Hormone-free versus FSH-primed infertility treatment of women with polycystic ovary syndrome using biphasic in vitro maturation: a randomized controlled trial.

OBJECTIVE: To compare oocyte maturation rates and pregnancy outcomes in women with polycystic ovary syndrome (PCOS) undergoing biphasic in vitro maturation (capacitation [CAPA]-IVM) with versus without follicle-stimulating hormone (FSH) priming. DESIGN: Randomized, controlled, assessor-blinded trial SUBJECTS: Women aged 18-37 years with PCOS and an indication for CAPA-IVM. INTERVENTION: Participants were randomized (1:1) to undergo CAPA-IVM with or without FSH priming. The FSH priming group had two days of FSH injections before oocyte pick-up; no FSH was given in the non-FSH group. After CAPA-IVM, day-5 embryos were vitrified for transfer in a subsequent cycle. MAIN OUTCOME MEASURE(S): The primary endpoint was number of matured oocytes. Secondary outcomes included rates of live birth, implantation, clinical pregnancy, ongoing pregnancy, pregnancy complications, obstetric and perinatal complications, and neonatal complications. RESULTS: The number [interquartile range] of matured oocytes did not differ significantly in the non-FSH versus FSH group (13 [9-18] vs. 14 [7-8]; absolute difference -1 [95% confidence interval (CI) -5, 4]); other oocyte and embryology outcomes did not differ between groups. Rates of ongoing pregnancy and live birth were both 38.3% in the non-FSH group and both 31.7% in the FSH group (risk ratio for both outcomes: 1.21, 95% CI 0.74-1.98). Maternal complications were infrequent and occurred at a similar rate in the two groups; there were no preterm deliveries before 32 weeks' gestation. CONCLUSION: These findings open the possibility of a new, hormone-free approach to infertility treatment of women with PCOS.

Periodic Flows in Microfluidics.

Microfluidics, the science and technology of manipulating fluids in microscale channels, offers numerous advantages, such as low energy consumption, compact device size, precise control, fast reaction, and enhanced portability. These benefits have led to applications in biomedical assays, disease diagnostics, drug discovery, neuroscience, and so on. Fluid flow within microfluidic channels is typically in the laminar flow region, which is characterized by low Reynolds numbers but brings the challenge of efficient mixing of fluids. Periodic flows are time-dependent fluid flows, featuring repetitive patterns that can significantly improve fluid mixing and extend the effective length of microchannels for submicron and nanoparticle manipulation. Besides, periodic flow is crucial in organ-on-a-chip (OoC) for accurately modeling physiological processes, advancing disease understanding, drug development, and personalized medicine. Various techniques for generating periodic flows have been reported, including syringe pumps, peristalsis, and actuation based on electric, magnetic, acoustic, mechanical, pneumatic, and fluidic forces, yet comprehensive reviews on this topic remain limited. This paper aims to provide a comprehensive review of periodic flows in microfluidics, from fundamental mechanisms to generation techniques and applications. The challenges and future perspectives are also discussed to exploit the potential of periodic flows in microfluidics.

Immunotherapy and Radiotherapy for Older Patients with Locally Advanced Non-Metastatic Non-Small-Cell Lung Cancer Who Are Not Candidates for or Decline Surgery and Chemotherapy: A Practical Proposal by the International Geriatric Radiotherapy Group.

The standard of care for locally advanced non-small-cell lung cancer (NSCLC) is either surgery combined with chemotherapy pre- or postoperatively or concurrent chemotherapy and radiotherapy. However, older and frail patients may not be candidates for surgery and chemotherapy due to the high mortality risk and are frequently referred to radiotherapy alone, which is better tolerated but carries a high risk of disease recurrence. Recently, immunotherapy with immune checkpoint inhibitors (ICIs) may induce a high response rate among cancer patients with positive programmed death ligand 1 (PD-L1) expression. Immunotherapy is also well tolerated among older patients. Laboratory and clinical studies have reported synergy between radiotherapy and ICI. The combination of ICI and radiotherapy may improve local control and survival for NSCLC patients who are not candidates for surgery and chemotherapy or decline these two modalities. The International Geriatric Radiotherapy Group proposes a protocol combining radiotherapy and immunotherapy based on the presence or absence of PD-L1 to optimize the survival of those patients.

The Cost of Opioid Use in High-Risk Hospitalized Infants.

INTRODUCTION: Hospitalizations of high-risk infants are among the most expensive in the United States, with many requiring surgery and months of intensive care. Healthcare costs and resource use associated with hospitalized infant opioid exposure are less well known. METHODS: A retrospective cohort of high-risk infants aged <1 y admitted from 47 children's hospitals from 2010 to 2020 was identified from Pediatric Healthcare Information System. High-risk infants were identified by International Classification of Diseases 9/10 codes for congenital heart disease procedures, medical and surgical necrotizing enterocolitis, extremely low birth weight, very low birth weight, hypoxemic ischemic encephalopathy, extracorporeal membrane oxygenation, and gastrointestinal tract malformations. Healthcare resource utilization was estimated using standardized unit costs (SUCs). The impact of opioid use on SUC was examined using general linear models and an instrumental variable. RESULTS: Overall, 126,897 high-risk infants were identified. The cohort was majority White (57.1%), non-Hispanic (72.0%), and male (55.4%). Prematurity occurred in 26.4% and a majority underwent surgery (77.9%). Median SUC was $120,585 (interquartile range: $57,602-$276,562) per infant. On instrumental variable analysis, each day of opioid use was associated with an increase of $4406 in SUC. When adjusting for biologic sex, race, ethnicity, insurance type, diagnosis category, number of comorbidities, mechanical ventilation, and total parental nutrition use, each day of opioid use was associated with an increase of $2177 per infant. CONCLUSIONS: Prolonged opioid use is significantly associated with healthcare utilization and costs for high-risk infants, even when accounting for comorbidities, intensive care, ventilation, and total parental nutrition use. Future studies are needed to estimate the long-term complications and additional costs resulting from prolonged opioid exposures in high-risk infants.

Molecular evolution and genotype shift of Porcine circoviruses type 2 in Vietnam.

Porcine Circovirus Type 2 (PCV2), a significant pathogen in the global swine industry, causes Porcine Circovirus Associated Diseases (PCVAD), contributing to substantial economic losses. This study investigates the genetic diversity and evolutionary dynamics of PCV2 in Vietnam from 2007 to 2023. We sequenced and analyzed 47 PCV2 genomes isolated from swine farms across Vietnam between 2022 and 2023, revealing predominant circulation of PCV2d (80.85%) followed by PCV2b (19.15%). Phylogenetic analysis identified PCV2 genotypes PCV2a, PCV2b, PCV2d, PCV2g, and PCV2h circulating in Vietnam, with PCV2d emerging as the most prevalent genotype. Comparison with historical data highlighted genotype shifts from PCV2b to PCV2d in 2014. Interestingly, PCV2h genotype was mainly observed between 2008 and 2012 but have not been detected since 2014. Regional analysis indicated varied PCV2 epidemiological patterns between northern and southern Vietnam. Amino acid substitutions within the capsid protein were identified, predominantly in antigenic regions critical for immune recognition. Positive selection analysis identified multiple sites under evolutionary pressure, indicating ongoing adaptation of Vietnamese PCV2 strains. These findings enhance understanding of PCV2 dynamics in Vietnam and underscore the importance of continuous surveillance and adaptive management strategies in controlling PCV2-associated diseases in swine populations.

Short-term effects of Kinesiotaping combined with a rehabilitation program for rotator cuff-related shoulder pain: a randomized, assessor-blinded clinical trial.

OBJECTIVES: This study aimed to determine the clinical efficacy of Kinesiotaping (KT) combined with a rehabilitation program to reduce symptoms and functional limitations in patients with Rotator Cuff-Related Shoulder Pain (RCRSP) in Vietnam. METHODS: In total, 82 participants who were diagnosed with RCRSP were randomly allocated into two groups. Both groups received a standard rehabilitation program; additionally, the intervention group was treated with KT. Outcomes, assessed at baseline, and 3, 7, and 14 days postintervention, included pain intensity (Visual Analogue Scale, VAS), functional disability (Shoulder Pain and Disability Index, SPADI), and active range of motion (ROM). RESULTS: The KT group exhibited significant improvements in all outcome measures. VAS scores decreased by an average of 13.3 points in the KT group at 14 days, which was notably greater than that in the control group (95% CI: -17.77 to -8.82). SPADI scores also improved significantly in the KT group, with reductions of -11.36, -15.27, and -13.3 at days 3, 7, and 14, respectively. Regarding ROM, the KT group showed notable improvements in flexion and external rotation, with flexion ROM differences of 10.78, 10.35, and 11.8 degrees at the respective time points. No significant changes were observed in the abduction or internal rotation ROM. After adjusting for age, baseline scores, and gender, there was a statistically significant interaction between Group and Time on the VAS, SPADI, and ROM abduction. CONCLUSION: Incorporating KT into a standard rehabilitation program for RCRSP demonstrated enhanced efficacy in reducing pain and improving shoulder function. The results suggest that KT can be a valuable component of the treatment regimen for RCRSP.

Mitogen-Activated Protein Kinase Kinase OsMEK2 Positively Regulates Ca2+ Influx and Ferroptotic Cell Death during Rice Immune Responses.

Mitogen-activated protein (MAP) kinase (MAPK) signaling pathway is important in plant immune responses, involved in iron- and reactive oxygen species (ROS)-dependent ferroptotic cell death mediated by Ca2+. High Ca2+ influx triggered iron-dependent ROS accumulation, lipid peroxidation, and subsequent hypersensitive response (HR) cell death in rice (Oryza sativa). Apoplastic Ca2+ chelation by EGTA during avirulent Magnaporthe oryzae infection altered Ca2+, ROS, and Fe2+ accumulation, increasing rice susceptibility to infection. By contrast, acibenzolar-S-methyl (ASM), a plant defense activator, significantly enhanced Ca2+ influx, and H2O2 accumulation, triggering rice ferroptotic cell death during virulent Magnaporthe oryzae infection. Here, we report a novel role of the MAPK signaling pathway in regulating cytoplasmic Ca2+ increase during ferroptotic cell death in rice immunity, using the ΔOsmek2 knockout mutant rice. The knockout of rice OsMEK2 impaired the ROS accumulation, lipid peroxidation, and iron accumulation during avirulent M. oryzae infection. This study has shown that OsMEK2 could positively regulate iron- and ROS-dependent ferroptotic cell death in rice by modulating the expression of OsNADP-ME, OsRBOHB, OsPLC, and OsCNGC. This modulation indicates a possible mechanism for how OsMEK2 participates in Ca2+ regulation in rice ferroptotic cell death, suggesting its broader role in plant immune responses in response to M. oryzae infection.

Understanding Acceptability and Willingness-to-pay for a C-reactive Protein Point-of-care Testing Service to Improve Antibiotic Dispensing for Respiratory Infections in Vietnamese Pharmacies: A Mixed-methods Study.

Background: Pharmacies are popular first points of contact for mild infections in the community. Pharmacy services in many countries have expanded to include vaccines and point-of-care tests. In low- and middle-income countries such as Vietnam, poor enforcement of regulations results in substantial volumes of over-the-counter antibiotic sales. Point-of-care tests could provide an economically viable way to reduce antibiotic sales, while still satisfying customer demand for convenient healthcare. C-reactive protein point-of-care testing (CRP-POCT) can reduce antibiotic prescribing for respiratory illness in primary care. Here, we explore the acceptability and feasibility of implementing CRP-POCT in pharmacies in Vietnam. Methods: We conducted a mixed-methods study between April and June 2021. A customer exit survey with 520 participants seeking acute respiratory infection treatment at 25 pharmacies evaluated acceptability and willingness-to-pay (WTP) for CRP-POCT and post-service satisfaction. Factors driving customers" acceptance and WTP were explored through mixed-effects multivariable regression. Three focus group discussions with customers (20 participants) and 12 in-depth interviews with pharmacists and other stakeholders were conducted and analyzed thematically. Results: Antibiotics were sold to 81.4% of patients with CRP levels <10 mg/L (antibiotics not recommended). A total of 96.5% of customers who experienced CRP-POCT supported its future introduction at pharmacies. Patients with antibiotic transactions (adjusted odds ratio [aOR], 2.25; 95% confidence interval [CI], 1.13-4.48) and those suffering acute respiratory infection symptoms for more than 3 days (aOR, 2.10; 95% CI, 1.08-4.08) were more likely to accept CRP-POCT, whereas customers visiting for children (aOR, 0.20; 95% CI, .10-.54) and those with preference for antibiotic treatment (aOR, 0.45; 95% CI, 0.23-0.89) were less likely to accept CRP-POCT. A total of 78.3% (95% CI, 74.8-81.7) of customers were willing to pay for CRP-POCT, with a mean cost of US$2.4 (±1.1). Customer's income and cost of total drug treatment were associated with increased WTP. Enablers for implementing CRP-POCT included customers' and pharmacists' perceived benefits of CRP-POCT, and the impact of COVID-19 on perceptions of POCT. Perceived challenges for implementation included the additional burden of service provision, lack of an enabling policy environment, and potential risks for customers. Conclusions: Implementing CRP-POCT at pharmacies is a feasible and well-accepted strategy to tackle the overuse of antibiotics in the community, with appeal for both supply and demand sides. Creating an enabling policy environment for its implementation, and transparent discussion of values and risks would be key for its successful implementation.

Dengue Hemorrhagic Fever in Quang Nam Province (Vietnam) from 2020 to 2022-A Study on Serotypes Distribution and Immunology Factors.

Background: Dengue hemorrhagic fever (DHF) is the most prevalent and fastest-growing vector-borne disease globally, with symptoms ranging from mild to severe and, in some cases, fatal. Quang Nam province in Vietnam can serve as a model for dengue epidemiological study, as it is an endemic region for DHF with a tropical climate, which significantly constrains the health system. However, there are very few epidemiological and microbiological reports on Dengue virus (DENV) serotypes in this region due to the limited availability of advanced surveillance infrastructure. Aims of the study: This study aims to (1) assess the PCR positivity rates among hospitalized patients with clinical Dengue presentation; (2) identify the circulating DENV serotypes; and (3) assess the impact of secondary DENV infections on outbreak severity by detecting the presence of DENV-specific IgG antibodies in the plasma of DENV-infected patients. Materials and methods: Blood samples from patients clinically diagnosed with DHF and admitted to Quang Nam General Hospital (2020-2022) were analyzed. RNA extraction was performed using the NKDNA/RNAprep MAGBEAD kit, followed by Multiplex Reverse Transcription real-time Polymerase Chain Reaction (MLP RT-rPCR) for DENV detection and serotype identification. Positive samples were further tested for DENV-specific IgG antibodies using an enzyme-linked immunosorbent assay (ELISA). Results: The PCR positivity rate among hospitalized patients was approximately 68% throughout the study period. A significant shift in DENV serotypes was observed, with DENV-2 initially dominant and later giving way to DENV-1. IgG was detected in nearly half of the MPL RT-rPCR-positive samples, indicating secondary DENV infections. Conclusions: Our study highlights persistent dengue prevalence and dynamic shifts in DENV serotypes in Quang Nam province, emphasizing the need for improved diagnostic strategies and timely sample collection. The significant serotype shifts and the presence of IgG in hospitalized patients suggest potential severe outcomes from recurrent DENV infections, possibly linked to antibody-dependent enhancement (ADE) effect, underscoring the importance of advanced surveillance, vector control, vaccination campaigns, and public education to predict and prevent future DHF epidemics.

PSA Levels and Mortality in Prostate Cancer Patients.

INTRODUCTION: Prostate cancer (PC) is the second most common cancer among men around the world. Several smaller studies have explored the relationship between elevated PSA and mortality, but results have been conflicting. Additionally, studies have shown that Black men are more likely to be diagnosed with PC at late-stages and may have a twofold increase in mortality risk. This study aims to evaluate the relationship between PSA levels and mortality in patients with PC and differences between Black versus White patients. METHODS: In this retrospective study, the TriNetX database, was used to extract de-identified EMRs of 198,083 patients. Patients were included if they were diagnosed with PC and had obtained a PSA level (measured in ng/mL) within 6 months prior to diagnosis. Cohorts were separated into 7 groups based on intervals of PSA, ranging from < 2 to ≥ 500 and compared to a control cohort with a PSA of 4 to 20 for differing 2-year mortality rates. A subgroup analysis was performed to compare mortality differences between Black and White patients. A posthoc analysis evaluated 5- and 10-year mortality amongst all patients with PC. RESULTS: After propensity matching, mortality risk was significantly lower for patients with PSA < 2 (5.9% vs. 7.5%; RR 0.784; P < .001) when compared to the control cohort. Mortality was significantly higher for all other subsequent PSA intervals > 20, with the lowest risk ratios at PSA 20-100 (24.1% vs. 10.0%; RR 2.419; P < .001) and highest at PSA 200 to 500 (50.4% vs. 10.8%; RR 4.673; P < .001). The sub-group analysis showed that when compared to White patients, Black patients with PSA < 20 had similar mortalities, but had significantly lower 2-year mortality rates at PSA levels ≥ 20. The posthoc analysis of PSA levels and 5- and 10-year mortality of all patients with PC showed similar trends to the 2-year outcomes. CONCLUSION: This study found that prostate cancer patients with significantly elevated PSA levels have a greater mortality, and Black patients have lower 2-year mortality rates than their White counterparts when matched for PSA levels greater than 20.

Integrated drug resistance and leukemic stemness gene-expression scores predict outcomes in large cohort of over 3500 AML patients from 10 trials.

In this study, we leveraged machine-learning tools by evaluating expression of genes of pharmacological relevance to standard-AML chemotherapy (ara-C/daunorubicin/etoposide) in a discovery-cohort of pediatric AML patients (N = 163; NCT00136084 ) and defined a 5-gene-drug resistance score (ADE-RS5) that was predictive of outcome (high MRD1 positivity p = 0.013; lower EFS p < 0.0001 and OS p < 0.0001). ADE-RS5 was integrated with a previously defined leukemic-stemness signature (pLSC6) to classify patients into four groups. ADE-RS5, pLSC6 and integrated-score was evaluated for association with outcome in one of the largest assembly of ~3600 AML patients from 10 independent cohorts (1861 pediatric and 1773 adult AML). Patients with high ADE-RS5 had poor outcome in validation cohorts and the previously reported pLSC6 maintained strong significant association in all validation cohorts. For pLSC6/ADE-RS5-integrated-score analysis, using Group-1 (low-scores for ADE-RS5 and pLSC6) as reference, Group-4 (high-scores for ADE-RS5 and pLSC6) showed worst outcome (EFS: p < 0.0001 and OS: p < 0.0001). Groups-2/3 (one high and one low-score) showed intermediate outcome (p < 0.001). Integrated score groups remained an independent predictor of outcome in multivariable-analysis after adjusting for established prognostic factors (EFS: Group 2 vs. 1, HR = 4.68, p < 0.001, Group 3 vs. 1, HR = 3.22, p = 0.01, and Group 4 vs. 1, HR = 7.26, p < 0.001). These results highlight the significant prognostic value of transcriptomics-based scores capturing disease aggressiveness through pLSC6 and drug resistance via ADE-RS5. The pLSC6 stemness score is a significant predictor of outcome and associates with high-risk group features, the ADE-RS5 drug resistance score adds further value, reflecting the clinical utility of simultaneous testing of both for optimizing treatment strategies.

Difference in Precocious Puberty Between Pre-COVID-19 and COVID-19 Periods: A Meta-Analysis.

We conducted this systematic review and meta-analysis to clarify the trend of precocious puberty (PP) incidence after the COVID-19 outbreak and explore potential contributing factors, such as age at presentation and body mass index standard deviation score (BMI SDS). Children visiting pediatric endocrinology clinics for the first time for suspected PP were included. We searched databases until February 28, 2023 for studies reporting various indicators of PP incidence before and during the pandemic. Total numbers of events and observations were recorded. A meta-analysis was performed to compare the odds of PP, BMI SDS, and age at presentation between the two periods. The dose-response relationships between time points (by number of years away from the pandemic) and PP risk were explored. In summary, a total of 32 studies including 24,200 participants were recruited. COVID-19 pandemic was associated with the increasing odds of PP among children referred for suspicious condition (OR 1.96; 95% CI 1.56-2.47; I2 = 54%; P < 0.001). Sensitivity analysis confirmed the robustness of the findings. BMI SDS did not vary between the two periods, while age at presentation was lower following the pandemic. PP incidence increased more rapidly during the pandemic period than during the prepandemic period.

Co-Expression of type 1 fimbriae and flagella in Escherichia coli: consequences for adhesion at interfaces.

Escherichia coli expresses surface appendages including fimbriae, flagella, and curli, at various levels in response to environmental conditions and external stimuli. Previous studies have revealed an interplay between expression of fimbriae and flagella in several E. coli strains, but how this regulation between fimbrial and flagellar expression affects adhesion to interfaces is incompletely understood. Here, we investigate how the concurrent expression of fimbriae and flagella by engineered strains of E. coli MG1655 affects their adhesion at liquid-solid and liquid-liquid interfaces. We tune fimbrial and flagellar expression on the cell surface through plasmid-based inducible expression of the fim operon and fliC-flhDC genes. We show that increased fimbrial expression increases interfacial adhesion as well as bacteria-driven actuation of micron-sized objects. Co-expression of flagella in fimbriated bacteria, however, does not greatly affect either of these properties. Together, these results suggest that interfacial adhesion as well as motion actuated by adherent bacteria can be altered by controlling the expression of surface appendages.

Immunotherapy and radiotherapy for older patients with invasive bladder cancer unfit for surgery or chemotherapy: practical proposal by the international geriatric radiotherapy group.

The standard of care for non-metastatic muscle invasive bladder cancer is either radical cystectomy or bladder preservation therapy, which consists of maximal transurethral bladder resection of the tumor followed by concurrent chemoradiation with a cisplatin-based regimen. However, for older cancer patients who are too frail for surgical resection or have decreased renal function, radiotherapy alone may offer palliation. Recently, immunotherapy with immune checkpoint inhibitors (ICI) has emerged as a promising treatment when combined with radiotherapy due to the synergy of those two modalities. Transitional carcinoma of the bladder is traditionally a model for immunotherapy with an excellent response to Bacille Calmette-Guerin (BCG) in early disease stages, and with avelumab and atezolizumab for metastatic disease. Thus, we propose an algorithm combining immunotherapy and radiotherapy for older patients with locally advanced muscle-invasive bladder cancer who are not candidates for cisplatin-based chemotherapy and surgery.

Computational Fluid-Structure Interaction in Microfluidics.

Micro elastofluidics is a transformative branch of microfluidics, leveraging the fluid-structure interaction (FSI) at the microscale to enhance the functionality and efficiency of various microdevices. This review paper elucidates the critical role of advanced computational FSI methods in the field of micro elastofluidics. By focusing on the interplay between fluid mechanics and structural responses, these computational methods facilitate the intricate design and optimisation of microdevices such as microvalves, micropumps, and micromixers, which rely on the precise control of fluidic and structural dynamics. In addition, these computational tools extend to the development of biomedical devices, enabling precise particle manipulation and enhancing therapeutic outcomes in cardiovascular applications. Furthermore, this paper addresses the current challenges in computational FSI and highlights the necessity for further development of tools to tackle complex, time-dependent models under microfluidic environments and varying conditions. Our review highlights the expanding potential of FSI in micro elastofluidics, offering a roadmap for future research and development in this promising area.

Towards a Wearable Feminine Hygiene Platform for Detection of Invasive Fungal Pathogens via Gold Nanoparticle Aggregation.

Candida albicans is an opportunistic fungus that becomes pathogenic and problematic under certain biological conditions. C. albicans may cause painful and uncomfortable symptoms, as well as deaths in immunocompromised patients. Therefore, early detection of C. albicans is essential. However, conventional detection methods are costly, slow, and inaccessible to women in remote or developing areas. To address these concerns, we have developed a wearable and discrete naked-eye detectable colorimetric platform for C. albicans detection. With some modification, this platform is designed to be directly adhered to existing feminine hygiene pads. Our platform is rapid, inexpensive, user-friendly, and disposable and only requires three steps: (i) the addition of vaginal fluid onto sample pads; (ii) the addition of gold nanoparticle gel and running buffer, and (iii) naked eye detection. Our platform is underpinned by selective thiolated aptamer-based recognition of 1,3-ß-D glucan molecules-a hallmark of C. albicans cell walls. In the absence of C. albicans, wearable sample pads turn bright pink. In the presence of C. albicans, the wearable pads turn dark blue due to significant nanoparticle target-induced aggregation. We demonstrate naked-eye colorimetric detection of 4.4 × 106C. albicans cells per ml and nanoparticle stability over a pH range of 3.0-8.0. We believe that this proof-of-concept platform has the potential to have a significant impact on women's health globally.

High Prevalence of Colistin-Resistant Encoding Genes Carriage among Patients and Healthy Residents in Vietnam.

Background and Objectives: We aimed to investigate the carriage of colistin-resistant genes among both patients with a history of antibiotic exposure and apparently healthy adults with no recent healthcare contact. Materials and Methods: Stool swabs were collected from healthy people, and specimens were collected at the infection foci from the patients. Eleven primer/probe sets were used to perform the Multiplex Real-Time PCR assay with the QuantiNova Multiplex Probe PCR kit for screening the carriage of colistin-resistant genes (mcr-1 to mcr-10) and 16S rRNA gene as internal control. Results: In total, 86 patients and 96 healthy residents were included. Twenty two patients (25.9%) were positive with at least one colistin-resistance encoding gene. The mcr-1 gene was the most frequent (16.5%), followed by mcr-9, mcr-6, and mcr-4 genes, where the prevalence was 11.8%, 10.6%, and 9.4%, respectively. No patient was positive with mcr-3, mcr-7, and mcr-8 genes. Eight patients (9.4%) were positive with multiple colistin-encoding genes. Twenty-three healthy people (24.0%) were positive with at least one colistin-resistance encoding gene, and the mcr-10 gene was the most frequent (27.0%), followed by the mcr-1, mcr-8, and mcr-9 genes, where the prevalence was 24.3%, 21.6%, and 13.5%, respectively. No person was positive with the mcr-2 and mcr-5 genes. Conclusions: Our findings underscore the urgent need for enhanced surveillance, infection control measures, and stewardship interventions to mitigate the spread of colistin resistance in Vietnam.

The NEOLETRIB trial: neoadjuvant treatment with Letrozole and Ribociclib in ER-positive, HER2-negative breast cancer.

Chemotherapy is used as neoadjuvant therapy for all subgroups of breast cancer, including ER-positive, and HER2-negative cases. However, studies have suggested that using aromatase inhibitors combined with CDK4/6-inhibitors might be an appropriate alternative in selected patients. Thus, the NEOLETRIB trial evaluates the response of ER-positive, HER2-negative luminal A/B breast cancer to the combination of letrozole and ribociclib in the neoadjuvant setting. Comprehensive molecular biology procedures, including sequential single-cell RNA-sequencing of tumor biopsies, are performed during 6 months of treatment with extensive biobanking of blood samples, tumor biopsies and gut microbiome specimens. Our findings will hopefully contribute to an improved selection of patients who may benefit from this drug combination and give new insights into the intra-tumoral changes during this treatment.Trial registration number: NCT05163106 (ClinicalTrials.gov).

[Box: see text].

Directed Evolution of Protein-Based Sensors for Anaerobic Biological Activation of Methane.

Microbial alkane degradation pathways provide biological routes for converting these hydrocarbons into higher-value products. We recently reported the functional expression of a methyl-alkylsuccinate synthase (Mas) system in Escherichia coli, allowing for the heterologous anaerobic activation of short-chain alkanes. However, the enzymatic activation of methane via natural or engineered alkylsuccinate synthases has yet to be reported. To address this, we employed high-throughput screening to engineer the itaconate (IA)-responsive regulatory protein ItcR (WT-ItcR) from Yersinia pseudotuberculosis to instead respond to methylsuccinate (MS, the product of methane addition to fumarate), resulting in genetically encoded biosensors for MS. Here, we describe ItcR variants that, when regulating fluorescent protein expression in E. coli, show increased sensitivity, improved overall response, and enhanced specificity toward exogenously added MS relative to the wild-type repressor. Structural modeling and analysis of the ItcR ligand binding pocket provide insights into the altered molecular recognition. In addition to serving as biosensors for screening alkylsuccinate synthases capable of methane activation, MS-responsive ItcR variants also establish a framework for the directed evolution of other molecular reporters, targeting longer-chain alkylsuccinate products or other succinate derivatives.

Highly Efficient Photon Energy Conversion and Ultrasensitive Self-Powered Photodetection via a Monolithic p-3C-SiC Nanothin Film on p-Si/n-Si Double Junction.

The pursuit of increased efficiency of photoelectric energy conversion through optimized semiconductor structures remains highly competitive, with current results yet to align with broad expectations. In this study, we discover a significant enhancement in photocurrent performance of a p-3C-SiC nanothin film on p-Si/n-Si double junction (DJ) heterostructure that integrates p-3C-SiC/p-Si heterojunction and p-Si/n-Si homojunction. The vertical photocurrent (VPC) and vertical photoresponsivity exhibit a substantial enhancement in the DJ heterostructure, surpassing by a maximum of 43-fold compared to the p-3C-SiC/n-Si single junction (SJ) counterpart. The p-3C-SiC layer and n-Si substrate of the two heterostructures have similar material and geometrical properties. More importantly, the fabrication costs for the DJ and SJ heterostructure devices are comparable. Our results demonstrate a significant potential for using DJ devices in energy harvesters, micro/nano electromechanical systems, and sensing applications. This research may also lead to the creation of advanced optoelectronic devices using DJ structures, where employing various semiconductor materials to achieve exceptional performance through the application of the concept and theoretical model described in this work.