Evolution of blaKPC Under the Pressure of Carbapenems and Ceftazidime/Avibactam in a Patient With Persistent Bacteremia Caused by Klebsiella pneumoniae.

A 30-year-old Korean man with myelodysplastic syndrome admitted hospital due to undifferentiated fever and recurrent skin lesions. He received combination therapy with high doses of meropenem, tigecycline and amikacin, yielding carbapenem resistant Klebsiella pneumoniae (CRKP) harboring K. pneumoniae carbapenemase (KPC)-2 from blood cultures on hospital day (HD) 23. Ceftazidime/avibactam was started at HD 37 and CRKP was eradicated from blood cultures after 5 days. However, ceftazidime/avibactam-resistant CRKP carrying KPC-44 emerged after 26 days of ceftazidime/avibactam treatment and then ceftazidime/avibactam-resistant, carbapenem-susceptible K. pneumoniae carrying KPC-135 was isolated on HD 65. The 3-D homology of KPC protein showed that hot spot changes in the omega loop could be attributed to ceftazidime/avibactam resistance and loss of carbapenem resistance. Whole genome sequencing of serial isolates supported that phenotypic variation was due to clonal evolution than clonal replacement. The treatment regimen was changed from CAZ/AVI to meropenem-based therapy (meropenem 1 g iv q 8 hours and amikacin 600 mg iv per day) starting with HD 72. CAZ/AVI-susceptible CRKP was presented again from blood cultures on HD 84, and the patient expired on HD 85. This is the first Korean report on the acquisition of ceftazidime/avibactam resistance through the emergence of blaKPC variants.

Effect of Thermal Oxidation of Carbon Nanotubes during Wet Spinning into Fibers Using Sodium Cholate Surfactant in Aqueous Dispersion.

Surfactant-based wet spinning is a promising route toward the eco-friendly production of carbon nanotube fibers (CNTFs). However, currently, the properties of surfactant-based wet-spun CNTFs lag behind those produced by other methods, indicating the need for further understanding and research. Here, we explored the surface characteristics of carbon nanotubes (CNTs) that are advantageous for the properties of CNTFs produced by wet spinning, using sodium cholate as a surfactant. Our finding indicates that appropriate thermal oxidation of CNTs enhances the fiber properties, while excessive oxidation undermines them. This implies that the bonding mechanism between CNTs and sodium cholate involves hydrophobic interaction and π-π interaction. Therefore, it is crucial to preserve a clean surface of CNTs in wet spinning using sodium cholate. We believe our research will contribute to the advancement of surfactant-based wet spinning of CNTFs.

Glass transition temperature as a unified parameter to design self-healable elastomers.

Self-healing ability of materials, particularly polymers, improves their functional stabilities and lifespan. To date, the designs for self-healable polymers have relied on specific intermolecular interactions or chemistries. We report a design methodology for self-healable polymers based on glass transition. Statistical copolymer series of two monomers with different glass transition temperatures (Tg) were synthesized, and their self-healing tendency depends on the Tg of the copolymers and the constituents. Self-healing occurs more efficiently when the difference in Tg between two monomer units is larger, within a narrow Tg range of the copolymers, irrespective of their functional groups. The self-healable copolymers are elastomeric and nonpolar. The strategy to graft glass transition onto self-healing would expand the scope of polymer design.

Nomogram for predicting pathologic complete response following preoperative chemoradiotherapy in patients with esophageal squamous cell carcinoma.

Background: In patients with esophageal squamous cell carcinoma (ESCC), accurately predicting a pathologic complete response (pCR) to preoperative chemoradiotherapy (PCRT) has the potential to enable an active surveillance strategy without esophagectomy. We aimed to establish a reliable multiparameter nomogram model that combines tumor characteristics, imaging modalities, and hematologic markers to predict pCR in patients with ESCC who underwent PCRT and esophagectomy. Methods: We retrospectively reviewed the medical records of 457 patients with ESCC who received PCRT followed by esophagectomy between January 2005 and October 2020. The nomogram model was developed using logistic regression analysis with a training cohort and externally validated with a validation cohort. Results: In the training and validation cohorts, 44.2% (126/285) and 48.3% (83/172) of patients, respectively, achieved pCR after PCRT. The 5-year rates of overall survival, progression-free survival, and freedom from local progression in the training cohort were 51.6%, 48.5%, and 77.6%, respectively. The parameters included in the nomogram were histologic grade, clinical N stage, maximum standardized uptake value on positron emission tomography, and post-PCRT biopsy. Hematologic markers were significantly associated with survival outcomes but not with pCR. The area under the receiver operating characteristic curve of the nomogram was 0.717, 0.704, and 0.707 for the training cohort, internal validation cohort, and external validation cohort, respectively. Conclusion: Our nomogram model based on four parameters obtained from standard clinical practice demonstrated good performance in both the training and validation cohorts and could be useful to aid clinical decision-making to determine whether surgery or active surveillance strategy should be pursued.

Analyzing small RNA sequences from canine stem cell-derived extracellular vesicles primed with TNF-α and IFN-γ and exploring their potential in lung repair.

Acute lung injury is an acute inflammation disorder that disrupts the lung endothelial and epithelial barriers. In this study, we investigated the extracellular vesicles (EVs) obtained via priming inflammatory cytokines such as tumor necrosis factor (TNF)-α and interferon (IFN)-γ on canine adipose mesenchymal stem cells in improving their anti-inflammatory and/or immunosuppressive potential, and/or their ability to alleviate lipopolysaccharide-induced lung injury in vitro. We also explored the correlation between epithelial-to-mesenchymal transition and the inflammatory repressive effect of primed EVs. Using small RNA-Seq, we confirmed that miR-16 and miR-502 significantly increased in EVs from TNF-α and IFN-γ-primed canine adipose mesenchymal stem cells. The pro and anti-inflammatory cytokines were analyzed in a lipopolysaccharide-induced lung injury model and we found that the EV anti-inflammatory effect improved on priming with inflammatory cytokines. EVs obtained from primed stem cells effectively suppress endothelial-to-mesenchymal transition in a lung injury model. Our results suggest a potential therapeutic approach utilizing EVs obtained from adipose mesenchymal stem cells primed with TNF-α and IFN-γ against lung inflammation and endothelial to mesenchymal transition.

Solvent Engineering of Thermo-Responsive Hydrogels Facilitates Strong and Large Contractile Actuations.

Thermo-responsive hydrogels can generate the actuation force through volumetric transitions in response to temperature changes. However, their weak mechanical properties and fragile actuation performance limit robust applications. Existing approaches to enhance these properties have typically depended on additional components, leading to an unavoidable interference to the actuation performance. In this work, robust thermo-responsive hydrogels are fabricated through solvent engineering. A particular solvent, N-methylformamide, interacts affinitively with the carbonyl group of N-isopropylacrylamide monomer, solubilizes the monomer with extremely high concentration, stabilizes chain propagation during polymerization, and greatly increases chain lengths and entanglements of the resulting polymer. The synthesized hydrogels are highly elastic, strong, and tough, displaying remarkable thermo-responsive contractile actuation. The simple synthetic process can broaden its applicability in designing robust functional hydrogel applications.

Genomic Biomarkers to Predict Response to Atezolizumab Plus Bevacizumab Immunotherapy in Hepatocellular Carcinoma: Insights from the IMbrave150 Trial.

Introduction: Combination immunotherapy, exemplified by atezolizumab plus bevacizumab, has become the standard of care for inoperable hepatocellular carcinoma (HCC). However, the lack of predictive biomarkers and limited understanding of response mechanisms remain a challenge. Methods: Using data from the IMbrave150plus cohort, we applied an immune signature score (ISS) predictor to stratify HCC patients treated with atezolizumab plus bevacizumab or with sorafenib alone into potential high and low response groups. By applying multiple statistical approaches including a Bayesian covariate prediction algorithm, we refined the signature to 10 key genes (ISS10) for clinical use while maintaining similar predictive power to the full model. We further validated ISS10 in an independent HCC cohort treated with nivolumab plus ipilimumab. Results: The study identified a significant association between the ISS and treatment response. Among patients classified as high responders, those treated with the atezolizumab plus bevacizumab combination exhibited improved overall and progression-free survival as well as better objective response rate compared to those treated with sorafenib. We also observed a significant correlation between ISS10 and response to nivolumab plus ipilimumab treatment. Analysis of immune cell subpopulations revealed distinct characteristics associated with ISS subtypes. In particular, the ISS10 high subtype displayed a more favorable immune environment with higher proportions of anti-tumor macrophages and activated T-cells, potentially explaining its better response. Conclusions: Our study suggests that ISS and ISS10 are promising predictive biomarkers for enhanced therapeutic outcomes in HCC patients undergoing combination immunotherapy. These markers are crucial for refining patient stratification and personalized treatment approaches to advance the effectiveness of standard-of-care regimens.

Dose-Escalated Radiotherapy for Primary Tracheobronchial Adenoid Cystic Carcinoma.

Primary tracheobronchial adenoid cystic carcinoma (ACC) is a rare malignancy, so the optimal radiotherapy (RT) dose remains unestablished. We aimed to evaluate the effectiveness of dose-escalated RT for primary tracheobronchial ACC. We retrospectively reviewed 48 patients who had undergone definitive or postoperative RT. Patients classified into the low- and high-dose groups received RT doses <70.0 and ≥70.0 Gy in EQD2, respectively. The primary endpoint was freedom from local progression (FFLP) and overall survival (OS). Throughout the follow-up period, seven patients (14.6%) experienced local progression, while 31 (64.6%) exhibited distant metastasis, most commonly in the lungs. In total, the 5-year FFLP and OS rates were 85.7 and 84.7%, respectively. Multivariate analysis revealed that regional lymph node metastasis at diagnosis and receipt of definitive RT were associated with poorer OS. In the subgroup analysis, the definitive RT group had a 5-year FFLP rate of 33.3 and 78.2% in the low- and high-dose groups (p = 0.065), whereas 5-year OS rates were 66.7 and 79.0%, respectively (p = 0.022). Four patients (8.3%) experienced Grade 3 toxicity with tracheal or main bronchus stenosis. Dose-escalated RT with conventional fractionation may be effective in patients with tracheobronchial ACC, especially for a definitive aim.

Synergistic Tailoring of Electronic and Thermal Transports in Thermoelectric Se-Free n-Type (Bi,Sb)2Te3.

Se-free n-type (Bi,Sb)2Te3 thermoelectric materials, outperforming traditional n-type Bi2(Te,Se)3, emerge as a compelling candidate for practical applications of recovering low-grade waste heat. A 100% improvement in the maximum ZT of n-type Bi1.7Sb0.3Te3 is demonstrated by using melt-spinning and excess Te-assisted transient liquid phase sintering (LPS). Te-rich sintering promotes the formation of intrinsic defects (TeBi), elevating the carrier concentration and enhancing the electrical conductivity. Melt-spinning with excess Te fine-tunes the electronic band, resulting in a high power-factor of 0.35 × 10-3 W·m-1 K-2 at 300 K. Rapid volume change during sintering induces the formation of dislocation networks, significantly suppressing the lattice thermal conductivity (0.4 W·m-1 K-1). The developed n-type legs achieve a high maximum ZT of 1.0 at 450 K resulting in a 70% improvement in the output power of the thermoelectric device (7.7 W at a temperature difference of 250 K). This work highlights the synergy between melt-spinning and transient LPS, advancing the tailored control of both electronic and thermal properties in thermoelectric technology.

4-O-Methylascochlorin Synergistically Enhances 5-Fluorouracil-Induced Apoptosis by Inhibiting the Wnt/ß-Catenin Signaling Pathway in Colorectal Cancer Cells.

4-O-Methyl-ascochlorin (MAC), a derivative of the prenyl-phenol antibiotic ascochlorin extracted from the fungus Ascochyta viciae, shows anticarcinogenic effects on various cancer cells. 5-Fluorouracil (5-FU) is used to treat colorectal cancer (CRC); however, its efficacy must be enhanced. In this study, we investigated the molecular mechanisms by which MAC acts synergistically with 5-FU to inhibit cell proliferation and induce apoptosis in CRC cells. MAC enhanced the cytotoxic effects of 5-FU by suppressing the Akt/mTOR/p70S6K and Wnt/ß-catenin signaling pathways. It also reduced the viability of 5-FU-resistant (5-FU-R) cells. Furthermore, expression of anti-apoptosis-related proteins and cancer stem-like cell (CSC) markers by 5-FU-R cells decreased in response to MAC. Similar to MAC, the knockdown of CTNNB1 induced apoptosis and reduced expression of mRNA encoding CRC markers in 5-FU-R cells. In summary, these results suggest that MAC and other ß-catenin modulators may be useful in overcoming the 5-FU resistance of CRC cells.

Uncommon Adverse Events of Immune Checkpoint Inhibitors in Small Cell Lung Cancer: A Systematic Review of Case Reports.

BACKGROUND: This study aimed to systematically review case reports documenting rare adverse events in patients with small cell lung cancer (SCLC) following the administration of immune checkpoint inhibitors (ICIs). METHODS: A systematic literature review was conducted to identify case reports detailing previously unreported adverse drug reactions to ICIs in patients with SCLC. The scope of the literature reviewed was restricted to case studies on SCLC published up to 31 December 2023. RESULTS: We analyzed twenty-four studies on ICI use for patients with SCLC. There were six reports on atezolizumab, four on durvalumab, and three on adverse events from monotherapy with nivolumab. Reports involving combination treatments were the most frequent, with a total of six, predominantly involving using nivolumab in combination with ipilimumab. Additionally, there was one report each on using pembrolizumab, nofazinilimab, sintilimab, tislelizumab, and toripalimab. We collected detailed information on the clinical course, including patient and disease characteristics, symptoms, treatment for each adverse event, and recovery status. Among the patients included in the case reports, 21 out of 24 (87.5%) had extensive-stage SCLC when initiating ICI therapy, with only 1 patient diagnosed with limited-stage SCLC. Respiratory system adverse events were most common, with seven cases, followed by neurological, endocrinological, and gastroenterological events. Three case reports documented adverse events across multiple systems in a single patient. In most cases, patients showed symptom improvement; however, four studies reported cases where patients either expired without symptom improvement or experienced sequelae. CONCLUSIONS: Efforts to develop reliable biomarkers for predicting irAEs continue, with ongoing research to enhance predictive precision. Immunotherapy presents diverse and unpredictable adverse events, underscoring the need for advanced diagnostic tools and a multidisciplinary approach to improve patient management.

Prognostic impact of muscle mass loss in elderly patients with oesophageal cancer receiving neoadjuvant chemoradiation therapy.

BACKGROUND: We aimed to identify the impact of muscle mass on locally advanced oesophageal cancer (LAEC) in elderly patients receiving neoadjuvant chemoradiation therapy (NACRT). METHODS: We reviewed the medical records of 345 patients diagnosed with LAEC who underwent NACRT and surgery. Physical variables, including height, weight, skeletal muscle mass, and laboratory values, were obtained before and after NACRT. Body mass index (BMI, kg/m2), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and prognostic nutritional index (PNI) were calculated as height/(weight)2, ANC/ALC, platelet count/ALC, and (10 × albumin + 0.05 × ALC), respectively. The cutoff for low muscle mass was 43.0 cm2/m2 for BMI below 25 kg/m2 and 53.0 cm2/m2 for BMI 25 kg/m2 or higher. The skeletal muscle index (SMI) was defined as skeletal muscle area/(height)2 (cm2/m2). The ΔSMI (%/50 days) was defined as (SMI after NACRT - SMI before NACRT)/interval (days) × 50 (days) to compare changes over the same period. The excessive muscle loss (EML) group was defined as patients with ΔSMI ≤-10% following NACRT. An elderly patient was defined as aged ≥65 years. The primary outcome measure was overall survival (OS). RESULTS: During a median follow-up of 32.8 months (range, 2.0-176.2), 192 patients died, with a median OS of 50.2 months. Elderly patients did not show inferior OS (young vs. elderly, 57.7% vs. 54.0% at 3 years, P = 0.247). 71.0% and 87.2% of all patients had low muscle mass before and after NACRT, respectively, which was not associated with OS (P = 0.270 and P = 0.509, respectively). Inflammatory (NLR and PLR) and nutritional index (PNI) values or their changes did not correlate with OS. However, the EML group had worse OS (41.6% vs. 63.2% at 3 years, P < 0.0001). In the multivariate analysis, EML was also a significant prognostic factor for OS. In the subgroup analysis by age, EML was a strong prognostic factor for OS in the elderly group. The 3-year OS was 36.8% in the EML group and 64.9% in the non-EML group (P < 0.0001) in elderly patients, and 47.4% and 62.1% (P = 0.063) in the young patients. In multivariate analysis of each subgroup, EML remained prognostic only in the elderly group (P = 0.008). CONCLUSIONS: EML may be strongly associated with a deteriorated OS in elderly patients undergoing NACRT, followed by surgery for LAEC. The strategies for decreasing muscle loss in these patients should be investigated.

Timely Pulmonary Tuberculosis Diagnosis Based on the Epidemiological Disease Spectrum: Population-Based Prospective Cohort Study in the Republic of Korea.

BACKGROUND: Timely pulmonary tuberculosis (PTB) diagnosis is a global health priority for interrupting transmission and optimizing treatment outcomes. The traditional dichotomous time-divided approach for addressing time delays in diagnosis has limited clinical application because the time delay significantly varies depending on each community in question. OBJECTIVE: We aimed to reevaluate the diagnosis time delay based on the PTB disease spectrum using a novel scoring system that was applied at the national level in the Republic of Korea. METHODS: The Pulmonary Tuberculosis Spectrum Score (PTBSS) was developed based on previously published proposals related to the disease spectrum, and its validity was assessed by examining both all-cause and PTB-related mortality. In our analysis, we integrated the PTBSS into the Korea Tuberculosis Cohort Registry. We evaluated various time delays, including patient, health care, and overall delays, and their system-associated variables in line with each PTBSS. Furthermore, we reclassified the scores into distinct categories of mild (PTBSS=0-1), moderate (PBTBSS=2-3), and severe (PBTBSS=4-6) using a multivariate regression approach. RESULTS: Among the 14,031 Korean patients with active PTB whose data were analyzed from 2018 to 2020, 37% (n=5191), 38% (n=5328), and 25% (n=3512) were classified as having a mild, moderate, and severe disease status, respectively, according to the PTBSS. This classification can therefore reflect the disease spectrum of PTB by considering the correlation of the score with mortality. The time delay patterns differed according to the PTBSS. In health care delays according to the PTBSS, greater PTB disease progression was associated with a shorter diagnosis period, since the condition is microbiologically easy to diagnose. However, with respect to patient delays, the change in elapsed time showed a U-shaped pattern as PTB progressed. This means that a remarkable patient delay in the real-world setting might occur at both apical ends of the spectrum (ie, in both mild and severe cases of PTB). Independent risk factors for a severe PTB pattern were age (adjusted odds ratio 1.014) and male sex (adjusted odds ratio 1.422), whereas no significant risk factor was found for mild PTB. CONCLUSIONS: Timely PTB diagnosis should be accomplished. This can be improved with use of the PTBSS, a simple and intuitive scoring system, which can be more helpful in clinical and public health applications compared to the traditional dichotomous time-only approach.

Effect of Tannic Acid Concentrations on Temperature-Sensitive Sol-Gel Transition and Stability of Tannic Acid/Pluronic F127 Composite Hydrogels.

Recently, interest in polyphenol-containing composite adhesives for various biomedical applications has been growing. Tannic acid (TA) is a polyphenolic compound with advantageous properties, including antioxidant and antimicrobial properties. Additionally, TA contains multiple hydroxyl groups that exhibit biological activity by forming hydrogen bonds with proteins and biomacromolecules. Furthermore, TA-containing polymer composites exhibit excellent tissue adhesion properties. In this study, the gelation behavior and adhesion forces of TA/Pluronic F127 (TA/PluF) composite hydrogels were investigated by varying the TA and PluF concentrations. PluF (above 16 wt%) alone showed temperature-responsive gelation behavior because of the closely packed micelle aggregates. After the addition of a small amount of TA, the TA/PluF hydrogels showed thermosensitive behavior similar to that of PluF hydrogels. However, the TA/PluF hydrogels containing more than 10 wt% TA completely suppressed the thermo-responsive gelation kinetics of PluF, which may have been due to the hydrogen bonds between TA and PluF. In addition, TA/PluF hydrogels with 40 wt% TA showed excellent tissue adhesion properties and bursting pressure in porcine intestinal tissues. These results are expected to aid in understanding the use of mixtures of TA and thermosensitive block copolymers to fabricate adhesive hydrogels for versatile biomedical applications.

Effect of complicated, untreated and uncontrolled diabetes and pre-diabetes on treatment outcome among patients with pulmonary tuberculosis.

BACKGROUND AND OBJECTIVE: Patients with tuberculosis and diabetes have a higher risk of unfavourable anti-tuberculosis treatment outcomes. In the present study, we aimed to evaluate the effects of various diabetes statuses on the outcomes of patients with pulmonary tuberculosis. METHODS: Among the patients with pulmonary tuberculosis enrolled in the Korea Tuberculosis Cohort (KTBC) registry and the multicentre prospective cohort study of pulmonary tuberculosis (COSMOTB), those with diabetes and complicated diabetes were identified. The primary and secondary outcomes were unfavourable outcomes and mortality, respectively. The effect of diabetes and complicated diabetes on the outcomes was assessed using multivariable logistic regression analysis. Using COSMOTB, subgroup analyses were performed to assess the association between various diabetes statuses and outcomes. RESULTS: In the KTBC, diabetes (adjusted odds ratio [aOR] = 1.93, 95% CI = 1.64-2.26) and complicated diabetes (aOR = 1.96, 95% CI = 1.67-2.30) were significantly associated with unfavourable outcomes, consistent with the COSMOTB data analysis. Based on subgroup analysis, untreated diabetes at baseline was an independent risk factor for unfavourable outcomes (aOR = 2.72, 95% CI = 1.26-5.61). Prediabetes and uncontrolled diabetes increased unfavourable outcomes and mortality without statistical significance. CONCLUSION: Untreated and complicated diabetes at the time of tuberculosis diagnosis increases the risk of unfavourable outcomes and mortality.

Local control and toxicity outcomes following consolidative radiation therapy in patients with high-risk neuroblastoma: a 20-year experience at a single center.

BACKGROUND: Intensive multimodal treatment can improve survival in patients with high-risk neuroblastoma, and consolidative radiation therapy has contributed to local control. We examined the clinical outcomes of patients who underwent consolidative radiation therapy at our institution. METHODS: We retrospectively reviewed the records of patients with high-risk neuroblastoma who underwent consolidative radiation therapy from March 2001 to March 2021 at Asan Medical Center. Patients underwent multimodal treatment including high-dose chemotherapy, surgery, stem cell transplantation, and maintenance therapy. Radiation (median, 21.0 Gy; range, 14-36) was administered to the primary site and surrounding lymph nodes. RESULTS: This study included 37 patients, and the median age at diagnosis was 2.8 years (range, 1.3-10.0). Four patients exhibited local failure, and 5-year free-from locoregional failure rate was 88.7%, with a median followup period of 5.7 years. The 5-year disease-free survival (DFS) and overall survival (OS) rates were 59.1% and 83.6%, respectively. Univariate analysis revealed that patients with neuron-specific enolase levels > 100 ng/mL had significantly worse DFS and OS (P = 0.036, 0.048), and patients with no residual disease before radiation therapy showed superior OS (P = 0.029). Furthermore, patients with 11q deletion or 17q gain exhibited poor DFS and OS, respectively (P = 0.021, 0.011). Six patients experienced grade 1 acute toxicity. Late toxicity was confirmed in children with long-term survival, predominantly hypothyroidism and hypogonadism, typically < grade 3, possibly attributed to combination treatment. Four patients experienced late toxicity ≥ grade 3 with chronic kidney disease, growth hormone abnormality, ileus, premature epiphyseal closure, and secondary tumor, and recovered by hospitalization or surgical treatment. CONCLUSIONS: In patients with high-risk neuroblastoma, consolidative radiotherapy to the primary tumor site resulted in excellent local control and a tolerable safety profile.

Biomedical Applications of CNT-Based Fibers.

Carbon nanotubes (CNTs) have been regarded as emerging materials in various applications. However, the range of biomedical applications is limited due to the aggregation and potential toxicity of powder-type CNTs. To overcome these issues, techniques to assemble them into various macroscopic structures, such as one-dimensional fibers, two-dimensional films, and three-dimensional aerogels, have been developed. Among them, carbon nanotube fiber (CNTF) is a one-dimensional aggregate of CNTs, which can be used to solve the potential toxicity problem of individual CNTs. Furthermore, since it has unique properties due to the one-dimensional nature of CNTs, CNTF has beneficial potential for biomedical applications. This review summarizes the biomedical applications using CNTF, such as the detection of biomolecules or signals for biosensors, strain sensors for wearable healthcare devices, and tissue engineering for regenerating human tissues. In addition, by considering the challenges and perspectives of CNTF for biomedical applications, the feasibility of CNTF in biomedical applications is discussed.

A Nationwide Study on HER2-low Breast Cancer in South Korea: Its Incidence of 2022 Real World Data and the Importance of Immunohistochemical Staining Protocols.

Purpose: Notable effectiveness of trastuzumab deruxtecan (T-DXd) in patients with HER2-low advanced breast cancer (BC) has focused pathologists' attention. We studied the incidence and clinicopathologic characteristics of HER2-low BC, and the effects of immunohistochemistry (IHC) associated factors on HER2 IHC results. Materials and Methods: The Breast Pathology Study Group of the Korean Society of Pathologists conducted a nationwide study using real-world data on HER2 status generated between January 2022 and December 2022. Information on HER2 IHC protocols at each participating institution was also collected. Results: Total 11,416 patients from twenty-five institutions included in this study. Of these patients, 40.7% (range: 6.0%-76.3%) were classified as HER2-zero, 41.7% (range: 10.5%-69.1%) as HER2-low, and 17.5% (range: 6.7%-34.0%) as HER2-positive. HER2-low tumors were associated with positive ER and PR statuses (p<0.001 and p<0.001, respectively). Antigen retrieval times (≥ 36 min vs. < 36 min) and antibody incubation times (≥ 12 min vs. < 12 min) affected on the frequency of HER2 IHC 1+ BC at institutions using the PATHWAY HER2 (4B5) IHC assay and BenchMark XT or Ultra staining instruments. Furthermore, discordant results between core needle biopsy (CNB) and subsequent resection specimen HER2 statuses were observed in 24.1% (787/3259) of the patients. Conclusion: The overall incidence of HER2-low BC in South Korea concurs with those reported in previously published studies. Significant inter-institutional differences in HER2 IHC protocols were observed, and it may have impact on HER2-low status. Thus, we recommend standardizing HER2 IHC conditions to ensure precise patient selection for targeted therapy.

A meta-analysis comparing efficacy and safety between proton beam therapy versus carbon ion radiotherapy.

BACKGROUND: This study aimed to compare the outcomes of proton beam therapy (PBT) and carbon ion radiotherapy (CIRT) by a systematic review and meta-analysis of the existing clinical evidence. METHODS: A systematic literature search was performed to identify studies comparing the clinical outcomes of PBT and CIRT. The included studies were required to report oncological outcomes (local control [LC], progression-free survival [PFS], or overall survival [OS]) or adverse events. RESULTS: Eighteen articles comprising 1857 patients (947 treated with PBT and 910 treated with CIRT) were included in the analysis. The pooled analysis conducted for the overall population yielded average hazard ratios of 0.690 (95% confidence interval (CI), 0.493-0.967, p = 0.031) for LC, 0.952 (95% CI, 0.604-1.500, p = 0.590) for PFS, and 1.183 (0.872-1.607, p = 0.281) for OS with reference to CIRT. The subgroup analyses included patients treated in the head and neck, areas other than the head and neck, and patients with chordomas and chondrosarcomas. These analyses revealed no significant differences in most outcomes, except for LC in the subgroup of patients treated in areas other than the head and neck. Adverse event rates were comparable in both groups, with an odds ratio (OR) of 1.097 (95% CI, 0.744-1.616, p = 0.641). Meta-regression analysis for possible heterogeneity did not demonstrate a significant association between treatment outcomes and the ratio of biologically effective doses between modalities. CONCLUSION: This study highlighted the comparability of PBT and CIRT in terms of oncological outcomes and adverse events.

Anisotropically Conductive Hydrogels with Directionally Aligned PEDOT:PSS in a PVA Matrix.

Electrical anisotropy, which is characterized by the efficient transmission of electrical signals in specific directions, is prevalent in both natural and engineered systems. However, traditional anisotropically conductive materials are often rigid and dry, thus limiting their utility in applications aiming for the seamless integration of various technologies with biological tissues. In the present study, we introduce a method for precisely controlling the microstructures of conductive and insulating polymers to create highly anisotropically conductive composite hydrogels. Our methodology involves combining aligned poly(vinyl alcohol) microfibrils, infused poly(3,4-ethylenedioxythiophene) polystyrenesulfonate, and sodium citrate precipitation to form dense, aligned conductive paths. This significantly enhances the electrical conductivity anisotropy (σ∥/σ⊥ ≈ 60.8) within these composite hydrogels.