bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrative single-cell transcriptomic analyses reveal the cellular ontological and functional heterogeneities of primary and metastatic liver tumors
Authors: Gui Menghui , Huang Shilin , Li Shizhou , Chen Yuying , Cheng Furong , Liu Yulin , Wang Ji-ao , Wang Yuting , Guo Rui , Lu Yiming , Cao Pengbo , Zhou Gangqiao
Published: February 2024

Background

The global cellular landscape of the tumor microenvironment (TME) combining primary and metastatic liver tumors has not been comprehensively characterized.

Methods

Based on the scRNA-seq and spatial transcriptomic data of non-tumor liver tissues (NTs), primary liver tumors (PTs) and metastatic liver tumors (MTs), we performed the tissue preference, trajectory reconstruction, transcription factor activity inference, cell–cell interaction and cellular deconvolution analyses to construct a comprehensive cellular landscape of liver tumors.

Results

Our analyses depicted the heterogeneous cellular ecosystems in NTs, PTs and MTs. The activated memory B cells and effector T cells were shown to gradually shift to inhibitory B cells, regulatory or exhausted T cells in liver tumors, especially in MTs. Among them, we characterized a unique group of TCF7+ CD8+ memory T cells specifically enriched in MTs that could differentiate into exhausted T cells likely driven by the p38 MAPK signaling. With regard to myeloid cells, the liver-resident macrophages and inflammatory monocyte/macrophages were markedly replaced by tumor-associated macrophages (TAMs), with TREM2+ and UBE2C+ TAMs enriched in PTs, while SPP1+ and WDR45B+ TAMs in MTs. We further showed that the newly identified WDR45B+ TAMs exhibit an M2-like polarization and are associated with adverse prognosis in patients with liver metastases. Additionally, we addressed that endothelial cells display higher immune tolerance and angiogenesis capacity, and provided evidence for the source of the mesenchymal transformation of fibroblasts in tumors. Finally, the malignant hepatocytes and fibroblasts were prioritized as the pivotal cell populations in shaping the microenvironments of PTs and MTs, respectively. Notably, validation analyses by using spatial or bulk transcriptomic data in clinical cohorts concordantly emphasized the clinical significance of these findings.

Conclusions

This study defines the ontological and functional heterogeneities in cellular ecosystems of primary and metastatic liver tumors, providing a foundation for future investigation of the underlying cellular mechanisms.
Ethnobotanical study of wild edible plants in Dibatie district, Metekel zone, Benishangul Gumuz Regional State, western Ethiopia
Authors: Anbessa Baressa , Lulekal Ermias , Getachew Paulos , Hymete Ariaya
Published: February 2024

Background

Plants deliver livelihood and food for millions of people in the world. Indeed, wild edible plants support rural communities in developing countries to overcome seasonal unfavorable conditions. In rural areas of Ethiopia, wild edible plants play an indispensable role in fighting food insecurity as emergency or supplementary foods. Hence, this research was aimed at studying the ethnobotanical assessment of wild edible plants in Dibatie district, Metekel zone, western Ethiopia.

Methods

Ethnobotanical data was collected using a semi-structured interview, field observation, focus group discussions, a market survey, and the ranking of selected plants. Besides, voucher specimens were collected and stored at the National Herbarium of Ethiopia. Descriptive statistics, preference ranking, direct matrix ranking, and familiarity index were computed for data analysis.

Results

This study has documented 54 wild edible plant species belonging to 33 plant families and 46 genera. Of these, most (38.90%) had tree growth habits. Wild edible plants bear mostly fruits (72.20%) as edible parts. Local people usually consume these plants freshly raw as complementary foods, though some wild edibles require processing. They were mostly harvested in the January (31.48%) and May (27.78%) months, with the least collected in September (7.41%). Most wild edible plants (78.57%) were available in uncontrolled habitats, while others (21.43%) live in farmlands, home gardens, and as live fences. Out of the recorded plants, about 98% had additional uses besides their nutritional values.

Conclusion

Wild edible plants assist the livelihoods of the local people in food security, agriculture, energy sources, construction, medicines, ecological services, aesthetics, income generation, and household utensils. Nevertheless, wild edible plants are recently threatened due to various anthropogenic factors in the study area. Thus, they need wise use and in-situ and ex-situ conservation measures from all the concerned bodies for sustainable use in the future.
The effect of the whole-process care model of the medical union on the improvement of kinesiophobia and bone mineral density in patients with osteoporosis
Authors: Qian Xiaoli , Cao Xiaodong , Zhu Liyan , Yao Xiaojuan , Gu Lina , Yu Xin
Published: February 2024

Objective

To observe the effect of the whole-process care model of the medical union on the improvement of kinesiophobia and bone mineral density in patients with osteoporosis.

Methods

In this descriptive study, a convenient sampling method was used to select 148 patients with osteoporosis who visited the hospital from January 2020 to December 2021. Patients aged ≥ 18 years and diagnosed with osteoporosis through quantitative computed tomography (QCT) were included in the study. They were able to cooperate during follow-up and had normal cognitive function. Patients with combined spinal curvature, thoracic deformity, and pulmonary dysfunction, accompanied by severe cardiovascular or limb dysfunction, and those who withdrew midway or participated in other clinical studies were excluded. According to whether to use the whole-process care model of the medical union, they were divided into intervention group and control group, with 74 cases each. The control group used conventional care, and the intervention group used the whole-process care model of the medical association. The occurrence of kinesiophobia between the two groups were compared. The dual-energy X-ray absorption detector is used to measure differences in bone density changes.

Results

There was no significant difference between the two groups in the TSK scale score and the incidence of kinesiophobia before intervention (P > 0.05). The TSK scale scores of patients in the intervention group were higher than those in the control group at 3 months and 6 months after operation (P < 0.05). The incidence of kinesiophobia in the intervention group for 3 months and 6 months was significantly lower than that in the control group (P < 0.05). There was no significant difference in bone mineral density between the two groups before and 3 months after intervention (P > 0.05). The bone mineral density of lumbar spine, femoral neck and total hip in the intervention group was significantly higher than that in the control group after 6 months of intervention (P < 0.05).

Conclusion

The whole-process care model of the medical association is used for osteoporosis patients, which might reduce the risk of kinesiophobia and improve the bone density of the lumbar spine and total hip in patients. But further promotion and improvement of relevant support systems are needed to achieve comprehensive promotion and maximize clinical benefits in this field.
Crucial role of TFAP2B in the nervous system for regulating NREM sleep
Authors: Nakai Ayaka , Kashiwagi Mitsuaki , Fujiyama Tomoyuki , Iwasaki Kanako , Hirano Arisa , Funato Hiromasa , Yanagisawa Masashi , Sakurai Takeshi , Hayashi Yu
Published: February 2024

The AP-2 transcription factors are crucial for regulating sleep in both vertebrate and invertebrate animals. In mice, loss of function of the transcription factor AP-2β (TFAP2B) reduces non-rapid eye movement (NREM) sleep. When and where TFAP2B functions, however, is unclear. Here, we used the Cre-loxP system to generate mice in which Tfap2b was specifically deleted in the nervous system during development and mice in which neuronal Tfap2b was specifically deleted postnatally. Both types of mice exhibited reduced NREM sleep, but the nervous system-specific deletion of Tfap2b resulted in more severe sleep phenotypes accompanied by defective light entrainment of the circadian clock and stereotypic jumping behavior. These findings indicate that TFAP2B in postnatal neurons functions at least partly in sleep regulation and imply that TFAP2B also functions either at earlier stages or in additional cell types within the nervous system.
Splicing targeting drugs highlight intron retention as an actionable vulnerability in advanced prostate cancer
Authors: Naro Chiara , Antonioni Ambra , Medici Vanessa , Caggiano Cinzia , Jolly Ariane , de la Grange Pierre , Bielli Pamela , Paronetto Maria Paola , Sette Claudio
Published: February 2024

Background

Advanced prostate cancer (PC) is characterized by insensitivity to androgen deprivation therapy and chemotherapy, resulting in poor outcome for most patients. Thus, advanced PC urgently needs novel therapeutic strategies. Mounting evidence points to splicing dysregulation as a hallmark of advanced PC. Moreover, pharmacologic inhibition of the splicing process is emerging as a promising option for this disease.

Method

By using a representative androgen-insensitive PC cell line (22Rv1), we have investigated the genome-wide transcriptomic effects underlying the cytotoxic effects exerted by three splicing-targeting drugs: Pladienolide B, indisulam and THZ531. Bioinformatic analyses were performed to uncover the gene structural features underlying sensitivity to transcriptional and splicing regulation by these treatments. Biological pathways altered by these treatments were annotated by gene ontology analyses and validated by functional experiments in cell models.

Results

Although eliciting similar cytotoxic effects on advanced PC cells, Pladienolide B, indisulam and THZ531 modulate specific transcriptional and splicing signatures. Drug sensitivity is associated with distinct gene structural features, expression levels and cis-acting sequence elements in the regulated exons and introns. Importantly, we identified PC-relevant genes (i.e. EZH2, MDM4) whose drug-induced splicing alteration exerts an impact on cell survival. Moreover, computational analyses uncovered a widespread impact of splicing-targeting drugs on intron retention, with enrichment in genes implicated in pre-mRNA 3’-end processing (i.e. CSTF3, PCF11). Coherently, advanced PC cells displayed high sensitivity to a specific inhibitor of the cleavage and polyadenylation complex, which enhances the effects of chemotherapeutic drugs that are already in use for this cancer.

Conclusions

Our study uncovers intron retention as an actionable vulnerability for advanced PC, which may be exploited to improve therapeutic management of this currently incurable disease.
Pediatric acute hospitalization for anorexia nervosa: an economic evaluation
Authors: Marchili Maria Rosaria , Bozzola Elena , Guolo Stefano , Marchesani Silvio , Spina Giulia , Mascolo Cristina , Vicari Stefano , De Jacobis Isabella Tarissi , Raponi Massimiliano , Villani Alberto
Published: February 2024

Background

Anorexia nervosa (AN) is a psychiatric disorders which may potentially led to a high risk of health medical complications, suicide and self-harming behaviour. Since Covid-19 pandemic onset in March 2020, evidence suggested an increase occurrence of AN. The main aim of the retrospective analysis is to define the cost of hospitalization in the acute phase (HAP) at IRCCS Bambino Gesù Children Hospital, Rome, Italy, over 2 years study. Secondary purposes are defining the main risk factors for a prolonged hospitalization (including age, sex and comorbidities) and the possible influence of Covid-19 pandemic on AN admission and hospital stay.

Methods

for the purpose of the study, we included children and adolescents aged less than 18 years, admitted to IRCCS Bambino Gesù Children Hospital, Rome, Italy, with a diagnosis of AN. Medical costs were calculated consulting the Lazio Regional Health Service Tariffs. Basing on the date of hospital admission, patients were later divided into two subgroups: subgroup A included patients hospitalized prior than Covid-19 onset (from March 2019 to February 2020) and subgroup B those admitted after (from March 2020 to October 2022).

Results

a total of 260 patients has been included in the study with a median age of 15 years (range 6–18 years). The total health care cost of AN hospitalized patients was of EUR 3,352,333 with a median cost of EUR 11,124 for each admission (range EUR 930 − 45,739) and a median daily cost of EUR 593 (range EUR 557–930). Median cost was higher in case of comorbidities, guarded patients, enteral feeding. A prolonged hospitalization has been documented in subgroup A with a higher economic burden.

Conclusions

the economic burden of eating disorders is of note. Adequate sanitary policies as well as health economic analyses are required to gain insight into the cost-effectiveness of AN management.

Trial registration

2526-OPBG-2021.
Genomic insight into the origin, domestication, dispersal, diversification and human selection of Tartary buckwheat
Authors: He Yuqi , Zhang Kaixuan , Shi Yaliang , Lin Hao , Huang Xu , Lu Xiang , Wang Zhirong , Li Wei , Feng Xibo , Shi Taoxiong , Chen Qingfu , Wang Junzhen , Tang Yu , Chapman Mark A. , Germ Mateja , Luthar Zlata , Kreft Ivan , Janovská Dagmar , Meglič Vladimir , Woo Sun-Hee , Quinet Muriel , Fernie Alisdair R. , Liu Xu , Zhou Meiliang
Published: February 2024

Background

Tartary buckwheat,Fagopyrum tataricum, is a pseudocereal crop with worldwide distribution and high nutritional value. However, the origin and domestication history of this crop remain to be elucidated.

Results

Here, by analyzing the population genomics of 567 accessions collected worldwide and reviewing historical documents, we find that Tartary buckwheat originated in the Himalayan region and then spread southwest possibly along with the migration of the Yi people, a minority in Southwestern China that has a long history of planting Tartary buckwheat. Along with the expansion of the Mongol Empire, Tartary buckwheat dispersed to Europe and ultimately to the rest of the world. The different natural growth environments resulted in adaptation, especially significant differences in salt tolerance between northern and southern Chinese Tartary buckwheat populations. By scanning for selective sweeps and using a genome-wide association study, we identify genes responsible for Tartary buckwheat domestication and differentiation, which we then experimentally validate. Comparative genomics and QTL analysis further shed light on the genetic foundation of the easily dehulled trait in a particular variety that was artificially selected by the Wa people, a minority group in Southwestern China known for cultivating Tartary buckwheat specifically for steaming as a staple food to prevent lysine deficiency.

Conclusions

This study provides both comprehensive insights into the origin and domestication of, and a foundation for molecular breeding for, Tartary buckwheat.
Rotator cuff tear patterns: MRI appearance and its surgical relevance
Authors: Yubran Alexeys Perez , Pesquera Luis Cerezal , Juan Eva Llopis San , Saralegui Fernando Idoate , Canga Alvaro Cerezal , Camara Antonio Cruz , Valdivieso Gustavo Matheus , Pisanti Lopez Carolina
Published: February 2024

A new perspective on rotator cuff anatomy has allowed a better understanding of the patterns of the different rotator cuff tears. It is essential for radiologists to be aware of these different patterns of tears and to understand how they might influence treatment and surgical approach. Our objective is to review the arthroscopy correlated magnetic resonance imaging appearance of the different types of rotator cuff tears based on current anatomical concepts.

Critical relevance statement Knowledge of the characteristics of rotator cuff tears improves our communication with the surgeon and can also make it easier for the radiologist to prepare a report that guides therapeutic conduct and serves as a prognosis for the patient.

Key points

• There is no universally accepted classification for RC tears.

• New patterns such as delamination or myotendinous junction tears have been defined.

• The most difficult feature to assess in full thickness tears on MRI is the pattern.

• Fatty infiltration of the RC tendons is crucial in the prognosis and outcome.

• The radiological report is an effective way of communication with the surgeon.

Graphical Abstract
Prediction of lymph node metastasis in operable cervical cancer using clinical parameters and deep learning with MRI data: a multicentre study
Authors: Qin Fengying , Sun Xinyan , Tian Mingke , Jin Shan , Yu Jian , Song Jing , Wen Feng , Xu Hongming , Yu Tao , Dong Yue
Published: February 2024

Objectives

To develop and validate a magnetic resonance imaging-based (MRI) deep multiple instance learning (D-MIL) model and combine it with clinical parameters for preoperative prediction of lymph node metastasis (LNM) in operable cervical cancer.

Methods

A total of 392 patients with cervical cancer were retrospectively enrolled. Clinical parameters were analysed by logistical regression to construct a clinical model (M1). A ResNet50 structure is applied to extract features at the instance level without using manual annotations about the tumour region and then construct a D-MIL model (M2). A hybrid model (M3) was constructed by M1 and M2 scores. The diagnostic performance of each model was evaluated by the area under the receiver operating characteristic curve (AUC) and compared using the Delong method. Disease-free survival (DFS) was evaluated by the Kaplan‒Meier method.

Results

SCC-Ag, maximum lymph node short diameter (LNmax), and tumour volume were found to be independent predictors of M1 model. For the diagnosis of LNM, the AUC of the training/internal/external cohort of M1 was 0.736/0.690/0.732, the AUC of the training/internal/external cohort of M2 was 0.757/0.714/0.765, and the AUC of the training/internal/external cohort of M3 was 0.838/0.764/0.835. M3 showed better performance than M1 and M2. Through the survival analysis, patients with higher hybrid model scores had a shorter time to reach DFS.

Conclusion

The proposed hybrid model could be used as a personalised non-invasive tool, which is helpful for predicting LNM in operable cervical cancer. The score of the hybrid model could also reflect the DFS of operable cervical cancer.

Critical relevance statement

Lymph node metastasis is an important factor affecting the prognosis of cervical cancer. Preoperative prediction of lymph node status is helpful to make treatment decisions, improve prognosis, and prolong survival time.

Key points

• The MRI-based deep-learning model can predict the LNM in operable cervical cancer.

• The hybrid model has the highest diagnostic efficiency for the LNM prediction.

• The score of the hybrid model can reflect the DFS of operable cervical cancer.

Graphical Abstract
T2WI-based MRI radiomics for the prediction of preoperative extranodal extension and prognosis in resectable rectal cancer
Authors: Li Hang , Chai Li , Pu Hong , Yin Long-lin , Li Mou , Zhang Xin , Liu Yi-sha , Pang Ming-hui , Lu Tao
Published: February 2024

Objective

To investigate whether T2-weighted imaging (T2WI)-based intratumoral and peritumoral radiomics can predict extranodal extension (ENE) and prognosis in patients with resectable rectal cancer.

Methods

One hundred sixty-seven patients with resectable rectal cancer including T3T4N + cases were prospectively included. Radiomics features were extracted from intratumoral, peritumoral 3 mm, and peritumoral-mesorectal fat on T2WI images. Least absolute shrinkage and selection operator regression were used for feature selection. A radiomics signature score (Radscore) was built with logistic regression analysis. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of each Radscore. A clinical-radiomics nomogram was constructed by the most predictive radiomics signature and clinical risk factors. A prognostic model was constructed by Cox regression analysis to identify 3-year recurrence-free survival (RFS).

Results

Age, cT stage, and lymph node-irregular border and/or adjacent fat invasion were identified as independent clinical risk factors to construct a clinical model. The nomogram incorporating intratumoral and peritumoral 3 mm Radscore and independent clinical risk factors achieved a better AUC than the clinical model in the training (0.799 vs. 0.736) and validation cohorts (0.723 vs. 0.667). Nomogram-based ENE (hazard ratio [HR] = 2.625, 95% CI = 1.233–5.586, p = 0.012) and extramural vascular invasion (EMVI) (HR = 2.523, 95% CI = 1.247–5.106, p = 0.010) were independent risk factors for predicting 3-year RFS. The prognostic model constructed by these two indicators showed good performance for predicting 3-year RFS in the training (AUC = 0.761) and validation cohorts (AUC = 0.710).

Conclusion

The nomogram incorporating intratumoral and peritumoral 3 mm Radscore and clinical risk factors could predict preoperative ENE. Combining nomogram-based ENE and MRI-reported EMVI may be useful in predicting 3-year RFS.

Critical relevance statement

A clinical-radiomics nomogram could help preoperative predict ENE, and a prognostic model constructed by the nomogram-based ENE and MRI-reported EMVI could predict 3-year RFS in patients with resectable rectal cancer.

Key points

• Intratumoral and peritumoral 3 mm Radscore showed the most capability for predicting ENE.

• Clinical-radiomics nomogram achieved the best predictive performance for predicting ENE.

• Combining clinical-radiomics based-ENE and EMVI showed good performance for 3-year RFS.

Graphical Abstract
The use of PET/MRI in radiotherapy
Authors: Yan Qi , Yan Xia , Yang Xin , Li Sijin , Song Jianbo
Published: February 2024

Positron emission tomography/magnetic resonance imaging (PET/MRI) is a hybrid imaging technique that quantitatively combines the metabolic and functional data from positron emission tomography (PET) with anatomical and physiological information from MRI. As PET/MRI technology has advanced, its applications in cancer care have expanded. Recent studies have demonstrated that PET/MRI provides unique advantages in the field of radiotherapy and has become invaluable in guiding precision radiotherapy techniques. This review discusses the rationale and clinical evidence supporting the use of PET/MRI for radiation positioning, target delineation, efficacy evaluation, and patient surveillance.

Critical relevance statement This article critically assesses the transformative role of PET/MRI in advancing precision radiotherapy, providing essential insights into improved radiation positioning, target delineation, efficacy evaluation, and patient surveillance in clinical radiology practice.

Key points

• The emergence of PET/MRI will be a key bridge for precise radiotherapy.

• PET/MRI has unique advantages in the whole process of radiotherapy.

• New tracers and nanoparticle probes will broaden the use of PET/MRI in radiation.

• PET/MRI will be utilized more frequently for radiotherapy.

Graphical Abstract
A retrospective study on adverse events of intravenous administration of sulfur hexafluoride microbubbles in abdominal and superficial applications in 83,778 patients
Authors: Li Di , Zhang Rui , Lan Huixia , Chen Mianni , Huang Zhenli , Zhao Huijuan , Guo Shan , Xu Ming , Lei Yangyang
Published: February 2024

Objectives

To investigate the rate of adverse events (AEs) caused by intravenous administration of sulfur hexafluoride microbubbles in abdominal and superficial applications retrospectively and to explore practical measures for prevention and treatment of them.

Materials and methods

This study enrolled 83,778 contrast-enhanced ultrasound (CEUS) examinations using sulfur hexafluoride microbubbles intravenously performed during 11 years. Age, gender, and target organs of all CEUS patients were recorded. For cases of AEs, their medical history and laboratory results were also collected. The process of AEs was assessed and categorized. Besides, the management of AEs were recorded.

Results

Twenty patients had sulfur hexafluoride microbubbles-related AEs. The AE rate was 0.024%. No significant difference was observed between patients with AEs and the whole group for age and sex distribution. All AEs happened in liver examinations. Among them, 7 (35%) were mild, 8 (40%) were moderate, and 5 (25%) were severe. They were categorized into 15 allergic-like reactions and 5 physiologic reactions. The manifestations of mild and moderate AEs mainly include urticaria, chills, and mild hypoxia, which could be eased by simple management. Severe cases had anaphylactic shock, generalized convulsions, and diffuse erythema with hypotension respectively. They need close monitoring and oxygen inhalation with anti-shock and anti-anaphylactic treatment. Most cases started within 30 min and recovered within 1 day.

Conclusions

Intravenous administration of sulfur hexafluoride microbubbles in abdominal and superficial applications was safe with rare AEs. AEs were more likely to happen in abdominal applications than superficial ones. A well-designed emergency plan should be available for clinical use of sulfur hexafluoride microbubbles to reduce AEs and to deal with AEs properly.

Critical relevance statement

Intravenous administration of sulfur hexafluoride microbubbles in abdominal and superficial applications reported few AEs and could be considered safe but severe AEs are life-threatening. We analyzed the influence factors of AEs and propose some methods for prevention and treatment of them, which can further improve the safety of sulfur hexafluoride microbubbles in clinical practice.

Key points

• The AE rate of sulfur hexafluoride microbubbles in abdominal and superficial applications was 0.024%.

• Patients were more likely to have AEs in abdominal applications than superficial ones.

• Severe AEs are life-threatening and need prompt identification and treatment.

• We summarized some detailed suggestions for clinical prevention and treatment of AEs.

Graphical Abstract
Deep learning model based on multi-lesion and time series CT images for predicting the benefits from anti-HER2 targeted therapy in stage IV gastric cancer
Authors: He Meng , Chen Zi-fan , Liu Song , Chen Yang , Zhang Huan , Zhang Li , Zhao Jie , Yang Jie , Zhang Xiao-tian , Shen Lin , Gao Jian-bo , Dong Bin , Tang Lei
Published: February 2024

Objective

To develop and validate a deep learning model based on multi-lesion and time series CT images in predicting overall survival (OS) in patients with stage IV gastric cancer (GC) receiving anti-HER2 targeted therapy.

Methods

A total of 207 patients were enrolled in this multicenter study, with 137 patients for retrospective training and internal validation, 33 patients for prospective validation, and 37 patients for external validation. All patients received anti-HER2 targeted therapy and underwent pre- and post-treatment CT scans (baseline and at least one follow-up). The proposed deep learning model evaluated the multiple lesions in time series CT images to predict risk probabilities. We further evaluated and validated the risk score of the nomogram combining a two-follow-up lesion-based deep learning model (LDLM-2F), tumor markers, and clinical information for predicting the benefits from treatment (Nomo-LDLM-2F).

Results

In the internal validation and prospective cohorts, the one-year AUCs for Nomo-LDLM-2F using the time series medical images and tumor markers were 0.894 (0.728–1.000) and 0.809 (0.561–1.000), respectively. In the external validation cohort, the one-year AUC of Nomo-LDLM-2F without tumor markers was 0.771 (0.510–1.000). Patients with a low Nomo-LDLM-2F score derived survival benefits from anti-HER2 targeted therapy significantly compared to those with a high Nomo-LDLM-2F score (all p < 0.05).

Conclusion

The Nomo-LDLM-2F score derived from multi-lesion and time series CT images holds promise for the effective readout of OS probability in patients with HER2-positive stage IV GC receiving anti-HER2 therapy.

Critical relevance statement

The deep learning model using baseline and early follow-up CT images aims to predict OS in patients with stage IV gastric cancer receiving anti-HER2 targeted therapy. This model highlights the spatiotemporal heterogeneity of stage IV GC, assisting clinicians in the early evaluation of the efficacy of anti-HER2 therapy.

Key points

• Multi-lesion and time series model revealed the spatiotemporal heterogeneity in anti-HER2 therapy.

• The Nomo-LDLM-2F score was a valuable prognostic marker for anti-HER2 therapy.

• CT-based deep learning model incorporating time-series tumor markers improved performance.

Graphical Abstract
Impact of tissue factor expression and administration routes on thrombosis development induced by mesenchymal stem/stromal cell infusions: re-evaluating the dogma
Authors: Hoang Van T. , Le Duc Son , Hoang Duc M. , Phan Trang Thi Kieu , Ngo Lan Anh Thi , Nguyen Trung Kien , Bui Viet Anh , Nguyen Thanh Liem
Published: February 2024

Background

Hyperactive coagulation might cause dangerous complications such as portal vein thrombosis and pulmonary embolism after mesenchymal stem/stromal cell (MSC) therapy. Tissue factor (TF), an initiator of the extrinsic coagulation pathway, has been suggested as a predictor of this process.

Methods

The expression of TF and other pro- and anticoagulant genes was analyzed in xeno- and serum-free manufactured MSCs. Furthermore, culture factors affecting its expression in MSCs were investigated. Finally, coagulation tests of fibrinogen, D-dimer, aPPTs, PTs, and TTs were measured in patient serum after umbilical cord (UC)-MSC infusions to challenge a potential connection between TF expression and MSC-induced coagulant activity. 

Results

Xeno- and serum-free cultured adipose tissue and UC-derived MSCs expressed the highest level of TF, followed by those from dental pulp, and the lowest expression was observed in MSCs of bone marrow origin. Environmental factors such as cell density, hypoxia, and inflammation impact TF expression, so in vitro analysis might fail to reflect their in vivo behaviors. MSCs also expressed heterogeneous levels of the coagulant factor COL1A1 and surface phosphatidylserine and anticoagulant factors TFPI and PTGIR. MSCs of diverse origins induced fibrin clots in healthy plasma that were partially suppressed by an anti-TF inhibitory monoclonal antibody. Furthermore, human umbilical vein endothelial cells exhibited coagulant activity in vitro despite their negative expression of TF and COL1A1. Patients receiving intravenous UC-MSC infusion exhibited a transient increase in D-dimer serum concentration, while this remained stable in the group with intrathecal infusion. There was no correlation between TF expression and D-dimer or other coagulation indicators.

Conclusions

The study suggests that TF cannot be used as a solid biomarker to predict MSC-induced hypercoagulation. Local administration, prophylactic intervention with anticoagulation drugs, and monitoring of coagulation indicators are useful to prevent thrombogenic events in patients receiving MSCs.

Trial registration NCT05292625. Registered March 23, 2022, retrospectively registered, https://www.clinicaltrials.gov/ct2/show/NCT05292625?term=NCT05292625&draw=2&rank=1. NCT04919135. Registered June 9, 2021, https://www.clinicaltrials.gov/ct2/show/NCT04919135?term=NCT04919135&draw=2&rank=1.
Ensemble coding of multiple facial expressions is not affected by attentional load
Authors: Liu Yujuan , Ji Luyan
Published: February 2024

Human observers can extract the mean emotion from multiple faces rapidly and precisely. However, whether attention is required in the ensemble coding of facial expressions remains debated. In this study, we examined the effect of attentional load on mean emotion processing with the dual-task paradigm. Individual emotion processing was also investigated as the control task. In the experiment, the letter string and a set of four happy or angry faces of various emotional intensities were shown. Participants had to complete the string task first, judging either the string color (low attention load) or the presence of the target letter (high attention load). Then a cue appeared indicating whether the secondary task was to evaluate the mean emotion of the faces or the emotion of the cued single face, and participants made their judgments on the visual analog scale. The results showed that compared with the color task, the letter task had a longer response time and lower accuracy, which verified the valid manipulation of the attention loads. More importantly, there was no significant difference in averaging performance between the low and high attention loads. By contrast, the individual face processing was impaired under the high attention load relative to the low attentional load. In addition, the advantage of extracting mean emotion over individual emotion was larger under the high attentional load. These results support the power of averaging and provide new evidence that a rather small amount of attention is needed in the ensemble coding of multiple facial expressions.
Perpetrators from Treblinka: interdisciplinary investigations of seven single graves with “Trawniki Men”
Authors: Drath Joanna , Jarzęcka-Stąporek Joanna , Zacharczuk Julia , Lisman Dagmara , Cytacka Sandra , Szargut Maria , Bulut Ozgur , Spradley Kate , Jasinski Marek E. , Parafiniuk Mirosław , Ossowski Andrzej
Published: February 2024

At the Treblinka extermination and forced labor camp only a few SS soldiers and around a hundred watchmen kept guard over thousands of prisoners. Despite their lower rank in the Nazi hierarchy than SS soldiers, watchmen were vital to implementing “Operation Reinhard” in the field. Prisoners in Nazi camps were terrified by their brutality and ruthlessness.

The guards were intermediaries between the camp’s inmates and the commanding crew, so in cases of a prisoners’ riot, they were the first target. The historical records mention several incidents where the watchmen died at the hands of the captives. However, little is known regarding how the dead bodies of the guards were treated nor what the funeral customs looked like in the camps.

In 2019, a row of individual burials was discovered at the former Treblinka extermination and forced labor camp. Seven of those graves were explored to identify the people buried in such an unusual manner and to find out what had caused their deaths. A thorough multidisciplinary study, combining the forensic disciplines of archaeology, anthropology, medicine, and genetics provided the answer.

Considering archaeological findings, it can be deduced that the graves belong to the Treblinka guards. The analysis conducted by an anthropologist indicates that the assessed biological profile aligns with the antemortem data of the Treblinka watchmen. Moreover, a study examining perimortem trauma has unveiled that out of the seven men studied, at least two met a violent demise. These findings are crucial in narrowing down the identification process.

The results of our study contribute to a general understanding of the funerary customs prevalent in concentration camps worldwide. Prior to this work, there had never been any analysis or publication of the characteristics of watchmen graves at Nazi camps, making our results unique.
Density, abundance, and activity of the chilla or grey fox (Lycalopex griseus) in Isla Grande de Tierra del Fuego, Chile
Authors: Zurita Carlos , Oporto Javier , Valverde Ignacio , Bernales Borja , Soto Nicolás , Rau Jaime R. , Jaksic Fabián M.
Published: February 2024

Background

The chilla or grey fox (Lycalopex griseus) is a native species from continental Chile and neighboring areas of Argentina. It was introduced to Isla Grande de Tierra del Fuego in 1951 and began to increase its abundance, to the chagrin of local sheep ranchers. Since 1998, its hunting has been authorized. Here we update information on the density, abundance, and activity of this fox in the Chilean sector of Tierra del Fuego Island, to evaluate its population trend since the last census conducted by the Servicio Agrícola y Ganadero (SAG) in 2007.

Methods and results

We carried out two fox censuses on a 941-km transect on public roads, divided into eight routes, from October to November (spring) of 2021 and 2022, following the same design used by SAG for the fox assessments carried out from 1999 to 2007. We report a reduction of > 50% in the density and abundance of chilla foxes with respect to the 2007 estimate, which could be attributed to the interference by free-ranging dogs (Canis lupus familiaris), through restricting the use of space by the fox, while transmitting diseases and parasites, and to human hunting pressure and vehicle collisions.

Discussion

The chilla fox decline highlights the need for an in-depth study to determine the ecological and socioeconomic impact of this exotic species on the ecosystems of Tierra del Fuego Island and the desirability of its management, if needed.
Bioinformatic analysis and experimental validation of cuproptosis-related LncRNA as a novel biomarker for prognosis and immunotherapy of oral squamous cell carcinoma
Authors: Liang Shuang , Ji Lanting , Yu Zhenyuan , Cheng YaHsin , Gao Ruifang , Yan Wenpeng , Zhang Fang
Published: February 2024

Background

The novel form of regulatory cell death, cuproptosis, is characterized by proteotoxicity, which ultimately leads to cell death. Its targeting has emerged as a promising therapeutic approach for oral squamous cell carcinoma (OSCC). Long noncoding RNAs (lncRNAs) participate in epigenetic regulation and have been linked to the progression, prognosis, and treatment of OSCC. Thus, this study aimed to identify new cuproptosis-related lncRNAs (CRLs), establish predictive models for clinical prognosis, immune response, and drug sensitivity, and provide novel insights into immune escape and tumor drug resistance.

Methods

The present study screened eight CRLs (THAP9-AS1, STARD4-AS1, WDFY3-AS2, LINC00847, CDKN2A-DT, AL132800.1, GCC2-AS1, AC005746.1) using Lasso Cox regression analysis to develop an eight-CRL prognostic model. Patients were categorized into high- and low-risk groups using risk scores. To evaluate the predictive ability of the model, Kaplan-Meier analysis, ROC curves, and nomograms were employed. Furthermore, the study investigated the differences in immune function and anticancer drug sensitivity between the high- and low-risk groups. To validate the expression of CRLs in the model, OSCC cell lines were subjected to quantitative real-time fluorescence PCR (qRT-PCR).

Results

The results of the study showed that the high-risk group had a shorter overall survival (OS) time in OSCC patients. Cox regression analysis demonstrated that the high-risk score was an independent risk factor for a poor prognosis. The validity of the model was confirmed using ROC curve analysis, and a nomogram was developed to predict the prognosis of OSCC patients. Furthermore, patients in the high-risk group with high TMB had a poorer prognosis. Patients in the low-risk group responded better to immunotherapy than those in the high-risk group. Additionally, the risk scores were significantly associated with drug sensitivity in OSCC patients. Finally, the findings of qRT-PCR supported the reliability of the proposed risk model.

Conclusion

The study identified and established the 8-CRL model, which represents a novel pathway of lncRNA regulation of cuproptosis in OSCC. This model provides guidance for the prognosis and treatment of OSCC and offers a new insight into immune escape and tumor drug resistance.
Characterization and bioassay of indigenous isolates of the fall armyworm, Spodoptera frugiperda nucleopolyhedrovirus in India
Authors: Pandi Ram Kumar , Gopalsamy Sivakumar , Onkarappa Dhanyakumar , Thiruvengadam Venkatesan , Muthugounder Mohan , Nand Sushil Satya
Published: February 2024

Background

Maize fall armyworm, Spodoptera frugiperda (J. E. Smith) (Lepidoptera: Noctuidae), is a highly migratory polyphagous insect pest that has posed itself as a very threatened insect invaded India since May 2018 and devastated the maize crop. This insect pest caused 62.5% damage on maize plants in Hassan district of Karnataka state, India. Surveys were undertaken in different parts of the country to assess the natural occurrences of all three categories of entomopathogens (bacteria, fungi, and viruses) associated with fall armyworm. Maximum occurrence of infection of entomopathogens (15.13%) was recorded from Chikkaballapura, Karnataka, followed by 12.23% from Hassan, Karnataka.

Results

Totally 13 isolates of S. frugiperda nucleopolyhedrovirus (SpfrNPV) were collected from 13 locations of the country. Electron microscopy studies clearly showed the tetrahedral shaped occlusion bodies of SpfrNPV with the size of 1.48–1.68 µm. The identity of highly virulent SpfrNPV NBAIR1 (Chikkaballapura isolate) was confirmed using conserved polyhedrin gene-specific primers and NCBI GenBank accession number was obtained (MT422725). Bioassay studies revealed that the SpfrNPV NBAIR1 Chikkaballapura isolate was highly virulent with the highest larval mortality (95.50%) and the lowest LC50 value of 2.11 × 103 OBs/ml. SpfrNPV is exclusively host specific and did not infect any other insect species other than S. frugiperda tested in this present study.

Conclusions

Among 13 isolates of SpfrNPV, SpfrNPV NBAIR1 Chikkaballapura isolate was highly virulent with respect to the larval mortality. Hence SpfrNPV NBAIR1 Chikkaballapura isolate is having a great potential to play in the management of maize fall armyworm S. frugiperda.
Primary Tumor Resection Before Systemic Therapy in Patients With Colon Cancer and Unresectable Metastases: Combined Results of the SYNCHRONOUS and CCRe-IV Trials
Authors: Rahbari Nuh N. , Biondo Sebastiano , Frago Ricardo , Feißt Manuel , Kreisler Esther , Rossion Inga , Serrano Monica , Jäger Dirk , Lehmann Monika , Sommer Florian , Dignass Axel , Bolling Claus , Vogel Ilka , Bork Ulrich , Büchler Markus W. , Folprecht Gunnar , Kieser Meinhard , Lordick Florian , Weitz Jürgen , Paty P.B. , Hermann R. , Schmoor C.
Published: February 2024

PURPOSE

Chemotherapy is established as primary treatment in patients with stage IV colorectal cancer and unresectable metastases. Data from nonrandomized clinical trials have fueled persistent uncertainty if primary tumor resection (PTR) before chemotherapy prolongs survival. We investigated the prognostic value of PTR in patients with newly diagnosed stage IV colon cancer who were not amenable to curative treatment.

PATIENTS AND METHODS

Patients enrolled in the multicenter, randomized SYNCHRONOUS and CCRe-IV trials were included in the analysis. Patients with colon cancer with synchronous unresectable metastases were randomly assigned at 100 sites in Austria, Germany, and Spain to undergo PTR or up-front chemotherapy (No PTR group). The chemotherapy regimen was left at discretion of the local team. Patients with tumor-related symptoms, inability to tolerate surgery and/or systemic chemotherapy, and history of another cancer were excluded. The primary end point was overall survival (OS), and the analyses were performed with intention-to-treat.

RESULTS

A total of 393 patients were randomly assigned to undergo PTR (n = 187) or no PTR (n = 206) between November 2011 and March 2017. Chemotherapy was not administered to 6.4% in the No PTR group and 24.1% in the PTR group. The median follow-up time was 36.7 months (95% CI, 36.6 to 37.3). The median OS was 16.7 months (95% CI, 13.2 to 19.2) in the PTR group and 18.6 months (95% CI, 16.2 to 22.3) in the No PTR group ( P = .191). Comparable OS between the study groups was further confirmed on multivariate analysis (hazard ratio, 0.944 [95% CI, 0.738 to 1.209], P = .65) and across all subgroups. Patients with serious adverse events were more common in the No PTR group (10.2% v 18.0%; P = .027).

CONCLUSION

Among patients with colon cancer and synchronous unresectable metastases, PTR before systemic chemotherapy was not associated with prolonged OS.
Relativistic energy density functional from momentum space to coordinate space within a coherent density fluctuation model
Authors: Yadav Praveen K. , Kumar Raj , Bhuyan M.
Published: February 2024

In this theoretical study, we have derived a simplified analytical expression for the binding energy per nucleon as a function of density and isospin asymmetry within the relativistic mean-field model. We have generated a new parameterization for the density-dependent DD-ME2 parameter set using the Relativistic-Hartree-Bogoliubov approach. Moreover, this work attempts to revisit the prior polynomial fitting in Kumar A. et al. Phys. Rev. C, 103 (2021) 024305 for the non-linear NL3 force parameter to provide a simplified set of equations for the energy density functional which is used for calculating the surface properties of finite nuclei. The current study improves the existing fitting procedure by effectively proposing a simpler model that provides comparably precise results while lowering the computational expense. To study the surface properties of finite nuclei with these parameterizations, we have adopted the coherent density fluctuation model, which effectively translates the quantities of nuclear matter from momentum space to coordinate space at local density. The isospin properties, such as symmetry energy and its surface and volume components, slope parameter, finite nuclear incompressibility, and surface incompressibility for even-even nuclei, are calculated for different mass regions. Moreover, we have studied the effect of density, weight function, and choice of relativistic force parameters on the surface properties. The significance of this work will help to determine the properties of nuclei along the nuclear landscape and can facilitate an improved understanding of the island of stability, heavy-ion collision, and nucleosynthesis, among others.
Higher Parametric Thyroid Feedback Quantile-based Index Is a Predictor of Type 2 Diabetes in a German Population Sample
Authors: Laclaustra Martin , Alonso-Ventura Vanesa , Schipf Sabine , Lou-Bonafonte Jose Manuel , Dörr Marcus , Trincado-Aznar Pablo , Völzke Henry , Nauck Matthias , Civeira Fernando , Ittermann Till
Published: February 2024

Context

Type 2 diabetes has been described to be associated with hypothyroidism but we recently found that a decrease in pituitary sensitivity to thyroid hormone is associated with diabetes, obesity, and metabolic syndrome.

Objective

We aimed to assess the longitudinal nature of this association in the population-based Study of Health in Pomerania (SHIP) in Germany.

Methods

Among a population-based sample of 4308 participants aged 20 to 79 years, 77% were followed for a period of 5 years. We studied 2542 participants without diabetes or thyroid medication at baseline and complete data in the variables of interest. Data of baseline free thyroxine (fT4) and thyrotropin (TSH) were used to calculate the Parametric Thyroid Feedback Quantile-based Index (PTFQI), which measures whether TSH remains elevated despite fT4 being high. It uses the average population response as reference. PTFQI association with incidence of type 2 diabetes over 5 years was estimated with Poisson regression models adjusted for age, sex, and body mass index (BMI).

Results

Compared with the first PTFQI quartile, incidence rate ratios for diabetes were 1.54 (95% CI, 0.97-2.46), 1.55 (0.94-2.57), and 1.97 (1.27-3.10) for the upper quartiles (P trend = .004) after adjusting for age and sex. The association remained statistically significant after additionally adjusting for BMI: 1.64 (1.05-2.59) for the fourth vs the first quartile (P trend = .043).

Conclusion

An elevation of the pituitary TSH-inhibition threshold is associated with incident type 2 diabetes independently of BMI. The PTFQI might have clinical potential for prognosis and metabolic status monitoring.