bluuebunny/crossref_metadata_2025 huggingface dataset:
Philosophy’s Resurrection: Richard Fishacre on Theology, Light, and the Stars
Authors: Crozier William
Published: February 2024

This article explores Richard Fishacre’s (1200–1248) thinking on the relationship between theology and philosophy. It shows how, despite constructing what, on the surface at least, appears to be a traditional understanding of theology’s relationship to philosophy, Fishacre in practice offers a very creative interpretation of how the two sciences interact. For Fishacre, theology does not simply illumine philosophy by guiding it away from error. Instead, it steps into the fray of ordinary philosophical dispute so as to uncover novel ways of reading natural phenomena, ones which philosophy, by itself at least, is blind to. To demonstrate how this is so, the article explores how Fishacre appeals to Christ’s resurrected body to justify some of his most controversial arguments in the field of natural philosophy. Two specific areas are considered: Fishacre’s claim that light in medio is a body and his assertion that the stars and planets are made from the terrestrial elements as opposed to the celestial quintessence, as Aristotle claims. Each of these aspects of Fishacre’s physics show how, for the Dominican, theology can, when appropriate, step onto the philosophical plane and help the natural philosopher to discover truths that go against the philosophical consensus.
Plane Hijackings between Cuba and the United States and the Opportunity for Diplomacy (1958–1973)
Authors: Porat Dan
Published: February 2024

Between 1958 and 1973, hijackings between Cuba and the US surged, prompting Cuban officials in the early 1960s to propose an extradition agreement for hijackers. However, the US, leveraging its superpower status, dismissed these initiatives, viewing hijackers as political asylum seekers rather than criminals. By the late 1960s, as hijackings escalated from the US to Cuba, the American approach shifted, seeking a bilateral agreement to address air piracy, only to be rebuffed by Cuba, which refused to accept the US’s categorization of specific hijackers as political asylum seekers while classifying others as criminals. Meanwhile, the US pressed its extradition stance through international bodies like the International Civil Aviation Organization. These diplomatic efforts underscored broader challenges in US–Cuban relations, with negotiations repeatedly missing opportunities for enhanced co-operation. A pivotal shift occurred after a significant incident threatened both nations, leading to a more balanced perspective between the US and Cuba. This change culminated in the 1973 signing of a ‘Memorandum of understanding’, marking a turning point that significantly curbed hijacking incidents and hinted at potential future improvements in bilateral relations.
From Natives to Foreigners: Bolivian Migration, Discrimination, and Ethnic-Labor Subsidiarity in Chuquicamata During the Guggenheim Ownership (Chile, 1912–1925)
Authors: Galaz-Mandakovic Damir , Rivera Francisco
Published: February 2024

The War of the Pacific (1879–1883) between Chile, Peru, and Bolivia marked a turning point in the political and socio-economic development of the Atacama Desert. Formerly part of Bolivia, this area came under the control and jurisdiction of Chile in 1884. This shift in sovereignty substantially altered the tri-national geopolitics, forcing the local Bolivian population to flee. The newly annexed region's rich mineral resources became subject to a mining colonization process. In 1912, the Guggenheim family founded The Chile Exploration Company and began the industrialization of the Chuquicamata copper mine. Located in the heart of the Atacama Desert, this was the world's largest copper mine during the twentieth century. Although the local Bolivian population had fled the Atacama Desert following the war, many returned to work in the Guggenheim mine almost thirty years later. Between 1912 and 1925, 239 Bolivians labeled as foreigners and “Indians” were employed in diverse production stages or subsidiary services. Bureaucratic migratory documents and newspaper archives allow us to quantify and characterize Bolivian migration to Chuquicamata. We argue that an ethnic-labor subsidiarity emerged, a historical process resulting from ethnic discrimination, expressed in the disposition and physical costs of mining work and low wages. While the war altered the mining territory of Atacama, ethnic-labor subsidiarity of the Bolivian workforce sustained the expansion of U.S. capitalism in the Chuquicamata copper mine.
Renegotiating Skills, Wages, and the Right to Work: On the Gender of Labor Activism around Rationalization in the Bulgarian Tobacco Industry in the Early 1930s
Authors: Masheva Ivelina Lyubenova
Published: February 2024

Starting from the early 1930s, structural changes in the Bulgarian tobacco industry, prompted by the advent of the world economic crisis and German economic expansionism into Southeastern Europe, led to a deep restructuring of the labor processes, known in the terminology of the time as rationalization, in the Bulgarian tobacco industry. The introduction of the tonga rationalization technology had a deskilling and deeply gendered effect on the industry, making a significant number of skilled male workers redundant, disproportionately decreasing average male wages and leading, in turn, to a further feminization of an already majority-female workforce.

The introduction of the new system provoked a strong response from the organized labor movement, which used a variety of tactics to fight against the new technology: from strikes to petitions to tripartite negotiations. Organized labor's reaction was deeply gendered, an aspect that only becomes truly visible if, in addition to gender and skill, we employ the analytical lens of scale. By following trade union policies on the local, national, and international levels, the article goes beyond the carefully crafted gender-neutral language in official documents to reveal tensions between the conservative attitudes of rank-and-file activists and the official trade union agenda. This is especially evident in communist labor politics, where Bulgarian trade union policies on the local and national levels provoked an intervention on the part of the Profintern between 1930 and 1931. The movement's internal contradictions resulted in a polyvalent, ambiguous, and non-linear trade union policy formed through the clash of and negotiations between local activists’ conservative notions of gendered work and family roles and the radical gender program of international communism.
Measuring children's metalinguistic awareness
Authors: Roehr-Brackin Karen
Published: February 2024

Research into young learners' metalinguistic awareness has led to both definitions of the construct and key findings about its role in children's cognitive and linguistic development. I briefly summarise this research before introducing two established theoretical models that can help us understand the concept of metalinguistic awareness more broadly: Ellen Bialystok's classic dichotomy of analysis of knowledge and control of processing, and Rod Ellis's notion of explicit (second language) knowledge. This is followed by an overview of measures of metalinguistic awareness that have been used in empirical studies to date as well as an illustration and critique of selected measures. As a result, I propose a model that combines features of the two previous frameworks by conceptualising knowledge representations and processes in terms of (1) how implicit/explicit and (2) how specific/schematic they are. I explain this model to illustrate how it can serve as a useful thinking tool. In particular, I argue that the model not only allows us to theorise measures of metalinguistic awareness more clearly and easily, but that it can also capture tasks aimed at assessing other linguistic and cognitive abilities. The article concludes with a brief outlook on future research into metalinguistic awareness.
Crystal structure of anthraquinone-2-carboxylic acid, C15H8O4
Authors: Ens Tawnee M. , Kaduk James A. , Dosen Anja , Blanton Thomas N.
Published: February 2024

The crystal structure of anthraquinone-2-carboxylic acid has been solved and refined using synchrotron X-ray powder diffraction data, and optimized using density functional theory techniques. Anthraquinone-2-carboxylic acid crystallizes in space group P-1 (#2) with a = 3.7942(2), b = 13.266(5), c = 22.835(15) Å, α = 73.355(30), β = 89.486(6), γ = 86.061(1)°, V = 1098.50(7) Å3, and Z = 4. The crystal structure contains two independent molecules of anthraquinone-2-carboxylic acid. Although the expected hydrogen-bonded dimers are present, the dimers are not centrosymmetric. The dimer contains one molecule of each planar low-energy conformation. The crystal structure consists of a herringbone array of centrosymmetric pairs of molecules parallel to the bc-plane. The molecules stack along the short a-axis. The powder pattern has been submitted to ICDD® for inclusion in the Powder Diffraction File™ (PDF®).
Commentary
Authors: Sterling Kathleen
Published: February 2024

Greer offers an excellent primer on some Black Studies scholars’ critiques of humanism, for which he uses the label ‘counter-humanism’ after Erasmus (2020), distinguishing these approaches from ‘posthumanism.’ He identifies two primary strains of posthumanism relevant to archaeological interpretation, symmetrical archaeology and posthuman feminism, though examples of the latter are drawn from a broader body of academic literature and are subject to less critique. Posthumanists are shown to prioritize dismantling a human–object divide, while counter-humanists critique the human–non-human split. This may appear to be more or less the same project, but the framing of ‘A/not-A’ rather than ‘A–B’ emphasizes the hegemonic relationships between these categories, the continuity within, and makes more explicit the fact that people are included in both the non-human and object categories.
The impact of the British Civil Wars on the meanings and uses of the urban topography of Colchester in the long nineteenth century
Authors: Sewell Michael
Published: February 2024

Although many towns repaired, restored or destroyed the ruins of Civil War sieges, there are a number of towns, villages and hamlets which still clearly bear marks of the conflict. By focusing on Colchester, this article will highlight how sites affected by the wars remained and survived in the local consciousness throughout the following centuries. This article traces the uses of such sites in the urban landscape in the eighteenth and nineteenth centuries to assess the long-term impact of the war on towns in the British Isles. By examining Colchester in 1648, the article will show how political parties, parishes, tourists and businesses all derived value from the sites of the siege centuries after it had ended.
Smugglers and innkeepers: physical and social mobility in early modern Gemona (fifteenth to seventeenth centuries)
Authors: Di Bari Alessandro
Published: February 2024

This article examines the mechanics of Niederlech (a law that obliged merchants travelling between Germany and Italy to spend the night in the city, change wagons and pay a small sum of money) and German–Italian mobility in early modern Gemona. It argues that the fragility of Venetian institutions and a lack of German–Italian border controls set the scene for criminal activities, especially contraband, in which Gemona innkeepers appear to have played a significant part. It will also show that this illegal trafficking led to a new ruling class forming, a key factor in the city’s reorganization of social hierarchies.
Critical Reflexivity and Intersectionality in Human	Rights
Authors: Gemignani Marco , Hernández-Albújar Yolanda
Published: February 2024

Abstract. Within traditional social, community, and clinical psychologies, the human rights framework has typically been interpreted and adopted from a person- or patient-based perspective. While useful and well meaning, ideological values concerning empowerment, agency, and resiliency have often framed human rights interventions or programs within psychology. We propose in this manuscript a theoretical shift for psychology to decentralize the role of the individual human being while at the same time avoiding forms of social behaviorism that tend to portray the person as passive or as reacting to external stimuli. Following this first shift from the individual to the collective, we suggest adopting anti-essentialist discourses about the parties, agents, and issues involved in human rights. To this goal, the philosophical framework of process or relational ontology may be especially useful. Based on critical theory, critical feminism, social constructionist, and post-human views of knowledge and reality, process ontology considers reality as complex, fluid, discursive, and dialogical. The separations between the personal and the political are questioned to underscore the entanglement and inseparability of dimensions of possibility and actions, which are continuous reconstructions. To conclude, we reflect on the ways in which these two movements toward anti-individualism and relational ontology might inform specific practices and reflections within human rights frameworks in psychology.
Human Rights, Dementia, and Identity
Authors: Butchard Sarah , Kinderman Peter
Published: February 2024

Abstract. Human rights are integral to the work of applied psychologists, particularly when supporting people who may be experiencing some form of vulnerability. As dementia progresses, potential vulnerability increases and the need to protect and promote the fundamental human rights of people living with dementia becomes even more important. However, we also need to translate complicated human rights law into practical strategies which facilitate upholding people’s rights on a day-to-day basis. The FREDA principles (of Fairness, Respect, Equality, Dignity, and Autonomy) provide a framework to make this translation. Recent research has highlighted the applicability of the FREDA principles to dementia but also added an important new element – identity – to this rubric. This paper explores the links between identity and human rights and the ways in which preserving identity can enhance human rights-based approaches. The similarity between human rights-based approaches to care and the more traditionally cited model of person-centered care are noted, and it is suggested that the legal underpinning of human rights-based approaches affords them weight that is sometimes lacking in other care frameworks. It concludes that no one single framework is sufficient to ensure optimum care but that recognizing a person’s right to maintain and express their identity, as well as the other FREDA principles, allows us to understand more fully the individual and her or his needs and in turn allows us to better apply the law and guide professionals in delivering care that is of the highest possible standards.
Investigating the Linkage Between Spiral Trough Morphology and Cloud Coverage on the Martian North Polar Layered Deposits
Authors: Lutz K. A. , Hawley R. L. , Palucis M. C.
Published: February 2024

The martian North Polar layered deposits (NPLD) are composed of alternating water‐ice and dust‐rich layers resulting from atmospheric deposition and are key to understanding Mars climate cycles. Within these deposits are spiral troughs whose migration affects deposition signals. To understand the relationship between NPLD stratigraphy and Martian climate, we must identify modern‐day drivers of NPLD ice migration. Prevailing theory posits migration driven by upstream‐migrating bed undulations bounded by hydraulic jumps, caused by katabatic winds flowing over trough walls with asymmetric cross‐sectional relief. This is supported by trough‐parallel clouds, whose formation has been attributed to hydraulic jumps. We present a cloud atlas across the Martian north pole using ∼13,800 THEMIS images spanning ∼18 Earth years. We find trough‐parallel clouds in ∼400 images, with regions nearer to the pole having higher cloud frequency. We compare spiral trough geometry to our cloud atlas and find regions with trough‐parallel clouds often correlate with metrics associated with modern‐day sublimation‐deposition cycles (i.e., relief and asymmetry), but not always. In some regions, troughs with morphologies conducive to cloud formation have no clouds. Overall, trough geometry varies greatly across the deposits, both within and between troughs, suggesting localized differences in deposition relative to migration, varying katabatic wind intensities, differing past climatic states influencing the troughs, varying trough initiation properties, or the possibility of additional mechanisms for trough initiation and migration (e.g., in situ trough erosion). Understanding what controls trough shape variability across the NPLD and how these controls change through time and space is key when interpreting Martian paleoclimate.
Linking Transpiration to Reef Nitrogen Supply on a Tropical Coral Island
Authors: Erler Dirk V. , Dudgeon Christine L. , Armstrong Asia O. , Banks Eddie W. , Ramirez‐Valle Orlando , Gutiérrez‐Jurado Hugo A. , Gilby Ben L. , Townsend Kathy A.
Published: February 2024

Coral reef islands are biodiversity hotspots with high conservation value, but we have a poor understanding of how island vegetation, through transpiration, influences groundwater nutrient supply to adjacent reef systems. Here we combine stable isotope tracing, geophysical surveys, and satellite analysis to unravel the links between transpiration and the discharge of groundwater nitrate to the waters surrounding a coral reef island (Lady Elliot Island in the Great Barrier Reef). Over a 2‐year study period (2020–2021) there was a net loss of freshwater from the island, that is, evapotranspiration (ET) exceeded rainfall, largely caused by high rates of transpiration (73% of ET). Transpiration was higher in forested areas, and groundwater salinity appeared to be higher there. By tracing the nitrogen stable isotope signature of groundwater nitrate into reef organism tissue we were able to map groundwater nitrogen discharge spatially and temporally. Groundwater nitrogen discharge was focussed on one side of the island and did not vary seasonally as expected, despite reduced rainfall and seabird guano inputs over the austral winter/spring. Based on our results, we propose that transpiration by island vegetation slows groundwater flow and concentrates nitrate in the groundwater being released to the surrounding reef system. High concentrations of nitrate in groundwater (up to 27 mmol L−) were observed on Lady Elliot Island and these seem to have increased since 2014, but further work is required to understand if this is a normal scenario for tropical coral islands or the result of the islands' revegetation program.
Post-transplant cyclophosphamide versus anti-thymocyte globulin after reduced intensity peripheral blood allogeneic cell transplantation in recipients of matched sibling or 10/10 HLA matched unrelated donors: final analysis of a randomized, open-label, multicenter, phase 2 trial
Authors: Brissot Eolia , Labopin Myriam , Labussière Helene , Fossard Gaelle , Chevallier Patrice , Guillaume Thierry , Yakoub-Agha Ibrahim , Srour Micha , Bulabois Claude-Eric , Huynh Anne , Chantepie Sylvain , Menard Anne-Lise , Rubio Marie-Therese , Ceballos Patrice , Dulery Rémy , Furst Sabine , Malard Florent , Blaise Didier , Mohty Mohamad
Published: February 2024

The use of post-transplantation cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis is not established after reduced intensity conditioning (RIC) hematopoietic stem cell transplantation (HSCT) from fully matched donors. This was a randomized, open-label, multicenter, phase 2 trial. All patients received a RIC regimen with fludarabine, intravenous busulfan for 2 days (Flu-Bu2), and a peripheral blood stem cell (PBSC) graft from a matched related or 10/10 HLA-matched unrelated donor. Patients were randomly assigned to receive anti-thymocyte globulin (ATG) 5 mg/kg plus standard GVHD prophylaxis or PTCy 50 mg/kg/d at days +3 and +4 plus standard GVHD prophylaxis. The primary endpoint was the composite endpoint of GVHD- and relapse-free survival (GRFS) at 12 months after HSCT. Eighty-nine patients were randomly assigned to receive either PTCy or control prophylaxis with ATG. At 12 months, disease-free survival was 65.9% in the PTCy group and 67.6% in the ATG group (P = 0.99). Cumulative incidence of relapse, non-relapse mortality, and overall survival were also comparable in the two groups. GRFS at 12 months was 54.5% in the PTCy group versus 43.2% in the ATG group (P = 0.27). The median time to neutrophil and platelet count recovery was significantly longer in the PTCy group compared to the ATG group. Except for day +30, where EORTC QLQ-C30 scores were significantly lower in the PTCy compared to the ATG group, the evolution with time was not different between the two groups. Although the primary objective was not met, PTCy is effective for GVHD prophylaxis in patients receiving Flu-Bu2 conditioning with a PBSC graft from a fully matched donor and was well tolerated in term of adverse events and quality of life. This trial was registered at clinicaltrials.gov: NCT02876679.
Perceptions and preferences for genetic testing for sickle cell disease or trait: a qualitative study in Cameroon, Ghana and Tanzania
Authors: Munung Nchangwi Syntia , Kamga Karen Kengne , Treadwell Marsha J , Dennis-Antwi Jemima , Anie Kofi A , Bukini Daima , Makani Julie , Wonkam Ambroise
Published: February 2024

Sickle cell disease (SCD) is a single gene blood disorder characterised by frequent episodes of pain, chronic anaemic, acute chest syndrome, severe disease complications and lifelong debilitating multi-system organ damage. Genetic testing and screening programs for SCD and the sickle cell trait (SCT) are valuable for early diagnosis and management of children living with SCD, and in the identification of carriers of SCT. People with SCT are for the most part asymptomatic and mainly identified as through genetic testing or when they have a child with SCD. This qualitative study explored perceptions towards genetic testing for SCD and SCT in Cameroon, Ghana, and Tanzania. The results show a general preference for newborn screening for SCD over prenatal and premarital/preconception testing, primarily due to its simpler decision-making process and lower risk for stigmatization. Premarital testing for SCT was perceived to be of low public health value, as couples are unlikely to alter their marriage plans despite being aware of their risk of having a child with SCD. Adolescents were identified as a more suitable population for SCT testing. In the case of prenatal testing, major concerns were centred on cultural, religious, and personal values on pregnancy termination. The study revealed a gender dimension to SCD/SCT testing. Participants mentionned that women bear a heightened burden of decision making in SCD/SCT testing, face a higher risk of rejection by potential in-laws/partners if the carriers of SCT, as well as the possibility of  divorce if they have a child with SCD. The study highlights the complex cultural, ethical, religious and social dynamics surrounding genetic testing for SCD and emphasises the need for public education on SCD and the necessity of incorporating genetic and psychosocial counselling into SCD/SCT testing programs.
Loss of TBC1D2B causes a progressive neurological disorder with gingival overgrowth
Authors: Harms Frederike L. , Rexach Jessica Erin , Efthymiou Stephanie , Aynekin Busra , Per Hüseyin , Güleç Ayten , Nampoothiri Sheela , Sampaio Hugo , Sachdev Rani , Stoeva Radka , Myers Kasiani , Pena Loren D. M. , Kalfa Theodosia A. , Chard Marisa , Klassen Megan , Pries Megan , Kutsche Kerstin
Published: February 2024

Biallelic loss-of-function variants in TBC1D2B have been reported in five subjects with cognitive impairment and seizures with or without gingival overgrowth. TBC1D2B belongs to the family of Tre2-Bub2-Cdc16 (TBC)-domain containing RAB-specific GTPase activating proteins (TBC/RABGAPs). Here, we report five new subjects with biallelic TBC1D2B variants, including two siblings, and delineate the molecular and clinical features in the ten subjects known to date. One of the newly reported subjects was compound heterozygous for the TBC1D2B variants c.2584C>T; p.(Arg862Cys) and c.2758C>T; p.(Arg920*). In subject-derived fibroblasts, TBC1D2B mRNA level was similar to control cells, while the TBC1D2B protein amount was reduced by about half. In one of two siblings with a novel c.360+1G>T splice site variant, TBC1D2B transcript analysis revealed aberrantly spliced mRNAs and a drastically reduced TBC1D2B mRNA level in leukocytes. The molecular spectrum included 12 different TBC1D2B variants: seven nonsense, three frameshifts, one splice site, and one missense variant. Out of ten subjects, three had fibrous dysplasia of the mandible, two of which were diagnosed as cherubism. Most subjects developed gingival overgrowth. Half of the subjects had developmental delay. Seizures occurred in 80% of the subjects. Six subjects showed a progressive disease with mental deterioration. Brain imaging revealed cerebral and/or cerebellar atrophy with or without lateral ventricle dilatation. The TBC1D2B disorder is a progressive neurological disease with gingival overgrowth and abnormal mandible morphology. As TBC1D2B has been shown to positively regulate autophagy, defects in autophagy and the endolysosomal system could be associated with neuronal dysfunction and the neurodegenerative disease in the affected individuals.
Prevalence and risk factors for impaired activities of daily living in patients with neo-vascular age-related macular degeneration who present for anti-VEGF treatment
Authors: Van Vu Kim , Mitchell Paul , Detaram Harshil Dharamdasani , Burlutsky George , Liew Gerald , Gopinath Bamini
Published: February 2024

Background/Objectives

To assess the prevalence and correlates of impaired activities of daily living (ADLs) in patients with neovascular age-related macular degeneration (nAMD) who present for anti-vascular endothelial growth factor (VEGF) therapy.

Methods

In a clinic-based cohort of 437 patients with nAMD who presented for anti-VEGF therapy, the Older American Resources and Services Scale (OARS) was administered to assess for impairments in basic, instrumental and total ADL. Logistic regression analyses were conducted to determine odds ratios (OR) and 95% confidence intervals (CI) for factors associated with ADL impairment.

Results

The prevalence of impaired basic, instrumental and total ADL was 37.76%, 67.82% and 39.59%, respectively. In multivariate-adjusted models, moderate visual impairment [OR 5.65, 95% CI (2.31–13.83) and blindness [OR 5.43, 95% CI (2.09–14.12)] were associated with greater odds of impaired total ADL. Depressive symptoms [OR 2.08, 95% CI (1.08–4.00)], the presence of any disability [OR 3.16, 95% CI (1.64–0.07)] and never driving [OR 4.00, 95% CI (1.60–10.00)] were also positively associated with total ADL impairment. Better vision-related quality of life (QoL) was inversely associated with impaired instrumental ADL whilst higher health-related QoL scores were associated with decreased odds of total ADL impairment.

Conclusions

There is a high prevalence rate of ADL impairment among nAMD patients presenting for therapy. Visual impairment, never driving, poor physical and mental health increased the odds of experiencing ADL impairment whilst better VRQoL and HRQoL reduced the odds of impairment.
Realization of all-band-flat photonic lattices
Authors: Yang Jing , Li Yuanzhen , Yang Yumeng , Xie Xinrong , Zhang Zijian , Yuan Jiale , Cai Han , Wang Da-Wei , Gao Fei
Published: February 2024

Flatbands play an important role in correlated quantum matter and have promising applications in photonic lattices. Synthetic magnetic fields and destructive interference in lattices are traditionally used to obtain flatbands. However, such methods can only obtain a few flatbands with most bands remaining dispersive. Here we realize all-band-flat photonic lattices of an arbitrary size by precisely controlling the coupling strengths between lattice sites to mimic those in Fock-state lattices. This allows us to go beyond the perturbative regime of strain engineering and group all eigenmodes in flatbands, which simultaneously achieves high band flatness and large usable bandwidth. We map out the distribution of each flatband in the lattices and selectively excite the eigenmodes with different chiralities. Our method paves a way in controlling band structure and topology of photonic lattices.
Current-induced switching of a van der Waals ferromagnet at room temperature
Authors: Kajale Shivam N. , Nguyen Thanh , Chao Corson A. , Bono David C. , Boonkird Artittaya , Li Mingda , Sarkar Deblina
Published: February 2024

Recent discovery of emergent magnetism in van der Waals magnetic materials (vdWMM) has broadened the material space for developing spintronic devices for energy-efficient computation. While there has been appreciable progress in vdWMM discovery, a solution for non-volatile, deterministic switching of vdWMMs at room temperature has been missing, limiting the prospects of their adoption into commercial spintronic devices. Here, we report the first demonstration of current-controlled non-volatile, deterministic magnetization switching in a vdW magnetic material at room temperature. We have achieved spin-orbit torque (SOT) switching of the PMA vdW ferromagnet Fe3GaTe2 using a Pt spin-Hall layer up to 320 K, with a threshold switching current density as low as $${J}_{{{{{{\rm{sw}}}}}}}=$$

J

sw

=
1.69 $$\times$$
×
106 A cm−2 at room temperature. We have also quantitatively estimated the anti-damping-like SOT efficiency of our Fe3GaTe2/Pt bilayer system to be $${\xi }_{{{{{{\rm{DL}}}}}}}=0.093$$

ξ

DL

=
0.093
, using the second harmonic Hall voltage measurement technique. These results mark a crucial step in making vdW magnetic materials a viable choice for the development of scalable, energy-efficient spintronic devices.
A transient protein folding response targets aggregation in the early phase of TDP-43-mediated neurodegeneration
Authors: San Gil Rebecca , Pascovici Dana , Venturato Juliana , Brown-Wright Heledd , Mehta Prachi , Madrid San Martin Lidia , Wu Jemma , Luan Wei , Chui Yi Kit , Bademosi Adekunle T. , Swaminathan Shilpa , Naidoo Serey , Berning Britt A. , Wright Amanda L. , Keating Sean S. , Curtis Maurice A. , Faull Richard L. M. , Lee John D. , Ngo Shyuan T. , Lee Albert , Morsch Marco , Chung Roger S. , Scotter Emma , Lisowski Leszek , Mirzaei Mehdi , Walker Adam K.
Published: February 2024

Understanding the mechanisms that drive TDP-43 pathology is integral to combating amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD) and other neurodegenerative diseases. Here we generated a longitudinal quantitative proteomic map of the cortex from the cytoplasmic TDP-43 rNLS8 mouse model of ALS and FTLD, and developed a complementary open-access webtool, TDP-map (https://shiny.rcc.uq.edu.au/TDP-map/). We identified distinct protein subsets enriched for diverse biological pathways with temporal alterations in protein abundance, including increases in protein folding factors prior to disease onset. This included increased levels of DnaJ homolog subfamily B member 5, DNAJB5, which also co-localized with TDP-43 pathology in diseased human motor cortex. DNAJB5 over-expression decreased TDP-43 aggregation in cell and cortical neuron cultures, and knockout of Dnajb5 exacerbated motor impairments caused by AAV-mediated cytoplasmic TDP-43 expression in mice. Together, these findings reveal molecular mechanisms at distinct stages of ALS and FTLD progression and suggest that protein folding factors could be protective in neurodegenerative diseases.
Stable water splitting using photoelectrodes with a cryogelated overlayer
Authors: Kang Byungjun , Tan Jeiwan , Kim Kyungmin , Kang Donyoung , Lee Hyungsoo , Ma Sunihl , Park Young Sun , Yun Juwon , Lee Soobin , Lee Chan Uk , Jang Gyumin , Lee Jeongyoub , Moon Jooho , Lee Hyungsuk
Published: February 2024

Hydrogen production techniques based on solar-water splitting have emerged as carbon-free energy systems. Many researchers have developed highly efficient thin-film photoelectrochemical (PEC) devices made of low-cost and earth-abundant materials. However, solar water splitting systems suffer from short lifetimes due to catalyst instability that is attributed to both chemical dissolution and mechanical stress produced by hydrogen bubbles. A recent study found that the nanoporous hydrogel could prevent the structural degradation of the PEC devices. In this study, we investigate the protection mechanism of the hydrogel-based overlayer by engineering its porous structure using the cryogelation technique. Tests for cryogel overlayers with varied pore structures, such as disconnected micropores, interconnected micropores, and surface macropores, reveal that the hydrogen gas trapped in the cryogel protector reduce shear stress at the catalyst surface by providing bubble nucleation sites. The cryogelated overlayer effectively preserves the uniformly distributed platinum catalyst particles on the device surface for over 200 h. Our finding can help establish semi-permanent photoelectrochemical devices to realize a carbon-free society.
Sintilimab with two cycles of chemotherapy for the treatment of advanced squamous non-small cell lung cancer: a phase 2 clinical trial
Authors: Zhang Mina , Zhang Guowei , Niu Yuanyuan , Zhang Guifang , Ji Yinghua , Yan Xiangtao , Zhang Xiaojuan , Wang Qichuan , Jing Xiaohui , Wang Junsheng , Ma Zhiyong , Wang Huijuan
Published: February 2024

This was a single-arm, multicenter phase 2 clinical trial (ChiCTR1900021726) involving advanced squamous non-small cell lung cancer (sq-NSCLC) patients undergoing 2 cycles of nab-paclitaxel/carboplatin and sintilimab (anti-PD-1), followed by sintilimab maintenance therapy. The median progression-free survival (PFS) was 11.4 months (95% CI: 6.7-18.1), which met the pre-specified primary endpoint. Secondary endpoints included objective response rate reaching 70.5% and a disease control rate of 93.2%, with a median duration of response of 13.6 months [95% CI: 7.0–not evaluable (NE)]. The median overall survival was 27.2 months (95% CI: 20.2–NE) with treatment-related adverse events grades ≥3 occurring in 10.9% of patients. Predefined exploratory endpoints comprised relationships between biomarkers and treatment efficacy, and the association between circulating tumor DNA (ctDNA) dynamics and PFS. Biomarker analysis revealed that the breast cancer gene 2, BMP/Retinoic Acid Inducible Neural Specific 3, F-box/WD repeat-containing protein 7, tyrosine-protein kinase KIT and retinoblastoma 1 abnormalities led to shorter PFS, while ctDNA negative at baseline or clearance at 2 cycles of treatment was associated with longer PFS (18.1 vs. 4.3 months). Taken together, sintilimab in combination with 2 cycles of nab-paclitaxel/carboplatin treatment produced encouraging PFS and better tolerability as first-line treatment for advanced sq-NSCLC.
Genetic influences on circulating retinol and its relationship to human health
Authors: Reay William R. , Kiltschewskij Dylan J. , Di Biase Maria A. , Gerring Zachary F. , Kundu Kousik , Surendran Praveen , Greco Laura A. , Clarke Erin D. , Collins Clare E. , Mondul Alison M. , Albanes Demetrius , Cairns Murray J.
Published: February 2024

Retinol is a fat-soluble vitamin that plays an essential role in many biological processes throughout the human lifespan. Here, we perform the largest genome-wide association study (GWAS) of retinol to date in up to 22,274 participants. We identify eight common variant loci associated with retinol, as well as a rare-variant signal. An integrative gene prioritisation pipeline supports novel retinol-associated genes outside of the main retinol transport complex (RBP4:TTR) related to lipid biology, energy homoeostasis, and endocrine signalling. Genetic proxies of circulating retinol were then used to estimate causal relationships with almost 20,000 clinical phenotypes via a phenome-wide Mendelian randomisation study (MR-pheWAS). The MR-pheWAS suggests that retinol may exert causal effects on inflammation, adiposity, ocular measures, the microbiome, and MRI-derived brain phenotypes, amongst several others. Conversely, circulating retinol may be causally influenced by factors including lipids and serum creatinine. Finally, we demonstrate how a retinol polygenic score could identify individuals more likely to fall outside of the normative range of circulating retinol for a given age. In summary, this study provides a comprehensive evaluation of the genetics of circulating retinol, as well as revealing traits which should be prioritised for further investigation with respect to retinol related therapies or nutritional intervention.
Metal-free photocatalytic cross-electrophile coupling enables C1 homologation and alkylation of carboxylic acids with aldehydes
Authors: Bonciolini Stefano , Pulcinella Antonio , Leone Matteo , Schiroli Debora , Ruiz Adrián Luguera , Sorato Andrea , Dubois Maryne A. J. , Gopalakrishnan Ranganath , Masson Geraldine , Della Ca’ Nicola , Protti Stefano , Fagnoni Maurizio , Zysman-Colman Eli , Johansson Magnus , Noël Timothy
Published: February 2024

In contemporary drug discovery, enhancing the sp3-hybridized character of molecular structures is paramount, necessitating innovative synthetic methods. Herein, we introduce a deoxygenative cross-electrophile coupling technique that pairs easily accessible carboxylic acid-derived redox-active esters with aldehyde sulfonyl hydrazones, employing Eosin Y as an organophotocatalyst under visible light irradiation. This approach serves as a versatile, metal-free C(sp3)−C(sp3) cross-coupling platform. We demonstrate its synthetic value as a safer, broadly applicable C1 homologation of carboxylic acids, offering an alternative to the traditional Arndt-Eistert reaction. Additionally, our method provides direct access to cyclic and acyclic β-arylethylamines using diverse aldehyde-derived sulfonyl hydrazones. Notably, the methodology proves to be compatible with the late-stage functionalization of peptides on solid-phase, streamlining the modification of intricate peptides without the need for exhaustive de-novo synthesis.
Clinical application of next generation sequencing for Mendelian disease diagnosis in the Iranian population
Authors: Abolhassani Ayda , Fattahi Zohreh , Beheshtian Maryam , Fadaee Mahsa , Vazehan Raheleh , Ahangari Fatemeh , Dehdahsi Shima , Faraji Zonooz Mehrshid , Parsimehr Elham , Kalhor Zahra , Peymani Fatemeh , Mozaffarpour Nouri Maryam , Babanejad Mojgan , Noudehi Khadijeh , Fatehi Fatemeh , Zamanian Najafabadi Shima , Afroozan Fariba , Yazdan Hilda , Bozorgmehr Bita , Azarkeivan Azita , Sadat Mahdavi Shokouh , Nikuei Pooneh , Fatehi Farzad , Jamali Payman , Ashrafi Mahmoud Reza , Karimzadeh Parvaneh , Habibi Haleh , Kahrizi Kimia , Nafissi Shahriar , Kariminejad Ariana , Najmabadi Hossein
Published: February 2024

Next-generation sequencing (NGS) has been proven to be one of the most powerful diagnostic tools for rare Mendelian disorders. Several studies on the clinical application of NGS in unselected cohorts of Middle Eastern patients have reported a high diagnostic yield of up to 48%, correlated with a high level of consanguinity in these populations. We evaluated the diagnostic utility of NGS-based testing across different clinical indications in 1436 patients from Iran, representing the first study of its kind in this highly consanguineous population. A total of 1075 exome sequencing and 361 targeted gene panel sequencing were performed over 8 years at a single clinical genetics laboratory, with the majority of cases tested as proband-only (91.6%). The overall diagnostic rate was 46.7%, ranging from 24% in patients with an abnormality of prenatal development to over 67% in patients with an abnormality of the skin. We identified 660 pathogenic or likely pathogenic variants, including 241 novel variants, associated with over 342 known genetic conditions. The highly consanguineous nature of this cohort led to the diagnosis of autosomal recessive disorders in the majority of patients (79.1%) and allowed us to determine the shared carrier status of couples for suspected recessive phenotypes in their deceased child(ren) when direct testing was not possible. We also highlight the observations of recessive inheritance of genes previously associated only with dominant disorders and provide an expanded genotype–phenotype spectrum for multiple less-characterized genes. We present the largest mutational spectrum of known Mendelian disease, including possible founder variants, throughout the Iranian population, which can serve as a unique resource for clinical genomic studies locally and beyond.
Flight test results for microgravity active vibration isolation system on-board Chinese Space Station
Authors: Liu Wei , Gao Yang , Zhang Long , Zou Tianji , Yu Mengxi , Zheng Tuo
Published: February 2024

The Fluid Physics Research Rack (FPR) is a research platform employed on-board the Chinese Space Station for conducting microgravity fluid physics experiments. The research platform includes the Microgravity Active Vibration Isolation System (MAVIS) for isolating the FPR from disturbances arising from the space station itself. The MAVIS is a structural platform consisting of a stator and floater that are monitored and controlled with non-contact electromagnetic actuators, high-precision accelerometers, and displacement transducers. The stator is fixed to the FPR, while the floater serves as a vibration isolation platform supporting payloads, and is connected with the stator only with umbilicals that mainly comprise power and data cables. The controller was designed with a correction for the umbilical stiffness to minimize the effect of the umbilicals on the vibration isolation performance of the MAVIS. In-orbit test results of the FPR demonstrate that the MAVIS was able to achieve a microgravity level of 1–30 μg0 (where g0 = 9.80665 m ∙ s−2) in the frequency range of 0.01–125 Hz under the microgravity mode, and disturbances with a frequency greater than 2 Hz are attenuated by more than 10-fold. Under the vibration excitation mode, the MAVIS generated a minimum vibration acceleration of 0.4091 μg0 at a frequency of 0.00995 Hz and a maximum acceleration of 6253 μg0 at a frequency of 9.999 Hz. Therefore, the MAVIS provides a highly stable environment for conducting microgravity experiments, and promotes the development of microgravity fluid physics.
Stretchable zein-coated alginate fiber for aligning muscle cells to artificially produce cultivated meat
Authors: Jeong Dayi , Jang Goo , Jung Woo Kyung , Park Yong Ho , Bae Hojae
Published: February 2024

Numerous studies have explored the cultivation of muscle cells using non-animal materials for cultivated meat production. Achieving muscle cell proliferation and alignment using 3D scaffolds made from plant-based materials remains challenging. This study introduces a technique to culture and align muscle cells using only plant-based materials, avoiding toxic chemical modifications. Zein-alginate fibers (ZA fibers) were fabricated by coating zein protein onto alginate fibers (A fibers). Zein’s excellent cell compatibility and biodegradability enable high cell adhesion and proliferation rates, and the good ductility of the ZA fibers enable a high strain rate (>75%). We demonstrate mature and aligned myotube formation in ZA fibers, providing a simple way to align muscle cells using plant-based materials. Additionally, cultivated meat was constructed by assembling muscle, fat, and vessel fibers. This method holds promise for the future mass production of cultivated meat.
Regorafenib plus nivolumab in unresectable hepatocellular carcinoma: the phase 2 RENOBATE trial
Authors: Kim Hyung-Don , Jung Seyoung , Lim Ho Yeong , Ryoo Baek-Yeol , Ryu Min-Hee , Chuah Samuel , Chon Hong Jae , Kang Beodeul , Hong Jung Yong , Lee Han Chu , Moon Deok-Bog , Kim Ki-Hun , Kim Tae Won , Tai David , Chew Valerie , Lee Jeong Seok , Finn Richard S. , Koh June-Young , Yoo Changhoon
Published: February 2024

Regorafenib has anti-tumor activity in patients with unresectable hepatocellular carcinoma (uHCC) with potential immunomodulatory effects, suggesting that its combination with immune checkpoint inhibitor may have clinically meaningful benefits in patients with uHCC. The multicenter, single-arm, phase 2 RENOBATE trial tested regorafenib–nivolumab as front-line treatment for uHCC. Forty-two patients received nivolumab 480 mg every 4 weeks and regorafenib 80 mg daily (3-weeks-on/1-week-off schedule). The primary endpoint was the investigator-assessed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The secondary endpoints included safety, progression-free survival (PFS) and overall survival (OS). ORR per RECIST version 1.1 was 31.0%, meeting the primary endpoint. The most common adverse events were palmar-plantar erythrodysesthesia syndrome (38.1%), alopecia (26.2%) and skin rash (23.8%). Median PFS was 7.38 months. The 1-year OS rate was 80.5%, and the median OS was not reached. Exploratory single-cell RNA sequencing analyses of peripheral blood mononuclear cells showed that long-term responders exhibited T cell receptor repertoire diversification, enrichment of genes representing immunotherapy responsiveness in MKI67+ proliferating CD8+ T cells and a higher probability of M1-directed monocyte polarization. Our data support further clinical development of the regorafenib–nivolumab combination as front-line treatment for uHCC and provide preliminary insights on immune biomarkers of response. ClinicalTrials.gov identifier: NCT04310709.
Generation of complex bone marrow organoids from human induced pluripotent stem cells
Authors: Frenz-Wiessner Stephanie , Fairley Savannah D. , Buser Maximilian , Goek Isabel , Salewskij Kirill , Jonsson Gustav , Illig David , zu Putlitz Benedicta , Petersheim Daniel , Li Yue , Chen Pin-Hsuan , Kalauz Martina , Conca Raffaele , Sterr Michael , Geuder Johanna , Mizoguchi Yoko , Megens Remco T. A. , Linder Monika I. , Kotlarz Daniel , Rudelius Martina , Penninger Josef M. , Marr Carsten , Klein Christoph
Published: February 2024

The human bone marrow (BM) niche sustains hematopoiesis throughout life. We present a method for generating complex BM-like organoids (BMOs) from human induced pluripotent stem cells (iPSCs). BMOs consist of key cell types that self-organize into spatially defined three-dimensional structures mimicking cellular, structural and molecular characteristics of the hematopoietic microenvironment. Functional properties of BMOs include the presence of an in vivo-like vascular network, the presence of multipotent mesenchymal stem/progenitor cells, the support of neutrophil differentiation and responsiveness to inflammatory stimuli. Single-cell RNA sequencing revealed a heterocellular composition including the presence of a hematopoietic stem/progenitor (HSPC) cluster expressing genes of fetal HSCs. BMO-derived HSPCs also exhibited lymphoid potential and a subset demonstrated transient engraftment potential upon xenotransplantation in mice. We show that the BMOs could enable the modeling of hematopoietic developmental aspects and inborn errors of hematopoiesis, as shown for human VPS45 deficiency. Thus, iPSC-derived BMOs serve as a physiologically relevant in vitro model of the human BM microenvironment to study hematopoietic development and BM diseases.