bluuebunny/crossref_metadata_2025 huggingface dataset:
A global land cover training dataset from 1984 to 2020
Authors: Stanimirova Radost , Tarrio Katelyn , Turlej Konrad , McAvoy Kristina , Stonebrook Sophia , Hu Kai-Ting , Arévalo Paulo , Bullock Eric L. , Zhang Yingtong , Woodcock Curtis E. , Olofsson Pontus , Zhu Zhe , Barber Christopher P. , Souza Carlos M. , Chen Shijuan , Wang Jonathan A. , Mensah Foster , Calderón-Loor Marco , Hadjikakou Michalis , Bryan Brett A. , Graesser Jordan , Beyene Dereje L. , Mutasha Brian , Siame Sylvester , Siampale Abel , Friedl Mark A.
Published: December 2023

State-of-the-art cloud computing platforms such as Google Earth Engine (GEE) enable regional-to-global land cover and land cover change mapping with machine learning algorithms. However, collection of high-quality training data, which is necessary for accurate land cover mapping, remains costly and labor-intensive. To address this need, we created a global database of nearly 2 million training units spanning the period from 1984 to 2020 for seven primary and nine secondary land cover classes. Our training data collection approach leveraged GEE and machine learning algorithms to ensure data quality and biogeographic representation. We sampled the spectral-temporal feature space from Landsat imagery to efficiently allocate training data across global ecoregions and incorporated publicly available and collaborator-provided datasets to our database. To reflect the underlying regional class distribution and post-disturbance landscapes, we strategically augmented the database. We used a machine learning-based cross-validation procedure to remove potentially mis-labeled training units. Our training database is relevant for a wide array of studies such as land cover change, agriculture, forestry, hydrology, urban development, among many others.
A dataset of proteomic changes during human heat stress and heat acclimation
Authors: Gagnon Daniel , Barry Hadiatou , Barhdadi Amina , Oussaid Essaid , Mongrain Ian , Lemieux Perreault Louis-Philippe , Dubé Marie-Pierre
Published: December 2023

Hotter climates have important impacts on human health and performance. Yet, the cellular and molecular responses involved in human heat stress and acclimation remain understudied. This dataset includes physiological measurements and the plasma concentration of 2,938 proteins collected from 10 healthy adults, before and during passive heat stress that was performed both prior to and after a 7-day heat acclimation protocol. Physiological measurements included body temperatures, sweat rate, cutaneous vascular conductance, blood pressure, and skin sympathetic nerve activity. The proteomic dataset was generated using the Olink Explore 3072 assay, enabling a high-multiplex antibody-based assessment of protein changes based on proximity extension assay technology. The data need to be interpreted in the context of the moderate level of body hyperthermia attained and the specific demographic of young, healthy adults. We have made this dataset publicly available to facilitate research into the cellular and molecular mechanisms involved in human heat stress and acclimation, crucial for addressing the health and performance challenges posed by rising temperatures.
Identification of a cancer associated fibroblasts-related index to predict prognosis and immune landscape in ovarian cancer
Authors: Ye Yingquan , Zhang Shuangshuang , Jiang Yue , Huang Yi , Wang Gaoxiang , Zhang Mengmeng , Gui Zhongxuan , Wu Yue , Bian Geng , Li Ping , Zhang Mei
Published: December 2023

Cancer-associated fibroblasts (CAFs) play a role in ovarian cancer (OV) evolution, immunosuppression and promotion of drug resistance. Exploring the value of CAFs-related biomarker in OV is of great importance. In the present work, we developed a CAFs-related index (CAFRI) based on an integrated analysis of single-cell and bulk RNA-sequencing and highlighted the value of CAFRI in predicting clinical outcomes in individuals with OV, tumour immune microenvironment (TIME) and response to immune checkpoint inhibitors (ICIs). The GSE151214 cohort was used for cell subpopulation localization and analysis, the TCGA-OV patients as a training set. Moreover, the ICGC-OV, GSE26193, GSE26712 and GSE19829 cohorts were used for the validation of CAFRI. The TIMER 2.0, CIBERSORT and ssGSEA algorithms were used for analysis of TIME characteristics based on the CAFRI. The GSVA, GSEA, GO, KEGG and tumour mutation burden (TMB) analyses were used for mechanistic exploration. Additionally, the IMvigor210 cohort was conducted to validate the predictive value of CAFRI on the efficacy of ICIs. Finally, CAFRI-based antitumour drug sensitivity was analysed. The findings demonstrate that the CAFRI can served as an excellent predictor of prognosis for individuals with OV, as well as identifying patients with different TIME characteristics, differentiating between immune ‘hot’ and ‘cold’ tumour populations, and providing new insights into the selection of ICIs and personalised treatment regimens. CAFRI provides new perspectives for the development of novel prognostic and immunotherapy efficacy predictive biomarkers for OV.
Enhancing the inherent NIR photoluminescence in SrLaLiTeO6 through Cr3+–Yb3+ co-substitution for high performance pc-LEDs
Authors: Lal Sariga C. , Jawahar I. N. , Ganesanpotti Subodh
Published: December 2023

NIR pc-LEDs developed with Cr3+ and Yb3+ co-doped SrLaLiTeO6 phosphor have promising applications in wearable biosensors and food analysis.
In situ sonochemical synthesis of flower-like N-graphyne/BiOCl0.5Br0.5 microspheres for efficient removal of levofloxacin
Authors: Li Shuyan , Sun Mingxuan , Huang Xiangzhi , Chen Haohao , Zhao Junjie , Li Ziyang
Published: December 2023

A series of flower-like N-graphyne/BiOCl0.5Br0.5 microspheres are constructed through an in situ sonochemical synthesis method. The improved adsorption and photocatalytic performance for the removal of levofloxacin are verified.
Contrasted redox-dependent structural control on Fe isotope fractionation during its adsorption onto and assimilation by heterotrophic soil bacteria
Authors: González Aridane G. , Poitrasson Franck , Jiménez-Villacorta Felix , Shirokova Liudmila S. , Pokrovsky Oleg S.
Published: December 2023

Despite the importance of structural control on metal stable isotope fractionation in inorganic and abiotic systems, the link between metal structural changes and related isotopic fractionation during reactions with organic surfaces and live cells remains poorly established.
How do certain atmospheric aerosols affect Cu-binding organic ligands in the oligotrophic coastal sea surface microlayer?
Authors: Strmečki Slađana , Dešpoja Iva , Penezić Abra , Milinković Andrea , Alempijević Saranda Bakija , Kiss Gyula , Hoffer András , Mitić Božena , Hruševar Dario , Frka Sanja
Published: December 2023

We showed that oligotrophic coastal marine areas are susceptible to the deposition of pollen and aerosols from open-fire biomass burning, which alter Cu-binding organic ligands in the sea surface microlayer.
Photoredox catalyzed release of carbon-based radicals from 2-substituted-1,3-imidazolidines
Authors: Luguera Ruiz Adrián , Mariani Elena , Protti Stefano , Fagnoni Maurizio
Published: December 2023

We describe herein easily oxidizable 2-substituted-1,3-imidazolidines for the photocatalyzed generation of (substituted) alkyl radicals for the forging of C(sp3)–C(sp3) bonds under metal-free conditions.
Regulation of Na+-K+-ATPase leads to disturbances of isoproterenol-induced cardiac dysfunction via interference of Ca2+-dependent cardiac metabolism
Authors: Yan Xiaofei , Li Meihe , Lan Ping , Xun Meng , Zhang Ying , Shi Jinghui , Wang Ruijia , Zheng Jin
Published: December 2023

Reductions in Na+-K+-ATPase (NKA) activity and expression are often observed in the progress of various reason-induced heart failure (HF). However, NKA α1 mutation or knockdown cannot cause spontaneous heart disease. Whether the abnormal NKA α1 directly contributes to HF pathogenesis remains unknown. Here, we challenge NKA α1+/- mice with isoproterenol to evaluate the role of NKA α1 haploinsufficiency in isoproterenol (ISO)-induced cardiac dysfunction. Genetic knockdown of NKA α1 accelerated ISO-induced cardiac cell hypertrophy, heart fibrosis, and dysfunction. Further studies revealed decreased Krebs cycle, fatty acid oxidation, and mitochondrial OXPHOS in the hearts of NKA α1+/- mice challenged with ISO. In ISO-treated conditions, inhibition of NKA elevated cytosolic Na+, further reduced mitochondrial Ca2+ via mNCE, and then finally down-regulated cardiac cell energy metabolism. In addition, a supplement of DRm217 alleviated ISO-induced heart dysfunction, mitigated cardiac remodeling, and improved cytosolic Na+ and Ca2+ elevation and mitochondrial Ca2+ depression in the NKA α1+/− mouse model. The findings suggest that targeting NKA and mitochondria Ca2+ could be a promising strategy in the treatment of heart disease.
Combined latissimus dorsi transfer and deltoid flap for irreparable rotator cuff tear: A retrospective analysis
Authors: Roukoz Sami , George Samuel , Aoun Marven , Daher Mohammad
Published: December 2023

Purpose: This study will evaluate the outcomes of the combined latissimus dorsi tendon transfer and deltoid flap for the management of irreparable posterosuperior rotator cuff tears. Methods: This is a retrospective study of 15 patients who have undergone double transfer surgery for their irreparable posterosuperior rotator cuff tears. These patients were followed up in three periods. Functional outcomes such as the constant score (CS), subjective shoulder value (SSV), and range of motion were assessed as well as radiographic outcomes such as the acromio–humeral distance. Results: Fifteen patients were included in the early and intermediate follow-up while only 8 remained at the latest follow-up. At the early follow-up the SSV (p = 0.001), CS (p = 0.021), and A–H distance (p = 0.008) showed a statistically significant improvement from their pre-operative values. At the latest follow-up, only the external rotation decreased from its value at the intermediate follow-up (p = 0.027). Conclusion: The double transfer technique showed sustainable improvement of the functional outcomes except for the external rotation. However, the loss of external rotation did not affect the remaining outcomes. Trials comparing this technique to other surgical managements or MIRCTs are needed to confirm these results.
Predictors of in-hospital mortality in older patients undergoing distal femur fracture surgery: A case-control study
Authors: Cheng Ting-An , Lai Po-Hsuan , Chuang Hao-Chun , Hsu Kai-Lan , Kuan Fa-Chuan , Su Wei-Ren , Hong Chih-Kai
Published: December 2023

Introduction: Geriatric fractures including distal femur and hip fractures are associated with high mortality rates. Currently, prognostic factors for in-hospital postoperative mortality are not identified. We aimed to evaluate overall in-hospital mortality and related potential risk factors in elderly patients who underwent distal femur fracture surgery. Materials and methods: A retrospective cohort study of patients older than 60 years, who underwent distal femur fracture surgery between January 01, 2003, and December 31, 2021, was conducted. A case-control study was conducted to compare two age-matched groups of elderly patients of equivalent ages at a 1:4 ratio. The in-hospital mortality rate was calculated and potential confounders were compared between groups. Results: A total of 170 patients were enrolled; five died during hospital stay after undergoing surgery, yielding a 2.94% in-hospital mortality rate. Twenty patients who did not die were included in the control group. Patients’ demographics were similar. The case-control comparison showed that the time from injury to surgery, preoperative hemoglobin level, estimated glomerular filtration rate (eGFR), and white blood cell count were significant factors correlated with in-hospital mortality. Discussion: The overall in-hospital mortality rate was 2.94%. Significant risk factors for in-hospital mortality included a longer time from injury to surgery, lower preoperative hemoglobin level and eGFR, and higher preoperative white blood cell count. In conclusion, preoperative comprehensive geriatric assessment, including cognitive, nutritional, and frailty status, should also be considered in the elderly fracture care model.
Assessing low laser damage densities of fused silica optics by means of a functional raster scan protocol
Authors: Lamaignère L. , Bouyer C. , Donval T. , Beau V. , Lacombe C.
Published: December 2023

The knowledge of the laser damage resistance of fused silica optics for their use in high-power lasers is of primary importance for the operation and maintenance of these facilities. Among the control procedures developed, one of the most relevant to date is the raster scan procedure [Lamaignère et al., Rev. Sci. Instrum. 78, 103105 (2007)]. This procedure is used to determine the damage density of optical components as a function of fluence. To date, this procedure takes into account all triggered damage sites, regardless of their size and/or morphology. We have added a step to this procedure, which consists in irradiating again all the damage sites with a series of shots to ascertain their ability to grow. This allows us to estimate the densities of growing damage sites, which are most critical for the safe operation of lasers. This pragmatic approach can be considered a functional test procedure. By applying this procedure to large optical areas, we were then able to measure extremely low damage densities (∼10−4 damage cm−2) over a wide range of fluences [0–18 J cm−2], corresponding to fluences to which the optics are irradiated during the operation of high-power lasers. We can then determine the damage law of a given set of optical components. This reference law makes it possible, on the one hand, to predict the lifetime of the optics. On the other hand, any deviation can then be analyzed with regard to this reference law. Thanks to the determination of confidence intervals, this functional procedure can also be used to delimit the reference law by upper and lower bounds.
Relationship between wake and cylinder dynamics for a cylinder undergoing modulated vortex-induced vibrations
Authors: Hassanpour Maziyar , Morton Chris , Martinuzzi Robert J.
Published: December 2023

Vortex-induced vibrations (VIV) in the initial branch are investigated for a 2-degree-of-freedom circular cylinder placed near a plane boundary (Re=UDν=200, where U is the inflow average streamwise velocity, D is the cylinder diameter, and ν is the kinematic viscosity) with imposed sinusoidal perturbations of the free stream at resonant, 2fo, and near-resonant conditions, 2.2fo (fo is the natural shedding frequency). The cylinder exhibits a quasi-periodic response, which challenges the comprehension of its relationship with the wake dynamics obtained through conventional VIV models. The total force acting on the cylinder is decomposed into a vortex-induced force, FV, linearly coupled to VIV, and a force induced by the effective mass of the cylinder, FS, which is non-linearly coupled to VIV. The proposed semi-empirical model reveals that the time-varying nature of the effective mass in FS drives the non-linear response. The model's physical consistency is verified against simulation results. While focusing on VIV in the initial branch, the validity of the proposed model is expected to extend to other branches of response, offering a promising avenue for developing a robust predictive model for VIV under various flow conditions.
Diversity and distribution of cetaceans in the Republic of Palau
Authors: Andrews Olive , Holm Tiare , Burns Daniel , Hom-Weaver Cory Ann , Olavarria Carlos , Orrukem David , Percy Rechelluul , Williams Rob
Published: December 2023

Context Until recently, very little was known about the species diversity and occurrence of cetaceans in the Republic of Palau. A dedicated scientific investigation into the occurrence and distribution of island associated cetaceans in Palau was conducted in 2012 and 2013. Aims The aim of this project was to investigate the diversity and distribution of cetaceans in Palau to inform management and build local capacity in cetacean science. Methods Following a feasibility study in 2010, a vessel-based visual and acoustic line transect survey was conducted in 2012, covering a survey area of 4319 km2. The survey was repeated and expanded in 2013 using aerial methods. Additionally, small boat work was conducted in areas with high cetacean density to obtain genetic, acoustic, and photographic samples. In 2019, a vessel-based visual and acoustic survey of the Southwest Islands was conducted. Key results By combining the survey results with anecdotal sightings, a cetacean species inventory for Palau was established. The presence of 15 species was confirmed, while four species were identified as probably present and three as likely. Conclusions Survey results contributed to the management of cetaceans in the Palau Marine Mammal Sanctuary. The surveys raised local interest in cetaceans and, through public outreach and training, precipitated advancements in capacity building for cetacean management, along with a baseline for ongoing monitoring. Implications This study provided the first systematic, scientific investigation using multiple survey methods into the occurrence and distribution of cetaceans in Palau, highlighting the importance of conserving cetacean populations in this region.
Neutrino production in blazar radio cores
Authors: Kalashev Oleg , Kivokurtseva Polina , Troitsky Sergey
Published: December 2023

Models of the origin of astrophysical neutrinos with energies from TeVs to PeVs are strongly constrained by multimessenger observations and population studies. Recent results point to statistically significant associations between these neutrinos and active galactic nuclei (AGN) selected by their radio flux observed with very-long-baseline interferometry (VLBI). This suggests that the neutrinos are produced in central parsecs of blazars, AGN with relativistic jets pointing to the observer. However, conventional AGN models tend to explain only the highest-energy part of the neutrino flux observationally associated with blazars. Here we discuss in detail how the neutrinos can be produced in the part of an AGN giving the dominant contribution to the VLBI radio flux, the radio core located close to the jet base. Physical conditions there differ both from the immediate environment of the central black hole and from the plasma blobs moving along the jet. Required neutrino fluxes, considerably smaller than those of photons, can be produced in interactions of relativistic protons, accelerated closer to the black hole, with radiation in the core.
Rotational Phase Dependent J − H Colour of the Dwarf Planet Eris*
Authors: Szakáts Róbert , Kiss Csaba
Published: December 2023

The largest bodies—or dwarf planets—constitute a different class among Kuiper Belt objects and are characterized by bright surfaces and volatile compositions remarkably different from that of smaller trans-Neptunian objects. These compositional differences are also reflected in the visible and near-infrared colors, and variegations across the surface can cause broadband colors to vary with rotational phase. Here we present near-infrared J and H-band observations of the dwarf planet (136199) Eris obtained with the GuideDog camera of the Infrared Telescope Facility. These measurements show that—as suspected from previous J − H measurements—the J − H color of Eris indeed varies with rotational phase. This suggests notable surface heterogenity in chemical composition and/or other material properties despite the otherwise quite homogeneous, high albedo surface, characterized by a very low amplitude visible range light curve. While variations in the grain size of the dominant CH4 may in general be responsible for notable changes in the J − H color, in the current observing geometry of the system it can only partially explain the observed J − H variation.
Uptake of plutonium isotopes by green onions in different growing mediums
Authors: Shavrina K E , Edomskaya M A , Lukashenko S N , Kuzmenkova N V
Published: December 2023

During the growing experiment, the uptake of plutonium isotopes by green onions (Allium cepa Centurion F1) grown on distilled water, Ellis nutrient solution and sod-podzolic soil was studied. The analysis of plutonium isotopes was carried out by alpha spectrometry with preliminary radiochemical separation. It has been determined that the uptake of 239+240Pu by the green onions decreases in a row: distilled water > Ellis nutrient solution ≫ sod-podzolic soil. The transfer factors of plutonium isotopes in green onions were 1.7 ± 0.4 for distilled water; 0.7 ± 0.2 for Ellis nutrient solution; 0.0054 ± 0.0014 for soddy-podzolic soil.
Deuterium recycling and wall retention characteristics during boron powder injection in EAST
Authors: Zuo G Z , Wang Z , Sun Z , Xu W , Zhou Z T , Guan Y H , Huang M , Maingi R , Hu J S
Published: December 2023

Boron (B), as a low-Z material, is widely employed for wall conditioning to enhance plasma performance in fusion devices. In the Experimental Advanced Superconducting Tokamak, a series of experiments involving real-time B powder injection has been conducted to investigate fuel particle behavior. It was observed that fuel particle recycling decreased with an increase in the amount of B powder injected, resulting in an increase in short-term fuel retention. The fuel recycling decreased by up to 80%, as indicated by divertor neutral pressure and Dα line emission. Furthermore, each B atom exhibited a trapping capacity of 0.3 D particles during B powder injection at a typical flow rate. The real-time B injection had no wall hysteresis effect on D retention, implying that cumulative B injection and deposited film did not affect long-term D retention. The possible mechanism for D retention is the formation of B-C-O-D compounds and co-deposition between B and D particles during discharges. This investigation would be valuable for evaluating T retention when B is used as wall conditioning material in future fusion reactor devices.
Assessing the potential of recycled fine aggregate from freeze-thawed parent concrete for structural concrete
Authors: Hong Wei , Shen Changjun , Zhu Xing
Published: December 2023

Recycled fine aggregate (RFA) generated from waste concrete, especially in harsh environment, can be considered as an alternative to natural sand. The yield rate, gradation and properties of RFA from natural aggregate concrete with the target strength of C40 as parent concrete (PC) every 200 freeze–thaw (FT) cycles are investigated. To more accurately evaluate the application potential of RFA, the mechanical properties and durability of recycled fine aggregate concrete (RFAC) is further studied. The results showed that as the FT cycles of PC increased, the yield rate of RFA decreases and the grading curve of RFA meets the requirements of Class II aggregate. The limit FT cycles of PC in Class II and III RFA are 148 and 450, respectively. For the compressive strength of RFAC that meets the design requirements, the FT cycles of PC are no more than 530. Based on 50 years of RFAC in Class D and Class E environments, the limit FT cycles of PC are 663 and 200, respectively. The limit FT cycles of PC are 221 based on 50 years of RFAC service in cold regions. Through the FT cycles of PC, the Class of RFA and the mechanical and durability of RFAC can be directly predicted. This provides a theoretical and data support for improving the utilization rate of waste concrete in FT environment.
Intake and growth histories modulate bone morphology, microarchitecture, and mineralization in juvenile green turtles (Chelonia mydas)
Authors: Abell Morgan C , Sánchez Hernández José A , Bast Robin , Bjorndal Karen A , Bolten Alan B , Roark Alison M
Published: December 2023

Compensatory growth (CG) is accelerated growth that occurs when food availability increases after food restriction. This rapid growth may be associated with sublethal consequences. In this study, we investigated the effects of food restriction and subsequent realimentation and CG on bone structure in juvenile green turtles (Chelonia mydas). Turtles were fed ad libitum food for 12 weeks (AL), restricted food for 12 weeks (R), or restricted food for 5 weeks followed by ad libitum food for 7 weeks (R-AL). R-AL turtles demonstrated partial CG via enhanced food conversion efficiency (FCE) upon realimentation. After the 12th week, gross morphology (GM), microarchitecture, and mineralization of the right humerus of each turtle were analyzed. Many GM measurements (including proximal and maximal bone lengths, bone widths, and shaft thickness), most measurements of bone microarchitecture (excluding cortical and trabecular thickness and trabecular separation), and all mineralization measurements were labile in response to intake. We examined the possibility that changes in nutrient allocation to bone structure during realimentation facilitated CG in previously food-restricted turtles. Restoration of bone lengths was prioritized over restoration of bone widths during CG. Furthermore, restoration of trabecular number, connectivity density, and bone volume fraction was prioritized over restoration of cortical bone volume fraction. Finally, diaphyseal bone mineralization was partially restored, whereas no restoration of epiphyseal bone mineralization occurred during CG. Shifts in nutrient allocation away from certain bone attributes during food restriction that were not rectified when food availability increased probably provided an energy surplus that enhanced the conversion of food to growth and thus powered the CG response. Our study revealed how resource allocation to various bone attributes is prioritized as nutritional conditions change during development. These “priority rules” may have detrimental consequences later in life, indicating that conservation of green turtle foraging grounds should be given high priority.
Behavioural digital biomarkers enable real-time monitoring of patient-reported outcomes: a substudy of the multicentre, prospective observational SafeHeart study
Authors: Kolk Maarten Z H , Frodi Diana M , Langford Joss , Meskers Caroline J , Andersen Tariq O , Jacobsen Peter Karl , Risum Niels , Tan Hanno L , Svendsen Jesper H , Knops Reinoud E , Diederichsen Søren Z , Tjong Fleur V Y
Published: December 2023

Aims

Patient-reported outcome measures (PROMs) serve multiple purposes, including shared decision-making and patient communication, treatment monitoring, and health technology assessment. Patient monitoring using PROMs is constrained by recall and non-response bias, respondent burden, and missing data. We evaluated the potential of behavioural digital biomarkers obtained from a wearable accelerometer to achieve personalized predictions of PROMs.

Methods and results

Data from the multicentre, prospective SafeHeart study conducted at Amsterdam University Medical Center in the Netherlands and Copenhagen University Hospital, Rigshospitalet in Copenhagen, Denmark, were used. The study enrolled patients with an implantable cardioverter defibrillator between May 2021 and September 2022 who then wore wearable devices with raw acceleration output to capture digital biomarkers reflecting physical behaviour. To collect PROMs, patients received the Kansas City Cardiomyopathy Questionnaire (KCCQ) and EuroQoL 5-Dimensions 5-Level (EQ5D-5L) questionnaire at two instances: baseline and after six months. Multivariable Tobit regression models were used to explore associations between digital biomarkers and PROMs, specifically whether digital biomarkers could enable PROM prediction. The study population consisted of 303 patients (mean age 62.9 ± 10.9 years, 81.2% male). Digital biomarkers showed significant correlations to patient-reported physical and social limitations, severity and frequency of symptoms, and quality of life. Prospective validation of the Tobit models indicated moderate correlations between the observed and predicted scores for KCCQ [concordance correlation coefficient (CCC) = 0.49, mean difference: 1.07 points] and EQ5D-5L (CCC = 0.38, mean difference: 0.02 points).

Conclusion

Wearable digital biomarkers correlate with PROMs, and may be leveraged for real-time prediction. These findings hold promise for monitoring of PROMs through wearable accelerometers.
Distinct Effects of Selective Serotonin Reuptake Inhibitors and Serotonin-Norepinephrine Reuptake Inhibitors on Soluble Biomarkers in Blood and Cerebrospinal Fluid of People With HIV
Authors: Trunfio Mattia , Tang Bin , Iudicello Jennifer E , Ma Qing , Franklin Donald R , Cookson Debra , Riggs Patricia K , Cherner Mariana , Moore David J , Heaton Robert K , Letendre Scott L , Ellis Ronald J
Published: December 2023

Background

Persistent inflammation affects people with HIV (PWH) despite antiretroviral therapy (ART). Selective serotonin and serotonin-norepinephrine reuptake inhibitors (SSRIs, SNRIs), HMG-CoA reductase-inhibitors (statins), and angiotensin-converting enzyme inhibitors (ACEIs) have immunomodulant properties. We evaluated the potential impact of these drugs on inflammation and neurodegeneration in PWH.

Methods

Cross-sectional single-center (United States) analysis in 184 PWH on ART with plasma HIV RNA < 200 copies/mL. All participants had 10 biomarkers measured in blood and cerebrospinal fluid (CSF). To reduce dimensionality, hierarchical clustering and principal components (PCs) analysis were employed. The analyses were adjusted for duration of the drugs and clinical conditions.

Results

Participants were mostly middle-aged men, with median CD4+ T cells of 620/µL. In adjusted models, SSRI use was associated with 3 PCs: higher CSF and plasma Aβ42 and CSF CCL2 (aβ=.14, P = .040); lower CSF 8-oxo-dG, total tau, and sCD14 (aβ=−.12, P = .042); and higher plasma sCD14 with lower sCD40L (aβ=.15, P = .042). SNRI use was associated with higher values of CSF and plasma neopterin and CSF sTNFR-II (aβ=.22, P = .004). Statins and ACEIs showed no association.

Conclusions

SSRIs and SNRIs had distinct biomarker signatures. SSRIs were associated with reduced neurodegeneration, immune activation, and oxidative stress in CSF, suggesting a role of SSRIs as adjunctive therapy in PWH.
Harnessing Endogenous Peptide Compounds as Potential Therapeutics for Severe Influenza
Authors: West Alison C , Harpur Christopher M , Le Page Mélanie A , Lam Maggie , Hodges Christopher , Ely Lauren K , Gearing Andrew J , Tate Michelle D
Published: December 2023

Background

Excessive pulmonary inflammation and damage are characteristic features of severe influenza virus infections. LAT8881 is a synthetic 16–amino acid cyclic peptide form of a naturally occurring C-terminal fragment of human growth hormone with therapeutic efficacy against influenza. Shorter linear peptides are typically easier to manufacture and formulate for delivery than larger cyclic peptides. A 6–amino acid linear peptide fragment of LAT8881, LAT9997, was investigated as a potential influenza therapy.

Methods

LAT9997 was evaluated for its potential to limit disease in a preclinical mouse model of severe influenza infection.

Results

Intranasal treatment of mice with either LAT8881 or LAT9997 from day 1 following influenza infection significantly improved survival outcomes. Initiating LAT9997 treatment at the onset of severe disease also significantly improved disease severity. Greater disease resistance in LAT9997-treated mice correlated with reduced lung immunopathology, damage markers, vascular leak, and epithelial cell death. Treatment reduced viral loads, cytokines, and neutrophil infiltration in the airways yet maintained protective alveolar macrophages in a dose-dependent manner. Sequential trimming of N- and C-terminal amino acids from LAT9997 revealed a structure-activity relationship.

Conclusions

These findings provide preclinical evidence that therapeutic LAT9997 treatment limits viral burden and characteristic features of severe influenza, including hyperinflammation and lung damage.

Excessive pulmonary inflammation and damage are characteristic features of severe influenza virus infections. LAT9997 is a linear peptide fragment derived from human growth hormone. This study provides preclinical evidence that therapeutic LAT9997 treatment limits viral burden, hyperinflammation, and lung damage.
A novel selective leukocyte depletion human whole blood model reveals the specific roles of monocytes and granulocytes in the cytokine response to Escherichia coli
Authors: Fageräng Beatrice , Lau Corinna , Mc Adam Karin Ekholt , Schjalm Camilla , Christiansen Dorte , Garred Peter , Nilsson Per H , Mollnes Tom Eirik
Published: December 2023

The lepirudin-based human whole blood model is a well-established ex vivo system to characterize inflammatory responses. However, the contribution of individual cell populations to cytokine release has not been investigated. Thus, we modified the model by selectively removing leukocyte subpopulations to elucidate their contribution to the inflammatory response. Lepirudin-anticoagulated whole blood was depleted from monocytes or granulocytes using StraightFrom Whole Blood MicroBeads. Reconstituted blood was incubated with Escherichia coli (108/mL) for 2 hours at 37 °C. CD11b, CD62P, and CD63 were detected by flow cytometry. Complement (C3bc, sC5b-9) and platelet activation (platelet factor 4, NAP-2) were measured by enzyme-linked immunosorbent assay. Cytokines were quantified by multiplex assay. A significant (P < 0.05) specific depletion of the monocyte (mean = 86%; 95% confidence interval = 71%–92%) and granulocyte (mean = 97%; 95% confidence interval = 96%–98%) population was obtained. Background activation induced by the depletion protocol was negligible for complement (C3bc and sC5b-9), leukocytes (CD11b), and platelets (NAP-2). Upon Escherichia coli incubation, release of 10 of the 24 cytokines was solely dependent on monocytes (interleukin [IL]-1β, IL-2, IL-4, IL-5, IL-17A, interferon-γ, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, macrophage inflammatory protein-1α, and fibroblast growth factor–basic), whereas 8 were dependent on both monocytes and granulocytes (IL-1ra, IL-6, IL-8, IL-9, IL-10, macrophage inflammatory protein-1β, tumor necrosis factor, and eotaxin). Six cytokines were not monocyte or granulocyte dependent, of which platelet-derived growth factor and RANTES were mainly platelet dependent. We document an effective model for selective depletion of leukocyte subpopulations from whole blood, without causing background activation, allowing in-depth cellular characterization. The results are in accordance with monocytes playing a major role in cytokine release and expand our knowledge of the significant role of granulocytes in the response to E. coli.
AIRE is expressed in breast cancer TANs and TAMs to regulate the extrinsic apoptotic pathway and inflammation
Authors: Källberg Eva , Mehmeti-Ajradini Meliha , Björk Gunnarsdottir Frida , Göransson Marcus , Bergenfelz Caroline , Allaoui Fredriksson Roni , Hagerling Catharina , Johansson Martin E , Welinder Charlotte , Jirström Karin , Leandersson Karin
Published: December 2023

The autoimmune regulator (AIRE) is a transcriptional regulator expressed in the thymus and is necessary for maintaining immunological self-tolerance. Extrathymic AIRE expression is rare, and a role for AIRE in tumor-associated innate immune cells has not yet been established. In this study, we show that AIRE is expressed in human pro-tumor neutrophils. In breast cancer, AIRE was primarily located to tumor-associated neutrophils (TANs), and to a lesser extent to tumor-associated macrophages (TAMs) and tumor cells. Expression of AIRE in TAN/TAMs, but not in cancer cells, was associated with an adverse prognosis. We show that the functional role for AIRE in neutrophils and macrophages is to regulate expression of immune mediators and the extrinsic apoptotic pathway involving the Fas/TNFR death receptors and cathepsin G. Here, we propose that the role for AIRE in TAN/TAMs in breast tumors is to regulate cell death and inflammation, thus promoting tumor progression.
A roadmap to establishing global oncology as a priority initiative within a National Cancer Institute–designated cancer center
Authors: Van Loon Katherine , Breithaupt Lindsay , Ng Dianna , DeBoer Rebecca J , Buckle Geoffrey C , Bialous Stella , Hiatt Robert A , Volberding Paul , Hermiston Michelle L , Ashworth Alan
Published: December 2023

As the burden of cancers impacting low- and middle-income countries is projected to increase, formation of strategic partnerships between institutions in high-income countries and low- and middle-income country institutions may serve to accelerate cancer research, clinical care, and training. As the US National Cancer Institute and its Center for Global Health continue to encourage cancer centers to join its global mission, academic cancer centers in the United States have increased their global activities. In 2015, the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco, responded to the call for international partnership in addressing the global cancer burden through the establishment of the Global Cancer Program as a priority initiative. In developing the Global Cancer Program, we galvanized institutional support to foster sustained, bidirectional, equitable, international partnerships in global cancer control. Our focus and intent in disseminating this commentary is to share experiences and lessons learned from the perspective of a US-based, National Cancer Institute–designated cancer center and to provide a roadmap for other high-income institutions seeking to strategically broaden their missions and address the complex challenges of global cancer control. Herein, we review the formative evaluation, governance, strategic planning, investments in career development, funding sources, program evaluation, and lessons learned. Reflecting on the evolution of our program during the first 5 years, we observed in our partners a powerful shift toward a locally driven priority setting, reduced dependency, and an increased commitment to research as a path to improve cancer outcomes in resource-constrained settings.
Successful management of portal hypertension with splenomegaly and cavernous transformation of the portal vein: a rare case report
Authors: Sharjeel Simrah , Abdullah Muhammad
Published: December 2023

Portal hypertension, often stemming from liver cirrhosis or vascular anomalies, can result in cavernous transformation of the portal vein, a rare condition associated with biliary obstruction, variceal hemorrhage, and splenomegaly. This case report details a unique occurrence of portal hypertension, splenomegaly, and cavernous transformation of the portal vein successfully managed through splenectomy and spleno-renal shunt. A 30-year-old female with a history of portal hypertension, portal gastropathy, and splenomegaly presented with left upper quadrant abdominal pain. She had previously undergone esophageal variceal ligation and required intermittent blood transfusions. Additional complications included easy bruising, heavy menstrual bleeding, and a prior episode of hematemesis. Clinical assessment confirmed splenomegaly, while a CT scan confirmed the diagnosis. A tailored surgical approach was chosen, leading to splenectomy and spleno-renal shunt.
Simultaneous stoma closure and type IV parastomal hernia repair after botulinum toxin and progressive pneumoperitoneum
Authors: Correia Penélope , Pereira Ana Marta , Matos Maria Leonor , Rodrigues Catarina Santos , Guimarães Marta , Nora Mário
Published: December 2023

Surgery is the only treatment for parastomal hernia (PH). When possible, stoma closure is the best way to manage this type of hernia, however, whether to perform it in a single approach with abdominal wall reconstruction (AWR) is still debatable. A 58-year-old woman with a type IV PH with loss of domain was submitted to preoperative optimization [botulinum toxin type A and progressive pneumoperitoneum (PPP)], followed by simultaneous stoma closure and AWR. Hospital discharge was on the eighth day with no complications. Six months later, no clinical evidence of recurrence or other complication was observed. Large PHs are technically challenging. Stoma closure and simultaneous AWR increase surgical risk. Preoperative optimization with a combination of adjuvants (including PPP) is feasible in PH and may overcome technical complexity, even though patient selection remains the key when choosing a PH repair with synchronous stoma closure.
An Ancestral Major Histocompatibility Complex Organization in Cartilaginous Fish: Reconstructing MHC Origin and Evolution
Authors: Veríssimo Ana , Castro L Filipe C , Muñoz-Mérida Antonio , Almeida Tereza , Gaigher Arnaud , Neves Fabiana , Flajnik Martin F , Ohta Yuko
Published: December 2023

Cartilaginous fish (sharks, rays, and chimeras) comprise the oldest living jawed vertebrates with a mammalian-like adaptive immune system based on immunoglobulins (Ig), T-cell receptors (TCRs), and the major histocompatibility complex (MHC). Here, we show that the cartilaginous fish “adaptive MHC” is highly regimented and compact, containing (i) a classical MHC class Ia (MHC-Ia) region containing antigen processing (antigen peptide transporters and immunoproteasome) and presenting (MHC-Ia) genes, (ii) an MHC class II (MHC-II) region (with alpha and beta genes) with linkage to beta-2-microglobulin (β2m) and bromodomain-containing 2, (iii) nonclassical MHC class Ib (MHC-Ib) regions with 450 million-year-old lineages, and (iv) a complement C4 associated with the MHC-Ia region. No MHC-Ib genes were found outside of the elasmobranch MHC. Our data suggest that both MHC-I and MHC-II genes arose after the second round of whole-genome duplication (2R) on a human chromosome (huchr) 6 precursor. Further analysis of MHC paralogous regions across early branching taxa from all jawed vertebrate lineages revealed that Ig/TCR genes likely arose on a precursor of the huchr9/12/14 MHC paralog. The β2m gene is linked to the Ig/TCR genes in some vertebrates suggesting that it was present at 1R, perhaps as the donor of C1 domain to the primordial MHC gene. In sum, extant cartilaginous fish exhibit a conserved and prototypical MHC genomic organization with features found in various vertebrates, reflecting the ancestral arrangement for the jawed vertebrates.
CRISPR-Cas immunity is repressed by the LysR-type transcriptional regulator PigU
Authors: Smith Leah M , Hampton Hannah G , Yevstigneyeva Mariya S , Mahler Marina , Paquet Zacharie S M , Fineran Peter C
Published: December 2023

Bacteria protect themselves from infection by bacteriophages (phages) using different defence systems, such as CRISPR-Cas. Although CRISPR-Cas provides phage resistance, fitness costs are incurred, such as through autoimmunity. CRISPR-Cas regulation can optimise defence and minimise these costs. We recently developed a genome-wide functional genomics approach (SorTn-seq) for high-throughput discovery of regulators of bacterial gene expression. Here, we applied SorTn-seq to identify loci influencing expression of the two type III-A Serratia CRISPR arrays. Multiple genes affected CRISPR expression, including those involved in outer membrane and lipopolysaccharide synthesis. By comparing loci affecting type III CRISPR arrays and cas operon expression, we identified PigU (LrhA) as a repressor that co-ordinately controls both arrays and cas genes. By repressing type III-A CRISPR-Cas expression, PigU shuts off CRISPR-Cas interference against plasmids and phages. PigU also represses interference and CRISPR adaptation by the type I-F system, which is also present in Serratia. RNA sequencing demonstrated that PigU is a global regulator that controls secondary metabolite production and motility, in addition to CRISPR-Cas immunity. Increased PigU also resulted in elevated expression of three Serratia prophages, indicating their likely induction upon sensing PigU-induced cellular changes. In summary, PigU is a major regulator of CRISPR-Cas immunity in Serratia.
Not Only Meningitis but Also Epiglottitis: An Emerging Clinical Presentation of Invasive Meningococcal Disease
Authors: Deghmane Ala-Eddine , Taha Samy , Taha Muhamed-Kheir
Published: December 2023

The rebound of invasive meningococcal disease cases in France since the fall of 2022 was accompanied by an increase in adult epiglottitis. These cases were provoked mainly by isolates of serogroup W belonging to the clonal complex 11 of Neisseria meningitidis. Awareness and surveillance should be reinforced.
Mathematical Explanations: An Analysis Via Formal Proofs and Conceptual Complexity
Authors: Poggiolesi Francesca
Published: December 2023

This paper studies internal (or intra-)mathematical explanations, namely those proofs of mathematical theorems that seem to explain the theorem they prove. The goal of the paper is a rigorous analysis of these explanations. This will be done in two steps. First, we will show how to move from informal proofs of mathematical theorems to a formal presentation that involves proof trees, together with a decomposition of their elements; secondly we will show that those mathematical proofs that are regarded as having explanatory power all display an increase of conceptual complexity from the assumptions to the conclusion.
Calcium regulation of the Arabidopsis Na+/K+ transporter HKT1;1 improves seed germination under salt stress
Authors: Chandran Ancy E J , Finkler Aliza , Hait Tom Aharon , Kiere Yvonne , David Sivan , Pasmanik-Chor Metsada , Shkolnik Doron
Published: December 2023

Calcium is known to improve seed-germination rates under salt stress. We investigated the involvement of calcium ions (Ca2+) in regulating HIGH-AFFINITY K+ TRANSPORTER 1 (HKT1; 1), which encodes a Na+/K+ transporter, and its post-translational regulator TYPE 2C PROTEIN PHOSPHATASE 49 (PP2C49), in germinating Arabidopsis (Arabidopsis thaliana) seedlings. Germination rates of hkt1 mutant seeds under salt stress remained unchanged by CaCl2 treatment in wild-type Arabidopsis, whereas pp2c49 mutant seeds displayed improved salt-stress tolerance in the absence of CaCl2 supplementation. Analysis of HKT1;1 and PP2C49 promoter activity revealed that CaCl2 treatment results in radicle-focused expression of HKT1;1 and reduction of the native radicle-exclusive expression of PP2C49. Ion-content analysis indicated that CaCl2 treatment improves K+ retention in germinating wild-type seedlings under salt stress, but not in hkt1 seedlings. Transgenic seedlings designed to exclusively express HKT1;1 in the radicle during germination displayed higher germination rates under salt stress than the wild type in the absence of CaCl2 treatment. Transcriptome analysis of germinating seedlings treated with CaCl2, NaCl, or both revealed 118 upregulated and 94 downregulated genes as responsive to the combined treatment. Bioinformatics analysis of the upstream sequences of CaCl2–NaCl-treatment-responsive upregulated genes revealed the abscisic acid response element CACGTGTC, a potential CaM-binding transcription activator-binding motif, as most prominent. Our findings suggest a key role for Ca2+ in mediating salt-stress responses during germination by regulating genes that function to maintain Na+ and K+ homeostasis, which is vital for seed germination under salt stress.
Noise in Expectations: Evidence from Analyst Forecasts
Authors: de Silva Tim , Thesmar David
Published: December 2023

Analyst forecasts outperform econometric forecasts in the short run but underperform in the long run. We decompose these differences in forecasting accuracy into analysts’ information advantage, forecast bias, and forecast noise. We find that noise and bias strongly increase with forecast horizon, while analysts’ information advantage decays rapidly. A noise increase with horizon generates a mechanical reversal in the sign of the error-revision (Coibion-Gorodnichenko) regression coefficient at longer horizons, independently of over-/underreaction. A parsimonious model with bounded rationality and a noisy cognitive default matches the term structures of noise and bias jointly.