bluuebunny/crossref_metadata_2025 huggingface dataset:
A proof-of-mechanism trial in asthma with lunsekimig, a bispecific nanobody® molecule
Authors: Deiteren Annemie , Krupka Emmanuel , Bontinck Lieselot , Imberdis Karine , Conickx Griet , Bas Selcuk , Patel Naimish , Staudinger Heribert W. , Suratt Benjamin T.
Published: January 2025

Background

Monovalent biologics blocking thymic stromal lymphopoietin or interleukin-13 have been shown to elicit pharmacodynamic responses in asthma following a single dose. Therefore, dual blockade of these cytokines may result in an enhanced response compared to single targeting and has the potential to break efficacy ceilings in asthma. This study assessed the safety and tolerability of lunsekimig, a bispecific NANOBODY®molecule that blocks thymic stromal lymphopoietin and interleukin-13, and its effect on Type 2 inflammatory biomarkers and lung function in asthma.

Methods

This was a Phase 1b, single-dose (subcutaneous lunsekimig 400 mg or placebo), randomised (2:1), double-blind, proof-of-mechanism study in 36 participants with mild-to-moderate asthma and elevated fractional exhaled nitric oxide (≥25 ppb), a marker of airway inflammation. The primary endpoint was safety and tolerability through Day 71. The main pharmacodynamic secondary endpoint was change from baseline in fractional exhaled nitric oxide at Day 29.

Results

Lunsekimig was well tolerated, with no serious treatment-emergent adverse events. Fractional exhaled nitric oxide was significantly reduced from Day 8 through Day 29 after a single dose, with change from baseline of −40.9 ppb (90% CI: −55.43 to −26.39; p<0.0001)versusplacebo at Day 29. Blood-based Type 2 biomarkers at Day 29 were significantly reduced from baseline. Lung function, particularly small airway dysfunction, was numerically improved at Day 29, most notably in participants with impaired lung function at baseline.

Conclusions

A single dose of lunsekimig was well tolerated, significantly suppressed Type 2 inflammation, and improved lung function in mild-to-moderate asthma.
Effectiveness and safety of tofacitinibversuscalcineurin inhibitor in interstitial lung disease secondary to anti-MDA5-positive dermatomyositis: a multi-centre cohort study
Authors: Wu Wanlong , Guo Bingpeng , Sun Wenjia , Chen Dan , Xu Wenwen , Chen Zhiwei , Fu Yakai , Ye Yan , Lyu Xia , Xue Zhixin , Wang Kaiwen , Zhao Jiangfeng , Xie Cuiying , Chen Yi , Ye Chunhua , Dai Min , Fan Wei , Li Jia , Wang Xiaodong , Xue Yu , Wan Weiguo , Sun Li , Wu Huaxiang , Luo Qun , Han Qian , Fu Qiong , Ye Shuang
Published: January 2025

Objective

To compare the effectiveness and safety of tofacitinib (TOF)versuscalcineurin inhibitor (CNI) as initial immunosuppressive regimen for anti-melanoma differentiation-associated gene 5-positive dermatomyositis with interstitial lung disease (MDA5+DM-ILD).

Methods

Adult Chinese patients with newly-diagnosed MDA5+DM-ILD (ILD course<3 months) from five tertiary referral centres between April 2014 and January 2023 were included for this retrospective cohort study. The primary effectiveness endpoint was lung transplantation-free survival within 1 year. Propensity score-based inverse probability of treatment weighting (IPTW) was applied for adjustment in this real-world study.

Results

: In the eligible cohort, a total of 94 (32.4%) and 105 (46.7%) patients died or underwent lung transplantation within 1 year in the TOF group (n=290) and the CNI group (n=225), respectively. After adjustment by IPTW, patients’ lung transplantation-free survival rate within 1 year was significantly higher in the TOF group compared to the CNI group (log-rank p=0.013). Multivariable Cox analysis performed in the IPTW dataset revealed the hazard ratio of TOFversusCNI for 1-year survival was 0.72 (95% CI, 0.56 to 0.94, p=0.013). The adjusted difference of survival rate was 9.3% (95%CI 2.8% to 15.8%). Alternative analytic strategies yielded consistent results in sensitivity analyses. Patients less than 60 years old, without RPILD, or with baseline PaO2/FiO2≥300 mmHg might benefit more from TOF. Opportunistic infection was the major treatment-related serious adverse event, with generally comparable incidence (42.4%versus45.3%).

Conclusion

In this large multi-centre cohort study, tofacitinib showed significantly more benefits for 1-year lung transplantation-free survival than calcineurin inhibitors in MDA5+DM-ILD.
Accelerated epigenetic aging worsens survival and mediates environmental stressors in fibrotic interstitial lung disease
Authors: Goobie Gillian C. , Marinescu Daniel-Costin , Adegunsoye Ayodeji , Bourbeau Jean , Carlsten Christopher , Clifford Rachel L. , Doiron Dany , Duan Qingling , Gibson Kevin F. , Grant-Orser Amanda , Hernandez Cordero Ana I. , Johannson Kerri A. , Kass Daniel J. , Kim Sharon E. , Leung Janice M. , Li Xiaoyun , Tan Wan , Xi Yang Chen , Nouraie S. Mehdi , Ryerson Christopher J. , Hackett Tillie L , Zhang Yingze
Published: January 2025

Background

The role of epigenetic aging in the environmental pathogenesis and prognosis of fibrotic interstitial lung disease (fILD) is unclear. We evaluated whether ambient particulate matter ≤2.5 μm (PM2.5) and neighbourhood disadvantage exposures are associated with accelerated epigenetic aging, and whether epigenetic age is associated with adverse clinical outcomes in patients with fILD.

Methods

This multicentre, international, cohort study included patients with fILD from the University of Pittsburgh (UPitt, n=306) and University of British Columbia (UBC, n=170). Five-year PM2.5exposures were estimated using satellite-derived models. Neighbourhood disadvantage was calculated using U.S. and Canadian Census-based metrics. Epigenetic age difference (EAD=epigenetic age – chronological age) was calculated using GrimAge analysis of blood DNA methylation data. Linear models assessed associations of exposures with EAD. Cox models assessed associations of EAD with transplant-free survival. Causal mediation analysis evaluated EAD mediation of exposure-survival relationships.

Results

Median epigenetic age was 11.7 years older than chronological age in patients with fILD. In combined cohort analysis, each interquartile range (IQR) PM2.5increase was associated with 2.88 years (95%CI 1.39–4.38, p<0.001) increased EAD. In UPitt, each IQR neighbourhood disadvantage increase was associated with 1.16 years (95%CI 0.22–2.09, p=0.02) increased EAD. Increased EAD was associated with worse transplant-free survival (HR=1.17 per 1-year increase EAD, 95%CI 1.10–1.24, p<0.001), with EAD mediating 40% of PM2.5-survival relationship and 59% of neighbourhood disadvantage-survival relationships. Epigenetic age was also more strongly associated with transplant-free survival than chronological age.

Conclusions

Epigenetic age acceleration is associated with worse survival and mediates adverse exposure impacts in fILD.
Single cell RNA sequencing improves the next generation of approaches to AML treatment: challenges and perspectives
Authors: Khosroabadi Zahra , Azaryar Samaneh , Dianat-Moghadam Hassan , Amoozgar Zohreh , Sharifi Mohammadreza
Published: January 2025

Acute myeloid leukemia (AML) is caused by altered maturation and differentiation of myeloid blasts, as well as transcriptional/epigenetic alterations, all leading to excessive proliferation of malignant blood cells in the bone marrow. Tumor heterogeneity due to the acquisition of new somatic alterations leads to a high rate of resistance to current therapies or reduces the efficacy of hematopoietic stem cell transplantation (HSCT), thus increasing the risk of relapse and mortality. Single-cell RNA sequencing (scRNA-seq) will enable the classification of AML and guide treatment approaches by profiling patients with different facets of the same disease, stratifying risk, and identifying new potential therapeutic targets at the time of diagnosis or after treatment. ScRNA-seq allows the identification of quiescent stem-like cells, and leukemia stem cells responsible for resistance to therapeutic approaches and relapse after treatment. This method also introduces the factors and mechanisms that enhance the efficacy of the HSCT process. Generated data of the transcriptional profile of the AML could even allow the development of cancer vaccines and CAR T-cell therapies while saving valuable time and alleviating dangerous side effects of chemotherapy and HSCT in vivo. However, scRNA-seq applications face various challenges such as a large amount of data for high-dimensional analysis, technical noise, batch effects, and finding small biological patterns, which could be improved in combination with artificial intelligence models.
A comprehensive allele specific expression resource for the equine transcriptome
Authors: Heath Harrison D. , Peng Sichong , Szmatola Tomasz , Ryan Stephanie , Bellone Rebecca R. , Kalbfleisch Theodore , Petersen Jessica L. , Finno Carrie J.
Published: January 2025

Background

Allele-specific expression (ASE) analysis provides a nuanced view of cis-regulatory mechanisms affecting gene expression.

Results

An equine ASE analysis was performed, using integrated Iso-seq and short-read RNA sequencing data from four healthy Thoroughbreds (2 mares and 2 stallions) across 9 tissues from the Functional Annotation of Animal Genomes (FAANG) project. Allele expression was quantified by haplotypes from long-read data, with 42,900 allele expression events compared. Within these events, 635 (1.48%) demonstrated ASE, with liver tissue containing the highest proportion. Genetic variants within ASE events were located in histone modified regions 64.2% of the time. Validation of allele-specific variants, using a set of 66 equine liver samples from multiple breeds, confirmed that 97% of variants demonstrated ASE.

Conclusions

This valuable publicly accessible resource is poised to facilitate investigations into regulatory variation in equine tissues. Our results highlight the tissue-specific nature of allelic imbalance in the equine genome.
Extracellular vesicle surface engineering with integrins (ITGAL & ITGB2) to specifically target ICAM-1-expressing endothelial cells
Authors: Bergqvist Markus , Park Kyong-Su , Karimi Nasibeh , Yu Lijuan , Lässer Cecilia , Lötvall Jan
Published: January 2025

Extracellular vesicles (EVs) are taken up by most cells, however specific or preferential cell targeting remains a hurdle. This study aims to develop an EV that targets cells involved in inflammation, specifically those expressing intercellular adhesion molecule-1 (ICAM-1). To target these cells, we overexpress the ICAM-1 binding receptor “lymphocyte function-associated antigen-1” (LFA-1) in HEK293F cells, by sequential transfection of plasmids of the two LFA-1 subunits, ITGAL and ITGB2 (CD11a and CD18). The LFA-1 receptor was strongly overexpressed on the EVs released by the transfected cells. We further loaded these EVs with a therapeutic peptide, targeting myeloid differentiation primary response 88 (Myd88; EVMyd88), through a developed EV open-and-close procedure. Myd88 is a downstream common intracellular messenger for most TLR-receptors. EV expression of LFA-1 increases EV binding to ICAM-1-expressing cells, an effect that was dose-dependently inhibited by a specific neutralizing ICAM-1 antibody. Further, activated human endothelial cells treated with LFA-1 EVMyd88 had increased uptake of these EVs, resulting in dose-dependent inhibition of induced release of IL-8, presumably by targeting Myd88. We conclude that LFA-1-expressing EVMyd88 may be a candidate suitable for delivering therapeutic peptides in inflammatory diseases associated with TLR-activation.

Graphical Abstract
Reproductive health literacy scale: a tool to measure the effectiveness of health literacy training
Authors: Rauf Maha , Goliaei Zahra , Machta Lana , Chang Jenny , Thiel de Bocanegra Heike
Published: January 2025

Background

Refugee women’s reproductive health (RH) outcomes have been impacted by several factors, including experiencing war, lack of access to healthcare, and possible gender-based violence. After resettlement, low health literacy, financial difficulties, cultural and linguistic barriers, and unfamiliarity with the healthcare system also add to the preexisting barriers. Although several efforts have focused on health education and improving health literacy among refugee women, there has not been a validated tool to measure the effectiveness of these trainings and their possible impact. This study aims to adapt a culturally and linguistically appropriate survey that helps address this gap.

Methods

We conducted a literature review to identify the existing tools and identified possible domains and items supporting RH literacy measures. The identified items were collected and adapted as a single scale with three domains: (a) general health literacy, measured with HLS-EU-Q6, (b) digital health literacy, measured with eHEALS, and (c) reproductive health literacy, measured through a composite of the Cervical Cancer Literacy Assessment Tool (C-CLAT) and the Refugee Reproductive Health Network (ReproNet) postpartum literacy scale. After content validity and face validity of the adapted scale, it was translated into Dari, Arabic, and Pashto and was administered to participants of RH literacy training sessions.

Results

A total of 67 Dari, 53 Arabic, and 64 Pashto-speaking refugee women completed the survey. The mean scores obtained between the three language groups were similar in the domains of digital health literacy and reproductive health literacy (p > 0.05), whereas the scores for general health literacy were not (p > 0.05). The inter-item reliability score for the domains of general health literacy, digital health literacy and RH literacy across all three language groups was above α = 0.7.

Conclusion

This scale addresses the need for validated tools to measure reproductive health literacy. It has the promise to provide a tool for assessing the effectiveness of health interventions on health literacy. Future applications can utilize this scale to investigate the differences in health literacy in refugee populations speaking Dari, Pashto, and Arabic.
From research to practice: bridging the implementation gap on the use of tranexamic acid in total knee arthroplasty
Authors: Pfister Robin M. , Pfister Benjamin F. , Hager Ronald L. , Sandholtz Nathan , Abulafia Daniel , Bradshaw David
Published: January 2025

Background

The use of intravenous tranexamic acid (TXA), an antifibrinolytic agent, has been shown to effectively reduce total blood loss and transfusion rates in total knee arthroplasty (TKA). The aim of this paper is to evaluate the implementation lag and clinical uptake of the use of TXA for primary TKA after publication of two landmark studies. Additionally, it assessed the efficacy of TXA use in TKA in reducing post-operative blood transfusions and hospital length of stay (LOS).

Methods

A total of 763 patients aged over 18 years of age underwent primary TKA at a level 4 metropolitan hospital in Australia between January 2011 and December 2017. Primary outcome measure was use of TXA at operative induction. Secondary outcome measures were post-operative blood transfusion, haemoglobin levels and in-hospital length of stay.

Results

The rate of TXA uptake was ≥ 50% by April–June 2013, 1.5 years following landmark paper publication. TXA use was ≥ 90% by April–June 2015, equating to 3.5 years after landmark publication. For each additional year since publication, the odds that TXA was used in a TKA surgery increased by 254.3%, 95% CI (confidence interval) [195.2%, 334.1%]. There was a negative association between TXA use and blood transfusion rate (p < 0.001), while controlling for other variables. TXA use reduced the odds of blood transfusions occurring by 73.5%, 95% CI [35.8% and 89.8%]. Analysis showed that reduced LOS was seen even after controlling for post-operative blood transfusion (p < 0.05).

Conclusion

The implementation lag from research to clinical practice, using ≥ 90% TXA use in TKA as a proxy, was 3.5 years. The use of TXA reduced LOS and blood transfusion rate in TKA patients.
The relationship between principals’ pedagogical leadership practices and teachers’ job performance: the role of sociodemographic characteristics
Authors: Berhanu Kelemu Zelalem
Published: January 2025

Background

Concerns about leadership style and job achievement are global priorities. Most previous investigations have concentrated on one or two of the variables rather than on the sociodemographic characteristics. To properly understand the impact of leadership styles on teacher performance, it is critical to grasp the sociodemographic characteristicsvia a holistic approach to rethinking and improving the existing level.

Objective

This study seeks to investigate the relationship between principals’ practice of pedagogical leadership style and teachers’ job performance by considering the effects of sociodemographic characteristics.

Methods

A cross-sectional survey research methodology was used, and in Ethiopia’s Gozamin and Dembecha districts, 539 teachers participated in the study.

Findings

Consequently, there were strong and moderate correlations between teachers’ job performance and pedagogical leadership. Sex did not significantly impact principals’ pedagogical leadership practices or teachers’ job performance. However, age and length of service significantly influenced principals’ pedagogical leadership practices but not teacher performance. Education level significantly affected teachers’ job performance but not leadership practices.

Conclusions and implications

- principals’ practice of pedagogical leaders plays a predictive role in teachers’ job performance. Specific sociodemographic factors also have a role in shaping leadership perceptions and performance outcomes. This study added to the body of knowledge in the fields of education and leadership about work performance and leadership style. In the end, the study inspired stakeholders in schools, government decision-makers, and other researchers to continue improving teachers’ jobs’ effectiveness by identifying factors influencing their success. These results can potentially make teachers more accessible to more students and schools and thus contribute to ensuring quality education (SDG 4).
Controlling injection conditions of a deep coaxial closed well heat exchanger to meet irregular heat demands: a field case study in Belgium (Mol)
Authors: Leontidis Vlasios , Hernandez Edgar , Pogacnik Justin , Wangen Magnus , Harcouët-Menou Virginie
Published: January 2025

Deep geothermal closed-loops have recently gained attention because of their advantages over classical geothermal applications (e.g., less dependence on the geology, no risk of induced seismicity) and technological advantages (e.g., in the drilling process, use of alternative to water fluids). This paper deals with the repurposing of an existing well in Mol, Belgium, by numerically evaluating the closed-loop concept. Two numerical tools are used to predict the evolution of the temperature and the produced energy over a period of 20 years considering the vertical coaxial well and the complete geological morphology. Full-scale simulations are initially carried out to estimate the maximum capacity of the well and to highlight the need to control the output of the well by adjusting the inlet conditions. Simulations are then performed either to deliver a constant power or to cover irregular thermal energy demands of two buildings by applying in both cases three process control operations. Through controlling the inlet temperature, the injected flow rate or successively both, the production of excess energy, resulting from the overdesign of the existing wellbore for the specific application, is limited. The simulations showed that continuous adjustments to the injection temperature and/or flow rate are needed to restrict the rapid drop in outlet temperature and consequent thermal depletion of the rocks, caused by the highly transient nature of the diffusive heat transfer from the rocks to the wellbore, as well as to supply a specific heat demand, constant or irregular, over the long term. In fact, the combination of both controls could be the ideal strategy for supplying the demand at the highest COP.
Enhancing Royal grape quality through a three-year investigation of soil management practices and organic amendments on berry biochemistry
Authors: Kaya Ozkan , Karakus Sinem , Ates Fadime , Daler Selda , Hatterman-Valenti Harlene
Published: January 2025

Background

Grape composition, characterized by mineral content, hormone levels, and antioxidant enzyme activities, fundamentally influences berry quality, nutritional value, and vine health. Various viticultural practices, particularly tillage methods and organic fertilization techniques, significantly impact these compositional parameters. This study investigates the effects of these agricultural practices on grape composition to establish optimal protocols for enhanced berry production and quality.

Methods

A three year study (2020–2022) evaluated the effects of soil management on grape quality in ‘Royal’ grapes (VIVC: 349). Using a Randomized Complete Block Design with four replicates of 12 vines, the study tested three tillage methods (chisel, disc harrow, and no-tillage) and four organic fertilizers (Antep radish, broccoli, olive blackwater, and a control). Treatments were analyzed for berry mineral content (macro and micronutrients), hormone levels (auxin, ABA, zeatin, SA, JA, cytokinin and GA), and antioxidant enzyme activities (SOD, POD, CAT, APX, GR, GST, G6PD and 6PGD).

Results

Based on our results, the disc harrow tillage method in conjunction with olive blackwater fertilizer demonstrated superior mineral accumulation, yielding peak concentrations of nitrogen (3.72%), phosphorus (0.40%), and magnesium (0.41 mg/kg) during the 2021 growing season. Endogenous hormone levels exhibited treatment-specific responses, with maximum indole-3-acetic acid (17.33 ng/g) accumulation observed under no tillage control conditions in 2022, while abscisic acid concentrations peaked (49,172.53 ng/g) under no tillage with broccoli fertilization. Antioxidant enzyme activities were significantly enhanced under chisel tillage combined with broccoli fertilizer treatment, leading to optimal superoxide dismutase (1426.54 EU) and peroxidase (14,936.81 EU) activities. Principal component analysis revealed that the first two components explained 51.35% of total variance, with distinct temporal clustering of treatment effects.

Conclusion

The optimal cultivation practice for ‘Royal’ grape variety was determined to be chisel tillage method combined with broccoli fertilization, which maximized both mineral nutrient content and hormone levels. These findings provide practical insights for viticulturists to optimize cultivation techniques for improved grape quality and nutritional value.

Graphical Abstract
Optimisation of low and ultra-low dose scanning protocols for ultra-extended field of view PET in a real-world clinical setting
Authors: Ingbritsen Johanna , Callahan Jason , Morgan Hugh , Munro Melissa , Ware Robert E. , Hicks Rodney J.
Published: January 2025

True total-body and extended axial field-of-view (AFOV) PET/CT with 1m or more of body coverage are now commercially available and dramatically increase system sensitivity over conventional AFOV PET/CT. The Siemens Biograph Vision Quadra (Quadra), with an AFOV of 106cm, potentially allows use of significantly lower administered radiopharmaceuticals as well as reduced scan times. The aim of this study was to optimise acquisition protocols for routine clinical imaging with FDG on the Quadra the prioritisation of reduced activity given physical infrastructure constraints in our facility. Low-dose (1 MBq/kg) and ultra-low dose (0.5 MBq/g) cohorts, each of 20 patients were scanned in a single bed position for 10 and 15 min respectively with list-mode data acquisition. These data were then reconstructed simulating progressively shorter acquisition times down to 30 s and 1 min, respectively and then reviewed by 2 experienced PET readers who selected the shortest optimal and minimal acquisition durations based on personal preferences. Quantitative analysis was also performed of image noise to assess how this correlated with qualitative preferences. At the consensus minimum acquisition durations at both dosing levels, the coefficient of variance in the liver as a measure of image noise was 10% or less and there was minimal reduction in this measure between the optimal and longest acquisition durations. These data support the reduction in both administered activity and scan acquisition times for routine clinical FDG PET/CT on the Quadra providing efficient workflows and low radiation doses to staff and patients, while achieving high quality images.
Impact of ethnicity on the relevance of the Alcohol Use Disorders Identification Test (AUDIT) in Nepal
Authors: Pandey Susmita
Published: January 2025

The Alcohol Use Disorders Identification Test (AUDIT) is a ten-item standardised questionnaire to assess an individual's vulnerability to alcohol use disorders. Three of these ten questions are related to alcohol consumption. Nepal has a distinct alcohol culture, where alcohol use is socially and religiously acceptable in some caste/ethnic groups and is prohibited in others, thereby influencing the scores of AUDIT questions related to all three conceptual domains. Identifying and endorsing subsets of AUDIT questions relevant to different ethnic groups could be the way forward for effective screening of alcohol use disorders in Nepal.
Developing the EPA guidance of pharmacological treatment of schizophrenia – results of a Delphi process
Authors: Falkai Peter , Wagner Elias , John Miriam , Yakimov Vladislav , Galderisi Silvana , Bitter Istvan , Dom Geert , Schmitt Andrea , Gaebel Wolfgang , Carpiniello Bernardo , Hasan Alkomiet
Published: January 2025

Background

The development of guidelines is time-consuming and cost-intensive. The heterogeneity of clinical practice, evidence, and patients’ needs is an issue across Europe. An European core guidance for a specific psychiatric disorder may help to overcome this issue. Here, we present a progress report on the European Psychiatric Association (EPA) proof-of-concept approach to develop a European consensus guidance on the pharmacological treatment of schizophrenia.

Methods

All national psychiatric associations in Europe were contacted to provide their schizophrenia guidelines. Six guidelines were rated by three experts, experienced in the development of national and international guidelines, from three different countries (Italy, Hungary, and Germany), and the German schizophrenia guideline published in 2019 was found to have the highest quality. For this proof-of-concept approach, 45 recommendations on the pharmacological treatment of schizophrenia from the German guideline were evaluated in a two-step Delphi process to determine their acceptability throughout the European continent.

Results

44 experts participated in the first round and 40 experts in the second round of the Delphi process. Agreement among the involved experts was reached for 75% of the presented recommendations from the German schizophrenia guidelines. 11 out of 45 recommendations (24.4%) did not reach this level of agreement.

Conclusions

This progress report highlights the possibility of developing a pan-European core guidance on the pharmacological treatment of schizophrenia by adapting national guidelines and reconciling their recommendations. However, several barriers in this adaptation process, such as non-agreement in recommendations with strong scientific evidence in the reconciling process, were identified and must be considered when developing the final guidance.
Evolution and Recent Radiation Therapy Advancement in Uganda: A Precedent on How to Increase Access to Quality Radiotherapy Services in Low- and Middle-Income Countries
Authors: Kavuma Awusi , Kibudde Solomon , Kanyike Daniel , Kigula-Mugambe Joseph , Zhao Tianyu , Gay Hiram , Sun Baozhou , Orem Jackson
Published: January 2025

The evolution of radiation therapy in Uganda has been a journey marked by significant milestones and persistent challenges. Since the inception of radiotherapy services in 1988-1989, there has been a concerted effort to enhance cancer treatment services. The early years were characterized by foundational developments, such as the installation of the first teletherapy units, low-dose-rate brachytherapy units, and conventional simulators, and the recognition of radiation oncologists and medical physicist professionals laid the groundwork for radiotherapy treatment modalities. With more support from the International Atomic Energy Agency, the acquisition of dosimetry equipment, treatment planning systems, and additional professional training signaled a new era in the fight against cancer. As we entered the second decade of the millennium, the Uganda Cancer Institute (UCI) witnessed a progression in sophisticated radiotherapy services, including high-dose-rate brachytherapy, initiation of intensity modulated radiation therapy (IMRT)/volumetric modulated arc therapy (VMAT), and use of artificial intelligence. These advancements improved the efficiency/precision of treatments and the time patients spent undergoing therapy. Around the second decade of radiotherapy services, about 600 new patients with cancer were annually treated compared with about 2,600 in 2023. Currently, an average of 1,440 brachytherapy insertions are done annually compared with 300 insertions for the first 20 years. Despite the technological strides, the UCI faced numerous obstacles, including limited equipment, knowledge gaps in appropriate tumor/organs at risk segmentations, treatment planning, and protocols. However, international support and collaboration efforts have led to significant improvement in the precision and effectiveness of treatments. Currently, about 51% of all patients are treated with image-guided techniques—IMRT/VMAT (42%) and three-dimensional conformal radiation treatment (10%). The Government has commenced the decentralization of radiotherapy services to other regions. This review can be a learning lesson for the more than 25 countries in Africa and other low-middle-income countries globally that do not have access to radiotherapy and/or are in the process of starting such facilities.
Randomized Trial of Fixed-Dose Capecitabine Compared With Standard-Dose Capecitabine in Metastatic Breast Cancer: X-7/7 Trial
Authors: Khan Qamar J. , Bohnenkamp Colleen , Monson Taylor E. , Phadnis Milind A. , Clark Lauren , Smith Holly E. , Raja Vinay , Elia Manana , O'Dea Anne , Fesen Mark R. , Crane Gregory J. , Nye Lauren E. , Baranda Joaquina C. , Pluenneke Robert E. , Hoffmann Marc , Al-Rajabi Raed Moh'd Taiseer , Kasi Anup , McKittrick Richard J. , Mitchell Laura , LaFaver Stephanie , Sharma Priyanka
Published: January 2025

PURPOSE

In metastatic breast cancer (MBC), oral capecitabine prescribed at the US Food and Drug Administration (FDA)–approved dose of 1,250 mg/m
2
twice daily, 14 days on, 7 days off, is associated with poor tolerance. Mathematical models suggest that a fixed-dose (FD), dose-dense schedule may optimize efficacy. We conducted a randomized, open-label trial to compare the efficacy and tolerability of FD capecitabine, 1,500 mg twice daily, 7 days on, 7 days off (FD-7/7), with the FDA-approved dose and schedule (standard-dose [SD]-14/7).

METHODS

Females with MBC and any previous lines of therapy were included. Patients were randomly assigned 1:1 to either FD-7/7 or SD-14/7. The primary end point was 3-month progression-free survival (PFS). Capecitabine-related toxicities were graded at each visit.

RESULTS

Between October 2015 and April 2021, 153 patients were enrolled (n = 80 FD-7/7, n = 73 SD-14/7). The 3-month PFS was 63.1% (95% CI, 52.0 to 74.2) in the FD-7/7 arm and 67.2% (95% CI, 54.5 to 79.9) in the SD-14/7 arm. Restricted mean survival time was used to report estimates of effect. The PFS (restricted mean) at 33 months was 10.1 months (95% CI, 7.6 to 12.6) in the FD-7/7 arm compared with 9.1 months (95% CI, 6.6 to 11.7) in the SD-14/7 arm. The overall survival (restricted mean) at 80 months was 30.6 months (95% CI, 23.6 to 37.6) in the FD-7/7 arm versus 24.5 months (95% CI, 18 to 31.1) in the SD-14/7 arm. Toxicity-related treatment discontinuation occurred in 24 patients (32.9%) in the SD-14/7 arm compared with seven patients (8.8%) in the FD-7/7 arm (
P
= .0002). Grade 2 to 4 toxicities occurred in 79.5% in the SD-14/7 arm compared with 37.5% in the FD-7/7 arm (
P
< .0001).

CONCLUSION

In MBC, FD capecitabine 1,500 mg twice daily on a 7/7 schedule has less toxicity and similar efficacy when compared with body surface area-based dosing on a 14/7 schedule.
The energetic cost of human walking as a function of uneven terrain amplitude
Authors: Hosseini-Yazdi Seyed-Saleh , Kuo Arthur D.
Published: January 2025

Humans expend more energy walking on uneven terrain, but the amount varies across terrains. Few experimental characterizations exist, each describing terrain qualitatively without any relation to others or flat ground. This precludes mechanistic explanation of the energy costs. Here we show that energy cost varies smoothly and approximately quadratically as a function of terrain amplitude. We tested this with healthy adults (N=10) walking on synthetic uneven terrain with random step heights of parametrically controlled maximum amplitude (four conditions 0 – 0.045 m), and at four walking speeds (0.8 – 1.4 m.s-1). Both net metabolic rate and the rate of positive work increased approximately with amplitude squared and speed cubed (R2 = 0.74,0.82 respectively), as predicted by a simple walking model. The model requires work to redirect the body center of mass velocity between successive arcs described by pendulum-like legs, at proportional metabolic cost. Humans performed most of the greater work with terrain amplitude early in the single stance phase, and with speed later in stance during push-off. Work and energy rates changed with approximately linear proportionality, with a ratio or delta efficiency of 49.5% (R2 = 0.68). The efficiency was high enough to suggest substantial work performed passively by elastic tendon and not only by active muscle. Simple kinematic measures such as mid-swing foot clearance also increased with terrain amplitude (R2 = 0.65), possibly costing energy as well. Nevertheless, most of the metabolic cost of walking faster or on more uneven terrain can be explained mechanistically by the work performed.
The Good Wife? Reputation Dynamics and Financial Decision-Making inside the Household
Authors: Buchmann Nina , Dupas Pascaline , Ziparo Roberta
Published: January 2025

We study reputation dynamics within the household in a setting where women regularly receive transfers from their husbands for household purchases. We propose a signaling model in which wives try to maintain a good reputation in the eyes of their husbands to receive high transfers. This leads them to (i) avoid risky purchases (goods with unknown returns) and (ii) knowingly overuse low-return goods to hide bad purchase decisions—we call this the intrahousehold sunk cost effect. We present supportive evidence for the model from a series of experiments with married couples in rural Malawi. (JEL D13, D82, J12, J16, O12, O18)
Empowering Adolescents to Transform Schools: Lessons from a Behavioral Targeting
Authors: Alan Sule , Kubilay Elif
Published: January 2025

We test the effectiveness of a behavioral program grounded in the idea that status granting and self-persuasion might yield a robust behavioral change in disadvantaged adolescents. We enlist socially connected senior middle school students with high emotional intelligence as “student-teachers” and entrust them with delivering a curriculum to their junior peers. The program empowers student-teachers, leading them to improve their social environment. It reduces disciplinary incidents and antisocial behavior among student-teachers and their friendship networks. The intervention significantly enhances the likelihood of admission to selective high schools for student-teachers, offering a cost-effective way to help disadvantaged adolescents escape neighborhood disadvantages. (JEL H52, I21, I24, I28, J13, O15)
Unveiling the Group A Streptococcus Vaccine-Based L-Rhamnose from Backbone of Group A Carbohydrate: Current Insight Against Acute Rheumatic Fever to Reduce the Global Burden of Rheumatic Heart Disease
Authors: Ambari Ade Meidian , Qhabibi Faqrizal Ria , Desandri Dwita Rian , Dwiputra Bambang , Baravia Pirel Aulia , Makes Indira Kalyana , Radi Basuni
Published: January 2025

Group A Streptococcus (GAS) is a widely distributed bacterium that is Gram-positive and serves as the primary cause of acute rheumatic fever (ARF) episodes. Rheumatic heart disease (RHD) is a sequela resulting from repeated ARF attacks which are also caused by repeated GAS infections. ARF/RHD morbidity and mortality rates are incredibly high in low- and middle-income countries. This is closely related to poor levels of sanitation which causes the enhanced incidence of GAS infections. Management of carditis in RHD cases is quite challenging, particularly in developing countries, considering that medical treatment is only palliative, while definitive treatment often requires more invasive procedures with high costs. Preventive action through vaccination against GAS infection is one of the most effective steps as a solution in reducing RHD morbidity and mortality due to curative treatments are expensive. Various developments of M-protein-based GAS vaccines have been carried out over the last few decades and have recently begun to enter the clinical stage. Nevertheless, this vaccination generates cross-reactive antibodies that might trigger ARF assaults as a result of the resemblance between the M-protein structure and proteins found in many human tissues. Consequently, the development of a vaccine utilizing L-Rhamnose derived from the poly-rhamnose backbone of Group A Carbohydrate (GAC) commenced. The L-Rhamnose-based vaccine was chosen due to the absence of the Rhamnose biosynthesis pathway in mammalian cells including humans thus this molecule is not found in any body tissue. Recent pre-clinical studies reveal that L-Rhamnose-based vaccines provide a protective effect by increasing IgG antibody titers without causing cross-reactive antibodies in test animal tissue. These findings demonstrate that the L-Rhamnose-based vaccine possesses strong immunogenicity, which effectively protects against GAS infection while maintaining a significantly higher degree of safety.
Biological properties of Moringa oleifera: A systematic review of the last decade
Authors: Soto Javier Andrés , Gómez Andrea Catalina , Vásquez Maryeli , Barreto Andrea Natalia , Molina Karen Shirley , Zuniga-Gonzalez C. A.
Published: January 2025

Background The growing incidence of chronic diseases such as cancer and the emergence of drug-resistant microorganisms constitute one of the greatest health challenges of the 21st century. Therefore, it is critical to search for new therapeutic alternatives. Moringa oleifera is a plant well known for the properties of its phytocomponents and its role has been analyzed in a variety of fields, from medicine to biotechnology. Methods In this work, the biological activity of Moringa oleifera in human health was explored through a review of 129 original articles published between 2010 and 2021 related to antitumor activity and its potential uses against chronic and infectious diseases. Results Moringa oleifera extracts showed antioxidant, hypoglycemic, antihypertensive and cytoprotective properties at neuronal, hepatic, renal and cardiac levels. Besides, cytotoxic effects, apoptotic and antiploriferative activity against several cancer cell lines has been demonstrated. On the other hand, the antimicrobial potential of M. oleifera was also evidenced, especially against multidrug-resistant strains. Conclusions Hence, it is supported that there is a wide range of clinical entities in which Moringa oleifera exhibits significant biological activity that could contribute to counteracting metabolic, infectious and chronic diseases in a similar or improved way to the drugs traditionally used.
Dual tasking as a predictor of falls in post-stroke: A cross-sectional analysis comparing Walking While Talking versus Stops Walking While Talking
Authors: Lamba Disha , Joshua Abraham M. , K Vijaya kumar , Nayak Akshatha , Mithra Prasanna , Pai Rohit , Pai Shivananda , Krishnan K. Shyam , Palaniswamy Vijayakumar
Published: January 2025

Background Dual-task assessments, including Walking While Talking (WWT) and Stops Walking While Talking (SWWT) tests, predict fall risk in stroke survivors. However, their effectiveness relative to established predictors, such as the Berg Balance Scale (BBS) and Falls Efficacy Scale (FES), remains unclear. This study evaluated the comparative predictive value of WWT and SWWT tests alongside BBS and FES among stroke survivors. Methods This cross-sectional study included 68 stroke survivors who completed WWT-Simple (WWT-S), WWT-Complex (WWT-C), and SWWT, as well as the BBS and FES. Spearman correlations assessed relationships between balance, fear of falling, and dual-task performance. Logistic regression identified fall risk predictors, and Receiver Operating Characteristic (ROC) analysis evaluated predictive accuracy. The study adhered to STROBE guidelines. Results BBS scores were strongly negatively correlated with WWT-S (r = -0.734, p < 0.0001) and WWT-C (r = -0.737, p < 0.0001), indicating poorer balance with slower dual-task completion. Positive correlations were found between WWT-S and FES (r = 0.668, p < 0.0001) and WWT-C and FES (r = 0.610, p < 0.0001), linking slower completion times with higher fear of falling. SWWT was significantly negatively correlated with BBS (r = -0.625, p < 0.0001). WWT tests had higher sensitivity (97.8%) and specificity (99%) than SWWT (sensitivity = 68.9%; specificity = 91.3%). Logistic regression identified SWWT (Positive) as a significant predictor of fall risk (p = 0.009), and ROC analysis showed an AUC of 0.911, indicating excellent predictive power. Conclusions Findings highlight the superior predictive value of WWT tests over SWWT in assessing fall risk among stroke survivors. Incorporating dual-task measures into clinical practice may enhance fall risk evaluation, supporting targeted stroke rehabilitation.
Association of myopia with screen time use in pediatric patients in a tertiary hospital in Saudi Arabia
Authors: AL Mulhim Noura , AlFares Maiadah , AlMehrij Shahd , Al Haidar Farah , AlOmair Manar , AlMutairi Reem , Abalkhail Rafeef , Rafique Nazish , Latif Rabia , Al-Asoom Lubna
Published: January 2025

Background Pediatric myopia is a growing global public health concern, exacerbated by the increasing screen time among children, who spend more time on devices for both entertainment and education. Understanding the link between myopia and screen media use is crucial for promoting children’s long-term eye health and mitigating the burden of myopia. Methods The study was a retrospective study design that investigated 94 complete medical records of myopic patients who had attended pediatric ophthalmology clinic at King Fahad University Hospital (KFUH) in Saudi Arabia between November 2021 and November 2023. Data was cleaned, coded and analyzed using SPSS version 20 to obtain important insights. Results The results revealed a statistically significant difference in total screen time between age groups (4–6 years, 7–9 years, and 10–12 years), with a p-value of 0.021. The most commonly used screen media devices among myopic children were smartphones (98.9%) and laptops (87.2%). Regression analysis indicated that the differences in screen time based on the children’s age at first use of screen media devices (smartphones, tablets, and laptops) were not statistically significant (p =0.196). Additionally, the study found a statistically significant association between patients’ age, the age at which they were first diagnosed with myopia, and their myopia category (p = 0.030 and p = 0.005, respectively). Conclusion The study established a significant association between myopia and screen use in pediatric patients, with total screen time increasing significantly with age. Smartphones and laptops were the most commonly used devices among myopic children. These findings highlight the need to understand the relationship between myopia and screen time in order to develop evidence-based guidelines for managing screen time, protecting children from the adverse effects of screen media exposure, and promoting their eye health and overall well-being.
A phylogenetic classification of the Je language family
Authors: Ferraz Gerardi Fabrício , Wientzek Tim , Gregorio de Souza Jonas , Roksandic Ivan , Orphão de Carvalho Fernando
Published: January 2025

Introduction This study investigates the Je language family, addressing a significant gap in previous research by applying quantitative methods to its classification. Dataset The dataset comprises 516 concepts from 14 languages, primarily sourced from Swadesh lists and culturally relevant terms, providing a robust foundation for phylogenetic analysis. Methods Bayesian phylogenetic inference and NeighborNet methods were employed to analyze the dataset. These approaches enabled the reconstruction of evolutionary relationships within the Je family, facilitating the identification of language divergence patterns and their historical dynamics. Results The analysis reveals well-supported Northern, Central, and Southern subgroups within the Je family, demonstrating clear geographical clustering. The phylogenetic tree aligns with existing hypotheses while offering new insights into the family’s structure. Discussion The findings were contextualized within pre-Columbian archaeological frameworks, drawing parallels between linguistic divergence and material culture. These connections support the hypothesis that the Macro-Je language family’s development aligns with distinct cultural and geographical distributions observed in archaeological records. Conclusion and Future Directions This study affirms the genetic coherence of the Je family and highlights opportunities for future research, including the incorporation of non-Je languages and expanded datasets to refine the understanding of this diverse linguistic group.
Social Personalism, Its Implications for Education and Implementation in Society
Authors: Chrost Sławomir
Published: January 2025

The human-person is, according to personalism, open to others, needs others and creates various forms of community. The socialization of the human-person is, most of all, the outcome of lack and excess. The human-person, colloquially speaking, needs other people to grow, and needs interpersonal relationships to ‘give and take.’ The purpose of this essay is to outline the theoretical underpinnings of social personalism, its implications for pedagogy and selected examples of how it is cultivated in practice. The author demonstrates that the ‘I’ directed to the ‘you’ also becomes the ‘I’ for the ‘you.’ Thus, the theory of the human being – the person – as a relational being translates into the teleology of education and pedagogical practice. ‘I’ is oriented ‘towards’ and ‘for’ ‘you’/‘You,’ being ‘with’ ‘you’/‘You.’ It is worth noting that social personalism is a path ‘between’ individualism and collectivism. It attempts to combine the individual good with the common good through the characteristic of participation in the community. The pedagogy of the person comes to fruition in the community, according to the principles of companionship through dialogue. It strives for the full development of the human being as a person – a development that materialises through active love towards the other in a spirit of solidarity.
Abandoned by My Self: Forms of Self-Rejection
Authors: Wałejko Małgorzata
Published: January 2025

Loneliness is usually defined as a feeling of lacking expected social relationships, being abandoned or being rejected by others. However, there is also the loneliness of self-rejection. There can be no deeper form of loneliness than being abandoned by one’s own self. In this article, I analyse what self-rejection is, how it is demonstrated and what forms it can take. I illustrate the ethical aspect of the phenomenon and propose the direction of possible intervention.