bluuebunny/crossref_metadata_2025 huggingface dataset:
Jan Fokkes Holwarda. A Gassendist in Franeker, Between Intellectual Debt and Plagiarism
Authors: Palmerino Carla Rita
Published: December 2023

This article explores Gassendi’s influence on the Franeker professor Jan Fokkes Holwarda (1618–1651), author of a posthumously published Philosophia naturalis, seu physica vetus-nova (1651). In the section of the book devoted to celestial physics, Holwarda pays homage to the ‘Gallic Lynx, Pierre Gassendi’ and discusses at length his astronomical observations. Gassendi’s name, by contrast, does not figure in the section on general physics, where Holwarda endorses atomism and the new science of motion. Some scholars suggested a possible influence of Gassendi on Holwarda’s matter theory, while others denied it. As the present article shows, most chapters of the Physica generalis are in fact extensively plagiarized from, or inspired by, Gassendi’s letters De apparente magnitudine solis humilis et sublimis (1642), De motu impresso a motore translato (1642), and the Animadversiones (1649). This dishonest practice conceals, however, a very good grasp of Gassendi’s philosophy. Holwarda manages to integrate the many bits and pieces he steals from Gassendi’s works into a coherent and concise account of the properties and behavior of atoms and compound bodies.
Nataša Jagdhuhn, “Post-Yugoslav Metamuseums: Reframing Second World War Heritage in Postconflict Croatia, Bosnia and Hercegovina, and Serbia”, Palgrave Macmillan, 2022, 259 pp.
Authors: Trajanovski Naum
Published: December 2023

The article is a review of Post-Yugoslav Metamuseums: Reframing Second World War Heritage in Postconflict Croatia, Bosnia and Herzegovina, and Serbia, by Nataša Jagdhuhn, Palgrave Studies in Cultural Heritage and Conflict; Palgrave Macmillan, 2022, 259 pp. ISBN 978-3-031-10227-1
Association of Endothelial Nitric Oxide Synthase and Angiotensin-Converting Enzyme Genes Polymorphism With In-Sent Restenosis of Bare Metal Stents vs Drug-Eluting Stents in Egyptians
Authors: Abdelaziz Tarek A , Mohamed Randa H , Saadawy Sara F
Published: December 2023

Despite its unequivocal superiority compared with balloon angioplasty, coronary stenting did not abolish restenosis. We aimed to evaluate the associations between a common single nucleotide polymorphism occurring in endothelial nitric oxide synthase (eNOS) and angiotensin-converting enzyme (ACE) genes and the risk of in-stent restenosis (ISR) of bare metal stents vs drug-eluting stents (BMS vs DES) implanted in Egyptian patients. Two hundred patients who had coronary stenting were divided into group I ( n = 98) who received a BMS and group II ( n = 102) who received a DES. eNOS and ACE genes polymorphism were analyzed by polymerase chain reaction (PCR). We found that the GA and AA genotypes of the eNOS gene were associated with the ISR with both BMS and DES. However, the ACE gene was not associated with ISR. We concluded that eNOS gene polymorphism is associated with ISR. Hypertension, stent length, and AA genotype of the eNOS gene were found to be independent predictors of the occurrence of ISR after both BMS and DES use.
Sitting Ducks Post-COVID? Work Organisation and Compounded Health Risks for Darjeeling Tea Workers
Authors: Rasaily Rinju
Published: December 2023

This article argues that burgeoning economic uncertainty, competitiveness of commodity production after COVID-19 and labour reforms may facilitate the industry to reorganise work arrangements through labour flexibilisation and mechanisation, accentuate health precarity, and nefariously push the disenfranchised Darjeeling tea labour further into oblivion. Workers’ access to basic healthcare services for illnesses and diseases such as fevers, diarrhoea, dysentery, anaemia, and hypertension pivots on the fragile lines of power and ethno-gender that are deeply embedded in plantation societies. Subsequently, social distancing as a preventive everyday measure during the pandemic appears to have reinforced both class and caste divide among these communities. The tangible absence of a robust health infrastructure in the Darjeeling hills exposes the undeniable shift in the responsibility of healthcare by the tea garden management on workers’ households and the samaj, as a social collective in managing illness and care.
High-modern Food Systems in the USA: A Framework for Analysis and Change
Authors: Berkenpas Josh
Published: December 2023

Food production in the USA is dominated by a high-modernist ideology and industrial agricultural practices. A wide range of scholars, journalists, and activists have documented the negative impacts of industrial agriculture on human health and welfare in the USA and the world. This article provides a framework for understanding the US food system to see how power is exercised, and to learn what avenues for reform are available to citizens today. This article develops a holistic approach to understanding food systems in the USA and the world. Also highlighted are increasing demands for food justice and the need for greater political activism in food democracy.
The Education ‘Fads’ in India
Authors: Tilak Jandhyala B. G.
Published: December 2023

This article makes a critical commentary on a few popular opinions on education, which are indeed based on distorted understanding of the nature and functions of education and myopic short-term perspectives and desires. Further, it stresses the need to correct them, so that education serves the broader social purposes.
Book review: Sebastian Schwecke, Debt, Trust, and Reputation: Extra-legal Finance in Northern India
Authors: Nath Maanik
Published: December 2023

Sebastian Schwecke, Debt, Trust, and Reputation: Extra-legal Finance in Northern India. Cambridge University Press, 2022, 384 pp., ₹1,195.00, ISBN: 978-1-316-51726-0 (Hardcover)
On Populism and Civil Society: The Challenge to Constitutional Democracy by Andrew Arato and Jean L. Cohen
Authors: Lara María Pía
Published: December 2023

I will critically explore Arato and Cohen’s work on populism acknowledging areas of agreement while noting gaps in their reasoning particularly regarding the complex relations between capitalism and democracy and the recent erosion of democracy replacing it with authoritarian regimes that are better suited for neoliberal policies.
Does Strategic Planning & Planning Resources Influence the Performance of Financial Institutions? Roles of Managerial Involvement and Institutional Capability
Authors: Ejigu Meseret Ebabu
Published: December 2023

This article examines how does strategic planning & planning resources influence the performance of financial institutions in Ethiopia? Besides this, the study investigates the mediating role of institutional capability & moderating role of managerial involvement. The study used cross-sectional research that relied on survey. This study employs Hierarchical Linear Model (HLM) and MLMED for mediation hypothesis. These data consisted of 142 managers from 35 different financial institutions. This study expands the knowledge edge in the field of strategic management through the discovery that strategic planning affects the performance of financial institutions directly, and indirectly through the mediation of institutional capability and managerial involvement has moderating role on the relationship between strategic planning & financial performance, which has a positive and significant effect. The results of this study have guidance for managers how to configure strategic planning & planning resources to obtain competitive advantage through institutional capability to enhance the performance of financial institutions. Implications of the findings are explained with theoretical contribution; recommendations and future research are discussed.
Anatomical and Physiological Changes Following Primary Palatoplasty Using “The Buccal Flap Approach”
Authors: Haenssler Abigail E. , Mann Robert , Gilbert Imani R. , Snodgrass Taylor , Mann Samuel , Kampfshulte Andy , Perry Jamie L.
Published: December 2023

Objective

The purpose of this study was to determine the anatomical differences among selected individuals with a cleft palate repaired using “The Buccal Flap Approach” during primary palatoplasty compared to aged-matched participants without cleft palate.

Design

Observational, prospective.

Setting

Two regional hospitals.

Participants

A total of 30 adult males consisting of 15 adults born with cleft palate who received the Double Opposing Z-Plasty plus Buccal Flaps (DOZP  +  BF) repair at the time of primary palatoplasty and no history of secondary speech surgery or orthognathic surgery and 15 adults without a history of cleft palate.

Interventions

All participants underwent MRI to visualize anatomy.

Main Outcome Measures

Ten velopharyngeal and craniofacial anatomical measures.

Results

No statistically significant differences between groups were observed for velar thickness, velar length, pharyngeal depth, NSBa angle, SNB angle, or levator veli palatini length. Individuals with the DOZP  +  BF presented with a greater effective velar length (p < .001), greater effective VP ratio (p < .001), smaller SNA angle (p < .001), and smaller maximal velar stretch (p < .001) compared to the control participants.

Conclusions

This study suggests that adult males who received the DOZP  +  BF repair at the time of primary palatoplasty and no history of secondary speech surgery or orthognathic surgery present with a longer effective velar length and larger effective VP ratio in comparison to the non-cleft group. Future research is needed to compare patients with and without favorable outcomes from multiple surgical types to fully understand how surgical techniques alter the anatomy.
Ablative 5-Fraction Stereotactic MRI-Guided Adaptive Radiotherapy for Oligometastatic Pancreatic Adenocarcinoma
Authors: Webking Samantha , Sandoval Maria L. , Chuong Michael D. , Ucar Antonio , Aparo Santiago , De Zarraga Fernando , Sahin Ibrahim , Biachi Tiago , Kim Dae W. , Hoffe Sarah E. , Frakes Jessica M. , Palm Russell F.
Published: December 2023

Introduction

Metastatic pancreatic ductal adenocarcinoma (PDAC) carries a poor prognosis and significant morbidity from local tumor progression. We investigated outcomes among oligometastatic PDAC patients treated with stereotactic magnetic resonance image-guided ablative radiotherapy (SMART) to primary disease.

Methods

We performed a retrospective multi-institutional analysis of oligometastatic PDAC at diagnosis or with metachronous oligoprogression during induction chemotherapy treated with primary tumor SMART. Outcomes of interest included overall survival (OS), progression-free survival (PFS), freedom from locoregional failure (FFLRF), and freedom from distant failure (FFDF). Acute and late toxicity were reported and in exploratory analyses patients were stratified by the number of metastases, SMART indication, and addition of metastasis-directed therapy.

Results

From 2019 to 2021, 22 patients with oligometastatic PDAC (range: 1–6 metastases) received SMART to the primary tumor with a median follow-up of 11.2 months from SMART. Nineteen patients had de novo synchronous metastatic disease and three had metachronous oligoprogression. Metastasis location most commonly was liver only (40.9%), multiple organs (27.3%), lungs only (13.6%), or abdominal/pelvic nodes (13.6%). All patients received either FOLFIRINOX (64%) or gemcitabine/nab-paclitaxel (36%) followed by SMART (median 50 Gy, 5 fractions) for local control (77%), pain control (14%), or local progression (9%). Additionally, 41% of patients received other metastasis-directed treatments. The median OS from diagnosis and SMART was 23.9 months and 11.6 months, respectively. Calculated from SMART, the median PFS was 2.4 months with 91% of patients having distant progression, and 1-year local control was 68. Two patients (9%) experienced grade 3 toxicities, gastric outlet obstruction, and gastrointestinal bleed without grade 4 or 5 toxicity.

Conclusion

There was minimal morbidity of local disease progression after SMART in this cohort of oligometastatic PDAC. As systemic therapy options improve, additional strategies to identify patients who may derive benefits from local consolidation or metastasis-directed therapy are needed.
Thinking methodologies with textiles, thinking textiles as methodologies in the context of transitional justice
Authors: Pérez-Bustos Tania , Bello-Tocancipá Andrea
Published: December 2023

In this paper, we examine the methodological possibilities of working with personal textile objects, such as clothes in need of mending, beloved personal blankets, and knotted rag dolls. Our focus is on a transdisciplinary project that sought to collectively explore how the bodies of professionals working for the Colombian Transitional Justice System are affected when engaging with narratives of war and conflict. We contend that textile making in this context serves a dual methodological purpose when facilitating spaces of careful research. Firstly, this material practice enables participants to pause and immerse themselves in their own experiences, something that in turn is generative of personal reflections. Secondly, the created objects become appreciation devices capable of documenting and eliciting memories that continually engage participants and researchers in new inquiries. Consequently, this paper contributes to the understanding of object-oriented methodologies as inherently relational and situated. Moreover, it aims to comprehend textile making practices as capable of unfolding care as a research practice.
Governance of religious diversity in Central Europe: A religious nationalism inspired illiberal turn in Hungary and Slovakia?
Authors: Vékony Dániel , Račius Egdūnas
Published: December 2023

Central European countries with a historically dominant Roman Catholic heritage belong to a particular cluster in respect to the governance of religion. This paper focuses on Hungary and Slovakia and addresses the effect of religious nationalism on the regimes of governance of religion in the two countries. After the fall of the Berlin Wall, there was a brief period of neutral stance towards religion, which was characterized by liberal values. With the introduction of the bilateral Concordat agreements with the Holy See, both countries started to treat traditional Christian Churches preferentially. By the 2010s legislation in both countries created restrictive entry barriers for “new” religions. This created two or multi-tiered systems for “old” and “new” religions, in which the former enjoyed closer relationship with the state. As a result, the separation of church and state has become blurred. Preferentially treated churches reappeared in the public space as providers of certain educational and social services. Preferentially treated churches and the state developed asymmetrically interdependent relationships, the state having the upper hand. Meanwhile, increasingly populist and nationalist parties instrumentalized religion by involving Christianity in their nationalistic political discourse. This helped create a normative space, in which the state is able to give further preferential treatment to certain religious groups over others. The emphasis on Christian national identity underpinned these governments’ narratives that conflates migration with security and Islam, which pushed those religious groups on the margins, which do not fit in the religious nationalist narrative of the increasingly right- and populism-leaning governing elite.
Simultaneous quantification of tiotropium bromide impurities G + H in capsule formulation by LC-MS/MS
Authors: Erkol Serdar , Güleli Müge , Çalışkan Cem , Kocaoba Sevgi
Published: December 2023

Tiotropium Bromide is a long-acting bronchodilator that is used in the treatment of chronic obstructive pulmonary disease (COPD) and asthma bronchodilator or bronchiolitis, which are substances that expand the bronchi and reduce resistance in the respiratory tract and increase airflow to the lungs. For Tiotropium Bromide found in inhaler capsules to treat COPD, determining the relevant impurities G and H, which are not UV active, is crucial. For this purpose, a new and sensitive liquid chromatography triple-quadrupole mass spectrometry (LC-MS/MS) detection with electrospray ionization by using multiple reaction monitoring in the positive mode method was developed and validated. The identity of the compounds was supported by using LC-Q/TOF. All chromatographic studies were performed with a Zorbax Eclipse XDB-C8 (150 mm x 4.6 mm, 5.0 µm) column with a total injection time of 13 min at a flow rate of 0.4 ml/min as a gradient. The limit of detection (LOD) and limit of quantitation (LOQ) in the current study range were determined as 1.0 ppb and 2.5 ppb, respectively. The results of the validation parameters following the ICH Q2(R1) guideline were determined within the acceptance criteria.
Diving Deep for Sleep: How pH and Blood Volume in the Lateral Hypothalamus Impact REM
Authors: Simeone Kristina
Published: December 2023

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KNOCK, KNOCK, KNOCK-IN ON GABA’S DOOR: GABRB3 Knock-in Mutation Causes Infantile Spasms in Mice
Authors: Stafstrom Carl E.
Published: December 2023

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What Is My IQ: Cognitive Outcomes in Children With Fetal Exposure to Newer Anti-Seizure Medications
Authors: Becker Danielle A.
Published: December 2023

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The innovative competence of university teachers to improve learning: A comparative study of Bolivia, Spain and Mexico
Authors: Rodríguez-Legendre Fidel , Fernández-Cruz Francisco José
Published: December 2023

The innovative competence of university teaching staff is a fundamental component in improving the quality of academic provision in higher education. The originality of the study lies in the contribution of a valid and reliable tool for the assessment of the innovative competence of university teaching staff. As a result, higher education institutions in different countries will be able to determine the training needs of their teachers in order to improve their innovative performance and, ultimately, student learning. The aim of the study is to identify, analyse and differentiate the innovative profile of a sample of university teachers working in Bolivia, Spain and Mexico. The research methodology (non-experimental and ‘ex-post-facto’) consists of applying a questionnaire to 1404 teachers from various universities in the countries involved. The results obtained suggest the need to structure specific teacher training strategies to remedy the deficiencies found in innovative competence in the three participating countries.
Resources and capability needs for teaching in dynamic technological environments: Evidence from schools in Harare, Zimbabwe
Authors: Chinakidzwa More , Chamba Lucy Tambudzai
Published: December 2023

The COVID-19 pandemic has necessitated the integration of digital technologies into teachers’ practice as most teaching moved online. However, an interrogation of the resource and capability needs for teaching in the dynamic technological environment remains missing. Therefore, the study sought to determine the resource and capability needs for teaching in a dynamic and technological online environment. The study was critical because learner context differs, thereby limiting the applicability of existing knowledge. In addition, existing knowledge remains inconclusive on the influence of various capabilities on teaching in dynamic technological environments. It was, therefore, crucial to provide empirical evidence from the Zimbabwean context. The study adopted a cross-sectional approach to data collection using a structured questionnaire. The population comprised teachers from selected schools in Harare. Due to the COVID-19 restrictions, the sample was conveniently chosen. A structural equation model was conducted using WarpPLS 7.0. The results show that technological capability (TechCap), technological experience (TechExp), and technological access (TechAcc) significantly influence teaching in technological environments (β = 0.41, p < .01; β = 0.31, p < .05 and β = 0.27, p < .01) respectively. Technological will (TechWill) was found not to significantly influence teaching (β = −0.05, p > .05). The study recommended the enhancement of teachers’ technological capability, experience and access. Further, the study made policy recommendations for pre-service and in-service training, capacity and infrastructure development programmes, and technology-integrated teaching and learning framework design.
A Study of Parent-Reported Internalizing Symptoms in Transgender Youths Before and After Childhood Social Transitions
Authors: Durwood Lily , Gallagher Natalie M. , Sifre Robin , Olson Kristina R.
Published: December 2023

Some children socially transition genders by changing their pronouns (and often names, hairstyles, and clothing) from those associated with their assigned sex at birth to those associated with their gender identity. We refer to children who have socially transitioned as transgender children. Using a prospective sample of children who socially transitioned during childhood (at or before the age of 12; age of transition: M = 6.82 years), we tested whether the parent-reported internalizing symptoms of transgender children were different before versus after they socially transitioned. The children were predominantly White (70.6% White) and girls (76.5% transgender girls, 23.5% transgender boys). Their parents tended to have high levels of education (74.5% bachelor’s degree or above) and lived in families with high household incomes (62.7% with household incomes of $75,000 or above). On average, youths showed lower levels of internalizing symptoms after socially transitioning versus before, suggesting a possible mental-health benefit of these transitions.
The perfect (shit)storm: Discourses around the proposal to introduce a ‘climate passport’ in Germany
Authors: Nash Sarah Louise
Published: December 2023

Since 2017 a debate has been ongoing in Germany around a proposal by the Green Party to introduce a ‘climate passport’ that would confer citizenship-like rights to people most likely to be displaced due to climate change. The debate, ranging from solidaristic work to open hostility, is highly Eurocentric, with the German border and affected people’s potential interactions with it providing a central ordering node in the debate. German voices and perspectives are foregrounded, and Germany is placed in a problem-solver position in relation to affected communities. By doing so, the positioning of Germany as able to control and define future acceptable human mobilities is centred. Affected people are positioned as the ‘other,’ which oscillates between Pacific Islanders and Africans depending on the speaker. Inhabitants of Pacific Islands are identified as recipients of the climate passport, as vulnerable individuals whose countries will inevitably be erased from the map by climate change. Africans, on the other hand, are portrayed as economic migrants waiting to take advantage of climate-related residency permits to migrate to Europe. Based on this analysis, I argue that the Eurocentrism of well-intentioned policy proposals to protect people forced to move in the context of climate change is a blind spot in policy circles and research that demands further attention.
Scoping Review to Identify Social Determinants of Maternal Health in Morocco
Authors: Moujahid Chaimae , Turman Jack E. , Houradi Hiba , Amahdar Loubna
Published: December 2023

To understand the mechanism of health inequities and their influence on maternal health, the Commission on Social Determinants of Health (CSDH) provides a framework to identify structural and intermediate causes of health inequity. This review maps and describes the current socioeconomic determinants of maternal health in Morocco according to the CSDH framework. A scoping study was carried out from six databases (Springer, Web of Science, Pubmed, Science Direct, Jstor, and Cochrane library) based on quantitative and qualitative research done since 1990. Structural factors such as women's employment and economic status, education level, culture, and gender equity were influenced by intermediary factors such as place of residence, age at marriage, maternal age at childbirth, and parity (either alone or in conjunction with other variables). Together these factors worked to influence maternal health service usage or affected maternal health outcomes. Power dynamics were identified in a variety of social situations that impacted access to health care for women across socioeconomic categories. Studies reveal how social determinants impact maternal health in Morocco. Addressing these determinants is required for sustainably improving maternal and infant health in Morocco.
Racial Disparities in Acute Myeloid Leukemia and Myelodysplastic Syndrome US FDA Drug Approval Trials
Authors: Shahzad Moazzam , Khalid Muhammad Fareed , Butt Atif , Khan Muhammad Haseeb , Amin Muhammad Kashif , Ammad Ud Din Mohammad , Jaglal Michael V.
Published: December 2023

Introduction

Young black patients with acute myeloid leukemia (AML) have remarkably worse outcomes than white patients of the same age. Compared to white patients, the death rate of young black patients is fivefold more within 30 days of starting treatment and twofold more within five years. Here we studied the demographic representation of different races in the AML and myelodysplastic syndrome (MDS) clinical trials that led to drug approval by the US Food and Drug Administration (FDA).

Methods

Data were collected from all the trials submitted to the FDA to support the approval of AML and MDS drugs from 2006 to 2022. A total of 17 trials were screened, and 10 trials that did not mention the race or ethnicity of the participants were excluded. Our analysis included six trials of AML drugs and one trial of MDS drugs. The methodological quality of the included studies was evaluated using the NIH quality assessment tool. The inter-study variance was calculated using the Der Simonian-Laird Estimator. Analysis for this study was performed using R version 4.1.2 and R Studio version 1.1.423 (R Project for Statistical Computing).

Results:

Seven FDA trials reported the race or ethnicity of the participants, and a total of 2484 patients from these trials were analyzed. (Table 1) Olutasidenib, glasdegib plus low dose cytarabine, gemtuzumab-ozogamicin, liposome-encapsulated combination of daunorubicin and cytarabine, ivosidenib, and midostaurin were approved for AML. An oral combination of decitabine and cedazuridine was approved for MDS. The median age of the participants was 69.5 years (0.003-94). The median follow-up time was 20.9 months (0-85.2), and 51% (n=1267) of the participants were male and female participants were 49 % (n=1217). The racial analysis of included patients showed 63.4% (n=1574) white, 5.7% (n=141) black, 3.9% (n=97) Asian, 0.2% (n=4) American Indian/Alaska Native, and 0.1% (n=2) Native Hawaiian or other Pacific Islander while 5.9% (n=147) of the patients belonged to other races. Data about race was not reported for 20.8% (n=519) of the patients. Cortes et al. (2018) reported the highest racial disparity with 97.7% (n=129) white patients and only 0.76% black patients (n=1), while Gamis et al. (2014) reported the highest number of black patients (n=116).

Conclusion:

Despite being affected adversely to a significant degree by AML, black patients are underrepresented in drug trials. More efforts should be made to include them in trials so that better treatment plans can be formulated for this underrepresented group of patients.
Alterations of Gut Microbiota Related with Status of Iron-Overload in Thalassemia Patients: A Cross-Sectional Pilot Study
Authors: Trirattanapa Kornkanok , Tantiworawit Adisak , Suparan Kanokphong , Sriwichaiin Sirawit , Kerdpoo Sasiwan , Punnachet Teerachat , Hantrakun Nonthakorn , Hantrakool Sasinee , Piriyakhuntorn Pokpong , Rattanathammethee Thanawat , Chaiadisaksopha Chatree , Ekarat Rattarittamrong Ekarat , Norasetthada Lalita , Chattipakorn Nipon , Chattipakorn Siriporn
Published: December 2023

Background: Gut dysbiosis can cause an impaired gut-barrier function and may contribute to the pathogenesis of various diseases. Iron overload is a common complication in thalassemia patients and can result in numerous complications, including those affecting the cardiovascular, endocrine, and immune systems. However, it is unclear how iron overload affects the gut microbiota of patients with thalassemia.

Objective: To characterize the profiles of the gut microbiome in thalassemia patients compared with healthy participants, as well as to determine the association of these profiles with iron status.

Method: Transfusion-dependent thalassemia (TDT) patients and healthy controls aged ≥ 18 years old were enrolled in the study. Stool samples were collected prior to receiving regular blood transfusions in the thalassemia group. Paired-end sequencing of 16s rRNA bacterial DNA extracted from each stool sample was performed. Serum ferritin levels were assessed in each participant to reflect iron status.

Results: A total of 14 adult TDT patients and 14 healthy controls were enrolled, with a similar proportion of age and sex. The TDT patients had a significantly higher iron overload status than the controls (median serum ferritin level = 1424 in the TDT group and 197 in the control group; p < 0.001). The Shannon diversity index demonstrated a significant increase in gut microbial diversity in TDT patients as compared to healthy controls (7.06 vs. 6.48; p = 0.001). The TDT group showed a higher abundance of several gram-negative bacterial phyla, such as Bacteroidota, but a reduction in the abundance of Actinobacteriota as compared to the control group. Serum ferritin levels showed a positive correlation with higher gut diversity index.

Conclusions: Our study suggests that TDT patients develop gut dysbiotic characteristics compared to the healthy population, with gut diversity associated with serum ferritin levels. This association suggests that iron overload induces gut dysbiosis.
Crosstalk between Megakaryocyte Niches Unveils the Origin of Immunoreactive Platelets
Authors: Rivera Cristobal , Silvestro Michele , Pratama Muhammad Yogi , Medvedovsky Steven , Ramkhelawon Bhama
Published: December 2023

Platelets play a prominent role in the pathophysiology of cardiovascular disease (CVD) however, the precise origin and function of pathological platelets remain elusive. While the bone marrow has been long established as a central site of platelet production, other important niches of platelet biogenesis have recently emerged. The role of platelets produced outside the bone marrow and the cross-communication between these niches remain incompletely understood. Here, we investigate the pathological role of lung-derived platelets in the development of immunothrombotic diseases. First, we show that blunting the Thrombopoietin receptor (TPOR) in the lungs of mice using CRISPR/Cas9 lentivirus modulates circulating platelet levels, adding support to existing literature that establishes the lungs as an important site of platelet biogenesis. Additionally, we designed a custom lead shield protecting the thoracic region in mice that conserved the lung hematopoietic niche following lethal irradiation. Combined lineage tracing and bone marrow transplantation from thrombocytopenic TPOR deficient donor mice into platelet/megakaryocyte reporter recipient mice (TdTomatoPF4 Cre)receiving lethal irradiation with shielding of the thorax, revealed that protection of hematopoietic niches in the lungs is sufficient to maintain serum platelet counts. Next, we explore the immunomodulatory role of lung-derived platelets by performing transplantation of TdTomatoPF4 Cre lung into wild-type donor mice. In the recipient mice, TdTomato platelets originating from the lungs were actively recruited to inflamed aortic sites, hijacked monocytes from the circulation, and regulated vascular remodeling. Additionally, targeted deletion of TPOR in the lungs by CRISPR/Cas9 lentivirus is protective against aortic inflammation and aneurysm development in mice. Secretome analysis identified a molecular signature of platelets that stems from the lungs that confer immunomodulatory properties to this subset. Our results reveal the critical role of the lungs as instrumental sites of molecularly distinct platelet subsets that could have far-reaching impacts on many immunothrombotic diseases.
A 46 Long Non-Coding RNAs Expression Signature Accurately Predicts Relapse and Acts As an Independent Prognostic Factor in Pediatric Acute Myeloid Leukemia
Authors: Ren Zhiyao , Vanhooren Jolien , Derpoorter Charlotte , De Moerloose Barbara , Lammens Tim
Published: December 2023

Risk stratification using cytogenetics, mutations and minimal residual disease (MRD) has allowed to increase the cure rates of pediatric acute myeloid leukemia (AML), reaching now up to 70% in contemporary protocols. Nevertheless, approximately 30% of patients still experience relapse, indicating that there is a need to optimize stratification strategies. Recently, long non-coding RNA (lncRNA) expression has been shown to hold prognostic power in multiple cancer types. Here, we built a 46 relapse-related lncRNAs prognostic signature, named AML lnc46, using 790 pediatric acute myeloid leukemia transcriptomes obtained from the Therapeutically Applicable Research To Generate Effective Treatments (TARGET) repository. Bootstrap validation (bootstrap resampling times = 1000) was used for internal validation and showed that the signature performed good in predicting the 1-, 2-, and 3-year relapse-free survival (RFS), with an area under the curve of 0.825, 0.824, and 0.822, respectively. Moreover, external validation using the TARGET repository validated the efficiency of the signature. Most importantly, we demonstrate that AML lnc46 not only is an independent predictor of RFS, but also identifies patients who were assigned a different risk-group by currently-used classification methods. In conclusion, the identified AML lnc46 might, after further prospective validation, provide additional information to guide management of pediatric AML patients.

Figure 1. (A) Kaplan-Meier survival curve of relapse-free survival of high-and-low risk AML lnc46 pediatric AML patients, (B) Univariate and multivariate independent Cox regression analyses of known clinical and molecular characteristics and the AML lnc46 signature.
Extracellular CD30 and ADAM10/17 Regulate Brentuximab Vedotin-Induced Cell Death in an Adult T-Cell Leukemia Cell Line
Authors: Sato Keisuke , Kozako Tomohiro , Nakano Akira , Ogata Kentaro , Kamimura Hidetoshi , Sasaki Hidenori , Takamatsu Yasushi , Takemoto Shigeki , Honda Shin-Ichiro
Published: December 2023

Adult T-cell leukemia/lymphoma (ATL) is a human T-cell leukemia virus 1 (HTLV-1)-induced malignancy of mature T lymphocytes with poor outcomes. Brentuximab vedotin (BV), which is an anti-CD30 antibody conjugated with monomethyl auristatin E, is included in the treatment of CD30-positive ATL, but there is no useful therapeutic marker for BV. Soluble CD30 (sCD30) in serum is increased in aggressive-type ATL at diagnosis, but the effects of extracellular CD30 on BV-induced cell death in ATL remain unclear. Similarly, a disintegrin and metalloproteinase (ADAM) 10 and 17 have CD30 sheddase activity in anaplastic large cell lymphoma, but this activity is unknown in ATL. The present study showed that sCD30 concentrations were related to BV activity in ATL-related cell lines. Extracellular vesicles (EVs) such as exosomes containing CD30 also inhibited BV activity. Additionally, the knockdown of ADAM10/17 significantly reduced sCD30 concentrations with increased cell death by BV. Our results suggest that ADAM10/17 are involved in sCD30 production in ATL. Moreover, endogenous extracellular CD30, such as sCD30 shed by ADAM10/17, and CD30-positive EVs may be responsible for the BV-induced cell death. Correctively, extracellular CD30 concentrations, including EV, may be useful as biomarkers for BV therapy in ATL.
Patient Characteristics and Outcomes of Nodular Lymphocyte Predominant Hodgkin Lymphoma at a Safety-Net System Compared to an Academic Comprehensive Cancer Center
Authors: Froessl Luise Josefine , Sottero Theo , Brown L. Steven , Li Hsiao Ching , Kainthla Radhika , Sadeghi Navid
Published: December 2023

Purpose:

Nodular lymphocyte predominant Hodgkin's lymphoma (NLPHL) is a rare subtype of Hodgkin lymphoma that often follows an indolent course although carries a risk of late recurrence and transformation. Given its rarity, there is significant variability in the treatment patterns at various healthcare centers. The aim of this study was to compare the patient characteristics and outcomes of NLPHL treated at a safety-net system compared to those treated at an academic comprehensive cancer center.

Materials and Methods:

Parkland Health (PH) is the safety-net system for uninsured/underinsured patients in Dallas County and is affiliated with the UT Southwestern NCI-designated Harold C. Simmons Comprehensive Cancer Center (SCCC). Electronic records of adult patients (age > 18) diagnosed with NLPHL between January 1st, 2007, and December 31st, 2022, at the two centers were reviewed and data on demographics, disease characteristics, treatments, and outcomes were collected.

Results:

A total of 53 patients were included in the study (25 at PH vs 28 at SCCC). The median age at diagnosis was 42 (IQR 32-54.5) and was not significantly different between the institutions (41.7 at PH vs 46.5 at SCCC). There was a trend towards male predominance at SCCC compared to PH, but this was not statistically significant. PH patients were more likely to belong to racial/ethnic minority groups (Black non-Hispanic 84% at PH vs 32% at SCCC; Hispanic 16% at PH vs 0% at SCCC, p <0.01) and to be uninsured (60% at PH vs 0% at SCCC, p <0.01). Overall, 38% of patients presented at a late stage (stage III-IV) and this was not different based on site of care (11 at PH vs 9 at SCCC; p=0.37). Patients were managed by observation alone (n=4), radiation only (n=11), combination chemotherapy and/or rituximab only (n= 22), or combined modality (n=12). Site of care (PH vs SCCC) or race/ethnicity did not impact the treatment choice. At a median follow up of 60 months (IQR 21-83), 6 recurrences and 5 transformations were noted. Only 3 deaths occurred during the follow up period, for an overall median survival of 62 months (IQR 21.5-84.5).

Conclusion:

Despite health inequities that typically impact safety-net patients, we did not observe any differences in treatment patterns or outcomes of Nodular lymphocyte predominant Hodgkin lymphoma between patients treated at Parkland Health compared to Simmons Comprehensive Cancer Center.
Pomab a Novel Monoclonal Type-I Antiphospholipid Antibody, Reduces Thrombin Generation By Selectively Binding to the Open Form of Prothrombin
Authors: Kumar Suresh , Merrill-Skoloff Glenn , Pengo Vittorio , Flaumenhaft Robert , Pozzi Nicola
Published: December 2023

Background. Anti-prothrombin (anti-PT) antibodies are a type of antiphospholipid antibodies frequently found in antiphospholipid syndrome (APS) patients. Previously, we identified two types of anti-PT antibodies, one binding to epitopes in kringle-1 that are hidden in the closed form but available in the open form (Type-I), and another one in which the epitopes are located in fragment-1 but accessible in both forms (Type-II). Our understanding of their functional characteristics remains limited. Goal. To identify Type-I monoclonal antibodies for mechanistic studies. Methods. Type-I anti-prothrombin antibodies were generated by immunizing mice with fragment-1 and producing monoclonal antibodies using hybridoma technology. Binding mechanisms and epitope recognition for one representative Type-I antibody, POmAb, were elucidated using surface plasmon resonance (SPR), single-molecule FRET (smFRET), and cryo-electron microscopy (cryo-EM). Functional evaluations were performed in human plasma and with purified components. In vivo hemostatic activity was assessed in a laser injury model of the cremasteric arteriole followed by intravital microscopy. Results. Type-I antibodies recognizing kringle-1 were obtained from immunization experiments. One of them, POmAb (Prothrombin Open monoclonal Antibody), was selected for in-depth mechanistic and structural studies. SPR studies showed that POmAb binds to the open form of prothrombin with low nanomolar affinity, and binding was impaired by the mutations S91A and Y93A in kringle-1. smFRET provided evidence of conformational selection, where POmAb preferentially selects the open conformation of prothrombin, thereby shifting the equilibrium towards the open form. Cryo-EM studies of the POmAb-prothrombin complex revealed an extended binding interface in kringle-1 which overlaps with the region occupied by the serine protease domain in the closed form, explaining why POmAb binds to the open form. In human plasma, POmAb prolonged the activated partial thromboplastin time and Russel's viper venom time, though the effect was modest. Further investigations using purified proteins and antibody fragments confirmed that POmAb reduces thrombin generation, although it does not completely abolish it, as the inhibition of thrombin generation occurs through a non-competitive mechanism with prothrombinase. In vivo studies corroborated in vitro findings, further proving reduced fibrin accumulation at the site of injury. Conclusions. We discovered POmAb, a Type-I antiphospholipid antibody. We demonstrated that it selectively binds to the open form of prothrombin, resulting in reduced thrombin generation. POmAb represents a novel tool for studying the role of Type-I antibodies in APS and advances the provocative new idea of conformational trapping of prothrombin as a novel class of anticoagulants.
Empowering Global Hematology-Oncology Education: Assessing the Impact of a 1.5-Year Virtual Platform in Combating Miseducation & Inequity
Authors: Leyfman Yan , Van de Kieft Alexandra , Joshi Muskan , Menon Gayathri P. , Balasubramanian Maduri , Heller Elizabeth J. , Smith Keira P. , Hashim Ahmed , Coloma Helena S. , Alves Gabriele , Wilkerson William B. , Park Chandler Howard
Published: December 2023

Introduction

Social media has revolutionized the global sharing of knowledge, with 77.4% of cancer patients relying on it as their primary medical information resource, especially in resource-limited regions (Ponce et al JCO). However, due to its rapid and unregulated nature, 1/3 of social media posts contain misinformation, with 76.9% of them containing harmful information leading to adverse outcomes. To address this, MedNews Week (MNW), a digital medical education platform dedicated to combating misinformation, was developed to contribute to global hematology-oncology education through its free programming. The Keynote Conference Lecture Series features live virtual presentations from oncology's premier global leaders discussing the latest developments in the field before a mainstream global audience. The aim of this study was to assess the worldwide reach and impact of this virtual oncology education platform.

Methods

From January 2022 to July 2023, MNW hosted 15 global hematology-oncology leaders (Mean H-index = 73.2) as Keynote Speakers. Viewership, impressions, and outreach data were collected from MNW's social media accounts, Symplur and TweepMaps. Data was analyzed to assess MNW's global viewership, reach, and engagement and stratified based on engagement sentiment, gender, age group, and occupation.

Results

In 2022, MNW produced a Healthcare Social Graph Score of 92.77%, placing it in the top 7.33 percentile of global healthcare influencers. Over a 12-month period, MNW generated more than 109,128 Twitter impressions with 4,731 engagements, reaching 1.9 million accounts globally ( Figure 1a). A large proportion of followers (73.44%) were from non-healthcare fields with slightly more males than females. The viewership showed a linear exponential increase from 20,527 (6 months) to 50,707 (1 Year) to 290,532 (1.5 Years) ( Figure 1b). The platform's outreach spanned over 150 cities and 70 countries, with 23 of these countries categorized as low-to-middle socioeconomic regions ( Figure 1c).

Conclusion

Given MNW's performance, it provides a novel model for engaging and disseminating medical information while attracting and sustaining a diverse, global, and growing audience. The platform's ability to spotlight the work of global leaders in the field, free of charge, particularly in lower SE regions, offers a promising approach to combat hematology-oncology educational inequity. Thus, MNW presents an opportunity to inspire audiences worldwide to be proactive, well-informed, and engaged, while narrowing the divide in oncology education.
Prevalence Trends of Anemia Impairment in Adolescents and Young Adults with HIV/AIDS
Authors: Zhang Nan , Li Xinqi , Ma Linlu , Liang Yuxing , Liu Xiaoyan , Zhou Fuling
Published: December 2023

Background

Anemia is a common complication of HIV/AIDS, particularly in adolescents and young adults. However, little is known about the changing prevalence trends of anemia impairment in this population over time.

Methods

Data on anemia in adolescents and young adults with HIV/AIDS from 1990 to 2019 were collected globally. Prevalence was calculated by gender, region, and country for individuals aged 10-24, and trends were measured using estimating annual percentage changes (EAPC).

Results

Globally, the prevalence of adolescents and young adults with HIV/AIDS increased from 103.95 per 100,000 population in 1990 to 203.78 in 2019. However, anemia impairment has decreased over the past three decades, with a global percentage decreasing from 70.6% in 1990 to 34.7% in 2019, mainly presenting as mild to moderate anemia and significantly higher in females than males. The largest decreases were observed in Central Sub-Saharan Africa, High-income North America, and Eastern Sub-Saharan Africa, with EAPCs of -2.8, -2.34, and -2.17, respectively. Tajikistan (78.76%) and Madagascar (74.65%) had the highest anemia impairment percentage in 2019, while China (16.61%) and Iceland (13.73%) had the lowest. Anemia impairment was closely related to sociodemographic index (SDI) levels, with a high proportion of impairment in low SDI regions but a stable decreasing trend (EAPC=-0.37). Hence, anemia impairment in HIV/AIDS-infected individuals varies by region, sex, and age group.

Conclusion

Continued anemia monitoring and management are crucial for HIV/AIDS patients, especially in high-prevalence regions and among females. Public health policies and interventions can improve the quality of life and reduce morbidity and mortality.

Keywords : Adolescents; Human immunodeficiency virus; Anemia; Prevalence; Global Burden of Diseases