bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of Weight Stigma in Medical Settings Among Reproductive-Aged Women in the All of Us Study
Authors: Kapera Olivia , Chen Baojiang , Almandoz Jaime P. , Byrd-Williams Courtney , Messiah Sarah E.
Published: May 2024

OBJECTIVE:

To analyze health care treatment experiences among a diverse cohort of reproductive-aged women from the All of Us study, focusing on variations due to body mass index (BMI).

METHODS:

We conducted a cross-sectional study that used data from the All of Us Research Program. We analyzed weight bias among reproductive-aged women aged 18–44 years. Weight bias was assessed using a proxy 7-item survey that evaluated discrimination in health care experiences, including courtesy, respect, service quality, being treated as competent, displaying fear, being treated as inferior, and being listened to during health care visits.

RESULTS:

Overall, 16,791 reproductive-aged women (mean [SD] age, 35.8 [6.3]) were included in the study. Of 11,592 patients with data available on BMI, 582 were Asian (5.0%), 1,984 (17.1%) were Hispanic or Latinx, 1,007 (8.7%) were non-Hispanic Black, and 7,370 (63.6%) were non-Hispanic White. Approximately 24.2% of participants (n=2,878) had obesity, and 11.1% of participants (n=1,292) had severe obesity. In general, participants in higher BMI categories had negative experiences in the health care setting. Women with severe obesity were 1.5 to 2 times more likely to report poor experiences with their health care clinicians compared with women with healthy weight.

CONCLUSION:

Results show significant disparities in the health care experiences among reproductive-aged women. As participants' BMI category increased, so did their negative experiences in the health care setting. These findings underscore the urgent need for targeted interventions to address these inequities. Health care systems must prioritize strategies to ensure that all individuals, regardless of weight or BMI, receive equitable and respectful care.
Cross-Cultural Adaptation, Translation, and Validation of Pain Self-Efficacy Questionnaire in Hindi Language in Patients With Chronic Neck Pain
Authors: Geete Dipti Baban , Mhatre Bhavana Suhas
Published: May 2024

Study Design.

Translation and psychometric testing.

Objectives.

The objective of this study was to translate and culturally adapt the Pain Self-Efficacy Questionnaire (PSEQ) into Hindi (PSEQ-H), the local language of India, and assess its psychometric properties.

Background.

The PSEQ is a commonly used outcome measure in patients with pain and related psychosocial aspects too. The PSEQ invites participants to consider their pain while assessing their self-efficacy views. Because about half of India’s population understands Hindi, there is a need to translate the PSEQ into Hindi for patient convenience and better comprehension, as well as for research purposes.

Materials and Methods.

The PSEQ has been translated and culturally adapted into Hindi. A total of 120 patients with chronic neck pain were recruited. The PSEQ-H’s content validity, construct validity, internal consistency, test-retest reliability, and responsiveness were all assessed. To determine test-retest reliability, the intraclass correlation coefficient was calculated. Cronbach alpha was used to determine internal consistency. Criterion validity was assessed using the neck disability index, NRS, and anxiety and depression measures. The area under the curve and the change cut-point were determined using the receiver operating characteristic curve analysis.

Results.

The PSEQ-H exhibited strong test-retest reliability (intraclass correlation coefficient = 0.90) and good internal consistency (Cronbach alpha = 0.88). Factor analysis confirmed a one-factor structure for the PSEQ-H. Furthermore, the PSEQ-H demonstrated a moderate correlation with the neck disability index, numerical pain rating scale, anxiety, and depression scales. A change detection threshold of 8.3 was established.

Conclusions.

The PSEQ-H is a reliable and valid measure for use in research and clinical purposes in the Indian population with chronic neck pain.

Level of Evidence.

Level II.
Assessment of Electronic Health Literacy Among Filipino Americans
Authors: Arigorat Ellen J. , Begonia Kathleen , Franklin Mary , Honsky Jesse
Published: May 2024

Health literacy requires skills of reading, understanding, and analyzing text, numbers, graphs, and diagrams to make well-informed decisions. The increase advancement in technologies has made health information accessible in electronic format. Individuals must apply health literacy in navigating through health information resources on the Internet. Filipino Americans originating from a diverse background are often underreported and underrepresented in health research. The study aim was to examine electronic health literacy among Filipino Americans using the Electronic Health Literacy Scale survey. The descriptive study recruited 103 participants. Overall Filipino Americans are electronic health literate, with a mean of 32.4 (SD = 4.6). Females (P = .017), those with graduate or professional degrees (P = .004) and working in healthcare (P = .040) tend to have higher electronic health literacy. The study provided valuable insight on electronic health literacy on a population that is underrepresented in research. The descriptive data gained from the study lays foundational work to help decrease health inequities experienced by Filipino Americans.
The health care experience of adults with metabolic dysfunction–associated steatohepatitis and influence of PNPLA3: A qualitative study
Authors: Stine Jonathan G. , Medic Nenad , Pettersson Billie , Venerus Meredith , Blau Jenny E.
Published: May 2024

Background:

Metabolic dysfunction–associated steatohepatitis (MASH) is a progressive form of metabolic dysfunction–associated steatotic liver disease, for which there is limited information about patient experience, including the patient journey.

Methods:

In this study, we conducted interviews with patients with MASH to qualitatively evaluate the patient journey and help elucidate the experiences of this patient population. We also investigated if the patatin‐like phospholipase domain‐containing protein 3 (PNPLA3) I148M variant (non-Hispanic) or being of Hispanic ethnicity may influence patient experiences because these 2 subgroups develop advanced liver disease more frequently than other patient groups.

Results:

One-to-one interviews were conducted with 28 adults (with PNPLA3 I148M genetic variant, n = 10; Hispanic, n = 8) living in the United States who had been diagnosed with MASH with liver fibrosis. Patients were asked open-ended questions about their experiences before, at, and after their diagnosis. The data collected found that patients experienced a long process of misdiagnoses before their diagnosis of MASH, a lack of clear information provided by clinicians, and limited accessibility to support groups. Hispanic patients reported “impact on family/friends” (75%) and “fear of disease progression” (75%) more frequently than the other patient cohorts interviewed. This is the first report of “fear of progression” in patients with MASH. No patients who were White and had the PNPLA3 I148M variant reported nausea/vomiting, in contrast to other patient cohorts.

Conclusions:

This qualitative study identified key aspects of the patient journey that are important for clinical providers and medical teams to recognize. We also propose a new algorithm that could be developed to help screen relatives of patients who are found to carry the PNPLA3 I148M variant.
Platelet-mediated circulating tumor cell evasion from natural killer cell killing through immune checkpoint CD155-TIGIT
Authors: Sun Yunfan , Li Tong , Ding Lin , Wang Jiyan , Chen Chen , Liu Te , Liu Yu , Li Qian , Wang Chuyu , Huo Ran , Wang Hao , Tian Tongtong , Zhang Chunyan , Pan Baishen , Zhou Jian , Fan Jia , Yang Xinrong , Yang Wenjing , Wang Beili , Guo Wei
Published: May 2024

Background and Aims:

Circulating tumor cells (CTCs) are precursors of cancer metastasis. However, how CTCs evade immunosurveillance during hematogenous dissemination remains unclear.

Approach and Results:

We identified CTC-platelet adhesions by single-cell RNA sequencing and multiplex immunofluorescence of blood samples from multiple cancer types. Clinically, CTC-platelet aggregates were associated with significantly shorter progression-free survival and overall survival in patients with HCC. In vitro, ex vivo, and in vivo assays demonstrated direct platelet adhesions gifted cancer cells with an evasive ability from NK cell killing by upregulating inhibitory checkpoint CD155 (PVR cell adhesion molecule), therefore facilitating distant metastasis. Mechanistically, CD155 was transcriptionally regulated by the FAK/JNK/c-Jun cascade in a platelet contact–dependent manner. Further competition assays and cytotoxicity experiments revealed that CD155 on CTCs inhibited NK-cell cytotoxicity only by engaging with immune receptor TIGIT, but not CD96 and DNAM1, another 2 receptors for CD155. Interrupting the CD155-TIGIT interactions with a TIGIT antibody restored NK-cell immunosurveillance on CTCs and markedly attenuated tumor metastasis.

Conclusions:

Our results demonstrated CTC evasion from NK-cell–mediated innate immunosurveillance mainly through immune checkpoint CD155-TIGIT, potentially offering an immunotherapeutic strategy for eradicating CTCs.
Defective natriuresis contributes to hyperkalemia in db/db mice during potassium supplementation
Authors: Shu Ting-Ting , Gao Zhong-Xiuzi , Mao Zi-Hui , Yang Yuan-Yuan , Fu Wen-Jia , Pan Shao-Kang , Zhao Qian-Qian , Liu Dong-Wei , Liu Zhang-Suo , Wu Peng
Published: May 2024

Objectives:

Potassium supplementation reduces blood pressure and the occurrence of cardiovascular diseases, with K+-induced natriuresis playing a potential key role in this process. However, whether these beneficial effects occur in diabetes remains unknown.

Methods:

In this study, we examined the impact of high-K+ intake on renal Na+/K+ transport by determining the expression of major apical Na+ transporters, diuretics responses (as a proxy for specific Na+ transporter function), urinary Na+/K+ excretion, and plasma Na+/K+ concentrations in db/db mice, a model of type 2 diabetes mellitus.

Results:

Although db/m mice exhibited increased fractional excretion of sodium (FENa) and fractional excretion of potassium (FEK) under high-K+ intake, these responses were largely blunted in db/db mice, suggesting impaired K+-induced natriuresis and kaliuresis in diabetes. Consequently, high-K+ intake increased plasma K+ levels in db/db mice, which could be attributed to the abnormal activity of sodium-hydrogen exchanger 3 (NHE3), sodium-chloride cotransporter (NCC), and epithelial Na+ channel (ENaC), as high-K+ intake could not effectively decrease NHE3 and NCC and increase ENaC expression and activity in the diabetic group. Inhibition of NCC by hydrochlorothiazide could correct the hyperkalemia in db/db mice fed a high-K+ diet, indicating a key role for NCC in K+-loaded diabetic mice. Treatment with metformin enhanced urinary Na+/K+ excretion and normalized plasma K+ levels in db/db mice with a high-K+ diet, at least partially, by suppressing NCC activity.

Conclusion:

Collectively, the impaired K+-induced natriuresis in diabetic mice under high-K+ intake may be primarily attributed to impaired NCC-mediated renal K+ excretion, despite the role of NHE3.
Thirty-five years of the European Society of Hypertension: from past to future
Authors: Grassi Guido
Published: May 2024

The European Society of Hypertension (ESH) was established 35 years ago. Since then, it promoted and coordinated a number of activities which include educational projects, epidemiological surveys and research investigations whose main focus includes different clinical and therapeutic aspects of the hypertensive disease. This article, which is based on data presented during the Presidential lecture held during the 33rd ESH Meeting in Berlin, will provide an overview of the main organization and structure of the ESH. Emphasis will be given to the relevance of the different society bodies, with a particular focus on the educational and research activities, such as the 15 working groups and the more than 120 excellence centers located in European and extra-European countries. Other main activities of the Society refer to the ESH Hypertension Specialist Program, the ESH Summer School, the ESH Young Fellow Program and the Annual Scientific Meeting of the Society. A special emphasis will be given to the central role of the Society in the organization of the various research projects and in the development and dissemination of the ESH Guideline document on hypertension diagnosis and treatment. Finally, the future perspectives of the ESH in the context of the European scientific framework will be highlighted.
RETINAL TOXICITY SECONDARY TO INADVERTENT SUBRETINAL MITOMYCIN C INJECTION
Authors: Alsberge Joseph B. , Hoffelt Zakary
Published: May 2024

Purpose:

To report a patient who developed retinal toxicity after inadvertent subretinal mitomycin C injection during glaucoma surgery.

Methods:

Case report and review of the literature.

Results:

A 73-year-old man underwent glaucoma tube shunt surgery with sub-Tenon mitomycin C injection. Postoperatively, he developed retinal edema, hemorrhages, and occlusive vasculopathy localized to the quadrant of the mitomycin C injection. It was determined that the sclera had been inadvertently punctured during mitomycin C injection, resulting in subretinal placement of the medication and resultant retinal toxicity. At postoperative month 1, there was diffuse chorioretinal atrophy in the area of the injection. The macula was spared and he retained his preoperative visual acuity.

Conclusion:

Inadvertent subretinal mitomycin C injection may occur when attempting to inject the drug into the sub-Tenon space and can result in localized retinal toxicity.
Clinical Efficacy of 2% Rebamipide in Patients With Video Display Terminal–Associated Dry Eye Disease: A Prospective, Randomized, Double-Blinded Study
Authors: Lee Yong Woo , Han Sang Beom
Published: May 2024

Purpose:

To compare the effects of 2% rebamipide clear solution and 0.1% sodium hyaluronate eye drops in patients with visual display terminal (VDT)-related dry eye disease (DED).

Design:

Prospective, randomized, double-blinded Study.

Methods:

This was a prospective, double-blind, and randomized controlled study. Patients with VDT-related DED were randomly allocated to a 2% rebamipide (REB) group or a 0.1% sodium hyaluronate (HYA) group (4 times/day for 4 weeks). The ocular surface disease index (OSDI), dry eye questionnaire-5 (DEQ-5), Placido disk-tear film analyzer, fluorescein-stained tear break-up time (FBUT), ocular surface staining score, and Schirmer 1 test were examined before and after the instillation of drug.

Results:

A total of 56 eyes of 28 patients (28 eyes of 14 patients in each group) were included. There were no significant differences in the baseline data. The OSDI, DEQ-5, FBUT, and conjunctival erosion scores improved significantly in both groups after treatment. In the REB group, corneal staining and bulbar nasal redness scores also improved significantly after treatment (P<0.001 and 0.036, respectively), whereas no significant differences were found in these parameters in the HYA group (P=0.326 and 0.118, respectively). The REB group showed a significantly larger decrease in the corneal staining score than the HYA group (P=0.016). No adverse reactions were observed.

Conclusions:

A 2% rebamipide clear solution effectively improved the symptoms and signs in patients with VDT-related DED and was superior to 0.1% sodium hyaluronate ophthalmic solution in improving corneal epithelial damage, making it a safe and effective treatment option for VDT-related DED.
Myopic Regression After FS-LASIK and SMILE
Authors: Lin Meng-Yin , Tan Hsin-Yuan , Chang Chao-Kai
Published: May 2024

Purpose:

To compare the degree of myopic regression after myopia correction with either femtosecond laser-assisted in situ keratomileusis (FS-LASIK) or small-incision lenticule extraction (SMILE) over 18 months.

Methods:

Patients undergoing FS-LASIK or SMILE surgery for myopia correction were retrospectively recruited. The propensity scores were used to match patients by age and preoperative manifest spherical equivalent (SEQ) from these 2 groups. Myopic regression was analyzed using the Cox proportional hazard model.

Results:

A total of 416 eyes of 416 patients undergoing FS-LASIK and 416 eyes of 416 patients undergoing SMILE were matched. Using 1-month SEQ as baseline, the SEQ regression values after FS-LASIK were 0D, −0.17 ± 0.69D, −0.24 ± 0.65D, −0.31 ± 0.65D, −0.32 ± 0.63D, and −0.33 ± 0.62D and the SEQ regression values after SMILE were 0D, −0.07 ± 0.75D, −0.18 ± 0.77D, −0.23 ± 0.82 D, −0.21 ± 0.77D, and −0.24 ± 0.68D at 1, 3, 6, 9, 12, and 18 months, respectively. The Cox proportional hazard model showed that preoperative manifest SEQ (P = 0.021) and designed optical zone (P = 0.048) are significant predictors. The selected surgical procedure had no significant effect on predicting myopic regression (P = 0.470). The cumulative survival rates of myopic regression were 54.74% and 42.10% in the FS-LASIK group and 58.66% and 43.83% in the SMILE group, at 12 and 18 months, respectively (log-rank test, P = 0.11).

Conclusions:

After matching based on age and preoperative manifest SEQ, we found that higher myopia and a smaller optical zone contribute significantly to the development of myopic regression after undergoing FS-LASIK or SMILE surgery at 18 months. The selected surgical procedure, however, does not affect the likelihood of myopic regression.
Diagnostic Abilities of Three-Dimensional Anterior Segment Optical Coherence Tomography in Detecting Angle Closure
Authors: Chansangpetch Sunee , Phinyo Phichayut , Patumanond Jayanton , Choovuthayakorn Janejit , Lin Shan C.
Published: May 2024

Précis:

Three-dimensional (3D) angle parameters and cutoff values for detecting angle closure were proposed. The 3D parameters demonstrated excellent diagnostic performance. Certain horizontal two-dimensional (2D) parameters [ie, trabecular iris space area (TISA)-750, angle opening distance (AOD)-750, and AOD-500] can attain similar performance to their high-performing 3D counterparts.

Objective:

To investigate the diagnostic performance of single horizontal 2D versus 3D angle parameters from swept-source anterior segment optical coherence tomography (CASIA2) in detecting angle closure.

Materials and Methods:

The cross-sectional study included 118 phakic patients (59 open angles, 59 closed angles). AOD, angle recess area (ARA), and TISA at 250, 500, and 750 μm from scleral spur were measured in 360-degree radial-scan images. The 3D information of each measurement was analyzed in 2 patterns: (1) average 3D parameter—the averaged value from 360-degree angle values and (2) estimate 3D parameter—the estimation of surface area of circumferential angle inlet (using AOD) or circumferential angle volume (using ARA and TISA). The areas under the receiver operating characteristic curve [areas under the curve (AUCs)] of eighteen 3D parameters were compared with 2D horizontal parameters.

Results:

Among 3D parameters, AOD-500 estimate 3D gave the highest AUC (AUC: 0.950, cutoff: 6.09 mm2), followed by AOD-750 estimate 3D (AUC: 0.948, cutoff: 8.26 mm2). 3D parameters significantly increased the AUC of ARA-250 and TISA-250 (all P < 0.02) compared with the 2D parameters. No significant improvement in AUC was demonstrated for AOD-250 and all parameters at 500 and 750 μm. No significant difference in AUC was found among the 6 maximum AUC parameters, which were AOD-750 horizontal 2D, AOD-500 estimate 3D, TISA-750 horizontal 2D, AOD-500 horizontal 2D, AOD-750 estimate 3D, and TISA-750 average 3D.

Conclusions:

The 3D-angle parameters had high performance in detecting angle closure. However, comparing a horizontal measurement to 3D parameters, the AUC improvement was mostly insignificant.
Examining Acute Symptoms After Sport-Related Concussion in Collegiate Athletes With Preinjury Migraines
Authors: Jo Jacob , Berkner Paul D. , Stephenson Katie , Maxwell Bruce A. , Iverson Grant L. , Zuckerman Scott L. , Terry Douglas P.
Published: May 2024

Objective:

To examine whether a personal history of migraines is associated with worse acute symptom burden after sport-related concussion (SRC).

Design:

Retrospective cohort study.

Setting:

National Collegiate Athletic Association Division III collegiate programs.

Participants:

Collegiate athletes from a prospective concussion surveillance system between 09, 2014, and 01, 2023.

Intervention:

Preinjury migraines (yes/no) were self-reported by athletes.

Main Outcome Measures:

Post-Concussion Symptom Scale (PCSS) were collected within 3 days postinjury. Mann–Whitney U tests compared total PCSS scores and individual symptom scores between athletes with and without preinjury migraines. Chi-squared tests were used to compare proportions of athletes endorsing individual symptoms (ie, item score ≥1) between 2 groups. Multivariable regression analyzed potential predictors of PCSS scores.

Results:

Of 1190 athletes with SRC, 93 (7.8%) reported a preinjury history of migraines. No significant difference in total PCSS scores was found between athletes with and without preinjury migraines (22.0 ± 16.4 vs 20.5 ± 15.8, U = 48 719.0, P = 0.471). Athletes with preinjury migraines reported greater severity of “sensitivity to light” (1.59 ± 1.59 vs 1.23 ± 1.41, P = 0.040) and “feeling more emotional” (0.91 ± 1.27 vs 0.70 ± 1.30; P = 0.008) and were more likely to endorse “feeling more emotional” (45.2% vs 29.5%, P = 0.002). No differences were found across all other symptoms, including headaches (migraine = 87.1% vs no migraine = 86.3%, P = 0.835). In a multivariable model, a history of migraine was not a significant predictor of acute PCSS scores, but those with a history of psychological disorders (β = 0.12, P <0 .001) and greater number of days to symptom evaluation (β = 0.08, P = 0.005) had higher PCSS scores.

Conclusions:

Collegiate athletes with a pre-existing history of migraines did not have higher acute symptom burden after SRC.
Process and Impact of Development of an Adolescent Emergency Psychiatry Unit at a Large Urban Hospital
Authors: Claudius Ilene , Tolles Juliana , Fleischman Ross , Muller Vikram , Padlipsky Patricia , Kelly Patrick , Saidinejad Mohsen
Published: May 2024

Objectives

Boarding of adolescent patients with mental health concerns requiring ongoing observation and treatment is of increasing concern across US emergency departments. The objective was a proof of concept of developing an adolescent psychiatric emergency unit and assessment of the impact of this unit on lengths of stay (LOS).

Methods

We describe the creation of the unit designed to allow safe assessment and boarding of patients, and appropriate interventions and services, while arranging transfer to inpatient facility or safe discharge home. Using a precreation and postcreation analysis and comparison with a similar facility that did not create such a unit, we utilized linear regression to investigate the primary outcome of total length of stay and secondary outcomes of psychiatric emergency department and pediatric emergency department length of stay for both unit-eligible patients and all patients.

Results

The overall length of stay was not associated with a statistically significant change for unit-eligible patients; however, there was a significant decrease in the pediatric emergency department LOS for unit-eligible patients. This was associated with a decrease in beds lost to boarding in the pediatric emergency department of 544 hours per month.

Conclusions

Creation of an adolescent psychiatric emergency unit without allotment of significant additional resources is an option to decrease pediatric emergency department boarding times for adolescent patients requiring ongoing emergent therapy for mental health concerns.
Age Impacts Clinical and Patient-Reported Outcomes following Postmastectomy Breast Reconstruction
Authors: Kim Minji , Ali Barkat , Zhang Kevin , Vingan Perri , Boe Lillian , Ly Catherine L. , Allen Robert J. , Stern Carrie S. , Matros Evan , Cordeiro Peter G. , Mehrara Babak , Nelson Jonas A.
Published: May 2024

Background:

Although the current literature indicates that age should not be a deterring factor in postmastectomy breast reconstruction, the true impact of increasing age on postoperative outcomes remains unknown. The purpose of this study is to understand the impact of age on complications and patient-reported outcomes (PROs) using the BREAST-Q longitudinally 5 years after postmastectomy breast reconstruction.

Methods:

The authors conducted a retrospective analysis of patients who underwent autologous (ABR) or implant-based reconstruction (IBR). Age was studied as both a categorical and a continuous variable. Outcome measures included complications and BREAST-Q scores preoperatively, at 6 months, and 1 to 5 years postoperatively.

Results:

A total of 4730 patients were included, of which 1536 (32.5%) underwent ABR and 3194 (67.5%) underwent IBR. Older age was significantly associated with increased risk of developing mastectomy skin flap/nipple necrosis, infection, and seroma. Older age was negatively correlated with Satisfaction with Breasts (β = −0.06 [95% CI, −0.12 to −0.01]; P = 0.033) and positively correlated with Psychosocial Well-being (β = 0.14 [95% CI, 0.09 to 0.20]; P < 0.001). Older age was not correlated with Physical Well-being of the Chest (β = −0.03 [95% CI, 0.08 to 0.02]; P = 0.2) or Sexual Well-being (β = −0.04 [95% CI, −0.12 to 0.02]; P = 0.2). Subgroup analyses of ABR and IBR patients demonstrated different complications and PRO profiles.

Conclusions:

The authors’ analysis of the impact of age on surgical outcomes and PROs suggests that complication rates increase with age, and older age is negatively correlated with Satisfaction with Breasts but positively correlated with Psychosocial Well-being. Overall, older patients should be informed about the potential associated risks and anticipated PROs.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, II.
Pleural Spindle Cell Sarcoma on 68Ga-DOTA-FAPI-04 PET/CT and 18F-FDG PET/CT
Authors: Cui Yan , Zhou Xin , Li Nan
Published: May 2024

A 67-year-old woman with pleural mass underwent 18F-FDG PET/CT, suspected of malignant pleural tumor with intense 18F-FDG uptake. Then she underwent 68Ga-DOTA-FAPI-04 PET/CT for staging, which showed similar uptake in pleural lesions and opposite uptake pattern in mediastinal and hilar lymph nodes. Finally, she was diagnosed with spindle cell sarcoma (G2) by histopathology. After 1 cycle chemotherapy, the pleural lesions progressed, while mediastinal lymph nodes shrunk. Half a month later, the patient died due to rapid disease progression. This case indicates that 68Ga-FAPI PET/CT might be a promising new tool in diagnosis and staging of pleural spindle cell sarcoma.
Spontaneous Dislocation of the Lens Nucleus Into the Anterior Chamber Observed in a Patient With Overmature Senile Cataract
Authors: Yu Xuemeng , Chen Xiao-Hu , Dai Yan
Published: May 2024

Overmature cataract refers to the advanced stage of cataract where timely surgical intervention is not performed, leading to further progression characterized by decreased water content in the lens, degradation of fibers, and liquefaction within its structure, which can cause a reduction in volume, wrinkling of the capsule, as well as calcification or cholesterol crystallization on its surface. In addition, it may result in deepening of the anterior chamber. If left promptly untreated, these complications may result in visual impairment or even blindness. The occurrence of spontaneous complete dislocation of the lens nucleus into the anterior chamber in overmature cataracts is extremely uncommon. The authors present a case study involving a 74-year-old female patient who was diagnosed with complete dislocation of the lens nucleus in an overmature senile cataract without any apparent ocular injury or any relevant medical records. After undergoing cataract removal combined with anterior vitrectomy, the patient experienced relief from eye discomfort and expressed satisfaction with the surgical outcome; however, her visual acuity did not show significant improvement.
Inheritance of somatic mutations can affect fitness in monkeyflowers
Authors: Streisfeld Matthew A. , Crown Jessie C. , McLean Jack J. , Short Aidan W. , Cruzan Mitchell B.
Published: May 2024

Plants possess the unique ability to transmit mutations to progeny that arise both through meiotic and mitotic (somatic) cell divisions. This is because the same meristem cells responsible for vegetative growth also generate gametes for sexual reproduction. Despite the potential for somatic mutations to be an additional source of genetic variation for adaptation, their role in plant evolution remains largely unexplored. We performed multiple experiments in the bush monkeyflower (Mimulus aurantiacus) to determine the fitness effects of somatic mutations inherited across generations. We tracked somatic mutations transmitted to progeny by generating self-pollinations within a flower (autogamy) or between stems of the same plant (geitonogamy). Autogamy and geitonogamy lead to different segregation patterns of somatic mutations among stems, making it possible to compare average fitness due to somatic variants. We found increased fecundity following autogamy, as well as significant impacts on drought tolerance, survival, and biomass. The variance in fitness was also greater following autogamy, consistent with the effects of somatic mutations impacting fitness. Effect sizes were small, but predictable, given thatM. aurantiacusis a long-lived, drought-adapted shrub. These results reveal the importance of inherited somatic mutations as a source of genetic variation that can be relevant for plant adaptation.
Determinants of Prevalence and Stages of Undiagnosed Hypertension
Authors: Zuzunaga-Montoya Fiorella E. , Vásquez-Romero Luisa Erika Milagros , Loayza-Castro Joan A. , Vigil-Ventura Enrique , Gutierrez De Carrillo Carmen Inés , Vera-Ponce Víctor Juan
Published: May 2024

Introduction

Hypertension (HTN) has been classified into stages according to elevated blood pressure levels. It has been detailed that higher levels correlate with an increased risk of long-term complications.

Objective

To determine the prevalence and trends of different hypertension stages among Peruvians and to identify factors associated with these stages.

Methods

Data from the Demographic and Family Health Survey from 2014 to 2022 were analyzed. Blood pressure levels were categorized into normotension, high blood pressure (HBP), and HTN stages I, II, and III. The study included individuals aged 18 years and older, excluding those who had not had their blood pressure measured or had known histories of hypertension.

Results

The prevalences of HBP, HTN stage I, II, and III were 14.73%, 9.64%, 2.16%, and 0.64%, respectively. Factors such as gender, age, wealth index, alcohol consumption, daily smoking, and health conditions like obesity and diabetes significantly influenced the prevalence of the various stages.

Conclusions

The prevalence of HTN varies significantly depending on the stage. These findings underscore the necessity for public health strategies that are personalized and differentiated according to the specific stage of HTN to enhance effectiveness.
Large Language Models for Social Determinants of Health Information Extraction from Clinical Notes – A Generalizable Approach across Institutions
Authors: Keloth Vipina K. , Selek Salih , Chen Qingyu , Gilman Christopher , Fu Sunyang , Dang Yifang , Chen Xinghan , Hu Xinyue , Zhou Yujia , He Huan , Fan Jungwei W. , Wang Karen , Brandt Cynthia , Tao Cui , Liu Hongfang , Xu Hua
Published: May 2024

The consistent and persuasive evidence illustrating the influence of social determinants on health has prompted a growing realization throughout the health care sector that enhancing health and health equity will likely depend, at least to some extent, on addressing detrimental social determinants. However, detailed social determinants of health (SDoH) information is often buried within clinical narrative text in electronic health records (EHRs), necessitating natural language processing (NLP) methods to automatically extract these details. Most current NLP efforts for SDoH extraction have been limited, investigating on limited types of SDoH elements, deriving data from a single institution, focusing on specific patient cohorts or note types, with reduced focus on generalizability. This study aims to address these issues by creating cross-institutional corpora spanning different note types and healthcare systems, and developing and evaluating the generalizability of classification models, including novel large language models (LLMs), for detecting SDoH factors from diverse types of notes from four institutions: Harris County Psychiatric Center, University of Texas Physician Practice, Beth Israel Deaconess Medical Center, and Mayo Clinic. Four corpora of deidentified clinical notes were annotated with 21 SDoH factors at two levels: level 1 with SDoH factor types only and level 2 with SDoH factors along with associated values. Three traditional classification algorithms (XGBoost, TextCNN, Sentence BERT) and an instruction tuned LLM-based approach (LLaMA) were developed to identify multiple SDoH factors. Substantial variation was noted in SDoH documentation practices and label distributions based on patient cohorts, note types, and hospitals. The LLM achieved top performance with micro-averaged F1 scores over 0.9 on level 1 annotated corpora and an F1 over 0.84 on level 2 annotated corpora. While models performed well when trained and tested on individual datasets, cross-dataset generalization highlighted remaining obstacles. To foster collaboration, access to partial annotated corpora and models trained by merging all annotated datasets will be made available on the PhysioNet repository.
Radiation dermatitis in the hairless mouse model mimics human radiation dermatitis
Authors: Lawrence Jessica , Seelig Davis , Demos-Davies Kimberly , Ferreira Clara , Ren Yanan , Wang Li , Alam Sk. Kayum , Yang Rendong , Guedes Alonso , Craig Angela , Hoeppner Luke H.
Published: May 2024

Over half of all people diagnosed with cancer receive radiation therapy. Moderate to severe radiation dermatitis occurs in most human radiation patients, causing pain, aesthetic distress, and a negative impact on tumor control. No effective prevention or treatment for radiation dermatitis exists. The lack of well-characterized, clinically relevant animal models of human radiation dermatitis contributes to the absence of strategies to mitigate radiation dermatitis. Here, we establish and characterize a hairless SKH-1 mouse model of human radiation dermatitis by correlating temporal stages of clinical and pathological skin injury. We demonstrate that a single ionizing radiation treatment of 30 Gy using 6 MeV electrons induces severe clinical grade 3 peak toxicity at 12 days, defined by marked erythema, desquamation and partial ulceration, with resolution occurring by 25 days. Histopathology reveals that radiation-induced skin injury features temporally unique inflammatory changes. Upregulation of epidermal and dermal TGF-ß1 and COX-2 protein expression occurs at peak dermatitis, with sustained epidermal TGF-ß1 expression beyond resolution. Specific histopathological variables that remain substantially high at peak toxicity and early clinical resolution, including epidermal thickening, hyperkeratosis and dermal fibroplasia/fibrosis, serve as specific measurable parameters for in vivo interventional preclinical studies that seek to mitigate radiation-induced skin injury.
Comparative Analysis of Within-Host Dynamics of Acute Infection and Viral Rebound Dynamics in Postnatally SHIV-Infected ART-Treated Infant Rhesus Macaques
Authors: Mainou Ellie , Berendam Stella J , Obregon-Perko Veronica , Uffman Emilie A , Phan Caroline T , Shaw George M , Bar Katharine J , Kumar Mithra R , Fray Emily J , Siliciano Janet M , Siliciano Robert F , Silvestri Guido , Permar Sallie R , Fouda Genevieve G , McCarthy Janice , Chahroudi Ann , Chan Cliburn , Conway Jessica M
Published: May 2024

Viral dynamics of acute HIV infection and HIV rebound following suspension of antiretroviral therapy may be qualitatively similar but must differ given, for one, development of adaptive immune responses. Understanding the differences of acute HIV infection and viral rebound dynamics in pediatric populations may provide insights into the mechanisms of viral control with potential implications for vaccine design and the development of effective targeted therapeutics for infants and children. Mathematical models have been a crucial tool to elucidate the complex processes driving viral infections within the host. Traditionally, acute HIV infection has been modeled with a standard model of viral dynamics initially developed to explore viral decay during treatment, while viral rebound has necessitated extensions of that standard model to incorporate explicit immune responses. Previous efforts to fit these models to viral load data have underscored differences between the two infection stages, such as increased viral clearance rate and increased death rate of infected cells during rebound. However, these findings have been predicated on viral load measurements from disparate adult individuals. In this study, we aim to bridge this gap, in infants, by comparing the dynamics of acute infection and viral rebound within the same individuals by leveraging an infant nonhuman primate Simian/Human Immunodeficiency Virus (SHIV) infection model. Ten infant Rhesus macaques (RMs) orally challenged with SHIV.C.CH505 375H dCT and given ART at 8 weeks post-infection. These infants were then monitored for up to 60 months post-infection with serial viral load and immune measurements. We use the HIV standard viral dynamics model fitted to viral load measurements in a nonlinear mixed effects framework. We find that the primary difference between acute infection and rebound is the increased death rate of infected cells during rebound. We use these findings to generate hypotheses on the effects of adaptive immune responses. We leverage these findings to formulate hypotheses to elucidate the observed results and provide arguments to support the notion that delayed viral rebound is characterized by a stronger CD8+ T cell response.
Different orthology inference algorithms generate similar predicted orthogroups among Brassicaceae species
Authors: Liao Irene T. , Sears Karen E. , Hileman Lena C. , Nikolov Lachezar A.
Published: May 2024

Premise – Orthology inference is crucial for comparative genomics, and multiple algorithms have been developed to identify putative orthologs for downstream analyses. Despite the abundance of proposed solutions, including publicly available benchmarks, it is difficult to assess which tool to best use for plant species, which commonly have complex genomic histories.

Methods – We explored the performance of four orthology inference algorithms – OrthoFinder, SonicParanoid, Broccoli, and OrthNet – on eight Brassicaceae genomes in two groups: one group comprising only diploids and another set comprising the diploids, two mesopolyploids, and one recent hexaploid genome.

Results – Orthogroup compositions reflect the species’ ploidy and genomic histories. Additionally, the diploid set had a higher proportion of identical orthogroups. While the diploid+higher ploidy set had a lower proportion of orthogroups with identical compositions, the average degree of similarity between the orthogroups was not different from the diploid set.

Discussion – Three algorithms – OrthoFinder, SonicParanoid, and Broccoli – are helpful for initial orthology predictions. Results from OrthNet were generally an outlier but could provide detailed information about gene colinearity. With our Brassicaceae dataset, slight discrepancies were found across the orthology inference algorithms, necessitating additional analyses, such as tree inference to fine-tune results.
Parkinson’s disease-associated alterations in DNA methylation and hydroxymethylation in human brain
Authors: Choza Juliana I. , Virani Mahek , Kuhn Nathan C. , Adams Marie , Kochmanski Joseph , Bernstein Alison I.
Published: May 2024

Epigenetic mechanisms are mediators of interactions between aging, genetics, and environmental factors in sporadic Parkinson’s disease (PD). Multiple studies have explored the DNA modifications in PD, but few focus on 5-hydroxymethylcytosine (5-hmC), which is important in the central nervous system and sensitive to environmental exposures. To date, studies have not differentiated between 5-methylcytosine (5-mC) and 5-hmC or have analyzed them separately. In this study, we modeled paired 5-mC and 5-hmC data simultaneously. We identified 108 cytosines with significant PD-associated shifts between these marks in an enriched neuronal population from PD postmortem parietal cortex, within 83 genes and 34 enhancers associated with 67 genes. These data potentially link epigenetic regulation of genes related to LRRK2 and endolysosomal sort (RAB32andAGAP1), and genes involved in neuroinflammation, the inflammasome, and neurodevelopment with early changes in PD and suggest that there are significant shifts between 5mC and 5hmC associated with PD in genes not captured by standard methods.
The effect of dipeptide repeat proteins on FUS/TDP43-RNA condensation in C9orf72 ALS/FTD
Authors: Driver Mark D. , Postema Jasper , Onck Patrick R.
Published: May 2024

Condensation of RNA binding proteins (RBPs) with RNA is essential for cellular function. The most common familial cause of the diseases ALS and FTD are C9orf72 repeat expansion disorders that produce dipeptide repeat proteins (DPRs). We explore the hypothesis that DPRs disrupt the native condensation behaviour of RBPs and RNA through molecular interactions resulting in toxicity. FUS and TDP43 are two RBPs known to be affected in ALS/FTD. We use our previously developed 1-bead-per-amino acid and a newly developed 3-bead-per-nucleic acid molecular dynamics model to explore ternary phase diagrams of FUS/TDP43-RNA-DPR systems. We show that the most toxic arginine containing DPRs (R-DPRs), can disrupt the RBP condensates through cation-πinteractions, and can strongly sequester RNA through electrostatic interactions. The native droplet morphologies are already modified at small additions of R-DPRs leading to non-native FUS/TDP43-encapsulated condensates with a marbled RNA/DPR core.
Enhanced thermal stability enables human mismatch-specific Thymine-DNA glycosylase to catalyse futile DNA repair
Authors: Manapkyzy Diana , Joldybayeva Botagoz , Ishchenko Alexander A. , Matkarimov Bakhyt T. , Zharkov Dmitry O. , Taipakova Sabira , Saparbaev Murat K.
Published: May 2024

Human thymine-DNA glycosylase (TDG) excises T mispaired with G in a CpG context to initiate the base excision repair (BER) pathway. TDG is also involved in epigenetic regulation of gene expression by participating in active DNA demethylation. Here we demonstrate that under extended incubation time the full-length TDG (TDGFL), but not its truncated catalytic domain TDG (TDGcat) or methyl-binding protein 4 (MBD4) DNA glycosylase, exhibits a significant excision activity towards T and C in regular non-damaged DNA duplex in TpG/CpA and CpG/CpG contexts. Time course of the cleavage product generation under single-turnover conditions shows that the maximal rate of base excision (kobs) of TDGFL-catalysed excision of T in the T•A base pair (0.0014 – 0.0069 min-1) is 85 - 330-fold lower than that of T in T•G mismatch (0.47 – 0.61 min-1). Unexpectedly, TDGFL, but not TDGcat, exhibits prolonged enzyme stability under 37°C when incubated in the presence of equimolar concentration of non-specific DNA duplex, suggesting that the disordered N- and C-terminal domains of TDG can interact with DNA and stabilize the overall conformation of the protein. Noteworthy, TDGFLis able to excise 5-hydroxymethylcytosine (5hmC), but not 5-methylcytosine residues, from duplex DNA with the efficiency that could be physiologically relevant in post-mitotic cells. Our findings demonstrate that, under the experimental conditions used, TDG catalyses sequence context-dependent removal of T, C and 5hmC residues in regular DNA duplexes. We propose thatin vivothis futile DNA repair may lead to formation of persistent single-strand breaks in non-methylated regions of chromosomal DNA.
Haspin kinase binds to a nucleosomal DNA supergroove
Authors: Hicks Chad W. , Gliech Colin R. , Zhang Xiangbin , Rahman Sanim , Vasquez Stacy , Holland Andrew J. , Wolberger Cynthia
Published: May 2024

Phosphorylation of histone H3 threonine 3 (H3T3) by Haspin recruits the chromosomal passenger complex to the inner centromere and ensures proper cell cycle progression through mitosis. The mechanism by which Haspin binds to nucleosomes to phosphorylate H3T3 is not known. We report here cryo-EM structures of the Haspin kinase domain bound to a nucleosome. In contrast with previous structures of histone-modifying enzymes, Haspin solely contacts the nucleosomal DNA, inserting into a supergroove formed by apposing major grooves of two DNA gyres. This unique binding mode provides a plausible mechanism by which Haspin can bind to nucleosomes in a condensed chromatin environment to phosphorylate H3T3. We identify key basic residues in the Haspin kinase domain that are essential for phosphorylation of nucleosomal histone H3 and binding to mitotic chromatin. Our structure is the first of a kinase domain bound to a nucleosome and is the first example of a histone-modifying enzyme that binds to nucleosomes solely through DNA contacts.
Linear models replicate the energy landscape and dynamics of resting-state brain activity
Authors: Hosaka Yuki , Hieda Takemi , Hayashi Kenji , Jimura Koji , Matsui Teppei
Published: May 2024

The spatiotemporal dynamics of resting-state brain activity can be characterized by switching between multiple brain states, and numerous techniques have been developed to extract such dynamic features from resting-state functional magnetic resonance imaging (fMRI) data. However, many of these techniques are based on momentary temporal correlation and co-activation patterns and merely reflect stationary, linear features of the data, suggesting that the non-stationary dynamic features extracted by these techniques may be misinterpreted. To examine whether such misinterpretations occur when using techniques that are not based on momentary temporal correlation or co-activation patterns, we addressed Energy Landscape Analysis (ELA), a statistical physics-inspired method that was designed to extract multiple brain states and dynamics of resting-state fMRI data. We found that the ELA-derived features were almost identical for real data and surrogate data suggesting that the features derived from ELA were accounted for by stationary and linear properties of the real data rather than non-stationary or non-linear properties. To confirm that surrogate data were distinct from the real data, we replicated a previous finding that some topological properties of resting-state fMRI data differed between the real and surrogate data. Overall, the present finding that the energy landscape and activity dynamics of resting-state fMRI data were well captured by stationary and linear surrogate data supports the notion that linear models sufficiently describe the dynamics of resting-state brain activity.