bluuebunny/crossref_metadata_2025 huggingface dataset:
Non-invasive quantification of bone (re) modeling dynamics in adults with osteogenesis imperfecta treated with Setrusumab using timelapse HR-pQCT
Authors: Hosseinitabatabaei Seyedmahdi , Vitienes Isabela , Rummler Maximillian , Birkhold Annette , Rauch Frank , Willie Bettina M
Published: January 2025

Timelapse imaging using high-resolution peripheral quantitative computed tomography (HR-pQCT) has emerged as a noninvasive method to quantify bone (re)modelling. However, there is no consensus on how to perform the procedure. As part of the ASTEROID phase-2b multicenter trial, we used 29 same-day repeated scans from adults with osteogenesis imperfecta (OI) to identify a method that minimized measurement error. We evaluated input image type, registration method, segmentation mask, and for grayscale images various values for the voxel density difference considered formed or resorbed, minimum formation/resorption cluster size, and Gaussian smoothing sigma. We verified the accuracy of our method and then used it on longitudinal scans (baseline, 6, 12, 18 and 24 month) from 78 participants to assess bone formation and resorption induced by an anabolic (setrusumab) and anti-catabolic (zoledronic acid) treatments as part of the ASTEROID trial. Regardless of image registration method, binary input images resulted in large errors ~13% and ~ 8% for first- and second-generation scanners, respectively. For the grayscale input images, errors were smaller for 3D compared to matched angle registration. For both scanner generations, a density threshold of 200mgHA/cm3 combined with Gaussian noise reduction resulted in errors <1%. We verified the method was accurate by showing that similar regions of bone formation and resorption were identified when comparing each scan from the same-day repeated scans with a scan from another timepoint. Timelapse analysis revealed a dose-dependent increase in bone formation and resorption with setrusumab treatment. Zoledronic acid altered bone changes in favor of formation, although no changes reached statistical significance. This study identifies a timelapse method that minimizes measurement error, which can be used in future studies to improve the uniformity of results. This noninvasive imaging biomarker revealed dose dependent bone (re) modeling outcomes from one year of setrusumab treatment in adults with OI.
Boundedly finite-to-one functions
Authors: Hu Xiao , Shen Guozhen
Published: January 2025

A function is boundedly finite-to-one if there is a natural number $k$ such that each point has at most $k$ inverse images. In this paper, we prove in $\textsf{ZF}$ (i.e. the Zermelo–Fraenkel set theory without the axiom of choice) several results concerning this notion, among which are the following:

(1)For each infinite set $A$ and natural number $n$, there is no boundedly finite-to-one function from $\mathcal{S}(A)$ to $\mathcal{S}_{\leq n}(A)$, where $\mathcal{S}(A)$ is the set of all permutations of $A$ and $\mathcal{S}_{\leq n}(A)$ is the set of all permutations of $A$ moving at most $n$ points.

(2) For each infinite set $A$, there is no boundedly finite-to-one function from $\mathcal{B}(A)$ to $\textrm{fin}(A)$, where $\mathcal{B}(A)$ is the set of all partitions of $A$ such that every block is finite and $\textrm{fin}(A)$ is the set of all finite subsets of $A$.
Clinicopathological background of local recurrence in high grade sarcoma of the extremity with preoperative chemotherapy: a supplementary analysis of JCOG0304
Authors: Tsukushi Satoshi , Tanaka Kazuhiro , Kunisada Toshiyuki , Machida Ryunosuke , Takenaka Satoshi , Kawai Akira , Katagiri Hirohisa , Takeyama Masanobu , Endo Makoto , Hayashi Katsuhiro , Nakayama Robert , Hatano Hiroshi , Emori Makoto , Yoshida Shinichirou , Kojima Toshio , Sakamoto Akio , Imanishi Jungo , Kita Ryosuke , Ozaki Toshifumi , Iwamoto Yukihide
Published: January 2025

Background

The mainstay of treatment for soft-tissue sarcomas is complete resection with negative surgical margins. However, treatment strategies for local control including the frequency of adjuvant radiotherapy (RT) and surgical margin differ greatly between Japan and other countries, and the optimal strategy of local control remains controversial.

Methods

A total of 70 patients with high-grade sarcoma who underwent surgery of the 72 patients enrolled in JCOG0304, were included. The primary endpoint was the proportion of local recurrence, and we investigated the clinicopathological background of local recurrence cases, including the surgical margins according to the Japanese Orthopedic Association (JOA) margin classification or histological margin, and use of adjuvant RT.

Results

Local recurrence occurred in five patients, with a 5-year local recurrence proportion of 7.1% (95% confidence interval, 2.6%–14.8%) in 70 patients. The histological subtype were four cases of undifferentiated pleomorphic sarcoma (UPS) and 1 case of liposarcoma. The 5-year local recurrence proportions for UPS and non-UPS were 19.0% and 2.0%, respectively. Two of the five recurrent cases (40%) had adjuvant RT. The recurrent cases were four males and one female, median age 54 years (range: 33–66), JOA margin classification showed wide resection in four cases and marginal resection in one case, and histological margin showed negative in all five cases.

Conclusion

Despite the low proportion of adjuvant RT, local control of high-grade soft tissue sarcoma with preoperative chemotherapy in JCOG0304 was good. However, more detailed surgical margin evaluation and the use of adjuvant RT should be further investigated in the future for UPS.
Dental Caries, Erosive Tooth Wear, and Periodontal Status of Military Student Pilots in Finland: A Comparative Cross-Sectional Study
Authors: Muhonen Annakaisa , Tanner Tarja , Päkkilä Jari , Huttunen Mika , Räsänen Sari , Moilanen Pernelle , Patinen Pertti , Leino Tuomo , Tjäderhane Leo , Anttonen Vuokko , Kämppi Antti
Published: January 2025

Introduction

Oral health is a crucial factor for service safety among military pilots, but studies specifically on pilots are still very few in Finland. The aim of this study was to assess the oral health status of military student pilots compared to other conscripts of the same age group.

Materials and Methods

The data were collected during the oral health examinations of the annual class of the Pilot Reserve Officer Course students at the beginning of their duty at the Air Force Academy (N = 38). A voluntary random sample of conscripts’ oral health data (N = 574) collected from the 8 largest garrisons was used as a peer group. The study included males born between 2000 and 2002. The examinations were conducted in accordance with the WHO guidelines. Values of decayed (DT), missing, and filled teeth as well as the combined decayed, missing, and filled teeth value were recorded along with Basic Erosive Wear Examination scoring and Community Periodontal Index. The study was designed in accordance with the STROBE guidelines.

Results

The proportion of student pilots without any decayed teeth (DT = 0) was 42.1% with third molars and 44.7% without third molars. Among other conscripts, the proportions were 29.1% and 30.8%, respectively. Mean DT values among student pilots were 1.16 (third molars included) and 1.11 (third molars not included) (P = .543), and among other conscripts 1.10 and 1.00 (P = .429), respectively.

The mean decayed, missing, and filled teeth values were 2.50 among student pilots and 3.34 among others (third molars included), and 2.18 and 3.10 (without third molars), respectively (P = .289 and .211).

The proportion of student pilots with at least moderate erosive tooth wear (Basic Erosive Wear Examination sum > 2) was 68.4%, while for other conscripts it was 22.1% (P = .000). None of the student pilots fell into Community Periodontal Index class 3 or 4, whereas 9.9% of other conscripts did (P = .006).

Conclusions

The student pilots exhibited good overall oral health, which differed from that of other conscripts, mainly in terms of erosive changes. Continuous monitoring is crucial, as maintaining optimal oral health is vital for reducing the risk of barodontalgia and thus improving flight safety. Therefore, it is important to be aware that those who aspire to be military pilots are at an increased risk of erosive changes to their teeth.
The importance of nuclear star clusters for massive black hole growth and nuclear star formation in simulated low-mass galaxies
Authors: Partmann Christian , Lahén Thorsten NaabNatalia , Rantala Antti , Hirschmann Michaela , Hislop Jessica M , Petersson Jonathan , Johansson Peter H
Published: January 2025

Observed low-mass galaxies with nuclear star clusters (NSCs) can host accreting massive black holes (MBH). We present simulations of dwarf galaxies ($M_{\mathrm{baryon}} \sim 0.6\hbox{--}2.4 \times 10^8 \rm \, M_\odot$) at solar mass resolution ($0.5\rm \, M_\odot < m_{\mathrm{gas}} < 4 \rm \, M_\odot$) with a multi-phase interstellar medium (ISM) and investigate the impact of NSCs on MBH growth and nuclear star formation (SF). The griffin simulation model includes non-equilibrium low temperature cooling, chemistry and the effect of H ii regions and supernovae (SN) from massive stars. Individual stars are sampled down to 0.08 $\rm M_\odot$ and their non-softened gravitational interactions with MBHs are computed with the regularised KETJU integrator. MBHs with masses in the range of $10^2 - 10^5 \, \rm M_\odot$ are represented by accreting sink particles without feedback. We find that the presence of NSCs boost nuclear SF (i.e. NSC growth) and MBH accretion by funneling gas to the central few parsecs. Low-mass MBHs grow more rapidly on ∼600 Myr timescales, exceeding their Eddington rates at peak accretion. MBH accretion and nuclear SF is episodic (i.e. leads to multiple stellar generations), coeval and regulated by SN explosions. On 40 – 60 Myr timescales the first SN of each episode terminates MBH accretion and nuclear SF. Without NSCs, low-mass MBHs do not grow and MBH accretion and reduced nuclear SF become irregular and uncorrelated. This study gives the first insights into the possible co-evolution of MBHs and NSCs in low-mass galaxies and highlights the importance of considering dense NSCs in galactic studies of MBH growth.
Incidence rates of tuberculosis and inflammatory bowel disease in patients with ankylosing spondylitis treated with biologics in Korea
Authors: Kwon Oh Chan , Lee Hye Sun , Yang Juyeon , Paul Thomas , Jin Hyerim , Lee Youkyung , Park Min-Chan
Published: January 2025

Objective

To describe the incidence rates of inflammatory bowel disease (IBD) and tuberculosis (TB) in Korean patients with ankylosing spondylitis receiving biologics.

Methods

Data from a Korean claims database between 2010 and 2021 was used to calculate crude incidence rates of TB and IBD using number of events and total patient-years (PYs).

Results

Overall, 43 643 and 43 396 patients were included in TB and IBD cohorts, respectively. Exposure-adjusted incidence rates (EAIRs) of TB for non-exposure, TNF inhibitors (TNFis), and IL-17 inhibitors (IL-17is) were 0.14, 0.25 and 0.12 and of IBD were 0.18, 0.19 and 0.44 per 100 PYs, respectively. Incidence rates during biologic DMARD (bDMARD) non-exposure, adalimumab, etanercept, golimumab, infliximab, secukinumab and ixekizumab exposures for TB were 13.96, 27.79, 14.28, 21.19, 33.62, 12.74 and 0.00 and for IBD were 18.29, 19.98, 22.41, 18.85, 15.73, 44.99 and 0.00 per 10 000 PYs, respectively. Compared with bDMARD non-exposure, adalimumab, golimumab and infliximab exposures were associated with a significantly higher risk of TB. Etanercept and secukinumab exposure showed no significant increase in risk of TB. Compared with bDMARD non-exposure, exposure to biologics did not show a significant difference in risk of IBD.

Conclusion

EAIRs of TB and IBD with use of IL-17is in patients with AS were within anticipated low range. IL-17is had numerically lower incidence of TB, and numerically higher incidence of IBD compared with TNFis. Notably, secukinumab showed no increased risk of TB compared with bDMARD non-exposure. Neither TNFis nor IL-17is showed increased risk of IBD compared with bDMARD non-exposure.
Intersectional Repertoires of Coping with Political Violence
Authors: Mügge Liza , Özvatan Özgür
Published: January 2025

Violence against elected representatives—be it physical or psychological, online or offline, threatened or realized—undermines democracy. This is particularly the case when violence targets politicians from historically underrepresented groups, whose members may choose not to run for office, self-censor, or drop out. Based on interviews with twenty-three former and current members of the German Bundestag with a migration background, our exploratory study examines their strategies to cope with violence and the intersectional mechanisms underpinning their repertoires. MPs’ strategies to both prevent and respond to violence drew on a combination of individual resources and those provided by their private, collective, professional, and institutional environments; their use of specific strategies and access to resources had clear intersectional patterns. Racialized female MPs who had to expend the most time and energy coping with violence that attacked their very presence in politics had the least resources at their disposal.
European labour law as part of an economic union, monetary union and community of values—between harmonization and subsidiarity
Authors: Schubert Claudia
Published: January 2025

The development of European labour law was neither straightforward nor continuous but followed the development of the European single market for a long time. Today, European labour law is an essential part of the social market economy in the European Union, even if there is no uniform European social model. The European Pillar of Social Rights is a commitment to a social Europe and accelerated regulatory practice. From a political science perspective, the development of European labour law was and is dependent on the legitimacy of its actions of the European Union. Therefore, unlike in nation-states, no clearly defined concept of (European) labour law has emerged. Rather, three central areas can be identified: (1) transnational labour law, primarily the free movement of workers, as nucleus of European labour law, (2) European labour law as a result of the interference of business-related fundamental freedoms with the welfare states in the Member States, and (3) European labour law as a result of a proactive social policy. However, the European Union has and will have to continue to organise its legislation in coordination with the welfare states in the Member States. Politically, it must prove that its measures are necessary because it can regulate the issues in question better than the Member States would be able to. Crises affecting several Member States are often the main driving force behind the deepening of the cooperation in the field of social policy. In addition, new developments can give the Member States reasons to take a standardised approach from the outset. Furthermore, the European Union should act primarily in connection with such social standards regarding which all Member States have already ratified international conventions without reservations and have thus agreed on a uniform standard.
Brain‐derived neurotrophic factor drives muscle adaptation similar to aerobic training in mice
Authors: Brown Alexander D. , Marko Alexander D. , Marko Daniel M. , Baranowski Bradley J. , Silvera Sebastian , Finch Michael S. , Yang Alex J. , Dhaliwal Roopan , Ryan Chantal R. , Roy Brian D. , Fajardo Val A. , MacPherson Rebecca E. K.
Published: January 2025

This study, in vivo and in vitro, investigated the role of brain‐derived neurotrophic factor (BDNF) in skeletal muscle adaptations to aerobic exercise. BDNF is a contraction‐induced protein that may play a role in muscle adaptations to aerobic exercise. BDNF is involved in muscle repair, increased fat oxidation, and mitochondrial biogenesis, all of which are adaptations observed with aerobic training. The purpose of this study was two‐pronged and investigated the skeletal muscle BDNF response to (1) acute and (2) chronic exercise in male C57BL/6J mice. It also examined if chronic BDNF treatment resulted in similar adaptations to chronic exercise. In aim 1, mice underwent a 2 hr. treadmill exercise bout. In aim 2, mice were assigned to one of four groups: (1) control (CON); (2) endurance training (ET; treadmill running 1 h/day, 5 days/wk); (3) BDNF (BDNF; 0.5 mg/kg·bw, 5 days/wk); (4) endurance training and BDNF (ET + BDNF) for 8 weeks. Results demonstrated that the soleus (SOL) had higher BDNF content compared with the extensor digitorum longus (EDL) and that SOL BDNF increased with acute exercise. After chronic exercise and BDNF treatment, treadmill testing to exhaustion demonstrated a main effect of BDNF and ET on increasing exercise capacity. In vitro contractile assessment of the EDL revealed BDNF treatment resulted in similar increases in the max rate of relaxation as ET. EDL force‐frequency analysis showed ET + BDNF produced higher force than CON and BDNF, indicating an additive effect. BDNF increased EDL mitochondrial proteins, COXIV, and CS. These results demonstrate that BDNF contributes to muscle adaptations observed with ET.
AGDMP1 alleviates insulin resistance by modulating heat shock protein 60‐mediated IRS‐1/AKT/GLUT4 pathway and adipose inflammation: A potential therapeutic peptide for gestational diabetes mellitus
Authors: Wang Shanshan , Zhang Yuting , Hu Shiman , Bai Xueqi , Zhu Jiamin , Hao Runrun , Cao Yan , Shi Zhonghua
Published: January 2025

Gestational Diabetes Mellitus (GDM) is the most frequent complication during pregnancy. Pharmacological interventions, such as peptide drugs that focused on improving the insulin sensitivity might be promising in the prevention and treatment of GDM. In this study, we aimed to investigate the role and mechanism of a novel peptide, named AGDMP1 (Anti‐GDM peptide 1), which we previously identified lower in the serum of GDM patients using mass spectrometry, on the adipose insulin resistance in GDM. We found that AGDMP1 had a high affinity for adipose tissues in vivo. AGDMP1 markedly improved glucose homeostasis and insulin resistance in GDM mice. This was associated with reduced inflammation and upregulated AKT/GLUT4 signaling pathway in white adipose tissue. In vitro, AGDMP1 could increase glucose uptake and insulin sensitivity of adipocytes by activating the IRS‐1/AKT/GLUT4 signaling pathway under basal, insulin‐stimulated, and insulin‐resistant conditions, respectively. Mechanistically, we found that AGDMP1 could bind to HSP60 to dampen its effects on AKT signaling and pro‐inflammatory response, which was reversed in the present of recombinant HSP60 protein. AGDMP1 ameliorated adipose insulin resistance and inflammation by targeting HSP60 and activating the IRS‐1/AKT/GLUT4 signaling pathway. These data supported AGDMP1 with therapeutic potential in GDM and associated pathologies.
Nursing Student and Faculty Attitudes, Perceptions, and Behavioral Intentions of Artificial Intelligence Use in Nursing Education
Authors: Ostick Mollie , Mariani Bette , Lovecchio Catherine , Moriarty Helene
Published: January 2025

AIM

This integrative review critiques and synthesizes current research on nursing faculty and students’ attitudes, perceptions, and behavioral intentions toward artificial intelligence (AI)-based tools in nursing education.

BACKGROUND

AI’s rapid integration into health care offers transformative potential in nursing across clinical care, education, policy, and research.

METHOD

Following Whittemore and Knafl’s methodology, Pubmed, CINAHL, and ERIC were searched for studies written in English assessing attitudes, perceptions, and behavioral intentions of nursing students and faculty regarding AI use in nursing education.

RESULTS

Six quantitative studies encompassing 2,430 participants across five countries were included. They revealed generally positive attitudes toward the use of AI in nursing education. Only one study included faculty.

CONCLUSION

A logical next step is to compare and contrast student and faculty perceptions of using AI. Generative AI tools must be studied within nursing education to allow for informed integration and the development of appropriate training programs.
Refractive accuracy of the new Barrett formula using segmented axial length compared with that of the traditional Barrett Universal II formula
Authors: Hata Seiichiro , Kobayashi Manabu
Published: January 2025

Purpose:

To compare the refractive accuracy of the Barrett True axial length (BTAL) formula, newly integrated into ARGOS, with that of the Barrett Universal II (BUII) formula calculated using axial length (AL) from IOL Master 700.

Setting:

Private clinics in Kanagawa, Japan.

Design:

Retrospective observational study.

Methods:

We assessed eyes of patients who underwent cataract surgery with SY60WF IOL implantation, using ARGOS and IOL Master 700. The predicted refraction for BTAL was back-calculated. Refractive prediction errors (RPEs) for BTAL, BUII with ARGOS (segmented BUII), and BUII with IOL Master 700 (composite BUII) were compared. We primarily aimed to demonstrate the non-inferiority of BTAL to composite BUII in absolute RPE.

Results:

We included 209 eyes from 209 patients. BTAL met the non-inferiority criteria, as the upper confidence interval (CI) boundary was below the non-inferiority margin of 0.10 diopters (D) for the difference in absolute RPE (−0.03 D; 95% CI: −0.06 to 0.01). In short eyes (AL ≤ 22.5 mm), the median absolute RPEs for BTAL, segmented BUII, and composite BUII were 0.25, 0.18, and 0.37 D, respectively, with significant differences between BTAL and composite BUII (p = 0.028) and segmented BUII and composite BUII (p = 0.018). In long eyes (AL > 26 mm), the median absolute RPEs were 0.21, 0.20, and 0.28 D for BTAL, segmented BUII, and composite BUII, respectively.

Conclusions:

BTAL was non-inferior to composite BUII in absolute RPE. BTAL is an accurate and useful intraocular lens power calculation formula, even in eyes with short and long AL.
The effect of dynamic neuromuscular stabilization technique combined with Kinesio Taping on neuromuscular function and pain self-efficacy in individuals with chronic nonspecific low back pain: A randomized trial
Authors: Hei Peng , Zhang Zhe , Wei Jiaxin , Lan Chaoyu , Wang Xinyu , Jing Xiongxiong , Chen Xuexue , Wu Zhigang
Published: January 2025

Background:

This study investigates the therapeutic efficacy of dynamic neuromuscular stabilization (DNS) technology paired with Kinesio Taping in patients with persistent nonspecific low back pain, as well as the effect on neuromuscular function and pain self-efficacy.

Methods:

A randomized controlled clinical study was conducted to collect clinical data on DNS combined with KT for the treatment of chronic nonspecific low back pain from November 2023 to April 2024. The inclusion criteria were patients with chronic nonspecific lower back pain, aged between 18 and 30 years old, and without serious underlying medical conditions, such as cardiac disease, hypertension, and diabetes. The control group received Kinesio Tape therapy, and the experimental group received a combination of Kinesio Tape therapy and DNS technology. The treatment lasted for 6 weeks, 3 times a week. Patients were examined before and after treatment using the Visual Analog Rating Scale, Oswestry Dysfunction Score, and Pain Self-Efficacy Questionnaire. Multifidus and transversus abdominis muscle strength was tested using surface electromyography signals, and the patient’s joint mobility, maximal isometric muscle strength, and muscular endurance were tested using the Davy Spine Rehabilitation System. Internal lumbar and abdominal pressures were assessed using stabilizer pressure biofeedback.

Results:

A total of 32 subjects (17 males and 15 females) were enrolled, of which 16 were in the experimental group and 16 in the control group. After the treatment, the patients in both groups showed significant improvements in the visual analogue scale, Oswestry disability index, Chinese version of Pain Self-Efficacy Questionnaire (PSEQ), joint mobility, maximum isometric strength, muscle endurance, abdominal pressure, transverse abdominal muscle and multifidus muscle scales compared with the pretreatment results. (Chinese version of Pain Self-Efficacy Questionnaire) scales were significantly improved compared with the pretreatment; joint mobility, maximal isometric muscle strength, muscular endurance, intra-abdominal pressure, transversus abdominis and multifidus AEMG (average electromyography) were more significantly improved, and the differences were statistically significant (P < .05). The experimental group showed more significant improvement than the control group (P < .05).

Conclusion:

DNS technology paired with Kinesio Taping can considerably improve neuromuscular function and enhance pain self-efficacy in chronic nonspecific low back pain patients, reducing discomfort and improving dysfunction.
Factors associated with higher caregiver burden among informal caregivers of Parkinson’s disease: A systematic review
Authors: Wu Jinwen , Liu Mengnan , Chen Mingtai , Xue Jinyi , Zou Yuan , Deng Ziwen , Zhao Shufei , Yang Xue
Published: January 2025

Background:

Parkinson’s disease is a progressive neurodegenerative disease and the care burden in informal caregivers is huge. Summarizing factors associated with the informal caregivers burden can improve our understanding of providing proactive support to informal caregivers caring for patients with Parkinson’s disease (PwP) at risk, and provides evidence for clinical practice.

Methods:

PRISMA guidelines were followed in this systematic review. We searched 9 databases in May 2024 for studies reporting data on factors associated with the care burden of informal caregivers for PwP.

Results:

We identified 16456 records of which 28 met inclusion criteria. Informal caregivers from 12 countries were included. There were 38 factors shown to be linked to higher care burden. The evidence indicated that informal caregivers who were depressed, caring for PwP with lower quality of life, caring for PwP with lower ADL scores, or caring for PwP with depression reported high care burden.

Conclusion:

Targeted interventions addressing those modifiable factors should be developed and investigated to lighten the care burden of informal caregivers for PwP.
Adjuvant radiation improves survival outcomes in adrenocortical carcinoma: A population-based study
Authors: Zhan Kunming , Ruan Xianguo , Jia Hongtao
Published: January 2025

The aim of this study was to evaluate the clinical benefits and outcomes of adjuvant radiation therapy on adrenocortical carcinoma (ACC) patients. All patients with ACC that were reported between 2010 and 2015 were identified from the Surveillance, Epidemiology, and End Results database. A forward-stepwise Cox proportional hazards regression was used to identify independent risk factors. A new nomogram was created to predict overall and cancer-free survival probabilities at 1, 3, and 5 years for ACC patients. The concordance index, the area under the receiver operating characteristic curve, calibration curves, and decision curve analysis were used to validate the accuracy and reliability of the model. A total of 426 ACC patients were enrolled in this study, of which 84 (19.7%) cases underwent adjuvant radiation therapy (RT). Six factors (age, T stage, type of surgery, radiation, and bone and liver metastases) were significantly related to overall survival (OS) (P < .05). Five factors (T stage, type of surgery, radiation, and bone and liver metastases) were significantly related to cancer-specific survival (CSS) (P < .05). A nomogram for OS and CSS was constructed. The area under the receiver operating characteristic curve values for 1-, 3-, and 5-year OS were 0.85, 0.818, and 0.814, respectively, and for CSS, they were 0.839, 0.803, and 0.796, respectively. C-indices were 0.756 and 0.749 for OS and CSS, respectively, indicating that the nomograms for OS and CSS had satisfactory discriminative power. A good consistency between the observed and the predicted survival was found in the calibration curves, and the nomogram has a good net clinical benefit, which is presented in the decision curve analysis curves. Our study demonstrates that adjuvant RT can produce a significant improvement in survival outcomes for ACC patients and suggests that adjuvant RT should routinely be applied in ACC patients.
Associations between 25-hydroxyvitamin D/calcium/alkaline phosphatase levels and the risk of developing kidney stones: Results from NHANES (2013–2018)-based and Mendelian randomization studies
Authors: Ran Yueli , Liu Zhenyu , Ma Hang , Li Chaofan , Zhou Jiangtao , Li Dongyang , Guo Ziqi , Dan Lifeng , Zhao Zecang , Zou Zhonglin , Su Shuai , Yin Zhikang
Published: January 2025

This study explores the relationship between 25-hydroxyvitamin D/calcium/alkaline phosphatase (ALP) levels and kidney stone development via cross-sectional and Mendelian randomization (MR) analyses. We used data from the National Health and Nutrition Examination Survey (NHANES) 2013 to 2018 to explore the associations of 25(OH)D metabolite, calcium, and ALP levels with kidney stone development, LDSC analysis to determine the associations between their genetically predicted levels and kidney stone development, and MR analysis to determine the causality of those relationship via genome-wide association studies (GWASs). The cross-sectional study revealed a relationship between ALP levels and kidney stone development (Model 1: OR = 1.004, 95% CI = 1.001–1.007, P = .005; Model 2: OR = 1.004, 95% CI = 1.001–1.007, P = .007; Model 3: OR = 1.003, 95% CI = 1.001–1.006, P = .011) in both men and women. LDSC analysis also revealed a genetic correlation between ALP concentrations and kidney stone development (ukb-b-18372: rg = 0.296, P = 1.45E-04; GCST90044237: rg = 0.157, P = .004). The results of both MR analyses demonstrated that kidney stones cause elevated ALP levels (IVW: OR = 2.233, 95% CI = 1.113–4.480, P = .024, preliminary analysis; OR = 1.003, 95% CI = 1.000–1.005, P = .025, validation analysis). MR analysis also revealed that elevated serum calcium levels increased the risk of developing kidney stones (IVW: OR = 1.002, 95% CI = 1.000–1.003, P = 4.258E-04, preliminary analysis; OR = 1.592, 95% CI = 1.365–1.858, P = 3.367E-09, validation analysis). Our study strongly supports a positive association between kidney stone development and ALP levels. Although observational studies did not reveal an association between calcium levels and kidney stone development, MR analysis suggested a positive association between calcium levels and kidney stone development. Our study provides new and more reliable evidence and research directions for the prevention, diagnosis and treatment of kidney stones.
Right coronary sinus of Valsalva pseudoaneurysm after a motorcycle accident: A case report
Authors: Cheng Yong , Zhang Yu , Liu Zixuan , Wang Ziwei , Shuai Tao
Published: January 2025

Rationale:

Traumatic pseudoaneurysm of the sinus of Valsalva (PSV) is a rare but life-threatening condition, often resulting from blunt chest trauma. Rapid progress and a high risk of rupture highlight the importance of prompt diagnosis and intervention. We present a case of a rare pseudoaneurysm linked to the right coronary sinus after blunt chest trauma.

Patient concerns:

A 54-year-old male presented with chest pain, loss of consciousness, and coma following a motorcycle accident. Initial management included invasive ventilation at a local hospital before transfer for specialized care.

Diagnoses:

Computed tomography angiography and transthoracic echocardiography confirmed a blunt traumatic PSV, along with an 8th rib fracture, findings later corroborated during open thoracotomy.

Interventions:

The pseudoaneurysm was surgically treated with an open thoracotomy, and the defect was sealed using a pericardial patch.

Outcomes:

The patient experienced an uneventful recovery, with follow-up confirming the restoration of normal daily activities.

Lessons:

Traumatic PSV, though rare, demands heightened clinical awareness in cases of blunt chest trauma. Noninvasive computed tomography angiography serves as a rapid and reliable diagnostic tool. Early surgical intervention remains the definitive treatment to prevent catastrophic outcomes.
Efficacy of wound care ointment in healing infectious wounds after anorectal surgery: A randomized controlled trial
Authors: Yu Lelai , Lei Yinfu , Yuan Ke
Published: January 2025

Background:

This study evaluates the efficacy of a novel bismuth subgallate-borneol compound ointment as an adjuvant therapy in promoting postoperative healing of infectious incisions after anorectal surgery.

Methods:

From June 2023 to October 2023, 46 patients with perianal abscess and anal fistula treated at our institution’s Anorectal Surgery Department were enrolled in this prospective randomized controlled study. Patients were randomly allocated into 2 groups: the experimental group (n = 23) received conventional wound care plus a proprietary ointment containing 4.5% bismuth subgallate and 0.7% d-borneol in a Vaseline base, while the control group (n = 23 cases) received conventional wound care alone (comprising daily wound cleansing, dressing changes and traditional Chinese medicine injection). Image J Software was used for collecting the data of wound area, and the wound healing rate and granulation growth rate of the 2 groups were calculated to evaluate the therapeutic effect of the 2 groups.

Results:

The growth rate of cured granulation in the experimental group was higher than that in the control group at all 3 predetermined observation points, with statistically significant difference (P < .05). Furthermore, the wound healing rate of the experimental group showed significant improvement by day 14 (P < .05).

Conclusion:

The bismuth subgallate-borneol compound ointment, when used as an adjuvant to standard wound care protocols, demonstrates significant efficacy in treating post-anorectal surgery infectious wounds. Its dual-active component formulation appears to effectively promote both granulation tissue formation and wound healing, potentially through its documented antibacterial properties.
Gated myocardial perfusion SPECT for evaluating left ventricular dyssynchrony in cardiac resynchronization therapy candidates: a systematic review
Authors: Stępień-Wroniecka Agnieszka , Dziewięcka Ewa , Graczyk Katarzyna , Holcman Katarzyna , Winiarczyk Mateusz , Przytuła Natalia , Kostkiewicz Magdalena , Podolec Piotr , Rubiś Paweł
Published: January 2025

Objectives

Cardiac resynchronization therapy (CRT) is an intervention for heart failure patients with reduced ejection fraction who exhibit specific electrocardiographic indicators of electrical dyssynchrony. However, electrical dyssynchrony does not universally correspond to left ventricular mechanical dyssynchrony (LVMD). Gated single-photon emission computed tomography (SPECT) myocardial perfusion allows for the assessment of LVMD, yet its role in the CRT selection process remains debated.

Methods

We conducted a systematic literature review to critically evaluate the evidence for the prediction and prognostic utility of SPECT for LVMD in assessing LVMD among CRT candidates. The review adhered to PRISMA 2020 Statement criteria and included articles from PubMed, Embase, and Cochrane databases. The quality of evidence was appraised using the Grading of Recommendations, Assessment, Development, and Evaluation framework.

Results

From an initial pool of 1055 records, 33 met the inclusion criteria and provided original data on the predictive value of myocardial perfusion SPECT for LVMD. Most of them measured LVMD according to established recommendations, focusing on phase histogram bandwidth (HBW) and phase histogram standard deviation (PSD). Out of 2066 patients from 27 studies, 62% (n = 1214) were qualified as CRT responders. Five studies reported SPECT-based cutoffs for predicting CRT response (HBW ranging 55°–152° and for PSD 20°–54°). Only five studies assessed the prognostic implications of baseline SPECT-measured LVMD, indicating that elevated baseline HBW and PSD values are associated with poorer outcomes.

Conclusion

The objective and reproducible measurement of LVMD provided by SPECT underscores its potential as a valuable tool. Such assessment seems to be emerging as a promising adjunctive technique with potential to enhance CRT outcomes.
Preoperative Anemia as a Prognostic Risk Factor for Inferior Oncological Survival Following Resection for Pancreatic Ductal Adenocarcinoma
Authors: Bos Mylena D. , Meyer N. Helge , Wijma Allard G. , Khatib-Chahidi Karl , van den Broek Evert , Ho Cassandra S.L. , Meerdink Mark , Klaase Joost M. , Bockhorn Maximilian , Hoogwater Frederik J.H. , Nijkamp Maarten W.
Published: January 2025

Objectives:

A significant proportion of patients undergoing surgery for pancreatic ductal adenocarcinoma (PDAC) are anemic at the time of resection. In these patients, blood transfusions are omitted due to their potential negative impact on oncological outcomes. The aim of the present study was to determine the prognostic value of preoperative anemia in resected PDAC patients, irrespective of blood transfusion status.

Methods:

In this retrospective two-center cohort study patients who underwent resection for histologically confirmed PDAC between 2013 and 2022 were included. The prognostic role of preoperative anemia was investigated using Cox proportional-hazard regression analysis. A subgroup analysis was performed in which PDAC patients who received a perioperative blood transfusion were excluded.

Results:

Among the 280 PDAC patients who were included, 110 (39%) were found to have anemia prior to surgery. Preoperative anemia was associated with increased use of blood transfusions, with a total of 44 patients (16%) requiring transfusion perioperatively. In the whole cohort, preoperative anemia was found to be an independent predictor of lower disease-free survival (DFS) (HR=1.518; 95% CI 1.103-2.090; P=0.011), but not overall survival (OS). However, when patients who received a perioperative blood transfusion were excluded from the analysis, preoperative anemia was independently associated with both lower DFS (HR=1.636; 95% CI 1.113-2.404; P=0.012) and OS (HR=1.484; 95% CI 1.036-2.127; P=0.031).

Conclusions:

Preoperative anemia was shown to be an independent risk factor for inferior oncological survival after resection for PDAC. These results support the need for increased awareness regarding the potential adverse effects of preoperative anemia on oncological outcomes in PDAC.
68Ga-FAPI-04 Outperforms 18F-FDG in Detecting Lesions for Primary Leiomyosarcoma of Bone
Authors: Jiang Yaqun , Tian Yueli , He Yong
Published: January 2025

Primary leiomyosarcoma of bone (PLB) is an ultrarare tumor, characterized by its aggressive clinical behavior, high heterogeneity, and dismal prognosis. Here, we present the 68Ga-FAPI-04 and 18F-FDG PET/CT findings in a case of PLB affecting the left femur. FAPI PET/CT showed more bone lesions and higher uptake in the multiple metastatic lesions compared with FDG PET/CT. More interestingly, FAPI PET/CT could clearly detect the tumor embolus on the left common femoral artery, which was negative on FDG. This case suggests that FAPI PET/CT is a promising method for the primary diagnosis and staging of PLB.
Diffuse Large B-Cell Lymphoma With the “Leopard Man” Appearance on 18F-FDG PET/CT
Authors: Wang Kangkang , Huang Hao
Published: January 2025

Subcutaneous nodules and masses as the primary manifestation of diffuse large B-cell lymphoma are exceedingly rare. We present 18F-FDG PET/CT findings of multiple hypermetabolic nodules and masses distributed throughout the body, creating a characteristic “leopard man” appearance on the MIP image, in a 65-year-old man. An excisional biopsy of the right thigh mass confirmed the diagnosis of diffuse large B-cell lymphoma.
Trauma-Informed Speech-Language Pathology
Authors: Koury Samantha P. , Green Susan A. , Evans Kelli
Published: January 2025

Speech-language pathologists (SLPs) often engage with individuals with histories of trauma. Rather than providing trauma treatment, SLPs are instead positioned to engage in universal precaution for trauma: assuming that trauma is more likely than not to be part of any individual’s story and intentionally responding in ways that do not create additional harm. SLPs are increasingly being encouraged to recognize the high prevalence of trauma, the ways trauma can impact communication and behavior, and to practice trauma-informed care (TIC) in their work. Yet, the application of TIC to SLP practice is still emerging in both research and practice. The purpose of this conceptual article is to begin to operationalize the four levels of TIC as related to SLP practice: (1) trauma awareness, (2) trauma-informed approach, (3) trauma-sensitive practices, and (4) interprofessional collaboration with trauma-specific treatment providers. Recommendations for trauma-informed SLP practice and continued application and discussion of TIC are provided.
R allele of ACTN3 R577X gene polymorphism is associated with Elite Indian Boxer Status
Authors: Grover Vijmendra Kumar , Verma Jai Prakash , Kumar Ashish , Sharma Nivedita , Tiwari Pramod Kumar
Published: January 2025

Genetic variations are considered important for athletic performance. In this regard, polymorphisms in angiotensin I-converting enzyme (ACE) and α-actinin-3 genes are widely studied for their association with elite athlete status. The ACE gene regulates circulatory homeostasis, with the I variant of the ACE insertion/deletion (ACE I/D) gene polymorphism being associated with endurance performance, while the R allele of the R577X polymorphism of the ACTN3 gene, crucial for fast glycolytic muscle fibers, has been associated with speed and power performances. The present study investigated the association of these genetic variants with elite boxer (N=57) status and compared it with elite power/speed athletes (N=40), endurance athletes (N=44) and nonathletes (N=98) in the Indian population. The R allele frequency was found significantly higher in boxers than the nonathletes (p< 0.05). The allele and genotype frequencies of boxers, endurance and power/speed athletes did not differ significantly (p> 0.05). After analyzing overall athletic cohort on the basis of their level of performance, the frequency of RR genotype (24.1%) and R allele (47.7%) in national level athletes was found significantly higher than in nonathletes (8.7% and 34.2%, respectively), with the significant difference (p< 0.05) between national level endurance athletes and nonathletes only. The ACE I/D gene polymorphism was not found associated with any of the athletic cohorts (p> 0.05). Taken altogether, our study showed that the R allele of ACTN3 gene polymorphism is associated with elite boxer status as compared to the nonathletes.

Highlights

Boxers had a higher ACTN3 gene R allele frequency than nonathletes; genotype did not differ.

Boxers with RR genotype had more than 3x higher odds versus nonathletes (p= 0.02) in the X dominant model (RR vs RX+XX).

ACTN3 gene allele and genotype frequencies differed between overall athletic cohort and nonathletes.

ACE gene frequencies showed no difference or association across athletic cohorts.
Global Profiling of N-terminal Cysteine-Dependent Degradation Mechanisms
Authors: Bekturova Aizat , Makaros Yaara , Ben-David Shahar , Koren Itay
Published: January 2025

Hypoxia, a condition characterized by insufficient oxygen supply, challenges cellular homeostasis and energy production, driving the activation of adaptive responses to maintain survival under these stress-inducing conditions. One key strategy involves enzymatic oxidation of N-terminal cysteine residues coupled with proteolysis through the Cys-Arg/N-degron pathway. Despite the presence of hundreds of proteins with N-terminal cysteine in humans, only two have been identified as substrates of this pathway, and its substrate selectivity remains unclear. Moreover, the biological role of this pathway in the cellular response to hypoxia is not well defined. By employing a systematic proteomics approach, we discovered that nearly half of the cysteine-commencing proteome could be regulated by the Cys-Arg/N-degron pathway. Mutagenesis experiments revealed the specificty of Cys-Arg/N-degron pathway showing a preference for hydrophobic and positively charged residues following cysteine. Furthermore, we uncovered substrates that are regulated by this pathway during hypoxia, including IP6K1. The loss of IP6K1 impaired glucose uptake, glycolytic ATP production, and overall mitochondrial morphology and function. As a result, IP6K1-deficient cells exhibited disrupted metabolic adaptation under hypoxic conditions and decreased survival under stress. These findings underscore the importance of the Cys-Arg/N-degron pathway in regulating metabolic responses and highlight its potential importance in hypoxia-related disorders.
Protein corona formed on lipid nanoparticles compromises delivery efficiency of mRNA cargo
Authors: Voke Elizabeth , Arral Mariah , Squire Henry J. , Lin Teng-Jui , Coreas Roxana , Lui Alison , Iavarone Anthony T. , Pinals Rebecca L. , Whitehead Kathryn A. , Landry Markita
Published: January 2025

Lipid nanoparticles (LNPs) are the most clinically advanced nonviral RNA-delivery vehicles, though challenges remain in fully understanding how LNPs interact with biological systems.In vivo, proteins form an associated corona on LNPs that redefines their physicochemical properties and influences delivery outcomes. Despite its importance, the LNP protein corona is challenging to study owing to the technical difficulty of selectively recovering soft nanoparticles from biological samples. Herein, we developed a quantitative, label-free mass spectrometry-based proteomics approach to characterize the protein corona on LNPs. Critically, this protein corona isolation workflow avoids artifacts introduced by the presence of endogenous nanoparticles in human biofluids. We applied continuous density gradient ultracentrifugation for protein-LNP complex isolation, with mass spectrometry for protein identification normalized to protein composition in the biofluid alone. With this approach, we quantify proteins consistently enriched in the LNP corona including vitronectin, C-reactive protein, and alpha-2-macroglobulin. We explore the impact of these corona proteins on cell uptake and mRNA expression in HepG2 human liver cells, and find that, surprisingly, increased levels of cell uptake do not correlate with increased mRNA expression in part likely due to protein corona-induced lysosomal trafficking of LNPs. Our results underscore the need to consider the protein corona in the design of LNP-based therapeutics.

Abstract Figure
Development of human skin equivalents with inducible ceramide depletion for in vitro modelling of lipid deficiency
Authors: Dina Durotimi O. , Maiellaro Miriam , Camera Emanuela , Connelly John T.
Published: January 2025

The lipid composition of the epidermis plays a critical role in the skin’s barrier function, and defects in lipid synthesis or assembly can cause a spectrum of skin diseases, ranging from dry skin to severe ichthyoses. The aim of this study was to develop an in vitro model of human skin with tuneable lipid deficiency. Human N/TERT keratinocytes were engineered to express doxycycline-inducible short hairpin RNAs targeting ceramide synthase 3 (CerS3), which is essential for synthesis of ultra long chain ceramides and skin barrier function. We show that 3D human skin equivalents (HSEs) with induced knockdown of CerS3 display normal stratification and terminal differentiation but have reduced Nile Red staining for polar lipids. Further analysis of the lipidome by mass spectrometry confirmed a significant reduction in specific classes of ceramides and ceramide chain length in the CerS3 depleted HSEs. We also show that CerS3 knockdown is reversible upon removal of doxycycline and can be used to study recovery and repair of epidermal lipids. Together, these findings provide an overall strategy for genetically tuning the lipid composition within human skin models and establish a new in vitro model of ceramide deficiency.