bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term follow-up of Bonebridge BCI 601 implantation in microtia patients with aural atresia: Acoustic and subjective benefits
Authors: Yeh Kuan-Ting , Ho Valerie Wai-Yee , Chen Tai-Yu , Tu Junior Chun-Yu , Lin Hsiao-Yun , Chan Kai-Chieh
Published: September 2024

Background:

This study evaluated the long-term acoustic and subjective outcomes of Bonebridge bone conduction implant (BCI) 601 implantation in Taiwanese patients with microtia and aural atresia (AA).

Methods:

A total of 41 microtia patients (28 males and 13 females; 26 with bilateral AA and 15 with unilateral AA) who received Bonebridge BCI 601 implantation between December 2014 and March 2021 at Chang Gung Memorial Hospital, Linkou, Taiwan, were included in this retrospective study. Acoustic outcomes assessed included functional hearing gain (FHG), speech reception threshold (SRT), and word recognition score (WRS), were assessed. Subjective outcomes were assessed using the Chinese versions of four questionnaires: the Abbreviated Profile of Hearing Aid Benefit (APHAB); the Speech, Spatial and Qualities of Hearing Scale; the International Outcome Inventory for Hearing Aids; and the Satisfaction with Amplification in Daily Living.

Results:

The mean age at the time of implantation was 18.9 years (range, 6.3–54.9), and the mean follow-up duration was 6.3 years (range, 2.8–9.1). The mean unaided air conduction pure tone average (PTA4) was 65.3 ± 8.8 decibels (dB) hearing level (HL) and the mean aided sound field PTA4 was 31.1 ± 9.1 dB HL, resulting in a FHG of 34.2 ± 11.7 dB HL (p < 0.05). After Bonebridge implantation, improvements (p < 0.05) in the mean SRT in quiet (from 58.3 ± 7.4 dB HL to 29.4 ± 7.0 dB HL), SRT in noise (from −1.4 ± 7.3 dB signal-to-noise ratio (SNR) to −9.6 ± 5.4 dB SNR), WRS in quiet (from 46.4 ± 26.9% to 93.8 ± 3.1%), and WRS in noise (from 46.7 ± 21.8% to 72.7 ± 19.3%) were found. Additionally, the bilateral AA group exhibited greater SRT and WRS improvements compared to the unilateral AA group (p < 0.05). All mean subscale scores in the four questionnaires showed improvement after Bonebridge implantation, except for the mean aversiveness to sounds subscale score in the APHAB questionnaire.

Conclusion:

Bonebridge BCI 601 implantation provided long-term acoustic and subjective benefits for patients with microtia and AA, particularly those with bilateral AA.
Aortic Dissection in a Neonate Receiving Extracorporeal Life Support Therapy: A Case Report
Authors: Medar Shivanand S. , Chopra Arun , Kumar T. K. Susheel , McKinstry Jaclyn , Kuenzler Keith , Chakravarti Sujata B. , Fisher Jason
Published: September 2024

Extracorporeal life support (ECLS) therapy is increasingly being used to support children with refractory cardiorespiratory failure, but its use is occasionally associated with complications.1Neonatal aortic dissection in association with ECLS is rare and the clinical sequelae of aortic dissection in neonates are poorly understood. We report a case of extensive type B aortic dissection in a neonate receiving ECLS therapy for refractory cardiogenic shock secondary to tachycardia-induced cardiomyopathy and Wolf Parkinson White (WPW) syndrome. The patient was noted to have aortic dissection along with multiple abdominal organ ischemic injury a day after ECLS arterial cannula position adjustment. The patient was rapidly decannulated from ECLS and the aortic dissection was managed conservatively with good outcome. We discuss our approach and rationale behind conservative management of this rarely reported complication associated with ECLS therapy and discuss available literature.
Prenatal and postnatal evaluation of differences of sex development: a user's guide for clinicians and families
Authors: Weidler Erica M. , Ochoa Brielle , van Leeuwen Kathleen
Published: September 2024

Purpose of review

Differences of sex development (DSD) are a group of chromosomal, gonadal, and anatomic conditions that are not often diagnosed during pregnancy. Families and clinicians need diagnostic guidance that supports all aspects of the care from the prenatal to postnatal period.

Recent findings

Noninvasive prenatal screening (NIPS) is obtained by sampling cell-free fetal DNA in the mother's bloodstream in the first trimester. While its primary purpose is to screen for genetic aneuploidies, it is also used to determine the sex of the fetus. When screening ultrasound shows genital anatomy that is discordant with the sex determination by NIPS, a DSD workup is warranted. The use of this relatively new screening tool may result in a higher number of prenatal referrals than in the past.

This review summarizes suggested prenatal counseling, neonatal management, and postnatal workup of the most common DSD diagnoses. All of these diagnoses are rare, but the common features that families face are addressed with particular emphasis on psychosocial support and a measured shared decision-making approach.
Practical considerations in diagnosing inborn errors of immunity according to the Middle East and North Africa guidelines
Authors: Kulhas Celik Ilknur , Azizi Gholamreza , Artac Hasibe
Published: September 2024

Purpose of review

The rate of inborn errors of immunity (IEI) in the Middle East and North Africa (MENA) region is generally higher than in other parts of the world. IEI patients in MENA exhibit more severe disease phenotypes. One of the most important reasons for this is delayed diagnosis. In this review, we examine issues pertinent to primary, secondary, and tertiary physicians in diagnosing IEI in children and discuss the key points for pediatricians according to the MENA guideline.

Recent findings

Protocols and stepwise approaches designed by a panel of clinical immunologists included in the MENA-IEI registry network can help physicians facilitate the diagnosis of patients with IEI by providing recommendations. These recommendations for diagnostic approaches improve the care of patients within the MENA region and can also be applied to IEI patients in other parts of the world other regions.

Physicians in the MENA region should be aware of IEI, obtain a detailed family history, request tests that can be ordered in primary care when IEI is suspected, and refer patients to clinical immunologists without delay. Primary and secondary care physicians should be aware that patients with IEI may present with noninfectious manifestations and increased infection frequency, severity, and atypical infections.
Genetic disease amongst the Plain community
Authors: Mascia Katherine L.
Published: September 2024

Purpose of review

The purpose of this review is to highlight recent genetic studies of the Amish and Mennonite (Plain) communities. For decades, the study of genetically isolated populations has improved our understanding and management of genetic diseases that affect all populations.

Recent findings

Major themes of current genetic research of the Amish and Mennonites include new causative gene and new candidate gene discovery, phenotype expansion of previously identified genetic disease, and a target for AAV9-mediated gene therapy. Additionally, several genome-wide association studies (GWAS) examining complex traits such as dementia, cardiometabolic disease, and age-related macular degeneration have been conducted. Finally, clinically relevant studies of attitudes of the Plain community towards genetic testing and telemedicine, as well as reviews of and management suggestions for the Amish variants of propionic acidemia and APOB-associated familial hypercholesterolemia have been recently published.

Recent genetic studies of the Plain community continue to highlight the value of studying isolated populations to propel genetic disease discovery and treatment. Additionally, population-specific polygenic risk scores are needed for underrepresented and minority populations, to avoid exacerbating disparities in medical genetics care. Finally, it is important for clinicians to develop management guidelines for variants common in this rapidly growing population, such as propionic acidemia.
Echocardiographic strain imaging in the pediatric heart: clinical value and utility in decision making
Authors: Martinez John P. , Ganieva Gulnigor , Harrington Jamie K.
Published: September 2024

Purpose of review

Speckle tracking echocardiography (STE)-derived measures of myocardial mechanics, referred to herewithin as strain measurements, directly assess myocardial contractility and provide a nuanced assessment of ventricular function. This review provides an overview of strain measurements and their current clinical value and utility in decision making in pediatric cardiology.

Recent findings

Strain measurements are advancing understanding of how cardiac dysfunction occurs in children with acquired and congenital heart disease (CHD). Global strain measurements can detect early changes in cardiac function and are reliable methods of serially monitoring systolic function in children. Global strain measurements are increasingly reported in echocardiographic assessment of ventricular function alongside ejection fraction. Research is increasingly focused on how strain measurements can help improve clinical management, risk stratification, and prognostic insight. Although more research is needed, preliminary studies provide hope that there will be clinical benefit for strain in pediatric cardiology management.

Strain measurements provide a more detailed assessment of ventricular function than conventional measures of echocardiographic functional assessment. Strain measurements are increasingly being used to advance understanding of normal and abnormal myocardial contractility, to increase sensitivity to detect early cardiac dysfunction, and to improve prognostic management in children with acquired and CHD.
Hereditary hemorrhagic telangiectasia – pediatric review
Authors: Iacobas Ionela , Hammill Adrienne M.
Published: September 2024

Purpose of review

Hereditary hemorrhagic telangiectasia (HHT) diagnostic and management approach for pediatrics underwent significant advances over the last couple of years.

Recent findings

In 2020, new guidelines for HHT were published that included a pediatric section thus attracting special focus into the childhood presentation.

Curacao criteria are specific, but not sensitive enough in children. Genetic testing is encouraged for all family members even if asymptomatic. Standardized scoring for epistaxis is strongly encouraged, as it allows monitoring and can stratify therapeutic approaches. Early screening for pulmonary and brain visceral arteriovenous malformations (AVMs) in pediatric patients with confirmed genetic alterations of HHT should be instituted. Graded trans-esophageal echocardiogram with agitated saline contrast can be used as screening method for pulmonary AVMs. As pulmonary AVMs can develop throughout lifetime, guidelines recommend repeated screening even in asymptomatic patients at least every 5 years. Signs of stroke in childhood are more subtle than in adults. Cerebral imaging in early childhood can identify brain AVMs that may benefit from early intervention. Embolization of high-risk pulmonary and cerebral AVMs should be performed at specialized centers even at pediatric age. One or two classic HHT telangiectasia can be considered diagnostic in children. Antibiotic prophylaxis with dental procedures continues to be recommended.
Purulent pericarditis and cardiac tamponade in HIV: a case report on a dreaded complication of Streptococcus pneumoniae
Authors: Wagle Laxman , Basnyat Parmartha , Timshina Anuj , Regmi Rashmita , Sherpa Lakpa Diku , Poudel Sishir
Published: September 2024

Introduction and importance:

Purulent pericarditis is an uncommon complication of Streptococcus pneumoniae, which commonly occurs in an immunocompromised state such as HIV and can lead to life-threatening complications such as cardiac tamponade and potentially death if untreated. Early identification, pericardiocentesis, and general measures such as antibiotics and anti-inflammatory medications can be life-saving.

Case presentation:

The authors present a case of a 64-year-old male with HIV who presented with clinical symptoms suggestive of pericarditis. Chest imaging revealed multifocal airspace diseases and moderate pericardial effusion. He had worsening lactic acidosis, and bedside point-of-care ultrasound showed pericardial effusion with features suggestive of cardiac tamponade. His lactic acidosis improved with emergency pericardiocentesis. Blood and pericardial fluid cultures revealed Streptococcus pneumoniae. He was further treated with intravenous antibiotics, colchicine, and ibuprofen.

Clinical discussion:

Although Streptococcus pneumoniae is a common etiology of community-acquired pneumonia (CAP), it has not been cited as the leading cause of pericarditis or pericardial effusion. In immunocompromised patients, it is necessary to consider a broad differential diagnosis as an etiology of acute chest pain, as it may be challenging to differentiate pleuritic and pericarditic chest pain from clinical presentation only. Moreover, infectious etiology of acute pericarditis and pericardial effusion should be considered in this patient population, especially those with HIV. At the same time, it is crucial to promptly identify and treat cardiac tamponade to prevent further deterioration.

Conclusion:

This case provides insight into the diagnosis and management of CAP and its potential complication of purulent pericarditis and cardiac tamponade in immunocompromised patients.
Expression profiles of urine exosomal tRNA-derived small RNAs and their potential roles in calcium oxalate stone disease
Authors: Hong Sen-Yuan , Miao Lin-Tao , Yang Yuan-Yuan , Wang Shao-Gang
Published: September 2024

Background and objective:

Exosomes have been confirmed to be implicated in the pathogenesis of calcium oxalate (CaOx) stones. tRNA-derived small RNAs (tsRNAs) are among the oldest small RNAs involved in exosome-mediated intercellular communication, yet their role in kidney stones remains unexplored. This pilot study aimed to identify differentially expressed tsRNAs (DEtsRNAs) in urine exosomes between CaOx stone patients and healthy controls and explore their potential roles in nephrolithiasis.

Method:

First-morning urine samples were collected from three CaOx stone patients and three healthy controls. Urinary exosomes were isolated and analyzed by high-throughput sequencing to generate the expression profiles of tsRNAs and detect DEtsRNAs. Predicted target genes of DEtsRNAs were subjected to functional enrichment analysis. The authors also combined the public dataset GSE73680 to investigate how DEtsRNAs were related to stone formation.

Results:

Four DEtsRNAs were significantly upregulated in CaOx stone patients compared to healthy controls. tRF-Lys-TTT-5005c was the most elevated, followed by tRF-Lys-CTT-5006c, tRF-Ala-AGC-5017b, and tRF-Gly-CCC-5004b. Bioinformatics analysis indicated that these four types of DEtsRNAs might serve distinct biological functions. Combined with data mining from the public dataset GSE73680, the authors assumed that exosomes carrying tRF-Lys-TTT-5005c and tRF-Lys-CTT-5006c could inhibit the expression of SMAD6, FBN1, and FZD1, thereby activating the BMP signaling pathway, which might induce an osteogenic-like transformation in target cells, resulting in the formation of Randall’s plaques and CaOx stones.

Conclusion:

The authors’ findings shed light on the potential roles of tsRNAs in the pathogenesis of CaOx stone disease, highlighting exosomal DEtsRNAs as promising diagnostic biomarkers and therapeutic targets in nephrolithiasis.
Non-neuronopathic Gaucher disease (Type I) in an elderly female: a case report
Authors: Bohara Sujan , Bhattarai Sanjeet , Khadka Manoj , Ghimire Deepak , Karki Samikshya , Poudel Nahakul , Aryal Gopi , Dhakal Sunil S.
Published: September 2024

Introduction and importance:

Gaucher disease is a rare autosomal recessive lysosomal storage disorder marked by a substantial reduction in beta-glucocerebrosidase activity. Historically, supportive treatments such as splenectomy and orthopedic interventions were employed, whereas recent advances have led to the approval of Enzyme Replacement Therapy (ERT) and Substrate Reduction Therapy (SRT) as therapeutic options.

Case presentation:

The authors present the case of a 61-year-old female with chronic abdominal pain, abdominal fullness, pancytopenia, and hepatosplenomegaly, all indicative of Gaucher’s disease, later confirmed by histopathological examination. The patient was informed about newer treatment options like ERT and SRT, as well as the traditional approach of splenectomy. However, due to financial constraints, she opted for splenectomy in conjunction with conservative management.

Discussion:

Gaucher disease is defined by a deficiency of glucocerebrosidase, leading to the accumulation of Gaucher cells (pathognomonic of the disease), particularly in the spleen, liver, bone marrow, and lungs. Type 1 Gaucher disease (GD1) can manifest at any age, from childhood to late adulthood. Definitive diagnosis is confirmed by reduced beta-glucocerebrosidase activity. Traditionally, treatment options for GD1 have been supportive, including splenectomy, blood transfusions, and orthopedic procedures. However, SRT and ERT, though effective, remain prohibitively expensive and often inaccessible in low-resource settings.

Conclusion:

Early diagnosis of Gaucher disease is challenging due to its rarity and should be considered in patients presenting with hepatosplenomegaly, pancytopenia, and low glucocerebrosidase activity.
Pediatric Off-Road Vehicle Injuries
Authors: Solano Mitchell A. , Gilbert Gunner R. , Krishnan Akshay R. , Siegel Eric R. , Morell Sean M.
Published: September 2024

Objectives

Side-by-side (SXS) and all-terrain vehicles (ATVs) are different off-road vehicles (ORVs) but often categorized together in the literature. We hypothesized pediatric upper extremity (UE) fracture patterns and injury severity scores (ISS) differ between ORV types.

Methods

The authors' home-state trauma repository identified 157 pediatric patients aged 0 to 17 years with UE fractures after ORV accidents during 2011–2021. ORV injuries, fracture type, and procedures were identified using International Classification of Diseases, 9th Revision and 10th Revision coding followed by manual chart review or phone calls. We identified specific ORV type, driver/passenger status, and restraint use to compare differences between fracture characteristics, number of surgeries, and ISS. Groups were compared for differences at P < 0.05 significance.

Results

Among 157 ORV injuries, 75 resulted from ATVs (48%), 50 SXSs (32%), and 32 from all other vehicles (20%). Average age was 12 years, and 49% (n = 77) required surgery. SXS injuries had significantly higher open fracture rates (42%, n = 21) compared with ATVs (7%, n = 5) and all other ORV types (16%, n = 5; P < 0.0001). Seventy percent of fractures (n = 35) sustained after SXS accidents required surgery compared with 41% (n = 31) for ATVs and 34% (n = 11) for all other ORV types (P < 0.001). SXS drivers had 71% left-sided injuries, whereas 85% passengers had right-sided injuries (P < 0.0001). Patients younger than 13 years (n = 73) had significantly higher surgery rates (59%) compared with 40% for those 13 years and older (n = 84; P = 0.02). There were no significant differences in mean ± SD ISS between ATV (8 ± 6), SXS (8 ± 6), and other vehicles (7 ± 4; P = 0.34).

Conclusions

UE fractures caused by SXS were more likely to be open and require surgery compared with ATVs and other ORVs. SXS drivers were more likely to sustain left-sided injuries, whereas passengers had significantly higher right-sided injuries. Patients younger than 13 years were more likely to require surgery compared with teenagers.
Measuring Overcrowding in a Large Academic Tertiary Care Pediatric Emergency Department
Authors: Jadcherla Yamini , Stoner Michael , Helwig Sara , Lo Charmaine , Shi Junxin , MacDowell Doug , Bennett Berkeley L.
Published: September 2024

Objective

Overcrowding scores have been studied extensively in adult emergency departments (EDs), but few studies have determined utility in the pediatric setting. The objective of this study was to determine the association between a modified National Emergency Department Overcrowding Score (mNEDOCS) and established ED metrics in a large academic tertiary care pediatric ED.

Methods

NEDOCS was modified to increase applicability in the pediatric setting by including the number of patients in resuscitation rooms instead of a number of patients on ventilators. Patient characteristics, ED disposition, ED length of stay (LOS), rate of left without being seen (LWBS), hospital LOS (HLOS), ED returns within 72 hours, and mNEDOCS were acquired retrospectively for every ED encounter in 2016–2019 using the electronic health record. Descriptive statistics, Spearman correlation, and multivariate analyses were calculated to evaluate the association between specific ED metrics and mNEDOCS.

Results

Modified NEDOCS positively correlated with ED LOS, LWBS, and rate of 72-hour return visits. A negative correlation was found between mNEDOCS and HLOS. When controlling for select covariates, the odds of LWBS doubled with each increase in mNEDOCS category (odds ratio, 2.03; 95% confidence interval [CI], 2.00–2.06), ED LOS was associated with an increase of 27 minutes as mNEDOCS category increased (β = 26.80; 95% CI, 26.44–27.16), and the odds of 72-hour return visits increased by 6% when mNEDOCS increased by one category (odds ratio, 1.06; 95% CI, 1.05–1.07). Hospital LOS was associated with a 100-minute decrease per increase in mNEDOCS category (β = −99.85; 95% CI, −180.68 to −18.48) when controlling for covariates.

Conclusion

Modified NEDOCS is positively associated with ED LOS, LWBS, and 72-hour return visits, consistent with adult data. Further investigation is needed to elucidate the association between mNEDOCS and HLOS. This study illustrates the utility of mNEDOCS as a measure of overcrowding in a pediatric ED.
The Effect of Step Stool Use on Chest Compression Quality During CPR in Young Children
Authors: Dutta Anuj K. , Donoghue Aaron , Sandler Alexis , Ahmed Ramzy , Neubrand Tara , Kerrey Benjamin , Myers Sage , O'Connell Karen J.
Published: September 2024

Objective

This study aimed to determine the effect of stepstool use on chest compression (CC) quality during cardiopulmonary resuscitation (CPR) in young children.

Methods

We conducted a prospective observational study of children <8 years of age who received CC for >2 minutes in the emergency department. Data were collected through CC monitor device and video review. Data were analyzed in “CC segments” (periods of CC by individual providers). CC segments were coded “yes” or “no” for stepstool use based on video review. Univariate analyses of CC rate and depth between stepstool use and hand positions were performed through nonparametric testing, stratified by age category.

Results

Forty-two patients received 566 minutes of CC. Overall, American Heart Association (AHA)–compliant (rate and depth) CPR was achieved in 10% of CC segments for children <1 year and only 6% in children >1 year. A stepstool was used in 73% of CC segments in children <1 year and 88% in children >1 year. In children >1 year, stepstool use was associated with deeper CCs (P < 0.001) and a more compliant CC rate (P < 0.01). In children >1 year, 7% of those with a stepstool in use achieved AHA compliance, compared to those without a stepstool, where none achieved AHA compliance.

Conclusions

In children >1 year, stepstool use resulted in greater CC depth and more AHA-compliant CC rate. No CC segments in children >1 year achieved AHA compliance without a stepstool. These data support uniform stepstool use during pediatric CPR in children >1 year of age.
Why Won’t Anyone Talk? Challenges Naming and Addressing Tokenism Within Health and Human Service Agencies Serving the LGBTQ+ Community
Authors: Levandowski Brooke A. , Rietberg-Miller Susan , Walton Brytelle
Published: September 2024

Workplace tokenism, the use of superficial efforts to appear equitable, which often leads to burnout of marginalized groups, is pervasive, even in health and human service organizations dedicated to improving their community’s health and well-being. An original research project to identify interventions addressing tokenism within Lesbian, Gay, Bisexual, Transgender, Queer plus serving health and human service agencies in New York was unable to engage staff in focus groups. A follow-up survey with 41 potential participants reported burnout as the main reason for nonparticipation. Qualitative data revealed desired aftercare for the retraumatizing nature of sharing individual experiences. Utilizing a community-based participatory research approach with an antiracism lens may mitigate challenges addressing tokenism, thereby increasing workplace inclusion of our Lesbian, Gay, Bisexual, Transgender, Queer plus community.
Transnasal Endoscopic Approach for Excision of Intracranial Nasal Dermoid Sinus Cysts
Authors: Woodyard De Brito Kiersten C. , Dembinski Douglas R. , Lawera Nathan G. , Buller Mitchell , de Alarcon Alessandro , Pan Brian S. , Skoch Jesse
Published: September 2024

Objective:

Nasal dermoid sinus cysts (NDSCs) with intracranial extension in the form of dermal sinus tracts require careful and complete resection to prevent recurrence. Resection techniques necessitate adequate intracranial exposure, but morbidity associated with historical resection approaches has presented unique multidisciplinary challenges for surgeons treating cysts with intracranial extension.

Methods:

The authors primarily employed a transnasal approach through a midline nasal incision, utilizing endoscopic or microscopic access between the lateral cartilages for resection of NDSCs with intracranial extension. A retrospective review was completed for patients treated for NDSCs at the authors' pediatric quaternary referral center from 2017 to 2023. Data collection included demographics, comorbidities, perioperative data, pre and postoperative imaging, surgical outcomes, and complications.

Results:

Eighteen patients with NDSCs with possible or confirmed intracranial extension were surgically treated from 2017 to 2023. Fifteen were treated with resection performed through a midline transnasal approach with endoscopic assistance, achieving successful total resection while avoiding nasal osteotomy or frontal craniotomy. One patient had a slow cerebrospinal fluid leak from an operative durotomy, successfully treated with a lumbar drain. No other complications occurred. No patients required transfusion. Incision length and postoperative scar burden were less than approaches that used osteotomies or craniotomies and demonstrated excellent cosmetic results. No patients have had cyst recurrence or required reoperation.

Conclusions:

A transnasal approach through a midline incision with endoscopic assistance is an effective approach for resection of NDSC with intracranial extension, but utility may vary with cyst size and complexity. This approach leverages appropriate exposure for resection with decreased morbidity and decreased incision length through avoidance of osteotomies.
Initial Frontal Sinus and Orbit Tumor Signaling Late Distant Metastasis in Kidney Cancer
Authors: Pavlovic Bojan , Jakovljevic Sasa , Jovanovic Katarina
Published: September 2024

Although metastases to the paranasal sinuses are exceedingly rare, when they do occur, renal clear cell carcinoma is the most frequent primary tumor involved. The aim of this work was to present a case of metastatic clear cell renal carcinoma in the frontal sinus and orbit region, 7 years after the initial diagnosis and treatment. The patient was referred to our clinic due to drooping of the left eyelid and displacement of the left eyeball. Computed tomography revealed an expansive lesion in the left frontal sinus and orbit, causing destruction of its anterior, lateral, and roof walls. Profuse bleeding from the tumor and left orbit hindered a comprehensive assessment of tumor extension into the orbit and residual tumor size. Therefore, complete tumor removal was not possible; instead, reduction was achieved. Subsequent histopathologic and immunohistochemical analysis confirmed the lesion as a metastasis of renal cell carcinoma in the sinonasal tract. Unfortunately, 10 weeks later, the patient passed away. Treatment of metastatic clear cell renal carcinoma depends on the localization of the disease as well as the overall condition of the patient. If there is a solitary metastatic lesion, as in the case of the sinonasal region, surgical treatment is recommended. Metastasis of clear cell renal carcinoma to the sinonasal region is a rare occurrence; however, it is essential to consider it in cases of rapidly growing tumor masses, typically presenting with symptoms such as epistaxis and nasal obstruction.
Analysis of the Status Quo and Influencing Factors of Revisiting Patients After Pituitary Tumor Resection: Based on a Chinese Patient Population
Authors: Wang Wei , Xiaoxu Han
Published: September 2024

Objective:

To investigate the status of patients’ post-pituitary tumor resection and analyze influencing factors, providing evidence for improved long-term management.

Methods:

The authors screened 1209 patients who underwent pituitary tumor resection at Zhejiang University’s Second Affiliated Hospital from August 2020 to July 2022 using electronic medical records. Patients were classified into return visits (≥2 reviews/y or within 6 mo) and missing visit groups. Demographic and disease-related data were extracted from inpatient records, whereas return visits and prognosis data were collected from outpatient records and phone inquiries. Propensity score matching (1:1) was used to balance the groups, followed by univariate and multivariate logistic regression analyses to identify influencing factors.

Results:

Of the 1209 patients, 113 were unreachable. The study included 1095 patients, with 553 (50.5%) in the missing visit group and 542 (49.5%) in the return visit group. The authors matched 421 pairs, achieving balanced baseline data. Univariate analysis revealed significant differences in residence, unplanned readmission history, and current outcomes (P < 0.05). Multivariate analysis identified unplanned readmission history (odds ratio = 0.495, 95% CI: 0.307–0.799) as a protective factor. City residents had higher return visit rates than those from other provinces (odds ratio = 0.269, 95% CI: 0.610–1.579).

Conclusion:

Postdischarge return rates for pituitary tumor resection patients are low and influenced by various factors. Improving return visit policies and systems is essential for facilitating outpatient follow-ups.
Intervention effects of Naoxintong capsules on psychological and cardiac status in depressed rats after heart failure
Authors: Zhao Jie , Ouyang Yi , Hu Shaowei , Tian Guanghuan , Kong Xixian , Pan Fuzhu , Wu Hongwei , Tang Liying , Yang Hongjun
Published: September 2024

Background

Depression is a common clinical phenomenon in the patients with heart failure (HF). In traditional Chinese medicine (TCM), diseases in the brain and heart are thought to be correlated and interact. Naoxintong capsules (NXT) has been used for treating cardio-cerebrovascular diseases, while its therapeutic effect on depression after HF remains unclear.

Objective

The aim of the study is to evaluate the intervention effect of NXT on depression after HF.

Methods

Sprague-Dawley rats were assigned into the following 5 groups: sham, model, NXT (250, 1000 mg/kg), and valsartan (8 mg/kg). Coronary artery occlusion was performed to induce HF and subsequent depression in rats. The cardiac function was evaluated by echocardiography, hematoxylin-eosin staining, and Masson trichrome staining. The sucrose preference test and Morris water maze test were carried out to assess the depressive behaviors in rats. The ultrastructure of hippocampal CA1 neurons was observed and the levels of corticotropin-releasing hormone in the hypothalamus, brain-derived neurotrophic factor in the cortex, and adrenocorticotropic hormone (ACTH) in the plasma were determined by enzyme-linked immunosorbent assay. The levels of dopamine, 5-hydroxytryptamine, norepinephrine, and γ-aminobutyric acid in the hippocampus were measured by UPLC-QQQ-MS.

Results

NXT reduced myocardial injury and pathological changes in the cardiac tissue and increased the left ventricular ejection fraction, left ventricular fractional shortening, and cardiac output. NXT increased the sugar preference rate and number of crossings and shortened the escape latency. Furthermore, the NXT treatment restored the levels of corticotropin-releasing hormone, adrenocorticotropic hormone, brain-derived neurotrophic factor, dopamine, and γ-aminobutyric acid to the baseline values.

Conclusions

NXT not only demonstrates cardioprotective effect but also attenuates depression in the rats after HF. It may exert the antidepressant effect by inhibiting the hyperactivity of the hypothalamic-pituitary-adrenal axis and recovering the levels of neurotrophic factors and neurotransmitters.
The C-terminus of CFAP410 forms a tetrameric helical bundle that is essential for its localization to the basal body
Authors: Stadler Alexander , De Liz Laryssa V. , Gabriel Heloisa B. , Alonso-Gil Santiago , Crickley Robbie , Korbula Katharina , Žagrović Bojan , Vaughan Sue , Sunter Jack D. , Dong Gang
Published: September 2024

Cilia are antenna-like organelles protruding from the surface of many cell types in the human body. Defects in ciliary structure or function often lead to diseases that are collectively called ciliopathies. Cilia and flagella-associated protein 410 (CFAP410) localizes at the basal body of cilia/flagella and plays essential roles in ciliogenesis, neuronal development and DNA damage repair. It remains unknown how its specific basal body location is achieved. Multiple single amino acid mutations in CFAP410 have been identified in patients with various ciliopathies. One of the mutations, L224P, is located in the C-terminal domain (CTD) of human CFAP410 and causes severe spondylometaphyseal dysplasia, axial (SMDAX). However, the molecular mechanism for how the mutation causes the disorder remains unclear. Here, we report our structural studies on the CTD of CFAP410 from three distantly related organisms,
Homo sapiens, Trypanosoma brucei
and
Chlamydomonas reinhardtii
. The crystal structures reveal that the three proteins all adopt the same conformation as a tetrameric helical bundle. Our work further demonstrates that the tetrameric assembly of the CTD is essential for the correct localization of CFAP410 in
T. brucei
, as the L224P mutation that disassembles the tetramer disrupts its basal body localization. Taken together, our studies reveal that the basal body localization of CFAP410 is controlled by the CTD and provide a mechanistic explanation for how the mutation L224P in CFAP410 causes ciliopathies in humans.
Uncovering Plaque-Glia Niches in Human Alzheimer’s Disease Brains Using Spatial Transcriptomics
Authors: Avey Denis R. , Ng Bernard , Vialle Ricardo A. , Kearns Nicola A. , de Paiva Lopes Katia , Iatrou Artemis , De Tissera Sashini , Vyas Himanshu , Saunders Devin M. , Flood Daniel J. , Xu Jishu , Tasaki Shinya , Gaiteri Chris , Bennett David A. , Wang Yanling
Published: September 2024

Amyloid-beta (Aβ) plaques and surrounding glial activation are prominent histopathological hallmarks of Alzheimer’s Disease (AD). However, it is unclear how Aβ plaques interact with surrounding glial cells in the human brain. Here, we applied spatial transcriptomics (ST) and immunohistochemistry (IHC) for Aβ, GFAP, and IBA1 to acquire data from 258,987 ST spots within 78 postmortem brain sections of 21 individuals. By coupling ST and adjacent-section IHC, we showed that low Aβ spots exhibit transcriptomic profiles indicative of greater neuronal loss than high Aβ spots, and high-glia spots present transcriptomic changes indicative of more significant inflammation and neurodegeneration. Furthermore, we observed that this ST glial response bears signatures of reported mouse gene modules of plaque-induced genes (PIG), oligodendrocyte (OLIG) response, disease-associated microglia (DAM), and disease-associated astrocytes (DAA), as well as different microglia (MG) states identified in human AD brains, indicating that multiple glial cell states arise around plaques and contribute to local immune response. We then validated the observed effects of Aβ on cell apoptosis and plaque-surrounding glia on inflammation and synaptic loss using IHC. In addition, transcriptomic changes of iPSC-derived microglia-like cells upon short-interval Aβ treatment mimic the ST glial response and mirror the reported activated MG states. Our results demonstrate an exacerbation of synaptic and neuronal loss in low-Aβ or high-glia areas, indicating that microglia response to Aβ-oligomers likely initiates glial activation in plaque-glia niches. Our study lays the groundwork for future pathology genomics studies, opening the door for investigating pathological heterogeneity and causal effects in neurodegenerative diseases.
Oxidative stress markers predict treatment outcomes in patients with generalized anxiety disorder treated with selective serotonin reuptake inhibitors
Authors: Cui Lijun , Lu Jingjing , Shen Zhongxia , Zhu Jielin , Chen Huanxin , Yang Shenliang , Wang Shikai , Shen Xinhua
Published: September 2024

Introduction

The etiology of generalized anxiety disorder (GAD) has not been fully understood, and oxidative stress may potentially contribute to its pathogenesis. However, there is no published evidence concerning the possible influence of oxidative stress on antidepressant treatment outcomes. This study investigated the ability of oxidative stress markers to predict treatment outcomes in GAD patients treated with selective serotonin reuptake inhibitors (SSRIs).

Methods

One hundred-one GAD patients and 100 healthy controls (HCs) were included in this study. The 101 GAD patients were selected for treatment with escitalopram (n=52) or sertraline (n=49) for eight weeks. Hamilton Anxiety Rating Scale (HAM-A) assessments were conducted before and after treatment. The serum levels of eight oxidative stress makers, malondialdehyde (MDA), lipid hydroperoxides (LPO), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), cortisol, high-density lipoprotein (HDL), and nitric oxide (NO) were measured using enzyme-linked immunosorbent assays (ELISA) before and after SSRI treatment in GAD patients and at the time of HCs enrollment.

Results

The serum levels of MDA, cortisol, and LPO were higher in GAD patients than in HCs (allp<.001), while SOD, GSH-Px, and CAT were lower than in HCs (allp<.001). The baseline MDA, LPO, NO, and cortisol levels were positively correlated with anxiety severity, while GSH-Px was negatively correlated. After eight weeks of SSRI treatment, the GSH-Px levels increased, and MDA and LPO decreased (allp<.05). Alterations in MDA levels co-varied with changes in anxiety measures (allp<.05). The ability of the receiver operating characteristic (ROC) area of the baseline MDA levels to predict the SSRI endpoint treatment response was 0.804 (p<.05).

Conclusion

The pathogenesis of GAD might involve oxidative stress. Moreover, serum MDA levels might predict treatment response to SSRIs. However, more research is warranted to confirm these findings.
Early life stress influences epilepsy outcomes in mice
Authors: Coleman Emanuel M , White Maya , Antonoudiou Pantelis , Weiss Grant L , Scarpa Garrett , Stone Bradly , Maguire Jamie
Published: September 2024

Stress is a common seizure trigger that has been implicated in worsening epilepsy outcomes. The neuroendocrine response to stress is mediated by the hypothalamic-pituitary-adrenal (HPA) axis and HPA axis dysfunction worsens epilepsy outcomes, increasing seizure burden, behavioral comorbidities, and risk for sudden unexpected death in epilepsy (SUDEP) in mice. Early life stress (ELS) reprograms the HPA axis into adulthood, impacting both the basal and stress-induced activity. Thus, we propose that ELS may influence epilepsy outcomes by influencing the function of the HPA axis. To test this hypothesis, we utilized the maternal separation paradigm and examined the impact on seizure susceptibility. We show that ELS exerts a sex dependent effect on seizure susceptibility in response to acute administration of the chemoconvulsant, kainic acid, which is associated with an altered relationship between seizure activity and HPA axis function. To further examine the impact of ELS on epilepsy outcomes, we utilized the intrahippocampal kainic acid model of chronic epilepsy in mice previously exposed to maternal separation. We find that the relationship between corticosterone levels and the extent of epileptiform activity is altered in mice subjected to ELS. We demonstrate that ELS impacts behavioral outcomes associated with chronic epilepsy in a sex-dependent manner, with females being more affected. We also observe reduced mortality (presumed SUDEP) in female mice subjected to ELS, consistent with previous findings suggesting a role for HPA axis dysfunction in SUDEP risk. These data demonstrate for the first time that ELS influences epilepsy outcomes and suggest that previous life experiences may impact the trajectory of epilepsy.
The chromatin remodeler DEK promotes proliferation of mammary epithelium and is associated with H3K27me3 epigenetic modifications
Authors: Johnstone Megan , Leck Ashley , Lange Taylor , Wilcher Katherine , Shephard Miranda S. , Paranjpe Aditi , Schutte Sophia , Wells Susanne , Kappes Ferdinand , Salomonis Nathan , Privette Vinnedge Lisa M.
Published: September 2024

The DEK chromatin remodeling protein was previously shown to confer oncogenic phenotypes to human and mouse mammary epithelial cells usingin vitroand knockout mouse models. However, its functional role in normal mammary gland epithelium remained unexplored. We developed two novel mouse models to study the role of Dek in normal mammary gland biologyin vivo. Mammary gland-specific Dek over-expression in mice resulted in hyperproliferation of cells that visually resembled alveolar cells, and a transcriptional profile that indicated increased expression of cell cycle, mammary stem/progenitor, and lactation-associated genes. Conversely, Dek knockout mice exhibited an alveologenesis or lactation defect, resulting in dramatically reduced pup survival. Analysis of previously published single-cell RNA-sequencing of mouse mammary glands revealed thatDekis most highly expressed in mammary stem cells and alveolar progenitor cells, and to a lesser extent in basal epithelial cells, supporting the observed phenotypes. Mechanistically, we discovered that Dek is a modifier of Ezh2 methyltransferase activity, upregulating the levels of histone H3 trimethylation on lysine 27 (H3K27me3) to control gene transcription. Combined, this work indicates that Dek promotes proliferation of mammary epithelial cells via cell cycle deregulation. Furthermore, we report a novel function for Dek in alveologenesis and histone H3 K27 trimethylation.
NMR at operational temperature for resonance assignments of a PET degrading enzyme
Authors: Gabrielli Valeria , Grga Jelena , Gavalda Sabine , Perrot Laura , Boll Emmanuelle , Lippens Guy , Charlier Cyril
Published: September 2024

PETases are enzymes that can break down the PET polymer in its constituent building blocks, and thereby recycle starting material for new high-quality plastics. NMR spectroscopy can help in the understanding and ultimately improvement of these PETases, but is always confronted with the lengthy step of acquisition and interpretation of triple resonance spectra for the spectral assignment. Here, we explore whether this step can be made more efficient by recording the spectra directly at high temperature, which also corresponds to more realistic working conditions for the enzyme. Taking the inactive variant of LCCICCGin which the Serine 165 has been replaced by an Alanine (LCCICCG-S165A) as an example, we evaluate spectral quality at 30°C and 50°C, and find that the latter condition greatly improves the Signal-to-Noise (S/N) ratio of the different spectra. As a result, we present an exhaustive backbone and side-chain assignment of LCCICCG-S165A based on a minimal set of triple resonance spectra acquired at 50°C, that can act as a basis for future work on bio-structural studies on this PETase.
First-principles quantum Monte Carlo study of charge-carrier mobility in organic molecular semiconductors
Authors: Ostmeyer Johann , Nematiaram Tahereh , Troisi Alessandro , Buividovich Pavel
Published: September 2024

We present a first-principles numerical study of charge transport in a realistic two-dimensional tight-binding model of organic molecular semiconductors. We use the hybrid Monte Carlo (HMC) algorithm to simulate the full quantum dynamics of phonons and either single or multiple charge carriers without any tunable parameters. We introduce a number of algorithmic improvements, including efficient Metropolis updates for phonon fields based on analytical insights, which lead to negligible autocorrelation times and allow sub-per-mille precisions to be reached at a low computational cost of O﻿(1) CPU hours. Our simulations produce charge-mobility estimates that are in good agreement with experiments and that also justify the phenomenological transient localization approach.

Published by the American Physical Society
2024
Prerelaxation in quantum, classical, and quantum-classical two-impurity models
Authors: Elbracht Michael , Potthoff Michael
Published: September 2024

We numerically study the relaxation dynamics of impurity-host systems, focusing on the presence of long-lived metastable states in the nonequilibrium dynamics after an initial excitation of the impurities. In generic systems, an excited impurity coupled to a large bath at zero temperature is expected to relax and approach its ground state over time. However, certain exceptional cases exhibit metastability, where the system remains in an excited state on timescales largely exceeding the typical relaxation time. We study this phenomenon for three prototypical impurity models: a tight-binding quantum model of independent spinless fermions on a lattice with two stub impurities, a classical-spin Heisenberg model with two weakly coupled classical impurity spins, and a tight-binding quantum model of independent electrons with two classical impurity spins. Through numerical integration of the fundamental equations of motion, we find that all three models exhibit similar qualitative behavior: complete relaxation for nearest-neighbor impurities and incomplete or strongly delayed relaxation for next-nearest-neighbor impurities. The underlying mechanisms leading to this behavior differ between models and include impurity-induced bound states, emergent approximately conserved local observables, and exact cancellation of local and nonlocal dissipation effects.

Published by the American Physical Society
2024
Low-excitation transport and separation of high-mass-ratio mixed-species ion chains
Authors: Lancellotti F. , Welte S. , Simoni M. , Mordini C. , Behrle T. , de Neeve B. , Marinelli M. , Negnevitsky V. , Home J. P.
Published: September 2024

We demonstrate low-excitation transport and separation of two-ion crystals consisting of one Be+9 and one Ca+40 ion, with a high mass ratio of 4.4. The full separation involves transport of the mixed-species chain, splitting each ion into separate potential wells, and then transport of each ion prior to detection. We find the high mass ratio makes the protocol sensitive to mode crossings between axial and radial modes, as well as to uncontrolled radial electric fields that induce mass-dependent twists of the ion chain, which initially gave excitations n¯≫10. By controlling these stages, we achieve excitation as low as n¯=1.40±0.08phonons for the calcium ion and n¯=1.44±0.09phonons for the beryllium ion. Separation and transport of mixed-species chains are key elements of the quantum charge-coupled device architecture and may also be applicable to quantum-logic-based spectroscopy of exotic species.

Published by the American Physical Society
2024