bluuebunny/crossref_metadata_2025_split huggingface dataset:
Palliative rehabilitation and quality of life: systematic review and meta-analysis
Authors: Pryde Katherine , Lakhani Ali , William Leeroy , Dennett Amy 
Published: October 2024

ImportanceInternational guidelines recommend the integration of multidisciplinary rehabilitation into palliative care services but its impact on quality of life across disease types is not well understood.ObjectiveTo determine the effect of multidisciplinary palliative rehabilitation on quality of life and healthcare service outcomes for adults with an advanced, life-limiting illness.Data sourcesElectronic databases CINAHL, EMBASE, MEDLINE and PEDro were searched from the earliest records to February 2024.Study selectionRandomised controlled trials examining the effect of multidisciplinary palliative rehabilitation in adults with an advanced, life-limiting illness and reported quality of life were eligible.Data extraction and synthesisStudy characteristics, quality of life and health service usage data were extracted, and the methodological quality was assessed using PEDro. Meta-analyses using random effects were completed, and Grades of Recommendation, Assessment, Development and Evaluation criteria were applied.Main outcomesQuality of life and healthcare service outcomes.Results27 randomised controlled trials (n=3571) were included. Palliative rehabilitation was associated with small improvements in quality of life (standardised mean difference (SMD) 0.40, 95% CI 0.23 to 0.56). These effects were significant across disease types: cancer (SMD 0.22, 95% CI 0.03 to 0.41), heart failure (SMD 0.37, 95% CI 0.61 to 0.05) and non-malignant respiratory diagnoses (SMD 0.77, 95% CI 0.29 to 1.24). Meta-analysis found low-certainty evidence, palliative rehabilitation reduced the length of stay by 1.84 readmission days.Conclusions and relevanceMultidisciplinary palliative rehabilitation improves quality of life for adults with an advanced, life-limiting illness and can reduce time spent in hospital without costing more than usual care. Palliative rehabilitation should be incorporated into standard palliative care.PROSPERO registration numberCRD42022372951.
BP-IMCA: An Energy-Efficient 8T SRAM-Based Bit-Parallel In-Memory Computing Architecture
Authors: Rajput Anil Kumar , Pattanaik Manisha , Kaushal Gaurav 
Published: October 2024

In-Memory Computing (IMC) is an emerging paradigm that aims to shift computational workload away from CPUs. The bit-serial IMC architecture suffers from larger latency when performing logic and arithmetic operations. In this paper, a general-purpose, energy-efficient Bit Parallel IMC Architecture (BP-IMCA) based on Area-Optimized (AO-8T) static random access memory (SRAM) bit-cell is proposed to perform In-Memory Boolean Logic Computation (IMBC) and Near-Memory Arithmetic (NMA) operations with variable bit-width from 1- to 8-bit. The decoupled read/write paths of the employed AO-8T SRAM bit-cell eliminate compute disturbance during IMBC and NMA operations. A self-terminating read word line decoding scheme is proposed to disconnect the RBL discharging path from GND, which decreases the energy consumption of the proposed IMC architecture by 27.71% at 1[Formula: see text]V for IMBC operations. In addition to this, a [Formula: see text]-based Low-offset Symmetric Differential Sense Amplifier (LSDSA) is proposed to achieve fast and reliable sensing for both normal read and IMBC operations in the proposed IMC architecture. Further, a 4[Formula: see text]Kb SRAM array is implemented in 65-nm technology to analyze the IMC architecture at a supply voltage of 1[Formula: see text]V. The operating frequency of 1,355[Formula: see text]MHz and average energy consumption of 7.04[Formula: see text]fJ/bit is achieved during logic (IMBC) operations. The 8-bit addition and 8-bit multiplication operations achieve an energy efficiency of 11.1 TOPS/W and 2.28 TOPS/W, respectively, at 1[Formula: see text]V and 970[Formula: see text]MHz. Cumulatively, the proposed architecture achieves the lowest figure of merit compared to the state-of-the-art IMC architectures.
Preparation and Characterization of Copper Oxide-Chitosan Nanocomposite for Colon-Targeted Drug Delivery System
Authors: Ghalee-Taki Ghazal Norouzi , Rastegari Ali Asghar , Hekmat Azadeh , Rezaee Malahat 
Published: October 2024

This work aimed at synthesizing the chitosan-based nanocomposite for concurrent diagnosis of colon tumors and targeted drug shipping with minimum toxicity. CuO-chitosan nanocomposite was developed using CuO nanoparticles (NPs), chitosan raw materials and 1% acetic acid. FE-SEM/EDX, TEM, XRD, DLSUV-Vis, FT-IR, as well as fluorescent emission spectrum methods were used to investigate the characteristics of nanocomposite gained throughout distinct levels. Bovine serum albumin (BSA) protein release rate was estimated. We investigated the antibacterial functioning of the nanocomposite against different bacteria types (like S. aureus, S. typhi, E. coli, L. monocytogene and P. aeruginosa), which can affect in causing tense colonic diseases. Qualitative and quantitative surveys were performed. The impact of the nanocomposite on cancerous and normal human colon cell lines, specifically HCT-116 and SW-948, was examined using the MTT assay. Eventually, loading BSA onto the CuO–chitosan nanocomposite enhances its potential as a drug carrier for treating colon cancer, causing minimal harm to surrounding normal cells. Additionally, the CuO-chitosan nanocomposite demonstrated significant antibacterial activity against Escherichia coli, a key pathogen associated with Crohn’s disease and ulcerative colitis.
Preterm Labor and Hypertensive Disorders in Adolescent Pregnancies With Diabetes Between 2006 and 2019
Authors: Everett Estelle , Han Christina S. , Richley Michael , Copeland Timothy P. , Moin Tannaz , Wisk Lauren E. 
Published: October 2024

Objective: We sought to evaluate the risk of preterm labor and hypertensive disorders in adolescent pregnancies with and without diabetes.Methods: We evaluated 1,843,139 adolescents (≤20 years old) with labor and delivery admissions in the national Kids’ Inpatient Database (KID) in years 2006, 2009, 2012, 2016, and 2019. International classification of disease codes was used to identify diabetes and medical factors affecting pregnancy. Weighted logistic regression was used to evaluate the association between diabetes and complications.Results: Among admissions, 0.2% had type 1 diabetes (T1D), 0.2% had type 2 diabetes (T2D), and 0.7% had gestational diabetes (GDM); 10.1% of admissions were complicated by hypertensive disorders and 5.8% by preterm labor. Compared to adolescents without diabetes, those with diabetes had a higher prevalence of hypertensive disorders (T1D: 35.4%, T2D: 37.8%, GDM: 24.9%, None: 9.9%; p < 0.001) and preterm labor (T1D: 21.5%, T2D: 16.8%, GDM: 6.8%, none: 5.7%; p < 0.001). In adjusted models, odds of hypertensive disorders were higher in later study years (2019 vs. 2006 OR 1.85, 95% CI 1.77–1.94), among those with T1D (OR 4.32, 95% CI 3.94–4.74), with T2D (OR 4.18, 95% CI 3.79–4.61), and with GDM (OR 1.99, 95% CI 1.89–2.10). Adjusted odds of preterm labor were higher among those with T1D (OR 4.53, 95% CI 4.09–5.02), with T2D (OR 3.35, 95% CI 2.96–3.78), and with GDM (OR 1.18, 95% CI 1.08–1.28); disparities were seen by race/ethnicity, insurance, and income.Conclusions: Diabetes, which is increasing among adolescents, is a significant risk factor for preterm labor and hypertensive disorders. Though the absolute number of adolescent pregnancies is decreasing, rates of hypertensive disorders have increased. Appropriate interventions are needed to ensure healthy outcomes for adolescents who are pregnant.
In Vitro Efficacy of Domestic Techniques for Disinfection of Toothbrushes Contaminated With Enterococcus faecalis
Authors: Donayre-Salvatierra Gina Alessandra , Dulanto-Vargas Julissa Amparo , Olaechea Raul M. , Reátegui Oscar , Carranza-Samanez Kilder Maynor 
Published: October 2024

Introduction: Oral hygiene education for patients is fundamental in preventive‐promotional dentistry. The disinfection of toothbrushes (TBs) must be integrated into this context due to their proximity to contaminant sources that make them vulnerable to cross infection in homes. The objective of this study was to compare the efficacy of domestic techniques for disinfection of TBs.Materials and Methods: We performed an in vitro study of 76 TBs contaminated with Enterococcus faecalis (Ef) ATCC 29212 subjected to different disinfection protocols: G1. Distilled water (DW; negative control; n = 8), G2. Dimethylsulfoxide (DMSO)10% (negative control; n = 8), G3. Chlorhexidine (CHX) 0.12% (positive control; n = 15), G4. 100% white vinegar (WV; n = 15), G5. Microwave (MW) at 700 W (n = 15), and G6. 200 mg/mL of certified alcoholic extract of purple garlic (GARLIC) from Arequipa (Allium sativum L; n = 15). Bacterial count was assessed by colony‐forming units (CFU/mL) categorized as contamination: low (<30), medium (30–300), and high (>300). The Kruskal–Wallis test with post hoc pairs was used at a significance level of p < 0.05.Results: Efficacy against Ef showed highly significant differences between groups (p < 0.001) with lower median CFU/mL in G3 and G4 (Me = 0 [IQR (interquartile range) = 0]: low) and G5 (Me = 6000 [IQR = 45,000]: low/medium) versus negative controls (Me = 378,500 and 5,020,000 [IQR = 4,605,000 and 6,760,000]: medium/high; p ≤ 0.019). The counts of the G5 were not statistically different than G3, G4, and G6 (p > 0.06). The G6 (Me = 1,510,000 [IQR = 590,000]: medium) was inferior to G3 and G4 (p < 0.001), but similar to both negative control groups (p > 0.999).Conclusions: Disinfection of TBs with CHX, WV, and MWs produces a significant effective reduction in the count of Ef.
Fish Consumption Once a Week Improves Sperm Quality and Testosterone Levels
Authors: Roussev Bogdan , Sokrateva Todorka , Nenkova Galina , Salim Ayshe , Ivanova Diana 
Published: October 2024

Background: The rate of male infertility has increased in the last decades. One factor that may improve sperm quality and testosterone is fish consumption, which supplies the organism with essential nutrients.Aim: To determine evidence of a relationship between the frequency of fish consumption and sperm quality.Methods: Seventy‐four healthy men, aged 25–45 years, were involved in this observational study. Semen quality was evaluated by spermogram analyses and testosterone was measured in blood. Volunteers were classified as low, moderate, and high fish consumption groups according to the replies indicated in a questionnaire they had to fill out.Results: The moderate fish consumption group showed better semen quality with all spermogram parameters in the reference range and the low fish consumption group manifested the worst semen quality with sperm morphology below the reference range. The low fish consumption group had lower testosterone levels (3.6 ± 0.9 vs. 4.3 ± 1.5; p = 0.04), decreased nonprogressive spermatozoa (11.9 ± 6.2 vs. 15.8 ± 8.2; p = 0.04), and lower semen volume (3.1 ± 2.0 vs. 3.6 ± 1.3; p = 0.06) compared to the moderate fish consumption group. Positive associations were detected between the frequency of fish consumption, the semen volume, and nonprogressive spermatozoa, respectively.Conclusions: Fish consumption at moderate level such as once a week leads to improvement in sperm quality and testosterone levels.
Phase Ib Study of the Immunocytokine Simlukafusp Alfa (FAP-IL2v) in Combination with Cetuximab in Patients with Head and Neck Squamous Cell Carcinoma
Authors: Hansen Aaron R. , Gomez-Roca Carlos A. , Robbrecht Debbie G. J. , Verlingue Loic , Italiano Antoine , Bauman Julie E. , Steeghs Neeltje , Prenen Hans , Fayette Jérôme , Spicer James , Niu Jiaxin , Habigt Christin , Schneider Meike , Evers Stefan , Sleiman Nassim , Dejardin David , Ardeshir Caroline , Schmid Daniela , Boetsch Christophe , Charo Jehad , Kraxner Anton , Teichgräber Volker , Keshelava Nino , Bonomi Marcelo R. 
Published: October 2024

Abstract
Purpose: This phase Ib trial evaluated fibroblast activation protein-α–targeted IL2 variant (FAP-IL2v), a novel immunocytokine engineered to minimize CD25-mediated toxicities, in combination with cetuximab, in patients with recurrent, unresectable, or metastatic head and neck squamous cell carcinoma (HNSCC).
Patients and Methods: Patients received FAP-IL2v either on a continuous weekly (QW) schedule or QW for 4 weeks and then every 2 weeks (Q2W). Cetuximab was dosed at QW or Q2W schedules. The primary objectives were to evaluate the safety and tolerability, maximum tolerated dose, pharmacokinetics, and clinical activity for the combination of FAP-IL2v with cetuximab. Exploratory objectives included pharmacodynamic analyses.
Results: A total of 58 patients were enrolled, 19 patients into the dose-escalation part, and 39 patients into the expansion part. The maximum tolerated dose of FAP-IL2v was defined as 10 mg (QW/Q2W) in combination with cetuximab (500 mg/m2, Q2W), which was further tested in the expansion part. The most common FAP-IL2v–related adverse events with a grade 3 or 4 severity were hypophosphatemia (19%), lymphopenia (16%), and infusion-related reaction (14%). The pharmacokinetics of FAP-IL2v in combination with cetuximab was similar to that after administration as monotherapy. Consistent with the proposed mode of action, FAP-IL2v preferentially expanded intratumoral NK and CD8 T cells. Four patients achieved a partial response, and the objective response rate was 7% (95% confidence interval, 3.2–14.7).
Conclusions: The safety profile of FAP-IL2v in combination with cetuximab was acceptable, and pharmacodynamic markers support the proposed mode of action of this combination, but the overall low antitumor activity does not warrant further clinical exploration in HNSCC. [Part C of Study BP29842 (NCT02627274).]
Abstract B016: Lactate uptake through MCT11 enforces dysfunction in terminally exhausted T cells
Authors: Peralta Ronal M. , Delgoffe Greg M. 
Published: October 2024

Abstract
CD8+ T cells are critical mediators of antitumor immunity but differentiate into a state of dysfunction, known as exhaustion, after experiencing persistent TCR stimulation and metabolic stress in the tumor microenvironment (TME). Exhausted T (Texh) cells are characterized by the sustained upregulation of co-inhibitory molecules and reduced stemness and polyfunctionality. The TME also creates an immunosuppressive metabolic environment via reduced levels of vital nutrients and oxygen combined with increased catabolic waste products. Additionally, highly glycolytic tumor and stromal cells secrete lactic acid, acidifying the extracellular space. How Texh cells survive and function in the face of this altered metabolite balance remains unclear. Recent studies have shown that lactate can be incorporated into the TCA cycle by CD8+ T cells and that it can be utilized in the TME as a fuel source by regulatory T cells and macrophages. We hypothesized that CD8+ tumor-infiltrating lymphocytes (TIL) may take also take up lactate as to meet their metabolic demands in the TME. Here, we show via RNAseq and flow cytometry staining that Texh cells upregulate a newly characterized monocarboxylate transporter, MCT11 (encoded by Slc16a11), enabling uptake of lactic acid which can drive their dysfunction in the TME. MCT11 expression requires both the core exhaustion program induced through chronic activation and metabolic stress signals, like hypoxia, originating within tissues. Overexpression of MCT11 in tumor- specific T cells decreased their polyfunctionality, while conditional deletion of MCT11 in T cells reduced lactic acid uptake in Texh cells and improved effector function and response to immunotherapy. Further, a monoclonal antibody targeting MCT11 reduced lactate uptake specifically in Texh cells, which, when used therapeutically in tumor- bearing mice, resulted in significantly reduced tumor growth, inducing complete regressions and immunologic memory in lactate-rich tumors. Our data support a model in which the exhaustion program upregulates MCT11, rendering exhausted T cells sensitive to toxic lactic acid present at high levels in the tumor microenvironment. MCT11 represents an attractive target to edit in therapeutic T cells or block using antibodies to render exhausted T cells impervious to lactic acid, allowing for tumor eradication.
Citation Format: Ronal M. Peralta, Greg M. Delgoffe. Lactate uptake through MCT11 enforces dysfunction in terminally exhausted T cells [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2024 Oct 18-21; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2024;12(10 Suppl):Abstract nr B016.
Abstract B018: CCL24+ monocytes drives resistance to anti-PD-L1 blockade in hepatocellular carcinoma
Authors: DENG HAIJING , Fu-Wan Sit Grace , Wing-Sum Cheu Jacinth , Zhang Yan , Liu Cindy Xinqi , Chen Yiling , Ooi Zher Yee , Wai-Hin Yuen Vincent , Oi-Lin Ng Irene , Chak-Lui Wong Carmen 
Published: October 2024

Abstract
Background: Immunotherapy has promising anti-tumor activity in patients with advanced Hepatocellular carcinoma (HCC). However, the objective response rate of PD-L1 blockade is limited. Therefore, there is an urgent need to explore resistance mechanisms in immunotherapy. Methods and Results: We used the anti-PD-L1 resistant trp53KO/c-mycOE mice to explore tumor immune microenvironment. Fresh isolated single cells were analysed by single-cell RNA sequencing (scRNA seq), TCR sequencing and Cytometry by Time-Of-Flight (CyTOF). Gene expression of the tumors samples was tested by bulk RNA sequencing. In vivo efficacy studies were executed in trp53KO/c-mycOE mice induced by hydrodynamic tail vein injection. The function of immune cells was evaluated by multiple flow cytometry. Results: We found although anti-PD-L1 treatment significantly improved T cells infiltration and TCR clonal expansion. These T cells exhibited highly exhausted status with highly exhausted markers (CD39, LAG3, PD-1) expression. Targeting the exhausted markers by specific antibodies cannot unleash the function of T cells, which suggested the persistent immunosuppressive microenvironment existed. Bulk RNA sequencing showed significantly activation of IFNG related pathway. scRNA seq exhibited increased monocytes ratio and the IFNG score prominently upregulated in monocytes after anti- PD-L1 treatment. Subclusters analysis showed that CCL24+ monocytes were increased remarkably after treatment. CCL24+ monocytes showed significant response to IFNG and these cells also significantly expressed IL10, VEGFA, ARG1 etc. Conclusion: Our data demonstrated anti-PD-L1 blockade induced IFNG related pathways and increased the CCL24+ monocytes infiltration. These cells maybe the potential targets mediating the resistant mechanisms for immunotherapy. Further exploration could facilitate the development of new combination therapies that synergistically enhance treatment efficacy for patients with HCC.
Citation Format: HAIJING DENG, Grace Fu-Wan Sit, Jacinth Wing-Sum Cheu, Yan Zhang, Cindy Xinqi Liu, Yiling Chen, Zher Yee Ooi, Vincent Wai-Hin Yuen, Irene Oi-Lin Ng, Carmen Chak-Lui Wong. CCL24+ monocytes drives resistance to anti-PD-L1 blockade in hepatocellular carcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2024 Oct 18-21; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2024;12(10 Suppl):Abstract nr B018.
Abstract B044: Development of Tumour-specific CD146 CAR-T Cells for Targeted Cancer Immunotherapy of Solid Tumours
Authors: Uzuner Erez , Mole Holly , Beyza GURLER Sevim , Wong Chun Wai , Fernandez Carro Macarena Lucia , Leshem Rotem , Sefton Kieran , Tovey Helen , Picken Andrew , Blot-Chabaud Marcel , Hurlstone Adam 
Published: October 2024

Abstract
Background: In comparison to the success with hematologic cancers, CAR-T cells for solid cancers have been held back by significant “on-target/off-tumour” toxicities caused by the absence of specific target proteins. Although CD146 (aka MCAM) is a glycoprotein expressed on benign cells, including endothelial cells, pericytes and smooth muscle cells, a conformation has been identified enriched in tumours that we call tumour-specific (ts) CD146. Herein, we attempt to engender tumour specificity of CAR-T cells by targeting tsCD146 widely expressed in several solid tumours, notably melanoma and ovarian cancer. Methods: We assessed the CAR activity using flow cytometry by measuring CD69 expression on CAR-expressing Jurkat cells, an early activation marker, after co-culturing with CD146-positive and CD146-negative human melanoma and ovarian cancer cell lines. The effector functions of CAR-T cells have been evaluated both in vitro by the relative luciferase activity of target cells and ELISA for IFN-g and TNF-a secretion after co-culturing and in vivo by assessing the tumour growth by IVIS bioluminescent imaging. Results: Through multiple rounds of protein engineering, we have developed several CAR constructs to respond to a tumour-enriched CD146 isoform. Our CAR demonstrated antigen-dependent activation of Jurkat cells when co-cultured with CD146-positive human melanoma and ovarian cancer cell lines, comparable to a CAR targeting pan-CD146. CAR primary T cells co-cultured with these cell lines exhibited proportional killing activity and other effector functions. Upon assessment of anti-tumour activities of CAR-T cells in mice engrafted with WM266-4 cells, CAR-T-treated mice showed reduced tumour burden and prolonged survival compared to mice treated with untransduced T cells. Conclusions: We have successfully integrated the antigen-binding domain of an anti-tsCD146 antibody into a CAR scaffold. The ability of tsCD146 CAR primary T cells to target CD146-expressing cancerous cells provides a novel approach for targeted immunotherapy of solid tumours.
Citation Format: Erez Uzuner, Holly Mole, Sevim Beyza GURLER, Chun Wai Wong, Macarena Lucia Fernandez Carro, Rotem Leshem, Kieran Sefton, Helen Tovey, Andrew Picken, Marcel Blot-Chabaud, Adam Hurlstone. Development of Tumour-specific CD146 CAR-T Cells for Targeted Cancer Immunotherapy of Solid Tumours [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2024 Oct 18-21; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2024;12(10 Suppl):Abstract nr B044.