bluuebunny/crossref_metadata_2025 huggingface dataset:
“The One Human Life That I Know Best”
Authors: Nahme Paul E
Published: August 2024

This chapter examines the intersections between the thought of W. E. B. Du Bois and Martin Buber, from their time spent studying at the University of Berlin under the influence of Wilhelm Dilthey to their similar trajectories in emphasizing “racial feeling” as a form of constructive flourishing to racial identity.
Conclusion
Authors: Nahme Paul E
Published: August 2024

Instead of a cruel optimism that seeks to overcome the ghostliness of Jewishness and become human, Jewish messianism presents a kind of melancholic rejection of the sovereignty of reason and the univocal interpretation of this world as the horizon for attachment and hope.
Plastic Moment: Kavi-Aitihāsik
Authors: Ghosh Ranjan
Published: August 2024

Working through what Ghosh calls the plastic rhythm, this chapter executes a close reading of Rabindranath Tagore’s writings on history; it tries to develop his theory of history and establish the character of his historical consciousness. Tagore’s philosophy of history can be distinguished from Western models of historical thinking and is resistant to any form of aligning with nationalist and revivalistic narratives that speak only of one culture, one nation, and one community. The chapter identifies plastic moments in historical thinking and works out a theoretical premise based on Tagore’s engagement with time, historical distance, the everyday, history as life view, historical fiction, historicality in literature, and the notion of the historical-now or presentism. Substantiated by the notion of a kavi-aitihāsik, ‘poet-historian’, Tagore’s historical theory works at the limits of ‘global history’, which is now often misappropriated through the principles of unifocality and bounded rationality. An inherent philosophy of plasticity frees Tagore’s sense of itihasa from the univocality of world history; it creates its own ‘worlding’, its historicality, enriching and disturbing our notions of global history.
The Plastic Kavi . . .
Authors: Ghosh Ranjan
Published: August 2024

This chapter reinvests the arguments in our understanding of plastic Tagore on different lines to make a resounding case for what we now accept as ‘the’ plastic kavi. In trying to do that, it commits to figure a few plastic moments in Tagore’s negotiations with nature. Plastic Tagore betrays an anxiety of a changing nature, a negative surplus that made him commit to a biocentric pedagogy or rural reconstruction within a nature–culture sambandha or a life amidst the nourishing and recuperative shelter of forests, trees, and plants—an inclusive and intensive green consciousness. He builds plastic lines that formulate new ideas of nature within the background of an anthropocenic unconscious and climaticenic becoming. The chapter in the end establishes the problematic of the plastic kavi and concludes that Tagore has never been outside the profound impacts of plasticity.
Volume electron microscopy analysis of synapses in primary regions of the human cerebral cortex
Authors: Cano-Astorga Nicolás , Plaza-Alonso Sergio , DeFelipe Javier , Alonso-Nanclares Lidia
Published: August 2024

Functional and structural studies investigating macroscopic connectivity in the human cerebral cortex suggest that high-order associative regions exhibit greater connectivity compared to primary ones. However, the synaptic organization of these brain regions remains unexplored. In the present work, we conducted volume electron microscopy to investigate the synaptic organization of the human brain obtained at autopsy. Specifically, we examined layer III of Brodmann areas 17, 3b, and 4, as representative areas of primary visual, somatosensorial, and motor cortex. Additionally, we conducted comparative analyses with our previous datasets of layer III from temporopolar and anterior cingulate associative cortical regions (Brodmann areas 24, 38, and 21). 9,690 synaptic junctions were 3D reconstructed, showing that certain synaptic characteristics are specific to particular regions. The number of synapses per volume, the proportion of the postsynaptic targets, and the synaptic size may distinguish one region from another, regardless of whether they are associative or primary cortex. By contrast, other synaptic characteristics were common to all analyzed regions, such as the proportion of excitatory and inhibitory synapses, their shapes, their spatial distribution, and a higher proportion of synapses located on dendritic spines. The present results provide further insights into the synaptic organization of the human cerebral cortex.
FatPlants: a comprehensive information system for lipid-related genes and metabolic pathways in plants
Authors: Xu Chunhui , Shaw Trey , Choppararu Sai Akhil , Lu Yiwei , Farooq Shaik Naveed , Qin Yongfang , Hudson Matt , Weekley Brock , Fisher Michael , He Fei , Da Silva Nascimento Jose Roberto , Wergeles Nicholas , Joshi Trupti , Bates Philip D , Koo Abraham J , Allen Doug K , Cahoon Edgar B , Thelen Jay J , Xu Dong
Published: August 2024

FatPlants, an open-access, web-based database, consolidates data, annotations, analysis results, and visualizations of lipid-related genes, proteins, and metabolic pathways in plants. Serving as a minable resource, FatPlants offers a user-friendly interface for facilitating studies into the regulation of plant lipid metabolism and supporting breeding efforts aimed at increasing crop oil content. This web resource, developed using data derived from our own research, curated from public resources, and gleaned from academic literature, comprises information on known fatty-acid-related proteins, genes, and pathways in multiple plants, with an emphasis on Glycine max, Arabidopsis thaliana, and Camelina sativa. Furthermore, the platform includes machine-learning based methods and navigation tools designed to aid in characterizing metabolic pathways and protein interactions. Comprehensive gene and protein information cards, a Basic Local Alignment Search Tool search function, similar structure search capacities from AphaFold, and ChatGPT-based query for protein information are additional features.

Database URL: https://www.fatplants.net/
Structure of the crust and upper mantle in Greenland and northeastern Canada: insights from anisotropic Rayleigh-wave tomography
Authors: Ajourlou Parviz , Darbyshire Fiona , Audet Pascal , Milne Glenn A
Published: August 2024

Seismic velocity models provide important constraints on Greenland’s deep structure, which, in turn, has profound implications for our understanding of the tectonic history of this region. However, the resolution of seismic models has been limited by a sparse network, particularly in northern and central Greenland. We address these limitations by generating new high-resolution Rayleigh-wave phase velocity maps encompassing Greenland and northeastern Canada by processing over three decades of teleseismic earthquake records and incorporating recently added stations in Greenland and Arctic Canada. These phase velocity maps are sensitive to structure from the lower crust down to the sub-lithospheric mantle (25–185 s period). We find significant heterogeneity and a strong correlation between isotropic and anisotropic seismic velocities with inferred geological structure. High seismic velocities associated with cratonic lithosphere are broadly divided into two regions, with a belt of reduced velocity spanning central Greenland, which we interpret as lithospheric erosion resulting from interaction between the Greenland continental keel and the Iceland plume. Within each region, we identify tectonic subdivisions that suggest fundamental differences between the blocks that make up Precambrian Greenland. In the south, the North Atlantic craton (NAC) has a high-velocity keel exhibiting anisotropic stratification. Between the NAC and the cratonic lithosphere further north, the Proterozoic Nagssugtoqidian orogenic belt shows a distinct signature of reduced seismic velocity to $\sim$75 s period, but then appears to pinch out at depth. The northern Greenland lithosphere exhibits significant isotropic heterogeneity, with a distinct core of high velocities in the northwest ($\sim$55–75 s period) giving way to a set of distinct east-west trending high-velocity belts at longer periods. At all periods sensitive to the lithospheric mantle in this region, anisotropic fast orientations are E–W, consistent with a north–south Precambrian assembly of the Greenland shield. In contrast to the NAC, there is no evidence of anisotropic stratification in the northern part of the cratonic keel. Based on both isotropic and anisotropic phase-velocity anomalies, we suggest that the Phanerozoic Caledonian and Ellesmerian-Franklinian fold belts are relatively thin-skinned features onshore Greenland, though the Caledonian belt may have a stronger signature off the east coast. At the longest periods, a prominent low-velocity anomaly initially centred on Iceland migrates northwards and spreads beneath central-eastern Greenland. Coupled with NW–SE trending anisotropy, this feature is interpreted as the effect of mantle flow radiating outward from the Iceland plume and interacting with the eroded Greenland lithosphere.
GLAD-M35: a joint P and S global tomographic model with uncertainty quantification
Authors: Cui Congyue , Lei Wenjie , Liu Qiancheng , Peter Daniel , Bozdağ Ebru , Tromp Jeroen , Hill Judith , Podhorszki Norbert , Pugmire David
Published: August 2024

We present our third and final generation joint P and S global adjoint tomography (GLAD) model, GLAD-M35, and quantify its uncertainty based on a low-rank approximation of the inverse Hessian. Starting from our second-generation model, GLAD-M25, we added 680 new earthquakes to the database for a total of 2160 events. New P-wave categories are included to compensate for the imbalance between P- and S-wave measurements, and we enhanced the window selection algorithm to include more major-arc phases, providing better constraints on the structure of the deep mantle and more than doubling the number of measurement windows to 40 million. Two stages of a Broyden–Fletcher–Goldfarb–Shanno (BFGS) quasi-Newton inversion were performed, each comprising five iterations. With this BFGS update history, we determine the model’s standard deviation and resolution length through randomized singular value decomposition.
The Changing Earth
Authors: Lomolino Mark V. , Riddle Brett R. , Whittaker Robert J.
Published: August 2024

This chapter provides an overview of geographical changes on Earth. Plate tectonics theory provides a framework for understanding Earth's landmasses and ocean basins, which has provided crucial advances in the understanding of biogeographic science. Earth system dynamics have driven countless episodes of biotic responses of speciation, dispersal, and extinction recorded in the evolutionary history of lineages and biotas. The chapter then focuses on the geological timescale at the same time as considering the tectonic history of the continents, Cenozoic tectonics, and the tectonic development of marine bases and island chains. It next discusses the biogeographic consequences of tectonic events. These determine the degrees of biotic isolation and opportunities for biotic exchange. This, in turn, influences regional and global climates.
Glaciation and Biogeographic Dynamics of the Pleistocene
Authors: Lomolino Mark V. , Riddle Brett R. , Whittaker Robert J.
Published: August 2024

This chapter discusses the glaciation and biogeographic dynamics of the Pleistocene. It highlights that the climatic upheavals of the Pleistocene caused major shifts in the geography of life across the planet. Earth experienced numerous glacial-interglacial cycles during the Pleistocene, so the cycle of glacial and interglacial periods affected the entire planet not just those specific regions covered by glaciers. The chapter looks into the biogeographic responses to climatic cycles of the Pleistocene. It also explains what Pleistocene refugia are. These are the areas to which species were displaced during glacial episodes. Finally, the chapter looks at extinctions of the Pleistocene megafauna.
Dust beyond the torus: revealing the mid-infrared heart of local Seyfert ESO 428-G14 with JWST/MIRI
Authors: Haidar Houda , Rosario David J , Alonso-Herrero Almudena , Pereira-Santaella Miguel , García-Bernete Ismael , Campbell Stephanie , Hönig Sebastian F , Ramos Almeida Cristina , Hicks Erin , Delaney Daniel , Davies Richard , Ricci Claudio , Harrison Chris M , Leist Mason , Lopez-Rodriguez Enrique , Garcia-Burillo Santiago , Zhang Lulu , Packham Chris , Gandhi Poshak , Audibert Anelise , Bellocchi Enrica , Boorman Peter , Bunker Andrew , Combes Françoise , Diaz Santos Tanio , Donnan Fergus R , Gonzalez Martin Omaira , Hermosa Muñoz Laura , Charidis Matthaios , Labiano Alvaro , Levenson Nancy A , May Daniel , Rigopoulou Dimitra , Rodriguez Ardila Alberto , Shimizu T Taro , Stalevski Marko , Ward Martin
Published: August 2024

Polar dust has been discovered in a number of local active galactic nuclei (AGN), with radiation-driven torus models predicting a wind to be its main driver. However, little is known about its characteristics, spatial extent, or connection to the larger scale outflows. We present the first JWST/MIRI study aimed at imaging polar dust by zooming on to the centre of ESO 428-G14, part of the Galaxy Activity, Torus, and Outflow Survey (GATOS) survey of local AGN. We detect extended mid-infrared (MIR) emission within 200 pc from the nucleus. This polar structure is co-linear with a radio jet and lies perpendicular to a molecular gas lane that feeds and obscures the nucleus. Its morphology bears a striking resemblance to that of gas ionized by the AGN in the narrow-line region. We demonstrate that part of this spatial correspondence is due to contamination within the JWST filter bands from strong emission lines. Correcting for the contamination, we find the morphology of the dust continuum to be more compact, though still clearly extended out to $r\approx 100 \, \rm pc$. We estimate the emitting dust has a temperature of $\sim 120\, \rm K$. Using simple models, we find that the heating of small dust grains by the radiation from the central AGN and/or radiative jet-induced shocks is responsible for the extended MIR emission. Radiation-driven dusty winds from the torus is unlikely to be important. This has important implications for scales to which AGN winds can carry dust and dense gas out into their host galaxies.
Can early dark energy be probed by the high-redshift galaxy abundance?
Authors: Liu Weiyang , Zhan Hu , Gong Yan , Wang Xin
Published: August 2024

The analysis of the cosmic microwave background data acquired by the Atacama Cosmology Telescope and the large-scale ($\ell \lesssim 1300$) Planck Telescope show a preference for the early dark energy (EDE) theory, which was set to alleviate the Hubble tension of the $\Lambda$ cold dark matter ($\Lambda$CDM) model by decreasing the sound horizon $r_{s}$, and gives $H_{0} \approx 72$ km s$^{-1}$ Mpc$^{-1}$. However, the EDE model is commonly questioned for exacerbating the $\sigma _8$ tension on top of the $\Lambda$CDM model, and its lack of preference from the late-time matter power spectrum observations, e.g. Baryon Oscillation Spectroscopic Survey. In light of the current obscurities, we inspect if the high redshift galaxy abundance, i.e. stellar mass function/density and luminosity function, can independently probe the EDE model. Our result shows that, compared to $\Lambda$CDM, the EDE model prediction at $z\gt 10$ displays better consistency with the unexpectedly high results observed by the JWST. At lower redshift, the EDE model only fits the most luminous/massive end, with the majority of the data presenting better consistency with $\Lambda$CDM, implying that adding an extra luminosity/mass-sensitive suppression mechanism of the galaxy formation is required for EDE to explain all data around $z\sim 7-10$.
Solar differential rotation coefficients fitted from synoptic magnetic maps
Authors: Chu Zhe , Gu Haihua
Published: August 2024

Based on the consecutive synoptic magnetic maps, we devise a new method to calculate the solar differential rotation coefficients. This method is very easy to implement and has a high accuracy. Firstly, based on the two-term or three-term differential rotation formula, we simulate a synoptic map CR$_{n}$ evolves one Carrington Rotation (CR) time only under the effect of the differential rotation, and thereby a stretched synoptic map CR$_{n*}$ is obtained. Then, through searching the maximum covariance between the maps CR$_{n*}$ and CR$_{n+1}$ by the grid search method, the rotation coefficients can be determined. Based on the synoptic maps of CRs 1625 to 2278 (during the years 1975–2023), the two-term coefficients A and B for latitude region between $\pm 40^{\circ }$ are calculated. The rotation coefficient B shows an obvious 11-yr period. From the time series of B, we find that the Sun usually rotates more differentially in the rising phases of the sunspot cycles than in the falling phases. Moreover, the strong magnetic field corresponds to an increasing of B (note that B has a negative sign) or decreasing of differential. The evolutionary trend of B also indicates that there are several years until the maximum value of B will be reached in solar cycle 25, and the coefficient B will be still in the rising phase in the few coming years. The two-term rotation coefficients for the two hemispheres are also calculated separately, and in the studied time-scale, the largest N–S asymmetry of the rotation rate appeared in October 2007.
Durable benefit and slowdown in tumor growth dynamics with erdafitinib in a FGFR3-TACC3 fusion-positive IDH-wild type glioblastoma
Authors: Cabezas-Camarero Santiago , Pérez-Alfayate Rebeca , Polidura Carmen , Gómez-Ruiz María Natividad , Gil-Martínez Lidia , Casado-Fariñas Isabel , Bartolomé Jorge , Pérez-Segura Pedro
Published: August 2024

FGFR3-TACC3 fusion-positive IDH-wild-type (IDH-WT) glioblastoma (GB) is a rare GB subtype occurring in approximately 3% of cases. It is clinical behavior and molecular profile is different from those of fusion-negative IDH-WT GBs. Evidence on the role of FGFR inhibitors in FGFR-altered gliomas is limited. We present the case of a patient with a FGFR3-TACC3 fusion-positive IDH-WT GB that at its second recurrence was treated with the FGFR inhibitor erdafitinib through a compassionate use program. Although no objective response was achieved, an overt deceleration in tumor growth was evidenced and the patient remained on treatment for 5.5 months.
77 Impact of CBM588 on gut microbiome composition and dysbiosis in patients receiving frontline immune checkpoint inhibitor (ICI) combinations for metastatic renal cell carcinoma (mRCC)
Authors: Dizman Nazli , Ebrahimi Hedyeh , Barragan-Carrillo Regina , Meza Luis A , Bergerot Paulo , Dorff Tanya , BSc JoAnn Hsu , Zengin Zeynep , Castro Daniela , Chehrazi-Raffle Alex , Triphathi Abhishek , Trent Jeffrey , Takahashi Motomichi , Oka Kentaro , Higashi Seiya , Caporaso Gregory , Lee Keehoon , Pal Sumanta K
Published: August 2024

Background

Two recent randomized phase I clinical trials have provided compelling evidence that CBM588, a Clostridium butyricum-based live biotherapeutic, holds potential to enhance clinical outcomes in patients with mRCC receiving frontline ICI combinations (Dizman et al Nature Medicine 2022; Ebrahimi et al ASCO 2023). We examined the impact of CBM588 on gut microbiome composition in a combined cohort of these two studies to further investigate its impact on gut microbiome

Methods

We analyzed stool samples from two phase I randomized clinical trials that enrolled patients with mRCC treated with (1) nivolumab/ipilimumab (nivo/ipi) +/- CBM588 and (2) cabozantinib/nivolumab (cabo/nivo) +/- CBM588. We compared gut microbiome diversity and composition at baseline and week 12 between patients in the standard of care (SOC) arms (nivo/ipi or cabo/nivo) and those who received CBM588 in combination with a SOC regimen (SOC/CBM). Taxonomic profiling was performed using MetaPhlan v4, and changes in the abundances of clinically relevant microbial species from baseline to week 12 were assessed using the Wilcoxon matched pairs test. The ratio of Firmicutes/Bacteroidetes, a measure of gut dysbiosis, was computed across time points in the two cohorts.

Results

Among 58 patients included in the analysis, 38 received SOC/CBM588 as first-line treatment. The median age was 60 years (range: 36-90) and the majority of patients were male (71%), had clear cell mRCC (88%), and intermediate/poor risk disease (79%). In both the SOC and SOC/CBM cohorts, there were no statistically significant differences in alpha and beta diversity between baseline and week 12. Among clinically relevant species compared between baseline and week 12, Alistipes senegalensis was found to decrease in both the SOC and SOC/CBM cohorts (log fold change [LFC] -0.82 [P=0.004] and LFC -0.36 [P=0.007], respectively), while Eubacterium siraeum decreased only in the SOC cohort (LFC -1.75 [P=0.005]). The Firmicutes/Bacteroidetes ratio increased from 89.0% to 96.4% in the SOC cohort, whereas a notable decrease was observed in this ratio from 100.0% to 75.7%. in the SOC/CBM cohort.

Conclusions

CBM588 leads to a marked correction of gut dysbiosis and prevents the depletion of species previously associated with ICI response (i.e., Eubacterium siraeum). These findings provide a plausible mechanism for the enhanced clinical outcome with CBM588 now seen across two small, randomized trials. A phase III study is planned within the cooperative groups to evaluate the clinical activity and gut microbiome modulation capacity of CBM588 in combination with ICIs in mRCC.
29 Pilot study of an implantable microdevice forin vivo evaluation of drug response in renal cell carcinoma (NCT05700461)
Authors: Xu Wenxin , Bhagavatula Sharath , Steiner Clara , Zhong Caiwei , Mossanen Matthew , Chang Steven , Hirsch Michelle , Ahn Sebastian , Matthew Destiny , Berg Stephanie , Serzan Michael , McGregor Bradley , Hata Nobuhiko , Viswanathan Srinivas , Silverman Stuart , Jonas* Oliver , Choueiri* Toni
Published: August 2024

Background

There are multiple therapies for renal cell carcinoma (RCC), yet no personalized biomarkers exist that can guide optimal treatment for individual patients. We developed implantable microdevices (IMD) that can be placed within a target tumor using a standard small-gauge interventional needle under imaging guidance. The IMDs deliver spatially segregated microdoses of up to 20 different drugs and/or combinations over multiple days, and then are retrieved surgically with surrounding tissue. This allows for the assessment of tumor response to multiple drugs in vivo within the native tumor microenvironment, without exposing the patient to systemic drug toxicity. We are conducting a trial to evaluate the safety and feasibility of IMD implantation in RCC tumors and subsequent collection of drug response data on targeted, cytotoxic, and immune-modulatory agents.

Methods

Eligible patients have suspected or confirmed RCC and are planned for standard surgical resection of either their primary tumor or metastasis. Three days prior to surgery, one or more IMDs are implanted percutaneously into the tumor under CT guidance. Following nephrectomy or excision of a metastasis, the microdevices with surrounding tumor are removed en bloc; subsequently, the tissue is fixed, embedded and sectioned. The tumor/IMD cross-sections are analyzed for drug effect for each of the spatially separate treatment effects using a wide range of techniques, including immunohistochemistry for proliferation and pathway markers, spatial immune profiling using a panel of 25 tumor microenvironment markers, and spatial transcriptomics. Patients receive subsequent standard of care systemic treatment as per their oncologist’s discretion.

Five patients have been enrolled and a total of 16 IMDs have been implanted to date. Enrollment is ongoing for a planned total of 20 patients. Success is defined as meeting both safety and feasibility endpoints. Safety is defined as two or fewer safety failures out of 20 enrolled patients. Feasibility is defined as 16 or more patients with successful microdevice implantation and retrieval of interpretable data.

IMDs will be analyzed to explore spatially segregated drug effects on the tumor microenvironment including tumor cell death and immune cell activation, as well as evidence of differential tumor drug sensitivity across treatments and patients.

Conclusions

Implantation of microdevices in RCC tumors may be a useful approach to improve treatment selection and accelerate drug development. Trial enrollment is ongoing.
27 Spatial Clustering of Immunosuppressive Macrophages in Papillary Renal Cell Carcinoma
Authors: Soupir Alex , Hayes Mitchell , Laborde Jose , Sabitov Mr Kirill , Peak Taylor , Nguyen Mr Jonathan , Moran-Segura Carlos , Saeed-Vafa Daryoush , Lopez-Blanco Neale , Echevarria Ms Paola Ramos , Guske Christopher , Blasi Jodi , Dhillon Jasreman , Kim Youngchul , Mulé James , Fridley Brooke , Manley Brandon
Published: August 2024

Background

Papillary renal cell carcinoma (pRCC) accounts for up to 15% of all kidney cancer cases, yet our understanding of its tumor immune microenvironment (TIME) remains limited. We utilized multiplex immunofluorescence (mIF) and spatial transcriptomics (ST) to evaluate immune cell spatial architecture in pRCC and compared to that of clear cell RCC (ccRCC).

Methods

Surgical tumor specimens were obtained from localized RCC tumors, followed by mIF using markers for T cells, B cells, and tumor-associated macrophages (TAMs). Spatial data were derived in regions of interest (ROIs) manually selected from spatially distinct tissue compartments of the TIME. Single-cell ST was performed on a subset of patient samples, utilizing probes against 960 transcripts. Cell abundance, cell spatial clustering, and spatially varying gene expression were analyzed to identify unique features of the TIME in pRCC.

Results

Sixteen pRCC and 70 ccRCC patient samples underwent mIF. Compared to ccRCC, global pRCC immune cell abundance was statistically lower amongst functional CD8 T cells, while global cell spatial clustering was higher amongst M2-like macrophages as measured by mIF, including PDL1+ subsets. Using ST, seven genes were significantly associated with spatial clustering of M2-like macrophages in pRCC. Three of seven genes (CCL18, GPNMB, CD9) are known markers of lipid-associated TAMs (LAMs) (adjusted p-value < 0.1).

Conclusions

Compared to ccRCC, pRCC has fewer T cells but greater M2-like macrophage spatial clustering. Using ST, we found that multiple LAM-associated genes are spatially enriched in pRCC. Additional resources should be dedicated to investigating myeloid biomarkers and the impact of myeloid modulating therapeutics in pRCC.
72 Impact of microbiome modulation on serum cytokine profile in a randomized, phase I trial of cabozantinib/nivolumab (cabo/nivo) with or without CBM588 in pts with metastatic renal cell carcinoma (mRCC)
Authors: Li Yu Jun , Ebrahimi Hedyeh , Meza Luis , Malhotra Jasnoor , Li Xiaochen , Dizman Nazli , Dorff Tanya , Frankel Paul , Llamas-Quitiquit Marian , Hsu JoAnn , Zengin Zeynep , Alcantara Marice , Castro Daniela , Mercier Benjamin , Chawla Neal , Chehrazi-Raffle Alexander , Barragan-Carrillo Regina , Gillece John , Trent Jeffrey , Lee Peter , Parks Thomas , Takahashi Motomichi , Hayashi Atsushi , Caporaso J Gregory , Lee Keehoon , Tripathi Abhishek , Pal Sumanta
Published: August 2024

Background

We have previously demonstrated that the orally administered, live bacterial product CBM588 can augment clinical outcomes with cabo/nivo in pts with mRCC (Ebrahimi et al ASCO 2023). As it is postulated this effect may be mediated through changes in systemic immunity, we sought to characterize changes in serum cytokine profile induced by CBM588.

Methods

Pts with previously untreated mRCC with clear cell, papillary or sarcomatoid histology were enrolled. Key eligibility criteria included Karnofsky performance status ≥ 70% and measurable disease. Pts were randomized to receive cabo/nivo on a standard schedule alone or the same regimen with CBM588 at 80 mg bid. Pts had blood collection performed at baseline and at weeks 9, 13, 17 and 25. Samples underwent processing within 4-6 hrs of collection, and a total of 30 cytokines and growth factors were assessed using the Luminex Flexmap 3D system (Biotechne). Changes in circulating cytokine levels between baseline and week 13 (± 7 days) were examined across the treatment arms to investigate the impact of CBM588 on the immune system. The Wilcoxon matched-pairs test was used to compare the levels of cytokines at the two timepoints.

Results

A total of 30 pts were enrolled; the majority were male (67%) and had intermediate- or poor-risk disease (60%). Most pts had clear cell histology (87%); 5 pts (17%) had sarcomatoid features. As previously reported, pts receiving cabo/nivo/CBM588 had a significantly higher response rate as compared to pts receiving cabo/nivo alone (74% vs 20%; P=0.01). Across baseline and week 13, a total of 53 samples were available for assessment. In pts receiving cabo/nivo/CBM588, there was a significant change in the level of IL-12, IL-13, eotaxin, interferon-γ, and granulocyte-macrophage colony stimulating factor (GM-CSF); this was not observed in the cabo/nivo alone arm. Additional flow cytometric analyses characterizing relevant CD4- and CD8-positive subsets will be presented.

Conclusions

Taken together with our previous study evaluating nivolumab/ipilimumab with CBM588 (Dizman et al Nat Med 2022), these results suggest that the augmented clinical outcome seen with the addition of CBM588 to cabo/nivo may be related to systemic immunomodulation. Combined analyses of the cohorts across studies are planned.
Well Leg Compartment Syndrome in the Thigh and Calf Caused by a Forced Prone Position after Syncope
Authors: Zhou Zhegang , Wen Jingjing , Yu Longbiao , Qi Tiantian , Fan Zhao , Luo Dan , Yan Jing , Xiao Yingfeng , Zeng Hui , Yu Fei
Published: August 2024

An 80-year-old male patient was admitted to the hospital due to swelling in the right lower limb with local blisters caused by a forced prone position for 9 hours after syncope. The patient got up in the middle of the night and fainted beside the bed due to a transient cerebral ischemia attack. The front of the right thigh and calf contacted the bed edge, presenting a forced prone position for 9 hours. The physical examination revealed swelling of the right lower limb, accompanied by local tension blisters, and the tension of the thigh and calf was increased. The patient had a history of diabetes, and no lower limb artery or vein thrombosis was found on B-ultrasound. Based on these findings, the patient was diagnosed with well leg compartment syndrome in the right thigh and calf. When the patient was admitted, the creatine phosphokinase level was 62,300 u/L, and the creatinine level was 2.66 mg/dL. Besides, the urea level of this patient was 11 mmol/L. He developed anuria with a high creatinine level, indicating acute kidney injury. Subsequently, temporary hemodialysis was performed for treatment. The patient underwent fasciotomy of the right thigh and calf, and the vacuum-assisted closure device was adopted for wound treatment. After 2 weeks of decompression, the wound was directly sutured under tension. After renal replacement therapy, the creatine phosphokinase level of this patient was 102 u/L, and the creatinine level was 95 mol/L, which tended to be normal.
Psoriasis pathogenesis: What’s new in angiogenesis and angiopoietins
Authors: Li Ya-Hui , Liu Jun-Lin
Published: August 2024

Psoriasis is a common chronic inflammatory skin disorder primarily characterized by scaly, erythematous plaques. Microvascular abnormalities are a major pathogenic mechanism, with early histological changes including tortuous dilation of capillaries in the papillary dermis. Increased vascular permeability and angiogenesis nourish proliferative keratinocytes, facilitate inflammatory cell migration, and significantly contribute to the onset and persistence of psoriasis. Angiopoietins, a class of proangiogenic factors, play a significant role in regulating vascular stability, angiogenesis under physiological and pathological conditions, and inflammatory processes. This paper provides a comprehensive review of the advancements in our understanding of angiogenesis and the role of angiopoietins in the context of psoriasis.
Effect of simulation-based emergency airway management education on the knowledge, skills and perceived confidence of medical interns
Authors: Basnet Samjhana , Shrestha Sailesh P. , Shrestha Roshana , Shrestha Anmol P. , Shrestha Ashish , Sahu Sandeep , Mhatre Bhavana , Silwal Prabhat
Published: August 2024

Background:

An effective airway management education program is a crucial part of the undergraduate medical education curriculum. Theoretical instructions and practical demonstrations are the major modalities of medical education in Nepal. Simulation-based education (SBE) programs have not yet been implemented effectively. The authors aimed to determine the effects of an SBE program on the knowledge, skills, and perceived confidence of medical interns regarding emergency airway management.

Methods:

This mixed methods study comprised both quantitative and qualitative components. The study participants were 47 medical interns who had participated in the SBE program.

Results:

The mean age of the 47 participants was 24.74 years. There were 33 (70.21%) male and 14 (29.79%) female participants. The knowledge, skills, and perceived confidence scores of the participants for airway management preparation, basic airway management, endotracheal intubation, and laryngeal mask airway (LMA) insertion improved significantly following the SBE program (P<0.001). Analysis of the participants’ feedback indicated that they largely approved of the SBE program. The majority of students and faculty expressed a willingness to include similar programs in the undergraduate medical education curriculum.

Conclusion:

This study demonstrated through quantitative and qualitative metrics that SBE can enhance the knowledge, skills, and perceived confidence in performing emergency airway management among medical interns. The authors recommend measures to include and effectively implement SBE in the undergraduate medical education curriculum of Nepal.
Outcomes of medial to lateral vs. lateral to medial approaches in laparoscopic colorectal cancer resections
Authors: Iqbal Muhammad Rafaih , Ari Kaso , Probert Spencer , Cai Wenyi , Ramadan Wafaa , Walton Sarah-Jane
Published: August 2024

Introduction:

Bowel cancer is a significant global health concern, ranking as the third most prevalent cancer worldwide. Laparoscopic resections have become a standard treatment modality for resectable colorectal cancer. This study aimed to compare the clinical and oncological outcomes of medial to lateral (ML) vs lateral to medial (LM) approaches in laparoscopic colorectal cancer resections.

Methods:

A retrospective cohort study was conducted at a UK district general hospital from 2015 to 2019, including 402 patients meeting specific criteria. Demographic, clinical, operative, postoperative, and oncological data were collected. Participants were categorised into LM and ML groups. The primary outcome was 30-day complications, and secondary outcomes included operative duration, length of stay, lymph node harvest, and 3-year survival.

Results:

A total of 402 patients (55.7% males) were included: 102 (51.6% females) in the lateral mobilisation (LM) group and 280 (58.9% males) in the medial mobilisation (ML) group. Right hemicolectomy (n=157, 39.1%) and anterior resection (n=150, 37.3%) were the most performed procedures. The LM group had a shorter operative time for right hemicolectomy (median 165 vs. 225 min, P<0.001) and anterior resection (median 230 vs. 300 min, P<0.001). There was no significant difference between the two groups in terms of wound infection (P=0.443), anastomotic leak (P=0.981), postoperative ileus (P=0.596), length of stay (P=0.446), lymph node yield (P=0.848) or 3-year overall survival rate (Log-rank 0.759).

Discussion:

The study contributes to the limited evidence on ML vs LM approaches. A shorter operative time in the LM group was noted in this study, contrary to some literature. Postoperative outcomes were comparable, with a non-significant increase in postoperative ileus in the LM group. The study emphasises the safety and feasibility of both approaches.
Navigating uncharted waters: assessing the impact of the COVID-19 pandemic on hematopoietic stem cell transplantation: challenges and innovations
Authors: Qureshi Zaheer , Altaf Faryal , Jamil Abdur , Siddique Rimsha , Shah Shivendra
Published: August 2024

The COVID-19 pandemic has significantly impacted hematopoietic stem cell transplantation (HSCT), necessitating adaptations across pre-transplant, transplantation, and post-transplant phases. HSCT recipients with compromised immune systems face heightened risks of severe COVID-19 outcomes, including increased mortality. The pandemic prompted significant changes in treatment strategies, with many patients experiencing delays or deferrals in autologous stem cell transplantation (ASCT), alongside adjustments to chemotherapy regimens to prevent disease recurrence. Clinical practices have evolved to address pandemic-related challenges, including a decrease in allo-HSCT procedures, a shift towards using domestic donors and peripheral blood stem cells over bone marrow grafts, and integration of telemedicine to reduce patient burden. These adaptations aim to balance COVID-19 exposure risks with the need for lifesaving HSCT. Innovations in response to the pandemic include stringent infection control measures, modified conditioning regimens, and revised post-transplant care protocols to mitigate infection risks. The importance of optimizing antiviral treatments, exploring new immunomodulatory interventions, and researching broadly neutralizing antibodies for HSCT recipients has been underscored. Despite the difficulties, the pandemic has catalyzed significant learning and innovation in HSCT practices, emphasizing the need for ongoing adaptation and research to protect this vulnerable patient population.
A Case of Metastatic Pulmonary Calcification Detected on 99mTc-MDP Bone Scan and 99mTc-FAPI Scan
Authors: Sahafi Pegah , Sabertanha Amin , Ataei Azimi Sajad , Aryana Kamran , Aghaee Atena
Published: August 2024

A 59-year-old woman with recent history of weakness, loss of appetite, and significant weight loss was referred for malignancy workup. On the first day, the patient underwent a 99mTc-MDP scan, which revealed diffuse pulmonary uptake in both lungs. Two days later, 99mTc-FAPI scan was performed and showed diffuse pulmonary uptake in the planar and SPECT/CT images. The study present an interesting case demonstrating FAPI-ligand uptake in metastatic pulmonary calcification.
The Early Perfusion Image Is Useful to Support the Visual Interpretation of Brain Amyloid-PET With 18F-Flutemetamol in Borderline Cases
Authors: Mathies Franziska L. , Heeman Fiona , Visser Pieter Jelle , den Braber Anouk , Yaqub Maqsood , Klutmann Susanne , Schöll Michael , van de Giessen Elsmarieke , Collij Lyduine E. , Buchert Ralph
Published: August 2024

Purpose

Visual interpretation of brain amyloid-β (Aβ) PET can be difficult in individuals with borderline Aβ burden. Coregistration with individual MRI is recommended in these cases, which, however, is not always available. This study evaluated coregistration with the early perfusion frames acquired immediately after tracer injection to support the visual interpretation of the late Aβ-frames in PET with 18F-flutemetamol (FMM).

Patients and Methods

Fifty dual-time-window FMM-PET scans of cognitively normal subjects with 0 to 60 Centiloids were included retrospectively (70.1 ± 6.9 years, 56% female, MMSE score 28.9 ± 1.3, 42% APOE ɛ4 carrier). Regional Aβ load was scored with respect to a 6-point Likert scale by 3 independent raters in the 10 regions of interest recommended for FMM reading using 3 different settings: Aβ image only, Aβ image coregistered with MRI, and Aβ image coregistered with the perfusion image. The impact of setting, within- and between-readers variability, region of interest, and Aβ-status was tested by repeated-measure analysis of variance of the Likert score.

Results

The Centiloid scale ranged between 2 and 52 (interquartile range, 7–19). Support of visual scoring by the perfusion image resulted in the best discrimination between Aβ-positive and Aβ-negative cases, mainly by improved certainty of excluding Aβ plaques in Aβ-negative cases (P = 0.030). It also resulted in significantly higher between-rater agreement. The setting effect was most pronounced in the frontal lobe and in the posterior cingulate cortex/precuneus area (P = 0.005).

Conclusions

The early perfusion image is a suitable alternative to T1-weighted MRI to support the visual interpretation of the late Aβ image in FMM-PET.
The Posterior Table for Primary Reconstruction of Frontal Sinus Fractures
Authors: Lima Luciano Henrique Ferreira , Brito Gabriel Conceição , Sverzut Alexander Tadeu
Published: August 2024

Frontal fractures can be associated with major facial defects and present, in some cases, a challenge in bone reconstruction. Due to this challenge, this work aims to describe the use of the posterior table of the frontal sinus as a fragment to reconstruct this region. However, this technique is reserved for cases where the posterior table will be removed due to its fracture and is more intact than the anterior table of the frontal sinus.
Prognostic Factors and Incidence for Postictal Agitation After Electroconvulsive Therapy
Authors: Ertman Melissa , van der Valk Bouman Emy S. , Clephas Pascal R.D. , Birkenhager Tom K. , Klimek Markus
Published: August 2024

Postictal agitation (PIA) is an adverse effect of electroconvulsive therapy (ECT) and is known to predict other side effects of ECT, but inconsistencies in the literature remain regarding PIA prognostic factors and incidence. Therefore, a systematic review and meta-analysis were conducted (1) to identify prognostic factors for PIA following ECT and (2) to elucidate the diverse incidences of PIA following ECT based on demographic and clinical characteristics. Specifically, electronic databases were searched for retrospective observational studies and randomized controlled trials (RCTs) that objectively reported PIA incidence. Additional inclusion criteria encompassed studies involving patients 18 years or older and allowed for the extraction of PIA prognostic factors. This resulted in the inclusion of 21 articles with 66,047 patients in total. A total of 35 prognostic factors were identified for PIA after ECT, consisting of 8 anesthesia-related, 19 patient-related, and 8 ECT-related prognostic factors. A meta-analysis was conducted for 7 prognostic factors. None of the prognostic factors demonstrated a significant effect on reducing or increasing PIA incidence. Mean PIA was 13.9% (18.0% adjusted) at the patient level and 12.4% (16.5% adjusted) at the session level. Overall risk of bias was generally moderate to low, except in the outcome measurement domain, where 43% of the studies had a high risk of bias. Although none of the prognostic factors in meta-analysis were significant, several other prognostic factors consistently indicated increased or decreased risk, providing direction for future research. A scarcity of (high-quality) data emphasizes the need for additional research on this topic to be conducted.
Selective and prolonged attention to emotional scenes in humans and bonobos
Authors: van Berlo Evy , Roth Tom S. , Kim Yena , Kret Mariska E.
Published: August 2024

Perceiving emotions in others is at the foundation of higher-order social cognition. The importance of emotions is evidenced by the fact that they receive prioritized attention at early stages of processing the environment in humans and some other primates. Nevertheless, we do not fully understand how emotion modulates attention over longer durations in primates, particularly in great apes. Bonobos, one of our closest relatives, stand out in emotion processing and regulation among great apes. This makes them an interesting comparison species and a valuable model for studying the evolution of emotion perception in hominids. We investigated how bonobos and humans spontaneously attend to emotionally valent scenes in a preferential looking task using eye-tracking. With Bayesian mixed modelling, we found that bonobos and humans generally looked longer at emotional scenes, mainly of conspecifics. Moreover, while bonobos did not have a bias toward emotional human scenes, humans sustained their attention toward bonobos playing, grooming and having sex. Furthermore, when exploring an immediate bias for emotions, humans showed a bias toward affiliative human scenes, and bonobos showed a bias away from bonobos-in-distress scenes. These findings suggest that emotions modulate attention at early and later attentional stages in bonobos, similar to humans.
Lack of weight gain and increased mortality during and after treatment among adults with drug-resistant tuberculosis in Georgia, 2009-2020
Authors: Chakhaia Tsira , Blumberg Henry M , Kempker Russell R , Luo Ruiyan , Dzidzikashvili Nino , Chincharauli Mamuka , Tukvadze Nestan , Avaliani Zaza , Stauber Christine , Magee Matthew J.
Published: August 2024

Background

While low body mass index (BMI) is associated with poor tuberculosis (TB) treatment outcomes, the impact of weight gain during TB treatment is unclear. To address this knowledge gap, we assessed if lack of weight gain is associated with all-cause mortality during and after TB treatment.

Methods

We conducted a retrospective cohort study among adults with newly diagnosed multi- or extensively drug-resistant (M/XDR) pulmonary TB in Georgia between 2009-2020. The exposure was a change in BMI during the first 3-6 months of TB treatment. All-cause mortality during and after TB treatment was assessed using the National Death Registry. We used competing-risk Cox proportional hazard models to estimate adjusted hazard ratios (aHR) between BMI change and all-cause mortality.

Results

Among 720 adult participants, 21% had low BMI (<18.5 kg/m2) at treatment initiation and 9% died either during (n=16) or after treatment (n=50). During the first 3-6 months of TB treatment, 17% lost weight and 14% had no weight change. Among 479 adults with normal baseline BMI ( ≥18.5–24.9 kg/m2), weight loss was associated with an increased risk of death during TB treatment (aHR=5.25; 95%CI: 1.31-21.10). Among 149 adults with a low baseline BMI, no change in BMI was associated with increased post-TB treatment mortality (aHR=4.99; 95%CI: 1.25-19.94).

Conclusions

Weight loss during TB treatment (among those with normal baseline BMI) or no weight gain (among those with low baseline BMI) was associated with increased rates of all-cause mortality. Our findings suggest that scaling up weight management interventions among those with M/XDR TB may be beneficial.

Among a cohort of persons with drug resistant tuberculosis (TB), failure to gain weight during TB treatment was associated with an increased risk of all-cause mortality during and after completion of treatment.