bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of clinical outcomes between conventional and underwater endoscopic mucosal resection for duodenal neuroendocrine tumors
Authors: Jang Jin Ook , Kim Tae Un , Choi Cheol Woong , Ryu Dae Gon , Park Su Bum , Lee Jung Wook , Kim Su Jin
Published: November 2024

Duodenal neuroendocrine tumors are relatively rare subepithelial tumors that arise from cells of the neuroendocrine system. Small duodenal neuroendocrine tumors can be treated endoscopically because of their low potential for metastasis. This study aimed to evaluate the clinical outcomes of conventional and underwater endoscopic mucosal resection for duodenal neuroendocrine tumors. Between March 2009 and March 2023, 15 patients with duodenal neuroendocrine tumors resected using conventional (n = 7) and underwater (n = 8) endoscopic mucosal resections were retrospectively enrolled. The median specimen size and median tumor size were 1.0 cm (interquartile range: 0.8–1.2 cm) and 0.6 cm (interquartile range: 0.4–0.6 cm), respectively. More than half of duodenal neuroendocrine tumors were located in the duodenal bulb (9/15, 60%). The en bloc and complete resection rates of both conventional and underwater endoscopic mucosal resections were 100%. Only one perforation event occurred in the conventional endoscopic mucosal resection group (14.3%). The patient with the perforation was treated with endoscopic clipping. The median follow-up period was 39.5 months (interquartile range: 19.5–57.3 months). There was no local recurrence or distant metastasis during the follow-up period. Underwater endoscopic mucosal resection is a safe and effective treatment option for small duodenal neuroendocrine tumors and is the preferred treatment option for flat-type duodenal neuroendocrine tumors.
Analysis of factors related to venous thrombosis after ankle fracture combined with type 2 diabetes mellitus applying tourniquet surgery
Authors: Wang Cheng-gui
Published: November 2024

The objective was to study the risk factors of venous thrombosis after ankle fracture with type 2 diabetes mellitus surgery using a tourniquet and to assess the effect of ischemic preconditioning and metformin combination therapy in preventing thrombosis. One hundred eighty patients with ankle fractures combined with type 2 diabetes mellitus treated with lower extremity tourniquet surgery between January 2020 and December 2023 were analyzed. Based on postoperative color Doppler ultrasound of both lower extremities, the patients were divided into thrombus-positive and negative groups. Multifactorial logistic regression analysis was utilized to determine the high-risk factors for venous thrombosis and construct a prediction model. There were 64 cases in the positive group and 116 cases in the negative group. The differences between the 2 groups in gender, age, fracture site, preoperative glycosylated hemoglobin, thromboelastography parameters, duration of surgery, D-dimer level at 1-week postoperatively, and thromboelastography K, α, and MA values were not statistically significant (P > .05); however, there was no statistically significant difference in the preoperative D-dimer level, tourniquet duration, bleeding volume, thromboelastography R-value at 1-week postoperatively, and ischemic preconditioning in combination with metformin treatment patient There was a significant difference in the proportion (P < .05). Multifactorial logistic regression analysis showed that preoperative high D-dimer, prolonged tourniquet application, massive bleeding, and increased thromboelastography R-value at 1-week postoperatively were independent risk factors, and ischemic preconditioning combined with metformin was a protective factor. Preoperative high D-dimer, prolonged tourniquet application, massive bleeding, and increased thromboelastography R-value at 1-week postoperatively were independent risk factors for postoperative venous thrombosis in patients with ankle fracture with type 2 diabetes mellitus and ischemic preconditioning combined with metformin treatment was a protective measure, and the prediction model is valuable in guiding clinical thrombosis risk assessment.
Role of IFN-γ, IL-33, and IL-35 concentrations in tuberculous pleural effusion in diagnosis and analysis of the effectiveness of combined tests
Authors: Wang Lin , Qi Ying , Nan Yan , Qi Suhong
Published: November 2024

This study examines the diagnostic utility of the combined interleukin-33 (IL-33), interferon-γ (IFN-γ), and interleukin-35 (IL-35) test in tuberculous pleural effusion. Forty patients with pleural effusion of unknown etiology admitted to the hospital between December 2020 and December 2023 were selected as the study group. The patients were further categorized into tuberculous (TB) (n = 20) and malignant (n = 20) groups on the basis of their relevant data, while sera from 20 healthy medical checkups were used as control group. Thoracentesis was used to collect pleural fluid, and after its collection, enzyme-linked immunosorbent assay was utilized to detect the concentration content of IL-35, IL-33, and IFN-γ in pleural fluid of patients with different types of diseases. Data processing and analysis were executed through SPSS23.0 software to plot the receiver operating characteristic curve and compare the area of the area under the line of each index. Adenosine deaminase level was statistically higher in TB group patients (59.91 U/L) than in malignant group (14.31 U/L) (P < .05). Pleural fluid lactate dehydrogenase levels did not differ significantly between the 2 groups (P > .05). T-SPOT test had a higher positive rate in the TB group (85%) and a lower positive rate in the malignant group (45%). The TB group exhibited significantly higher levels of IFN-γ expression than the malignant group (P < .05). The TB group had higher levels of IL-33 and IL-35 compared to the malignant group, with a statistically significant difference (P < .05). The TB group had a greater level of IL-33 (81.05 ± 10.11 pg/mL) than the cytology-positive group (39.37 ± 9.63 pg/mL), while the difference was not statistically significant (P > .05). The level of IL-35 (70.11 ± 10.37 pg/mL) in the TB group was lower than the level of IL-35 (72.13 ± 9.58 pg/mL) in the cytology-positive group. The specificity of the series of combined tests reached 95.81%, which was statistically superior to the single-factor test (P < .05). In the TB group, IFN-γ and IL-33, IFN-γ and IL-35, and IL-33 and IL-35 showed positive correlation. Combined determination of the concentration levels of IL-35, IL-33, and IFN-γ is of value in the diagnosis of tuberculous pleurisy.
Anxiety depression levels, anxiety sensitivity, and quality of life in children with chronic spontaneous urticaria: A cross-sectional study
Authors: Cömertoğlu Arslan Semiha , Çelik Velat
Published: November 2024

Existing literature offers some insights into the prevalence of anxiety and depression in children with chronic spontaneous urticaria (CSU). However, the literature on anxiety sensitivity (AS) and quality of life (QoL) in these children remains poorly understood. This study aimed to evaluate psychiatric diagnoses, anxiety and depression levels, AS, and QoL in children with CSU compared to healthy controls. The CSU group consisted of 44 children aged 8 to 17 years who were diagnosed with CSU, while the control group consisted of 44 healthy children. A child psychiatrist conducted the psychiatric assessment of the children. The Revised Child Anxiety and Depression Scales (RCADS), the Childhood Anxiety Sensitivity Index (CASI), and the Children’s Dermatology Life Quality Index (CDLQI) were administered. Multiple linear regression analysis was conducted to identify independent predictors of QoL, considering several potential factors, including the urticaria activity score, duration of urticaria, presence of a psychiatric diagnosis, scores on the RCADS major depression disorder, RCADS-total anxiety, and total CASI. A significantly higher prevalence of psychiatric diagnoses and anxiety disorders was observed in the CSU group (P < .05). In the CSU group with a psychiatric diagnosis, CASI-total (0.011), CASI-physical (0.049), CASI-social (0.022), and CDLQI scores (P < .001) were significantly higher than those without a psychiatric diagnosis. In the multiple linear regression analysis, only the presence of a psychiatric diagnosis was found to be a significant predictor of CDLQI scores (OR, 5.918; 95% CI, 2.505–9.330; P: .001). This study indicated that children with CSU exhibited a higher prevalence of psychiatric diagnoses than controls. Additionally, children with psychopathology in the CSU group demonstrated higher AS and greater impairment of QoL than those without psychiatric diagnoses. Furthermore, the most significant predictor of a decline in QoL was the presence of a psychiatric diagnosis.
Analysis of clinical characteristics and laboratory examination data of 112 cases of Mycoplasma pneumoniae pneumonia in children
Authors: Wang Pingping , Yao Jin , Li Yaqiong , Huang Xiaorong , Deng Chenhui
Published: November 2024

The aim of this study was to analyze the clinical characteristics of Mycoplasma pneumoniae (MP) infection in children and provide a basis for the diagnosis and treatment of MP and refractory Mycoplasma pneumoniae pneumonia (MPP) in children. A total of 112 children with MPP admitted to Luoyang Maternal and Child Health Hospital between January 31, 2023 and December 31, 2023 were studied, and their clinical characteristics were retrospectively analyzed, including children’s general data, clinical symptoms, imaging changes, bronchoscopy, and laboratory data, including inflammatory factors such as C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6), bacterial culture results of bronchoalveolar lavage or sputum, and results of MP culture and detection of MP drug resistance gene loci 23sRNA A2063G and A2064G. Among the 112 children with MPP included in the analysis, 48 were males (42.86%), 64 were females (57.14%), with an average age of 5.74 ± 2.62 years old, 55 cases were older than 6 years old (49.11%), 35 cases were 3 to 6 years old (31.25%), and 22 cases were <3 years old (19.64%), with the older children being the most; 103 cases were fever (91.96%), 94 cases were cough (83.93%), and 46 cases were dyspnea (41.07%). Fiber bronchoscopy showed that 112 cases were mucosal congestion and edema (100.00%), 69 cases were sputum embolism (61.61%), and 19 cases were mucosal erosion (16.96%); the incidence of CRP, PCT, IL-6, and bacterial infection in the MPP group were lower than those in the RMPP group (P < .05), and there was no significant difference in the mutation rate of 23sRNA A2063G and A2064G between the 2 groups (P > .05); logistic regression analysis showed that CRP, PCT, IL-6, alanine aminotransferase, lactate dehydrogenase, immunoglobulin A, IgG, and immunoglobulin M were the main influencing factors of RMPP (P < .05); the length of hospital stay, biochemical treatment of alanine aminotransferase, lactate dehydrogenase, cardiac troponin I, and inflammatory factors of CRP, PCT, and IL-6 in the bronchoalveolar lavage treatment group were lower than those in the general treatment group (P < .05). Children with MPP have more fever, cough, and dyspnea as the starting point, and mucosal congestion, edema, sputum embolism are the most common in bronchoscopy. Children with RMPP may be accompanied by decreased immune function and increased inflammation.
Evaluation of ixabepilone efficacy and tolerability in metastatic breast cancer
Authors: Erciyestepe Mert , Ekinci Ömer Burak , Seçmeler Şaban , Selvi Oğuzhan , Öztürk Ahmet Emin , Aydin Okan , Büyükkuşcu Asli , Atasever Tugay , Çelik Emir , Ertürk Kayhan , Atci Muhammed Mustafa
Published: November 2024

Although microtubule inhibitors are generally used in advanced stages, they provide the opportunity to prolong survival as an alternative when medical oncologists have difficulty finding options in their patients, who typically have a poor prognosis and most of whom are unresponsive to treatment. For this reason, we wanted to investigate the effect of ixabepilone treatment on survival in earlier metastatic lines. Our study also examined the frequency of side effects and survival differences in patients whose dose was reduced or whose treatment was discontinued. Our study includes patients diagnosed with metastatic breast cancer who received ixabepilone treatment between January 2011 and January 2021. Median overall survival (OS) in the group receiving ixabepilone on the 5th line and before was 22.0 months (95% CI: 21.0–22.9), in the group receiving ixabepilone after the 5th line was calculated as 10.0 months (95% CI: 8.9–11.0) (P < .001). Median OS (months) in the group receiving ixabepilone on the 4th line and before was 26.0 (95% CI: 23.6–28.3), in the group receiving ixabepilone after the 4th line was determined as 12.0 (95% CI: 10.5–13.4) (P < .001). Dose reduction or discontinuation of ixabepilone treatment in patients due to side effects did not affect OS and progression-free survival with ixabepilone statistically significantly. Ixabepilone treatment has side effects, similar to all other treatments used in metastatic breast cancer, however, these side effects are manageable. Additionally, since ixabepilone treatment is preferred in patients who have previously received many different chemotherapeutics and experienced cumulative toxicity, the side effects of ixabepilone may seem to be greater than they are. In our study, we showed that ixabepilone treatment has a statistically significant positive effect on survival if preferred in earlier metastatic lines. As similar studies increase in centers where ixabepilone treatment is generally given in advanced metastatic lines, treatment approaches may change in the coming years.
Rectal foreign body of a cosmetic bottle treated successfully by transanal retrieval: A case report
Authors: Liu Congcong , Li Yuantao
Published: November 2024

Rationale:

Retained rectal foreign bodies (RFBs) are unusual clinical presentations whose management is challenging for emergency physicians owing to variations in the object types, anorectal anatomy, sacral curvature, insertion times, and local contamination. Here, we present the diagnosis and treatment in 1 case of retained rectal foreign body.

Patient concerns:

A 62-year-old male presented to the emergency department with a cosmetic bottle inserted into the rectum while bathing. He had difficulty defecating and denied any underlying psychiatric illness. Before coming to the hospital, the patient attempted to remove the cosmetic bottle with a screwdriver but failed, causing the cosmetic bottle to penetrate further into the intestinal lumen. The patient felt that the anal bulging was gradually worsening.

Diagnoses:

Investigations, a digital rectal examination, and coronal abdominal computed tomography revealed a foreign body stuck in the rectum.

Interventions and outcomes:

After lateral internal sphincterotomy, the cosmetic bottle’s plastic cap was pinched using a towel clamp and rotated slowly. The patient had an uneventful recovery period; the difficult defecation and anal bulging were relieved.

Lessons:

This case proves that lateral internal sphincterotomy can be performed to remove retained rectal foreign bodies if sufficient sphincter relaxation and anal dilatation cannot be achieved with proper anesthesia.
Effect of K-line (−) or (+) on surgical outcomes in cervical ossification of the posterior longitudinal ligament: A systematic and meta-analysis
Authors: Wang Yongping , Chen Xiao , Luo Yuan , Chen Chang , Cui Ran
Published: November 2024

Background:

To conduct a systematic review and meta-analysis assessing the influence of K-line status on postoperative clinical outcomes in patients with cervical posterior longitudinal ligament ossification (OPLL).

Methods:

We searched PubMed, Embase, OVID, Cochrane Library, and Web of Science databases for English-language literature related to K-line and OPLL up to June 7, 2024. The study underwent rigorous selection, quality assessment, and data extraction, followed by meta-analysis using Review Manager 5.3 and Stata 17.0 software. This study has been registered with the international PROSPERO registry (registration number: CRD42024558578).

Results:

Seventeen articles encompassing 1247 patients were included. The meta-analysis revealed that patients with a positive K-line (K-line (+)) exhibited significantly enhanced Japanese Orthopaedic Association score recovery rate (mean differences [MD] = 19.28, 95% confidence interval [CI]: 12.28–26.28, P < .00001), Japanese Orthopaedic Association score (MD = 1.51, 95% CI: 0.64–2.37, P = .0007), C2-C7 Cobb angle (MD = 6.45, 95% CI: 3.73–9.17, P < .00001), alongside reduced occupation ratio (MD = −7.67, 95% CI: −10.86 to −4.49, P < .00001), C2-C7 sagittal vertical axis (MD = −6.18, 95% CI: −8.36 to −3.99, P < .00001), and neck disability index (MD = −1.85, 95% CI: −3.18 to −0.52, P = .006) at final follow-up compared to those with a negative K-line (K-line (−)). No significant differences were observed in postoperative complication rates (odds ratio = 1.15, 95% CI: 0.41–3.20, P = .79), final follow-up visual analog scale scores (MD = −0.10, 95% CI: −0.80 to 0.59, P = .77), or T1 slope (MD = 2.66, 95% CI: −0.20 to 5.52, P = .07) between the 2 groups.

Conclusion:

A positive preoperative K-line (K-line (+)) is a better predictor of prognosis and is associated with improved clinical outcomes in patients with multi-segmental cervical OPLL compared to a negative K-line (K-line (−)).
Roles of NOC3L and DDX17 in acquired immunodeficiency complicated with viral myocarditis and osteoporosis
Authors: Xiao Liping , Li Xin , Wang Jing-Jing , Quan Xue-Min , Zhao Chang-Song
Published: November 2024

Acquired immunodeficiency syndrome is a systemic infectious disease caused by human immunodeficiency virus infection, which could attack the bones and heart. However, the relationship between Nuclear Complex Associated 3 Homolog (NOC3L) and DEAD box helicase 17 (DDX17) and acquired immunodeficiency complicated with viral myocarditis and osteoporosis is unclear. The acquired immune deficiency dataset GSE140713, GSE147162 and the osteoporosis dataset (GSE230665), and viral myocarditis dataset (GSE150392) configuration files were generated from gene expression omnibus. The differentially expressed genes (DEGs) were screened and performed weighted gene co-expression network analysis. Construction and analysis of protein–protein interaction network. Functional enrichment analysis, gene set enrichment analysis, immune infiltration analysis, gene expression heatmap, and comparative toxicogenomics database analysis were performed. TargetScan screens miRNAs of DEGs. Thousand three hundred thirty-five DEGs were identified. According to gene ontology, they are mainly concentrated in the regulation of RNA biosynthesis, cytoplasmic ribosome, and the DNA binding transcription factor activity. In Kyoto Encyclopedia of Genes and Genomes analysis, they are mainly concentrated in TGF-β signal pathway, Notch signaling pathway, cAMP signaling pathway, and Apelin signaling pathway. Gene set enrichment analysis shows that DEGs are mainly enriched in cytoplasmic ribosome, transcriptional regulator activity, DNA binding transcription factor activity, TGF-β signal pathway, and Notch signal pathway. In the enrichment project of Metascape, tyrosine kinase receptor signaling, growth regulation, and enzyme-linked receptor protein signaling pathways can be seen in the gene ontology enrichment project. Four core genes (NOC3L, WDR46, SDAD1, and DDX17) were obtained. Core genes (NOC3L, WDR46, SDAD1, and DDX17) were low expressed in both acquired immunodeficiency and osteoporosis samples. Comparative toxicogenomics database analysis showed that core genes (NOC3L, WDR46, SDAD1, and DDX17) were associated with inflammation necrosis. The expressions of NOC3L and DDX17 are low in acquired immunodeficiency combined with viral myocarditis and osteoporosis.
Sublingual glyceryl trinitrate given during adenosine sestamibi myocardial perfusion imaging causes apparent transient ischaemic dilation in a propensity-matched analysis
Authors: Rose David S. , Hector Bradley M. , Kannan Shanthi , Lee Joseph C.
Published: November 2024

Objectives

Administration of sublingual glyceryl trinitrate (GTN) prior to resting radiotracer injection during myocardial perfusion imaging (MPI) has been advocated to aid detection of viable myocardium and increase the extent of reversible perfusion defects. However, GTN is also known to reduce resting left ventricular volume and could thus increase the transient ischaemic dilation (TID) ratio, independently of severe or extensive coronary artery disease. We aimed to determine if GTN administration causes an increase in the TID ratio.

Methods

Causal inference using propensity score matched analysis was used to assess the effect of GTN on TID ratios in subjects undergoing adenosine sestamibi MPI.

Results

From 597 consecutive patients undergoing MPI, we selected a treatment group of 51 who received 400 μg of sublingual GTN before resting sestamibi injection and 51 propensity score matched controls. Mean TID ratios were 1.24 in treated subjects and 1.10 in controls (mean difference 0.15; 95% CI, 0.05–0.25; P = 0.0018). The mean difference in TID ratio fell progressively in each quartile of time elapsed between GTN administration and image acquisition. The proportion with TID ratios equal and greater than an abnormal threshold of 1.39 was 17.6% among the treated and 0% in controls (P = 0.0010). The effect on TID ratio was not restricted to those with moderate-to-severe stress perfusion defects or accompanied by greater reversible perfusion defects.

Conclusions

There is evidence of a cause-and-effect relationship between administering GTN before resting sestamibi injection and increased TID ratio on MPI. This may be a source of misleading false positive TID findings.
Prevalence and Predictors of the Unmet Supportive Needs of Patients With Cancer in Oman
Authors: Al Qadire Mohammad , Abdelrahman Hanan , Al Sabei Sulaiman , Aljezawi Ma’en , Al Omari Omar , Al Salmi Nasser , Al Awaisi Huda , Aljezawi Hala
Published: November 2024

Background

Unmet supportive needs are directly correlated with more frequent psychological distress, reduced quality of life, and low patient satisfaction with healthcare and indirectly connected with low compliance with treatment and increased care-related costs.

Objective

To assess the spectrum of unmet needs among patients with cancer in Oman and identify predictors of these needs and their relationship with psychological distress and symptom burden.

Method

A descriptive, correlational study design was used, involving 551 patients with cancer from 2 major healthcare facilities in Muscat, Oman. Data on patients’ unmet needs were collected between January and June 2023 using the Supportive Care Needs Survey Short-Form 34.

Results

Participants had a mean age of 45.8 (SD, 15.6) years, with female patients comprising 65.5% of the sample. Breast cancer was the most prevalent type of cancer. The mean unmet need score was 31.0/100 (SD, 20.1). Statistical analysis revealed significant predictors of unmet needs, including marital status, treatment type, performance status, symptom interference, and psychological distress, with the regression model explaining 26% of the variance in unmet needs.

Conclusions

Healthcare providers must regularly assess supportive needs, recognizing that they may vary across populations and are influenced by cultural factors. Additionally, individuals identified as having characteristics that predict higher levels of need should receive focused and prioritized supportive care.

Implications for Practice

By adopting regular tailored assessments that address the comprehensive supportive needs of patients with cancer, clinicians can significantly enhance patients’ quality of life and optimize treatment outcomes.
Long-Term Moderating Effect of Resilience Capacity on the Impact of Stressful Life Events on Depressive Symptoms After 6 Years in Outpatients With Depression and/or Anxiety
Authors: Chen Yi-Xin , Lin Shih-Hsien , Chen Po See , Lu Tsung-Hua , Huang Huei-Lin , Lee I Hui
Published: November 2024

Previous cross-sectional studies have utilized scales to explore potential indications of the moderating effect of resilience on the relationship between stressful life events (SLEs) and mental health. However, there remains a notable dearth of psychometrically driven models in longitudinal resilience research, especially concerning the prognosis of individuals with affective disorders and/or anxiety. This study aimed to investigate whether baseline resilience capacity, measured by the Connor-Davidson Resilience Scale, could mitigate the impact of SLEs on depressive symptoms assessed using the Beck Depression Inventory-II among 66 outpatients with depression and/or anxiety disorders during a follow-up period ranging from 4–8 years. Hierarchical linear regression analysis revealed that baseline resilience capacity significantly moderated the effect of SLEs on depressive symptoms at the end point, but neither SLEs nor baseline resilience capacity was significantly correlated with depressive symptoms at the end point after controlling for potential confounders. Patients with higher levels of baseline resilience capacity showed fewer depressive symptoms in response to SLEs. These findings underscore the potential of resilience capacity as a promising target for therapeutic interventions.
A Review of Stereotactic Body Radiotherapy in the Management of Gastrointestinal Malignancies
Authors: Hollis Emily , Nganga David W. , Yanagihara Ted K.
Published: November 2024

In this review, we explore the role of stereotactic body radiotherapy (SBRT) and other advanced radiotherapy techniques in the treatment of gastrointestinal malignancies, which primarily involves primary and secondary liver cancers and pancreatic cancers. The review examines radiotherapy in both curative and palliative settings, emphasizing the evolution of SBRT and hypofractionation as alternatives to conventional radiotherapy. We review the recent literature evaluating radiotherapy in the management of unresectable, borderline resectable, and metastatic pancreatic cancer, highlighting recent advances in radiotherapy techniques that aim to improve local control, reduce toxicity, and increase resectability in appropriate patients. For primary liver cancers (hepatocellular carcinoma and cholangiocarcinoma), SBRT has emerged as a potential noninvasive alternative to surgery, particularly in patients with unresectable tumors or those awaiting liver transplantation. The review also provides insights into ongoing clinical trials, comparative studies between SBRT and other local therapies such as radiofrequency ablation, and the use of radiotherapy in managing liver metastases from various primary cancers. Throughout, we emphasize limitations in the available literature and highlight areas of ongoing and future investigation.
Advances in Stereotactic Body Radiation Therapy for Lung Cancer
Authors: Lee Katie N. , Owen Dawn
Published: November 2024

Stereotactic body radiation therapy (SBRT) delivers curative-intent radiation to patients with early-stage non-small cell lung cancer and inoperable thoracic lesions. With improved techniques in tumor delineation, motion management, and delivery of radiation treatments, the therapeutic window within the thorax is able to be maximized. Ongoing technological advances enable highly targeted ablative radiation therapy while sparing adjacent sensitive organs at risk. Further applications of SBRT with combinatorial immunotherapy, the usage of particle therapy, and for patients with more advanced stages of lung cancer and other histologies mark exciting possibilities for the role of SBRT within the thorax.
Technical and Quality Considerations for Stereotactic Radiation Treatment Techniques
Authors: Covington Elizabeth L. , Popple Richard A.
Published: November 2024

Stereotactic radiosurgery (SRS) and stereotactic body radiation therapy (SBRT), collectively termed SRS-SBRT, are advanced treatment modalities delivering high doses of radiation in a single treatment or condensed treatment phase. Due to the small margins and steep dose gradient used in SRS-SBRT, the technical and safety considerations are more stringent than traditional radiation therapy and may include more advanced simulation, patient immobilization, treatment planning, and treatment delivery techniques. Respiratory motion management and intrafraction motion monitoring are often used during SRS-SBRT to ensure treatments are robust to both internal organ motion and patient movement during treatment. To ensure optimal treatment quality, SRS-SBRT programs should use multidisciplinary coordination of care to ensure patient-specific treatment strategies are used for optimal patient outcomes. Quality and safety considerations are presented, including peer review and external validation, for optimizing quality and adhering to national guidelines for stereotactic techniques.
Contrast-Enhanced Ultrasound Compared With Hepatobiliary Agent MRI for Differentiation of Focal Nodular Hyperplasia and Hepatic Adenoma: A Prospective Trial
Authors: Swensson Jordan , McCrate Mary , Halappa Vivek Gowdra , Stethen Taylor , Akisik Fatih
Published: November 2024

Magnetic resonance imaging (MRI) may be time-consuming, expensive, or poorly tolerated by patients with liver lesions. This is a prospective clinical trial designed to evaluate if contrast-enhanced ultrasound (CEUS) can be used to differentiate focal nodular hyperplasia (FNH) from hepatocellular adenoma (HCA) with similar accuracy compared with hepatobiliary agent MRI.

Institutional review board approval was obtained (1805450097), and the trial was registered with ClinicalTrials.gov (NCT03652636). From 2018 through 2023, 40 patients who had lesions consistent with FNH or HCA on HBA-MRI underwent 1-time prospective CEUS of up to 2 hepatic lesions. Sonographic images obtained before and after intravenous administration of 2 mL sulfur hexafluoride lipid-type A microspheres (Lumason) per lesion totaling 59 lesions (27 FNHs/32 HCAs). Two blinded radiologists provided a diagnosis of FNH or HCA.

Thirty-eight female and 2 male patients (age 36.7 ± 9.9) were scanned. Radiologists provided diagnosis of FNH or HCA with respective sensitivity (66.7/64.0%), specificity (71.9/90.6%), and accuracy (69.5/78.0%). For 38 lesions greater than or equal to 2 cm in size (17 FNHs/21 HCAs), readers had sensitivity (70.6/84.2%), specificity (70.6/84.2%), and accuracy (81.5/86.8%). Interobserver agreement for all lesions was fair (κ = 0.34), whereas agreement for lesions 2 cm or larger was substantial (κ = 0.67).

Contrast-enhanced ultrasound can differentiate FNH from HCA with accuracy approaching that of hepatobiliary agent MRI for lesions 2 cm or greater. Interobserver agreement is improved with larger lesions. CEUS may have utility as an alternate diagnostic tool for FNH/HCA, especially in patients who cannot or do not desire to undergo MRI.
Electroconvulsive Therapy in a Severely Depressed, Bipolar I Disorder Patient, Who Is a 3-Time Liver Transplant Recipient Due to Primary Sclerosing Cholangitis
Authors: Ilic Thomas D. , McCarthy Caitlin J. , Steele Ian
Published: November 2024

Patients with bipolar I disorder who develop major depressive episodes with psychotic features and suicide ideations following severe episodes of mania can be difficult to treat with medications alone. Electroconvulsive therapy (ECT) is a treatment modality that can be quite helpful to these patients and lead to remission of depressive symptoms also while providing protection against mania. However the literature about using ECT in medically complex patients is sparse, which can limit guidance and knowledge on the specific risks of the procedure in specialized patient populations. We report in our own case the use of ECT to treat a major depressive episode in a young adult with bipolar I disorder who also has a history of 3 liver transplants in his childhood due to primary sclerosing cholangitis. Despite prior case reports relating the safety of ECT in liver transplant recipients, we discuss that our patient had a large intracranial hemorrhage during his first ECT that required 2 decompressive craniotomies and extensive physical rehabilitation. This case serves to expand the limited literature on the use of ECT in patients with history of liver transplants and to increase understanding of risks of the procedure in his specialized patient population.
CAIRS: A causal artificial intelligence recommendation system for digital mental health
Authors: Varidel Mathew , An Victor , Hickie Ian B. , Cripps Sally , Marchant Roman , Scott Jan , Crouse Jacob J. , Poulsen Adam , O’Dea Bridianne , Iorfino Frank
Published: November 2024

Digital mental health tools have the prospect to enhance and expand access to care for those in need. Some tools provide interventional recommendations to individuals, typically using simple static rule-based systems (e.g., if-else statements) or by incorporating predictive artificial intelligence. However, interventional recommendations require a decision based on the comparison of future outcomes under different interventions, which requires causal considerations. Here we develop CAIRS, a causal artificial intelligence recommendation system that provides personalised interventional recommendations using an individual’s current presentation and the learned dynamics between domains to identify and rank intervention targets that have the greatest impact on future outcomes. Our approach was applied to longitudinal data of multiple mental health and related domains at two timepoints (1 week - 6 months from baseline) collected from a digital mental health tool. In our example, psychological distress was found to be the key influential domain that affected multiple domains (e.g., personal functioning, social connection), and thus was typically the preferred target in complex cases where multiple domains were unhealthy. Our approach is broadly applicable to recommendation contexts where causal considerations are important, and the framework could be incorporated within a live app to enhance digital mental health tools.
Deep Learning of Cellular Metabolic Flux Distributions Predicts Lifespan
Authors: Hilsabeck Tyler A.U. , Rea Shane L.
Published: November 2024

It is a common observation that individuals within a species age at different rates. Variation in both genetics and environmental interaction are generally thought responsible. Surprisingly, even genetically identical organisms cultured under environmentally homogeneous conditions age at different rates, implying a more fundamental cause of aging. Here we have examined the basis for lifespan variance in haploid, single-celled yeast ofSaccharomyces cerevisiae. The probabilistic nature of metabolism means metabolites often, but not always, follow the same route through the metabolic network. We speculate redundancy in metabolic pathway choice is sufficient to explain lifespan variance. To interrogate the reaction flux space ofS. cerevisiaewe used a model of its intermediary metabolism, comprising 1,150 genes, 4,058 reactions, and 2,742 metabolites (yeast GEM_v8.5.0). We restricted traffic through the metabolic network by knocking out each of the 1,150 genes, then generated a total of 406,500 flux distributions spanning the solution space of the resulting 812 viable mutants. We collected replicative life span (RLS) data for the 812 viable mutants, corresponding to 66,400 individual cells. Four approaches were then employed to test whether reaction flux configuration could be used to predict lifespan: Principal Component Analysis (PCA) in conjunction with non-linear modeling of RLS; deep learning of RLS using either a Regression Neural Network (RNN) or a Classification Neural Network (CfNN); and deep learning using a convolutional neural network (CNN) following conversion of flux distributions to pixelated images. The four approaches reveal a core network of highly correlated reactions controlling aging rate that is sufficient to explain all lifespan variance. It includes biosynthetic pathways encompassing ceramides, monolysocardiolipins, phosphoinositides, porphyrin and glycerolipids. Our data lead to two novel conclusions. First, variance in the replicative lifespan ofS. cerevisiaeis an emergent property of its metabolic network. Second, there is convergence among metabolic configurations toward three meta-stable flux states – one associated with extended life, another with shortened life, and a third with wild type life span.

One Sentence Summary

Traffic routes and rates through the metabolic network ofS. cerevisiaefully account for variance in replicative lifespan.
Scaling down for efficiency: Medium-sized protein language models perform well at transfer learning on realistic datasets
Authors: Vieira Luiz C. , Handojo Morgan L. , Wilke Claus O.
Published: November 2024

Protein language models (pLMs) can offer deep insights into evolutionary and structural properties of proteins. While larger models, such as the 15 billion parameter model ESM-2, promise to capture more complex patterns in sequence space, they also present practical challenges due to their high dimensionality and high computational cost. We systematically evaluated the performance of various pLMs across multiple biological datasets to assess the impact of model size on transfer learning. Surprisingly, we found that larger models not necessarily outperform smaller ones, in particular when data is limited. Medium-sized models, such as ESM-2 650M and ESM C 600M, demonstrated consistently good performance, falling only slightly behind their larger counterparts—ESM-2 15B and ESM C 6B—despite being many times smaller. Additionally, we compared various methods of compressing embeddings prior to transfer learning, and we found that mean embeddings consistently outperformed other compression methods. In summary, ESM C 600M with mean embeddings offers an optimal balance between performance and efficiency, making it a practical and scalable choice for transfer learning in realistic biological applications.

Significance Statement

This work challenges the common belief that larger language models always yield better results, here in the context of protein biochemistry. By systematically comparing transformer models of different sizes in transfer learning tasks, we demonstrate that medium size models, such as ESM C 600M, frequently perform as well as or better than larger variants, especially when data is limited. These findings provide an efficient strategy for machine learning-based protein analysis. Smaller and more efficient models help democratize cutting-edge AI approaches, making them more accessible to researchers with limited computational resources.
Insights into the conformational dynamics of the cytoplasmic domain of metal-sensing sensor histidine kinase ZraS
Authors: Mahapatra Nilima , Mahanta Pranjal , Pandey Shubhant , Acharya Rudresh
Published: November 2024

ZraS is a metal sensor integral to ZraPSR, a two-component signaling system found in enterobacters. It belongs to a family of bifunctional sensor histidine kinases (SHKs) and is speculated to sense zinc-induced stress on the bacterial envelope. Information on the structure-function relationship of sensor kinases is elusive due to the lack of full-length structures, intrinsically dynamic behavior, and difficulty trapping them in active state conformations. While the kinase domains of a few sensor histidine kinases are well-characterized, they exhibit significant functional diversity attributed to their modular multi-domain arrangement in the cytoplasmic region, combined with other signal transducing elements such as simple helices, HAMP and PAS domains. We report the crystal structure of the entire cytoplasmic region ofEscherichia coliZraS (EcZraS-CD) resolved at resolution 2.49 Å, comprising of a unique helical linker and the kinase domain. In the asymmetric unit, four molecules of ZraS assemble as homodimers trapped as two ligand-bound occluded conformers. Our analysis using these conformers show that modulation of the dimer bundle through segmental helical bending, sliding, and rotation leads to reorganization of the dimerization interface during kinase activation. Further, our analysis reveals the significance of aromatic amino acid interactions and loop residues at the dimer base in regulating the directionality of rotation during autophosphorylation. We also performed an invitro coupled assay to determine ATPase activity. Overall, our findings provide structure-based mechanistic insights into the process of autophosphorylation in trans-acting sensor histidine kinases.
Implication of S-1 biomarkers on aging and prognosis in elderly patients with lung cancer treated by adjuvant S-1 chemotherapy: Accompanying results of the Setouchi Lung Cancer Group Study 1201
Authors: Soh Junichi , Yamamoto Hiromasa , Okumura Norihito , Suzuki Hiroyuki , Nakata Masao , Fujiwara Toshiya , Gemba Kenichi , Sano Isao , Fujinaga Takuji , Kataoka Masafumi , Terasaki Yasuhiro , Fujimoto Nobukazu , Kataoka Kazuhiko , Kosaka Shinji , Yamashita Motohiro , Inokawa Hidetoshi , Inoue Masaaki , Nakamura Hiroshige , Yamashita Yoshinori , Takahashi Yuta , Torigoe Hidejiro , Sato Hiroki , Tomida Shuta , Hotta Katsuyuki , Yoshioka Hiroshige , Morita Satoshi , Matsuo Keitaro , Sakamoto Junichi , Date Hiroshi , Toyooka Shinichi
Published: November 2024

BACKGROUNDS

The management of elderly patients presents several challenges due to age-related declines; however recent recommendations advocate for age not being the sole determinant for adjuvant treatment decisions in patients with non-small cell lung cancer (NSCLC). Aging may alter expression levels of 5-fluorouracil (5-FU) biomarkers.

METHODS

Expression changes with aging were explored using The Cancer Genome Atlas (TCGA) database. 5-FU-related biomarker expressions, including thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyltransferase, epidermal growth factor receptor (EGFR), and excision repair cross-complementation group-1 (ERCC1), were assessed by the quantitative reverse-transcription PCR assays in 89 NSCLCs elderly patients (≥ 75 years old) receiving adjuvant S-1, an oral fluoropyrimidine agent, therapy in a SLCG1201 trial.RESULTS:TCGA database analysis (n=955) indicated decreasedTSexpression with aging, particularly in those 75 or older. In the SCLG1201 trial, univariate analysis revealed that highEGFRand lowTSexpressions correlated with favorable recurrence-free survival (RFS)(p=0.0264) and overall survival (OS)(p=0.0365), respectively. Multivariable analysis confirmed pathological stage as an independent prognostic factor for both RFS and OS (p=0.0052 and 0.0352, respectively).EGFRmutant tumors (n=27) showed significantly higherDPD(p=0.0066) andEGFR(p<0.0001) expressions, and lowerTS(p=0.0125) andERCC1(p=0.0015) expressions.

CONCLUSION

Despite pathological stage being an independent prognostic factor, highEGFRand lowTSexpressions may predict better clinical outcomes in elderly NSCLC patients using adjuvant S-1. The age-related decrease in TS expression supports the potential benefit of 5-FU-based therapy in them compared to younger patients. Further research is warranted to validate these clinical implications.
The conserved landscape of RNA modifications and transcript diversity across mammalian evolution
Authors: Santos-Rodriguez G , Srivastava A , Ravindran A , Oyelami F , Ip KH , Gupta P , Villanueva J , King HE , Grootveld A , Blackburn J , Gupta I , Vieira HGS , Shirokikh NE , Eyras E , Weatheritt RJ
Published: November 2024

Gene expression programs underpin the development of shared phenotypes, yet the importance of transcript complexity in shaping mammalian evolution remains unclear. Here we present a comprehensive long-read direct RNA sequencing atlas of full-length transcripts and their m6A modifications across six tissues (hippocampus, frontal cortex, cerebellum, testes, skeletal muscle, and liver) in five mammals (human, mouse, rat, dog, and cow) and a non-mammalian out-group (chicken). Our analysis reveals that 29% of genes have multiple mammalian-conserved alternative transcripts, with 31% of these genes showing tissue-specific switching of the major transcript isoforms. We uncover extensive conservation of coordinated splicing events, primarily driven by tissue-specific mutually associated exon splicing, particularly in neural tissues and cytoskeletal genes. At the epitranscriptome level, we find that 14.2% of m6A RNA modifications are conserved across mammals, with 39% of analysed genes containing a conserved m6A RNA modification. Our work provides unprecedented insight into the evolution of transcript complexity and the epitranscriptome, highlighting their potential roles in shaping mammalian phenotypic diversity and providing a valuable resource for understanding post-transcriptional regulation across mammalian evolutionary time.
Separating three variability and noise sources in the response fluctuation of brain stimulation
Authors: Ma K. , Goetz S. M.
Published: November 2024

Motor-evoked potentials (MEPs) are among the few directly observable responses to suprathreshold brain stimulation and serve a variety of applications. If the MEP size is graphed over the stimulation strength, they form an input–output (IO), recruitment, or dose–response curve. Previous statistical models with two variability sources inherently consider the small MEPs at the low plateau as part of the neural recruitment properties. However, recent studies demonstrated that small MEP responses are contaminated and over-shadowed by background noise of mostly technical quality and suggested that the recruitment curve should continue below this noise level. This work intends to separate physiological variability from background noise and improve the description of recruitment behaviour. We developed a model with three variability sources and a logarithmic logistic function without a lower plateau. Compared to previous models, we incorporated an additional source for background noise from amplifiers, electrode impedance, and remote bioelectric activity, which form the obesrved low-side plateau. Compared to the dual-variability source modes, our approach better described IO characteristics, evidenced by lower Bayesian Information Criterion scores across all subjects and pulse shapes. The model independently extracted hidden variability information across the stimulated neural system and isolated it from background noise, which led to an accurate estimation of the IO curve parameters. This new model offers a robust tool to analyse brain stimulation IO curves in clinical and experimental neuroscience, reducing the risk of spurious results from inappropriate statistical methods. By providing a more accurate representation of MEP responses and variability sources, this approach advances our understanding of cortical excitability and may improve the assessment of neuromodulation effects.
Antibody Data Analysis from Diverse Immune Libraries
Authors: Fahad Ahmed S. , Gutiérrez-Gonzalez Matías F. , Madan Bharat , DeKosky Brandon J.
Published: November 2024

Antibody functional screening studies and next-generation sequencing require careful processing and interpretation of sequence data for optimal results. Here, we provide a detailed protocol for the functional analysis of antibody gene data, including antibody repertoire quantification and functional mapping of high-throughput screening data based on enrichment ratio values, which are a simple way to determine the enrichment of each sequenced antibody after sorting a display library against desired antigens. This protocol enables a user to apply a set of simple yet powerful bioinformatic tools for high-throughput analysis and interpretation of antibody data that is especially well suited for display library screening and for antibody discovery applications.