bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Critical Role of Hydrological Distance in Shaping Nutrient Dynamics Along the Watershed‐Lake Continuum
Authors: Huang Jiacong , Arhonditsis George B. , Zhang Yinjun , Zhang Shuai , Ji Yulai , Paerl Hans W. , Jeppesen Erik , Gao Junfeng 
Published: October 2024

AbstractTerrestrial hydrological and nutrient cycles are subjected to major disturbances by agricultural operations and urbanization that profoundly influence freshwater resources. Non‐point source pollution is one of the primary causes for water quality deterioration, and thus an emerging imperative in limnology is establishing empirical models that connect watershed attributes and hydrological drivers with lake nutrient dynamics. Here, we compiled three nation‐wide nutrient, meteorological, and watershed‐landscape data sets, to develop Generalized Linear Models that predict lake phosphorus and nitrogen concentrations as a function of the surrounding watershed characteristics within various hydrological distances across 104 Chinese lakes and reservoirs. Our national‐scale investigation revealed that lake nutrient concentrations can be satisfactorily predicted by proxies of natural drivers and anthropogenic activities, reflecting the properties of the surrounding watershed. Counter to previous studies, we found that China's lake nutrient concentrations strongly depend on watershed characteristics within a hydrological distance of less than 45 km rather than the entire watershed. Furthermore, extensive human activities in watersheds not only compromise our predictive capacity, but also increase the hydrological distance that is relevant to predict lake nutrients. This national‐scale characterization can inform one of the most contentious issues in the context of China's lake management, that is, the determination of the extent of the nearshore area, where nutrient control should be prioritized. As far as we know, our study represents the first attempt to apply the concept of hydrological distance and establish statistical models that can delineate the critical spatial domain primarily responsible for the nutrient conditions along the watershed‐lake continuum.
Modeling Sediment Fluxes From Debris‐Rich Basal Ice Layers
Authors: Pierce Ethan , Overeem Irina , Jouvet Guillaume 
Published: October 2024

AbstractSediment erosion, transport, and deposition by glaciers and ice sheets play crucial roles in shaping landscapes, provide important nutrients to downstream ecosystems, and preserve key indicators of past climate conditions in the geologic record. While previous work has quantified sediment fluxes from subglacial meltwater, we also observe sediment entrained within basal ice, transported by the flow of the glacier itself. However, the formation and evolution of these debris‐rich ice layers remains poorly understood and rarely represented in landscape evolution models. Here, we identify a characteristic sequence of basal ice layers at Mendenhall Glacier, Alaska. We develop a numerical model of frozen fringe and regelation processes that describes the co‐evolution of this sequence and explore the sensitivity of the model to key properties of the subglacial sedimentary system, using the Instructed Glacier Model to parameterize ice dynamics. Then, we run numerical simulations over the spatial extent of Mendenhall Glacier, showing that the sediment transport model can predict the observed basal ice stratigraphy at the glacier's terminus. From the model results, we estimate basal ice layers transport between 23,300 and 39,800 of sediment, mostly entrained in the lowermost ice layers nearest to the bed, maximized by high effective pressures and slow, convergent flow fields. Overall, our results highlight the role of basal sediment entrainment in delivering eroded material to the glacier terminus and indicate that this process should not be ignored in broader models of landscape evolution.
Realizing Orthogonal Modes in Compact Cavity‐Backed Dual‐Polarized Antenna Through Simple Feeding Structures for Millimeter‐Wave AiP Applications
Authors: Huang Tzu‐Ming , Lin Yi‐Cheng 
Published: October 2024

AbstractThis paper presents a dual‐polarized cavity‐backed antenna designed for mm‐wave applications, featuring simple feeding structures with a high‐isolation for 60 GHz compact AiP applications. The dual‐polarization design relies on two separate feed ports that excite two orthogonal modes within the same resonant cavity, achieving very high port isolation of up to 40 dB over the entire band. We conducted a detail analysis of the antenna, including its working principles and parametric studies. For verification, we fabricated an antenna test kit using standard printed process on substrates and measured the kit from the back‐side of a GSG probing platform. The proposed antenna demonstrates a wide impedance bandwidth, stable radiation patterns, very low cross‐polarization levels, and a high radiation efficiency. The co‐located cavity‐backed design ensures the compactness and facilitates easy integration with ICs in a very small AiP module. These features make the proposed antenna highly suitable for 60 GHz AiP applications, such as high‐data‐rate wireless communication and mmW polarimetric radar systems.
Immune effector cell-associated enterocolitis following chimeric antigen receptor T-cell therapy in multiple myeloma
Authors: Fortuna Gliceida Galarza , Banerjee Rahul , Savid-Frontera Constanza , Song Jinming , Morán-Segura Carlos M. , Nguyen Jonathan V. , Lekakis Lazaros , Fernandez-Pol Sebastian , Samraj Annie N. , Naresh Kikkeri N. , Vazquez-Martinez Mariola , Baz Rachid C. , Spiegel Jay Y. , Mikkilineni Lekha , Gubatan John M. , Sidana Surbhi , de Menezes Silva Corraes Andre , Kalariya Nilesh M. , Patel Krina K. , Shim Kevin G. , Fonseca Rafael , Ferreri Christopher , Voorhees Peter M. , Richard Shambavi , Valdes Cesar Rodriguez , Sireesha Asoori  , Wolf Jeffrey L. , Cowan Andrew J. , Sborov Douglas W. , Locke Frederick L. , Lin Yi , Wang Yinghong , Hansen Doris K. 
Published: October 2024

AbstractWe report 14 cases of immune effector cell (IEC)-associated enterocolitis following chimeric antigen receptor T-cell (CAR-T) therapy in multiple myeloma, with a 1.2% incidence overall (0.2% for idecabtagene vicleucel and 2.2% for ciltacabtagene autoleucel). Patients developed acute-onset symptoms (typically non-bloody Grade 3+ diarrhea) with negative infectious workup beginning a median of 92.5 days (range: 22–210 days) after CAR-T therapy and a median of 85 days after cytokine release syndrome resolution. Gut biopsies uniformly demonstrated inflammation, including intra-epithelial lymphocytosis and villous blunting. In one case where CAR-specific immunofluorescence stains were available, CAR T-cell presence was confirmed within the lamina propria. Systemic corticosteroids were initiated in 10 patients (71%) a median of 25.5 days following symptom onset, with symptom improvement in 40%. Subsequent infliximab or vedolizumab led to improvement in 50% and 33% of corticosteroid-refractory patients, respectively. Five patients (36%) have died from bowel perforation or treatment-emergent sepsis. In conclusion, IEC-associated enterocolitis is a distinct but rare complication of CAR-T therapy typically beginning 1–3 months after infusion. Thorough diagnostic workup is essential, including evaluation for potential T-cell malignancies. The early use of infliximab or vedolizumab may potentially hasten symptom resolution and lower reliance on high-dose corticosteroids during the post-CAR-T period.
Venetoclax triggers sublethal apoptotic signaling in venetoclax-resistant acute myeloid leukemia cells and induces vulnerability to PARP inhibition and azacitidine
Authors: Tambe Mahesh , Unterberger Sarah , Kriegbaum Mette C. , Vänttinen Ida , Olgac Ezgi June , Vähä-Koskela Markus , Kontro Mika , Wennerberg Krister , Heckman Caroline A. 
Published: October 2024

AbstractVenetoclax plus azacitidine treatment is clinically beneficial for elderly and unfit acute myeloid leukemia (AML) patients. However, the treatment is rarely curative, and relapse due to resistant disease eventually emerges. Since no current clinically feasible treatments are known to be effective at the state of acquired venetoclax resistance, this is becoming a major challenge in AML treatment. Studying venetoclax-resistant AML cell lines, we observed that venetoclax induced sublethal apoptotic signaling and DNA damage even though cell survival and growth were unaffected. This effect could be due to venetoclax inducing a sublethal degree of mitochondrial outer membrane permeabilization. Based on these results, we hypothesized that the sublethal apoptotic signaling induced by venetoclax could constitute a vulnerability in venetoclax-resistant AML cells. This was supported by screens with a broad collection of drugs, where we observed a synergistic effect between venetoclax and PARP inhibition in venetoclax-resistant cells. Additionally, the venetoclax-PARP inhibitor combination prevented the acquisition of venetoclax resistance in treatment naïve AML cell lines. Furthermore, the addition of azacitidine to the venetoclax-PARP inhibitor combination enhanced venetoclax induced DNA damage and exhibited exceptional sensitivity and long-term responses in the venetoclax-resistant AML cell lines and samples from AML patients that had clinically relapsed under venetoclax-azacitidine therapy. In conclusion, we mechanistically identify a new vulnerability in acquired venetoclax-resistant AML cells and identify PARP inhibition as a potential therapeutic approach to overcome acquired venetoclax resistance in AML.
All-optical reporting of inhibitory receptor driving force in the nervous system
Authors: Selfe Joshua S. , Steyn Teresa J. S. , Shorer Eran F. , Burman Richard J. , Düsterwald Kira M. , Kraitzick Ariel Z. , Abdelfattah Ahmed S. , Schreiter Eric R. , Newey Sarah E. , Akerman Colin J. , Raimondo Joseph V. 
Published: October 2024

AbstractIonic driving forces provide the net electromotive force for ion movement across receptors, channels, and transporters, and are a fundamental property of all cells. In the nervous system, fast synaptic inhibition is mediated by chloride permeable GABAA and glycine receptors, and single-cell intracellular recordings have been the only method for estimating driving forces across these receptors (DFGABAA). Here we present a tool for quantifying inhibitory receptor driving force named ORCHID: all-Optical Reporting of CHloride Ion Driving force. We demonstrate ORCHID’s ability to provide accurate, high-throughput measurements of resting and dynamic DFGABAA from genetically targeted cell types over multiple timescales. ORCHID confirms theoretical predictions about the biophysical mechanisms that establish DFGABAA, reveals differences in DFGABAA between neurons and astrocytes, and affords the first in vivo measurements of intact DFGABAA. This work extends our understanding of inhibitory synaptic transmission and demonstrates the potential for all-optical methods to assess ionic driving forces.
Genetic architecture of routinely acquired blood tests in a British South Asian cohort
Authors: Jacobs Benjamin M. , Stow Daniel , Hodgson Sam , Zöllner Julia , Samuel Miriam , Kanoni Stavroula , Bidi Saeed ,   Genes & Health Research Team, Akhtar Shaheen , Anwar Mohammad , Arciero Elena , Asgar Omar , Ashraf Samina , Bidi Saeed , Breen Gerome , Broster James , Chung Raymond , Collier David , Curtis Charles J. , Chaudhary Shabana , Clinch Megan , Colligan Grainne , Deloukas Panos , Durham Ceri , Durrani Faiza , Eto Fabiola , Finer Sarah , Gafton Joseph , Garcia Ana Angel , Griffiths Chris , Harvey Joanne , Heng Teng , Hodgson Sam , Huang Qin Qin , Hurles Matt , Hunt Karen A. , Hussain Shapna , Islam Kamrul , Iyer Vivek , Jacobs Ben , Khan Ahsan , Lavery Cath , Lee Sang Hyuck , Lerner Robin , MacArthur Daniel , Malawsky Daniel , Martin Hilary , Mason Dan , Mathur Rohini , Mazid Mohammed Bodrul , McDermott John , Morton Caroline , Newman Bill , Owor Elizabeth , Qureshi Asma , Rahman Samiha , Ramachandrappa Shwetha , Reza Mehru , Russell Jessry , Safa Nishat , Samuel Miriam , Simpson Michael , Solly John , Spreckley Marie , Stow Daniel , Taylor Michael , Trembath Richard C. , Tricker Karen , Uddin Nasir , van Heel David A. , Walter Klaudia , Winckley Caroline , Wood Suzanne , Wright John , Zollner Julia , Walter Klaudia , Langenberg Claudia , Dobson Ruth , Finer Sarah , Morton Caroline , Siddiqui Moneeza K. , Martin Hilary C. , Pietzner Maik , Mathur Rohini , van Heel David A. 
Published: October 2024

AbstractUnderstanding the genetic basis of routinely-acquired blood tests can provide insights into several aspects of human physiology. We report a genome-wide association study of 42 quantitative blood test traits defined using Electronic Healthcare Records (EHRs) of ~50,000 British Bangladeshi and British Pakistani adults. We demonstrate a causal variant within the PIEZO1 locus which was associated with alterations in red cell traits and glycated haemoglobin. Conditional analysis and within-ancestry fine mapping confirmed that this signal is driven by a missense variant - chr16-88716656-G-TT - which is common in South Asian ancestries (MAF 3.9%) but ultra-rare in other ancestries. Carriers of the T allele had lower mean HbA1c values, lower HbA1c values for a given level of random or fasting glucose, and delayed diagnosis of Type 2 Diabetes Mellitus. Our results shed light on the genetic basis of clinically-relevant traits in an under-represented population, and emphasise the importance of ancestral diversity in genetic studies.
On-chip phonon-enhanced IR near-field detection of molecular vibrations
Authors: Bylinkin Andrei , Castilla Sebastián , Slipchenko Tetiana M. , Domina Kateryna , Calavalle Francesco , Pusapati Varun-Varma , Autore Marta , Casanova Fèlix , Hueso Luis E. , Martín-Moreno Luis , Nikitin Alexey Y. , Koppens Frank H. L. , Hillenbrand Rainer 
Published: October 2024

AbstractPhonon polaritons – quasiparticles formed by strong coupling of infrared (IR) light with lattice vibrations in polar materials – can be utilized for surface-enhanced infrared absorption (SEIRA) spectroscopy and even for vibrational strong coupling with nanoscale amounts of molecules. Here, we introduce and demonstrate a compact on-chip phononic SEIRA spectroscopy platform, which is based on an h-BN/graphene/h-BN heterostructure on top of a metal split-gate creating a p-n junction in graphene. The metal split-gate concentrates the incident light and launches hyperbolic phonon polaritons (HPhPs) in the heterostructure, which serves simultaneously as SEIRA substrate and room-temperature infrared detector. When thin organic layers are deposited directly on top of the heterostructure, we observe a photocurrent encoding the layer’s molecular vibrational fingerprint, which is strongly enhanced compared to that observed in standard far-field absorption spectroscopy. A detailed theoretical analysis supports our results, further predicting an additional sensitivity enhancement as the molecular layers approach deep subwavelength scales. Future on-chip integration of infrared light sources such as quantum cascade lasers or even electrical generation of the HPhPs could lead to fully on-chip phononic SEIRA sensors for molecular and gas sensing.
Spatial transcriptomics of a parasitic flatworm provides a molecular map of drug targets and drug resistance genes
Authors: Gramberg Svenja , Puckelwaldt Oliver , Schmitt Tobias , Lu Zhigang , Haeberlein Simone 
Published: October 2024

AbstractThe spatial organization of gene expression dictates tissue functions in multicellular parasites. Here, we present the spatial transcriptome of a parasitic flatworm, the common liver fluke Fasciola hepatica. We identify gene expression profiles and marker genes for eight distinct tissues and validate the latter by in situ hybridization. To demonstrate the power of our spatial atlas, we focus on genes with substantial medical importance, including vaccine candidates (Ly6 proteins) and drug resistance genes (glutathione S-transferases, ABC transporters). Several of these genes exhibit unique expression patterns, indicating tissue-specific biological functions. Notably, the prioritization of tegumental protein kinases identifies a PKCβ, for which small-molecule targeting causes parasite death. Our comprehensive gene expression map provides unprecedented molecular insights into the organ systems of this complex parasitic organism, serving as a valuable tool for both basic and applied research.
Evidence of a 4.33 billion year age for the Moon’s South Pole–Aitken basin
Authors: Joy K. H. , Wang N. , Snape J. F. , Goodwin A. , Pernet-Fisher J. F. , Whitehouse M. J. , Liu Y. , Lin Y. T. , Darling J. R. , Tar P. , Tartèse R. 
Published: October 2024

Abstract
The Moon’s farside South Pole–Aitken (SPA) basin is the largest and oldest visible impact basin in the inner Solar System. Determining the timing of this catastrophic event is key to understanding the onset of the lunar basin-forming epoch, with implications for understanding the impact bombardment history of the inner Solar System. Despite this, the formation age of the SPA basin remains poorly constrained. Here we show that the chemical composition of the lunar meteorite Northwest Africa 2995 is in good agreement with lithologies exposed within the southern region of the SPA basin. Radiometric dating of a range of mineral and rock components in Northwest Africa 2995 yielded consistent dates of ~4.32–4.33 billion years old. We interpret these dates as the age of SPA basin formation, inferring that this event occurred ~120 million years before the formation of the main cluster of lunar impact basins between ~4.2 Ga and 3.8 Ga. This weakens support for a narrow period of lunar late heavy impact bombardment and also implies that the earliest formed impact basins on the Moon (that is, >4.33–4.5 Ga old) were erased either by the SPA impact itself when its formation caused massive resurfacing of the lunar surface or through other geological processes.
An ancient ecospecies of Helicobacter pylori
Authors: Tourrette Elise , Torres Roberto C. , Svensson Sarah L. , Matsumoto Takashi , Miftahussurur Muhammad , Fauzia Kartika Afrida , Alfaray Ricky Indra , Vilaichone Ratha-Korn , Tuan Vo Phuoc ,   Helicobacter Genomics Consortium, Aftab Hafeza , Tshering Lotay , Prasad Dhakal Guru , Tshibangu-Kabamba Evariste , Tumba Ghislain Disashi , de Jesus Ngoma-Kisoko Patrick , Tshimpi-Wola Antoine , Ngoyi Dieudonné Mumba , Kashala Pascal Tshiamala , Cruz Modesto , Abreu José Jiménez , Hosking Celso , Ronkainen Jukka , Aro Pertti , Sugihartono Titong , Syam Ari Fahrial , Waskito Langgeng Agung , Maulahela Hasan , Rezkitha Yudith Annisa Ayu , Panirani Shaho Negahdar , Aghdaei Hamid Asadzadeh , Zali Mohammad Reza , Mirzaei Nasrin , Latifi-Navid Saeid , Matsuhisa Takeshi , Subsomwong Phawinee , Terao Hideo , Saruuljavkhlan Batsaikhan , Shimoyama Tadashi , Kinjo Nagisa , Kinjo Fukunori , Murakami Kazunari , Myint Thein , Aye Than Than , Ni New , Yee Than Than , Htet Kyaw , Shrestha Pradeep Krishna , Sharma Rabi Prakash , Rathnayake Jeewantha , Lamawansa Meegahalande Durage , Rudbeck Emilio , Agreus Lars , Andreasson Anna , Engstrand Lars , Mahachai Varocha , Ratanachu-Ek Thawee , Pawa Kammal Kumar , Thi Huyen Trang Tran , Binh Tran Thanh , Khien Vu Van , Dung Ho Dang Quy , Narith Dou , Wang Difei , Yadegar Abbas , Olsson Lisa M. , Zhou Zhemin , Yamaoka Yoshio , Thorell Kaisa , Falush Daniel 
Published: October 2024

AbstractHelicobacter pylori disturbs the stomach lining during long-term colonization of its human host, with sequelae including ulcers and gastric cancer1,2. Numerous H. pylori virulence factors have been identified, showing extensive geographic variation1. Here we identify a ‘Hardy’ ecospecies of H. pylori that shares the ancestry of ‘Ubiquitous’ H. pylori from the same region in most of the genome but has nearly fixed single-nucleotide polymorphism differences in 100 genes, many of which encode outer membrane proteins and host interaction factors. Most Hardy strains have a second urease, which uses iron as a cofactor rather than nickel3, and two additional copies of the vacuolating cytotoxin VacA. Hardy strains currently have a limited distribution, including in Indigenous populations in Siberia and the Americas and in lineages that have jumped from humans to other mammals. Analysis of polymorphism data implies that Hardy and Ubiquitous coexisted in the stomachs of modern humans since before we left Africa and that both were dispersed around the world by our migrations. Our results also show that highly distinct adaptive strategies can arise and be maintained stably within bacterial populations, even in the presence of continuous genetic exchange between strains.
Spatial proteomics identifies JAKi as treatment for a lethal skin disease
Authors: Nordmann Thierry M. , Anderton Holly , Hasegawa Akito , Schweizer Lisa , Zhang Peng , Stadler Pia-Charlotte , Sinha Ankit , Metousis Andreas , Rosenberger Florian A. , Zwiebel Maximilian , Satoh Takashi K. , Anzengruber Florian , Strauss Maximilian T. , Tanzer Maria C. , Saito Yuki , Gong Ting , Thielert Marvin , Kimura Haruna , Silke Natasha , Rodriguez Edwin H. , Restivo Gaetana , Nguyen Hong Ha , Gross Annette , Feldmeyer Laurence , Joerg Lukas , Levesque Mitchell P. , Murray Peter J. , Ingen-Housz-Oro Saskia , Mund Andreas , Abe Riichiro , Silke John , Ji Chao , French Lars E. , Mann Matthias 
Published: October 2024

AbstractToxic epidermal necrolysis (TEN) is a fatal drug-induced skin reaction triggered by common medications and is an emerging public health issue1–3. Patients with TEN undergo severe and sudden epidermal detachment caused by keratinocyte cell death. Although molecular mechanisms that drive keratinocyte cell death have been proposed, the main drivers remain unknown, and there is no effective therapy for TEN4–6. Here, to systematically map molecular changes that are associated with TEN and identify potential druggable targets, we utilized deep visual proteomics, which provides single-cell-based, cell-type-resolution proteomics7,8. We analysed formalin-fixed, paraffin-embedded archived skin tissue biopsies of three types of cutaneous drug reactions with varying severity and quantified more than 5,000 proteins in keratinocytes and skin-infiltrating immune cells. This revealed a marked enrichment of type I and type II interferon signatures in the immune cell and keratinocyte compartment of patients with TEN, as well as phosphorylated STAT1 activation. Targeted inhibition with the pan-JAK inhibitor tofacitinib in vitro reduced keratinocyte-directed cytotoxicity. In vivo oral administration of tofacitinib, baricitinib or the JAK1-specific inhibitors abrocitinib or upadacitinib ameliorated clinical and histological disease severity in two distinct mouse models of TEN. Crucially, treatment with JAK inhibitors (JAKi) was safe and associated with rapid cutaneous re-epithelialization and recovery in seven patients with TEN. This study uncovers the JAK/STAT and interferon signalling pathways as key pathogenic drivers of TEN and demonstrates the potential of targeted JAKi as a curative therapy.