bluuebunny/crossref_metadata_2025 huggingface dataset:
Gut microbiota and metabolite interface-mediated hepatic inflammation
Authors: Yang Ming , Massad Katina , Kimchi Eric T. , Staveley-O’Carroll Kevin F. , Li Guangfu
Published: January 2024

Immunologic and metabolic signals regulated by gut microbiota and relevant metabolites mediate bidirectional interaction between the gut and liver. Gut microbiota dysbiosis, due to diet, lifestyle, bile acids, and genetic and environmental factors, can advance the progression of chronic liver disease. Commensal gut bacteria have both pro- and anti-inflammatory effects depending on their species and relative abundance in the intestine. Components and metabolites derived from gut microbiota–diet interaction can regulate hepatic innate and adaptive immune cells, as well as liver parenchymal cells, significantly impacting liver inflammation. In this mini review, recent findings of specific bacterial species and metabolites with functions in regulating liver inflammation are first reviewed. In addition, socioeconomic and environmental factors, hormones, and genetics that shape the profile of gut microbiota and microbial metabolites and components with the function of priming or dampening liver inflammation are discussed. Finally, current clinical trials evaluating the factors that manipulate gut microbiota to treat liver inflammation and chronic liver disease are reviewed. Overall, the discussion of microbial and metabolic mediators contributing to liver inflammation will help direct our future studies on liver disease.
Incarcerated Men: Pain Experiences Shaped by Altered Independence and Loss of Autonomy
Authors: MacLennan Duncan Stewart , Mayan Maria , Kunyk Diane , Lasiuk Gerri
Published: January 2024

Background

Individuals experiencing pain while incarcerated depend on nurses, security structures, processes, and regulations for relief.

Purpose

The intent of this research was to understand men's experience of pain during incarceration to inform correctional nursing practice.

Method

Interpretive description, co-positioned with relational ethics, guided this study. Twelve incarcerated men participated in a single 1-hour interview that was audio-recorded and transcribed. The resultant text was analyzed for themes.

Findings

The two main themes were dependence on staff and institutional processes and dependence on oneself and others who were incarcerated. Participants reported a substantial loss in their ability to access pain-relieving medications, products, and services. Unresponsive or delayed pain-relieving interventions from nurses contributed to their sense of indignity, disrespect, and injustice. The participants employed whatever was available, mainly exercise equipment and social support, to manage their pain.

Discussion

Nurses must engage with incarcerated patients meaningfully to understand and respond to contextual factors that influence their pain experiences. Participants identified loss of autonomy and dependence on nurses as barriers to their pain relief.

Conclusion

Nurse engagement and responsiveness are crucial to altering incarcerated men's perceptions of injustice or helplessness while improving their pain experiences. Nurses must also foster autonomous pain-management approaches that men can use without limitations within correctional settings.
A Comparison of Physical Therapist Educational Outcomes Before and During the COVID-19 Pandemic: A Multicenter Study
Authors: Pucillo Evan M. , Crowder Jennifer , Andrea Catherine M. , Brim Sean , Pilgrim Leiselle , Belleza Norman
Published: January 2024

Introduction.

The purpose of this study was to analyze and compare educational outcomes of Doctor of Physical Therapy (DPT) graduates before and during the COVID-19 pandemic.

Review of Literature.

Reports show increased stress, anxiety, and burnout during the COVID-19 pandemic, which may have negatively affected academic performance. Historically, academic performance is predictive of National Physical Therapy Examination (NPTE) scores. Yet, there is little evidence analyzing student outcomes during the pandemic.

Subjects.

Doctor of Physical Therapy graduate records (N= 1,897) were retrospectively collected from a multicenter convenience sample consisting of 5 blended programs. Records were sampled from existing “prepandemic” graduates of Fall 2018–2019 (n= 988) and “pandemic” graduates of Fall 2021–2022 (n= 909).

Methods.

A causal comparative and correlational study design was used. Grade point average (GPA) and NPTE scores were collected. A general linear model examined differences between groups, and a multiple linear regression examined predictors of NPTE performance.

Results.

Grade point average was a significant predictor of NPTE score (r2= 0.56;P< .01) for the overall sample and for the prepandemic and pandemic cohorts (r2= 0.38,P< .01;r2= 0.45,P< .01, respectively). Grade point average was not significantly different between the groups (P= .09), nor did it significantly influence differences in NPTE scores (P= .13). Pandemic graduates displayed a significantly lower NPTE pass rate (85.1%) compared with prepandemic graduates (89.7%;P< .01). Pandemic graduates experienced higher rates of academic difficulty (20%;P< .01) and had a approximately 5 times higher likelihood of not passing the NPTE.

Discussion and Conclusion.

This is the first study to report on DPT graduate outcomes spanning the COVID-19 pandemic. Similar to previous studies, GPA remained the most significant predictor of NPTE scores. Pandemic graduates demonstrated significantly lower NPTE scores and higher rates of academic difficulty (GPA < 3.0). Continued monitoring of NPTE performance is warranted between prepandemic, pandemic, and postpandemic cohorts across modes of program delivery.
Surgical Treatment for Troublesome Mastoid Cavities: Canal Wall Reconstruction With Bony Obliteration Versus Subtotal Petrosectomy
Authors: Kemps Glen , Geven Leontien , Kunst Henricus , Mylanus Emmanuel , Mulder Jef , Lanting Cris , Pennings Ronald
Published: January 2024

Introduction

A chronically discharging modified radical mastoid cavity may require surgical intervention. We aim to explore two techniques.

Objective

To compare outcomes of subtotal petrosectomy (STP) and canal wall reconstruction with bony obliteration technique (CWR-BOT).

Study Design

Retrospective cohort study.

Setting

A tertiary referral center.

Patients

All patients with a chronically discharging mastoid cavity surgically treated at the Radboud University Medical Center by STP or CWR-BOT in 2015 to 2020, excluding patients with preoperative cholesteatoma.

Main Outcome Measures

Dry ear rate, audiometry, and rehabilitation.

Secondary Outcome measures

Healing time, number of postoperative visits, complications, cholesteatoma, and need for revision surgeries.

Results

Thirty-four (58%) patients underwent STP, and 25 (42%) CWR-BOT. A dry ear was established in 100% of patients (STP) and 87% (CWR-BOT). The air–bone gap (ABG) increased by 12 dB in STP, and decreased by 11 dB in CWR-BOT. Postoperative ABG of CWR-BOT patients was better when preoperative computed tomography imaging showed aerated middle ear aeration. ABG improvement was higher when ossicular chain reconstruction took place. Mean follow-up time was 32.5 months (STP) versus 40.5 months (CWR-BOT). Healing time was 1.2 months (STP) versus 4.1 months (CWR-BOT). The number of postoperative visits was 2.5 (STP) versus 5 (CWR-BOT). Cholesteatoma was found in 15% (STP) versus 4% (CWR-BOT) of patients. Complication rate was 18% (STP) and 24% (CWR-BOT) with a need for revision in 21% (STP) and 8% (CWR-BOT), including revisions for cholesteatoma.

Conclusion

STP and CWR-BOT are excellent treatment options for obtaining a dry ear in patients with a chronically discharging mastoid cavity. This article outlines essential contributing factors in counseling patients when opting for one or the other. Magnetic resonance imaging with diffusion-weighted imaging follow-up should be conducted at 3 and 5 years postoperatively.
Prevalence and assessment of risk factors of chronic kidney disease in the ASIR region of Saudi Arabia
Authors: Alshahrani Mona , Almalki Laila Zawan , Hasoosah Noura Abdullah , Alahmari Alhanouf Hussein , Alqahtani Alya Musfer , Alqahtani Amjad Ali , AL Muarfaj Afrah Mohammed , Al Ghaseb Lamia Saeed , Alkahtani Faten Saad , Alsharif Raghd Yahya
Published: January 2024

Introduction:

Chronic kidney disease (CKD) is a major health concern in Saudi Arabia. The prevalence of CKD and associated risk factors in Saudi Arabia’s general population are not efficiently studied. The goal of this research is to determine the prevalence rate of CKD in the ASIR region and its associated epidemiological risk factors.

Methodology:

This is a cross-sectional study that used a comprehensive direct questionnaire to collect data on CKD prevalence and risk factors in the ASIR region of Saudi Arabia. The study was carried out in different age groups. Demographic characteristics, presence of CKD, and associated factors such as a history of acute kidney disease, obstructive sleep apnoea, family history, history of non-steroid anti-inflammatory drugs (NSAID), smoking status, comorbidities, and history of periodontal diseases were asked. The survey tool was validated through a pilot study, and a statistical p value of 0.05 was considered significant.

Results:

A total of 967 participants were included in the study, with a CKD prevalence rate of 1.9%. Sex, history of acute kidney disease, obstructive sleep apnoea, family history of kidney disease, smoking, diabetes, peptic ulcer disease, hypertension and hyperlipidemia were commonly found to be associated with CKD. A binary logistic regression model was carried out to assess the risk factors for CKD. Sex, history of acute kidney disease, family history of kidney disease, obstructive sleep apnoea, smoking status, peptic ulcer, diabetes, hypertension, hyperlipidemia, hypertension and diabetes, two or more comorbidities and NSAID use had an increased risk of CKD.

Conclusion:

Sex, history of acute kidney disease, obstructive sleep apnoea, family history, smoking, diabetes, hypertension, peptic ulcer, hyperlipidemia, multi-comorbidity, and use of NSAIDs are all associated with an increased risk of CKD. The prevalence of CKD in this study is comparatively lower when compared to other regions in Saudi Arabia.
The Association of Federal Medicaid Abortion Funding Restrictions With Adverse Obstetric Outcomes Among United States Medicaid Recipients
Authors: Rodriguez Maria I. , Meath Thomas H. A. , Daly Ashley , Watson Kelsey , McConnell K. John
Published: January 2024

(Abstracted from Contraception 2023;126:110116)

Obstetric care in the United States is predominantly paid for by Medicaid, which covers nearly half of all births. An essential component of comprehensive obstetric care is legal, safe abortion, and restricted access to such procedures is related to increased maternal mortality and morbidity.
Penetrance of Pathogenic Genetic Variants Associated With Premature Ovarian Insufficiency
Authors: Shekari Saleh , Stankovic Stasa , Gardner Eugene J. , Hawkes Gareth , Kentistou Katherine A. , Beaumont Robin N. , Mörseburg Alexander , Wood Andrew R. , Prague Julia K. , Mishra Gita D. , Day Felix R. , Baptista Julia , Wright Caroline F. , Weedon Michael N. , Hoffmann Eva R. , Ruth Katherine S. , Ong Ken K. , Perry John R. B. , Murray Anna
Published: January 2024

(Abstracted from Nat Med 2023;29:1692–1699)

Premature ovarian insufficiency (POI), defined as the loss of ovarian activity and permanent cessation of menstruation occurring before age 40 years, affects 1% of women and is a leading cause of infertility. Up to 90% of POI cases are idiopathic, with up to 30% of those having some familial association, suggesting a genetic basis.
Connected Community Classification (C3): Development, Validation, and Geospatial Application for Population Health Promotion and Equity
Authors: Skiba Meghan B. , Lind Kimberly E. , Felion Carlie M. , Krupnik Christopher , Segrin Chris
Published: January 2024

Context:

Social determinants of health (SDOH) impact population health. Leveraging community-level strengths related to SDOH through a social infrastructure perspective can optimize health behaviors and health outcomes to promote health equity.

Objective:

Our aims were to develop, validate, and apply the Connected Community Classification (C3) as comprehensive community-level measure of protective SDOH and structural factors in the Four Corners states region of the United States.

Design:

C3 was developed using an iterative principal component analysis of publicly available data mapped to 5 SDOH domains. Regional clustering of C3 by zip code tabulation area (ZCTA) was identified using spatial autocorrelation methods.

Main Outcomes:

In adjusted spatial autoregressive models, we analyzed the association of C3 with high-risk health behaviors and chronic disease prevalence using publicly available data for population-level estimates of fruit and vegetable intake, physical activity, obesity, smoking, alcohol use, coronary heart disease (CHD), diabetes, and cancer.

Results:

C3 was found to be reliable and valid; a C3 value of 10 indicates communities with greater connection (high), while a value of 1 indicates communities with greater separation (low) to social infrastructure. Lower connection, as measured by C3, was significantly inversely associated with lower fruit and vegetable intake, lower physical activity, and higher rates of obesity, smoking, CHD, diabetes, and cancer. C3 was significantly positively associated with heavy alcohol use.

Conclusions:

These findings demonstrate that communities connected to social infrastructure have better population health outcomes. C3 captures protective community attributes and can be used in future applications to assist health researchers, practitioners, nonprofits, and policymakers to advance social connection and health equity in geographically diverse underserved regions.
Advancing Data Science Among the Federal Public Health Workforce: The Data Science Upskilling Program, Centers for Disease Control and Prevention
Authors: Bertulfo Mary Catherine P. , Kirkcaldy Robert D. , Franzke Laura H. , Papagari Sangareddy Sridhar R. , Reza Faisal
Published: January 2024

Context:

Data can guide decision-making to improve the health of communities, but potential for use can only be realized if public health professionals have data science skills. However, not enough public health professionals possess the quantitative data skills to meet growing data science needs, including at the Centers for Disease Control and Prevention (CDC).

Program:

The Data Science Upskilling (DSU) program increases data science literacy among staff and fellows working and training at CDC. The DSU program was established in 2019 as a team-based, project-driven, on-the-job applied upskilling program. Learners, within interdisciplinary teams, use curated learning resources to advance their CDC projects. The program has rapidly expanded from upskilling 13 teams of 31 learners during 2019-2020 to upskilling 36 teams of 143 learners during 2022-2023.

Evaluation:

All 2022-2023 cohort respondents to the end-of-project survey reported the program increased their data science knowledge. In addition, 90% agreed DSU improved their data science skills, 93% agreed it improved their confidence making data science decisions, and 96% agreed it improved their ability to perform data science work that benefits CDC.

Discussion:

DSU is an innovative, inclusive, and successful approach to improving data science literacy at CDC. DSU may serve as an upskilling model for other organizations.
Performance of the 2019 ACR/EULAR Classification Criteria for IgG4-Related Disease in a Large Chinese Cohort
Authors: An Zhuo-Yu , Fu Jiang-Nan , Zeng Qiao-Zhu , Zhufeng Yun-Zhi , Ning Xiao-Ran , Li Hui-Juan , Ma Xiang-Bo , Wang Kun-Kun , Bian Wen-Jie , Zhang Yu-Xin , Li Zhan-Guo , Liu Yan-Ying
Published: January 2024

Objective

The purpose of this research was to ascertain the effectiveness of the newly established criteria for classifying IgG4-related disease (IgG4-RD), as applied to a large Chinese cohort in real-world clinical settings.

Methods

Patient data were procured from the digital health records of 4 prominent academic hospitals. The criterion standard for identifying IgG4-RD patients was from a seasoned rheumatologist. The control group consisted of individuals with other ailments such as cancer, other forms of pancreatitis, infectious diseases, and illnesses that mimic IgG4-RD.

Results

A total of 605 IgG4-RD patients and 760 mimickers were available for analysis. The 2019 EULAR/ACR criteria have a sensitivity of 69.1% and a specificity of 90.9% in this large Chinese cohort. IgG4-RD had a greater proportion of males (55.89% vs 36.25%, p < 0.001), an older average age at diagnosis (54.91 ± 13.44 vs 48.91 ± 15.71, p < 0.001), more pancreatic (29.59% vs 6.12%, p < 0.001) and salivary gland (63.30% vs 27.50%, p < 0.001) involvement, and a larger number of organ involvement (3.431 ± 2.054 vs 2.062 ± 1.748, p < 0.001) compared with mimickers.

Conclusions

The 2019 EULAR/ACR criteria are effective in classifying IgG4-RD in Chinese patients, demonstrating high specificity and moderate sensitivity.
SPECT/CT for Early Detection of Stress Reactions After Reverse Shoulder Arthroplasty
Authors: Park Jong Hun , Kim Hyun Gon , Kim Jae Soo , Kim Su Cheol , Yoo Jae Chul
Published: January 2024

The altered biomechanics after reverse shoulder arthroplasty, combined with the accumulation of various stress risers, can lead to stress fractures (SFs) around the prosthesis. The incidence of stress reactions (SRs) after reverse shoulder arthroplasty, characterized by pain and tenderness without radiographic or CT evidence of fractures, is approximately 4.2%, which is comparable to the incidence of SF (6.4%). Among patients with SR, a substantial 32% eventually progress to fractures during clinical follow-up. SPECT/CT is a promising tool that combines morphologic and metabolic information for assessing mechanical bone stress. Therefore, early detection of SR through SPECT/CT can help prevent SF.
Incidental Prostate-Specific Membrane Antigen–Avid Vestibular Schwannoma Detected on 68Ga–Prostate-Specific Membrane Antigen PET/CT
Authors: Chen Jeffrey , Bui Paul , Bui Chuong , Mansberg Robert
Published: January 2024

A 62-year-old man was referred for a 68Ga–prostate-specific membrane antigen (PSMA) PET/CT scan for newly diagnosed prostate cancer (ISUP grade 5), on the background of left vestibular schwannoma treated with surgical excision 25 years ago. PSMA PET study confirmed the presence of PSMA-avid malignancy in the left prostate lobe with no evidence of PSMA-avid nodal or distant metastasis. An incidental PSMA-avid focus (SUVmax, 4.3) was identified in the region of the left cerebellopontine angle, which corresponded to a homogeneous enhancing lesion centered at the left internal acoustic canal and left cerebellopontine angle on MRI. The combined PSMA PET findings and MRI characteristics were consistent with recurrent vestibular schwannoma.
FAPI PET Missed Widespread Bone Marrow Metastases From Follicular Thyroid Cancer That Were Detected by FDG PET
Authors: Shi Xuan , Lan Wei , Bin Ji
Published: January 2024

A 62-year-old woman with follicular thyroid cancer who had received total thyroidectomy and multiple rounds of radioactive iodine therapy underwent both 18F-FDG and 18F-FAPI PET/CT. 18F-FAPI PET failed to reveal widespread bone marrow metastases that were clear visualized on 18F-FDG PET. This case highlights that FAPI PET may not be used to describe bone metastases in detail in follicular thyroid cancer patients, as it is not a sensitive method to detect bone marrow metastases.
Hypermetabolic Axillary Lymphadenopathy After Shingrix Vaccination for Varicella Zoster Virus
Authors: Eshet Yael , Eifer Michal , Domachevsky Liran , Tau Noam
Published: January 2024

A 67-year-old woman underwent staging 18F-FDG PET/CT scan for recently diagnosed breast cancer. Her scan showed a highly hypermetabolic right breast mass, with ipsilateral hypermetabolic axillary lymph nodes. The contralateral axillary lymph nodes were also enlarged with avid FDG uptake, alongside focal increased uptake in the left deltoid muscle. Upon investigation, the patient reported receiving the new zoster recombinant adjuvanted varicella zoster vaccine (Shingrix, GlaxoSmithKline) 4 days before the scan. The lymph node uptake could be potential pitfall for cancer staging.
18F-FAPI-42 PET/CT Findings in a Patient With Left Ventricular Mural Thrombus
Authors: Wang Shu , Cheng Zhiming , Cui Yan , Li Xuena , Li Yaming
Published: January 2024

18F-FAPI-42 PET/CT is a novel imaging tool targeting fibroblast activation protein (FAP). We describe the 18F-FAPI-42 PET/CT findings of a left ventricular mural thrombus in a 50-year-old man who had chest tightness. The 18F-FAPI-42 PET/CT showed annular uptake at the apex of the left ventricle, but there was no uptake of 18F-FDG. This case showed that abnormal 18F-FAPI-42 uptake in the heart may be associated with mural thrombus and should be evaluated clinically.
Significantly Higher 68Ga-FAPI Than 18F-FDG Uptake by Hidradenocarcinoma of Head and Neck on PET/CT
Authors: Ding Haoyuan , Wang Yudi , Liang Juan , Liu Ya , Chen Yue
Published: January 2024

Hidradenocarcinoma is quite rare in clinical practice. Herein, we describe the 68Ga-FAPI and 18F-FDG PET/CT findings of hidradenocarcinoma of the head and neck in a 75-year-old man. In the present case, the primary tumor and secondary lesions showed intense accumulation of 68Ga-FAPI but only slight 18F-FDG uptake. This case demonstrates that 68Ga-FAPI PET/CT might be used as a helpful tool for evaluating hidradenocarcinoma.
18F-FAPI-04 PET/CT in a Case of Primary Gastric Plasmacytoma
Authors: Dong Yiyuan , Zhao Tingting , Ma Liqiong , Dong Aisheng , Zhao Qian
Published: January 2024

Primary plasmacytoma of the stomach is very rare. We describe contrast-enhanced CT and 18F-FAPI-04 PET/CT findings in a patient with primary gastric plasmacytoma and Helicobacter pylori infection. The gastric tumor appeared as a large hypervascular polypoid mass on contrast-enhanced CT and showed intense 18F-FAPI-04 uptake with SUVmax of 11.8 on 18F-FAPI-04 PET/CT.
Approach to Imaging of Patients Presenting With Acute Coronary Syndrome With No Culprit Lesion Identified at Angiography
Authors: Ni Tiffany T. , Tsang Wendy , Nguyen Elsie T.
Published: January 2024

Chest pain is a common chief complaint among patients presenting to the emergency department. However, in the scenario where the clinical presentation is consistent with acute coronary syndrome and no culprit lesions are identified on angiography, clinicians and cardiac imagers should be informed of the differential diagnosis and appropriate imaging modalities used to investigate the potential causes. This review describes an imaging-based algorithm that highlights the diagnostic possibilities, their differentiating imaging features, and the important role of cardiovascular magnetic resonance imaging for narrowing the differential diagnosis.
Cranio-Maxillofacial Injuries in Mixed Martial Arts
Authors: Ferretti Fabrizio , Iocca Oreste , Gallesio Cesare , Quaglia Paolo , Ramieri Guglielmo
Published: January 2024

Purpose:

To describe a case of a maxillofacial trauma that occurred during a mixed martial arts (MMA) match and to perform a literature review of maxillofacial injuries related to MMA match to determine whether preventive models are applicable.

Methods:

The authors described a maxillofacial injury with orbital and optic nerve involvement that happened during a professional MMA match. A literature review on maxillofacial trauma in MMA was conducted on Scopus and Pubmed with specific keywords.

Results:

Open reduction and internal fixation of the maxillofacial complex fractures with right eye optic neuropathy following an MMA match is described. Six articles were selected for the description of trauma in the maxillofacial complex associated with MMA fights.

Discussion:

Literature has paid little attention to injuries during MMA matches. The most common injury locations that emerged from the literature review were the head, face, and neck. Middle facial third injuries were the most common type. Frequently the injury involved the ophthalmic area.

Conclusions:

The timing of maxillofacial trauma in MMA is critical. Protective devices should be strongly promoted to prevent catastrophic consequences.
Effects of an Ultra-Polished Scalpel on Incisional Wounds in a Diabetic Model
Authors: Park Hojin , Oh Somin , Kim Young Sam , Spiro Clifford L. , Hong Joon Pio , Choi Jong Woo
Published: January 2024

Inflammation after surgical incisions is related to the degree of tissue damage. Healing with low inflammation is desirable, especially in patients with compromised healing potential. This experimental study was conducted to assess the degree of inflammatory reaction and scar formation from incisions made by an ultra-polished scalpel (UPS). Two paravertebral incisions were made with a conventional scalpel (CS) and a UPS in 18 individual rats with diabetes. The fibrotic tissue (scar) area and expression levels of collagen, transforming growth factor, and matrix metalloproteinases were quantified on postoperative days 3, 7, and 30. The scar widths and areas were significantly lower in the UPS group than in the CS group. The scar widths were 64.3 ± 14.7 µm and 86.8 ± 12.1 µm in the UPS and CS groups, respectively (P = 0.03). The scar areas were 11,398 ± 1595 µm2 in the UPS group and 17,433 ± 3487 µm2 in the CS group (P = 0.014). The UPS group had less inflammation on day 3, less transforming growth factor synthesis on days 3 and 7, lower levels of matrix metalloproteinases, and less collagen synthesis on day 7 than did the CS group. The UPS achieved less local inflammation by reducing the local tissue damage in diabetic rat models, enabling better healing, and resulting in less scar formation. The UPS warrants further clinical study as it may bring beneficial outcomes for patients with impaired healing capability and patients who seek to reduce scarring.
Traumatic Neuroma in the External Auditory Canal
Authors: Shin Seung Ho , Kim Hye Min , Son Eun Jin
Published: January 2024

Traumatic neuroma is the reparative proliferation of axons and Schwann cells at the proximal end of a severed nerve following injury or surgery. Traumatic neuromas with or without clinical symptoms have rarely been reported in the external auditory canal. A 50-year-old woman with a history of trauma visited our otorhinolaryngology clinic with a 7 × 5-mm mass localized on the anterior wall of the external auditory canal. The mass was easily removed via surgical excision and was histopathologically diagnosed as a neuroma. No signs of recurrence were observed after excision. Herein, the authors present this case, along with a review of the literature.
Clinical Efficacy of Laparoscopic Sentinel Node Navigation Surgery for Stomach Preservation in Patients With Early Gastric Cancer
Authors: Hur Hoon , Lee Young Joon , Kim Young-Woo , Min Jae-Seok , Yoon Hong Man , An Ji Yeong , Eom Bang Wool , Cho Gyu Seok , Park Young-Kyu , Jung Mi Ran , Park Ji-Ho , Hyung Woo Jin , Jeong Sang-Ho , Kook Myeong-Cherl , Han Mira , Nam Byung-Ho , Ryu Keun Won
Published: January 2024

Objective:

This study aimed to compare laparoscopic standard gastrectomy (LSG) and laparoscopic sentinel node navigation surgery (LSNNS) for early gastric cancer (EGC) in terms of 5-year long-term oncologic outcomes.

Background:

The oncological safety of LSNNS for EGC has not been confirmed. Three-year disease-free survival (DFS), which is the primary endpoint of phase III multicenter randomized controlled clinical trial [SEntinel Node ORIented Tailored Approach (SENORITA) trial], did not show the noninferiority of LSNNS relative to LSG.

Methods:

The SENORITA trial, a multicenter randomized clinical trial, was designed to show that LSNNS is noninferior to LSG in terms of 3-year DFS. In the present study, we collected 5-year follow-up data from 527 patients recruited in the SENORITA trial as the full analysis set. DFS, overall survival (OS), disease-specific survival (DSS), and recurrence patterns were evaluated using the full analysis set of both LSG (n=269) and LSNNS (n=258).

Results:

The 5-year DFS was not significantly different between the LSG and LSNNS groups (P=0.0561). During the 5-year follow-up, gastric cancer–related events, such as metachronous cancer, were more frequent in the LSNNS group than in the LSG group. However, 10 recurrent cancers in the remnant stomach of both groups were curatively resected by additional gastrectomy and 1 by additional endoscopic resection. Two of the 198 patients who underwent local resection for stomach preservation based on the LSNNS results developed distant metastasis. However, there was no statistically significant difference in the 5-year OS and DSS (P=0.7403 and P=0.9586, respectively) between the two groups.

Conclusions:

The 5-year DFS, DSS, and OS did not differ significantly between the two groups. Considering the benefits of LSNNS on postoperative quality of life, LSNNS could be recommended as an alternative treatment option for EGC.
Stratification of Kidney Transplant Recipients Into Five Subgroups Based on Temporal Disease Trajectories
Authors: Jørgensen Isabella F. , Muse Victorine P. , Aguayo-Orozco Alejandro , Brunak Søren , Sørensen Søren S.
Published: January 2024

Background.

Kidney transplantation is the treatment of choice for patients with end-stage renal disease. Considerable clinical research has focused on improving graft survival and an increasing number of kidney recipients die with a functioning graft. There is a need to improve patient survival and to better understand the individualized risk of comorbidities and complications. Here, we developed a method to stratify recipients into similar subgroups based on previous comorbidities and subsequently identify complications and for a subpopulation, laboratory test values associated with survival.

Methods.

First, we identified significant disease patterns based on all hospital diagnoses from the Danish National Patient Registry for 5752 kidney transplant recipients from 1977 to 2018. Using hierarchical clustering, these longitudinal patterns of diseases segregate into 3 main clusters of glomerulonephritis, hypertension, and diabetes. As some recipients are diagnosed with diseases from >1 cluster, recipients are further stratified into 5 more fine-grained trajectory subgroups for which survival, stratified complication patterns as well as laboratory test values are analyzed.

Results.

The study replicated known associations indicating that diabetes and low levels of albumin are associated with worse survival when investigating all recipients. However, stratification of recipients by trajectory subgroup showed additional associations. For recipients with glomerulonephritis, higher levels of basophils are significantly associated with poor survival, and these patients are more often diagnosed with bacterial infections. Additional associations were also found.

Conclusions.

This study demonstrates that disease trajectories can confirm known comorbidities and furthermore stratify kidney transplant recipients into clinical subgroups in which we can characterize stratified risk factors. We hope to motivate future studies to stratify recipients into more fine-grained, homogenous subgroups to better discover associations relevant for the individual patient and thereby enable more personalized disease-management and improve long-term outcomes and survival.
Indirect CD4+ T cell protection against persistent MCMV infection by NK cells requires IFNγ
Authors: Xie Wanxiaojie , Bruce Kimberley , Stevenson Philip G. , Farrell Helen E.
Published: January 2024

Host control of mouse cytomegalovirus (MCMV) infection of MHCII- salivary gland acinar cells is mediated by CD4+ T cells, but how they protect is unclear. Here, we show CD4+ T cells control MCMV indirectly in the salivary gland, via IFNγ engagement with uninfected, but antigen+ MHCII+ APC and recruitment of NK cells to infected cell foci. This immune mechanism renders direct contact of CD4+ T cells with infected cells unnecessary and may represent a host strategy to overcome viral immune evasion.
AImedReport: A Prototype Tool to Facilitate Research Reporting and Translation of AI Technologies in Healthcare
Authors: Brereton Tracey A. , Malik Momin M. , Rost Lauren M. , Ohde Joshua W. , Zheng Lu , Jose Kristelle A. , Peterson Kevin J. , Vidal David , Lifson Mark A. , Melnick Joe , Flor Bryce , Greenwood Jason D. , Fisher Kyle , Overgaard Shauna M.
Published: January 2024

AImedReport is a proof-of-concept team-based documentation strategy that consolidates available AI research reporting guidelines and centrally tracks and organizes any information provided as part of following various guidelines. It functions to assist teams by a) outlining phases of the AI lifecycle and clinical evaluation; b) iteratively developing a comprehensive documentation deliverable and historical archive; and c) addressing translation, implementation, and accountability gaps. By acting as a hub for determining what information to capture, it helps navigate team responsibilities, simplify compliance with evaluation and reporting measures, and fulfill requirements to support clinical trial documentation and publications. Here, we give an overview of this system and describe how it can be used to address documentation and collaboration challenges in AI translation.
Evaluating GPT-4 as a Clinical Decision Support Tool in Ischemic Stroke Management
Authors: Haim Amit , Katson Mark , Cohen-Shelly Michal , Peretz Shlomi , Aran Dvir , Shelly Shahar
Published: January 2024

Cerebrovascular diseases are the second most common cause of death worldwide and one of the major causes of disability burden. Advancements in artificial intelligence (AI) have the potential to revolutionize healthcare delivery, particularly in critical decision-making scenarios such as ischemic stroke management. This study evaluates the effectiveness of GPT-4 in providing clinical decision support for emergency room neurologists by comparing its recommendations with expert opinions and real-world treatment outcomes. A cohort of 100 consecutive patients with acute stroke symptoms was retrospectively reviewed. The data used for decision making included patients’ history, clinical evaluation, imaging studies results, and other relevant details. Each case was independently presented to GPT-4, which provided a scaled recommendation (1-7) regarding the appropriateness of treatment, the use of tissue plasminogen activator (tPA), and the need for endovascular thrombectomy (EVT). Additionally, GPT-4 estimated the 90-day mortality probability for each patient and elucidated its reasoning for each recommendation. The recommendations were then compared with those of a stroke specialist and actual treatment decision. The agreement of GPT-4’s recommendations with the expert opinion yielded an Area Under the Curve (AUC) of 0.85 [95% CI: 0.77-0.93], and with real-world treatment decisions, an AUC of 0.80 [0.69-0.91]. In terms of mortality prediction, out of 13 patients who died within 90 days, GPT-4 accurately identified 10 within its top 25 high-risk predictions (AUC = 0.89 [95% CI: 0.8077-0.9739]; HR: 6.98 [95% CI: 2.88-16.9]), surpassing supervised machine-learning models. This study demonstrates the potential of GPT-4 as a viable clinical decision support tool in the management of ischemic stroke. Its ability to provide explainable recommendations without requiring structured data input aligns well with the routine workflows of treating physicians. Future studies should focus on prospective validations and exploring the integration of such AI tools into clinical practice.
Safety of BNT162b2 mRNA COVID-19 vaccine batches: A nationwide cohort study
Authors: Hviid Anders , Bech Svalgaard Ingrid
Published: January 2024

Background

The safety of the BNT162b2 mRNA COVID-19 vaccine has been extensively evaluated since the global rollout began. While serious adverse events are rare, safety issues continue to arise. This study evaluates the claim that earlier small vaccine batches were associated with higher rates of serious adverse events compared to later batches.

Methods

A nationwide cohort study was conducted in Denmark, comprising individuals vaccinated with the BNT162b2 vaccine from 52 pre-defined batches classified into three pre-defined groups. Vaccinated individuals were matched 1:1 between batch groups on age, sex, and vaccination priority group. The study outcomes, included 27 serious adverse events, 2 negative control outcomes and all-cause mortality. Cox regression was used to estimate hazard ratios (HRs) comparing rates between batch groups in the 28-days following vaccination. We conducted two comparisons of the early small batches to two groups of larger batches used later in the pandemic.

Results

In the study period, 9,983,448 vaccinations were administered from batches in the three pre-defined groups. Slightly increased rates of arrhythmia were observed in both study comparisons, HRs 1.25 (95% CI,1.05-1.50) and 1.15 (1.00-1.31), respectively, but sensitivity analyses did not robustly support these associations. For the remaining outcomes, increased rates in both study comparisons were not observed.

Conclusion

This nationwide cohort study provides reassurance regarding the safety of the BNT162b2 vaccine across different batches used in Denmark. The findings support the overall safety of the vaccine, with no clinically relevant variations in serious adverse event rates between batches.
Targeting the mSWI/SNF Complex in POU2F-POU2AF Transcription Factor-Driven Malignancies
Authors: He Tongchen , Xiao Lanbo , Qiao Yuanyuan , Klingbeil Olaf , Young Eleanor , Wu Xiaoli S. , Mannan Rahul , Mahapatra Somnath , Eyunni Sanjana , Tien Jean Ching-Yi , Wang Xiaoju , Zheng Yang , Kim NamHoon , Zheng Heng , Hou Siyu , Su Fengyun , Miner Stephanie J. , Mehra Rohit , Cao Xuhong , Abbineni Chandrasekhar , Samajdar Susanta , Ramachandra Murali , Parolia Abhijit , Vakoc Christopher R. , Chinnaiyan Arul M.
Published: January 2024

The POU2F3-POU2AF2/3 (OCA-T1/2) transcription factor complex is the master regulator of the tuft cell lineage and tuft cell-like small cell lung cancer (SCLC). Here, we found that the POU2F3 molecular subtype of SCLC (SCLC-P) exhibits an exquisite dependence on the activity of the mammalian switch/sucrose non-fermentable (mSWI/SNF) chromatin remodeling complex. SCLC-P cell lines were sensitive to nanomolar levels of a mSWI/SNF ATPase proteolysis targeting chimera (PROTAC) degrader when compared to other molecular subtypes of SCLC. POU2F3 and its cofactors were found to interact with components of the mSWI/SNF complex. The POU2F3 transcription factor complex was evicted from chromatin upon mSWI/SNF ATPase degradation, leading to attenuation of downstream oncogenic signaling in SCLC-P cells. A novel, orally bioavailable mSWI/SNF ATPase PROTAC degrader, AU-24118, demonstrated preferential efficacy in the SCLC-P relative to the SCLC-A subtype and significantly decreased tumor growth in preclinical models. AU-24118 did not alter normal tuft cell numbers in lung or colon, nor did it exhibit toxicity in mice. B cell malignancies which displayed a dependency on the POU2F1/2 cofactor, POU2AF1 (OCA-B), were also remarkably sensitive to mSWI/SNF ATPase degradation. Mechanistically, mSWI/SNF ATPase degrader treatment in multiple myeloma cells compacted chromatin, dislodged POU2AF1 and IRF4, and decreased IRF4 signaling. In a POU2AF1-dependent, disseminated murine model of multiple myeloma, AU-24118 enhanced survival compared to pomalidomide, an approved treatment for multiple myeloma. Taken together, our studies suggest that POU2F-POU2AF-driven malignancies have an intrinsic dependence on the mSWI/SNF complex, representing a therapeutic vulnerability.
Refinement of a published gene-physical activity interaction impacting HDL-cholesterol: role of sex and lipoprotein subfractions
Authors: Westerman Kenneth E. , Kilpeläinen Tuomas O. , Sevilla-Gonzalez Magdalena , Connelly Margery A. , Wood Alexis C. , Tsai Michael Y. , Taylor Kent D. , Rich Stephen S. , Rotter Jerome I. , Otvos James D. , Bentley Amy R. , Mora Samia , Aschard Hugues , Rao DC , Gu Charles , Chasman Daniel I. , Manning Alisa K.
Published: January 2024

Large-scale gene-environment interaction (GxE) discovery efforts often involve compromises in the definition of outcomes and choice of covariates for the sake of data harmonization and statistical power. Consequently, refinement of exposures, covariates, outcomes, and population subsets may be helpful to establish often-elusive replication and evaluate potential clinical utility. Here, we used additional datasets, an expanded set of statistical models, and interrogation of lipoprotein metabolism via nuclear magnetic resonance (NMR)-based lipoprotein subfractions to refine a previously discovered GxE modifying the relationship between physical activity (PA) and HDL-cholesterol (HDL-C). This GxE was originally identified by Kilpeläinen et al., with the strongest cohort-specific signal coming from the Women’s Genome Health Study (WGHS). We thus explored this GxE further in the WGHS (N = 23,294), with follow-up in the UK Biobank (UKB; N = 281,380), and the Multi-Ethnic Study of Atherosclerosis (MESA; N = 4,587). Self-reported PA (MET-hrs/wk), genotypes at rs295849 (nearest gene:LHX1), and NMR metabolomics data were available in all three cohorts. As originally reported, minor allele carriers of rs295849 in WGHS had a stronger positive association between PA and HDL-C (pint= 0.002). When testing a range of NMR metabolites (primarily lipoprotein and lipid subfractions) to refine the HDL-C outcome, we found a stronger interaction effect on medium-sized HDL particle concentrations (M-HDL-P;pint= 1.0×10-4) than HDL-C. Meta-regression revealed a systematically larger interaction effect in cohorts from the original meta-analysis with a greater fraction of women (p= 0.018). In the UKB, GxE effects were stronger both in women and using M-HDL-P as the outcome. In MESA, the primary interaction for HDL-C showed nominal significance (pint= 0.013), but without clear differences by sex and with a greater magnitude using large, rather than medium, HDL-P as an outcome. Towards reconciling these observations, further exploration leveraging NMR platform-specific HDL subfraction diameter annotations revealed modest agreement across all cohorts in the interaction affecting medium-to-large particles. Taken together, our work provides additional insights into a specific known gene- PA interaction while illustrating the importance of phenotype and model refinement towards understanding and replicating GxEs.
Larval zebrafish maintain elevation with multisensory control of posture and locomotion
Authors: Davis Samantha N. , Zhu Yunlu , Schoppik David
Published: January 2024

Fish actively control posture in the pitch axis (nose-up/nose-down) to counter instability and regulate their elevation in the water column. To test the hypothesis that environmental cues shape strategies fish use to control posture, we leveraged a serendipitous finding: larval zebrafish (Danio rerio) sink mildly after acute loss of lateral line hair cells. Using long-term (48 h) recordings of unrestrained swimming, we discovered that sinking larvae compensated differently depending on light conditions. In the dark, they swim more frequently with an increased nose-up posture. In contrast, larvae in the light do not swim more frequently, but do climb more often. Finally, after lateral line regeneration, larvae returned to normal buoyancy and swam comparably to control siblings. We conclude that larvae can switch postural control strategies depending on the availability of visual information. Our findings complement and extend morphological and kinematic analyses of locomotion. More broadly, by quantifying the variation in strategies our work speaks to the evolutionary substrate for different balance behaviors.
Cross-omic Transcription Factors meta-analysis: an insight on TFs accessibility and expression correlation
Authors: Martini Lorenzo , Bardini Roberta , Savino Alessandro , Di Carlo Stefano
Published: January 2024

It is well-known how sequencing technologies propelled cellular biology research in recent years, giving an incredible insight into the basic mechanisms of cells. Single-cell RNA sequencing is at the front in this field, with Single-cell ATAC sequencing supporting it and becoming more popular. In this regard, multi-modal technologies play a crucial role, allowing the possibility to perform the mentioned sequencing modalities simultaneously on the same cells. Yet, there still needs to be a clear and dedicated way to analyze this multi-modal data. One of the current methods is to calculate the Gene Activity Matrix (GAM), which summarizes the accessibility of the genes at the genomic level, to have a more direct link with the transcriptomic data. However, this concept is not well-defined, and it is unclear how various accessible regions impact the expression of the genes. Moreover, the transcription process is highly regulated by the Transcription Factors that binds to the different DNA regions. Therefore, this work presents a continuation of the meta-analysis of Genomic-Annotated Gene Activity Matrix (GAGAM) contributions, aiming to investigate the correlation between the TFs expression and motif information in the different functional genomic regions to understand the different Transcription Factors (TFs) dynamics involved in different cell types.
The immunological profile of RC17 hESC-derived dopaminergic neural progenitor cellsin vitro: implications for the STEM-PD clinical trial
Authors: Curle Annabel J , Fazal Shaline V , Qarin Shamma , Howlett Sarah K , He Xiaoling , Barker Roger A , Jones Joanne L
Published: January 2024

Parkinson’s Disease involves the progressive loss of dopaminergic neurons (DAn), prompting clinical trials replacing cell loss with neural grafts. This includes the transplantation of pluripotent stem cell-derived DAn progenitor cells (NPC) currently under investigation in the STEM-PD trial. To determine the likelihood of immune rejection post-grafting, we characterised the immunogenicity of the STEM-PD product (RC17-hESC-derived NPCs), comparing them to human foetal ventral mesencephalic tissue (hfVM) previously tested in trials, including our own TRANSEURO trial. Despite MHC-Class I expression, upregulated by proinflammatory cytokines, no immune response to NPCs was detectedin vitro. Instead, they were immunosuppressive. Transcriptomic analysis revealed similarities between RC17-NPCs and hfVM, both strongly upregulating antigen processing and presentation pathways in response to IFNγ. Furthermore, immunosuppressant mycophenolate mofetil detrimentally affected NPC survival and differentiationin vitro. Overall, our data suggest that aggressive immunosuppression is not required following hESC-NPC transplantation and that caution should be exercised when selecting the immunosuppressive regimen.