bluuebunny/crossref_metadata_2025 huggingface dataset:
Testing spatial out-of-sample area of influence for grain forecasting models
Authors: Davenport F , Lee D , Shukla S , Husak G , Funk C , Budde M , Rowland J
Published: October 2024

We examine the factors that determine if a grain forecasting model fit to one region can be transferred to another region. Prior research has proposed examining the area of applicability (AoA) of a model based on structurally similar characteristics in the Earth Observation predictors and weights based on the model derived feature importance. We expand on and evaluate this approach in the context of grain yield forecasting in Sub-Saharan Africa. Specifically, we evaluate an AoA methodology established for generating raster surfaces and apply it to vector supported grain data. We fit a series of ensemble tree models both within single countries and across multiple sets of countries and then test those models in countries excluded from the training set. We then calculate and decompose AoA measures and examine several different performance metrics. We find that the spatial transfer accuracy does not vary across season but does vary by average rainfall and across high, medium, and low yielding regions. In general, areas with higher yields and medium to high average rainfall tend to have higher accuracy for both model training and transfer. Finally, we find that fitting models with multiple countries provides more accurate out-of-sample estimates when compared to models fitted to a single country.
Innovation in distributed energy services for sustainable development: case studies from sub-Saharan Africa
Authors: Pachauri Shonali , Coldrey Olivia , Falchetta Giacomo , Pelz Setu
Published: October 2024

In this work, we explore how locally led innovations can advance sustainable energy access in low-income regions of Africa. Given the emphasis of the Sustainable Development Goals on the importance of affordable, reliable, and sustainable energy, we critically assess how local innovations can address the unique challenges of regions characterized by informality and low purchasing power and where existing grid-based electricity supply is weak. Through case studies, we highlight successful initiatives in expanding energy services access, including product bundling, pay-as-you-go financial models, leveraging existing supply chains, and securing strong funding support. Our findings underscore the importance of local ownership, contextual knowledge, and the adaptation of innovations to specific socio-economic and cultural conditions. By comparing the case studies, we identify common strategies that can contribute to the effectiveness of local innovations in improving energy access and sustainability that can inform efforts to replicate and scale up such initiatives. We conclude by identifying common elements contributing to the success of these cases and their significance, focusing on those crucial for achieving speed, scale, and impact.
Fluidized solidified soil using construction slurry improved by fly ash and slag: preparation, mechanical property, and microstructure
Authors: Feng Tianhong , Lin Kaihao , Zhang De , Yu Yanfei , Jiang Yiming , Jiang Ping , Li Na , Wang Wei
Published: October 2024

Fluidized solidified soil (FSS) is a cement-based engineering matergood working performance and mechanical properties. Based on fixed cement and desulphurisation gypsum (DG), fly ash (FA) and ground granulated blast furnace slag (GGBS) were added as admixtures to the construction slurry to prepare three types of FSS: namely cement-GGBS-DG FSS (CGD-FSS), cement-FA-GGBS-DG FSS (CFGD-FSS), and cement-FA-DG FSS (CFD-FSS). Considering 7 d, 14 d, and 28 d three curing times, compressive, flexural, scanning electron microscopy (SEM), and x-ray diffraction (XRD) analyses were conducted to explore the time-dependent mechanical properties and microscopic characterisation of FSS. The mechanical test showed that CFGD-FSS doped with FA and GGBS had better fluidity, compressive strength, and flexural strength than CGD-FSS doped with FA alone and CFD-FSS doped with GGBS. The CFGD-FSS specimen with a cement:FA:GGBS:DG ratio of 30: 10: 40: 20 in the curing agent had the best mechanical properties, i.e., the CFGD01 specimens. It has fluidity of 189 mm, compressive strength of 671 kPa, and flexural strength of 221 kPa with a 28d curing time, which can meet the working requirements of FSS for filling narrow engineering spaces. And compared with other specimens, it has the shortest setting time, which can effectively shorten the construction period. Microscopic analysis showed that a large number of hydration products, such as calcium silicate hydrate, calcium aluminate hydrate, and ettringite (Aft), were well-formed in the FSS, resulting in good mechanical properties, especially for the CFGD-01 specimens. Finally, two empirical models were established to describe the compressive strength–porosity and flexural strength–porosity relationships. Moreover, the investigated data agreed well with the modelling results.
New Property in International Law
Authors: Ho Jean
Published: October 2024

New Property in International Law is a story of how international law constantly falls short when it comes to property regulation because its stakeholders have consistently failed to define what property is. Until now, property in international law has been an enigma. We are told that international law possesses sufficient content to regulate property, we are shown provisions in international instruments addressing property rights, and we bear witness to the resolution of property disputes in accordance with international law. Yet, when we are asked what the defining attributes of property in international law are, we draw a collective blank. The absence of reformist agitation from the international community towards an international law that brazenly regulates what it cannot or will not even define represents the turning of a collective blind eye to a critical knowledge gap. In the same way that driving a car with closed eyes is a possibly fatal accident in the making, driving the content of international law on property regulation without discerning the object of regulation is a possibly fatal anomaly in the laborious, and supposedly progressive, enterprise of legal development. Duly defined, newer forms of property push international law to a regulatory breaking point. When treaties as stalwart sources of international law prescribe obligations without properly identifying the object and penalizing the violators of those obligations, regulatory regimes built on treaties—such as the ones currently applicable to cultural, common, and contingent property—resemble a mirage. They offer victims shimmering hope and reprieve from a distance but vanish when the victim gets close enough to contemplate and formulate redress for the wrong suffered.
Introduction
Authors: Ho Jean
Published: October 2024

The Introduction eases the reader into the five substantive chapters of the monograph by outlining why international law is deficient when it comes to new property regulation. It offers a definitional preview of new property from Chapter 1, before setting out three categories of new property—cultural property from Chapter 2, common property from Chapter 3, and contingent property from Chapter 4—which showcase this deficiency. It then draws the reader’s attention to the paradox explored in Chapter 5 of how international law recognizes but fails to sanction actors and actions that interfere with new property. The Introduction asks if international law can be rendered fit for the purpose of new property regulation and invites the reader to join in the search for answers in this intellectual journey.
The Struggle and Shape of New Property
Authors: Ho Jean
Published: October 2024

Chapter 1 challenges prevailing complacency in international law’s contemporary relevance to property regulation by peeling back a façade spun by treaties that have long obscured international law’s content deficiency on the notion of property. The knowledge gap is particularly significant for newer forms of property which are no less susceptible to disputed use and interference as basic property but find no expression or equivalence in existing doctrine. In depicting the struggle of new property for formal acknowledgement and articulation, and in delineating the shape of new property, this chapter supplies the definitional backbone to the argument made throughout the rest of the book—that an international law unresponsive to the needs and nuances of new property is no longer fit for the purpose of property regulation. Section 2 explains how the fragmentation of international law into specialized subfields governed by different treaties created a knowledge gap on the notion of property. Section 3 explains how this knowledge gap in international law was entrenched by the influence of select Western property theories espousing private property ownership. It compares and analyses distinctive notions of property from four major juristic traditions for common ground to fill the gap with a more representative and more adaptable notion of property. Section 4 observes the rise of new property and elaborates on the four core attributes of new property distilled from the comparative analysis conducted in Section 3: (i) imputable ownership, (ii) separability, (iii) responsiveness to contextual factors, and (iv) conferral of benefit. Section 5 concludes.
The Effect of the Presence and Absence of DNA Repair Genes on the Rate and Pattern of Mutation in Bacteria
Authors: Kalogiannis Georgios , Eyre-Walker Adam
Published: October 2024

Bacteria lose and gain repair genes as they evolve. Here, we investigate the consequences of gain and loss of 11 DNA repair genes across a broad range of bacteria. Using synonymous polymorphisms from bacteria and a set of 50 phylogenetically independent contrasts, we find no evidence that the presence or absence of these 11 genes affects either the overall level of diversity or the pattern of mutation. Using phylogenetic generalized linear squares yields a similar conclusion. It seems likely that the lack of an effect is due to variation in the genetic background and the environment which obscures any effects that the presence or absence of individual genes might have.
Trans-aconitic acid assimilation system as a widespread bacterial mechanism for environmental adaptation
Authors: Zheng Cao , Liu Dingqi , Lu Xinyu , Wu Huijun , Hua Jingyi , Zhang Chuang , Liu Kang , Li Changchun , He Jin , Du Cuiying
Published: October 2024

The ability of bacteria to use natural carbon sources greatly affects their growth and survival in the environment. Bacteria have evolved versatile abilities to use environmental carbon sources, but their diversity and assimilation pathways remain largely unexplored. Trans-aconitic acid (TAA), a geometric isomer of cis-aconitic acid involved in the tricarboxylic acid cycle, has long been considered a natural carbon source metabolizable by bacteria. However, its catabolism and ecological role in linking bacterial interactions with the environment remain unclear. Here, we identify a regulatory system in Bacillus velezensis FZB42 that is capable of sensing and catabolizing TAA. The system consists of a tar operon, an adjacent positive regulatory gene tarR, and a shared promoter. After receiving the TAA signal, the TarR protein interacts directly with the promoter, initiating the expression of the membrane transporter TarB and aconitate isomerase TarA encoded by the operon, which function in importing the TAA and isomerizing it into the central intermediate cis-aconitic acid. Subsequent soil colonization experiments reveal that TAA assimilating ability can give its coding bacteria a growth and competitive advantage. Bioinformatics analyses coupled with bacterial isolation experiments further show that the assimilation system of TAA is widely distributed in the bacterial domain, and its assimilating bacteria are also extensively distributed in nature, indicating an important role of TAA metabolism in bacterial carbon acquisition. This work emphasizes the importance of metabolic adaptation to environmental carbon sources for bacterial survival and may provide inspiration for engineering microbes with enhanced environmental competitiveness.
The MADS-box gene XAANTAL1 participates in Arabidopsis thaliana primary root growth and columella stem cell patterns in response to ROS, via direct regulation of PEROXIDASE 28 and RETINOBLASTOMA-RELATED genes
Authors: Zluhan-Martínez Estephania , Castañón-Suárez Claudio A , Gutiérrez-Rodríguez Mario A , Lledías Fernando , Zhang Tao , Peng Jesús T , Dickinson Jazz , Sánchez Rodríguez Diana Belén , Sánchez María de la Paz , García-Ponce Berenice , Álvarez-Buylla Elena R , Garay-Arroyo Adriana
Published: October 2024

The balance between cell growth, proliferation, and differentiation emerges from gene regulatory networks coupled to various signal transduction pathways, including reactive oxygen species (ROS) and transcription factors (TFs), enabling developmental responses to environmental cues. The primary root of Arabidopsis thaliana has become a valuable system for unravelling such networks. Recently, the role of TFs that mediate ROS inhibition of primary root growth has begun to be characterized. This study demonstrates that the MADS-box TF gene XAANTAL1 (XAL1) is an essential regulator of hydrogen peroxide (H2O2) in primary root growth and root stem cell niche identity. Interestingly, our findings indicated that XAL1 acts as a positive regulator of H2O2 concentration in the root meristem by directly regulating genes involved in oxidative stress response, such as PEROXIDASE 28 (PER28). Moreover, we found that XAL1 is necessary for the H2O2-induced inhibition of primary root growth through the negative regulation of peroxidase and catalase activities. Furthermore, XAL1, in conjunction with RETINOBLASTOMA-RELATED (RBR), is essential for positively regulating the differentiation of columella stem cells and for participating in primary root growth inhibition in response to oxidative stress induced by H2O2 treatment.
Emerging perspectives of copper-mediated transcriptional regulation in mammalian cell development
Authors: Fitisemanu Fa'alataitaua M , Padilla-Benavides Teresita
Published: October 2024

Copper (Cu) is a vital micronutrient necessary for proper development and function of mammalian cells and tissues. Cu mediates the function of redox active enzymes that facilitate metabolic processes and signaling pathways. Cu levels are tightly regulated by a network of Cu-binding transporters, chaperones, and small molecule ligands. Extensive research has focused on the mammalian Cu homeostasis (cuprostasis) network and pathologies, which result from mutations and perturbations. There are roles for Cu-binding proteins as transcription factors (Cu-TFs) and regulators that mediate metal homeostasis through the activation or repression of genes associated with Cu handling. Emerging evidence suggests that Cu and some Cu-TFs may be involved in the regulation of targets related to development—expanding the biological roles of Cu-binding proteins. Cu and Cu-TFs are implicated in embryonic and tissue-specific development alongside the mediation of the cellular response to oxidative stress and hypoxia. Cu-TFs are also involved in the regulation of targets implicated in neurological disorders, providing new biomarkers and therapeutic targets for diseases such as Parkinson's disease, prion disease, and Friedreich's ataxia. This review provides a critical analysis of the current understanding of the role of Cu and cuproproteins in transcriptional regulation.
Evaluating the Glycemic Effects of Dolutegravir and Its Predictors Among People With Human Immunodeficiency Virus in Uganda: A Prospective Cohort Study
Authors: Ankunda Collins , Agolor Curthbert , Karamagi Yvonne , Nakubulwa Susan , Namasambi Sharon , Kasamba Ivan , Christopher Semei Mukama , Kukundakwe Patience , Odiit Mary , Mubangizi Ivan , Emunyu Jude , Kesi Diana Nakitto , Nambasa Victoria , Ndagije Helen Byomire , Mukasa Barbara
Published: October 2024

Background

Dolutegravir (DTG), a key component of the recommended human immunodeficiency virus (HIV) treatment regimens in Uganda, has been associated with hyperglycemia. We evaluated its influence on hyperglycemia risk to create a hyperglycemia risk stratification tool for patient monitoring.

Methods

We conducted a prospective cohort study at 3 sites with 628 HIV-positive patients on tenofovir disoproxil fumarate, lamivudine, and dolutegravir (TLD). Participants included both nucleoside reverse transcriptase inhibitor–experienced (exposed) and antiretroviral therapy (ART)–naive (nonexposed) groups. Follow-up occurred every 6 months with random blood sugar (RBS) testing every 3 months. Participants with RBS ≥7 mmol/L were classified as hyperglycemic and underwent glycated hemoglobin (HbA1c) testing, confirming diabetes with a 6.5% cut-off.

Results

The study found a hyperglycemia incidence rate of 24.5 (95% confidence interval [CI], 19.3–31.1) cases per 100 person-years (PY) and a diabetes incidence rate of 5.8 cases (95% CI, 3.6–9.3) per 100 PY. Hyperglycemia incidence was slightly lower in nonexposed (20.8 cases per 100 PY) versus exposed groups (25.2 cases per 100 PY). Multivariable analysis indicated a trend toward lower hyperglycemia risk (adjusted hazard ratio [aHR], 0.78 [95% CI, .37–1.66]; P = .52) and substantially lower diabetes incidence (aHR, 0.34 [95% CI, .04–2.82]; P = .32) in the nonexposed group. Significant factors for hyperglycemia included age (P < .001), study site (P < .001), and DTG-based ART duration (P = .02).

Conclusions

Our study showed an increased incidence of hyperglycemia with age, study site, and duration of DTG exposure in people with HIV on TLD. We suggest integrated screening and care for hyperglycemia and diabetes in HIV services, especially when initiating DTG regimens.
Brain health
Authors: Bonhomme Vincent , Putensen Christian , Böttiger Bernd W. , Stevens Markus F. , Marczin Nandor , Arnal Daniel , Brotfain Evgeni , Raz Aeyal , Defresne Aline , Bogossian Elisa , Sviri Sigal , Cardone Paolo , Mair Alexander , Robba Chiara , Dilmen Ozlem Korkmaz , Ly Julien , Crisan Maria I. , De Graaff Jurgen C. , Najafi Nadia , Vutskits Laszlo , Absalom Anthony , Abramovich Igor , Souberbielle Quentin , Momeni Mona , Campbell Douglas , Evered Lisbeth , Vacas Susana , Saxena Sarah , Bruder Nicolas , Oksuz Dilara A. , Lobo Francisco A. , van Putten Michel , Sahinovic Marko , Hawryluk Gregory W.J. , Kustura Antonia , Yürek Fatima , Baron Shahaf Dana , Shahaf Goded , Radke Finn , Khalifa Celine
Published: October 2024

Damage to the brain can have disastrous and long-lasting consequences. The European Society of Anaesthesiology and Intensive Care (ESAIC) is aware of the importance of taking good care of the brain, both of patients and of anaesthesia and intensive care unit (ICU) caregivers, and has organised a complete learning track on brain health to bring this concern to the attention of practitioners. This learning track included an online Focus Meeting on Brain Health (November 25, 2023). We here provide readers with a digest of the information that was delivered during that meeting in an opinion paper driven by the authors’ own reading of the literature. It is divided according to the meeting's sessions, including how to improve the health of an injured brain, how to keep a young or old brain healthy, how to keep a healthy adult brain unimpaired, how monitoring can impact brain health in the operating room and in the intensive care unit, and how to keep the anaesthesia and ICU caregivers’ brain healthy. Each part is a brief and focused summary. The main delivered messages are that the management of injured brain patients involves an adequate choice of sedation, adequate brain monitoring, and focused attention to specific points depending on the underlying pathology; that several measures can be undertaken to protect the brain of the very young needing anaesthesia; that it is possible to detect older patients at risk of postoperative neurocognitive disorders, and that dedicated perioperative management by a multidisciplinary expert team may improve their outcomes; that apparently healthy adult brains may suffer during anaesthesia; that the electroencephalogram may track peri-operative brain dysfunction, and that female patients should be given special care in this respect; that multimodal brain monitoring helps to detect pathological processes and to maintain brain homeostasis; and that burnout in anaesthesiologists can be effectively fought using personal, organisational, managerial and legal approaches.
HIGH-DOSE INTRAVITREAL TOPOTECAN FOR RECURRENT RETINOBLASTOMA, SUBRETINAL SEEDS, AND VITREOUS SEEDS
Authors: Shields Carol L. , Medina Robert , Evans Haley , Valdes-Perez Nicole , Burak acar Ahmet , Bansal Rolika , Lally Sara E. , Shields Jerry A.
Published: October 2024

Purpose:

To evaluate the efficacy and safety of high-dose intravitreal topotecan (IvitTopo) for recurrent retinoblastoma.

Methods:

There were 13 patients with recurrent retinoblastoma treated with high-dose IvitTopo (90 micrograms [μg]/0.18cc–100 µg/0.20cc). The primary outcome measures were tumor control, globe salvage, and treatment complications.

Results:

At date first seen, median patient age was 9 months, and the affected eye was classified as International Classification of Retinoblastoma Group B (n = 2, 15%), Group C (n = 3, 23%), or Group D (n = 8, 62%) retinoblastoma with initial therapy of intravenous chemotherapy (n = 9, 69%) or intraarterial chemotherapy (n = 4, 31%). Recurrent tumor was detected at median 10 months as solid tumor (n = 3), subretinal seeds (n = 10), and/or vitreous seeds (n = 3) and high-dose IvitTopo (median three injections) delivered at monthly intervals. Additional chemotherapy was delivered by intraarterial (n = 8, 62%) or intravenous (n = 1, 8%) routes, and one eye received additional cryotherapy (n = 1, 8%). In three cases (23%), there was no additional therapy. At mean follow-up of 9 months, regression of solid tumor, subretinal seeds, and vitreous seeds was achieved in 12 cases (92%), and globe salvage was achieved in all cases (n = 13, 100%). Of those three eyes treated with high-dose IvitTopo alone, tumor control was initially achieved in all cases (100%), but one case that previously demonstrated massive vitreous seeding showed late recurrence of a solitary vitreous seed at 8 months. There were no complications.

Conclusion:

High-dose IvitTopo is an effective and safe therapy for recurrent retinoblastoma, in conjunction with other therapy, and possibly as a stand-alone therapy.
Surge in Eye Drop Safety Concerns and Interest in Alternative Dry Eye Disease Therapy Following Eye Drop Recalls: A Cross-Sectional Google Trends Analysis
Authors: Martinyan Jack , Starr Christopher E.
Published: October 2024

Objectives:

Beginning in January 2023, numerous eye drops were recalled following reports of contamination. To investigate hesitancy in topical therapies for dry eye disease (DED), we analyzed trends in Internet search traffic for alternative DED therapies and eye drop safety concerns following initial recalls.

Methods:

Google Trends (GT) was used to measure the popularity of specific search terms during a given time period. The main GT output metric for gauging interest in a search term is the Search Volume Index (SVI). We collected worldwide SVI data for terms “dry eye vitamin,” “are eye drops safe,” “stop eye drops,” “lipiflow,” “ilux treatment,” “dry eye mask,” “dry eye warm compress,” “omega-3 for dry eyes,” “dry eye plugs,” “dry eye humidifier,” “itear,” and “IPL dry eye” from April 24, 2022, to October 29, 2023. Statistical analysis was performed with Microsoft Excel v.16.77.1, and comparisons between groups were performed using paired t tests.

Results:

A significant increase in SVI was observed for most keywords. When comparing the 40-week period before and after the initial recall, 7/10 alternative DED therapies demonstrated a statistically significant surge in Internet search traffic after recall (P < 0.05). Furthermore, 2/2 keywords pertaining to eye drop safety concerns demonstrated an increase in SVI (P < 0.0001).

Conclusions:

We identified a significant surge in Internet search activity for eye drop safety and alternative DED therapies following eye drop recalls. Public health agencies and physicians may find this information valuable while attempting to address safety concerns and navigating noncompliance of routine eye drop therapy.
Use pembrolizumab may cause acute and severe adverse reactions: a case report and review
Authors: Ouyang Linna , Liu Huixing , Tang Zhixiang , Wu Rui , Zhong Yujie , Chen Haibin
Published: October 2024

Introduction:

Immune checkpoint inhibitors (ICIs) have emerged as pivotal therapeutics for personalized cancer treatment. Programmed death protein receptor 1/ligand 1 (PD-1/PD-L1) inhibitors represent the most extensively utilized immune checkpoint blockade agents. Among these, pembrolizumab has gained approval for advanced cancer management. By engaging with PD-1 on T cells, pembrolizumab orchestrates the immune response against tumor cells; however, it is also associated with a spectrum of adverse events, including an infrequent manifestation of fulminant type 1 diabetes.

Case presentation:

ICIs-induced fulminant type 1 diabetes mellitus (FT1DM) in breast cancer patients has been rarely documented. To provide further evidence of such adverse events, this paper presents the case of a 58-year-old Chinese patient with breast cancer and multi-organ metastasis, who had no prior history of diabetes. Following five courses of pembrolizumab, she developed severe fulminant type 1 diabetes accompanied by ketoacidosis.

Discussion:

Pembrolizumab is commonly utilized in the treatment of patients with advanced cancer. While it offers significant benefits to patients, it can also lead to numerous adverse reactions, with immune-related diabetes being the most prevalent among them as a result of pembrolizumab usage.

Conclusions:

FT1DM complicated with ketoacidosis represents a critical and potentially life-threatening medical condition, necessitating immediate attention. Our case study underscores the inherent risks associated with pembrolizumab administration and offers valuable insights for its safe utilization in patients.
CD38 and the mitochondrial calcium uniporter contribute to age-related hematopoietic stem cell dysfunction
Authors: Jankowski Connor S. R. , Weichhart Thomas
Published: October 2024

Hematopoietic stem cells (HSCs) are the multipotent progenitors of all immune cells. During aging, their regenerative capacity decreases for reasons that are not well understood. Recently, Song et al investigated the roles of two metabolic proteins in age-related HSC dysfunction: CD38 (a membrane-bound NADase) and the mitochondrial calcium uniporter that transports calcium into the mitochondrial matrix. They found that the interplay between these proteins is deranged in aged HSCs, contributing to their diminished renewal capacity. These findings implicate compromised nicotinamide adenine dinucleotide metabolism as underlying HSC dysfunction in aging.
Implementing Clinical Practice Guidelines for Improving Function in Cerebral Palsy: Development of a Fidelity Tool
Authors: Jackman Michelle , Thorley Megan , Toovey Rachel , Burgess Andrea , Blatch-Williams Remy , Sakzewski Leanne , Boyd Roslyn N. , Novak Iona
Published: October 2024

Purpose:

To develop a fidelity tool to support the implementation of clinical practice guidelines to improve physical function for children and young people with cerebral palsy.

Methods:

Fidelity tool development followed a 5-step process: the pilot study, using a mixed-methods action research approach, and including focus groups, questionnaires, and field notes.

Results:

A 21-item fidelity tool representing the core components of the clinical practice guidelines was developed, including subsections of goal setting, intervention, and elements seen throughout therapeutic intervention. Clinicians and supervisors reported this tool as acceptable and feasible, especially when used as a self-reflection tool.

Conclusions:

A fidelity tool has been developed that clinicians, supervisors and organizations can use to reflect on current practice and plan for changes to align practice with guidelines to improve function in children with cerebral palsy.
Drug Development Considerations for Additives to Organ Preservation Solutions
Authors: O’Brien Laramy Matthew , Robinson Jamie , Venkatramani C.J. , Horn Stephanie , Steiner Carine , Son Yoen-Ju
Published: October 2024

The addition of a novel therapeutic agent to an organ preservation solution has the potential to address unmet needs in organ transplantation and enhance outcomes for transplant recipients. However, the development expectations for novel therapeutic agents in this context are unclear because of limited precedence and published regulatory guidance documents. To address these gaps, we have articulated a drug development strategy that leverages expectations for parenteral drug products administered via more conventional routes (eg, intravenous) and provided considerations for when deviations may be justified. We have supplemented this strategy with a comparison to available regulatory guidance from the US Food and Drug Administration to highlight potential areas for further clarification. The strategy articulated here is based on Genentech’s internal experience for a program intended for use in kidney transplantation.
Current Practices and Recent Advances in Perioperative Pain Management for Liver Transplantation Living Donors and Recipients
Authors: Gitman Marina , Bezinover Dmitri , Pai Sher-Lu
Published: October 2024

Analgesia in liver transplantation patients has been traditionally considered a secondary priority where perioperative management principally focused on survival rates in these critically ill patients. With recent advancements in both surgical and medical management, posttransplant survival rates have steadily improved. Outcome measurements are no longer limited to short-term mortality rates and hospital length of stay but are also measured by patient-centered outcomes, such as pain control and quality of life. As living donor liver transplantation has increased access to transplantation, it has also added a different patient population to manage in the perioperative period. For healthy patients undergoing living donor hepatectomies, it is important to reduce the impact of the surgery with proper perioperative pain management. We performed a literature search for articles related to perioperative pain management for liver transplantation living donors and recipients to identify current practices and recent advances. Neuraxial techniques, peripheral nerve blocks, and enteral and parenteral medications were all found to be feasible analgesia modalities for patients undergoing either liver transplant or donor hepatectomy. Patients may also benefit from nonpharmacological interventions and preoperative counseling. No particular perioperative analgesic modality was deemed superior to any other. For liver transplant living donors and recipients, perioperative pain management should emphasize the application of sustainable patient-centered pain control protocols.
Atlantic bluefin tuna tagged off Norway show extensive annual migrations, high site-fidelity and dynamic behaviour in the Atlantic Ocean and Mediterranean Sea
Authors: Ferter Keno , Pagniello Camille M. L. S. , Block Barbara A. , Bjelland Otte , Castleton Michael R. , Tracey Sean R. , Reimer Theodore E. J. , Sundelöf Andreas , Onandia Iñigo , Wiech Martin , Alemany Francisco , Nøttestad Leif
Published: October 2024

Atlantic bluefin tuna (ABFT;
Thunnus thynnus
) is a highly migratory species. To investigate the migrations and vertical behaviours of ABFT migrating to Nordic waters, we deployed pop-up satellite archival transmitting tags on 25 ABFT off Norway (curved fork length: 228–292 cm). We obtained 16 full-year migrations, which differed between individuals, and physically recovered 13 tags, which provided 4699 days of archival depth and temperature data. ABFT occupied waters from the Arctic Circle to as far south as Cabo Verde, Africa, and occupied depths down to 1190 m and temperatures from 0.5 to 27.8°C. During their annual migrations, ABFT spent, on average, 68 days in Norwegian waters, 65 days in the Newfoundland Basin, 35 days around the Canary Islands and 33 days in the West European Basin. Most ABFT entered the Mediterranean Sea with a mean entry date of 13 May and visited known spawning grounds, staying, on average, 44 days. All ABFT with full-year deployments returned to Norwegian waters. ABFT displayed high site-fidelity and dynamic vertical diving behaviours that varied between hotspots and seasons. These spatiotemporal data provide important ecological knowledge for sustainable management and the conservation of the recently recovered eastern ABFT stock.
Variation in the thermal plasticity of avian embryos is produced by the developmental environment, not genes
Authors: Cones Alexandra G. , Westneat David F.
Published: October 2024

Limited evidence suggests that variation in phenotypic plasticity within populations may arise largely from environmental sources, thereby constraining its evolvability. This is of concern for temperature-sensitive metabolism in the face of climate change. We quantified the relative influence of the developmental environment versus genes on the metabolic plasticity of avian embryos to temperature. We partially cross-fostered 602 house sparrow eggs (
Passer domesticus
), measured the heart rate plasticity of these embryos to egg temperature and partitioned variance in plasticity. We found that the foster (incubation) environment was the sole meaningful source of variance in embryonic plasticity (not genes, pre-laying effects or ambient conditions). In contrast to heart rate plasticity, offspring growth was influenced by the foster environment, genes/pre-laying parental effects and ambient conditions. Although embryonic plasticity to temperature varied in this population, these results suggest that it is unlikely to evolve quickly. Nevertheless, the expression of this plasticity may be able to shift between generations in response to changes in the developmental environment. Whether the multidimensional plasticity of heart rate to both current temperature and the developmental environment is itself an adaptive, evolved trait allowing avian embryos to optimize their metabolic plasticity to their current environment remains to be tested.
Modeling the Effects of Propofol on Brain Activity: Insights from Computational EEG Studies
Authors: Zahran Saeed
Published: October 2024

The effects of anesthetic agents like propofol on brain activity provide critical insights into how consciousness is altered during anesthesia. This article presents a computational approach to modeling the impact of propofol on the brain’s electrical activity using the COALIA model, a large-scale neural mass model of human EEG designed for consciousness research. Propofol enhances GABA_A-mediated synaptic inhibition, leading to characteristic EEG signatures such as alpha oscillations (8-12 Hz) and slow-wave oscillations (0.1-1.5 Hz). We model these effects by modulating the parameters of postsynaptic potentials and synaptic strength, simulating the action of propofol at both the molecular and network levels. COALIA’s detailed representation of thalamo-cortical and cortico-cortical networks provides realistic simulations of brain dynamics under anesthesia, closely replicating experimental EEG data. Our findings highlight the importance of network-level interactions in producing the distinctive EEG changes seen during propofol-induced unconsciousness. This research paves the way for future applications in personalized anesthesia monitoring and consciousness assessment through EEG modeling.
Psychological aspects of caregiving after stroke: a systematic scoping review and thematic synthesis of theories
Authors: Harcourt Bethany J. , Brown Richard J. , Bowen Audrey
Published: October 2024

Informal caregiving comprises a core part of stroke survivors’ rehabilitation. Providing informal care can encompass positive elements, yet adopting and sustaining this role can affect carers’ physical and mental health. Understanding carers’ experiences is important for clinical psychologists, to highlight their potential role in supporting carers’ unmet needs. Theories of stroke informal carers’ experiences exist, yet no previous attempt has been made to identify, organise and describe them, and synthesise their key themes. This PRISMA-ScR guided scoping review aimed to identify theories of stroke informal caregiving and generate new knowledge of the experience and psychological impact of caregiving, to guide stroke service improvements. Six databases were systematically searched, identifying relevant theoretical and empirical papers. Seventeen papers, presenting thirteen distinct theories, were included and the theories thematically synthesised. Two overarching themes were developed - ‘Systemic and Cultural factors’ and ‘A staged process’– containing three main themes – ‘Adjustment to aspects of post-stroke life’, ‘Emotional and psychological aspects of caregiving’, ‘Carer Needs’– and four subthemes constituting relevant stroke pathway stages. Substantial theoretical knowledge exists that was useful in generating key themes of the experiences and psychological impact of caregiving across the stroke pathway, to guide clinical psychology practice and future research directions.
Evaluation of Some Serum Minerals in Type 2 Diabetic Patients Attending Federal Medical Centre Owo
Authors: Ajao Fiyinfoluwa Olamide , Olusegun Timothy God-Giveth , Oyeromi Blessing Oluwatosinmile , Obeagu Emmanuel Ifeanyi
Published: October 2024

Minerals and trace elements play crucial roles in physiological processes, and alterations in their levels can have significant consequences for metabolic health. This study aimed to investigate serum mineral levels in patients with type 2 diabetes mellitus (T2DM) compared to healthy controls and explore their potential implications for disease pathophysiology. A total of 50 T2DM patients and 30 healthy individuals were included in the study. Serum levels of iron, copper, calcium, magnesium, and zinc were analysed using flame atomic absorption spectrometry. The results revealed significantly higher levels of iron and copper in T2DM patients compared to controls, while lower levels of calcium, magnesium, and zinc were observed in the T2DM group. These findings are consistent with previous research, highlighting the importance of mineral homeostasis in T2DM. Further analysis showed weak interrelationships among the studied minerals in T2DM patients, suggesting complex mechanisms underlying mineral metabolism in the disease. The discussion delved into potential mechanisms contributing to these alterations, including glycosuria-induced urinary loss of zinc and calciuresis due to hyperglycemia. Additionally, the study emphasised the importance of zinc and manganese in insulin production and release, as well as the contradictory findings regarding calcium levels in T2DM. Overall, this study provides valuable insights into serum mineral levels in T2DM and highlights the need for further research to elucidate their roles in disease progression and management.
APOE4impacts cortical neurodevelopment and alters network formation in human brain organoids
Authors: Meyer-Acosta Karina K. , Diaz-Guerra Eva , Varma Parul , Aruk Adyasha , Mirsadeghi Sara , Perez Aranis Muniz , Rafati Yousef , Hosseini Ali , Nieto-Estevez Vanesa , Giugliano Michele , Navara Christopher , Hsieh Jenny
Published: October 2024

Apolipoprotein E4 (APOE4) is the leading genetic risk factor for Alzheimer’s disease. While most studies examine the role ofAPOE4in aging, imaging, and cognitive assessments reveal thatAPOE4influences brain structure and function as early as infancy. Here, we examined human-relevant cellular phenotypes across neurodevelopment using induced pluripotent stem cell (iPSC) derived cortical and ganglionic eminence organoids (COs and GEOs). In COs, we showed thatAPOE4decreased BRN2+ and SATB2+ cortical neurons, increased astrocytes and outer radial glia, and was associated with increased cell death and dysregulated GABA-related gene expression. In GEOs,APOE4accelerated maturation of neural progenitors and neurons. Multi-electrode array recordings in assembloids revealed thatAPOE4disrupted network formation and altered response to GABA, resulting in heightened excitability and synchronicity. Together, our data provides new insights into howAPOE4may influence cortical neurodevelopmental processes and network formation in the human brain.
The expanding truffle environment: a study of the microbial dynamics in old and newTuber magnatumPicco habitat
Authors: Rondolini M. , Zotti M. , Bragato G. , Baciarelli Falini L. , Reale L. , Donnini D.
Published: October 2024

Truffles are valuable underground mushrooms with significant economic importance. In recent years, their cultivation has achieved satisfactory results, but not for all species. The harvesting of white truffles (Tuber magnatumPicco) is still dependent on natural production, which is at risk due to various issues, such as improper forest management. A useful practice to protect natural resources is to promote the expansion of productive forests. In this study, we investigate the dynamics of the microbiome in an old and new truffle forest using an amplicon sequencing approach of the fungal ITS region and the prokaryotic 16S rRNA gene. We will monitor the soil biological community’s development to compare differences and similarities between the primary productive forest and the expanding area over a two-year sampling period. In particular, we observed the colonization of vacant ecological niches by certain fungi, such as those belonging to the genusMortierella. Additionally, we examined the competitive interactions between saprotrophs and ectomycorrhizal fungi (ECM). In both study areas, the bacterial community was dominated by Pseudomonadota, Planctomycetota, and Actinomycetota. The behavior of theTubergenus differed significantly from other ECMs and displayed positive correlations with bacterial taxa such asKtedonobacter, Zavarzinella, andSphingomonas. The present work provides an initial overview of expanding white truffle habitats. Further, more specific research is needed to explore potential connections between individualtaxa.
Corporate political action and R&D investments: complementary effects and the role of communication in overcoming ex-post transaction costs
Authors: Westphal Fernando Kaname , Feldmann Paulo Roberto , Mrtvi Valdete de Oliveira
Published: October 2024

Purpose

This study aims to investigate the role of interfirm communication on the complementary effect between corporate political action (CPA) and research and development (R&D) investments under transaction costs.

Design/methodology/approach

A quasi-experiment study design was used, combining business game simulation and a public goods experiment with communication as a controlled variable. A fixed-effect regression analysis was performed on panel data collected from 72 students.

Findings

The findings indicate that collective CPA is positively and significantly associated with R&D investments, particularly when interfirm communication is present. Conversely, for non-communicating firms, the effect is limited to the relationship between individual CPA and R&D investment.

Research limitations/implications

Despite advancing the research on political ties and innovation, the study acknowledges limitations related to framing effects and institutional variability.

Practical implications

The complementary effects indicate that institutional arrangements (i.e. business associations) may foster interfirm communication and cooperation in CPA efforts, mitigating opportunistic behaviours and legitimising CPA strategy towards innovation.

Social implications

This study contributes to understanding how firms’ political and R&D decisions can positively impact innovation, despite the challenges of ex post transaction costs.

Originality/value

The positive effect of communication on political action and cooperation on firms’ innovation, even in weak institutional environments, is highlighted. An innovative methodological approach combining business games and economic experiments was used to examine participants’ decisions under transaction costs.
A comprehensive evaluation of factors influencing offsite construction and BIM integration in the construction industry
Authors: Kordestani Nazanin , Babaeian Jelodar Mostafa , Paes Daniel , Sutrisna Monty , Rahmani Diyako
Published: October 2024

Purpose

The construction industry's transformation of prefabrication into large-scale offsite manufacturing continues to grow. While the Offsite Construction (OSC) transition has brought positive changes to the industry, it also presents various challenges. Literature suggests that to address the challenges, advanced technologies such as Building Information Modeling (BIM) can be applied for effective mitigation. Nonetheless, the combined application of BIM and OSC is in its infancy and faces challenges in many countries. This study aims to investigate the factors influencing OSC and BIM integration, including challenges and strategies within the New Zealand construction industry.

Design/methodology/approach

This study explores which specific factors impact integration positively or negatively through a comprehensive literature review and confirmatory survey. Factor Analysis (FA) was used as the data analysis method, resulting in eight groups of underlying factors. Next, three Structural Equation Models (SEM) were developed and tested to analyze the impact of latent and observed variables on OSC and BIM integration.

Findings

Significant underlying factors affecting OSC and BIM integration were identified, and recommendations to enhance integration were provided. Specifically, the findings demonstrated that three underlying factors for challenges, two for strategies and three for integration were identified through EFA and confirmed by CFA. This step was followed by SEM, which employed three different path analysis models for integration variables. It clarified that not all variables have similar impacts on integration; some exhibit significant positive or negative effects, while others are not significant at all.

Originality/value

The identified challenges and strategies for OSC and BIM integration and their impact on integration factors can contribute to developing standardized integration guidelines and frameworks to assist stakeholders in focusing on their specific integration goals.
Health service quality and patients’ satisfaction among hospitals: the cohesive care of human beings and accomplishment of human rights
Authors: Abdelwahed Nadia A. Abdelmegeed , Zehri Abdul Wahid
Published: October 2024

Purpose

In this study, the researchers explored the influence of service quality-related constructs on patients’ satisfaction with Egyptian health-care centers.

Design/methodology/approach

In this study, the researchers used a quantitative approach and concluded the study based on 316 valid cases collected from patients of Egyptian health-care centers.

Findings

Using path analysis with analysis of moment structures (AMOS), this study's results demonstrate that reliability and responsiveness, empathy, nursing care and medical care positively affect patients' satisfaction. On the other hand, the tangibles have a negative effect on patient satisfaction.

Practical implications

This study’s findings benefit policymakers by shaping evidence-based policies. Health-care managers can implement strategies that prioritize the identified factors and can foster a more patient-centric and effective health-care system. Also, this study’s findings guide health-care institutes to maintain human rights by serving poor and needy patients. More generally, this study's outcomes enrich the depth of the domain literature.

Originality/value

This study’s findings add to the existing knowledge and fill contextual gaps by confirming patients’ satisfaction with the service quality of Egyptian health-care centers.