bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selective enhanced cytotoxicity of amino acid deprivation for cancer therapy using thermozyme functionalized nanocatalyst
Authors: Tang Xiuhui , Zhang Lijuan , Huang Mingwang , Wang Fang , Xie Guiqiu , Huo Rui , Gao Renjun 
Published: February 2024

Abstract
Background
Enzyme therapy based on differential metabolism of cancer cells has demonstrated promising potential as a treatment strategy. Nevertheless, the therapeutic benefit of reported enzyme drugs is compromised by their uncontrollable activity and weak stability. Additionally, thermozymes with high thermal-stability suffer from low catalytic activity at body temperature, preventing them from functioning independently.

Results
Herein, we have developed a novel thermo-enzymatic regulation strategy for near-infrared (NIR)-triggered precise-catalyzed photothermal treatment of breast cancer. Our strategy enables efficient loading and delivery of thermozymes (newly screened therapeutic enzymes from thermophilic bacteria) via hyaluronic acid (HA)-coupled gold nanorods (GNRs). These nanocatalysts exhibit enhanced cellular endocytosis and rapid enzyme activity enhancement, while also providing biosafety with minimized toxic effects on untargeted sites due to temperature-isolated thermozyme activity. Locally-focused NIR lasers ensure effective activation of thermozymes to promote on-demand amino acid deprivation and photothermal therapy (PTT) of superficial tumors, triggering apoptosis, G1 phase cell cycle arrest, inhibiting migration and invasion, and potentiating photothermal sensitivity of malignancies.

Conclusions
This work establishes a precise, remotely controlled, non-invasive, efficient, and biosafe nanoplatform for accurate enzyme therapy, providing a rationale for promising personalized therapeutic strategies and offering new prospects for high-precision development of enzyme drugs.

Graphical Abstract
The impact of COVID-19 on life expectancy across socioeconomic groups in Denmark
Authors: Strozza Cosmo , Vigezzi Serena , Callaway Julia , Aburto José Manuel 
Published: February 2024

AbstractBackgroundDenmark was one of the few countries that experienced an increase in life expectancy in 2020, and one of the few to see a decrease in 2021. Because COVID-19 mortality is associated with socioeconomic status (SES), we hypothesize that certain subgroups of the Danish population experienced changes in life expectancy in 2020 and 2021 that differed from the country overall. We aim to quantify life expectancy in Denmark in 2020 and 2021 by SES and compare this to recent trends in life expectancy (2014–2019).MethodsWe used Danish registry data from 2014 to 2021 for all individuals aged 30+. We classified the study population into SES groups using income quartiles and calculated life expectancy at age 30 by year, sex, and SES, and the differences in life expectancy from 2019 to 2020 and 2020 to 2021. We compared these changes to the average 1-year changes from 2014 to 2019 with 95% confidence intervals. Lastly, we decomposed these changes by age and cause of death distinguishing seven causes, including COVID-19, and a residual category.ResultsWe observed a mortality gradient in life expectancy changes across SES groups in both pandemic years. Among women, those of higher SES experienced a larger increase in life expectancy in 2020 and a smaller decrease in 2021 compared to those of lower SES. Among men, those of higher SES experienced an increase in life expectancy in both 2020 and 2021, while those of lower SES experienced a decrease in 2021. The impact of COVID-19 mortality on changes in life expectancy in 2020 was counterbalanced by improvements in non-COVID-19 mortality, especially driven by cancer and cardiovascular mortality. However, in 2021, non-COVID-19 mortality contributed negatively even for causes as cardiovascular mortality that has generally a positive impact on life expectancy changes, resulting in declines for most SES groups.ConclusionsCOVID-19 mortality disproportionally affected those of lower SES and exacerbated existing social inequalities in Denmark. We conclude that in health emergencies, particular attention should be paid to those who are least socially advantaged to avoid widening the already existing mortality gap with those of higher SES. This research contributes to the discussion on social inequalities in mortality in high-income countries.
Motor skill competence and moderate- and vigorous-intensity physical activity: a linear and non-linear cross-sectional analysis of eight pooled trials
Authors: Barnett L. M. , Verswijveren S. J. J. M. , Colvin B. , Lubans D. R. , Telford R. M. , Lander N. J. , Schott N. , Tietjens M. , Hesketh K. D. , Morgan P. J. , Hinkley T. , Downing K. L. , Telford R. D. , Cohen K. E. , Ridgers N. D. , Abbott G. 
Published: February 2024

Abstract
Background
Few studies have examined the relationship between motor skill competence and device-measured physical activity in large samples and none have used non-linear modelling. This study assessed the linear and non-linear associations between motor skill competence and physical activity in children using pooled data from eight studies.

Methods
Cross-sectional ActiGraph accelerometer and motor skills competence data from 988 children (50.8% boys) aged 3–11 years were included. Total, object control and locomotor skill competence were assessed using the Test of Gross Motor Skill Development. Linear mixed models were fitted to examine linear associations between motor skill competence and physical activity. Then, restricted cubic splines models were used to assess potential non-linear relationships. Interactions by sex and age were assessed.

Results
There was evidence of positive linear associations between total skill, and object control and locomotor skills, with moderate- and vigorous-intensity physical activity; however, the associations with total skill competence and object control better fitted a non-linear model. Non-linear models indicated associations were positive but relatively weak in the low to mid ranges of TGMD/object control scores but at high ranges (~ > 70 out of 100/ and ~ 35 out of 50) the association strength increased for both moderate- and vigorous-intensity physical activity. There were sex interactions for locomotor skills only, specifically for vigorous activity with boys having a stronger positive association than girls.

Conclusions
There appears to be a threshold for object control skill proficiency that children need to reach to enhance their physical activity levels which provides support for a motor skill “proficiency barrier”. This provides a tangible benchmark for children to achieve in motor competence programs.
Cancer testis antigen burden (CTAB): a novel biomarker of tumor-associated antigens in lung cancer
Authors: Seager R. J. , Senosain Maria-Fernanda , Van Roey Erik , Gao Shuang , DePietro Paul , Nesline Mary K. , Dash Durga Prasad , Zhang Shengle , Ko Heidi , Hastings Stephanie B. , Strickland Kyle C. , Previs Rebecca A. , Jensen Taylor J. , Eisenberg Marcia , Caveney Brian J. , Severson Eric A. , Ramkissoon Shakti , Conroy Jeffrey M. , Pabla Sarabjot 
Published: February 2024

Abstract
Background
Cancer-testis antigens (CTAs) are tumor antigens that are normally expressed in the testes but are aberrantly expressed in several cancers. CTA overexpression drives the metastasis and progression of lung cancer, and is associated with poor prognosis. To improve lung cancer diagnosis, prognostic prediction, and drug discovery, robust CTA identification and quantitation is needed. In this study, we examined and quantified the co-expression of CTAs in lung cancer to derive cancer testis antigen burden (CTAB), a novel biomarker of immunotherapy response.

Methods
Formalin fixed paraffin embedded (FFPE) tumor samples in discovery cohort (n = 5250) and immunotherapy and combination therapy treated non-small cell lung cancer (NSCLC) retrospective (n = 250) cohorts were tested by comprehensive genomic and immune profiling (CGIP), including tumor mutational burden (TMB) and the mRNA expression of 17 CTAs. PD-L1 expression was evaluated by IHC. CTA expression was summed to derive the CTAB score. The median CTAB score for the discovery cohort of 170 was applied to the retrospective cohort as cutoff for CTAB “high” and “low”. Biomarker and gene expression correlation was measured by Spearman correlation. Kaplan–Meier survival analyses were used to detect overall survival (OS) differences, and objective response rate (ORR) based on RECIST criteria was compared using Fisher’s exact test.

Results
The CTAs were highly co-expressed (p < 0.05) in the discovery cohort. There was no correlation between CTAB and PD-L1 expression (R = 0.011, p = 0.45) but some correlation with TMB (R = 0.11, p = 9.2 × 10–14). Kaplan–Meier survival analysis of the immunotherapy-treated NSCLC cohort revealed better OS for the pembrolizumab monotherapy treated patients with high CTAB (p = 0.027). The combination group demonstrated improved OS compared to pembrolizumab monotherapy group (p = 0.04). The pembrolizumab monotherapy patients with high CTAB had a greater ORR than the combination therapy group (p = 0.02).

Conclusions
CTA co-expression can be reliably measured using CGIP in solid tumors. As a biomarker, CTAB appears to be independent from PD-L1 expression, suggesting that CTAB represents aspects of tumor immunogenicity not measured by current standard of care testing. Improved OS and ORR for high CTAB NSCLC patients treated with pembrolizumab monotherapy suggests a unique underlying aspect of immune response to these tumor antigens that needs further investigation.
Validation of a modified version of the gross motor function measure in PPPR5D related neurodevelopmental disorder
Authors: Kanner Cara H. , Uher David , Zreibe Kyle , Beard Gabriella , Patterson Madison , Harris Matthew , Doerger Jerome , Calamia Sean , Chung Wendy K. , Montes Jacqueline 
Published: February 2024

Abstract
Background
Protein phosphatase 2 regulatory subunit B’ Delta (PPP2R5D)-related neurodevelopmental disorder is a rare genetic condition caused by pathogenic variants in the PPP2R5D gene. Clinical signs include hypotonia, gross motor delay, intellectual disability (ID), epilepsy, speech delays, and abnormal gait among other impairments. As this disorder was recognized within the last decade, there are only 103 people published diagnoses to date. A thorough understanding of the motor manifestations of this disorder has not yet been established. Knowledge of the natural history of PPP2R5D related neurodevelopmental disorder will lead to improved standard of care treatments as well as serve as a baseline foundation for future clinical trials. Appropriate outcome measures are necessary for use in clinical trials to uniformly measure function and monitor potential for change. The aim of this study was to validate the gross motor function measure (GMFM) in children and adults with PPP2R5D-related neurodevelopmental disorder in order to better characterize the disorder.

Results
Thirty-eight individuals with PPP2R5D pathogenic variants, median age 8.0 years (range 1–27) were evaluated. Gross motor, upper limb and ambulatory function were assessed using the GMFM-66, six-minute walk test (6MWT), 10-meter walk run (10MWR), timed up and go (TUG), and revised upper limb module (RULM). The pediatric disability inventory computer adapted test (PEDI-CAT) captured caregiver reported assessment. Median GMFM-66 score was 60.6 (SD = 17.3, range 21.1–96.0). There were strong associations between the GMFM-66 and related mobility measures, 10MWR (rs = −0.733; p < 0.001), TUG (rs= −0.747; p = 0.003), 6MWT (r = 0.633; p = 0.006), RULM (r = 0.763; p < 0.001), PEDICAT-mobility (r = 0.855; p < 0.001), and daily activities (r = 0.822; p < 0.001) domains.

Conclusions
The GMFM is a valid measure for characterizing motor function in individuals with PPP2R5D related neurodevelopmental disorder. The GMFM-66 had strong associations with the RULM and timed function tests which characterized gross motor, upper limb and ambulatory function demonstrating concurrent validity. The GMFM-66 was also able to differentiate between functional levels in PPP2R5D related neurodevelopmental disorder demonstrating discriminant validity. Future studies should examine its sensitivity to change over time, ability to identify sub-phenotypes, and suitability as an outcome measure in future clinical trials in individuals with PPP2R5D variants.
Are better AI algorithms for breast cancer detection also better at predicting risk? A paired case–control study
Authors: Santeramo Ruggiero , Damiani Celeste , Wei Jiefei , Montana Giovanni , Brentnall Adam R. 
Published: February 2024

Abstract
Background
There is increasing evidence that artificial intelligence (AI) breast cancer risk evaluation tools using digital mammograms are highly informative for 1–6 years following a negative screening examination. We hypothesized that algorithms that have previously been shown to work well for cancer detection will also work well for risk assessment and that performance of algorithms for detection and risk assessment is correlated.

Methods
To evaluate our hypothesis, we designed a case-control study using paired mammograms at diagnosis and at the previous screening visit. The study included n = 3386 women from the OPTIMAM registry, that includes mammograms from women diagnosed with breast cancer in the English breast screening program 2010–2019. Cases were diagnosed with invasive breast cancer or ductal carcinoma in situ at screening and were selected if they had a mammogram available at the screening examination that led to detection, and a paired mammogram at their previous screening visit 3y prior to detection when no cancer was detected. Controls without cancer were matched 1:1 to cases based on age (year), screening site, and mammography machine type. Risk assessment was conducted using a deep-learning model designed for breast cancer risk assessment (Mirai), and three open-source deep-learning algorithms designed for breast cancer detection. Discrimination was assessed using a matched area under the curve (AUC) statistic.

Results
Overall performance using the paired mammograms followed the same order by algorithm for risk assessment (AUC range 0.59–0.67) and detection (AUC 0.81–0.89), with Mirai performing best for both. There was also a correlation in performance for risk and detection within algorithms by cancer size, with much greater accuracy for large cancers (30 mm+, detection AUC: 0.88–0.92; risk AUC: 0.64–0.74) than smaller cancers (0 to < 10 mm, detection AUC: 0.73–0.86, risk AUC: 0.54–0.64). Mirai was relatively strong for risk assessment of smaller cancers (0 to < 10 mm, risk, Mirai AUC: 0.64 (95% CI 0.57 to 0.70); other algorithms AUC 0.54–0.56).

Conclusions
Improvements in risk assessment could stem from enhancing cancer detection capabilities of smaller cancers. Other state-of-the-art AI detection algorithms with high performance for smaller cancers might achieve relatively high performance for risk assessment.
Patients with obesity have more inflamed joints and higher CRP levels during the disease course in ACPA-positive RA but not in ACPA-negative RA
Authors: Hollander N. K. den , Boeren A. M. P , van der Helm-van Mil A. H. M. , van Steenbergen H. W. 
Published: February 2024

Abstract
Background
Obese RA patients have higher disease activity scores (DAS). Previous research showed that obese RA patients have higher tender joint count (TJC) and VAS general health. However, it remains unclear whether DAS components measuring local and systemic inflammation (swollen joint count (SJC), CRP) are increased and if this is present in the total RA population or confined to an ACPA subgroup. As ACPA is suggested to enhance inflammatory responses, we hypothesized that the association of obesity with SJC and CRP is present especially in ACPA-positive RA. We therefore studied associations of obesity with courses of DAS components in ACPA subgroups.

Methods
We studied 649 RA patients (291 ACPA-positive), included in the Leiden Early Arthritis Clinic. Five-year courses of DAS44 and DAS44 components (SJC—44, TJC—53, CRP, VAS (0–100)) were compared between RA patients with normal weight (BMI 18.5–24.9), overweight (25.0–29.9), and obesity (≥ 30.0), stratified for ACPA. Linear/Poisson mixed models with a knot at 4 months were used.

Results
Obese RA patients had + 0.32 higher DAS compared to normal weight during the 5-year follow-up. In ACPA-positive RA, obese patients had + 0.43 (95% CI: 0.22, 0.64) higher DAS, whereas in ACPA-negative RA, this difference was smaller and not statistically significant: + 0.19 (95% CI: − 0.01, 0.38). In ACPA-positive RA, all DAS components were significantly higher in obese patients compared to normal weight: SJC + 60% (IRR1.60; 95% CI: 1.18, 2.16), CRP + 3.7 mg/L (95% CI:0.95, 6.53), TJC + 55% (IRR1.55; 95% CI:1.15, 2.10), and VAS + 9 (95% CI: 4.0, 14.2). ACPA-negative obese RA patients tended to have higher TJC (IRR1.22; 95% CI: 0.96, 1.55) and VAS (β4.3; 95% CI: − 0.4, 9.0), while SJC (IRR1.07; 95% CI:0.85, 1.33) and CRP (β0.24; 95% CI: − 1.29, 3.32) were unaffected.

Conclusion
The association of obesity with a worse DAS course is mainly present in ACPA-positive RA; especially SJC and CRP levels remain higher in ACPA-positive RA patients with obesity but not ACPA-negative RA patients. This is the first demonstration that obesity influences the disease course of ACPA-positive and ACPA-negative RA differently.
Radiological complete response with regorafenib for multiple lung metastases of ascending colon cancer: a case report
Authors: Kikuchi Koji , Ogawa Masaaki , Sasaki Akira 
Published: February 2024

Abstract
Background
Regorafenib is an oral diphenylurea multikinase inhibitor and currently approved for use following third-line therapy for metastatic colorectal cancer (CRC) patients. Only one case has previously been reported of metastatic CRC showing a complete response (CR) to regorafenib.

Case presentation
A 68-year-old Japanese man underwent laparoscopy-assisted ileocecal resection and D3 lymphadenectomy due to his ascending colon cancer. Eighteen months after surgery, a laparoscopic hepatic left lateral segmentectomy was performed due to a liver tumor, and a pathological diagnosis of colorectal liver metastasis was made. Three months after the second surgery, contrast-enhanced computed tomography (CT) revealed multiple lung metastases. The patient had undergone 18 courses of the FOLFOX + bevacizumab chemotherapy regimen as their first-line therapy and 11 courses of the FOLFIRI + ramucirumab chemotherapy regimen as their second-line therapy. As their third-line therapy, the patient was administered the regorafenib chemotherapy regimen. We evaluated the chemotherapy treatment’s effect on the lung tumors by CT after 3, 7, 11, and 17 courses of the regorafenib chemotherapy regimen, finding that the lung tumors had shrunk with time; thus, each tumor was considered a partial response (PR) based on the RECIST guidelines. After 21 courses of the regorafenib chemotherapy regimen, the chemotherapy was discontinued in response to the patient’s wishes. Even at 1 and 3 months after the discontinuation of the chemotherapy, CT revealed that the lung tumors had shrunk, with each considered a PR. Furthermore, 9 months after the discontinuation of the chemotherapy, CT revealed scarring of the lung tumors. This was considered a CR, rather than a PR. The patient remains disease-free 18 months after the discontinuation of chemotherapy.

Conclusions
In this paper, we present the second case of radiological CR with regorafenib for multiple lung metastases of ascending colon cancer. Currently, there is no consensus on a treatment strategy for patients with radiological CR.
Natural compounds and mesenchymal stem cells: implications for inflammatory-impaired tissue regeneration
Authors: Li Wen , Xiang Zichao , Yu Wenjing , Huang Xiaobin , Jiang Qian , Abumansour Arwa , Yang Ying , Chen Chider 
Published: February 2024

AbstractInflammation is a common and important pathological process occurring in any part of the body and relating to a variety of diseases. Effective tissue repair is critical for the survival of impaired organisms. Considering the side effects of the currently used anti-inflammatory medications, new therapeutic agents are urgently needed for the improvement of regenerative capacities of inflammatory-impaired tissues. Mesenchymal stromal stem/progenitor cells (MSCs) are characterized by the capabilities of self-renewal and multipotent differentiation and exhibit immunomodulatory capacity. Due to the ability to modulate inflammatory phenotypes and immune responses, MSCs have been considered as a potential alternative therapy for autoimmune and inflammatory diseases. Natural compounds (NCs) are complex small multiple-target molecules mostly derived from plants and microorganisms, exhibiting therapeutic effects in many disorders, such as osteoporosis, diabetes, cancer, and inflammatory/autoimmune diseases. Recently, increasing studies focused on the prominent effects of NCs on MSCs, including the regulation of cell survival and inflammatory response, as well as osteogenic/adipogenic differentiation capacities, which indicate the roles of NCs on MSC-based cytotherapy in several inflammatory diseases. Their therapeutic effects and fewer side effects in numerous physiological processes, compared to chemosynthetic drugs, made them to be a new therapeutic avenue combined with MSCs for impaired tissue regeneration. Here we summarize the current understanding of the influence of NCs on MSCs and related downstream signaling pathways, specifically in pathological inflammatory conditions. In addition, the emerging concepts through the combination of NCs and MSCs to expand the therapeutic perspectives are highlighted. A promising MSC source from oral/dental tissues is also discussed, with a remarkable potential for MSC-based therapy in future clinical applications.