Analysis of Response and Progression Patterns of Tyrosine Kinase Inhibitors in Recurrent or Metastatic Adenoid Cystic Carcinoma: A Post Hoc Analysis of Two KCSG Phase II Trials.

Purpose: In this study, we evaluated 66 patients diagnosed with adenoid cystic carcinoma (ACC) enrolled in two Korean Cancer Study Group trials to investigate the response and progression patterns in recurrent and/or metastatic ACC treated with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs). Materials and Methods: We evaluated 66 patients diagnosed with ACC who were enrolled in the Korean Cancer Study Group trials. The tumor measurements, clinical data, treatment outcomes, and progression patterns of therapy were analyzed. Results: In the 66 patients (53 receiving axitinib and 13 receiving nintedanib), the disease control rate was 61%, and 3 patients achieved partial response. The median follow-up, median progression-free survival (PFS), overall survival, and 6-month PFS rate were 27.6, 12.4, and 18.1 months and 62.1%, respectively. Among 42 patients who experienced progression, 27 (64.3%) showed target lesion progression. Bone metastasis was an independent poor prognostic factor. Conclusion: Overall, most patients demonstrated stable disease with prolonged PFS; however, prominent target lesion progression occurred in some patients. Thus, PFS may capture VEGFR-TKI efficacy better than the objective response rate.

Exercise training mode effects on myokine expression in healthy adults: A systematic review with meta-analysis.

BACKGROUND: The benefits of exercise are well known; however, many of the underlying molecular mechanisms are not fully understood. Skeletal muscle secretes myokines, which mediate muscle-organ crosstalk. Myokines regulate satellite-cell proliferation and migration, inflammatory cascade, insulin secretion, angiogenesis, fatty oxidation, and cancer suppression. To date, the effects of different exercise modes (namely, aerobic and resistance exercise) on myokine response remain to be elucidated. This is crucial considering the clinical implementation of exercise to enhance general health and wellbeing and as a medical treatment. METHODS: A systematic search was undertaken in PubMed, Medline, CINAHL, Embase, SPORTDiscus, and Web of Science in April 2023. Eligible studies examining the effects of a single bout of exercise on IL-15, irisin, SPARC, OSM, and decorin were included. A random-effects meta-analysis was also undertaken to quantify the magnitude of change. RESULTS: Sixty-two studies were included (n = 1193). Overall, exercise appeared to induce small to large increases in myokine expression, with effects observed immediately after to 60 min post-exercise, although these were mostly not statistically significant. Both aerobic and resistance exercise resulted in changes in myokine levels, without any significant difference between training modes, and with the magnitude of change differing across myokines. Myokine levels returned to baseline levels within 180 min to 24 h post-exercise. However, owing to potential sources of heterogeneity, most changes were not statistically significant, indicating that precise conclusions cannot be drawn. CONCLUSION: Knowledge is limited but expanding with respect to the impact of overall and specific effects of exercise on myokine expression at different time points in the systemic circulation. Further research is required to investigate the effects of different exercise modes at multiple time points on myokine response.

Current technology and industrialization status of cell-cultivated meat.

Interest and investment in cultivated meat are increasing because of the realization that it can effectively supply sufficient food resources and reduce the use of livestock. Nevertheless, accurate information on the specific technologies used for cultivated meat production and the characteristics of cultivated meat is lacking. Authorization for the use of cultivated meat is already underway in the United States, Singapore, and Israel, and other major countries are also expected to approve cultivated meat as food once the details of the intricate process of producing cultivated meat, which encompasses stages such as cell proliferation, differentiation, maturation, and assembly, is thoroughly established. The development and standardization of mass production processes and safety evaluations must precede the industrialization and use of cultivated meat as food. However, the technology for the industrialization of cultivated meat is still in its nascent stage, and the mass production process has not yet been established. The mass production process of cultivated meat may not be easy to disclose because it is related to the interests of several companies or research teams. However, the overall research flow shows that equipment development for mass production and cell acquisition, proliferation, and differentiation, as well as for three-dimensional production supports and bioreactors have not yet been completed. Therefore, additional research on the mass production process and safety of cultivated meat is essential. The consumer's trust in the cultivated meat products and production technologies recently disclosed by some companies should also be analyzed and considered for guiding future developments in this industry. Furthermore, close monitoring by academia and the government will be necessary to identify fraud in the cultivated meat industry.

Preliminary study on comparison of egg extraction methods for development of fetal bovine serum substitutes in cultured meat.

Fetal bovine serum (FBS) substitution remains one of the challenges to the realization of cultured meat production in the marketplace. In this study, three methods were developed to extract a substitute for FBS using egg white extract (EWE): using 25 mM CaCl2/2.5 % ammonium sulfate/citric acid (A); ethyl alcohol (B); and 5 % ammonium sulfate/citric acid (C). B EWE can effectively replace up to 50 % of FBS in growth media (10 % of the total). Ovalbumin in the extracts can promote cell proliferation, and components along the 12 kDa protein band have the potential to inhibit cell proliferation. Chick primary muscle cells applied with B EWE, an edible material that improved the cost and time efficiency of cultured meat production, effectively proliferated/differentiated. Therefore, EWE extracted using ethyl alcohol may be used as an FBS substitute to reduce animal sacrifices and should be considered a viable alternative to FBS for cultured meat.

Serious Complications of the Percutaneous A1 Pulley Release: Case Reports and Literature Review.

Percutaneous first annular pulley (A1 pulley) release, which has been increasingly used to treat trigger fingers, has been widely established as a safe and simple procedure. Multiple studies have reported positive results of percutaneous A1 pulley release. In this study, however, we report cases of patients who developed complications after undergoing percutaneous A1 pulley release at local clinics. A total of six patients visited our hospital for infectious complications after percutaneous A1 pulley release. Various sequelae such as damage to normal structures, insufficient procedure, and tissue necrosis were observed during the exploration. A retrospective study was conducted to identify the cause and trend of the observed complications by instruments (HAKI knife or needle). In the HAKI knife group, there was a tendency for damage to normal structures, while in the needle group, an insufficient release or serious soft tissue necrosis was observed. Based on these cases, our findings confirm the existence and characteristics of infectious complications following the percutaneous A1 pulley release. We further identify that the type of instrument used predicts the nature of complications. Thus, reliable and skilled performance of the procedure by experts is essential for safe treatment.

Hand Reconstruction Using Anterolateral Thigh Free Flap by Terminal Perforator-to-Digital Artery Anastomosis: Retrospective Analysis.

This study aimed to analyze cases of anterolateral thigh (ALT) free flap used for hand reconstruction with terminal perforator-to-digital artery anastomosis. Patients who underwent ALT free flap placement with terminal perforator-to-digital artery anastomosis for hand reconstruction between January 2011 and August 2021 were included. The number, length, and diameter of the perforators and veins, flap size, and operative time were investigated through a retrospective review of charts and photographs. The occurrences of arterial thrombosis, venous thrombosis, arterial spasm, and flap necrosis were analyzed. In total, 50 patients were included in this study. The mean diameter and length of the perforators were 0.68 mm and 3.25 cm, respectively, and the mean number of veins anastomosed was 1.88, with a mean diameter of 0.54 mm. Complications included four cases of arterial thrombosis, one case of venous thrombosis, seven cases of partial necrosis, and one case of total flap failure. Regression analysis showed that a longer perforator was associated with arterial thrombosis whereas larger flap size and number of anastomosed veins were associated with partial necrosis ( p < 0.05). The terminal perforator-to-digital artery anastomosis offers advantages in using compact free flaps with short pedicle lengths to cover small hand defects.

The "Swing-Door" Regrafting of Donor Site: An Alternative Method for Split-Thickness Skin Graft in the Hand.

Background Skin defects in the hands are common injuries, and autologous skin grafting is the ideal treatment. However, complications can occur at the donor and recipient sites. This study compares the "Swing-door" technique with conventional skin grafting. Methods From August 2019 to February 2023, 19 patients with skin defects of hand underwent the "Swing-door" split-thickness skin graft (STSG) technique. The thin epithelial layer was elevated with proximal part attached. Skin graft was harvested beneath. Donor site was then closed with epithelial flap like a "Swing-door". The outcomes were evaluated in terms of healing time, scar formation, and pain at the donor and recipient sites. The data were compared with the conventional STSG. Results The "Swing-door" group had lower graft take percentages, but complications did not significantly differ between the two groups. The "Swing-door" technique resulted in better cosmetic outcomes, as evidenced by lower Vancouver Scar Scale scores, faster donor site epithelialization, and reduced pain and discomfort during the early postoperative period, as measured by Visual Analog Scale. Conclusion The "Swing-door" STSG is a useful alternative for treating hand skin defects.

Importance of dietary supplementation of soluble and insoluble fibers to sows subjected to high ambient temperatures during late gestation and effects on lactation performance.

Heat stress adversely affects sows' performance, which can be improved by applying proper nutritional strategies. This study was conducted to investigate the interactive effects of dietary fiber levels and sources on sows' reproductive performance, metabolic response during gestation, and the carry-over influence on litter performance in the lactation period during heat stress (average room temperature of 27.1 °C). Fifty-four multiparous sows (Landrace × Yorkshire; initial body weight of 236.3 ± 16 kg; 2, 3 and 4 parities) at d 90 of gestation were assigned to a 2 × 3 factorial arrangement (9 sows/treatment), involving 2 dietary fiber levels (4.5% and 6% crude fiber) and 3 dietary fiber sources (wheat bran [WB], palm kernel meal [PK], and beet pulp [BP]). Sows fed the BP diet had highest (P < 0.01) feed intake and constipation index and lowest (P < 0.01) farrowing duration. Piglet weight (P = 0.041) and litter weight (P < 0.01) at weaning were higher in sows in the BP treatment compared to PK treatment. Sows in the BP treatment showed the greatest (P < 0.01) digestibility of crude protein and neutral detergent fiber. The fecal concentration of acetate was the lowest (P < 0.01) in the PK treatment. Total short-chain fatty acid production was increased in the WB and BP treatments compared with the PK. Sows in the BP treatment showed the lowest (P = 0.036) hair cortisol. The blood insulin concentration of sows was higher (P = 0.026) in the high fiber (6%) treatment compared with the low fiber (4.5%) treatment at 90 min and 120 min after the meal. The concentration of phthalic acid, succinic acid, phenylethylamine, hydrocinnamic acid, iron, linoleic acid, glycerol, ketone, and formamide were increased (P < 0.05) in the BP treatment compared with the WB. The BP treatment with high soluble fiber content improved the constipation index, farrowing duration, and litter performance, while high insoluble fibers increased sows comfort and reduced stress factors including respiratory rate and rectal temperature. Therefore, both soluble and insoluble sources of fiber are necessary to be added to the diet of gestating sows.

Improvement in Photoelectrochemical Water Splitting Performance of GaN-nanowire Photoanode Using MXene.

The photoelectrochemical water splitting (PEC-WS) performance of a photoanode consisting of GaN nanowires (NWs) is significantly improved using a Ti3C2-MXene coating as an intermediate layer to promote carrier transfer toward the electrolyte. The maximum current density and applied-bias photon-to-current efficiency of the photoanode comprising GaN NWs coated with Ti3C2-MXene (MGNWs) are measured to be 34.24 mA/cm2 and 14.47% at 1.2 and 0.4 V versus a reversible hydrogen electrode (RHE), respectively. These values are much higher than those of the GaN-NW photoanode without Ti3C2-MXene (4.04 mA/cm2 and 1.95%) and also markedly exceed those of previously reported photoanodes. After 8 days of PEC-WS, the current density was measured to be 31.07 mA/cm2, which corresponds to 97.58% of that measured immediately after the reaction started. Based on the time dependence of the current density, the hydrogen evolution rate over the reaction time is calculated to be 0.58 mmol/cm2·h. The results confirm that the PEC-WS performance of the optimized MGNW photoanode is superior to and more stable than those of previously reported photoanodes.

Engineering TALE-linked deaminases to facilitate precision adenine base editing in mitochondrial DNA.

DddA-derived cytosine base editors (DdCBEs) and transcription activator-like effector (TALE)-linked deaminases (TALEDs) catalyze targeted base editing of mitochondrial DNA (mtDNA) in eukaryotic cells, a method useful for modeling of mitochondrial genetic disorders and developing novel therapeutic modalities. Here, we report that A-to-G-editing TALEDs but not C-to-T-editing DdCBEs induce tens of thousands of transcriptome-wide off-target edits in human cells. To avoid these unwanted RNA edits, we engineered the substrate-binding site in TadA8e, the deoxy-adenine deaminase in TALEDs, and created TALED variants with fine-tuned deaminase activity. Our engineered TALED variants not only reduced RNA off-target edits by >99% but also minimized off-target mtDNA mutations and bystander edits at a target site. Unlike wild-type versions, our TALED variants were not cytotoxic and did not cause developmental arrest of mouse embryos. As a result, we obtained mice with pathogenic mtDNA mutations, associated with Leigh syndrome, which showed reduced heart rates.

Current Technologies and Future Perspective in Meat Analogs Made from Plant, Insect, and Mycoprotein Materials: A Review.

This study reviewed the current data presented in the literature on developing meat analogs using plant-, insect-, and protein-derived materials and presents a conclusion on future perspectives. As a result of this study, it was found that the current products developed using plant-, insect-, and mycoprotein-derived materials still did not provide the quality of traditional meat products. Plant-derived meat analogs have been shown to use soybean-derived materials and beta-glucan or gluten, while insect-derived materials have been studied by mixing them with plant-derived materials. It is reported that the development of meat analogs using mycoprotein is somewhat insufficient compared to other materials, and safety issues should also be considered. Growth in the meat analog market, which includes products made using plant-, insect-, and mycoprotein-derived materials is reliant upon further research being conducted, as well as increased efforts for it to coexist alongside the traditional livestock industry. Additionally, it will become necessary to clearly define legal standards for meat analogs, such as their classification, characteristics, and product-labeling methods.

Trends in Childhood Glaucoma Prevalence and Incidence in South Korea, 2002-2019: A Nationwide Population-Based Study.

PRCIS: This nationwide analysis identified the prevalence and incidence of childhood glaucoma for an 18-year period. The prevalence and incidence of primary congenital glaucoma showed increasing trends. Juvenile open-angle glaucoma, meanwhile, showed a decreasing tendency. PURPOSE: We aimed to determine the trends in the prevalence and incidence of childhood glaucoma in the entire population of South Korea. PATIENTS AND METHODS: A nationwide retrospective cohort study was performed with an age- and sex-specific population of South Korea. The Korean National Health Insurance Service (KNHIS) claims database for 2002 to 2019 was accessed to identify cases of ophthalmologist-confirmed primary childhood glaucoma (i.e., primary congenital glaucoma [PCG] and juvenile open-angle glaucoma [JOAG]). Incidence for PCG was estimated for a same-birth-year population, while that for JOAG was estimated using age- and sex-specific population figures. To verify the glaucoma cases, we also analyzed the diagnostic codes as well as any information on medication prescriptions and/or ocular-surgery history. RESULTS: During the 18-year observational period, totals of 505 and 7538 patients were diagnosed as PCG and JOAG, respectively. The mean prevalences of PCG and JOAG were 3.96±0.72 and 14.17±5.18, respectively. The prevalence of PCG showed an overall increasing trend during the study period, but the pattern was not significant (ß=0.049, P=0.143); that of JOAG, meanwhile, showed a significant decreasing tendency (ß=-0.713, P=0.001). PCG prevalence showed no difference between urban and rural areas, but JOAG showed a higher prevalence in rural areas (P<0.001). As for mean incidence, the rates for PCG and JOAG were 1.54±0.49 and 5.02±1.95 (per 100,000 person-years), respectively, and were higher in males (P<0.001 and P=0.013). CONCLUSION: This study identified childhood glaucoma prevalence and incidence in a general population of East Asian ethnicity. This data could help to promote better understanding of the typical epidemiological features and clinical courses of childhood glaucoma patients.

Inactivation of Human Norovirus GII.4's Infectivity in Fresh Oysters (Crassostrea gigas) through Thermal Treatment in Association with Propidium Monoazide.

The current study investigated the effects of heat treatment (85 °C or 100 °C for 5-20 min) on human norovirus (HuNoV) GII.4's capsid stability in fresh oysters. In addition, propidium monoazide (PMA) was used in viral samples to distinguish infectious viruses and evaluated using real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR). Further, we explored the effect of the heat treatment on oyster quality (Hunter color and hardness). The titer of HuNoV for oysters significantly (p < 0.05) decreased to 0.39-1.32 and 0.93-2.27 log10 copy number/µL in the non-PMA and PMA-treated groups, respectively, after heat treatment. HuNoV in oysters not treated with PMA showed a decrease of <1.5 - log10, whereas in PMA-treated oysters, a decrease of >1 - log10 was observed after treatment at 85 °C for 10 min. Treatments for both 15 min and 20 min at 100 °C showed a >99% log10 reduction using PMA/RT-qPCR. In the Hunter color, an increase in heat temperature and duration was associated with a significant decrease in 'L' (brightness+, darkness-) and an increase in 'a' (redness+, greenness-) and 'b' (yellowness+, blueness-) (p < 0.05). Our findings confirmed that the hardness of oyster meat significantly increased with increasing temperature and time (p < 0.05). This study demonstrated that PMA/RT-qPCR was effective in distinguishing HuNoV viability in heat-treated oysters. The optimal heat treatment for oysters was 10 min at 85 °C and 5 min at 100 °C.

A risk-adjusted cumulative sum analysis of the progression from a novice to an expert surgeon at a single institution.

BACKGROUND/OBJECTIVE: Laparoscopic surgery for rectal cancer is challenging for novice surgeons because it requires a sharp dissection in a narrow pelvis with visual limitations. Therefore, this study aimed to analyze the learning curve and clinical outcomes of laparoscopic surgery for rectal cancer performed by a novice surgeon en route to becoming an expert. METHODS: In total, 119 patients who underwent laparoscopic surgery for rectal cancer performed by a single surgeon between June 2010 and December 2019 were analyzed. A single hybrid model based on the operative time, open conversion, complications, and resection margin involvement was generated to assess the success of laparoscopic surgery. Furthermore, the learning curve was evaluated using the risk-adjusted cumulative sum (RA-CUSUM) method. RESULTS: The learning period was categorized into three phases according to the RA-CUSUM method (phase 1, 1st-33rd cases; phase 2, 34th-84th cases; and phase 3, 85th-119th cases). Tumor size (p = 0.004), distal resection margin (p = 0.003), and the number of harvested lymph nodes (p < 0.001) significantly increased with the learning period. The time to tolerable soft diet became shorter according to the learning period (p = 0.017). Advanced T stage (p = 0.024) and adjuvant chemotherapy (p = 0.012) were more common in phase 3. CONCLUSIONS: This study suggested that the initial technical competence of laparoscopic surgery for rectal cancer was acquired in the 33rd case. Technical mastery was achieved in the 84th case. After mastering the technique, the surgeon tended to challenge more advanced cases, however, the complication rates did not increase.

Improvement of weanling pigs immune status and metabolic condition using ultraweak light.

Weaning stress is the most common issue in swine farms, which increases mortality and morbidity. The use of artificial light is an option for modifying the immune system and metabolic pathways. This study aimed to evaluate the influence of ultraweak light (Photonia) on growth performance, immune system and metabolism of weanling pigs, and the carry-over effect on the growth performance in postweanling growing stages. A total of 30 weaned pigs with an average initial body weight of 7.06 ± 0.11 kg (age: 21 days) were allotted two treatments (Control and Photonia) with 15 replicates. The pelleted form diets were prepared for pigs in three phases including phase 1 (Days 0-14), phase 2 (Days 15-28) and phase 3 (Days 29-48). The gain-to-feed ratio (G:F) of pigs was significantly greater in the Photonia treatment. On Day 28, a higher concentration of immunoglobin A (IgA) (p < 0.01) and IgG (p < 0.01) was observed in the Photonia pigs. On Day 48, the Photonia treatment showed a greater serum IgA (p < 0.01) and IgG (p < 0.05). The concentration of interleukin (IL)-6 was decreased (p < 0.05) in the Photonia treatment. At Day 48, the concentrations of tumour necrotic factor-α, IL-1ß and IL-6 in serum were decreased (p < 0.05) in pigs in the Photonia treatment. Metabolic pathways analysis showed that the Photonia treatment increased the d-glutamine, d-glutamate, alanine, aspartate, glutamate and phenylalanine compared with the control treatment. In conclusion, the use of Photonia for weanling pigs is recommended due to improved G:F, immune status and activation of amino acids metabolic pathways including d-glutamine, d-glutamate, alanine, aspartate, glutamate and phenylalanine.

Lazertinib versus Gefitinib as First-Line Treatment for EGFR-mutated Locally Advanced or Metastatic NSCLC: LASER301 Korean Subset.

PURPOSE: This subgroup analysis of the Korean subset of patients in the phase 3 LASER301 trial evaluated the efficacy and safety of lazertinib versus gefitinib as first-line therapy for epidermal growth factor receptor mutated (EGFRm) non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Patients with locally advanced or metastatic EGFRm NSCLC were randomized 1:1 to lazertinib (240 mg/day) or gefitinib (250 mg/day). The primary endpoint was investigator-assessed progression-free survival (PFS). RESULTS: In total, 172 Korean patients were enrolled (lazertinib, n=87; gefitinib, n=85). Baseline characteristics were balanced between the treatment groups. One-third of patients had brain metastases (BM) at baseline. Median PFS was 20.8 months (95% confidence interval [CI], 16.7 to 26.1) for lazertinib and 9.6 months (95% CI, 8.2 to 12.3) for gefitinib (hazard ratio [HR], 0.41; 95% CI, 0.28 to 0.60). This was supported by PFS analysis based on blinded independent central review. Significant PFS benefit with lazertinib was consistently observed across predefined subgroups, including patients with BM (HR, 0.28; 95% CI, 0.15 to 0.53) and those with L858R mutations (HR, 0.36; 95% CI, 0.20 to 0.63). Lazertinib safety data were consistent with its previously reported safety profile. Common adverse events (AEs) in both groups included rash, pruritus, and diarrhoea. Numerically fewer severe AEs and severe treatment-related AEs occurred with lazertinib than gefitinib. CONCLUSION: Consistent with results for the overall LASER301 population, this analysis showed significant PFS benefit with lazertinib versus gefitinib with comparable safety in Korean patients with untreated EGFRm NSCLC, supporting lazertinib as a new potential treatment option for this patient population.

Base editing of organellar DNA with programmable deaminases.

Mitochondria and chloroplasts are organelles that include their own genomes, which encode key genes for ATP production and carbon dioxide fixation, respectively. Mutations in mitochondrial DNA can cause diverse genetic disorders and are also linked to ageing and age-related diseases, including cancer. Targeted editing of organellar DNA should be useful for studying organellar genes and developing novel therapeutics, but it has been hindered by lack of efficient tools in living cells. Recently, CRISPR-free, protein-only base editors, such as double-stranded DNA deaminase toxin A-derived cytosine base editors (DdCBEs) and adenine base editors (ABEs), have been developed, which enable targeted organellar DNA editing in human cell lines, animals and plants. In this Review, we present programmable deaminases developed for base editing of organellar DNA in vitro and discuss mitochondrial DNA editing in animals, and plastid genome (plastome) editing in plants. We also discuss precision and efficiency limitations of these tools and propose improvements for therapeutic, agricultural and environmental applications.

A Phase II Trial of Nintedanib in Patients with Metastatic or Recurrent Head and Neck Squamous Cell Carcinoma: In-Depth Analysis of Nintedanib Arm from the KCSG HN 15-16 TRIUMPH Trial.

PURPOSE: Precision oncology approach for recurrent and metastatic head and neck squamous cell carcinoma (HNSCC) is necessary due to its dismal prognosis. We performed a genomic profile-based umbrella trial of patients with platinum-refractory HNSCC (KCSG-TRIUMPH). Here, we present an in-depth report of the the nintedanib arm (arm 3) of the current trial. MATERIALS AND METHODS: The TRIUMPH study was a multicenter, open-label, single-arm phase 2 trial, in which patients were assigned to treatment arms based on next-generation sequencing (NGS)-based, matching genomic profiles. Patients whose tumors harbor fibroblast growth factor receptor (FGFR) alteration were enrolled in the nintedanib arm (arm 3) as part of the TRIUMPH study. The primary endpoint was the overall response rate (ORR), and secondary endpoints included overall survival (OS), progression-free survival (PFS), safety, and biomarker analysis. RESULTS: Between October 2017 and August 2020, 207 were enrolled in the TRIUMPH study, and eight were enrolled in the nintedanib arm. ORR and disease control rate were 42.9% and 57.1%, respectively. The median PFS was 5.6 months and the median duration of response was 9.1 months. Median OS was 11.1 months. One patient maintained the partial response for 36 months. Overall, the toxicity profiles were manageable. CONCLUSION: Single-agent nintedanib has demonstrated significant efficacy in FGFR-mutated, recurrent or metastatic HNSCC patients, with tolerable toxicity profiles. The results from the study have provided the basis for routine NGS screening and FGFR-targeted therapy. Because of the small number of patients due to slow accrual in this study, further studies with a larger cohort are warranted for statistical power.

A metanalysis to evaluate the effects of substrate sources on the nutritional performance of black soldier fly larvae: implications for sustainable poultry feed.

This meta-analysis presents an evaluation of substrate sources and their impact on the growth performance of black soldier fly (BSF) larva. The database, compiled from Google Scholar, PubMed, and Science Direct, focuses on data concerning substrate sources, environmental conditions, and the performance parameters of BSF. Seven types of substrates were analyzed, including Feed Waste, Manure, Fruits, Mix, Animal Source, Fermentation Residue, and Food Waste. The Feed Waste group demonstrated the highest DM content, while the highest CP content was found in the Animal Source group. Higher CP and DM content were found in larva meal from Fermentation Residues and Feed Waste diets, respectively. Higher survival rates were observed in BSF larvae fed on Feed Waste, Fermentation Residues, Food Waste, Fruits, Mix, and Manure substrates compared to Vegetable and Animal Source substrates. Fresh larval weight was lower when Manure was used as a feed substrate than in the Animal Source, Feed Waste, and Vegetable substrates. The prepupal Wet Weight was highest in BSF larvae fed on Animal Source, surpassing those fed on Fermentation Residue, Manure, and Vegetable substrates. Substrate CP content exhibited a positive relationship with fresh larva weight, prepupal wet weight, dry larval weight; larval length, mortality until prepupal, protein conversion, feed conversion ratio, food consumption, substrate reduction rate bioconversion ratio, waste reduction index, and efficiency conversion of digested feed in BSF larva. In conclusion, our findings underline that the source and composition of substrates are correlated to the nutritional composition and conversion efficiency of BSF larva meal.