A pilot study on gamified and conventional e-quizzes reinforcing human histology among first-year medical and physiotherapy students.

The present retrospective, descriptive, and quasi-experimental study aimed to explore students' perceptions of traditional teaching combined with gamified and nongamified e-tests for postlecture reinforcement. Midterm knowledge retention and academic performance were also analyzed. The study was conducted from February 2021 to May 2022, involving a single group of first-year medical and physiotherapy students enrolled in equivalent core subjects on human histology at the University of Las Palmas de Gran Canaria (ULPGC). Lectures were supplemented with gamified Quizizz (QQ) or nongamified Moodle questionnaires (MQ) after lecture (t0) and 30 days later (t30). From 171 attendees, 162 volunteers were surveyed on their perceptions on the experience. Furthermore, 97 volunteers participated in the DOCENTIA-ULPGC survey on the students' satisfaction, and 123 participants individually answered 20 QQ and 20 MQ. Data were analyzed using the program Jamovi 2.3.24. The survey on volunteers' perception comprised 11 Likert items and 3 numerical scale items. The former showed acceptable internal consistency (ω-McDonald, 0.70) and validity (KMO, 0.58). Both types of e-questionnaires facilitated learning and motivated pre-reading contents but QQs were preferred. Reinforced lectures were rated higher than those unreinforced. Volunteers expressed higher overall satisfaction though DOCENTIA-ULPGC survey than the prepandemic control group. Average scores peaked at t0 with higher MQ rates. At t30, MQ and QQ scores were acceptable and similar. Participants' outcomes in the final exam tended to improve compared to the prepandemic control group, but without statistical significance. In summary, gamified and nongamified e-quizzes enhanced the student satisfaction and motivation and facilitated midterm knowledge retention.

Effects of the COVID-19 pandemic on gestational diabetes in Castilla-La Mancha (Spain).

SUBJECT-MATTER: To assess the effect of the 2019 coronavirus (COVID-19) pandemic on gestational diabetes (GDM). MATERIAL AND METHODS: In this retrospective, multicentre, non-interventional study carried out in Castilla-La Mancha, Spain, we compared 663 women with GDM exposed to the pandemic (pandemic group), with 622 women with GDM seen one year earlier (pre-pandemic group). The primary endpoint was a Large for Gestational Age (LGA) newborn as an indicator of poor GDM control. Secondary endpoints included obstetric and neonatal complications. RESULTS: During the pandemic, the gestational week at diagnosis (24.2 ±â€¯7.4 vs 22.9 ±â€¯7.7, p = 0.0016) and first visit to Endocrinology (26.6 ±â€¯7.2 vs 25.3 ±â€¯7.6, p = 0.0014) were earlier. Face-to-face consultations were maintained in most cases (80.3%). The new diagnostic criteria for GDM were used in only 3% of cases. However, in the pandemic group, the final HbA1c was higher (5.2 ±â€¯0.48 vs 5.29 ±â€¯0.44%, p = 0.047) and there were more LGA newborns (8.5% vs 12.8%, p = 0.015). There were no differences in perinatal complications. CONCLUSIONS: Care for GDM in our Public Health System did not significantly deteriorate during the COVID-19 pandemic. However, this did not prevent a higher number of LGA newborns.

Understanding species-specific and conserved RNA-protein interactions in vivo and in vitro.

While evolution is often considered from a DNA- and protein-centric view, RNA-based regulation can also impact gene expression and protein sequences. Here we examined interspecies differences in RNA-protein interactions using the conserved neuronal RNA binding protein, Unkempt (UNK) as model. We find that roughly half of mRNAs bound in human are also bound in mouse. Unexpectedly, even when transcript-level binding was conserved across species differential motif usage was prevalent. To understand the biochemical basis of UNK-RNA interactions, we reconstituted the human and mouse UNK-RNA interactomes using a high-throughput biochemical assay. We uncover detailed features driving binding, show that in vivo patterns are captured in vitro, find that highly conserved sites are the strongest bound, and associate binding strength with downstream regulation. Furthermore, subtle sequence differences surrounding motifs are key determinants of species-specific binding. We highlight the complex features driving protein-RNA interactions and how these evolve to confer species-specific regulation.

Effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide in HIV late presenters.

OBJECTIVES: The efficacy of BIC/FTC/TAF in HIV late presenters initiating antiretroviral therapy (ART) has not been sufficiently evaluated. METHODS: The aim of this study was to assess the effectiveness and tolerability of BIC/FTC/TAF compared to other first-line antiretroviral regimens in treatment-naïve adult individuals from the CoRIS Cohort starting ART with CD4 counts <200 cells/mm3 and/or AIDS-defining conditions between January 1st 2019 and November 30th 2020. Logistic regression models were used to estimate odds ratios (ORs) of association between initial regimen and achievement of viral suppression (VS) (primary objective), defined as HIV RNA <50 cop/mL, and immunological recovery (IR) (secondary objective), defined as CD4 count >200 cells/mm3, at weeks 24 and 48 after initiation of ART. RESULTS: We evaluated 314 individuals (84.7% men, median age 40 years). Of them, 158 initiated with BIC/FTC/TAF. At inclusion, 117 had an AIDS-defining condition. In multivariable analyses, individuals with AIDS-defining conditions initiating ART with BIC/FTC/TAF achieved higher rates of VS at 24 weeks than other regimens (aOR: 0.2; 95% CI: 0.06-0.64) and, at 48 weeks, than DTG/ABC/3TC (aOR: 0.06; 95% CI: 0.01-0.76) and DTG + TDF/3TC (aOR: 0.2; 95% CI: 0.47-0.9). No other differences in VS or IR were observed. At 24 and 48 weeks after ART initiation, treatment discontinuations were lower with BIC/FTC/TAF than with other regimens (3.2% and 7.6% vs. 24.4% and 37.8%, respectively; P < 0.005). CONCLUSION: Our results suggest that BIC/FTC/TAF could be a preferred regimen as initial therapy in HIV late presenters because of its high effectiveness and good tolerability.

Reciprocal stabilization of coagulation factor XIII-A and -B subunits is a determinant of plasma FXIII concentration.

ABSTRACT: Transglutaminase factor XIII (FXIII) is essential for hemostasis, wound healing, and pregnancy maintenance. Plasma FXIII is composed of A and B subunit dimers synthesized in cells of hematopoietic origin and hepatocytes, respectively. The subunits associate tightly in circulation as FXIII-A2B2. FXIII-B2 stabilizes the (pro)active site-containing FXIII-A subunits. Interestingly, people with genetic FXIII-A deficiency have decreased FXIII-B2, and therapeutic infusion of recombinant FXIII-A2 (rFXIII-A2) increases FXIII-B2, suggesting FXIII-A regulates FXIII-B secretion, production, and/or clearance. We analyzed humans and mice with genetic FXIII-A deficiency and developed a mouse model of rFXIII-A2 infusion to define mechanisms mediating plasma FXIII-B levels. Like humans with FXIII-A deficiency, mice with genetic FXIII-A deficiency had reduced circulating FXIII-B2, and infusion of FXIII-A2 increased FXIII-B2. FXIII-A-deficient mice had normal hepatic function and did not store FXIII-B in liver, indicating FXIII-A does not mediate FXIII-B secretion. Transcriptional analysis and polysome profiling indicated similar F13b levels and ribosome occupancy in FXIII-A-sufficient and -deficient mice and in FXIII-A-deficient mice infused with rFXIII-A2, indicating FXIII-A does not induce de novo FXIII-B synthesis. Unexpectedly, pharmacokinetic/pharmacodynamic modeling of FXIII-B antigen after rFXIII-A2 infusion in humans and mice suggested FXIII-A2 slows FXIII-B2 loss from plasma. Accordingly, comparison of free FXIII-B2 vs FXIII-A2-complexed FXIII-B2 (FXIII-A2B2) infused into mice revealed faster clearance of free FXIII-B2. These data show FXIII-A2 prevents FXIII-B2 loss from circulation and establish the mechanism underlying FXIII-B2 behavior in FXIII-A deficiency and during rFXIII-A2 therapy. Our findings reveal a unique, reciprocal relationship between independently synthesized subunits that mediate an essential hemostatic protein in circulation. This trial was registered at www.ClinicalTrials.com as #NCT00978380.

The Effect of Honey, Aloe Vera, and Hydrocolloid Dressing on the Healing Process of Murine Excisional Wounds.

Chronic ulcers are a major health problem associated with high costs and a loss of quality of life. Because of this, the search for products that accelerate wound healing is a constant, given the need for alternatives that help to alleviate this serious health problem. We analyzed the efficacy of 2 natural products-honey and aloe vera-versus hydrocolloid (HC) dressings as a control group in healing full-thickness wounds. For this purpose, we performed full-thickness excisions of the skin, including the panniculus carnosus, in mice. We inserted a nitrile ring into the subcutaneous cellular tissue simulating the second-intention wound healing course. We found that aloe vera reduced the diameter of the wounds compared to honey (p < .001) and the control group (p < .001).

Competing endogenous RNAs in human astrocytes: crosstalk and interacting networks in response to lipotoxicity.

Neurodegenerative diseases (NDs) are characterized by a progressive deterioration of neuronal function, leading to motor and cognitive damage in patients. Astrocytes are essential for maintaining brain homeostasis, and their functional impairment is increasingly recognized as central to the etiology of various NDs. Such impairment can be induced by toxic insults with palmitic acid (PA), a common fatty acid, that disrupts autophagy, increases reactive oxygen species, and triggers inflammation. Although the effects of PA on astrocytes have been addressed, most aspects of the dynamics of this fatty acid remain unknown. Additionally, there is still no model that satisfactorily explains how astroglia goes from being neuroprotective to neurotoxic. Current incomplete knowledge needs to be improved by the growing field of non-coding RNAs (ncRNAs), which is proven to be related to NDs, where the complexity of the interactions among these molecules and how they control other RNA expressions need to be addressed. In the present study, we present an extensive competing endogenous RNA (ceRNA) network using transcriptomic data from normal human astrocyte (NHA) cells exposed to PA lipotoxic conditions and experimentally validated data on ncRNA interaction. The obtained network contains 7 lncRNA transcripts, 38 miRNAs, and 239 mRNAs that showed enrichment in ND-related processes, such as fatty acid metabolism and biosynthesis, FoxO and TGF-ß signaling pathways, prion diseases, apoptosis, and immune-related pathways. In addition, the transcriptomic profile was used to propose 22 potential key controllers lncRNA/miRNA/mRNA axes in ND mechanisms. The relevance of five of these axes was corroborated by the miRNA expression data obtained in other studies. MEG3 (ENST00000398461)/hsa-let-7d-5p/ATF6B axis showed importance in Parkinson's and late Alzheimer's diseases, while AC092687.3/hsa-let-7e-5p/[SREBF2, FNIP1, PMAIP1] and SDCBP2-AS1 (ENST00000446423)/hsa-miR-101-3p/MAPK6 axes are probably related to Alzheimer's disease development and pathology. The presented network and axes will help to understand the PA-induced mechanisms in astrocytes, leading to protection or injury in the CNS under lipotoxic conditions as part of the intricated cellular regulation influencing the pathology of different NDs. Furthermore, the five corroborated axes could be considered study targets for new pharmacologic treatments or as possible diagnostic molecules, contributing to improving the quality of life of millions worldwide.

Incidence and time trends of childhood hematological neoplasms: a 36-year population-based study in the southern European context, 1983-2018.

Background: Hematological neoplasms (HNs) are the first and most common childhood cancers globally. Currently, there is a lack of updated population-based data on the incidence of these cancers in the Spanish pediatric population. This study aimed to describe the incidence and incidence trends of HNs in children (0-14 years) in Spain using data from the Spanish Network of Cancer Registries and to compare the results with other southern European countries. Methods: Data were extracted from 15 Spanish population-based cancer registries between 1983 and 2018. Cases were coded according to the International Classification of Diseases for Oncology, third edition, first revision, and grouped according to the International Classification of Childhood Cancer, third edition. Crude rates (CRs), age-specific rates, and age-standardized incidence rates using the 2013 European population (ASRE) were calculated and expressed as cases per 1,000,000 child-years. Incidence trends and annual percentage changes (APCs) were estimated. Results: A total of 4,747 HNs were recorded (59.5% boys). Age distribution [n (%)] was as follows: <1 year, 266 (5.6%); 1-4 years, 1,726 (36.4%); 5-9 years, 1,442 (30.4%); and 10-14 years, 1,313 (27.6%). Leukemias were the most common group, with a CR and an ASRE of 44.0 (95%CI: 42.5; 45.5) and 44.1 (95%CI: 42.6; 45.7), respectively. The CR and ASRE of lymphomas were 20.1 (95%CI: 19.1; 21.1) and 20.0 (95%CI: 19.0; 21.1), respectively. The comparable incidence rates between our results and those of other southern European countries were similar for lymphomas, while some differences were observed for leukemias. From 1988 to 2016, the trend in leukemia incidence was stable for both sexes, with an APC of 0.0 (95%CI: -0.5; 0.7), whereas a constant overall increase was observed for lymphoma in both sexes, with an APC of 1.0 (95%CI: 0.4; 1.6). Conclusion: Leukemias are the most common HNs in children, and their incidence has remained stable since 1988, whereas the incidence of lymphomas has increased every year. Lymphoma incidence is like that of other southern European countries, while leukemia incidence is similar only to that of southwestern European countries. Collaborative cancer registry projects allow for assessing epidemiological indicators for cancers such as HNs, which helps health authorities and clinicians provide more knowledge about these malignancies.

Around the World in 60 Minutes: How a Virtual Morning Report has Created an International Community for Clinical Reasoning and Medical Education.

Problem: Traditionally, clinical reasoning is developed with purposeful exposure to clinical problems through case-based learning and clinical reasoning conferences that harvest a collaborative exchange of information in real-life settings. While virtual platforms have greatly expanded access to remote clinical learning, case-based clinical reasoning opportunities are scarce in low and middle income countries. Intervention: The Clinical Problem Solvers (CPSolvers), a nonprofit organization focused on clinical reasoning education, launched Virtual Morning Report (VMR) during the COVID-19 pandemic. VMR is an open-access, case-based clinical reasoning virtual conference on the Zoom platform modeled after an academic morning report format available to participants worldwide. The authors conducted 17 semi-structured interviews with CPSolvers' VMR participants from 10 different countries to explore the experiences of the international participants of VMR. Context: The CPSolvers was founded by US physicians and has now expanded to include international members throughout all levels of the organization. VMR is open-access to all learners. Preliminary survey data collected from VMR sessions revealed 35% of the attendees were from non-English speaking countries and 53% from non US countries. Impact: Analysis generated four themes that captured the experiences of international participants of VMR: 1) Improving clinical reasoning skills where participants had little to no access to this education or content; 2) Creating a global community from a diverse, safe, and welcoming environment made possible by the virtual platform; 3) Allowing learners to become agents of change by providing tools and skills that are directly applicable in the setting in which they practice medicine; 4) Establishing a global platform, with low barriers to entry and open-access to expertise and quality teaching and content. Study participants agreed with the themes, supporting trustworthiness. Lessons Learned: Findings suggest VMR functions as and has grown into a global community of practice for clinical reasoning. The authors propose strategies and guiding principles based on the identified themes for educators to consider when building effective global learning communities. In an interdependent world where the virtual space eliminates the physical boundaries that silo educational opportunities, emphasis on thoughtful implementation of learning communities in a global context has the potential to reduce medical education disparities in the clinical reasoning space and beyond.

Incidence and survival of lymphoid neoplasms in Spain, 2002-2013: A population-based study from the Spanish Network of Cancer Registries (REDECAN).

Introduction: The aim of this study was to describe incidence, incidence trends and survival patterns of lymphoid neoplasms (LNs) and its subtypes in Spain in the period 2002-2013 using data from the Spanish Network of Cancer Registries (REDECAN). Materials and Methods: Data were extracted from 13 Spanish population-based cancer registries. LNs incident cases were codified using the International Classification of Diseases for Oncology, third edition (ICD-O-3) and grouped according to the WHO 2008 classification. Age-standardized incidence rates to the 2013 European standard population (ASIRe) were obtained. Poisson regression models were used to analyze trends in incidence rates and estimate the annual percentage change (APC) for each subtype. The number of cases in Spain for 2023 was estimated by applying the estimated age-specific rates for the year 2023 to the 2023 Spanish population. Observed survival (OS) was estimated by the Kaplan-Meier method and net survival (NS) by the Pohar-Perme method. Sex- and age-specific estimates of 5-year NS were calculated, as well as its changes according to two periods of diagnosis (2002-2007 and 2008-2013). Results: LNs accounted for 69% (n=39,156) of all hematological malignancies (n=56,751) diagnosed during the period of study. Median age at diagnosis was 67 years (interquartile range (IQR) = 52-77). The overall ASIRe was 34.23 (95% confidence interval (CI): 33.89, 34.57) and showed a marked male predominance in almost all subtypes (global sex ratio = 1.45). During the study period, incidence trends of LNs remained stable (APC: 0.3; 95% CI: -0.1, 0.6), nevertheless some subtypes showed statistically significant variations, such as LNs NOS category (APC: -5.6; 95% CI: -6.8, -4.3). Around 17,926 new cases of LNs will be diagnosed in 2023 in Spain. Survival rates differed considerably across age-groups, while they were similar between men and women. Five- year NS was 62.81% (95% CI: 62.1, 63.52) for all LNs, and varied widely across LNs subtypes, ranging from 39.21% to 90.25%. NS for all LNs improved from the first period of diagnosis to the second one, being 61.57% (95% CI: 60.56, 62.61) in 2002-2007 and 64.17% (95% CI: 63.29, 65.07) in 2008-2013. Conclusions: This study presents the first complete and extensive population-based analysis of LNs incidence and survival in Spain. These population-based data provide relevant information to better understand the epidemiology of LNs in Southern Europe and it features some useful points for public health authorities and clinicians. However, additional improvements regarding the registration of these hematological neoplasms can be implemented.

Efanesoctocog alfa elicits functional clot formation that is indistinguishable to that of recombinant factor VIII.

BACKGROUND: Factor VIII (FVIII) binding to endogenous von Willebrand factor (VWF) has constrained half-life extension of recombinant FVIII (rFVIII) products for hemophilia A. Efanesoctocog alfa (rFVIIIFc-VWF-XTEN; BIVV001) is a novel fusion protein designed to decouple FVIII from VWF in circulation and maximize half-life prolongation by XTEN® polypeptides and Fc fusion. FVIII, VWF, and platelets interact to achieve normal hemostasis. Thus, bioengineered FVIII replacement products, such as efanesoctocog alfa, require comprehensive assessment of their hemostatic potential. OBJECTIVES: We compared functional clot formation and injury-induced platelet accumulation between efanesoctocog alfa and rFVIII. PATIENTS/METHODS: The hemostatic potential of efanesoctocog alfa and rFVIII were assessed by measuring their dose-dependent effects on in vitro fibrin generation in hemophilic plasma and in vivo injury-induced platelet accumulation using intravital microscopy and repeat saphenous vein laser-induced injuries in hemophilia A mice. RESULTS: Equal concentrations of efanesoctocog alfa or rFVIII (up to 1 IU/ml) added to plasma from patients with hemophilia A elicited similar kinetics for dose-dependent fibrin polymerization between factor products. In the presence of tissue plasminogen activator (tPA), clots formed had similar stability between products. Single intravenous doses (50, 100, or 150 IU/kg) of efanesoctocog alfa or rFVIII shortly before repeat saphenous vein laser-induced injuries increased platelet accumulation over time in a dose-dependent manner in hemophilia A mice. Platelet deposition kinetics were similar between products. CONCLUSIONS: Equivalent doses of efanesoctocog alfa and rFVIII had similar efficacy in promoting fibrin clot formation and injury-induced platelet accumulation. The hemostatic potential of efanesoctocog alfa was indistinguishable from that of rFVIII.

Quantitative profiling of adaptation to cyclin E overproduction.

Cyclin E/CDK2 drives cell cycle progression from G1 to S phase. Despite the toxicity of cyclin E overproduction in mammalian cells, the cyclin E gene is overexpressed in some cancers. To further understand how cells can tolerate high cyclin E, we characterized non-transformed epithelial cells subjected to chronic cyclin E overproduction. Cells overproducing cyclin E, but not cyclins D or A, briefly experienced truncated G1 phases followed by a transient period of DNA replication origin underlicensing, replication stress, and impaired proliferation. Individual cells displayed substantial intercellular heterogeneity in cell cycle dynamics and CDK activity. Each phenotype improved rapidly despite high cyclin E-associated activity. Transcriptome analysis revealed adapted cells down-regulated a cohort of G1-regulated genes. Withdrawing cyclin E from adapted cells only partially reversed underlicensing indicating that adaptation is at least partly non-genetic. This study provides evidence that mammalian cyclin E/CDK inhibits origin licensing indirectly through premature S phase onset and provides mechanistic insight into the relationship between CDKs and licensing. It serves as an example of oncogene adaptation that may recapitulate molecular changes during tumorigenesis.

LIN28B alters ribosomal dynamics to promote metastasis in MYCN-driven malignancy.

High expression of LIN28B is associated with aggressive malignancy and poor survival. Here, probing MYCN-amplified neuroblastoma as a model system, we showed that LIN28B expression was associated with enhanced cell migration in vitro and invasive and metastatic behavior in murine xenografts. Sequence analysis of the polyribosome fraction of LIN28B-expressing neuroblastoma cells revealed let-7-independent enrichment of transcripts encoding components of the translational and ribosomal apparatus and depletion of transcripts of neuronal developmental programs. We further observed that LIN28B utilizes both its cold shock and zinc finger RNA binding domains to preferentially interact with MYCN-induced transcripts of the ribosomal complex, enhancing their translation. These data demonstrated that LIN28B couples the MYCN-driven transcriptional program to enhanced ribosomal translation, thereby implicating LIN28B as a posttranscriptional driver of the metastatic phenotype.

easyCLIP analysis of RNA-protein interactions incorporating absolute quantification.

Quantitative criteria to identify proteins as RNA-binding proteins (RBPs) are presently lacking, as are criteria to define RBP target RNAs. Here, we develop an ultraviolet (UV) cross-linking immunoprecipitation (CLIP)-sequencing method, easyCLIP. easyCLIP provides absolute cross-link rates, as well as increased simplicity, efficiency, and capacity to visualize RNA libraries during sequencing library preparation. Measurement of >200 independent cross-link experiments across >35 proteins identifies an RNA cross-link rate threshold that distinguishes RBPs from non-RBPs and defines target RNAs as those with a complex frequency unlikely for a random protein. We apply easyCLIP to the 33 most recurrent cancer mutations across 28 RBPs, finding increased RNA binding per RBP molecule for KHDRBS2 R168C, A1CF E34K and PCBP1 L100P/Q cancer mutations. Quantitating RBP-RNA interactions can thus nominate proteins as RBPs and define the impact of specific disease-associated RBP mutations on RNA association.

Intrinsic differences between FVIIIa mimetic bispecific antibodies and FVIII prevent assignment of FVIII-equivalence.

Essentials Non-factor VIII (FVIII) therapies for hemophilia A, such as bispecific antibodies (bsAbs), are in development. Bispecific antibodies are intrinsically different from FVIII and lack many of the same regulatory mechanisms. These differences complicate assignment and interpretation of FVIII-equivalent activity. Inability to assign FVIII equivalence compromises our capacity to assess hemostatic potential of bsAb therapies. BACKGROUND: Activated factor VIII (FVIIIa) mimetic bsAbs aim to enable prophylactic treatment of hemophilia A patients with and without inhibitors. With different mechanisms of action, benchmarking their activity against FVIII to determine efficacious yet safe dosage is difficult. OBJECTIVE: To compare the activities of sequence identical emicizumab (SI-Emi) and another bsAb, BS-027125, to recombinant FVIII (rFVIII) using clinical and nonclinical assays and to evaluate our ability to assign a FVIII-equivalent value to bsAbs and implications thereof. METHODS: Activities of SI-Emi, BS-027125, and rFVIII were measured by one-stage clotting assay, chromogenic factor Xa generation assay, and thrombin generation assay. We also assessed the activity of anti-FIXa and anti-FX bivalent homodimers of each bsAb and probed the effect of different reagents in thrombin generation assay (TGA). RESULTS: The FVIII-like activity of SI-Emi and BS-027125 ranged greatly across each assay, varying both by parameter measured within an assay and by reagents used. Notably, SI-Emi anti-FIXa bivalent homodimer had meaningful activity in several assays, whereas BS-027125 anti-FIXa bivalent homodimer only had activity in the chromogenic assay. Surprisingly, SI-Emi displayed activity in the absence of phospholipids, while BS-027125 had minimal phospholipid-independent activity. CONCLUSIONS: Bispecific antibodies demonstrate little consistency between assays tested here owing to intrinsic differences between FVIII and bsAbs. While some trends are shared, the bsAbs also differ in mechanism. These inconsistencies complicate assignment of FVIII-equivalent values to bsAbs. Ultimately, a deeper mechanistic understanding of bsAbs as well as bsAb-tailored assays are needed to monitor and predict their hemostatic potential and long-term efficacy and safety confidently.