bluuebunny/crossref_metadata_2025 huggingface dataset:
A Review on Engineering Transition Metal Compound Catalysts to Accelerate the Redox Kinetics of Sulfur Cathodes for Lithium–Sulfur Batteries
Authors: Chen Liping , Cao Guiqiang , Li Yong , Zu Guannan , Duan Ruixian , Bai Yang , Xue Kaiyu , Fu Yonghong , Xu Yunhua , Wang Juan , Li Xifei
Published: January 2024

Engineering transition metal compounds (TMCs) catalysts with excellent adsorption-catalytic ability has been one of the most effective strategies to accelerate the redox kinetics of sulfur cathodes. Herein, this review focuses on engineering TMCs catalysts by cation doping/anion doping/dual doping, bimetallic/bi-anionic TMCs, and TMCs-based heterostructure composites. It is obvious that introducing cations/anions to TMCs or constructing heterostructure can boost adsorption-catalytic capacity by regulating the electronic structure including energy band, d/p-band center, electron filling, and valence state. Moreover, the electronic structure of doped/dual-ionic TMCs are adjusted by inducing ions with different electronegativity, electron filling, and ion radius, resulting in electron redistribution, bonds reconstruction, induced vacancies due to the electronic interaction and changed crystal structure such as lattice spacing and lattice distortion. Different from the aforementioned two strategies, heterostructures are constructed by two types of TMCs with different Fermi energy levels, which causes built-in electric field and electrons transfer through the interface, and induces electron redistribution and arranged local atoms to regulate the electronic structure. Additionally, the lacking studies of the three strategies to comprehensively regulate electronic structure for improving catalytic performance are pointed out. It is believed that this review can guide the design of advanced TMCs catalysts for boosting redox of lithium sulfur batteries.
An Environment-Tolerant Ion-Conducting Double-Network Composite Hydrogel for High-Performance Flexible Electronic Devices
Authors: Zhao Wenchao , Zhou Haifeng , Li Wenkang , Chen Manlin , Zhou Min , Zhao Long
Published: January 2024

High-performance ion-conducting hydrogels (ICHs) are vital for developing flexible electronic devices. However, the robustness and ion-conducting behavior of ICHs deteriorate at extreme temperatures, hampering their use in soft electronics. To resolve these issues, a method involving freeze–thawing and ionizing radiation technology is reported herein for synthesizing a novel double-network (DN) ICH based on a poly(ionic liquid)/MXene/poly(vinyl alcohol) (PMP DN ICH) system. The well-designed ICH exhibits outstanding ionic conductivity (63.89 mS cm−1 at 25 °C), excellent temperature resistance (− 60–80 °C), prolonged stability (30 d at ambient temperature), high oxidation resistance, remarkable antibacterial activity, decent mechanical performance, and adhesion. Additionally, the ICH performs effectively in a flexible wireless strain sensor, thermal sensor, all-solid-state supercapacitor, and single-electrode triboelectric nanogenerator, thereby highlighting its viability in constructing soft electronic devices. The highly integrated gel structure endows these flexible electronic devices with stable, reliable signal output performance. In particular, the all-solid-state supercapacitor containing the PMP DN ICH electrolyte exhibits a high areal specific capacitance of 253.38 mF cm−2 (current density, 1 mA cm−2) and excellent environmental adaptability. This study paves the way for the design and fabrication of high-performance multifunctional/flexible ICHs for wearable sensing, energy-storage, and energy-harvesting applications.
Patient preferences in geriatric wards, a survey of health care professionals’ practice, experience and attitudes
Authors: Ihle-Hansen Hege , Pedersen R. , Westbye S. F. , Sævareid T. J. L. , Brøderud L. , Larsen M. H. , Hermansen K. , Rostoft S. , Romøren M.
Published: January 2024

Purpose

We aimed to identify whether health care professionals (HCP) examine their patient and next-of-kin preferences, and to study whether medical decisions follow these preferences.

Method

A cross-sectional web-based survey was conducted with multidisciplinary HCP from 12 geriatric wards in the South-Eastern Norway Regional Health Authority.

Results

Of the 289 HCPs responding (response rate 61%), mean age 37.8 years (SD 11.3), 235 (81.3%) women, 12.4 (SD 9.6) years of experience and 67 (23.2%) medical doctors, only half report clarifying patients’ preferences. The majority reported that they did not inform, involve and treat in line with such preferences. However, 53% believe that HCP, patients and next-of-kin should make clinical decisions together.

Discussion

Our findings indicate a lack of engagement in conversation and inclusion of patient preferences when providing health interventions in geriatric wards. Measures for change of culture are needed.
Postdigital Duoethnography: An Inquiry into Human-Artificial Intelligence Synergies
Authors: Brailas Alexios
Published: January 2024

In this article, I explore the evolving affordances of artificial intelligence technologies. Through an evocative dialogue with ChatGPT, a form of a postdigital duoethnography between a human and an artificial intelligence algorithm, I discuss issues of knowledge production, research methods, epistemology, creativity, entropy, and self-organization. By reflecting on my own lived experience during this dialogue, I explore how human-artificial intelligence synergies can facilitate new insights and amplify human creative potential. As human-artificial intelligence entanglements activate multiple possibilities, I emphasize how understanding the impact of technology on individuals and communities becomes a critical challenge. In an era where the postdigital becomes the dominant narrative of science and education, the human mind will never be the same again. However, it is not given how human beings and artificial intelligence technologies are going to coevolve as parts of a complex postdigital confluence. Although I make no specific prediction of the future, I make the call for a relationship between humans and technology, informed by complex living systems epistemology, that will promote a more empowering postdigital narrative for individuals and communities. To this direction, this article introduces a methodological framework for the practice of postdigital duoethnography.
Nutritional Considerations for Female Rock Climbers
Authors: Leslie-Wujastyk Mina , Gibson-Smith Edward
Published: January 2024

Despite growing participation, there is limited research into the nutritional needs of climbers and none specific to female climbers. Female athletes in general are still significantly under-represented in sport and nutritional science research. The physiological requirements of climbing are extensive and variable, demanding both highly developed anaerobic and aerobic energy systems. Finger strength, upper body power and training hours have been highlighted as the key determinants of climbing performance in females. Nutritional implications of this include adequate energy and carbohydrate availability, appropriate protein intake and timing for recovery, and use of specific supplements. As a weight sensitive sport, energy intake and availability are key areas of consideration for female climbers’ health and performance. Consideration of macronutrient intake and timing with an understanding of sex hormone interaction across the menstrual cycle confers some considerations to nutritional guidelines. Micronutrients of particular interest to the female climber include iron, vitamin D and calcium. Appropriate supplement use may be beneficial, however more research is needed to provide any female specific dosing strategies. It may be premature to prescribe generalised female specific nutrition recommendations for climbers. A personalised approach that considers the individual’s menstrual cycle and experience is recommended. Further research into nutrition for the female climber is warranted.
Educational disparities in cancer incidence, stage, and survival in Oslo
Authors: Al-Rammahy Afaf , Fadum Elin Anita , Nilssen Yngvar , Larsen Inger Kristin , Hem Erlend , Bringedal Berit Horn
Published: January 2024

Objectives

This study aimed to examine disparities in cancer incidence, stage at diagnosis, and survival rates across districts with differences in education levels in Oslo, Norway.

Methods

Aggregated data from the Cancer Registry of Norway in the period 2013-2021 were used to describe the distribution of cancer incidence and survival across Oslo’s 15 administrative districts, subsequently grouped into three areas based on the population’s level of education. Age-standardised incidence rates and five-year relative survival were calculated for colon, rectal, lung, melanoma, breast, and prostate cancer. The stage at the time of diagnosis was categorised as localised, regional, distant, and unknown for all cancer types except breast cancer, which was categorised into stage I-IV and unknown.

Results

Mid- and high-education areas had higher incidences of breast, melanoma, and prostate cancer, while the low-education area had higher incidence rates for lung cancer. The low-education area had a higher proportion diagnosed at a distant stage than the other groups for all cancer types studied, except breast cancer. The mid- and high-education areas had higher five-year relative survival rates overall.

Conclusions

Incidence, stage at diagnosis, and survival varied between education areas. The variation indicates disparities in healthcare access, quality of care, and health behaviours. Addressing these disparities can help improve overall health outcomes and promote health equity.
On the Solution of Caputo Fractional High-Order Three-Point Boundary Value Problem with Applications to Optimal Control
Authors: Shivanian Elyas
Published: January 2024

This research paper establishes the existence and uniqueness of solutions for a non-integer high-order boundary value problem, incorporating the Caputo fractional derivative with a non-local type boundary condition. The analytical approach involves the introduction of the fractional Green’s function. To analyze our findings effectively, we apply the Banach contraction fixed point theorem as the primary principle. Furthermore, we illustrate our results through the presentation of various examples.
A human antibody derived from original SARS-CoV-2 infection effectively neutralizes omicron
Authors: Li Tingting , Zhou Bingjie , Dong Haoyu , Lavillette Dimitri , Li Dianfan
Published: January 2024

SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) Variants of Concern (VOCs), such as the Omicron sub-variants, present significant challenges in pandemic control due to their capacity to escape antibodies and breach vaccine protections. Discovering antibodies that can tolerate mutations in VOCs and understanding their underlying mechanisms is crucial for developing therapeutics for COVID-19 patients, particularly those for whom other therapies may be unsuitable. Here, we report the neutralization of the Omicron variant by FD20, a broadly active human monoclonal antibody. In contrast to a clinically approved control antibody, FD20 neutralizes Omicron with comparable IC50 values to those observed for previously circulating VOCs and the original strain reported in Wuhan. Leveraging structural information, we provide insights into its resilience against mutations in Omicron. The results encourage the prospective development of FD20 as a therapeutic option for COVID-19 caused by current and potentially future VOCs.
Captive Objects
Authors: Hershenzon Daniel
Published: January 2024

Catholic artifacts—images and sculptures of Christ, the Virgin, and various saints, as well as rosaries, crucifixes, and liturgical objects—circulated in their thousands throughout the early modern western Mediterranean. This mobility was largely an indirect byproduct of privateering and human trafficking, which bound together Spain’s Mediterranean territories, Morocco, and Ottoman Algiers. The disruptive moment of captivity set these otherwise disparate objects on common trajectories, making it interesting to study them as a category. The article argues that Catholic artifacts played surprising roles in the experience of Catholic captives, renegades, and their Muslim masters, and in the economy of ransom that facilitated the rescue of captives. Against the design of their initial distributors, such objects provided captives, converts, and masters with unexpected affordances, and in so doing helped blur the boundary between the religions, creating new entanglements between members of these groups and Catholic materiality. The argument is developed in three stages. First, the article claims that the surge in captivity following the Spanish-Ottoman truce of 1581 meant that more devotional objects were sent from Spain to Catholics held captive in the Maghrib. Second, it asserts that some of these artifacts ended up serving converts to Islam, while others were plundered by Algerian and Moroccan rulers. Third, the article contends that plunder and repurposing afforded captives the power to redeem an emblem of their God, provided Trinitarians and Mercedarians with opportunities to ransom objects and gain fame back home, and helped Maghribi rulers to secure religious privileges for their subjects enslaved in Spain. Focusing on their mobility demonstrates the degree to which Catholic objects continued to articulate and mediate social, political, and economic relations in the western Mediterranean over the long seventeenth century.
Particle tracking in snow avalanches with in situ calibrated inertial measurement units
Authors: Winkler Robert , Neuhauser Michael , Neurauter Rene , Erlacher Felix , Steinkogler Walter , Fischer Jan-Thomas
Published: January 2024

In the course of an artificially triggered avalanche, a particle tracking procedure is combined with supplementary measurements, including Global Navigation Satellite System (GNSS) positioning, terrestrial laser scanning and Doppler radar measurements. Specifically, an intertial measurement unit is mounted inside a rigid sphere, which is placed in the avalanche track. The sphere is entrained by the moving snow, recording translational accelerations, angular velocities and the flux density of Earth's magnetic field. Based on the recorded data, we present a threefold analysis: (i) a qualitative data interpretation, identifying different particle motion phases which are associated with corresponding flow regimes, (ii) a quantitative time integration algorithm, determining the corresponding particle trajectory and associated velocities on the basis of standard sensor calibration, and (iii) an improved quantitative evaluation relying on a novel in situ sensor calibration technique, which is motivated by the limitations of the given dataset. The final results, i.e. the evolution of the angular orientation of the sensor unit, translational and rotational velocities and estimates of the sensor trajectory, are assessed with respect to their reliability and relevance for avalanche dynamics as well as for future design of experiments.
Greater than the sum of its parts: optical remote sensing and sediment core data provide a holistic perspective on glacial processes
Authors: Gage Henry Jacob Miller , Eyles Carolyn Hope
Published: January 2024

In this letter we make the case that closer integration of sediment core and passive optical remote sensing data would provide new insights into past and contemporary glacio-sedimentary processes. Sediment cores are frequently used to study past glacial processes and environments as they contain a lengthy geochemical and sedimentological record of changing conditions. In contrast, optical remote sensing imagery is used extensively to examine contemporary glacial processes, including meltwater dynamics, glacial retreat, calving, and ice accumulation. While paleoenvironmental data from sediment cores and optical remote sensing imagery are rarely used in tandem, they are complementary. Sediment core records are spatially discrete, providing long-term paleoenvironmental proxy data which require assumptions about environment-sediment linkages. Optical imagery offers precise, spatially extensive data to visualize contemporary processes often limited in their temporal extent. We suggest that methodologies which integrate optical remotely sensing with sediment core data allow direct observation of processes interpolated from sedimentological analysis and achieve a more holistic perspective on glacial processes. This integration addresses the limitations of both data sources and can achieve a stronger understanding of glacier dynamics by expanding the spatiotemporal extent of data, reducing the uncertainty of interpretations, and broadening the local analyses to regional and global scales.
Introduction of hospital-based health technology assessment in China: experiences from seven pilot hospitals
Authors: Lyu Lanting , Shi Wenkai , Kidholm Kristian , Bai Fei , Lin Xia , Fu Jinlan , Li Tianqing , Li Guoxun , Luo Li , Wang Ting , Yang Hai
Published: January 2024

Objectives

This study aimed to introduce a pilot program for hospital-based health technology assessment (HB-HTA) in China and present the participants’ experiences based on seven case studies from seven tertiary hospitals.

Methods

One-year pilot projects were initiated at the beginning of 2018. Seven pilot hospitals were closely followed from the beginning until the completion of their pilot HTA project. Regular interviews were conducted with the hospital managers leading the HB-HTA projects and key members of the special HTA teams. Observations were made based on field trips and written HTA reports.

Results

Three pilot projects evaluated the use of medical consumables, three evaluated the use of surgical or medical interventions, and one evaluated an innovative management model for ventilators. Real-world data were collected from all the pilot projects to assist with the assessments. Most HB-HTA pilot projects achieved remarkable results such as improvements in economic efficiency; however, there were also obvious deficiencies such as the lack of a necessary cost-effectiveness analysis.

Conclusions

The results varied among the seven HB-HTA pilot projects. The HB-HTA pilot program was implemented to promote the use of HB-HTA in hospital decision making in China. At the same time, HB-HTA in China faces challenges. We have made some policy recommendations based on the findings of the pilot projects.
Environmental obligations of business entities during armed conflicts
Authors: Traoré Sâ Benjamin , Cirimwami Ezéchiel Amani
Published: January 2024

International humanitarian law (IHL) does not address business entities, except in situations where they directly participate in hostilities, and there is no reference to business actors in the International Committee of the Red Cross's recent Guidelines on the Protection of the Natural Environment in Armed Conflict. Yet, there has been an increasing reaffirmation of specific “duties”, “obligations” or “responsibilities” imposed on private companies operating in conflict zones. For instance, the UN Guiding Principles on Business and Human Rights suggest that business entities should respect IHL rules in addition to human rights during armed conflicts, and the third revised draft of the international legally binding instrument on transnational corporations and other business enterprises refers to IHL as an interpretative framework of human rights obligations of States and businesses. The International Law Commission's 2022 Draft Principles on the Protection of the Environment during Armed Conflicts are even more specific, providing that corporations should exercise due diligence concerning the protection of the environment when acting in conflict-affected areas. However, these references to IHL as applicable to business activities remain vague and lack elaboration. This paper intends to close this gap by clarifying whether and, if so, the extent to which IHL imposes environmental obligations upon private companies in conflict situations. It submits that business entities bear environmental duties during armed conflicts deriving from IHL rules and other complementary sources of international law. The paper further discusses the content of the obligation of business entities not to harm the environment as well as their due diligence obligation.
The efficacy of different torque profiles for weight compensation of the hand
Authors: van der Burgh Bas J. , Filius Suzanne J. , Radaelli Giuseppe , Harlaar Jaap
Published: January 2024

Orthotic wrist supports will be beneficial for people with muscular weakness to keep their hand in a neutral rest position and prevent potential wrist contractures. Compensating the weight of the hands is complex since the level of support depends on both wrist and forearm orientations. To explore simplified approaches, two different weight compensation strategies (constant and linear) were compared to the theoretical ideal sinusoidal profile and no compensation in eight healthy subjects using a mechanical wrist support system. All three compensation strategies showed a significant reduction of 47–53% surface electromyography activity in the anti-gravity m. extensor carpi radialis. However, for the higher palmar flexion region, a significant increase of 44–61% in the m. flexor carpi radialis was found for all compensation strategies. No significant differences were observed between the various compensation strategies. Two conclusions can be drawn: (1) a simplified torque profile (e.g., constant or linear) for weight compensation can be considered as equally effective as the theoretically ideal sinusoidal profile and (2) even the theoretically ideal profile provides no perfect support as other factors than weight, such as passive joint impedance, most likely influence the required compensation torque for the wrist joint.
Un violador en tu camino: An artistic intervention against patriarchal injustice in Chile
Authors: PINZAUTI GIORGIA
Published: January 2024

In 2019, Chile’s artistic collective Las Tesis staged the viral feminist performance “Un violador en tu camino” (A Rapist in Your Path), as a popular protest against Sebastián Piñera’s government. This article analyzes the geopolitical context behind Las Tesis, focusing on Chile’s 2019 events and the motivations behind the performance in Valparaíso. Subsequently, I explore the performance’s structure and lyrics as a form of artivism, emphasizing its impact. The third section of this article will be dedicated to exploring the linguistic and musical adaptations of the same performance undertaken by various women’s collectives, associations, or informal groups across the globe.
Late-Life Bipolar Disorder Subtypes According to Age Onset
Authors: Regala Joana , Costa Pedro , Costa Rafael , Reis João
Published: January 2024

Abstract: This article characterizes the clinical differences between bipolar disorder (BD) subtypes in 44 early-onset (EOBD), 32 late-onset (LOBD), and 30 very-late-onset (VLOBD) disorders. We considered vascular mania in five LOBD and 17 VLOBD, with an association with right-sided lesions for VLOBD. Other nonvascular-related brain injuries preceded the emergence of mania: traumatic brain injury (one LOBD, two VLOBD), epilepsy/brain tumor (one LOBD), multiple sclerosis (one LOBD), and HIV-encephalopathy/cerebral toxoplasmosis (two VLOBD). No secondary mania was identified in 21.4% of the VLOBD and 64% of the LOBDd, corresponding to presumptive idiopathic/primary BD. A transdiagnostic conversion within the affective disorder spectrum occurred in 50% of the VLOBD, 30.8% of the LOBD, and 20.5% of the EOBD across the lifespan. An interplay between genetics and age-specific processes may underlie the neurobiological underpinnings of late-life-onset idiopathic/primary BD.
Qualitative Diary Methods in Mental Health Research
Authors: McCombie Catherine , Esponda Georgina Miguel , Schmidt Ulrike , Lawrence Vanessa
Published: January 2024

Abstract: Qualitative diary methods (QDMs) have great potential for mental health research, as they provide rich data about experiences and phenomena as and when they happen, from the perspectives of participants themselves. They provide unique insight into behavior, cognitions, and change over time in greater depth and detail than other quantitative or qualitative methods might offer. This paper presents the results of a scoping review of QDMs in mental health research, aimed at clarifying how diary methods are used in mental health research, and outlining key decisions and considerations in planning and conducting a qualitative diary study. Forty-eight papers were reviewed, and the findings highlight different elements of QDMs. The research aims, suitability for participants, and ethical issues are first discussed, followed by elements of diary study design including diary format, administration, intervals, timeline, sample size, diary structure and guidance, and additional data collection methods. Finally, analysis approaches and the strengths and challenges of QDMs are reviewed. Discussion around the future of QDMs follows, including a checklist for conducting and reporting a qualitative diary study.
N1-methylation of adenosine (m1A) in ND5 mRNA leads to complex I dysfunction in Alzheimer’s disease
Authors: Jörg Marko , Plehn Johanna E. , Kristen Marco , Lander Marc , Walz Lukas , Lietz Christine , Wijns Julie , Pichot Florian , Rojas-Charry Liliana , Wirtz Martin Katja M. , Ruffini Nicolas , Kreim Nastasja , Gerber Susanne , Motorin Yuri , Endres Kristina , Rossmanith Walter , Methner Axel , Helm Mark , Friedland Kristina
Published: January 2024

One mechanism of particular interest to regulate mRNA fate post-transcriptionally is mRNA modification. Especially the extent of m1A mRNA methylation is highly discussed due to methodological differences. However, one single m1A site in mitochondrial ND5 mRNA was unanimously reported by different groups. ND5 is a subunit of complex I of the respiratory chain. It is considered essential for the coupling of oxidation and proton transport. Here we demonstrate that this m1A site might be involved in the pathophysiology of Alzheimer’s disease (AD). One of the pathological hallmarks of this neurodegenerative disease is mitochondrial dysfunction, mainly induced by Amyloid β (Aβ). Aβ mainly disturbs functions of complex I and IV of the respiratory chain. However, the molecular mechanism of complex I dysfunction is still not fully understood. We found enhanced m1A methylation of ND5 mRNA in an AD cell model as well as in AD patients. Formation of this m1A methylation is catalyzed by increased TRMT10C protein levels, leading to translation repression of ND5. As a consequence, here demonstrated for the first time, TRMT10C induced m1A methylation of ND5 mRNA leads to mitochondrial dysfunction. Our findings suggest that this newly identified mechanism might be involved in Aβ-induced mitochondrial dysfunction.
Deletion of the prorenin receptor in the ureteric bud in mice inhibits Dot1/H3K79 pathway
Authors: Song Renfang , Yosypiv Ihor V.
Published: January 2024

Background

The prorenin receptor (PRR) plays a critical role in ureteric bud (UB) branching morphogenesis. DOT1 Like (DOT1L), a histone methyltransferase specific for Histone 3 lysine 79 (H3K79), is important for differentiation of the UB-derived renal collecting duct cells. In this study, we tested whether DOT1L/H3 dimethyl K79 (H3m2K79) are regulated by PRR deletion in the UB and UB-derived collecting ducts in the embryonic mouse kidneys.

Methods

Mutant Hoxb7Cre+/PRRflox/flox (PRRUB-/-) and control PRRUB+/+, mice were studied on embryonic (E) day E17.5. DOT1L mRNA and protein expression in the kidney was examined by real-time qRT-PCR and immunohistochemistry, respectively. H3m2K79 protein expression was determined by immunohistochemistry and Western blot analysis.

Results

DOT1L mRNA levels were decreased in mutant compared to control mice (0.68 ± 0.06 vs. 1.0 ± 0.01, p < 0.01). DOT1L and H3m2K79 immunostaining was reduced in the mutant vs. control kidneys (Dot1: 0.62 ± 0.03 vs. 1.0 ± 0.01, p < 0.05; H3m2K79: 0.64 ± 0.04 vs.1.1 ± 0.01. p < 0.05.). Western blot analysis revealed decreased H3m2K79 protein levels in mutant compared to control kidneys (1.0 ± 0.06 vs. 1.5 ± 0.02, p < 0.05).

Conclusion

Targeted deletion of the PRR in the UB and UB-derived collecting ducts results in reduced DOT1L gene/protein and H3m2K79 protein expression in the embryonic mouse metanephroi in vivo.

Impact

The role of histone methylation in mediating the effect of the prorenin receptor on the ureteric bud branching (UB) morphogenesis and urine acidification during kidney development is unknown.

We demonstrate that histone H3 lysine (K) 79 dimethylation by methyltransferase Dot1 is reduced in the embryonic kidney of mice that lack the prorenin receptor in the UB lineage.
The Swiss Spinal Cord Injury Cohort Study (SwiSCI) biobank: from concept to reality
Authors: Zeh Ramona M. , Glisic Marija , Capossela Simona , Bertolo Alessandro , Valido Ezra , Jordan Xavier , Hund-Georgiadis Margret , Pannek Jürgen , Eriks-Hoogland Inge , Stucki Gerold , Stoyanov Jivko
Published: January 2024

Objectives

To describe the concept, establishment and the operationalization of the biobank of the Swiss Spinal Cord Injury Cohort Study (SwiSCI), the available biosamples, and demographic and clinical characteristics of study participants.

Setting

The SwiSCI biobank is a platform for research within SwiSCI. It collects and processes serum, plasma, PBMCs, RNA, DNA, and urine from three rehabilitation centers. Samples are collected at admission to first rehabilitation and at discharge. Additionly, the biobank provides services to projects nested in SwiSCI or otherclinical trials among Spinal Cord Injury population.

Methods

Descriptive statistics were used for an overview of available biosamples, study participant characteristics, and comparison of the participating centers.

Results

Between the SwiSCI biobank establishment on June 27th, 2016, and October 19th, 2023, the SwiSCI Study has obtained informed consent from 524 individuals. Of these, 315 (60.1%) have agreed to donate biospecimens to the biobank. The average age of the contributors was 54 years (range: 38–65), with the majority being male (80%). Most participants suffered from traumatic injuries (66%) and were classified as paraplegic (64%). Approximately 80% presented with motor and sensory-incomplete SCI. The median Spinal Cord Independence Measure (SCIM) score was 31 (Interquartile Range: 19–58). The proportion of individuals providing paired biosamples at two distinct time points ranged from 63% (for RNA) to 65% (for urine and urine sediment).

Conclusions

The SwiSCI biobank is a unique platform designed to serve as a basis for collaborative SCI research, including multi-omics approaches. The longitudinal collection of biospecimens and cryopreservation of multiple aliquots for each participant are fundamental for scrutinizing the temporal associations, ensuring research reproducibility, and achieving an adequate sample size for future investigations.
Inhibition of Aurora B kinase (AURKB) enhances the effectiveness of 5-fluorouracil chemotherapy against colorectal cancer cells
Authors: Shah Esha T. , Molloy Christopher , Gough Madeline , Kryza Thomas , Samuel Selwin G. , Tucker Amos , Bhatia Maneet , Ferguson Genevieve , Heyman Rebecca , Vora Shivam , Monkman James , Bolderson Emma , Kulasinghe Arutha , He Yaowu , Gabrielli Brian , Hooper John D. , Richard Derek J. , O’Byrne Kenneth J. , Adams Mark N.
Published: January 2024

Background

5-Fluorouracil (5-FU) remains a core component of systemic therapy for colorectal cancer (CRC). However, response rates remain low, and development of therapy resistance is a primary issue. Combinatorial strategies employing a second agent to augment the therapeutic effect of chemotherapy is predicted to reduce the incidence of treatment resistance and increase the durability of response to therapy.

Methods

Here, we employed quantitative proteomics approaches to identify novel druggable proteins and molecular pathways that are deregulated in response to 5-FU, which might serve as targets to improve sensitivity to chemotherapy. Drug combinations were evaluated using 2D and 3D CRC cell line models and an ex vivo culture model of a patient-derived tumour.

Results

Quantitative proteomics identified upregulation of the mitosis-associated protein Aurora B (AURKB), within a network of upregulated proteins, in response to a 24 h 5-FU treatment. In CRC cell lines, AURKB inhibition with the dihydrogen phosphate prodrug AZD1152, markedly improved the potency of 5-FU in 2D and 3D in vitro CRC models. Sequential treatment with 5-FU then AZD1152 also enhanced the response of a patient-derived CRC cells to 5-FU in ex vivo cultures.

Conclusions

AURKB inhibition may be a rational approach to augment the effectiveness of 5-FU chemotherapy in CRC.
Deubiquitinase USP7 stabilizes KDM5B and promotes tumor progression and cisplatin resistance in nasopharyngeal carcinoma through the ZBTB16/TOP2A axis
Authors: Zhang Bin , Li Jie , Wang Yijun , Liu Xixi , Yang Xiao , Liao Zhiyun , Deng Suke , Deng Yue , Zhou Zhiyuan , Tian Yu , Wei Wenwen , Meng Jingshu , Hu Yan , Wan Chao , Zhang Zhanjie , Huang Fang , Wen Lu , Wu Bian , Sun Yajie , Li Yan , Yang Kunyu
Published: January 2024

Cisplatin-based chemotherapy improves the control of distant metastases in patients with nasopharyngeal carcinoma (NPC); however, around 30% of patients fail treatment due to acquired drug resistance. Epigenetic regulation is known to contribute to cisplatin resistance; nevertheless, the underlying mechanisms remain poorly understood. Here, we showed that lysine-specific demethylase 5B (KDM5B) was overexpressed and correlates with tumor progression and cisplatin resistance in patients with NPC. We also showed that specific inhibition of KDM5B impaired the progression of NPC and reverses cisplatin resistance, both in vitro and in vivo. Moreover, we found that KDM5B inhibited the expression of ZBTB16 by directly reducing H3K4me3 at the ZBTB16 promoter, which subsequently increased the expression of Topoisomerase II- α (TOP2A) to confer cisplatin resistance in NPC. In addition, we showed that the deubiquitinase USP7 was critical for deubiquitinating and stabilizing KDM5B. More importantly, the deletion of USP7 increased sensitivity to cisplatin by disrupting the stability of KDM5B in NPC cells. Therefore, our findings demonstrated that USP7 stabilized KDM5B and promoted cisplatin resistance through the ZBTB16/TOP2A axis, suggesting that targeting KDM5B may be a promising cisplatin-sensitization strategy in the treatment of NPC.
Repurposing proteasome inhibitors for improved treatment of triple-negative breast cancer
Authors: Larsson Peter , Pettersson Daniella , Olsson Maxim , Sarathchandra Sithumini , Abramsson Alexandra , Zetterberg Henrik , Ittner Ella , Forssell-Aronsson Eva , Kovács Anikó , Karlsson Per , Helou Khalil , Parris Toshima Z.
Published: January 2024

Triple-negative breast cancer (TNBC) is associated with poor prognosis and limited treatment options due to the lack of important receptors (estrogen receptor [ER], progesterone receptor [PR], and human epidermal growth factor receptor 2 [HER2]) used for targeted therapy. However, high-throughput in vitro drug screening of cell lines is a powerful tool for identifying effective drugs for a disease. Here, we determine the intrinsic chemosensitivity of TNBC cell lines to proteasome inhibitors (PIs), thereby identifying potentially potent 2-drug combinations for TNBC. Eight TNBC cell lines (BT-549, CAL-148, HCC1806, HCC38, HCC70, MDA-MB-436, MDA-MB-453, and MDA-MB-468) and two controls (MCF-10A and MCF-7) were first exposed to 18 drugs (11 PIs and 7 clinically relevant chemotherapeutic agents) as monotherapy, followed by prediction of potent 2-drug combinations using the IDACombo pipeline. The synergistic effects of the 2-drug combinations were evaluated with SynergyFinder in four TNBC cell lines (CAL-148, HCC1806, HCC38, and MDA-MB-468) and three controls (BT-474, MCF-7, and T47D) in vitro, followed by further evaluation of tumor regression in zebrafish tumor models established using HCC1806 and MCF-7 cells. Monotherapy identified nine effective drugs (bortezomib, carfilzomib, cisplatin, delanzomib, docetaxel, epoxomicin, MLN-2238, MLN-9708, and nedaplatin) across all cell lines. PIs (e.g., bortezomib, delanzomib, and epoxomicin) were highly potent drugs in TNBC cells, of which bortezomib and delanzomib inhibited the chymotrypsin-like activity of the 20 S proteasome by 100% at 10 µM. Moreover, several potent 2-drug combinations (e.g., bortezomib+nedaplatin and epoxomicin+epirubicin) that killed virtually 100% of cells were also identified. Although HCC1806- and MCF-7-derived xenografts treated with bortezomib+nedaplatin and carboplatin+paclitaxel were smaller, HCC1806 cells frequently metastasized to the trunk region. Taken together, we show that PIs used in combination with platinum agents or topoisomerase inhibitors exhibit increased efficiency with almost 100% inhibition in TNBC cell lines, indicating that PIs are therefore promising compounds to use as combination therapy for TNBC.
Expression of E-cadherin by CD8+ T cells promotes their invasion into biliary epithelial cells
Authors: Davies Scott P. , Ronca Vincenzo , Wootton Grace E. , Krajewska Natalia M. , Bozward Amber G. , Fiancette Rémi , Patten Daniel A. , Yankouskaya Katharina , Reynolds Gary M. , Pat Sofia , Osei-Bordom Daniel C. , Richardson Naomi , Grover Liam M. , Weston Christopher J. , Oo Ye H.
Published: January 2024

The presence of CD8+ T cells in the cytoplasm of biliary epithelial cells (BEC) has been correlated with biliary damage associated with primary biliary cholangitis (PBC). Here, we characterise the mechanism of CD8+ T cell invasion into BEC. CD8+ T cells observed within BEC were large, eccentric, and expressed E-cadherin, CD103 and CD69. They were also not contained within secondary vesicles. Internalisation required cytoskeletal rearrangements which facilitated contact with BEC. Internalised CD8+ T cells were observed in both non-cirrhotic and cirrhotic diseased liver tissues but enriched in PBC patients, both during active disease and at the time of transplantation. E-cadherin expression by CD8+ T cells correlated with frequency of internalisation of these cells into BEC. E-cadherin+ CD8+ T cells formed β-catenin-associated interactions with BEC, were larger than E-cadherin- CD8+ T cells and invaded into BEC more frequently. Overall, we unveil a distinct cell-in-cell structure process in the liver detailing the invasion of E-cadherin+ CD103+ CD69+ CD8+ T cells into BEC.
Competition-driven eco-evolutionary feedback reshapes bacteriophage lambda’s fitness landscape and enables speciation
Authors: Doud Michael B. , Gupta Animesh , Li Victor , Medina Sarah J. , De La Fuente Caesar A. , Meyer Justin R.
Published: January 2024

A major challenge in evolutionary biology is explaining how populations navigate rugged fitness landscapes without getting trapped on local optima. One idea illustrated by adaptive dynamics theory is that as populations adapt, their newly enhanced capacities to exploit resources alter fitness payoffs and restructure the landscape in ways that promote speciation by opening new adaptive pathways. While there have been indirect tests of this theory, to our knowledge none have measured how fitness landscapes deform during adaptation, or test whether these shifts promote diversification. Here, we achieve this by studying bacteriophage $$\lambda$$
λ
, a virus that readily speciates into co-existing receptor specialists under controlled laboratory conditions. We use a high-throughput gene editing-phenotyping technology to measure $$\lambda$$
λ
’s fitness landscape in the presence of different evolved-$$\lambda$$
λ
competitors and find that the fitness effects of individual mutations, and their epistatic interactions, depend on the competitor. Using these empirical data, we simulate $$\lambda$$
λ
’s evolution on an unchanging landscape and one that recapitulates how the landscape deforms during evolution. $$\lambda$$
λ
heterogeneity only evolves in the shifting landscape regime. This study provides a test of adaptive dynamics, and, more broadly, shows how fitness landscapes dynamically change during adaptation, potentiating phenomena like speciation by opening new adaptive pathways.
CaMK4 controls follicular helper T cell expansion and function during normal and autoimmune T-dependent B cell responses
Authors: Scherlinger Marc , Li Hao , Pan Wenliang , Li Wei , Karino Kohei , Vichos Theodoros , Boulougoura Afroditi , Yoshida Nobuya , Tsokos Maria G. , Tsokos George C.
Published: January 2024

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by dysregulated B cell compartment responsible for the production of autoantibodies. Here, we show that T cell-specific expression of calcium/calmodulin-dependent protein kinase IV (CaMK4) leads to T follicular helper (Tfh) cells expansion in models of T-dependent immunization and autoimmunity. Mechanistically, CaMK4 controls the Tfh-specific transcription factor B cell lymphoma 6 (Bcl6) at the transcriptional level through the cAMP responsive element modulator α (CREMα). In the absence of CaMK4 in T cells, germinal center formation and humoral immunity is impaired in immunized mice, resulting in reduced anti-dsDNA titres, as well as IgG and complement kidney deposition in the lupus-prone B6.lpr mouse. In human Tfh cells, CaMK4 inhibition reduced BCL6 expression and IL-21 secretion ex vivo, resulting in impaired plasmablast formation and IgG production. In patients with SLE, CAMK4 mRNA levels in Tfh cells correlated with those of BCL6. In conclusion, we identify CaMK4/CREMα as a driver of T cell-dependent B cell dysregulation in autoimmunity.
A high affinity switch for cAMP in the HCN pacemaker channels
Authors: Porro Alessandro , Saponaro Andrea , Castelli Roberta , Introini Bianca , Hafez Alkotob Anahita , Ranjbari Golnaz , Enke Uta , Kusch Jana , Benndorf Klaus , Santoro Bina , DiFrancesco Dario , Thiel Gerhard , Moroni Anna
Published: January 2024

Binding of cAMP to Hyperpolarization activated cyclic nucleotide gated (HCN) channels facilitates pore opening. It is unclear why the isolated cyclic nucleotide binding domain (CNBD) displays in vitro lower affinity for cAMP than the full-length channel in patch experiments. Here we show that HCN are endowed with an affinity switch for cAMP. Alpha helices D and E, downstream of the cyclic nucleotide binding domain (CNBD), bind to and stabilize the holo CNBD in a high affinity state. These helices increase by 30-fold cAMP efficacy and affinity measured in patch clamp and ITC, respectively. We further show that helices D and E regulate affinity by interacting with helix C of the CNBD, similarly to the regulatory protein TRIP8b. Our results uncover an intramolecular mechanism whereby changes in binding affinity, rather than changes in cAMP concentration, can modulate HCN channels, adding another layer to the complex regulation of their activity.
Microbiome convergence enables siderophore-secreting-rhizobacteria to improve iron nutrition and yield of peanut intercropped with maize
Authors: Wang Nanqi , Wang Tianqi , Chen Yu , Wang Ming , Lu Qiaofang , Wang Kunguang , Dou Zhechao , Chi Zhiguang , Qiu Wei , Dai Jing , Niu Lei , Cui Jianyu , Wei Zhong , Zhang Fusuo , Kümmerli Rolf , Zuo Yuanmei
Published: January 2024

Intercropping has the potential to improve plant nutrition as well as crop yield. However, the exact mechanism promoting improved nutrient acquisition and the role the rhizosphere microbiome may play in this process remains poorly understood. Here, we use a peanut/maize intercropping system to investigate the role of root-associated microbiota in iron nutrition in these crops, combining microbiome profiling, strain and substance isolation and functional validation. We find that intercropping increases iron nutrition in peanut but not in maize plants and that the microbiota composition changes and converges between the two plants tested in intercropping experiments. We identify a Pseudomonas secreted siderophore, pyoverdine, that improves iron nutrition in glasshouse and field experiments. Our results suggest that the presence of siderophore-secreting Pseudomonas in peanut and maize intercropped plays an important role in iron nutrition. These findings could be used to envision future intercropping practices aiming to improve plant nutrition.
Peculiar band geometry induced giant shift current in ferroelectric SnTe monolayer
Authors: Jin Gan , He Lixin
Published: January 2024

The bulk photovoltaic effect (BPVE) occurs when homogeneous noncentrosymmetric materials generate photocurrent or photovoltage under illumination. The intrinsic contribution to this effect is known as the shift current effect. We calculate the shift current conductivities of the ferroelectric SnTe monolayer using first-principles methods. Our results reveal a giant shift-current conductivity near the valley points in the SnTe monolayer. More remarkably, the linear optical absorption coefficient at this energy is very small, resulting in an enormous Glass coefficient that is four orders of magnitude larger than that of BaTiO3. To understand these giant shift-current effects, we employ a three-band model and find that they arise from the nontrivial energy band geometries near the valley points, where the shift-vector diverges. This serves as a prominent example highlighting the crucial role of band geometry in determining the fundamental properties of solids.
AutoTransOP: translating omics signatures without orthologue requirements using deep learning
Authors: Meimetis Nikolaos , Pullen Krista M. , Zhu Daniel Y. , Nilsson Avlant , Hoang Trong Nghia , Magliacane Sara , Lauffenburger Douglas A.
Published: January 2024

The development of therapeutics and vaccines for human diseases requires a systematic understanding of human biology. Although animal and in vitro culture models can elucidate some disease mechanisms, they typically fail to adequately recapitulate human biology as evidenced by the predominant likelihood of clinical trial failure. To address this problem, we developed AutoTransOP, a neural network autoencoder framework, to map omics profiles from designated species or cellular contexts into a global latent space, from which germane information for different contexts can be identified without the typically imposed requirement of matched orthologues. This approach was found in general to perform at least as well as current alternative methods in identifying animal/culture-specific molecular features predictive of other contexts—most importantly without requiring homology matching. For an especially challenging test case, we successfully applied our framework to a set of inter-species vaccine serology studies, where 1-to-1 mapping between human and non-human primate features does not exist.
Whole-genome resource sequences of 57 indigenous Ethiopian goats
Authors: Belay Shumuye , Belay Gurja , Nigussie Helen , Jian-Lin Han , Tijjani Abdulfatai , Ahbara Abulgasim M. , Tarekegn Getinet M. , Woldekiros Helina S. , Mor Siobhan , Dobney Keith , Lebrasseur Ophelie , Hanotte Olivier , Mwacharo Joram M.
Published: January 2024

Domestic goats are distributed worldwide, with approximately 35% of the one billion world goat population occurring in Africa. Ethiopia has 52.5 million goats, ~99.9% of which are considered indigenous landraces deriving from animals introduced to the Horn of Africa in the distant past by nomadic herders. They have continued to be managed by smallholder farmers and semi-mobile pastoralists throughout the region. We report here 57 goat genomes from 12 Ethiopian goat populations sampled from different agro-climates. The data were generated through sequencing DNA samples on the Illumina NovaSeq 6000 platform at a mean depth of 9.71x and 150 bp pair-end reads. In total, ~2 terabytes of raw data were generated, and 99.8% of the clean reads mapped successfully against the goat reference genome assembly at a coverage of 99.6%. About 24.76 million SNPs were generated. These SNPs can be used to study the population structure and genome dynamics of goats at the country, regional, and global levels to shed light on the species’ evolutionary trajectory.