bluuebunny/crossref_metadata_2025_split huggingface dataset:
CircNAP1L4 regulates pulmonary artery smooth muscle cell proliferation via the NAP1L4‐mediated super‐enhancer‐driven glycolysis gene hexokinase II (HK II) in pulmonary hypertension
Authors: Wang Xiaoying , Guan Xiaoyu , Zhu Xiangrui , Zhang Lixin , Ma Cui , He Siyu , Bai June , Mei Jian , Li Qian , Sun Na , Wu Bingxiang , Zhu Daling 
Published: August 2024

AbstractGlycolysis is a major determinant of pulmonary artery smooth muscle cell (PASMC) proliferation in pulmonary hypertension (PH). Circular RNAs (circRNAs) are powerful regulators of glycolysis in multiple diseases; however, the role of circRNAs in glycolysis in PH has been poorly characterized. The aim of this study was to uncover the regulatory mechanism of a new circRNA, circNAP1L4, in human pulmonary artery smooth muscle cell (HPASMC) proliferation through the host protein NAP1L4 to regulate the super‐enhancer‐driven glycolysis gene hexokinase II (HK II). CircNAP1L4 was downregulated in hypoxic HPASMCs and plasma of PH patients. Functionally, circNAP1L4 overexpression inhibited glycolysis and proliferation in hypoxic HPASMCs. Mechanistically, circNAP1L4 directly bound to its host protein NAP1L4 and affected the ability of NAP1L4 to move into the nucleus to regulate the epigenomic signals of the super‐enhancer of HK II. Intriguingly, circNAP1L4 overexpression inhibited the proliferation but not the migration of human pulmonary arterial endothelial cells (HPAECs) cocultured with HPASMCs. Furthermore, pre‐mRNA‐processing‐splicing Factor 8 (PRP8) was found to regulate the production ratio of circNAP1L4 and linear NAP1L4. In vivo, targeting circNAP1L4 alleviates SU5416 combined with hypoxia (SuHx)‐induced PH. Overall, these findings reveal a new circRNA that inhibits PASMC proliferation and serves as a therapeutic target for PH.
The Impact of COVID-19 on Substance Use and Related Consequences Among Patients in Office-based Opioid Use Disorder Treatment
Authors: Weinstein Zoe M. , Magane Kara M. , Lodi Sara , Ventura Alicia S. , Bazzi Angela R. , Blodgett Juliana , Fielman Sarah , Davoust Melissa , Shea Margaret G. , Chen Clara A. , Cheng Anna , Theisen Jacqueline , Blakemore Samantha , Saitz Richard 
Published: August 2024

Objectives
The COVID-19 pandemic led to increased substance-related morbidity and mortality and transformed care for opioid use disorder (OUD). We assessed the perceived impacts of the pandemic on substance use and related consequences among patients in office-based addiction treatment (OBAT).

Methods
We recruited patients with OUD on buprenorphine from July 2021 to July 2022, with data collection at baseline and 6 months. Exposures of interest were the following 6 domains potentially impacted by COVID-19: personal or family infection, difficulty accessing healthcare/medication, economic stressors, worsening physical or mental health, social isolation, and conflicts/disruptions in the home. Outcomes were past 30-day alcohol and other substance use, increased use, and substance-related consequences at baseline and 6 months. Generalized estimating equations Poisson regression models quantified associations between increasing impact domain scores and relative risks of each outcome.

Results
All participants (N = 150) reported at least one domain negatively impacted by COVID-19 at both time points. Higher “worsening physical or mental health” domain scores were associated with increased relative risk of recent alcohol or drug use (adjusted risk ratio [aRR] 1.04, 95% confidence interval [CI]: 1.01–1.07). Relative risks of experiencing substance-related consequences increased with higher scores in the domains of economic stressors (aRR 1.07, 95% CI: 1.02–1.13), difficulty accessing healthcare/medication (aRR 1.11, 95% CI: 1.04–1.19), and worsening physical or mental health (aRR 1.08, 95% CI: 1.04–1.12).

Conclusions
Among patients with OUD, stressors from COVID-19 were common. Three life domains impacted by COVID-19 appeared to be associated with consequential substance use, highlighting opportunities to address barriers to healthcare access and economic stressors.
Plantar Compartment Block Improves Enhanced Recovery after Hallux Valgus Surgery: A Randomized, Comparative, Double-blind Study
Authors: Swisser Fabien , Brethe Yann , Choquet Olivier , Herteleer Matthias , Bernard Nathalie , Laffont Isabelle , Bringuier Sophie , Capdevila Xavier 
Published: August 2024

Background
Walking ability is a key factor in enhanced recovery after foot ambulatory surgery. Plantar compartment block offers an analgesic alternative to popliteal sciatic nerve block (PSNB) for hallux valgus surgery. The objective of this study was to compare these two regional anesthesia strategies on patients’ ability to recover a painless unaided walk.

Methods
This prospective double-blinded (patient; observing anesthesiologist) randomized study compared patients scheduled for hallux valgus surgery receiving PSNB with 1% mepivacaine, then combined plantar and peroneal nerve blocks (plantar compartment block [PCB] group) with ropivacaine 0.5% and dexamethasone, or PSNB with ropivacaine 0.5% and dexamethasone (control group). The primary outcome was the patient’s ability to walk unaided 6 h after PSNB. The test was performed on a GAITRite, spatio-temporal gait analysis mat. For 3 days, the number of patient steps, pain levels, rescue analgesics, patient’s experience, and adverse events were assessed.

Results
Sixty patients were included and 59 were analyzed. The number of patients walking unaided on the GAITRite mat was significantly higher in the PCB group (21 of 30, 70%) than in the control group (4 of 29, 13.8%; P < 0.001). Gait quality using the Functional Ambulation Profile score was 63 ± 13.6 in the PCB group and 49.5 ± 4.7 in the control group (P < 0.001). Median time to free ambulation at home was significantly lower in the PCB group (9 h [8.2 to 11.8]) than in the control group (33.5 h [24 to 47]; P < 0.001). Postoperative pain did not differ between the groups (β = −0.41 [−1.78 to 0.95]; P = 0.548). The number of steps on day 3, the time of first rescue analgesic, the number of patients using rescue analgesia, consumption of morphine, and patient’s experience did not differ between the groups.

Conclusions
PCB decreased the time to return to unaided walking, with improved gait, compared with PSNB, improving effective analgesia and low consumption of rescue analgesics. This innovative regional anesthesia strategy enhanced recovery after surgery.

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New
Outcomes of the Modified Dunn Procedure Versus Delayed Imhauser Osteotomy for Moderate to Severe Stable Slipped Capital Femoral Epiphysis
Authors: Chau Michael M. , Osborne Lauren , Mayfield Laura M. , Jo Chan-Hee , Morris William Z. , Podeszwa David A. , Sucato Daniel J. 
Published: August 2024

Background:
Traditional management of moderate to severe stable slipped capital femoral epiphysis (SCFE) has been in situ fixation followed by reconstructive surgery if symptoms arise. This delayed approach may lead to irreversible intra-articular damage of the hip over time. The purpose of this study was to compare radiographic and clinical outcomes of the modified Dunn procedure (MDP) versus in situ fixation followed by delayed Imhauser osteotomy (DIO).

Methods:
This was a retrospective study from a single institution between 2001 and 2021. Among 250 patients diagnosed with SCFE, a total of 18 (18 hips) treated with MDP and 16 (18 hips) treated with DIO for moderate to severe stable SCFE were included. Most patients who underwent DIO either had concomitant (11/18 hips) or subsequent (2/18 hips) open osteochondroplasty. Mean follow up was 4.7 years (range: 1 to 12.8 y). Radiographs were reviewed to measure Southwick angle, anteroposterior and lateral alpha (α) angles, and femoral head-neck offset ratio preoperatively and at latest follow up. Charts were reviewed for demographics, subsequent surgeries, complications, and Heyman-Herndon clinical outcomes.

Results:
The amount of deformity correction was greater in the MDP than DIO group based on anteroposterior α angles (mean: 22.3 vs. 11.9 degrees, P=0.046) and femoral head-neck offset ratios (mean: 0.26 vs. 0.12, P=0.001). There was no significant difference in Heyman-Herndon scores (both 16/18, 88.9% good to excellent outcomes, P>0.999). Less reoperations were performed in the MDP than DIO group (2/18, 11.1% vs. 9/18, 50%; P=0.004). AVN occurred in 2/18 hips (11.1%) in the MDP group with both surgeries performed early in the series and underwent prior in situ screw fixation compared with 0/18 hips (0%) in the DIO group (P=0.486). One patient in the DIO group was later diagnosed with osteoarthritis.

Conclusions:
MDP resulted in more anatomic coronal and sagittal plane deformity correction, less reoperations, and similar Heyman-Herndon clinical outcomes compared with DIO. AVN occurred in the MDP group whereas osteoarthritis occurred in the DIO group. These complications must be weighed against improved long-term clinical results for patients who would otherwise be at risk for premature degenerative joint disease due to residual proximal femoral deformity.

Level of Evidence:
Level III—retrospective comparative study.
Academic Productivity at Orthopedic Spine Surgery Fellowships Is Positively Correlated With Nonresearch Lifetime Industry Earnings
Authors: Baumann Anthony N. , Gong Davin C. , Bae Seung-Ho , Hitchman Kyle , Anastasio Albert T. , Walley Kempland C. , Rocos Brett 
Published: August 2024

Study Design:
Retrospective Analysis.

Objective:
The objective of the study was to assess the impact of academic productivity at both individual and program levels on lifetime industry earnings within US orthopedic spine fellowships.

Summary of Background Data:
Physician-industry transparency was codified by the Physician Payments Sunshine Act (PSSA) in 2010. No study has explored the relationship between academic productivity and industry earnings at the fellowship level.

Methods:
Inclusion criteria encompassed physicians with complete academic and industry data from orthopedic spine fellowship programs listed on the North American Spine Society (NASS) 2022–2023 fellowship directory. Academic productivity was defined via H-index on the Scopus website, and industry productivity by total lifetime earnings on the Open Payments Database (OPD).

Results:
This analysis included 75 orthopedic spine fellowship programs with 320 individual physicians. Median individual physician lifetime earnings were $86,852.71 (mean: $666,580.23 ± $1,887,734.64; minimum–maximum: $10.86–$27,164,431.49) and the median individual physician (n=320 physicians) H-index was 17.0 (mean: 21.82 ± 19.28; minimum–maximum: 0–109). Median combined physician H-index per fellowship (n=75 fellowships) was 65.0 (mean: 93.08 ± 85.67; minimum–maximum: 3–434) and median combined physician lifetime earnings was $927,771.60 (mean: $2,844,075.64 ± $4,942,089.56; minimum–maximum: $1,112.32–$29,983,900.69). A positive correlation was observed between academic productivity and industry productivity at an individual level (P<0.001; Spearman’s rho = 0.467). This correlation was stronger at the fellowship level (P<0.001; Spearman’s rho = 0.734). There was no significant difference in total lifetime earnings (P=0.369) or H-index per fellowship (P=0.232) when stratified by region of the fellowship program in the United States.

Conclusion:
Orthopedic spine surgery fellowship programs in the United States exhibit a positive correlation between academic productivity and nonresearch industry lifetime earnings at both individual and program levels. This correlation is stronger at the program level, and regional differences among fellowship programs do not significantly impact academic or industry productivity.
The Effects of Mandala Coloring and Free Coloring on Mindfulness and the Score of Posttraumatic Stress Disorder in Veterans
Authors: Nasiri Mohammad-Amin , Sajadi Seyedeh Azam , Farsi Zahra , Heidarieh Marzie 
Published: August 2024

Due to the nature of the events in war, posttraumatic stress disorder (PTSD) is more difficult to treat in veterans than in other people. Nowadays, using art-making methods such as mandala coloring has attracted the attention of researchers. This randomized controlled trial was conducted with 84 male veterans diagnosed with PTSD. Veterans were recruited by convenience sampling method and randomly assigned to an intervention group (n = 42) and a control group (n = 42). Participants in the intervention group colored a mandala, whereas the control group colored freely for 15 minutes 2 times a week for 3 weeks. All participants completed Brown and Ryan’s Mindful Attention Awareness Scale and Posttraumatic Stress Disorder Checklist for diagnostic and statistical manual of mental disorders, fifth edition (DSM-5). Mean baseline mindfulness scores were not significantly different between the mandala coloring group and the free coloring group (41.73 ± 5.29 vs 40.23 ± 4.59, P = .169). After the intervention, the mean mindfulness score was significantly higher in the mandala coloring group than in the free coloring group (52.23 ± 5.89 vs 46.04 ± 7.28, P < .001). Mean baseline PTSD scores were not significantly different between the mandala coloring group and the free coloring group (65.45 ± 5.89 vs 67.47 ± 4.66, P = .085). After the intervention, the mean PTSD score was significantly lower in the mandala coloring group than in the free coloring group (47.21 ± 5.77 vs 52.38 ± 5.52, P < .001). Both mandala coloring and free coloring increase mindfulness and decrease PTSD symptom severity. However, the mandala coloring method was more effective.
Optimizing Regulatory Reviews for Clinical Protocols That Use Radiopharmaceuticals: Findings of the University of Pennsylvania Radiation Research Safety Committee
Authors: Rhodes Sylvia S. , Jesikiewicz Janelle E. , Yegya-Raman Nikhil , Prasad Kavya , Dreyfuss Alexandra , Mankoff David A. , Taunk Neil K. 
Published: August 2024

Abstract
Institutional radiation safety committees review research studies with radiation exposure. However, ensuring that the potential patient benefit and knowledge gained merit the radiation risks involved often necessitates revisions that inadvertently delay protocol activations. This quality-improvement study analyzed protocols, identified factors associated with approval time by a radiation safety committee, and developed guidelines to expedite reviews without compromising quality. Clinical protocols submitted to the University of Pennsylvania’s Radiation Research Safety Committee (RRSC) for review between 2017 and 2021 were studied. Protocol characteristics, review outcome, stipulations, and approval times were summarized. Statistical analysis (Spearman's rho) was used to investigate stipulations and approval time; rank-sum analysis (Kruskal-Wallis or Wilcoxon) was used to determine whether approval time differed by protocol characteristics. One hundred ten (110) protocols were analyzed. Approximately two-thirds of protocols used approved radiopharmaceuticals to aid investigational therapy trials. Twenty-three percent (23%) of protocols received RRSC approval, and 73% had approval withheld with stipulations, which included requests for edits or additional information. Submissions had a median of three stipulations. Median and mean RRSC approval times were 62 and 80.1 d, and 41% of protocols received RRSC approval after IRB approval. RRSC approval time was positively correlated with stipulations (Spearman’s rho = 0. 632, p < 0.001). RRSC approval time was longer for studies using investigational new drugs (median 80 d) than approved radiopharmaceuticals (median 57 d, p = 0.05). The review process is lengthy and may benefit from changes, including publishing standardized radiation safety language and commonly required documents and encouraging timely response to stipulations.
Uranium in Drinking Water and Bladder Cancer: A Case-control Study in Michigan
Authors: Uduba Perpetua , Soares Lissa , Babalola Tesleem , Slotnick Melissa , Linder Aaron , Meliker Jaymie R. 
Published: August 2024

Abstract
Uranium is naturally occurring in groundwater used for drinking; however, health risks from naturally occurring concentrations are uncertain. Uranium can cause both radiological and chemical toxicity following ingestion. Bladder and kidneys receive a dose when uranium is excreted into the urine. Investigate the association between uranium in drinking water and bladder cancer risk in a case-control study. A population-based bladder cancer case-control study was conducted in 11 counties of southeastern Michigan. A total of 411 cases and 566 controls provided drinking water and toenail samples and answered questions about lifestyle and residential history. Uranium was measured in drinking water and toenails, and its association with bladder cancer was assessed via unconditional logistic regression models. Median uranium concentration in water was 0.12 μg L−1, with a maximum of 4.99 μg L−1, and median uranium concentration in toenails was 0.0031 μg g−1. In adjusted regression models, there was a suggestion of a protective effect among those exposed to the upper quartile of uranium in drinking water (HR = 0.64, 95% CI: 0.43, 0.96) and toenails (HR 0.66; 95% CI 0.45, 0.96) compared to those in the lowest quartile. Our objective is to investigate additional adjustment of drinking water source at home residence at time of recruitment to address potential selection bias and confounding attenuated results toward the null for drinking water uranium (HR = 0.68, 95% CI: 0.44, 1.05) and toenail uranium (HR = 0.80, 95% CI: 0.53, 1.20). This case-control study showed no increased risk of bladder cancer associated with uranium found in drinking water or toenails.
Influence of Neighborhood Disadvantage and Individual Sociodemographic Conditions on Heart Failure Self-care
Authors: Meraz Rebecca , Osteen Kathryn , McGee Jocelyn , Noblitt Paul , Viejo Henry 
Published: August 2024

Background
Residence in socioeconomically disadvantaged neighborhoods and individual sociodemographic conditions contribute to worse heart failure (HF) outcomes and may influence HF self-care. However, associations between neighborhood disadvantage, socioeconomic conditions, and HF self-care are unclear.

Objective
The purpose of this secondary analysis was to investigate whether neighborhood disadvantage and individual socioeconomic conditions predicted worse HF self-care.

Methods
This study was a secondary analysis of baseline data from a mixed-method study of 82 adults with HF. Participant zip codes were assigned a degree of neighborhood disadvantage using the Area Deprivation Index. Those in the top 20% most disadvantaged neighborhoods (Area Deprivation Index ≥ 80) were compared with those in the least disadvantaged neighborhoods. The Self-Care of Heart Failure Index was used to measure self-care maintenance and monitoring. Multiple linear regression was conducted.

Results
Of all participants, 59.8% were male, 59.8% were persons of color, and the mean age was 64.87 years. Residing in a disadvantaged neighborhood and living alone predicted worse HF self-care maintenance and monitoring. Having no college education was also a predictor of worse HF self-care maintenance. Although persons of color were more likely to reside in disadvantaged neighborhoods, race was not associated with HF self-care.

Conclusion
Residing in a disadvantaged neighborhood and living alone may be important risk factors for worse HF self-care. Differences in self-care cannot be attributed solely to the individual sociodemographic determinants of race, gender, age, annual household income, or marital status. More research is needed to understand the connection between neighborhood disadvantage and HF self-care.
Significance of incidental thyroid 18F-fluorocholine uptake in patients with hyperparathyroidism imaged for localizing hyperfunctioning parathyroid glands
Authors: Grünig Hannes , Strobel Klaus , Zander Andrea , Pérez Lago Maria del Sol , Lima Thiago , Wicke Corinna , Fischli Stefan , Bhure Ujwal 
Published: August 2024

Objective

18F-fluorocholine PET/CT is considered the imaging gold standard for detection of hyperfunctioning parathyroid glands . However, increased uptake might also occur in the thyroid gland. The aim of our study was to assess the incidence and significance of 18F-fluorocholine uptake in the thyroid gland in patients with hyperparathyroidism.

Materials and methods
This retrospective study includes 195 consecutive patients with hyperparathyroidism, who underwent 18F-fluorocholine PET/CT, for detection of hyperfunctioning parathyroid glands. PET/CT images were reviewed by two nuclear medicine physicians for the presence of focal or diffuse thyroid uptake. PET/CT results were compared with laboratory parameters, ultrasonography, EU-TIRADS classification in the presence of thyroid nodules, cytology, and final histology.

Results
25 patients (13%) showed 18F-fluorocholine uptake in the thyroid gland: focal thyroid uptake (FTU) in 7 patients (4%), diffuse thyroid uptake (DTU) in 8 patients (4%), and combined uptake (FTU + DTU) in 10 patients (5%), with a total of 20 active thyroid nodules. There was no correlation between EU-TIRADS classification and PET parameters. One highly 18F-fluorocholine active thyroid nodule and one isoactive thyroid nodule turned out to be papillary thyroid cancers in the final histology; 50% of the patients with DTU had Hashimoto’s thyroiditis.

Conclusion
Incidental 18F-fluorocholine uptake in the thyroid gland was observed in 13% of patients. As reported for 18F-FDG, focal 18F-fluorocholine uptake might represent thyroid cancer and should be evaluated with ultrasound and, if indicated, with fine-needle aspiration cytology. Diffuse 18F-fluorocholine uptake most likely represents multinodular goiter or Hashimoto’s thyroiditis.
Immature ovarian teratoma with gliomatosis peritonei, paraneoplastic hyponatremia and growing teratoma syndrome: a case report and literature review
Authors: Mira Ana Rita , Brincat Mark R. , Zalawadia Shruti , Sideris Michail , Dilley James 
Published: August 2024

Introduction and relevance:
Paraneoplastic hyponatremia is often secondary to syndrome of inappropriate antidiuretic hormone secretion (SIADH) by tumour cells. Immature ovarian teratomas (IOT) are uncommon and may present with SIADH.

Case report:
A 26-year-old female presented with a 3-month history of abdominal pain and constipation. Imaging identified a mixed solid-cystic right ovarian mass containing fat and peritoneal deposits. Biochemistry showed severe, refractory hyponatremia (117 mmol/l). She underwent diagnostic fertility-preserving right salpingo-oophorectomy and resection of peritoneal nodules with the aim to achieve symptom control and hyponatraemia resolution. Pathology revealed a FIGO Stage 2 Grade 2 IOT with extensive benign peritoneal gliomatosis. Initial management was conservative. After 6 months of active follow-up, a rise in AFP, and recurrent hyponatremia supported the decision to administer three cycles of Bleomycin-Etoposide-Cisplatin chemotherapy. One month later, given radiological disease progression despite satisfactory biomarker response, cytoreductive surgery with complete macroscopic resection was performed. Pathology consisted solely of peritoneal mature glial elements: a growing teratoma syndrome (GTS). The patient remains disease-free after 2 years of surveillance.

Clinical discussion:
Specimen histological assessment from the patient’s initial surgery showed immature neuroectodermal tubules, which are thought to be the source of vasopressin secretion. The authors hypothesise that recurrent hyponatremia and rising AFP levels represented postoperative disease relapse. Biochemical response despite radiological disease progression was pathognomonic of a GTS.

Conclusion:
Paraneoplastic SIADH secondary to an IOT must be considered in female patients presenting with abdominal symptoms and hyponatremia. Management requires a multidisciplinary approach. Serum electrolytes are useful surveillance biomarkers supplementary to tumour markers.