bluuebunny/crossref_metadata_2025 huggingface dataset:
Health-related quality of life and its determinants among cancer patients: evidence from 12,148 patients of Indian database
Authors: Dixit Jyoti , Gupta Nidhi , Kataki Amal , Roy Partha , Mehra Nikita , Kumar Lalit , Singh Ashish , Malhotra Pankaj , Gupta Dharna , Goyal Aarti , Rajsekar Kavitha , Krishnamurthy Manjunath Nookala , Gupta Sudeep , Prinja Shankar
Published: March 2024

Background

Cancer survivors experience a decrement in health-related quality of life (HRQoL) resulting from the disease as well as adverse effects of therapy. We evaluated the HRQoL of cancer patients, stratified by primary cancer site, stage, treatment response and associated adverse events, along with its determinants.

Methods

Data were collected from 12,148 patients, sampled from seven purposively chosen leading cancer hospitals in India, to elicit HRQoL using the EuroQol questionnaire comprising of 5-dimensions and 5-levels (EQ-5D-5L). Multiple linear regression was used to determine the association between HRQoL and various socio-demographic as well as clinical characteristics.

Results

Majority outpatients (78.4%) and inpatients (81.2%) had solid cancers. The disease was found to be more prevalent among outpatients (37.5%) and inpatients (40.5%) aged 45–60 years and females (49.3–58.3%). Most patients were found to be in stage III (40–40.6%) or stage IV (29.4–37.3%) at the time of recruitment. The mean EQ-5D-5 L utility score was significantly higher among outpatients [0.630 (95% CI: 0.623, 0.637)] as compared to inpatients [0.553 (95% CI: 0.539, 0.567)]. The HRQoL decreased with advancing cancer stage among both inpatients and outpatients, respectively [stage IV: (0.516 & 0.557); stage III (0.609 & 0.689); stage II (0.677 & 0.713); stage I (0.638 & 0.748), p value < 0.001]. The outpatients on hormone therapy (B = 0.076) showed significantly better HRQoL in comparison to patients on chemotherapy. However, palliative care (B=-0.137) and surgery (B=-0.110) were found to be associated with significantly with poorer HRQoL paralleled to chemotherapy. The utility scores among outpatients ranged from 0.305 (bone cancer) to 0.782 (Leukemia). Among hospitalized cases, the utility score was lowest for multiple myeloma (0.255) and highest for testicular cancer (0.771).

Conclusion

Older age, lower educational status, chemotherapy, palliative care and surgery, advanced cancer stage and progressive disease were associated with poor HRQoL. Our study findings will be useful in optimising patient care, formulating individualized treatment plan, improving compliance and follow-up.
CD19/CD20 dual-targeted chimeric antigen receptor-engineered natural killer cells exhibit improved cytotoxicity against acute lymphoblastic leukemia
Authors: Yang Na , Zhang Caili , Zhang Yingchun , Fan Yuting , Zhang Jing , Lin Xiaojin , Guo Ting , Gu Yangzuo , Wu Jieheng , Gao Jianmei , Zhao Xing , He Zhixu
Published: March 2024

Background

Chimeric antigen receptor natural killer (CAR-NK) cells represent a promising advancement in CAR cell therapy, addressing limitations observed in CAR-T cell therapy. However, our prior study revealed challenges in CAR-NK cells targeting CD19 antigens, as they failed to eliminate CD19+ Raji cells in NSG tumor-bearing mice, noting down-regulation or loss of CD19 antigen expression in some Raji cells. In response, this study aims to enhance CD19 CAR-NK cell efficacy and mitigate the risk of tumor recurrence due to target antigen escape by developing CD19 and CD20 (CD19/CD20) dual-targeted CAR-NK cells.

Methods

Initially, mRNA encoding anti-CD19 CARs (FMC63 scFv-CD8α-4-1BB-CD3ζ) and anti-CD20 CARs (LEU16 scFv-CD8α-4-1BB-CD3ζ) was constructed via in vitro transcription. Subsequently, CD19/CD20 dual-targeted CAR-NK cells were generated through simultaneous electrotransfection of CD19/CD20 CAR mRNA into umbilical cord blood-derived NK cells (UCB-NK).

Results

Following co-electroporation, the percentage of dual-CAR expression on NK cells was 86.4% ± 1.83%, as determined by flow cytometry. CAR expression was detectable at 8 h post-electric transfer, peaked at 24 h, and remained detectable at 96 h. CD19/CD20 dual-targeted CAR-NK cells exhibited increased specific cytotoxicity against acute lymphoblastic leukemia (ALL) cell lines (BALL-1: CD19+CD20+, REH: CD19+CD20−, Jurkat: CD19−CD20−) compared to UCB-NK, CD19 CAR-NK, and CD20 CAR-NK cells. Moreover, CD19/CD20 dual-targeted CAR-NK cells released elevated levels of perforin, IFN-γ, and IL-15. Multiple activation markers such as CD69 and cytotoxic substances were highly expressed.

Conclusions

The creation of CD19/CD20 dual-targeted CAR-NK cells addressed the risk of tumor escape due to antigen heterogeneity in ALL, offering efficient and safe 'off-the-shelf' cell products. These cells demonstrate efficacy in targeting CD20 and/or CD19 antigens in ALL, laying an experimental foundation for their application in ALL treatment.
Assessing adverse events associated with chiropractic care in preschool pediatric population: a feasibility study
Authors: Dolbec Anne , Doucet Chantale , Pohlman Katherine A , Sobczak Stéphane , Pagé Isabelle
Published: March 2024

Background

Manual therapies are commonly used by healthcare professionals when caring for children. However, few prospective studies have evaluated their adverse events (AEs). This study aims to assess the feasibility of a pragmatic prospective study aiming to report the immediate and delayed (48-hours post-treatment) AEs associated with manual therapies in children aged 5 or younger. Preliminary data on AEs frequency are also reported.

Methods

Between July 2021 and March 2022, chiropractors were recruited through purposive sampling and via a dedicated Facebook group for Quebec chiropractors interested in pediatrics. Legal guardians of patients aged 5 or younger were invited to fill out an online information and consent form. AEs were collected using the SafetyNET reporting system, which had been previously translated by the research team. Immediate AEs were collected through a questionnaire filled out by the legal guardian immediately after the treatment, while delayed AEs were collected through a questionnaire sent by email to the legal guardian 48 h after the treatment. Feasibility was assessed qualitatively through feedback from chiropractors and quantitatively through recruitment data.

Results

Overall, a total of 28 chiropractors expressed interest following the Facebook publication, and 5 participated. An additional two chiropractors were enrolled through purposive sampling. In total, 80 legal guardians consented to their child’s participation, and data from 73 children were included for the analysis of AEs. At least one AE was reported in 30% of children (22/73), and AEs were mainly observed immediately following the treatment (16/22). The most common AEs were irritability/crying (11 children) or fatigue/tiredness (11 children). Feasibility analysis demonstrated that regular communication between the research team and clinicians, as well as targeting clinicians who showed great interest in pediatrics, were key factors for successful research.

Conclusion

Results suggest that it is feasible to conduct a prospective pragmatic study evaluating AEs associated with manual therapies in private practices. Direct communication with the clinicians, a strategic clinicians’ recruitment plan, and the resulting administrative burden should be considered in future studies. A larger study is required to confirm the frequency of AEs reported in the current study.

Trial registration

ClinicalTrials.gov., NCT05409859, Registered on June 3 2022. https://clinicaltrials.gov/study/NCT05409859.
Mucin-producing tumors of the ovary——preoperative differentiation between metastatic ovarian mucinous carcinoma and primary mucinous malignant tumors
Authors: Cai Song-Qi , Wu Min-Rong , Ma Xiao-Liang , Lu Jing-Jing , Qiang Jin-Wei , Guan Yin-Yin , Zeng Meng-Su , Zhou Jian-Jun
Published: March 2024

Objective

To investigate the clinical and magnetic resonance imaging (MRI) features for preoperatively discriminating  primary ovarian mucinous malignant tumors (POMTs) and metastatic mucinous carcinomas involving the ovary (MOMCs).

Methods

This retrospective multicenter study enrolled 61 patients with 22 POMTs and 49 MOMCs, which were pathologically proved between November 2014 to Jane 2023. The clinical and MRI features were evaluated and compared between POMTs and MOMCs. ﻿Univariate and multivariate analyses were performed to identify the significant variables between the two groups, which were then incorporated into a predictive nomogram, and ROC curve analysis was subsequently carried out to evaluate diagnostic performance.

Results

35.9% patients with MOMCs were discovered synchronously with the primary carcinomas; 25.6% patients with MOMCs were bilateral, and all of the patients with POMTs were unilateral. The biomarker CEA was significantly different between the two groups (p = 0.002). There were significant differences in the following MRI features: tumor size, configuration, enhanced pattern, the number of cysts, honeycomb sign, stained-glass appearance, ascites, size diversity ratio, signal diversity ratio. The locular size diversity ratio (p = 0.005, OR = 1.31), and signal intensity diversity ratio (p = 0.10, OR = 4.01) were independent predictors for MOMCs. ﻿The combination of above independent criteria yielded the largest area under curve of 0.922 with a sensitivity of 82.3% and specificity of 88.9%.

Conclusions

Patients with MOMCs were more commonly bilaterally and having higher levels of CEA, but did not always had a malignant tumor history. For ovarian mucin-producing tumors, the uniform locular sizes and signal intensities were more predict MOMCs.
Efficacy of a virtual reality-based cognitive interactive training program for children with traumatic brain injuries: study protocol for a parallel-group randomized controlled trial
Authors: Shen Jiabin , Wang Yan , Quinn Susan , Suskauer Stacy J. , Birch Julia , Busch Tyler , Svingos Adrian , Crawfis Roger , Yeates Keith Owen , Taylor H. Gerry
Published: March 2024

Background

Traumatic brain injury (TBI) is a leading cause of disability in children. Cognitive rehabilitation for this population is critical for their long-term health outcomes. This trial aims to evaluate the efficacy of a virtual reality-based program (VICT) for training executive functions in children with TBI.

Methods

A parallel group randomized controlled trial will be conducted among up to 32 children with TBI. Children in the intervention group will receive the VICT training while children in the control group will play a comparable VR game without executive function training. Each participant will be assessed at baseline, post-intervention, and 1-month follow-up. Outcomes will include core executive functions, attention, and health-related quality of life measured by computerized tasks or standardized questionnaires.

Discussion

Cognitive rehabilitation is among the top healthcare needs for pediatric TBI patients. Virtual reality-based training is promising due to its versatile content, flexibility, and potential cost savings for both patients and providers. Findings of this trial will provide data on the efficacy of the VICT program on core executive functions, attention problems, and health-related quality of life and serve as the empirical foundation for future larger multi-site effectiveness trials.

Trial registration

ClinicalTrials.gov NCT04526639. Registered on August 18, 2020.
Wildlife parasitology: sample collection and processing, diagnostic constraints, and methodological challenges in terrestrial carnivores
Authors: Rojas Alicia , Germitsch Nina , Oren Stephanie , Sazmand Alireza , Deak Georgiana
Published: March 2024

Wild terrestrial carnivores play a crucial role as reservoir, maintenance, and spillover hosts for a wide parasite variety. They may harbor, shed, and transmit zoonotic parasites and parasites of veterinary importance for domestic hosts. Although wild carnivores are globally distributed and comprise many different species, some living in close proximity to human settlements, only a few studies have investigated parasites of wild terrestrial carnivores using non-specific techniques. Access to samples of wild carnivores may be challenging as some species are protected, and others are secretive, possibly explaining the data paucity. Considering the importance of wild carnivores’ health and ecological role, combined with the lack of specific diagnostic methodologies, this review aims to offer an overview of the diagnostic methods for parasite investigation in wild terrestrial carnivores, providing the precise techniques for collection and analysis of fecal, blood, and tissue samples, the environmental impact on said samples, and the limitations researchers currently face in analyzing samples of wild terrestrial carnivores. In addition, this paper offers some crucial information on how different environmental factors affect parasite detection postmortem and how insects can be used to estimate the time of death with a specific highlight on insect larvae. The paper contains a literature review of available procedures and emphasizes the need for diagnostic method standardization in wild terrestrial carnivores.

Graphical Abstract
Deep learning-based automated lesion segmentation on pediatric focal cortical dysplasia II preoperative MRI: a reliable approach
Authors: Zhang Siqi , Zhuang Yijiang , Luo Yi , Zhu Fengjun , Zhao Wen , Zeng Hongwu
Published: March 2024

Objectives

Focal cortical dysplasia (FCD) represents one of the most common causes of refractory epilepsy in children. Deep learning demonstrates great power in tissue discrimination by analyzing MRI data. A prediction model was built and verified using 3D full-resolution nnU-Net for automatic lesion detection and segmentation of children with FCD II.

Methods

High-resolution brain MRI structure data from 65 patients, confirmed with FCD II by pathology, were retrospectively studied. Experienced neuroradiologists segmented and labeled the lesions as the ground truth. Also, we used 3D full-resolution nnU-Net to segment lesions automatically, generating detection maps. The algorithm was trained using fivefold cross-validation, with data partitioned into training (N = 200) and testing (N = 15). To evaluate performance, detection maps were compared to expert manual labels. The Dice-Sørensen coefficient (DSC) and sensitivity were used to assess the algorithm performance.

Results

The 3D nnU-Net showed a good performance for FCD lesion detection at the voxel level, with a sensitivity of 0.73. The best segmentation model achieved a mean DSC score of 0.57 on the testing dataset.

Conclusion

This pilot study confirmed that 3D full-resolution nnU-Net can automatically segment FCD lesions with reliable outcomes. This provides a novel approach to FCD lesion detection.

Critical relevance statement

Our fully automatic models could process the 3D T1-MPRAGE data and segment FCD II lesions with reliable outcomes.

Key points

• Simplified image processing promotes the DL model implemented in clinical practice.

• The histopathological confirmed lesion masks enhance the clinical credibility of the AI model.

• The voxel-level evaluation metrics benefit lesion detection and clinical decisions.

Graphical Abstract
Deep learning-based predictive classification of functional subpopulations of hematopoietic stem cells and multipotent progenitors
Authors: Wang Shen , Han Jianzhong , Huang Jingru , Islam Khayrul , Shi Yuheng , Zhou Yuyuan , Kim Dongwook , Zhou Jane , Lian Zhaorui , Liu Yaling , Huang Jian
Published: March 2024

Background

Hematopoietic stem cells (HSCs) and multipotent progenitors (MPPs) play a pivotal role in maintaining lifelong hematopoiesis. The distinction between stem cells and other progenitors, as well as the assessment of their functions, has long been a central focus in stem cell research. In recent years, deep learning has emerged as a powerful tool for cell image analysis and classification/prediction.

Methods

In this study, we explored the feasibility of employing deep learning techniques to differentiate murine HSCs and MPPs based solely on their morphology, as observed through light microscopy (DIC) images.

Results

After rigorous training and validation using extensive image datasets, we successfully developed a three-class classifier, referred to as the LSM model, capable of reliably distinguishing long-term HSCs, short-term HSCs, and MPPs. The LSM model extracts intrinsic morphological features unique to different cell types, irrespective of the methods used for cell identification and isolation, such as surface markers or intracellular GFP markers. Furthermore, employing the same deep learning framework, we created a two-class classifier that effectively discriminates between aged HSCs and young HSCs. This discovery is particularly significant as both cell types share identical surface markers yet serve distinct functions. This classifier holds the potential to offer a novel, rapid, and efficient means of assessing the functional states of HSCs, thus obviating the need for time-consuming transplantation experiments.

Conclusion

Our study represents the pioneering use of deep learning to differentiate HSCs and MPPs under steady-state conditions. This novel and robust deep learning-based platform will provide a basis for the future development of a new generation stem cell identification and separation system. It may also provide new insight into the molecular mechanisms underlying stem cell self-renewal.
Cholangiocyte organoids to study drug-induced injury
Authors: Wang Zhenguo , Xing Chen , van der Laan Luc J. W. , Verstegen Monique M. A. , Spee Bart , Masereeuw Rosalinde
Published: March 2024

Background

Drug induced bile duct injury is a frequently observed clinical problem leading to a wide range of pathological features. During the past decades, several agents have been identified with various postulated mechanisms of bile duct damage, however, mostly still poorly understood.

Methods

Here, we investigated the mechanisms of chlorpromazine (CPZ) induced bile duct injury using advanced in vitro cholangiocyte cultures. Intrahepatic cholangiocyte organoids (ICOs) were driven into mature cholangiocyte like cells (CLCs), which were exposed to CPZ under cholestatic or non-cholestatic conditions through the addition of a bile acid cocktail.

Results

CPZ caused loss of monolayer integrity by reducing expression levels of tight junction protein 1 (TJP1), E-cadherin 1 (CDH1) and lysyl oxidase homolog 2 (LOXL2). Loss of zonula occuludens-1 (ZO-1) and E-cadherin was confirmed by immunostaining after exposure to CPZ and rhodamine-123 leakage further confirmed disruption of the cholangiocyte barrier function. Furthermore, oxidative stress seemed to play a major role in the early damage response by CPZ. The drug also decreased expression of three main basolateral bile acid transporters, ABCC3 (ATP binding cassette subfamily C member 3), SLC51A/B (solute carrier family 51 subunit alpha/beta) and multidrug resistance transporter ABCB1 (ATP binding cassette subfamily B member 1), thereby contributing to bile acid accumulation. CPZ did not induce an inflammatory response by itself, but addition of TNFα revealed a synergistic effect.

Conclusion

These results show that ICOs present a model to identify toxic drugs affecting the bile ducts while providing mechanistic insights into hepatotoxicity.
Dynamic of land use and vegetation change in the eastern bank of Bénoué (North Cameroon)
Authors: Azaria Djosebe , Moksia Froumsia , Tchobsala  , Pierre Kamblaba , Tezore Bakary Prudence
Published: March 2024

The eastern part of the Benoue River bank is undergoing degradation marked by a significant decrease in vegetation cover and woody resources due to anthropogenic activities and climatic. The main objective of this study is to analyze the farmers’ knowledge of vegetation evolution and the dynamics of land use using satellite images in the east of the bank of the Benoue. The methodological approach used is an integrated one combining field surveys, remote sensing, mapping, and modeling. The results obtained show that 88% of the population surveyed believe that the area covered by vegetation has decreased. The reasons for this decrease are numerous, but the main one remains the strong anthropic activity that would be at the origin of the progressive degradation of the land. The evolutionary trend of plant formations is essentially regressive for natural formations from 1991 to 2021. The analysis of the evolution of land use showed that in the Rey-Bouba district during 1991, 58.24% of the area formerly made up of dense woody formations regressed considerably to 25.77% in 2021. The same is true for the Bibemi district where the area of wooded zone has decreased from 65.47% in 1991 to 28.45% of the total area in 2021. This regression of the surface area of wooded formations was done to the benefit of anthropized occupation classes whose area has increased. They suggest an effective awareness in the monitoring of the dynamics of the vegetation cover subjected to anthropic pressures and climatic variations for a better-integrated management of the vegetation of this area.
Microanalysis and mineralogy of Asian and Saharan dust
Authors: Jeong Gi Young
Published: March 2024

Mineral dust is transported over long distances from desert sources, interacting with Earth environments. The mineralogy and microstructures of individual dust particles are required to understand the interactions. Here, I summarize recent findings from electron microscopy of dust particles, focusing on Asian and Saharan dust. Dust particles are heterogeneous mixtures of clay and nonclay minerals. Clay minerals account for more than half of the mass of mineral dust. Fine grains of clay minerals form their own aggregates, coat coarse nonclay minerals, or become a matrix of composite particles. The most abundant clay minerals are illite‒smectite series clay minerals (ISCMs) dominated by illite and interstratified illite‒smectite. Saharan dust is distinct from Asian dust by the high contents of palygorskite and hexagonal kaolinite. Common nonclay silicates are quartz, K-feldspar, and Na-rich plagioclase. Amorphous silica is associated with clays in Saharan dust. Calcite occurs as nanofibers as well as coarse grains, reacting with atmospheric acids to precipitate gypsum. The submicron grains of iron oxides and titanium oxides are scattered through the fine matrix of dust particles. ISCMs, chlorite, biotite, and iron oxides are iron carriers to remote ecosystems. The shapes of dust particles approximate ellipsoids whose aspect ratios increase with clay contents. The mineralogical classification of dust particles has led to the determination of the bulk mineral composition of a very small quantity of samples. The constituent mineralogy of dust particles is discussed in an environmental context with a brief introduction of the geological backgrounds of the minerals in their source areas.
Acne Vulgaris and adherence to the mediterranean diet among university students: a case‒control study
Authors: Taha Sari , Shakhshir Muna , Zyoud Sa’ed H.
Published: March 2024

Background

Western diets, characterized by a high glycemic index and dairy content, can be risk factors for acne vulgaris. A few studies have suggested that adherence to non-Western diets, such as the Mediterranean diet (MD), may be protective against acne. This study aimed to explore the relationships between adherence to the MD and acne diagnosis and severity.

Methods

This was a matched case‒control study carried out among university students studying health sciences to explore the relationship between adhering to the MD and an acne diagnosis. Convenience sampling was utilized for the initial recruitment of eligible participants, who were then 1:1 individually matched for age, gender, and body mass index (BMI). Adherence to the MD was assessed using the Mediterranean Diet Adherence Screener (MEDAS) tool, and acne severity was assessed using the Global Acne Grading System (GAGS). The data were analyzed using descriptive statistics, bivariate analysis, and conditional logistic regression, which included two models based on clinical data and the backward elimination technique.

Results

A final sample of 121 cases was individually matched to 121 controls. Each group consisted of 28.9% males and 71.1% females, with most having a BMI within the healthy range (71.9%). Both the case (80.2%) and control groups (77.7%) demonstrated a predominant pattern of low adherence to the MD. At the bivariate level, family history significantly differed between the case and control groups (OR = 2.01, CI = 1.17–3.44), while adherence to the MD (OR = 0.86, CI = 0.46–1.60) did not reach statistical significance. According to the regression analysis, family history remained significant in the backward elimination model (aOR = 1.94, CI = 1.14–3.34), while it disappeared in the full model (aOR = 1.95, CI = 1.14–3.34). Neither model revealed a significant association between acne and the other variables. Among the participants in the case group, neither adherence to the MD nor adherence to its components was significantly associated with acne severity, except for vegetables (p = 0.022).

Conclusions

Adherence to the MD was not correlated with acne diagnosis or clinical severity. More research on the association between acne and adherence to the MD is needed, as earlier studies are few, were conducted in specific settings, and used variable methodologies. To improve the validity and reliability of the research methodology, the development of detailed and culturally adapted MD definitions and practical guides is recommended.
Global impacts of fire regimes on wildland bird diversity
Authors: Arrogante-Funes Fátima , Aguado Inmaculada , Chuvieco Emilio
Published: March 2024

Background

Fire is a natural disturbance that significantly impacts ecosystems and plays a crucial role in the distribution and preservation of biota worldwide. The effects of fires on bird diversity can be both positive, as they can create new habitats, and negative, as they can reduce nesting success. To fully understand the ecological implications of wildfires, we need to understand the spatial distribution of wildland bird diversity and fire regimes and how fire regimes affect wildland bird diversity ecosystems. Using data collected at a global scale, we examined effects of time-averaged fire regimes on the spatial diversity of wildland bird species. Initially, we used the MaxEnt algorithm to model the potential distribution of 1,115 wildland bird species over a 20-year period. We also processed satellite observations of burned areas (FIRECCI51) during the same period to estimate fire regime characteristics, including the average proportion of burnt vegetation, interannual variability in the burnt area, and fire intensity. Finally, the association between wild bird diversity and fire variables in each biome was determined through Spearman, Bonferroni, and Kruskal-Wallis statistics.

Results

Our findings revealed that (I) the most affected wildland bird communities are those found in tropical ecosystems, where the majority of fires occur; (II) high fire intensity values and a substantial proportion of burned vegetation have a positive impact on maintaining a diverse population of wildland birds in biomes characterized by savannah or grassland covers, as seen in temperate or tropical zones. Conversely, low fire intensity values and a smaller proportion of burned vegetation also promote greater diversity of wildland birds in boreal or temperate zones, and (III) in Mediterranean ecosystems, a clear association between wildland bird diversity and wildfires could not be established.

Conclusions

This research could help identify areas that are ecologically vulnerable to wildfires. It could also be useful in guiding regional studies aligned with developing sustainable landscape management practices and conserving priority ecological zones in tropical ecosystems.
Clinical and biological significance of microRNA-127 and microRNA-138 expression in women with breast cancer: response to treatment and survival impact
Authors: Nasr Ghada M. , Elshal Mohamed F. , Gobran Eman Abdel-Ghani , Nasr Mohamed Younis , Badr Eman A. E. , Abdel-Aziz Reham Ahmed , Abdel-Aziz Amal , AboShabaan Hind S.
Published: March 2024

Background and Objective

Genetic and epigenetic changes characterize the multi-step process of breast carcinogenesis. It is believed that abnormal microRNA (miRNA) expression has a role in the onset and progression of breast cancer. This study aimed to examine the link between miRNA-127 and miRNA-138 and metastasis, tumor invasion, and apoptosis in Egyptian women with breast cancer, as well as their correlation with its molecular types.

Methodology

A total of 150 participants were included in this study, including 75 women with breast cancer and 75 supposedly healthy women who were age and gender-matched. Every patient underwent a thorough physical examination, a general clinical examination, a mammogram, and lab tests, such as the determination of the levels of miRNA-127 and miRNA-138 expression by real-time PCR and the measurement of blood carcinoembryonic antigen (CEA) and carcinoma antigen 15–3 (CA15-3) and CA15-3 and CEA levels.

Results

There was a significant low expression of miRNA-127 in favor of high TNM stage (Classification of Malignant Tumors), left-sided tumor, metastasis, high-grade disease, increased axillary nodal involvement, absence of estrogen and progesterone receptors, and low antigen Kiel 67 (Ki67) expression. Also, a significant expression of miRNA 127 in triple-negative breast cancer was found, followed by human epidermal growth factor receptor 2 (HER2/neu) overexpression, then luminal B, and the highest expression was with the Luminal A molecular subtype. A significant negative correlation existed between miRNA 127 and miRNA 138 with CEA and CA15.3 levels.

Conclusion

The miRNA-127 and miRNA-138 suppression may promote metastasis. Consequently, the restoration of miRNA-127 and miRNA-138 in breast cancer may have therapeutic potential; so, the miRNA-127 and miRNA-138 may play a role in breast cancer development.
Racial and Ethnic Disparities in Intensity of Care at the End of Life for Patients With Lung Cancer: A 13-Year Population-Based Study
Authors: Rodriguez Gladys M. , Popat Rita , Rosas Lisa G. , Patel Manali I.
Published: March 2024

PURPOSE

Lung cancer is the leading cause of cancer death in the United States. Disparities in lung cancer mortality among racial and ethnic minorities are well documented. Less is known as to whether racial and ethnic minority patients with lung cancer experience higher rates of intensity of care at the end of life (EOL) compared with non-Hispanic White (NHW) patients.

METHODS

We conducted a population-based analysis of patients 18 years and older with a lung cancer diagnosis who died between 2005 and 2018 using the California Cancer Registry linked to patient discharge data abstracts. Our primary outcome was intensity of care in the last 14 days before death (defined as any hospital admission or emergency department [ED] visit, intensive care unit [ICU] admission, intubation, cardiopulmonary resuscitation [CPR], hemodialysis, and death in an acute care setting). We used multivariable logistic regression models to evaluate associations between race and ethnicity and intensity of EOL care.

RESULTS

Among 207,429 patients with lung cancer who died from 2005 to 2018, the median age was 74 years (range, 18-107) and 106,821 (51%) were male, 146,872 (70.8%) were NHW, 1,045 (0.5%) were American Indian, 21,697 (10.5%) were Asian Pacific Islander (API), 15,490 (7.5%) were Black, and 22,325 (10.8%) were Hispanic. Compared with NHW patients, in the last 14 days before death, API, Black, and Hispanic patients had greater odds of a hospital admission, an ICU admission, intubation, CPR, and hemodialysis and greater odds of a hospital or ED death.

CONCLUSION

Compared with NHW patients, API, Black, and Hispanic patients who died with lung cancer experienced higher intensity of EOL care. Future studies should develop approaches to eliminate such racial and ethnic disparities in care delivery at the EOL.
Cannabis and Cannabinoids in Adults With Cancer: ASCO Guideline Q&A
Authors: Braun Ilana M. , Bohlke Kari , Roeland Eric J.
Published: March 2024

@JCO_ASCO guideline on #cannabis in cancer with @JCOOP_ASCO companion Q&A addressing key clinical questions
Advanced progress of network resilience
Authors: Liu Min , Guo Qiang , Liu Jianguo
Published: March 2024

Network resilience measures complex systems’ ability to adjust its activity to retain the basic functionality for systematic errors or failures, which has attracted increasingly attention from various fields. Resilience analyses play an important role for early warning, prediction, and proposing potential strategies or designing optimal resilience systems. This letter reviews the advanced progress of network resilience from three aspects: Resilience measurement, resilience analysis, as well as resilience recovery strategies. We outline the challenges of network resilience which should be investigated in the future.
The Effects of Calorie Restriction and Bariatric Surgery on Circulating Proneurotensin Levels
Authors: Miskelly Michael G , Berggren Johan , Svensson Malin , Koffert Jukka , Honka Henri , Kauhanen Saila , Nuutila Pirjo , Hedenbro Jan , Lindqvist Andreas , Melander Olle , Wierup Nils
Published: March 2024

Context

Proneurotensin (pNT) is associated with obesity and type 2 diabetes (T2D), but the effects of Roux-en-Y gastric bypass (RYGB) on postprandial pNT levels are not well studied.

Objective

This work aimed to assess the effects of RYGB vs a very low-energy diet (VLED) on pNT levels in response to mixed-meal tests (MMTs), and long-term effects of RYGB on fasting pNT.

Methods

Cohort 1: Nine normoglycemic (NG) and 10 T2D patients underwent MMT before and after VLED, immediately post RYGB and 6 weeks post RYGB. Cohort 2: Ten controls with normal weight and 10 patients with obesity and T2D, who underwent RYGB or vertical sleeve gastrectomy (VSG), underwent MMTs and glucose-dependent insulinotropic polypeptide (GIP) infusions pre surgery and 3 months post surgery. Glucagon-like peptide-1 (GLP-1) infusions were performed in normal-weight participants. Cohort 3: Fasting pNT was assessed pre RYGB (n = 161), 2 months post RYGB (n = 92), and 1year post RYGB (n = 118) in NG and T2D patients. pNT levels were measured using enzyme-linked immunosorbent assay.

Results

Reduced fasting and postprandial pNT were evident after VLED and immediately following RYGB. Reintroduction of solid food post RYGB increased fasting and postprandial pNT. Prior to RYGB, all patients lacked a meal response in pNT, but this was evident post RYGB/VSG. GIP or GLP-1 infusion had no effect on pNT levels. Fasting pNTs were higher 1-year post RYGB regardless of glycemic status.

Conclusion

RYGB causes a transient reduction in pNT as a consequence of caloric restriction. The RYGB/VSG-induced rise in postprandial pNT is independent of GIP and GLP-1, and higher fasting pNTs are maintained 1 year post surgically.
Reference Values for Serum Calcium in Neonates Should Be Established in a Population of Vitamin D–Replete Subjects
Authors: Levaillant Lucie , Linglart Agnès , Gajdos Vincent , Benachi Alexandra , Souberbielle Jean-Claude
Published: March 2024

Context

Serum calcium is frequently measured during the neonatal period, and it is known to be influenced by the vitamin D status.

Objective

We hypothesized that the 25-hydroxyvitamin D (25OHD) concentration may influence the lower limit of the serum calcium normal range in neonates.

Methods

We included in our prospective cohort study 1002 mother-newborn pair recruited from April 2012 to July 2014, in 2 centers located in the neighborhoods of Paris, France, whose serum calcium was measured at 3 days of life. We established, after exclusion of outliers, a 95% CI for serum calcium (i) in our whole population of 1002 neonates; (ii) in neonates with a cord blood 25OHD concentration ≥ 30 nmol/L; and (iii) in those with a 25OHD ≥ 50 nmol/L.

Results

The mean serum total calcium was 2.46 ± 0.13 nmol/L (95% CI: 2.19-2.72 mmol/L), 2.47 ± 0.25 mmol/L (95% CI: 2.22-2.72 mmol/L), and 2.50 ± 0.25 mmol/L (95% CI: 2.25-2.75 mmol/L) in the whole group, in the 514 neonates with 25OHD ≥ 30 nmol/L, and in the 202 neonates with 25OHD ≥ 50 nmol/L respectively. The lower limit of the 95% range was significantly higher in neonates with 25 OHD ≥ 30 nmol/L (P < 0.05) and ≥ 50 nmol/L (P < .001) than in the entire cohort.

Conclusion

We show that the lower limit of the normal serum calcium range is higher in groups with a higher 25OHD than in unselected subjects. We propose that the reference range for serum calcium in neonates is 2.25 to 2.75 mmol/L.
Cardiovascular Safety of Romosozumab vs PTH Analogues for Osteoporosis Treatment: A Propensity-Score-Matched Cohort Study
Authors: Stokar Joshua , Szalat Auryan
Published: March 2024

Context

Romosozumab, a monoclonal sclerostin antibody, is a recently approved highly potent antiosteoporotic agent with osteoanabolic properties. Clinical use of romosozumab is hindered by the fear of adverse cardiovascular (CV) events raised following the pivotal ARCH trial.

Objective

This work aimed to assess real-world CV safety of romosozumab vs alternative osteoanabolic therapies used for treatment of severe osteoporosis.

Methods

Data were obtained from TriNetX, a global federated health research network including real-time electronic medical records from 113 health care organizations with 136 460 930 patients across 16 countries at time of analysis. Inclusion criteria were age 40 years or older, a diagnosis of osteoporosis and prescription of romosozumab or a parathyroid hormone (PTH) analogue (teriparatide/abaloparatide) during August 2019 through August 2022. Propensity-score-matched cohorts were created 1:1 using demographic variables, comorbidities, and medications. Kaplan-Meier analysis was used to estimate the probability of the outcomes. Outcome measures included incident 3-point major adverse CV event or death (3P-MACE) during 1-year of follow-up after the initial prescription.

Results

A total of 5626 and 15 986 patients met the criteria for romosozumab and PTH analogue cohorts, respectively, with 5610 patients per group following propensity score matching. 3P-MACE was significantly less frequent in the romosozumab vs PTH analogue cohort (158 vs 211 patients with an outcome; P = .003) with reductions in the individual components of the composite outcome: myocardial ischemic events (31 vs 58; P = .003); cerebrovascular events 56 vs 79; P = .037; deaths (83 vs 104; P = .099).

Conclusion

In a diverse, real-world setting, prescription of romosozumab for osteoporosis is associated with fewer adverse CV events when compared to PTH analogue therapy.
What Science Can't Know: On Scientific Objectivity and the Human Subject
Authors: Kjeldgaard-Christiansen Jens
Published: March 2024

The humanities are centrally concerned with such human subjectivity—such thinking, feeling, and wondering—as goes into the appreciation of a painting or the absorbed and responsive reading of a novel. It is often argued that the intrinsic subjectivity of these experiences renders them inaccessible to objective science, which seeks to avoid subjectivity. However, this fallacious argument confuses an ontological and an epistemic sense of the distinction between subjectivity and objectivity. The subjectivity of “thinking, feeling, and wondering” describes the mode of existence of these mental states, whereas the objectivity of science describes a mode of investigation, and it is in fact very possible to investigate human mental life by means of objective methods. This article expounds the fallacy and examines its appearances in recent scholarly writings against the use of objective methods in the humanities. The fallacy, as is argued, promotes a widespread misconception that the use of objective methods in the humanities would entail a discounting, or “reduction,” of human subjectivity. By countering this misconception, this article aims to encourage humanists who are drawn to empirical methods.
Do Poems about Guns Make Guns Poetic?
Authors: Savage Elizabeth
Published: March 2024

Poems by Dean Rader, Montana Ray, Danez Smith, Brian Turner, and Elizabeth Willis register a perplexing trend in American poetry: the use of gun and bullet tropes in poems indirectly or not at all about guns. Many of the poets employing these tropes publicly oppose gun violence and promote poetry as a refuge from it, yet their poetry, paradoxically, affirms guns’ literary power. The five poets selected for this study represent different styles emitting from diverse histories, ages, and literary backgrounds. Their poems likewise branch across a range of contexts and levels of abstraction. Studied together, their poetry exposes the centrality of guns not only to US America's collective self-image as a social body and national power but also to the American literary imagination. In light of this apparent contradiction, this essay considers what the pervasiveness of gun and bullet tropes suggests about the efficacy of poetry as enemy, accomplice, or rival of guns.
Assessing Narrative Space: From Setting to Narrative Environments
Authors: Puxan-Oliva Marta
Published: March 2024

This essay addresses the insufficient attention paid in narrative theory to the reformulated concept of space resulting from the spatial turn in the analysis of narrative space. To address this lack of attention, the essay proposes the concept of “narrative environments” as a new lens for conceiving of narrative space that distinguishes it from setting. Narrative environments are the formal narrative expression of space: the combined social contextualization and historicization and environmental imaginings that have historically produced that space and are called forth in the narrative to build narrative space and its interactions with other narrative components. These are distinguished from “setting” in that the latter has been interpreted as textually self-sufficient, not relying on social and cultural knowledge. The article reviews recent debates on narrative space and their branching into the fields of critical geography and ecocriticism in order to bring the reenvisioned concept of space resulting from the spatial turn into the discussion. The functioning of this new perspective on space is illustrated through the analysis of island and ocean space and its narrative effects in J. M. Coetzee's Foe.
Adhesion and shrinkage transform the rounded pupal horn into an angular adult horn in Japanese rhinoceros beetle
Authors: Matsuda Keisuke , Adachi Haruhiko , Gotoh Hiroki , Inoue Yasuhiro , Kondo Shigeru
Published: March 2024

Clarifying the mechanisms underlying shape alterations during insect metamorphosis is important for understanding exoskeletal morphogenesis. The large horn of the Japanese rhinoceros beetle Trypoxylus dichotomus is the result of drastic metamorphosis, wherein it appears as a rounded shape during pupation and then undergoes remodeling into an angular adult shape. However, the mechanical mechanisms underlying this remodeling process remain unknown. In this study, we investigated the remodeling mechanisms of the Japanese rhinoceros beetle horn by developing a physical simulation. We identified three factors contributing to remodeling by biological experiments – ventral adhesion, uneven shrinkage, and volume reduction – which were demonstrated to be crucial for transformation using a physical simulation. Furthermore, we corroborated our findings by applying the simulation to the mandibular remodeling of stag beetles. These results indicated that physical simulation applies to pupal remodeling in other beetles, and the morphogenic mechanism could explain various exoskeletal shapes.
The art of observation: bridging science and art to see the unexpected
Authors: Gonzalez Lauren E. , Wei Haoyang , Greco Valentina , Friedlaender Linda K.
Published: March 2024

Observation is the heart of research, but it can be challenging to observe deeply and go beyond expected observations. Here, we describe activities designed for scientists to enhance their observational skills by engaging with art. In collaboration with an art gallery at our university, our lab practiced observing representational paintings in a systematic way, separating the act of observation from interpretation. Applying this skill to our microscopy images allowed us to access information in the data that may otherwise have been overlooked. In addition, these activities highlighted the power of collecting observations from multiple observers before generating interpretations, as well as the value of discussing the creative and emotional aspects of data collection and interpretation. We provide concrete examples of how we will incorporate these skills into our research processes, as well as details that other groups can use to engage in similar art-based training activities to enhance their own observational skills.
Widespread nuclear lamina injuries defeat proteostatic purposes of α-synuclein amyloid inclusions
Authors: Mansuri Shemin , Jain Aanchal , Singh Richa , Rawat Shivali , Mondal Debodyuti , Raychaudhuri Swasti
Published: March 2024

Biogenesis of inclusion bodies (IBs) facilitates protein quality control (PQC). Canonical aggresomes execute degradation of misfolded proteins while non-degradable amyloids sequester into insoluble protein deposits. Lewy bodies (LBs) are filamentous amyloid inclusions of α-synuclein, but PQC benefits and drawbacks associated with LB-like IBs remain underexplored. Here, we report that crosstalk between filamentous LB-like IBs and aggresome-like IBs of α-synuclein (Syn-aggresomes) buffer the load, aggregation state, and turnover of the amyloidogenic protein in mouse primary neurons and HEK293T cells. Filamentous LB-like IBs possess unorthodox PQC capacities of self-quarantining α-synuclein amyloids and being degradable upon receding fresh amyloidogenesis. Syn-aggresomes equilibrate biogenesis of filamentous LB-like IBs by facilitating spontaneous degradation of α-synuclein and conditional turnover of disintegrated α-synuclein amyloids. Thus, both types of IB primarily contribute to PQC. Incidentally, the overgrown perinuclear LB-like IBs become degenerative once these are misidentified by BICD2, a cargo-adapter for the cytosolic motor-protein dynein. Microscopy indicates that microtubules surrounding the perinuclear filamentous inclusions are also distorted, misbalancing the cytoskeleton-nucleoskeleton tension leading to widespread lamina injuries. Together, nucleocytoplasmic mixing, DNA damage, and deregulated transcription of stress chaperones defeat the proteostatic purposes of the filamentous amyloids of α-synuclein.