Identifying Dietary Timing of Organic Trace Minerals to Reduce the Incidence of Osteomyelitis Lameness in Broiler Chickens Using the Aerosol Transmission Model.

Our prior research demonstrated a 20% to 25% reduction in bacterial chondronecrosis with osteomyelitis (BCO) lameness in broilers with organic Zn, Mn, and Cu (Availa® ZMC) supplementation. Expanding on this, we investigated the optimal timing for Availa® ZMC feeding to mitigate BCO lameness and reduce feed additive costs in the poultry industry. In this study, we compared the application of 0.15% Availa® ZMC for 56 days, the first 28 days, and the last 28 days. The experimental design was a randomized block design involving 1560 one-day-old chicks distributed across two wire-floor pens as BCO source infection and four treatment groups with six replicates. The source of BCO infection exhibited a cumulative lameness incidence of 83%, whereas the negative control group showed a 77% cumulative incidence of lameness (p = 0.125). Administering 0.15% of Availa® ZMC during the initial 28 d resulted in a 41.3% reduction in BCO incidence, significantly different from the supplementation during the last 28 d (p < 0.05). However, this reduction did not differ substantially (p > 0.05) from the 56d application period. Hence, administering 0.15% Availa® ZMC during the first four weeks emerges as the optimal timing protocol, providing a defense against lameness comparable to the continuous supplementation throughout the complete production duration. Implementing this feeding approach reduces the cost of feed additive, promotes the health of skeletal bones, and effectively protects against BCO lameness in broilers, offering a valuable consideration for producers seeking optimal outcomes in the poultry industry.

Efficiency of freeze- and spray-dried microbial preparation as active dried starter culture in kombucha fermentation.

BACKGROUND: Kombucha is a widely consumed fermented beverage produced by fermenting sweet tea with a symbiotic culture of bacteria and yeast (SCOBY). The dynamic nature of microbial communities in SCOBY may pose challenges to production scale-up due to unpredictable variations in microbial composition. Using identified starter strains is a novel strategy to control microorganism composition, thereby ensuring uniform fermentation quality across diverse batches. However, challenges persist in the cultivation and maintenance of these microbial strains. This study examined the potential of microencapsulated kombucha fermentation starter cultures, specifically Komagataeibacter saccharivorans, Levilactobacillus brevis and Saccharomyces cerevisiae, through spray-drying and freeze-drying. RESULTS: Maltodextrin and gum arabic-maltodextrin were employed as carrier agents. Our results revealed that both spray-dried and freeze-dried samples adhered to physicochemical criteria, with low moisture content (2.18-7.75%) and relatively high solubility (65.75-87.03%) which are appropriate for food application. Freeze-drying demonstrated greater effectiveness in preserving bacterial strain viability (88.30-90.21%) compared to spray drying (74.92-78.66%). Additionally, the freeze-dried starter strains demonstrated similar efficacy in facilitating kombucha fermentation, compared to the SCOBY group. The observations included pH reduction, acetic acid production, α-amylase inhibition and elevated total polyphenol and flavonoid content. Moreover, the biological activity, including antioxidant potential and in vitro tyrosinase inhibition activity, was enhanced in the same pattern. The freeze-dried strains exhibited consistent kombucha fermentation capabilities over a three-month preservation, regardless of storage temperature at 30 or 4 °C. CONCLUSION: These findings highlight the suitability of freeze-dried starter cultures for kombucha production, enable microbial composition control, mitigate contamination risks and ensure consistent product quality. © 2024 Society of Chemical Industry.

Minimally invasive left axillary thoracotomy for the total repair of fallot, dextrocardia, situs inversus and anomalous coronary artery origins.

We present a rare case of tetralogy of Fallot accompanied with dextrocardia, situs inversus and anomalous origin of the right coronary artery. Total repair was accomplished successfully using a minimally invasive left axillary thoracotomy.

Assessing the Impact of Spraying an Enterococcus faecium-Based Probiotic on Day-Old Broiler Chicks at Hatch on the Incidence of Bacterial Chondronecrosis with Osteomyelitis Lameness Using a Staphylococcus Challenge Model.

Bacterial chondronecrosis with osteomyelitis (BCO) lameness is a bone disease characterized by the translocation of bacteria from the gastrointestinal tract, which colonize microfractures in broiler leg bones caused by rapid animal growth rate and weight gain, resulting in lameness. As such, BCO lameness represents a significant challenge for the poultry industry. This study aims to evaluate the effect of spraying broiler chicks on d0 at hatch with an Enterococcus faecium probiotic on the incidence of BCO-induced lameness, utilizing a Staphylococcus aureus challenge model. There were four treatments: (1) negative control (no probiotic + no challenge, NC); (2) positive control (no probiotic + challenge, PC); (3) low dosage (4.0 × 108 CFU/chick + challenge, LOW); and (4) high dosage (2.0 × 109 CFU/chick + challenge, HIGH). On d5, groups two through four were challenged with Staphylococcus aureus through the drinking water at a concentration of 1.0 × 105 CFU/mL. Cumulative lameness incidence was determined through daily evaluations and necropsies conducted on lame birds starting from d22. Data were subjected to a binomial general regression analysis (significant p < 0.05). On d56, the PC group exhibited the highest cumulative lameness incidence (58.0%; p < 0.05), followed by LOW (36.0%), HIGH (28.7%), and NC groups (25.3%), respectively. These results suggest early probiotic application at day-of-hatch successfully reduced the incidence of lameness in challenged birds, thus contributing to understanding of efficient and sustainable broiler production.

Real-world analysis of afatinib as a first-line treatment for patients with advanced stage non-small-cell lung cancer with uncommon EGFR mutations: a multicenter study in Vietnam.

Background: Afatinib is indicated for advanced-stage non-small-cell lung cancer (NSCLC) with Epidermal Growth Factor Receptor (EGFR) and uncommon mutations. However, real-world studies on this topic are limited. This study aimed to evaluate afatinib as first-line therapy for locally advanced and metastatic NSCLC with uncommon EGFR mutations. Patients and methods: A retrospective study included 92 patients with advanced NSCLC with uncommon and compound EGFR mutations, treated with afatinib as first-line therapy. Patients were followed up and evaluated every 3 months or when symptoms of progressive disease arose. The endpoints were objective response rate (ORR), time-to-treatment failure (TTF), and adverse events. Results: The G719X EGFR mutation had the highest occurrence rate (53.3% for both monotherapy and the compound). By contrast, the compound mutation G719X-S768I was observed at a rate of 22.8%. The ORR was 75%, with 15.2% of patients achieving complete response. The overall median TTF was 13.8 months. Patients with the G719X EGFR mutation (single and compound) had a median TTF of 19.3 months, longer than that of patients with other mutations, who had a median TTF of 11.2 months. Patients with compound EGFR mutations (G719X and S768I) demonstrated a median TTF of 23.2 months compared to that of 12.3 months for other mutations. Tolerated doses of 20 or 30 mg achieved a longer median TTF of 17.1 months compared to 11.2 months with 40 mg. Median TTF differed between patients with and without brain metastasis, at 11.2 and 16.9 months, respectively. Rash (55.4%) and diarrhea (53.3%) were the most common adverse events, primarily grades 1 and 2. Other side effects occurred at a low rate. Conclusion: Afatinib is effective for locally advanced metastatic NSCLC with uncommon EGFR mutations. Patients with G719X, compound G719X-S768I mutations, and tolerated doses of 20 or 30 mg had a longer median TTF than those with other mutations.

Evaluating the impact of delayed study startup on accrual in cancer studies.

Background: Drug development in cancer medicine depends on high-quality clinical trials, but these require large investments of time to design, operationalize, and complete; for oncology drugs, this can take 8-10 years. Long timelines are expensive and delay innovative therapies from reaching patients. Delays often arise from study startup, a process that can take 6 months or more. We assessed how study-specific factors affected the study startup duration and the resulting overall success of the study. Method: Data from The University of Kansas Cancer Center (KUCC) were used to analyze studies initiated from 2018 to 2022. Accrual percentage was computed based on the number of enrolled participants and the desired enrollment goal. Accrual success was determined by comparing the percentage of enrollments to predetermined threshold values (50%, 70%, or 90%). Results: Studies that achieve or surpass the 70% activation threshold typically exhibit a median activation time of 140.5 days. In contrast, studies that fall short of the accrual goal tend to have a median activation time of 187 days, demonstrating the shorter median activation times associated with successful studies. Wilcoxon rank-sum test conducted for the study phase (W=13607, p-value=0.001) indicates that late-phase projects took longer to activate compared to early-stage projects. We also conducted the study with 50% and 90% accrual thresholds; our findings remained consistent. Conclusions: Longer activation times are linked to reduced project success, and early-phase studies tend to have higher success than late-phase studies. Therefore, by reducing impediments to the approval process, we can facilitate quicker approvals, increasing the success of studies regardless of phase.

CSF proteomic profiling with amyloid/tau positivity identifies distinctive sex-different alteration of multiple proteins involved in Alzheimer's disease.

In Alzheimer's disease (AD), the most common cause of dementia, females have higher prevalence and faster progression, but sex-specific molecular findings in AD are limited. Here, we comprehensively examined and validated 7,006 aptamers targeting 6,162 proteins in cerebral spinal fluid (CSF) from 2,077 amyloid/tau positive cases and controls to identify sex-specific proteomic signatures of AD. In discovery (N=1,766), we identified 330 male-specific and 121 female-specific proteomic alternations in CSF (FDR <0.05). These sex-specific proteins strongly predicted amyloid/tau positivity (AUC=0.98 in males; 0.99 in females), significantly higher than those with age, sex, and APOE-ε4 (AUC=0.85). The identified sex-specific proteins were well validated (r≥0.5) in the Stanford study (N=108) and Emory study (N=148). Biological follow-up of these proteins led to sex differences in cell-type specificity, pathways, interaction networks, and drug targets. Male-specific proteins, enriched in astrocytes and oligodendrocytes, were involved in postsynaptic and axon-genesis. The male network exhibited direct connections among 152 proteins and highlighted PTEN, NOTCH1, FYN, and MAPK8 as hubs. Drug target suggested melatonin (used for sleep-wake cycle regulation), nabumetone (used for pain), daunorubicin, and verteporfin for treating AD males. In contrast, female-specific proteins, enriched in neurons, were involved in phosphoserine residue binding including cytokine activities. The female network exhibits strong connections among 51 proteins and highlighted JUN and 14-3-3 proteins (YWHAG and YWHAZ) as hubs. Drug target suggested biperiden (for muscle control of Parkinson's disease), nimodipine (for cerebral vasospasm), quinostatin and ethaverine for treating AD females. Together, our findings provide mechanistic understanding of sex differences for AD risk and insights into clinically translatable interventions.

LOXL1-AS1 contributes to metastasis in sonic-hedgehog medulloblastoma by promoting cancer stem-like phenotypes.

BACKGROUND: Medulloblastomas (MBs) are one of the most common malignant brain tumor types in children. MB prognosis, despite improvement in recent years, still depends on clinical and biological risk factors. Metastasis is the leading cause of MB-related deaths, which highlights an unmet need for risk stratification and targeted therapy to improve clinical outcomes. Among the four molecular subgroups, sonic-hedgehog (SHH)-MB harbors clinical and genetic heterogeneity with a subset of high-risk cases. Recently, long non-coding (lnc)RNAs were implied to contribute to cancer malignant progression, but their role in MB remains unclear. This study aimed to identify pro-malignant lncRNAs that have prognostic and therapeutic significance in SHH-MB. METHODS: The Daoy SHH-MB cell line was engineered for ectopic expression of MYCN, a genetic signature of SHH-MB. MYCN-associated lncRNA genes were identified using RNA-sequencing data and were validated in SHH-MB cell lines, MB tissue samples, and patient cohort datasets. SHH-MB cells with genetic manipulation of the candidate lncRNA were evaluated for metastatic phenotypes in vitro, including cell migration, invasion, sphere formation, and expressions of stemness markers. An orthotopic xenograft mouse model was used to evaluate metastasis occurrence and survival. Finally, bioinformatic screening and in vitro assays were performed to explore downstream mechanisms. RESULTS: Elevated lncRNA LOXL1-AS1 expression was identified in MYCN-expressing Daoy cells and MYCN-amplified SHH-MB tumors, and was significantly associated with lower survival in SHH-MB patients. Functionally, LOXL1-AS1 promoted SHH-MB cell migration and cancer stemness in vitro. In mice, MYCN-expressing Daoy cells exhibited a high metastatic rate and adverse effects on survival, both of which were suppressed under LOLX1-AS1 perturbation. Integrative bioinformatic analyses revealed associations of LOXL1-AS1 with processes of cancer stemness, cell differentiation, and the epithelial-mesenchymal transition. LOXL1-AS1 positively regulated the expression of transforming growth factor (TGF)-ß2. Knockdown of TGF-ß2 in SHH-MB cells significantly abrogated their LOXL1-AS1-mediated prometastatic functions. CONCLUSIONS: This study proved the functional significance of LOXL1-AS1 in SHH-MB metastasis by its promotion of TGF-ß2-mediated cancer stem-like phenotypes, providing both prognostic and therapeutic potentials for targeting SHH-MB metastasis.

A real-world cohort study of first-line afatinib in patients with EGFR-mutant advanced non-small cell lung cancer in Vietnam.

BACKGROUND: This study aimed to evaluate the efficacy and side effects of first-line afatinib treatment in a real-world setting in Vietnam. METHODS: This retrospective study was conducted across nine hospitals in Vietnam. Advanced epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients who received afatinib as first-line therapy between April 2018 and June 2022 were included, and patient medical records were reviewed. Key outcomes were overall response rate (ORR), time-to-treatment failure (TTF), and tolerability. RESULTS: A total of 343 patients on first-line afatinib were eligible for the study. EGFR exon 19 deletion (Del19) alone was detected in 46.9% of patients, L858R mutation alone in 26.3%, and other uncommon EGFR mutations, including compound mutations, in 26.8%. Patients with brain metastases at baseline were 25.4%. Patients who received 40 mg, 30 mg, and 20 mg as starting doses of afatinib were 58.6%, 39.9%, and 1.5%, respectively. The ORR was 78.1% in the overall population, 82.6% in the Del19 mutation subgroup, 73.3% in the L858R mutation subgroup, and 75.0% in the uncommon mutation subgroup (p > 0.05). The univariate and multivariate analyses indicate that the ORR increased when the starting dose was 40 mg compared to starting doses below 40 mg (83.9% vs. 74.3%, p = 0.034). The median TTF (mTTF) was 16.7 months (CI 95%: 14.8-18.5) in all patients, with a median follow-up time of 26.2 months. The mTTF was longer in patients in the common EGFR mutation subgroup (Del19/L858R) than in those in the uncommon mutation subgroup (17.5 vs. 13.8 months, p = 0.045) and in those without versus with brain metastases at baseline (17.5 vs. 15.1 months, p = 0.049). There were no significant differences in the mTTF between subgroups based on the starting dose of 40 mg and < 40 mg (16.7 vs. 16.9 months, p > 0.05). The most common treatment-related adverse events (any grade/grade ≥ 3) were diarrhea (55.4%/3.5%), rash (51.9%/3.2%), paronychia (35.3%/5.0%), and stomatitis (22.2%/1.2%). CONCLUSIONS: Afatinib demonstrated clinical effectiveness and good tolerability in Vietnamese EGFR-mutant NSCLC patients. In our real-world setting, administering a starting dose below 40 mg might result in a reduction in ORR; however, it might not have a significant impact on TTF.

Inducing experimental bacterial chondronecrosis with osteomyelitis lameness in broiler chickens using aerosol transmission model.

Lameness disease attributed to bacterial chondronecrosis with osteomyelitis in broilers affects production, animal welfare, and food safety in the poultry industry. The disease is characterized by necrotic degeneration of the rapidly growing femora and tibiae due to bacterial translocation from the respiratory or gastrointestinal tracts into the blood circulation, eventually colonizing the growth plate of the long bones. To investigate the etiology, pathogenesis, and intervention measures for BCO, developing an experimental model that reliably induces BCO lameness is of the utmost importance. In the past, we have employed a wire-flooring model and a litter-flooring model administered with a bacterial challenge to investigate strategies for mitigating BCO. However, multiple issues on labor-intensive barn setup and cleanout efforts for the wire-flooring system and concern of direct pathogenic exposure to the broilers for the litter-flooring models rendered these research models less effective. Thus, we investigated a new approach to induce experimental BCO lameness using an aerosol transmission model employing a group of birds reared on wire-flooring pens as a BCO infection source, and the disease is further disseminated through the airborne transmission to other birds reared on litter flooring in the same housing environment. The effectiveness of the aerosol transmission model in inducing BCO lameness was concluded from 4 independent experiments. The cumulative lameness generated from the BCO source group on the wire floors versus negative control treatments on the litter floors from Experiments 1, 2, 3, and 4 were 84% vs. 69.33%, P = 0.09; 54.55% vs. 60%, P = 0.56; 78% vs. 73.50%, P = 0.64; 81% vs. 74.50%, P = 0.11. Overall, the cumulative lameness generated from the wire floors was successfully transmitted to the birds on litter floors without significant statistical differences (P > 0.05). The effectiveness of the aerosol transmission model for experimentally triggering BCO lameness provides a reliable system for evaluating practical intervention strategies for BCO lameness in broilers.

Zona pellucida removal resulted in a successful live birth: Report on a case with recurrent implantation failure due to embryonic bacteria contamination.

Key clinical message: In in vitro fertilization (IVF), laser offers several advantages. In this study, we employed laser to eliminate the zona pellucida of a contaminated embryo. This approach helps to rescue embryo with bacterial contamination, and improve embryo-endometrium interaction. Abstract: To present a case report on the removal of a contaminated zona pellucida from an embryo of patient with a history of recurrent implantation failure (RIF), which was followed by a successful live birth. We present the case of a 34-year-old patient with a history of 3 years of infertility who underwent in vitro fertilization. During the culture process, the embryos became contaminated, leading to three failed implantations. Despite the aneuploidy of the embryo and the implementation of a washing technique, the contamination persisted. In the final attempt, the contaminated zona pellucida was successfully removed using laser, followed by embryo transfer, resulting in a live birth. We provided detailed clinical information, including patient demographics, infertility history, ovarian response, evidence of bacterial contamination, embryo development, treatment protocols, and outcomes. Laser excision of the zona pellucida is a safe and effective method for addressing bacterial infection in embryos.

Multi-cohort cerebrospinal fluid proteomics identifies robust molecular signatures for asymptomatic and symptomatic Alzheimer's disease.

Changes in Amyloid-ß (A), hyperphosphorylated Tau (T) in brain and cerebrospinal fluid (CSF) precedes AD symptoms, making CSF proteome a potential avenue to understand the pathophysiology and facilitate reliable diagnostics and therapies. Using the AT framework and a three-stage study design (discovery, replication, and meta-analysis), we identified 2,173 proteins dysregulated in AD, that were further validated in a third totally independent cohort. Machine learning was implemented to create and validate highly accurate and replicable (AUC>0.90) models that predict AD biomarker positivity and clinical status. These models can also identify people that will convert to AD and those AD cases with faster progression. The associated proteins cluster in four different protein pseudo-trajectories groups spanning the AD continuum and were enrichment in specific pathways including neuronal death, apoptosis and tau phosphorylation (early stages), microglia dysregulation and endolysosomal dysfuncton(mid-stages), brain plasticity and longevity (mid-stages) and late microglia-neuron crosstalk (late stages).

Coffee Husk By-Product as Novel Ingredients for Cascara Kombucha Production.

Kombucha, a fermented beverage, is gaining popularity due to its numerous beneficial health effects. Various substrates such as herbs, fruits, flowers, and vegetables, have been used for kombucha fermentation in order to enhance the flavor, aroma, and nutritional composition. This study aims to investigate the potential suitability of cascara as a novel ingredient for kombucha production. Our findings suggested that cascara is a suitable substrate for kombucha production. Fermentation elevated the total phenolic and flavonoid content in cascara, which enhanced the antioxidant, antibacterial, and prebiotic characteristics of the product. Furthermore, the accumulation of acetic acid-induced the pH lowering reached 2.7 after 14 days of fermentation, which achieved the microbiological safety of the product. Moreover, 14 days of fermentation resulted in a balanced amalgamation of acidity, sweetness, and fragrance according to sensory evaluation. Our findings not only highlight the potential of cascara kombucha as a novel substrate for kombucha production but also contribute to repurposing coffee by-products, promoting environmentally friendly and sustainable agricultural development.

Systematic proteomics in Autosomal dominant Alzheimer's disease reveals decades-early changes of CSF proteins in neuronal death, and immune pathways.

Background: To date, there is no high throughput proteomic study in the context of Autosomal Dominant Alzheimer's disease (ADAD). Here, we aimed to characterize early CSF proteome changes in ADAD and leverage them as potential biomarkers for disease monitoring and therapeutic strategies. Methods: We utilized Somascan® 7K assay to quantify protein levels in the CSF from 291 mutation carriers (MCs) and 185 non-carriers (NCs). We employed a multi-layer regression model to identify proteins with different pseudo-trajectories between MCs and NCs. We replicated the results using publicly available ADAD datasets as well as proteomic data from sporadic Alzheimer's disease (sAD). To biologically contextualize the results, we performed network and pathway enrichment analyses. Machine learning was applied to create and validate predictive models. Findings: We identified 125 proteins with significantly different pseudo-trajectories between MCs and NCs. Twelve proteins showed changes even before the traditional AD biomarkers (Aß42, tau, ptau). These 125 proteins belong to three different modules that are associated with age at onset: 1) early stage module associated with stress response, glutamate metabolism, and mitochondria damage; 2) the middle stage module, enriched in neuronal death and apoptosis; and 3) the presymptomatic stage module was characterized by changes in microglia, and cell-to-cell communication processes, indicating an attempt of rebuilding and establishing new connections to maintain functionality. Machine learning identified a subset of nine proteins that can differentiate MCs from NCs better than traditional AD biomarkers (AUC>0.89). Interpretation: Our findings comprehensively described early proteomic changes associated with ADAD and captured specific biological processes that happen in the early phases of the disease, fifteen to five years before clinical onset. We identified a small subset of proteins with the potentials to become therapy-monitoring biomarkers of ADAD MCs. Funding: Proteomic data generation was supported by NIH: RF1AG044546.

Harmonization of CSF and imaging biomarkers in Alzheimer's disease: Need and practical applications for genetics studies and preclinical classification.

In Alzheimer's disease (AD) research, cerebrospinal fluid (CSF) Amyloid beta (Aß), Tau and pTau are the most accepted and well validated biomarkers. Several methods and platforms exist to measure those biomarkers, leading to challenges in combining data across studies. Thus, there is a need to identify methods that harmonize and standardize these values. We used a Z-score based approach to harmonize CSF and amyloid imaging data from multiple cohorts and compared GWAS results using this approach with currently accepted methods. We also used a generalized mixture model to calculate the threshold for biomarker-positivity. Based on our findings, our normalization approach performed as well as meta-analysis and did not lead to any spurious results. In terms of dichotomization, cutoffs calculated with this approach were very similar to those reported previously. These findings show that the Z-score based harmonization approach can be applied to heterogeneous platforms and provides biomarker cut-offs consistent with the classical approaches without requiring any additional data.

Effect of Mass Fraction on Leaching Kinetics of Hydrophobic Ultraviolet Stabilizers in Low-Density Polyethylene.

The leaching kinetics of five hydrophobic ultraviolet (UV) stabilizers from low-density polyethylene (LDPE) (micro)fibers into water was evaluated in this study, with variation of the mass fraction (ω = 0.1-2.0 wt %) of the stabilizers. A one-dimensional convection-diffusion model for a cylindrical geometry, requiring partitioning between the LDPE fibers and water (KLDPEw) and the internal diffusion coefficients (DLDPE), was used to evaluate the leaching process and the leaching half-life of the target UV stabilizers at ω < 0.5 wt % (Case I). Diffusion through the aqueous boundary layer is the rate-determining step, and the leaching half-life is predicted to be very long (a few months to years) under unaffected conditions. When the UV stabilizers are supersaturated within LDPE fibers (i.e., ω > 0.5 wt %, Case II), the possible formation of a surficial crystal layer of the additives on the LDPE fiber extends the time scale for leaching compared to that in Case I due to the requirement of overcoming the crystallization energy. This study provides a fundamental understanding of the leaching profiles of plastic additives for assessing their potential chemical risks in aquatic environments; further studies under the relevant environmental conditions are required.

Targeting of RRM2 suppresses DNA damage response and activates apoptosis in atypical teratoid rhabdoid tumor.

BACKGROUND: Atypical teratoid rhabdoid tumors (ATRT) is a rare but aggressive malignancy in the central nervous system, predominantly occurring in early childhood. Despite aggressive treatment, the prognosis of ATRT patients remains poor. RRM2, a subunit of ribonucleotide reductase, has been reported as a biomarker for aggressiveness and poor prognostic conditions in several cancers. However, little is known about the role of RRM2 in ATRT. Uncovering the role of RRM2 in ATRT will further promote the development of feasible strategies and effective drugs to treat ATRT. METHODS: Expression of RRM2 was evaluated by molecular profiling analysis and was confirmed by IHC in both ATRT patients and PDX tissues. Follow-up in vitro studies used shRNA knockdown RRM2 in three different ATRT cells to elucidate the oncogenic role of RRM2. The efficacy of COH29, an RRM2 inhibitor, was assessed in vitro and in vivo. Western blot and RNA-sequencing were used to determine the mechanisms of RRM2 transcriptional activation in ATRT. RESULTS: RRM2 was found to be significantly overexpressed in multiple independent ATRT clinical cohorts through comprehensive bioinformatics and clinical data analysis in this study. The expression level of RRM2 was strongly correlated with poor survival rates in patients. In addition, we employed shRNAs to silence RRM2, which led to significantly decrease in ATRT colony formation, cell proliferation, and migration. In vitro experiments showed that treatment with COH29 resulted in similar but more pronounced inhibitory effect. Therefore, ATRT orthotopic mouse model was utilized to validate this finding, and COH29 treatment showed significant tumor growth suppression and prolong overall survival. Moreover, we provide evidence that COH29 treatment led to genomic instability, suppressed homologous recombinant DNA damage repair, and subsequently induced ATRT cell death through apoptosis in ATRT cells. CONCLUSIONS: Collectively, our study uncovers the oncogenic functions of RRM2 in ATRT cell lines, and highlights the therapeutic potential of targeting RRM2 in ATRT. The promising effect of COH29 on ATRT suggests its potential suitability for clinical trials as a novel therapeutic approach for ATRT.

Effects of Roasting Conditions on Antibacterial Properties of Vietnamese Turmeric (Curcuma longa) Rhizomes.

Processing with heat treatment has been reported to alter several therapeutic effects of turmeric. In Vietnamese traditional medicine, turmeric has been long used for bacterial infections, and roasting techniques are sometimes applied with this material. However, there have been no studies investigating the effects of these thermal processes on the plant's antibacterial properties. Our study was therefore performed to examine the changes that roasting produced on this material. Slices of dried turmeric were further subjected to light-roasting (80 °C in 20 min) or dark-roasting (160 °C in 20 min) processes. Broth dilution and agar-well diffusion methods were applied to examine and compare the effects of ethanol extracts obtained from non-roasted, light-roasted and dark-roasted samples, on a set of 6 gram-positive and gram-negative bacteria. In both investigations, dark-roasted turmeric was significantly less antibacterial than non-roasted and light-roasted materials, as evident by the higher values of minimum inhibitory concentrations and the smaller diameters of induced inhibitory zones. In addition, dark-roasting was also found to clearly reduce curcumin contents, total polyphenol values and antioxidant activities of the extracts. These results suggest that non-roasting or light-roasting might be more suitable for the processing of turmeric materials that are aimed to be applied for bacterial infections.

Toward sustainable development goals in gender inequality: an analysis of gender preferences among urban pregnant women in a Southeast Asian country.

BACKGROUND: Gender-biased discrimination and preferences are global phenomena, particularly son preferences. However, updated evidence about this issue in Vietnam has not yet been provided. Therefore, this study aimed to examine the gender preferences among pregnant women and identify associated factors of such preferences. METHODS: A cross-sectional survey was conducted in two hospitals in Vietnam with 732 pregnant women. Gender preferences for their child were asked, along with socio-demographic (e.g., education, occupation) and pregnancy characteristics (e.g., pressure to have a son, gender of first child, the importance to have a son of family members, and information sources on pregnancy care) by using face-to-face interviews and a structured questionnaire. Multinomial logistic regression was performed to determine factors associated with gender preferences. RESULTS: About 51.9% of the participants had no gender preference, while, among those who had a gender preference, 26.5% preferred sons, and 21.6% preferred daughters. Only 6.2% had pressure to have a son. Having the first child who was female (OR = 4.16, 95%CI = 1.54-11.25), having the pressure to have a son (OR = 6.77, 95%CI = 2.06-22.26), and higher self-perceived importance to have a son (OR = 3.05, 95%CI = 1.85-5.02) were positively associated with son preference. Otherwise, women having partners with high school education or above (OR = 2.04, 95%CI = 1.06-3.91), living with parents-in-law (OR = 2.33; 95%CI = 1.25-4.34), the higher number of pregnancies, and a higher degree of importance in having a son regarding parents-in-law (OR = 2.15, 95%CI = 1.38-3.35) associated with higher odds of preferring daughter. CONCLUSION: This study showed that gender preference was common among pregnant women, but the pressure to have a son was low. Further education programs and legal institutions should be implemented to improve gender inequality and gender preference in society.