Longitudinal registration of thoracic CT images with radiation-induced lung diseases: A divide-and-conquer approach based on component structure wise registration using coherent point drift.

BACKGROUND AND OBJECTIVE: Registration of pulmonary computed tomography (CT) images with radiation-induced lung diseases (RILD) was essential to investigate the voxel-wise relationship between the formation of RILD and the radiation dose received by different tissues. Although various approaches had been developed for the registration of lung CTs, their performances remained clinically unsatisfactory for registration of lung CT images with RILD. The main difficulties arose from the longitudinal change in lung parenchyma, including RILD and volumetric change of lung cancers, after radiation therapy, leading to inaccurate registration and artifacts caused by erroneous matching of the RILD tissues. METHODS: To overcome the influence of the parenchymal changes, a divide-and-conquer approach rooted in the coherent point drift (CPD) paradigm was proposed. The proposed method was based on two kernel ideas. One was the idea of component structure wise registration. Specifically, the proposed method relaxed the intrinsic assumption of equal isotropic covariances in CPD by decomposing a lung and its surrounding tissues into component structures and independently registering the component structures pairwise by CPD. The other was the idea of defining a vascular subtree centered at a matched branch point as a component structure. This idea could not only provide a sufficient number of matched feature points within a parenchyma, but avoid being corrupted by the false feature points resided in the RILD tissues due to globally and indiscriminately sampling using mathematical operators. The overall deformation model was built by using the Thin Plate Spline based on all matched points. RESULTS: This study recruited 30 pairs of lung CT images with RILD, 15 of which were used for internal validation (leave-one-out cross-validation) and the other 15 for external validation. The experimental results showed that the proposed algorithm achieved a mean and a mean of maximum 1 % of average surface distances <2 and 8 mm, respectively, and a mean and a maximum target registration error <2 mm and 5 mm on both internal and external validation datasets. The paired two-sample t-tests corroborated that the proposed algorithm outperformed a recent method, the Stavropoulou's method, on the external validation dataset (p < 0.05). CONCLUSIONS: The proposed algorithm effectively reduced the influence of parenchymal changes, resulting in a reasonably accurate and artifact-free registration.

Hydrogen sulfide coordinates glucose metabolism switch through destabilizing tetrameric pyruvate kinase M2.

Most cancer cells reprogram their glucose metabolic pathway from oxidative phosphorylation to aerobic glycolysis for energy production. By reducing enzyme activity of pyruvate kinase M2 (PKM2), cancer cells attain a greater fraction of glycolytic metabolites for macromolecule synthesis needed for rapid proliferation. Here we demonstrate that hydrogen sulfide (H2S) destabilizes the PKM2 tetramer into monomer/dimer through sulfhydration at cysteines, notably at C326, leading to reduced PKM2 enzyme activity and increased PKM2-mediated transcriptional activation. Blocking PKM2 sulfhydration at C326 through amino acid mutation stabilizes the PKM2 tetramer and crystal structure further revealing the tetramer organization of PKM2-C326S. The PKM2-C326S mutant in cancer cells rewires glucose metabolism to mitochondrial respiration, significantly inhibiting tumor growth. In this work, we demonstrate that PKM2 sulfhydration by H2S inactivates PKM2 activity to promote tumorigenesis and inhibiting this process could be a potential therapeutic approach for targeting cancer metabolism.

Robotic versus laparoscopic pelvic lateral lymph node dissection in locally advanced rectal cancer: a systemic review and meta-analysis.

BACKGROUND: There are few available studies that compare the feasibility, efficacy, and safety of robotic pelvic lateral lymph node dissection compared to laparoscopic pelvic lateral lymph node dissection (LPLND) in advanced rectal cancer. This meta-analysis aims to compare perioperative outcomes between robotic and LPLND. METHODS: We performed a systemic literature review of PubMed, Embase, and Web of Science databases. Perioperative parameters were extracted and pooled for analysis. This meta-analysis provided an analysis of heterogeneity and prediction intervals. RESULTS: Five studies were included: 567 patients divided between 266 robotic and 301 LPLND. Overall operation time was longer in the robotic group than laparoscopic group (difference in means = 67.11, 95% CI [30.80, 103.42], p < 0.001) but the difference in the pelvic lateral lymph dissection time was not statistically significant (difference in means = - 1.212, 95% CI [ - 11.594, 9.171], p = 0.819). There were fewer overall complications in the robotic than in the laparoscopic group (OR = 1.589, 95% CI [1.009, 2.503], p = 0.046), especially with respect to urinary retention (OR = 2.23, 95% CI [1.277, 3.894], p = 0.005). More pelvic lateral lymph nodes were harvested by robotic surgery than by laparoscopy (differences in means = - 1.992, 95% CI [ - 2.421, 1.563], p < 0.001). CONCLUSIONS: In this meta-analysis, robotic pelvic lateral lymph node dissection was associated with more pelvic lateral lymph nodes harvested and lower overall complications, especially urinary retention when compared to LPLND. Further studies are needed to reinforce these findings.

The NTE domain of PTENα/ß promotes cancer progression by interacting with WDR5 via its SSSRRSS motif.

PTENα/ß, two variants of PTEN, play a key role in promoting tumor growth by interacting with WDR5 through their N-terminal extensions (NTEs). This interaction facilitates the recruitment of the SET1/MLL methyltransferase complex, resulting in histone H3K4 trimethylation and upregulation of oncogenes such as NOTCH3, which in turn promotes tumor growth. However, the molecular mechanism underlying this interaction has remained elusive. In this study, we determined the first crystal structure of PTENα-NTE in complex with WDR5, which reveals that PTENα utilizes a unique binding motif of a sequence SSSRRSS found in the NTE domain of PTENα/ß to specifically bind to the WIN site of WDR5. Disruption of this interaction significantly impedes cell proliferation and tumor growth, highlighting the potential of the WIN site inhibitors of WDR5 as a way of therapeutic intervention of the PTENα/ß associated cancers. These findings not only shed light on the important role of the PTENα/ß-WDR5 interaction in carcinogenesis, but also present a promising avenue for developing cancer treatments that target this pathway.

Anthraquinone/activated carbon electrochemical sensor and its application in acetaminophen analysis.

Acetaminophen (AC) can inhibit the synthesis of prostaglandins in the body, and has antipyretic and analgesic effects. In this paper, a two-step microwave impregnation method was used to prepare anthraquinone (AQ)-doped carbon composite, which were applied to the surface modification of glassy carbon electrodes (GCE) for the determination of acetaminophen (AC) using differential pulse voltammetry (DPV). The composites were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), Raman and Fourier infrared spectroscopy (FT-IR). The results showed that anthraquinone was successfully modified on the surface of activated carbon. The peak current of AC increased with its concentration in the range of 0.1 µM to 700 µM (R2 = 0.998) and a detection limit of 0.05 µM was obtained with 20%AQ doped carbon electrochemical sensor (20%AQ-C/GCE). Electrochemical Impedance Spectroscopy (EIS) test results indicated that the charge transfer resistance (Rct) of 20%AQ-C/GCE is only the one-fourth of that of bare GCE. The proposed 20%AQ-C/GCE sensor has good stability, reproducibility and selectivity for the detection of AC. The sensor is also suitable for the detection of real samples, indicating its good practicality.

Pluripotent stem cells for target organ developmental toxicity testing.

Prenatal developmental toxicity research focuses on understanding the potential adverse effects of environmental agents, drugs, and chemicals on the development of embryos and fetuses. Traditional methods involve animal testing, but ethical concerns and the need for human-relevant models have prompted the exploration of alternatives. Pluripotent stem cells (PSCs) are versatile cells with the unique ability to differentiate into any cell type, serving as a foundational tool for studying human development. Two-dimensional (2D) PSC models are often chosen for their ease of use and reproducibility for high-throughput screening. However, they lack the complexity of an in vivo environment. Alternatively, three-dimensional (3D) PSC models, such as organoids, offer tissue architecture and intercellular communication more reminiscent of in vivo conditions. However, they are complicated to produce and analyze, usually requiring advanced and expensive techniques. This review discusses recent advances in the use of human PSCs differentiated into brain and heart lineages and emerging tools and methods that can be combined with PSCs to help address important scientific questions in the area of developmental toxicology. These advancements and new approach methods align with the push for more relevant and predictive developmental toxicity assessment, combining innovative techniques with organoid models to advance regulatory decision-making.

Chemical inhibitors targeting histone methylation readers.

Histone methylation reader domains are protein modules that recognize specific histone methylation marks, such as methylated or unmethylated lysine or arginine residues on histones. These reader proteins play crucial roles in the epigenetic regulation of gene expression, chromatin structure, and DNA damage repair. Dysregulation of these proteins has been linked to various diseases, including cancer, neurodegenerative diseases, and developmental disorders. Therefore, targeting these proteins with chemical inhibitors has emerged as an attractive approach for therapeutic intervention, and significant progress has been made in this area. In this review, we will summarize the development of inhibitors targeting histone methylation readers, including MBT domains, chromodomains, Tudor domains, PWWP domains, PHD fingers, and WD40 repeat domains. For each domain, we will briefly discuss its identification and biological/biochemical functions, and then focus on the discovery of inhibitors tailored to target this domain, summarizing the property and potential application of most inhibitors. We will also discuss the structural basis for the potency and selectivity of these inhibitors, which will aid in further lead generation and optimization. Finally, we will also address the challenges and strategies involved in the development of these inhibitors. It should facilitate the rational design and development of novel chemical scaffolds and new targeting strategies for histone methylation reader domains with the help of this body of data.

Results of streamlining TAVR procedure towards a minimalist approach: a single center experience in Taiwan.

Trans-femoral transcatheter aortic valve replacement (TF-TAVR) performed under conscious sedation (LACS) is not yet become routine practice in Taiwan. We aimed to compared the results between patients received general anesthesia (GA) versus LACS. Our cohort was divided into 3 groups: initial 48 patients received TF-TAVR under routine GA (GA group), subsequent 50 patients under routine LACS (LACS group 1), and recent 125 patients under LACS (LACS group 2). The baseline, procedural characteristics and all outcomes were prospectively collected and retrospectively compared. From Sep 2010 to July 2019, a total of 223 patients were included. The procedure time (157.6 ± 39.4 min vs 131.6 ± 30.3 vs 95.2 ± 40.0, < 0.0001), contrast medium consumption (245.6 ± 92.6 ml vs 207.8 ± 77.9 vs 175.1 ± 64.6, < 0.0001), length of intensive care unit (2 [1-5] days vs 2 [1-3] vs 1 [1-1], P = 0.0001) and hospital stay (9 [7-13] days vs 8 [6-11] vs 6 [5-9], P = 0.0001) decreased significantly with LACS, combined with a trend of less hospital acquired pneumonia (12.5% vs 6.0% vs 5.6%, P = 0.427). 1-year survival rate were also different among 3 groups (83.3% vs 90.0% vs 93.6%, P = 0.053). In our single center experience, a "minimalist" approach of TF-TAVR procedure resulted in less medical resources usage, along with more favorable clinical outcomes.

Relieving Stress Concentration through Anion-Cation Codoping toward Highly Stable Nickel-Rich Cathode.

Nickel-rich LiNi0.8Co0.15Al0.015O2 (NCA) with excellent energy density is considered one of the most promising cathodes for lithium-ion batteries. Nevertheless, the stress concentration caused by Li+/Ni2+ mixing and oxygen vacancies leads to the structural collapse and obvious capacity degradation of NCA. Herein, a facile codoping of anion (F-)-cation (Mg2+) strategy is proposed to address these problems. Benefiting from the synergistic effect of F- and Mg2+, the codoped material exhibits alleviated Li+/Ni2+ mixing and demonstrates enhanced electrochemical performance at high voltage (≥4.5 V), outperformed the pristine and F-/Mg2+ single-doped counterparts. Combined experimental and theoretical studies reveal that Mg2+ and F- codoping decreases the Li+ diffusion energy barrier and enhances the Li+ transport kinetics. In particular, the codoping synergistically suppresses the Li+/Ni2+ mixing and lattice oxygen escape, and alleviates the stress-strain accumulation, thereby inhibiting crack propagation and improving the electrochemical performance of the NCA. As a consequence, the designed Li0.99Mg0.01Ni0.8Co0.15Al0.05O0.98F0.02 (Mg1+F2) demonstrates a much higher capacity retention of 82.65% than NCA (55.69%) even after 200 cycles at 2.8-4.5 V under 1 C. Furthermore, the capacity retention rate of the Mg1+F2||graphite pouch cell after 500 cycles is 89.6% compared to that of the NCA (only 79.4%).

Quantification of cardiac pumping mechanics in TAVI patients: A pilot study utilizing minimally invasive method for pressure-volume analysis.

The ventriculo-arterial coupling (VAC) and left ventricle (LV) mechanics are crucial and play an important role in the pathophysiology of aortic stenosis (AS). The pressure-volume (PV) analysis is a powerful tool to study VAC and LV mechanics. We proposed a novel minimally-invasive method for PV analysis in patients with severe AS receiving transcatheter aortic valve implantation (TAVI). Patients with severe AS were prospectively enrolled in a single center. LV pressure and cardiac output were recorded before and after TAVI. We constructed the PV loop for analysis by analyzing LV pressure and the assumed flow. 26 patients were included for final analysis. The effective arterial elastance (Ea) decreased after TAVI (3.7 ± 1.3 vs. 2.9 ± 1.1 mmHg/mL, p < 0.0001). The LV end-systolic elastance (Ees) did not change immediately after TAVI (2.4 ± 1.3 vs. 2.6 ± 1.1 mmHg/mL, p = 0.3670). The Ea/Ees improved after TAVI (1.8 ± 0.8 vs. 1.2 ± 0.4, p < 0.0001), demonstrating an immediate improvement of VAC. The stroke work (SW) did not change (7669.6 ± 1913.8 vs. 7626.2 ± 2546.9, p = 0.9330), but the pressure-volume area (PVA) decreased (14469.0 ± 4974.1 vs. 12177.4 ± 4499.9, p = 0.0374) after TAVI. The SW/PVA increased after TAVI (0.55 ± 0.12 vs. 0.63 ± 0.08, p < 0.0001) representing an improvement of LV efficiency. We proposed a novel minimally invasive method for PV analysis in patients with severe AS receiving TAVI. The VAC and LV efficiency improved immediately after TAVI.

Factors associated with Tourette syndrome among adolescents in Taiwan: A cross-sectional correlational study.

PURPOSE: Adolescents with Tourette syndrome (TS) may suffer from learning difficulties (attention-deficit/hyperactivity disorder), challenges in interpersonal interactions (especially with peers), disruptions of daily routines (disruptive behavior disorders), and increased psychosocial stress, which can result in internalizing and externalizing behavioral problems, such as venting depression and stress through self-harm. The aim of this study was to investigate peer attachment in adolescents with TS and associated risk factors. DESIGN AND METHODS: Adolescents with TS aged 13-18 years were recruited from the outpatient departments of 2 hospitals in Taiwan. Participants completed a basic data sheet, the Beck Depression Inventory-II, the Chinese version of the State-Trait Anxiety Inventory, and the Chinese version of the Youth Self-Report. Descriptive statistics were performed. Structural equation modeling was used to verify the model proposed in this study and to analyze the overall fit and internal structure. RESULTS: A total of 452 adolescents with TS aged 10-19 years participated in this study, which aimed to investigate factors affecting peer attachment, depression, anxiety, and psychosocial maladaptation and to explore causal relationships between these factors. Peer attachment was significantly associated with grade point average (rs = -0.240, p < .001), birth order (rs = -0.118, p = .012), parental marital status (rs = -0.111, p = .018), parenting style (rs = -0.138, p = .003), family monthly income (rs = 0.124, p = .008), and weekly hours on the internet (r = -0.164, p < .001). CONCLUSIONS: These results suggest that depression, anxiety, and peer attachment affect psychosocial development. PRACTICAL IMPLICATIONS: The findings may help clinical staff manage adolescents' severe emotional distress and psychosocial maladaptation.

Effects of a Moodle-based E-learning environment on E-collaborative learning, perceived satisfaction, and study achievement among nursing students: A cross-sectional study.

BACKGROUND: Studies suggest that e-learning environments (ELEMs) in nursing education may be more effective than traditional face-to-face teaching, as they lead to learning outcomes that equal or exceed those of face-to-face teaching. OBJECTIVES: To determine whether using ELEM for educational applications can significantly improve e-collaborative learning, perceived satisfaction, and study achievement among nursing students in a paediatric nursing course. DESIGN: Nonrandomized pretest-posttest quasi-experimental research design. SETTINGS: A medical college in northern Taiwan. PARTICIPANTS: Eighty-four students (52 in the non-ELEM group and 32 in the ELEM group) completed both the pretest and posttest. METHODS: Third-year nursing students were recruited and nonrandomly assigned to an experimental group (ELEM) and a nonexperimental group (non-ELEM) of their choice. Students in the former group received traditional classroom teaching without the use of Moodle-based ELEMs, while those in the latter completed the course through Moodle-based ELEMs and classroom lectures. RESULTS: Regarding perceived satisfaction, e-collaborative learning, and study achievement, the overall test results indicated a significant difference in the posttest between the two groups (F (1,82) = 10.622, P = 0.002), (F (1,82) = 9.481, P = 0.003), (F (1,82) = 59.301, P < 0.001, respectively). The explanatory power η2 reached 11.5 %, 10.4 %, and 42.0 %, respectively. CONCLUSION: The students who used Moodle-based ELEMs combined with classroom teaching showed significantly higher levels of e-collaborative learning, perceived satisfaction, and study achievement in the paediatric nursing course. ELEMs for educational purposes can serve as effective complementary learning tools for paediatric nursing courses.

A comparative analysis of aerosol exposure and prevention strategies in bystander, pre-hospital, and inpatient cardiopulmonary resuscitation using simulation manikins.

To evaluate aerosol exposure risk and prevention strategies during bystander, pre-hospital, and inpatient cardiopulmonary resuscitation (CPR). This study compared hands-only CPR, CPR with a surgical or N95 mask, and CPR with a non-rebreather mask at 15 L/min. 30:2 compression-ventilation ratio CPR was tested with face-mask ventilation (FMV), FMV with a high efficiency particulate air (HEPA) filter; supraglottic airway (SGA), SGA with a surgical mask, SGA with a HEPA filter, or SGA with both. Continuous CPR was tested with an endotracheal tube (ET), ET with a surgical mask, a HEPA filter, or both. Aerosol concentration at the head, trunk, and feet of the mannequin were measured to evaluate exposure to CPR personnel. Hands-only CPR with a surgical or N95 face mask coverings and ET tube ventilation CPR with filters showed the lowest aerosol exposure among all study groups, including CPR with NRM oxygenation, FMV, and SGA ventilation. NRM had a mask effect and reduced aerosol exposure at the head, trunk, and feet of the mannequin. FMV with filters during 30:2 CPR reduced aerosol exposure at the head and trunk, but increased at the feet of the mannequin. A tightly-sealed SGA when used with a HEPA filter, reduced aerosol exposure by 21.00-63.14% compared with a loose-fitting one. Hands-only CPR with a proper fit surgical or N95 face mask coverings is as safe as ET tube ventilation CPR with filters, compared with CPR with NRM, FMV, and SGA. FMV or tight-sealed SGA ventilation with filters prolonged the duration to achieve estimated infective dose of SARS-CoV-2 2.4-2.5 times longer than hands-on CPR only. However, a loose-fitting SGA is not protective at all to chest compressor or health workers standing at the foot side of the victim, so should be used with caution even when using with HEPA filters.

Crystal structure of Tudor domain of TDRD3 in complex with a small molecule antagonist.

Tudor domain-containing protein 3 (TDRD3) is involved in regulating transcription and translation, promoting breast cancer progression, and modulating neurodevelopment and mental health, making it a promising therapeutic target for associated diseases. The Tudor domain of TDRD3 is essential for its biological functions, and targeting this domain with potent and selective chemical probes may modulate its engagement with chromatin and related functions. Here we reported a study of TDRD3 antagonist following on our earlier work on the development of the SMN antagonist, Compound 1, and demonstrated that TDRD3 can bind effectively to Compound 2, a triple-ring analog of Compound 1. Our structural analysis suggested that the triple-ring compound bound better to TDRD3 due to its smaller side chain at Y566 compared to W102 in SMN. We also revealed that adding a small hydrophobic group to the N-methyl site of Compound 1 can improve binding. These findings provide a path for identifying antagonists for single canonical Tudor domain-containing proteins such as TDRD3 and SMN.

The Human Activity Radar Challenge: benchmarking based on the 'Radar signatures of human activities' dataset from Glasgow University.

Radar is an extremely valuable sensing technology for detecting moving targets and measuring their range, velocity, and angular positions. When people are monitored at home, radar is more likely to be accepted by end-users, as they already use WiFi, is perceived as privacy-preserving compared to cameras, and does not require user compliance as wearable sensors do. Furthermore, it is not affected by lighting condi-tions nor requires artificial lights that could cause discomfort in the home environment. So, radar-based human activities classification in the context of assisted living can empower an aging society to live at home independently longer. However, challenges remain as to the formulation of the most effective algorithms for radar-based human activities classification and their validation. To promote the exploration and cross-evaluation of different algorithms, our dataset released in 2019 was used to benchmark various classification approaches. The challenge was open from February 2020 to December 2020. A total of 23 organizations worldwide, forming 12 teams from academia and industry, participated in the inaugural Radar Challenge, and submitted 188 valid entries to the challenge. This paper presents an overview and evaluation of the approaches used for all primary contributions in this inaugural challenge. The proposed algorithms are summarized, and the main parameters affecting their performances are analyzed.

Improving the tumor selectivity of T cell engagers by logic-gated dual tumor-targeting.

Targeting single tumor antigens makes it difficult to provide sufficient tumor selectivity for T cell engagers (TCEs), leading to undesirable toxicity and even treatment failure, which is particularly serious in solid tumors. Here, we designed novel trispecific TCEs (TriTCEs) to improve the tumor selectivity of TCEs by logic-gated dual tumor-targeting. TriTCE can effectively redirect and activate T cells to kill tumor cells (∼18 pM EC50) by inducing the aggregation of dual tumor antigens, which was ∼70- or 750- fold more effective than the single tumor-targeted isotype controls, respectively. Further in vivo experiments indicated that TriTCE has the ability to accumulate in tumor tissue and can induce circulating T cells to infiltrate into tumor sites. Hence, TriTCE showed a stronger tumor growth inhibition ability and significantly prolonged the survival time of the mice. Finally, we revealed that this concept of logic-gated dual tumor-targeted TriTCE can be applied to target different tumor antigens. Cumulatively, we reported novel dual tumor-targeted TriTCEs that can mediate a robust T cell response by simultaneous recognition of dual tumor antigens at the same cell surface. TriTCEs allow better selective T cell activity on tumor cells, resulting in safer TCE treatment.

Cationic lipid-assisted nanoparticles for simultaneous delivery of CD47 siRNA and R848 to promote antitumor immune responses.

Introduction: Triple-negative breast cancer (TNBC) usually has a poor prognosis. Although the immunotherapy of TNBC has achieved great progress, only a few patients can benefit from the current treatment. CD47 is widely expressed on the surface of TNBC cells and may become an immune checkpoint for TNBC treatment. Nevertheless, increasingly more attention has been paid to systemic side effects since the ubiquitous expression of CD47 on normal cells. The toll-like receptor (TLR) agonist resiquimod (R848) can activate dendritic cells (DCs) and promote the maturation of immune cells in the tumor microenvironment, which further enhances the tumor inhibition ability of the immune system and synergizes with CD47 small interfering RNA (siRNA) for TNBC therapy. However, ideal delivery platforms such as nanocarriers are still needed because its weakness of hydrophobicity. Methods: In order to improve efficacy and reduce toxicity, R848 and siCD47 were entrapped in amphiphilic PEG-PLGA nanoparticles by double emulsification and stable nanoparticles NP/R848/siCD47 were generated to investigate their anti-tumor effects in a TNBC tumor-bearing mouse model. Results: Here, we show that PEG-PLGA nanoparticles are effective nanocarriers that can safely and effectively deliver siCD47 and R848 to tumor tissue, as demonstrated by retarded tumor growth. Mechanistically, downregulation of CD47 expression and activation of DCs took part in promoting the immune response of cytotoxic T cells (CTLs). Meanwhile, a decrease of myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) indicated the modulating of the tumor immune microenvironment. Discussion: To our best knowledge, our study pioneered co-delivery system for hydrophilic siCD47 and hydrophobic R848. It can maximize break tumor immune escape caused by CD47 and simultaneously enhance antigen presentation by activating DCs for effector T cell killing while regulating the tumor microenvironment as expected. Not only does it conform to the reports of previous basic research, but also it can break the bottleneck of their clinical application hopefully. Collectively, our findings could lay the foundation for future therapeutic strategies of TNBC.

Pelvic Neoadjuvant Radiotherapy for Stage M1a Rectal Adenocarcinoma Patients Treated With Systemic Therapy Followed by Proctectomy and Metastasectomy: A Nationwide Retrospective Cohort Study.

BACKGROUND/AIM: The effect of pelvic neoadjuvant radiotherapy (nRT) for stage M1a rectal adenocarcinoma patients treated with systemic therapy followed by proctectomy and metastasectomy was scarcely investigated in the literatures. PATIENTS AND METHODS: The eligible rectal cancer patients diagnosed between 2011-2019 were identified via the Taiwan Cancer Registry. In the primary analysis, we used propensity score weighting to balance observable potential confounders and compared the hazard ratio (HR) of death for the nRT group vs. without RT group. We also compared the incidence of rectal cancer mortality (IRCM) and performed various supplementary analyses. RESULTS: Our primary analyses included 145 patients. nRT was associated with improved OS (HR=0.51, p=0.01). The numerical trends remained similar for IRCM and in supplementary analyses. CONCLUSION: nRT was associated with improved OS in our study population.