bluuebunny/crossref_metadata_2025 huggingface dataset:
The psychological syndrome associated with Long-COVID: A study protocol
Authors: Gómez Bravo Raquel , Infanti Alexandre , Billieux Joël , Ritzen Mark ,   Psy-Long-COVID Consortium, Vögele Claus , Benoy Charles
Published: August 2023

Introduction

Chronic post-viral syndromes, including Long-COVID, are characterized by a range of persistent symptoms that occur following a viral infection. Psychological symptoms are prevalent in Long-COVID patients and can have a significant impact on their quality of life. However, the specific patterns of psychological symptoms, their associations with physical symptoms, and the factors predicting their severity remain poorly understood.

Aims

This study aims to explore and systematically assess psychological symptoms in Long-COVID, to identify syndrome clusters based on these symptoms, to examine their relationship with physical symptoms, and to investigate the influence of pandemic-related variables.

Methods

Descriptive, cross-sectional study with data collected through an online questionnaire across several EU countries, from February 2020 to December 2022. Participants were recruited using public relations, the social media and information campaigns directed at the public and health professionals using snowball sampling.

Results

The findings will allow to phenotype Long-COVID related psychological symptom clusters based on self-reports. facilitating improved assessment and treatment approaches.

Conclusions

The results will provide important knowledge for the public health management of the public healh management of Long COVID. The findings will contribute to a better understanding of the psychological symptoms associated with Long-COVID and the development of specific treatment guidelines for psychological burden associated with Long-COVID, thereby supporting management strategies to combat the after-effects of the COVID-19 pandemic, enhancing their overall well-being and quality of life.
Induction of liver-resident memory T cells and protection at liver-stage malaria by mRNA-containing lipid nanoparticles
Authors: Nakamae Sayuri , Miyagawa Satoshi , Ogawa Koki , Kamiya Mariko , Taniguchi Mayumi , Ono Akari , Kawaguchi Maho , Teklemichael Awet Alem , Jian Jiun-Yu , Araki Tamasa , Katagami Yukimi , Mukai Hidefumi , Annoura Takeshi , Yui Katsuyuki , Hirayama Kenji , Kawakami Shigeru , Mizukami Shusaku
Published: August 2023

Recent studies have suggested that CD8+ liver-resident memory T (TRM) cells are crucial in the protection against liver-stage malaria. We used liver-directed mRNA-containing lipid nanoparticles (mRNA-LNPs) to induce liver TRM cells in a murine model. Single-dose intravenous injections of ovalbumin mRNA-LNPs effectively induced antigen-specific cytotoxic T lymphocytes in a dose-dependent manner in the liver on day 7. TRM cells (CD8+ CD44hi CD62Llo CD69+ KLRG1-) were induced 5 weeks after immunization. To examine the protective efficacy, mice were intramuscularly immunized with two doses of circumsporozoite protein mRNA-LNPs at 3-week intervals and challenged with sporozoites of Plasmodium berghei ANKA. Sterile immunity was observed in some of the mice, and the other mice showed a delay in blood-stage development when compared with the control mice. mRNA-LNPs therefore induce memory CD8+ T cells that can protect against sporozoites during liver-stage malaria and may provide a basis for vaccines against the disease.
Pseudotemporal ordering of spatial lymphoid tissue microenvironment profiles trails Unclassified DLBCL at the periphery of the follicle
Authors: Tripodo Claudio , Bertolazzi Giorgio , Cancila Valeria , Morello Gaia , Iannitto Emilio
Published: August 2023

We have established a pseudotemporal ordering for the transcriptional signatures of distinct microregions within reactive lymphoid tissues, namely germinal center dark zones (DZ), germinal center light zones (LZ), and peri-follicular areas (Peri). By utilizing this pseudotime trajectory derived from the functional microenvironments of DZ, LZ, and Peri, we have ordered the transcriptomes of Diffuse Large B-cell Lymphoma cases. The apex of the resulting pseudotemporal trajectory, which is characterized by enrichment of molecular programs fronted by TNFR signaling and inhibitory immune checkpoint overexpression, intercepts a discrete peri-follicular biology. This observation is associated with DLBCL cases that are enriched in the Unclassified/type-3 COO category, raising questions about the potential extra-GC microenvironment imprint of this peculiar group of cases. This report offers a thought-provoking perspective on the relationship between transcriptional profiling of functional lymphoid tissue microenvironments and the evolving concept of the cell of origin in Diffuse Large B-cell Lymphomas.
Dichotomous sperm in Lepidopteran insects: a biorational target for pest management
Authors: Seth Rakesh K. , Yadav Priya , Reynolds Stuart E.
Published: August 2023

Lepidoptera are unusual in possessing two distinct kinds of sperm, regular nucleated (eupyrene) sperm and anucleate (apyrene) sperm (‘parasperm’). Sperm of both types are transferred to the female and are required for male fertility. Apyrene sperm play ‘helper’ roles, assisting eupyrene sperm to gain access to unfertilized eggs and influencing the reproductive behavior of mated female moths. Sperm development and behavior are promising targets for environmentally safer, target-specific biorational control strategies in lepidopteran pest insects. Sperm dimorphism provides a wide window in which to manipulate sperm functionality and dynamics, thereby impairing the reproductive fitness of pest species. Opportunities to interfere with spermatozoa are available not only while sperm are still in the male (before copulation), but also in the female (after copulation, when sperm are still in the male-provided spermatophore, or during storage in the female’s spermatheca). Biomolecular technologies like RNAi, miRNAs and CRISPR-Cas9 are promising strategies to achieve lepidopteran pest control by targeting genes directly or indirectly involved in dichotomous sperm production, function, or persistence.
Temporal variations of the two oxygen depleted zones in the Bohai Sea
Authors: Wang Hanzheng , Zhang Haiyan , Wei Hao , Zuo Han
Published: August 2023

The Bohai Sea (BS) has been experiencing prominent deoxygenation in recent years that forms a typically coastal oxygen depleted region in summer. A three-dimensional coupled physical-biogeochemical model was used in this study to investigate temporal variations of the two separately-developing oxygen depleted zones in the BS. Comparison with observations shows a good model performance for multi-year’s oxygen depletion simulation. Two separately-developing oxygen depleted cores are always identified in these years with a threshold of oxygen concentration less than 3 mg/L. The oxygen depletion in the northern core is generally more severe with larger areas and lower oxygen minima. During the evolution of oxygen depletion, the bottom oxygen concentration decreases more smoothly in the northern core, while fluctuates frequently in the southern core. Nonetheless, the oxygen depletion in both cores fades away almost simultaneously, with a sudden oxygen increase in late summer or early autumn. Oxygen budget estimation indicates that the biological oxygen consumption in the southern core is greater than that in the northern core, but compensated by the oxygen replenishment of oxygen-rich water from the Bohai Strait and vertical diffusion of the water column, which is less in the northern core, so that the oxygen depletion in the northern core is more severe. During oxygen depletion development in June and July, bottom oxygen in the southern core is more susceptible to strong winds than the northern core attributed to differences in topography, with a shallower and smoother bathymetry leading to weaker water column stability in summer. Recognition of characteristics of the two separate oxygen depleted cores would advance understanding spatial pattern of oxygen dynamics and provide a basis for statistical seasonal prediction of coastal oxygen depletion with consideration of spatial heterogeneity.
Bioinformatics-based and multiscale convolutional neural network screening of herbal medicines for improving the prognosis of liver cancer: a novel approach
Authors: Chen Zeshan , Peng Peichun , Wang Miaodong , Deng Xin , Chen Rudi
Published: August 2023

Background

Liver cancer is one of the major diseases threatening human life and health, and this study aims to explore new methods for treating liver cancer.

Methods

A deep learning model for the efficacy of clinical herbal medicines for liver cancer was constructed based on NDCNN, combined with the natural evolutionary rules of a genetic algorithm to obtain the herbal compound for liver cancer treatment. We obtained differential genes between liver cancer tissues and normal tissues from the analysis of TCGA database, screened the active ingredients and corresponding targets of the herbal compound using the TCMSP database, mapped the intersection to obtain the potential targets of the herbal compound for liver cancer treatment in the Venny platform, constructed a PPI network, and conducted GO analysis and KEGG analysis on the targets of the herbal compound for liver cancer treatment. Finally, the key active ingredients and important targets were molecularly docked.

Results

The accuracy of the NDCNN training set was 0.92, and the accuracy of the test set was 0.84. After combining with the genetic algorithm for 1,000 iterations, a set of Chinese herbal compound prescriptions was finally the output. A total of 86 targets of the herbal compound for liver cancer were obtained, mainly five core targets of IL-6, ESR1, JUN, IL1β, and MMP9. Among them, quercetin, kaempferol, and stigmasterol may be the key active ingredients in hepatocellular carcinoma, and the herbal compound may be participating in an inflammatory response and the immune regulation process by mediating the IL-17 signaling pathway, the TNF signaling pathway, and so on. The anticancer effects of the herbal compound may be mediated by the IL-17 signaling pathway, the TNF signaling pathway, and other signaling pathways involved in inflammatory response and immune regulation. Molecular docking showed that the three core target proteins produced stable binding to the two main active ingredients.

Conclusion

The screening of effective herbal compounds for the clinical treatment of liver cancer based on NDCNN and genetic algorithms is a feasible approach and will provide ideas for the development of herbal medicines for the treatment of liver cancer and other cancers.
Case report: Endoscopic retrieval of a proximally migrated pancreatic stent using the basket-through- the-sphincterotome technique
Authors: Yi Hang , Liu Qin , He Song , Zhong Li , Guo Xiaodong , Wu Suhua , Ning Bo
Published: August 2023

Background

The retrieval of a proximally migrated pancreatic duct (PD) stent via endoscopic retrograde cholangiopancreatography (ERCP) is technically challenging, often requiring surgical intervention. We report a case with proximal migration of a pancreatic stent that was successfully removed by a basket-through-the-sphincterotome technique.

Case presentation

A 46-year-old man with prior history of chronic pancreatitis was admitted to our hospital with 1 month history of epigastric discomfort. 9 months prior he had undergone ERCP with Endoscopic sphincterotomy (EST) and a 5 Fr × 9 cm plastic pancreatic stent placement to relieve pancreatic duct stricture and abdominal pain. Magnetic retrograde cholangiopancreatography (MRCP) done this time revealed PD dilation and a stent-shaped signal inside the PD. The subsequent endoscopic ultrasonography (EUS) verified total pancreatic stent proximal migration with no visible distal end of the stent in the papilla. ERCP was performed again with an attempt to retrieve the stent. General techniques of PD cannulation with a 0.035-in guidewire over the migrated stent and balloon extraction failed. We used a mini-basket (Endoflex Germany) to replace the guidewire, which was inserted into the PD and advanced over the proximal end of the stent through the channel of the sphincterotome. The distal end of the stent was easily caught by manipulating the tip of the sphincterotome, and the stent was then pulled out. A naso-pancreatic drainage tube was placed in the main PD, and the patient was discharged 2 days after tube withdrawal.

Conclusion

This was a successful case of proximally migrated pancreatic stent retrieval using the unique idea of basket-through-the-sphincterotome technique, which has rarely been reported. The basket-through-the-sphincterotome technique provides the endoscopist another way to catch the distal end without difficulty. It can improve the success rate of proximally migrated pancreatic stent retrieval, especially the pig-tail pancreatic stent, of which the sticking of the proximal end into pancreatic duct branches often makes the distal end the only choice to retrieve.
Bridging the gap: safety and outcomes of intensivist-led ECMO retrievals
Authors: Mihu Mircea R. , Maybauer Marc O. , Cain Kaitlyn , Swant Laura V. , Harper Michael D. , Schoaps Robert S. , Brewer Joseph M. , Sharif Ammar , Benson Clayne , El Banayosy Ahmed M. , El Banayosy Aly
Published: August 2023

Purpose

Most extracorporeal membrane oxygenation (ECMO) cannulations are performed by cardiothoracic surgeons (CTS). Due to an increase in utilization of ECMO and limited availability of CTS, there is a mismatch between ECMO demand and CTS accessibility for remote cannulations. We report our intensivist-led program’s experience in remote ECMO cannulations, retrievals, complications, and outcomes.

Materials and methods

A prospective, single-center, observational study was performed on patients that required ECMO cannulation at the referring facilities and were transported to our institution between program initiation, on October 1, 2014 to September 30, 2022. Results were presented as mean ± SD, median (min – max) or number (%).

Results

Since program commencement, 305 patients were accepted for ECMO retrieval. Three hundred and three patients were placed on ECMO at the 47 referring hospitals among 5 states. In our study, 185 (61%) patients required veno-arterial ECMO and 115 (38%) were placed on veno-venous ECMO. Three patients (1%) were cannulated for veno-arteriovenous ECMO. Twenty patients were cannulated under cardio-pulmonary resuscitation. Most of the patients were transported by ambulance (79%), 14% by helicopter, and 7% by airplane. Six out of the 303 patients did not leave the referring facility. All patients that left the referring hospitals arrived safely to our institution. No major complications occurred in route.

Conclusion

Our study’s findings indicate that non-CTS physicians can successfully cannulate and retrieve patients with a low complication profile.
Mitochondrial calcium signaling and redox homeostasis in cardiac health and disease
Authors: Popoiu Tudor-Alexandru , Maack Christoph , Bertero Edoardo
Published: August 2023

The energy demand of cardiomyocytes changes continuously in response to variations in cardiac workload. Cardiac excitation-contraction coupling is fueled primarily by adenosine triphosphate (ATP) production by oxidative phosphorylation in mitochondria. The rate of mitochondrial oxidative metabolism is matched to the rate of ATP consumption in the cytosol by the parallel activation of oxidative phosphorylation by calcium (Ca2+) and adenosine diphosphate (ADP). During cardiac workload transitions, Ca2+ accumulates in the mitochondrial matrix, where it stimulates the activity of the tricarboxylic acid cycle. In this review, we describe how mitochondria internalize and extrude Ca2+, the relevance of this process for ATP production and redox homeostasis in the healthy heart, and how derangements in ion handling cause mitochondrial and cardiomyocyte dysfunction in heart failure.
The association between retina thinning and hippocampal atrophy in Alzheimer’s disease and mild cognitive impairment: a meta-analysis and systematic review
Authors: Chen Shuntai , Zhang Dian , Zheng Honggang , Cao Tianyu , Xia Kun , Su Mingwan , Meng Qinggang
Published: August 2023

Introduction

The retina is the “window” of the central nervous system. Previous studies discovered that retinal thickness degenerates through the pathological process of the Alzheimer’s disease (AD) continuum. Hippocampal atrophy is one of the typical clinical features and diagnostic criteria of AD. Former studies have described retinal thinning in normal aging subjects and AD patients, yet the association between retinal thickness and hippocampal atrophy in AD is unclear. The optical coherence tomography (OCT) technique has access the non-invasive to retinal images and magnetic resonance imaging can outline the volume of the hippocampus. Thus, we aim to quantify the correlation between these two parameters to identify whether the retina can be a new biomarker for early AD detection.

Methods

We systematically searched the PubMed, Embase, and Web of Science databases from inception to May 2023 for studies investigating the correlation between retinal thickness and hippocampal volume. The Newcastle-Ottawa Quality Assessment Scale (NOS) was used to assess the study quality. Pooled correlation coefficient r values were combined after Fisher’s Z transformation. Moderator effects were detected through subgroup analysis and the meta-regression method.

Results

Of the 1,596 citations initially identified, we excluded 1,062 studies after screening the titles and abstract (animal models, n = 99; irrelevant literature, n = 963). Twelve studies met the inclusion criteria, among which three studies were excluded due to unextractable data. Nine studies were eligible for this meta-analysis. A positive moderate correlation between the retinal thickness was discovered in all participants of with AD, mild cognitive impairment (MCI), and normal controls (NC) (r = 0.3469, 95% CI: 0.2490–0.4377, I2 = 5.0%), which was significantly higher than that of the AD group (r = 0.1209, 95% CI:0.0905–0.1510, I2 = 0.0%) (p < 0.05). Among different layers, the peripapillary retinal nerve fiber layer (pRNFL) indicated a moderate positive correlation with hippocampal volume (r = 0.1209, 95% CI:0.0905–0.1510, I2 = 0.0%). The retinal pigmented epithelium (RPE) was also positively correlated [r = 0.1421, 95% CI:(−0.0447–0.3192), I2 = 84.1%]. The retinal layers and participants were the main overall heterogeneity sources. Correlation in the bilateral hemisphere did not show a significant difference.

Conclusion

The correlation between RNFL thickness and hippocampal volume is more predominant in both NC and AD groups than other layers. Whole retinal thickness is positively correlated to hippocampal volume not only in AD continuum, especially in MCI, but also in NC.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/, CRD42022328088.
Case report: Hereditary spastic paraplegia with a novel homozygous mutation in ZFYVE26
Authors: Lai Ze-hua , Liu Xiao-ying , Song Yuan-yue , Zhou Hai-yan , Zeng Li-li
Published: August 2023

Hereditary spastic paraplegia (HSP) is a group of neurodegenerative diseases with genetic and clinical heterogeneity characterized by spasticity and weakness of the lower limbs. It includes four genetic inheritance forms: autosomal dominant inheritance (AD), autosomal recessive inheritance (AR), X-linked inheritance, and mitochondrial inheritance. To date, more than 82 gene loci have been found to cause HSP, and SPG15 (ZFYVE26) is one of the most common autosomal recessive hereditary spastic paraplegias (ARHSPs) with a thin corpus callosum (TCC), presents with early cognitive impairment and slowly progressive leg weakness. Here, we reported a homozygous pathogenic variant in ZFYVE26. A 19-year-old Chinese girl was admitted to our hospital presenting with a 2-year progressive bilateral leg spasticity and weakness; early cognitive impairment; corpus callosum dysplasia; chronic neurogenic injury of the medulla oblongata supplied muscles; and bilateral upper and lower limbs on electromyogram (EMG). Based on these clinical and electrophysiological features, HSP was suspected. Exome sequencing of the family was performed by high-throughput sequencing, and an analysis of the patient showed a ZFYVE26 NM_015346: c.7111dupA p.(M2371Nfs*51) homozygous mutation. This case reported a new ZFYVE26 pathogenic variant, which was different from the SPG15 gene mutation reported earlier.
Audiogenic epileptic DBA/2 mice strain as a model of genetic reflex seizures and SUDEP
Authors: Bosco Francesca , Guarnieri Lorenza , Leo Antonio , Tallarico Martina , Gallelli Luca , Rania Vincenzo , Citraro Rita , De Sarro Giovambattista
Published: August 2023

Epilepsy is a chronic neurological disease characterized by abnormal brain activity, which results in repeated spontaneous seizures. Sudden unexpected death in epilepsy (SUDEP) is the leading cause of seizure-related premature death, particularly in drug-resistant epilepsy patients. The etiology of SUDEP is a structural injury to the brain that is not fully understood, but it is frequently associated with poorly controlled and repeated generalized tonic–clonic seizures (GTCSs) that cause cardiorespiratory and autonomic dysfunctions, indicating the involvement of the brainstem. Both respiratory and cardiac abnormalities have been observed in SUDEP, but not much progress has been made in their prevention. Owing to the complexity of SUDEP, experimental animal models have been used to investigate cardiac and/or respiratory dysregulation due to or associated with epileptic seizures that may contribute to death in humans. Numerous rodent models, especially mouse models, have been developed to better understand epilepsy and SUDEP physiopathology. This review synthesizes the current knowledge about dilute brown agouti coat color (DBA/2) mice as a possible SUDEP model because respiratory arrest (RA) and sudden death induced by audiogenic generalized seizures (AGSs) have been observed in these animals. Respiratory/cardiac dysfunction, brainstem arousal system dysfunction, and alteration of the neurotransmitter systems, which are observed in human SUDEP, have also been observed in these mice. In particular, serotonin (5-HT) alteration and adenosine neurotransmission appear to contribute to not only the pathophysiological mechanisms of medication but also seizure-related respiratory dysfunctions in this animal model. These neurotransmitter systems could be the relevant targets for medication development for chronic epilepsy and SUDEP prevention. We reviewed data on AGSs in DBA/2 mice and the relevance of this model of generalized tonic–clonic epilepsy to human SUDEP. Furthermore, the advantages of using this strain prone to AGSs for the identification of possible new therapeutic targets and treatment options have also been assessed.
4E-BP1 expression in embryonic postmitotic neurons mitigates mTORC1-induced cortical malformations and behavioral seizure severity but does not prevent epilepsy in mice
Authors: Nguyen Lena H. , Sharma Manas , Bordey Angelique
Published: August 2023

Hyperactivation of the mechanistic target of rapamycin complex 1 (mTORC1) pathway during neurodevelopment leads to focal cortical malformations associated with intractable seizures. Recent evidence suggests that dysregulated cap-dependent translation downstream of mTORC1 contributes to cytoarchitectural abnormalities and seizure activity. Here, we examined whether reducing cap-dependent translation by expressing a constitutively active form of the translational repressor, 4E-BP1, downstream of mTORC1 would prevent the development of cortical malformations and seizures. 4E-BP1CA was expressed embryonically either in radial glia (neural progenitor cells) that generate cortical layer 2/3 pyramidal neurons or in migrating neurons destined to layer 2/3 using a conditional expression system. In both conditions, 4E-BP1CA expression reduced mTORC1-induced neuronal hypertrophy and alleviated cortical mislamination, but a subset of ectopic neurons persisted in the deep layers and the white matter. Despite the above improvements, 4E-BP1CA expression in radial glia had no effects on seizure frequency and further exacerbated behavioral seizure severity associated with mTORC1 hyperactivation. In contrast, conditional 4E-BP1CA expression in migratory neurons mitigated the severity of behavioral seizures but the seizure frequency remained unchanged. These findings advise against targeting 4E-BPs by 4E-BP1CA expression during embryonic development for seizure prevention and suggest the presence of a development-dependent role for 4E-BPs in mTORC1-induced epilepsy.
Case Report: A rare case of recurrent ascites after anti-Claudin18.2 antibody therapy for metastatic gastric cancer while responding sustainingly
Authors: Liu Jinlu , Jiang Dan , Lei Qingqiang , Zhu Qing , Zhu Hong
Published: August 2023

Background

Gastric cancer remains one of the deadliest malignancies in the world, thus urgently requiring effective and safe therapeutics. Claudin18.2 is a member of the tight junction protein family specifically expressed in gastric cancer cells. Monoclonal antibodies targeting Claudin18.2 have been receiving increasing attention recently. ASKB589 is a humanized monoclonal antibody targeting Claudin18.2.

Case presentation

This case described a 65-year-old Chinese man diagnosed with gastric cancer metastasizing to the liver and multiple lymph nodes. The biomarker examination revealed that he had proficient mismatch repair (pMMR), human epidermal growth factor receptor 2 (HER2) was negative, and the combined proportion score (CPS) of PD-L1 (22C3) was 1. After being proven to be moderately positive for Claudin18.2 expression, he received ASKB589 and CAPOX (oxaliplatin and capecitabine) chemotherapy. After a six-cycle therapy (from 14 July 2022 to 29 November 2022), the target tumor was evaluated for partial response (PR) by the investigator based on the enhanced CT scan according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. However, this patient also suffered from intolerable ascites that gradually aggravated during the therapy, which was not controlled well by the supporting therapy. Therefore, the patient stopped receiving the combined therapy in our hospital and did not receive any other anti-tumor treatment. After 4 months of discontinuation of the drug, the patient’s ascites almost disappeared, while the tumor continued to reduce and almost achieved clinically complete relapse (cCR). His progression-free survival (PFS) reached at least 10 months.

Conclusion

This is the first case of severe ascites reported after anti-Claudin18.2 monoclonal antibody treatment for advanced gastric cancer. At the same time, the patient still benefited significantly from this incomplete treatment even after discontinuation of the drug and the PFS reached at least 10 months. The ascites might be an immune adverse effect related to the monoclonal antibody-induced antibody-dependent cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Further mechanisms remain to be investigated.
CT-based radiomics for predicting radio-chemotherapy response and overall survival in nonsurgical esophageal carcinoma
Authors: Li Chao , Pan Yuteng , Yang Xianghui , Jing Di , Chen Yu , Luo Chenhua , Qiu Jianfeng , Hu Yongmei , Zhang Zijian , Shi Liting , Shen Liangfang , Zhou Rongrong , Lu Shanfu , Xiao Xiang , Chen Tingyin
Published: August 2023

Background

To predict treatment response and 2 years overall survival (OS) of radio-chemotherapy in patients with esophageal cancer (EC) by radiomics based on the computed tomography (CT) images.

Methods

This study retrospectively collected 171 nonsurgical EC patients treated with radio-chemotherapy from Jan 2010 to Jan 2019. 80 patients were randomly divided into training (n=64) and validation (n=16) cohorts to predict the radiochemotherapy response. The models predicting treatment response were established by Lasso and logistic regression. A total of 156 patients were allocated into the training cohort (n=110), validation cohort (n=23) and test set (n=23) to predict 2-year OS. The Lasso Cox model and Cox proportional hazards model established the models predicting 2-year OS.

Results

To predict the radiochemotherapy response, WFK as a radiomics feature, and clinical stages and clinical M stages (cM) as clinical features were selected to construct the clinical-radiomics model, achieving 0.78 and 0.75 AUC (area under the curve) in the training and validation sets, respectively. Furthermore, radiomics features called WFI and WGI combined with clinical features (smoking index, pathological types, cM) were the optimal predictors to predict 2-year OS. The AUC values of the clinical-radiomics model were 0.71 and 0.70 in the training set and validation set, respectively.

Conclusions

This study demonstrated that planning CT-based radiomics showed the predictability of the radiochemotherapy response and 2-year OS in nonsurgical esophageal carcinoma. The predictive results prior to treatment have the potential to assist physicians in choosing the optimal therapeutic strategy to prolong overall survival.
Refractory microsatellite stable metastatic colorectal cancer with ERBB2/ERBB3 mutation may be preferred population for regorafenib plus PD-1 inhibitor therapy: a real-world study
Authors: Dai Xuan , Ding Wenjun , He Yongshan , Huang Shiyong , Liu Yun , Wu Tingyu
Published: August 2023

Background

Microsatellite stable (MSS) colorectal cancer (CRC) has been referred to as the “cold tumor” because of almost no response to anti–programmed death-1 (PD-1) antibody. A recent REGONIVO trial showed that regorafenib plus nivolumab had an encouraging efficacy in MSS metastatic CRC (mCRC). However, only a small subset of patients may benefit from the combination therapy. We aim to evaluate the efficacy and safety data of immune checkpoint inhibitors combined with regorafenib in refractory MSS mCRC and to discover biomarkers that can effectively stratify the beneficial patient population.

Methods

We retrospectively analyzed patients with MSS mCRC who received regorafenib combined with anti–PD-1 antibody therapy. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and status of gene mutation were reviewed and evaluated.

Results

Twenty-one patients received combination treatment. At a median treatment duration of 4 months, one patient achieved complete response, three patients achieved partial response, and two patients achieved stable disease as the best response. The ORR and DCR were 19% and 28.5% in the overall population, respectively. The median PFS was 4 months, and the median OS was 25 months. Only erbb2 receptor tyrosine kinase 2/erbb3 receptor tyrosine kinase 3 (ERBB2/ERBB3) mutation status was confirmed to be a potential predictive factor for effective treatment. In patients with ERBB2/ERBB3 mutation, ORR, DCR, and PFS exhibited significant improvements in comparison with that in wild-type patients. Grade 3 or higher treatment-related adverse events occurred in three patients (14.3%).

Conclusions

Regorafenib in combination with PD-1 inhibitor provides a feasible treatment regimen for refractory MSS mCRC with tolerated toxicity. Patients with ERBB2/ERBB3 mutation may be the preferred population for this combination regimen.
Interventional effects of oral microecological agents on perioperative indicators of colorectal cancer: a meta-analysis
Authors: Wang Xueyan , Pan Lijun , Wang Feiqing , Long Fengxi , Yang Bing , Tang Dongxin
Published: August 2023

Purpose

To investigate the efficacy of the application of microecological agents in patients with perioperative colorectal cancer.

Methods

The seven electronic databases including PubMed, Cochrane Library, Excerpt Medica Database (Embase), Web of Science (WOS), Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), and Wan-fang Database were systematically searched for eligible studies from 2000 to February 2023.

Results

A total of 38 randomized controlled clinical trials were included in this study, with a total of 1765 patients in the microecological preparation group and 1769 patients in the control group. All data were analyzed using Review Manager 5.4 and R 4.2.2 software. Meta-analysis showed that in the perioperative period of colorectal cancer, the microecological agents group reduced patients’ adverse drug reactions, improved intestinal flora with Lactobacillus (SMD, 3.0858, [2.0197; 4.1520], p< 0. 0001), Bifidobacterium (SMD, 2.1551, [1.6145; 2.6956], p< 0.0001) and Escherichia coli (SMD, -1.1393, [-1.6247; -0.6538], p< 0.0001); protection of intestinal mucosal barrier function, endotoxin (SMD, -2.6850 [-4.1399; -1.2301], p=0.0003), DAO (SMD, -2.5916, [-3.4694; -1.7137], p<0.0001) and plasma D-lactate (SMD, -5.4726, [-9.8901; -1.0551], p= 0.0152), reduced inflammatory response, IL-6 (SMD, -3.1279 [-5.7706; -0.4852], p=0.0204) and CRP (SMD, -3.9698 [-7.6296; -0.3100], p=0.0335); improved the immune function of the organism, CD4+ (SMD, 1.5817 [1.0818; 2.0817], p< 0.0001), CD4+/CD8+ (SMD, 1.2938 [0.9693; 1.6183] p< 0.0001) and IgG (SMD, 1.1376 [0.2993; 1.9759] p=0.0078), improved short-term clinical efficacy, ORR (RR, 1.5105 [1.2306; 1.8541], p< 0.0001) and DCR (RR, 0.3896 [0.2620; 0.5795], p< 0.0001).

Conclusion

By increasing the number of beneficial flora such as Lactobacillus and Bifidobacterium and decreasing the number of harmful flora such as Escherichia coli, the micro-ecological preparation group is beneficial in improving the ecological dysregulation in colorectal cancer patients receiving different treatments in the perioperative period. The microecological preparation group was able to reduce many types of adverse drug reactions, such as infections and gastrointestinal discomfort, compared to the control group. The microecological agents also reduced inflammatory responses, decreased the increase in harmful metabolites, enhanced patients’ immune function, protected intestinal mucosal barrier function, and improved short-term clinical outcomes.

Systematic review registration

https://inplasy.com/inplasy-2023-4-0051/, identifier INPLASY202340051.
Longitudinal prospective anthropometric evaluation in Caucasian prepubertal children with lactose intolerance
Authors: Lizzi Mauro , Sgrazzutti Laura , Porreca Annamaria , Di Filippo Paola , Cauzzo Chiara , Di Pillo Sabrina , Chiarelli Francesco , Attanasi Marina
Published: August 2023

Introduction

The health consequences of lactose intolerance remain unclear. We studied the association of lactose intolerance with growth in children.

Methods

In this prospective case–control study, we compared Caucasian prepubertal children with lactose intolerance (LI) [n = 30, median age = 7.87 years (3.00–12.75)] to healthy controls [(n = 75, median age = 2.25 years (2.00–7.25)]. A lactose tolerance test was performed for lactose intolerance diagnosis. The gastrointestinal symptom score was administered at baseline and after a lactose-free diet for a median period of 9.0 months [range 5%–95% (6.0–24.0)]. The anthropometric parameters were measured at baseline and follow-up. All the anthropometric data were converted into standard deviation scores (SDS). A linear regression model was used to investigate the association of lactose intolerance with growth parameters.

Results

We found no difference in height velocity SDS between the LI and control groups [SDS difference (95% CI): 0.52 (−1.86 to 2.90)]. In addition, we found a significant reduction in the clinical score of the LI group after a lactose-free diet [median (5%–95%): 7.5 (4.0–15.0) and 3 (0.0–8.0); p-value <0.001].

Conclusions

The LI group exhibited no difference in height velocity compared with the control group. Nonetheless, due to the small sample size, the results on the anthropometric profile of the LI group require careful interpretation. More large-scale studies in the pediatric population are required to better understand the association of LI with anthropometric and metabolic profiles.
The changes of Treg and Th17 cells relate to serum 25(OH)D in patients with initial-onset childhood systemic lupus erythematosus
Authors: Jiang Li-jun , Rong Zan-hua , Zhang Hui-feng
Published: August 2023

Background

T helper 17 (Th17) cells and regulatory T cells (Treg) are known to play a crucial role in the pathogenesis of systemic lupus erythematosus (SLE). Improving the balance between Treg and Th17 cells can be a promising new therapeutic target in SLE patients. Vitamin D has a significant impact on the immune inflammatory process and the immune cells involved in this process. The purpose of this study is to investigate the relationship between Th17, Treg, cytokines, and serum 25 hydroxyvitamin D [25(OH)D] in patients with initial-onset childhood SLE.

Methods

A total of 82 children aged <18 years with initial-onset SLE were included, as well as 60 healthy subjects during the same period at the Pediatrics Department of the Second Hospital of Hebei Medical University. The chemiluminescence method was performed to detect serum 25(OH)D levels. Flow cytometry was used to evaluate Treg and Th17 cells. An enzyme-linked immunosorbent assay kit was used to evaluate plasma interleukin (IL)-23, IL-17, IL-10, IL-6, and tumor necrosis factor alpha (TNF-α) concentrations.

Result

The serum 25(OH)D levels in patients with initial-onset childhood SLE were significantly lower than those in the healthy controls. The proportion of lupus nephritis (LN) was higher in the vitamin D insufficiency group (71.4%) compared with the vitamin D sufficiency group (30.3%) (p < 0.05). The SLE disease activity index (SLEDAI) was higher in the vitamin D insufficiency group (median = 14) than that in the vitamin D sufficiency group (median = 9) (p < 0.05).The 25(OH)D level was positively correlated with the Treg ratio (r = 0.337, p = 0.002), and it was negatively correlated with the Th17 cell ratio (r = −0.370, p = 0.001). The serum 25(OH)D level had a negative correlation with IL-23 (r = −0.589, p < 0.001), IL-17(r = −0.351, p = 0.001), TNF-α (r = −0.283, p = 0.01), IL-6 (r = −0.392, p < 0.001), and IL-10 (r = −0.313, p = 0.004) levels.

Conclusion

The serum 25(OH)D levels decreased in patients with initial-onset childhood SLE. There was a negative correlation between the serum 25(OH)D levels and SLEDAI. The serum 25(OH)D levels in patients with initial-onset childhood SLE were negatively correlated with the Th17 ratio and related cytokines, while positively correlated with the Treg ratio.
Body mass index-associated responses to an ABVD-like regimen in newly-diagnosed patients with Hodgkin lymphoma
Authors: Hu Min , Ding Yiduo , Zhang Haizhou , Guo Wei , Li Yun , Jin Zhengming , Qu Changju , Xia Fan
Published: August 2023

Background: The role of body mass index (BMI) in the treatment outcomes of lymphoma patients is controversial. While investigating the efficacy of ABVD-like regimen in Hodgkin lymphoma (HL) patients, we observed that obese patients had poor responses. To better understand this clinical phenomenon, we evaluated the effect of BMI on responses to ABVD-like chemotherapy in HL patients.

Methods: This retrospective cohort study evaluated the clinical outcomes of all 67 patients with confirmed HL who were treated at the First Affiliated Hospital of Soochow University from November 2016 to March 2023 with an ABVD-like regimen as first-line chemotherapy. Baseline patient characteristics and clinical outcomes were compared across different BMI categories. The primary end-point was the overall response rate defined as the proportion of the HL patients who achieved complete response or partial response. The additional end-points included progression-free survival and overall survival.

Results: The median age of the HL patients was 31 years old. Of the patients, 10.4% were obese, and 17.9% patients were overweight. Interim and end-term response evaluations revealed overall response rates of 98.5% and 83.6%, respectively. The proportion of patients with potential poor prognostic factors (IPS risk factors) did not differ significantly in the responders versus non-responders. However, non-responders had a higher average BMI when compared with responders (p = 0.002). Poor overall response rates in higher BMI patients indeed manifested with shorter progression free survival (p = 0.013). The minimum relative dose of the ABVD-like regimen in the overweight and obese groups was significantly lower than in the normal weight group (p < 0.001).

Conclusion: Our analyses show that >80% of newly-diagnosed HL patients responded to the ABVD-like regimen. We find that being obese or overweight at the time of diagnosis correlated with a poorer overall response rate and that BMI was an independent risk factor in HL patients treated with the ABVD-like regimen. Lower doses of ABVD-like regimen contributed to the discrepant findings of responses in the high BMI groups. These findings indicate that newly-diagnosed, obese HL patients receiving an ABVD-like regimen require personalized treatment.
Optical coherence tomography angiography allows longitudinal monitoring of angiogenesis in the critical-sized defect model
Authors: Shen Yiyang , Bu Jin , Yu Lan , Yao Lin , Feng Xiaoyan , Lin Jun , Li Peng
Published: August 2023

Purpose: This study aims to evaluate the capability of optical coherence tomography angiography (OCTA) for imaging the microvasculature within a critical bone defect, to longitudinally observe vascular alterations, and quantify the microvascular density and morphology in a model of a critical-sized defect.

Methods: An OCTA system was used to longitudinally monitor angiogenesis in four rat models presenting critical-sized defects with observations recorded on days 7, 14, and 28 post-defect creation. Simultaneously, angiogenesis in three additional rat models was evaluated through a conventional histological analysis involving hematoxylin and eosin staining.

Results: OCTA was successful in acquiring in vivo 3D vascular perfusion mapping within the critical-sized defect, and it allowed for quantitative analysis of the microvasculature’s density and morphology. The OCTA imagery of the blood microvasculature revealed a noticeable augmentation in the number and size of vessels, with more extensive vessel convergence observed on day 14 compared to both days 7 and 28. Complementing these observations, quantitative analysis demonstrated that the vessel area density (VAD) and maximum vascular diameter index (MVDI) were significantly larger on day 14 in comparison to measurements taken on days 7 and 28.

Conclusion: Leveraging its ability to capture high-resolution images, OCTA facilitated longitudinal monitoring of angiogenesis in models of critical-sized defects. Therefore, it potentially serves as a non-invasive experimental tool beneficial for bone regeneration research.
Integrated transcriptome and metabolome analysis reveals a possible mechanism for the regulation of lipid metabolism via vitamin A in rice field eel (Monopterus albus)
Authors: Huo Huanhuan , Hu Chonghua , Zhou Qiubai , Xiong Liufeng , Peng Mo
Published: August 2023

To understand the effects of vitamin A on lipid deposition in rice field eels, integrated liver transcriptome and metabolome were conducted and the changes in the genes and metabolites were assessed. Three groups of rice field eel were fed with 0, 200, and 16,000 IU/kg vitamin A supplementations in their diets for 70 days. The total lipid content in the whole body of the rice field eels was significantly increased with the vitamin A supplementations (p < 0.05). Comparative transcriptome analysis revealed 14 pathways and 46 differentially expressed genes involved in lipid metabolism. Sphingolipid metabolism, glycerolipid metabolism, primary bile acid biosynthesis and steroid hormone biosynthesis were significantly enriched pathways. In these pathways, three differential genes phospholipid phosphatase 1a (PLPP1a), phospholipid phosphatase 2b (PLPP2b), cytochrome P450 21a2 (CYP21a2) were consistent with the change trend of lipid content, and the other three differential genes aldo-keto reductase family 1 member D1 (AKR1D1), uridine diphosphate glucuronic acid transferase 1a1 (UGT1a1), cytochrome P450 1a (CYP1a) were opposite. Metabolomic analysis revealed that primary bile acid biosynthesis, sphingolipid metabolism, steroid hormone biosynthesis and biosynthesis of unsaturated fatty acids were all critical for rice field eel metabolic changes in response to vitamin A. Six important differential metabolites (eicosapentaenoic acid, sphinganine, 11-beta-hydroxyprogesterone, hydroxyeicosatetraenoic acid, cholic acid, and glycochenodeoxycholate) were identified and have provided new insights into how vitamin A regulates lipid deposition. Integrated transcriptome and metabolome analyses revealed that primary bile acid biosynthesis was the only remarkably enriched pathway in both the transcriptome and metabolome while that sphingosine was the main metabolite. Based on the above results, we have concluded that vitamin A promotes lipid deposition in the rice field eel through the primary bile acid synthesis pathway, and lipid deposits are widely stored in cell membranes, mainly in the form of sphingosine. These results will provide reference data to help improve our understanding of how vitamin A regulates lipid metabolism.
Chromosome-level reference genome assembly provides insights into the evolution of Pennisetum alopecuroides
Authors: Teng Ke , Guo Qiang , Liu Lingyun , Guo Yidi , Xu Yue , Hou Xincun , Teng Wenjun , Zhang Hui , Zhao Chunqiao , Yue Yuesen , Wen Haifeng , Wu Juying , Fan Xifeng
Published: August 2023

Pennisetum alopecuroides is an important forage grass resource, which plays a vital role in ecological environment improvement. Therefore, the acquisition of P. alopecuroides genome resources is conducive to the study of the adaptability of Pennisetum species in ecological remediation and forage breeding development. Here we assembled a P. alopecuroides cv. 'Liqiu' genome at the chromosome level with a size of approximately 845.71 Mb, contig N50 of 84.83Mb, and genome integrity of 99.13% as assessed by CEGMA. A total of 833.41-Mb sequences were mounted on nine chromosomes by Hi-C technology. In total, 60.66% of the repetitive sequences and 34,312 genes were predicted. The genomic evolution analysis showed that P. alopecuroides cv. 'Liqiu' was isolated from Setaria 7.53–13.80 million years ago and from Cenchrus 5.33–8.99 million years ago, respectively. The whole-genome event analysis showed that P. alopecuroides cv. 'Liqiu' underwent two whole-genome duplication (WGD) events in the evolution process, and the duplication events occurred at a similar time to that of Oryza sativa and Setaria viridis. The completion of the genome sequencing of P. alopecuroides cv. 'Liqiu' provides data support for mining high-quality genetic resources of P. alopecuroides and provides a theoretical basis for the origin and evolutionary characteristics of Pennisetum.