RAPTOR: Recursive Abstractive Processing for Tree-Organized Retrieval

Retrieval-augmented language models can better adapt to changes in world state and incorporate long-tail knowledge. However, most existing methods retrieve only short contiguous chunks from a retrieval corpus, limiting holistic understanding of the overall document context. We introduce the novel approach of recursively embedding, clustering, and summarizing chunks of text, constructing a tree with differing levels of summarization from the bottom up. At inference time, our RAPTOR model retrieves from this tree, integrating information across lengthy documents at different levels of abstraction. Controlled experiments show that retrieval with recursive summaries offers significant improvements over traditional retrieval-augmented LMs on several tasks. On question-answering tasks that involve complex, multi-step reasoning, we show state-of-the-art results; for example, by coupling RAPTOR retrieval with the use of GPT-4, we can improve the best performance on the QuALITY benchmark by 20% in absolute accuracy

Fatigue predicts future reduced social participation, not reduced physical function or quality of life in people with systemic sclerosis

Funding: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by a grant from the Patient Centered Outcomes Research Institute (PCORI; Poole/Khanna co-PIs) (Award CER-1310-08323 to J.L.P. and D.K.). The statements presented in this publication are solely the responsibility of the authors and do not necessarily represent the views of PCORI. Dr. Khanna’s work was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases at National Institutes of Health (K24-AR-063129)Peer reviewedPostprin

Fatigue and its Association with Social Participation, Functioning and Quality of Life in Systemic Sclerosis

Supported by the Patient-Centered Outcomes Research Institute (grant CER-1310-08323 to Drs. Poole and Khanna as co–principal investigators). Dr. Khanna’s work was supported by the NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases grant K24-AR-063129).Peer reviewedPostprin

Social Networks, High-Risk anal Hpv and Coinfection With Hiv in Young Sexual Minority Men

OBJECTIVES: Young sexual minority men (SMM) exhibit a high prevalence and incidence of high-risk genotypes of human papillomavirus (hrHPV) anal infections and a confluence of a high prevalence of HIV and rectal STIs. Social determinants of health (SDOHs) are linked to social network contexts that generate and maintain racial disparities in HIV and STIs. A network perspective was provided to advance our knowledge of drivers of genotype-specific hrHPV infection and coinfection with HIV. The study also examined whether socially connected men are infected with the same high-risk HPV genotypes and, if so, whether this tendency is conditioned on coinfection with HIV. METHODS: Our sample included 136 young SMM of predominantly black race and their network members of other races and ethnicities, aged 18-29 years, who resided in Houston, Texas, USA. These participants were recruited during 2014-2016 at the baseline recruitment period by network-based peer referral, where anal exfoliated cells and named social and sexual partners were collected. Exponential random graph models were estimated to assess similarity in genotype-specific hrHPV anal infection in social connections and coinfection with HIV in consideration of the effects of similarity in sociodemographic, sexual behavioural characteristics, SDOHs and syphilis infection. RESULTS: Pairs of men socially connected to each other tend to be infected with the same hrHPV genotypes of HPV-16, HPV-45 and HPV-51 or HPV-16 and/or HPV-18. The tendency of social connections between pairs of men who were infected with either HPV-16 or HPV-18 were conditioned on HIV infection. CONCLUSIONS: Networked patterns of hrHPV infection could be amenable to network-based HPV prevention interventions that engage young SMM of predominantly racial minority groups who are out of HIV care and vulnerable to high-risk HPV acquisition

Effects of nintedanib in patients with limited cutaneous systemic sclerosis and interstitial lung disease

OBJECTIVES: To investigate the course of interstitial lung disease (ILD) and the effects of nintedanib in patients with limited cutaneous systemic sclerosis (lcSSc). METHODS: In the SENSCIS trial, patients with SSc-ILD were randomised to receive nintedanib or placebo. Patients who completed the SENSCIS trial were eligible to enter SENSCIS-ON, in which all patients received open-label nintedanib. RESULTS: Among 277 patients with lcSSc treated in the SENSCIS trial, the rate (SE) of decline in FVC (mL/year) over 52 weeks was -74.5 (19.2) in the placebo group and -49.1 (19.8) in the nintedanib group (difference: 25.3 [95% CI -28.9, 79.6]). Among 249 patients with data at week 52, mean (SE) changes in FVC at week 52 were -86.4 (21.1) mL in the placebo group and -39.1 (22.2) mL in the nintedanib group. Among 183 patients with lcSSc who participated in SENSCIS-ON and had data at week 52, mean (SE) changes in FVC from baseline to week 52 of SENSCIS-ON were -41.5 (24.0) mL in patients who took placebo in the SENSCIS trial and initiated nintedanib in SENSCIS-ON and -45.1 (19.1) mL in patients who took nintedanib in the SENSCIS trial and continued it in SENSCIS-ON. CONCLUSION: Patients with lcSSc may develop progressive fibrosing ILD. By targeting pulmonary fibrosis, nintedanib slows decline in lung function in patients with lcSSc and ILD. TRIAL REGISTRATION: ClinicalTrials.gov (https://www.clinicaltrials.gov), NCT02597933 and NCT03313180

Effect of nintedanib in patients with systemic sclerosis-associated interstitial lung disease and risk factors for rapid progression

OBJECTIVE: To investigate the rate of decline in forced vital capacity (FVC), and the effect of nintedanib on the rate of decline in FVC, in subjects with systemic sclerosis-associated interstitial lung disease (SSc-ILD) who had risk factors for rapid decline in FVC. METHODS: The SENSCIS trial enrolled subjects with SSc and fibrotic ILD of ≥10% extent on high-resolution CT. The rate of decline in FVC over 52 weeks was analysed in all subjects and in those with early SSc (<18 months since first non-Raynaud symptom), elevated inflammatory markers (C reactive protein ≥6 mg/L and/or platelets ≥330×109/L) or significant skin fibrosis (modified Rodnan skin score (mRSS) 15-40 or mRSS ≥18) at baseline. RESULTS: In the placebo group, the rate of decline in FVC was numerically greater in subjects with <18 months since first non-Raynaud symptom (-167.8 mL/year), elevated inflammatory markers (-100.7 mL/year), mRSS 15-40 (-121.7 mL/year) or mRSS ≥18 (-131.7 mL/year) than in all subjects (-93.3 mL/year). Nintedanib reduced the rate of FVC decline across subgroups, with a numerically greater effect in patients with these risk factors for rapid FVC decline. CONCLUSION: In the SENSCIS trial, subjects with SSc-ILD who had early SSc, elevated inflammatory markers or extensive skin fibrosis had a more rapid decline in FVC over 52 weeks than the overall trial population. Nintedanib had a numerically greater effect in patients with these risk factors for rapid ILD progression

Impact of Post-incarceration Care Engagement interventions On Hiv Transmission among Young Black Men Who Have Sex With Men and their Sexual Partners: an agent-Based Network Modeling Study

BACKGROUND: Understanding the impact of incarceration on HIV transmission among Black men who have sex with men is important given their disproportionate representation among people experiencing incarceration and the potential impact of incarceration on social and sexual networks, employment, housing, and medical care. We developed an agent-based network model (ABNM) of 10,000 agents representing young Black men who have sex with men in the city of Chicago to examine the impact of varying degrees of post-incarceration care disruption and care engagement interventions following release from jail on HIV incidence. METHODS: Exponential random graph models were used to model network formation and dissolution dynamics, and network dynamics and HIV care continuum engagement were varied according to incarceration status. Hypothetical interventions to improve post-release engagement in HIV care for individuals with incarceration (e.g., enhanced case management, linkage to housing and employment services) were compared to a control scenario with no change in HIV care engagement after release. FINDING: HIV incidence at 10 years was 4.98 [95% simulation interval (SI): 4.87, 5.09 per 100 person-years (py)] in the model population overall; 5.58 (95% SI 5.38, 5.76 per 100 py) among those with history of incarceration, and 12.86 (95% SI 11.89, 13.73 per 100 py) among partners of agents recently released from incarceration. Sustained post-release HIV care for agents with HIV and experiencing recent incarceration resulted in a 46% reduction in HIV incidence among post-incarceration partners [incidence rate (IR) per 100 py = 5.72 (95% SI 5.19, 6.27) vs. 10.61 (95% SI 10.09, 11.24); incidence rate ratio (IRR) = 0.54; (95% SI 0.48, 0.60)] and a 19% reduction in HIV incidence in the population overall [(IR per 100 py = 3.89 (95% SI 3.81-3.99) vs. 4.83 (95% SI 4.73, 4.92); IRR = 0.81 (95% SI 0.78, 0.83)] compared to a scenario with no change in HIV care engagement from pre-to post-release. INTERPRETATION: Developing effective and scalable interventions to increase HIV care engagement among individuals experiencing recent incarceration and their sexual partners is needed to reduce HIV transmission among Black men who have sex with men. FUNDING: This work was supported by the following grants from the National Institutes of Health: R01DA039934; P20 GM 130414; P30 AI 042853; P30MH058107; T32 DA 043469; U2C DA050098 and the California HIV/AIDS Research Program: OS17-LA-003; H21PC3466

Distribution of Aspergillus Species and Prevalence of Azole Resistance in Respiratory Samples From Swiss Tertiary Care Hospitals

Among 400 Aspergillus species from respiratory samples in Switzerland, Aspergillus fumigatus was the most frequent species. Non-fumigatus Aspergillus spp were more prevalent among solid organ transplant recipients and after azole exposure. Azole resistance was detected in 4 A fumigatus isolates, 3 of them with the "environmental" mutation TR$_{34}$/L98H in the cyp51A gene

Molecular chaperone Hsp90 stabilizes Pih1/Nop17 to maintain R2TP complex activity that regulates snoRNA accumulation

Hsp90 is a highly conserved molecular chaperone that is involved in modulating a multitude of cellular processes. In this study, we identify a function for the chaperone in RNA processing and maintenance. This functionality of Hsp90 involves two recently identified interactors of the chaperone: Tah1 and Pih1/Nop17. Tah1 is a small protein containing tetratricopeptide repeats, whereas Pih1 is found to be an unstable protein. Tah1 and Pih1 bind to the essential helicases Rvb1 and Rvb2 to form the R2TP complex, which we demonstrate is required for the correct accumulation of box C/D small nucleolar ribonucleoproteins. Together with the Tah1 cofactor, Hsp90 functions to stabilize Pih1. As a consequence, the chaperone is shown to affect box C/D accumulation and maintenance, especially under stress conditions. Hsp90 and R2TP proteins are also involved in the proper accumulation of box H/ACA small nucleolar RNAs