bluuebunny/crossref_metadata_2025 huggingface dataset:
Regional differences of Mycobacterium tuberculosis complex infection and multidrug resistance epidemic in Luoyang
Authors: Wang Zhenzhen , Guo Tengfei , Xu Liyang , Liu Jinwei , Hou Yi , Jin Junrong , Zhang Qing , Jiang Tao , Zhao Zhanqin , Xue Yun
Published: June 2024

Background

Tuberculosis (TB) remains a global public health event of great concern, however epidemic data on TB covering entire areas during the special period of the COVID-19 epidemic have rarely been reported. We compared the dissemination and multidrug-resistance patterns of Mycobacterium tuberculosis complex (MTBC) in the main urban area of Luoyang City, China (including six municipal jurisdictions) and nine county and township areas under its jurisdiction, aimed to establish the epidemiology of TB in this region and to provide reference for precision anti-TB in places with similar settings.

Methods

From 2020 to 2022, sputum samples were collected from 18,504 patients with confirmed, suspected and unexcluded TB in 10 designated TB medical institutions. Insertion sequence 6110 was amplified by PCR (rpoB gene detection if necessary) to confirm the presence of MTBC. PCR-positive specimens were analyzed by multicolor melting curve analysis to detect multidrug resistance.

Results

Among the 18,504 specimens, 2675 (14.5%) were MTBC positive. The positive rate was higher in the main urban area than in the county and township areas (29.8% vs. 10.9%, p < 0.001). Male, re-treated and smear-positive groups were high-burden carriers of MTBC. Individuals aged > 60 years were the largest group infected with MTBC in the main urban area, compared with individuals aged < 61 years in the county and township areas. The detection of multidrug-resistant TB (MDR-TB) was higher in the main urban area than in the county and township areas (13.9% vs. 7.8%, p < 0.001). In all areas, MDR-TB groups were dominated by males, patients with a history of TB treatment, and patients aged < 61 years. Stratified analysis of MDR-TB epidemiology showed that MDR4 (INH þ RIF þ EMB þ SM) was predominant in the main urban area, while MDR3 (INH þ RIF þ SM) was predominant in the county and township areas. MDR-TB detection rate and epidemiology differed among the county and township areas.

Conclusions

For local TB control, it is necessary to plan more appropriate and accurate prevention and control strategies according to the regional distribution of MTBC infection.
Global, regional and national burdens of Nasopharynx cancer in the adolescents and young adults from 1990 to 2019 and its predictions
Authors: Huang Guoxin , Wang Yaojie , Qin Bingqing , Zeng Jing , tan Huazhang , Zhang Dongdong , Wang Qiuyang
Published: June 2024

Purpose

To use data from the Global Burden of Disease (GBD) Study 2019 to report the global, regional and national rates and trends of deaths incidence, prevalence, disability-adjusted life years (DALYs) for Nasopharynx cancer (NPC) in adolescents and young adults (AYAs).

Methods

Data from the GBD 2019 were used to analyze deaths incidence, prevalence and DALYs due to NPC at global, regional, and national levels. Joinpoint regression analysis was used to calculate the average annual percentage changes (AAPC). The association between incidence, prevalence and DALYs and socioeconomic development was analyzed using the GBD Socio-demographic Index (SDI). Finally, projections were made until 2030 and calculated in Nordpred.

Results

The incidence, prevalence, death and DALYs rates (95%UI) due to NPC 0.96 (0.85–1.09, 6.31 (5.54–7.20),0.20 (0.19–0.22), and 12.23(11.27–13.29) in 2019, respectively. From 1990 to 2019, the incidence and prevalence rates increased by 1.79 (95% CI 1.03 to 2.55) and 2.97(95% CI 2.13 to 3.82) respectively while the deaths and DALYs rates declined by 1.64(95%CI 1.78 to 1.49) and 1.6(95%CI 1.75 to 1.4) respectively. Deaths and DALYs rates in South Asia, East Asia, North Africa and Middle East decreased with SDI. Incidence and prevalence rates in East Asia increased with SDI. At the national level, the incidence and prevalence rates are high in China, Taiwan(China), Singapore, Malaysia, Brunel Darussalam, Algeria, Tunisia, Libya and Malta. Meanwhile, the deaths and DALYs rates are still high in Malaysia, Brunel Darussalam, Greenland and Taiwan(Province of China). The deaths and DALYs rates are low in Honduras, Finland and Norway. From the 2020 to 2030, ASIR、ASPR and ASDR in most regions are predicted to stable, but DALYs tends to decline.

Conclusion

NPC in AYAs is a significant global public problem. The incidence, prevalence, and DALYs rates vary widely by region and country. Therefore different regions and countries should be targeted to improve the disease burden of NPC.
Clinical features of primary and compound forms of wide macular posterior staphyloma in high myopia
Authors: Yoon Chang Ki , Lee Eun Kyoung , Bae Kunho , Park Un Chul
Published: June 2024

Background

To compare the ocular features of highly myopic eyes with posterior staphyloma of wide macular type according to its morphological complexity.

Methods

In this cross-sectional study, wide macular posterior staphyloma (WMPS) was classified into the primary (Curtin type I) and the compound (Curtin types VI to X) forms based on the configuration within the staphyloma. The grades of myopic maculopathy and the thicknesses of choroid and sclera were compared between the primary and compound forms of WMPS.

Results

A total of 154 eyes (103 patients) with primary WMPS and 65 eyes (49 patients) with compound WMPS were included. Eyes with compound WMPS had worse visual acuity (P = 0.001) and greater axial length (P < 0.001) than those with primary WMPS. Compared to primary WMPS, compound WMPS had a higher grade of myopic macular degeneration (P < 0.001) and a higher frequency of lamellar or full-thickness macular hole associated with myopic traction (21.5% vs. 10.4%; P = 0.028) and active or scarred myopic choroidal neovascularization (33.8% vs. 20.1%; P = 0.030). On swept-source optical coherence tomography, eyes with compound WMPS had significantly thinner choroid and sclera.

Conclusions

The compound form of WMPS had more severe myopic macular changes and worse visual prognosis compared to the primary form of WMPS, and these were associated with more structural deformation in the posterior eyeball. Compound WMPS should be considered as an advanced form of staphyloma.
The impact of retirement on blood pressure: evidence from a nationwide survey in China
Authors: Mi Jiarun , Han Xueyan , Cao Man , Cheng Hanchao , Pan Zhaoyang , Guo Jian , Sun Wei , Liu Yuanli , Zheng Congyi , Wang Xin , Cao Xue , Hu Zhen , Tian Yixin , Wang Zengwu , Guan Tianjia
Published: June 2024

Introduction

The health impact of retirement is controversial. Most previous studies have been based on self-reported health indicators or the endpoints of some chronic diseases (e.g., morbidity or mortality), but objective physiological indicators (e.g., blood pressure) have rarely been used. The objective of this study is to elucidate the health effects of retirement on blood pressure, thereby offering empirical evidence to facilitate the health of retirees and to optimize retirement policies.

Methods

From 2012 to 2015, 84,696 participants of the Chinese Hypertension Survey (CHS) were included in this study. We applied the fuzzy regression discontinuity design (FRDD) to identify retirement’s causal effect on systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse pressure. We also explored the heterogeneity in the effects of retirement across different sex and education level groups.

Results

Based on the fully adjusted model, we estimated that retirement increased SBP by 5.047 mm Hg (95% CI: -2.628-12.723, P value: 0.197), DBP by 0.614 mm Hg (95% CI: -3.879-5.108, P value: 0.789) and pulse pressure by 4.433 mm Hg (95% CI: -0.985-9.851, P value: 0.109). We found that retirement led to a significant increase in male participants’ SBP and pulse pressure as well as a possible decrease in female participants’ blood pressure. Additionally, the blood pressure levels of low-educated participants were more vulnerable to the shock of retirement.

Conclusion

Retirement is associated with an increase in blood pressure level. There is a causal relationship between the increase in blood pressure levels of men and retirement. Policy-makers should pay extra attention to the health status of men and less educated people when adjusting retirement policies in the future.
Utilization of machine learning for dengue case screening
Authors: Bohm Bianca Conrad , Borges Fernando Elias de Melo , Silva Suellen Caroline Matos , Soares Alessandra Talaska , Ferreira Danton Diego , Belo Vinícius Silva , Lignon Julia Somavilla , Bruhn Fábio Raphael Pascoti
Published: June 2024

Dengue causes approximately 10.000 deaths and 100 million symptomatic infections annually worldwide, making it a significant public health concern. To address this, artificial intelligence tools like machine learning can play a crucial role in developing more effective strategies for control, diagnosis, and treatment. This study identifies relevant variables for the screening of dengue cases through machine learning models and evaluates the accuracy of the models. Data from reported dengue cases in the states of Rio de Janeiro and Minas Gerais for the years 2016 and 2019 were obtained through the National Notifiable Diseases Surveillance System (SINAN). The mutual information technique was used to assess which variables were most related to laboratory-confirmed dengue cases. Next, a random selection of 10,000 confirmed cases and 10,000 discarded cases was performed, and the dataset was divided into training (70%) and testing (30%). Machine learning models were then tested to classify the cases. It was found that the logistic regression model with 10 variables (gender, age, fever, myalgia, headache, vomiting, nausea, back pain, rash, retro-orbital pain) and the Decision Tree and Multilayer Perceptron (MLP) models achieved the best results in decision metrics, with an accuracy of 98%. Therefore, a tree-based model would be suitable for building an application and implementing it on smartphones. This resource would be available to healthcare professionals such as doctors and nurses.
Supporting whānau during COVID-19 pandemic in Aotearoa New Zealand: a systems thinking case study
Authors: Sharma Sudesh , Davies Cheryl , Mana Helena Rattray-Te , Baker Michael , Kvalsvig Amanda , Walton Mat
Published: June 2024

Background

The Aotearoa New Zealand COVID-19 pandemic response has been hailed as a success story, however, there are concerns about how equitable it has been. This study explored the experience of a collective of Māori health and social service providers in the greater Wellington region of Aotearoa New Zeland delivering COVID-19 responses.

Methods

The study was a collaboration between a large urban Māori health and social service provider, Tākiri Mai Te Ata whānau ora collective, and public health researchers in Aotearoa New Zealand. Two online workshops were held with staff of the Māori service provider, collectively developing a qualitative causal loop diagram and generating systemic insights. The causal loop diagram showed interactions of various factors affecting COVID-19 response for supporting whānau (Māori family/households) at a community level. The iceberg model of systems thinking offered insights for action in understanding causal loop diagrams, emphasizing impactful changes at less visible levels.

Results

Six interacting subsystems were identified within the causal loop diagram that highlighted the systemic barriers and opportunities for effective COVID-19 response to Māori whānau. The medical model of health service produces difficulties for delivering kaupapa Māori services. Along with pre-existing vulnerability and health system gaps, these difficulties increased the risk of negative impacts on Māori whānau as COVID-19 cases increased. The study highlighted a critical need to create equal power in health perspectives, reducing dominance of the individual-focused medical model for better support of whānau during future pandemics.

Conclusions

The study provided insights on systemic traps, their interactions and delays contributing to a relatively less effective COVID-19 response for Māori whānau and offered insights for improvement. In the light of recent changes in the Aotearoa New Zealand health system, the findings emphasize the urgent need for structural reform to address power imbalances and establish kaupapa Māori approach and equity as a norm in service planning and delivery.
Segregation of endosymbionts in complex symbiotic system of cicadas providing novel insights into microbial symbioses and evolutionary dynamics of symbiotic organs in sap-feeding insects
Authors: Huang Zhi , Wang Dandan , Zhou Jinrui , He Hong , Wei Cong
Published: June 2024

The most extraordinary systems of symbiosis in insects are found in the suborder Auchenorrhyncha of Hemiptera, which provide unique perspectives for uncovering complicated insect-microbe symbiosis. We investigated symbionts associated with bacteriomes and fat bodies in six cicada species, and compared transmitted cell number ratio of related symbionts in ovaries among species. We reveal that Sulcia and Hodgkinia or a yeast-like fungal symbiont (YLS) are segregated from other host tissues by the bacteriomes in the nymphal stage, then some of them may migrate to other organs (i.e., fat bodies and ovaries) during host development. Particularly, YLS resides together with Sulcia in the “symbiont ball” of each egg and the bacteriomes of young-instar nymphs, but finally migrates to the fat bodies of adults in the majority of Hodgkinia-free cicadas, whereas it resides in both bacteriome sheath and fat bodies of adults in a few other species. The transmitted Sulcia/YLS or Sulcia/Hodgkinia cell number ratio in ovaries varies significantly among species, which could be related to the distribution and/or lineage splitting of symbiont(s). Rickettsia localizes to the nuclei of bacteriomes and fat bodies in some species, but it was not observed to be transmitted to the ovaries, indicating that this symbiont may be acquired from environments or from father to offspring. The considerable difference in the transovarial transmission process of symbionts suggests that cellular mechanisms underlying the symbiont transmission are complex. Our results may provide novel insights into insect-microbe symbiosis.
Inflammatory rhabdomyoblastic tumor, pheochromocytoma, and pulmonary hamartoma in a patient with neurofibromatosis type 1: a case report
Authors: Jokelainen Otto , Myllykangas Heidi , Rajala Katri , Marttila Jarkko , Sironen Reijo
Published: June 2024

Background

Inflammatory rhabdomyoblastic tumors are relatively recently recognized soft tissue tumors with a low malignant potential. Here, we present a case of concurrent inflammatory rhabdomyoblastic tumor (IRMT), adrenal pheochromocytoma, and pulmonary hamartoma in a patient with neurofibromatosis type 1 (NF1). To our knowledge, this is the first time that this constellation of tumors has been described in the literature.

Case presentation

A female patient in her late 20s with known NF1 was diagnosed with an inflammatory rhabdomyoblastic tumor, pheochromocytoma, and pulmonary hamartoma in a short succession. IRMT was found to harbor a near-haploid genome and displayed a typical immunohistochemical profile as well as a focal aberrant p53 expression pattern.

Conclusions

This case report strengthens the theory that defects in the tumor suppressor NF1 play a central role in the pathogenesis of inflammatory rhabdomyoblastic tumors and that IRMT may be part of the spectrum of neurofibromatosis type 1 related tumors.
Improvement effects of a novel Chinese herbal formula in imiquimod and IL-23-stimulated mouse models of psoriasis
Authors: Wang Lan , Dou Yao-Xing , Yu Qiu-Xia , Hu Zhen , Ip Siu-Po , Xian Yan-Fang , Lin Zhi-Xiu
Published: June 2024

Background

Psoriasis is a long-term inflammatory skin disease. A novel herbal formula containing nine Chinese herbal medicines, named Inflammation Skin Disease Formula (ISDF), has been prescribed in clinics for decades.

Aims

To investigate the efficacy and action mechanisms of ISDF on psoriasis using imiquimod (IMQ) and Interleukin-23 (IL-23)-induced models in mice and reveal the pharmacokinetics profile of ISDF in rats.

Methods

Topical administration of IMQ and intradermal injection with IL-23 respectively induced skin lesions like psoriasis on the dorsal area of Balb/c and C57 mice. The mice's body weight, skin thickness, and psoriasis area and severity index (PASI) were assessed weekly. SD rats were used in the pharmacokinetics study and the contents of berberine and baicalin were determined.

Results

The PASI scores and epidermal thickness of mice were markedly decreased after ISDF treatment in both models. ISDF treatment significantly decreased the contents of IL-17A and IL-22 in the serum of IMQ- and IL-23-treated mice. Importantly, ISDF markedly downregulated IL-4, IL-6, IL-1β, and tumor necrosis factor α (TNF-α) gene expression, and the phosphorylation of NF-κB p65, JNK, ERKs and MAPK p38 in IMQ-treated mice. The protein phosphorylation of Jak1, Jak2, Tyk2 and Stat3 was significantly mitigated in the ISDF-treated groups. The absorption of baicalin and berberine of ISDF through the gastrointestinal tract of rats was limited, and their distribution and metabolism in rats were also very slow, which suggested ISDF could be used in the long-term application.

Conclusions

ISDF has a strong anti-psoriatic therapeutic effect on mouse models induced with psoriasis through IMQ and IL-23, which is achieved by inhibiting the activation of the Jak/Stat3-activated IL-23/Th17 axis and the downstream NF-κB signalling and MAPK signalling pathways. ISDF holds great potential to be a therapy for psoriasis and should be further developed for this purpose.
Unveiling wearables: exploring the global landscape of biometric applications and vital signs and behavioral impact
Authors: Del-Valle-Soto Carolina , Briseño Ramon A. , Valdivia Leonardo J. , Nolazco-Flores Juan Arturo
Published: June 2024

The development of neuroscientific techniques enabling the recording of brain and peripheral nervous system activity has fueled research in cognitive science. Recent technological advancements offer new possibilities for inducing behavioral change, particularly through cost-effective Internet-based interventions. However, limitations in laboratory equipment volume have hindered the generalization of results to real-life contexts. The advent of Internet of Things (IoT) devices, such as wearables, equipped with sensors and microchips, has ushered in a new era in behavior change techniques. Wearables, including smartwatches, electronic tattoos, and more, are poised for massive adoption, with an expected annual growth rate of 55% over the next five years. These devices enable personalized instructions, leading to increased productivity and efficiency, particularly in industrial production. Additionally, the healthcare sector has seen a significant demand for wearables, with over 80% of global consumers willing to use them for health monitoring. This research explores the primary biometric applications of wearables and their impact on users’ well-being, focusing on the integration of behavior change techniques facilitated by IoT devices. Wearables have revolutionized health monitoring by providing real-time feedback, personalized interventions, and gamification. They encourage positive behavior changes by delivering immediate feedback, tailored recommendations, and gamified experiences, leading to sustained improvements in health. Furthermore, wearables seamlessly integrate with digital platforms, enhancing their impact through social support and connectivity. However, privacy and data security concerns must be addressed to maintain users’ trust. As technology continues to advance, the refinement of IoT devices’ design and functionality is crucial for promoting behavior change and improving health outcomes. This study aims to investigate the effects of behavior change techniques facilitated by wearables on individuals’ health outcomes and the role of wearables in promoting a healthier lifestyle.
Gene silencing in the aedine cell lines C6/36 and U4.4 using long double-stranded RNA
Authors: Omokungbe Bodunrin , Centurión Alejandra , Stiehler Sabrina , Morr Antonia , Vilcinskas Andreas , Steinbrink Antje , Hardes Kornelia
Published: June 2024

Background

RNA interference (RNAi) is a target-specific gene silencing method that can be used to determine gene functions and investigate host–pathogen interactions, as well as facilitating the development of ecofriendly pesticides. Commercially available transfection reagents (TRs) can improve the efficacy of RNAi. However, we currently lack a product and protocol for the transfection of insect cell lines with long double-stranded RNA (dsRNA).

Methods

We used agarose gel electrophoresis to determine the capacity of eight TRs to form complexes with long dsRNA. A CellTiter-Glo assay was then used to assess the cytotoxicity of the resulting lipoplexes. We also measured the cellular uptake of dsRNA by fluorescence microscopy using the fluorophore Cy3 as a label. Finally, we analyzed the TRs based on their transfection efficacy and compared the RNAi responses of Aedes albopictus C6/36 and U4.4 cells by knocking down an mCherry reporter Semliki Forest virus in both cell lines.

Results

The TRs from Biontex (K4, Metafectene Pro, and Metafectene SI+) showed the best complexing capacity and the lowest dsRNA:TR ratio needed for complete complex formation. Only HiPerFect was unable to complex the dsRNA completely, even at a ratio of 1:9. Most of the complexes containing mCherry-dsRNA were nontoxic at 2 ng/µL, but Lipofectamine 2000 was toxic at 1 ng/µL in U4.4 cells and at 2 ng/µL in C6/36 cells. The transfection of U4.4 cells with mCherry-dsRNA/TR complexes achieved significant knockdown of the virus reporter. Comparison of the RNAi response in C6/36 and U4.4 cells suggested that C6/36 cells lack the antiviral RNAi response because there was no significant knockdown of the virus reporter in any of the treatments.

Conclusions

C6/36 cells have an impaired RNAi response as previously reported. This investigation provides valuable information for future RNAi experiments by showing how to mitigate the adverse effects attributed to TRs. This will facilitate the judicious selection of TRs and transfection conditions conducive to RNAi research in mosquitoes.

Graphical Abstract
Exploring histone deacetylases in type 2 diabetes mellitus: pathophysiological insights and therapeutic avenues
Authors: Kumar Kukkala Kiran , Aburawi Elhadi Husein , Ljubisavljevic Milos , Leow Melvin Khee Shing , Feng Xu , Ansari Suraiya Anjum , Emerald Bright Starling
Published: June 2024

Diabetes mellitus is a chronic disease that impairs metabolism, and its prevalence has reached an epidemic proportion globally. Most people affected are with type 2 diabetes mellitus (T2DM), which is caused by a decline in the numbers or functioning of pancreatic endocrine islet cells, specifically the β-cells that release insulin in sufficient quantity to overcome any insulin resistance of the metabolic tissues. Genetic and epigenetic factors have been implicated as the main contributors to the T2DM. Epigenetic modifiers, histone deacetylases (HDACs), are enzymes that remove acetyl groups from histones and play an important role in a variety of molecular processes, including pancreatic cell destiny, insulin release, insulin production, insulin signalling, and glucose metabolism. HDACs also govern other regulatory processes related to diabetes, such as oxidative stress, inflammation, apoptosis, and fibrosis, revealed by network and functional analysis. This review explains the current understanding of the function of HDACs in diabetic pathophysiology, the inhibitory role of various HDAC inhibitors (HDACi), and their functional importance as biomarkers and possible therapeutic targets for T2DM. While their role in T2DM is still emerging, a better understanding of the role of HDACi may be relevant in improving insulin sensitivity, protecting β-cells and reducing T2DM-associated complications, among others.
Material energy citizenship through participation in citizen-financed photovoltaic projects
Authors: Sierro Fabienne , Blumer Yann
Published: June 2024

Background

Citizens are recognized as key actors in the energy system’s transformation by assuming novel roles beyond being mere energy consumers. Participation in renewable energy projects increases societal support and renders the decarbonization of the energy system more inclusive. Increasing numbers of citizen-financed photovoltaic (CiFi PV) projects exemplify this. Empirical studies on individuals who participate in CiFi PV, their perceived role(s), and their motivations, however, are scarce. This study addresses this gap through the lens of energy citizenship by analyzing individual participation.

Methods

The study surveyed CiFi PV participants across five projects in Switzerland (N = 510). After a comparison of the participants’ characteristics to the general public and a descriptive analysis of the perceived roles to participate, the study explores the individual motivations of participants. To that end, a motivational attributes scale, including finance, environment, local value creation, and symbolism, was adapted from a previous study. A hierarchical multiple linear regression was used to analyze which motivational attributes predict participants’ willingness to participate in future CiFi PV projects.

Results

While participants were primarily male, more affluent, better educated and politically more left-leaning than the average Swiss population, participants covered a wide range of sociodemographic characteristics and worldviews. Though CiFi PV is primarily marketed toward tenants, half of the participants were homeowners. Participants perceived themselves as energy citizens contributing to the energy transition and environmental preservation rather than as investors or energy producers. The regression analysis shows that motivations are relevant in explaining willingness to participate in future CiFi PV projects. We found that environmental, financial and local value creation-related motivational attributes are highly significant predictors, as well as slightly less significant symbolic attributes.

Conclusions

These results suggest that CiFi PV projects represent a material form of energy citizenship going beyond mere consumerism by enabling individuals to contribute to the energy transition. Given their capacity to engage diverse publics, policymakers should endorse projects emphasizing individual participation alongside non-commercial community-based models. This would require their integration into existing regulatory frameworks. Future energy citizenship studies should further explore how individuals perceive and conceptualize what it means to be an energy citizen.
Totally thoracoscopic atrial fibrillation surgery following massive small bowel resection due to superior mesenteric artery embolization: report of two cases
Authors: Nakayama Taisuke , Nakamura Yoshitsugu , Niitsuma Kusumi , Ushijima Masaki , Yasumoto Yuto , Kuroda Miho , Nakamae Kosuke , Minamidate Naoshi , Hayashi Yujiro , Tsuruta Ryo , Ito Yujiro , Furutachi Akira , Yusa Hiroaki
Published: June 2024

Background

Thromboembolic occlusion of the superior mesenteric artery (SMA) is a grave complication in individuals diagnosed with atrial fibrillation (AF). This condition often necessitates extensive bowel resection, culminating in short bowel syndrome, which presents challenges for anticoagulant administration and/or antiarrhythmic therapy.

Case presentation

Presented here are findings of two patients, aged 78 and 72 years, respectively, who underwent comprehensive thoracoscopic AF surgery subsequent to extensive small bowel resection following SMA embolization. In each, onset of AF precipitated an embolic event, while the concurrent presence of short bowel syndrome complicated anticoagulation management. Total thoracoscopic AF surgery, comprised stapler-closure of the left atrial appendage (LAA) and bilateral epicardial clamp-isolation of the pulmonary veins, an operative modality aimed at addressing AF rhythm control and mitigating embolic events such as cerebral infarction, led to favorable outcomes in both cases. Additionally, computed tomography (CT) conducted one month post-surgery revealed the absence of residual tissue in the LAA, with the left atrium demonstrating a well-rounded, spherical shape. At the time of writing, the patients have remained asymptomatic following surgery regarding thromboembolic and arrhythmic manifestations for 29 and 10 months, respectively, notwithstanding the absence of anticoagulant or antiarrhythmic pharmacotherapy. Additionally, electrocardiographic surveillance has revealed persistent sinus rhythm.

Conclusions

The present findings underscore the feasibility and efficacy of a total thoracoscopic AF surgery procedure for patients presented with short bowel syndrome complicating SMA embolization, thus warranting consideration for its broader clinical application.
One Health Risk and Disease (OHRAD): a tool to prioritise the risks for epidemic-prone diseases from One Health perspective
Authors: Yasobant Sandul , Bhavsar Priya , Lekha K. Shruti , Patil Shailee , Falkenberg Timo , Bruchhausen Walter , Saxena Deepak
Published: June 2024

Background

The rise in epidemic-prone diseases daily poses a serious concern globally. Evidence suggests that many of these diseases are of animal origin and contribute to economic loss. Considering the limited time and other resources available for the animal and human health sectors, selecting the most urgent and significant risk factors and diseases is vital, even though all epidemic-prone diseases and associated risk factors should be addressed. The main aim of developing this tool is to provide a readily accessible instrument for prioritising risk factors and diseases that could lead to disease emergence, outbreak or epidemic.

Methods

This tool uses a quantitative and semi-quantitative multi-criteria decision analysis (MCDA) method that involves five steps: Identifying risk factors and diseases, Weighting the criteria, Risk and disease scoring, Calculating risk impact and disease burden score, and Ranking risks and diseases. It is intended to be implemented through a co-creation workshop and involves individual and group activities. The last two steps are automated in the MS Excel score sheet.

Results

This One Health Risk and Disease (OHRAD) prioritisation tool starts with an individual activity of identifying the risks and diseases from the more extensive list. This, then, leads to a group activity of weighing the criteria and providing scores for each risk and disease. Finally, the individual risk and disease scores with the rankings are generated in this tool.

Conclusions

The outcome of this OHRAD prioritisation tool is that the top risks and diseases are prioritised for the particular context from One Health perspective. This prioritised list will help experts and officials decide which epidemic-prone diseases to focus on and for which to develop and design prevention and control measures.
Addressing the Historic Challenges of BRCA1 and BRCA2 Variant Curation and the Need for More Diverse Representation
Authors: Chavarri-Guerra Yanin , Weitzel Jeffrey N.
Published: June 2024

Advancements in variant curation challenges: minority representation and incomplete data reporting
Enhancing Cancer Care Through Quality Initiatives: The Uganda Cancer Institute Experience With the Quality Oncology Practice Initiative
Authors: Bogere Naghib , Were Erick , Asasira Judith , Orem Jackson
Published: June 2024

Cancer care in low- and middle-income countries (LMICs) faces numerous challenges, such as limited resources, infrastructure constraints, and a shortage of specialized training. To address these challenges, innovative quality improvement (QI) approaches are required. The Quality Oncology Practice Initiative (QOPI) by the ASCO provides a framework for improving care quality through evidence-based standards. This article explores how QOPI has been adapted to the local context of the Uganda Cancer Institute (UCI) and highlights the importance of aligning international best practices with local health care realities to bridge disparities in care standards. The adaptation of the QOPI program at UCI commenced with a collaborative meeting with the ASCO-QOPI team in 2020. A tailored implementation plan was developed focusing on incorporating ASCO's QOPI measures and additional metrics relevant to the Ugandan context, engaging multidisciplinary teams, and optimizing resource use by leveraging existing resources for data collection and analysis. The execution of the plan relied heavily on staff training, participatory data collection, and continuous quality improvement processes that utilized data-driven methodologies. A retrospective analysis of QOPI data of UCI from 2020 to 2023 shows significant improvements in oncology care quality, highlighted by an upward trend in QOPI assessment scores across various metrics. These reflect the journey of UCI toward aligning its oncology care practices with international standards despite facing significant challenges. UCI's experience demonstrated the feasibility and impact of implementing international QI programs in LMICs. The success demonstrates that significant improvements in cancer care quality can be achieved in resource-constrained settings through adaptability, stakeholder engagement, and strategic resource optimization. UCI's journey is a model for other LMICs seeking to raise their cancer care standards, demonstrating that QI is necessary and attainable worldwide.
Obecabtagene autoleucel (obe-cel, AUTO1) in adults with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL): Overall survival (OS), event-free survival (EFS) and the potential impact of chimeric antigen receptor (CAR)-T cell persistency and consolidative stem cell transplantation (SCT) in the open-label, single-arm FELIX phase Ib/II study.
Authors: Jabbour Elias , Tholouli Eleni , Sandhu Karamjeet S. , Shaughnessy Paul , Barba Pere , Guerreiro Manuel , Yallop Deborah , Logan Aaron , Abedi Mehrdad , Lao-Sirieix Pierre , Zhang Yiyun , Brugger Wolfram , Pule Martin A. , Shah Bijal D. , Bishop Michael Russell , Park Jae H. , DeAngelo Daniel J. , Peggs Karl , Roddie Claire
Published: June 2024

6504

Background: Obe-cel is an autologous CAR-T cell product with a fast off-rate CD19 binder designed to mitigate immunotoxicity and improve expansion/persistence. Pooled results from the pivotal FELIX phase Ib/II study (NCT04404660) of obe-cel in adults with R/R B-ALL were recently presented (Roddie C et al. Blood 2023;142[Suppl 1]:222). Here, OS and EFS in all patients (pts) treated with obe-cel are reported, alongside the impact of CAR-T cell persistency and consolidative SCT for pts in remission. Methods: Pts aged ≥18 yrs with R/R B-ALL were enrolled. CAR-T products were generated via an automated process (Roddie C et al. Blood 2023;142[Suppl 1]:222). Pts received bridging therapy as appropriate and underwent lymphodepletion (fludarabine, 4×30mg/m2; cyclophosphamide, 2×500mg/m2), followed by obe-cel split dose infusions on Days 1 and 10 based on pre-lymphodepletion leukemic burden at a target dose of 410×106 CAR-T cells. Results: A total of 127/153 (83%) enrolled pts were infused. At screening, pts’ median age was 47 yrs; 42%/31%/44% had received prior blinatumomab/inotuzumab ozogamicin/allogeneic SCT; median bone marrow blast burden was 36% (range: 0−100). At data cut-off (13 September 2023), median follow-up was 16.6 mos (range 3.7−36.6 mos). The overall complete remission or complete remission with incomplete count recovery rate among infused pts was 78%. Among responding pts, 17/99 (17%) proceeded to consolidative SCT while in remission; all 17 (100%) were in measurable residual disease (MRD)-negative remission (≤10–4 leukemic blasts) and 10/17 (59%) showed CAR-T cell persistency prior to SCT. Loss of CAR-T cell persistency was associated with a hazard risk of relapse or death 2.9 times compared with pts who had ongoing CAR-T cell persistency. Pts who experienced B-cell recovery had a hazard risk of relapse or death 1.7 times compared with pts without B-cell recovery. At 12 mos, the EFS rate was 50% and 43% with or without censoring for consolidative SCT or new therapies, respectively; the OS rate was 61% and 59% with or without censoring for SCT, respectively. Conclusions: Ongoing CAR-T cell persistency and B-cell aplasia were associated with improved EFS without further consolidation post-obe-cel. At the current follow-up, consolidative SCT for pts in MRD-negative remission post-obe-cel did not improve EFS or OS. Clinical trial information: NCT04404660 .
Phase I study of CN201, a novel CD3xCD19 IgG4 bispecific antibody, in adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia.
Authors: Wang Ying , Yin Qingsong , Ren Jinhai , Zhou Hongsheng , Gong Tiejun , Zhu Feng , Zhang Xi , Wen Qin , Mei Heng , Huang Wei , Li Haiying , Wang Jianxiang
Published: June 2024

6505

Background: Patients with relapsed or refractory B-cell acute lymphoblastic leukaemia (B-ALL) still need more and better treatment options. CN201 is a novel CD19-targeting T-cell-engaging IgG4 bispecific antibody. This phase I study is to investigate the safety, tolerability and preliminary efficacy of CN201 in B-ALL (ClinicalTrials.gov identifier: NCT05579132). The data from the dose escalation and expansion of the ongoing study is presented. Methods: The study is enrolling patients with B-ALL who are refractory to primary induction therapy or to salvage therapy, or relapse. Patients with Philadelphia chromosome-positive after two or more tyrosine kinase inhibitors (TKIs) were eligible. Single-agent CN201 was administered intravenously once per week with a step-up dose approach during cycle 1, a priming dose on Day 1 followed by an intermediate dose on Day 8 and the target dose administered on Day 15 and thereafter. The patients will receive 2 cycles of CN201 for induction. Responders will continue to receive a further 3 cycles for consolidation, and up to an additional 7 cycles for maintenance treatment or until PD or unacceptable toxicity. Results: As of January 31, 2024, 42 adult patients received CN201 with full dose from 600 μg to 40mg. 37 patients were evaluable for efficacy (Table1). Maximum tolerated dose has not reached. The most common adverse events (≥20%) of grade 3 or higher were leukopenia (47.6%), lymphopenia (42.9%), neutropenia (38%), thrombopenia (33.3%) , anaemia (26.2%). 6 patients (14.3%) had infections of grade 3 or higher. Cytokine release syndrome occurred in 13 (30.9%) patients, mainly occurred following the first dose, most were low-grade, except for one patient with grade 3. No immune effector cell-associated neurotoxicity syndrome was observed. Overall, 11 (30%) of 37 patients had complete remission (CR), 1 (2.7%) patient had complete remission with incomplete haematological recovery (CRi), 75% of responders had MRD negativity. The CR rate significantly increased with dose descalation, reached 50% (4 of 8 patients) with 10mg target dose, two of those occurred within the first two weeks following CN201 treatment. Among those responders, 100% were MRD negative. The CR rate in patients with higher dose levels are under investigation. Conclusions: Preliminary data show CN201 has a well tolerable safety profile and promising activity in adult patients with relapsed or refractory ALL. Clinical trial information: NCT05579132 . [Table: see text]
Recombinant Erwinia asparaginase (JZP458) in acute lymphoblastic leukemia/lymphoblastic lymphoma (ALL/LBL): Post hoc analysis of adverse events of interest from AALL1931.
Authors: Aoki Etsuko , Maese Luke Devon , Loh Mignon , Agarwal Shirali , Chandrasekaran Vijayalakshmi , Liang Yali , Dronamraju Nalina , Iannone Robert , Silverman Lewis B. , Raetz Elizabeth A. , Rau Rachel
Published: June 2024

6521

Background: The pivotal Children’s Oncology Group Study AALL1931 (NCT04145531) evaluated JZP458, a recombinant Erwinia asparaginase (ASP), in patients with ALL/LBL who developed hypersensitivity/silent inactivation to E. coli-derived ASPs, leading to approval of JZP458 by the FDA and EMA. Primary efficacy and safety data have been reported; here, we report on adverse events of interest (AEIs: allergic reaction, pancreatitis, thrombosis, hepatotoxicity) and nausea/vomiting, and summarize post hoc descriptive analyses of AEIs by timing and known risk factors (eg, age and ethnicity). Methods: Each pegylated E. coli ASP remaining on treatment was replaced by 6 doses of JZP458 administered Monday/Wednesday/Friday (MWF). Three intramuscular (IM) cohorts (1a [25 mg/m2 MWF], n=33; 1b [37.5 mg/m2 MWF], n=83; and 1c [25/25/50 mg/m2 MWF], n=51) and 1 intravenous (IV) cohort (25/25/50 mg/m2 MWF, n=61) were evaluated. Results: Rates of any-grade treatment-related allergic reactions, pancreatitis, thrombosis, increased ALT/AST, and increased bilirubin were 11%, 7%, 1%, 16%, and 7% in the total IM cohort and 26%, 5%, 2%, 18%, and 5% in the IV cohort, respectively. Rates of treatment-related grade ≥2 nausea/vomiting (N/V) were 32% and 64% in the total IM and IV cohorts. Table shows the median number of JZP458 doses on or before the first AEI. Notably, rates of grade ≥2 N/V events were similar after 25 and 50 mg/m2 dosing. Subgroup analyses showed no consistent trends in the rates of any-grade AEIs by age except for pancreatitis where rates were numerically higher in patients aged 12 to <18 (9/62 [15%]) and ≥18 years (4/31 [13%]) than in those aged 6 to <12 (1/71 [1%]) or <6 years (1/64 [2%]). Overall, incidences of any-grade treatment-related allergic reactions, pancreatitis, thrombosis, increased ALT/AST, and increased bilirubin among Hispanic patients (n=74) were 12%, 5% 1%, 19%, and 7% respectively, similar to non-Hispanic patients (n=140). Conclusions: The safety profile of JZP458 is consistent with other ASPs in patients with ALL/LBL and generally similar across age and ethnicity subgroups. Clinical trial information: NCT04145531 . [Table: see text]
Safety and efficacy of olutasidenib treatment in elderly patients with relapsed/refractory mIDH1 acute myeloid leukemia.
Authors: De Botton Stéphane , Jonas Brian Andrew , Ferrell P. Brent , Chao Mwe Mwe , Mims Alice S.
Published: June 2024

6527

Background: Elderly patients with relapsed/refractory (R/R AML) are a special population that may elevate safety concerns, which must be balanced with clinical benefit. Olutasidenib (OLU), a targeted therapy for m IDH1 AML, was well tolerated in a registrational, Ph2, open-label, multicenter trial and, in the pivotal cohort, demonstrated complete remission (CR) or CR with partial hematologic recovery (CRh) in 35% of patients (age 32-87 years, y) for a median duration of 25.9 months. We evaluated safety and efficacy of OLU in the elderly subgroup (≥75y) with m IDH1 AML. Methods: In the Phase 2 trial, the pivotal cohort enrolled adults with R/R m IDH1AML. OLU was administered at 150 mg BID. Adverse events (AE) and lab values were collected at least monthly and graded based on the NCI CTCAE Version 4.03. Efficacy was based on response criteria of the International Working Group in AML (2003). Results: 153 patients received OLU monotherapy, 147 had centrally-confirmed mIDH1 AML, , and 45 were ≥75y (range 75-87) at study entry. Of the 45 elderly patients, 27 (60%) were male, 51% had ECOG=1, 16% had ECOG =2, 71% were relapsed, 29% had refractory AML, 58% had prior HMA, 11% received prior venetoclax, and none had prior stem cell transplant. Median bone marrow blasts were 43% (5-93). Genetic co-mutations included FLT3 in 9%, NPM1 in 20%, and TP53 in 2%. Grade 3 or 4 adverse events were reported in 45.8% of elderly patients; the most common were decreases in red blood cells (31%), platelets (13%) and neutrophils (10%) as well as febrile neutropenia (15%). AEs were consistent with published pivotal Phase 2 results, with no new safety signals. Deaths occurred in 19 patients due to disease progression (9), pneumonia (2), sepsis (2), GI haemorrhage (1), aortic stenosis (1), atrioventricular block (1), cardiac failure congestive (1), acute kidney injury (1) and other (1). The response to OLU therapy is summarized in the table. 31% of patients ≥75 y achieved CR/CRh; median time to CR/CRh was 1.5 mos (0.9-5.6) and median duration of CR/CRh was 25.9 mos (95%CI 7.4, not reached). Conclusions: Olutasidenib was generally well tolerated in elderly patients with R/R m IDH1AML and induced durable remissions. Despite the challenges of treating elderly patients who had already failed prior AML treatment, the results suggest that elderly patients can benefit from therapy with olutasidenib. Clinical trial information: NCT02719574 . [Table: see text]
Improved survival for myeloid malignancy patients receiving thiotepa/cyclophosphamide (TT/Cy) versus total body irradiation/cyclophosphamide (TBI/Cy) conditioning and allogeneic stem cell transplantation.
Authors: Nichols Cydney , Ervin Kirsten , Schmidt Caitlin , Schwartz Jennifer E. , Abu Zaid Mohammad Issam , Robertson Michael J. , Abonour Rafat , Grove Meagan , Thakrar Teresa , Farag Sherif
Published: June 2024

6555

Background: TBI/Cy is a commonly used conditioning regimen prior to allogeneic stem cell transplant (SCT). Chemotherapy only regimens, mostly containing busulfan, have been shown to be effective and less toxic in patients with myeloid malignancies. Here, we present the largest reported experience with a non-busulfan myeloablative chemotherapy regimen of TT/Cy in myeloid malignancy patients undergoing allogeneic SCT and compare outcomes with TBI/Cy. Methods: Patients with myeloid malignancies receiving allogeneic SCT at Indiana University from 2007-2020 were included. TT/Cy consisted of TT 15 mg/kg and Cy 120 mg/kg. TBI/Cy consisted of 13.2 Gy in 8 fractions and Cy 3600 mg/m2. The primary endpoint was overall survival (OS). Secondary endpoints included relapse-free survival (RFS), engraftment, and toxicities within the first 100 days. Median follow up for surviving patients is 2,046 (range 816-5,572) days. Results: 225 patients with AML (n=160), CML (n=45), and MDS (n=30) of median age 44 (range 19-59 years) received conditioning with TT/Cy (n=159) or TBI/Cy (n=66). Baseline characteristics were similar. For TT/Cy patients, the median OS was not reached, and 4-year OS was 57.2% (95% confidence interval [CI], 49.2-65.2%), which was significantly better than with TBI/Cy, with median OS 373 days and 4-year OS 33.9% (95% CI, 22.3-45.5%; p<.001). Similarly, for TT/Cy patients, the median RFS was not reached and 4-year RFS was 59.2% (95% CI, 52-67.2%), significantly better than median RFS of 341 days and 4-year RFS 35.2% (95% CI, 23.7-46.9%; p<.001) for recipients of TBI/Cy. On multivariable analysis adjusting for age, sex, diagnosis, disease risk, comorbidity index (HCI), and degree of stem cell source, TT/Cy had significantly lower risk of death (HR 0.44, 95% CI, 0.30-0.65; p<.001) together with female sex (p=.03) and lower HCI (p=.046). As shown in the Table summarizing secondary endpoints, TBI/Cy was associated with significantly higher rates of mucositis, sinusoidal obstruction syndrome (SOS), TPN usage, multiorgan failure, and length of stay of primary admission. Conclusions: TT/Cy is an efficacious regimen for patients with myeloid malignancies undergoing myeloablative allogeneic SCT with less toxicity and improved RFS and OS compared with TBI/Cy. TT/Cy should be compared to other non-TBI containing busulfan-based regimens. [Table: see text]