bluuebunny/crossref_metadata_2025 huggingface dataset:
Phenotypic immune characterization of gastric and esophageal adenocarcinomas reveals profound immune suppression in esophageal tumor locations
Authors: Groen-van Schooten Tessa S. , Harrasser Micaela , Seidel Jens , Bos Emma N. , Fleitas Tania , van Mourik Monique , Pouw Roos E. , Goedegebuure Ruben S. A. , Doeve Benthe H. , Sanders Jasper , Bos Joris , van Berge Henegouwen Mark I. , Thijssen Victor L. J. L. , van Grieken Nicole C. T. , van Laarhoven Hanneke W. M. , de Gruijl Tanja D. , Derks Sarah
Published: April 2024

Background

Tumors in the distal esophagus (EAC), gastro-esophageal junction including cardia (GEJAC), and stomach (GAC) develop in close proximity and show strong similarities on a molecular and cellular level. However, recent clinical data showed that the effectiveness of chemo-immunotherapy is limited to a subset of GEAC patients and that EACs and GEJACs generally benefit less from checkpoint inhibition compared to GACs. As the composition of the tumor immune microenvironment drives response to (immuno)therapy we here performed a detailed immune analysis of a large series of GEACs to facilitate the development of a more individualized immunomodulatory strategy.

Methods

Extensive immunophenotyping was performed by 14-color flow cytometry in a prospective study to detail the immune composition of untreated gastro-esophageal cancers (n=104) using fresh tumor biopsies of 35 EACs, 38 GEJACs and 31 GACs. The immune cell composition of GEACs was characterized and correlated with clinicopathologic features such as tumor location, MSI and HER2 status. The spatial immune architecture of a subset of tumors (n=30) was evaluated using multiplex immunohistochemistry (mIHC) which allowed us to determine the tumor infiltration status of CD3+, CD8+, FoxP3+, CD163+ and Ki67+ cells.

Results

Immunophenotyping revealed that the tumor immune microenvironment of GEACs is heterogeneous and that immune suppressive cell populations such as monocytic myeloid-derived suppressor cells (mMDSC) are more abundant in EACs compared to GACs (p<0.001). In contrast, GACs indicated a proinflammatory microenvironment with elevated frequencies of proliferating (Ki67+) CD4 Th cells (p<0.001), Ki67+ CD8 T cells (p=0.002), and CD8 effector memory-T cells (p=0.024). Differences between EACs and GACs were confirmed by mIHC analyses showing lower densities of tumor- and stroma-infiltrating Ki67+ CD8 T cells in EAC compared to GAC (both p=0.021).

Discussions

This comprehensive immune phenotype study of a large series of untreated GEACs, identified that tumors with an esophageal tumor location have more immune suppressive features compared to tumors in the gastro-esophageal junction or stomach which might explain the location-specific responses to checkpoint inhibitors in this disease. These findings provide an important rationale for stratification according to tumor location in clinical studies and the development of location-dependent immunomodulatory treatment approaches.
D-amino acid/gentamicin loaded zwitterionic hydrogel coatings with optimized mechanical stability and biofilm inhibition capabilities
Authors: Yang Jingzhi , Ran Yami , Zhao Junsen , Xing Taiwei , Hao Xiangping , Zhang Dawei
Published: April 2024

Biofilms associated bacterial infections on material surfaces have become a tremendous biomedical challenge. Developing antimicrobial coatings on biomaterial surfaces and endowing them with decent mechanical stability and biofilm inhibition capabilities is an efficient way to resist bacterial attachment and biofilm formation. Herein, we integrated 2-hydroxyethyl methacrylate (HEMA) and D-amino acid mixtures based antibiofilm combinations with sulfobetaine methacrylate (SBMA) hydrogel coatings. The obtained hydrogel coatings demonstrated high stability in various transport and service environments. The proper incorporation of the HEMA achieves only ∼3% weight loss of SBMA hydrogel coatings after swelling, flushing and abrasion damages. In addition, both biofilm formation inhibiting D-amino acid mixtures and bacteria-killing gentamicin components were loaded in the coatings. The synergistic action of these two components was able to significantly reduce the bacterial numbers with up to 2.3 log reduction. The bacteria exposed to D-amino acid mixtures was difficult to form biofilm, which was more susceptive to the harm of gentamicin. This work provides an effective paradigm to integrate mechanically stable SBMA-HEMA hydrogel with natural D-amino acid mixtures based antibiofilm agents to generate biomedical surfaces to combat biofilms associated bacterial infections.
The role of muscle forces in neck comfort for static seating: a pilot study
Authors: Alawneh Obidah , Rassas Basaam , Zhong Xianzhi , Xi Jason , Faieghi Reza , Xi Fengfeng
Published: April 2024

Aircraft seats play a key role in the competition between aircraft companies seeking to differentiate themselves in terms of passengers’ inflight experience. The seat design process relies on computational and experimental methods based on subjective measures, such as comfort rating questionnaires, and objective comfort indicators of seat-occupant interaction, such as contact pressure distribution and muscle activation. Previous studies around muscle activity for seating comfort assessment have primarily focused on more active scenarios or active systems. As such, there are limited studies about the role of muscle force in normal and relaxed sitting conditions, common in aircraft settings. This paper explores the relationship between activities of the neck muscles, sternocleidomastoid, and upper trapezius, measured from human participants seated sedentarily on conventional business aircraft seats and their perceived comfort with different backrest inclinations. The results show, for normal seating without neck pillow, no significant association is found between the backrest inclination and the neck’s comfort or muscle activation. For general seating across different backrest inclinations, a positive medium correlation between muscle activation and comfort is found in upper trapezius (R = 0.5332, p = 0.0187). This work serves as a pilot study of this new approach of comfort evaluation using muscle feedback in seat designing processes and highlights the posterior’s effect to seating experience in the neck region.
Prolidase could be considered a sign of inflammation associated with cigarette smoking
Authors: Yıldırım Berna Botan , Kulaksızoglu Sevsen
Published: April 2024

Objectives

Smoking causes inflammation, thickening, and narrowing of the airways. This inflammatory process is a reaction to free radicals and oxidants. Smoking affects collagen metabolism and tissue remodeling. Prolidase enzyme hydrolyzes iminodipeptides with hydroxyproline and C terminal proline. It plays a crucial role in the metabolism of collagen and the remodeling of the matrix. The present study aims to reveal the association of prolidase with inflammation caused by smoking and to compare serum prolidase levels with oxidative-antioxidative status in healthy individuals.

Methods

A total of 76 participants (38 smokers and 38 nonsmokers) were involved in the present study. Serum cotinine levels were measured to show the exposure to nicotine in tobacco smoke by using the competitive inhibition enzyme immunoassay method. Serum prolidase, total oxidant status (TOS), and total antioxidant status (TAS) were determined by the enzyme-linked immunosorbent (ELISA) method, respectively. The correlation between smoking, serum prolidase levels, TOS, and TAS was investigated.

Results

TAS and serum prolidase levels of smokers were considerably lower than those in non-smokers (p < 0.001, p = 0.012 respectively). However, no differences were observed in TOS between the two groups. There was no statistically significant correlation between serum prolidase levels, TAS, and TOS. Moreover, no relationship was observed between respiratory function parameters and serum prolidase levels.

Conclusion

To the best of our knowledge, the present study is the first study to demonstrate the role of prolidase in smoking-related inflammation. The results achieved in the present study suggest that smoking creates an imbalance in the oxidant-antioxidant activity. Smoking decreases prolidase levels, leading to decreased collagen turnover. Chronic pulmonary disease might be related to this decrease in collagen turnover.
Influence of ethnic origin on the clinical characteristics and intestinal flora of irritable bowel syndrome: a prospective study between Han and Tibetan patients
Authors: Ma Xiao , Huan Hui , Liu Chao , Hu Hong , Ren Tao
Published: April 2024

Background

Few studies have focused on the clinical characteristics and intestinal flora of Tibetan patients with irritable bowel syndrome (IBS). The study aimed to compare the difference of between Tibetan and Han patients with IBS.

Methods

Patients who met inclusion and exclusion criteria were divided into the Tibet and Han groups. A simplified Gastrointestinal Symptom Rating Scale (GSRS)-based questionnaire was used to assess the IBS severity. Fecal samples from all subjects were collected for the analysis of gut microbiota using 16sRNA Illumina sequencing.

Results

No significant difference was found in the total symptom scores between two groups. However, Tibetans with IBS are more prone to bloating than Hans (17.41% vs 9.09%, p < 0.001). A profit shift in the gut microbiota was shown between the two groups. The ratio of Firmicutes/Bacteroidetes was significantly lower in the Tibet group than in the Han group (2.954 ± 0.78 vs 8.23 ± 2.04, p = 0.004). In the Tibet group, the level of the genus Blautia decreased significantly compared to the Han group, and there was a significant negative correlation between the level of Blautia and the bloating scores (Pearson r = −0.33, p = 0.025).

Conclusion

The characteristics of Tibetan patients differ from those of Han patients with IBS, not only in terms of the clinical symptoms, but also in the characteristics of intestinal flora. Tibetans with IBS are more prone to bloating, which might be due to the different gut microbiota. The genus Blautia may play a role in this mechanism.
Global, regional, and national burden and trends analysis of gallbladder and biliary tract cancer from 1990 to 2019 and predictions to 2030: a systematic analysis for the Global Burden of Disease Study 2019
Authors: Su Jiao , Liang Yuanhao , He Xiaofeng
Published: April 2024

Objectives

Our aim was to explore the disease burden caused by gallbladder and biliary tract cancer globally, regionally, and nationally, by age and sex.

Methods

The absolute number of cases and age-standardized rates (ASR) of incidence, prevalence, mortality, and disability-adjusted life years (DALYs) due to gallbladder and biliary tract cancer were extracted from the Global Burden of Disease (GBD) Study 2019. We estimated the trends in disease burden by calculating the percentage change in the absolute number of cases and the estimated annual percentage change (EAPC) in ASR, by social development index (SDI), region, nation, sex, and age.

Results

From 1990 to 2019, the number of incident cases, prevalent cases, deaths, and DALYs worldwide significantly increased by 1.85-fold, 1.92-fold, 1.82-fold, and 1.68-fold, respectively. However, the age-standardized rates of incidence, prevalence, mortality, and DALYs tend to decrease globally over time. Nevertheless, heterogeneous disease burden patterns exist between geographic regions due to different geographical risk factors, distinct epidemiologically predominant gallbladder and biliary tract cancer subtypes, and potential genetic predispositions or ethnicity. Additionally, socioeconomic status mediates the regional variation in disease burden, with increasing SDI or HDI scores associated with downward trends in the age-standardized rates of incidence, prevalence, mortality, and DALYs. Older individuals and females are at higher risk of gallbladder and biliary tract cancer, but the increasing burden of early-onset gallbladder and biliary tract cancer is a cause for concern, especially for those living in lower SDI areas and males. High BMI is the primary risk factors underlying gallbladder and biliary tract cancer, accounted for 15.2% of deaths and 15.7% DALYs globally in 2019.

Conclusion

Our study comprehensively elucidated the distribution and dynamic trends of gallbladder and biliary tract cancer burden over the past three decades, from multiple dimensions. These findings emphasize the importance of promoting a healthy lifestyle as a population-level cancer prevention strategy and tailoring cancer control actions based on localized risk factors and the epidemic profiles of gallbladder and biliary tract cancer by anatomical subtype.
Exploring untapped bacterial communities and potential polypropylene-degrading enzymes from mangrove sediment through metagenomics analysis
Authors: Pawano Onnipa , Jenpuntarat Nuttarin , Streit Wolfgang R. , Pérez-García Pablo , Pongtharangkul Thunyarat , Phinyocheep Pranee , Thayanukul Parinda , Euanorasetr Jirayut , Intra Bungonsiri
Published: April 2024

The versatility of plastic has resulted in huge amounts being consumed annually. Mismanagement of post-consumption plastic material has led to plastic waste pollution. Biodegradation of plastic by microorganisms has emerged as a potential solution to this problem. Therefore, this study aimed to investigate the microbial communities involved in the biodegradation of polypropylene (PP). Mangrove soil was enriched with virgin PP sheets or chemically pretreated PP comparing between 2 and 4 months enrichment to promote the growth of bacteria involved in PP biodegradation. The diversity of the resulting microbial communities was accessed through 16S metagenomic sequencing. The results indicated that Xanthomonadaceae, unclassified Gaiellales, and Nocardioidaceae were promoted during the enrichment. Additionally, shotgun metagenomics was used to investigate enzymes involved in plastic biodegradation. The results revealed the presence of various putative plastic-degrading enzymes in the mangrove soil, including alcohol dehydrogenase, aldehyde dehydrogenase, and alkane hydroxylase. The degradation of PP plastic was determined using Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy (ATR-FTIR), Scanning Electron Microscopy (SEM), and Water Contact Angle measurements. The FTIR spectra showed a reduced peak intensity of enriched and pretreated PP compared to the control. SEM images revealed the presence of bacterial biofilms as well as cracks on the PP surface. Corresponding to the FTIR and SEM analysis, the water contact angle measurement indicated a decrease in the hydrophobicity of PP and pretreated PP surface during the enrichment.
The role of VdSti1 in Verticillium dahliae: insights into pathogenicity and stress responses
Authors: Wu Yutao , Zhou Jinglong , Wei Feng , Zhang Yalin , Zhao Lihong , Feng Zili , Feng Hongjie
Published: April 2024

Sti1/Hop, a stress-induced co-chaperone protein, serves as a crucial link between Hsp70 and Hsp90 during cellular stress responses. Despite its importance in stress defense mechanisms, the biological role of Sti1 in Verticillium dahliae, a destructive fungal pathogen, remains largely unexplored. This study focused on identifying and characterizing Sti1 homologues in V. dahliae by comparing them to those found in Saccharomyces cerevisiae. The results indicated that the VdSti1-deficient mutant displayed increased sensitivity to drugs targeting the ergosterol synthesis pathway, leading to a notable inhibition of ergosterol biosynthesis. Moreover, the mutant exhibited reduced production of microsclerotia and melanin, accompanied by decreased expression of microsclerotia and melanin-related genes VDH1, Vayg1, and VaflM. Additionally, the mutant’s conidia showed more severe damage under heat shock conditions and displayed growth defects under various stressors such as temperature, SDS, and CR stress, as well as increased sensitivity to H2O2, while osmotic stress did not impact its growth. Importantly, the VdSti1-deficient mutant demonstrated significantly diminished pathogenicity compared to the wild-type strain. This study sheds light on the functional conservation and divergence of Sti1 homologues in fungal biology and underscores the critical role of VdSti1 in microsclerotia development, stress response, and pathogenicity of V. dahliae.
Immediate fall prevention: the missing key to a comprehensive solution for falling hazard in older adults
Authors: Misaghian Khashayar , Lugo Jesus Eduardo , Faubert Jocelyn
Published: April 2024

The world is witnessing an unprecedented demographic shift due to increased life expectancy and declining birth rates. By 2050, 20% of the global population will be over 60, presenting significant challenges like a shortage of caregivers, maintaining health and independence, and funding extended retirement. The technology that caters to the needs of older adults and their caregivers is the most promising candidate to tackle these issues. Although multiple companies and startups offer various aging solutions, preventive technology, which could prevent trauma, is not a big part of it. Trauma is the leading cause of morbidity, disability, and mortality in older adults, and statistics constitute traumatic fall accidents as its leading cause. Therefore, an immediate preventive technology that anticipates an accident on time and prevents it must be the first response to this hazard category to decrease the gap between life expectancy and the health/wellness expectancy of older adults. The article outlines the challenges of the upcoming aging crisis and introduces falls as one major challenge. After that, falls and their mechanisms are investigated, highlighting the cognitive functions and their relation to falls. Moreover, since understanding predictive cognitive mechanisms is critical to an effective prediction-interception design, they are discussed in more detail, signifying the role of cognitive decline in balance maintenance. Furthermore, the landscape of available solutions for falling and its shortcomings is inspected. Finally, immediate fall prevention, the missing part of a wholesome solution, and its barriers are introduced, and some promising methodologies are proposed.
Can lower-limb exoskeletons support sit-to-stand motions in frail elderly without crutches? A study combining optimal control and motion capture
Authors: Lau Jan C. L. , Mombaur Katja
Published: April 2024

With the global geriatric population expected to reach 1.5 billion by 2050, different assistive technologies have been developed to tackle age-associated movement impairments. Lower-limb robotic exoskeletons have the potential to support frail older adults while promoting activities of daily living, but the need for crutches may be challenging for this population. Crutches aid safety and stability, but moving in an exoskeleton with them can be unnatural to human movements, and coordination can be difficult. Frail older adults may not have the sufficient arm strength to use them, or prolonged usage can lead to upper limb joint deterioration. The research presented in this paper makes a contribution to a more detailed study of crutch-less exoskeleton use, analyzing in particular the most challenging motion, sit-to-stand (STS). It combines motion capture and optimal control approaches to evaluate and compare the STS dynamics with the TWIN exoskeleton with and without crutches. The results show trajectories that are significantly faster than the exoskeleton's default trajectory, and identify the motor torques needed for full and partial STS assistance. With the TWIN exoskeleton's existing motors being able to support 112 Nm (hips) and 88 Nm (knees) total, assuming an ideal contribution from the device and user, the older adult would need to contribute a total of 8 Nm (hips) and 50 Nm (knees). For TWIN to provide full STS assistance, it would require new motors that can exert at least 121 Nm (hips) and 140 Nm (knees) total. The presented optimal control approaches can be replicated on other exoskeletons to determine the torques required with their mass distributions. Future improvements are discussed and the results presented lay groundwork for eliminating crutches when moving with an exoskeleton.
Individual differences in auditory perception predict learning of non-adjacent tone sequences in 3-year-olds
Authors: Mueller Jutta L. , Weyers Ivonne , Friederici Angela D. , Männel Claudia
Published: April 2024

Auditory processing of speech and non-speech stimuli oftentimes involves the analysis and acquisition of non-adjacent sound patterns. Previous studies using speech material have demonstrated (i) children’s early emerging ability to extract non-adjacent dependencies (NADs) and (ii) a relation between basic auditory perception and this ability. Yet, it is currently unclear whether children show similar sensitivities and similar perceptual influences for NADs in the non-linguistic domain. We conducted an event-related potential study with 3-year-old children using a sine-tone-based oddball task, which simultaneously tested for NAD learning and auditory perception by means of varying sound intensity. Standard stimuli were A × B sine-tone sequences, in which specific A elements predicted specific B elements after variable × elements. NAD deviants violated the dependency between A and B and intensity deviants were reduced in amplitude. Both elicited similar frontally distributed positivities, suggesting successful deviant detection. Crucially, there was a predictive relationship between the amplitude of the sound intensity discrimination effect and the amplitude of the NAD learning effect. These results are taken as evidence that NAD learning in the non-linguistic domain is functional in 3-year-olds and that basic auditory processes are related to the learning of higher-order auditory regularities also outside the linguistic domain.
Expanded expression of pro-neurogenic factor SoxB1 during larval development of gastropod Lymnaea stagnalis suggests preadaptation to prolonged neurogenesis in Mollusca
Authors: Kurtova Anastasia I. , Finoshin Alexander D. , Aparina Margarita S. , Gazizova Guzel R. , Kozlova Olga S. , Voronova Svetlana N. , Shagimardanova Elena I. , Ivashkin Evgeny G. , Voronezhskaya Elena E.
Published: April 2024

Introduction

The remarkable diversity observed in the structure and development of the molluscan nervous system raises intriguing questions regarding the molecular mechanisms underlying neurogenesis in Mollusca. The expression of SoxB family transcription factors plays a pivotal role in neuronal development, thereby offering valuable insights into the strategies of neurogenesis.

Methods

In this study, we conducted gene expression analysis focusing on SoxB-family transcription factors during early neurogenesis in the gastropod Lymnaea stagnalis. We employed a combination of hybridization chain reaction in situ hybridization (HCR-ISH), immunocytochemistry, confocal microscopy, and cell proliferation assays to investigate the spatial and temporal expression patterns of LsSoxB1 and LsSoxB2 from the gastrula stage to hatching, with particular attention to the formation of central ring ganglia.

Results

Our investigation reveals that LsSoxB1 demonstrates expanded ectodermal expression from the gastrula to the hatching stage, whereas expression of LsSoxB2 in the ectoderm ceases by the veliger stage. LsSoxB1 is expressed in the ectoderm of the head, foot, and visceral complex, as well as in forming ganglia and sensory cells. Conversely, LsSoxB2 is mostly restricted to the subepithelial layer and forming ganglia cells during metamorphosis. Proliferation assays indicate a uniform distribution of dividing cells in the ectoderm across all developmental stages, suggesting the absence of distinct neurogenic zones with increased proliferation in gastropods.

Discussion

Our findings reveal a spatially and temporally extended pattern of SoxB1 expression in a gastropod representative compared to other lophotrochozoan species. This prolonged and widespread expression of SoxB genes may be interpreted as a form of transcriptional neoteny, representing a preadaptation to prolonged neurogenesis. Consequently, it could contribute to the diversification of nervous systems in gastropods and lead to an increase in the complexity of the central nervous system in Mollusca.
Association between dietary inflammation index and cataract: a population-based study from NHANES 2005–2008
Authors: Zhang Yi , Zhou Jingxin , Shen Wenyue , Grzybowski Andrzej , Jin Kai , Ye Juan
Published: April 2024

Importance

Various studies have widely explored the association between index of dietary inflammation (DII) and occurrence of diseases. Accumulating evidence have revealed that a lower DII seems to be protective against a variety of diseases. Nevertheless, the association between DII and age-related cataract remains unclear.

Objective

To investigate the correlation between DII and age-related cataract in a representative sample of the American population.

Design, setting, and participants

This cross-sectional population-based study comprised 6,395 participants from the National Health and Nutrition Examination Survey (NHANES) conducted in cycles from 2005 to 2008. DII was calculated using dietary recall information, with higher scores indicating greater inflammatory potential of the diet. Age-related cataract was evaluated using cataract surgery as a surrogate measure. Covariates included sociodemographic factors, lifestyle factors, physical measures, and comorbidities. Logistic regression models were employed to assess the association between DII and cataract. The presence of a non-linear relationship was examined using restricted cubic spline analysis. Subgroup analysis was conducted to explore potential interaction effects. Data analysis was performed from September 1 to December 30, 2022.

Main outcomes and measures

Age-related cataract assessed through cataract surgery information obtained from a self-reported questionnaire.

Results

A total of 6,395 participants were included, with a mean (standard deviation, SD) age of 48.7 (15.3) years. Of these, 3,115 (48.7%) were male, 3,333 (52.1%) were non-Hispanic white, and 683 (10.7%) had cataract. The mean (SD) DII was −4.78 (1.74). After adjusting for all included covariates, DII showed a positive association with cataract, both as a continuous variable (odds ratio (OR): 1.054, 95% confidence interval (CI): 1.007–1.103, p = 0.023) and in quartiles, with the highest quartile compared to the lowest (OR: 1.555, 95% CI: 1.233–1.967, p < 0.001). Restricted cubic spline analysis revealed no evidence of a non-linear relationship (p for non-linearity 0.085). Subgroup analysis indicated no interaction effects among the studied covariates.

Conclusions and relevance

These findings suggest that a pro-inflammatory diet serves as a risk factor for the occurrence of cataracts.
A novel approach for segmentation and quantitative analysis of breast calcification in mammograms
Authors: Tong Yunfei , Jiang Jianrong , Chen Fang , Guo Guanghua , Zhang Chaoren , Deng Tiana
Published: April 2024

Background

Breast cancer is a major threat to women’s health globally. Early detection of breast cancer is crucial for saving lives. One important early sign is the appearance of breast calcification in mammograms. Accurate segmentation and analysis of calcification can improve diagnosis and prognosis. However, small size and diffuse distribution make calcification prone to oversight.

Purpose

This study aims to develop an efficient approach for segmenting and quantitatively analyzing breast calcification from mammograms. The goal is to assist radiologists in discerning benign versus malignant lesions to guide patient management.

Methods

This study develops a framework for breast calcification segmentation and analysis using mammograms. A Pro_UNeXt algorithm is proposed to accurately segment calcification lesions by enhancing the UNeXt architecture with a microcalcification detection block, fused-MBConv modules, multiple-loss-function training, and data augmentation. Quantitative features are then extracted from the segmented calcification, including morphology, size, density, and spatial distribution. These features are used to train machine learning classifiers to categorize lesions as malignant or benign.

Results

The proposed Pro_UNeXt algorithm achieved superior segmentation performance versus UNet and UNeXt models on both public and private mammogram datasets. It attained a Dice score of 0.823 for microcalcification detection on the public dataset, demonstrating its accuracy for small lesions. For quantitative analysis, the extracted calcification features enabled high malignant/benign classification, with AdaBoost reaching an AUC of 0.97 on the private dataset. The consistent results across datasets validate the representative and discerning capabilities of the proposed features.

Conclusion

This study develops an efficient framework integrating customized segmentation and quantitative analysis of breast calcification. Pro_UNeXt offers precise localization of calcification lesions. Subsequent feature quantification and machine learning classification provide comprehensive malignant/benign assessment. This end-to-end solution can assist clinicians in early diagnosis, treatment planning, and follow-up for breast cancer patients.
Clinicopathologic and endoscopic features of sessile serrated lesions and conventional adenomas: a large inpatient population-based study in China
Authors: Tan Chang , Qin Geng , Wang Qian-Qian , Zhou Yuan-Chen , Yao Shu-Kun
Published: April 2024

Objectives

Sessile serrated lesions (SSLs) are precursors of sporadic colorectal cancer (CRC) and have distinct characteristics compared with conventional adenomas (CAs). Several lifestyle and environmental factors may play critical roles in the development of advanced lesions. Our aim is to describe the features of SSLs and CAs and further explore risk factors for advanced lesions.

Methods

This is an observational study that collected demographic, endoscopic, and histological data from the China-Japan Friendship Hospital among the inpatient population with pathologically reported as SSL or CA between 2015 and 2022. We analyzed the clinicopathology and endoscopic differences between SSL alone, CA alone, and synchronous SSL+CA groups, and identified risk factors using multiple regression analysis.

Results

A total of 9236 polyps from 6598 patients were included in the cohort. Patients with SSL+CA were more likely to be older (p=0.008), while individuals with SSL alone had a higher proportion of early-onset polyps (p<0.001), and SSLs were more common in advanced polyps than CAs (p<0.001). A greater proportion of advanced polyps in the SSL and CA groups were diagnosed as Yamada III, Yamada IV, and laterally spreading tumor (p=0.002, p<0.001, respectively), and multiple SSLs and CAs were more represented in nonadvanced polyps than in advanced polyps. In multiple regression analysis, older patients were more likely to develop advanced SSLs (aOR 1.05, 95% CI 1.02-1.09, p=0.005).

Conclusion

SSLs and CAs have diverse demographic, endoscopic, and histological characteristics, and their advanced lesions share different risk factors, which advances the understanding of the etiology and progression of SSLs.
Efficacy of befotertinib in non-small cell lung cancer harboring uncommon compound EGFR mutations G719X and S768I: a case report
Authors: Zhang Zhedong , Huang Yu , Gu Haihua , Zhao Lufeng , Zhao Baiqin
Published: April 2024

The discovery of epidermal growth factor receptor (EGFR) somatic mutations and the availability of tyrosine kinase inhibitors (TKIs) as targeted therapies have transformed the treatment landscape for advanced non-small cell lung cancer (NSCLC). p.G719X and p.S768I mutations, often present in the form of complex mutations, are considered rare. This study firstly reported the treatment outcome of a locally advanced unresectable NSCLC patient with a rare complex EGFR p.G719X/p.S768I mutations who received befotertinib. After treatment, the patient achieved partial response (PR), and no severe adverse events were observed. This case report supported befotertinib as a promising treatment option for advanced NSCLC patients with the rare p.G719X/p.S768I complex mutations.
FOLFOXIRI plus cetuximab as conversion therapy for unresectable RAS/BRAF wild-type left-sided colorectal cancer with liver-limited metastases: a prospective dual-center pilot study
Authors: Yang Wenwei , Chen Dong , Niu Yaru , Wu Guifu , Huang Zhangkan , Bi Xinyu , Zhao Hong , Che Xu , Sun Yongkun
Published: April 2024

Purpose

To explore the efficacy and safety of FOLFOXIRI plus cetuximab regimen as conversion therapy for patients with unresectable RAS/BRAF wild-type colorectal liver-limited metastases (CLM).

Patients and methods

This was a dual-center, phase II trial with the rate of no evidence of disease (NED) achieved as the primary endpoint. All enrolled patients with initially unresectable left-sided RAS/BRAF wild-type colorectal liver-limited metastases received a modified FOLFOXIRI plus cetuximab regimen as conversion therapy.

Results

Between October 2019 and October 2021, fifteen patients were enrolled. Nine patients (60%) achieved NED. The overall response rate (ORR) was 92.9%, and the disease control rate (DCR) was 100%. The median relapse‐free survival (RFS) was 9 (95% CI: 0–20.7) months. The median progression-free survival (PFS) was 13.0 months (95% CI: 5.7-20.5), and the median overall survival (OS) was not reached. The most frequently occurring grade 3-4 adverse events were neutropenia (20%), peripheral neurotoxicity (13.3%), diarrhea (6.7%), and rash acneiform (6.7%).

Conclusion

The FOLFOXIRI plus cetuximab regimen displayed tolerable toxicity and promising anti-tumor activity in terms of the rate of NED achieved and response rate in patients with initially unresectable left-sided RAS/BRAF wild-type CLM. This regimen merits further investigation.
Moving pain management programmes into the digital age: development and evaluation of an online PMP for people with chronic pain
Authors: Herron Katie , Bradshaw Alison , Liptrot Matthew , Wieringa Gina , Mathews Kerry , Wiles John , Johnson Selina
Published: April 2024

Introduction

In response to Coronovirus Disease (COVID-19) health care restrictions, the pain management programme delivered group treatment digitally (OPMP). We aimed to: 1) evaluate pain related outcomes of the OPMP, 2) evaluate patient satisfaction and qualitive feedback of the OPMP and 3) compare OPMP outcomes with the pre-pandemic face to face (F2F) PMP outcomes.

Methods

Age, gender, pain duration, occupational status, referral information and patient satisfaction data were collected. Pre- and post-treatment pain related outcomes were compared by calculating mean difference, benchmarking with effect size (Cohen's d) and determining clinically significant change (CSC) for OPMP and F2F PMP.

Results

Two-hundred and thirty-seven patients provided outcome data, with 60 completing the OPMP and 177 completing the F2F PMP. OPMP patients were 10 years younger than the F2F PMP (44.8 vs 53.3), more were female (6.5:1 vs 2.8:1), more were working (45% vs 27%) and fewer were retired (3% vs 17%). The OPMP showed improvements comparable to the F2F PMP. Large effect size was reported across all outcome domains including objective physical outcomes. Eighty-one percent of OPMP patients were ‘extremely likely’ to recommend the programme but just over 50% of patients felt F2F would provide greater clinical benefits.

Conclusion

The results support that OPMP is effective for carefully selected patients following a multidisciplinary team assessment however more complex cases still require F2F PMP.
Capnography waveforms: basic interpretation in neonatal intensive care
Authors: Williams Emma E. , Dassios Theodore , Harris Christopher , Greenough Anne
Published: April 2024

End-tidal capnography can provide useful clinical information displayed on the ventilator screen or bedside monitor. It is important that clinicians can assess and utilise this information to assist in identifying underlying complications and pulmonary pathology. Sudden change or loss of the CO2 waveform can act as a safety measure in alerting clinicians of a dislodged or blocked endotracheal tube, considering the concurrent flow and volume waveforms. Visual pattern recognition by the clinicians of commonly seen waveform traces may act as an adjunct to other modes of ventilatory monitoring techniques. Waveforms traces can aid clinical management, help identify cases of ventilation asynchrony between the infant and the ventilator. We present some common clinical scenarios where tidal capnography can be useful in the timely identification of pulmonary complication and for practical troubleshooting at the cot-side.
A comprehensive review of Siraitia grosvenorii (Swingle) C. Jeffrey: chemical composition, pharmacology, toxicology, status of resources development, and applications
Authors: Huang Huaxue , Peng Zhi , Zhan Shuang , Li Wei , Liu Dai , Huang Sirui , Zhu Yizhun , Wang Wei
Published: April 2024

Siraitia grosvenorii (Swingle) C. Jeffrey (S. grosvenorii), a perennial indigenous liana from the Cucurbitaceae family, has historically played a significant role in southern China’s traditional remedies for various ailments. Its dual classification by the Chinese Ministry of Health for both medicinal and food utility underscores its has the potential of versatile applications. Recent research has shed light on the chemical composition, pharmacological effects, and toxicity of S. grosvenorii. Its active ingredients include triterpenoids, flavonoids, amino acids, volatile oils, polysaccharides, minerals, vitamins, and other microconstituents. Apart from being a natural sweetener, S. grosvenorii has been found to have numerous pharmacological effects, including alleviating cough and phlegm, preventing dental caries, exerting anti-inflammatory and anti-allergic effects, anti-aging and anti-oxidative, hypoglycemic, lipid-lowering, anti-depression, anti-fatigue, anti-schizophrenic, anti-Parkinson, anti-fibrotic, and anti-tumor activities. Despite its versatile potential, there is still a lack of systematic research on S. grosvenorii to date. This paper aims to address this gap by providing an overview of the main active components, pharmacological efficacy, toxicity, current status of development and application, development dilemmas, and strategies for intensive exploitation and utilization of S. grosvenorii. This paper aims to serve as a guide for researchers and practitioners committed to exploiting the biological resources of S. grosvenorii and further exploring its interdisciplinary potential.
Effects of species mixing on maximum size–density relationships in Chinese fir (Cunninghamia lanceolata (Lamb.) Hook.)-dominated mixed forests converted from even-aged pure stands
Authors: Han Yuanyuan , Wang Baichang , Sun Honggang
Published: April 2024

Introduction

Density management is a key silvicultural tool in management programs that enhances compositional and structural diversity and hence forest growth during the conversion of even-aged pure stands into mixed forests.

Methods

To determine the optimum stand density, a model of maximum size–density relationships was employed to explore the relationship of the self-thinning trajectory with growth, species mixing, latitude, and site conditions during the transition of even-aged pure Chinese fir stands to Chinese fir-dominated mixed forests using stochastic frontier analysis. Data were obtained from a total of 591 permanent plots located in Fujian, Jiangxi, Zhejiang, and Anhui provinces in southern China.

Results

The results showed that (1) the slope of the maximum size–density relationship of Chinese fir-dominated mixed forests increased and plateaued over time; (2) the slope of the maximum size–density relationship of Chinese fir-dominated mixed forests did not deviate from Reineke’s assumed universal slope of -1.605; and (3) mixing proportion had a positive effect on maximum size–density relationships, and latitude and site conditions had the opposite effect on maximum size–density relationships.

Conclusions

Our findings will provide valuable guidance for the forest management of areas in which even-aged pure stands are being converted to mixed forests (i.e., when broadleaved tree species are planted after thinning to improve overall stand density and promote stand growth).
Low mutation rate of spontaneous mutants enables detection of causative genes by comparing whole genome sequences
Authors: Suganami Mao , Kojima Soichi , Yoshida Hideki , Mori Masaki , Kawamura Mayuko , Koketsu Eriko , Matsuoka Makoto
Published: April 2024

In the early 1900s, mutation breeding to select varieties with desirable traits using spontaneous mutation was actively conducted around the world, including Japan. In rice, the number of fixed mutations per generation was estimated to be 1.38-2.25. Although this low mutation rate was a major problem for breeding in those days, in the modern era with the development of next-generation sequencing (NGS) technology, it was conversely considered to be an advantage for efficient gene identification. In this paper, we proposed an in silico approach using NGS to compare the whole genome sequence of a spontaneous mutant with that of a closely related strain with a nearly identical genome, to find polymorphisms that differ between them, and to identify the causal gene by predicting the functional variation of the gene caused by the polymorphism. Using this approach, we found four causal genes for the dwarf mutation, the round shape grain mutation and the awnless mutation. Three of these genes were the same as those previously reported, but one was a novel gene involved in awn formation. The novel gene was isolated from Bozu-Aikoku, a mutant of Aikoku with the awnless trait, in which nine polymorphisms were predicted to alter gene function by their whole-genome comparison. Based on the information on gene function and tissue-specific expression patterns of these candidate genes, Os03g0115700/LOC_Os03g02460, annotated as a short-chain dehydrogenase/reductase SDR family protein, is most likely to be involved in the awnless mutation. Indeed, complementation tests by transformation showed that it is involved in awn formation. Thus, this method is an effective way to accelerate genome breeding of various crop species by enabling the identification of useful genes that can be used for crop breeding with minimal effort for NGS analysis.
Genome-wide QTL mapping for agronomic traits in the winter wheat cultivar Pindong 34 based on 90K SNP array
Authors: Zhang Liangqi , Luo Yuqi , Zhong Xiao , Jia Guoyun , Chen Hao , Wang Yuqi , Zhou Jianian , Ma Chunhua , Li Xin , Huang Kebing , Yang Suizhuang , Wang Jianfeng , Han Dejun , Ren Yong , Cai Lin , Zhou Xinli
Published: April 2024

Introduction

Agronomic traits are key components of wheat yield. Exploitation of the major underlying quantitative trait loci (QTLs) can improve the yield potential in wheat breeding.

Methods

In this study, we constructed a recombinant inbred line (RIL) population from Mingxian 169 (MX169) and Pindong 34 (PD34) to determine the QTLs for grain length (GL), grain width (GW), grain length-to-width ratio (LWR), plant height (PH), spike length (SL), grain number per spike (GNS), and the thousand grain weight (TGW) across four environments using wheat 90K SNP array.

Results

A QTL associated with TGW, i.e., QTGWpd.swust-6BS, was identified on chromosome 6B, which explained approximately 14.1%–16.2% of the phenotypic variation. In addition, eight QTLs associated with GL were detected across six chromosomes in four different test environments. These were QGLpd.swust-1BL, QGLpd.swust-2BL, QGLpd.swust-3BL.1, QGLpd.swust-3BL.2, QGLpd.swust-5DL, QGLpd.swust-6AL, QGLpd.swust-6DL.1, and QGLpd.swust-6DL.2. They accounted for 9.0%–21.3% of the phenotypic variation. Two QTLs, namely, QGWpd.swust-3BS and QGWpd.swust-6DL, were detected for GW on chromosomes 3B and 6D, respectively. These QTLs explained 12.8%–14.6% and 10.8%–15.2% of the phenotypic variation, respectively. In addition, two QTLs, i.e., QLWRpd.swust-7AS.1 and QLWRpd.swust-7AS.2, were detected on chromosome 7A for the grain LWR, which explained 10.9%–11.6% and 11.6%–11.2% of the phenotypic variation, respectively. Another QTL, named QGNSpd-swust-6DS, was discovered on chromosome 6D, which determines the GNS and which accounted for 11.4%–13.8% of the phenotypic variation. Furthermore, five QTLs associated with PH were mapped on chromosomes 2D, 3A, 5A, 6B, and 7B. These QTLs were QPHpd.swust-2DL, QPHpd.swust-3AL, QPHpd.swust-5AL, QPHpd.swust-6BL, and QPHpd.swust-7BS, which accounted for 11.3%–19.3% of the phenotypic variation. Lastly, a QTL named QSLpd.swust-3AL, conferring SL, was detected on chromosome 3A and explained 16.1%–17.6% of the phenotypic variation. All of these QTLs were defined within the physical interval of the Chinese spring reference genome.

Discussion

The findings of this study have significant implications for the development of fine genetic maps, for genomic breeding, and for marker-assisted selection to enhance wheat grain yield.
Ecology, genetic diversity, and population structure among commercial varieties and local landraces of Capsicum spp. grown in northeastern states of India
Authors: Verma Veerendra Kumar , Pandey Avinash , Thirugnanavel Anbazhagan , Rymbai Heiplanmi , Dutta Niharika , Kumar Amit , Bhutia Tshering Lhamu , Jha Anjani Kumar , Mishra Vinay Kumar
Published: April 2024

Northeastern states of India are known for unique landraces of Capsicum spp. with geographical indications. However, little information is available about these valuable landraces of chillies. Surveys and collections were carried out in niche areas to find out their ecology and diversity through morphological traits and molecular analysis using microsatellite markers. Our result characterized the ecology of niche areas as cool (11.0°C–20.7°C) and humid (>60% relative humidity) climates for dalle-chilli (Capsicum annuum L.); mild-warm (12.2°C–28.6°C) and humid for king-chilli (C. chinense Jacq.); and cool to warm (11.3°C–33.1°C) and humid for bird’s eye chilli (C. frutescens L.) during the crop period. The canonical correspondence analysis has shown the significant impact of temperature on the agro-morphological traits and distribution of the landraces in their niche areas. A wide variability was observed for different quantitative traits and yield attributing characters (fruit length, diameter, weight, and yield), showing high heritability (97.0%–99.0%), and genetic advance as a percentage of the mean (119.8%–434.0%). A total of 47 SSR markers used for the molecular analysis generated 230 alleles, ranging from 2 (HPMSE-7) to 10 (HPMSE-5), with an average of 4.89 alleles per locus. The average polymorphism information content was also high (0.61) and ranged from 0.20 (HPMSE-7) to 0.85 (CAMS-91). The observed average heterozygosity was lower than the expected value. Analysis of molecular variance has shown significant variation within (69%) and between (31%) of the populations of Capsicum spp. Based on Nei’s genetic distance, bird’s eye chilli and king-chilli were found to be closer to each other, whereas dalle-chilli, a tretraploid species, was closer to hot pepper (C. annuum). However, the flower size of dalle-chilli was large and found closer to king-chilli in color and differs from C. chinense due to the presence of calyx teeth. For quality traits, landraces king-chilli, dalle-chilli, and bird’s eye chilli have shown 2.8, 2.0, and 1.4 times higher average capsaicin and 0.46, 0.25, and 0.22 times higher average oleoresin content over the hot pepper, respectively. The knowledge of ecology and diversity can be used in identifying new areas for production, selection of elite lines, conservation, and crop improvement.