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关键词： Pediatric pneumonia   sTREM-1   CD64   mHLA-DR  

摘要： Background Traditional biomarkers like C-reactive protein (CRP) have limited diagnostic and prognostic utility in pediatric community-acquired pneumonia (CAP).This hospital-based case-control study evaluated non-classic immune biomarkers-neutrophil CD64 (nCD64), soluble Triggering Receptor Expressed on Myeloid cells-1 (sTREM-1), and monocyte HLA-DR (mHLA-DR) for CAP diagnosis and outcome prediction. Methods We enrolled 120 children (24-60 months): 60 with CAP and 60 age/sex-matched healthy controls. Primary endpoints were diagnostic accuracy (CAP vs. controls) and associations with disease severity (Clinical Respiratory Score), hospitalization duration, ICU admission, mechanical ventilation, and mortality. Plasma sTREM-1 was measured by ELISA;nCD64 and mHLA-DR expression by flow cytometry. Results sTREM-1, nCD64, and nCD64/lymphocyte ratio were significantly higher, while mHLA-DR was lower in CAP cases versus controls (all p < 0.001). All biomarkers correlated significantlywith CRP (r = 0.724, 0.760, 0.687, and-0.369, respectively;p<0.001). Levels increased stepwise with disease severity and adverse *** nCD64/lympho-cyte ratio showed superior diagnostic accuracy (AUC 0.97, 95% CI 0.93-0.99;90% sensitivity, 99% specificity), outperforming CRP (AUC 0.89, 95% CI 0.82-0.94). Deceased children (n = 4, 6.7%) exhibited the most pronounced biomarker alterations. Conclusion The nCD64/lymphocyte ratio is a highly accurate diagnostic biomarker for pediatric CAP. nCD64, sTREM-1, and mHLA-DR demonstrate significant prognostic value, effectively stratifying severity and predicting outcomes. Integrating these biomarkers may enhance clinical management and antibiotic stewardship.

关键词： 6G   beamformer   beam-steering   CMOS   dielectric resonator antenna (DRA)   phased array   sub-THz   wideband  

摘要： This work presents a 230-GHz 1 x 2 phased-array signal source (SS) that integrates a voltage-controlled oscillator (VCO), two 360 degrees phase-shifting amplifier-frequency-multiplier chains (AMCs), and two high-resistivity Si dielectric resonator antennas (DRAs). Each AMC comprises a driver amplifier (DA) and a frequency tripler (FT). The DA employs a phase-shifter-embedded impedance-matching network (IMN) that simultaneously provides balun functionality, >120 degrees phase shifting, and impedance transformation, effectively reducing power loss and chip area. The FT employs a fundamental voltage-tuning technique to tolerate higher input power without voltage breakdown issues, improving the output power by 2.5dB. The DRA utilizes a tapered feeding structure to broaden the bandwidth (BW), achieving an antenna gain of 3.9 dBi and a fractional BW of similar to 10% at 230 GHz. Fabricated in a 40-nm CMOS process, the proposed SS provides frequency tuning from 215 to 240 GHz, an equivalent isotropically radiated power (EIRP) of 8.5 dBm, and a 60 degrees beam-steering range at 225 GHz.

关键词： alcohol   flurbiprofen   Alda-1   ALDH2   ibuprofen   PC-12 cells   UChB rats   molecular docking  

摘要： Excessive alcohol consumption causes millions of deaths annually, yet current pharmacological treatments for alcohol use disorders show limited efficacy and poor adherence, creating an urgent need for new therapeutic alternatives. Aldehyde dehydrogenase 2 (ALDH2) metabolizes acetaldehyde, a key mediator of the rewarding effects of alcohol in the brain, making ALDH2 activation a promising therapeutic target. This study investigated whether flurbiprofen, an FDA-approved nonsteroidal anti-inflammatory drug that activates ALDH2, reduces alcohol intake compared to the experimental ALDH2 activator Alda-1 and the structurally similar NSAID ibuprofen. Male alcohol-preferring UChB rats received oral flurbiprofen (2.5-10 mg/kg), Alda-1 (5 mg/kg), or ibuprofen (5 mg/kg) during acquisition and chronic phases of voluntary alcohol consumption under a two-bottle free-choice paradigm. Both flurbiprofen and Alda-1 reduced alcohol intake by approximately 60% and similarly increased ALDH2 activity 3-4-fold in brain and liver tissues. Ibuprofen showed modest effects (25% alcohol intake reduction). In vitro assays confirmed that flurbiprofen and Alda-1, but not ibuprofen, activated ALDH2 in PC-12 cells. Enzymatic assays and molecular docking revealed that Alda-1 lacks cyclooxygenase-inhibitory activity, unlike flurbiprofen, suggesting that ALDH2 activation is the primary mechanism underlying reduced alcohol consumption. These findings identify flurbiprofen as a clinically available ALDH2 activator with significant translational potential for treating alcohol use disorders.

关键词： Antiretroviral drug resistance mutations   Factors   HIV  

摘要： Human Immunodeficiency Virus / Acquired Immunodeficiency Syndrome (HIV/AIDS) is a major public health problem affecting an estimated 38.4 million people globally, with 54% of them being from the Eastern and Southern African regions. Despite progress in the availability of multiple classes of antiretroviral drugs and early initiation of treatment with cART, many patients still fail to achieve viral suppression on first and second-line regimens due to drug resistance that is driven by continuous acquisition of drug resistance mutation (DRMs). DRMs are prevalent among adults failing treatment regimens, ranging between 50 and 97%. This study aimed to determine the prevalence and factors associated with drug resistance mutations among patients failing to achieve virologic suppression on second-line treatment in Tanzania. A facility-based analytical retrospective study was conducted at Temeke Hospital, Dar es Salaam, Tanzania. Data was extracted from medical records of 176 patients with viral load > 1000c/ml who underwent drug resistance testing during the period between February 2021 and July 2023. Data was analyzed using SPSS V26 and summarized using descriptive statistics. A multivariable logistic regression model was used to estimate the adjusted odds ratio with a 95% confidence interval for biodemographic factors associated with antiretroviral drug resistance mutations. We found high prevalence of DRMs at 71.1% (95% CI; 63.7–77.6) whereby NNRTI mutations were present in 69.3% (n = 122), NRTI in 52.8%(n = 93) and PI in 23.9% (n = 42) while 26.7%(n = 47) had triple class DRMs. Protease inhibitors had the lowest prevalence of DRMs while NNRTI was the highest. Older age [AOR = 1.037, 95% CI; (1.004–1.071)] and number of regimen changes [AOR = 1.479, 95% CI; (1.026–2.131)] were independently significantly associated with higher DRMs at p < 0.05. The prevalence of DRM is high. PI appear to have the least prevalence of DRM, followed NRTIs. This supports the utili