bluuebunny/crossref_metadata_2025 huggingface dataset:
Computational approaches for discovering significant microRNAs, microRNA-mRNA regulatory pathways, and therapeutic protein targets in endometrial cancer
Authors: Ajabnoor Ghada , Alsubhi Fai , Shinawi Thoraia , Habhab Wisam , Albaqami Walaa F. , Alqahtani Hussain S. , Nasief Hisham , Bondagji Nabeel , Elango Ramu , Shaik Noor Ahmad , Banaganapalli Babajan
Published: January 2023

Endometrial cancer (EC) is a urogenital cancer affecting millions of post-menopausal women, globally. This study aims to identify key miRNAs, target genes, and drug targets associated with EC metastasis. The global miRNA and mRNA expression datasets of endometrial tissue biopsies (24 tumors +3 healthy tissues for mRNA and 18 tumor +4 healthy tissues for miRNAs), were extensively analyzed by mapping of DEGs, DEMi, biological pathway enrichment, miRNA-mRNA networking, drug target identification, and survival curve output for differentially expressed genes. Our results reveal the dysregulated expression of 26 miRNAs and their 66 target genes involved in focal adhesions, p53 signaling pathway, ECM-receptor interaction, Hedgehog signaling pathway, fat digestion and absorption, glioma as well as retinol metabolism involved in cell growth, migration, and proliferation of endometrial cancer cells. The subsequent miRNA-mRNA network and expression status analysis have narrowed down to 2 hub miRNAs (hsa-mir-200a, hsa-mir-429) and 6 hub genes (PTCH1, FOSB, PDGFRA, CCND2, ABL1, ALDH1A1). Further investigations with different systems biology methods have prioritized ALDH1A1, ABL1 and CCND2 as potential genes involved in endometrial cancer metastasis owing to their high mutation load and expression status. Interestingly, overexpression of PTCH1, ABL1 and FOSB genes are reported to be associated with a low survival rate among cancer patients. The upregulated hsa-mir-200a-b is associated with the decreased expression of the PTCH1, CCND2, PDGFRA, FOSB and ABL1 genes in endometrial cancer tissue while hsa-mir-429 is correlated with the decreased expression of the ALDH1A1 gene, besides some antibodies, PROTACs and inhibitory molecules. In conclusion, this study identified key miRNAs (hsa-mir-200a, hsa-mir-429) and target genes ALDH1A1, ABL1 and CCND2 as potential biomarkers for metastatic endometrial cancers from large-scale gene expression data using systems biology approaches.
Identification of molecular subtypes and a prognostic signature based on chromatin regulators related genes in prostate cancer
Authors: Ma Hangbin , Zhou Cheng , Ge Jianchao , Yu Wandong , Zhou Yinghao , Wang Pengyu , Zhang Xuehu , Zhang Jun , Shi Guowei
Published: January 2023

The clinical and molecular phenotypes of prostate cancer (PCa) exhibit substantial heterogeneity, ranging from indolent to metastatic disease. In this study, we aimed to identify PCa subtypes and construct a gene signature that can predict the recurrence-free survival (RFS) of PCa patients based on chromatin regulators genes (CRGs). Strikingly, we identified two heterogeneous subtypes with distinct clinical and molecular characteristics. Furthermore, by performing differential analysis between the two CRGs subtypes, we successfully constructed a gene signature to predict PCa prognosis. The signature, comprising four genes (MXD3, SSTR1, AMH and PPFIA2), was utilized to classify PCa patients into two risk groups; the high-risk group was characterized by poor prognosis and more aggressive clinical features. Moreover, we investigated the immune profile, mutation landscape and molecular pathways in each of the groups. Additionally, drug-susceptibility testing was performed to explore sensitive drugs for high-risk patients. Furthermore, we found that MXD3 downregulation suppressed the proliferation of PCa cell lines in vitro. Overall, our results highlight the signature based on CRGs as a powerful tool for predicting RFS of PCa patients, as well as an indicator for personalized treatment of those patients.
The frequency of differentiated CD3+CD27-CD28- T cells predicts response to CART cell therapy in diffuse large B-cell lymphoma
Authors: Worel Nina , Grabmeier-Pfistershammer Katharina , Kratzer Bernhard , Schlager Martina , Tanzmann Andreas , Rottal Arno , Körmöczi Ulrike , Porpaczy Edit , Staber Philipp B. , Skrabs Cathrin , Herkner Harald , Gudipati Venugopal , Huppa Johannes B. , Salzer Benjamin , Lehner Manfred , Saxenhuber Nora , Friedberg Eleonora , Wohlfarth Philipp , Hopfinger Georg , Rabitsch Werner , Simonitsch-Klupp Ingrid , Jäger Ulrich , Pickl Winfried F.
Published: January 2023

Background

Chimeric antigen receptor T (CART) cell therapy targeting the B cell specific differentiation antigen CD19 has shown clinical efficacy in a subset of relapsed/refractory (r/r) diffuse large B cell lymphoma (DLBCL) patients. Despite this heterogeneous response, blood pre-infusion biomarkers predicting responsiveness to CART cell therapy are currently understudied.

Methods

Blood cell and serum markers, along with clinical data of DLBCL patients who were scheduled for CART cell therapy were evaluated to search for biomarkers predicting CART cell responsiveness.

Findings

Compared to healthy controls (n=24), DLBCL patients (n=33) showed significant lymphopenia, due to low CD3+CD4+ T helper and CD3-CD56+ NK cell counts, while cytotoxic CD3+CD8+ T cell counts were similar. Although lymphopenic, DLBCL patients had significantly more activated HLA-DR+ (P=0.005) blood T cells and a higher frequency of differentiated CD3+CD27-CD28- (28.7 ± 19.0% versus 6.6 ± 5.8%; P<0.001) T cells. Twenty-six patients were infused with CART cells (median 81 days after leukapheresis) and were analyzed for the overall response (OR) 3 months later. Univariate and multivariate regression analyses showed that low levels of differentiated CD3+CD27-CD28- T cells (23.3 ± 19.3% versus 35.1 ± 18.0%) were independently associated with OR. This association was even more pronounced when patients were stratified for complete remission (CR versus non-CR: 13.7 ± 11.7% versus 37.7 ± 17.4%, P=0.001). A cut-off value of ≤ 18% of CD3+CD27-CD28- T cells predicted CR at 12 months with high accuracy (P<0.001). In vitro, CD3+CD8+CD27-CD28- compared to CD3+CD8+CD27+CD28+ CART cells displayed similar CD19+ target cell-specific cytotoxicity, but were hypoproliferative and produced less cytotoxic cytokines (IFN-γ and TNF-α). CD3+CD8+ T cells outperformed CD3+CD4+ T cells 3- to 6-fold in terms of their ability to kill CD19+ target cells.

Interpretation

Low frequency of differentiated CD3+CD27-CD28- T cells at leukapheresis represents a novel pre-infusion blood biomarker predicting a favorable response to CART cell treatment in r/r DLBCL patients.
Alpha-1 antitrypsin limits neutrophil extracellular trap disruption of airway epithelial barrier function
Authors: Hudock K. M. , Collins M. S. , Imbrogno M. A. , Kramer E. L. , Brewington J. J. , Ziady A. , Zhang N. , Snowball J. , Xu Y. , Carey B. C. , Horio Y. , O’Grady S. M. , Kopras E. J. , Meeker J. , Morgan H. , Ostmann A. J. , Skala E. , Siefert M. E. , Na C. L. , Davidson C. R. , Gollomp K. , Mangalmurti N. , Trapnell B. C. , Clancy J. P.
Published: January 2023

Neutrophil extracellular traps contribute to lung injury in cystic fibrosis and asthma, but the mechanisms are poorly understood. We sought to understand the impact of human NETs on barrier function in primary human bronchial epithelial and a human airway epithelial cell line. We demonstrate that NETs disrupt airway epithelial barrier function by decreasing transepithelial electrical resistance and increasing paracellular flux, partially by NET-induced airway cell apoptosis. NETs selectively impact the expression of tight junction genes claudins 4, 8 and 11. Bronchial epithelia exposed to NETs demonstrate visible gaps in E-cadherin staining, a decrease in full-length E-cadherin protein and the appearance of cleaved E-cadherin peptides. Pretreatment of NETs with alpha-1 antitrypsin (A1AT) inhibits NET serine protease activity, limits E-cadherin cleavage, decreases bronchial cell apoptosis and preserves epithelial integrity. In conclusion, NETs disrupt human airway epithelial barrier function through bronchial cell death and degradation of E-cadherin, which are limited by exogenous A1AT.
Distinct systemic immune networks define severe vs. mild COVID-19 in hematologic and solid cancer patients
Authors: Pignataro-Oshiro Flávio , Figueiredo Amanda B. , Galdino Nayane A. L. , Morais Katia L. P. , Dutra Walderez O. , Silva Bianca Grassi de Miranda , Feriani Diego , Abrantes Flávia de Azevedo , Silva Ivan Leonardo Avelino França e , Filho Jayr Schmidt , Framil Juliana Valéria de Souza , Cesca Marcelle Goldner , Riechelmann Rachel Simões Pimenta , Batista Marjorie V. , Gollob Kenneth J.
Published: January 2023

Introduction

The COVID-19 pandemic, caused by the coronavirus SARS-CoV-2, has impacted health across all sectors of society. A cytokine-release syndrome, combined with an inefficient response of innate immune cells to directly combat the virus, characterizes the severe form of COVID-19. While immune factors involved in the development of severe COVID-19 in the general population are becoming clearer, identification of the immune mechanisms behind severe disease in oncologic patients remains uncertain.

Methods

Here we evaluated the systemic immune response through the analysis of soluble blood immune factors and anti-SARS-CoV-2 antibodies within the early days of a positive SARS-CoV-2 diagnostic in oncologic patients.

Results

Individuals with hematologic malignancies that went on to die from COVID-19 displayed at diagnosis severe leukopenia, low antibody production against SARS-CoV-2 proteins, and elevated production of innate immune cell recruitment and activation factors. These patients also displayed correlation networks in which IL-2, IL-13, TNF-alpha, IFN-gamma, and FGF2 were the focal points. Hematologic cancer patients that showed highly networked and coordinated anti-SARS-CoV-2 antibody production, with central importance of IL-4, IL-5, IL-12A, IL-15, and IL-17A, presented only mild COVID-19. Conversely, solid tumor patients that had elevated levels of inflammatory cytokines IL-6, CXCL8, and lost the coordinate production of anti-virus antibodies developed severe COVID-19 and died. Patients that displayed positive correlation networks between anti-virus antibodies, and a regulatory axis involving IL-10 and inflammatory cytokines recovered from the disease. We also provided evidence that CXCL8 is a strong predictor of death for oncologic patients and could be an indicator of poor prognosis within days of the positive diagnostic of SARS-CoV-2 infection.

Conclusion

Our findings defined distinct systemic immune profiles associated with COVID-19 clinical outcome of patients with cancer and COVID-19. These systemic immune networks shed light on potential immune mechanisms involved in disease outcome, as well as identify potential clinically useful biomarkers.
Conversion therapy for advanced intrahepatic cholangiocarcinoma with lenvatinib and pembrolizumab combined with gemcitabine plus cisplatin: A case report and literature review
Authors: Zhang Wei , Luo Chu , Zhang Zun-Yi , Zhang Bi-Xiang , Chen Xiao-Ping
Published: January 2023

Background

Intrahepatic cholangiocarcinoma (ICC) is a highly malignant biliary tumor. Patients with unresectable and advanced ICC have a poor prognosis with current gemcitabine-based chemotherapy. Combination therapy strategies based on immunotherapy have achieved promising results in various tumor types.

Case presentation

We reported a patient with unresectable ICC who received lenvatinib and pembrolizumab in combination with gemcitabine plus cisplatin (GP) chemotherapy and subsequently underwent radical liver resection. A 46-year-old male with a history of chronic hepatitis B and hypertension was diagnosed with ICC. Multiple liver tumors with ring-like enhancement were detected on abdominal contrast-enhanced CT and MRI. Enlarged lymph nodes were found in the hilar and retroperitoneal areas. The tumor was clinically staged as T2N1M0 (stage IIIB). Lenvatinib and pembrolizumab in combination with GP chemotherapy were adopted as first-line treatments for the patient. After six cycles of scheduled treatment, the diameter of the largest liver lesion and the number of liver lesions were markedly reduced. The level of the tumor marker CA19-9 decreased to a normal range. A partial response according to the mRECIST criteria was achieved without severe toxicities. Non-anatomical liver resection (segment 4b, 5,6 + segment 7 + segment 8), cholecystectomy and hilar lymph node dissection were performed one month after stopping combination therapy. Pathological examination confirmed a diagnosis of moderate-to-poorly differentiated ICC with lymph node metastasis. The patient has survived 15 months following resection of the tumors, with no evidence of local recurrence or distant metastasis.

Conclusion

Lenvatinib and anti-PD1 antibody pembrolizumab in combination with GP chemotherapy provided promising antitumor efficacy with reasonable tolerability, which may be a potentially feasible and safe conversion therapy strategy for patients with initially unresectable and advanced ICC.
IP-score correlated to endogenous tumour antigen peptide processing: A candidate clinical response score algorithm of immune checkpoint inhibitors therapy in multiple cohorts
Authors: Wang Yutao , Yan Kexin , Guo Ye , Lu Yi , Su Hao , Li Hongjun
Published: January 2023

The processing of endogenous tumour antigen peptides was essential for anti-tumour immunity in the tumour microenvironment. A high degree of Endogenous tumour antigen peptide processing has been demonstrated to improve the prognosis of carcinoma patients. However, there is insufficient evidence to prove its effect on the clinical response to immune checkpoint inhibitor therapy. To undertake a more in-depth analysis of the effects of the aforementioned genes on immunotherapy, we constructed a gene set evaluation score system relevant to tumour endogenous antigen peptide therapy using the GSVA approach. This rating mechanism is known as IP score (IPs). Immediately afterwards, we used the TCGA pan-cancer cohorts to conduct a comprehensive analysis of 6 genes in the IPs, and the analysis results showed that these six genes were related to the proportion of CD8+ T lymphocytes in a variety of solid tumours. As a prognostic protective factor for solid tumours, patients had better prognosis outcomes in the group with high expression levels of the above genes. We analysed the differential expression of six genes between immune checkpoint inhibitor treatment response and disease progression groups using several treatment cohorts. The results revealed that after treatment with PD-1 or CTLA4 inhibitors, the expression levels of the above six genes were comparatively high in the effective group, but the expression of the signature genes was dramatically downregulated in the ICI-insensitive groups. This indicates that the 6 genes are related to the clinical response to ICI treatment. Finally, we used the GSVA method to evaluate the above signatures, and the results showed that PDCD1, CTAL4, CD274 and LAG3 were significantly higher expressed in the IPs high-expression group; therefore, based on the processing of endogenous antigenic peptides in tumours, a predictive score of clinical response to immune checkpoint inhibitor therapy composed of 6 genes(PSMB8/PSMB9/PSMB10/PSME1/PSME2/IRF1) was constructed, and the role of each independent variable in the signature in the solid tumour microenvironment and the impact on ICI treatment were comprehensively analysed. This study provides a candidate evaluation score for predicting clinical response to immune checkpoint inhibitor therapy.
Intratumoral STING activation causes durable immunogenic tumor eradication in the KP soft tissue sarcoma model
Authors: Marritt Kayla L. , Hildebrand Karys M. , Hildebrand Kurt N. , Singla Arvind K. , Zemp Franz J. , Mahoney Douglas J. , Jirik Frank R. , Monument Michael J.
Published: January 2023

Introduction

Soft tissue sarcomas (STS) are highly metastatic, connective-tissue lineage solid cancers. Immunologically, sarcomas are frequently characterized by a paucity of tumor infiltrating lymphocytes and an immune suppressive microenvironment. Activation of the STING pathway can induce potent immune-driven anti-tumor responses within immunogenic solid tumors; however, this strategy has not been evaluated in immunologically cold sarcomas. Herein, we assessed the therapeutic response of intratumoral STING activation in an immunologically cold murine model of undifferentiated pleomorphic sarcoma (UPS).

Materials and Results

A single intratumoral injection of the murine STING agonist, DMXAA resulted in durable cure in up to 60% of UPS-bearing mice. In mice with synchronous lung metastases, STING activation within hindlimb tumors resulted in 50% cure in both anatomic sites. Surviving mice all rejected UPS re-challenge in the hindlimb and lung. Therapeutic efficacy of STING was inhibited by lymphocyte deficiency but unaffected by macrophage deficiency. Immune phenotyping demonstrated enrichment of lymphocytic responses in tumors at multiple timepoints following treatment. Immune checkpoint blockade enhanced survival following STING activation.

Discussion

These data suggest intratumoral activation of the STING pathway elicits local and systemic anti-tumor immune responses in a lymphocyte poor sarcoma model and deserves further evaluation as an adjunctive local and systemic treatment for sarcomas.
Leukemia-associated truncation of granulocyte colony-stimulating factor receptor impacts granulopoiesis throughout the life-course
Authors: Bulleeraz Vilasha , Goy Michelle , Basheer Faiza , Liongue Clifford , Ward Alister C.
Published: January 2023

Introduction

The granulocyte colony-stimulating factor receptor (G-CSFR), encoded by the CSF3R gene, is involved in the production and function of neutrophilic granulocytes. Somatic mutations in CSF3R leading to truncated G-CSFR forms are observed in acute myeloid leukemia (AML), particularly those subsequent to severe chronic neutropenia (SCN), as well as in a subset of patients with other leukemias.

Methods

This investigation introduced equivalent mutations into the zebrafish csf3r gene via genome editing and used a range of molecular and cellular techniques to understand the impact of these mutations on immune cells across the lifespan.

Results

Zebrafish harboring truncated G-CSFRs showed significantly enhanced neutrophil production throughout successive waves of embryonic hematopoiesis and a neutrophil maturation defect in adults, with the mutations acting in a partially dominant manner.

Discussion

This study has elucidated new insights into the impact of G-CSFR truncations throughout the life-course and created a bone fide zebrafish model for further investigation.
Inequitable distribution of plastic benefits and burdens on economies and public health
Authors: Karasik Rachel , Lauer Nancy E. , Baker Anne-Elisabeth , Lisi Niki E. , Somarelli Jason A. , Eward William C. , Fürst Kathinka , Dunphy-Daly Meagan M.
Published: January 2023

Plastic heterogeneously affects social systems – notably human health and local and global economies. Here we discuss illustrative examples of the benefits and burdens of each stage of the plastic lifecycle (e.g., macroplastic production, consumption, recycling). We find the benefits to communities and stakeholders are principally economic, whereas burdens fall largely on human health. Furthermore, the economic benefits of plastic are rarely applied to alleviate or mitigate the health burdens it creates, amplifying the disconnect between who benefits and who is burdened. In some instances, social enterprises in low-wealth areas collect and recycle waste, creating a market for upcycled goods. While such endeavors generate local socioeconomic benefits, they perpetuate a status quo in which the burden of responsibility for waste management falls on downstream communities, rather than on producers who have generated far greater economic benefits. While the traditional cost-benefit analyses that inform decision-making disproportionately weigh economic benefits over the indirect, and often unquantifiable, costs of health burdens, we stress the need to include the health burdens of plastic to all impacted stakeholders across all plastic life stages in policy design. We therefore urge the Intergovernmental Negotiating Committee to consider all available knowledge on the deleterious effects of plastic across the entire plastic lifecycle while drafting the upcoming international global plastic treaty.
Hydrodynamics affected by submerged vegetation with different flexibility under unidirectional flow
Authors: Wu Chenhui , Wu Shiqiang , Wu Xiufeng , Zhang Yu , Feng Kedong , Zhang Weile , Zhao Yuhang
Published: January 2023

Submerged vegetation changes the hydrodynamic characteristics of rivers, lakes, wetlands, and coastal zones. However, only a few studies have focused on the effect of flexible submerged vegetation on hydrodynamic characteristics under unidirectional flow. Therefore, laboratory experiments were conducted to study the effects of submerged vegetation with different flexibility on the flow structure and turbulence characteristics under unidirectional flow. The results showed that the reconfiguration and coordination of wave motion of flexible submerged vegetation redistribute flow velocity, Reynolds stress, and turbulent kinetic energy inside and outside of the vegetation canopy. With a gradual decrease in the deflection height of vegetation, the differences in dimensionless velocity, dimensionless mixed layer thickness, bulk drag coefficient, averaged turbulent kinetic energy, and the averaged contribution rate of its shear production term for the vegetation canopy also decrease; the trend of the penetration depth of Reynolds stress is opposite. Based on the turbulent kinetic energy budget equation, a turbulent kinetic energy model (TKE model) was established, which can be used to predict the turbulent kinetic energy and its shear production term within the vegetation canopy. Here, the scaling factor was determined by the vegetation canopy Cauchy number. The TKE model can be applied under unidirectional flow conditions for submerged vegetation with different flexibilities with high accuracy. It is a simple method to predict vegetation-induced turbulence and the characteristics of sediment and material transport under the influence of submerged vegetation with different flexibility.
Case report: Streptococcus pneumoniae pneumonia characterized by diffuse centrilobular nodules in both lungs
Authors: Zhang Fangqi , Qin Shaowen , Xia Fei , Mao Congzheng , Li Long
Published: January 2023

Background

Streptococcus pneumoniae (S. pneumoniae) is the most common pathogen in community-acquired pneumonia (CAP) and takes the form of lobar pneumonia as typical computed tomography (CT) findings. Various patterns of radiological manifestation have also been reported in patients with S. pneumoniae pneumonia; however, the appearance of diffuse centrilobular nodules in both lungs is rarely reported.

Case presentation

We report the case of a patient with a history of chronic lymphocytic leukemia (CLL) for 9 years who presented with new-onset fever, cough, excess sputum, and shortness of breath for 1 week. He was given intravenous antibacterial (cephalosporin) treatment for 4 days, but his condition did not improve and dyspnea became more serious. The chest CT indicated diffuse centrilobular nodules in both lungs at admission. Patient’s bronchoalveolar (BAL) fluid was sent for metagenomic next-generation sequencing, which only supported a diagnosis of S. pneumoniae infection. His condition improved gradually after antimicrobial treatment (moxifloxacin) and a follow-up CT showed that the diffuse centrilobular nodules in both lungs were absorbed completely.

Conclusion

This case highlights a rare CT presentation of S. pneumoniae pneumonia that should alert clinicians, so as to avoid taking unnecessary treatment measures.
Clinical characteristics, risk factors and diagnostic outcomes of patients presented with indeterminate biliary stricture: A multicenter study
Authors: Tag-Adeen Mohammed , Malak Mohamed , Abdel-Gawad Muhammad , Abu-Elfatth Ahmed , Eldamarawy Ramadan H. , Alzamzamy Ahmed , Elbasiony Mohamed , Elsharkawy Ramy M. , El-Raey Fathiya , Basiony Ahmed N. , Qasem Ahmed , Shady Zakarya , Abdelmohsen Ahmed S. , Abdeltawab Doaa , Farouk Mahmoud , Fouad Ola M. , Rabie Ahmed , Erian Abdul-Hakim , Sapra Ahlam , Shaibat-Alhamd Wael , Aboubakr Ashraf , Omran Dalia , Alboraie Mohamed
Published: January 2023

Background and aim

Indeterminate biliary stricture (IBS) is a frequently encountered clinical problem. In this study, we aimed to highlight the clinical characteristics, risk factors and diagnostic outcomes of patients presented with indeterminate biliary stricture.

Method

A Retrospective multicenter study included all patients diagnosed with IBS in the participating centers between 2017 and 2021. Data regarding IBS such as presentations, patient characteristics, diagnostic and therapeutic modalities were collected from the patients' records and then were analyzed.

Results

Data of 315 patients with IBS were retrospectively collected from 7 medical centers with mean age: 62.6 ± 11 years, females: 40.3% and smokers: 44.8%. For diagnosing stricture; Magnetic resonance imaging/Magnetic resonance cholangiopancreatography (MRI/MRCP) was the most frequently requested imaging modality in all patients, Contrast enhanced computerized tomography (CECT) in 85% and endoscopic ultrasound (EUS) in 23.8%. Tissue diagnosis of cholangiocarcinoma was achieved in 14% only. The used therapeutic modalities were endoscopic retrograde cholangiopancreatography (ERCP)/stenting in 70.5%, percutaneous trans-hepatic biliary drainage (PTD): 17.8%, EUS guided drainage: 0.3%, and surgical resection in 8%. The most frequent type of strictures was distal stricture in 181 patients, perihilar in 128 and intrahepatic in 6. Distal strictures had significant male predominance, with higher role for EUS for diagnosis and higher role for ERCP/stenting for drainage, while in the perihilar strictures, there was higher role for CECT and MRI/MRCP for diagnosis and more frequent use of PTD for drainage.

Conclusion

Indeterminate biliary stricture is a challenging clinical problem with lack of tissue diagnosis in most of cases mandates an urgent consensus diagnostic and treatment guidelines.
Establishment of an interdisciplinary vascular anomalies program in Tanzania, East Africa
Authors: Puhr-Westerheide Daniel , Masthoff Max , Shah Jay , Krechel Alina , Shemwetta Mwivano , Naif Azza A. , Ukweh Ofonime N. , Abdul Ziad , Sarkar Abizer , Baraka Balowa Musa , Malecela Furaha , Lekasio Praygod Justin , Rajab Latifa , Mungia Abbas , Sianga William , Manji Karim P. , Mbuguje Eric M. , Khoncarly Sarah , Minja Frank J. , Laage Gaupp Fabian M. , Wildgruber Moritz
Published: January 2023

Purpose

The aim of this project is the sustainable implementation of a vascular anomalies (VA) program in Tanzania.

Materials and methods

In 2021 the first interdisciplinary VA program was initiated at Muhimbili National Hospital (MNH), Dar Es Salaam, Tanzania in a stepwise approach. During the planning phase the clinical need for minimally-invasive therapies of VAs and the preexisting structures were assessed by the local Interventional Radiology (IR) team at MNH. During the initiation phase, an IR team from two German VA centers joined the interdisciplinary team at MNH for clinical workup, image-guided procedures and follow-up. VA patients were recruited from existing patient records or seen at clinics as de novo presentations following nationwide advertisement. In the post-processing phase joined online conferences for follow-up and support in management of new patients were established. Further follow-up was supported by attending providers from other established VA centers, traveling to bolster the primary operators of MNH.

Results

The first interdisciplinary VA program was successfully launched in Tanzania. Minimally-invasive treatments were successfully trained, by performing ultrasound-guided sclerotherapy with polidocanol and bleomycin in twelve patients with slow-flow malformations, one endovascular embolization of a high-flow malformation, and medical treatment of an aggressive infantile hemangioma. Regular online follow-up presentations have been initiated. Follow-up evaluation and required treatment was sustained when appropriate.

Conclusion

The presented “hands-on” training set the ground for the first interdisciplinary VA program in Tanzania. This framework is expected to establish comprehensive and sustainable care of patients with VAs in East Africa and can serve as a blueprint for other sites.
Role of the blue light receptor gene Icwc-1 in mycelium growth and fruiting body formation of Isaria cicadae
Authors: Song Linhao , Shrivastava Neeraj , Gai Yunpeng , Li Dong , Cai Weiming , Shen Yingyue , Lin Fu-Cheng , Liu Jingyu , Wang Hongkai
Published: January 2023

The Isaria cicadae, is well known highly prized medicinal mushroom with great demand in food and pharmaceutical industry. Due to its economic value and therapeutic uses, natural sources of wild I. cicadae are over-exploited and reducing continuously. Therefore, commercial cultivation in controlled environment is an utmost requirement to fulfill the consumer’s demand. Due to the lack of knowledge on fruiting body (synnemata) development and regulation, commercial cultivation is currently in a difficult situation. In the growth cycle of macrofungi, such as mushrooms, light is the main factor affecting growth and development, but so far, specific effects of light on the growth and development of I. cicadae is unknown. In this study, we identified a blue light receptor white-collar-1 (Icwc-1) gene homologue with well-defined functions in morphological development in I. cicadae based on gene knockout technology and transcriptomic analysis. It was found that the Icwc-1 gene significantly affected hyphal growth and fruiting body development. This study confirms that Icwc-1 acts as an upstream regulatory gene that regulates genes associated with fruiting body formation, pigment-forming genes, and related genes for enzyme synthesis. Transcriptome data analysis also found that Icwc-1 affects many important metabolic pathways of I. cicadae, i.e., amino acid metabolism and fatty acid metabolism. The above findings will not only provide a comprehensive understanding about the molecular mechanism of light regulation in I. cicadae, but also provide new insights for future breeding program and improving this functional food production.
Interactive impact of potassium and arbuscular mycorrhizal fungi on the root morphology and nutrient uptake of sweet potato (Ipomoea batatas L.)
Authors: Yuan Jie , Shi Kun , Zhou Xiaoyue , Wang Lei , Xu Cong , Zhang Hui , Zhu Guopeng , Si Chengcheng , Wang Jidong , Zhang Yongchun
Published: January 2023

Sweet potato is a typical “potassium (K)-favoring” food crop and strongly dependent on arbuscular mycorrhizal fungi (AMF). Recent studies show the importance of K and AMF to morphology optimization and nutrient uptake regulation of sweet potato; meanwhile, the interaction exists between K and K use efficiency (KIUE) in sweet potato. To date, only a few studies have shown that AMF can improve plant K nutrition, and whether the benefits conferred by AMF on plant are related to K remains unclear. In this study, low-KIUE genotype “N1” and high-KIUE genotype “Xu28” were used as experimental sweet potato; Funneliformis mosseae (FM) and Claroideoglomus etunicatum (CE) were used as experimental AMF. In a pot experiment, plants “N1” and “Xu28” were inoculated with FM or CE, and applied with or without K fertilizer to uncover the effects of K application and AMF inoculation on the root morphology and nutrient absorption of sweet potato during their growing period. Results demonstrated that AMF inoculation-improved root morphology of sweet potato highly relied on K application. With K application, AMF inoculation significantly increased root tip number of “N1” in the swelling stage and optimized multiple root morphological indexes (total root length, root surface area, root volume, root diameter, root branch number, and root tip number) of “Xu28” and CE had the best optimization effect on the root morphology of “Xu28”. In addition, CE inoculation significantly promoted root dry matter accumulation of “Xu28” in the swelling and harvesting stages, coordinated aerial part and root growth of “Xu28”, reduced the dry matter to leaf and petiole, and was beneficial to dry matter allocation to the root under conditions of K supply. Another promising finding was that CE inoculation could limit K allocation to the aboveground and promote root K accumulation of “Xu28” under the condition with K application. The above results lead to the conclusion that K and CE displayed a synergistic effect on root development and K acquisition of high-KIUE “Xu28”. This study could provide a theoretical basis for more scientific application of AMF in sweet potato cultivation and will help further clarify the outcomes of plant-K–AMF interactions.
LDMD: A database of microbes in human lung disease
Authors: Xu Li-Qun , Yang Jing , Liang Weicheng , Chen Jiang , Sun Zepeng , Zhang Qiang , Liu Xinlong , Qiao Feng , Li Jian
Published: January 2023

Background

Lungs were initially thought to be sterile. However, with the development of sequencing technologies, various commensal microorganisms, especially bacteria, have been observed in the lungs of healthy humans. Several studies have also linked lung microbes to infectious lung diseases. However, few databases have focused on the metagenomics of lungs to provide microbial compositions and corresponding metadata information. Such a database would be handy for researching and treating lung diseases.

Methods

To provide researchers with a preliminary understanding of lung microbes and their research methods, the LDMD collated nearly 10,000 studies in the literature covering over 30 diseases, gathered basic information such as the sources of lung microbe samples, sequencing methods, and processing software, as well as analyzed the metagenomic sequencing characteristics of lung microbes. Besides, the LDMD also contained data collected in our laboratory.

Results

In this study, we established the Lung Disease Microorganisms Database (LDMD), a comprehensive database of microbes involved in lung disease. The LDMD offered sequence analysis capabilities, allowing users to upload their sequencing results, align them with the data collated in the database, and visually analyze the results.

Conclusion

In conclusion, the LDMD possesses various functionalities that provide a convenient and comprehensive resource to study the lung metagenome and treat lung diseases.
Carbon dioxide equivalent emissions from corn silage fermentation
Authors: Krueger Lucas A. , Koester Lucas R. , Jones David F. , Spangler David A.
Published: January 2023

The European Climate Law recently codified the goal for European climate neutrality by 2050, highlighting the need for sustainable farming practices within a robust and transparent carbon dioxide equivalent (CO2e) accounting system. In the present study, a series of equations were proposed for the estimation of CO2e emissions from corn silage fermentation. Systematic review of previous meta-analyses of corn silage fermentation identified the mean and standard deviation statistics for key model inputs of acetic acid, ethanol, lactic acid, ammonia, and volatile-corrected dry matter loss. Estimates of CO2e emissions were determined for a mock dataset comprising 1,000 iterations of randomly-generated values for each metric in accordance with mean and variance statistics of the source data. Estimates for CO2e emissions of corn silage based on meta-analysis review of laboratory experiments were 1.9 ± 5.6% (GWP20) and 0.2 ± 5.5% (GWP100) of silage dry matter. Furthermore, model results demonstrated a precedent for CO2 recycling by silage microorganisms, which was supported by genome annotation of strains belonging to common silage species. Linear model equations for GWP20 and GWP100 with inputs and outputs in mg kg−1 silage dry matter were developed, where inputs are acetic acid (A), ethanol (E), lactic acid (L), and volatile corrected dry matter loss (DV). Linear equations are (for GWP20; Eq. 11):

GWP20=−3626.1−0.04343A+0.8011E−0.03173L+1.46573DV

and for GWP100; Eq. 12:

GWP100=−8526.10−0.22403A−0.11963E−0.03173L+1.46573DV.
Non-deacetylated poly-N-acetylglucosamine-hyperproducing Staphylococcus aureus undergoes immediate autoaggregation upon vortexing
Authors: Kutsuno Shoko , Hayashi Ikue , Yu Liansheng , Yamada Sakuo , Hisatsune Junzo , Sugai Motoyuki
Published: January 2023

Biofilms are microbial communities of cells embedded in a matrix of extracellular polymeric substances generated and adhering to each other or to a surface. Cell aggregates formed in the absence of a surface and floating pellicles that form biofilms at the air-liquid interface are also considered to be a type of biofilm. Staphylococcus aureus is a well-known cause of biofilm infections and high-molecular-weight polysaccharides, poly-N-acetylglucosamine (PNAG) is a main constituent of the biofilm. An icaADBC operon comprises major machinery to synthesize and extracellularly secrete PNAG. Extracellular PNAG is partially deacetylated by IcaB deacetylase, and the positively charged PNAG hence interacts with negatively charged cell surface to form the major component of biofilm. We previously reported a new regulator of biofilm (Rob) and demonstrated that Rob binds to a unique 5-bp motif, TATTT, present in intergenic region between icaADBC operon and its repressor gene icaR in Yu et al. The deletion of the 5-bp motif induces excessive adherent biofilm formation. The real function of the 5-bp motif is still unknown. In an attempt to isolate the 5-bp motif deletion mutant, we isolated several non-adherent mutants. They grew normally in turbid broth shaking culture but immediately auto-aggregated upon weak vortexing and sedimented as a lump resulting in a clear supernatant. Whole genome sequencing of the mutants identified they all carried mutations in icaB in addition to deletion of the 5-bp motif. Purification and molecular characterization of auto-aggregating factor in the culture supernatant of the mutant identified that the factor was a massively produced non-deacetylated PNAG. Therefore, we created a double deficient strain of biofilm inhibitory factors (5-bp motif, icaR, rob) and icaB to confirm the aggregation phenomenon. This peculiar phenomenon was only observed in Δ5bpΔicaB double mutant but not in ΔicaR ΔicaB or ΔrobΔicaB mutant. This study explains large amount of extracellularly produced non-deacetylated PNAG by Δ5bpΔicaB double mutation induced rapid auto-aggregation of S. aureus cells by vortexing. This phenomenon indicated that Staphylococcus aureus may form biofilms that do not adhere to solid surfaces and we propose this as a new mechanism of non-adherent biofilm formation of S. aureus.
Survey on technical management of strawberries in Morocco and evaluation of their post-harvest microbial load
Authors: El-araby Abir , Azzouzi Amal , Ayam Iman Msegued , Samouh Khaoula Filali , Errachidi Faouzi
Published: January 2023

The climatic conditions of the growing regions influence the fruit’s microbiological quality and their tolerance to post-harvest pathogens. The present work aims to identify the prevalence of bacterial and fungal strains of strawberries (Fragaria × ananassa) in the Gharb and Loukkos regions of Morocco. Thus, to establish a correlation between the microbial load and the climatic conditions of the two targeted regions. The bacteriological analyses were studied according to the International Organization for Standardization (ISO) methodologies. Regarding the mycological study, fungal species determination was performed using identification keys. Yeast species determination was done using genus analysis, assimilation, and fermentation tests. Emberger bioclimatic quotients (Q2) were calculated for the Gharb and Loukkos regions and bioclimatic stages were determined. Salmonella spp. was not detected in the studied samples. However, Listeria monocytogenes and Escherichia coli were isolated from the Gharb samples. Sulfite-reducing clostridia spores were found in two Gharb samples versus one Loukkos sample. Coagulase-positive staphylococci were negative in all samples analyzed. Loukkos and Gharb regions were contaminated by Bacillus cereus with percentages of occurrence of 5.2 and 7.8%, respectively. The fungi found in strawberries from both regions were Aspergillus niger, Botrytis cinerea, Fusarium spp., Penicillium spp., Rhizopus spp., and Alternaria alternata with a significant predominance in the Loukkos samples. Indeed, a marked presence is noted for Candida sake and Rhodotorula glutinis in strawberries from Loukkos. Gharb is located on the semi-arid stage, while Loukkos is located on the sub-humid stage. Climatic conditions have a strong influence on plant microbial load, which explains the prevalence of bacteria in strawberries from Gharb and the prevalence of fungi in strawberries from Loukkos.
Increased functional connectivity patterns in mild Alzheimer’s disease: A rsfMRI study
Authors: Penalba-Sánchez Lucía , Oliveira-Silva Patrícia , Sumich Alexander Luke , Cifre Ignacio
Published: January 2023

Background

Alzheimer’s disease (AD) is the most common age-related neurodegenerative disorder. In view of our rapidly aging population, there is an urgent need to identify Alzheimer’s disease (AD) at an early stage. A potential way to do so is by assessing the functional connectivity (FC), i.e., the statistical dependency between two or more brain regions, through novel analysis techniques.

Methods

In the present study, we assessed the static and dynamic FC using different approaches. A resting state (rs)fMRI dataset from the Alzheimer’s disease neuroimaging initiative (ADNI) was used (n = 128). The blood-oxygen-level-dependent (BOLD) signals from 116 regions of 4 groups of participants, i.e., healthy controls (HC; n = 35), early mild cognitive impairment (EMCI; n = 29), late mild cognitive impairment (LMCI; n = 30), and Alzheimer’s disease (AD; n = 34) were extracted and analyzed. FC and dynamic FC were extracted using Pearson’s correlation, sliding-windows correlation analysis (SWA), and the point process analysis (PPA). Additionally, graph theory measures to explore network segregation and integration were computed.

Results

Our results showed a longer characteristic path length and a decreased degree of EMCI in comparison to the other groups. Additionally, an increased FC in several regions in LMCI and AD in contrast to HC and EMCI was detected. These results suggest a maladaptive short-term mechanism to maintain cognition.

Conclusion

The increased pattern of FC in several regions in LMCI and AD is observable in all the analyses; however, the PPA enabled us to reduce the computational demands and offered new specific dynamic FC findings.
DRFnet: Dynamic receptive field network for object detection and image recognition
Authors: Tan Minjie , Yuan Xinyang , Liang Binbin , Han Songchen
Published: January 2023

Biological experiments discovered that the receptive field of neurons in the primary visual cortex of an animal's visual system is dynamic and capable of being altered by the sensory context. However, in a typical convolution neural network (CNN), a unit's response only comes from a fixed receptive field, which is generally determined by the preset kernel size in each layer. In this work, we simulate the dynamic receptive field mechanism in the biological visual system (BVS) for application in object detection and image recognition. We proposed a Dynamic Receptive Field module (DRF), which can realize the global information-guided responses under the premise of a slight increase in parameters and computational cost. Specifically, we design a transformer-style DRF module, which defines the correlation coefficient between two feature points by their relative distance. For an input feature map, we first divide the relative distance corresponding to different receptive field regions between the target feature point and its surrounding feature points into N different discrete levels. Then, a vector containing N different weights is automatically learned from the dataset and assigned to each feature point, according to the calculated discrete level that this feature point belongs. In this way, we achieve a correlation matrix primarily measuring the relationship between the target feature point and its surrounding feature points. The DRF-processed responses of each feature point are computed by multiplying its corresponding correlation matrix with the input feature map, which computationally equals to accomplish a weighted sum of all feature points exploiting the global and long-range information as the weight. Finally, by superimposing the local responses calculated by a traditional convolution layer with DRF responses, our proposed approach can integrate the rich context information among neighbors and the long-range dependencies of background into the feature maps. With the proposed DRF module, we achieved significant performance improvement on four benchmark datasets for both tasks of object detection and image recognition. Furthermore, we also proposed a new matching strategy that can improve the detection results of small targets compared with the traditional IOU-max matching strategy.
Research on the network handoff strategy based on the best access point name decision
Authors: Shu Zhong , Shu Ya-Jie , Zhang Qian , Ye Hui-Rong
Published: January 2023

To improve the network switching performance and efficiency of mobile phone terminals and establish an efficient mobile communication network connection, this paper constructs the SDN+MPTCP+CP (Software Defined Network, Multi-Path TCP, and Mobile Terminal) mobile communication network model and designs a network switching algorithm with a preselected available access point name (APN) based on the potential game method. The constructed network model integrates a 5G mobile communication network, satellite communication, the SDN network, and the MPTCP multi-way communication technology. APN access point is preselected by using Kalman filtering theory, and dual problems are resolved with the Lagrange function. To determine the MPTCP sub-flow transmission path, the differential derivative calculation is introduced. The performance of the network switching strategy is evaluated based on the Jacobian matrix. Then, the game coefficient is designed, and the game function is calculated. A potential game balance point is found, and an updating strategy is formulated to determine the best APN access point. The simulation network model is constructed, and the parameters of the performance evaluation are defined to find the performance comprehensively. The experimental results demonstrated the extreme reliability, stability, and compatibility of the proposed algorithm.