bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and Validation of a New Nomogram for Predicting Early Neurological Deterioration in Young and Middle‐Aged Individuals With Stroke in the Neurocritical Care Unit
Authors: Li Xin , Li Junzhuo , Liao Jia , Zhu Yueping , Quan Fengying
Published: November 2024

Objective

To analyse risk factors for early neurological damage in young and middle‐aged stroke cases.

Methods

Totally 405 young and middle‐aged stroke patients in the neurocritical care unit (NCU) were selected and divided into the developmental (260 patients) and validation (145 patients) sets. The 405 cases were also grouped based on whether early neurological deterioration (END) occurred. The influencing factors of END were analysed by logistic regression, followed by the construction of a nomogram for predicting the risk of END. The Bootstrap method was applied to internally verify the predictive value of the model, using validation set data.

Results

Age, type of stroke, diabetes, mechanical ventilation, pulse, initial National Institute of Health stroke scale (NIHSS), Barthel index (BI), haemoglobin, hypersensitive C‐reactive protein (hs‐CRP), triglyceride glucose (TyG) index and CONUT showed statistically significant differences (p < 0.05). Logistic regression analysis revealed type of stroke, initial NIHSS, CONUT, TyG index and hs‐CRP were risk factors for END in young and middle‐aged stroke cases (OR > 1, p < 0.05). The area under the curve (AUC) for the developmental set was 0.842, and internal validation results showed a C‐index of 0.843; the AUC for the validation set was 0.843.

Conclusion

The nomogram constructed in this study has good predictive efficacy and can provide reference for early clinical prediction of END in young and middle‐aged stroke cases.

Relevance to Clinical Practice

The importance of this research lies in shedding light on the significant impact of early neurological deterioration on the health outcomes of young and middle‐aged stroke patients, particularly in the short term. To guide clinical workers to identify risk factors early and improve the prognosis of stroke patients.
Exploring Post‐Fall Management Interventions in Long‐Term Care Facilities and Hospitals for Older Adults: A Scoping Review
Authors: Parekh Abhishek , Hill Keith D. , Guerbaai Raphaëlle Ashley
Published: November 2024

Background

The population is rapidly growing, significantly impacting healthcare settings such as hospitals and long‐term care. Falls are a major concern, being a leading cause of hospitalisations and injuries especially among adults aged 60 and above. Despite extensive research on falls prevention and risk factors, there is limited study on effective post‐fall management strategies, making it crucial to review and develop interventions to improve care and safety for older adults in healthcare settings.

Aim

To explore the interventions implemented for post‐fall management for residents and patients within healthcare settings, including hospitals and long‐term care facilities.

Design

A scoping literature review.

Methods

We used the Joanna Briggs Institute guidance and the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis extension for scoping reviews (PRISMA‐ScR). Eligible articles included hospital and long‐term care post‐fall management interventions. Data were manually extracted by two independent reviewers using the AACTT (Actor, Action, Context, Target and Time) Framework to detail intervention characteristics and guide the data charting process, allowing for thematic analysis and narrative synthesis of key findings.

Data Sources

Medline, CINAHL, PsychINFO and Scopus were searched from inception until 30th September 2024.

Results

Eighteen articles were included. Over half the studies (55.5%) focused on post‐fall interventions in LTCFs, testing assessment tools (50%), structured protocols (27.7%), huddles (11.1%) or multifactorial approaches (11.1%), with varied effectiveness. While assessment tools and huddles showed mixed results, structured protocols showed encouraging results with reduced unnecessary hospital transfers and hospitalisations.

Conclusion

This scoping review identified a variety of interventions used after falls in healthcare settings. However, there is inconclusive evidence about the effectiveness of interventions to reduce hospitalisation and injuries. This review identified areas for research that may help to inform post‐fall management, including the need for further research into various interventions (e.g., standardised toolkit) to enhance care immediately following a fall.

Patient or Public Contribution

No Patient or Public Contribution.
Promoting the Concept Healthy Ageing for Use in Gerontological Health and Social Care Policy and Practice
Authors: Donnellan C.
Published: November 2024

Aims

The concept of healthy or successful ageing dates back to the 1960s, where its goal is more realistic in today's ageing society as a result of effective interventions to control and reduce disability and health risks. The aim of this paper is to outline the importance of defining ageing, the semantics and indicators used, and to identify common challenges for health professionals' understanding and application of a healthy ageing approach in their everyday clinical practice.

Design and Methods

This discursive paper demonstrates how realistic ageing indicators are for highlighting the variation and impact of challenges associated with ageing. It examines the proportion of older adults requiring aged‐care services and allocation of resources, focusing on health maintenance and secondary ageing prevention.

Results

Indicators of ageing commonly used in clinical healthcare settings are reviewed, and their appropriateness for determining functional and intrinsic capacity of older adults. Other indicators are introduced, i.e., the Healthy Life Expectancy (HLE), Disability Free Life Expectancy (DFLE), the Human Development Index (HDI), and the Active Ageing Index (AAI), for enhancing and promoting a healthy ageing model of healthcare. Healthy ageing models of health and social care are also considered.

Conclusions

Outlining evidence on healthy ageing may facilitate health professionals to address realistic challenges regarding age‐related health and social care provision, using a personalised approach for every older adult as opposed to cutting off chronological age parameters.

Relevance to Clinical Practice

Increasing health professionals' focus on healthy ageing will maintain good health in at least 80% of the ageing population for longer.

Patient or Public Contribution

No patient or public contribution.
Comparative evaluation of human oral fibroblast proliferation on 3D‐printed zirconia and silicon nitride as new ceramic materials for implant abutment
Authors: Khurana Saumya , Li Yingzi , Kesterke Matthew , Liu Xiaohua , Zandinejad Amirali
Published: November 2024

Purpose

Cell adhesion and subsequent proliferation on material surfaces depend on the physical and chemical characteristics of the material. There is a lack of literature on human gingival fibroblast proliferation on comparatively newer additively manufactured materials like silicon nitride. This study focused on the physical characteristics of the materials with the aim to compare the adhesion and proliferation of human gingival fibroblasts on additively manufactured silicon nitride (AMSN) with additively manufactured zirconia, conventional milled titanium (MTi), and milled zirconia.

Materials and Methods

Surface roughness and water contact angle were measured by profilometer and goniometer, respectively. CCK‐8 assay was done to assess the cell growth at 24 h (day 1), 48 h (day 2), and 72 h (day 3) in the same well. The morphologies of fibroblasts after cell attachment and proliferation were evaluated using scanning electron microscopy (SEM) after 72 h.

Results

At the end of 24 h (day 1) additively manufactured zirconia showed the best proliferation among the experimental groups, which was around 50% of the positive control group proliferation. There was no statistically significant difference among the experimental groups. At 48 h (day 2) and 72 h (day 3), a loss of cell growth was seen in almost all the experimental group wells. A positive cell proliferation on the AMSN was observed on day 3.

Conclusion

Comparable cell proliferation was observed in the experimental groups. No conclusive correlation could be drawn between cell proliferation and surface roughness and water contact angle values in the experimental groups.
Oxygen and pH fluxes in shallow bay habitats: Evaluating the effectiveness of a macroalgal forest restoration
Authors: Galobart Cristina , Sitjà Cèlia , de Caralt Sònia , Santamaría Jorge , Vergés Alba , Boada Jordi , Cebrian Emma
Published: November 2024

Marine macroalgae are important primary producers in coastal ecosystems. Within sheltered and shallow bays in the Mediterranean, various Fucalean macroalgae and seagrasses coexist, creating habitats of high ecological importance. These habitats have historically suffered from various disturbances, and on this basis, active restoration actions have been proposed as potential solutions for their recovery. Here, we assessed the restoration success of a 10‐year restored macroalgal forest by evaluating the recovery in terms of oxygen and pH fluxes and comparing those data with those of a healthy marine forest and a degraded habitat counterpart. We estimated the overall changes in dissolved oxygen and pH using light and dark community in situ incubations. We also determined the biomass and composition of macroalgal and macroinvertebrate compartments of each assemblage. During light incubations, the healthy and restored forest assemblages showed similar average net oxygen production, 5.7 times higher than in the degraded one, and a greater increase in pH. More than 95% of the incubated biomass corresponded to macroalgal and seagrass species. The restored forest showed a six‐fold increase in biomass, most likely being responsible for the recovery of primary production. This work provides empirical evidence that the restoration of a single structural species, once successful in the early stages, can yield positive results by recovering processes such as primary production and dark respiration. Moreover, these results showcase differences in ecosystem functions between healthy (either mature or restored) and degraded habitats, highlighting the importance of protecting and preserving coastal marine forests.
Mesaconate from Bacillus subtilis R0179 Supernatant Attenuates Periodontitis by Inhibiting Porphyromonas gingivalis in Mice
Authors: Zhao Weiwei , Ji Lingli , Li Jie , Liu Dandan , Yan Changqing , Zhang Chenying , Wang Xiaozhe , Liu Yang , Zheng Shuguo
Published: November 2024

Aims

This research sought to assess the efficacy of Bacillus subtilis (B. subtilis) R0179 and explore potential metabolites in mitigating experimental periodontitis in mice induced by Porphyromonas gingivalis (P. gingivalis) ATCC 33277.

Methods

B. subtilis R0179 was administered to 8‐week‐old male C57BL/6J mice with periodontitis. Oral load of P. gingivalis ATCC 33277 and periodontal tissue loss were quantified. The cell‐free supernatant (CFS) was separated to assess its anti‐P. gingivalis effect. Proteomic and metabolomic analyses identified potential antibacterial components in the CFS, further evaluated for anti‐P. gingivalis effects.

Results

B. subtilis R0179 significantly reduced P. gingivalis ATCC 33277 levels and mitigated periodontal tissue loss in mice. The CFS, rather than inactivated B. subtilis R0179 cells, exhibited antibacterial activity. Proteomic and metabolomic analyses identified mesaconate and citraconate as key antibacterial agents. Disk diffusion assays confirmed the efficacy of mesaconate against P. gingivalis, while citraconate had no effect. Mesaconate showed a dose‐dependent reduction in P. gingivalis ATCC 33277 population and periodontal tissue loss in mice.

Conclusion

These findings highlight B. subtilis R0179 and its metabolite mesaconate as promising candidates for therapeutic development against periodontitis by inhibiting P. gingivalis ATCC 33277 effectively.
Transformation‐based gene silencing and functional characterization of an ISC effector reveal how a powdery mildew fungus disturbs salicylic acid biosynthesis and immune response in the plant
Authors: Yin Jinyao , Li Xiao , Dong Linpeng , Zhu Xuehuan , Chen Yalong , Zhao Wenyuan , Liu Yuhan , Shan Jiaxin , Liu Wenbo , Lin Chunhua , Miao Weiguo
Published: November 2024

Obligate biotrophic powdery mildew fungi infect a wide range of economically important plants. These fungi often deliver effector proteins into the host tissues to suppress plant immunity and sustain infection. The phytohormone salicylic acid (SA) is one of the most important signals that activate plant immunity against pathogens. However, how powdery mildew effectors interact with host SA signalling is poorly understood. Isochorismatase (ISC) effectors from two other filamentous pathogens have been found to inhibit host SA biosynthesis by hydrolysing isochorismate, the main SA precursor in the plant cytosol. Here, we identified an ISC effector, named EqIsc1, from the rubber tree powdery mildew fungus Erysiphe quercicola. In ISC enzyme assays, EqIsc1 displayed ISC activity by transferring isochorismate to 2,3‐dihydro‐2,3‐dihydroxybenzoate in vitro and in transgenic Nicotiana benthamiana plants. In EqIsc1‐expressing transgenic Arabidopsis thaliana, SA biosynthesis and SA‐mediated immune response were significantly inhibited. In addition, we developed an electroporation‐mediated transformation method for the genetic manipulation of E. quercicola. Inoculation of rubber tree leaves with EqIsc1‐silenced E. quercicola strain induced SA‐mediated immunity. We also detected the translocation of EqIsc1 into the plant cytosol during the interaction between E. quercicola and its host. Taken together, our results suggest that a powdery mildew effector functions as an ISC enzyme to hydrolyse isochorismate in the host cytosol, altering the SA biosynthesis and immune response.
Mechanism of zju‐miR156c‐mediated network in regulating witches' broom symptom of Chinese jujube
Authors: Wang Yunjie , Luo Zhi , Zhao Xuan , Sun Hongqiang , Liu Jiaxin , Zhang Dongfeng , Cao Haonan , Ai Changfeng , Wang Lihu , Dai Li , Liu Mengjun , Wang Lixin , Liu Zhiguo
Published: November 2024

Jujube witches' broom, caused by phytoplasma, is a destructive disease of Chinese jujube. Studies have shown that zju‐miR156s play an important role in phytoplasma infection in jujube, but the regulatory mechanism between zju‐miR156c and witches' broom remains unexplored. In the current study, miRNA‐seq and gene expression analysis showed that zju‐miR156c was more highly induced in infected jujube plants than the other miRNAs and its target gene was ZjSPL3. In addition, the expression levels of thymidylate kinase gene (TMKJWB) and secreted jujube protein (SJP1JWB) in diseased materials were higher than those in healthy controls. The expression level of zju‐miR156c was significantly upregulated, while ZjSPL3 was sharply downregulated and the content of cytokinin (CTK) significantly increased. Overexpression of zju‐miR156c in Arabidopsis significantly reduced the expression of AtSPL10 (homologous gene of ZjSPL3) but increased the content of CTK, and the transgenic plants exhibited witches' broom symptoms. In addition, yeast two‐hybrid and co‐immunoprecipitation assays confirmed that SJP1JWB interacted with ZjERF18. Yeast one‐hybrid analysis showed that ZjERF18 could interact with the promoter of zju‐MIR156c. In conclusion, our results demonstrated a novel pathogenic module of ZjERF18‐zju‐miR156c‐ZjSPL3‐CTK has an important function in the formation of witches' broom caused by SJP1JWB.
Development of COVID‐19 Infection Prevention and Control Training Program Based on ADDIE Model for Clinical Nurses: A Pretest–Posttest Study
Authors: Liang Bing , Zhang Jiaxin , Qu Zhifei , Jiang Nan , Chen Chen , Cheng Siming , Li Li
Published: November 2024

Scientific and effective training is important to enhance the theoretical knowledge and practical skills of clinical nurses in coronavirus disease 2019 (COVID‐19) prevention and control (IPC), so as to improve the IPC capacity. The study aimed to design and implement a COVID‐19 IPC training program for clinical nurses based on the ADDIE model, and to evaluate its clinical application effects. This was a pretest–posttest study in which 389 clinical nurses were recruited through convenience sampling. The IPC training program for clinical nurses was developed based on the five stages of ADDIE model. Data were analyzed using pared‐sample t test, McNemar's test, and Wilcoxon test. After training, nurses' theoretical scores and operational scores except for hand hygiene were improved significantly (p < 0.001). Compared to pre‐training assessment, their job performances were also significantly improved (p < 0.001). And they had higher satisfaction with the program post‐training. Under the situation of COVID‐19, training based on the ADDIE model can effectively improve the IPC ability of clinical nurses. Besides, it provides new ideas, methods, and approaches for future clinical IPC training.
Health Professionals on Cross‐Sectoral Collaboration Between Mental Health Hospitals and Municipalities: A Critical Discourse Analysis
Authors: Jørgensen Kim , Jørgensen Kristine Bro , Frederiksen Jesper , Watson Emma , Hansen Morten , Karlsson Bengt
Published: November 2024

This study investigates the role of language in cross‐sector collaboration between mental health hospitals and municipalities, focusing on the challenges of maintaining continuity of care and integrating patient‐centered approaches. Using Fairclough's framework for critical discourse analysis, we examined focus group interviews with 21 healthcare professionals, including nurses, social workers, and psychiatrists, to identify key themes and patterns in how cross‐sector collaboration is discussed. The analysis revealed a dominant medicalized discourse in hospital settings, which often emphasized structured care processes like treatment plans and medication management, overshadowing more flexible, patient‐centered approaches common in community‐based services. Power dynamics were evident, with hospital professionals frequently positioned as active agents, while patients and community‐based workers were portrayed in more passive roles. Although efforts to involve patients in decision‐making were noted, these were often controlled by professionals, reflecting a mediated approach to patient empowerment. The findings highlight the cultural and structural divides between hospital and community services and suggest the need for improved communication strategies, integrated care pathways, and a shift toward more inclusive, patient‐centered care models. Addressing these discursive barriers is crucial for achieving more effective, integrated, and patient‐centered care, ultimately improving outcomes for patients.
Is Generative AI Increasing the Risk for Technology‐Mediated Trauma Among Vulnerable Populations?
Authors: Abdulai Abdul‐Fatawu
Published: November 2024

The proliferation of Generative Artificial Intelligence (Generative AI) has led to an increased reliance on AI‐generated content for designing and deploying digital health interventions. While generative AI has the potential to facilitate and automate healthcare, there are concerns that AI‐generated content and AI‐generated health advice could trigger, perpetuate, or exacerbate prior traumatic experiences among vulnerable populations. In this discussion article, I examined how generative‐AI‐powered digital health interventions could trigger, perpetuate, or exacerbate emotional trauma among vulnerable populations who rely on digital health interventions as complementary or alternative sources of seeking health services or information. I then proposed actionable strategies for mitigating AI‐generated trauma in the context of digital health interventions. The arguments raised in this article are expected to shift the focus of AI practitioners against prioritizing dominant narratives in AI algorithms into seriously considering the needs of vulnerable minority groups who are at the greatest risk for trauma but are often invisible in AI data sets, AI algorithms, and their resultant technologies.
AAAAI–EAACI PRACTALL: Standardizing oral food challenges—2024 Update
Authors: Sampson Hugh A. , Arasi Stefania , Bahnson Henry T. , Ballmer‐Weber Barbara , Beyer Kirsten , Bindslev‐Jensen Carsten , Bird J. Andrew , Blumchen Katarina , Davis Carla , Ebisawa Motohiro , Nowak‐Wegrzyn Anna , Patel Nandinee , Peters Rachel L. , Sicherer Scott , Spergel Jonathan , Turner Paul J. , Yanagida Noriyuki , Eigenmann Philippe A.
Published: November 2024

This common statement of the American Academy of Allergy, Asthma and Immunology (AAAAI) and The European Academy of Allergy and Clinical Immunology (EAACI) provides an update of the 2012 published guidelines on food challenges. The guidelines equally address food challenges in the research and the clinical settings. They first address the diagnostic tests which can guide the decision to conduct a challenge. Safety of food challenges is prime, and the various procedures and safety issues as well as medications potentially involved in challenges are extensively discussed. Challenges are suggested to be conducted with semi‐logarithmic incremental doses based on the protein content, typically for IgE‐mediated food allergy with intervals of 20–30 min between doses. Specific protocols for other types of reactions such atopic dermatitis or gastrointestinal food allergy are detailed separately. Proper stopping criteria are essential in order to reduce the risk of false‐positive diagnoses, but also severe reactions. The guidelines recommend criteria based on “go on,” “stop,” or “observation.” These revised guidelines will clearly provide much needed guidance for food challenges in the research and clinical settings. They will continue to evolve with new diagnostic tests or new needs in the field of food allergy.
The influence of pain on community reintegration after spinal cord injury
Authors: Henderson Valerie , Mashola Mokgadi Kholofelo
Published: November 2024

Background

Community reintegration is an important goal for people living with a spinal cord injury (SCI), and pain is suspected to limit reintegration due to its limitations in daily functioning, mood, and sleep.

Objectives

To determine the influence of pain on community reintegration in manual wheelchair users with SCI.

Methods

The Reintegration to Normal Living Index was used to determine community reintegration, while the DN4 and the Wheelchair User's Shoulder Pain Index were used to determine the presence of neuropathic and shoulder pain respectively. Associations and differences between the pain variables and participants with and without pain were analyzed with Spearman correlations and Mann–Whitney U‐tests using SPSS v27 at 0.05 significance level and 95% confidence interval.

Results

Of the 122 participants, 85.2% reported current pain, with a 77.7% median for community reintegration. Neuropathic pain (53.3%) was more common and severe than nociceptive shoulder pain (14.8%). There was no significant difference in community reintegration between participants with and without pain, nor any correlation between the overall presence of pain and community reintegration. The severity of pain, particularly shoulder pain, was negatively associated with taking trips out of town (p < 0.01), and overall community reintegration (p < 0.05).

Conclusion

It is not the mere presence of pain that influences community reintegration, but rather the severity and the location of pain. Shoulder care and pain management need to be included in the rehabilitation program, as these are important considerations when rehabilitating people with SCI back into their communities.
Decoding the Double Stress Puzzle: Investigating Nutrient Uptake Efficiency and Root Architecture in Soybean Under Heat‐ and Water‐Stresses
Authors: Maslard Corentin , Arkoun Mustapha , Leroy Fanny , Girodet Sylvie , Salon Christophe , Prudent Marion
Published: November 2024

In the context of climate change, associated with increasingly frequent water deficits and heat waves, there is an urgent need to maintain the performance of soybean, a leading legume crop worldwide, before its yield declines. The objective of this study was to explore which plant traits improve soybean tolerance to heat and/or water stress, with a focus on traits involved in plant architecture and nutrient uptake. For this purpose, two soybean genotypes were grown under controlled conditions in a high‐throughput phenotyping platform where either optimal conditions, heat waves, water stress or both heat waves and water stresses were applied during the vegetative stage. By correlating architectural to functional traits, related to water, carbon allocation and nutrient absorption, we were able to explain the stress susceptibility level of the two genotypes. We have shown that water flow in the plant is central to the uptake and allocation of mineral elements in the plant, despite its modulation by stress and in a genotype‐dependent manner. This cross‐analysis of plant ecophysiology and plant nutrition under different stresses provides new information, especially on the importance of mineral elements in the different plant organs, and can inform future crop design, particularly under changing climatic conditions.
Decreasing Endomyocardial Biopsy Frequency in Pediatric Heart Transplantation Using A Rejection Risk Prediction Score—A Single Center Study
Authors: Tolani Drishti , Butts Ryan J. , Sutcliffe David L. , Power Alyssa
Published: November 2024

Background

Rejection remains an important cause of morbidity and mortality after pediatric heart transplantation (HT). Endomyocardial biopsy (EMB) is the gold standard for rejection diagnosis, but it comes with procedural risk. The frequency of EMB varies significantly across centers. Since April 2018, our center's surveillance EMB schedule is based on a rejection risk prediction score employing age, pre‐HT diagnosis, and panel reactive antibodies (PRA). We aimed to evaluate outcomes in the 1st year post‐HT before and after risk score implementation.

Methods

Patients who underwent HT at our center at ≤ 18 years of age from January 2015 to December 2020 were reviewed. The primary endpoint was rejection‐free survival at 1 year‐post‐ HT. Clinical characteristics were compared for patients transplanted in Era 1 (January 2015–April 2018) and Era 2 (April 2018–December 2020). Cumulative 1‐year survival free from rejection and from rejection with hemodynamic compromise (RHC) was compared between eras using Kaplan‐Meier survival analysis.

Results

115 patients underwent HT during our study period (52 in Era 1 and 63 in Era 2). There was an increase in VAD utilization between eras (19% in Era 1 vs. 40% in Era 2, p = 0.025), but otherwise no significant difference in demographic or clinical variables between the two eras. No statistically significant difference in freedom from rejection or freedom from RHC was identified between the two eras. There was a 60% reduction in the median number of EMB per patient in the first year post‐HT after employing the score (5 in Era 1 vs. 2 in Era 2, p < 0.001).

Conclusions

After employing a rejection risk prediction score, our center decreased the frequency of EMB without worsening early post‐HT outcomes, thus establishing the clinical applicability of this tool.
Discordance Between Caregiver and Transplant Clinician Priorities Regarding Post‐Heart Transplant Education
Authors: Goldart Evan M. , McCormick Amanda D. , Lim Heang M. , Batazzi Adriana , Yu Sunkyung , Duimstra Ashley , Lowery Ray , Uzark Karen , Glenn Thomas , Cousino Melissa K.
Published: November 2024

Background

Patient and caregiver education following pediatric heart transplant (HTx) is a cornerstone of post‐HTx care. Despite the importance of post‐HTx education, there are no standardized guidelines for topics and content. Education practices vary across clinicians and centers. Patient and caregiver priorities regarding post‐HTx education are unknown. This national survey study aimed to characterize adolescent HTx recipient, caregiver, and clinician values specific to post‐HTx educational topics.

Methods

A cross‐sectional, national electronic survey was performed. Eligible participants included pediatric HTx recipients between the ages of 13–18, adult caregivers of pediatric HTx recipients, and pediatric HTx clinicians. An investigator‐designed survey was developed to assess the importance of 20 educational topics. Average scores on educational topics were compared between HTx recipients/caregivers and HTx clinicians using two‐sample t‐tests.

Results

120 survey responses were included, with a majority completed by HTx caregivers (N = 73; 61%) and clinicians (N = 43; 36%). Of the 20 educational topics assessed, there was a significant difference (p < 0.05) between educational values of HTx recipients/caregivers compared to HTx clinicians for 40% (N = 8) of the topics. For each educational topic that revealed a significant difference, HTx recipients/caregivers consistently placed greater value on the educational topic compared to HTx clinicians.

Conclusions

Priorities regarding post‐HTx education do not always align between HTx recipients/caregivers and HTx clinicians. Results suggest that HTx recipients/caregivers place higher value on educational topics regarding daily life after HTx compared to HTx clinicians. We hope these findings better inform the approach to post‐HTx education and care for future pediatric HTx patients.
Scenes From a Sociolegal Career: An Informal Memoir
Authors: Kagan Robert A.
Published: November 2024

This memoir describes the 40‐year unfolding, project by project, of my sociolegal field research on legal and regulatory processes. It provides brief accounts of my interactions and interviews with regulatory officials and with businesspeople responsible for regulatory compliance. It also describes my ventures into the cross‐national comparison of legal and regulatory institutions and the political systems that shape and support them.
The Amazonian snakebite burden: Unveiling seasonal dynamics in a region with tenfold higher incidence compared to the Brazilian average
Authors: Rocha Jorge Emanuel Cordeiro , Gomides Samuel Campos
Published: November 2024

Background

Accidents caused by snakes constitute a serious public health problem in Latin America and worldwide. The situation in the Brazilian Amazon region is neglected, resulting in the highest incidence of cases per capita in the country. Furthermore, the distance from urban areas makes it difficult for the population to access timely and effective medical care, including antivenom treatment. The Brazilian Amazon is characterised by high ethnic and cultural diversity, yet it lacks robust epidemiological information that would allow for the development of surveillance and prevention policies. This study aimed to assess the epidemiological profile of individuals affected by snakebite accidents from 2007 to 2021 in a poorly studied region of the Brazilian Amazon.

Methods

To assess the relationship between snakebite accidents, rainfall and river flood levels, cross‐correlation functions were employed. Data from the public healthcare system database was used for this analysis.

Results

The results indicate that the study area experiences a snakebite rate 10 times greater than the Brazilian average and double that of other Amazonian regions. The most affected victims consist of adult males residing in rural areas, with snakebite accidents being more common during the rainy season. Viperid snakes were responsible for most bites, with the lower limbs being the most common location of injury. The data revealed a positive correlation between the number of snakebite accidents both rainfall and fluvial data.

Conclusions

The accident peak coincides with the Brazil nut harvest season, a highly significant forest product for the economy of rural communities. Our data reinforces the need for public policies focused on environmental education and prevention, such as the use of boots and leg guards. These preventive measures have the potential to reduce the number of snakebites accidents by approximately 85%.
Hemostatic function, immunomodulatory capacity, and effects of lipemia in cold‐stored whole blood
Authors: Tan Joanne C. G. , Aung Htet Htet , Marks Denese C.
Published: November 2024

Background

Whole blood (WB) is increasingly being used for resuscitation of trauma patients. Although platelet‐, red blood cell (RBC)‐ and plasma‐specific parameters in cold‐stored WB are well characterized, there has been limited investigation of biological response modifiers (BRMs), which may induce adverse reactions in recipients. The aim of this study was to evaluate the quality and function of RBC, platelets, plasma proteins, and BRMs in cold‐stored WB during storage.

Methods

WB (n = 24) was collected into collected into citrate‐phosphate‐dextrose (CPD) anticoagulant, held overnight, processed through a platelet‐sparing filter, and stored at 2–6°C for 21 days. RBC, platelet, coagulation factor quality and function, and BRM concentrations were measured throughout the duration of storage.

Results

WB was effectively leukoreduced, with 99.98% reduction in leukocyte count and 81% platelet count recovery following filtration. Five WB units were significantly lipemic, with a visible lipid layer appearing after being cold storage overnight. These were more turbid with higher hemolysis compared to non‐lipemic units (p = .023). Despite a decrease in platelet count during storage (p < .001), hemostatic function as measured by thromboelastography was maintained for at least 21 days (R time and maximum amplitude; both p < .001). There was a significant increase in PF4, CD62P, and RANTES during cold storage (all p < .001).

Discussion

WB retains hemostatic potential for at least 21 days of cold storage, and with further development, may be suitable for transfusion in Australia. Before implementation in Australia, quality control measures for lipemia and hemolysis would need to be defined as part of our manufacturing processes.
Coagulation assay results at birth in preterm infants: A cohort study highlighting the relevance of local reference values for interpretation
Authors: Houben Nina , Fustolo‐Gunnink Suzanne , Caram‐Deelder Camila , Visser Remco , Bosma Madeleen , Fijnvandraat Karin , Eikenboom Jeroen , van der Bom Johanna , Lopriore Enrico
Published: November 2024

Background and Objectives

Routine coagulation screens at birth are still standard in some European neonatal intensive care units (NICUs), although interpretation of these results is complex in preterm infants. It is unclear to what extent local coagulation assay results agree with published reference ranges when using different analysers and reagents. We aimed to assess coagulation assay results on day 1 of life in very preterm infants admitted to the NICU.

Materials and Methods

We included all preterm infants born below 32 weeks gestational age (GA) admitted to the Leiden University Medical Center between 2004 and 2020 in whom coagulation assays (prothrombin time [PT] and activated partial thromboplastin time [APTT]) were obtained during the first 24 h of life. Infants either diagnosed with major intraventricular haemorrhage or who received plasma transfusion before coagulation assay were excluded. We assessed coagulation assay results and compared the results between <28 weeks (extremely preterm) and 28–32 weeks (very preterm) GA groups.

Results

Coagulation assays were obtained at birth in 144 infants (144/2577; 5.5%) of whom 104 fulfilled the inclusion criteria. We found similar median PT and APTT values for extremely and very preterm infants (PT: 18.1 vs. 18.7 s [p‐value = 0.400]; APTT: 44.2 vs. 47.7 s [p‐value = 0.252], respectively).

Conclusion

We found similar coagulation assay results at birth for extremely and very preterm infants; however, results deviated considerably from some of the published reference ranges. This may be due to differences between analysers and reagents, underlining the need for reference ranges calibrated to the equipment used per NICU.
POTENTIAL FOR ACCELERATED REPLICATION OF FRAXINUS SOGDIANA USING IN VITRO CULTURE AND IDENTIFICATION OF A RELIC TREE USING DNA-BARCODING
Authors: Amangeldinova M.K. , Bekkuzhina S.S. , Zhumabay N.B. , Tussipkan D. , Manabayeva S.A.
Published: November 2024

Four species of Fraxinus including F. angustifolia subsp. syriaca (Boiss.) Yalt., F. sogdiana Bunge, F. pennsylvanica Marshall and F. americana L. grow in Kazakhstan. The study aimed to determine the conditions for awakening endogenous dormancy in vitro of F. sogdiana. In the control group without vernalization, the sterile culture yield at room temperature was 30%. However, with cold treatment, this yield increased to 60%, which is twice as high. It was  observed that on MS medium without the addition of hormones, 22 microshoots were obtained from unwounded seeds, whereas 39 microshoots were obtained from wounded seeds during microclonal propagation.Phylogenetic relationships and species identification were analyzed using three DNA barcoding markers, comparing F. sogdiana with species from the NCBI database. rbcL and ITS markers did not show satisfactory interspecific genetic variability among F. species. Notably, matK gene sequences effectively differentiated F. sogdiana from other species. These results provide fundamental information that is valuable for future biotechnological and molecular studies.
The
Neosartorya (Aspergillus) fischeri
antifungal protein NFAP2 has low potential to trigger resistance development in
Candida albicans in vitro
Authors: Bende Gábor , Zsindely Nóra , Laczi Krisztián , Kristóffy Zsolt , Papp Csaba , Farkas Attila , Tóth Liliána , Sáringer Szabolcs , Bodai László , Rákhely Gábor , Marx Florentine , Galgóczy László
Published: November 2024

Due to the increase in the number of drug-resistant
Candida albicans
strains, new antifungal compounds with limited potential for the development of resistance are urgently needed. NFAP2, an antifungal protein (AFP) secreted by
Neosartorya
(
Aspergillus
)
fischeri
, is a promising candidate. We investigated the ability of
C. albicans
to develop resistance to NFAP2 in a microevolution experiment compared with generic fluconazole (FLC).
C. albicans
adapted to only 1× minimum inhibitory concentration (MIC) of NFAP2, which can be considered tolerance rather than resistance, compared with 32× MIC of FLC. Genome analysis revealed non-silent mutations in only two genes in NFAP2-tolerant strains and in several genes in FLC-resistant strains. Tolerance development to NFAP2 did not influence cell morphology. The susceptibility of NFAP2-tolerant strains did not change to FLC, amphotericin B, micafungin, and terbinafine. These strains did not show altered susceptibility to AFPs from
Penicillium chrysogenum
, except one which had less susceptibility to
Penicillium chrysogenum
antifungal protein B. FLC-resistant strains had decreased susceptibility to terbinafine and NFAP2, but not to other drugs and AFPs from
P. chrysogenum
. NFAP2-tolerant and FLC-resistant strains showed decreased and increased NFAP2 binding and uptake, respectively. The development of tolerance to NFAP2 decreased tolerance to cell wall, heat, and UV stresses. The development of FLC resistance increased tolerance to cell wall stress and decreased tolerance to heat and UV stresses. Tolerance to NFAP2 did not have significant metabolic fitness cost and could not increase virulence, compared with resistance to FLC.

IMPORTANCE

Due to the increasing number of (multi)drug-resistant strains, only a few effective antifungal drugs are available to treat infections caused by opportunistic
Candida
species. Therefore, the incidence of hard-to-treat candidiasis has increased dramatically in the past decade, and the demand to identify antifungal compounds with minimal potential to trigger resistance is substantial. The features of NFAP2 make it a promising candidate for the topical treatment of
Candida
infection. Data on the development of resistance to antifungal proteins in
Candida albicans
are lacking. In this study, we provide evidence that NFAP2 has a low potential to trigger resistance in
C. albicans in vitro
, and the developed tolerance to NFAP2 is not associated with severe phenotypic changes compared with development of resistance to generic fluconazole. These results suggest the slow emergence of NFAP2-resistant
Candida
strains, and NFAP2 can reliably be used long-term in the clinic.
Lack of activity of HIV-1 integrase strand-transfer inhibitors on recombinase activating gene (RAG) activity at clinically relevant concentrations
Authors: Demirdjian Sally , Duong Vincent N. , Byrum Jennifer N. , Nayak Arabinda , McKinney Cooper B. , Perry Jason K. , Callebaut Christian , Rodgers Karla K. , Falkard Brie , Feng Joy Y.
Published: November 2024

Human immunodeficiency virus 1 (HIV-1) infection remains a global health concern, with nearly 30 million people on antiretroviral (ARV) treatment. Integrase strand-transfer inhibitors (INSTIs) that block HIV-1 integrase are crucial components of first-line combination ARV therapies recommended in most international guidelines and have significantly improved HIV-1 treatment due to their efficacy and safety. This study evaluates potential off-target effects of INSTIs on recombinase activating genes (RAG1 and RAG2), which are essential for adaptive immune system function. We performed a comprehensive assessment of the off-target effects of clinically approved INSTIs on RAG activity, utilizing both biochemical and cellular assays. We purified the first catalytically active recombinant human core RAG1–RAG2 complex and tested it in the presence of the co-factor human HMGB1 protein for the gel-based biochemical RAG DNA cleavage assay. Additionally, we optimized an extrachromosomal V(D)J recombination cellular assay using murine mCherry-core RAG1, full-length murine mCherry-RAG2, and a plasmid substrate green fluorescent protein (GFP) reporter system, transfecting them into cells in the absence or presence of inhibitors. This setup enabled high-throughput analysis of V(D)J recombination for multiple compounds in a dose–response manner via flow cytometry. Physiologically relevant concentrations of INSTIs were examined for their potential impact on RAG activity and V(D)J recombination, with approved INSTIs showing minimal to no effects on recombinase activity. Consequently, the findings support the continued use of INSTIs in HIV-1 treatment without substantial concern for adverse effects on V(D)J recombination and immune system function.

IMPORTANCE

INSTIs are a crucial component of antiretroviral treatments for HIV-1 infection. This study provides a careful and thorough analysis of the impact of approved INSTIs on recombinase activating gene (RAG1 and RAG2) activity, which plays a pivotal role in the adaptive immune system. The concentrations tested were derived from several clinical studies and accounted for the maximum free fraction of the drug available in patients. This approach ensures that our findings are directly applicable to clinical scenarios by providing meaningful insights into the potential drug side effects in patients. We developed biochemical and cellular assays to measure the impact of INSTIs on RAG activity. All tested INSTIs did not inhibit RAG at supratherapeutic concentrations in the RAG1/RAG2 biochemical cleavage and cellular V(D)J recombination assays. Our assessment supports the continued use of INSTIs in HIV-1 treatments without concern for adverse effects.
Microbiome profiling suggests novel endosymbiont associations of insect pests of stored grain
Authors: Fajardo Janice , Harrison Brian , Hervet Vincent A.D. , Bakker Matthew G.
Published: November 2024

Many arthropods, including economically important pests of stored grains, host intracellular bacterial symbionts. These symbionts can have diverse impacts on host morphology, stress tolerance, and reproductive success. The ability to rapidly determine the infection status of host insects and the identity of intracellular symbionts, if present, is vital to understanding the biology and ecology of these organisms. We used a microbiome profiling method based on amplicon sequencing to rapidly screen 35 captive insect colonies. This method effectively revealed single and mixed infections by intracellular bacterial symbionts, as well as the presence or absence of a dominant symbiont, when that was the case. Because no a priori decisions are required about probable host-symbiont pairing, this method is able to quickly identify novel associations. This work highlights the frequency of endosymbionts, indicates some unexpected pairings that should be investigated further, such as dominant bacterial taxa that are not among the canonical genera of endosymbionts, and reveals different colonies of the same host insect species that differ in the presence and identity of endosymbiotic bacteria.
About this title - Sedimentary Dynamics in the Albertine Rift Valley, Equatorial East Africa
Authors: Nicholas C.J.
Published: November 2024

The Albertine Rift of East Africa is a prime example of active early continental rifting in the world today. Geological field surveying of onshore modern-day sedimentary depositional environments here interprets older outcrop and constructs a chronostratigraphic framework based on global glacial–interglacial climatic cyclicity for the past 1.1 million years.
ParSEL: Parameterized Shape Editing with Language
Authors: Ganeshan Aditya , Huang Ryan , Xu Xianghao , Jones R. Kenny , Ritchie Daniel
Published: November 2024

The ability to edit 3D assets with natural language presents a compelling paradigm to aid in the democratization of 3D content creation. However, while natural language is often effective at communicating general intent, it is poorly suited for specifying exact manipulation. To address this gap, we introduce ParSEL, a system that enablescontrollableediting of high-quality 3D assets with natural language. Given a segmented 3D mesh and an editing request, ParSEL produces aparameterizedediting program. Adjusting these parameters allows users to explore shape variations with exact control over the magnitude of the edits. To infer editing programs which align with an input edit request, we leverage the abilities of large-language models (LLMs). However, we find that although LLMs excel at identifying the initial edit operations, they often fail to infer complete editing programs, resulting in outputs that violate shape semantics. To overcome this issue, we introduce Analytical Edit Propagation (AEP), an algorithm which extends a seed edit with additional operations until a complete editing program has been formed. Unlike prior methods, AEP searches for analytical editing operations compatible with a range of possible user edits through the integration of computer algebra systems for geometric analysis. Experimentally, we demonstrate ParSEL's effectiveness in enabling controllable editing of 3D objects through natural language requests over alternative system designs.