Muscle Ratio Research Articles

Abstract A005: 18F-Fluorthanatrace PARP inhibitor PET tracer: Potential implications for theranostics

Abstract Objective: PARP (poly [ADP-ribose] polymerase) inhibitors are approved for a variety of malignancies including those with a breast, prostate, and ovarian carcinoma, particularly in the setting of a germline or somatic pathogenic BRCA mutation. There is active interest in the development of theranostics including those with a PARP inhibitor backbone. Methods: We evaluate a novel PARP inhibitor (PARPi) PET tracer 18-Fluorine [18F] Fluorthanatrace (FTT). Patients with primary or metastatic solid tumors with measurable disease initiating therapy with a PARP inhibitor monotherapy or in combination with another systemic agent were eligible. Patients underwent 18F-FTT PET/CT prior to initiation of PARPi and a second 18F-FTT PET 2-4 weeks after initiation of a PARP inhibitor. Hematologic toxicity on PARPi monotherapy or combination was assessed using the CTCAEv5.0 criteria. Regions of interest were drawn over the uninvolved bone marrow (usually taken at L3) and normal muscle to obtain the maximum standardized uptake value. Bone marrow to muscle ratio (B/M) was calculated at baseline and on PARPi. Spearman rank correlation coefficient was used. Results: A total of 21 patients were enrolled and underwent 18F-FTT PET. Patients had a median of 0 (range 0-7) prior lines of systemic therapy. The primary disease site included breast (9), ovary (6), primary peritoneal (1), pancreas (1)and other (4). Measurable uptake of 18F-FTT within the tumor and bone marrow was observed in all patients. Median L3 SUVmax at baseline was 4.3 (range 2.1-11.8) vs. 2.33 (range 1.4-2.9) while on PARP inhibitor. Baseline B/M was associated with highest grade hematologic toxicity in patients (n=10) who received talazoparib monotherapy or combination (r=0.65, p=0.042). While B/M was not associated with hematologic toxicity in patients (n=11) who received olaparib monotherapy or combination (r=0.098, p=0.77). Conclusions: 18F-FTT PET can measure target engagement of PARP inhibitors in bone marrow and may have implications for PARP inhibitor-based theranostics and dosing. Results suggest there may be differential impact of different PARPi on bone marrow and should be considered when selecting a backbone for theranostics. Citation Format: Lilie Lin, Mahmoud Hammad, Franklin Wong, Timothy A. Yap. 18F-Fluorthanatrace PARP inhibitor PET tracer: Potential implications for theranostics. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr A005.

The role of paraspinal muscle degeneration in cervical spondylosis.

To explore the relationship between paraspinal muscle degeneration and cervical spondylosis through cervical spine MRI and lateral X-ray. A retrospective study included 83 cervical spondylosis patients as the experimental group, consisting of 28 axial joint pain (Group A), 29 cervical radiculopathy (Group B), and 26 myelopathy (Group C), as well as 29 healthy individuals as the control group (Group D). The cross-sectional area (CSA) of paraspinal muscles at the C3-4, C4-5, and C5-6 segments was measured, including the deep extensor area (DEA), deep flexor area (DFA), and superficial extensor area (SEA). Additionally, fatty infiltration (FI) ratio was calculated, namely the deep extensor fatty infiltration ratio (DEFIR), deep flexor fatty infiltration ratio (DFFIR), and superficial extensor fatty infiltration ratio (SEFIR). Correlations of CSA and FI ratio with age, body mass index, Pfirrmann grading, and Cobb angle were analyzed. (1) Pfirrmann grading in groups A, B, and C was significantly higher than that in group D (P < 0.001), with group C higher than groups A and B (P < 0.05), but the difference between groups A and B was not statistically significant (P > 0.05). (2) There was no significant difference in the CSA among groups (P > 0.05). For DEFIR and DFFIR, group C > group B > group A > group D, with significant differences (P < 0.05). For SEFIR, groups A, B, and C were significantly higher than group D (P < 0.001), with no significant differences between the other pairs (P > 0.05). (3) The CSA of males was significantly greater than females (P < 0.001), while the difference in FI ratio was not significant (P > 0.05). (4) In the control group, DEFIR and DFFIR were positively correlated with age (r = 0.538, P = 0.003; r = 0.829, P < 0.001) and negatively correlated with Cobb angle (r=-0.523, P = 0.004; r=-0.535, P = 0.003). In the experimental group, DEFIR and DFFIR were positively correlated with age (r = 0.731, P < 0.001; r = 0.741, P < 0.001) and Pfirrmann grading (r = 0.778, P < 0.001; r = 0.812, P < 0.001), and negatively correlated with Cobb angle (r=-0.507, P < 0.001; r=-0.539, P < 0.001). There were no correlations between the other parameters. In cervical spondylosis patients, the FI ratio of the deep cervical muscle is linked to both worsening disc degeneration and changes in cervical spine alignment. Among the different subtypes, cervical myelopathy shows the highest FI ratio of the deep cervical muscle and disc degeneration, indicating its significant impact on spinal structure and muscular integrity.

Effect of electroacupuncture on denervated skeletal muscle atrophy in rats based on p38 MAPK signaling pathway

To assess the impacts of electroacupuncture (EA) on the gait, oxidative stress, inflammatory reaction, and protein degradation in the rats of denervated skeletal muscle atrophy, and explore the potential mechanism of EA for alleviating denervated skeletal muscle atrophy. Forty male SD rats, 8 weeks old, were randomly assigned to a sham-surgery group, a model group, an EA group, and a p38 MAPK inhibitor group, with 10 rats in each group. The right sciatic nerve was transected to establish a rat model of denervated skeletal muscle atrophy in the model group, the EA group and the p38 MAPK inhibitor group. In the sham-surgery group, the nerve was exposed without transection. One day after successful modeling, the rats in the EA group received EA at "Huantiao" (GB30) and "Zusanli" (ST36) on the right side, using a continuous wave with a frequency of 2 Hz and current intensity of 1 mA, for 15 min in each session, EA was delivered once a day, 6 times a week. In the p38 MAPK inhibitor group, the rats received the intraperitoneal injection with SB203580 (5 mg/kg), once a day, 6 times a week. The intervention was composed of 3 weeks in each group. After the intervention completion, the CatWalk XT 10.6 animal gait analysis system was used to record the gait parameters of rats. The wet weight ratio of the gastrocnemius muscle was calculated after the sample collected. Using HE staining, the fiber morphology and cross-sectional area of the gastrocnemius muscle were observed; ELISA was employed to measure the content of interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α in the gastrocnemius muscle; the biochemical hydroxyamine method was adopted to detect the content of superoxide dismutase (SOD) and malondialdehyde (MDA) in the gastrocnemius muscle; with immunohistochemistry and Western blot used, the expression of p38 mitogen-activated protein kinase (p38 MAPK), phosphorylated (p)-p38 MAPK, muscle atrophy F-box gene (Atrogin-1), muscle RING finger 1 (Murf-1), nuclear factor E2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) was detected in the gastrocnemius muscle. Compared to the sham-surgery group, in the model group, the standing duration, the swing time and the step cycle were increased (P<0.001), the footprint area of the maximum contact time, the print area, the average intensity of the maximum contact time, the average intensity, the swing speed, and the step length were decreased (P<0.001); the wet weight ratio of gastrocnemius muscle and fiber cross-sectional area were reduced (P<0.001); the content of IL-6, IL-1β, TNF-α and MDA in gastrocnemius muscle elevated (P<0.001), and that of SOD reduced (P<0.001); the positive and protein expression of p-p38 MAPK, Atrogin-1 and Murf-1 elevated (P<0.001) and that of Nrf2 and HO-1 dropped (P<0.001). When compared with the model group, in the EA group and the p38 MAPK inhibitor group, the standing duration, the swing time and the step cycle decreased (P<0.01), the footprint area of the maximum contact time, the print area, the average intensity of the maximum contact time, the average intensity, the swing speed, and the step length increased (P<0.01); the wet weight ratio of gastrocnemius muscle and fiber cross-sectional area were improved (P<0.01, P<0.05); the content of IL-6, IL-1β, TNF-α and MDA in gastrocnemius muscle dropped (P<0.05, P<0.01), and that of SOD elevated (P<0.01, P<0.05); the positive and protein expression of p-p38 MAPK, Atrogin-1 and Murf-1 dropped (P<0.01, P<0.05) and that of Nrf2 and HO-1 increased (P<0.01, P<0.05). Electroacupuncture may alleviate skeletal muscle atrophy in denervated skeletal muscle atrophy rats by mediating the p38 MAPK activity, thereby suppressing oxidative stress, inflammatory reaction, and protein degradation.

Contraction ratio of multifidus and erector spinae muscles in unilateral sacroiliac joint pain: A cross-sectional trial

Sacroiliac joint (SIJ) pain is one of the most prevalent reasons for disability, it affects the contraction ratio of the muscles of the back. Imaging is critical for diagnosing back muscles. The purpose of this study was to look at changes in the muscle contraction ratio of the lumbar multifidus (LM) and erector spinae (ES) in unilateral SIJ pain. This research included 60 individuals (30 with unilateral SIJ pain and 30 healthy people (who served as matching controls). The contraction ratio of back muscles such as ES and LM was assessed using real-time ultrasonography, and the results were compared between the affected and non-affected sides in patients with unilateral SIJ pain, and healthy participants as well. In the study group, the contraction ratio of ES and LM muscles on the non-affected side was significantly higher than on the affected side (p < 0.05). as well as a significant increase in contraction ratio of the ipsilateral side (affected matched control side) LM of the healthy group compared with that of the non-affected side of the study group (p < 0.001), while there was no significant difference in contraction ratio of the contralateral (unaffected matched control side) ES of the healthy group compared with that of the non-affected side of the study group. The results of this trial demonstrate that patients with unilateral SIJ pain exhibited a substantially lower muscle contraction ratio in the ES and LM of the affected side than the non-affected side in the study group, as well as a significant increase in the contraction ratio of the ES and MF on the ipsilateral side of the control group compared with that of the study group. However, there was no significant change in the contraction ratio of the contralateral ES in healthy individuals compared to the non-affected side of the study group. The findings of the study may help in designing an appropriate exercise program to deal with patients with SIJ pain.

Effect of Combining Exercise with Adipose-Derived Mesenchymal Stem Cells in Muscle Atrophy Model of Sarcopenia.

Deterioration in muscle mass, strength, and physical performance due to conditions such as sarcopenia can affect daily activities and quality of life in the elderly. Exercise and mesenchymal stem cells (MSCs) are potential therapies for sarcopenia. This study evaluates the combined effects of exercise and adipose-derived MSCs (ADMSCs) in aged rats with sarcopenia. Eighteen-month-old rats were randomly divided into four groups: control, exercise (Ex), ADMSCs injection (MSC), and ADMSCs injection with exercise (MSC + Ex). Gastrocnemius (GCM) muscle mass increased in the Ex, MSC, and MSC + Ex groups compared to the control group. Although the mean CSA did not differ significantly between the groups, the size distribution of myofibers shifted toward larger sizes in the Ex and MSC + Ex groups. The MSC + Ex group performed best in functional tests, including the rotarod and hot plate tests. The protein expression levels of tumor necrosis factor (TNF) and the p-AMP-activated protein kinase (AMPK)/AMPK ratio in the GCM muscle were the lowest in the MSC + Ex group. This study demonstrates that combining exercise and ADMSC interventions was the most effective treatment for aged sarcopenic rats, suggesting a potential synergistic approach for sarcopenia treatment.

The Impact of Levothyroxine and Testosterone Administration on Bladder Contractility in the Rat Model of Propylthiouracil-Induced Hypothyroidism.

To investigate the effects of testosterone (T) treatment, with or without levothyroxine, the most widely used and least effective medication for managing hypothyroidism, on the functional and histological changes in propylthiouracil (PTU)- induced hypothyroid rat bladders. Male rats (n=35) were split into control, hypothyroid, hypothyroid rats treated with levothyroxine (20 µg/kg/day, oral, 2-weeks), hypothyroid rats treated with Sustanon (10 mg/kg,iIM, once/week, 2-weeks), and hypothyroid rats treated with combined treatment groups. Hypothyroidism was induced by PTU (0.05% in drinking water, 6 weeks). The serum concentration of triiodothyronine (T3), thyroxine (T4), total T, and the detrusor muscle's contractile responses were determined. A morphological study was conducted using Masson trichrome staining. Triiodothyronine, T4, and T levels were considerably reduced in rats with hypothyroidism; however, these hormones were restored by levothyroxine and Sustanon. Compared to controls, the combination therapy improved the ratio of smooth muscle to collagen and the contractile responses to carbachol, electrical field stimulation, and adenosine triphosphate in the hypothyroid bladder. The authors' research suggests that hypothyroidism may affect the contractility and morphology of the bladder. In males with hypothyroidism and urogenital system dysfunction, combination therapy with thyroid hormones and T has a major impact on repairing detrusor smooth muscle contractility and bladder histomorphology.

Muscle Pathology Associated With Cardiac Function in Duchenne Muscular Dystrophy.

To compare the progression of muscle fibrosis of various site and its relation between cardiac deterioration in Duchenne muscular dystrophy (DMD). In this study aimed to examine the associations between echocardiogram-based cardiac function indices and fibrosis of the abdominal and lower extremity muscles in patients with DMD to facilitate early detection of cardiac dysfunction and identify its predictors. Twenty-one patients with DMD patients were enrolled in the study. The association between cardiac dysfunction and fibrosis of the abdominal and lower extremity muscles was determined by analyzing the echocardiography and elastography. Non-parametric Spearman rank correlation coefficients were used to examine the pairwise relationships between cardiac function and muscle elasticity. All patients were male and non-ambulant. Their mean age was 18.45±4.28 years. The strain ratios of the abdominal muscle and quadriceps muscles were significantly higher than those of the medial gastrocnemius. The strain ratio of the rectus abdominis muscle has a significant negative correlation with left ventricular ejection fraction. Cardiac function and valvular insufficiency were not significantly correlated with muscle strain ratio. According to the result of our study, the only skeletal muscle which showed significant correlation with cardiac dysfunction was degree abdominal muscle fibrosis. The degree of fibrosis of respiratory muscles was also significantly associated with cardiac dysfunction; therefore, it can be used as a predictor of cardiac dysfunction in patients with DMD in clinical practice.

Evaluation of fibroinflammatory activity in thyroid eye disease using [18F]AlF-NOTA-FAPI-04 PET/CT: A prospective study.

This study evaluates the value of [18F]AlF-NOTA-FAPI-04PET/CT in assessing the disease activity of thyroid eye disease (TED). Twenty-three TED patients and ten healthy controls were prospectively recruited and underwent [18F]AlF-NOTA-FAPI-04 PET/CT scans. TED eyes were classified by Clinical Activity Score (CAS) as active (CAS +) or inactive (CAS-). PET analysis included qualitative and quantitative evaluations. Qualitative analysis categorized TED eyes as positive (FAPI +) or negative (FAPI-), while quantitative analysis including SUVmax and target-to-backgroud ratio (TBR) of each extraocular muscle (EOM). Pathological assessment of 16 EOM samples from 15 TED eyes was used as a gold standard to evaluate the diagnostic accuracy of CAS-driven and FAPI-driven assessments. Eye-based analysis included 42 TED eyes and 20 control eyes. SUVmax did not differ significantly between CAS-/FAPI + (n = 8) and CAS + /FAPI + (n = 17) eyes; though both groups had significantly higher SUVmax than CAS-/FAPI- (n = 16), CAS + /FAPI- (n = 1), and control eyes (n = 20) (all P < .05). Diffuse high FAPI uptake with excellent TBR was observed in pathologically active EOMs and had higher SUVmax and TBR than inactive EOMs (SUVmax: 9.57 ± 2.79 vs. 4.04 ± 1.02, TBR: 2.99 ± 1.00 vs. 1.00 ± 0.35, both P < .001). An SUVmax cutoff value of 5.95 yielded an area under the receiver operating characteristic curve of 0.98 for predicting active disease. Sensitivity and specificity of CAS-driven and FAPI-driven assessments for TED activity were 72.7% and 100%, 100% and 100%, respectively. SUVmax positively correlated with pathological fibroinflammatory score (r = 0.68, P = .004). The diffuse high FAPI uptake with excellent TBR in the EOMs could illustrate the activity of TED, positively correlated with pathological fibroinflammatory scores. These findings suggest that [18F]AlF-NOTA-FAPI-04 PET/CT may serve as a promising reliable non-invasive approach for assessing disease activity in TED, potentially superior to the CAS.

Combination of flaxseed and clarified tomato juice in bread: Delayed effect on metabolic disorders during long-term unbalanced diet in an in vivo experiment.

The objective of study was to evaluate the biological effects occurring in the animal body in conditions of a regular consumption of bread with a combination of flaxseed and clarified tomato juice in its composition. The animals (Soviet Chinchilla breed) were randomly distributed between six groups. Group 1 is intact animals. The food of Group 2 (control) included traditional bread. Animals of experimental groups were fed as follows: bread, in which 75% of water were replaced with clarified tomato juice (Group 3); bread with the addition of 20% of flaxseed, soaked beforehand in clarified tomato juice (Group 4); bread similar to Group 4, but juice with dissolved flaxseed hydrocolloids was used during dough kneading (Group 5); bread similar to Group 4, but instead of juice, drinking water was used (Group 6). We studied blood biochemistry. After 6 months, we took liver samples and identified the ratio of muscle, fat, bone, and connective tissues. We established that the introduction of clarified tomato juice into the bread recipe yielded a decrease in cholesterol and creatinine levels (p = .029 and p = .031, respectively), while the addition of flaxseed soaked in water can promote the activation of protective effects against nonalcoholic fatty liver disease via reducing the levels of bilirubin (p = .040) and transaminases (p = .013) in the blood of experimental animals. The introduction of a combination of flaxseed and clarified tomato juice into the bread recipe in conjunction with its daily consumption contributed to the manifestation of protective effects for the liver of rabbits.

Evaluating the Clinical Applicability of Multifrequency Bioelectrical Impedance Analysis for Nutritional Status Prediction in Hospitalized Persons With Severe Motor and Intellectual Disabilities.

Persons with severe motor and intellectual disabilities (SMID) have difficulty using general nutritional assessments in the elderly and other populations because of their physical characteristics. The purpose of this study was to investigate the clinical utility of body composition, which has been suggested to be related to biochemical tests in persons with SMID. We calculated cutoff values of body composition predicting malnutrition and compared the usage of peripheral parenteral nutrition for the two groups divided by each body composition cutoff value. We also compared body composition at the baseline between nonsurvivors and survivors. Only group comparisons based on skeletal muscle ratio and extracellular water to total body water (ECW/TBW) cutoffs showed significant differences in the usage of peripheral parenteral nutrition. Nonsurvivors had significantly higher ECW/TBW than survivors at the baseline. In persons with SMID, skeletal muscle ratio and ECW/TBW measured using multifrequency bioelectrical impedance were associated with biochemical indices and ill health. Furthermore, ECW/TBW was also associated with mortality, suggesting that ECW/TBW is a significant measure for nutritional assessment in clinical practice.

Levator Veli Palatini Muscle Ratio Is a Clinically Significant Anatomic Predictor for Velopharyngeal Surgical Need.

Velopharyngeal insufficiency (VPI) poses challenges for normal speech production, often necessitating surgical intervention. Determining optimal candidates for surgery remains complex and requires a nuanced understanding of underlying anatomic factors contributing to VPI. This study aimed to identify anatomic predictors that drive surgical recommendations for VPI. Prospective observational cohort study. Pediatric tertiary care hospital. Magnetic resonance imaging data were acquired from 150 children (aged 4-17) to identify anatomic predictors of VPI and surgical need. Fourteen velopharyngeal variables were measured in the oblique coronal and midsagittal imaging planes. Calculations included differences in levator veli palatini (LVP) muscle angles of origin, mean extravelar length, differences between left and right extravelar segments, the VP Needs ratio, and a newly developed LVP ratio. Multivariate logistic regression models with k-fold cross validation were utilized to identify anatomic profiles predictive of VPI and receiving a surgical recommendation. The models demonstrated high accuracy, sensitivity, and specificity. Among anatomic variables, the LVP ratio emerged as the strongest determinant of surgical need (β = 11.256, p < .001). Notably, an increase in the LVP ratio of 0.10 is associated with a 3.08-fold increase in the likelihood of receiving a surgical recommendation. LVP ratios above 1.0 were significant for both VPI classification and surgical need. The LVP ratio significantly differentiates individuals with VPI and is predictive of surgical need for VPI management. Inclusion of the LVP ratio into clinical evaluations may refine patient stratification, enabling more precise surgical decision-making tailored to individual anatomic variations.

Assessment of Quadriceps Muscle in Advanced Knee Osteoarthritis and Correlation with Lower Limb Alignment

Background and Objectives: Despite extensive studies of the role of quadriceps and quadriceps/hamstring balance in knee osteoarthritis (OA), the roles of the vastus intermedius, medialis, and lateralis in OA remain unclear. The purpose of this study was to investigate the relationship of lower limb alignment and the ratio of the quadriceps femoris muscle to the knee extensor muscle. Materials and Methods: This study included 50 patients with advanced knee OA (Kellgren/Lawrence grade of 3 or 4) and 25 healthy control persons between June 2021 and May 2022. The osteoarthritis grade and anatomical tibiofemoral angle were measured based on plain radiography and scanography. All participants were divided into normal (0~5°), mild varus (5°~10°), and severe varus (&gt;10°) groups. Using MRI, muscle size was determined by calculating the cross-sectional area (CSA) of the total quadriceps (rectus femoris, vastus intermedius, vastus medialis, and vastus lateralis) and its components. Results: The CSA ratio of the vastus lateralis was significantly smaller in the severe varus group than in the normal or mild varus groups. There was a significant positive correlation between the mechanical tibiofemoral angle and vastus lateralis CSA (ρ = 0.282, p = 0.014) and between the anatomical tibiofemoral angle and vastus lateralis CSA (ρ = 0.294, p = 0.011). There was a significant negative correlation between the mechanical tibiofemoral angle and vastus intermedius CSA (ρ = −0.263, p = 0.023) and between the anatomical tibiofemoral angle and vastus intermedius CSA (ρ = −0.243, p = 0.036). Conclusions: Patients with severe varus alignment exhibited vastus lateralis atrophy. This study highlights vastus lateralis atrophy in severe varus alignment, though causality between atrophy and varus knee OA remains uncertain. We think that patients with severe varus may require strengthening exercises focused on the vastus lateralis before and after surgery for alignment correction.

Identification of differentially expressed genes and polymorphisms related to intramuscular oleic-to-stearic fatty acid ratio in pigs.

The intramuscular oleic-to-stearic fatty acid ratio (C18:1n-9/C18:0) is an important indicator of the biosynthesis and desaturation of fatty acids in muscle. By using an RNA-Seq approach in muscle samples from 32 BC1_DU (25% Iberian and 75% Duroc) pigs with divergent values (high: H and low: L) of C18:1n-9/C18:0 fatty acids ratio, a total of 81 differentially expressed genes (DEGs) were identified. Functional analyses of DEGs indicate that mainly peroxisome proliferator-activated receptor signaling pathway (associated genes: PPARG, SCD, PLIN1, and FABP3) was overrepresented. Notably, SCD is directly involved in the conversion of C18:0 to C18:1n-9, and PPARG is a transcription factor regulating lipid metabolism genes, including SCD. However, other DEGs (e.g., ACADVL, FADS3, EPHB2, HGFAC, NGFR, NR0B2, MDH1, MMAA, PPP1R1B, SFRP5, RAB30, and TRARG1) are plausible candidate genes to explain the phenotypic differences of the C18:1n-9/C18:0 ratio. Interestingly, seven genetic variants within the SCD (including the well-known AY487830:g.2228T>C SNP and other novel genotyped polymorphisms) are associated with two haplotypes. Although the haplotypes are segregating at different frequencies in the H and L groups, they do not fully explain the desaturation ratios or the SCD expression levels. A more complex model, including polyunsaturated fatty acids such as C18:2n-6, C20:4n-6, and C18:3n-3, is suggested to explain the regulation of the C18:1n-9/C18:0 desaturation ratio in porcine muscle.

Subscapularis Muscle Radiographic Integrity and Patient-Reported Outcomes Following Arthroscopic Anatomic Glenoid Reconstruction With Distal Tibial Allograft

Background: Shoulder stabilization surgery has evolved over time, and bony augmentation procedures on the glenoid side are being performed more often. The Latarjet procedure modifies subscapularis anatomy because the conjoined tendon divides the subscapularis muscle fibers through a split/takedown, which has structural and functional implications. Arthroscopic anatomic glenoid reconstruction (AAGR) re-creates anatomy. This technique uses the Halifax portal to deploy and fix a distal tibial allograft (DTA) through the rotator interval, thus preserving the subscapularis anatomy. Purpose/Hypothesis: The purpose was to analyze the radiographic properties of the subscapularis muscle after AAGR. It was hypothesized that the subscapularis muscle structure remains preserved postoperatively. Study Design: Case series; Level of evidence, 4. Methods: A retrospective review was performed comprising a consecutive series of patients treated with AAGR with DTA between November 2012 and April 2021 for traumatic anterior shoulder instability with glenoid bone loss. Patients were excluded if they had posterior instability, glenoid fracture, missing pre- or postoperative computed tomography (CT) scans, or only CT arthrogram available. Radiographic variables measured on CT scans included estimates of subscapularis muscle volume, subscapularis/infraspinatus muscle ratio, and fatty infiltration according to the Goutallier classification. Pre- and postoperative Western Ontario Shoulder Instability index scores were collected as a secondary outcome of this study. Results: Ninety-three patients were included in the study with a clinical follow-up of 2.3 ± 1.5 years (mean ± SD). The subscapularis volume increased from 185.91 ± 45.85 mL preoperatively to 194.1 ± 49.0 mL postoperatively (P = .006). The subscapularis to infraspinatus muscle ratio showed a significant increase from 0.96 ± 0.27 to 1.05 ± 0.30 after surgery (P = .002). All patients had a Goutallier stage of 0 before and after surgery. The Western Ontario Shoulder Instability scores showed a significant improvement from 64.8 ± 15.5 preoperatively to 28.2 ± 24.0 postoperatively (P < .001). Conclusion: Patients who undergo AAGR with DTA for traumatic shoulder instability with glenoid bone loss have a preserved subscapularis muscle volume with no fatty infiltration, while showing a significant improvement in clinical outcomes.

EGR1 mRNA expression levels and polymorphisms are associated with slaughter performance in chickens

With the implementation of the policy of “centralized slaughtering and chilled to market” and the development of the livestock processing industry, numerous researchers have begun to focus on the selection and breeding of broilers bred for slaughter. The selection of breeds with excellent slaughtering performance and high meat production performance has become one of the most important selective breeding goals. In our previous study, we conducted transcriptome sequencing on chicken breast tissues with high and low breast muscle rates and found higher early growth response protein 1 (EGR1) expression in breast tissues with a low breast muscle ratio, thus hypothesizing that the EGR1 gene is involved in the growth and development process of chicken muscle tissues. Therefore, we analyzed the gene functions and polymorphisms of EGR1 to investigate its association with slaughter traits. We used various experimental methods, including RT-qPCR, Cell Counting Kit 8, 5-ethynyl-2′-deoxyuridine, western blot, flow cytometry, and immunofluorescence, to validate EGR1’s role in chicken primary myoblasts. The results of our functional validation experiments indicate that EGR1 is highly expressed in breast tissues with a low breast muscle content and plays a key role in regulating of muscle growth and development by promoting proliferation and inhibiting the differentiation of chicken primary myoblasts. In addition, we explored the relationship between the EGR1 gene polymorphisms and slaughter traits using mixed linear models for the first time. In a population of Jiangfeng M3 lineage partridge chickens, we identified 4 EGR1 single-nucleotide polymorphisms, 2 of which were significantly associated with slaughter traits, including live weight, slaughter weight, semi-eviscerated weight, eviscerated weight, leg weight, wing weight, and breast muscle rate. In summary, ectopic expression of EGR1 promotes the proliferation and differentiation of chicken primary myoblasts. In addition, polymorphisms in EGR1 were associated with slaughter performance, providing a potential basis for further utilization of EGR1 as a breeding marker.

Design, preclinical evaluation, and first-in-human PET study of [68Ga]Ga-PSFA-01: a PSMA/FAP heterobivalent tracer.

Prostate cancer (PCa), characterized by tumor heterogeneity, may exhibit low or absent prostate-specific membrane antigen (PSMA) expression in cancerous lesions, limiting the detection sensitivity of monospecific probes. Given that fibroblast activation protein (FAP) is frequently overexpressed in the tumor microenvironment (TME), we developed a PSMA/FAP dual-targeting tracer to address this limitation. The precursor (PSFA-01) was synthesized by coupling a quinolone-based FAP-targeting scaffold and EuK with HBED-CC via amide bonds. The dual-receptor-binding affinity and cell uptake of PSFA-01 and [natGa]Ga-PSFA-01 was evaluated in vitro. Micro-PET/CT imaging was performed on 22Rv1 and U87MG tumor-bearing mice. The feasibility of [68Ga]Ga-PSFA-01 PET/CT in a clinical setting was evaluated in a metastatic prostate cancer patient, and the results were compared with those of [68Ga]Ga-FAPI-04 and [68Ga]Ga-PSMA-11 PET/CT. PSFA-01 and [natGa]Ga-PSFA-01 showed high affinity for both FAP and PSMA proteins (Ki = 0.14-1.02 nM). On micro-PET/CT imaging, the 22Rv1 tumor uptake of [68Ga]Ga-PSFA-01 (SUVmax = 3.89 ± 0.47) was higher than that of [68Ga]Ga-PSMA-11 (SUVmax = 2.96 ± 0.48). The U87MG tumor uptake of [68Ga]Ga-PSFA-01 was significantly higher (SUVmax = 7.29 ± 1.13) than [68Ga]Ga-FAPI-04 (SUVmax = 0.28 ± 0.12), showing tumor to muscle ratio as 12.68 ± 1.93 at 1h p.i. On clinical trial, the primary tumor and metastatic lesions were distinctly identified by [68Ga]Ga-PSFA-01 (21 lesions), demonstrating superior performance compared to [68Ga]Ga-FAPI-04 (3 lesions) and [68Ga]Ga-PSMA-11 (13 lesions) in terms of lesion count and specificity. [68Ga]Ga-PSFA-01 exhibited satisfactory PSMA and FAP dual-receptor-targeting properties both in vitro and in vivo. This study highlights the clinical feasibility of [68Ga]Ga-PSFA-01 PET/CT for detecting metastatic tumors of prostate cancer more sensitively compared to monomeric [68Ga]Ga-PSMA-11 and [68Ga]Ga-FAPI-04, which also suggests that a PSMA/FAP dual-targeted radionuclide therapy could potentially overcome challenges related to tumor heterogeneity and insufficient PSMA expression in PCa. Clinical trial registry NCT06387381, Registered 1 May 2024.

Kinetic Analysis and Metabolism of Poly(Adenosine Diphosphate-Ribose) Polymerase-1-Targeted 18F-Fluorthanatrace PET in Breast Cancer.

The poly(adenosine diphosphate-ribose) polymerase inhibitors (PARPi) have demonstrated efficacy in ovarian, breast, and prostate cancers, but current biomarkers do not consistently predict clinical benefit. 18F-fluorthanatrace (18F-FTT) is an analog to rucaparib, a clinically approved PARPi, and is a candidate biomarker for PARPi response. This study intends to characterize 18F-FTT pharmacokinetics in breast cancer and optimize image timing for clinical trials. A secondary aim is to determine whether 18F-FTT uptake in breast cancer correlates with matched frozen surgical specimens as a reference standard for PARP-1 protein. Methods: Thirty prospectively enrolled women with a new diagnosis of breast cancer were injected with 18F-FTT and imaged dynamically 0-60 min after injection over the chest, with an optional static scan over multiple bed positions starting around 70 min. Kinetic analysis of lesion uptake was performed using blood-pool activity with population radiometabolite corrections. Normal breast and normal muscle reference tissue models were compared with PARP-1 protein expression in 10 patients with available tissue. Plasma radiometabolite concentrations and uptake in tumor and normal muscle were investigated in mouse xenografts. Results: Pharmacokinetics of 18F-FTT were well fit by Logan plot reference region models of reversible binding. However, fits of 2-tissue compartment models assuming negligible metabolite uptake were unstable. Rapid metabolism of 18F-FTT was demonstrated in mice, and similar uptake of radiometabolites was found in tumor xenografts and normal muscle. Tumor 18F-FTT distribution volume ratios relative to normal muscle reference tissue correlated with tissue PARP-1 expression (P < 0.02, n = 10). The tumor-to-normal muscle ratio from a 5-min frame between 50 and 60 min after injection, a potential static scan protocol, closely corresponded to the distribution volume ratio relative to normal muscle and correlated to PARP-1 expression (P < 0.02, n = 10). Conclusion: This study of PARPi analog 18F-FTT showed that uptake kinetics invivo corresponded to expression of PARP-1 and that 18F-FTT quantitation is influenced by radiometabolites that are increasingly present late after injection. Radiometabolites can be controlled by using optimal image acquisition timing or normal muscle reference tissue modeling in dynamic imaging or a tumor-to-normal muscle ratio. Optimal image timing for tumor-to-normal muscle quantification in humans appears to be between 50 and 60 min after injection. Therefore, a clinically practical static imaging protocol commencing 45-55 min after injection may sufficiently balance 18F-FTT uptake with background clearance and radiometabolite interference for quantitative interpretation of PARP-1 expression invivo.

Stimulated echo acquisition mode (STEAM) diffusion tensor imaging with different diffusion encoding times in the supraspinatus muscle: Test-retest reliability and comparison to spin echo diffusion tensor imaging.

Diffusion tensor imaging (DTI) provides insight into the skeletal muscle microstructure and can be acquired using a stimulated echo acquisition mode (STEAM)-based approach to quantify time-dependent tissue diffusion. This study examined diffusion metrics and signal-to-noise ratio (SNR) in the supraspinatus muscle obtained with a STEAM-DTI sequence with different diffusion encoding times (Δ) and compared them to measures from a spin echo (SE) sequence. Ten healthy subjects (mean age 31.5 ± 4.7years; five females) underwent 3-Tesla STEAM and SE-DTI of the shoulder in three sessions. STEAM was acquired with Δ of 100/200/400/600 ms. The diffusion encoding time in SE scans was 19ms (b = 500s/mm2). Region of interest-based measurement of fractional anisotropy (FA), mean diffusivity (MD), and SNR was performed. Intraclass correlation coefficients (ICCs) were computed to assess test-retest reliability. ANOVA with post-hoc pairwise tests was used to compare measures between different Δ of STEAM as well as STEAM and SE, respectively. FA was significantly higher (FASTEAM: 0.38-0.46 vs. FASE: 0.26) and MD significantly lower (MDSTEAM: 1.20-1.33 vs. MDSE: 1.62×10-3mm2/s) in STEAM compared to SE (p < 0.001, respectively). SNR was significantly higher for SE (72.3 ± 8.7) than for STEAM (p < 0.001). ICCs were excellent for FA in STEAM (≥0.911) and SE (0.960). For MD, ICCs were good for STEAM100ms-600ms (≥0.759) and SE (0.752). STEAM and SE exhibited excellent reliability for FA and good reliability for MD in the supraspinatus muscle. SNR was significantly higher in SE compared to STEAM.

Lumbar localized fat distribution parameters are independent predictors of osteoporotic vertebral compression re-fractures (OVCRFs) following Percutaneous Kyphoplasty (PKP): a retrospective matched case-control study.

To investigate potential risk factors for osteoporotic vertebral compression re-fractures (OVCRFs) following percutaneous kyphoplasty (PKP). Patients who underwent PKP from January 2012 to January 2020 were included in this study within the same institution. Cases were defined as patients who experienced OVCRFs, while controls were matched based on corresponding clinical characteristics from those patients without OVCRFs. The lumbar localized fat distribution parameters, including the fat infiltration ratio (FIR) in muscles [multifidus (MF), erector spinae (ES), paravertebral muscles (PVM), and psoas major (PS)] and subcutaneous fat thickness (SFT), were compared between the two groups through radiological data. And other clinical data that may be relevant were also compared. Independent risk factors for OVCRFs after PKP were identified through a binary logistic regression analysis. A total of 1391 patients who underwent PKP were included in this study. 51 patients were categorized into the re-fracture group, and 102 patients were selected as matched controls from the remaining cohort. There were statistically significant differences between the two groups in metrics including MF-FIR, ES-FIR, PVM-FIR, PS-FIR, bone mineral density (BMD), body-mass index (BMI), SFT, hemoglobin (Hb), albumin (ALB), alkaline phosphatase (ALP), and triglycerides (TG) (P < 0.05). Binary logistic regression analysis demonstrated that PVM-FIR (P = 0.003), SFT (P < 0.001), BMD (P = 0.011), and ALP (P = 0.005) were independent predictors for the occurrence of OVCRFs. This study discovered that lumbar localized fat distribution parameters including PVM-FIR and SFT are independent predictors of OVCRFs. Additionally, BMD and ALP were found to be independent predictors of OVCRFs.

Body Composition and Progression of Biopsy-Proven Non-Alcoholic Fatty Liver Disease in Patients With Obesity.

Obesity is a significant risk factor for the progression of non-alcoholic fatty liver disease (NAFLD). However, a convenient and efficacious non-invasive test for monitoring NAFLD progression in patients with obesity is currently lacking. This study aims to investigate the associations between CT-based body composition and the progression of biopsy-proven NAFLD in patients with obesity. Liver biopsy was conducted in patients with obesity, and the progression of NAFLD was evaluated by the NAFLD activity score (NAS). Body composition was assessed through abdominal computed tomography (CT) scans. A total of 602 patients with an average age of 31.65 (±9.33) years old were included, comprising 217 male patients and 385 female patients. The wall skeletal muscle index (SMI), total SMI, and visceral fat index (VFI) were positively correlated with NAS in both male and female patients. Multivariate regression analysis demonstrated significant associations between high liver steatosis and wall SMI (HR: 1.60, 95% CI: 1.12 to 2.30), total SMI (HR: 1.50, 95% CI: 1.02 to 2.08), VSI (HR: 2.16, 95% CI: 1.48 to 3.14), visceral fat to muscle ratio (HR: 1.51, 95% CI: 1.05 to 2.18), and visceral to subcutaneous fat ratio (HR: 1.51, 95% CI: 1.07 to 2.12). Non-alcoholic steatohepatitis (NASH) was significantly associated with wall SMI (HR: 1.52, 95% CI: 1.06 to 2.19) and VSI (HR: 1.50, 95% CI: 1.03 to 2.17). Liver fibrosis ≥ F2 was significantly associated with psoas muscle index (HR: 0.64, 95% CI: 0.44 to 0.93) and psoas skeletal muscle density (HR: 0.61, 95% CI: 0.41 to 0.89). Our study suggested that certain CT-based body composition indicators, notably high VFI, were significantly associated with the progression of NAFLD in patients with obesity. Great attentions and timely managements should be given to these patients with body composition characteristics associated with the risk of NAFLD progression.