bluuebunny/crossref_metadata_2025 huggingface dataset:
The Design of Fast Delta Encoding for Delta Compression Based Storage Systems
Authors: Tan Haoliang , Xia Wen , Zou Xiangyu , Deng Cai , Liao Qing , Gu Zhaoquan
Published: May 2024

Delta encoding is a data reduction technique capable of calculating the differences (i.e., delta) among very similar files and chunks. It is widely used for various applications, such as synchronization replication, backup/archival storage, cache compression, and so on. However, delta encoding is computationally costly due to its time-consuming word-matching operations for delta calculation. Existing delta encoding approaches either run at a slow encoding speed, such as Xdelta and Zdelta, or at a low compression ratio, such as Ddelta and Edelta. In this article, we propose Gdelta, a fast delta encoding approach with a high compression ratio. The key idea behind Gdelta is the combined use of five techniques: (1) employing an improved Gear-based rolling hash to replace Adler32 hash for fast scanning overlapping words of similar chunks, (2) adopting a quick array-based indexing for word-matching, (3) applying a sampling indexing scheme to reduce the cost of traditional building full indexes for base chunks’ words, (4) skipping unmatched words to accelerate delta encoding through non-redundant areas, and (5) last but not least, after word-matching, further batch compressing the remainder to improve the compression ratio. Our evaluation results driven by seven real-world datasets suggest that Gdelta achieves encoding/decoding speedups of 3.5X∼25X over the classic Xdelta and Zdelta approaches while increasing the compression ratio by about 10%∼240%.
Fixed-point Encoding and Architecture Exploration for Residue Number Systems
Authors: Deng Bobin , Nadendla Bhargava , Suo Kun , Xie Yixin , Lo Dan Chia-Tien
Published: May 2024

Residue Number Systems (RNS) demonstrate the fascinating potential to serve integer addition/ multiplication-intensive applications. The complexity of Artificial Intelligence (AI) models has grown enormously in recent years. From a computer system’s perspective, ensuring the training of these large-scale AI models within an adequate time and energy consumption has become a big concern. Matrix multiplication is a dominant subroutine in many prevailing AI models, with an addition/multiplication-intensive attribute. However, the data type of matrix multiplication within machine learning training typically requires real numbers, which indicates that RNS benefits for integer applications cannot be directly gained by AI training. The state-of-the-art RNS real-number encodings, including floating-point and fixed-point, have defects and can be further enhanced. To transform default RNS benefits to the efficiency of large-scale AI training, we propose a low-cost and high-accuracy RNS fixed-point representation:
Single RNS Logical Partition (S-RNS-Logic-P) representation with Scaling-down Postprocessing Multiplication (SD-Post-Mul)
. Moreover, we extend the implementation details of the other two RNS fixed-point methods:
Double RNS Concatenation
and
S-RNS-Logic-P representation with Scaling-down Preprocessing Multiplication
. We also design the architectures of these three fixed-point multipliers. In empirical experiments, our
S-RNS-Logic-P representation with SD-Post-Mul
method achieves less latency and energy overhead while maintaining good accuracy. Furthermore, this method can easily extend to the Redundant Residue Number System to raise the efficiency of error-tolerant domains, such as improving the error correction efficiency of quantum computing.
Deep Learning Assessment of Small Renal Masses at Contrast-enhanced Multiphase CT
Authors: Dai Chenchen , Xiong Ying , Zhu Pingyi , Yao Linpeng , Lin Jinglai , Yao Jiaxi , Zhang Xue , Huang Risheng , Wang Run , Hou Jun , Wang Kang , Shi Zhang , Chen Feng , Guo Jianming , Zeng Mengsu , Zhou Jianjun , Wang Shuo
Published: May 2024

A deep learning algorithm based on contrast-enhanced multiphase CT demonstrated good performance for characterizing small (≤3 cm) renal masses as benign lesions.
The Future Role of Abdominal US in Hepatocellular Carcinoma Surveillance
Authors: Mendiratta-Lala Mishal , Fetzer David , Kamaya Aya , Parikh Neehar D. , Singal Amit G.
Published: May 2024

Promising imaging- and blood-based surveillance strategies appear poised to reduce, albeit not eliminate, the role of abdominal US in hepatocellular carcinoma surveillance, but they require validation before adoption in clinical practice.
Analysis of Kinetic and Ohmic Resistances in PEM Water Electrolysis through Reference Electrode Measurements
Authors: Bühre Lena V. , Mourali Mustafa , Trinke Patrick , Brandt Jonathan , Brinker Debora , Kardeş Gözde , Weber André , Bensmann Boris , Hanke-Rauschenbach Richard
Published: May 2024

We investigated a three electrode setup utilized in a temperature variation study to extract the activation energy for the half-cell reactions in PEM water electrolysis and the contributions of electronic resistances to ohmic resistance. The reference electrode configuration used in this investigation is an improved version of a setup previously introduced by our group. Enhancements have been made to minimize the influence of the reference electrode and improve the accuracy of electrochemical impedance spectroscopy.
A Novel MXene@MOF@Pt NPs-Based Enzyme-Free Electrochemical Sensor for Highly Sensitive Detection of Hydrogen Peroxide Released from Living Cells
Authors: Wen Wenbin , Dang Yuan , Tang Jieli , Su Changluo , Yu Sha , Ma Junping , Zhou Yuanzhen
Published: May 2024

Rapid and accurate detection of hydrogen peroxide (H2O2), an important reactive oxygen species (ROS) released from living cells, is of great significance for early diagnosis of tumors. Here, a high sensitive enzyme-free electrochemical sensor for the detection of H2O2 released from living cells was constructed based on MXene@ZIF-8@Pt NPs nanocomposites. Through the characterization of physical and chemical properties, it was observed that Pt NPs with excellent catalytic activity were uniformly supported on MXene@ZIF-8, which exhibited excellent conductivity and large specific surface area. Thanks to the significantly enhanced catalytic activity derived from the successful integration of MXene, ZIF-8 and Pt NPs, under the optimal conditions, the sensing platform based on MXene@ZIF-8@Pt NPs exhibited a wide linear range from 355.4 nM to 21.75 mM, with a limit of detection as low as 120.9 nM, while showing satisfactory reproducibility and selectivity. Furthermore, the developed electrochemical sensor enables real-time monitoring of H2O2 released from living Hela cells under N-formylmethionyl-leucyl-phenylalanine stimulation. Overall, the MXene@ZIF-8@Pt NPs developed in this article will become a promising candidate in monitoring physiological processes.
Green Electrochemical Sensing: Novel Ion-Selective Electrode Method for Precise Determination of Dimenhydrinate and its Metabolite along with Cinnarizine in Pharmaceutical and Plasma Samples
Authors: Boltia Shereen A. , Morgan Eman M. , Obaydo Reem H. , Fayez Yasmin M. , Abdelkawy M. , Lotfy Hayam M.
Published: May 2024

Green and sustainable scientific research is crucial for health and environmental improvement. Electrochemical analysis simplifies complex processes, saving time and cost. Ion selective electrode method, a key in green analytical chemistry, was utilized. A highly selective solid contact sensor was developed for two applications, detecting cinnarizine (CIN) and dimenhydrinate (DMH) in pharmaceuticals, and identifying CIN and diphenhydramine (DIP) in human plasma. Careful selection of ionophores ensured accurate detection. Multi-wall carbon-nanotubes (MWCNTs) facilitate rapid and precise measurement. The concentration range for CIN, DMH, and DIP was 1 × 10−6 M to 1 × 10−2 M, with mean recovery% of 100.07 ± 0.80, 100.12 ± 0.76, and 100.07 ± 0.53, respectively. Validation parameters exhibited accuracy and precision, with accuracy results of 100.87 ± 0.89, 99.96 ± 0.42, and 99.82 ± 0.31, and LODs of 0.5 × 10−6, 1.0 × 10−7, and 0.2 × 10−6 for CIN, DMH, and DIP, respectively. The study highlighted benefits like speed, economy, and sustainability, emphasizing the electrode’s reusability. SWOT analysis and environmental assessments further underscored its advantages, promising applications in pharmaceutical analysis and quality control.
Thermal Performance Assessment of Concrete Walls Using Different Phase Change Materials
Authors: Usman Muhammad , Hussain Mahmood , Mushtaq Arslan , Farooq Syed H. , Mehmood Atif , Hanif Asad
Published: May 2024

Energy demand is continuously increasing around the globe, and the building sector contributes 40% of the total energy consumption, as per the studies. Fossil fuels are the primary cause of harmful gas emissions, thus causing environmental pollution. There is a dire need to introduce innovative techniques to fulfill energy demands while reducing environmental pollution. Phase change materials (PCMs) are the latent thermal storage materials that store thermal energy during phase change from solid to liquid state and vice versa. Thus, using PCMs in structural engineering offers one of the best options for rapidly developing energy‐saving materials. To do so, ascaled model, concrete walls room, encapsulating locally available PCMs, was constructed in this study. Three locally available PCMs (glycerin, vegetable ghee, and ferric chloride hexahydrate) have been tested in a controlled environment. The model response is then evaluated for the energy‐storing capacity of each PCM while considering the human comfort zone. From the test results, it is concluded that PCMs have a significant effect on improving the thermal energy efficiency of the model without any notable adverse effects. Over the completion of the test, after 12 hr, all the incorporated PCM showed positive results, and a maximum temperature loss of 2.25 K was observed. Among different PCMs, the optimal performance was observed for vegetable ghee, which showed a drop in temperature for all the points at the inner side of the wall, i.e., T3, T4, and T5.
An On‐Treatment Decreased Trend of Serum IL‐6 and IL‐8 as Predictive Markers Quickly Reflects Short‐Term Efficacy of PD‐1 Blockade Immunochemotherapy in Patients with Advanced Gastric Cancer
Authors: Liu Jiameng , Mao Yufei , Mao Chaoming , Wang Deqiang , Dong Liyang , Zhu Wei
Published: May 2024

Objective. Immunotherapy has proven effective in treating advanced gastric cancer (AGC), yet its benefits are limited to a subset of patients. Our aim is to swiftly identify prognostic biomarkers using cytokines to improve the precision of clinical guidance and decision‐making for PD‐1 inhibitor‐based cancer immunotherapy in AGC. Materials and Methods. The retrospective study compared 36 patients with AGC who received combined anti‐PD‐1 immunotherapy and chemotherapy (immunochemotherapy) with a control group of 20 patients who received chemotherapy alone. The concentrations of TNF‐α, IL‐1β, IL‐2R, IL‐6, IL‐8, IL‐10, and IL‐17 in the serum were assessed using chemiluminescence immunoassay at three distinct time intervals following the commencement of immunochemotherapy. Results. When compared to controls, patients undergoing immunochemotherapy demonstrated a generalized rise in cytokine levels after the start of treatment. However, patients who benefited from immunochemotherapy showed a decrease in IL‐6 or IL‐8 concentrations throughout treatment (with varied trends observed for IL‐1β, IL‐2R, IL‐10, IL‐17, and TNF‐α) was evident in patients benefiting from immunochemotherapy but not in those who did not benefit. Among these markers, the combination of IL‐6, IL‐8, and CEA showed optimal predictive performance for short‐term efficacy of immunochemotherapy in AGC patients. Conclusion. Reductions in IL‐6/IL‐8 levels observed during immunochemotherapy correlated with increased responsiveness to treatment effectiveness. These easily accessible blood‐based biomarkers are predictive and rapid and may play a crucial role in identifying individuals likely to derive benefits from PD‐1 blockade immunotherapy.
Sternal Dislocation and Associated Lung Lobe Hernia in a Cat
Authors: Hamon Martin , Haudiquet Philippe , Bruwier Aurelie
Published: May 2024

Sternal luxation/dislocation is a rare condition and is most often the result of trauma. Medical and surgical management have been described, with scarce information regarding the best treatment option for these cases. A 1-year-old domestic shorthair cat was presented for severe sternal dislocation and a left humeral fracture. Given the displacement observed at the level of the sternum and pain associated, surgical stabilization was elected. A partial lung lobe hernia was identified during the open stabilization of the sternum. Management of the hernia and sternal luxation stabilization were performed with the aid of video-assisted thoracoscopy. The cat recovered uneventfully, and no postoperative complications were reported.
Population Pharmacokinetic Analysis of Selumetinib and Its N‐desmethyl Metabolite in Japanese and Non‐Japanese Pediatric Patients with Neurofibromatosis Type 1 and Inoperable Plexiform Neurofibromas
Authors: Shinbo Takumi , Higashimori Mitsuo , González-García Ignacio , Learoyd Maria
Published: May 2024

Background. Selumetinib, a mitogen‐activated protein kinase kinase 1/2 inhibitor, has been approved in several countries and regions, including Japan, for the treatment of pediatric patients with neurofibromatosis type 1 who have symptomatic, inoperable plexiform neurofibromas at a body surface area (BSA)‐based dose of 25 mg/m2 twice daily. The objective of this population pharmacokinetic analysis was to evaluate ethnic sensitivity in the pharmacokinetics of selumetinib and N‐desmethyl selumetinib between Japanese and non‐Japanese pediatric patients. Methods. This population pharmacokinetic analysis was based on data from 80 pediatric patients enrolled in two clinical trials, one conducted in Japan and one conducted in the United States, comprising 12 Japanese participants and 68 non‐Japanese participants. Both clinical trials used BSA‐based dosing schemes. A two‐compartment model with first‐order elimination and sequential zero‐order and first‐order delayed absorption for selumetinib, combined with a one‐compartment model with first‐order elimination for N‐desmethyl selumetinib, was used for this analysis. Ethnic sensitivity in pharmacokinetics was evaluated by covariate modeling and comparison of model‐predicted exposures. Results. Covariate modeling showed that BSA had a clinically relevant impact on the pharmacokinetics of selumetinib. None of the other investigated covariates, such as race, had a significant impact. The predicted exposure in Japanese and non‐Japanese patients showed a considerably overlapping distribution, and no clinically relevant difference in exposure was apparent. Conclusions. These findings support the use of the same BSA‐based dosing regimen for Japanese and non‐Japanese pediatric patients with neurofibromatosis type 1 and inoperable plexiform neurofibromas. Subsequent to this analysis, selumetinib was approved at the BSA‐based dose of 25 mg/m2 in Japan, which is consistent with the recommended dosage and administration in other regions and countries. This analysis used data from trial registered with NCT04495127, and NCT01362803.
Ciliary Functional Analysis in Chronic Rhinosinusitis with Polyps after Multimodal Intervention: Oral Corticosteroid, Functional Endoscopic Sinus Surgery, and Omalizumab Injection
Authors: Benchimol Lionel , Bouchain Olivier , Bricmont Noemie , Bonhiver Romane , Kempeneers Celine , Lefebvre Philippe , Poirrier Anne-Lise
Published: May 2024

In her late 50 s, a woman with a medical history of endoscopic sinus surgery for chronic rhinosinusitis with nasal polyps (CRSwNP) experienced a relapse of nasal polyps, significantly impacting her breathing and sense of smell. She underwent a multifaceted treatment approach, including oral corticosteroids, functional endoscopic sinus surgery, and omalizumab injections. Digital high-speed videomicroscopy (DHSV) revealed only partial improvement in ciliary beat pattern and ciliary beat frequency with oral corticosteroid treatment, while significant improvement in these ciliary parameters was observed with omalizumab injections. Furthermore, administration of omalizumab resulted in a decrease in her SNOT-22 (Sinonasal Outcome Test 22) score. Notably, this case report represents the first study investigating ciliary function using DHSV in a patient treated with omalizumab.
Effective Removal of Ibuprofen from Aqueous Solution Using Cationic Surface‐Active Agents in Dissolved Air‐Flotation Process
Authors: Pooja G. , Senthil Kumar P. , Chitra B. , Rangasamy Gayathri
Published: May 2024

This research paper focuses on the removal of the nonsteroidal anti‐inflammatory drug, ibuprofen, from an aqueous solution using a dissolved air flotation process. The comparison of different types of cationic surface‐active agents such as cetyltrimethyl ammonium bromide (CTAB), tetrabutyl ammonium bromide (TBAB), and octyltrimethyl ammonium bromide (OTAB) have been employed to scrutinize the effective removal of the ecotoxic pharmaceutically active compound. The work included the influencing parameters such as pressure, contact time, surfactant dosage, pH, flow rate, and initial concentration owing to the best‐optimized conditions. The maximum removal rate of 96.09% was achieved at 15 min for CTAB, TBAB had 62.36% at 45 min, and 89.6% was obtained for OTAB at 30 min, with 50 mg L−1 as the initial concentration and pH = 4. The removal rate was better with the optimized dosage of CTAB at 0.6 g, TBAB at 1.2 g, and OTAB at 1.0 g. It was observed that the geometric shape of the surface‐active agents had greater impacts on the contaminants’ efficiency. CTAB and OTAB were combined to find out the best possible removal rate of contaminants. The synergistic effect augments surfactant‐based occurrence to be better in forming a good foaming effect and tends to have a lower critical micelle concentration (CMC). From the evaluation of kinetic models, pseudo‐second‐order flotation kinetics fitted the experimental data best. Furthermore, the formed metabolites that had been identified using gas chromatography‐mass spectrometry were found to be less toxic than the parenting compounds.
Neem Leaf Glycoprotein Disrupts Exhausted CD8+ T-Cell–Mediated Cancer Stem Cell Aggression
Authors: Chakravarti Mohona , Bera Saurav , Dhar Sukanya , Sarkar Anirban , Choudhury Pritha Roy , Ganguly Nilanjan , Das Juhina , Sultana Jasmine , Guha Aishwarya , Biswas Souradeep , Das Tapasi , Hajra Subhadip , Banerjee Saptak , Baral Rathindranath , Bose Anamika
Published: May 2024

Targeting exhausted CD8+ T-cell (TEX)–induced aggravated cancer stem cells (CSC) holds immense therapeutic potential. In this regard, immunomodulation via Neem Leaf Glycoprotein (NLGP), a plant-derived glycoprotein immunomodulator is explored. Since former reports have proven immune dependent–tumor restriction of NLGP across multiple tumor models, we hypothesized that NLGP might reprogram and rectify TEX to target CSCs successfully. In this study, we report that NLGP’s therapeutic administration significantly reduced TEX-associated CSC virulence in in vivo B16-F10 melanoma tumor model. A similar trend was observed in in vitro generated TEX and B16-F10/MCF7 coculture setups. NLGP rewired CSCs by downregulating clonogenicity, multidrug resistance phenotypes and PDL1, OCT4, and SOX2 expression. Cell cycle analysis revealed that NLGP educated–TEX efficiently pushed CSCs out of quiescent phase (G0G1) into synthesis phase (S), supported by hyper-phosphorylation of G0G1–S transitory cyclins and Rb proteins. This rendered quiescent CSCs susceptible to S-phase–targeting chemotherapeutic drugs like 5-fluorouracil (5FU). Consequently, combinatorial treatment of NLGP and 5FU brought optimal CSC-targeting efficiency with an increase in apoptotic bodies and proapoptotic BID expression. Notably a strong nephron-protective effect of NLGP was also observed, which prevented 5FU-associated toxicity. Furthermore, Dectin-1–mediated NLGP uptake and subsequent alteration of Notch1 and mTOR axis were deciphered as the involved signaling network. This observation unveiled Dectin-1 as a potent immunotherapeutic drug target to counter T-cell exhaustion. Cumulatively, NLGP immunotherapy alleviated exhausted CD8+ T-cell-induced CSC aggravation.

Implications: Our study recommends that NLGP immunotherapy can be utilized to counter ramifications of T-cell exhaustion and to target therapy elusive aggressive CSCs without evoking toxicity.
Figure S3 from Identification of MUC1-C as a Target for Suppressing Progression of Head and Neck Squamous Cell Carcinomas
Authors: Nakashoji Ayako , Haratake Naoki , Bhattacharya Atrayee , Mao Weipu , Xu Kangjie , Wang Keyi , Daimon Tatsuaki , Ozawa Hiroki , Shigeta Keisuke , Fushimi Atsushi , Yamashita Nami , Morimoto Yoshihiro , Shimokawa Mototsugu , Saito Shin , Egloff Ann Marie , Uppaluri Ravindra , Long Mark D. , Kufe Donald
Published: May 2024

Effects of targeting MUC1-C on effectors of the type I and II IFN pathways.
Figure S1 from Identification of MUC1-C as a Target for Suppressing Progression of Head and Neck Squamous Cell Carcinomas
Authors: Nakashoji Ayako , Haratake Naoki , Bhattacharya Atrayee , Mao Weipu , Xu Kangjie , Wang Keyi , Daimon Tatsuaki , Ozawa Hiroki , Shigeta Keisuke , Fushimi Atsushi , Yamashita Nami , Morimoto Yoshihiro , Shimokawa Mototsugu , Saito Shin , Egloff Ann Marie , Uppaluri Ravindra , Long Mark D. , Kufe Donald
Published: May 2024

Effects of silencing MUC1-C on HNSCC cell clonogenic survival.
FIGURE 7 from Identification of MUC1-C as a Target for Suppressing Progression of Head and Neck Squamous Cell Carcinomas
Authors: Nakashoji Ayako , Haratake Naoki , Bhattacharya Atrayee , Mao Weipu , Xu Kangjie , Wang Keyi , Daimon Tatsuaki , Ozawa Hiroki , Shigeta Keisuke , Fushimi Atsushi , Yamashita Nami , Morimoto Yoshihiro , Shimokawa Mototsugu , Saito Shin , Egloff Ann Marie , Uppaluri Ravindra , Long Mark D. , Kufe Donald
Published: May 2024

Single-cell profiling of the expression of MUC1 and related genes in HNSCC. A–C, UMAP representation of total cells analyzed from the GSE118389 dataset of HPV-negative/HPV-positive HNSCC samples (A), GSE118389 dataset of HPV-negative samples (B), and GSE118389 dataset of HPV-positive samples (C) (left). Distributions of MUC1 expression in individual cells (middle). MUC1 expression in individual cells in each cell type (right). D, Model depicting the current findings that MUC1-C integrates activation of STAT1, IFN type I/II signaling and ISG expression with regulation of ∆Np63, SOX2, and NOTCH3 in driving the HNSCC CSC state that promotes DNA damage resistance and immune evasion.
FIGURE 1 from Identification of MUC1-C as a Target for Suppressing Progression of Head and Neck Squamous Cell Carcinomas
Authors: Nakashoji Ayako , Haratake Naoki , Bhattacharya Atrayee , Mao Weipu , Xu Kangjie , Wang Keyi , Daimon Tatsuaki , Ozawa Hiroki , Shigeta Keisuke , Fushimi Atsushi , Yamashita Nami , Morimoto Yoshihiro , Shimokawa Mototsugu , Saito Shin , Egloff Ann Marie , Uppaluri Ravindra , Long Mark D. , Kufe Donald
Published: May 2024

Expression of MUC1 in HNSCC tumors and effects of silencing MUC1-C on HNSCC cell clonogenicity. A, Analysis of primary (P) and metastatic (M) HNSCC tissues for MUC1 expression using the GSE136037 dataset. B, CAL27/CshRNA and MUC1shRNA cells were analyzed for MUC1-C mRNA levels (left). The results (mean ± SD of four determinations) are expressed as relative levels compared with that obtained for CshRNA cells (assigned a value of 1; left). Lysates were immunoblotted with antibodies against the indicated proteins (right). C, The indicated CAL27 cells were analyzed for colony formation. Shown are representative photomicrographs of stained colonies (left). The results (mean ± SD of three determinations) are expressed as relative colony formation compared with that for CshRNA cells (assigned a value of 1; right). D, Amino acid sequence of the MUC1-C cytoplasmic domain (CD) highlighting direct interactions with JAK1 and STAT1. E and F, CAL27 cells expressing the indicated vectors were treated with vehicle or DOX for 7 days. Lysates were immunoblotted with antibodies against the indicated proteins (E). Cells were analyzed for colony formation (F). Shown are representative photomicrographs of stained colonies (top). The results (mean ± SD of three determinations) are expressed as relative colony formation compared with that for control cells (assigned a value of 1; bottom).
Data from Identification of MUC1-C as a Target for Suppressing Progression of Head and Neck Squamous Cell Carcinomas
Authors: Nakashoji Ayako , Haratake Naoki , Bhattacharya Atrayee , Mao Weipu , Xu Kangjie , Wang Keyi , Daimon Tatsuaki , Ozawa Hiroki , Shigeta Keisuke , Fushimi Atsushi , Yamashita Nami , Morimoto Yoshihiro , Shimokawa Mototsugu , Saito Shin , Egloff Ann Marie , Uppaluri Ravindra , Long Mark D. , Kufe Donald
Published: May 2024

Abstract
The MUC1-C protein is aberrantly expressed in adenocarcinomas of epithelial barrier tissues and contributes to their progression. Less is known about involvement of MUC1-C in the pathogenesis of squamous cell carcinomas (SCC). Here, we report that the MUC1 gene is upregulated in advanced head and neck SCCs (HNSCC). Studies of HNSCC cell lines demonstrate that the MUC1-C subunit regulates expression of (i) RIG-I and MDA5 pattern recognition receptors, (ii) STAT1 and IFN regulatory factors, and (iii) downstream IFN-stimulated genes. MUC1-C integrates chronic activation of the STAT1 inflammatory pathway with induction of the ∆Np63 and SOX2 genes that are aberrantly expressed in HNSCCs. In extending those dependencies, we demonstrate that MUC1-C is necessary for NOTCH3 expression, self-renewal capacity, and tumorigenicity. The findings that MUC1 associates with ∆Np63, SOX2 and NOTCH3 expression by single-cell RNA sequencing analysis further indicate that MUC1-C drives the HNSCC stem cell state and is a target for suppressing HNSCC progression.
Significance:
This work reports a previously unrecognized role for MUC1-C in driving STAT1-mediated chronic inflammation with the progression of HNSCC and identifies MUC1-C as a druggable target for advanced HNSCC treatment.
A Systematic Review of Female Participation in Randomized Controlled Trials of Post-Stroke Upper Extremity Rehabilitation in Low- to Middle-Income Countries and High-Income Countries and Regions
Authors: Mehrabi Sarvenaz , Cameron Lindsay , Bowman Andrew , Fleet Jamie L. , Eng Janice , Bayley Mark Theodore , Teasell Robert
Published: May 2024

Introduction: Female participation is lower than males in both acute stroke and stroke rehabilitation trials. However, less is known about how female participation differs across countries and regions. This study aimed to assess the percentage of female participants in randomized controlled trials (RCTs) of post-stroke rehabilitation of upper extremity (UE) motor disorders in low-middle-income (LMICs) and high-income countries (HICs) as well as different high-income world regions. Methods: CINAHL, Embase, PubMed, Scopus, and Web of Science were searched from 1960 to April 1, 2021. Studies were eligible for inclusion if they (1) were RCTs or crossovers published in English; (2) ≥50% of participants were diagnosed with stroke; 3) included adults ≥18 years old; and (4) applied an intervention to the hemiparetic UE as the primary objective of the study. Countries were divided into HICs and LMICs based on their growth national incomes. The HICs were further divided into the three high-income regions of North America, Europe, and Asia and Oceania. Data analysis was performed using SPSS and RStudio v.4.3.1. Results: A total of 1,276 RCTs met inclusion criteria. Of them, 298 RCTs were in LMICs and 978 were in HICs. The percentage of female participants was significantly higher in HICs (39.5%) than LMICs (36.9%). Comparing high-income regions, there was a significant difference in the overall female percentages in favor of RCTs in Europe compared to LMICs but not North America or Asia and Oceania. There was no significant change in the percentage of female participants in all countries and regions over the last 2 decades, with no differences in trends between the groups. Conclusions: Sufficient female representation in clinical trials is required for the generalizability of results. Despite differences in overall percentage of female participation between countries and regions, females have been underrepresented in both HICs and LMICs with no considerable change over 2 decades.
Murine Ribonuclease 6 Limits Bacterial Dissemination During Experimental Urinary Tract Infection
Authors: Cortado Hanna , Kercsmar Macie , Li Birong , Vasquez-Martinez Gabriela , Gupta Sudipti , Ching Christina , Ballash Gregory , Cotzomi-Ortega Israel , Sanchez-Zamora Yuriko I. , Boix Ester , Zepeda-Orozco Diana , Jackson Ashley R. , Spencer John David , Ruiz-Rosado Juan de Dios , Becknell Brian
Published: May 2024

Introduction: The Ribonuclease (RNase) A superfamily encodes cationic antimicrobial proteins with potent microbicidal activity toward uropathogenic bacteria. Ribonuclease 6 (RNase6) is an evolutionarily conserved, leukocyte-derived antimicrobial peptide with potent microbicidal activity toward uropathogenic Escherichia coli (UPEC), the most common cause of bacterial urinary tract infections (UTI). In this study, we generated Rnase6 deficient mice to investigate the hypothesis that endogenous RNase 6 limits host susceptibility to UTI.

Methods: We generated a Rnase6EGFP knock-in allele to identify cellular sources of Rnase6 and determine the consequences of homozygous Rnase6 deletion on antimicrobial activity and UTI susceptibility.

Results: We identified monocytes and macrophages as the primary cellular sources of Rnase6 in bladders and kidneys of Rnase6EGFP/+ mice. Rnase6 deficiency (i.e., Rnase6EGFP/EGFP) resulted in increased upper urinary tract UPEC burden during experimental UTI, compared to Rnase6+/+ controls. UPEC displayed increased intracellular survival in Rnase6 deficient macrophages.

Conclusion: Our findings establish that RNase6 prevents pyelonephritis by promoting intracellular UPEC killing in monocytes and macrophages and reinforce the overarching contributions of endogenous antimicrobial RNase A proteins to host UTI defense.
Clinical Characteristics of Children with THRA Mutations: Variable Phenotype and Good Response to Recombinant Human Growth Hormone Therapy
Authors: Andrade Nathalia L.M. , Rezende Raissa C. , Crisostomo Lindiane G. , Dantas Naiara C.B. , Cellin Laurana P. , de Souza Vinicius , Quedas Elisangela P.S. , Lerario Antonio M. , Vasques Gabriela A. , Jorge Alexander A.L.
Published: May 2024

Introduction: Mutations in the thyroid hormone receptor alpha (THRA) gene are a rare cause of thyroid hormone resistance, which leads to a pleomorphic phenotypic spectrum. Hormonal profiles are variable and subtle, making laboratory diagnoses challenging. Genetic evaluation can be a helpful tool in diagnosing these cases. Case Presentation: Three patients (P1, P2, and P3) from unrelated families presented to their endocrinologists with short stature and abnormalities in thyroid function results. P1 showed hypoactivity and mild thyroid-stimulating hormone (TSH) elevation. P2 presented with a mild developmental delay and a hormonal profile initially interpreted as central hypothyroidism. Patient P3 had severe symptoms, including hypotonia, developmental delay, normal TSH, hypercholesterolemia, severe hypertriglyceridemia, high amylase levels, and mild pericardial effusion. All the patients had low free thyroxine (FT4) levels, mild constipation, and short stature. The patients underwent exome sequencing analysis that identified three different heterozygous variants in the THRA gene (P1 and P2 had missense variants, and P3 had a stop codon variant). All patients were treated with levothyroxine replacement, improving their clinical symptoms, such as constipation, and neurological symptoms. P1 and P2 were also treated with the recombinant human growth hormone (rhGH). The improvements in growth velocity and height standard deviation scores (SDS) were remarkable. Notably, P1 had a total height gain of 2.5 SDS, reaching an adult height within the normal range. Conclusion: THRA gene defects can lead to growth disorders with different phenotypes. Children with THRA mutations can benefit from adequate treatment with levothyroxine and may respond well to rhGH treatment.
Female Diana Monkeys Have Complex Calls
Authors: Coye Camille , Veselinović Dunja , Candiotti Agnès , Schlenker Philippe , Lemasson Alban , Chemla Emmanuel
Published: May 2024

We argue that female Diana monkeys (Cercopithecus diana) can form complex calls by combining an A call with other elementary calls. We reject (on both empirical and conceptual grounds) a combination-free analysis based on accidental homophony, and we consider two main analyses: the Acoustic Theory takes the combination to be merely acoustic, whereas the Affixal Theory takes A to function as a suffix. We provide limited arguments for the Affixal Theory, and through comparison with another closely related monkey species, we date these combinations to at least 6 million years ago.
Molecular characterisation and diagnostics of the red ring nematode, Bursaphelenchus cocophilus, from Mexico
Authors: Subbotin Sergei A. , Cid del Prado-Vera Ignacio
Published: May 2024

The red ring nematode, Bursaphelenchus cocophilus, vectored by the South American palm weevil, Rhynchophorus palmarum, is the causal agent of red ring disease in coconut and other palms in countries of Central and South America. The populations of B. cocophilus collected in the states of Guerrero and Tabasco, Mexico, were molecularly characterised using the D2-D3 expansion segments of 28S rRNA, ITS rRNA and COI gene sequences. Mexican B. cocophilus populations were molecularly different from other Central and South American populations. Comparative analysis of available rRNA sequences obtained from several countries showed that B. cocophilus consists of molecularly different populations and its species structure is likely congruent with that of the beetle vector. Conventional PCR, real-time PCR and recombinase polymerase amplification (RPA) with lateral flow dipstick (LF) assays have been developed for the identification of the red ring nematode in this study. The specificity of the ITS rRNA primers in the assays were examined using B. cocophilus and other 15 species of family Aphelenchoididae. Detection sensitivity levels, determined by using a dilution series of B. cocophilus extracts, was 0.13 nematode per reaction tube for real-time PCR and 0.25 nematode per reaction tube for conventional PCR and LF-RPA assays. The application of the LF-RPA assay has great potential for diagnosing infestation of this species with a minimal laboratory infrastructure.
Sensitivity of Arctic Clouds to Ice Microphysical Processes in the NorESM2 Climate Model
Authors: Sotiropoulou Georgia , Lewinschal Anna , Georgakaki Paraskevi , Phillips Vaughan T. J. , Patade Sachin , Ekman Annica M. L. , Nenes Athanasios
Published: May 2024

Ice formation remains one of the most poorly represented microphysical processes in climate models. While primary ice production (PIP) parameterizations are known to have a large influence on the modeled cloud properties, the representation of secondary ice production (SIP) is incomplete and its corresponding impact is therefore largely unquantified. Furthermore, ice aggregation is another important process for the total cloud ice budget, which also remains largely unconstrained. In this study, we examine the impact of PIP, SIP, and ice aggregation on Arctic clouds, using the Norwegian Earth System Model, version 2 (NorESM2). Simulations with both prognostic and diagnostic PIP show that heterogeneous freezing alone cannot reproduce the observed cloud ice content. The implementation of missing SIP mechanisms (collisional breakup, drop shattering, and sublimation breakup) in NorESM2 improves the modeled ice properties, while improvements in liquid content occur only in simulations with prognostic PIP. However, results are sensitive to the description of collisional breakup. This mechanism, which dominates SIP in the examined conditions, is very sensitive to the treatment of the sublimation correction factor, a poorly constrained parameter that is included in the utilized parameterization. Finally, variations in ice aggregation treatment can also significantly impact cloud properties, mainly through their impact on collisional breakup efficiency. Overall, enhancement in ice production through the addition of SIP mechanisms and the reduction in ice aggregation (in line with radar observations of shallow Arctic clouds) result in enhanced cloud cover and decreased TOA radiation biases, compared to satellite measurements, especially during the cold months.

Significance Statement

Arctic clouds remain a large source of uncertainty in projections of the future climate due to the poor representation of the microphysical processes that govern their life cycle. Ice formation is among the least understood processes. While it is widely recognized that better constraints on primary ice production (PIP) are needed to improve existing parameterizations, we show that secondary ice production (SIP) and ice aggregation can have also a significant impact on ice number concentrations. Constraining ice formation through the addition of missing SIP mechanisms and reducing ice aggregation can improve the representation of the cloud macrophysical properties and enhance total cloud cover in the Arctic region, which in turn contributes to decreased TOA radiation biases in the cold months.
Observations and Numerical Simulations of the Onset and Growth of Langmuir Circulations
Authors: Andriatis Alexander , Lenain Luc , Alford Matthew H. , Winstead Nathaniel , Geiman Joseph
Published: May 2024

We report novel observations of the onset and growth of Langmuir circulations (LCs) from simultaneous airborne and subsurface in situ measurements. Under weak, fetch-limited wind–wave forcing with stabilizing buoyancy forcing, the onset of LCs is observed for wind speeds greater than about 1 m s−1. LCs appear nonuniformly in space, consistent with previous laboratory experiments and suggestive of coupled wave–turbulence interaction. Following an increase in wind speed from <1 m s−1 to sustained 3 m s−1 winds, a shallow (<0.7 m) diurnal warm layer is observed to deepen at 1 m h−1, while the cross-cell scales of LCs grow at 2 m h−1, as observed in sea surface temperature collected from a research aircraft. Subsurface temperature structures show temperature intrusions into the base of the diurnal warm layer of the same scale as bubble entrainment depth during the deepening period and are comparable to temperature structures observed during strong wind forcing with a deep mixed layer that is representative of previous LC studies. We show that an LES run with observed initial conditions and forcing is able to reproduce the onset and rate of boundary layer deepening. The surface temperature expression however is significantly different from observations, and the model exhibits large sensitivity to the numerical representation of surface radiative heating. These novel observations of Langmuir circulations offer a benchmark for further improvement of numerical models.

Significance Statement

The purpose of this study is to better understand the structure and dynamics of Langmuir circulations (LCs), coherent turbulent vortices in the surface ocean. Using observations of the ocean surface boundary layer from aircraft and autonomous instruments, we show the onset and growth of LCs. We compare the observations to a numerical model and find that while the model can reproduce the deepening of a shallow surface warm layer, the representation of coherent vortices differs from observations. Future studies can improve on the numerical representation of coherent upper ocean structures which are important to modeling upper ocean turbulence, air–sea exchanges, biology, ocean acoustics, and the distribution of anthropogenic pollutants like oil and microplastics.
The dilemma of constitutional mobilization: The housing and the environmental social movements at the Chilean Constitutional Convention
Authors: Rodríguez Juan Pablo , Rojas Soto Bruno , Cuadros Emilia
Published: May 2024

During the last decade, processes of constitutional change in different parts of the world have taken place in response to massive mobilizations, in contexts of social and political crises. What do social movements do when they participate in a body created to formulate a new constitution? The constitutional change process of 2021–2022 in Chile provides a unique opportunity to analyze how social movements act when they actively intervene in the constitutional arena. For the first time, activists from independent social movements participated as representatives in a constitutional body and significantly influenced the content of the new proposal. The movements analyzed in this article succeeded in incorporating most demands that have been collectively developed over the past 10 years in the context of a new cycle of mobilizations in Chile into the final proposal. Yet, the proposed constitutional draft was rejected. How did they attempt to influence the constitutional debate within the convention? What were the consequences of these strategies? Based on qualitative research, which included interviews, observations during the constitutional debate in the Constitutional Convention, and document analysis, this article examines the strategies and consequences of the constitutional mobilization carried out by these movements. We argue that some of the conditions for the success of these social movements within the Convention partially explain the failure of the process.
Infant Mortality Rate Convergence across Indian States: Relative Club Convergence Evidence
Authors: Akram Vaseem , Usmani Gulnawaz , Rath Badri Narayan , Praveen Bushra
Published: May 2024

This article investigates the relative convergence of infant mortality rate (IMR) across the 15 major Indian states for the period 1987–2020. To test this hypothesis, this study applies Phillips and Sul’s (2007) panel convergence test. Further, for the robustness of our findings, this study implements the extension of Phillips and Sul’s relative club convergence test, which Kwak propounded in 2021. The results based on Phillips and Sul show divergence in IMR among the states; however, the existence of convergence when 15 states are grouped into different clubs. Four final clubs emerged based on the Kwak test, suggesting that each club has its unique transition path. One group is also identified, suggesting neither convergence nor divergence. From the policy perspective, it is important for the government to target reducing IMR by emphasising at the club level rather than focusing on all states together.

JEL Codes: I140, H75
Stimulus Selection Based on Gender Ratios: Gender Ratios are Indicative of Both Stereotypical and Conceptual Gender
Authors: Kim Jonathan D. , Gabriel Ute , Gygax Pascal , Siyanova- Chanturia Anna
Published: May 2024

This paper explores how the use of gender ratios to inform stimulus selection affects the activation of gendered social information. It investigates if stimuli selected this way can activate gender stereotype knowledge and/or conceptual gender knowledge. This was tested through attribute naming (Study 1) and rating (Study 2) tasks, with component and regression analysis allowing for examination of the nature of gender ratios at both attribute and component levels. The results provide rich information about the nature of gender ratio information as a means of stimulus selection, and in doing so support both conceptualisations as long as researchers acknowledge their overlap. The results also indicate that these roles elicited both positive/prescriptive (i.e., the role is appropriate for a given gender) and negative/proscriptive beliefs (i.e., the role is not appropriate for a given gender). These findings hold important implications for future research using gender ratios.
The Prevalence and Influence of New or Worsened Neck Pain After a Sport-Related Concussion in Collegiate Athletes: A Study From the CARE Consortium
Authors: King Jeffrey A. , Nelson Lindsay D. , Cheever Kelly , Brett Benjamin , Gliedt Jordan , Szabo Aniko , Dong Huaying , Huber Daniel L. , Broglio Steven P. , McAllister Thomas W. , McCrea Michael , Pasquina Paul , Feigenbaum Luis A. , Hoy April , Mihalik Jason P. , Duma Stefan M. , Buckley Thomas , Kelly Louise A. , Miles Chris , Goldman Joshua T. , Benjamin Holly J. , Master Christina L. , Ortega Justus , Kontos Anthony , Clugston James R. , Cameron Kenneth L. , Kaminski Thomas W. , Chrisman Sara P. , Eckner James T. , Port Nicholas , McGinty Gerald
Published: May 2024

Background:

Neck pain in a concussion population is an emerging area of study that has been shown to have a negative influence on recovery. This effect has not yet been studied in collegiate athletes.

Hypothesis:

New or worsened neck pain is common after a concussion (>30%), negatively influences recovery, and is associated with patient sex and level of contact in sport.

Study Design:

Cohort study; Level of evidence, 2.

Methods:

Varsity-level athletes from 29 National Collegiate Athletic Association member institutions as well as nonvarsity sport athletes at military service academies were eligible for enrollment. Participants completed a preseason baseline assessment and follow-up assessments at 6 and 24 to 48 hours after a concussion, when they were symptom-free, and when they returned to unrestricted play. Data collection occurred between January 2014 and September 2018.

Results:

A total of 2163 injuries were studied. New or worsened neck pain was reported with 47.0% of injuries. New or worsened neck pain was associated with patient sex (higher in female athletes), an altered mental status after the injury, the mechanism of injury, and what the athlete collided with. The presence of new/worsened neck pain was associated with delayed recovery. Those with new or worsened neck pain had 11.1 days of symptoms versus 8.8 days in those without ( P < .001). They were also less likely to have a resolution of self-reported symptoms in ≤7 days ( P < .001). However, the mean duration of the return-to-play protocol was not significantly different for those with new or worsened neck pain (7.5 ± 7.7 days) than those without (7.4 ± 8.3 days) ( P = .592).

Conclusion:

This novel study shows that neck pain was common in collegiate athletes sustaining a concussion, was influenced by many factors, and negatively affected recovery.