bluuebunny/crossref_metadata_2025 huggingface dataset:
Value Creation Through Communication and Co-creation: The Key Retailers’ Perspective
Authors: Trabelsi Rym EL Amri
Published: November 2024

This research provides insights into how communication contributes to improving the co-creation of value in supplier–key retailer relationships and identifies the drivers of communication in an emerging context. By adopting the S-D logic approach and the literature on business-to-business communication, this article aims to gain an in-depth understanding of the role of effective communication in enhancing co-creation between suppliers and large retailers to generate high perceived value. Through a grounded theory approach, interviews with 15 fast-moving consumer goods purchasing managers reveal the importance of the co-creation process through effective communication with suppliers to capture greater value. Co-creation concerns product design, marketing and logistics services, and private labels. The results show the multidimensional nature of communication based on four drivers: needs identification, transparency, sharing of information and closer interactions.
Financial cost of end-of-life cancer care in palliative care units (PCUs) and non-PCUs in Iran: insights from low- and middle-income countries
Authors: Darrudi Ali , Poupak Amir Hossein , Darroudi Rajabali , Sargazi Nasrin , Zendehdel Kazem , Sallnow Libby , Ghanbari Motlagh Ali , Tahmasebi Mamak , Nahvijou Azin
Published: November 2024

Background:

End-of-life care for patients with advanced cancer can impose a significant financial burden. However, data on the economic impact of end-of-life care in low- and middle-income countries are limited.

Objective:

This study aims to compare the costs associated with palliative care units (PCUs) and non-PCU settings for cancer patients in Iran.

Design:

We designed a retrospective study at the largest hospital in the country.

Methods:

We conducted a comprehensive evaluation of hospitalization costs and care service delivery for 150 patients in the final 5 days of life, who were admitted to the largest hospital complex in Iran. All costs were adjusted based on the 2018 USD exchange rate.

Results:

Among the 150 patients included in the study, 56 (37%) were admitted to the PCU. The average total treatment cost during the final 5 days of life was three times higher in general wards compared to PCUs. In non-PCU settings, the total cost of care during this period amounted to $2873, while in PCU settings, it was $909.63.

Conclusion:

The establishment of PCUs within tertiary hospitals and the provision of palliative consultation services to patients with advanced cancer can yield significant benefits, even when resources are limited.
Gastrointestinal langerhans cell histiocytosis in an adult presenting with anal protrusion and multiple colorectal ulcers: a case report
Authors: Tran Nhu Tung , Truong Quoc Thanh , Nguyen Khuyen Thi , Lai The Anh Khoa , Trinh Cong Thao , Hoang Van Trung
Published: November 2024

Langerhans cell histiocytosis (LCH) is a rare disorder characterized by the proliferation of Langerhans cells, a type of dendritic cell essential for immune response. While LCH predominantly affects children, its manifestation in adults, especially within the gastrointestinal (GI) tract, is exceedingly rare. We present a unique case of a 56-year-old female with rare GI manifestations of LCH. The patient initially noticed pimple-like lesions around her anal orifice, which evolved into prominent protruding lesions over 3 months. Subsequent colonoscopy revealed multiple ulcers in the colorectal area, particularly concentrated in the sigmoid colon. Histopathological examination of biopsy samples, combined with immunohistochemical staining, confirmed the diagnosis of LCH. This case underscores the importance of a comprehensive diagnostic approach, especially when patients are present with atypical symptoms. The current literature suggests that such GI manifestations of LCH in adults are infrequent, making this case a valuable contribution to the understanding of LCH’s clinical spectrum.
The Bridge to Somewhere How Practitioners Can UNITE to Support Adults With Extensive Support Needs in Inclusive Employment Opportunities
Authors: Baine Caitlin , Gilson Carly B. , Hashemi Hoda
Published: November 2024

The transition to employment for young adults with intellectual and developmental disabilities (IDD) is a growing field of research and practice in need of increased attention. For many adults with IDD, the transition planning process can seem like a bridge to nowhere. In particular, adults with extensive support needs (ESN) are often excluded from employment opportunities due to lower rates of participation in school or community-based employment preparation experiences and the loss of special education services and collaborative support provided under the Individuals with Disabilities Education Improvement Act (IDEIA) during the school years. We present an overview of the post-school realities and employment challenges for many people with ESN and introduce a person-centered, collaborative approach uniquely designed to guide educators and practitioners who support adults with ESN. We provide recommendations for self-advocates, teachers, and employers to UNITE (U = Understand, N = Navigate, I = Invest, T = Train, and E = Elevate) to increase opportunities for inclusive work experiences that will sustain throughout the lifespan.
Examining the Role of Medical School Faculty in Developing Students’ Cultural Humility Skills: Insights From a Single-Center Multimethod Study
Authors: Binda Dhanesh D. , Harris Angelique C. , Tan Taralyn , Fischer Krisztina , Molina Rose L. , Mehta Darshan
Published: November 2024

Background

While the Liaison Committee on Medical Education emphasizes the teaching of cultural competence in medical education, the concept of cultural humility, focusing on self-reflection and lifelong learning, has been proposed as a more effective approach. Although there have been numerous discussions on both topics, understanding how faculty in clinical settings help students develop cultural humility skills remains limited.

Objective

Our multimethod study utilized a survey and semi-structured interviews to identify strategies that faculty at one institution use to help students develop cultural humility skills.

Methods

We administered a 10-question survey to assess faculty demographics, teaching characteristics, and familiarity with cultural humility. Participants most familiar with cultural humility were invited for semi-structured interviews. Survey data were analyzed with descriptive statistics, and interview data were thematically analyzed to identify key teaching strategies.

Results

In our study of 49 medical faculty members, the majority of participants were female (61%) and predominantly White (67%), covering a wide range of specialties and years of teaching. Of the participants, 74% expressed being at least somewhat familiar with cultural humility, and 10 consented to interviews. Strategies for cultural humility education included one-on-one instruction, feedback, and reflections. Thematic analysis underscored fostering learner curiosity about cultures, early patient exposure, and incorporating diverse learning perspectives as essential in developing students’ cultural humility skills.

Conclusion

Cultural humility is an important attribute for healthcare professionals that can enhance patient-centered care. Through focused interviews with faculty in our study and subsequent thematic analysis, our results suggest the need for longitudinal and multimodal educational strategies to cultivate cultural humility among medical students. By understanding current teaching methods, educators can design and assess more effective curricula to prepare future doctors for a culturally diverse patient population.
Of sartorial mimicry and woman: Indian women emulating or rejecting English dress in women’s late colonial writing
Authors: Bhamburkar Tarini
Published: November 2024

This article scrutinizes two texts written or based in late colonial India, authored by a British and an Indian woman: “Feroza” by Flora Annie Steel from her anthology The Flower of Forgiveness (1894) and Saguna: The Story of Native Christian Life (1895) by Krupabai Satthianadhan, which was reissued in 1998 as Saguna: The First Autobiographical Novel in English by an Indian Woman. Taking into account the dressed body, Christian conversion, and interactions with missionaries in these texts, this article argues about the consequences and repercussions of Indian women assuming English dress or refusing to do so in a reforming late Victorian India. I unpack how the narratives punctuate the social factors of anglicisation, the expected outcomes of Christian conversion, and women’s agency in choosing their own dress, using the theory of the “dressed body” and colonial mimicry. The female body is racialized and determined by social structures but also constitutes the individual’s social and personal identity. Dress, in adding an envelope and a visual metaphor to the woman’s body becomes part of her bodily presentation, becoming an embodied practice, and making an embodied subject out of the wearer. I use dress and the “dressed body” as methodological media within a postcolonial framework in analysing how the women’s sartorial choices affect their encounters and their overall existence in late colonial India.
Migration as resistance and compromise: From cosmopolitan ideals to postmigrant beginnings in The Good Immigrant and The Good Immigrant USA
Authors: Englund Lena
Published: November 2024

The two essay collections The Good Immigrant (edited by Nikesh Shukla) and The Good Immigrant USA (edited by Nikesh Shukla and Chimene Suleyman) present experiences of migration, racialization, and minoritization in British and American contexts, addressing the extent to which the two nations accommodate people of multiple and sometimes complex origins and arguing for the need for acknowledgement of specific experiences, locations, and histories. The analysis of the essays draws on ideas of cosmopolitanism and postmigration, the former of which engages with the idea of conversation without consensus in Appiah’s terms, and the latter which recognizes the need to go beyond divisions into minority and majority society and to see migration as a process that affects societies in their entirety. The essays indicate that compromise in terms of living together despite differences comes at the cost of those who have roots elsewhere, or nowhere, those who are often racialized and minoritized. The essay collections demand the right to be complex, complicated, to resist categorization, and to belong anywhere.
Seismic loss comparison for buildings designed with ductile steel seismic force-resisting systems and with controlled rocking braced frames
Authors: Banihashemi MirAmir , Wiebe Lydell
Published: November 2024

Observations from past earthquakes have highlighted the structural damage and significant residual deformations experienced by ductile steel seismic force-resisting systems (SFRSs), such as special moment resisting frames (SMRFs), special concentrically braced frames (SCBFs), and buckling-restrained braced frames (BRBFs). To mitigate these challenges, controlled rocking braced frames (CRBFs) have emerged as a promising low-damage alternative SFRS. However, concerns have been raised about whether the reduction in structural damage with CRBFs may come at the cost of increased acceleration demands and associated nonstructural damage. This study offers a comprehensive investigation of such trade-offs by analyzing three buildings of different heights, each designed with the three ductile SFRSs identified above and with CRBFs. After examining the structural response at different earthquake intensities, the focus of the paper is on earthquake-induced economic losses. Among the considered SFRSs, greater total expected annual losses (EAL) are observed in the SMRF and SCBF buildings, primarily due to demolition losses and repairable losses, including repairs of structural and nonstructural components. The total EAL is lower for the BRBFs and lowest for the CRBFs, with the losses in the BRBF buildings primarily attributed to demolition loss, considered as irreparable loss, while the losses in the CRBF buildings are mainly due to acceleration-sensitive nonstructural components, considered as reparable loss. To provide a more detailed comparison, cost-effectiveness analyses are also performed, indicating that a modest cost premium for CRBFs is justified to reduce earthquake economic costs over the building lifetime.
Pliocene to modern sediment routing in the Aare valley: implications for sediment recycling
Authors: Stutenbecker Laura , Hinderer Matthias , Berndt Jasper , Glotzbach Christoph , Schlunegger Fritz , Schwenk Michael
Published: November 2024

Rivers transport sediment from source to sink, forming an essential part of sediment routing systems. Sediment generation is often assumed to be focused on the upstream reaches of mountainous rivers, characterized by high topographic gradients and high denudation rates. However, sediment recycling from uplifted and incised basin fills with relatively low topography, for example in foreland basins, may contribute significant amounts of material to the sediment cascade. Identifying and quantifying sediment recycling from such lowlands, however, is complicated by the lack of proxies sensitive to sediment recycling. Nevertheless, it is a crucial task in sedimentary system analysis, because any interpretation of allogenic or autogenic factors that control sediment dynamics in sedimentary systems strongly depends on where and how sediment is generated. We here present a sedimentary provenance study on the Aare river, a tributary to the Rhine river, which is sourced in the Swiss Alps and drains the Alpine foreland basin fill in its middle and lower reaches. Using garnet geochemistry as a proxy, the sediment sources in the Aare catchment can be precisely determined. We show that the modern Aare river carries garnet types incompatible with the crystalline rocks outcropping in the present-day catchment area, but compatible with Miocene sandstones of the foreland basin fill. By comparing modern-day fluvial sediment to Pleistocene and Pliocene paleo-Aare deposits we show that recycling from the foreland basin has been a dominant sediment generation process since the onset of the Pleistocene glaciation and the incision of river valleys. Instead, garnet compositions in a Pliocene terrace are more compatible with sediment sources in the Alpine crystalline core, pointing towards first-cycle sediment. Our study further emphasizes that (1) sediment recycling can be identified using appropriate provenance proxies, (2) provenance data are crucial to understanding the sediment dynamics and drainage evolution in Alpine river valleys, and (3) recycling from lowland basin fills may be a significant source of sediment that should be considered to prevent erroneous provenance interpretations.
Risk factors for proximal radial abnormalities in children with untreated chronic Monteggia fractures: a review of 142 cases
Authors: Wang WenTao , Mei QianQian , Liu Hang , Guo YueMing , Mei HaiBo , Canavese Federico , Andreacchio Antonio , Lyu HanQing , Chen ShunYou , He ShengHua
Published: November 2024

Background

The risk factors for proximal radial abnormalities (PRA) in paediatric patients with untreated chronic Monteggia fractures (CMFs) are unclear. This multicentre study aimed to evaluate the risk factors for PRA in children with untreated CMFs.

Materials and methods

The clinical data of 142 patients (mean age at the time of injury: 5.73 years) with untreated unilateral CMFs were retrospectively reviewed. The radial neck-shaft angle (RNSAP) and radial head size (RHL) were measured on anteroposterior (AP) and lateral (L) radiographs, respectively. The RHL size was the ratio of the widest width of the proximal radial metaphysis to the narrowest radial neck width. The En-RNSAP and En-RHL were the ratios of the enlargement (En) of the RNSAP angle and RHL size of the injured elbow to those of the uninjured elbow, respectively. Paired-sample t-tests, single-factor analyses and multiple linear regression analyses were performed to evaluate the correlation between the differences in these parameters between the injured and uninjured elbows and the assessed risk factors. These risk factors included institution, sex, laterality, age at injury, time from injury to diagnosis, direction of RH dislocation, distance of RH dislocation (DD-RH), presence of radial or median nerve injury, heterotopic ossification and immobilization of the elbow after injury.

Results

In children with untreated CMFs (mean time from injury to diagnosis: 14.6 months), Student’s t-test revealed a significant difference in the RHL size (P < 0.001) but not in the RNSAP angle (P = 0.075) between the injured and uninjured elbows. Pearson correlation analysis revealed a potential correlation between En-RHL and age at the time of injury (P = 0.069), time from injury to diagnosis (P < 0.001) and DD-RH (P < 0.001), excluding other risk factors (P > 0.05). Multiple linear regression analysis revealed that age at the time of injury (P = 0.047), time from injury to diagnosis (P = 0.007) and DD-RH (P = 0.001) were risk factors for an increased En-RHL in patients with untreated CMFs; the variability in En-RHL among the other three risk factors was 21.4%.

Conclusions

In paediatric patients with unilateral untreated CMFs, PRA of the injured elbow consisted mainly of RH enlargement or radial neck narrowing rather than valgus deformities of the proximal radius. Older age at injury, increased time from injury to diagnosis and DD-RH were risk factors for more severe PRA.

Level of evidence

III.
Validation of two predictive models for survival in anaplastic thyroid cancer (ATC)
Authors: Käsmann Lukas , Nieto Alexander , Rennollet Robert , Gurtner Ralph , Oliinyk Dmytro , Augustin Teresa , Koehler Viktoria Florentine , Neu Maria , Belka Claus , Spitzweg Christine , Rauch Josefine
Published: November 2024

Background

The prognosis of patients with anaplastic thyroid cancer (ATC) remains dismal. A small portion of patients experience longterm survival and need to be identified before treatment allocation. Survival scores may guide clinicians making more informed decisions about treatment options and improve the understanding of patients’ prognosis. The aim of this study was to validate two prognostic scores using an independent dataset to analyze which prognostic index is superior in discriminating survival.

Methods

Thirty-four patients with histologically confirmed ATC diagnosed between January 2009 and December 2019 were consecutively treated at our department and evaluated. Next generation sequencing was performed in 7 (21%) patients, but no druggable mutation was found. 50% of all patients received surgery and 56% were treated with chemoradiotherapy. The median radiation dose in equivalent dose in 2 Gy fractions (EQD2) was 50 Gy (SD:21 Gy). The study compared the discrimination of the Sugitani Prognostic Index (SPI) and the Marchand-Crety Prognostic Score (MCPS) using concordance statistics, area under the receiver-operating characteristics curve (AUC), net reclassification index, and integrated discrimination improvement for 6-month survival.

Results

The median survival of the entire cohort was 5 months (range: 1-133). The AUC for 6-month survival was 0.85 (95% confidence interval [CI]:0.72–0.97) for SPI and 0.69 (95% CI: 0.56–0.83) for MCPS (p < 0.0001). Using the net reclassification index (NRI), 73% of patients were correctly reclassified using SPI instead of MCPS for 6-month survival (p = 0.0237).

Conclusion

The SPI was more accurate than the MCPS to determine patients’ life expectancies and should be recommended for clinical guidance and treatment allocation. In the last decade, comprehensive genetic profiling of actionable mutations in ATC has become vital to guide targeted therapy.
Public perception of the physician associate profession in the UK: a systematic review
Authors: Swainston Rhys , Zhao Yingxi , Harriss Eli , Leckcivilize Attakrit , English Mike , Nagraj Shobhana
Published: November 2024

Background

The physician associate (PA) role within the NHS is currently under scrutiny due to recent legislative changes and concerns about their scope of practice within primary and secondary healthcare. There is currently limited knowledge of public understanding of PAs and their levels of satisfaction with PAs. This review synthesises the evidence relating to patients’ and potential patients’ understanding of and satisfaction with the PA profession in the UK.

Methods

We systematically searched Ovid MEDLINE, Ovid EMBASE, Ovid PsycINFO, EBSCOhost CINAHL, Education Resources Information Centre (ERIC), ProQuest Dissertations and Theses Global, and Scopus databases for empirical studies of patient understanding of PAs or satisfaction with PAs. We included quantitative, qualitative, and mixed-methods studies looking at PAs in primary and/or secondary care. Quality appraisal was conducted using the CASP Critical Appraisal checklists. A reflexive thematic analysis was used to synthesise data and the GRADE-CERqual method was used to assess the certainty of the themes.

Results

A total of 18 papers involving 15 studies were included in the review. Findings revealed that patients had limited understanding of the PA role with many mistaking PAs for doctors and other healthcare professionals. Patients were confused by the lack of PA prescribing rights. There was receptivity to learn more about the PA role. The evidence suggests that patients had a largely positive view of PAs after an encounter, despite their lack of knowledge about the role. Many patients expressed a willingness to be seen by PAs in future and viewed them as a useful part of the wider healthcare system.

Conclusion

In the UK, there is limited information about, and understanding of, the PA role. Nevertheless, patients were largely satisfied with the quality of care they receive from PAs during consultations. Our findings suggest a need for comprehensive public information regarding the roles and scope of practice of PA’s, and to provide the public and patients with clear expectations of their relative strengths and limitations. Further research might determine if these findings are specific to PAs, or reflect wider issues affecting public perception of other cadres of healthcare professionals.
Comparison of anatomical visual features of the eyeball, lens, and retina the diurnal common kestrel (Falco tinnunculus rupicilaeformis) and the nocturnal little owl (Athene noctua glaux)
Authors: Shalaby Walaa , Kandyel Ramadan , Abumandour Mohamed , Al-Ghamdi Fawzyah A. , Gewily Doaa
Published: November 2024

Our study aimed to compare the anatomical features of the eyeball, lens, and retina between the two raptor birds of different visual active clock hours: the diurnal common kestrel (Falco tinnunculus rupicilaeformis) and the nocturnal little owl (Athene noctua glaux) using gross, morphometric analysis, histological, and scanning and transmission electron microscopy techniques. The semi-spherical eyeball of the kestrel had less convexity on the anterior surface than on the posterior surface; meanwhile, it was relatively larger in the owl. There is a relationship between the corneal diameter (CD) and the eye axial length (AL). There were significant differences in the retinal layer thickness between the two raptors, in which the diurnal kestrel had a thinner pigmented epithelium and photoreceptor layers compared to the nocturnal owl. Moreover, the inner nuclear and outer nuclear, inner plexiform, and outer plexiform layers in the diurnal kestrel were larger than those in the nocturnal owl. The differences in the pigmented epithelium layer lead to the higher visual acuity and better color vision of the diurnal kestrel compared to the nocturnal owl. The photoreceptor layer in diurnal kestrel was composed of single large and double cones, which are composed of chief cones and accessory cones; meanwhile, the photoreceptor layer in nocturnal owl had only single elongated rods. We concluded that the lens and retina of the two raptors revealed great variations in reflecting the adaptation of each bird to different modes of life. The statistical analysis found a strong positive correlation between the axial length of the eye and the corneal diameter in both birds, as indicated by the Pearson correlation coefficient.
Influence of garden cress seeds supplementation on immunity, hormonal status, and milk quality during the last third of pregnancy and lactation period of rabbit does
Authors: El-Gindy Yassmine M. , Zahran Soliman M. , Ahmed Mohamed H. , Idres Azza Y. , Morshady Sabrin A.
Published: November 2024

During the last third of pregnancy period, rabbits are exposed to many challenges, such as health complications and oxidative stress. The present study aims to use garden cress seeds (GAC) as a natural antioxidant to mitigate these challenges and evaluate its effects on reproductive performance, immunity, hormones, protein profile and milk quality. A total of 24 pregnant V-Line rabbits (pregnant at 20 days proved by palpation), with an initial body weight of 2395.83 g and about 6–7 months of age, were randomly distributed to 4 groups, the control group was fed the basal diet without GAC, the other treated groups GAC 3, GAC 4.5 and GAC 6 were fed the basal diet supplemented with 3, 4.5, and 6% GAC, respectively. The experiment lasted six weeks. The results revealed that treated female rabbits with different levels of GAC did not have a noticeable effect on milk yield, average daily milk yield, or most of the milk analysis parameters (milk density, total solids, solids not fat, lactose, ash, and protein). On the other hand, GAC showed a significant increase in milk fat, and GAC 3% rabbits displayed a higher percentage of milk fat (p < 0.050) than the other groups. Likewise, treatment with GAC also had a significant impact on serum total protein, globulin, IgG, and IgM. The 3% GAC rabbits showed significantly higher total protein, globulin, and IgM values than the control group. However, all GAC treatments significantly improved serum IgG and the best value was found in the 3% GAC group. In conclusion, our results demonstrated that feeding lactating rabbits a diet supplemented with GAC could be considered a good strategy to enhance immunity, protein profile, MY and milk fat. The best results were obtained with the GAC 3% treatment.
A micro-costing study of mass-spectrometry based quantitative proteomics testing applied to the diagnostic pipeline of mitochondrial and other rare disorders
Authors: Santos Gonzalez Francisco , Hock Daniella H. , Thorburn David R. , Mordaunt Dylan , Williamson Nicholas A. , Ang Ching-Seng , Stroud David A. , Christodoulou John , Goranitis Ilias
Published: November 2024

Background

Mass spectrometry-based quantitative proteomics has a demonstrated utility in increasing the diagnostic yield of mitochondrial disorders (MDs) and other rare diseases. However, for this technology to be widely adopted in routine clinical practice, it is crucial to accurately estimate delivery costs. Resource use and unit costs required to undertake a proteomics test were measured and categorized into consumables, equipment, and labor. Unit costs were aggregated to obtain a total cost per patient, reported in 2023 Australian dollars (AUD). Probabilistic and deterministic sensitivity analysis were conducted to evaluate parameter uncertainty and identify key cost drivers.

Results

The mean cost of a proteomics test was $897 (US$ 607) per patient (95% CI: $734-$1,111). Labor comprised 53% of the total costs. At $342 (US$ 228) per patient, liquid chromatography coupled tandem mass spectrometry (LC-MS/MS) was the most expensive non-salary component. An integrated analysis pipeline where all the standard analysis are performed automatically, as well as discounts or subsidized LC-MS/MS equipment or consumables can lower the cost per test.

Conclusions

Proteomics testing provide a lower-cost option and wider application compared to respiratory chain enzymology for mitochondrial disorders and potentially other functional assays in Australia. Our analysis suggests that streamlining and automating workflows can reduce labor costs. Using PBMC samples may be a cheaper and more efficient alternative to generating fibroblasts, although their use has not been extensively tested yet. Use of fibroblasts could potentially lower costs when fibroblasts are already available by avoiding the expense of isolating PBMCs. A joint evaluation of the health and economic implications of proteomics is now needed to support its introduction to routine clinical care.
Off-label use of medicines in South Africa: a review
Authors: Ngcobo N. N. , Mathibe L. J.
Published: November 2024

Background

Off-label use of medicinal products has become an important part of mainstream and legitimate medical practice worldwide. This practice is common in oncology, obstetrics, paediatrics, and in the management of infectious diseases (notably HIV), and inflammatory conditions as well as in rare and/or orphan diseases. However, the off-label use of medicines recently-raised many clinical and legal difficulties, not only among medical practitioners but also among pharmacists and other healthcare professionals.

Aim

This paper, therefore, highlights the advantages (such as cost saving for both the patient and the country/insurance that is paying for the medication) and disadvantages (insufficient evidence available) of the use of medicines to treat specific conditions or indications for which they are currently not registered.

Conclusion

Off-label drug use can be likened to a double-edged sword, offering valuable opportunities for medical practitioners while carrying potential risks. When the scientific basis for off-label use is unclear, it may place patients at risk of unapproved experimentation, unforeseen health hazards, and ineffective treatments. Hence, there is a pressing need in South Africa for clear regulatory guidelines on off-label drug use. Additionally, the timely review and approval of new indications for medicines, backed by robust scientific evidence, are essential. This would reduce the significant burden and inherent risks faced by medical practitioners when using medicines off-label to provide compassionate care.
Taurine potentiates artemisinin efficacy against malaria by modulating the immune response in Plasmodium berghei-infected mice
Authors: Li Xin , Jiang Ning , Li Qilong , Zheng Kexin , Zhang Yiwei , Sang Xiaoyu , Feng Ying , Chen Ran , Chen Qijun
Published: November 2024

Background

Artemisinin (ART) is a frontline drug for the treatment of malaria; however, the emergence of ART-resistant Plasmodium strains necessitates increasing ART sensitivity. Given that taurine (TAU) has been shown to have immunomodulatory activity, we investigated the effects of TAU as an adjunct therapy to ART in mice infected with Plasmodium berghei.

Methods

Mice infected with P. berghei ANKA strain (P. berghei ANKA) were treated with TAU alone, ART alone or a combination of TAU and ART (TAU + ART), and their survival time and parasitaemia were recorded. The cytotoxic effects of TAU and ART were subsequently assessed. The expression levels of inflammasome-related genes and inflammatory factors in mice infected with P. berghei ANKA were analysed in relation to those in mice treated with TAU alone, ART alone or the TAU + ART combination. The therapeutic effects were further evaluated by histological analysis and measurement of the spleen index.

Results

Compared with the control mice, P. berghei ANKA-infected mice treated with ART in combination with TAU presented significantly lower parasitaemia and prolonged survival. The combined treatment resulted in significant reductions in the expression levels of inflammasome-related genes in the spleen, including absent in melanoma 2 (AIM2), caspase-1, NOD-, LRR- and pyrin domain-containing protein 3 (Nlrp3), Nlrp1b, Nlrp1b, NLR family CARD domain containing 4 (Nlrc4), Nlrp6, nucleotide binding oligomerization domain containing 1 (NOD1) and NOD2, and decreases in the levels of inflammatory cytokines in the serum, including interleukin (IL)-12p70, tumour necrosis factor-alpha, monocyte chemoattractant protein-1, IL-10 and IL-6. Histopathological analysis confirmed that TAU + ART combination treatment reduced spleen pathology caused by P. berghei ANKA infection.

Conclusions

The findings indicate that TAU potentiates ART efficacy by modulating the immune response in P. berghei-infected mice.

Graphical Abstract
Correlation between right atrial pressure measured via right heart catheterization and venous excess ultrasound, inferior vena cava diameter, and ultrasound-measured jugular venous pressure: a prospective observational study
Authors: Klangthamneam Suppawee , Meemook Krissada , Petnak Tananchai , Sonkaew Anchana , Assavapokee Taweevat
Published: November 2024

Background

Venous congestion is associated with adverse cardiovascular outcomes, necessitating accurate venous pressure assessment. Current methods, such as right heart catheterization (RHC), have limitations. Non-invasive techniques, including venous excess ultrasound (VExUS), inferior vena cava (IVC) assessment, and ultrasound-measured jugular venous pressure (uJVP), show promise but require validation in diverse populations.

Aims

We aimed to assess the correlation between right atrial pressure (RAP) via RHC and non-invasive methods, including VExUS, IVC diameter with collapsibility index (CI) by American Society of Echocardiography (ASE) classification, and uJVP.

Methods

In a prospective study involving 73 patients undergoing RHC, we evaluated the correlation between RAP and VExUS, IVC CI by ASE classification, and uJVP. We introduced and compared a modified VExUS grading system.

Results

VExUS significantly correlated with RAP (p < 0.001), especially between VExUS grade 0 and grade 3. RAP significantly differed across IVC classifications by ASE (P < 0.001). VExUS grade 0 correlated with IVC class 1, and VExUS grade 3 correlated with IVC class 3. The modified VExUS grading system improved low and high RAP differentiation. uJVP exhibited a robust, highly significant positive correlation with invasively measured RAP (ρ = 0.67, P < 0.001).

Conclusion

This study establishes a strong correlation between non-invasive ultrasound measurements (VExUS, IVC diameter with CI, and uJVP) and invasively measured RAP. These findings underscore the clinical potential of these non-invasive techniques in venous congestion assessment and patient risk stratification.
Onset of Type 2 diabetes in adults aged 50 and older in Europe: an intersectional multilevel analysis of individual heterogeneity and discriminatory accuracy
Authors: O’Sullivan Julie Lorraine , Alonso-Perez Enrique , Färber Francesca , Fuellen Georg , Rudolf Henrik , Heisig Jan Paul , Kreyenfeld Michaela , Gellert Paul
Published: November 2024

Background

Disparities in the development of Type 2 Diabetes (T2D) are associated with various social determinants, including sex/gender, migration background, living arrangement, education, and household income. This study applied an intersectional perspective to map social disparities and investigate intersectional effects regarding the onset of T2D among older adults across Europe.

Methods

We used data from the Survey of Health and Retirement in Europe (SHARE) to conduct an Intersectional Multilevel Analysis of Individual Heterogeneity and Discriminatory Accuracy (I-MAIHDA) of T2D onset. Individuals aged 50 years or older without known T2D at Wave 4 (2011, baseline) were included and followed through Waves 5 (2013), 6 (2015), 7 (2016), and 8 (2019–2020). Intersectional models were used to estimate additive main effects of sex/gender, migration background, living arrangement, education level, and household income and intersectional interactions.

Results

A total of 39,108 individuals were included (age at baseline M = 65.18 years (SD = 9.62), 57.4% women). T2D onset was reported for 9.2% of the sample over the 9-year observation period. In the fully adjusted model, all social determinants showed significant additive associations with T2D onset, while the discriminatory accuracy of the social strata was found to be low (Variance Partition Coefficient = 0.3%).

Conclusions

This study provides a comprehensive mapping of intersectional disparities in onset of T2D among older adults in Europe. The results highlight the risk heterogeneity within the population and show social disadvantages faced by certain groups. However, while the T2D risks were higher in some strata than in others, the intersectional effects were small overall and mostly attributable to the additive main effects. The results suggest that public health strategies to prevent T2D should be universal but tailored to meet the specific situation of the different intersectional strata.
Canadian Society of Allergy and Clinical Immunology position statement: panel testing for food allergies
Authors: Al Ghamdi Abdulrahman , Abrams Elissa M. , Carr Stuart , Hanna Mariam A. , Herman Sari M. , Lavine Elana , Kim Harold , Vander Leek Timothy K. , Mack Douglas P.
Published: November 2024

This position statement addresses the critical concerns and recommended practices surrounding the use of panel food testing for diagnosing food allergies. Food allergies are a significant public health concern, and the misdiagnosis of food allergies remains a prevalent concern, made worse by the ongoing use of panel food testing. The practice of screening patients for multiple food allergens, regardless of clinical relevance, is commonly referred to as “panel food testing.” Fundamentally, a panel food test is not simply a single test; a panel food test is a series of several distinct tests for multiple foods, each with its own variable predictive value. These tests have not been adequately validated as screening tests and carry a considerable false positive rate. The resulting false diagnoses lead to unnecessary dietary restrictions, increased healthcare costs, and significant psychosocial distress for patients and their families.
Late relapse of anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis: a case report
Authors: Amiri Hamidreza , Karimi Mehdi , Shariatmadari Fakhreddin
Published: November 2024

Background

Anti-N-methyl-d-aspartate receptor encephalitis is a sporadic autoimmune disorder of the brain that presents in a variety of neuropsychiatric manifestations, including seizures, psychosis, and alterations in behavior. N-methyl-d-aspartate receptor is primarily seen in young females. Although this disease can be treated, it can relapse in rare cases. Relapsing typically occurs within the early years following the initial episode and is exceedingly rare after 5 years.

Case presentation

In this case study, we report on a 16-year-old Iranian female experiencing a relapse of anti-N-methyl-d-aspartate receptor encephalitis 8 years after her initial diagnosis. She was admitted to the hospital with dysphasia (a speech disorder) and dyslexia (reading and writing impairment). A thorough clinical evaluation revealed the presence of anti-glutamate receptor type N-methyl-d-aspartate receptor antibodies in her serum and cerebrospinal fluid, confirming the diagnosis. Following treatment with immunotherapy and plasmapheresis, she made a complete recovery.

Conclusion

This case of relapsing anti-N-methyl-d-aspartate receptor encephalitis, occurring more than 5 years after the initial episode, is exceptionally rare. This late relapse underscores the importance of long-term follow-up for patients with this condition.
Golodirsen restores DMD transcript imbalance in Duchenne Muscular Dystrophy patient muscle cells
Authors: Rossi Rachele , Torelli Silvia , Moore Marc , Ala Pierpaolo , Morgan Jennifer , Malhotra Jyoti , Muntoni Francesco
Published: November 2024

Background

Antisense oligonucleotides (AON) represent a promising treatment for Duchenne muscular dystrophy (DMD) carrying out-of-frame deletions, but also show limitations. In a completed clinical trial golodirsen, approved by FDA to induce skipping of DMD gene exon 53 in eligible patients, we demonstrated increase in DMD expression and protein production, albeit with inter-patient variability.

Methods

Here, we investigate further the golodirsen mechanism of action using myotubes derived from MyoD transfected fibroblasts isolated from DMD patients at the baseline of the clinical trial SRP-4053.

Results

We confirm golodirsen’s selectivity and efficiency in removing only exon 53. For the first time in human cells, we revealed a significant reduction in the so called DMD “transcript imbalance”, in golodirsen-treated DMD muscle cultures. The transcript imbalance is a unique DMD phenomenon characterized by non-homogeneous transcript expression along its entire length and responsible for the reduced stability of the transcript. Our in-vivo study also showed that the efficiency of exon skipping did not always correspond to a proportional restoration of the dystrophin protein. Predominant nuclear localization of the DMD transcript, observed in patients and animal models, persists even after exon skipping.

Conclusion

All these findings suggest challenges other than AON delivery for high level of protein restoration in DMD, highlighting the importance of investigating the biological mechanisms upstream of protein production to further enhance the efficiency of any AON treatment in this condition.
Identification and validation of respiratory subphenotypes in patients with COVID-19 acute respiratory distress syndrome undergoing prone position
Authors: da Cruz Mônica R. , Azambuja Pedro , Torres Kátia S. C. , Lima-Setta Fernanda , Japiassú André M. , Medeiros Denise M.
Published: November 2024

Background

The heterogeneity of acute respiratory distress syndrome (ARDS) patients is a challenge for the development of effective treatments. This study aimed to identify and characterize novel respiratory subphenotypes of COVID-19 ARDS, with potential implications for targeted patient management.

Methods

Consecutive ventilated patients with PCR-confirmed COVID-19 infection, in which prone positioning was clinically indicated for moderate or severe ARDS, were included in a prospective cohort. The patients were assigned to development or validation cohorts based on a temporal split. The PaO2/FiO2 ratio, respiratory compliance, and ventilatory ratio were assessed longitudinally throughout the first prone session. The subphenotypes were derived and validated using machine learning techniques. A K-means clustering implementation designed for joint trajectory analysis was utilized for the unsupervised classification of the development cohort. A random forest model was trained on the labeled development cohort and used to validate the subphenotypes in the validation cohort.

Results

718 patients were included in a prospective cohort analysis. Of those, 504 were assigned to the development cohort and 214 to the validation cohort. Two distinct subphenotypes, labeled A and B, were identified. Subphenotype B had a lower PaO2/FiO2 response during the prone session, higher ventilatory ratio, and lower compliance than subphenotype A. Subphenotype B had a higher proportion of females (p < 0.001) and lung disease (p = 0.005), higher baseline SAPS III (p = 0.002) and SOFA (p < 0.001) scores, and lower body mass index (p = 0.05). Subphenotype B had also higher levels of the pro-inflammatory biomarker IL-6 (p = 0.017). Subphenotype B was independently associated with an increased risk of 60-day mortality (OR 1.89, 95% CI 1.51–2.36). Additionally, Subphenotype B was associated with a lower number of ventilator-free days on day 28 (p < 0.001) and a lower hospital length of stay (p < 0.001). The subphenotypes were reproducible in the validation cohort.

Conclusion

Our study successfully identified and validated two distinct subphenotypes of COVID-19 ARDS based on key respiratory parameters. The findings suggest potential implications for better patient stratification, risk assessment, and treatment personalization. Future research is warranted to explore the utility of these novel subphenotypes for guiding targeted therapeutic strategies in COVID-19 ARDS.
Sexual orientation discrimination and eating disorder symptoms in early adolescence: a prospective cohort study
Authors: Nagata Jason M. , Diep Thang , Helmer Christiane K. , Domingue Sydnie K. , Al-Shoaibi Abubakr A. , Raney Julia H. , Ganson Kyle T. , Testa Alexander , He Jinbo , Brindis Claire D. , Baker Fiona C.
Published: November 2024

Background

Sexual orientation discrimination increases the risks of negative health outcomes for sexual minorities. Previous studies have found increased rates of eating disorder symptoms in sexual minority individuals, which is attributable to minority stress and discrimination that they experience. Emerging research suggests relationships between sexual orientation discrimination and eating disorder symptoms. However, there is a lack of studies focusing on early adolescents. The objective of this study was to determine prospective associations between discrimination based on sexual orientation and eating disorder symptoms in a national sample of 10–13-year-old early adolescents in the U.S.

Methods

We examined prospective data from Year 2 (2018–2020) and Year 3 (2019–2021) of the Adolescent Brain Cognitive Development (ABCD) Study (N = 8976). Multiple logistic regression analyses were used to estimate associations between self-reported experiences of sexual orientation discrimination in Year 2 and eating disorder symptoms in Year 3, adjusting for potential confounders, including eating disorder symptoms in Year 2. Sexual orientation discrimination was assessed based on the Perceived Discrimination Scale, which measures adolescents’ perception of being treated unfairly based on various sociodemographic characteristics. Eating disorder symptoms were based on the parent-reported Kiddie Schedule for Affective Disorders and Schizophrenia (KSADS-5).

Results

In this demographically diverse sample of early adolescents (N = 8976, age range 10–13 years at Year 2), 5.5% of adolescents reported sexual orientation discrimination in Year 2. The prevalence of parent-reported eating disorder symptoms in Year 3 varied from 1.0 to 8.3%. In the adjusted models, sexual orientation discrimination was prospectively associated with worry about weight gain (adjusted odds ratio [aOR] 2.33, 95% confidence interval [CI] 1.15–4.69) and self-worth tied to weight (aOR 1.60, 95% CI 1.01–2.53) one year later.

Conclusions

Early adolescents who have experienced sexual orientation discrimination have higher odds of experiencing eating disorder symptoms, particularly worrying about weight gain and tying self-worth to weight. Clinicians may consider screening for sexual orientation discrimination and providing affirmative, trauma-informed care when evaluating and treating even younger sexual minority adolescents for eating disorder symptoms.