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  1. Fraundorf SH, Watson DG, Benjamin AS
    Psychol Aging, 2012 Mar;27(1):88-98.
    PMID: 21639646 DOI: 10.1037/a0024138
    In two experiments, we investigated age-related changes in how prosodic pitch accents affect memory. Participants listened to recorded discourses that contained two contrasts between pairs of items (e.g., one story contrasted British scientists with French scientists and Malaysia with Indonesia). The end of each discourse referred to one item from each pair; these references received a pitch accent that either denoted contrast (L + H* in the ToBI system) or did not (H*). A contrastive accent on a particular pair improved later recognition memory equally for young and older adults. However, older adults showed decreased memory if the other pair received a contrastive accent (Experiment 1). Young adults with low working memory performance also showed this penalty (Experiment 2). These results suggest that pitch accents guide processing resources to important information for both older and younger adults but diminish memory for less important information in groups with reduced resources, including older adults.
  2. Yau MQ, Wan AJ, Tiong ASH, Yiap YS, Loo JSE
    Chem Biol Drug Des, 2024 Jul;104(1):e14591.
    PMID: 39010276 DOI: 10.1111/cbdd.14591
    Computational target fishing plays an important role in target identification, particularly in drug discovery campaigns utilizing phenotypic screening. Numerous approaches exist to predict potential targets for a given ligand, but true targets may be inconsistently ranked. More advanced simulation methods may provide benefit in such cases by reranking these initial predictions. We evaluated the ability of binding pose metadynamics to improve the predicted rankings for three diverse ligands and their six true targets. Initial predictions using pharmacophore mapping showed no true targets ranked in the top 50 and two targets each ranked within the 50-100, 100-150, and 250-300 ranges respectively. Following binding pose metadynamics, ranking of true targets improved for four out of the six targets and included the highest ranked predictions overall, while rankings deteriorated for two targets. The revised rankings predicted two true targets ranked within the top 50, and one target each within the 50-100, 100-150, 150-200, and 200-250 ranges respectively. The findings of this study demonstrate that binding pose metadynamics may be of benefit in refining initial predictions from structure-based target fishing algorithms, thereby improving the efficiency of the target identification process in drug discovery efforts.
  3. Alahmad B, Al-Hemoud A, Kang CM, Almarri F, Kommula V, Wolfson JM, et al.
    Environ Pollut, 2021 Aug 01;282:117016.
    PMID: 33848912 DOI: 10.1016/j.envpol.2021.117016
    BACKGROUND: Kuwait and the Gulf region have a desert, hyper-arid and hot climate that makes outdoor air sampling challenging. The region is also affected by intense dust storms. Monitoring challenges from the harsh climate have limited data needed to inform appropriate regulatory actions to address air pollution in the region.

    OBJECTIVES: To compare gravimetric measurements with existing networks that rely on beta-attenuation measurements in a desert climate; determine the annual levels of PM2.5 and PM10 over a two-year period in Kuwait; assess compliance with air quality standards; and identify and quantify PM2.5 sources.

    METHODS: We custom-designed particle samplers that can withstand large quantities of dust without their inlet becoming overloaded. The samplers were placed in two populated residential locations, one in Kuwait City and another near industrial and petrochemical facilities in Ali Sabah Al-Salem (ASAS) to collect PM2.5 and PM10 samples for mass and elemental analysis. We used positive matrix factorization to identify PM2.5 sources and apportion their contributions.

    RESULTS: We collected 2339 samples during the period October 2017 through October 2019. The beta-attenuation method in measuring PM2.5 consistently exceeded gravimetric measurements, especially during dust events. The annual levels for PM2.5 in Kuwait City and ASAS were 41.6 ± 29.0 and 47.5 ± 27.6 μg/m3, respectively. Annual PM2.5 levels in Kuwait were nearly four times higher than the U.S. National Ambient Air Quality Standard. Regional pollution was a major contributor to PM2.5 levels in both locations accounting for 44% in Kuwait City and 46% in ASAS. Dust storms and re-suspended road dust were the second and third largest contributors to PM2.5, respectively.

    CONCLUSIONS: The premise that frequent and extreme dust storms make air quality regulation futile is dubious. In this comprehensive particulate pollution analysis, we show that the sizeable regional anthropogenic particulate sources warrant national and regional mitigation strategies to ensure compliance with air quality standards.

  4. Tan KS, Pandian JD, Liu L, Toyoda K, Leung TWH, Uchiyama S, et al.
    Cerebrovasc Dis Extra, 2024;14(1):58-75.
    PMID: 38657577 DOI: 10.1159/000538928
    BACKGROUND: There is a significant burden of stroke in Asia. Asia has the largest population in the world in 2023, estimated at 4.7 billion. Approximately 9.5-10.6 million strokes will be anticipated annually in the backdrop of a diverse group of well-developed and less developed countries with large disparities in stroke care resources. In addition, Asian countries are in varying phases of epidemiological transition.

    SUMMARY: In this review, we examined recent epidemiological features of ischaemic stroke and intracerebral haemorrhage in Asia with recent developments in hyperacute stroke reperfusion therapy and technical improvements in intracerebral haemorrhage. The article also discussed the spectrum of cerebrovascular diseases in Asia, which include intracranial atherosclerosis, intracerebral haemorrhage, infective aetiologies of stroke, moyamoya disease, vascular dissection, radiation vasculopathy, and cerebral venous thrombosis.

    KEY MESSAGES: The review of selected literature and recent updates calls for attention to the different requirements for resources within Asia and highlights the breadth of cerebrovascular diseases still requiring further research and more effective therapies.

  5. Zhou C, Tang KJ, Cho BC, Liu B, Paz-Ares L, Cheng S, et al.
    N Engl J Med, 2023 Nov 30;389(22):2039-2051.
    PMID: 37870976 DOI: 10.1056/NEJMoa2306441
    BACKGROUND: Amivantamab has been approved for the treatment of patients with advanced non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertions who have had disease progression during or after platinum-based chemotherapy. Phase 1 data showed the safety and antitumor activity of amivantamab plus carboplatin-pemetrexed (chemotherapy). Additional data on this combination therapy are needed.

    METHODS: In this phase 3, international, randomized trial, we assigned in a 1:1 ratio patients with advanced NSCLC with EGFR exon 20 insertions who had not received previous systemic therapy to receive intravenous amivantamab plus chemotherapy (amivantamab-chemotherapy) or chemotherapy alone. The primary outcome was progression-free survival according to blinded independent central review. Patients in the chemotherapy group who had disease progression were allowed to cross over to receive amivantamab monotherapy.

    RESULTS: A total of 308 patients underwent randomization (153 to receive amivantamab-chemotherapy and 155 to receive chemotherapy alone). Progression-free survival was significantly longer in the amivantamab-chemotherapy group than in the chemotherapy group (median, 11.4 months and 6.7 months, respectively; hazard ratio for disease progression or death, 0.40; 95% confidence interval [CI], 0.30 to 0.53; P<0.001). At 18 months, progression-free survival was reported in 31% of the patients in the amivantamab-chemotherapy group and in 3% in the chemotherapy group; a complete or partial response at data cutoff was reported in 73% and 47%, respectively (rate ratio, 1.50; 95% CI, 1.32 to 1.68; P<0.001). In the interim overall survival analysis (33% maturity), the hazard ratio for death for amivantamab-chemotherapy as compared with chemotherapy was 0.67 (95% CI, 0.42 to 1.09; P = 0.11). The predominant adverse events associated with amivantamab-chemotherapy were reversible hematologic and EGFR-related toxic effects; 7% of patients discontinued amivantamab owing to adverse reactions.

    CONCLUSIONS: The use of amivantamab-chemotherapy resulted in superior efficacy as compared with chemotherapy alone as first-line treatment of patients with advanced NSCLC with EGFR exon 20 insertions. (Funded by Janssen Research and Development; PAPILLON ClinicalTrials.gov number, NCT04538664.).

  6. Global Retinoblastoma Study Group, Fabian ID, Abdallah E, Abdullahi SU, Abdulqader RA, Adamou Boubacar S, et al.
    JAMA Oncol, 2020 May 01;6(5):685-695.
    PMID: 32105305 DOI: 10.1001/jamaoncol.2019.6716
    IMPORTANCE: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale.

    OBJECTIVES: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis.

    DESIGN, SETTING, AND PARTICIPANTS: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017.

    MAIN OUTCOMES AND MEASURES: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis.

    RESULTS: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]).

    CONCLUSIONS AND RELEVANCE: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs.

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