Real-world use of venetoclax in the treatment of paediatric and teenage/young adult haematological malignancies.

Early-phase trials of venetoclax in children and teenagers/young adults with leukaemia have yielded promising results, but there remains a paucity of real-world data. To address this, we report a cohort of 41 children treated with venetoclax for a range of haematological malignancies, demonstrating complete remission in 43.6%, with most achieving minimal residual disease (MRD) negativity. Venetoclax was particularly effective as a bridge to transplant, with bridging successful in 75% of patients. Patients with MRD <1% at initiation of venetoclax were more likely to achieve MRD negativity (81.8% vs. 34.5%, p = 0.007) and had improved overall survival (54.5% vs. 17.9%, p = 0.004).

Generalized overview infographic: a customizable library instructional material on the NIH Data Management and Sharing Policy.

The Generalized Overview of the NIH Data Management and Sharing Policy Effective 2023.01.15 (Generalized Overview) is an instructional material that provides a basic, clear, and linear understanding of the NIH policy and its requirements. While not developing or utilizing new technology, the Generalized Overview is innovative and notable for creatively using a freely available graphic design tool to translate government policy language into an accessible and understandable infographic that can disseminate important information about the NIH DMS Policy needed by researchers and by those who support them. Shared via a Creative Commons license, others may fully adapt the infographic or may simply add their own institutional contact information. The Generalized Overview can be used by any who find themselves responsible for publicizing and/or teaching the NIH Data Management and Sharing Policy at their respective libraries and institutions. It is intended for educational purposes only and should not be used as a substitute for official guidance from the NIH.

The DMPTool NIH DMSP Templates Project.

The DMPTool NIH Data Management and Sharing Plan (DMSP) Templates Project was launched in response to the 2023 NIH Data Management and Sharing (DMS) Policy. This new policy introduced a more structured framework for DMS Plans, featuring six key elements, a departure from the 2003 NIH DMS policy. The project aimed to simplify the process for data librarians, research administrators, and researchers by providing a template with curated guidance, eliminating the need to navigate various policies and guidelines. The template breaks out each Plan section and subsection and provides related guidance and examples at the point of need. This effort has resulted in two NIH DMSP Templates. The first is a generic template (NIH-Default) for all ICs, complying with NOT-OD-21-013 and NOT-OD-22-198. More recently, an NIMH-specific template (NIH-NIMH) was added based on NOT-MH-23-100. As of October 2023, over 5,000 DMS Plans have been written using the main NIH-Default template and the NIH-NIMH alternative template.

Defining the proteomic landscape of cultured macrophages and their polarization continuum.

Macrophages have previously been characterized based on phenotypical and functional differences into suggested simplified subtypes of MØ, M1, M2a and M2c. These macrophage subtypes can be generated in a well-established primary monocyte culture model that produces cells expressing accepted subtype surface markers. To determine how these subtypes retain functional similarities and better understand their formation, we generated all four subtypes from the same donors. Comparative whole-cell proteomics confirmed that four distinct macrophage subtypes could be induced from the same donor material, with > 50% of 5435 identified proteins being significantly altered in abundance between subtypes. Functional assessment highlighted that these distinct protein expression profiles are primed to enable specific cell functions, indicating that this shifting proteome is predictive of meaningful changes in cell characteristics. Importantly, the 2552 proteins remained consistent in abundance across all macrophage subtypes examined, demonstrating maintenance of a stable core proteome that likely enables swift polarity changes. We next explored the cross-polarization capabilities of preactivated M1 macrophages treated with dexamethasone. Importantly, these treated cells undergo a partial repolarization toward the M2c surface markers but still retain the M1 functional phenotype. Our investigation of polarized macrophage subtypes therefore provides evidence of a sliding scale of macrophage functionality, with these data sets providing a valuable benchmark resource for further studies of macrophage polarity, with relevance for cell therapy development and drug discovery.

Intraocular lens power calculation in patients with irregular astigmatism.

PURPOSE: Accurate intraocular lens (IOL) calculation in subjects with irregular astigmatism is challenging. This study evaluated the accuracy of using Scheimpflug-derived central 2-mm equivalent keratometry reading (EKR) values for IOL calculation in irregular astigmatism. METHODS: This retrospective study included subjects (31 eyes of 30 patients) who underwent cataract surgery and IOL calculation using the 2-mm central EKR methods. We compared prediction error (PE) and absolute PE (APE) outcomes using SRK/T and Barrett Universal II formulas for keratometry data obtained from the IOLMaster 500 and Pentacam (anterior corneal sim k) devices. RESULTS: Cataract surgery and IOL calculation using the 2-mm central EKR methods resulted in improved visual acuity (uncorrected: from 1.13 ± 0.38 to 0.65 ± 0.46 logMar, p < 0.01; best-corrected: from 0.45 ± 0.24 to 0.26 ± 0.20 logMar, p < 0.01) after surgery. The percentage of subjects with best-corrected visual acuity of 6/6 was 22%, < 6/9 was 58%, and < 6/12 was 71%. For both the SRK/T and the Barrett formulas, the PE was similar to those obtained by IOLMaster (> 0.14) but lower than those obtained by the anterior corneal sim k (p < 0.02). IOLMaster provided keratometry reading in only 23/31 (74.1%) of cases. CONCLUSIONS: The use of Scheimpflug central 2-mm EKR for IOL calculation in irregular astigmatism was beneficial in terms of visual acuity improvement. It had comparable refractive prediction performance to the IOLMaster 500 and better than the anterior corneal sim K. The 2-mm EKR method can be used when IOLMaster cannot provide a reliable reading in abnormal corneas.

Hair mercury concentrations in residents of Sundarban and Calcutta, India.

Few studies on hair mercury have been conducted in India despite the fact that India is the world's third largest producer of coal and coal is India's primary energy source. No studies have been conducted in the Indian state of West Bengal which has a coastline with the Bay of Bengal. This study examined the concentration of mercury in hair in two diverse populations in West Bengal, India: Sundarban, a mangrove wetland where fishing is a common occupation, and Calcutta, a megacity and India's oldest functioning port. Individuals from whom scalp hair was collected (N=100) were asked a series of questions on occupation, education, age, smoking and alcohol consumption, and fish consumption. SAS was utilized to generate descriptive statistics including frequency and univariate analyses and to perform regression analyses to determine significant predictors of hair mercury in this population. The mean hair mercury increased across the first three age categories (<21, 21-30, 31-45) and decreased in the fourth category (>45). Hair mercury concentration was significantly higher among residents of Sundarban compared to Calcutta (p=0.0005). In multivariable analysis, location (Sundarban vs. Calcutta) and age were significant predictors of hair mercury concentration (p=0.0120 and p=0.0161, respectively). Average hair mercury concentrations in this study were not particularly elevated. Smoking and alcohol consumption were predictors of hair mercury concentration. The hair mercury in Sundarban residents compared to Calcutta residents may be elevated due to greater consumption of fish and type of fish consumed.

Quantifying Fatigue Using Electrophysiological Techniques and Non-invasive Brain Stimulation in People With Multiple Sclerosis- A Review and Discussion.

Objective: The purpose of this literature review article is to provide a synthesis of recent research focused on the use of 3 techniques to evaluate MS-related fatigue: electroencephalography [EEG], transcranial direct-current stimulation (tDSC), and transcranial- magnetic stimulation (TMS). Method: We performed a literature search in the Cumulative Index to Nursing and Allied Health Literature (CINAHL, EBSCOhost), MEDLINE (OVID), APA PsycInfo (OVID), Scopus (Elsevier), and Web of Science (Clarivate) databases, limited to 2015 and after. Results: Our review revealed that fatigue in MS patients can be quantified and predicted using electrophysiological techniques. Such techniques, which yield objective data, are historically assessed in relation to subjective data, or perceived fatigue. We identified studies using EEG, TMS, and/or tDCS to study fatigue in people with MS. In total, 220 records were identified with 19 studies meeting inclusion criteria. Quality appraisal revealed that the level of evidence was generally graded "good". Conclusions: Despite the heterogenous nature of reviewed the studies and selected the varied self-report fatigue measures, our literature synthesis suggests promise for the use of EEG, TMS, and/or tDCS approaches in more accurately assessing fatigue in people with MS. Further research is needed in this arena.

Coding with the machines: machine-assisted coding of rare event data.

While machine coding of data has dramatically advanced in recent years, the literature raises significant concerns about validation of LLM classification showing, for example, that reliability varies greatly by prompt and temperature tuning, across subject areas and tasks-especially in "zero-shot" applications. This paper contributes to the discussion of validation in several different ways. To test the relative performance of supervised and semi-supervised algorithms when coding political data, we compare three models' performances to each other over multiple iterations for each model and to trained expert coding of data. We also examine changes in performance resulting from prompt engineering and pre-processing of source data. To ameliorate concerns regarding LLM's pre-training on test data, we assess performance by updating an existing dataset beyond what is publicly available. Overall, we find that only GPT-4 approaches trained expert coders when coding contexts familiar to human coders and codes more consistently across contexts. We conclude by discussing some benefits and drawbacks of machine coding moving forward.

A Problem Shared Is a Community Created: Recommendations for Cross-Institutional Collaborations.

Committee work is a requisite job function for many in academia, yet designing a productive collaborative experience often remains a challenge. In this article, we reflect on our experiences as part of a successful cross-institutional working group and describe strategies to improve leadership structure, group dynamics, accountability, and incentives for collaborative projects. As of January 2023, the National Institutes of Health (NIH) Data Management & Sharing (DMS) Policy requires investigators applying for funding to submit a Data Management and Sharing Plan (DMS Plan) that describes how scientific data will be managed, preserved, and shared. In response to this new policy, a community of more than 30 librarians and other research data professionals convened the Working Group on NIH DMSP Guidance, collaboratively producing comprehensive guidance about the policy for researchers and research support staff. In less than a year, the working group produced glossaries of NIH and data management jargon, an example data management and sharing plan, a directory of existing example plans, checklists for researchers and librarians, and an interactive repository finder. This group was a successful grassroots effort by contributors with diverse expertise and backgrounds. We discuss practical strategies for each stage of activity throughout the lifecycle of the working group; from recruiting members, designing pathways to encourage participation from busy professionals, structuring the meetings to facilitate progress and productivity, and disseminating final products broadly. We invite fellow librarians, data professionals, and academics to apply and build upon these strategies to tackle cross-institutional challenges.

Pulvinar inactivation disrupts selection of movement plans.

The coordinated movement of the eyes and hands under visual guidance is an essential part of goal-directed behavior. Several cortical areas known to be involved in this process exchange projections with the dorsal aspect of the thalamic pulvinar nucleus, suggesting that this structure may play a central role in visuomotor behavior. Here, we used reversible inactivation to investigate the role of the dorsal pulvinar in the selection and execution of visually guided manual and saccadic eye movements in macaque monkeys. We found that unilateral pulvinar inactivation resulted in a spatial neglect syndrome accompanied by visuomotor deficits including optic ataxia during visually guided limb movements. Monkeys were severely disrupted in their visually guided behavior regarding space contralateral to the side of the injection in several domains, including the following: (1) target selection in both manual and oculomotor tasks, (2) limb usage in a manual retrieval task, and (3) spontaneous visual exploration. In addition, saccades into the ipsilesional field had abnormally short latencies and tended to overshoot their mark. None of the deficits could be explained by a visual field defect or primary motor deficit. These findings highlight the importance of the dorsal aspect of the pulvinar nucleus as a critical hub for spatial attention and selection of visually guided actions.

Landscape influences on headwater streams on Fort Stewart, Georgia, USA.

Military landscapes represent a mixture of undisturbed natural ecosystems, developed areas, and lands that support different types and intensities of military training. Research to understand water-quality influences of military landscapes usually involves intensive sampling in a few watersheds. In this study, we developed a survey design of accessible headwater watersheds intended to improve our ability to distinguish land-water relationships in general, and training influences, in particular, on Fort Stewart, GA. We sampled and analyzed water from watershed outlets. We successfully developed correlative models for total suspended solids (TSS), total nitrogen (TN), organic carbon (OC), and organic nitrogen (ON), which dominated in this blackwater ecosystem. TSS tended to be greater in samples after rainfall and during the growing season, and models that included %Wetland suggested a "build-and-flush" relationship. We also detected a positive association between TSS and tank-training, which suggests a need to intercept sediment-laden runoff from training areas. Models for OC showed a negative association with %Grassland. TN and ON both showed negative associations with %Grassland, %Wetland, and %Forest. Unexpected positive associations were observed between OC and equipment-training activity and between ON and %Bare ground + Roads. Future studies that combine our survey-based approach with more intensive monitoring of the timing and intensity of training would be needed to better understand the mechanisms for these empirical relationships involving military training. Looking beyond local effects on Fort Stewart streams, we explore questions about how exports of OC and nitrogen from coastal military installations ultimately influence estuaries downstream.

Improving the rate and quality of medicaid well child care exams in primary care practices.

BACKGROUND: Providing recommended well child care to children insured bythe Medicaid Program can be challenging. Members of the Department of Family and Preventive Medicine (DFPM) at the University of Oklahoma Health Sciences Center contracted to help practices improve the rates and quality of well child care visits within the Oklahoma Medicaid Program. METHODS: Sixteen pediatric and family medicine practices in three Oklahoma counties chose to participate in this quality improvement initiative. The records of Sooner Care-insured children age 0-20 were reviewed for both rate and quality of well child care visits made during the previous twelve months. Performance feedback was provided. Practice guidelines, Sooner Care requirements, and tips from exemplary practices were provided. In two of the counties, a case manager helped practices with challenging patients. Practice Enhancement Assistants (PEAs) then helped practices implement a variety of strategies to increase visit rates and improve the quality of early and periodic screening, diagnosis, and treatment (EPSDT) visits. Information technology (IT) support was provided when needed. RESULTS: The average rates of visits, for all counties combined, increased. Visit rates increased more in the younger age groups (birth to two years). There was significant improvement in quality of visits. Rates and quality improved much more in some practices than in others. CONCLUSIONS: A combination of academic detailing, performance feedback, practice facilitation, case management, and IT support produced increases in the quality and rates of EPSDT exams.

Time from diagnosis to 2nd treatment is a promising surrogate for overall survival in patients with advanced stage follicular lymphoma.

It is difficult to demonstrate an overall survival (OS) benefit in trials of immediate therapy vs observation in follicular lymphoma (FL). Time to 2nd treatment (TT2T) may be a preferred endpoint. We identified 584 consecutive patients at our institution with advanced stage FL grade 1-3 A for whom intention was observation (n = 248) or therapy (n = 338). Median time to 1st treatment (TT1T), TT2T, and OS were estimated (subdistribution function). Modified Kendall's tau (mKτ) was used to assess correlation between survival endpoints. Among initially observed patients, median TT1T was 3.3 years, TT2T was 12.1 years, 10-year treatment-free survival was 23%, and 10-year OS was 82%. TT2T was strongly correlated with OS following initial observation (mKτ 0.46, p = .004) or therapy (mKτ 0.53, p < .0001), while duration of observation was not. TT2T is a potential surrogate for OS. Given the outstanding survival in this population, early intervention trials should focus on identifying high risk patients.

Follicular lymphoma in the modern era: survival, treatment outcomes, and identification of high-risk subgroups.

Patients with follicular lymphoma (FL) frequently require multiple treatments during their disease course; however, survival based on lines of treatment remains poorly described in the post-rituximab era. Also, the Follicular Lymphoma International Prognostic Index (FLIPI) score was developed to predict survival at diagnosis, yet it remains unknown whether increase in FLIPI score following an initial observation period is associated with less-favorable outcomes. To address these knowledge gaps, we retrospectively studied 1088 patients with FL grade 1-3A managed between 1998 and 2009 at our institution. Median overall survival (OS) and progression-free survival (PFS) after first-line treatment were not reached and 4.73 years, respectively. Following successive lines of treatment, years of median OS and PFS were, respectively: after second-line, 11.7 and 1.5; third-line, 8.8 and 1.1; fourth-line, 5.3 and 0.9; fifth-line, 3.1 and 0.6; sixth-line, 1.9 and 0.5. In initially observed, subsequently treated patients, FLIPI score increase after observation was associated with inferior survival following first-line treatment. The reduced survival we observed after second-line and later therapy supports the development of new treatments for relapsed patients and benchmarks historical targets for clinical endpoints. This study also highlights the utility of changes in FLIPI score at diagnosis and after observation in identifying patients likely to have worse outcomes.

Positron-emission tomography-based staging reduces the prognostic impact of early disease progression in patients with follicular lymphoma.

BACKGROUND: Previous studies reported that early progression of disease (POD) after initial therapy predicted poor overall survival (OS) in patients with follicular lymphoma (FL). Here, we investigated whether pre-treatment imaging modality had an impact on prognostic significance of POD. METHODS: In this retrospective study, we identified 1088 patients with grade I-IIIA FL; of whom, 238 patients with stage II-IV disease were initially treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP), and 346 patients were treated with rituximab-based chemotherapy. Patients (N = 484) from the FOLL05 study served as an independent validation cohort. We risk-stratified patients based on pre-treatment radiographic imaging (positron-emission tomography [PET] versus computed tomography [CT]) and early POD status using event-defining and landmark analyses. A competing risk analysis evaluated the association between early POD and histologic transformation. RESULTS: In the discovery cohort, patients with POD within 24 months (PFS24) of initiating R-CHOP therapy had a 5-year OS of 57.6% for CT-staged patients compared with 70.6% for PET-staged patients. In the validation cohort, the 5-year OS for patients with early POD was 53.9% and 100% in CT- and PET-staged patients, respectively. The risk of histologic transformation in patients whose disease progressed within one year of initiating therapy was higher in CT-staged patients than in PET-staged patients (16.7% versus 6.3%, respectively), which was associated with a 9.7-fold higher risk of death. CONCLUSION: In FL, pre-treatment PET staging reduced the prognostic impact of early POD compared with CT staging. Patients with early POD and no histologic transformation have an extended OS with standard therapy.

Patient-physician e-mail communication revisited a decade later: an OKPRN study.

In private community-based primary care practices in Oklahoma, approximately two thirds of patients now have access to a computer and e-mail either at home or work. A substantial majority would like to use e-mail to communicate with their primary care clinicians. Since 1997, rural patients have caught up with urbanites in their access to computers.

Relationship of Maternal Weight Status Before, During, and After Pregnancy with Breast Milk Hormone Concentrations.

OBJECTIVE: The aim of this study was to test associations of prepregnancy BMI, gestational weight gain, oral glucose challenge test results, and postpartum weight loss as predictors of breast milk leptin, insulin, and adiponectin concentrations and whether these relationships vary over time. METHODS: Milk was collected at 1 and 3 months from 135 exclusively breastfeeding women from the longitudinal Mothers and Infants Linked for Healthy Growth (MILk) study. Hormones were assayed in skimmed samples using ELISA. Mixed-effects linear regression models were employed to assess main effects and effect-by-time interactions on hormone concentrations. RESULTS: In adjusted models, BMI was positively associated with milk leptin (P < 0.001) and insulin (P = 0.03) and negatively associated with milk adiponectin (P = 0.02); however, the association was stronger with insulin and weaker with adiponectin at 3 months than at 1 month (time interaction P = 0.017 for insulin and P = 0.045 for adiponectin). Gestational weight gain was positively associated and postpartum weight loss was negatively associated with milk leptin (both P < 0.001), independent of BMI. Oral glucose challenge test results were not associated with these milk hormone concentrations. CONCLUSIONS: Maternal weight status before, during, and after pregnancy contributes to interindividual variation in human milk composition. Continuing work will assess the role of these and other milk bioactive factors in altering infant metabolic outcomes.

Trends of and factors associated with cesarean section related surgical site infections in Guinea.

Since the adoption of free obstetric care policy in Guinea in 2011, no study has examined the surgical site infections in maternity facilities. The objective of this study was to assess the trends of and factors associated with surgical site infection following cesarean section in Guinean maternity facilities from 2013 to 2015. This was a retrospective cohort study using routine medical data from ten facilities. Overall, the incidence of surgical site infections following cesarean section showed a declining trend across the three periods (10% in 2013, 7% in 2014 and 5% in 2015, P<0.001). Women who underwent cesarean section in 2014 (AOR: 0.70; 95%CI: 0.57-0.84) and 2015 (AOR: 0.43; 95%CI: 0.34-0.55) were less likely to develop surgical site infections during hospital stay than women operated in 2013. In the contrary, women with comorbidities were more likely to experience surgical site infection (AOR: 1.54; 95% CI: 1.25-1.90) than those who did not have comorbidities. The reductions achieved in 2014 and 2015 (during the Ebola outbreak) should be sustained in the post-Ebola context.