: Acute respiratory distress syndrome (ARDS) is a serious pathological process with high mortality. Ferroptosis is pivotal in sepsis, whose regulatory mechanisms in sepsis-induced ARDS remains unknown. We aimed to determine key ferroptosis-related genes in septic ARDS and investigate therapeutic traditional Chinese medicine. Method: Sepsis-induced ARDS dataset obtained from Gene Expression Omnibus was analyzed to identify ferroptosis-related differentially expressed genes. Enrichment analysis and protein-protein interaction network construction were performed to identify hub genes. Immune cells infiltration was analyzed and competitive endogenous RNA network was constructed. The diagnostic value of hub genes in septic ARDS was analyzed and the occurrence of ferroptosis and the expression of hub genes were detected. Traditional Chinese medicine targeting hub genes was predicted via SymMap database and was verified. Results: Sixteen ferroptosis-related differentially expressed genes were obtained, among which the top four genes (IL1B, TXN, MAPK3, HSPB1) were selected as hub genes, which may be potential diagnostic markers of septic ARDS. Immunoassay showed that sepsis-induced ARDS and hub genes were closely related to immune cells. The competitive endogenous RNA network showed 26 microRNAs and 38 long noncoding RNA. Ferroptosis occurred and the expressions of IL1B, MAPK3, and TXN were increased in septic ARDS mice and LPS-challenged human pulmonary alveolar epithelial cells. Sea buckthorn alleviated septic lung injury and affected hub genes expression. Conclusions: Ferroptosis-related genes of IL1B, MAPK3, and TXN serve as potential diagnostic genes for sepsis-induced ARDS. Sea buckthorn may be therapeutic medication for ARDS. This study provides a new direction for septic ARDS treatment.
Individual Factors in Young Female Athletes’ Bladder Health (the Y-FAB Study)
Authors: Bennis Stacey , Joyce Cara , Mueller Elizabeth R. , Fitzgerald Colleen M.
Published: September 2024

Importance

Bladder health in high school and collegiate females is not well understood.

Objective

The objective of this study was to compare toileting behaviors, lower urinary tract symptoms (LUTSs), and fluid intake in female athletes and nonathletes.

Study Design

English-speaking nulliparous females aged 13–23 years were recruited. Participants completed the Toileting Behaviors: Women’s Elimination Behaviors Scale, Bristol Female LUTS Questionnaire, and Beverage Questionnaire. Statistical analysis included univariable analyses and multivariable comparisons of athletes to nonathletes adjusting for age and fluid intake.

Results

One hundred athletes and 98 nonathletes participated (mean age 20 ± 2, mean body mass index 23 ± 4). Athletes’ sports were predominantly high impact. Dysmenorrhea and anxiety were higher in nonathletes (P < 0.01) versus more stress fractures in athletes (P < 0.001). Problematic toileting behaviors were prevalent regardless of athletic status; nonathletes were more likely to hold urine until home and empty away from home without the urge (both P = 0.04). Lower urinary tract symptoms were prevalent regardless of athletic status, including frequency (34.2%), hesitancy (33.3%), urgency (32.8%), stress incontinence (15.3%), and urgency incontinence (11.8%). Athletes had significantly more stress incontinence and urgency and higher incontinence subscores on univariable analysis, although the difference was attenuated after multivariable adjustment. Athletes consumed lower total fluids (P = 0.03).

Conclusions

Problematic toileting behaviors and LUTSs were prevalent in high school and collegiate females, regardless of athletic status. Athletes had higher stress urinary incontinence and urgency and lower fluid intake. These findings support future work toward enhancing early bladder health interventions (screening, education, and LUTS prevention) among high school and collegiate females.
Informing biologically relevant signal from spatial transcriptomic data
Authors: Radkevich Emir , D'Souza Darwin , Mattiuz Raphael , Merand Raphael , Chen Rachel , Morgenroth-Rebin Jarod , Angeliadis Krista , Nelson Daniella , Kara Anis , Dawson Travis , De Souza Igor , Nie Kai , Hamon Pauline , Hegde Samarth , Boumelha Jesse , Brody Rachel , Ozbey Sinem , Hennequin Clotilde , Feng Di , Dai Jie , Gonzalez-Kozlova Edgar , Chen Zhihong , Kim-Schulze Seunghee , Gnjatic Sacha , Merad Miriam , Roudko Vladimir
Published: September 2024

Visium is a spatial sequencing technology that utilizes messenger RNA (mRNA) to spatially map gene expression within tissues. Despite its potential, research utilizing deconvolution tools and exploring microenvironment dynamics remains challenging. We address this gap by benchmarking deconvolution tools across diverse biological contexts, identifying optimal methodologies. Subsequently, we introduce a novel pipeline integrating advanced deconvolution techniques and novel tools for reproducible tissue microenvironment analysis. Through this approach, we uncover intricate immune aggregate biology, highlighting the power of our methodology in unraveling complex biological phenomena.
Epigenomic, transcriptomic and proteomic characterizations of reference samples
Authors: Nepal Chirag , Chen Wanqiu , Chen Zhong , Wrobel John A. , Xie Ling , Liao Wenjing , Xiao Chunlin , Farmer Adrew , Moos Malcolm , Jones Wendell , Chen Xian , Wang Charles
Published: September 2024

A variety of newly developed next-generation sequencing technologies are making their way rapidly into the research and clinical applications, for which accuracy and cross-lab reproducibility are critical, and reference standards are much needed. Our previous multicenter studies under the SEQC-2 umbrella using a breast cancer cell line with paired B-cell line have produced a large amount of different genomic data including whole genome sequencing (Illumina, PacBio, Nanopore), HiC, and scRNA-seq with detailed analyses on somatic mutations, single-nucleotide variations (SNVs), and structural variations (SVs). However, there is still a lack of well-characterized reference materials which include epigenomic and proteomic data. Here we further performed ATAC-seq, Methyl-seq, RNA-seq, and proteomic analyses and provided a comprehensive catalog of the epigenomic landscape, which overlapped with the transcriptomes and proteomes for the two cell lines. We identified >7,700 peptide isoforms, where the majority (95%) of the genes had a single peptide isoform. Protein expression of the transcripts overlapping CGIs were much higher than the protein expression of the non-CGI transcripts in both cell lines. We further demonstrated the evidence that certain SNVs were incorporated into mutated peptides. We observed that open chromatin regions had low methylation which were largely regulated by CG density, where CG-rich regions had more accessible chromatin, low methylation, and higher gene and protein expression. The CG-poor regions had higher repressive epigenetic regulations (higher DNA methylation) and less open chromatin, resulting in a cell line specific methylation and gene expression patterns. Our studies provide well-defined reference materials consisting of two cell lines with genomic, epigenomic, transcriptomic, scRNA-seq and proteomic characterizations which can serve as standards for validating and benchmarking not only on various omics assays, but also on bioinformatics methods. It will be a valuable resource for both research and clinical communities.
Targeting the Schwann Cell EP2/cAMP Nanodomain to Block Pain but not Inflammation
Authors: Nassini Romina , Landini Lorenzo , Marini Matilde , Chieca Martina , Souza Monteiro de Araujo Daniel , Montini Marco , Pensieri Pasquale , Abruzzese Vittorio Donato , De Siena Gaetano , Zhang Jin , De Giorgi Vincenzo , Romitelli Antonia , Brancolini Giulia , Tonello Raquel , Peach Chloe J. , Mastricci Alessandra , Scuffi Irene , Tesi Martina , Jensen Dane D. , Schmidt Brian L. , Bunnett Nigel W. , De Logu Francesco , Geppetti Pierangelo
Published: September 2024

Analgesia by non-steroidal anti-inflammatory drugs (NSAIDs) is ascribed to inhibition of prostaglandin (PG) biosynthesis and ensuing inflammation. However, NSAIDs have life-threatening side effects, and inhibition of inflammation delays pain resolution. Decoupling the mechanisms underlying PG-evoked pain vs. protective inflammation would facilitate pain treatment. Herein, we reveal that selective silencing of the PGE2 EP2 receptor in Schwann cells via an adeno-associated viral vector abrogates the indomethacin-sensitive component of pain-like responses in mice elicited by inflammatory stimuli without affecting inflammation. In human Schwann cells and in mice, EP2 activation and optogenetic stimulation of adenylyl cyclase evokes a plasma membrane-compartmentalized cyclic adenosine monophosphate (cAMP) signal that, via A-kinase anchor protein-associated protein kinase A, sustains inflammatory pain-like responses, but does not delay their resolution. Thus, an unforeseen and druggable EP2 receptor in Schwann cells, via specific cAMP nanodomains, encodes PG-mediated persistent inflammatory pain but not protective inflammation.
Quantum mechanics predicts Bicoid interpretation times of less than a second
Authors: Lone Irfan
Published: September 2024

The establishment and interpretation of the concentration distribution of the morphogen Bicoid (Bcd) is considered crucial for the successful embryonic development of fruit flies. However, the biophysical mechanisms behind the timely formation and subsequent interpretation of this prototypical morphogenetic system by its target genes are not yet completely understood. Recently a discrete time, one-dimensional quantum walk model ofBcdgradient formation has been successfully used to explain the observed multiple dynamic modes of theBcdsystem. However, the question of its precise interpretation by its primary target gene hunchback (hb) remains still unanswered. In this paper it will be shown that the interpretation of theBcdgradient by its primary target genehb, with the observed precision of ∼10%, takes a time period of less than a second, as expected on the basis of recent experimental observations. Furthermore, the quantum walk model is also used to explain certain key observations of recent optogenetic experiments concerning the time windows forBcdinterpretation. Finally, it is concluded that the incorporation of quantum effects into the treatment ofBcdgradient represents a viable step in exploring the dynamics of morphogen gradients.
Bimodal dendritic processing in basket cells drives distinct memory-related oscillations
Authors: Tzilivaki Alexandra , Larkum Matthew Evan , Schmitz Dietmar
Published: September 2024

Hippocampal oscillations regulate distinct memory stages and behavioral states, yet the mechanisms by which interneurons contribute to these rhythms remain elusive. Here, we establish a novel link between the bimodal nonlinear dendritic processing of PV+ fast-spiking basket cells (FSBCs) and hippocampal oscillations. Our model predicts that FSBCs can flexibly adjust their activity without changes in synaptic input quantity, leveraging their supralinear and sublinear dendritic branches to selectively shape network dynamics. Supralinear dendritic activation enhances high-frequency oscillations, while sublinear dendritic activation amplifies slow oscillatory power, dynamically modulating the excitation/inhibition (E/I) balance. These findings reveal a previously unrecognized role of FSBC dendritic integration in memory-related oscillatory dynamics, offering new insights into the cellular mechanisms governing hippocampal rhythm generation.

Significance Statement

Hippocampal oscillations play a crucial role in memory processes, yet how interneurons dynamically regulate these rhythms remains unresolved. Our study reveals that fast-spiking basket cells (FSBCs) exploit bimodal nonlinear dendritic processing to selectively shape slow and fast oscillatory components, independently of synaptic input quantity. This energy-efficient mechanism allows FSBCs to fine-tune the excitation-inhibition balance, modulating network dynamics essential for learning and consolidation. By challenging the conventional view of interneuron function, our findings redefine how inhibitory circuits contribute to hippocampal rhythm generation, providing new insights into the cellular basis of memory-related oscillations.
U2AF1 S34Fenhances tumorigenic potential of lung cells by exhibiting synergy withKRASmutation and altering response to environmental stress
Authors: Liang Cindy E , Hrabeta-Robinson Eva , Behera Amit , Arevalo Carlos , Fetter Isobel J. , Soulette Cameron M. , Thornton Alexis M. , Sikandar Shaheen S. , Brooks Angela N.
Published: September 2024

AlthoughU2AF1S34Fis a recurrent splicing factor mutation in lung adenocarcinoma (ADC),U2AF1S34Falone is insufficient for producing tumors in previous models. Because lung ADCs withU2AF1S34Ffrequently have co-occurringKRASmutations and smoking histories, we hypothesized that tumor-forming potential arises fromU2AF1S34Finteracting with oncogenicKRASand environmental stress. To elucidate the effect ofU2AF1S34Fco-occurring with a second mutation, we generated human bronchial epithelial cells (HBEC3kt) with co-occurringU2AF1S34FandKRASG12V. Transcriptome analysis revealed that co-occurringU2AF1S34FandKRASG12Vdifferentially impacts inflammatory, cell cycle, and KRAS pathways. Subsequent phenotyping found associated suppressed cytokine production, increased proliferation, anchorage-independent growth, and tumors in mouse xenografts. Interestingly, HBEC3kts harboring onlyU2AF1S34Fdisplay increased splicing in stress granule protein genes and viability in cigarette smoke concentrate. Our results suggest thatU2AF1S34Fmay potentiate transformation by granting precancerous cells survival advantage in environmental stress, permitting accumulation of additional mutations likeKRASG12V, which synergize withU2AF1S34Fto transform the cell.
First imported Cases of MPXV Clade Ib in Goma, Democratic Republic of the Congo: Implications for Global Surveillance and Transmission Dynamics
Authors: Mukadi-Bamuleka Daniel , Kinganda-Lusamaki Eddy , Mulopo-Mukanya Noella , Amuri-Aziza Adrienne , O’Toole Áine , Modadra-Madakpa Brigitte , Ndongala Guy Mutombo , Vakaniaki Emmanuel Hasivirwe , Merritt Sydney , Kacita Cris , Maboko Gaston Lubambo , Makangara-Cigolo Jean-Claude , Ngimba Michel , Lokilo Emmanuel , Pukuta-Simbu Elisabeth , Luakanda Gradi , Bodisa-Matamu Tavia , Kalimuli Zephanie Paluku , Akil-Bandali Prince , Kavira Sifa , Jansen Daan , Kamaliro Adèle Kavira , Muhindo-Milonde Emile , Mufungizi Jeriel , Hamisi Yves Birindwa , Kavunga Hugo , Tshiani Olivier , Nundu Sabin S. , Liesenborghs Laurens , Hoff Nicole A. , Nachega Jean , Shongo Robert , Ayouba Ahidjo , Pilarowski Genay , Mangolopa Alain Kakule , Ebondo Amos Kiuka , Low Nicola , Shaw Souradet Y. , Wilkinson Sam , Tessema Sofonias Kifle , Subissi Lorenzo , Delaporte Eric , Vercauteren Koen , Wawina-Bokalanga Tony , Rimoin Anne W , Peeters Martine , Loman Nicholas , Rambaut Andrew , Muyembe-Tamfum Jean-Jacques , Hensley Lisa E. , Kindrachuk Jason , Mbala-Kingebeni Placide , Ahuka-Mundeke Steve
Published: September 2024

The ongoing national mpox outbreak in the Democratic Republic of the Congo has resulted in more >30,000 suspected cases in the country from January 2023 to August 2024. While these historic case totals have been driven by primarily by zoonosis, the emergence of Clade Ib monkeypox virus (MPXV), which is connected to more sustained human-to-human transmission, has been associated with increasing public health impacts in eastern DRC. First identified in South Kivu province, Clade Ib MPXV has been identified in multiple non-endemic East African countries for the first time. In DRC, there have been concerns over broader Clade Ib expansion in the country that could further complicate containment and mitigation responses. Here, we report the first introductions of Clade Ib into North Kivu province, including within internal displacement camps, with suspected close contact transmission that includes non-intimate contacts and children. These findings demonstrate that mpox case investigations and community messaging campaigns should include considerations for non-sexual contact-mediated transmission of Clade Ib that includes children <15 years.