DTR-SHIELD: Mutual Synchronization for Protecting against DoS Attacks on the SHIELD Protocol with AES-CTR Mode.

To enhance security in the semiconductor industry's globalized production, the Defense Advanced Research Projects Agency (DARPA) proposed an authentication protocol under the Supply Chain Hardware Integrity for Electronics Defense (SHIELD) program. This protocol integrates a secure hardware root-of-trust, known as a dielet, into integrated circuits (ICs). The SHIELD protocol, combined with the Advanced Encryption Standard (AES) in counter mode, named CTR-SHIELD, targets try-and-check attacks. However, CTR-SHIELD is vulnerable to desynchronization attacks on its counter blocks. To counteract this, we introduce the DTR-SHIELD protocol, where DTR stands for double counters. DTR-SHIELD addresses the desynchronization issue by altering the counter incrementation process, which previously solely relied on truncated serial IDs. Our protocol adds a new AES encryption step and requires the dielet to transmit an additional 100 bits, ensuring more robust security through active server involvement and message verification.

Determination of Flunixin and 5-Hydroxy Flunixin Residues in Livestock and Fishery Products Using Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS).

Flunixin is a veterinary nonsteroidal anti-inflammatory agent whose residues have been investigated in their original form within tissues such as muscle and liver. However, flunixin remains in milk as a metabolite, and 5-hydroxy flunixin has been used as the primary marker for its surveillance. This study aimed to develop a quantitative method for detecting flunixin and 5-hydroxy flunixin in milk and to strengthen the monitoring system by applying to other livestock and fishery products. Two different methods were compared, and the target compounds were extracted from milk using an organic solvent, purified with C18, concentrated, and reconstituted using a methanol-based solvent. Following filtering, the final sample was analyzed using liquid chromatography- tandem mass spectrometry. Method 1 is environmentally friendly due to the low use of reagents and is based on a multi-residue, multi-class analysis method approved by the Ministry of Food and Drug Safety. The accuracy and precision of both methods were 84.6%-115% and 0.7%-9.3%, respectively. Owing to the low matrix effect in milk and its convenience, Method 1 was evaluated for other matrices (beef, chicken, egg, flatfish, and shrimp) and its recovery and coefficient of variation are sufficient according to the Codex criteria (CAC/GL 71-2009). The limits of detection and quantification were 2-8 and 5-27 µg/kg for flunixin and 2-10 and 6-33 µg/kg for 5-hydroxy flunixin, respectively. This study can be used as a monitoring method for a positive list system that regulates veterinary drug residues for all livestock and fisheries products.

Microbial upcycling of methane to phytoene using metabolically engineered Methylocystis sp. MJC1 strain.

Methane, a potent greenhouse gas, requires sustainable mitigation strategies. Here, the microbial upcycling of methane to phytoene, a valuable colorless carotenoid with applications in the cosmeceutical industry was demonstrated. To achieve this goal, a stepwise metabolic engineering approach was employed in Methylocystis sp. MJC1, a methane-oxidizing bacterium. The incorporation of crtE and crtB genes from Deinococcus radiodurans R1 established the phytoene biosynthetic pathway. This pathway was fine-tuned through promoter optimization, resulting in a phytoene production of 450 µg/L from 37 mmol/L methane. Disrupting the ackA gene reduced a by-product, acetate, by 50 % and increased phytoene production by 56 %. Furthermore, overexpressing the dxs gene boosted phytoene titer 3-fold. The optimized strain produced 15 mg/L phytoene from 2 mol/L methane in fed-batch fermentation, a 4-fold increase in phytoene titer and 4-fold in yield. This demonstrates Methylocystis sp. MJC1's potential for efficient phytoene production and presents a novel approach for greenhouse gas reduction.

Tricaprylin-based drug crystalline suspension for intramuscular long-acting delivery of entecavir with alleviated local inflammation.

In order to ensure prolonged pharmacokinetic profile along with local tolerability at the injection site, tricaprylin-based drug crystalline suspension (TS) was designed and its local distribution, pharmacokinetics, and inflammatory response, were evaluated with conventional aqueous suspension (AS). As model drug particles, entecavir 3-palmitate (EV-P), an ester lipidic prodrug for entecavir (EV), was employed. The EV-P-loaded TS was prepared by ultra-sonication method. Prepared TS and conventional AS exhibited comparable morphology (rod or rectangular), median diameter (2.7 and 2.6 µm), crystallinity (melting point of 160-165°C), and in vitro dissolution profile. However, in vivo performances of drug microparticles were markedly different, depending on delivery vehicle. At AS-injected site, drug aggregates of up to 500 µm were formed upon intramuscular injection, and were surrounded with inflammatory cells and fibroblastic bands. In contrast, no distinct particle aggregation and adjacent granulation was observed at TS-injected site, with >4 weeks remaining of the oily vehicle in micro-computed tomographic observation. Surprisingly, TS exhibited markedly alleviated local inflammation compared to AS, endowing markedly lessened necrosis, fibrosis thickness, inflammatory area, and macrophage infiltration. The higher initial systemic exposure was observed with TS compared to AS, but TS provided prolonged delivery of EV for 3 weeks. Therefore, we suggest that the novel TS system can be a promising tool in designing parenteral long-acting delivery, with improved local tolerability.

Clinical Utility of Tumor-Naïve Pre-surgical ctDNA Detection in Early-stage NSCLC.

PURPOSE: The use of tumor-informed circulating tumor DNA (ctDNA) testing in early-stage patients before surgery is limited mainly due to restricted tissue access and extended turnaround times. This study aimed to evaluate the clinical value of a tumor-naïve, methylation-based cell-free DNA assay in a large cohort of patients with resected non-small cell lung cancer (NSCLC). METHOD: We analyzed pre-surgical plasma samples from 895 patients with EGFR and ALK-wild-type, clinical stage I or II NSCLC. The ctDNA status was evaluated for its prognostic significance in relation to tumor volume, metabolic activity, histology, histological subtypes, and clinical-to-pathological TNM upstaging. RESULTS: Pre-surgical ctDNA detection was observed in 55 out of 414 (13%) patients with clinical stage I lung adenocarcinoma (LUAD) and was associated with poor recurrence-free survival (RFS) (2-year RFS 69% versus 91%; log-rank P<0.001), approaching that of clinical stage II LUAD. Pre-surgical ctDNA detection was not prognostic in patients with clinical stage II LUAD or non-LUAD. Within LUAD, tumor volume and positron emission tomography avidity interacted to predict pre-surgical ctDNA detection. Moreover, pre-surgical ctDNA detection was predictive of the post-surgical discovery of IASLC G3 tumors (P<0.001) and pathological TNM upstaging (P<0.001). Notably, pre-surgical ctDNA detection strongly correlated with higher PD-L1 expression in tumors (positive rates 28% vs. 55%, P<0.001), identifying a subgroup likely to benefit from anti-PD-(L)-1 therapies. CONCLUSION: These findings support the integration of ctDNA testing into routine diagnostic workflows in early-stage NSCLC without the need of tumor tissue profiling. Furthermore, it is clinically useful in identifying high-risk patients who might benefit from innovative treatments, including neoadjuvant immune checkpoint inhibitors.

Roles of SMAD and SMAD-Associated Signaling Pathways in Nerve Regeneration Following Peripheral Nerve Injury: A Narrative Literature Review.

Although several methods are being applied to treat peripheral nerve injury, a perfect treatment that leads to full functional recovery has not yet been developed. SMAD (Suppressor of Mothers Against Decapentaplegic Homolog) plays a crucial role in nerve regeneration by facilitating the survival and growth of nerve cells following peripheral nerve injury. We conducted a systematic literature review on the role of SMAD in this context. Following peripheral nerve injury, there was an increase in the expression of SMAD1, -2, -4, -5, and -8, while SMAD5, -6, and -7 showed no significant changes; SMAD8 expression was decreased. Specifically, SMAD1 and SMAD4 were found to promote nerve regeneration, whereas SMAD2 and SMAD6 inhibited it. SMAD exerts its effects by promoting neuronal survival and growth through BMP/SMAD1, BMP/SMAD4, and BMP/SMAD7 signaling pathways. Furthermore, it activates nerve regeneration programs via the PI3K/GSK3/SMAD1 pathway, facilitating active regeneration of nerve cells and subsequent functional recovery after peripheral nerve damage. By leveraging these mechanisms of SMAD, novel strategies for treating peripheral nerve damage could potentially be developed. We aim to further elucidate the precise mechanisms of nerve regeneration mediated by SMAD and explore the potential for developing targeted nerve treatments based on these findings.

Grazing impact of the calanoid copepods Acartia spp. on the toxic dinoflagellate Alexandrium pseudogonyaulax in the western coastal waters of Korea.

Marine dinoflagellate species in the genus Alexandrium are well known to produce paralytic shellfish poison as well as common coastal species with cosmopolitan distribution. However, few studies on the feeding of copepods on Alexandrium species have been conducted. The toxic dinoflagellate Alexandrium pseudogonyaulax contains goniodomin A and causes red tides in many countries. To investigate the relationship between the toxic dinoflagellate A. pseudogonyaulax and the calanoid copepods Acartia spp., we quantified the ingestion rates of Acartia spp. feeding on A. pseudogonyaulax as a function of prey concentration. Additionally, we estimated grazing coefficients by integrating data from field observations of Acartia spp. and coexisting A. pseudogonyaulax with laboratory measurements of ingestion rates obtained during this investigation. Furthermore, we compared the ingestion rates of Acartia spp. and other predators feeding on Alexandrium species as previously reported. The ingestion rates of Acartia spp. on A. pseudogonyaulax increased continuously with increasing mean prey concentration. The highest values among the ingestion rate of Acartia spp. feeding on A. pseudogonyaulax was 3,407 cells predator-1 d-1 (4,872 ng C predator-1 d-1) at the given prey concentration. The calculated grazing coefficients for Acartia spp. on A. pseudogonyaulax in Shiwha Bay, Korea, were up to 0.073 d-1. The results of this study suggest that A. pseudogonyaulax may decrease or maintain the population of Acartia spp. in marine food webs.

Validation of the conceptual framework and intervention scope of oral function rehabilitation exercise.

OBJECTIVES: This study used a Delphi survey to define the concept of oral function rehabilitation exercise (OFRE) based on the International Classification of Functioning, Disability, and Health (ICF) and to categorise intervention domains for community-dwelling older adults. BACKGROUND: While numerous studies have been conducted to improve oral function through exercise interventions, the conceptual definition of oral exercise remains unclear and there is a lack of systematic categorisation of oral exercise intervention domains. METHODS: A preliminary model was developed based on the key findings of 19 papers selected from a prior systematic review. Its validity was confirmed through a Delphi survey conducted twice with eight expert panellists. Consensus was achieved by evaluating the validity of the OFRE conceptual framework, the accuracy of OFRE conceptual definitions, and intervention domains. RESULTS: Through expert consensus, an ICF-based OFRE conceptual framework was developed that includes 21 factors that affect the oral health status of the older adults. The OFRE intervention domain for improving the health status consisted of oral function rehabilitation warm-up exercise, masticatory function exercise, swallowing function exercise, articulatory function exercise, salivary function exercise, and oral function rehabilitation cool-down exercise, and 11 specific intervention methods were derived. CONCLUSIONS: The OFRE intervention can be used for planning and applying successful interventions to improve oral function and life function of older adults.

Pharmacokinetic drug-drug interactions of JBPOS0101 mediated by cytochrome P450 3A4 and UDP-glucuronosyltransferases.

JBPOS0101 is a new antiepileptic drug and is a substrate of UDP-glucuronosyltransferases (UGTs) in in vitro test. In vitro experiments showed different results regarding whether JBPOS0101 induces (EC50 136 µM) or inhibits (IC50 95.4-386.5 µM) cytochrome P450 (CYP) 3A4. As co-medication of JBPOS0101 and carbamazepine (CBZ) is expected in clinical settings, drug-drug interactions (DDIs) between them should be determined. This study aimed to investigate pharmacokinetic (PK) interactions of JBPOS0101 influenced by CYP3A4 and UGTs using midazolam (MDZ) and CBZ. A two-cohort, open-label, fixed-sequence study was conducted in healthy Koreans. In cohort A, subjects received MDZ IV alone, and then JBPOS0101 were co-administered with MDZ after oral doses of JBPOS0101 for 7 days. In cohort B, multiple doses of JBPOS0101 and CBZ were administered respectively, and subjects received both together for 7 days. Serial blood samples were collected for PK analysis. When MDZ and JBPOS0101 were co-administered, the systemic exposure of MDZ decreased by 30%. Meanwhile, JBPOS0101 did not significantly changed the PK of CBZ. CBZ decreased the systemic exposure of JBPOS0101 at steady state by 40%, respectively. With IV administration of MDZ, JBPOS0101 acted as a weak inducer of hepatic CYP3A4 and decreased systemic exposure of MDZ. The ability of JBPOS0101 to similarly modulate gut CYP3A4 activity will require further evaluation. Co-administration of multiple doses of JBPOS0101 and CBZ did not significantly alter CBZ pharmacokinetics, but the clinical impact of decreased systemic exposure of JBPOS0101 by CBZ should be further considered.

Toloese Generates Nitric Oxide through Natural Radiation of Far Infrared Rays, Reducing Serum Glucose, Cholesterol, and Triglycerides.

Toloese, a bed composition, is formulated with a combination of minerals of various wavelengths by utilizing a specific ratio and particle size. A maturation mixing technique is used without additional compression processes, resulting in the natural formation of numerous fine pores in the bed structure. At 40 °C, far infrared radiation in the range of 5-20 µm is emitted with a 0.916 radiant ratio, and the measured emitted radiant energy is 3.69 × 102 W/m2·µm. This study aimed to investigate the influence of far infrared radiation emitted from a Toloese bed on endogenous nitric oxide production. Clinical trials were conducted with 20 healthy adults aged 20 years. Blood samples were collected before and after Toloese bed usage for 1 h daily for 3 weeks. Nitric oxide levels in the saliva and blood of men and women significant increased after they used the Toloese bed for 1 h. Additionally, sweating sharply increased in the upper and lower body regions after Toloese bed usage. No hematological changes or adverse effects were observed, but blood glucose, cholesterol, and triglycerides decreased after Toloese bed usage compared with those before Toloese bed usage. These findings demonstrated that far infrared radiation emitted by the Toloese bed induced endogenous nitric oxide production and contributed to significant reductions in blood glucose, cholesterol, and triglyceride levels.

Multi-Objective Bayesian Optimization for Laminate-Inspired Mechanically Reinforced Piezoelectric Self-Powered Sensing Yarns.

Piezoelectric fiber yarns produced by electrospinning offer a versatile platform for intelligent devices, demonstrating mechanical durability and the ability to convert mechanical strain into electric signals. While conventional methods involve twisting a single poly(vinylidene fluoride-co-trifluoroethylene)(P(VDF-TrFE)) fiber mat to create yarns, by limiting control over the mechanical properties, an approach inspired by composite laminate design principles is proposed for strengthening. By stacking multiple electrospun mats in various sequences and twisting them into yarns, the mechanical properties of P(VDF-TrFE) yarn structures are efficiently optimized. By leveraging a multi-objective Bayesian optimization-based machine learning algorithm without imposing specific stacking restrictions, an optimal stacking sequence is determined that simultaneously enhances the ultimate tensile strength (UTS) and failure strain by considering the orientation angles of each aligned fiber mat as discrete design variables. The conditions on the Pareto front that achieve a balanced improvement in both the UTS and failure strain are identified. Additionally, applying corona poling induces extra dipole polarization in the yarn state, successfully fabricating mechanically robust and high-performance piezoelectric P(VDF-TrFE) yarns. Ultimately, the mechanically strengthened piezoelectric yarns demonstrate superior capabilities in self-powered sensing applications, particularly in challenging environments and sports scenarios, substantiating their potential for real-time signal detection.

Induction of Nitric Oxide and Its Role in Facial Nerve Regeneration According to the Method of Facial Nerve Injury.

Nitric oxide (NO) is an important molecule in cell communication that also plays an important role in many biological processes. Given the dual role of NO in nerve degeneration and regeneration after facial nerve injury, we sought to delve deeper into its role through a systematic literature review. A comprehensive review of the literature employing SCOPUS, PubMed, Cochrane Library, EMBASE, and Google Scholar databases was conducted to evaluate the induction and role of NO in neurodegeneration and regeneration after facial nerve injury. From the 20 papers ultimately reviewed, the central findings were that neuronal nitric oxide synthase(nNOS), endothelial nitric oxide synthase (eNOS), and induced nitric oxide synthase (iNOS) increased or decreased depending on the method of facial nerve damage, damaged area, harvested area, and animal age, and were correlated with degeneration and regeneration of the facial nerve. Research conducted on rats and mice demonstrated that NO, nNOS, eNOS, and iNOS play significant roles in nerve regeneration and degeneration. However, the relationship between nerve damage and NO could not be defined by a simple causal relationship. Instead, the involvement of NOS depends on the type of nerve cell, source of NO, timing, and location of expression, age of the target animal, and proximity of the damage location to the brainstem. Consequently, nNOS, eNOS, and iNOS expression levels and functions may vary significantly.

Effect of Surgeon-Performed Thoracic Paravertebral Block on Postoperative Pain in Adolescent Idiopathic Scoliosis Surgery: A Prospective Randomized Controlled Trial.

Posterior spinal fusion for adolescent idiopathic scoliosis (AIS) causes severe postoperative pain. Thoracic paravertebral block (PVB) provides excellent analgesia during various surgeries. We examined the effects of PVB on postoperative analgesia in children undergoing AIS surgery. In this study, 32 children scheduled for AIS surgery were randomly assigned to receive either PVB (PVB group) or no block (control group). The PVB group underwent surgeon-performed PVB with 0.5 mL/kg of adrenalized 0.2% ropivacaine on each side. The primary outcome was the pain score at rest at 6 h postoperatively. Secondary outcomes included pain scores both at rest and during movement and analgesic use for 48 h postoperatively. The postoperative resting pain scores at 6 h were comparable between the control and PVB groups (5.2 ± 2.0 and 5.1 ± 1.8, respectively), with no significant differences. However, at 1 h postoperatively, the control group showed significantly higher resting and mean moving pain scores than the PVB group (p < 0.05). The pain scores at other time points and analgesic use were comparable between the groups. Initial benefits of surgeon-performed bilateral PVB were observed but diminished at 6 h postoperatively. Future research using various anesthetics is needed to extend the effects of PVB.

SLIRP promotes autoimmune diseases by amplifying antiviral signaling via positive feedback regulation.

The abnormal innate immune response is a prominent feature underlying autoimmune diseases. One emerging factor that can trigger dysregulated immune activation is cytosolic mitochondrial double-stranded RNAs (mt-dsRNAs). However, the mechanism by which mt-dsRNAs stimulate immune responses remains poorly understood. Here, we discover SRA stem-loop interacting RNA binding protein (SLIRP) as a key amplifier of mt-dsRNA-triggered antiviral signals. In autoimmune diseases, SLIRP is commonly upregulated, and targeted knockdown of SLIRP dampens the interferon response. We find that the activation of melanoma differentiation-associated gene 5 (MDA5) by exogenous dsRNAs upregulates SLIRP, which then stabilizes mt-dsRNAs and promotes their cytosolic release to activate MDA5 further, augmenting the interferon response. Furthermore, the downregulation of SLIRP partially rescues the abnormal interferon-stimulated gene expression in autoimmune patients' primary cells and makes cells vulnerable to certain viral infections. Our study unveils SLIRP as a pivotal mediator of interferon response through positive feedback amplification of antiviral signaling.

Radial Type Low-Intensity Extracorporeal Shockwave Therapy Enhances Penile Microvascular Perfusion in an Aging Rat Model: A Novel Interventional Strategy to Treat Erectile Dysfunction.

PURPOSE: Physiological aging is associated with microvascular dysfunction, including in the penis, and this may contribute to age-related erectile dysfunction (ED). Low-intensity extracorporeal shockwave therapy (Li-ESWT) is a non-invasive intervention for ED, but its effect on penile microvascular function, remains unclear. Our objectives are to (i) evaluate the effect of Li-ESWT (specifically radial type ESWT [rESWT]) on penile microvascular perfusion (PMP) in aging rats, (ii) elucidate a possible mechanism, and (iii) evaluate its impact on angiogenic and smooth muscle biomarkers in cavernosal tissue. MATERIALS AND METHODS: Male rats (n=9; 15-18 months) were anesthetized and subjected to rESWT while monitoring PMP. The nitric oxide (NO) pathway involvement was assessed by measuring the effect of rESWT on PMP following an intracavernosal injection of N(G)-nitroarginine methyl ester (L-NAME) (NO synthase inhibitor). To elucidate the cellular mechanism, another group of rats received repeated rESWT (n=4) or no treatment (n=4) three times/week for two weeks. Rats were euthanized at the end of the study and penile tissues were analyzed for angiogenic markers (vascular endothelial growth factor-A [VEGF-A], endothelial nitric oxide synthase [eNOS]) and smooth muscle content (α-actin) using immunostaining, Western blot, and quantitative polymerase chain reaction (qPCR). RESULTS: rESWT resulted in more than a 2-fold increase in PMP (from 68.5 arbitrary units; 163.7 AU). L-NAME injection produced a <40%-50% decrease (185.3 to 101.0 AU) in rESWT-induced PMP response. Immunostaining revealed increased α-actin, eNOS, and VEGF-A in the cavernosum and these findings were confirmed by qPCR and Western blot results. CONCLUSIONS: rESWT improved PMP, which may be mediated via increased VEGF expression, which stimulates the NO/cyclic guanosine monophosphate pathway, resulting in sustained PMP. rESWT devices could offer a safe, non-invasive treatment for age-related ED.

Circular economy approach: Nutrient recovery and economical struvite production from wastewater sources by using modified biochars.

The enrichment of phosphorus (P) and nitrogen (N) in aquatic systems can cause eutrophication. Moreover, P rocks may become exhausted in the next 100 years. A slow-release fertilizer called struvite (MgNH4PO4.6H2O) can reduce surface runoff. However, the high cost of raw material or chemicals is a bottleneck in their economical production. Therefore, incinerated sewage sludge ash, food wastewater, and bittern were combined as the sources of P, N, and Mg, respectively. Sawdust biochar was used to enhance the adsorptive recovery of nutrients. First, recovery kinetics was studied by comparing bittern-impregnated biochar (BtB) with the Mg-impregnated biochar (MgB). Subsequently, the synergistic physical and chemical interactions were observed for P and N recovery. Almost complete PO43-P recoveries were achieved within 10 min for both biochars. However, NH4+-N recovery was stable after 2 h, with 26% recovery by MgB and 20% recovery by BtB. Biochars activated with steam (steam-activated biochar) and KOH (KOH-activated biochar) gave superior activities to those of unactivated biochars and activated carbon (AC) nutrient recovery and struvite purity. Moreover, the activated biochars showed a lower risk of surface runoff, similar to that of AC. Therefore, activated biochars can be used as an alternative to AC for economical struvite production from a combination of wastewater sources.

Factors determining tropical upper-level cloud radiative effect in the radiative-convective equilibrium framework.

Investigation of the major factors determining tropical upper-level cloud radiative effect (TUCRE) is crucial for understanding cloud feedback mechanisms. We examined the TUCRE inferred from the outputs of historical runs and AMIP runs from CMIP6 models employing a radiative-convective equilibrium (RCE). In this study, we incorporated the RCE model configurations of atmospheric dynamics and thermodynamics from the climate models, while simplifying the intricate systems. Using the RCE model, we adjusted the global mean surface temperature to achieve energy balance, considering variations in tropical cloud fraction, regional reflectivity, and emission temperature corresponding to each climate model. Subsequently, TUCRE was calculated as a unit of K/%, representing the change in global mean surface temperature (K) in response to an increment in the tropical upper-level clouds (%). Our RCE model simulation indicates that the major factors determining the TUCRE are the emission temperatures of tropical moist-cloudy and moist-clear regions, as well as the fraction of tropical upper-level clouds. The higher determination coefficients between TUCRE and both the emission temperature of tropical moist regions and the upper-level cloud fraction are attributable to their contribution to the trapping effect on the outgoing longwave radiations, which predominantly determines TUCRE. Consequently, the results of this study underscore the importance of accurately representing the upper-level cloud fraction and emission temperature in tropical moist regions to enhance the representation of TUCRE in climate models.

The Influence of Environmental Factors on Site Selection Augment Breeding Success in Honey Bees: An Insight of Honey Bee Genetic Resource Conservation.

Honey bee reproductive behavior involves a complicated mating system that embodies a number of factors, including environmental and human-induced factors. Controlled breeding in isolated mating stations is a prerequisite to maintain the genetic resources of honey bees through natural mating. The concept of controlled mating is a challenge in most beekeeping operations due to its low mating success rate. Therefore, a detailed investigation into the suitability of isolated mating stations is of interest. Thus, we bred two subspecies of honey bees (Apis cerana koreana and Apis mellifera L.) in isolated mating stations (island) from 2021 to 2023 and in an open breeding station in 2023. Our results demonstrate that the highest percentage of the mating success rate in isolated mating stations was recorded in the Wido Island, which had the highest percentage of bare land, coniferous forests, deciduous forests, fields, and mixed forests. The mating success rate was higher in the summer and spring for A. cerana and A. mellifera, respectively. The mating success rate was higher in open mating compared to controlled mating (Island) and did not vary between pure-breeding and cross-breeding lines. Our findings suggested that mating stations with mixed forest and fields are potential sites for the successful breeding of honey bees.

Practice pattern and risk of not receiving planned surgery after neoadjuvant chemoradiotherapy for locally advanced oesophageal squamous cell carcinoma.

OBJECTIVES: Unlike the initial plan, some patients with oesophageal squamous cell carcinoma cannot or do not receive surgery after neoadjuvant chemoradiotherapy (nCRT). This study aimed to report the epidemiology of patients not receiving surgery after nCRT and to evaluate the potential risk of refusing surgery. METHODS: We analysed patients with clinical stage T3-T4aN0M0 or T1-T4aN1-N3M0 oesophageal squamous cell carcinoma who underwent nCRT as an initial treatment intent between January 2005 and March 2020. Patients not receiving surgery were categorized using predefined criteria. To evaluate the risk of refusing surgery, a propensity-matched comparison with those who received surgery was performed. Recurrence-free (RFS) and overall survival (OS) was compared between groups, according to clinical response to nCRT. RESULTS: Among the study population (n = 715), 105 patients (14.7%) eventually failed to reach surgery. There were three major patterns of not receiving surgery: disease progression before surgery (n = 25), functional deterioration at reassessment (n = 47), and patient's refusal without contraindications (n = 33). After propensity-score matching, the RFS curves of the surgery group and the refusal group were significantly different (P < 0.001), while OS curves were not significantly different (P = 0.069). In patients who achieved clinical complete response on re-evaluation, no significant difference in the RFS curves (P = 0.382) and in the OS curves (P = 0.290) was observed between the surgery group and the refusal group. However, among patients who showed partial response or stable disease on re-evaluation, the RFS and OS curves of the refusal group were overall significantly inferior compared to those of the surgery group (both P < 0.001). The 5-year RFS rates were 10.3% for the refusal group and 48.2% for the surgery group, and the 5-year OS rates were 8.2% for the refusal group and 46.1% for the surgery group. CONCLUSIONS: Patient's refusal remains one of the major obstacles in completing the trimodality therapy for oesophageal squamous cell carcinoma. Refusing surgery when offered may jeopardize oncological outcome, particularly in those with residual disease on re-evaluation after nCRT. These results provide significant implications for consulting patients who are reluctant to oesophagectomy after nCRT.