bluuebunny/crossref_metadata_2025_split huggingface dataset:
A new cell death program regulated by toll-like receptor 9 through p38 mitogen-activated protein kinase signaling pathway in a neonatal rat model with sepsis associated encephalopathy
Authors: Zhou Ruixi , Ying Junjie , Qiu Xia , Yu Luting , Yue Yan , Liu Qian , Shi Jing , Li Xihong , Qu Yi , Mu Dezhi 
Published: March 2022

Abstract

Background:
Sepsis, a serious condition with high mortality, usually causes sepsis associated encephalopathy (SAE) that involves neuronal cell death. However, the cell death programs involved and their underlying mechanisms are not clear. This study aimed to explore the regulatory mechanisms of different cell death programs in SAE.

Methods:
A neonatal rat model of SAE was established by cecal ligation and perforation. Survival rate and vital signs (mean arterial pressure and heart rate) were monitored, nerve reflexes were evaluated, and cortical pathological changes were observed by hematoxylin and eosin staining. The expression of pyroptosis, apoptosis, and necroptosis (PANoptosis)-related proteins, mitogen- activated protein kinase (MAPK), and its upstream regulator toll-like receptor 9 (TLR9) were detected. The expression of TLR9 in neurons was observed by immunofluorescence staining. The ultrastructure of neurons was observed by transmission electron microscope.

Results:
First, PANoptosis was found in cortical nerve cells of the SAE rats. Meanwhile, the subunits of MAPKs, p38 MAPK, Jun N- terminal kinase, and extracellular signal-regulated kinase (ERK) were activated. After pharmacologically inhibiting each of the subunits, only p38 MAPK was found to be associated with PANoptosis. Furthermore, blocking the p38 MAPK signaling pathway activated necroptosis but inhibited apoptosis and pyroptosis. When necroptosis was pharmacologically inhibited, apoptosis and pyroptosis were reactivated. Finally, we found that the expression of TLR9, a regulator of MAPKs, was significantly increased in this model. After down-regulation of TLR9, p38 MAPK, and ERK signaling pathways were inhibited, which led to the inhibition of PANoptosis. Further analysis found that down-regulation of TLR9 improved the survival rate and reduced the pathological changes in SAE rats.

Conclusions:
Our study showed that the programs comprising PANoptosis are activated simultaneously in SAE rats. TLR9 activated PANoptosis through the p38 MAPK signaling pathway. TLR9 may work as a potential target for SAE treatment.
Features of hyperintense white matter lesions and clinical relevance in systemic lupus erythematosus
Authors: Guo Qian , He Yang , Liu Xia , Gao Xuguang , Xu Jing , Li Xue , Sun Yue , Xiang Yajuan , Li Ru , Li Zhanguo 
Published: March 2022

Abstract

Background:
Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease characterized by complex and various clinical manifestations. The study aimed to analyze clinical features and cerebral magnetic resonance imaging (MRI) changes of hyperintense white matter (WM) lesions in SLE patients.

Methods:
This was a retrospective study based on a consecutive cohort of 1191 SLE patients; 273 patients for whom cerebral MRI data were available were enrolled to assess hyperintense WM lesions associated with SLE. Patients were assigned to two groups, i.e., with or without hyperintense WM lesions. The MRI assessment showed that the hyperintense WM lesions could be classified into three categories: type A, periventricular hyperintense WM lesions; type B, subcortical hyperintense WM lesions; and type C, multiple discrete hyperintense WM lesions. The clinical and MRI characteristics were analyzed. Factors related to hyperintense WM lesions were identified by multivariate logistic regression analysis.

Results:
Among the 273 SLE patients with available cerebral MRI scans, 35.9% (98/273) had hyperintense WM lesions associated with SLE. The proportions of types A, B, and C were 54.1% (53/98), 11.2% (11/98), and 92.9% (91/98), respectively. Fifty-one percents of the patients showed an overlap of two or three types. Type C was the most common subgroup to be combined with other types. Compared with those without hyperintense WM lesions, the patients with hyperintense WM lesions were associated with neuropsychiatric SLE (NPSLE), lupus nephritis (LN), hypertension, and hyperuricemia (P = 0.002, P = 0.018, P = 0.045, and P = 0.036, respectively). Significantly higher rates of polyserous effusions and cardiac involvement were found in the patients with hyperintense WM lesions (P = 0.029 and P = 0.027, respectively), and these patients were more likely to present with disease damage (P < 0.001). In addition, the patients with hyperintense WM lesions exhibited a higher frequency of proteinuria (P = 0.009) and higher levels of CD8
+
T cells (P = 0.005). In the multivariate logistic analysis, hyperuricemia and higher CD8+ T cells percentages were significantly correlated with hyperintense WM lesions in SLE patients (P = 0.019; OR 2.129, 95% confidence interval [CI] 1.313–4.006 and P < 0.001; OR 1.056, 95% CI 1.023–1.098, respectively).

Conclusions:
Hyperintense WM lesions are common in SLE patients and significantly associated with systemic involvement, including NPSLE, LN, polyserous effusions, cardiac involvement, and disease damage. Hyperuricemia and a higher number of CD8+ T cells were independent factors associated with hyperintense WM lesions in SLE.
Corneal endothelial wound healing after Descemet tear with a rho kinase inhibitor
Authors: Azhari Jamal , Patel Umangi , Vakharia Mitul 
Published: March 2022

Introduction:
To the authors’ knowledge, this is the first report of Descemet tear postcataract surgery that was successfully treated with ripasudil hydrochloride hydrate.

Patient and Clinical Findings:
An 85-year-old pseudophakic man presented with blurry vision and mild photophobia in the left eye. Slitlamp biomicroscopy showed moderate corneal edema and a central Descemet tear from cataract surgery 7 years earlier.

Diagnosis, Intervention, and Outcomes:
The patient was treated for 1 month with prednisolone acetate 1% and sodium chloride 5% hyperosmotic ophthalmic solution with no clinical improvement. He declined surgical intervention and opted for medical management with ripasudil 0.4% ophthalmic solution, a rho kinase inhibitor. He applied it topically 4 times daily for 3 months, with improvement of corneal edema and corrected distance visual acuity. After discontinuation of ripasudil, his edema and vision worsened and then improved again after retreatment, showing a strong clinical response. 2 years after starting ripasudil therapy, the patient had continued to use ripasudil 3 times daily and reported worsened vision at lower doses.

Conclusions:
The use of topical ripasudil may be a viable medical intervention for corneal edema due to Descemet tear instead of surgery, although chronic use may be required.
Enthesopathy, a Cause for Persistent Peristomal Pain after Treatment with an Osseointegrated Bone-Anchor: A Retrospective Case Series
Authors: Kang Norbert Venantius , Woollard Alexander , Gupta Sanjay , Michno Dominika , Davison Eliza , Langley Beth 
Published: March 2022

ABSTRACT

Introduction
After limb loss, many patients undergo treatment with an osseointegrated implant. Unfortunately, some develop persistent peristomal pain after surgery. This can be sufficiently severe to reduce the speed of their rehabilitation or may halt the process altogether. The pain may be due to an enthesopathy of the residual muscles. We describe the phenomenon and outcomes of treatment in a series of patients who underwent treatment with an osseointegrated prosthetic limb, bone-anchor.

Materials and Methods
Over 36 months, we followed 14 patients with symptoms consistent with enthesopathy. Thirteen had undergone treatment with a transfemoral bone-anchor and one underwent treatment with a transhumeral bone-anchor.
One patient had a bilateral transfemoral amputation. Analysis of the patients' ages, heights, weight at the time of surgery, length of residual femur, or preoperative dual-energy x-ray absorptiometry scans showed no correlation with the development of enthesopathy pain. Thirteen patients received steroid injections. Most received at least one injection of Adcortyl™ and bupivacaine. Patients were then encouraged to follow a program of physiotherapy to stretch out their enthesis, after injection.

Results
All patients experienced relief from their symptoms, but only two were rendered completely pain free. The remaining 11 patients gained sufficient control of their symptoms to allow them to continue daily use of their prosthesis with less difficulty or, where rehabilitation had been delayed or halted completely, to resume this process.

Conclusion
Enthesopathy seems to be a common phenomenon after bone-anchor surgery in individuals with transfemoral amputation. Steroid injections can help to relieve pain, allowing physiotherapy to be carried out. Patients undergoing treatment with a bone-anchor should be advised of the possibility of enthesopathy pain but can be reassured that there is a solution that works well in most cases.

Clinical Relevance
This article may be of benefit to clinicians who are struggling to manage patients with persistent peristomal pain after insertion of a bone-anchor. It may also encourage further research into measures for securing the soft tissues around the stoma for patients undergoing bone-anchor surgery.
Current Estimates of Cochlear Implant Utilization in the United States
Authors: Nassiri Ashley M. , Sorkin Donna L. , Carlson Matthew L. 
Published: March 2022

Objective:
To present key data from a private marketing report that characterizes U.S. cochlear implant (CI) utilization, potential CI candidate and recipient population sizes, and CI market growth.

Patients:
Individuals who may benefit from CI and CI recipients in the United States.

Interventions:
Cochlear implantation.

Main outcome measures:
CI utilization, potential CI candidate and recipient population sizes, and CI market size and value.

Results:
As of 2015, a cumulative 170,252 people (240,056 devices) had undergone cochlear implantation in the United States. In the year 2015, approximately 30% of devices were implanted in bilateral CI patients, through simultaneous or sequential implantation. When considering traditional audiometric CI candidacy criteria (patients with severe to profound sensorineural hearing loss in the better hearing ear), utilization rates among the population who may benefit from CI approximated 12.7%. When considering expanded criteria including individuals with single-sided deafness or asymmetrical hearing loss (severe to profound hearing loss in the worse hearing ear), utilization rates approximated 2.1%. In 2015, there was a net increase of 20,093 individuals who may have benefited from CI who had not undergone CI, adding to the group of about 1.3 M untreated audiometric CI candidates who existed prior to that year. The CI market was valued at $450.8 M in 2015, with an average device selling price of $25,701 per device.

Conclusions:
CI utilization rates remain low among individuals who meet audiometric criteria for CI. Although the annual proportion of CI recipients to new audiometric candidates has increased, the total population of untreated audiometric CI candidates continues to rise.
Misplaced Cochlear Implant Electrodes Outside the Cochlea: A Literature Review and Presentation of Radiological and Electrophysiological Findings
Authors: Cheung Linnea L. , Kong Jonathan , Chu Pui Yin , Sanli Halit , Walton Joanna , Birman Catherine S. 
Published: March 2022

Hypothesis:
It is possible to detect when misplacement and malposition of the cochlear implant (CI) electrode array has occurred intraoperatively through different investigations. We aim to explore the literature surrounding cochlear implant misplacements and share our personal experience with such cases to formulate a quick-reference guide that may be able to help cochlear implant teams detect misplacements early.

Background:
Misplacement and malposition of a cochlear implant array can lead to poor hearing outcomes. Where misplacements go undetected during the primary surgery, patients may undergo further surgery to replace the implant array into the correct intracochlear position.

Methods:
Systematic literature review on cochlear implant misplacements and malpositions and a retrospective review of our program's cases in over 6,000 CI procedures.

Results:
Twenty-nine cases of CI misplacements are reported in the English literature. Sixteen cases of cochlear implant misplacements are reported from our institution with a rate of 0.28%. A further 12 cases of intracochlear malpositions are presented. The electrophysiological (CI electrically evoked auditory brainstem response, transimpedance matrix) and radiological (X-ray and computed tomography scan) findings from our experience are displayed in a tabulated quick-reference guide to show the possible characteristics of misplaced and malpositioned cochlear implant electrode arrays.

Conclusion:
Both intraoperative electrophysiological and radiological tests can show when the array has been misplaced or if there is an intracochlear malposition, to prompt timely intra-operative reinsertion to yield better outcomes for patients.
Inter and Intraobserver Agreement of the IOOG SAMEO ATO Classification for Tympanomastoid Surgery
Authors: Hickson Craig , Gao Chuanyu , Parsons Nicholas , Neumann Codruta 
Published: March 2022

Introduction
In 2018 the International Otology Outcome Group (IOOG) introduced the stage of surgery, approach, mastoidectomy, external ear canal reconstruction, obliteration of mastoid cavity, access to middle ear, tympanic membrane, ossicular chain (SAMEO ATO) categorization framework for tympanomastoid surgery to develop a classification system that encompasses all aspects of surgical technique that are likely to influence the outcome of tympanomastoid surgery. To date there is no study that examines inter or intraobserver reliability of this classification system.

Objective
To assess inter and intraobserver reliability of the SAMEO ATO classification.

Study Design and Setting
Retrospective single center study.

Intervention
Two observers independently categorized 167 tympanomastoid surgeries using the SAMEO-ATO system to allow for interobserver analysis. Categorization was performed retrospectively from operation notes. Intraobserver reliability was evaluated for one observer.

Patients
One hundred sixty seven tympanomastoid surgeries performed by a single surgeon between 2018 and 2021.

Main Outcome Measure
Inter and intraobserver reliability calculated using Cohen’s kappa.

Results
Almost perfect interobserver agreement was seen for stage of surgery (S), approach (A), mastoidectomy (M), and ossicular chain (O) with kappa scores ranging from of 0.957 to 0.848.
Almost perfect intraobserver agreement was seen for approach (A), mastoidectomy (M), external ear reconstruction (E), obliteration of mastoid cavity (O), access to middle ear (A), and ossicular chain (O) with kappa ranging from 0.929 to 08.21.

Conclusion
The SAMEO ATO classification is a reliable system for recording surgical procedures. Given the complexity of the SAMEO ATO classification it is vital that those using it have a thorough knowledge of the classification.
Spanish-Speaking Caregivers' Perception of Emergency Physicians' Interpersonal and Communication Skills in a Pediatric Emergency Department
Authors: Russell Eric A. , Hsu Deborah , Camp Elizabeth A. , Soto-Ruiz Karina , Leaming-Van Zandt Katherine 
Published: March 2022

Objectives
Medical communication is more than just the delivery of information; language differences between physicians and patients/caregivers create a challenge to providing effective care in the pediatric emergency department (ED). Overcoming this barrier is vital to providing high-quality care. We evaluated Spanish- versus English-speaking caregivers' perception of their pediatric ED physicians' interpersonal and communication skills. We also compared perceptions of Spanish- versus English-speaking caregivers who self-identified as Hispanic.

Methods
This study is a retrospective analysis of data from surveys administered in an urban, free-standing children's hospital ED. Surveys were administered in English and Spanish to pediatric patient caregivers. In person, video, and telephonic interpretations were available during patient encounters.

Results
There were 2542 (82.4%) surveys completed in English and 543 (17.6%) in Spanish. There were significant differences in demographic data of English versus Spanish survey respondents, including level of education, insurance status, and rates of nonpublic insurance. Spanish survey respondents rated their physicians' interpersonal skills lower than English survey respondents. There were 1455 (47%) surveys completed by the respondents who self-identified as Hispanic. Within this group, 928 (63.8%) respondents completed the survey in English and 527 (36.2%) in Spanish. Among this Hispanic population, the Spanish survey respondents rated their physicians' interpersonal and communication skills lower than English survey respondents. After adjusting for education level and insurance type, these differences persisted.

Conclusions
Language barriers have a meaningful impact on physician ability to communicate effectively in the pediatric ED. Improving physicians' ability to overcome this barrier is essential toward enriching patient outcomes and experience in the ED.
Predictive Analytics Using Machine Learning to Identify ART Clients at Health System Level at Greatest Risk of Treatment Interruption in Mozambique and Nigeria
Authors: Stockman Jeni , Friedman Jonathan , Sundberg Johnna , Harris Emily , Bailey Lauren 
Published: March 2022

Background:
A core objective of HIV/AIDS programming is keeping clients on treatment to improve their health outcomes and to limit spread. Machine learning and artificial intelligence can combine client, temporal, and locational attributes to identify which clients are at greatest risk of loss to follow-up (LTFU) and enable health providers to direct support interventions accordingly.

Setting:
The analysis was part of a project funded by U.S. President's Emergency Plan for AIDS Relief and United States Agency for International Development, Data for Implementation, and applied to data from publicly available sources (health facility data, geospatial data, and satellite imagery) and de-identified electronic medical record data on antiretroviral therapy clients in Nigeria and Mozambique.

Methods:
The project applied binary classification techniques using temporal cross-validation to predict the risk that patients would be LTFU. Classifiers included logistic regression, neural networks, and tree-based models.

Results:
Models showed strong predictive power in both settings. In Mozambique, the best-performing model, a Random Forest, achieved an area under the precision–recall curve of 0.65 compared against an underlying LTFU rate of 23%. In Nigeria, the best-performing model, a boosted tree, achieved an area under the precision–recall curve of 0.52 compared against an underlying LTFU rate of 27%.

Conclusions:
Machine-learned models outperformed current classification techniques and showed potential to better direct health worker resources toward patients at greatest risk of LTFU. Moreover, models performed equally across sex and age groups, supporting the model's generalizability and wider application.
Brief Report: Adolescent Girls Who Sell Sex in Zimbabwe: HIV Risk, Behaviours, and Service Engagement
Authors: Rice Brian , Machingura Fortunate , Maringwa Galven , Magutshwa Sitholubuhle , Kujeke Tatenda , Jamali Gracious , Busza Joanna , de Wit Mariken , Fearon Elizabeth , Hanisch Dagmar , Yekeye Raymond , Mugurungi Owen , Hargreaves James R. , Cowan Frances M. 
Published: March 2022

Background:
To reduce HIV incidence among adolescent girls who sell sex (AGSS) in Zimbabwe, we need to better understand how vulnerabilities intersect with HIV infection and how those living with HIV engage in care.

Methods:
In 2017, we conducted social mapping in 4 locations in Zimbabwe and recruited girls aged 16–19 years who sell sex, using respondent-driven sampling or census sampling methods. Participants completed a questionnaire and provided finger prick blood samples for HIV antibody testing.

Results:
Of 605 AGSS recruited, 74.4% considered themselves sex workers, 24.4% reported experiencing violence in the past year, 91.7% were not in school, and 83.8% had less than a complete secondary education. Prevalence of HIV increased steeply from 2.1% among those aged 16 years to 26.9% among those aged 19 years; overall, 20.2% of AGSS were HIV-positive. In the multivariate analysis, age, education, marital status, and violence from a client were associated with HIV. Among the 605 AGSS, 86.3% had ever tested for HIV, with 64.1% having tested in the past 6 months. Among AGSS living with HIV, half (50.8%) were aware of their status, among whom 83.9% reported taking antiretroviral therapy.

Conclusion:
The steep rise in HIV prevalence among those aged between 16 and 19 years suggests the window to engage with AGSS before HIV acquisition is short. To accelerate reductions in incidence among AGSS, intensified combination prevention strategies that address structural factors and tailor services to the needs of AGSS are required, particularly ensuring girls enroll and remain in school.
68Ga-FAPI and 18F-FDG PET/CT Findings in a Patient With Pancreatic Tuberculosis Mimicking Malignant Tumor
Authors: Sun Rui , Huang Zhanwen , Wei Jing , Zeng Chengrun , Chen XiaoLiang 
Published: March 2022

Abstract
We report the case of a 24-year-old man who presented with abdominal pain and jaundice. 18F-FDG and 68Ga-FAPI PET/CT showed increased radioactivity in the region of the pancreatic head, which suggested malignant tumor. However, postoperative pathological finding demonstrated the presence of tuberculosis. This case documents that the pancreatic tuberculosis may cause FAPI uptake, and nuclear medicine physician evaluating 68Ga-FAPI imaging should be aware of this potential pitfall.