bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-CD7 allogeneic WU-CART-007 in patients with relapsed/refractory T-cell acute lymphoblastic leukemia/lymphoma: a phase 1/2 trial
Authors: Ghobadi Armin , Aldoss Ibrahim , Maude Shannon , Bhojwani Deepa , Wayne Alan , Bajel Ashish , Dholaria Bhagirathbhai , Faramand Rawan , Mattison Ryan , Rijneveld Anita , Zwaan C. , Calkoen Frisco , Baruchel Andre , BOISSEL Nicolas , Rettig Michael , Wood Brent , Jacobs Kenneth , Christ Stephanie , Irons Haley , Capoccia Ben , Gonzalez Justo , Wu Tony , Rosario Maria del , Hamil Alexander , Bakkacha Ouiam , Muth John , Ramsey Brett , McNulty Eileen , Cooper Matthew , Baughman Jan , Davidson-Moncada Jan , DiPersio John 
Published: August 2024

Abstract

Relapsed/refractory T-cell acute lymphoblastic leukemia (ALL)/lymphoma (LBL) represent a significant unmet medical need. WU-CART-007 is a CD7-targeting, allogeneic, fratricide-resistant chimeric antigen receptor T cell product generated from healthy donor T cells. WU-CART-007 was evaluated in a phase 1/2 study with a 3 + 3 dose-escalation design followed by cohort expansion in relapsed/refractory T-ALL/LBL. Patients received one infusion of WU-CART-007 after standard or enhanced lymphodepleting chemotherapy. The primary objectives, to characterize safety and assess the composite complete remission rate, were met. Of 26 patients enrolled, 13 received the recommended phase 2 dose (RP2D) of 900 million cells of WU-CART-007 with enhanced lymphodepletion. The most common treatment-related adverse event was cytokine release syndrome (88.5%; 19.2% grade 3–4). Biochemical abnormalities consistent with grade 2 hemophagocytic lymphohistiocytosis were seen in one patient (3.8%). Grade 1 immune effector cell-associated neurotoxicity syndrome events (7.7%) and one grade 2 acute graft-vs-host disease event occurred. Grade 5 events (11.5%) were due to fungal infection and multi-organ failure. The composite complete remission rate was 81.8% among 11/13 patients evaluable for response at the RP2D. WU-CART-007 at the RP2D demonstrated a high response rate in patients with relapsed/refractory T-ALL/LBL and has the potential to provide a new treatment option. ClinicalTrials.gov registration: NCT04984356.
Revamped dynamic opposite learning the hiking optimization algorithm for global optimization and engineering applications
Authors: P Rajasekar , M Jayalakshmi 
Published: August 2024

Abstract

In recent decades, numerous notable meta-heuristic algorithms have been developed to tackle complex optimization problems. Nevertheless, these existing meta-heuristics need to be enhanced with various evolutionary techniques to tackle new challenges in engineering applications. This analysis aims to improve the efficiency of the recently introduced Hiking Optimization Algorithm (HOA), a human-inspired method that simulates the complexities of a hiking journey aiming to reach a peak. The hiking environment, featuring rugged terrain with multiple local peaks and a global peak, mirrors an optimization search landscape. Like other algorithms, HOA has limitations, such as becoming trapped in local optima and lacking sufficient exploration capability, leading to premature convergence in challenging optimization problems. This study offers an upgraded version of HOA incorporating a revamped dynamic opposite learning (RDOL) strategy, called the revamped dynamic opposite learning HOA (RDOLHOA). RDOLHOA dynamically adjusts the weighting factor using a nonlinear function to balance exploration and exploitation. This innovation aims to reduce the randomness of the initial population and decrease the search effort required to find the optimal solution. Experiments on twenty-three diverse functions from the CEC 2005 test suites and various real world engineering problems show that RDOLHOA outperforms HOA with a faster convergence rate. Additionally statistical tests, particularly the Wilcoxon rank-sum test, demonstrate that RDOLHOA exceeds the performance of other competing algorithms in real world engineering design problems.
Community perceptions of ethics and professionalism of community health workers – a qualitative exploration
Authors: Gopichandran Vijayaprasad , Subramaniam Sudharshini , Palanisamy Balasubramanian , Chidambaram Priyadarshini 
Published: August 2024

Abstract

Background
Community health workers (CHW) work closely with communities and therefore encounter several important ethical issues in their work. Community perceptions about their practice of ethics and professionalism is important.
Methods
We conducted 4 focus group discussions (FGD) among pregnant women and lactating mothers, 4 FGDs among women in the community, 3 in depth interviews (IDI) among women and 2 IDIs among men in two districts of Tamil Nadu, India. We explored the various practices of ethics and professionalism in these discussions and interviews. We transcribed the data, coded the transcripts, and built themes by combining the codes meaningfully.
Results
The CHWs ensure good quality of services by effective use of mobile phone and by going beyond the call of duty. They face several challenges in doing good to the community. On the other hand, there were many instances where they failed to deliver their duties which led to harms. Living far away from the community, spending less time there, delegating their work to lay persons all compromised the performance of their duties. CHW’s lack of good communication skills, lack of updated knowledge, and inefficient work were pointed out by the community. Treating the people as mere statistics and not caring for them as people was a reason for dissatisfaction. The quality of a CHW’s work was assessed relatively in comparison with other CHWs who were perceived as good and not in comparison with standards or expectations. Lack of honesty, demanding bribes, disrespectful treatment, discrimination of the marginalized communities, coercion, and lack of privacy and confidentiality were also reported in the CHW’s work. Reports of such unethical practices were more from people belonging to scheduled castes and tribes compared to those from dominant castes. The attributes of professionalism of a CHW reported by the community were altruism, empathy, inspiring confidence and trust, honesty, humility, kindness, relatability, adaptability, care, and tolerance.
Conclusions
The community identified important good and bad practices among CHWs. There is a need to share this information with CHWs and train them to improve practices of ethics and professionalism in their work.
Antarctic ice microstructure and experimental study of Brazilian splitting
Authors: Luo Yaolong , Lv Jianguo , Xu Haoran , Jia Xiamin , Xie Pengfei , Wei Mingsheng 
Published: August 2024

Abstract

Tensile strength is one of the fundamental mechanical parameters of Antarctic ice. Due to the challenges associated with direct tensile testing, this study employs the Brazilian disc splitting test to indirectly measure the tensile strength of Antarctic ice. Initially, ice cores drilled from the ice cap near Zhongshan Station in Antarctica were processed into Brazilian split disc specimens using a lathe. The microstructure and chemical composition of the ice specimens, including concentrations of\(\:{\text{C}\text{l}}^{-},{\text{N}\text{O}}_{3}^{-}\),and\(\:{\text{S}\text{O}}_{4}^{2-}\),were analyzed.Simultaneously, a high-pressure low-temperature triaxial instrument was utilized for loading to obtain stress-strain relationship curves under different loading rates, thereby exploring the effects of loading rate on tensile strength and elastic modulus.Using near-field dynamics and deformation field analysis, the Brazilian splitting damage process was simulated to elucidate the tensile damage behavior of the ice samples. The results indicate that the Antarctic ice structure is granular and isotropic, with mechanical properties independent of crystal orientation. Consequently, loading in vertical and horizontal directions does not affect the tensile strength of Antarctic ice. Among the four primary ions,chloride (\(\:{\text{C}\text{l}}^{-})\)has the highest concentration, reflecting ocean-atmosphere interactions; sulfate (\(\:{\text{S}\text{O}}_{4}^{2-}\)) is the second most abundant, originating from ocean spray and human activities; and nitrate (\(\:{\text{N}\text{O}}_{3}^{-}\))primarily derives from atmospheric nitrogen oxides.Both the tensile strength and elastic modulus of the ice samples increase with loading rate.At a loading rate of 0.12mm/min,the minimum tensile strength is 0.32MPa,whereas at a loading rate of 3.72mm/min,the maximum tensile strength is 0.453MPa.Similarly,at a loading rate of 0.12mm/min,the minimum elastic modulus is 0.183GPa, and at a loading rate of 1.98mm/min,the maximum elastic modulus is 0.479GPa.Simulation of the damage process morphology and transverse displacement field distribution reveals the tensile damage behavior of Antarctic ice: under high loading rates (1.98 ~ 3.72mm/min) the ice specimens rapidly exhibit significant cracking;under low loading rates (0.11 ~ 0.35mm/min) the damage process predominantly involves three stages: crack initiation, crack propagation, and specimen failure.
Impact of Nutrient Composition on Rumen Microbiome Dynamics and Roughage Degradation
Authors: Ye Xiaoxing , Li Keyao , Li Yafei , Gu Mingming , OMOOR IBRAHIM N.A. , Liu Haoyu , Qiu Shuiling , Jiang Xinhui , Lu Jianing , Ma Zhiyi , Wu Jiyao , Gan Qianfu 
Published: August 2024

Abstract

Background: Ruminant animals such as goats rely on rumen microbial communities to degrade fibrous nutrients from roughages, facilitating their growth and development. This study investigates dynamic shifts in surface-attached rumen microbes in representative roughages: rice straw (RS), bamboo shoot sheet (BSS), and alfalfa (ALF). Four 14-month-old Min Dong goats with rumen fistulas were used, and the roughages were assessed at 4 h, 12 h, 24 h, 36 h, 48 h, and 72 h intervals. Microbiome composition and function were revealed through 16S rRNA and metagenomics sequencing.
Results: Prevotella and Treponema were the predominant genera in roughage degradation. Nutritional composition and tissue structure of roughages affected microbial attachment, causing variations in nutrient degradation rates. Microbials related to dry matter (DM) and crude protein (CP) degradation were abundant in early fermentation stages (4-12h) but decreased over time, while fiber-degrading microbials increased after 24 hours. Surface-attached microbials produced enzymes such as β-Glucosidase (BG), Endo-β-1,4-glucanase (C1), Exo-β-1,4-glucanase (Cx), and Neutral xylanase (NEX), with enzymatic activity correlating with the fiber content of the roughages.
Conclusions: These findings advance our understanding of microbial roles in ruminant nutrition and digestion. The interaction between microbial communities and rumen fermentation is pivotal for understanding collaborative gene encoding by goat rumen microbiota, which is critical for fiber degradation.
Association of systemic inflammatory biomarkers with hearing loss: Results from NHANES 1999–2020 analyses
Authors: Wang Yaojie , He Lisha , Huang Guoxin , Li Xiaodan , Qin Chenge , Cheng Sheng , Tan Huazhang , Tian Jing , Wang Qiuyang 
Published: August 2024

Abstract

Background:Hearing loss (HL) is a prevalent global health issue with a complex etiology in whichinflammation plays a significant role. The systemic immune inflammatory index (SII), a novel biomarker reflecting systemic inflammation, is hypothesized to correlate with HL.
Methods: Utilizing National Health and Nutritional Health Survey (NHANES) data from 1999–2020, this study analyzed the relationship between the SII and HL, categorized ashigh-frequency hearing loss (HFHL) orspeech-frequency hearing loss (SFHL). Blood samples were collected to calculate the SII. Weighted multivariate linear and logistic regression analyses were used to examine the linear relationship between the SII and hearing loss. After the SII was categorized into quartiles, a trend test was applied to assess the linear association between the SII and HL. Subgroup analysis was conducted to explore the correlation between the SII and HL across different sexes.
Results: Univariate logistic regression analysis revealed no significant correlation between the SII and the occurrence of hearing loss or SFHL (p>0.05), but there was a correlation between the SII and HFHL. Multivariate logistic regression revealed a significant positive correlation between the third quartile of the SII and hearing loss. In the second quartile, there was a significant positive correlation between the SII and SFHL. For HFHL, a significant positive correlation between the SII and HFHL was present only in the crude model and in the second and third quartiles. Stratified analysis of clinical variables revealed a positive correlation between SII and the onset of hearing loss in those with never alcohol intake and moderate alcohol intake, a positive correlation between the SII and HFHL in those with moderate alcohol intake,and a negative correlation between the SII and SFHL in those with a normal BMI, aged older than 60 years, and who were former smokers. In the RCSplot, a reverse U-shaped association was observed between the SII and the prevalence of hearing loss and SFHL (nonlinear p<0.05). There was a positive correlation between the SII and the incidence of HFHL. After stratification by sex, the SII showed a reverse U-shaped association with hearing loss in males and a positive correlation in females.
Conclusion: The SII is positively correlated with HFHL and shows a potential U-shaped relationship with HL and SFHL. In males, there was a reverse U-shaped association between the SII and hearing loss, while in females, there was a positive correlation.
Understanding the Perspectives and Experiences of Patients with Acute Severe Ulcerative Colitis in the Hospital: A Qualitative Analysis
Authors: Romain Dustin , Larson Charlotte , Kathuria Priya Kathuria , Aintabi Daniel , Tedesco Nicholas , Saunyama Queen , DeJonckheere Melissa , Bishu Shrinivas , Cohen-Mekelburg Shirley , Higgins Peter , Berinstein Jeffrey 
Published: August 2024

Abstract

Introduction:
Acute severe ulcerative colitis (ASUC) is a life-treating presentation of ulcerative colitis (UC) that requires prompt initiation of treatment to avoid complication. Unfortunately, outcomes for ASUC are suboptimal, with as many as 20-30% of patients requiring colectomy. This can be challenging for patients and highlights the need to understand patient experiences and perspectives navigating ASUC.
Methods:
A qualitative descriptive study utilizing semi-structured interviews was conducted to understand perspectives and experiences of patients navigating ASUC. Adult patients hospitalized for ASUC between January 2017 and March 2024 were eligible. Interviews were conducted both retrospectively among patients with a recent hospitalization and prospectively among patients within 24 hours of hospitalization for ASUC. Interviews were analyzed using a well-established hybrid inductive-deductive approach.
Results:
Thirty-four patients (44.2% response rate) hospitalized for ASUC were interviewed. Hybrid thematic analysis uncovered five major themes: 1) the pervasive impact of UC on QoL and mental health, 2) challenges associated with navigating uncertainty 3) prioritizing colon preservation, 4) bridging the divide between outpatient expectations and inpatient realities, and 5) balancing rapid symptom improvement with steroid safety. Our findings advocate for transparent approach to care, emphasizing the need for effective communication, education, and better alignment with patient values and expectations.
Conclusions:
Five key themes were identified, each with significant implications for developing a more patient-centered approach to ASUC care. These themes captured meaningful insight into patient perceptions and experiences, identifying multiple areas for actionable interventions to improve care.
Novel biological age model using explainable automated CT-based cardiometabolic biomarkers for phenotypic prediction of longevity
Authors: Pickhardt Perry , Kattan Michael , Lee Matthew , Pooler B. Dustin , Pyrros Ayis , Liu Daniel , Zea Ryan , Summers Ronald , Garrett John 
Published: August 2024

Abstract

We derived and tested a CT-based biological age (CTBA) model for predicting longevity, using an automated pipeline of explainable deep learning AI algorithms that quantify skeletal muscle, abdominal fat, aortic calcification, bone density, and solid abdominal organs. These AI tool were applied to abdominal CT scans from 123,281 adults (mean age, 53.6 years; 47% women; median clinical follow-up, 5.3 years). Final weighted CT biomarker selection was based on index of prediction accuracy (IPA). The CTBA model significantly outperformed standard demographic data for predicting longevity (IPA = 29.2 vs. 21.7; 10-year AUC = 0.880 vs. 0.779; p < 0.001), despite any knowledge of the latter. Age- and sex-corrected survival hazard ratio (HR) for the highest-vs-lowest risk CTBA quartile was 8.73 (95% CI,8.14–9.36). Muscle density, aortic plaque burden, visceral fat density, and bone density contributed most. Unlike (epi)genetic and metabolomic approaches, this personalized phenotypic CTBA model can be opportunistically-derived, regardless of clinical indication, to better inform risk assessment.
Orbital Dynamics of Lunar Frozen Orbits around Triaxial Moon in the Presence a Third Body Influences
Authors: Ramla O. M. , El-Salam F. A. Abd , Rahoma W. A. , Khattab E. H. 
Published: August 2024

Abstract

This research explores the existence of some new families of frozen orbits for satellites orbiting the triaxial Moon. The Hamiltonian of the problem incorporates the Moon's gravitational zonal harmonic coefficients up to \({J_6}\), along with the most significant triaxiality terms \({J_{22}}\), \({J_{31}}\),\({J_{32}}\), \({J_{33}}\), and the third-body perturbation due to Earth. By applying canonical Lie transforms, the short periodic terms are eliminated from the Hamiltonian, retaining the long periodic terms up to the second order. This study uncovers new families of critical inclination roots, with one set close to polar orbits and another near the typical critical inclination. It examines the dynamical variations in critical inclination due to changes in eccentricity, semi-major axis, and argument of periapsis. A family of frozen orbits with a fixed apsidal line is derived and graphically represented. To ensure the stability of these orbits, the periapsis argument solution imposes specific restrictions on selecting the inclination that satisfies the frozen argument of periapsis condition. Perturbations in the critical inclination become notably significant for high lunar orbits due to 3rd body perturbation from Earth.
Deciphering Molecular Specificity in MCL-1/BAK Interaction and Its Implications for Designing Potent MCL-1 Inhibitors
Authors: Chen Yongheng , Wei Hudie , Wang Haolan , Xiang Shuang , Wang Jiaqi , Qu Lingzhi , Chen Xiaojuan , Guo Ming , Lu Xiaoyun 
Published: August 2024

Abstract

The intricate interplay among BCL-2 family proteins governs mitochondrial apoptosis, with the anti-apoptotic protein MCL-1 primarily exerting its function by sequestering the pore-forming effector BAK. Understanding the MCL-1/BAK complex is pivotal for the sensitivity of cancer cells to BH3 mimetics, yet the precise molecular mechanism underlying their interaction remains elusive. Herein, we demonstrate that a canonical BH3 peptide from BAK inadequately binds to MCL-1 proteins, whereas an extended BAK-BH3 peptide with five C-terminal residues exhibits a remarkable 65-fold increase in affinity. By elucidating the complex structures of MCL-1 bound to these two BAK-BH3 peptides at 2.08 Å and 1.98 Å resolutions, we uncover their distinct binding specificities. Notably, MCL-1 engages in critical hydrophobic interactions with the extended BAK-BH3 peptide, particularly at an additional p5 sub-pocket, featuring a π-π stacking interaction between MCL-1 Phe319 and BAK Tyr89. Mutations within this p5 sub-pocket substantially disrupt the MCL-1/BAK protein-protein interaction. Furthermore, the p5 sub-pocket of MCL-1 significantly influences the efficacy of MCL-1 inhibitors. Overall, our findings elucidate the molecular specificity underlying MCL-1 binding to BAK and underscore the significance of the p5 hydrophobic sub-pocket in their high-affinity interaction, thus providing novel insights for the development of BH3 mimetics targeting the MCL-1/BAK interaction as potential therapeutics for cancer treatment.
Effectiveness and reversibility test of electrochemical modification of mudstone hydro-mechanical parameters
Authors: Liu Peng , Han Liu 
Published: August 2024

Abstract

To study the modification effect of the hydromechanical parameters of mudstone after electrochemical modification and the reversibility of this modification, AlCl3 solution and Fe were selected as the electrolyte and electrode materials for the electrochemical modification test. The shear strength of the mudstone specimens was used as an evaluation index to evaluate the effect of electrochemical modification. The results of the electrochemical modification test of mudstone, using the controlled variable method, showed that the shear strength of the modified mudstone increased by about 1.4 times compared to the unmodified mudstone when a 20% AlCl3 solution and Fe electrode were used. The saturated water content of the modified mudstone, after re-absorption of water, was significantly reduced. The saturated water content of the specimens in the anode and cathode groups of the Fe electrode were 23.2% and 18.2%, respectively. The liquid limit water content after modification was 32.489%, which was lower than the 35.266% of unmodified mudstone, while the plastic limit water content increased from 20.728–22.697%. The water absorption rate of the modified mudstone specimens decreased significantly, with an average water absorption rate of 0.13 g/h, compared to 0.19 g/h for the unmodified mudstone. Through electrochemical modification, the mechanical strength of the mudstone was significantly improved, and its hydrophilicity and water absorption capacity were significantly reduced. The mudstone also exhibited an obvious strain softening feature after re-absorption but still showed a certain enhancement compared to the as-reinstated soil. This indicates that the electrochemically modified soil has a certain degree of reversibility after softening again upon contact with water.
Preparation of restricted access media-methacrylic resin and its application in the Lamotrigine determination in human plasma by solid-phase extraction
Authors: Wang Xiaofei , Peng Qian , Dong Yummei , Dou Xiping , Li Ping , Bai Yinliang 
Published: August 2024

Abstract

Restricted access media-methacrylic resin with the ability of protein exclusion was prepared by the free radical polymerization using methacrylic acid, ethylene glycol dimethacrylate and glycidyl methacrylateas as monomer, cross-linker and comonomer, respectively. Protein exclusion ability of this material was studied. The results showed that the material was able to eliminate 93.6% of protein after bovine serum albumin solution was added and shaken for 220 min. Adsorption kinetics and adsorption isotherms of lamotrigine on this material were investigated, the experimental data were the most suitable for the pseudo-second-order kinetics model and Freundlich isotherm model. Restricted access media-methacrylic resin was used as sorbent for solid-phase extraction to extract lamotrigine from human plasma. The method for the determination of lamotrigine in human plasma by SPE coupled to the HPLC presented linear range from 0.999 to 66.6 µg/ml with correlation coefficient 0.9930 for lamotrigine, assay precision with relative standard deviation value 6.24%, and assay accuracy 94.7% -104.7% with relative standard deviation values 4.33%-5.81. SPEs filled with this material were used at least 7 times without any significant changes in their performance. Analytical validation parameters demonstrated that the method could be applied to the determination of lamotrigine at the therapeutic plasma levels without other treatments.