bluuebunny/crossref_metadata_2025 huggingface dataset:
Local administration of irinotecan using an implantable drug delivery device stops high-grade glioma tumor recurrence in a glioblastoma tumor model
Authors: Abdelnabi Dina , Lastakchi Sarah , Watts Colin , Atkins Hannah , Hingtgen Shawn , Valdivia Alain , McConville Christopher
Published: February 2024

The treatment for Glioblastoma is limited due to the presence of the blood brain barrier, which restricts the entry of chemotherapeutic drugs into the brain. Local delivery into the tumor resection margin has the potential to improve efficacy of chemotherapy. We developed a safe and clinically translatable irinotecan implant for local delivery to increase its efficacy while minimizing systemic side effects. Irinotecan-loaded implants were manufactured using hot melt extrusion, gamma sterilized at 25 kGy, and characterized for their irinotecan content, release, and drug diffusion. Their therapeutic efficacy was evaluated in a patient-derived xenograft mouse resection model of glioblastoma. Their safety and translatability were evaluated using histological analysis of brain tissue and serum chemistry analysis. Implants containing 30% and 40% w/w irinotecan were manufactured without plasticizer. The 30% and 40% implants showed moderate local toxicity up to 2- and 6-day post-implantation. Histopathology of the implantation site showed signs of necrosis at days 45 and 14 for the 30% and 40% implants. Hematological analysis and clinical chemistry showed no signs of serious systemic toxicity for either implant. The 30% implants had an 80% survival at day 148, with no sign of tumor recurrence. Gamma sterilization and 12-month storage had no impact on the integrity of the 30% implants. This study demonstrates that the 30% implants are a promising novel treatment for glioblastoma that could be quickly translated into the clinic.

Graphical Abstract
Numerical approximation of the boundary control for the wave equation in a square domain with a spectral collocation method
Authors: Boumimez Somia , Castro Carlos
Published: February 2024

We propose a spectral collocation method to approximate the exact boundary control of the wave equation in a square domain. The idea is to introduce a suitable approximate control problem that we solve in the finite-dimensional space of polynomials of degree $$N\in {\mathbb {N}}$$

N
∈
N

in space. We prove that we can choose a sequence of controls $$f^N$$

f
N

associated with the approximate control problem in such a way that they converge, as $$N\rightarrow \infty $$

N
→
∞

, to a control of the continuous wave equation. Unlike other numerical approximations tried in the literature, this one does not require regularization techniques and can be easily adapted to other equations and systems where the controllability of the continuous model is known. The method is illustrated with several examples in 1-d and 2-d in a square domain. We also give numerical evidence of the highly accurate approximation inherent to spectral methods.
Multi-class Facial Emotion Expression Identification Using DL-Based Feature Extraction with Classification Models
Authors: Anand M. , Babu S.
Published: February 2024

Facial expression detection from images and videos has recently gained attention due to the wide variety of applications it has found in the field of computer vision such as advanced driving assistance systems (ADAS), augmented and virtual reality (AR/VR), video retrieval, and security systems. Facial terms, body language, hand gestures, and eye contact have all been researched as a means of deciphering and understanding human emotions. Automated facial expression recognition (FER) is a significant visual recognition procedure because human emotions are a worldwide signal used in non-verbal communication. The six primary universal manifestations of emotion are characterized as happiness, sadness, anger, contempt, fear, and surprise. While the accuracy of deep learning (DL)-based approaches has improved significantly across many domains, automated FER remains a difficult undertaking, especially when it comes to real-world applications. In this research work, two publicly available datasets such as FER2013 and EMOTIC are considered for validation process. Initially, pre-processing includes histogram equalization, image normalization and face detection using Multi-task Cascaded Convolutional Network (MT-CNN) is used. Then, DL-based EfficinetNetB0 is used to extract the features of pre-processed images for further process. Finally, the Weighted Kernel Extreme Learning Machine (WKELM) is used for classification of emotions, where the kernel parameters are optimized by Red Fox Optimizer (RFO). From the experimental analysis, the proposed model achieved 95.82% of accuracy, 95.81% of F1-score and 95% of recall for the testing data.
Addressing global environmental pollution using environmental control techniques: a focus on environmental policy and preventive environmental management
Authors: Awewomom Jonathan , Dzeble Felicia , Takyi Yaw Doudu , Ashie Winfred Bediakoh , Ettey Emil Nana Yaw Osei , Afua Patricia Eyram , Sackey Lyndon N. A. , Opoku Francis , Akoto Osei
Published: February 2024

Global environmental pollution presents formidable obstacles to the long-term viability of the planet. This study synthesized current relevant literature with statistical snapshots from pollution statistics and reports and presented feasible recommendations to address the ramifications of global environmental pollution. A central focus is laid on the importance of preventive environmental management (PEM) and the strategic enforcement of environmental policies (EP), with a detailed exploration of history evolution and current application challenges. Specifically, the study centers on the significance of environmental policy and preventive environmental management in combatting global pollution. The examination encompasses an overview of environmental pollution and its implications for the environment and human health. It explores the role of environmental policy in mitigating environmental pollution, scrutinizes the principles underlying preventive environmental management, and evaluates the effectiveness of environmental management systems in curbing pollution. Furthermore, the study identifies and analyzes the challenges of implementing environmental control techniques, offering recommendations to overcome these obstacles. The outcomes of this research contribute to a more comprehensive understanding of the potential of environmental control methods in tackling global environmental pollution. The study underscores the crucial nature of robust environmental policies and proactive approaches to prevent pollution and foster sustainable development. Additionally, it offers insights into the necessity for collaboration and cooperation among stakeholders at various levels to attain effective pollution control and environmental management.
Periodic flow features in a planar sudden expansion with pulsatile inflow velocity
Authors: Sarkar Nandan , Roy Somnath
Published: February 2024

Flow through sudden expansion finds its application in several engineering and biological processes. Though the stability of flow through steady sudden expansion has garnered much attention, little to none is given to the pulsatile flow through sudden expansion. Hence, in the present work we study the influence of inflow pulsatility on flow characteristics in a sudden expansion. The inflow velocity is a sinusoidal waveform that is modulated to encompass a wide range of amplitudes,${{a}}$, and reduced velocities,${{U_{r}}}$. We report four different modes, namely, synchronized growth of the recirculation region (at high${{U_{r}}}$), necking and diffusion of the recirculation region (at moderately high${{U_{r}}}$), splitting and convection of the recirculation region (at moderate${{U_{r}}}$) and inverse growth of the recirculation region (at low${{U_{r}}}$). In each mode, the symmetry-breaking critical Reynolds number is obtained through numerical experiments and compared with those of Floquet stability analysis. We found that diffusion and the convection mode of the recirculation region increases the stability of the flow while the inverse growth mode of the recirculation region decreases the same. The effect of the expansion ratio,${{ER}}$, is also explored, and we found that as${{ER}}$increases, the absolute stability of flow decreases, but relative stability between the modes remains similar. Finally, we explain the dynamics of the modes by using terms involving the vorticity transport equation.
Do It Right the First Time? Exploring the First Cross-border Acquisition and Expansion Frequency of Emerging Market Multinationals
Authors: Wu Sihong , Fan Di , Soo Christine
Published: February 2024

Do it right the first time! But, how? Current dialogue on the expansion of emerging market multinational enterprises (EMNEs) is pervasive. Nonetheless, it ought to have examined strategic attributes and the speed of implementing different strategies for their first venture. Drawing on the springboard perspective, this study tests the impact of EMNEs' first cross-border acquisition (CBA) strategy and speed on their consequential expansion frequency and performance. We also examine the boundary conditions of comparative nationalism between countries, in view of the resurgence of nationalism in an era of deglobalization. Findings reveal that EMNEs' rapid adoption of a focused strategy for their first CBA increases their expansion frequency, while the adoption of a conglomerate strategy decreases it. These relationships are affected in reverse by high comparative nationalism, and the performance consequences of expansion vary with firms using different strategies for their first attempt. This study enriches the EMNE literature and highlights the role of national ideologies in international business research.
The Role of Emotions in the Capabilities Approach: A Critical Analysis
Authors: Sacco Giulio
Published: February 2024

The capabilities approach is the theory according to which, in order to assess people's quality of life and reflect on the basic political entitlements, we should consider what people are capable of doing and being. Focusing mostly on Nussbaum's account, a number of scholars analysed the metaethical structure underlying the approach, showing her Aristotelian and Kantian sources. This article explores another aspect of Nussbaum's theory which has so far been somewhat overlooked: the role of emotions in the justification and motivational support of the approach. After showing the importance Nussbaum places on compassion (and other benevolent emotions) to warrant her moral theory, I argue that – assuming her own cognitive account of compassion – her argument begs the question. I will then contend that Nussbaum's case does not have the inner tools to overcome such a circularity, trying to suggest, in conclusion, a possible way out which is consistent with it.
Suicidal Ideation in Canadian Family Caregivers for a Person with Dementia: A Portrait of the Situation
Authors: Teasdale-Dubé Audrée , Viau-Quesnel Charles , Lapierre Sylvie
Published: February 2024

This study aimed to explore the prevalence of suicidal thoughts and potential associations (i.e., strength and direction) with caregiver characteristics or factors. A targeted survey was distributed to dementia caregivers aged 55+ years. Questions concerning psychological distress, suicidal thoughts while caregiving and antecedents of suicidal behaviours were administered. A sample of 71 French-speaking Canadian caregivers completed the survey between May and October 2019. Among them, 52.1 per cent (n = 37) reported suicidal ideation while providing care to a relative or a friend living with dementia. Caregivers who presented suicidal ideation reported more abusive behaviour toward the care recipient. Caregivers who reported suicidal thoughts were significantly more distressed than caregivers without them on measures of burden, depression, and anxiety. Suicidal thoughts in caregivers are important evaluation targets, primarily for the prevention of suicide, but also because caregivers who report suicidal thoughts also present a heightened risk for abusing the care recipient.
Agricultural subsidies: cutting into forest conservation?
Authors: Moffette Fanny , Alix-Garcia Jennifer
Published: February 2024

We examine how agricultural subsidies may induce deforestation and interact with conservation programs by analyzing two large-scale national programs in Mexico that have existed simultaneously for more than a decade: an agricultural subsidy for livestock (PROGAN) and a program of payments for ecosystem services (PES). Looking across the entire Mexican landscape, we exploit the surprises in the timing of enrollment in PROGAN's waves, fluctuations in program payments, and the change in the value of the subsidy induced by inflation and currency fluctuations to identify the impacts of the livestock subsidy on environmental outcomes. We find that PROGAN increased municipal deforestation by 7 per cent. The deforestation effects of PROGAN were smaller in municipalities with higher concentrations of PES recipients. We suggest that livestock subsidies could be better targeted to places with low deforestation risk and high livestock productivity to maximize food production and minimize negative externalities caused by deforestation.
Evaluation of a digital FFQ using 24 h recalls as reference method, for assessment of habitual diet in women with South Asian origin in Norway
Authors: Carlsen Monica H , Totland Torunn Holm , Kumar Radhika , Lensnes Therese ML , Sharma Archana , Suntharalingam A Anita , Tran Anh Thi , Birkeland Kåre I , Sommer Christine
Published: February 2024

Objective:

Dietary assessment tools should be designed for the target population. We developed an FFQ designed to assess diet in South Asian women in Norway. The study objective was to evaluate this FFQ using 24-h dietary recalls as reference method.

Design:

Approximately 3 weeks after the participants (n 40) had filled in the FFQ, the first of three non-consecutive 24-h dietary recalls was completed. The recalls were telephone-based, unannounced and performed by a trained dietitian, with 2–3 weeks between each interview.

Setting:

The DIASA 1 study, in Oslo, Norway.

Participants:

Women of South Asian ethnic origin participating in the DIASA 1 study were invited to participate in the evaluation study.

Results:

The WebFFQasia significantly overestimated the absolute intake of energy, protein, fat and carbohydrates compared with the 24-h dietary recalls. Absolute intakes of sugar, starch and fibre did not differ significantly between the methods. For energy percentages (E%), there were no significant differences, except for monounsaturated fat. Correlations were strong for E% from sugar and saturated fat and moderate for E% from fibre, carbohydrate, total fat and protein. Fourteen food groups out of twenty three were not significantly different compared with the reference method, and sixteen groups showed strong to moderate correlations.

Conclusion:

The WebFFQasia may be used to assess E% from habitual diet and can adequately estimate intakes and rank participants according to nutrient intake and main food categories at group level.
‘It is human work’: qualitatively exploring community roles that facilitate cultural food security for people from refugee backgrounds
Authors: Gingell Tina , Adhikari Rishita , Eltahir Nehal , Ntahomvukiye Fulgence , Pe Evelyn , Murray Kate , Correa-Velez Ignacio , Gallegos Danielle
Published: February 2024

Objectives:

Cultural food security is crucial for cultural health and, for people from refugee backgrounds, supports the settlement journey. Cultural communities are vital in facilitating access to cultural foods; however, it is not understood how refugee-background communities sustain cultural food security in the Australian context. This study aimed to explore key roles in refugee-background communities to understand why they were important and how they facilitate cultural food security.

Design:

Interviews were conducted by community researchers, and data analysis was undertaken using best-practice framework for collaborative data analysis.

Setting:

Greater Brisbane, Australia.

Participants:

Six interviews were conducted between August and December 2022 with people from a refugee-background community, lived in Greater Brisbane and who fulfilled a key food role in the community that facilitated access to cultural foods.

Results:

Fostering improved cultural food security supported settlement by creating connections across geographical locations and cultures and generated a sense of belonging that supported the settlement journey. Communities utilised communication methods that prioritised the knowledge, wisdom and experience of community members. It also provided community members with influence over their foodways. Community leaders had an ethos that reflected collectivist values, where community needs were important for their own health and well-being.

Conclusions:

Communities are inherently structured and communicate in a way that allows collective agency over foodways. This agency promotes cultural food security and is suggestive of increased food sovereignty. Researchers and public health workers should work with communities and recognise community strengths. Food security interventions should target cultural food security and autonomy.
Why Are All of the Children Perceived to Be Above Average? Stakeholders and the Lake Wobegon Effect in Attitudes toward Public Schools
Authors: Vercellotti Timothy , Fairman Peter
Published: February 2024

The Lake Wobegon effect, named for the fictional town where all children are above average, is well documented in surveys about education. Respondents tend to rate their local public schools higher in quality than schools overall in the state or nation, even despite contrary evidence. One potential explanation for this disconnect is a psychological construct known as “illusory superiority.” While the superiority aspect of illusory superiority is well studied, the illusory nature of these attitudes typically is assumed rather than empirically demonstrated. Further, the predictors of these attitudes also merit exploration. We seek to address both of these points. We hypothesize that illusory superiority in the context of attitudes toward public education may be driven in part by self-interest, and thus may be more likely to be found among those with the biggest stake in local schools, such as parents of students, homeowners, and longtime residents. Using survey data from Massachusetts, we find a factual basis for illusory superiority by comparing perceptions of local school performance on standardized tests to actual scores. We also model predictors of illusory superiority, including property ownership, length of residency, and having children enrolled in public schools, and the role that illusory superiority may play in school ratings. We then assess the effects of overstatement of test scores on attitudes toward a key educational issue – whether to increase taxes to provide additional funding for local schools.
Durch ein Online-Self-Assessment angeregte Selbstreflexion von Lernerfahrungen im Praktikum
Authors: Grassinger Robert , Schnebel Stefanie
Published: February 2024

Zusammenfassung: Online-Self-Assessments werden als Instrument zur Unterstützung selbstregulierenden Lernverhaltens Studierender diskutiert. Hierbei kann ein Online-Self-Assessment eine Selbstreflexion aktueller Lernerfahrungen, eine Phase selbstregulierten Lernverhaltens, anregen und sich in einer elaborierteren Selbstreflexionserkenntnis manifestieren. Es wurde angenommen, dass die durch ein Online-Self-Assessment angeregte Selbstreflexionserkenntnis in Zusammenhang mit individuellen Lern- und Arbeitsvermeidungszielen steht (H1) und mit dem Erleben motivationaler Erwartungsdiskrepanz sowie einer Verunsicherung ob der passenden Studienwahl einhergeht (H2). An einer Stichprobe von 299 Lehramtsstudierenden wurden diese beiden Hypothesen geprüft. Die Befunde zeigten, dass Lernziele eine Selbsterkenntnis zur Lernsituation durch ein Online-Self-Assessment begünstigten, Arbeitsvermeidungsziele jedoch nicht damit in Zusammenhang standen. Eine erhöhte durch ein Online-Self-Assessment angeregte Selbstreflexionserkenntnis war zudem mit dem Erleben einer positiven motivationalen Erwartungsdiskrepanz assoziiert, nicht jedoch mit einer Verunsicherung ob der passenden Studienwahl.
Graft-versus-host disease and impact on relapse in myelofibrosis undergoing hematopoietic stem cell transplantation
Authors: Oechsler Sofia , Gagelmann Nico , Wolschke Christine , Janson Dietlinde , Badbaran Anita , Klyuchnikov Evgeny , Massoud Radwan , Rathje Kristin , Richter Johanna , Schäfersküpper Mathias , Niederwieser Christian , Kunte Ameya , Heidenreich Silke , Ayuk Francis , Kröger Nicolaus
Published: February 2024

Allogeneic hematopoietic stem cell transplantation (alloHSCT) remains the only curative treatment for myelofibrosis (MF). Relapse occurs in 10–30% and remains a major factor for dismal outcomes. Previous work suggested that graft-versus-host disease (GVHD) might be associated with risk of relapse. This study included 341 patients undergoing their first (n = 308) or second (n = 33) alloHSCT. Anti-T-lymphocyte or antithymocyte globulin was used for GVHD prophylaxis in almost all patients. Median time to neutrophile and platelet engraftment was 13 days and 19 days, respectively. The cumulative incidence of acute GVHD grade II-IV was 41% (median, 31 days; range, 7–112). Grade III-IV acute GVHD was observed in 22%. The cumulative incidence of chronic GVHD was 61%. Liver was affected in 23% of acute GVHD cases and 46% of chronic GVHD cases. Severe acute GVHD was associated with high non-relapse mortality. The development of acute GVHD grade II and moderate GVHD was an independent factor for reduced risk for relapse after transplantation without increased risk for non-relapse mortality, while especially acute GVHD grade IV was associated with high non-relapse mortality. Last, we identified that ongoing response to ruxolitinib, accelerated-phase MF at time of transplantation and splenectomy prior to transplantation were independent predictors for relapse.
Publics’ knowledge of, attitude to and motivation towards health-related genomics: a scoping review
Authors: Pearce Angela , Mitchell Lucas A. , Best Stephanie , Young Mary-Anne , Terrill Bronwyn
Published: February 2024

The use of genomic data in research and genomic information in clinical care is increasing as technologies advance and sequencing costs decrease. Using Rogers’ Diffusion of Innovation (DOI) theory as a framework we reviewed recent literature examining publics’ current knowledge of, attitude to, and motivation towards health-related genomics in clinical and research settings. The population of interest was described as ‘publics’ to denote the heterogeneity of ‘the public’. Eligible studies were published in English between 2016–2022. We retrieved 1657 records, with 278 full-text reviewed against the eligibility criteria and concept definitions. In total, 99 articles were included in the review and descriptive numerical summaries were collated. Knowledge literature was categorized using deductive thematic analysis. For attitude and motivation, literature was coded using an analytic framework developed by the authors. There was wide variability in concept definition and measurement across studies. Overall, there was general positivity about genomics, with high awareness but little familiarity or factual knowledge. Publics had high expectations of genomics and perceived that it could provide them with information for their future. Only a few key attitudes were found to be important as motivators or barriers for participation in genomics; these were related to personal and clinical utility of the information. Context was often missing from studies, decreasing the utility of findings for implementation or public engagement. Future research would benefit by using theory-driven approaches to assess relevant publics’ knowledge and attitudes of specific contexts or applications to support genomic implementation and informed decision-making.
Interplay of the forces governing steroid hormone micropollutant adsorption in vertically-aligned carbon nanotube membrane nanopores
Authors: Nguyen Minh N. , Jue Melinda L. , Buchsbaum Steven F. , Park Sei Jin , Vollnhals Florian , Christiansen Silke , Fornasiero Francesco , Schäfer Andrea I.
Published: February 2024

Vertically-aligned carbon nanotube (VaCNT) membranes allow water to conduct rapidly at low pressures and open up the possibility for water purification and desalination, although the ultralow viscous stress in hydrophobic and low-tortuosity nanopores prevents surface interactions with contaminants. In this experimental investigation, steroid hormone micropollutant adsorption by VaCNT membranes is quantified and explained via the interplay of the hydrodynamic drag and friction forces acting on the hormone, and the adhesive and repulsive forces between the hormone and the inner carbon nanotube wall. It is concluded that a drag force above 2.2 × 10−3 pN overcomes the friction force resulting in insignificant adsorption, whereas lowering the drag force from 2.2 × 10−3 to 4.3 × 10−4 pN increases the adsorbed mass of hormones from zero to 0.4 ng cm−2. At a low drag force of 1.6 × 10−3 pN, the adsorbed mass of four hormones is correlated with the hormone−wall adhesive (van der Waals) force. These findings explain micropollutant adsorption in nanopores via the forces acting on the micropollutant along and perpendicular to the flow, which can be exploited for selectivity.
A triple increase in global river basins with water scarcity due to future pollution
Authors: Wang Mengru , Bodirsky Benjamin Leon , Rijneveld Rhodé , Beier Felicitas , Bak Mirjam P. , Batool Masooma , Droppers Bram , Popp Alexander , van Vliet Michelle T. H. , Strokal Maryna
Published: February 2024

Water security is at stake today. While climate changes influence water availability, urbanization and agricultural activities have led to increasing water demand as well as pollution, limiting safe water use. We conducted a global assessment of future clean-water scarcity for 2050s by adding the water pollution aspect to the classical water quantity-induced scarcity assessments. This was done for >10,000 sub-basins focusing on nitrogen pollution in rivers by integrating land-system, hydrological and water quality models. We found that water pollution aggravates water scarcity in >2000 sub-basins worldwide. The number of sub-basins with water scarcity triples due to future nitrogen pollution worldwide. In 2010, 984 sub-basins are classified as water scarce when considering only quantity-induced scarcity, while 2517 sub-basins are affected by quantity & quality-induced scarcity. This number even increases to 3061 sub-basins in the worst case scenario in 2050. This aggravation means an extra 40 million km2 of basin area and 3 billion more people that may potentially face water scarcity in 2050. Our results stress the urgent need to address water quality in future water management policies for the Sustainable Development Goals.
MAIVeSS: streamlined selection of antigenically matched, high-yield viruses for seasonal influenza vaccine production
Authors: Gao Cheng , Wen Feng , Guan Minhui , Hatuwal Bijaya , Li Lei , Praena Beatriz , Tang Cynthia Y. , Zhang Jieze , Luo Feng , Xie Hang , Webby Richard , Tao Yizhi Jane , Wan Xiu-Feng
Published: February 2024

Vaccines are the main pharmaceutical intervention used against the global public health threat posed by influenza viruses. Timely selection of optimal seed viruses with matched antigenicity between vaccine antigen and circulating viruses and with high yield underscore vaccine efficacy and supply, respectively. Current methods for selecting influenza seed vaccines are labor intensive and time-consuming. Here, we report the Machine-learning Assisted Influenza VaccinE Strain Selection framework, MAIVeSS, that enables streamlined selection of naturally circulating, antigenically matched, and high-yield influenza vaccine strains directly from clinical samples by using molecular signatures of antigenicity and yield to support optimal candidate vaccine virus selection. We apply our framework on publicly available sequences to select A(H1N1)pdm09 vaccine candidates and experimentally confirm that these candidates have optimal antigenicity and growth in cells and eggs. Our framework can potentially reduce the optimal vaccine candidate selection time from months to days and thus facilitate timely supply of seasonal vaccines.
Repeated upslope biome shifts in Saxifraga during late-Cenozoic climate cooling
Authors: Carruthers Tom , Moerland Michelangelo S. , Ebersbach Jana , Favre Adrien , Folk Ryan A. , Hawkins Julie A. , Muellner-Riehl Alexandra N. , Röser Martin , Soltis Douglas E. , Tkach Natalia , Baker William J. , de Vos Jurriaan M. , Eiserhardt Wolf L.
Published: February 2024

Mountains are among the most biodiverse places on Earth, and plant lineages that inhabit them have some of the highest speciation rates ever recorded. Plant diversity within the alpine zone - the elevation above which trees cannot grow—contributes significantly to overall diversity within mountain systems, but the origins of alpine plant diversity are poorly understood. Here, we quantify the processes that generate alpine plant diversity and their changing dynamics through time in Saxifraga (Saxifragaceae), an angiosperm genus that occurs predominantly in mountain systems. We present a time-calibrated molecular phylogenetic tree for the genus that is inferred from 329 low-copy nuclear loci and incorporates 73% (407) of known species. We show that upslope biome shifts into the alpine zone are considerably more prevalent than dispersal of alpine specialists between regions, and that the rate of upslope biome shifts increased markedly in the last 5 Myr, a timeframe concordant with a cooling and fluctuating climate that is likely to have increased the extent of the alpine zone. Furthermore, alpine zone specialists have lower speciation rates than generalists that occur inside and outside the alpine zone, and major speciation rate increases within Saxifraga significantly pre-date increased rates of upslope biome shifts. Specialisation to the alpine zone is not therefore associated with speciation rate increases. Taken together, this study presents a quantified and broad scale perspective of processes underpinning alpine plant diversity.
Spatio-spectral 4D coherent ranging using a flutter-wavelength-swept laser
Authors: Jeong Dawoon , Jang Hansol , Jung Min Uk , Jeong Taeho , Kim Hyunsoo , Yang Sanghyeok , Lee Janghyeon , Kim Chang-Seok
Published: February 2024

Coherent light detection and ranging (LiDAR), particularly the frequency-modulated continuous-wave LiDAR, is a robust optical imaging technology for measuring long-range distance and velocity in three dimensions (3D). We propose a spatio-spectral coherent LiDAR based on a unique wavelength-swept laser to enable both axial coherent ranging and lateral spatio-spectral beam scanning simultaneously. Instead of the conventional unidirectional wavelength-swept laser, a flutter-wavelength-swept laser (FWSL) successfully decoupled bidirectional wavelength modulation and continuous wavelength sweep, which overcame the measurable distance limited by the sampling process. The decoupled operation in FWSL enabled sequential sampling of flutter-wavelength modulation across its wide spectral bandwidth of 160 nm and, thus, allowed simultaneous distance and velocity measurement over an extended measurable distance. Herein, complete four-dimensional (4D) imaging, combining real-time 3D distance and velocity measurements, was implemented by solid-state beam scanning. An acousto-optic scanner was synchronized to facilitate the other lateral beam scanning, resulting in an optimized solid-state coherent LiDAR system. The proposed spatio-spectral coherent LiDAR system achieved high-resolution coherent ranging over long distances and real-time 4D imaging with a frame rate of 10 Hz, even in challenging environments.
AAV-delivered muscone-induced transgene system for treating chronic diseases in mice via inhalation
Authors: Wu Xin , Yu Yuanhuan , Wang Meiyan , Dai Di , Yin Jianli , Liu Wenjing , Kong Deqiang , Tang Shasha , Meng Meiyao , Gao Tian , Zhang Yuanjin , Zhou Yang , Guan Ningzi , Zhao Shangang , Ye Haifeng
Published: February 2024

Gene therapies provide treatment options for many diseases, but the safe and long-term control of therapeutic transgene expression remains a primary issue for clinical applications. Here, we develop a muscone-induced transgene system packaged into adeno-associated virus (AAV) vectors (AAVMUSE) based on a G protein-coupled murine olfactory receptor (MOR215-1) and a synthetic cAMP-responsive promoter (PCRE). Upon exposure to the trigger, muscone binds to MOR215-1 and activates the cAMP signaling pathway to initiate transgene expression. AAVMUSE enables remote, muscone dose- and exposure-time-dependent control of luciferase expression in the livers or lungs of mice for at least 20 weeks. Moreover, we apply this AAVMUSE to treat two chronic inflammatory diseases: nonalcoholic fatty liver disease (NAFLD) and allergic asthma, showing that inhalation of muscone—after only one injection of AAVMUSE—can achieve long-term controllable expression of therapeutic proteins (ΔhFGF21 or ΔmIL-4). Our odorant-molecule-controlled system can advance gene-based precision therapies for human diseases.
Plastid ancestors lacked a complete Entner-Doudoroff pathway, limiting plants to glycolysis and the pentose phosphate pathway
Authors: Evans Sonia E. , Franks Anya E. , Bergman Matthew E. , Sethna Nasha S. , Currie Mark A. , Phillips Michael A.
Published: February 2024

The Entner–Doudoroff (ED) pathway provides an alternative to glycolysis. It converts 6-phosphogluconate (6-PG) to glyceraldehyde-3-phosphate and pyruvate in two steps consisting of a dehydratase (EDD) and an aldolase (EDA). Here, we investigate its distribution and significance in higher plants and determine the ED pathway is restricted to prokaryotes due to the absence of EDD genes in eukaryotes. EDDs share a common origin with dihydroxy-acid dehydratases (DHADs) of the branched chain amino acid pathway (BCAA). Each dehydratase features strict substrate specificity. E. coli EDD dehydrates 6-PG to 2-keto-3-deoxy-6-phosphogluconate, while DHAD only dehydrates substrates from the BCAA pathway. Structural modeling identifies two divergent domains which account for their non-overlapping substrate affinities. Coupled enzyme assays confirm only EDD participates in the ED pathway. Plastid ancestors lacked EDD but transferred metabolically promiscuous EDA, which explains the absence of the ED pathway from the Viridiplantae and sporadic persistence of EDA genes across the plant kingdom.
Tumor reactive γδ T cells contribute to a complete response to PD-1 blockade in a Merkel cell carcinoma patient
Authors: Lien Scott C. , Ly Dalam , Yang S. Y. Cindy , Wang Ben X. , Clouthier Derek L. , St. Paul Michael , Gadalla Ramy , Noamani Babak , Garcia-Batres Carlos R. , Boross-Harmer Sarah , Bedard Philippe L. , Pugh Trevor J. , Spreafico Anna , Hirano Naoto , Razak Albiruni R. A. , Ohashi Pamela S.
Published: February 2024

Immunotherapies targeting PD-1/PD-L1 are now widely used in the clinic to treat a variety of malignancies. While most of the research on T cell exhaustion and PD-1 blockade has been focused on conventional αβ T cells, the contribution of innate-like T cells such as γδ T cells to anti-PD-1/PD-L1 mediated therapy is limited. Here we show that tumor reactive γδ T cells respond to PD-1 blockade in a Merkel cell carcinoma (MCC) patient experiencing a complete response to therapy. We find clonally expanded γδ T cells in the blood and tumor after pembrolizumab treatment, and this Vγ2Vδ1 clonotype recognizes Merkel cancer cells in a TCR-dependent manner. Notably, the intra-tumoral γδ T cells in the MCC patient are characterized by higher expression of PD-1 and TIGIT, relative to conventional CD4 and CD8 T cells. Our results demonstrate that innate-like T cells could also contribute to an anti-tumor response after PD-1 blockade.
Potential and electric double-layer effect in electrocatalytic urea synthesis
Authors: Wu Qian , Dai Chencheng , Meng Fanxu , Jiao Yan , Xu Zhichuan J.
Published: February 2024

Electrochemical synthesis is a promising way for sustainable urea production, yet the exact mechanism has not been fully revealed. Herein, we explore the mechanism of electrochemical coupling of nitrite and carbon dioxide on Cu surfaces towards urea synthesis on the basis of a constant-potential method combined with an implicit solvent model. The working electrode potential, which has normally overlooked, is found influential on both the reaction mechanism and activity. The further computational study on the reaction pathways reveals that *CO-NH and *NH-CO-NH as the key intermediates. In addition, through the analysis of turnover frequencies under various potentials, pressures, and temperatures within a microkinetic model, we demonstrate that the activity increases with temperature, and the Cu(100) shows the highest efficiency towards urea synthesis among all three Cu surfaces. The electric double-layer capacitance also plays a key role in urea synthesis. Based on these findings, we propose two essential strategies to promote the efficiency of urea synthesis on Cu electrodes: increasing Cu(100) surface ratio and elevating the reaction temperature.
Efficient prime editing in two-cell mouse embryos using PEmbryo
Authors: Kim-Yip Rebecca P. , McNulty Ryan , Joyce Bradley , Mollica Antonio , Chen Peter J. , Ravisankar Purnima , Law Benjamin K. , Liu David R. , Toettcher Jared E. , Ivakine Evgueni A. , Posfai Eszter , Adamson Britt
Published: February 2024

Using transient inhibition of DNA mismatch repair during a permissive stage of development, we demonstrate highly efficient prime editing of mouse embryos with few unwanted, local byproducts (average 58% precise edit frequency, 0.5% on-target error frequency across 13 substitution edits at 8 sites), enabling same-generation phenotyping of founders. Whole-genome sequencing reveals that mismatch repair inhibition increases off-target indels at low-complexity regions in the genome without any obvious phenotype in mice.
Immobilized enzyme cascade for targeted glycosylation
Authors: Makrydaki Elli , Donini Roberto , Krueger Anja , Royle Kate , Moya Ramirez Ignacio , Kuntz Douglas A. , Rose David R. , Haslam Stuart M. , Polizzi Karen M. , Kontoravdi Cleo
Published: February 2024

Glycosylation is a critical post-translational protein modification that affects folding, half-life and functionality. Glycosylation is a non-templated and heterogeneous process because of the promiscuity of the enzymes involved. We describe a platform for sequential glycosylation reactions for tailored sugar structures (SUGAR-TARGET) that allows bespoke, controlled N-linked glycosylation in vitro enabled by immobilized enzymes produced with a one-step immobilization/purification method. We reconstruct a reaction cascade mimicking a glycosylation pathway where promiscuity naturally exists to humanize a range of proteins derived from different cellular systems, yielding near-homogeneous glycoforms. Immobilized β-1,4-galactosyltransferase is used to enhance the galactosylation profile of three IgGs, yielding 80.2–96.3% terminal galactosylation. Enzyme recycling is demonstrated for a reaction time greater than 80 h. The platform is easy to implement, modular and reusable and can therefore produce homogeneous glycan structures derived from various hosts for functional and clinical evaluation.
Phenomenon of multiple reentrant localization in a double-stranded helix with transverse electric field
Authors: Ganguly Sudin , Sarkar Suparna , Mondal Kallol , Maiti Santanu K.
Published: February 2024

The present work explores the potential for observing multiple reentrant localization behavior in a double-stranded helical (DSH) system, extending beyond the conventional nearest-neighbor hopping (NNH) interaction. The DSH system is considered to have hopping dimerization in each strand, while also being subjected to a transverse electric field. The inclusion of an electric field serves the dual purpose of inducing quasi-periodic disorder and strand-wise staggered site energies. Two reentrant localization regions are identified: one exhibiting true extended behavior in the thermodynamic limit, while the second region shows quasi-extended characteristics with partial spreading within the helix. The DSH system exhibits three distinct single-particle mobility edges linked to localization transitions present in the system. The analysis in this study involves examining various parameters such as the single-particle energy spectrum, inverse participation ratio, local probability amplitude, and more. Our proposal, combining achievable hopping dimerization and induced correlated disorder, presents a unique opportunity to study phenomenon of reentrant localization, generating significant research interest.
Reduced health-related quality of life, fatigue, anxiety and depression affect COVID-19 patients in the long-term after chronic critical illness
Authors: Egger Marion , Wimmer Corinna , Stummer Sunita , Reitelbach Judith , Bergmann Jeannine , Müller Friedemann , Jahn Klaus
Published: February 2024

The term chronic critical illness describes patients suffering from persistent organ dysfunction and prolonged mechanical ventilation. In severe cases, COVID-19 led to chronic critical illness. As this population was hardly investigated, we evaluated the health-related quality of life, physical, and mental health of chronically critically ill COVID-19 patients. In this prospective cohort study, measurements were conducted on admission to and at discharge from inpatient neurorehabilitation and 3, 6, and 12 months after discharge. We included 97 patients (61 ± 12 years, 31% women) with chronic critical illness; all patients required mechanical ventilation. The median duration of ICU-treatment was 52 (interquartile range 36–71) days, the median duration of mechanical ventilation was 39 (22–55) days. Prevalences of fatigue, anxiety, and depression increased over time, especially between discharge and 3 months post-discharge and remained high until 12 months post-discharge. Accordingly, health-related quality of life was limited without noteworthy improvement (EQ-5D–5L: 0.63 ± 0.33). Overall, the burden of symptoms was high, even one year after discharge (fatigue 55%, anxiety 42%, depression 40%, problems with usual activities 77%, pain/discomfort 84%). Therefore, patients with chronic critical illness should receive attention regarding treatment after discharge with a special focus on mental well-being.

Trial registration: German Clinical Trials Register, DRKS00025606. Registered 21 June 2021—Retrospectively registered, https://drks.de/search/de/trial/DRKS00025606.
Proportional impact prediction model of coating material on nitrate leaching of slow-release Urea Super Granules (USG) using machine learning and RSM technique
Authors: Swain Sidhartha Sekhar , Khura Tapan Kumar , Sahoo Pramod Kumar , Chobhe Kapil Atmaram , Al-Ansari Nadhir , Kushwaha Hari Lal , Kushwaha Nand Lal , Panda Kanhu Charan , Lande Satish Devram , Singh Chandu
Published: February 2024

An accurate assessment of nitrate leaching is important for efficient fertiliser utilisation and groundwater pollution reduction. However, past studies could not efficiently model nitrate leaching due to utilisation of conventional algorithms. To address the issue, the current research employed advanced machine learning algorithms, viz., Support Vector Machine, Artificial Neural Network, Random Forest, M5 Tree (M5P), Reduced Error Pruning Tree (REPTree) and Response Surface Methodology (RSM) to predict and optimize nitrate leaching. In this study, Urea Super Granules (USG) with three different coatings were used for the experiment in the soil columns, containing 1 kg soil with fertiliser placed in between. Statistical parameters, namely correlation coefficient, Mean Absolute Error, Willmott index, Root Mean Square Error and Nash–Sutcliffe efficiency were used to evaluate the performance of the ML techniques. In addition, a comparison was made in the test set among the machine learning models in which, RSM outperformed the rest of the models irrespective of coating type. Neem oil/ Acacia oil(ml): clay/sulfer (g): age (days) for minimum nitrate leaching was found to be 2.61: 1.67: 2.4 for coating of USG with bentonite clay and neem oil without heating, 2.18: 2: 1 for bentonite clay and neem oil with heating and 1.69: 1.64: 2.18 for coating USG with sulfer and acacia oil. The research would provide guidelines to researchers and policymakers to select the appropriate tool for precise prediction of nitrate leaching, which would optimise the yield and the benefit–cost ratio.
Epidemiology and clinical characteristics of patients with healthcare-acquired multidrug-resistant Gram-negative bacilli: a retrospective study from a tertiary care hospital
Authors: Aiesh Banan M. , Natsheh Mustafa , Amar Mohammad , AbuTaha Shatha , Qadi Mohammad , AbuTaha Adham , Sabateen Ali , Zyoud Sa’ed H.
Published: February 2024

The numbers of infections caused by Gram-negative bacteria (GNB) that produce extended-spectrum beta-lactamases (ESBLs) and those that are carbapenem resistant, especially Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae), are increasing, and these infections are becoming a global public health problem. The aim of this study was to assess the prevalence of infections caused by ESBL-producing and carbapenem-resistant Gram-negative bacilli in patients hospitalized at An-Najah National University Hospital in Nablus, Palestine, and to provide healthcare workers with valuable information on the treatment of these infections. A retrospective cross-sectional investigation was conducted at a large tertiary care teaching hospital. The study included patients admitted to the hospital between January and December 2021, from whom ESBL-producing and carbapenem-resistant Gram-negative bacilli were isolated. The patients' clinical and demographic information was obtained from the hospital information system. In addition, information regarding the bacterial isolates and antibiotic resistance was obtained from the hospital's microbiology laboratory. This study included a total of 188 patients—91 males (48.4%) and 97 females (51.6%). The general surgical ward accounted for the highest proportion of infections (30.9%), followed by the surgical ICU (12.2%). The most common infections were caused by ESBL-producing E. coli, which accounted for 62.8% of the cases. Among them, urinary tract infections caused by this microorganism were the most prevalent (44.7% of patients). Over 50% of the patients (54.2%) had a history of antibiotic use, and 77.8% had been hospitalized within the past three months. ESBL-producing E. coli was significantly isolated from blood cultures (p-value = 0.000), and CR-K. pneumoniae was significantly isolated from endotracheal isolates (p-value = 0.001). This study emphasizes the concerning frequency of healthcare-acquired infections caused by ESBL-producing and carbapenem-resistant GNB in a tertiary care hospital. The substantial prevalence of antibiotic resistance presents considerable obstacles to the successful administration of routinely employed antibiotics. The results highlight the immediate need for improved antimicrobial stewardship and the implementation of infection control strategies to reduce the effects of multidrug-resistant GNB on patient well-being and public health.