Protein Discrimination Using a Fluorescence-Based Sensor Array of Thiacarbocyanine-GUMBOS

Sensitive and selective detection of proteins from complex samples has gained substantial interest within the scientific community. Early and precise detection of key proteins plays an important role in potential clinical diagnosis, treatment of different diseases, and proteomic research. In the study reported here, six different compounds belonging to a group of uniform materials based on organic salts (GUMBOS) have been synthesized using three thiacarbocyanine (TC) dyes and employed as fluorescent sensors. Fluorescence properties of micro- and nanoaggregates of these TC-based GUMBOS formed in phosphate buffer solutions are studied in the absence and presence of seven proteins. Fluorescence response patterns of these TC-based GUMBOS were analyzed by linear discriminant analysis (LDA). The constructed LDA model allowed discrimination of these seven proteins at various concentrations with 100% accuracy. The sensing and discrimination abilities of these TC-based GUMBOS were further evaluated in mixtures of two major proteins, i.e., human serum albumin and hemoglobin. Fluorescence response patterns of these mixtures were analyzed by LDA. This model allowed discrimination of various mixtures with 100% accuracy. Moreover, spiked urine samples were prepared and the responses of these sensors were collected and analyzed by LDA. Remarkably, discrimination of these seven proteins was also achieved with 100% accuracy

HLA Class I and Class II Associations in Dengue Viral Infections in a Sri Lankan Population

BACKGROUND: HLA class I and class II alleles have been shown to be associated with the development of dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS) in different populations. However, the majority of studies have been based on limited numbers of patients. In this study we aimed to investigate the HLA-class I and class II alleles that are positively and negatively associated with the development of DSS in a cohort of patients with DHF and also the alleles associated with development of DHF during primary dengue infections in a Sri Lankan population. METHODOLOGY/PRINCIPAL FINDINGS: The allele frequencies of HLA class I and class II alleles were compared in 110 patients with DHF and 119 individuals from the population who had never reported a symptomatic dengue infection at the time of recruitment. We found that HLA-A*31 (corrected P = 0.01) and DRB1*08 (corrected P = 0.009) were associated with susceptibility to DSS when infected with the dengue virus, during secondary dengue infection. The frequency of DRB1*08 allele was 28.7 times higher than in the normal population in patients with DSS. HLA-A*31 allele was increased 16.6 fold in DHF who developed shock when compared to those who did not develop shock. A*24 (corrected P = 0.03) and DRB1*12 (corrected P = 0.041) were strongly associated with the development of DHF during primary dengue infection. CONCLUSIONS/SIGNIFICANCE: These data suggest that certain HLA alleles confer susceptibility/protection to severe dengue infections. As T cell epitope recognition depend on the HLA type of an individual, it would be now important to investigate how epitope specific T cells associate with primary and secondary dengue infections and in severe dengue infections

Dengue Infection and Miscarriage: A Prospective Case Control Study

Dengue is the most prevalent mosquito-borne infection with two billion of the world's population at risk and 100 million infections every year. Dengue is increasingly important due to expansion in the vector's range, increased population density in endemic areas from urbanisation, social and environment change. Miscarriage and stillbirth is associated with dengue when the illness is severe. Dengue can also be transmitted directly from the ill mother through the placenta to the fetus in later pregnancy with variable effect to the fetus. However, dengue infection is asymptomatic to mild only in almost 90% of cases and up to 20% of pregnancies miscarry. Little is known if dengue infection in early pregnancy particularly when it is asymptomatic or mild has an effect on miscarriage. Our study explored the relationship between dengue and miscarriage by looking at recent infection rates amongst women who had miscarried and those whose pregnancies were healthy in an area were dengue is common. Our study finds a positive association between recent dengue infection and miscarriage. This finding may be important in explaining some of the miscarriages in areas where dengue is common. It is also relevant to newly pregnant women from non-dengue travelling to dengue endemic areas

Maternal and perinatal outcomes of dengue in PortSudan, Eastern Sudan

<p>Abstract</p> <p>Aim</p> <p>To investigate maternal and perinatal outcomes (maternal death, preterm delivery, low birth weight and perinatal mortality) of dengue at PortSudan and Elmawani hospitals in the eastern Sudan.</p> <p>Method</p> <p>This was a retrospective Cohort study where medical files of women with dengue were reviewed.</p> <p>Results</p> <p>There were 10820 deliveries and 78 (0.7%) pregnant women with confirmed dengue IgM serology at the mean (SD) gestational age of 29.4(8.2) weeks. While the majority of these women had dengue fever (46, 58.9%), hemorrhagic fever and dengue shock syndrome were the presentations in 18 (23.0%) and 12, (15.3%) of these women, respectively. There were 17(21.7%) maternal deaths. Fourteen (17.9%) of these 78 women had preterm deliveries and 19 (24.3%) neonates were admitted to neonatal intensive care unit. Nineteen (24.3%) women gave birth to low birth weight babies. There were seven (8.9%) perinatal deaths. Eight (10.2%) patients delivered by caesarean section due to various obstetrical indications.</p> <p>Conclusion</p> <p>Thus dengue has poor maternal and perinatal outcomes in this setting. Preventive measures against dengue should be employed in the region, and more research on dengue during pregnancy is needed.</p

Mitochondrial reprogramming by activating OXPHOS via glutamine metabolism in African American patients with bladder cancer

Bladder cancer (BLCA) mortality is higher in African American (AA) patients compared with European American (EA) patients, but the molecular mechanism underlying race-specific differences are unknown. To address this gap, we conducted comprehensive RNA-Seq, proteomics, and metabolomics analysis of BLCA tumors from AA and EA. Our findings reveal a distinct metabolic phenotype in AA BLCA characterized by elevated mitochondrial oxidative phosphorylation (OXPHOS), particularly through the activation of complex I. The results provide insight into the complex I activation-driven higher OXPHOS activity resulting in glutamine-mediated metabolic rewiring and increased disease progression, which was also confirmed by [U]13C-glutamine tracing. Mechanistic studies further demonstrate that knockdown of NDUFB8, one of the components of complex I in AA BLCA cells, resulted in reduced basal respiration, ATP production, GLS1 expression, and proliferation. Moreover, preclinical studies demonstrate the therapeutic potential of targeting complex I, as evidenced by decreased tumor growth in NDUFB8-depleted AA BLCA tumors. Additionally, genetic and pharmacological inhibition of GLS1 attenuated mitochondrial respiration rates and tumor growth potential in AA BLCA. Taken together, these findings provide insight into BLCA disparity for targeting GLS1-Complex I for future therapy

Artificial Intelligence for the Electron Ion Collider (AI4EIC)

The Electron-Ion Collider (EIC), a state-of-the-art facility for studying the strong force, is expected to begin commissioning its first experiments in 2028. This is an opportune time for artificial intelligence (AI) to be included from the start at this facility and in all phases that lead up to the experiments. The second annual workshop organized by the AI4EIC working group, which recently took place, centered on exploring all current and prospective application areas of AI for the EIC. This workshop is not only beneficial for the EIC, but also provides valuable insights for the newly established ePIC collaboration at EIC. This paper summarizes the different activities and R&D projects covered across the sessions of the workshop and provides an overview of the goals, approaches and strategies regarding AI/ML in the EIC community, as well as cutting-edge techniques currently studied in other experiments.Comment: 27 pages, 11 figures, AI4EIC workshop, tutorials and hackatho

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Artificial Intelligence for the Electron Ion Collider (AI4EIC)

The Electron-Ion Collider (EIC), a state-of-the-art facility for studying the strong force, is expected to begin commissioning its first experiments in 2028. This is an opportune time for artificial intelligence (AI) to be included from the start at this facility and in all phases that lead up to the experiments. The second annual workshop organized by the AI4EIC working group, which recently took place, centered on exploring all current and prospective application areas of AI for the EIC. This workshop is not only beneficial for the EIC, but also provides valuable insights for the newly established ePIC collaboration at EIC. This paper summarizes the different activities and R and D projects covered across the sessions of the workshop and provides an overview of the goals, approaches and strategies regarding AI/ML in the EIC community, as well as cutting-edge techniques currently studied in other experiments

Artificial Intelligence for the Electron Ion Collider (AI4EIC)

The Electron-Ion Collider (EIC), a state-of-the-art facility for studying the strong force, is expected to begin commissioning its first experiments in 2028. This is an opportune time for artificial intelligence (AI) to be included from the start at this facility and in all phases that lead up to the experiments. The second annual workshop organized by the AI4EIC working group, which recently took place, centered on exploring all current and prospective application areas of AI for the EIC. This workshop is not only beneficial for the EIC, but also provides valuable insights for the newly established ePIC collaboration at EIC. This paper summarizes the different activities and R and D projects covered across the sessions of the workshop and provides an overview of the goals, approaches and strategies regarding AI/ML in the EIC community, as well as cutting-edge techniques currently studied in other experiments