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The decrease in sequencing expenses has facilitated the creation of reference genomes and proteomes for an expanding array of organisms. Nevertheless, no established repository that details organism-specific genomic and proteomic sequences of specific lengths, referred to as kmers, exists to our knowledge. In this article, we present kmerDB, a database accessible through an interactive web interface that provides kmer-based information from genomic and proteomic sequences in a systematic way. kmerDB currently contains 202,340,859,107 base pairs and 19,304,903,356 amino acids, spanning 54,039 and 21,865 reference genomes and proteomes, respectively, as well as 6,905,362 and 149,305,183 genomic and proteomic species-specific sequences, termed quasi-primes. Additionally, we provide access to 5,186,757 nucleic and 214,904,089 peptide sequences absent from every genome and proteome, termed primes. kmerDB features a user-friendly interface offering various search options and filters for easy parsing and searching. The service is available at: www.kmerdb.com.

Aducanumab selectively targets aggregated forms of amyloid beta (Aβ), a neuropathological hallmark of Alzheimer\'s disease (AD).
PRIME was a Phase 1b, double-blind, randomized clinical trial of aducanumab. During the 12-month placebo-controlled period, participants with prodromal AD or mild AD dementia were randomized to receive aducanumab or placebo. At week 56, participants could enroll in a long-term extension (LTE), in which all participants received aducanumab. The primary endpoint was safety and tolerability.
Amyloid-related imaging abnormalities-edema (ARIA-E) were the most common adverse event. Dose titration was associated with a decrease in the incidence of ARIA-E. Over 48 months, aducanumab decreased brain amyloid levels in a dose- and time-dependent manner. Exploratory endpoints suggested a continued benefit in the reduction of clinical decline over 48 months.
The safety profile of aducanumab remained unchanged in the LTE of PRIME. Amyloid plaque levels continued to decrease in participants treated with aducanumab.
PRIME was a Phase 1b, double-blind, randomized clinical trial of aducanumab. We report cumulative safety and 48-month efficacy results from PRIME. Amyloid-related imaging abnormalities-edema (ARIA-E) were the most common adverse event (AE); 61% of participants with ARIA-E were asymptomatic. Dose titration was associated with a decrease in the incidence of ARIA-E. Aducanumab decreased levels of amyloid beta (Aβ) in a dose- and time-dependent manner.

BACKGROUND: A standard blood prime for cardiopulmonary bypass (CPB) in congenital cardiac surgery may possess non-physiologic values for electrolytes, glucose, and lactate. Pre-bypass Ultrafiltration (PBUF) can make these values more physiologic and standardized prior to bypass initiation. We aimed to determine if using PBUF on blood primes including packed red blood cells and thawed plasma would make prime values more predictable and physiologic. Additionally, we aimed to evaluate whether the addition of PBUF had an impact on outcome measures.
METHODS: Retrospective review of consecutive patients ≤ 1 year of age undergoing an index cardiac operation on CPB between 8/2017 and 9/2021. As PBUF was performed at the perfusionists\' discretion, a natural grouping of patients that received PBUF vs. those that did not occur. Differences in electrolytes, glucose, and lactate were compared at specific time points using Fisher\'s exact test for categorical variables and the Wilcoxon rank sum test for continuous variables. Clinical outcomes were also assessed.
RESULTS: In both cohorts, the median age at surgery was 3 months and 47% of patients were female; 308/704 (44%) of the PBUF group and 163/414 (39%) of the standard prime group had at least one preoperative risk factor. The proportion of PBUF circuits which demonstrated more physiologic values for glucose (318 [45%]), sodium (434, [62%]), potassium (688 [98%]), lactate (612 [87%]) and osmolality (595 [92%]) was significantly higher when compared to standard prime circuit levels for glucose (8 [2%]), sodium (13 [3%], potassium (150 [36%]), lactate (56 [13%]) and osmolality (23 [6%]) prior to CPB initiation. There were no differences in clinical outcomes or rates of major adverse events between the two cohorts.
CONCLUSIONS: PBUF creates standardized and more physiologic values for electrolytes, glucose, and lactate before the initiation of bypass without significant impacts on in-hospital outcomes.

In 2000, the European Union (EU) introduced the orphan pharmaceutical legislation to incentivize the development of medicinal products for rare diseases. The Committee for Orphan Medicinal Products (COMP), the European Medicines Agency committee responsible for evaluation of applications for orphan designation (OD), received an increasing flow of applications in the field of gene therapies over the last years. Here, the COMP has conducted a descriptive analysis of applications regarding gene therapies in non-oncological rare diseases, with respect to (a) targeted conditions and their rarity, (b) characteristics of the gene therapy products proposed for OD, with a focus on the type of vector used, and (c) regulatory aspects pertaining to the type of sponsor and development, by examining the use of available frameworks offered in the EU such as protocol assistance and PRIME. It was noted that gene therapies are being developed by sponsors from different backgrounds. Most conditions being targeted are monogenic, the most common being lysosomal disorders, and with a very low prevalence. Generally, adeno-associated viral vectors were being used to deliver the transgene. Finally, sponsors are not frequently using the incentives that may support the development and the reasons for this are unclear.

The strength of the affective priming effect is influenced by various factors, including the duration of the prime. Surprisingly, short-duration primes that are around the threshold for conscious awareness typically result in stronger effects compared to long-duration primes. The misattribution effect theory suggest that subliminal primes do not provide sufficient cognitive processing time for the affective feeling to be attributed to the prime. Instead, the neutral target being evaluated is credited for the affective experience. In everyday social interactions, we shift our gaze from one face to another, typically contemplating each face for only a few seconds. It is reasonable to assume that no affective priming takes place during such interactions. To investigate whether this is indeed the case, participants were asked to rate the valence of faces displayed one by one. Each face image simultaneously served as both a target (primed by the previous trial) and a prime (for the next trial). Depending on the participant\'s response time, images were typically displayed for about 1-2 s. As predicted by the misattribution effect theory, neutral targets were not affected by positive affective priming. However, non-neutral targets showed a robust priming effect, with emotional faces being perceived as even more negative or positive when the previously seen face was emotionally congruent. These results suggest that a \"correct attribution effect\" modulates how we perceive faces, continuously impacting our social interactions. Given the importance of faces in social communication, these findings have wide-ranging implications.

OBJECTIVE: As the French West Indies are facing an ongoing nutrition transition with increasing type-2 diabetes mellitus (T2DM) prevalence, our study aimed to evaluate the effect of potential shifts in dietary patterns on T2DM risk in French West Indian adults according to several scenarios.
METHODS: We used a cross-sectional multistage sampling survey on dietary intake conducted in 2013 on a representative sample of Guadeloupeans and Martinicans adults (n = 1063). From previously identified current dietary patterns, we used PRIME-Diabetes, a comparative risk assessment model, to estimate the effect of potential shifts from the \"transitioning\" pattern to the \"convenient,\" the \"prudent,\" and the \"traditional\" ones on T2DM risks.
RESULTS: Potential shift in dietary intakes from the \"transitioning\" pattern to the \"traditional\" one reduced the T2DM risk in women (- 16% [- 22; - 10]) and in men - 14% [- 21; - 7]), as the shift in dietary intakes toward the \"prudent\" pattern (- 23% [- 29; - 17] and - 19% - 23; - 14], respectively). These risk reductions were mostly driven by increased whole grains, fruits, green leafy vegetable intakes, and decreases in potatoes, red meats, processed meats, and sugar-sweetened beverages. The shift in dietary intakes toward the \"convenient\" pattern did not affect the T2DM risks.
CONCLUSIONS: To curb the increase in T2DM prevalence and reduce this burden, one public health action could be to target transitioning adults and help them to shift towards a diet associated with a reduced risk of T2DM as a prudent or a traditional diet.

In the European Union (EU), advanced therapy medicinal products (ATMPs) undergo evaluation by the European Medicines Agency\'s (EMA) Committee for Advanced Therapies (CAT) to obtain marketing authorization under the centralized procedure. Because of the diversity and complexity of ATMPs, a tailored approach to the regulatory process is required that needs to ensure the safety and efficacy of each product. Since ATMPs often target serious diseases with unmet medical need, the industry and authorities are interested in providing treatment to patients in a timely manner through optimized and expedited regulatory pathways. EU legislators and regulators have implemented various instruments to support the development and authorization of innovative medicines by offering scientific guidance at early stages, incentives for small developers and products for rare diseases, accelerated evaluation of marketing authorization applications, different types of marketing authorizations, and tailored programs for medicinal products with the orphan drug designation (ODD) and the Priority Medicines (PRIME) scheme. Since the regulatory framework for ATMPs was established, 20 products have been licenced, 15 with orphan drug designation, and 7 supported by PRIME. This chapter discusses the specific regulatory framework for ATMPs in the EU and highlights previous successes and remaining challenges.

UNASSIGNED: Hybrid immunity is associated with more durable protection against coronavirus disease 2019 (COVID-19). We describe the antibody responses following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in vaccinated and unvaccinated individuals.
UNASSIGNED: The 55 vaccine arm COVID-19 cases diagnosed during the blinded phase of the Coronavirus Efficacy trial were matched with 55 placebo arm COVID-19 cases. Pseudovirus neutralizing antibody (nAb) activity to the ancestral strain and binding antibody (bAb) responses to nucleocapsid and spike antigens (ancestral and variants of concern [VOCs]) were assessed on disease day 1 (DD1) and 28 days later (DD29).
UNASSIGNED: The primary analysis set was 46 vaccine cases and 49 placebo cases with COVID-19 at least 57 days post-first dose. For vaccine group cases, there was a 1.88-fold rise in ancestral antispike bAbs 1 month post-disease onset, although 47% had no increase. The vaccine-to-placebo geometric mean ratios for DD29 antispike and antinucleocapsid bAbs were 6.9 and 0.04, respectively. DD29 mean bAb levels were higher for vaccine vs placebo cases for all VOCs. DD1 nasal viral load positively correlated with bAb levels in the vaccine group.
UNASSIGNED: Following COVID-19, vaccinated participants had higher levels and greater breadth of antispike bAbs and higher nAb titers than unvaccinated participants. These were largely attributable to the primary immunization series.

The United States Food and Drug Administration and the European Medicines Agency (EMA) each have programs to expedite development of products identified as having potential to address unmet medical needs: the Breakthrough therapy (BT) and Regenerative Medicines Advanced Therapies designation programs in the US and the Priority Medicines (PRIME) scheme at EMA. We reviewed commonalities and differences in requests submitted and products designated through these programs, with the intent to explore ways to better support global development. During the period from PRIME\'s launch in April 2016 to 31 December 2020, 151 requests were made to both BT and PRIME programs and the agencies reached concordant outcomes to grant or deny requests for almost two thirds of the cases (93/151, 62%), suggesting similar perspectives across international regulators on the potential of the products under study. Forty-two (42/151, 28%) products were granted both BT and PRIME, thus found by both Agencies to have the potential to address an unmet need for a serious condition, and thereby products for which efficient development would be highly desirable. Working toward better engagement on global development strategies is in the best interests of patients and public health. With this in mind, Agencies and sponsors should take advantage of existing collaborative opportunities, such as parallel scientific advice, and work to identify fresh approaches to support global development of products for unmet medical needs.