Simplifying summaries of scholarly publications has been a popular method for conveying scientific discoveries to a broader audience. While text summarization aims to shorten long documents, simplification seeks to reduce the complexity of a document. To accomplish these tasks collectively, there is a need to develop machine learning methods to shorten and simplify longer texts. This study presents a new Simplification Aware Text Summarization model (SATS) based on future n-gram prediction. The proposed SATS model extends ProphetNet, a text summarization model, by enhancing the objective function using a word frequency lexicon for simplification tasks. We have evaluated the performance of SATS on a recently published text summarization and simplification corpus consisting of 5,400 scientific article pairs. Our results in terms of automatic evaluation demonstrate that SATS outperforms state-of-the-art models for simplification, summarization, and joint simplification-summarization across two datasets on ROUGE, SARI, and CSS1 . We also provide human evaluation of summaries generated by the SATS model. We evaluated 100 summaries from eight annotators for grammar, coherence, consistency, fluency, and simplicity. The average human judgment for all evaluated dimensions lies between 4.0 and 4.5 on a scale from 1 to 5 where 1 means low and 5 means high.

To unveil possible changes in diatom communities in Cypriot streams over the last ten years or so, we selected samples from the years 2020, 2021, and 2022 for the \"recent\" dataset (N = 119) and samples from the years 2010 and 2011 for the \"historical\" dataset (N = 108). Biotic homogenization has become a truly global phenomenon. Here we show that, over the last ten years, in response to increased water temperature, conductivity, and discharge variability due to climate-change, Cypriot stream diatom communities include a higher number of trivial (= widespread, tolerant, and opportunistic), aerial, and thermophilic species, have reduced β-diversity and increased nestedness. Moreover, IndVal analysis shows that indicator species from the historical dataset were characteristic, often relatively rare species, while the indicators of the recent dataset were a group of typical trivial, eutraphentic, and thermophilic species. As is almost always the case, the diatom communities we studied were subjected to multiple stressors, often affecting them in opposite ways. Besides the increase in trivial species, the reduction in β-diversity, and the rise in nestedness mentioned above, the diatom assemblages we studied also showed an increase in α-diversity that could be due to a moderate reduction in nutrients in several sites. High-ecological-integrity ecosystems, such as springs, waterfalls, and dripping rock-walls, in particular springs that were shown to be excellent hydrologic refugia in climates heavily affected by climate change, and the stream sites close to them should be carefully protected, as they can be refugia for sensitive and characteristic species that can recolonize the adjacent streams after adverse climatic events.

The management of type 2 diabetes (T2D) often necessitates treatment intensification, and sometimes simplification to achieve glycaemic targets and mitigate complications. This expert opinion paper evaluates the use and positioning of the fixed-ratio combinations (FRCs) of basal insulin (BI) and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) in optimising T2D management. On the basis of the evidence presented and discussions, these FRCs offer a promising approach for both treatment intensification and simplification in people with suboptimal glucose control despite receiving various therapies. In treatment intensification, FRCs provide a synergistic effect by addressing multiple pathophysiological defects contributing to hyperglycaemia. These FRCs effectively control both fasting and postprandial glucose (PPG) excursions, offering significantly improved glycaemic control with a lower hypoglycaemia risk and weight neutrality compared to traditional or complex insulin regimens. Moreover, the reduced injection frequency (once daily) and flexibility in the dosing schedule (with any major meal of the day) help mitigate patient resistance to insulin initiation or titration. This further reduces treatment burden, facilitating treatment adherence and enhancing patient convenience. These key benefits of FRCs over complex insulin regimens play a crucial role in long-term glycaemic management and overall treatment outcomes. Hence, the timely use of FRCs in the treatment algorithm for people with T2D represents a valuable strategy for optimising glycaemic control, addressing treatment barriers and enhancing patient-reported outcomes.

UNASSIGNED: Antiretroviral therapy (ART) can be personalized through simple formulations with high resistance barriers, favorable safety profiles, and novel administration routes. Switching treatments has become a key clinical strategy for addressing drug toxicity and interactions and enhancing adherence and convenience. This strategy aims to improve the quality of life and long-term efficacy, even in challenging cases like people living with HIV (PLWH) with multiple comorbidities, prior virological failure, and drug resistance.
UNASSIGNED: The authors reviewed clinical trials and cohort studies providing evidence of benefits and risks of current antiretroviral (ARV) drugs as switching options for PLWH in various scenarios. The literature search included clinical trials, meta-analyses, observational studies, and review articles in English published after 2000, and current HIV treatment guidelines in English and Spanish as of February 2024.
UNASSIGNED: New ARV drugs offer advantages in efficacy and safety over previous options but may also have adverse effects. Second-generation integrase inhibitors and tenofovir alafenamide show benefits as switching options in various scenarios, though more research is needed on potential weight gain and metabolic issues. Injectable long-acting ART is promising for switching strategies, but finding the optimal combination of new drugs remains challenging.

The growing complexity of biopharmaceutical sponsored trials has adverse impacts on increased burdens on participants, clinical sites, and sponsors, including greater difficulty recruiting and retaining participants, difficulty engaging sites to participate in trials, excessive cost of trials, and increased cycle times. The schedule of assessments (SoAs) is the origin of and blueprint for complexity that is often generated by copying and pasting from previous SoAs. We developed an approach, termed Lean Design, for redesigning the assessments in SoAs that generate data, the \'Data SoA.\' It starts with a simple \"ground zero\" SoA. Any addition is challenged using several principles of trial design. We employed a system, the Faro Trial Designer Tool, to quantify the impacts of changes in an SoA to provide real-time feedback to the team and sponsor. We applied the approach in workshops with teams for six clinical trials in various stages of design and implementation. The approach resulted in recommendation for substantial potential savings in participant and site staff time, costs, and complexity of the trials. Application of this approach to very early stages of protocol design has the potential to reduce the complexity of biopharmaceutical sponsored trials and its consequences.

OBJECTIVE: We performed an observational, retrospective, cohort study to assess changes in insulin sensitivity after a switch from dolutegravir/lamivudine (DOL/3TC) or bictegravir/emtricitabine/tenofovir alafenamide (BIC/F/TAF) to doravirine/tenofovir disoproxil fumarate/3TC (DOR/TDF/3TC) in virologically suppressed people living with HIV with recent significant weight gain.
METHODS: All non-diabetic patients with HIV treated with DOL/3TC or BIC/F/TAF for ≥12 months, with HIV RNA <20 copies/mL, and with a weight increase ≥3 kg in the last year, who underwent a switch to DOR/TDF/3TC were enrolled into the study. Serum levels of glucose, insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) index were evaluated every 6 months during a 12-month follow-up.
RESULTS: Overall, 81 patients were enrolled: 41 were treated with DOL/3TC and 40 with BIC/F/TAF. At baseline, median HOMA-IR index was 3.18 and insulin resistance (HOMA-IR index >2.5) was present in 49 subjects (60%). At 12 months after the switch to DOR/TDF/3TC, change in mean serum glucose concentration was not significant, but the reduction in median concentration of insulin was significant (-3.54 mcrUI/L [interquartile range -4.22 to -2.87]; p = 0.012), associated with a significant reduction in mean HOMA-IR index (-0.54 [interquartile range -0.91 to -0.18]; p = 0.021). A significant reduction in total and low-density lipoprotein cholesterol was also reported, whereas decreases in mean body weight and mean body mass index were not significant.
CONCLUSIONS: In our retrospective study in virologically suppressed people living with HIV treated with DOL/3TC or BIC/F/TAF and with recent weight gain, the switch to DOR/TDF/3TC led to a significant improvement in insulin sensitivity and plasma lipids, with a trend to decreased body weight.

暂无摘要。

The continuous pharmacological advances in antiretroviral treatment (ART) and the increasing understanding of HIV drug resistance has led to a change in the paradigm of ART optimization in the setting of the viral suppression of treatment-experienced patients with the emerging evidence of the effectiveness and safety of dual therapies. The aim of this study is to determine the antiviral efficacy and safety of switching to Dolutegravir + Lamivudine in people living with HIV, and to analyze the rate of patients with virologic failure (VF). A total of 200 patients were included with a median age of 51 years, 189 cells/µL of nadir CD4+, 13 years on ART and four previous ART regimens. Among the 168 patients who completed a follow-up at 48 weeks, a total of five VFs occurred, resulting in a 2.98% (5/168) VF rate. The results of the intention-to-treat analysis were a VF rate of 2.54% (5/197), and the rate of patients/year with viral suppression was 98.3% (298/303) in the observed data analysis. We observed a significant improvement in mean CD4 lymphocytes, the CD4/CD8 ratio and lipid profiles. The optimization of ART to DTG plus 3TC is a cost-effective switch option for treatment-experienced HIV patients, and also improves their lipid profiles.

UNASSIGNED: Treatment-simplification strategies are important tools for patient-centred management. We evaluated long-term outcomes from a PI monotherapy switch strategy.
UNASSIGNED: Eligible participants attending 43 UK treatment centres had a viral load (VL) below 50 copies/ml for at least 24 weeks on combination ART. Participants were randomised to maintain ongoing triple therapy (OT) or switch to a strategy of physician-selected PI monotherapy (PI-mono) with prompt return to combination therapy if VL rebounded. The primary outcome, previously reported, was loss of future drug options after 3 years, defined as new intermediate/high level resistance to at least one drug to which the participant\'s virus was considered sensitive at trial entry. Here we report resistance and disease outcomes after further extended follow-up in routine care. The study was registered as ISRCTN04857074.
UNASSIGNED: We randomised 587 participants to OT (291) or PI-mono (296) between Nov 4, 2008, and July 28, 2010 and followed them for a median of more than 8 years (100 months) until 2018. At the end of this follow-up time, one or more future drug options had been lost in 7 participants in the OT group and 6 in the PI-mono group; estimated cumulative risk by 8 years of 2.7% and 2.1% respectively (difference -0.6%, 95% CI -3.2% to 2.0%). Only one PI-mono participant developed resistance to the protease inhibitor they were taking (atazanavir). Serious clinical events (death, serious AIDS, and serious non-AIDS) were infrequent; reported in a total of 12 (4.1%) participants in the OT group and 23 (7.8%) in the PI-mono group (P = 0.08) over the entire follow-up period.
UNASSIGNED: A strategy of PI monotherapy, with regular VL monitoring and prompt reintroduction of combination treatment following rebound, preserved future treatment options. Findings confirm the high genetic barrier to resistance of the PI drug class that makes them well suited for creative, patient-centred, treatment-simplification approaches. The possibility of a small excess risk of serious clinical events with the PI monotherapy strategy cannot be excluded.
UNASSIGNED: The National Institute for Health Research Health Technology Assessment programme.

People aging with 4 antiretroviral class resistant HIV are a very challenging population. It is difficult to build up a fully suppressive regimen, and the high prevalence of comorbidities and polypharmacy may cause drug-drug interactions and put adherence at risk. We herein present the case of an 80-year-old man, participating in the PRESTIGIO registry, asking for a reduction in his antiretroviral burden while on polypharmacy for his comorbidities.