The landscape of real-world evidence of rituximab utilization and clinical outcomes in patients with cancer, rheumatoid arthritis, and multiple sclerosis: A scoping review.

BACKGROUND: Rituximab (RTX) is an anti-CD20 monoclonal antibody that is used to treat various conditions in cancer, rheumatoid arthritis (RA), and multiple sclerosis (MS). Although RTX has been used in the United States for almost 3 decades, questions remain regarding its real-world utilization and effectiveness. OBJECTIVE: To describe the state of observational research and real-world evidence evaluating RTX in oncology, RA, and off-label use in MS. METHODS: A broad search was conducted in MEDLINE, Embase, and CINAHL covering the period of January 2010 to June 2022. Two reviewers independently screened all identified records for each disease category (cancer, RA, MS) beginning with title review, followed by abstract, and full-text review to identify relevant publications to include in the final analysis. Data were extracted and summarized for each disease based on overall trends, similarities, and differences across included studies and stratified by disease state. RESULTS: A total of 260 studies met eligibility criteria, with 79 studies for the RA cohort, 144 for cancer, and 37 for MS. Across all disease cohorts, most studies (n = 189; 72.7%) were retrospective. 171 (65.8%) studies used hospital or electronic health record data as their data source and 65 (23.2%) used registry databases. Most studies (n = 153; 58.8%) assessed the effectiveness of RTX measured by disease-specific endpoints, followed by safety (n = 60; 23.1%), treatment patterns (n = 32; 12.3%), and descriptive analyses assessing treatment adherence and economic burden of disease (n = 16; 6.2%). Although safety was not the primary outcome for most studies, the majority of studies across all disease states still reported some form of safety measure. Conclusive statements on RTX's benefit varied across disease states, with MS having the most (n = 30; 81.1%) studies suggesting the drug's positive benefit. There were limited studies assessing RTX use, associated economic burden, and biosimilar switching. CONCLUSIONS: The findings underscore the need for health care providers to better understand the treatment landscape and utilization of RTX, particularly in terms of patient selection, timing of initiation, and long-term outcomes. Real-world evidence can help support health care decisions and treatment using rituximab.

Fragility of overactive bladder medication clinical trials: A systematic review.

PURPOSE: Overactive bladder (OAB) syndrome significantly impairs quality of life, often necessitating pharmacological interventions with associated risks. The fragility of OAB trial outcomes, as measured by the fragility index (FI: smallest number of event changes to reverse statistical significance) and quotient (FQ: FI divided by total sample size expressed as a percentage), is critical yet unstudied. MATERIALS AND METHODS: We conducted a systematic search for randomized controlled trials on OAB medications published between January 2000 and August 2023. Inclusion criteria were trials with two parallel arms reporting binary outcomes related to OAB medications. We extracted trial details, outcomes, and statistical tests employed. We calculated FI and FQ, analyzing associations with trial characteristics through linear regression. RESULTS: We included 57 trials with a median sample size of 211 participants and a 12% median lost to follow-up. Most studies investigated anticholinergics (37/57, 65%). The median FI/FQ was 5/3.5%. Larger trials were less fragile (median FI 8; FQ 1.0%) compared to medium (FI: 4; FQ 2.5%) and small trials (FI: 4; FQ 8.3%). Double-blinded studies exhibited higher FQs (median 2.9%) than unblinded trials (6.7%). Primary and secondary outcomes had higher FIs (median 5 and 6, respectively) than adverse events (FI: 4). Each increase in 10 participants was associated with a +0.19 increase in FI (p < 0.001). CONCLUSIONS: A change in outcome for a median of five participants, or 3.5% of the total sample size, could reverse the direction of statistical significance in OAB trials. Studies with larger sample sizes and efficacy outcomes from blinded trials were less fragile.

Case presentation and review of renal autotransplantation for nutcracker syndrome.

Nutcracker Syndrome (NCS) is characterized by entrapment of the left renal vein, leading hematuria, flank pain, and proteinuria. We evaluated the efficacy of renal autotransplantation as a curative treatment for NCS through a review and case report. 55 patients from 18 studies were analyzed, with a combined 91% success rate of symptom resolution or improvement post-autotransplantation. In our case report, a 25-year-old man with severe NCS received laparoscopic nephrectomy and autotransplant, resulting in symptom resolution at 3.1 years follow up. Further research should confirm these findings and refine patient selection criteria and surgical techniques.

Estimated Average-Risk Colorectal Cancer Screening-Eligible Population in the US.

This cross-sectional study estimates the number of average-risk colorectal cancer screening­eligible individuals in the US since the US Preventive Services Task Force updated its recommendations in 2021.

TacticAI: an AI assistant for football tactics.

Identifying key patterns of tactics implemented by rival teams, and developing effective responses, lies at the heart of modern football. However, doing so algorithmically remains an open research challenge. To address this unmet need, we propose TacticAI, an AI football tactics assistant developed and evaluated in close collaboration with domain experts from Liverpool FC. We focus on analysing corner kicks, as they offer coaches the most direct opportunities for interventions and improvements. TacticAI incorporates both a predictive and a generative component, allowing the coaches to effectively sample and explore alternative player setups for each corner kick routine and to select those with the highest predicted likelihood of success. We validate TacticAI on a number of relevant benchmark tasks: predicting receivers and shot attempts and recommending player position adjustments. The utility of TacticAI is validated by a qualitative study conducted with football domain experts at Liverpool FC. We show that TacticAI's model suggestions are not only indistinguishable from real tactics, but also favoured over existing tactics 90% of the time, and that TacticAI offers an effective corner kick retrieval system. TacticAI achieves these results despite the limited availability of gold-standard data, achieving data efficiency through geometric deep learning.

United States house dust Pb concentrations are influenced by soil, paint, and house age: insights from a national survey.

BACKGROUND: Lead (Pb) in house dust contributes significantly to blood lead levels (BLLs) in children which may result in dire health consequences. Assessment of house dust Pb in the United States, relationships with Pb in soil and paint, and residential factors influencing Pb concentrations are essential to probing drivers of house dust Pb exposure. OBJECTIVE: Pb concentrations in vacuum-collected house dust are characterized across 346 homes participating in the American Health Homes Survey II (AHHS II), a US survey (2018-2019) evaluating residential Pb hazards. Connections between house dust Pb and soil Pb, paint Pb, and other residential factors are evaluated, and dust Pb concentration data are compared to paired loading data to understand Pb hazard standard implications. RESULTS: Mean and median vacuum dust Pb concentrations were 124 µg Pb g-1 and 34 µg Pb g-1, respectively. Vacuum-collected dust concentrations and dust wipe Pb loading rates were significantly correlated within homes (α < 0.001; r ≥ 0.4). At least one wipe sample exceeded current house dust Pb loading hazard standards (10 µg ft-2 or 100 µg Pb ft-2 for floors and windowsills, respectively) in 75 of 346 homes (22%). House dust Pb concentrations were correlated with soil Pb (r = 0.64) and Pb paint (r = 0.57). Soil Pb and paint Pb were also correlated (r = 0.6). IMPACT: The AHHS II provides a window into the current state of Pb in and around residences. We evaluated the relationship between house dust Pb concentrations and two common residential Pb sources: soil and Pb-based paint. Here, we identify relationships between Pb concentrations from vacuum-collected dust and paired Pb wipe loading data, enabling dust Pb concentrations to be evaluated in the context of hazard standards. This relationship, along with direct ties to Pb in soil and interior/exterior paint, provides a comprehensive assessment of dust Pb for US homes, crucial for formulating effective strategies to mitigate Pb exposure risks in households.

Barriers and facilitators to utilizing HIV prevention and treatment services among migrant youth globally: A scoping review.

Both migrants and young people experience disproportionately high rates of HIV acquisition and poor access to HIV prevention and treatment services. To develop effective interventions and reach epidemic control, it is necessary to understand the barriers and facilitators to accessing HIV services among migrant youth. We conducted a scoping review to identify these factors for migrant youth ages 15-24, globally. We conducted a PRISMA-concordant scoping review using keyword searches in PUBMED and Web of Science for peer-reviewed primary literature published between January 2012 and October 2022. We included studies that investigated barriers and facilitators to accessing services for migrant youth participants. We used the Socio-Ecological Model as an analytical framework. The 20 studies meeting the inclusion criteria spanned 10 countries, of which 80% (n = 16) were low- and middle-income countries. Study methods included were quantitative (40%), qualitative (55%), and mixed methods (5%). Six studies included refugee youth (30%), 6 included migrant worker youth (30%), 3 included immigrant youth (15%), 2 included rural migrant youth (10%), and 1 included immigrants and refugees. The remainder represented unspecified migrant youth populations (10%). At the individual level, education level and fear of infection acted as barriers and facilitators to HIV services. At the relationship level, social support and power in relationships acted as barriers and facilitators to HIV services. At the community level, barriers to HIV services included discrimination and stigma, while community and religious outreach efforts facilitated access to HIV services. At the structural level, barriers to HIV services included stigmatizing social norms, lack of health insurance, and legal barriers. Migrant youth face significant, unique barriers to accessing HIV services. However, facilitators exist that can be leveraged to enable access. Future implementation science research, enabling policies, and adapted programmatic interventions should prioritize migrant youth as a distinctive sub-population to receive targeted HIV services.

Hydrated Formic Acid Clusters and their Interaction with Electrons.

We investigate ion formation in hydrated formic acid (FA) clusters upon collision with electrons of variable energy, focusing on electron ionization at 70 eV (EI) and low-energy (1.5-15 eV) electron attachment (EA). To uncover details about the composition of neutral clusters, we aim to elucidate the ion formation processes in FAM ⋅ WN clusters initiated by interaction with electrons and determine the extent of cluster fragmentation. EI predominantly produces protonated [FAm +H]+ ions, and in FA-rich clusters, the stable ring structures surrounding H3 O+ ions are formed. In contrast, EA leads to a competition between the formation of intact [FAm ⋅ Wn ]- and dissociated [FAm ⋅ Wn -H]- fragment ions, influenced by the cluster size, level of hydration, and electron energy. Our findings reveal a predisposition of low-energy EA towards forming [FAm ⋅ Wn ]- , while higher electron energies tend to favor the formation of [FAm ⋅ Wn -H]- due to intracluster ion-molecule reactions. The comparison of positive and negative ion spectra suggests that the mass spectra of FA-rich clusters may indicate their actual size and composition. On the other hand, the more weakly bound water evaporation from the clusters depends strongly on the ionization. Thus, for the hydrated clusters, the neutral cluster size can hardly be estimated from the mass spectra.

Electric Bicycle Injuries and Hospitalizations.

This cross-sectional study investigates injury trends associated with electric bicycles in the US from 2017 to 2022.

Treatment of metastatic rectal squamous cell carcinoma in a pregnant patient.

Rectal squamous cell carcinoma is an exceedingly rare form of rectal cancer, with limited data available regarding its presentation and effective treatment. Rectal cancer occurring during pregnancy is uncommon as well. This is a case of metastatic rectal squamous cell carcinoma presenting in a 22-week pregnant, female patient in her early 30s. The patient was treated with 5-fluorouracil and cisplatin and delivered a healthy male child born via uncomplicated vaginal delivery at 35 weeks. This article demonstrates that despite the rare nature of this cancer, in the already rare context of pregnancy, effective and safe treatment is possible with a multidisciplinary team.

Not just crop or forest: an integrated land cover map for agricultural and natural areas.

Due to the key role surrounding landscape plays in ecological processes, a detailed characterization of land cover is critical for researchers and conservation practitioners. Unfortunately, in the United States, land cover data are split across thematic datasets that emphasize agricultural or natural vegetation, but not both. To address this gap, we merged two datasets, the LANDFIRE National Vegetation Classification (NVC) and USDA-NASS Cropland Data Layer (CDL), to produce integrated 'Spatial Products for Agriculture and Nature' (SPAN). Our workflow leveraged strengths of the NVC and the CDL to create detailed rasters comprising both agricultural and natural land-cover classes. We generated SPAN annually from 2012-2021 for the conterminous United States, quantified agreement and accuracy of SPAN, and published the complete computational workflow. In our validation analyses, we found that approximately 5.5% of NVC agricultural pixels conflicted with the CDL, but we resolved most conflicts, leaving only 0.6% of agricultural pixels unresolved in SPAN. These ready-to-use rasters characterizing both agricultural and natural land cover will be widely useful in environmental research and management.

Expanding the role of justice in secondary research using digital psychological data.

Secondary analysis of digital psychological data (DPD) is an increasingly popular method for behavioral health research. Under current practices, secondary research does not require human subjects research review so long as data are de-identified. We argue that this standard approach to the ethics of secondary research (i.e., de-identification) does not address a range of ethical risks and that greater emphasis should be placed on the ethical principle of justice. We outline the inadequacy of an individually focused research ethic for DPD and describe unaddressed "social risks" generated by secondary research of DPD. These risks exist in the "circumstances of justice": that is, a circumstance where individuals must cooperate to create a public good (e.g., research knowledge), and where it is impractical to individually exempt individuals. This requires researchers to emphasize the just allocation of benefits and burdens against a background of social cooperation. We explore six considerations for researchers who wish to conduct research with DPD without explicit consent: (a) create socially valuable knowledge, (b) fairly share the benefits and burdens of research, (c) be transparent about data use, (d) create mechanisms for withdrawal of data, (e) ensure that stakeholders can provide input into the design and implementation of the research, and (f) responsibly report results. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Outcomes with HLA-matched unrelated donor versus haploidentical hematopoietic cell transplantation.

We investigated the outcomes after adult haploidentical (haplo) and matched unrelated donor (MUD) hematopoietic cell transplantation (HCT) in a single-center study (n = 452) including 276 MUD and 176 haplo transplants. Myeloablative (37%) and reduced-intensity conditioning (63%) were performed. Graft sources included peripheral blood (50%) and bone marrow (50%). GVHD prophylaxis included tacrolimus/methotrexate (53%) and post-transplant cyclophosphamide-based (47%). In MUD versus haplo HCT recipients, a similar incidence of neutrophil engraftment (18 vs 17 days, p = 0.895), grade II-IV acute GVHD (51% vs 50%, p = 0.773), relapse (26% vs 23%, p = 0.578), non-relapse mortality (22% vs 23%, p = 0.817), 1-year disease-free survival (62% vs 63%. p = 0.921), and 1-year overall survival (73% vs 74%, p = 0.744) were observed. Earlier platelet engraftment (22 vs 27 days, p < 0.001) and higher chronic GVHD (45% vs 35%, p = 0.040) were noted in MUD as compared to haplo HCT. Allogeneic transplantation should be done promptly whenever indicated, utilizing either matched unrelated or haploidentical donors.

APOE3ch alters microglial response and suppresses Aß-induced tau seeding and spread.

A recent case report described an individual who was a homozygous carrier of the APOE3 Christchurch (APOE3ch) mutation and resistant to autosomal dominant Alzheimer's Disease (AD) caused by a PSEN1-E280A mutation. Whether APOE3ch contributed to the protective effect remains unclear. We generated a humanized APOE3ch knock-in mouse and crossed it to an amyloid-ß (Aß) plaque-depositing model. We injected AD-tau brain extract to investigate tau seeding and spreading in the presence or absence of amyloid. Similar to the case report, APOE3ch expression resulted in peripheral dyslipidemia and a marked reduction in plaque-associated tau pathology. Additionally, we observed decreased amyloid response and enhanced microglial response around plaques. We also demonstrate increased myeloid cell phagocytosis and degradation of tau aggregates linked to weaker APOE3ch binding to heparin sulfate proteoglycans. APOE3ch influences the microglial response to Aß plaques, which suppresses Aß-induced tau seeding and spreading. The results reveal new possibilities to target Aß-induced tauopathy.

Real-World Complications of the SpaceOAR Hydrogel Spacer: A Review of the Manufacturer and User Facility Device Experience Database.

OBJECTIVE: To characterize adverse events related to use of the perirectal spacing agent SpaceOAR, we examined the Manufacturer and User Facility Device Experience (MAUDE) database. METHODS: The MAUDE database was queried for "SpaceOAR" and "Augmenix" from June 2015 (when SpaceOAR was approved by the Food and Drug Administration) to October 2022. Reports were reviewed for adverse events (AEs), operative procedures performed because of the AE, and changes to the radiation plan. AEs were categorized using Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. RESULTS: Six hundred fifty-four reports were reviewed. Eighty-four were excluded and 4 reports reviewed 2 separate cases of SpaceOAR administration. Five hundred seventy-four cases were ultimately included. Three deaths were reported (0.5% of all AEs). One point six percent of cases represented CTCAE grade 4 injuries (life-threatening consequences; urgent intervention indicated), 15.9% grade 3 (severe but not immediately life-threatening; hospitalization), 24.2% grade 2 (moderate; local/noninvasive intervention), and 57% of events were CTCAE grade 1 (mild; asymptomatic or mild symptoms). Bowel diversion occurred in 29 cases (9%). CONCLUSION: Both asymptomatic (n = 311) and debilitating (n = 12) complications of SpaceOAR hydrogel use were identified. Death, gel embolization, anaphylaxis, rectal ulcerations, and infections requiring bowel or urinary diversions were among the complications reviewed. Providers should consider these potential complications before perirectal spacer administration and during patient counseling.

Dynamics of self-hybridized exciton-polaritons in 2D halide perovskites.

Excitons, bound electron-hole pairs, in two-dimensional hybrid organic inorganic perovskites (2D HOIPs) are capable of forming hybrid light-matter states known as exciton-polaritons (E-Ps) when the excitonic medium is confined in an optical cavity. In the case of 2D HOIPs, they can self-hybridize into E-Ps at specific thicknesses of the HOIP crystals that form a resonant optical cavity with the excitons. However, the fundamental properties of these self-hybridized E-Ps in 2D HOIPs, including their role in ultrafast energy and/or charge transfer at interfaces, remain unclear. Here, we demonstrate that >0.5 µm thick 2D HOIP crystals on Au substrates are capable of supporting multiple-orders of self-hybridized E-P modes. These E-Ps have high Q factors (>100) and modulate the optical dispersion for the crystal to enhance sub-gap absorption and emission. Through varying excitation energy and ultrafast measurements, we also confirm energy transfer from higher energy E-Ps to lower energy E-Ps. Finally, we also demonstrate that E-Ps are capable of charge transport and transfer at interfaces. Our findings provide new insights into charge and energy transfer in E-Ps opening new opportunities towards their manipulation for polaritonic devices.

Negative Nonlinear CD-ee Dependence in Polycrystalline BINOL Thin Films.

Generally, the relationship between the observed circular dichroism and the enantiomeric excess in chiral systems (CD-ee dependence) is linear. While positive nonlinear behavior has often been reported in the past, examples of negative nonlinear (NN) behavior in CD-ee dependence are rare and not well understood. Here, we present a strong NN CD-ee dependence within polycrystalline thin films of BINOL by using second-harmonic-generation circular dichroism (SHG-CD) and commercial CD spectroscopy studies. Theoretical calculations, microscopy, and FTIR studies are employed to further clarify the underlying cause of this observation. This behavior is attributed to the changing supramolecular chirality of the system. Systems exhibiting NN CD-ee dependence hold promise for highly accurate enantiomeric excess characterization, which is essential for the refinement of enantio-separating and -purifying processes in pharmaceuticals, asymmetric catalysis, and chiral sensing. Our findings suggest that a whole class of single-species systems, i.e., racemate crystals, might possess NN CD-ee dependence and thus provide us a vast playground to better understand and exploit this phenomenon.

Explainable machine learning identifies multi-omics signatures of muscle response to spaceflight in mice.

The adverse effects of microgravity exposure on mammalian physiology during spaceflight necessitate a deep understanding of the underlying mechanisms to develop effective countermeasures. One such concern is muscle atrophy, which is partly attributed to the dysregulation of calcium levels due to abnormalities in SERCA pump functioning. To identify potential biomarkers for this condition, multi-omics data and physiological data available on the NASA Open Science Data Repository (osdr.nasa.gov) were used, and machine learning methods were employed. Specifically, we used multi-omics (transcriptomic, proteomic, and DNA methylation) data and calcium reuptake data collected from C57BL/6 J mouse soleus and tibialis anterior tissues during several 30+ day-long missions on the international space station. The QLattice symbolic regression algorithm was introduced to generate highly explainable models that predict either experimental conditions or calcium reuptake levels based on multi-omics features. The list of candidate models established by QLattice was used to identify key features contributing to the predictive capability of these models, with Acyp1 and Rps7 proteins found to be the most predictive biomarkers related to the resilience of the tibialis anterior muscle in space. These findings could serve as targets for future interventions aiming to reduce the extent of muscle atrophy during space travel.