bluuebunny/crossref_metadata_2025 huggingface dataset:
Urinary iodine clearance after iodinated contrast administration to healthy cats
Authors: Allegrini Gabriella , Poirier Valerie J. , Pezzali Julia G. , Beaufrère Hughes H. , Shoveller Anna K. , Kopke Matthew A. , Beeler‐Marfisi Janet
Published: September 2024

Background

Exogenous iodine interferes with the uptake of radioactive iodine (131I) by the thyroid gland. This has potential implications for the treatment of cats with hyperthyroidism that have recently undergone computed tomography (CT) with IV administration of iodinated contrast medium (ICM).

Hypothesis

To determine the time to normalize urinary iodine clearance after administration of ICM. We hypothesized that it would require 4 weeks for urinary iodine concentration (UIC) to decrease to baseline after IV administration of ICM.

Animals

Ten healthy adult neutered male cats.

Methods

All cats were sedated and received Iopamidol at a dose of 2 mL/kg (600 mg/kg). Urinary iodine and creatinine concentrations were measured before administration of Iopamidol and on days 1, 2, 3, 7, 10 and weeks 2 to 6 after administration. The urinary iodine‐to‐creatinine ratio (UICR) was calculated. Outcome variables were modeled using a linear mixed‐effects model.

Results

Urinary iodine concentration increased 37‐ to 884‐fold on Day 1 after ICM injection and returned to baseline during Week 2. Compared with baseline, UIC was significantly increased for Days 1 to 7 (all P < .001); UC was significantly lower for Days 1 to 10 (all P < .03); and UICR was significantly increased from Days 1 to 10 (all P < .001, except Day 10 P = .05).

Conclusions

Urinary clearance of iodine after IV administration of ICM requires 10 days to return to baseline in healthy cats. A 2‐week interval between the iodinated contrast study and 131I treatment could be appropriate but needs to be confirmed in hyperthyroid cats.
Ultrasound characteristics of hepatic epithelioid hemangioendothelioma: a multi-center case series study
Authors: Zhang Tonglong , Wang Meng , Ruan Lei , Chen Juanping , Zheng Wuwu , Han Sen , Jiang Tianan
Published: September 2024

Aims: Hepatic epithelioid hemangioendothelioma (HEHE) is a rare vascular tumor that primarily affects the liver. This study aimed to analyze the characteristics of conventional ultrasound (US) and contrast-enhanced ultrasonography (CEUS) in HEHE.Material and methods: This multi-center case series study enrolled patients diagnosed with HEHE from five hospitals in China between August 2004 and October 2022. Data on conventional US and CEUS characteristics were collected and analyzed.Results: A total of 41 patients with HEHE were included, comprising 14 males and 27 females with a mean age of 50.62±11.43 years. The mean size of the lesion was 4.51±2.92 cm. Among these patients, 29 were confirmed through surgical resection and 12 through liver biopsy. Conventional US imaging identified three types of HEHE: multifocal type in 35 patients (85.4%), single nodular type in 1 patient (2.4%), and giant type in 5 patients (12.2%). US revealed proximity to the liver capsule in 29 patients (71%), hypoechoic appearance in 36 patients (88%), heterogeneity in 4 patients (10%), and hyperechoic appearance in 1 patient (2.4%). CEUS also demonstrated three distinct enhancement patterns: peripheral marginal enhancement with centripetal filling in the arterial phase and washout in the portal venous and venous phases (23 patients), eterogeneous enhancement in the arterial phase with washout in the subsequent phases (7 patients), and mild hyperenhancement in the arterial phase with resolution in later phases (9 patients). A hypo-enhancement pattern in the portal venous and venous phases was observed in 38 patients, suggesting a higher degree of malignancy.Conclusion: HEHE exhibits specific US findings, primarilypresenting as multiple hypoechoic lesions distributed under the liver capsule.
A comparison of smartphone and infrasound microphone data from a fuel air explosive and a high explosive
Authors: Takazawa S. K. , Popenhagen S. K. , Ocampo Giraldo L. A. , Cardenas E. S. , Hix J. D. , Thompson S. J. , Chichester D. L. , Garcés M. A.
Published: September 2024

For prompt detection of large (>1 kt) above-ground explosions, infrasound microphone networks and arrays are deployed at surveyed locations across the world. Denser regional and local networks are deployed for smaller explosions, however, they are limited in number and are often deployed temporarily for experiments. With the expanded interest in smaller yield explosions targeted at vulnerable areas such as population centers and key infrastructures, the need for more dense microphone networks has increased. An “attritable” (affordable, reusable, and replaceable) and flexible alternative can be provided by smartphone networks. Explosion signals from a fuel air explosive (thermobaric bomb) and a high explosive with trinitrotoluene equivalent yields of 6.35 and 3.63 kg, respectively, were captured on both an infrasound microphone and a network of smartphones. The resulting waveforms were compared in time, frequency, and time-frequency domains. The acoustic waveforms collected on smartphones produced a filtered explosion pulse due to the smartphone's diminishing frequency response at infrasound frequencies (<20 Hz) and was found difficult to be used with explosion characterization methods utilizing waveform features (peak overpressure, impulse, etc.). However, the similarities in time frequency representations and additional sensor inputs are promising for other explosion signal identification and analysis. As an example, a method utilizing the relative acoustic amplitudes for source localization using the smartphone sensor network is presented.
Persistent polarization: The unexpected durability of political animosity around US elections
Authors: Fasching Neil , Iyengar Shanto , Lelkes Yphtach , Westwood Sean J.
Published: September 2024

The scholarly literature suggests that, as elections approach, political tensions intensify, and, as they pass, tensions return to pre-election levels. Using a massive new dataset of 66,000 interviews (cross-sectional and panel), we find that animosities are durable and consistent over the course of the 2022 US election. Individuals with more exposure to the campaign tend to be more polarized, and this sentiment endures post-election. Contrary to expectations, partisans who voted for the winning candidate are no less polarized post-election than those on the losing side. In closing, we note that the durability of polarization has important implications not only for our understanding of the scope of partisan divides but also for efforts designed to ameliorate polarization.
Cerebrospinal fluid flow extends to peripheral nerves further unifying the nervous system
Authors: Ligocki Alexander P. , Vinson Augustine V. , Yachnis Anthony T. , Dunn William A. , Smith Douglas E. , Scott Elizabeth A. , Alvarez-Castanon Jimena V. , Baez Montalvo Daniel E. , Frisone Olivia G. , Brown Gary A. J. , Pessa Joel E. , Scott Edward W.
Published: September 2024

Cerebrospinal fluid (CSF) is responsible for maintaining brain homeostasis through nutrient delivery and waste removal for the central nervous system (CNS). Here, we demonstrate extensive CSF flow throughout the peripheral nervous system (PNS) by tracing distribution of multimodal 1.9-nanometer gold nanoparticles, roughly the size of CSF circulating proteins, infused within the lateral cerebral ventricle (a primary site of CSF production). CSF-infused 1.9-nanometer gold transitions from CNS to PNS at root attachment/transition zones and distributes through the perineurium and endoneurium, with ultimate delivery to axoplasm of distal peripheral nerves. Larger 15-nanometer gold fails to transit from CNS to PNS and instead forms “dye-cuffs,” as predicted by current dogma of CSF restriction within CNS, identifying size limitations in central to peripheral flow. Intravenous 1.9-nanometer gold is unable to cross the blood-brain/nerve barrier. Our findings suggest that CSF plays a consistent role in maintaining homeostasis throughout the nervous system with implications for CNS and PNS therapy and neural drug delivery.
Adaptive cognitive control circuit changes associated with problem-solving ability and depression symptom outcomes over 24 months
Authors: Zhang Xue , Pines Adam , Stetz Patrick , Goldstein-Piekarski Andrea N. , Xiao Lan , Lv Nan , Tozzi Leonardo , Lavori Philip W. , Snowden Mark B. , Venditti Elizabeth M. , Smyth Joshua M. , Suppes Trisha , Ajilore Olusola , Ma Jun , Williams Leanne M.
Published: September 2024

Mechanistically targeted behavioral interventions are a much-needed strategy for improving outcomes in depression, especially for vulnerable populations with comorbidities such as obesity. Such interventions may change behavior and outcome by changing underlying neural circuit function. However, it is unknown how these circuit-level modifications unfold over intervention and how individual differences in early circuit-level modifications may explain the heterogeneity of treatment effects. We addressed this need within a clinical trial of problem-solving therapy for participants with depression symptoms and comorbid obesity, focusing on the cognitive control circuit as a putative neural mechanism of action. Functional magnetic resonance imaging was applied to measure the cognitive control circuit activity at five time points over 24 months. Compared with participants who received usual care, those receiving problem-solving therapy showed that attenuations in cognitive control circuit activity were associated with enhanced problem-solving ability, which suggests that this circuit plays a key role in the mechanisms of problem-solving therapy. Attenuations in circuit activity were also associated with improved depression symptoms. Changes in cognitive control circuit activity at 2 months better predicted changes in problem-solving ability and depression symptoms at 6, 12, and 24 months, with predictive improvements ranging from 17.8 to 104.0%, exceeding baseline demographic and symptom characteristics. Our findings suggest that targeting the circuit mechanism of action could enhance the prediction of treatment outcomes, warranting future model refinement and improvement to pave the way for its clinical application.
PTPRT loss enhances anti–PD-1 therapy efficacy by regulation of STING pathway in non–small cell lung cancer
Authors: Chen Zhuo , Ji Wenxiang , Feng Wenxin , Cui Jingchuan , Wang Yuchen , Li Fan , Chen Jiachen , Guo Ziheng , Xia Liliang , Zhu Xiaokuan , Niu Xiaomin , Zhang Yanshuang , Li Ziming , Wong Alice S. T. , Lu Shun , Xia Weiliang
Published: September 2024

With the revolutionary progress of immune checkpoint inhibitors (ICIs) in non–small cell lung cancer, identifying patients with cancer who would benefit from ICIs has become critical and urgent. Here, we report protein tyrosine phosphatase receptor type T (PTPRT) loss as a precise and convenient predictive marker independent of PD-L1 expression for anti–PD-1/PD-L1 axis therapy. Anti–PD-1/PD-L1 axis treatment markedly increased progression-free survival in patients with PTPRT-deficient tumors. PTPRT-deficient tumors displayed cumulative DNA damage, increased cytosolic DNA release, and higher tumor mutation burden. Moreover, the tyrosine residue 240 of STING was identified as a direct substrate of PTPRT. PTPRT loss elevated phosphorylation of STING at Y240 and thus inhibited its proteasome-mediated degradation. PTPRT-deficient tumors released more IFN-β, CCL5, and CXCL10 by activation of STING pathway and increased immune cell infiltration, especially of CD8 T cells and natural killer cells, ultimately enhancing the efficacy of anti–PD-1 therapy in multiple subcutaneous and orthotopic tumor mouse models. The response of PTPRT-deficient tumors to anti–PD-1 therapy depends on the tumor-intrinsic STING pathway. In summary, our findings reveal the mechanism of how PTPRT-deficient tumors become sensitive to anti–PD-1 therapy and highlight the biological function of PTPRT in innate immunity. Considering the prevalence of PTPRT mutations and negative expression, this study has great value for patient stratification and clinical decision-making.
Inhibition of CCL7 improves endothelial dysfunction and vasculopathy in mouse models of diabetes mellitus
Authors: Chang Ting-Ting , Li You-Zhen , Mo Hsiao-Wei , Chen Ching , Lin Liang-Yu , Chang Chia-Chi , Chen Jaw-Wen
Published: September 2024

Diabetic vascular disease is a major complication of diabetes mellitus (DM). Chemokine C-C motif ligand 7 (CCL7) attracts macrophages and monocytes, amplifying inflammatory processes in the vasculature. We hypothesized a causal role for CCL7 in diabetic vasculopathy. CCL7 concentrations were higher in the plasma of patients with type 2 DM, as well as in supernatants from their endothelial progenitor cells (EPCs). High-glucose stimulation increased the secretion of CCL7 from human dermal microvascular endothelial cells (HDMECs) through the c-Fos and c-Jun signaling pathways. CCL7 inhibition using knockdown or neutralization antibody treatment reversed the high glucose–induced impaired tube formation and migration abilities of EPCs, human aortic endothelial cells, human coronary artery endothelial cells, and HDMECs. Administration of recombinant human CCL7 protein impaired tube formation and migration abilities by down-regulating the AKT–endothelial nitric oxide synthase and AKT/nuclear factor erythroid 2–related factor 2/heme oxygenase–1/vascular endothelial growth factor/stromal cell–derived factor–1 pathways and by up-regulating ERK/phosphorylated p65/interleukin-1β/interleukin-6/tumor necrosis factor–α pathways through CC chemokine receptor 3 in endothelial cells.
Ccl7
knockout in streptozotocin-treated mice showed improved neovasculogenesis in ischemic limbs and accelerated wound repair, with increased circulating EPCs and capillary density. CCL7 antibody treatment in
db/db
mice and high-fat diet–induced hyperglycemia mice showed improved neovasculogenesis in ischemic limbs and wound areas, accompanied by up-regulation of angiogenic proteins and down-regulation of inflammatory proteins. Endothelial cell–specific
Ccl7
-knockout mice showed ameliorated diabetic vasculopathy in streptozotocin-induced DM. This study highlights the potential of CCL7 as a therapeutic target for diabetic vasculopathy.
Beyond morphogenesis and secondary metabolism: function of Velvet proteins and LaeA in fungal pathogenesis
Authors: Calvo Ana M. , Dabholkar Apoorva , Wyman Elizabeth M. , Lohmar Jessica M. , Cary Jeffrey W.
Published: September 2024

Velvet proteins, as well as the epigenetic regulator LaeA, are conserved in numerous fungal species, where, in response to environmental cues, they control several crucial cellular processes, including sexual and asexual morphogenesis, secondary metabolism, response to oxidative stress, and virulence. During the last two decades, knowledge of their mechanism of action as well as understanding their functional roles, has greatly increased, particularly in
Aspergillus
species. Research efforts from multiple groups followed, leading to the characterization of other Velvet and LaeA homologs in species of other fungal genera, including important opportunistic plant and animal pathogens. This review focuses mainly on the current knowledge of the role of Velvet and LaeA function in fungal pathogenesis. Velvet proteins and LaeA are unique to fungi, and for this reason, additional knowledge of these critical regulatory proteins will be important in the development of targeted control strategies to decrease the detrimental impact of fungal pathogens capable of causing disease in plants and animals.
A three-way interface of the Nipah virus phosphoprotein X-domain coordinates polymerase movement along the viral genome
Authors: Wolf Josef D. , Plemper Richard K.
Published: September 2024

Nipah virus (NiV) is a highly pathogenic paramyxovirus causing frequently lethal encephalitis in humans. The NiV genome is encapsidated by the nucleocapsid (N) protein. RNA synthesis is mediated by the viral RNA-dependent RNA polymerase (RdRP), consisting of the polymerase (L) protein complexed with the homo-tetrameric phosphoprotein (P). The advance of the polymerase along its template requires iterative dissolution and reformation of transient interactions between P and N protomers in a highly regulated process that remains poorly understood. This study applied functional and biochemical NiV polymerase assays to the problem. We mapped three distinct protein interfaces on the C-terminal P-X domain (P-XD), which form a triangular prism and engage L, the C-terminal N tail, and the globular N core, respectively. Transcomplementation assays using NiV L and N-tail binding-deficient mutants revealed that only one XD of a P tetramer binds to L, whereas three must be available for N-binding for efficient polymerase activity. The dissolution of the N-tail complex with P-XD was coordinated by a transient interaction between N-core and the α−1/2 face of this XD but not unoccupied XDs of the
P
tetramer, creating a timer for coordinated polymerase advance.

IMPORTANCE

Mononegaviruses comprise major human pathogens such as the Ebola virus, rabies virus, respiratory syncytial virus, measles virus, and Nipah virus (NiV). For replication and transcription, their polymerase complexes must negotiate a protein-encapsidated RNA genome, which requires the highly coordinated continuous formation and resolution of protein-protein interfaces as the polymerase advances along the template. The viral P protein assumes a central role in this process, but the molecular mechanism of ensuring polymerase mobility is poorly understood. Studying NiV polymerase complexes, we applied functional and biochemical assays to map three distinct interfaces in the NiV P XD and identified transient interactions between XD and the nucleocapsid core as instrumental in coordinating polymerase advance. These results define a conserved molecular principle regulating paramyxovirus polymerase dynamics and illuminate a promising druggable target for the structure-guided development of broad-spectrum polymerase inhibitors.
Supplemental Material: Enhanced global terrestrial moisture from the Early Triassic to the Late Triassic: Evidence from extensive Neocalamites forests in North China
Authors: Wang Yuchong , Hongwei Kuang , et al.
Published: September 2024

Figure S1: Macrophotographs of some of Neocalamites fossils on the Luohe, Huangling. Figure S2: The 3-D model drawing of a Neocalamites fossil by 3-D stereophotogrammetry. Figure S3: Neocalamites  fossils were found in its present location. Table S1: The location of the areas where the Neocalamites are reported in references. Table S2: Diameters and nearest neighbor distance of Neocalamites fossil forest. Table S3: Measurement of long axis and minor axis from Neocalamites. Table S4: Mean diameter and mean height of bamboos and extant Equisetum.
Polymicrobial pericarditis caused by bacterial and fungal translocation from an oesophageal ulcer
Authors: Holman Michael , Kambam Greeshma , Lap Coen , Siegel Marc O
Published: September 2024

This case report discusses a rare instance of polymicrobial pericarditis in a man in his early 60s with a history of substance abuse. The patient presented with chest pain and shortness of breath, later diagnosed as pericarditis caused byStreptococcus anginosus,S. intermediusandCandida glabrata, likely originating from a large adjacent oesophageal ulcer. The condition led to critical illness, requiring pericardiocentesis, antibiotic and antifungal therapy. Despite initial improvement, the patient experienced recurrence and ultimately underwent pericardectomy. The article emphasises the rarity and severity of polymicrobial pericarditis, often associated with high mortality. It underscores the importance of prompt recognition, broad-spectrum antibiotics and source control, particularly when the gastrointestinal tract is implicated. The case highlights the challenges in managing such cases and the potential need for surgical intervention for optimal outcomes.
Converging pathways: acquired von Willebrand disease in systemic lupus erythematosus with antiphospholipid antibodies presenting with persistent menstrual bleeding
Authors: Garg Ankush , Gupta Gaurav , Gupta Ranjan , Mishra Ritesh Kumar
Published: September 2024

We present a case of a woman in her 20s with inadequately treated systemic lupus erythematosus (SLE). She presented with heavy menstrual bleeding, along with nasal and gum bleeding worsening over 3 months. There was no bleeding history in her family, childhood, dental procedures or childbirth. Evaluation ruled out structural causes, revealing prolonged activated partial thromboplastin time (incomplete correction on mixing studies), normal prothrombin time, moderate thrombocytopenia, and lupus anticoagulant and anti-phosphatidylserine/prothrombin antibody positivity twice, 12 weeks apart. Further evaluation showed very low von Willebrand factor (vWF) levels (<5%). She was treated with pulse methylprednisolone for 3 days, resulting in complete symptom resolution and improvement in vWF levels to 130%. The absence of bleeding history, family history, presence of very low vWF and its response to corticosteroids led to a diagnosis of acquired vWF syndrome as the cause of mucosal bleeding in an SLE patient with concomitant positive antiphospholipid antibody. She was discharged on hydroxychloroquine, mycophenolate mofetil and tapering oral corticosteroids.
Eosinophilic jejunitis presenting as acute abdomen with eosinophilic ascites
Authors: Yalçın Eren , Döngelli Hüseyin , Dolu Süleyman , Akarsu Mesut
Published: September 2024

Eosinophilic gastroenteritis (EG) is an inflammatory bowel condition characterised by eosinophilic infiltration of the stomach and small bowel. Smoking and certain foods can trigger EG.

A man in his 40s presented to the emergency department with acute abdominal pain. He had rebound tenderness and guarding on his initial abdominal examination. A subsequent CT scan showed jejunal wall thickening and ascites

He had similar attacks of abdominal pain and was misdiagnosed with familial Mediterranean fever and Crohn’s disease.

Paracentesis revealed eosinophilic ascites. No mucosal abnormality was detected on gastroduodenoscopy and colonoscopy. A double-balloon enteroscopy revealed mucosal inflammation in the jejunum and a biopsy was taken. In this biopsy, eosinophilic jejunitis was detected. He was given corticosteroids and montelukast and his condition was resolved promptly. After discharge, he had attacks of EG until he quit smoking. After quitting smoking, he had an attack once in the last 2 years after consuming eggplant.
Experiences and needs of Chinese women after a stillbirth: a qualitative phenomenological study
Authors: Chen Li , Qian Qiyu , Zhu Yan , Zhang Xu , Zhang Yueming , Jiang Feizhou , Chu Guangping , Shi Jia , Pu Li
Published: September 2024

Objectives

We aimed to explore the lived experiences and needs of women after a recent stillbirth event.

Design

Qualitative phenomenological study.

Setting

The current study was conducted in a tertiary obstetric hospital in East China between 25 January 2024 and 29 March 2024.

Participants

14 women having experienced a stillbirth within the last 6 months.

Results

Researchers agreed on four key themes including individual variations in emotional reaction and recovery, physical recovery and concerns about future pregnancies, the critical role of social support systems and variations in perceptions of stillbirth as the death of a fetus versus a human being, along with related mourning rituals. These themes collectively highlight the multifaceted nature of the stillbirth experience, underscoring the complex interplay between personal, cultural and medical factors that shape women’s emotional and physical responses.

Conclusions

Post-stillbirth experiences among Chinese women are deeply individualised and influenced by a complex interplay of personal emotions, cultural contexts and medical interactions. It is imperative for healthcare systems to implement tailored care strategies beyond standard protocols to proactively address their varied emotional landscapes and physical concerns with an enhanced awareness of cultural sensitivities. Specialised training for healthcare providers should be devised to recognise and respond to the unique grief processes. Comprehensive support systems should be established to significantly enhance the recovery journey by providing essential resources and community connections.
Current state of the pain medicine match: perspective and an eye to the future
Authors: Aggarwal Anuj Kailash , Barad Meredith , Chai Nu Cindy , Furnish Timothy , Mishra Puneet , Kohan Lynn , Moeschler Susan , Reddy Rajiv D , Yalamuru Bhavana
Published: September 2024

The National Resident Matching Program (NRMP) for pain medicine fellowships marked its 10th anniversary in 2023, coinciding with growing discussions within the Association of Pain Program Directors (APPD) regarding the program’s future in the context of a recent decline of applicants into pain medicine. This letter explores the rationale behind reassessing the NRMP’s utility for pain medicine, examining historical and current trends, and considering the implications of withdrawing from the match. Despite a recent decline in applicants and an increase in unfilled positions, the APPD advocates for continued participation in the match. The match ensures equitable and stable recruitment, preventing the chaotic pre-match environment of competitive, early offers. Data from similar specialties highlight the pitfalls of non-match systems, such as increased applicant pressure and reduced program visibility. The APPD supports maintaining the NRMP match while implementing reforms like preference signaling to address evolving challenges. The APPD aims to preserve the match’s benefits and ensure a stable future for pain medicine fellowship recruitment.
Mechanisms of secondary carbonate precipitation on felsic, intermediate and mafic igneous rocks: a case study for NW Scotland
Authors: Stubbs Amanda R. , MacDonald John , Neill Iain
Published: September 2024

Silicate weathering is a natural regulator of atmospheric carbon dioxide (CO
2
), where the majority of carbonate is stored in the oceans. In some instances, carbonates may form via bedrock weathering in terrestrial landscapes, but this is commonly noted in ultramafic rock owing to its desirable mineralogy. In NW Scotland, carbonate minerals surround felsic, intermediate and mafic igneous bedrock. Their abundance suggests that these rocks could potentially be targeted for carbonation, given the absence of other known cation sources nearby. We present geochemical and mineralogical data for bedrock samples and mineralogy and stable carbon and oxygen isotope data for the carbonate samples. Whole-rock geochemistry demonstrates that major abundances of CaO and MgO are present in the bedrock samples and would be sourced from plagioclase and pyroxene, which are target minerals for CO
2
mineralization. The stable carbon and oxygen isotope data demonstrate that there are probably mixed carbon sources (atmospheric and organic), and other environmental factors including temperature, CO
2
degassing or evaporation and nearby waters influence the isotopic composition. Results suggest that rocks traditionally overlooked in CO
2
mineralization studies have the potential to serve as a feedstock for carbonation, given the abundance of secondary carbonates found in NW Scotland.
Private Crypto Versus Public Digital
Authors: Cusumano Michael A.
Published: September 2024

The looming battle over currencies and payment platforms.
AutoRIC: Automated Neural Network Repairing Based on Constrained Optimization
Authors: Sun Xinyu , Liu Wanwei , Wang Shangwen , Chen Tingyu , Tao Ye , Mao Xiaoguang
Published: September 2024

Neural networks are important computational models used in the domains of artificial intelligence and software engineering. Parameters of a neural network are obtained via training it against a specific dataset with a standard process, which guarantees each sample within that set is mapped to the correct class. In general, for a trained neural network, there is no warranty of high-level properties, such as fairness, robustness, and so forth. In this case, one need to tune the parameters in an alternative manner, and it is called repairing. In this paper, we present AutoRIC (
Auto
mated
R
epair w
I
th
C
onstraints), an analytical-approach-based white-box repairing framework against general properties that could be quantitatively measured. Our approach is mainly based on constrained optimization, namely, we treat the properties of neural network as the optimized objective described by a quadratic formula about the faulty parameters. To ensure the classification accuracy of the repaired neural network, we impose linear inequality constraints to the inputs that obtain incorrect outputs from the neural network. In general, this may generate a huge amount of constraints, resulting in the prohibitively high cost in the problem solving, or even making the problem unable to be solved by the constraint solver. To circumvent this, we present a selection strategy to diminish the restrictions, i.e., we always select the most ‘strict’ ones into the constraint set each time. Experimental results show that repairing with constraints performs efficiently and effectively. AutoRIC tends to achieve a satisfactory repairing result whereas brings in a negligible accuracy drop. AutoRIC enjoys a notable time advantage and this advantage becomes increasingly evident as the network complexity rises. Moreover, experiment results also demonstrate that repairing based on unconstrained optimizations are not stable, which embodies the necessity of constraints.
Radiation Shielding Analysis of Multi-Component Glasses: Effects of Varying BaO, PbO2 and Gd2O3 Concentrations
Authors: Al Huwayz Maryam , Almuqrin Aljawhara H. , Alharbi F. F. , Sayyed M. I. , Albarzan B.
Published: September 2024

This work investigates the impact of BaO, PbO2, and Gd2O3 on newly developed borate glasses’ radiation shielding characteristics. The transmission factor (TF) of the glasses is almost zero at the low energy of 0.0395 MeV, which indicates favorable low-energy photon shielding. The maximum TF is reported at 1.46 MeV for the free Gd2O3 glass sample, ranging from 0.89 (0.5 cm thickness) to 0.73 (1.5 cm thickness). Moreover, with more BaO, PbO2, and Gd2O3 content added to the glasses, the TF decreases, indicating an enhancement in the efficiency of the glasses’ radiation protection with the introduction of BaO, PbO2, and Gd2O3. There is a 4.309 to 5.068 g cm−3 increase in the glasses’ density, and, as a result, the mean free path decreases, suggesting improved performance for radiation protection with the adding of more BaO, PbO2, and Gd2O3 contents to the glasses. At 0.122 MeV, the free Gd2O3 glass’s half value layer value is 0.098 cm, while the tenth value layer is 0.325 cm.
Double Metal Gate Macaroni Nanowire FET (DMGM-NFET) for Improved Performance and Off-State Leakage Reduction
Authors: Kaul Aapurva , Rewari Sonam , Nand Deva
Published: September 2024

A pioneering strategy is introduced to enhance band-to-band tunnelling (BTBT) and diminish gate leakages within a double metal gate macaroni-nanowire field-effect transistor (DMGM-NFET). After fine-tuning the threshold voltage, performance is juxtaposed with that of the single metal gate macaroni nanowire FET (SMGM-NFET), DMG-NFET, and single metal gate nanowire FET (SMG-NFET). A hollow pillar is integrated into the architecture of both the SMGM-NFET and the DMGM-NFET along the channel center. Consequently, the DMGM-NFET exhibits a noteworthy reduction in gate-induced drain leakage current, reaching levels as low as 10−11 A, along with a subthreshold slope that surpasses the optimum value by 9.7 mV/decade. Qualitative analysis indicates that the DMGM-NFET achieves the highest ION/IOFF ratio, surpassing the SMG-NFET by 3109 times, the DMG-NFET by 233 times, and the SMGM-NFET by 2 times. When compared to the others, the DMGM-NFET excels in such metrics as quality factor, Av, VEA, fT, TGF, ION/IOFF ratio, Gd, ID-VG, and ID-VD. The significant improvements in these parameters are attributed to the integration of a dual metal gate for enhanced channel regulation and the incorporation of a vacuum filler at the channel’s center, which effectively confines hot electron injections and impedes electron propagation in the OFF-state. These advancements position the DMGM-NFET as an exceptional solution for BTBT applications and for mitigating leakage currents.
Characterization of Ucp1-iCre knockin mice reveals the recombination activity in male germ cells
Authors: Li Meng-Yue , Lu Ming , Cao Dong-Mei , Han Qing , Ma Xian-Hua , Wei Chun-Chun , Zhang Weiping J.
Published: September 2024

Ucp1 promoter-driven Cre transgenic mice are useful in the manipulation of gene expression specifically in thermogenic adipose tissues. The widely used Ucp1-Cre mouse line (Ucp1-CreEvdr), which was generated using the bacterial artificial chromosome (BAC) strategy, exhibits major brown and white fat transcriptomic dysregulation and ectopic activity beyond adipose tissues. Here, we comprehensively validate Ucp1-iCre knockin mice, which serve as another optional model besides Ucp1-CreEvdr mice for specific genetic manipulation in thermogenic tissue.
Polycaprolactone Fiber and Laminin and Collagen IV Protein Incorporation in Implants Enhances Wound Healing in a Novel Mouse Skin Splint Model
Authors: Gadalla Dina , Kennedy Maeve , Ganem Jamie , Suppah Mustafa , Schmitt Alessandra , Lott David G.
Published: September 2024

Wound healing is an intricate process involving multiple cells and distinct phases, presenting challenges for comprehensive investigations. Currently available treatments for wounds have limited capacity to fully restore tissue and often require significant investments of time in the form of repetitive dressing changes and/or reapplications. This article presents a novel study that aims to enhance wound healing by developing biomaterial scaffolds using Medpor®, a porous polyethylene implant, as a model scaffold. The study incorporates electrospun poly(e‐caprolactone) (PCL) fibers and a protein mixture (PM) containing collagen IV and laminin onto the Medpor® scaffolds. To evaluate the impact of these implants on wound healing, a unique splinted wound model in mice is employed. The wounds were evaluated for closure, inflammation, collagen deposition, angiogenesis, epithelialization, and proliferation. The results show that wounds treated with Medpor® + PCL + PM implants demonstrate accelerated closure rates, improved epithelialization, and enhanced angiogenesis compared to other implant groups. However, there were no significant differences observed in collagen deposition and inflammatory response among the implant groups. This study provides valuable insights into the potential benefits of incorporating PCL fibers and a PM onto scaffolds to enhance wound healing. Furthermore, the developed splinted wound model with integrated implants offers a promising platform for future studies on implant efficacy and the advancement of innovative wound healing strategies.
Optical Surface Management System and BladderScan for Patient Setup During Radiotherapy of Postoperative Prostate Cancer
Authors: Chen Hao , Liu Yandong , Qin Songbin , Gan Guanghui
Published: September 2024

Background: The precision of postoperative prostate cancer radiotherapy is significantly influenced by setup errors and alterations in bladder morphology. Utilizing daily cone beam computed tomography (CBCT) imaging allows for the correction of setup errors. However, this naturally leads to the question of the issue of peripheral dose and workload. Thus, a zero‐dose, noninvasive technique to reproduce the bladder volume and improve patient setup accuracy was needed.

Purpose: The aim of this study is to investigate if the setup method by combining Optical Surface Management System (OSMS) and BladderScan can improve the accuracy of setup and accurately reproduce the bladder volume during radiotherapy of postoperative prostate cancer and to guide CTV‐PTV margins for clinic.

Method: The experimental group consisted of 15 postoperative prostate cancer patients who utilized a setup method that combined OSMS and BladderScan. This group recorded 103 setup errors, verified by CBCT. The control group comprised 25 patients, among whom 114 setup errors were recorded using the conventional setup method involving skin markers; additionally, patients in this group also exhibited spontaneous urinary suppression. The errors including lateral (Lat), longitudinal (Lng), vertical directions (Vrt), Pitch, Yaw, and Roll were analyzed between the two methods. The Dice similarity coefficient (DSC) and volume differences of the bladder between CBCT and planning CT were compared as the bladder concordance indicators.

Results: The errors in the experimental group at Vrt, Lat, and Lng were 0.17 ± 0.12, 0.22 ± 0.17, and 0.18 ± 0.12 cm, and the control group were 0.25 ± 0.15, 0.31 ± 0.21, 0.34 ± 0.22 cm. The rotation errors of Pitch, Roll, and Yaw in the experimental group were 0.18 ± 0.12°, 0.11 ± 0.1°, and 0.18 ± 0.13°, and in the control group, they were 0.96 ± 0.89°, 1.01 ± 0.86°, and 1.02 ± 0.84°. The DSC and volume differences were 92.52 ± 1.65% and 39.99 ± 28.75 cm3 in the patients with BladderScan, and in the control group, they were 62.98 ± 22.33%, 273.89 ± 190.62 cm3. The P < 0.01 of the above performance indicators indicates that the difference is statistically significant.

Conclusion: The accuracy of the setup method by combining OSMS and BladderScan was validated by CBCT in our study. The method in our study can improve the setup accuracy during radiotherapy of postoperative prostate cancer compared to the conventional setup method.
Supplementary Figure S5 from WNK1 Interaction with KEAP1 Promotes NRF2 Stabilization to Enhance the Oxidative Stress Response in Hepatocellular Carcinoma
Authors: Li Li , Xie Dacheng , Yu Shijun , Ma Muyuan , Fan Kailing , Chen Jingde , Xiu Mengxi , Xie Keping , Li Yandong , Gao Yong
Published: September 2024

Supplementary Figure S5
Supplementary Figure 10 from Comprehensive Proteogenomic Profiling Reveals the Molecular Characteristics of Colorectal Cancer at Distinct Stages of Progression
Authors: Li Lingling , Jiang Dongxian , Liu Hui , Guo Chunmei , Zhang Qiao , Li Xuedong , Chen Xiaojian , Chen Zheqi , Feng Jinwen , Tan Subei , Huang Wen , Huang Jie , Xu Chen , Liu Chen-Ying , Yu Wei , Hou Yingyong , Ding Chen
Published: September 2024

Supplementary Figure 10 and related legend of the revised manuscript.
Data from RUVBL1/2 Blockade Targets YTHDF1 Activity to Suppress m6A-Dependent Oncogenic Translation and Colorectal Tumorigenesis
Authors: Chen Danyu , Ji Fenfen , Zhou Qiming , Cheung Henley , Pan Yasi , Lau Harry C.-H. , Liang Cong , Yang Zhenjie , Huang Pingmei , Wei Qinyao , Cheung Alvin H.-K. , Kang Wei , Chen Huarong , Yu Jun , Wong Chi Chun
Published: September 2024

Abstract
The N6-methyladenosine (m6A) RNA-binding protein YTHDF1 is frequently overexpressed in colorectal cancer and drives chemotherapeutic resistance. To systematically identify druggable targets in colorectal cancer with high expression of YTHDF1, this study used a CRISPR/Cas9 screening strategy that revealed RUVBL1 and RUVBL2 as putative targets. RUVBL1/2 were overexpressed in primary colorectal cancer samples and represented independent predictors of poor patient prognosis. Functionally, loss of RUVBL1/2 preferentially impaired the growth of YTHDF1-high colorectal cancer cells, patient-derived primary colorectal cancer organoids, and subcutaneous xenografts. Mechanistically, YTHFD1 and RUVBL1/2 formed a positive feedforward circuit to accelerate oncogenic translation. YTHDF1 bound to m6A-modified RUVBL1/2 mRNA to promote translation initiation and protein expression. Coimmunoprecipitation and mass spectrometry identified that RUVBL1/2 reciprocally interacted with YTHDF1 at 40S translation initiation complexes. Consequently, RUVBL1/2 depletion stalled YTHDF1-driven oncogenic translation and nascent protein biosynthesis, leading to proliferative arrest and apoptosis. Ribosome sequencing revealed that RUVBL1/2 loss impaired the activation of MAPK, RAS, and PI3K-AKT signaling induced by YTHDF1. Finally, the blockade of RUVBL1/2 by the pharmacological inhibitor CB6644 or vesicle-like nanoparticle-encapsulated siRNAs preferentially arrested the growth of YTHDF1-expressing colorectal cancer in vitro and in vivo. Our findings show that RUVBL1/2 are potential prognostic markers and druggable targets that regulate protein translation in YTHDF1-high colorectal cancer.

Significance: RUVBL1/2 inhibition is a therapeutic strategy to abrogate YTHDF1-driven oncogenic translation and overcome m6A dysregulation in colorectal cancer.
Data from Ku70 Binding to YAP Alters PARP1 Ubiquitination to Regulate Genome Stability and Tumorigenesis
Authors: Shu Yinyin , Jin Xiaoni , Ji Mintao , Zhang Zhisen , Wang Xiuxiu , Liang Haisheng , Lu Shuangshuang , Dong Shuai , Lin Yiping , Guo Yuhan , Zhuang Qiuyu , Wang Yuhong , Lei Zhe , Guo Lingchuan , Meng Xuanyu , Zhou Guangming , Zhang Wensheng , Chang Lei
Published: September 2024

Abstract
Yes-associated protein (YAP) is a central player in cancer development, with functions extending beyond its recognized role in cell growth regulation. Recent work has identified a link between YAP/transcriptional coactivator with PDZ-binding motif (TAZ) and the DNA damage response. Here, we investigated the mechanistic underpinnings of the cross-talk between DNA damage repair and YAP activity. Ku70, a key component of the nonhomologous end joining pathway to repair DNA damage, engaged in a dynamic competition with TEAD4 for binding to YAP, limiting the transcriptional activity of YAP. Depletion of Ku70 enhanced interaction between YAP and TEAD4 and boosted YAP transcriptional capacity. Consequently, Ku70 loss enhanced tumorigenesis in colon cancer and hepatocellular carcinoma (HCC) in vivo. YAP impeded DNA damage repair and elevated genome instability by inducing PARP1 degradation through the SMURF2-mediated ubiquitin-proteasome pathway. Analysis of samples from patients with HCC substantiated the link between Ku70 expression, YAP activity, PARP1 levels, and genome instability. In conclusion, this research provides insight into the mechanistic interactions between YAP and key regulators of DNA damage repair, highlighting the role of a Ku70-YAP-PARP1 axis in preserving genome stability.

Significance: Increased yes-associated protein transcriptional activity stimulated by loss of Ku70 induces PARP1 degradation by upregulating SMURF2 to inhibit DNA damage, driving genome instability and tumorigenesis.
Supplementary Methods from MYTX-011: A pH-Dependent Anti–c-MET Antibody–Drug Conjugate Designed for Enhanced Payload Delivery to c-MET–Expressing Tumor Cells
Authors: Gera Nimish , Fitzgerald Kyle M. , Ramesh Vijay , Patel Purvi , Kanojia Deepak , Colombo Federico , Kien Lena , Aoyama Simon , Xu Lihui , Jean Jussekia , Deshpande Amit M. , Comb William C. , Chittenden Thomas , Fiske Brian P.
Published: September 2024

Supplementary Methods.
Table S1 from HPN328, a Trispecific T Cell–Activating Protein Construct Targeting DLL3-Expressing Solid Tumors
Authors: Molloy Mary E. , Aaron Wade H. , Barath Manasi , Bush Mabel C. , Callihan Evan C. , Carlin Kevin , Cremin Michael , Evans Thomas , Guerrero Maria G. , Hemmati Golzar , Hundal Avneel S. , Lao Llewelyn , Laurie Payton , Lemon Bryan D. , Lin S.J. , O’Rear Jessica , Patnaik Purbasa , Sotelo Rocha Sony , Santiago Linda , Strobel Kathryn L. , Valenzuela Laura B. , Wu Chi-Heng , Yu Stephen , Yu Timothy Z. , Anand Banmeet S. , Law Che-Leung , Sun Liping L. , Wesche Holger , Austin Richard J.
Published: September 2024

Markers used for immunophenotyping hCD3ε syngeneic model.
Figure S17 from HPN328, a Trispecific T Cell–Activating Protein Construct Targeting DLL3-Expressing Solid Tumors
Authors: Molloy Mary E. , Aaron Wade H. , Barath Manasi , Bush Mabel C. , Callihan Evan C. , Carlin Kevin , Cremin Michael , Evans Thomas , Guerrero Maria G. , Hemmati Golzar , Hundal Avneel S. , Lao Llewelyn , Laurie Payton , Lemon Bryan D. , Lin S.J. , O’Rear Jessica , Patnaik Purbasa , Sotelo Rocha Sony , Santiago Linda , Strobel Kathryn L. , Valenzuela Laura B. , Wu Chi-Heng , Yu Stephen , Yu Timothy Z. , Anand Banmeet S. , Law Che-Leung , Sun Liping L. , Wesche Holger , Austin Richard J.
Published: September 2024

HPN328 treatment in cynomolgus monkeys leads to transient reduction in circulating T cells.
Figure S14 from HPN328, a Trispecific T Cell–Activating Protein Construct Targeting DLL3-Expressing Solid Tumors
Authors: Molloy Mary E. , Aaron Wade H. , Barath Manasi , Bush Mabel C. , Callihan Evan C. , Carlin Kevin , Cremin Michael , Evans Thomas , Guerrero Maria G. , Hemmati Golzar , Hundal Avneel S. , Lao Llewelyn , Laurie Payton , Lemon Bryan D. , Lin S.J. , O’Rear Jessica , Patnaik Purbasa , Sotelo Rocha Sony , Santiago Linda , Strobel Kathryn L. , Valenzuela Laura B. , Wu Chi-Heng , Yu Stephen , Yu Timothy Z. , Anand Banmeet S. , Law Che-Leung , Sun Liping L. , Wesche Holger , Austin Richard J.
Published: September 2024

Stimulation with anti-human CD3 and anti-mouse CD28 beads induces proliferation and activation of T cells from hCD3ε mice.
Supplementary Table 1 from Prognostic Significance of SASP-Related Gene Signature of Radiation Therapy in Head and Neck Squamous Cell Carcinoma
Authors: Lee Min Kyeong , Woo Seon Rang , Noh Joo Kyung , Min Soonki , Kong Moonkyoo , Lee Young Chan , Ko Seong-Gyu , Eun Young-Gyu
Published: September 2024

Supplementary Table 1
Supplementary Figure Legends from Prognostic Significance of SASP-Related Gene Signature of Radiation Therapy in Head and Neck Squamous Cell Carcinoma
Authors: Lee Min Kyeong , Woo Seon Rang , Noh Joo Kyung , Min Soonki , Kong Moonkyoo , Lee Young Chan , Ko Seong-Gyu , Eun Young-Gyu
Published: September 2024

Supplementary Figure Legends full
Figure S2 from Pretargeted Radioimmunotherapy with the Novel Anti-oxMIF/HSG Bispecific Antibody ON105 Results in Significant Tumor Regression in Murine Models of Cancer
Authors: Puchol Tarazona Alejandro A. , Schinagl Alexander , Mirkina Irina , Rossmueller Gregor , Kerschbaumer Randolf J. , Bachmann Friedmund , Thiele Michael
Published: September 2024

Figure S2
Supplementary Table S1 from A Senescence-Mimicking (Senomimetic) VEGFR TKI Side Effect Primes Tumor Immune Responses via IFN/STING Signaling
Authors: Dolan Melissa , Shi Yuhao , Mastri Michalis , Long Mark D. , McKenery Amber , Hill James W. , Vaghi Cristina , Benzekry Sebastien , Barbi Joseph , Ebos John M.L.
Published: September 2024

Supplementary Table S1: MySigDB and Published gene sets used for Gene Set Enrichement Analysis (GSEA).
Supplementary Files from A Senescence-Mimicking (Senomimetic) VEGFR TKI Side Effect Primes Tumor Immune Responses via IFN/STING Signaling
Authors: Dolan Melissa , Shi Yuhao , Mastri Michalis , Long Mark D. , McKenery Amber , Hill James W. , Vaghi Cristina , Benzekry Sebastien , Barbi Joseph , Ebos John M.L.
Published: September 2024

Supplemental Results, Key Resources Table, Supplementary Data Files