bluuebunny/crossref_metadata_2025 huggingface dataset:
Operating outside the spirit of the law: How police employ “legal” standards to justify questionable searches and seizures
Authors: Nir Esther , Liu Siyu
Published: March 2022

The Fourth Amendment protects individuals against unreasonable searches and seizures. Over the years, court precedents have guided determinations of reasonableness and provided a legal structure for police to follow. In two influential decisions, the Supreme Court validated pretextual traffic stops in which the motorist committed a minor traffic violation ( Whren v United States, 1996), and established the standard of reasonable suspicion for brief investigatory stops and limited weapon searches ( Terry v Ohio, 1968). Using 42 suppression motions filed in a US state, we examine whether and how police apply these legal parameters to case patterns to justify stops, searches and seizures. We find that police use pretexts to justify traffic stops, and often rely on conclusory and laconic descriptions to support determinations of reasonable suspicion. Although often upheld by courts, these applications of the law are contrary to the spirit of the Fourth Amendment.
Intersectional elaboration: Using a multiracial feminist co-design technique with Latina teens for emotional health
Authors: Vacca Ralph
Published: March 2022

Underlying the growing epidemic of mental distress and suicidal ideation amongst certain marginalised groups (e.g. Latina teens) are complex intersections of ecologies and interrelated structures of inequality such as class, culture, race and gender. Through the use of a multiracial feminist framework, the proposed intersectional elaboration technique examines how technology might be designed in ways that explicitly consider intersecting structures of inequality and eco-developmental contexts. The core of this technique involves co-constructing narratives using prompts that directly address specific layers of one's ecology and the interactions across ecological layers – purposely addressing intersecting systems of inequality acting along these ecologies. This article describes the application of the intersectional elaboration technique in co-design research with adolescent Latinas, in a highly urbanised context, towards designing emotional health technology. Findings suggest that intersectional elaborations can serve as a useful generative co-design technique to inform designs that address complex arrangements of intra-ecological conflicts and cultural legitimacy.
A collective-evolutionary alternative for appraising entrepreneurship theory
Authors: Wood Matthew S , Fisher Greg
Published: March 2022

In a recent Strategic Organization essay, Arend analyzed four papers as contributions to entrepreneurship theory. He concluded that progress toward building unique-to-field conceptualizations is impeded because contributions in the domain are not sufficiently novel, do not cover the breadth of the phenomenon, and fail to offer normative guidance to practicing entrepreneurs. In this essay, we respond to these conclusions by examining the premise behind the evaluation of theory progress used to derive them, and then drawing on insights from the philosophy of science research to introduce a collective-evolutionary perspective as an alternative for the appraisal of entrepreneurship theory. Our alternative view shifts the focus from single papers toward evaluating theory as a collection of contributions that appear over time. Under this perspective, it is the degree to which newer theories take up insights from prior theory in an evolutionary fashion that serves as a key indicator of progress. Recognizing this, we advocate for a path toward productive theorizing in entrepreneurship where borrowing insights from prior cross-disciplinary theory is a strength rather than weakness, where wide-scope theory is important at the research program level while narrow scope is appropriate for individual contributions, and where obsession over the novelty of theory concepts undermines the continuity needed to produce a reliable body of knowledge.
Thirty Years of Implementing the Photovoice Method: Insights From a Review of Reviews
Authors: Seitz Christopher M. , Orsini Muhsin Michael
Published: March 2022

As the use of the photovoice method has proliferated over the past three decades, several literature reviews have been conducted about implementing the method in the context of health promotion research and practice. Challenges emerged from the literature frequently enough to be reported in several reviews. As such, the purpose of this “review of reviews” was to identify and describe the various challenges to implementing photovoice as reported in published literature reviews. Taken together, the sum of the reviews’ critiques about photovoice may be of particular use for developing solutions regarding challenges that limit the utility and outcomes of the method. The literature reviews included in this study were identified using PubMed, CINAHL, Google Scholar, and backward/forward chaining. The final 15 review articles included in the study were analyzed for the challenges of implementing photovoice described in each review. Four major themes emerged from the reviews: (1) inconsistent adherence to the photovoice method, (2) inconsistent evaluation of photovoice outcomes and impacts, (3) implementation challenges with specific populations, and (4) inconsistent reporting and adherence to ethical procedures. For those conducting photovoice projects in the future, the implications of the findings include maximizing participant engagement in the project from start to finish, evaluating photovoice projects for effectiveness in producing community change, and reporting ethical procedures.
Critical and Creative Thinking and Photovoice: Strategies for Strengthening Participation and Inclusion
Authors: Lorenz Laura , Bush Erin
Published: March 2022

Researchers, nonprofit organizations, and others have long used photovoice as a participatory action research method with vulnerable groups to depict, reflect on, and describe their realities, and advocate for change. Paulo Freire, whose scholarship is a foundation of photovoice, encouraged critical thinking in a popular education process to understand “the ‘why’ of things and facts.” Creative thinking, a complementary concept that emerged in the field of education in the 1990s, involves, at its core, development, implementation, and communication of multiple original ideas. We provide a model of critical and creative thinking as an integrated process that generates knowledge as participants complete four key photovoice steps: (1) answer questions with a camera, (2) communicate in the group, (3) observe commonalities, and (4) communicate to power. We argue that each step involves teachable skills and provide practical, low-tech strategies that photovoice facilitators can use to enhance critical and creative thinking by any participant who finds it challenging to complete the four steps. Bringing a critical and creative thinking process to photovoice facilitation grounds the method in its education roots. It can enhance participation and inclusion of any vulnerable group, including people with cognitive and communication disorders due to acquired brain injury, mental illness, or substance use disorder for example. We suggest that use of the suggested strategies will result in an authentic, meaningful process that helps equalize power relationships, respects individuals as experts on their own lives, and increases the potential for data that prompt action.
Through Our Eyes, Hear Our Stories: A Virtual Photovoice Project to Document and Archive Asian American and Pacific Islander Community Experiences During COVID-19
Authors: To Phuc Duy Nhu , Huynh Julia , Wu Judy Tzu-Chun , Vo Dang Thuy , Lee Cevadne , Tanjasiri Sora Park
Published: March 2022

Through Our Eyes, Hear Our Voices is a virtual photovoice project that documents the impact of COVID-19 on Asian American and Pacific Islander (AAPI) communities. Quantitative studies on the disproportionate impact of COVID-19 are still emerging, but they do not reveal qualitative experiences of a racialized pandemic exacerbated by political leaders labeling it “China virus.” As a qualitative participatory action research approach, photovoice is an ideal archival and pedagogical tool to capture the lived experience of AAPI communities. However, we had to adapt photovoice to a virtual research environment. We did so by adopting a variety of digital learning and information sharing platforms. In addition, we enlisted community-based organizations who are providing essential services for underrepresented communities to serve as research mentors for university student researchers. Finally, given the historic nature of the pandemic and the underrepresentation of AAPI experiences in mainstream archives, we emphasized the importance of students as co-producers of archival knowledge.
Predictors of Digital Amputation in Diabetic Patients With Surgically Treated Finger Infections
Authors: Gibson Ella , Bettlach Carrie R. , Payne Emma , Daines John , Vuong Linh , Merrill Corinne , Fox Ida K. , Pet Mitchell A.
Published: March 2022

Background:

Diabetes is a well-established risk factor for severe digital infection, and patients are more likely to require digital amputation for adequate source control. This study aims to identify factors predictive of digital amputation compared with preservation in patients with diabetes who present with surgically treated finger infections.

Methods:

Current Procedural Terminology (CPT) and International Classification of Diseases Versions 9 and 10 (ICD-9/10) databases from a single academic medical center were queried to identify patients with type 1 or type 2 diabetes mellitus who underwent surgical treatment in the operating room for treatment of a digital infection from 2010 to 2020. Electronic medical records were reviewed to obtain historical and acute clinical variables at the time of hospital presentation. Bivariate and multivariable regression were used to identify factors associated with amputation.

Results:

In total, 145 patients (61 digital amputation, 84 digital preservation) met inclusion criteria for this retrospective cohort study. Mean hospital stay was 6 days, and the average patient underwent 2 operations. Multivariable analysis revealed that the presence of osteomyelitis, ipsilateral upper extremity dialysis fistula, end-stage renal disease, and vascular disease each had significant independent predictive value for amputation rather than digital preservation.

Conclusions:

Digital amputation is common in the setting of diabetic finger infection. The 4 variables found to independently predict the outcome of amputation can be understood as factors which decrease the likelihood of successful digital salvage and increase the potential consequence of ongoing uncontrolled infection. Further study should focus on clinical factors affecting surgical decision making and how the treatment rendered affects patient outcomes.
Benefit from successful recanalization in an Italian cohort of stroke patients receiving endovascular treatments according to the DIRECT-MT trial criteria
Authors: Cappellari Manuel , Saia Valentina , Pracucci Giovanni , Sallustio Fabrizio , Zini Andrea , Bergui Mauro , Zivelonghi Cecilia , Mangiafico Salvatore , Toni Danilo
Published: March 2022

Introduction

To identify predictors of 3-month mRS score and to estimate the benefit from successful recanalization across baseline subgroups of Italian Registry of Endovascular Treatment in Acute Stroke (IRETAS) cohort of stroke patients receiving endovascular treatments according to the DIRECT-MT criteria.

Methods

Using a model of propensity score matching, we retrospectively identified an IRETAS cohort of 137 patients receiving bridging who were matched with 137 patients receiving MT alone according to the DIRECT-MT criteria.

Results

Differences were found between DIRECT-MT and IRETAS cohorts for 3-month mRS score 0 to 1 (23.5% vs. 33.1%) and 0 to 2 (36.7% vs. 47.1%), successful (82% vs. 76.7%) and complete recanalization (32.3% vs. 58.8%). Among unfavorable predictors for 3-month mRS shift, diabetes mellitus (18.9% vs. 13.9%) and asymptomatic intracerebral hemorhage (ICH) (34.8% vs. 25.5%) were more frequent in the DIRECT-MT, whereas age ≥80 years (23.7% vs. 15.3%) and pre-stroke mRS score >0 (16.1% vs. 7.8%) were more frequent in the IRETAS. The direction of effect on the 3-month mRS shift (6 to 0) favored successful recanalization across all strata. Greatest benefit from successful recanalization was observed in patients with most severe strokes (NIHSS ≥20, OR:4.002; 16–19, OR:3.292; 2–5, OR:2.470) and most proximal occlusion site (intra-cranial ICA, OR:4.092; M1-MCA, OR:3.705; M2-MCA, OR:2.001), in younger patients (18–59 years, OR:3.677; 60–79, OR:3.267; ≥80, OR:1.993), and in patients who started the treatment earlier (onset-to-groin time ≤205 min, OR:4.361; onset-to-groin time >205, OR:2.326).

Conclusions

The benefit from successful recanalization for 3-month mRS shift in the direction of favorable outcome was different across baseline subgroups.
Negotiating Research Participant Consent With, for and by Adults With Developmental Disabilities in Interaction With Their Third-Party Consent Providers
Authors: Boettcher Nick , Duque Camille , Lashewicz Bonnie M.
Published: March 2022

We illuminate third-party research participant consent with, for, and by adults with developmental disabilities by examining consent as an iterative, ongoing process. We use an instrumental case study of three adults with developmental disabilities who, together with their third-party consent providing parents, participated in a broader conversation and video analysis study of how family members are part of decision-making by adults with developmental disabilities. Adults with developmental disabilities comprising our case demonstrated discomfort that left us with questions about the relational nature of third-party consent. We performed a directed content analysis of transcripts and video data corresponding to moments of discomfort, resulting in categories of one- distress, two- non-disclosure, and three- evasion. Our findings illustrate ambiguities where consent was at stake and where there appeared to be no ultimate “Yes” or “No” interpretation. We conclude that expressions of resistance to research participation by adults with developmental disabilities displayed in our data were assertions of autonomy that occurred in relation, yet ran counter to, the agendas of researchers and third-party consent providing parents. We offer recommendations for researchers in the developmental disability field and for qualitative researchers more broadly who might encounter similar ambiguities amidst the relational workings of consent. Greater analytic attention to the relational dynamics of consent has potential to expand ethical commitments of qualitative researchers beyond the limited range of meanings offered in ethics board approvals and signed consent forms.
Puerperal sepsis-related knowledge and reported self-care practices among postpartum women in Dar es salaam, Tanzania
Authors: Nchimbi Dorice B , Joho Angelina A
Published: March 2022

Background:

Knowledge and reported self-care practices of postpartum women are important for early detection, prevention and treatment of puerperal sepsis.

Objectives:

This study analyzes the knowledge and self-care practices for prevention of puerperal sepsis and their determinants among postpartum women.

Methods:

A hospital-based analytical cross-sectional study which included 343 postpartum women was conducted from February to March 2021. Data were collected using interviewer-administered questionnaire. Predictors of knowledge and self-care reported practice were determined using binary logistic regression. p < 0.05 was considered significant.

Results:

More than half ( n = 213, 62.1%) of the postpartum women had adequate knowledge on prevention of puerperal sepsis. Only 39 (11.4%) of the women reported adequate self-care practices toward prevention of puerperal sepsis. Secondary education (adjusted odds ratio = 0.18, 95% confidence interval = 0.06–0.49, p = 0.001), tertiary education (adjusted odds ratio = 0.52, 95% confidence interval = 0.19–1.38, p = 0.021) and getting information from healthcare providers (adjusted odds ratio = 1.06, 95% confidence interval = 0.55–2.06, p = 0.049) were significant determinants of knowledge on prevention of puerperal sepsis. Also, secondary education (adjusted odds ratio = 0.11, 95% confidence interval = 0.04–0.30, p = 0.001), tertiary education (adjusted odds ratio = 0.16, 95% confidence interval = 0.06–0.39, p = 0.001), and having more than four antenatal care visits (adjusted odds ratio = 1.21, 95% confidence interval = 0.49–3.27, p = 0.041) were significant determinants of reported self-care practices for prevention of puerperal sepsis.

Conclusion:

A significant gap in reported self-care practices to prevent puerperal sepsis was evidence. Secondary and tertiary education were significant predictors for both knowledge and self-care reported practices. Special attention should be given to women with low education level.
The Whiston Snare Technique for Loop Extraction of Stents (WHISTLES): A novel technique for the intraureteric assembly of a loop snare for the retrograde extraction of a migrated ureteric stent
Authors: Napier-Hemy Timothy Peter , Floyd Michael S , Samsudin Azizan
Published: March 2022

Background:

While ureteric stent removal remains a frequently performed endourological procedure stent migration either proximally or distally can present the endourologist with a significant intraoperative dilemma. In cases where the stent is of large calibre or impacted into the mucosa of the ureter, retrieval may prove refractory to traditional approaches.

Objective:

To present a further novel procedure: The Whiston Snare Technique for Loop Extraction of Stents (WHISTLES) which allows for intraureteric assembly of a tightening loop through a ureteric catheter thus permitting safe retrieval of a migrated stent.

Methods:

We describe the procedure as it was performed and have recreated the steps in a laboratory environment. This demonstrates an adaptation of existing materials readily found in most urological theatres and is not a prototypical device.

Results:

The procedure was successfully performed to allow extraction of the migrated ureteric stent.

Conclusion:

WHISTLES is a reproducible method for the retrieval of migrated ureteric stents where traditional techniques have failed.

Level of evidence:

5
Indoor positioning systems in hospitals: A scoping review
Authors: Wichmann Johannes
Published: March 2022

Background

Indoor navigation within closed facilities has been subject of studies with different application areas, particularly in recent years (e.g. the navigation requirements of people or the location of objects). Hospitals are of specific interest in this regard as the multitude of technical equipment used is potentially interfering with navigation systems.

Objective

This research examines relevant studies regarding Indoor Positioning Systems (IPS) in hospitals and IPS that are designed for hospitals and in preparation for implementation, by investigating the respective technologies, techniques, prediction-improving methods, evaluation results, and limitations of the IPS.

Methods

To gather current and future IPS in hospitals, the methodology of a Scoping Review was used. The study has been conducted by applying the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Framework to the context of IPS in hospitals. The results and limitations concerning current and future IPS in hospitals were gathered and structured by using a highly cited evaluation framework for IPS.

Results

Thirty-eight studies were considered for this research. The IPS technologies investigated were Bluetooth Low Energy ( n = 17), Wireless-Fidelity ( n = 10), Hybrids ( n = 4), Radio-Frequency Identification ( n = 4), Ultra-Wideband ( n = 1), Infrared ( n = 1) and ZigBee ( n = 1).

Conclusions

This study presents current and future IPS in hospitals. For future IPS research and IPS in hospitals, the theoretical implications contribute to our knowledge about IPS technologies, techniques, prediction-improving methods, evaluation results and limitations during testing/implementing IPS in hospitals. As practical implications, the insights of this study can be used by developers to improve IPS and by hospitals to facilitate IPS implementation.
Subjective theories of illness in fibroid and endometriosis patients: Similarities, differences, and influencing factors
Authors: Münch Friederike , Ebert Andreas D , Mechsner Sylvia , Richter Rolf , David Matthias
Published: March 2022

Introduction:

The aim of this study was to compare the subjective theories of illness in patients with fibroids and patients with endometriosis, and to identify potential factors influencing them.

Methodology:

Participating patients were recruited via three specialized centers for fibroids and endometriosis. To assess their subjective theories concerning the cause of their illness, we used a questionnaire based on the revised Illness Perceptions Questionnaire (IPQ-R). We also gathered and evaluated data relating to sociodemographic factors and psychological distress or possible anxieties using the Kessler Psychological Distress Scale (K10) and the Generalised Anxiety Disorder Assessment (GAD-7).

Results:

We were able to analyze data from 201 patients with fibroids and 212 patients with endometriosis. About 94.4% of the patients had one or more subjective theories concerning the cause of their illness. Both groups perceived “stress or worry” to be the most probable cause of their illness. Compared to endometriosis patients, patients with fibroids were more likely to assume “aging” and “heredity” as the cause of their illness. Endometriosis patients, on the other hand, were more likely to choose theories pertaining to the “environmental influences and immune system” category. The patients’ age, formal education, and conspicuous score values in the K10 or GAD-7 questionnaire proved to be important factors influencing their beliefs about the cause of illness.

Conclusion:

Patients perceive stress and psychological strain as possible causes for their illness. It might be beneficial to take this information into account in conversations between doctors and patients and when drawing up psychosomatic-gynecological treatment plans.
Dramatic Improvement of Trichotillomania with 6 Months of Treatment With N-Acetylcysteine
Authors: Popova Lilia , Mancuso Jennifer
Published: March 2022

We present a case of a 17-year-old male with recurrent hair twirling resulting in patchy alopecia, who improved dramatically on N-acetylcysteine (NAC). Trichotillomania is characterized by repetitive hair pulling, twisting, or twirling and can vary from a mild habit to an impulse-control disorder. Standard treatment for pediatric trichotillomania includes cognitive behavioral therapy or medical therapy with selective serotonin reuptake inhibitors. NAC is a more recently utilized, safe, and well-tolerated over-the-counter supplement with some evidence of benefit for habitual skin and hair disorders. For this patient, we recommended 600 mg twice daily, increasing to 1200 mg twice daily as tolerated. After 6 months, our patient reported decreased desire to twirl his hair and his hair had almost completely regrown. Pediatricians who see patients with trichotillomania or other habitual disorders can consider treating these patients with NAC given its potential benefits and favorable side effect profile.
Bail-Out Percutaneous Intervention for Chronic Total Occlusion of the Left Renal Artery Secondary to Takayasu’s Arteritis in a Pediatric Patient Using Drug-Eluting Stent
Authors: Jariwala Pankaj , Jadhav Kartik , Madhawar Dilip Babu , Giragani Suresh
Published: March 2022

Renal-artery stenosis/occlusion is the cause of ischemic nephropathy, which is associated with hypertension due to renovascular system involvement. Acute renal failure in patients with bilateral renal artery stenosis can occur for a variety of reasons, including administration of an angiotensin-converting enzyme inhibitor or spontaneous progression of renal-artery stenosis leading to bilateral total occlusion or high-grade stenosis. Rapid diagnosis and prompt treatment are the basis of kidney survival. The root cause of renal-artery occlusion must be elucidated in younger age patients after revascularization, such as Takayasu’s arteritis (TA) or fibromuscular dysplasia. We discuss the case of a preadolescent girl who had bilateral complete renal artery occlusion due to TA and acute kidney injury, needing renal replacement therapy. She had a bailout percutaneous renal intervention to the left renal artery, which resulted in remarkable clinical improvement.
Barriers and Facilitators to Chronic Red Cell Transfusion Therapy in Pediatric Sickle Cell Anemia
Authors: Schlenz Alyssa M. , Phillips Shannon M. , Mueller Martina , Melvin Cathy L. , Adams Robert J. , Kanter Julie
Published: March 2022

Background: Chronic red cell transfusion (CRCT) therapy is one of a few effective disease-modifying therapies for children with sickle cell anemia (SCA). CRCT is recommended for primary and secondary stroke prevention for at-risk children with SCA and is sometimes used for other disease-related complications. However, CRCT can be resource- and time-intensive for patients/families, providers, and organizations. This study was conducted to provide a comprehensive, multilevel examination of barriers and facilitators to transfusion therapy in children with SCA from health care provider and caregiver perspectives. Methods: A qualitative descriptive approach was used to conduct key informant interviews in a sample of 26 caregivers and 25 providers across the United States. Interviews were analyzed using directed content analysis with the Multilevel Ecological Model of Health as an initial coding framework and the constant comparison method. Results: Ten barrier themes and 10 facilitator themes emerged across all ecological levels. Themes most commonly occurred on the patient and organizational levels. Key barriers themes included Logistical Challenges, Obtaining and Maintaining Venous Access, Alloantibodies/Alloimmunization and Reactions, and Iron Overload and Adherence to Chelation Therapy. Key facilitator themes included Nursing and Non-nursing Staff Support, Positive Child/Family Experiences, Logistical Help and Social Resources, Blood Bank and Access to Blood, and Transfusion-Specific Resources. Discussion: The comprehensive understanding of multilevel barriers and facilitators to transfusion therapy, including the role of nursing, in children with SCA can inform strategies to improve CRCT for patients/families and providers and can also be applied by organizations seeking to implement transfusion services for SCA.
How I manage pregnancy in women with Glanzmann thrombasthenia
Authors: Fiore Mathieu , Sentilhes Loïc , d’Oiron Roseline
Published: March 2022

Glanzmann thrombasthenia (GT) is a rare inherited platelet function disorder caused by a quantitative and/or qualitative defect of the αIIbβ3 integrin. Pregnancy and delivery are recognized risk periods for bleeding in women with GT. The newborn may also be affected by fetal and neonatal immune thrombocytopenia induced by the transplacental passage of maternal anti-αIIbβ3 antibodies, which can lead to severe hemorrhage and fetal loss. Pregnancy in women with GT thus requires a multidisciplinary approach, including prepregnancy counseling and a treatment plan for delivery for both the mother and child. In this article, we summarize the current knowledge on pregnancy in women with GT and describe how we manage this severe platelet disorder in our clinical practice.
HMGA1 chromatin regulators induce transcriptional networks involved in GATA2 and proliferation during MPN progression
Authors: Li Liping , Kim Jung-Hyun , Lu Wenyan , Williams Donna M. , Kim Joseph , Cope Leslie , Rampal Raajit K. , Koche Richard P. , Xian Lingling , Luo Li Z. , Vasiljevic Marija , Matson Daniel R. , Zhao Zhizhuang Joe , Rogers Ophelia , Stubbs Matthew C. , Reddy Karen , Romero Antonio-Rodriguez , Psaila Bethan , Spivak Jerry L. , Moliterno Alison R. , Resar Linda M. S.
Published: March 2022

Myeloproliferative neoplasms (MPNs) transform to myelofibrosis (MF) and highly lethal acute myeloid leukemia (AML), although the actionable mechanisms driving progression remain elusive. Here, we elucidate the role of the high mobility group A1 (HMGA1) chromatin regulator as a novel driver of MPN progression. HMGA1 is upregulated in MPN, with highest levels after transformation to MF or AML. To define HMGA1 function, we disrupted gene expression via CRISPR/Cas9, short hairpin RNA, or genetic deletion in MPN models. HMGA1 depletion in JAK2V617F AML cell lines disrupts proliferation, clonogenicity, and leukemic engraftment. Surprisingly, loss of just a single Hmga1 allele prevents progression to MF in JAK2V617F mice, decreasing erythrocytosis, thrombocytosis, megakaryocyte hyperplasia, and expansion of stem and progenitors, while preventing splenomegaly and fibrosis within the spleen and BM. RNA-sequencing and chromatin immunoprecipitation sequencing revealed HMGA1 transcriptional networks and chromatin occupancy at genes that govern proliferation (E2F, G2M, mitotic spindle) and cell fate, including the GATA2 master regulatory gene. Silencing GATA2 recapitulates most phenotypes observed with HMGA1 depletion, whereas GATA2 re-expression partially rescues leukemogenesis. HMGA1 transactivates GATA2 through sequences near the developmental enhancer (+9.5), increasing chromatin accessibility and recruiting active histone marks. Further, HMGA1 transcriptional networks, including proliferation pathways and GATA2, are activated in human MF and MPN leukemic transformation. Importantly, HMGA1 depletion enhances responses to the JAK2 inhibitor, ruxolitinib, preventing MF and prolonging survival in murine models of JAK2V617F AML. These findings illuminate HMGA1 as a key epigenetic switch involved in MPN transformation and a promising therapeutic target to treat or prevent disease progression.
Impact of diagnostic genetics on remission MRD and transplantation outcomes in older patients with AML
Authors: Murdock H. Moses , Kim Haesook T. , Denlinger Nathan , Vachhani Pankit , Hambley Bryan , Manning Bryan S. , Gier Shannon , Cho Christina , Tsai Harrison K. , McCurdy Shannon , Ho Vincent T. , Koreth John , Soiffer Robert J. , Ritz Jerome , Carroll Martin P. , Vasu Sumithira , Perales Miguel-Angel , Wang Eunice S. , Gondek Lukasz P. , Devine Steven , Alyea Edwin P. , Lindsley R. Coleman , Gibson Christopher J.
Published: March 2022

Older patients with acute myeloid leukemia (AML) have high relapse risk and poor survival after allogeneic hematopoietic cell transplantation (HCT). Younger patients may receive myeloablative conditioning to mitigate relapse risk associated with high-risk genetics or measurable residual disease (MRD), but older adults typically receive reduced-intensity conditioning (RIC) to limit toxicity. To identify factors that drive HCT outcomes in older patients, we performed targeted mutational analysis (variant allele fraction ≥2%) on diagnostic samples from 295 patients with AML aged ≥60 years who underwent HCT in first complete remission, 91% of whom received RIC, and targeted duplex sequencing at remission in a subset comprising 192 patients. In a multivariable model for leukemia-free survival (LFS) including baseline genetic and clinical variables, we defined patients with low (3-year LFS, 85%), intermediate (55%), high (35%), and very high (7%) risk. Before HCT, 79.7% of patients had persistent baseline mutations, including 18.3% with only DNMT3A or TET2 (DT) mutations and 61.4% with other mutations (MRD positive). In univariable analysis, MRD positivity was associated with increased relapse and inferior LFS, compared with DT and MRD-negative mutations. However, in a multivariable model accounting for baseline risk, MRD positivity had no independent impact on LFS, most likely because of its significant association with diagnostic genetic characteristics, including MDS-associated gene mutations, TP53 mutations, and high-risk karyotype. In summary, molecular associations with MRD positivity and transplant outcomes in older patients with AML are driven primarily by baseline genetics, not by mutations present in remission. In this group of patients, where high-intensity conditioning carries substantial risk of toxicity, alternative approaches to mitigating MRD-associated relapse risk are needed.
Pharmacokinetic analysis identifies a factor VIII immunogenicity threshold after AAV gene therapy in hemophilia A mice
Authors: Lundgren Taran S. , Denning Gabriela , Stowell Sean R. , Spencer H. Trent , Doering Christopher B.
Published: March 2022

Advances in the development of novel treatment options for hemophilia A are prevalent. However, the anti–factor VIII (FVIII) neutralizing antibody (inhibitor) response to existing FVIII products remains a major treatment challenge. Although some novel products are designed to function in the presence of inhibitors, they do not specific address the immunogenicity risk or mechanistic causes of inhibitor development, which remain unclear. Furthermore, most preclinical studies supporting clinical gene therapy programs have reported immunogenicity signals in animal models, especially at higher vector doses and sometimes using multiple vector designs. In these settings, immunogenicity risk factor determination, comparative immunogenicity of competing vector designs, and the potential for obtaining meaningful prognostic data remain relatively unexplored. Additionally, there remains the opportunity to investigate clinical gene therapy as an alternative to standard immune tolerance induction therapy. The current study was designed to address these issues through longitudinal dose-response evaluation of 4 adeno-associated viral (AAV) vector candidates encoding 2 different FVIII transgenes in a murine model of hemophilia A. Plasma FVIII activity and anti-FVIII antibody data were used to generate a pharmacokinetic model that (1) identifies initial AAV-FVIII product expression kinetics as the dominant risk factor for inhibitor development, (2) predicts a therapeutic window where immune tolerance is achieved, and (3) demonstrates evidence of gene therapy–based immune tolerance induction. Although there are known limitations to the predictive value of preclinical immunogenicity testing, these studies can uncover or support the development of design principles that can guide the development of safe and effective genetic medicines.
Donor-recipient sex is associated with transfusion-related outcomes in critically ill patients
Authors: Alshalani Abdulrahman , Uhel Fabrice , Cremer Olaf L. , Schultz Marcus J. , de Vooght Karen M. K. , van Bruggen Robin , Acker Jason P. , Juffermans Nicole P.
Published: March 2022

Transfusion of red blood cells (RBCs) from female donors has been associated with increased risk of mortality. This study aims to investigate the associations between donor-recipient sex and posttransfusion mortality and morbidity in critically ill patients who received RBC transfusions from either male-only donors or from female-only donors (unisex-transfusion cases). Survival analysis was used to compare 4 groups: female-to-female, female-to-male, male-to-female, and male-to-male transfusion. Multivariate logistic model was used to evaluate the association between donor sex and intensive care unit (ICU) mortality. Associations between transfusion and acute kidney injury (AKI), acute respiratory distress syndrome (ARDS), and nosocomial infections were assessed. Of the 6992 patients included in the original cohort study, 403 patients received unisex-transfusion. Survival analysis and the logistic model showed that transfusion of female RBCs to male patients was associated with an increased ICU mortality compared with transfusion of female RBCs to female patients (odds ratio, 2.43; 95% confidence interval, 1.02-5.77; P < .05). There was a trend toward increased ARDS in patients receiving RBC from female donors compared with those receiving blood from males (P = .06), whereas AKI was higher in donor-recipient sex-matched transfusion groups compared with sex-mismatched groups (P = .05). This was an exploratory study with potential uncontrolled confounders that limits broad generalization of the findings. Results warrant further studies investigating biological mechanisms underlying the association between donor sex with adverse outcomes as well as studies on the benefit of matching of blood between donor and recipient.
CEACAM1 is a novel culture-compatible surface marker of expanded long-term reconstituting hematopoietic stem cells
Authors: Ansari Unain , Tomellini Elisa , Chagraoui Jalila , Lehnertz Bernhard , Mayotte Nadine , Bordeleau Marie-Eve , Roux Philippe P. , Sauvageau Guy
Published: March 2022

Key Points

CEACAM1 is a novel cell surface marker of ex vivo expanded LT-HSCs. Sorting umbilical cord blood cells based on CEACAM1 and known HSC marker expression allows purification of LT-HSCs with improved purity.
Evaluation of the right atrial phasic functions in patients with anterior ST-elevation myocardial infarction: a 2D speckle-tracking echocardiography study
Authors: Eisvand Mokhtar , Mohseni-Badalabadi Reza , Hosseinsabet Ali
Published: March 2022

Background

Evidence suggests that changes in left ventricular systolic and diastolic functions may affect right atrial (RA) phasic functions. We aimed to evaluate RA phasic functions in the presence of anterior ST-elevation myocardial infarction (ASTEMI) as an acute event and to compare the findings with those in a control group.

Methods

We recruited 92 consecutive ASTEMI patients without accompanying significant stenosis in the proximal and middle parts of the right coronary artery and 31 control subjects, matched for age, sex, diabetes, and hypertension. RA phasic functions were evaluated concerning their longitudinal 2D speckle-tracking echocardiography-derived markers. The ASTEMI group was followed up for all-cause mortality or reinfarction.

Results

In the ASTEMI group, RA strain was reduced during the reservoir (33.2% ± 4.3% vs 30.5% ± 8.1%; P = 0.021) and conduit (16% [12–18%] vs 14% [9–17%]; P = 0.048) phases. The other longitudinal 2D speckle-tracking echocardiography-derived markers of RA phasic functions were not different between the 2 groups. RA strain and strain rate during the contraction phase were predictive of all-cause mortality or reinfarction (hazard ratio = 0.80; P = 0.024 and hazard ratio = 0.39; P = 0.026, respectively).

Conclusions

Based on 2D speckle-tracking echocardiography, in the ASTEMI group, compared with the control group, RA reservoir and conduit functions were reduced, while RA contraction function was preserved. RA contraction function was predictive of all-cause mortality or reinfarction during the follow-up period.
Metabolically healthy versus unhealthy obese phenotypes in relation to hypertension incidence; a prospective cohort study
Authors: Hamzeh Behrooz , Pasdar Yahya , Moradi Shima , Darbandi Mitra , Rahmani Negin , Shakiba Ebrahim , Najafi Farid
Published: March 2022

Background

Although obesity increases the risk of hypertension, the effect of obesity based on metabolic status on the incidence of hypertension is not known. This study aimed to determine the association between obesity phenotypes including metabolically unhealthy obesity (MUO) and metabolically healthy obesity (MHO) and the risk of hypertension incidence.

Methods

We conducted a prospective cohort study on 6747 adults aged 35–65 from Ravansar non-communicable diseases (RaNCD) study. Obesity was defined as body mass index above 30 kg/m2 and metabolically unhealthy was considered at least two metabolic disorders based on the International Diabetes Federation criteria. Obesity phenotypes were categorized into four groups including MUO, MHO, metabolically unhealthy non obesity (MUNO), and metabolically healthy non obesity (MHNO). Cox proportional hazards regression models were applied to analyze associations with hypertension incidence.

Results

The MHO (HR: 1.37; 95% CI: 1.03–1.86) and MUO phenotypes (HR: 2.44; 95% CI: 1.81–3.29) were associated with higher hypertension risk compared to MHNO. In addition, MUNO phenotype was significantly associated with risk of hypertension incidence (HR: 1.65; 95% CI: 1.29–2.14).

Conclusions

Both metabolically healthy and unhealthy obesity increased the risk of hypertension incidence. However, the increase in metabolically unhealthy phenotype was higher.
Early fluid management affects short-term mortality in patients with end-stage kidney disease undergoing chronic hemodialysis and requiring continuous renal replacement therapy
Authors: Kim Kyun Young , Ryu Jung-Hwa , Kang Duk-Hee , Kim Seung-Jung , Choi Kyu Bok , Lee Shina
Published: March 2022

Background

Early fluid management is considered a key element affecting mortality in critically ill patients requiring continuous renal replacement therapy (CRRT). Most studies have primarily focused on patients with intrinsic acute kidney injury requiring CRRT, although end-stage kidney disease (ESKD) patients generally exhibit greater vulnerability. We investigated the association between fluid balance and short-term mortality outcomes in ESKD patients undergoing chronic hemodialysis and requiring CRRT.

Methods

This retrospective study included 110 chronic hemodialysis patients who received CRRT between 2017 and 2019 at Ewha Womans University Mokdong Hospital. The amounts of daily input and output, and cumulative 3-day and 7-day input and output, were assessed from the initiation of CRRT. The participants were classified into two groups based on 7-day and 14-day mortalities. Cox regression analyses were carried out on the basis of the amounts of daily input and output, cumulative input and output, and cumulative fluid balance.

Results

During follow-up, 7-day and 14-day mortalities were observed in 24 (21.8%) and 34 (30.9%) patients. The patients were stratified into two groups (14-day survivors vs. non-survivors), and there were no significant differences in demographic characteristics between the two groups. However, diabetes mellitus was more common among survivors than among non-survivors. Univariate analyses showed that the amounts of daily output at 48, and 72 h, and 3-day cumulative input and output, were significantly associated with 7-day mortality risk regardless of the cumulative fluid balance (HR: 0.28, 95% CI: 0.12–0.70, p = 0.01 for daily output at 48 h; HR: 0.34, 95% CI: 0.13–0.85, p = 0.02 for daily output at 72 h.; HR: 0.72, 95% CI: 0.61–0.86, p = 0.01 for 3-day cumulative input; HR: 0.65, 95% CI: 0.41–0.90, p = 0.01 for 3-day cumulative output). Adjusted multivariate analyses showed that the lower 3-day cumulative output is an independent risk factor for 7-day and 14-day mortality.

Conclusions

In our study, increased cumulative output were significantly associated with reduced short-term mortality risk in chronic hemodialysis patients undergoing CRRT regardless of cumulative fluid balance. Further prospective studies to investigate the association between fluid balance and mortality in ESRD patients requiring CRRT are warranted.
Late effects of high-dose methotrexate treatment in childhood cancer survivors—a systematic review
Authors: Daetwyler Eveline , Bargetzi Mario , Otth Maria , Scheinemann Katrin
Published: March 2022

Background

High-dose methotrexate (HD-MTX) is used in the treatment of different childhood cancers, including leukemia, the most common cancer type and is commonly defined as an intravenous dose of at least 1 g/m2 body surface area per application. A systematic review on late effects on different organs due to HD-MTX is lacking.

Method

We conducted a systematic literature search in PubMed, including studies published in English or German between 1985 and 2020. The population of each study had to consist of at least 75% childhood cancer survivors (CCSs) who had completed the cancer treatment at least twelve months before late effects were assessed and who had received HD-MTX. The literature search was not restricted to specific cancer diagnosis or organ systems at risk for late effects. We excluded case reports, case series, commentaries, editorial letters, poster abstracts, narrative reviews and studies only reporting prevalence of late effects. We followed PRISMA guidelines, assessed the quality of the eligible studies according to GRADE criteria and registered the protocol on PROSPERO (ID: CRD42020212262).

Results

We included 15 out of 1731 identified studies. Most studies included CCSs diagnosed with acute lymphoblastic leukemia (n = 12). The included studies investigated late effects of HD-MTX on central nervous system (n = 10), renal (n = 2) and bone health (n = 3). Nine studies showed adverse outcomes in neuropsychological testing in exposed compared to non-exposed CCSs, healthy controls or reference values. No study revealed lower bone density or worse renal function in exposed CCSs. As a limitation, the overall quality of the studies per organ system was low to very low, mainly due to selection bias, missing adjustment for important confounders and low precision.

Conclusions

CCSs treated with HD-MTX might benefit from neuropsychological testing, to intervene early in case of abnormal results. Methodological shortcomings and heterogeneity of the tests used made it impossible to determine the most appropriate test. Based on the few studies on renal function and bone health, regular screening for dysfunction seems not to be justified. Only screening for neurocognitive late effects is warranted in CCSs treated with HD-MTX.
Transarterial chemoembolization combined with camrelizumab for recurrent hepatocellular carcinoma
Authors: Guo Yusheng , Ren Yanqiao , Chen Lei , Sun Tao , Zhang Weihua , Sun Bo , Zhu Licheng , Xiong Fu , Zheng Chuansheng
Published: March 2022

Purpose

To evaluate the efficacy and safety of transarterial chemoembolization (TACE) combined with camrelizumab (hereafter, TACE-camrelizumab) in the treatment of patients with recurrent hepatocellular carcinoma (R-HCC) after curative resection.

Patients and methods

R-HCC patients who underwent TACE plus camrelizumab or TACE-alone from January 2016 to August 2021 were retrospectively evaluated. Patients were assessed for tumor response, progression-free survival, survival rates and adverse events.

Results

Seventy-one patients were included in this study, including 20 patients in the TACE- camrelizumab group and 51 patients in the TACE-alone group. The objective response rate was 56.9% in the TACE-alone group and 40% in the TACE-camrelizumab group at 3 months (P = 0.201). The disease control rates were 84.3% in TACE-alone group and 80% in TACE-camrelizumab group at 3 months (P = 0.663). The progression-free survival (PFS) of the TACE-alone group was slightly longer than those of the TACE- camrelizumab group (9 months vs. 6 months). However, there were no statistically significant differences in the median PFS (P = 0.586). Similarly, there were no significant differences in the half-year and one-year survival rates (P = 0.304, P = 0.430). Multivariate analysis revealed that Neutrophil-to-lymphocyte ratio (NLR) was associated with PFS significantly. 75% patients developed at least one type of AEs related to camrelizumab in TACE-camrelizumab group, and no patients developed severe AEs.

Conclusion

Comparing with TACE-Alone, the efficacy of TACE-camrelizumab for patients with R-HCC was similar. Meanwhile, the results of this study also indicated that TACE is still a better choice for patients with R-HCC.