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We investigate whether more accurate representation of syntacticinformation in Transformer-based language models isassociated with better alignment to brain activity. We use fMRIrecordings from a large dataset (MOUS) of a Dutch sentencereading task, and perform Representational Similarity Analysisto measure alignment with 2 mono- and 3 multilinguallanguage models. We focus on activity in a region knownfor syntactic processing (the Left posterior Medial TemporalGyrus). We correlate model-brain similarity scores with theaccuracy of dependency structures extracted from model internalstates using a labelled structural probe. We report three keyfindings: 1) Accuracy of syntactic dependency representationscorrelates with brain similarity, 2) The link between brain similarityand dependency accuracy persists regardless of sentencecomplexity, although 3) Sentence complexity decreases dependencyaccuracy while increasing brain similarity. These resultshighlight how interpretable, linguistic features such as syntacticdependencies can mediate the similarity between languagemodels and brains

Abstract Background Learning health systems (LHSs) iteratively generate evidence that can be implemented into practice to improve care and produce generalizable knowledge. Pragmatic clinical trials fit well within LHSs as they combine real‐world data and experiences with a degree of methodological rigor which supports generalizability. Objectives We established a pragmatic clinical trial unit (“RapidEval”) to support the development of an LHS. To further advance the field of LHS, we sought to further characterize the role of health information technology (HIT), including innovative solutions and challenges that occur, to improve LHS project delivery. Methods During the period from December 2021 to February 2023, eight projects were selected out of 51 applications to the RapidEval program, of which five were implemented, one is currently in pilot testing, and two are in planning. We evaluated pre‐study planning, implementation, analysis, and study closure approaches across all RapidEval initiatives to summarize approaches across studies and identify key innovations and learnings by gathering data from study investigators, quality staff, and IT staff, as well as RapidEval staff and leadership. Implementation (Results) Implementation approaches spanned a range of HIT capabilities including interruptive alerts, clinical decision support integrated into order systems, patient navigators, embedded micro‐education, targeted outpatient hand‐off documentation, and patient communication. Study approaches include pre‐post with time‐concordant controls (1), randomized stepped‐wedge (1), cluster randomized across providers (1) and location (3), and simple patient level randomization (2). Conclusions Study selection, design, deployment, data collection, and analysis required close collaboration between data analysts, informaticists, and the RapidEval team.

Isolating and characterizing emerging SARS-CoV-2 variants is key to understanding virus pathogenesis. In this study, we isolated samples of the SARS-CoV-2 R.1 lineage, categorized as a variant under monitoring by the World Health Organization, and evaluated their sensitivity to neutralizing antibodies and type I interferons. We used convalescent serum samples from persons in Canada infected either with ancestral virus (wave 1) or the B.1.1.7 (Alpha) variant of concern (wave 3) for testing neutralization sensitivity. The R.1 isolates were potently neutralized by both the wave 1 and wave 3 convalescent serum samples, unlike the B.1.351 (Beta) variant of concern. Of note, the R.1 variant was significantly more resistant to type I interferons (IFN-α/β) than was the ancestral isolate. Our study demonstrates that the R.1 variant retained sensitivity to neutralizing antibodies but evolved resistance to type I interferons. This critical driving force will influence the trajectory of the pandemic.

Abstract Context Treatment-related toxicities in DLBCL (diffuse large B cell lymphoma) patients are higher in the initial phase of treatment (first cycle effect). Implementation of pre-phase treatment before definitive chemotherapy had been shown to alleviate some of these side-effects in a non-randomized study conducted earlier in our institute (Lakshmaiah et. al., Eur J Haematol 100:644-8, 2018). Aims This study was aimed at validating the role of pre-phase treatment in newly diagnosed DLBCL patients. Settings and design All newly diagnosed patients with DLBCL above the age of 18 years were evaluated for eligibility and prospectively enrolled. A single-arm prospective study was conducted at the Department of Medical Oncology, in our institute from July 2015 to December 2019. Methods and material Patients received vincristine and prednisolone as pre-phase treatment for 7 days after which definitive chemotherapy was instituted on day 1. They were followed up for 30 days post-first cycle chemotherapy. Statistical analysis used Paired Student’s t tests and Wilcoxon signed-ranks test were used for comparison of various clinical variables as appropriate. P value of less than 0.05 was considered significant. Results Among the 180 patients who were included in study, performance status improvement was noted in significant number of patients (p < 0.001). 38.4% achieved an ECOG (Eastern Cooperative Oncology Group) performance status of 0 post-pre-phase therapy. Febrile neutropenia was observed in 12.8% in the present cohort as compared to the historical non-pre-phase cohort (34%). Conclusions Pre-phase therapy significantly improves the performance status and diminishes neutropenia rates in DLBCL patients.

Cardiogenic shock (CS) is a hemodynamic syndrome that can progress to systemic metabolic derangements and end-organ dysfunction. Prior studies have reported hemodynamic parameters at the time of admission to be associated with mortality but hemodynamic trajectories in CS have not been well described. We studied the association between hemodynamic profiles and their trajectories and in-hospital mortality in patients with CS due to heart failure (HF-CS) and acute myocardial infarction (MI-CS). Using data from the large multicenter Cardiogenic Shock Working Group (CSWG) registry, we analyzed hemodynamic data obtained at the time of pulmonary artery catheter (PAC) insertion (dataset at baseline) and at PAC removal or death (dataset at final time point). Univariable regression analyses for prediction of in-hospital mortality were conducted for baseline and final hemodynamic values, as well as the interval change (delta-P). Data was further analyzed based on CS etiology and survival status. A total of 2260 patients with PAC data were included (70% male, age 61 ± 14 years, 61% HF-CS, 27% MI-CS). In-hospital mortality was higher in the MI-CS group (40.1%) compared with HF-CS (22.4%, P <.01). In the HF-CS cohort, survivors exhibited lower right atrial pressure (RAP), pulmonary artery pressure (PAP), cardiac output/index (CO/CI), lactate, and higher blood pressure (BP) than nonsurvivors at baseline. In this cohort, during hospitalization, improvement in metabolic (aspartate transaminase, lactate), BP, hemodynamic (RAP, pulmonary artery pulsatility index [PAPi], pulmonary artery compliance for right-sided profile and CO/CI for left-sided profile), had association with survival. In the MI-CS cohort, a lower systolic BP and higher PAP at baseline were associated with odds of death. Improvement in metabolic (lactate), BP, hemodynamic (RAP, PAPi for right-sided profile and CO/CI for left-sided profile) were associated with survival. In a large contemporary CS registry, hemodynamic trajectories had a strong association with short-term outcomes in both cohorts. These findings suggest the clinical importance of timing and monitoring hemodynamic trajectories to tailor management in patients with CS. • Baseline hemodynamics impact mortality in HF-CS more so than MI-CS. • Hemodynamics indicative of end-organ perfusion and congestion have distinct trajectories between survivors and non-survivors in CS. • Hemodynamic trajectories have strong association with hospital outcomes in both HF- and MI-CS • Changes in hemodynamics should be closely monitored to tailor management practices in CS [ABSTRACT FROM AUTHOR]

Background: The novel virus SARS-CoV-2 has caused a pandemic of coronavirus disease 2019 (COVID-19). There is emerging evidence of post-COVID-19 manifestations among patients who sustain acute COVID-19. Most studies report fatigue, dyspnea, and myalgia as the common symptoms; however, currently, there is limited knowledge of these post-COVID manifestations and their risk factors, especially in India. Methods: A descriptive cross-sectional study was conducted among patients who had attended the district post-COVID clinic, Wayanad district, Kerala, from October 2020 to June 2021. Data were collected by direct/telephonic patient interviews and from their existing case records, using a pretested semi-structured proforma. Results: The sample size was 667. The mean age of the study population was 45 years (standard deviation [SD]: 14.55). The majority of the population presented with dyspnea (48%), fatigue (32%), and cough (25.6%). Mental health problems were also reported in 6% of participants. The respiratory system was commonly involved (61.2%). Around one-third of the patients (36.4%) had dyspnea on exertion and 11.8% had dyspnea at rest. One-fifth of the population reported aggravation of pre-existing co-morbidity and half of the respondents had persistence of at least one symptom after 6 months. There exist statistically significant associations between identified risk factors, especially gender, increasing age, the severity of COVID-19 infection, history of tobacco/alcohol use, and co-morbidities with outcomes. Conclusion: As post-COVID syndrome is a multisystem disease, integrated rehabilitation is required with targeted intervention for survivors based on their symptoms and needs.

Acalabrutinib is a Bruton tyrosine kinase inhibitor approved for patients with chronic lymphocytic leukemia (CLL). ASCEND is the pivotal phase 3 study of acalabrutinib versus investigator’s choice of idelalisib plus rituximab (IdR) or bendamustine plus rituximab (BR) in patients with relapsed/refractory (R/R) CLL. In the primary ASCEND analysis (median 16.1-month follow-up), acalabrutinib showed superior efficacy with an acceptable tolerability profile versus IdR/BR; here, we report final ~4 year follow-up results. Patients with R/R CLL received oral acalabrutinib 100 mg twice daily until progression or unacceptable toxicity, or investigator’s choice of IdR or BR. A total of 310 patients (acalabrutinib, n = 155; IdR, n = 119; BR, n = 36) were enrolled. At median follow-up of 46.5 months (acalabrutinib) and 45.3 months (IdR/BR), acalabrutinib significantly prolonged investigator-assessed progression-free survival (PFS) versus IdR/BR (median, not reached [NR] vs 16.8 months; P < 0.001); 42-month PFS rates were 62% (acalabrutinib) versus 19% (IdR/BR). Median overall survival (OS) was NR (both arms); 42-month OS rates were 78% (acalabrutinib) versus 65% (IdR/BR). Adverse events led to drug discontinuation in 23%, 67%, and 17% of patients in the acalabrutinib, IdR, and BR arms, respectively. Events of clinical interest (acalabrutinib vs IdR/BR) included all-grade atrial fibrillation/flutter (8% vs 3%), all-grade hypertension (8% vs 5%), all-grade major hemorrhage (3% vs 3%), grade ≥3 infections (29% vs 29%), and second primary malignancies excluding nonmelanoma skin cancer (7% vs 2%). At ~4 years follow-up, acalabrutinib maintained favorable efficacy versus standard-of-care regimens and a consistent tolerability profile in patients with R/R CLL.

Objectives Bone marrow aspiration although being a common procedure is associated with significant pain and its reduction remains an unmet need. We evaluated the use of tramadol and eutectic mixture of local anesthetics (prilocaine plus lignocaine) (EMLA) for reducing the severity of pain. Materials and Methods In this pilot study, we compared the addition of either tramadol 50 mg per oral (T) or EMLA local application (E) or no intervention (L) in addition to the usual procedure of local infiltration with lignocaine 2% before bone marrow aspiration and biopsy (BMAB) in adults suspected/confirmed with malignancy. Both, tramadol and EMLA were administered 1 hour prior to the procedure. Primary end point was reduction in pain intensity with these interventions compared with local infiltration alone. Pain was assessed using numerical FACES pain scale, a visual analogue scale. Secondary end points were to see the effect on pre procedure apprehension and to find out the other factors associated with increased pain related to the procedure. Statistical Analysis and Results A total of 300 patients were included in the study, 100 each in tramadol (T), EMLA (E), and only lignocaine local infiltration (L) arms, respectively. The mean pain intensity on the visual scale was significantly lower in the tramadol arm (T, E, L—3.4, 4.4, 4.7, respectively) (p < 0.0005). There was a significant reduction in percentage of patients who experienced moderate/severe pain (four or more) in the tramadol arm (T, E, L—45, 77, 82%, respectively) (p < 0.0005). Duration of procedure >10 minutes, body mass index >30, ECOG (Eastern Oncology Group) performance status ≥3, and age >50 years were positively correlated with more pain. Leukemia patients experienced significantly more pain compared with patients with lymphoma and other solid malignancies. Tramadol was well tolerated. No significant effect on pre-procedure apprehension was noted in any of the arms. Conclusion Tramadol appears to have a preventive effect on bone marrow aspiration/biopsy-associated pain and appears to be well tolerated, whereas EMLA was not associated with such an effect. Larger studies may be done to ascertain the same.

Introduction: Haematological malignancies contribute to a significant number (8.2%) among cancer patientsin India. Bursa-Acute Lymphoblastic Leukaemia (B-ALL), ThymusAcute Lymphoblastic Leukaemia (T-ALL) and Acute Myeloid Leukaemia (AML) are the three main types of leukaemias distinguished based on flow cytometry. Expression of Cluster of Differentiation (CD) markers of a lineage distinct to the blast population is termed as aberrant expression (expression of B/T cell markers in AML or myeloid markers in ALL). Role of aberrant marker expression in leukaemias remain an enigma till date. Aberrant expression of antigens may be associated with adverse outcomes. Aim: To study the expression of aberrant markers and their association with the remission status postinduction therapy in ALL and AML. Materials and Methods: A retrospective cross-sectional study done accessing the medical records of Acute Leukaemia patients admitted from 1st January 2019 to 31st December 2019 at Kidwai Memorial Institute of Oncology, Bengaluru. A total of 144 cases were included of which 86 cases were of AML and 58 cases were ALL. ALL was further divided into B-ALL and T-ALL with 40 and 18 cases respectively, 18 cases of T-ALL and 86 cases of AML were included. Demographic and clinicohaematological parameters were recorded. All quantitative variables were described as Mean {Standard deviation(SD)} and all qualitative variables were depicted as number (proportion). Statistical significance assessed by Chi-square and Fischer-Exact test using Statistical Package for the Social Sciences (SPSS) version 22.0. Results: Majority of patients belonged to 16-25 years age group with a male preponderance of 58.3%. Aberrant marker expression was associated with the remission status with a p-value of 0.23 and 0.185 in ALL and AML patients respectively and was statistically not significant. While the Chi-square test when applied to the total cases (both ALL and AML combined) the p-value was 0.03 and statistically significant. Conclusion: Aberrant marker expression might predict poor response to induction therapy in acute leukaemias. However, larger studies are needed to confirm these results

Multiple myeloma constitutes a wide spectrum of diseases ranging from slow-growing monoclonal gammopathy of undetermined significance to rapidly progressing plasma cell leukemia. It is a very rarely diagnosed hematological malignancy in those less than 30 years. A 25-year-old male presented with complaints of fatigue, and low-grade fever. On investigations, he was found to have bicytopeina and features of tumor lysis syndrome. This was initially thought to be consistent with a diagnosis of acute leukemia. Upon further analysis with bone marrow biopsy, serum protein electrophoresis, and immunofixation, the rare diagnosis of IgG myeloma with plasmablastic morphology was confirmed. However, it rapidly progressed and peripheral smear started showing clusters of plasma cells. Despite aggressive treatment, the patient succumbed to aggressive plasma cell leukemia with an underlying plasmablastic morphology. This case highlights the possibility of myeloma as one of the differentials in young patients especially the rare plasmablastic variant that can get misdiagnosed as acute leukemia. This aggressive morphology may also show rapid progression to plasma cell leukemia and has an adverse prognosis.

Objective Follicular lymphoma (FL) is a disease of the elderly. It is postulated that younger patients have distinct tumor biology and treatment outcomes. Various lymphoma groups across the world have studied this to understand if young adults (YAs) need a different treatment approach. Our study fills the void in data from an Asian country on YA population with FL. Patients and Methods We retrospectively analyzed young patients (age ≤40 years) diagnosed with FL at our center from 2012 to 2018. Their disease characteristics, treatment details, and outcomes were studied to examine any association between various parameters and survival. Results There were 28 young FL patients included in our study that constituted 14.6% of FL cases (males: 53.5% and females: 46.5%). The median age at diagnosis was 36.5 years. Most of the patients presented in an advanced stage, 57% had extranodal involvement, and 39.3% had bone marrow involvement at the time of presentation. The most common chemotherapy regimen used was cyclophosphamide, vincristine, and prednisone. Half of them received chemoimmunotherapy and only 18% continued rituximab as maintenance therapy. The overall response rate was 92.9% (n = 26), and the remaining two patients had progressive disease while on treatment. The median progression free survival (PFS) was 6.1 years and median overall survival (OS) was not reached. On univariate analysis, extranodal disease was associated with a lower PFS (p = 0.06) and low hemoglobin showed a significant association with OS (p = 0.005). On multivariate analysis, none of the factors showed a significant association with survival. Conclusion Most YAs present with advanced disease with a good response to treatment and favorable outcomes.