bluuebunny/crossref_metadata_2025 huggingface dataset:
Adipose tissue-derived microvascular fragments promote lymphangiogenesis in a murine lymphedema model
Authors: Frueh Florian S , Gassert Laura , Scheuer Claudia , Müller Andreas , Fries Peter , Boewe Anne S , Ampofo Emmanuel , Rübe Claudia E , Menger Michael D , Laschke Matthias W
Published: July 2022

Chronic lymphedema after cancer treatment is common and there is still no cure for this disease. We herein investigated the lymphangiogenic capacity of adipose tissue-derived microvascular fragments (MVF), which contain stem cells and lymphatic vessel fragments. Secondary lymphedema was induced in the hindlimbs of C57BL/6J mice. Green fluorescence protein (GFP)+ MVF were isolated from transgenic C57BL/6Tg (CAG-EGFP)1Osb/J mice, suspended in collagen hydrogel, and injected in the lymphadenectomy defect of wild-type animals. This crossover model allowed the detection of MVF-derived blood and lymphatic vessels after transplantation. The MVF group was compared with animals receiving collagen hydrogel only or a sham intervention. Lymphangiogenic effects were analyzed using volumetry, magnetic resonance (MR) lymphography, histology, and immunohistochemistry. MVF injection resulted in reduced hindlimb volumes when compared to non-treated controls. MR lymphography revealed lymphatic regeneration with reduced dermal backflow after MVF treatment. Finally, MVF transplantation promoted popliteal angiogenesis and lymphangiogenesis associated with a significantly increased microvessel and lymphatic vessel density. These findings indicate that MVF transplantation represents a promising approach to induce therapeutic lymphangiogenesis.
Prophylactic administration of HPA-1a–specific antibodies prevents fetal/neonatal alloimmune thrombocytopenia in mice
Authors: Zhi Huiying , Sheridan Douglas , Newman Debra K. , Newman Peter J.
Published: July 2022

Fetal/neonatal alloimmune thrombocytopenia (FNAIT) is a life-threatening bleeding disorder caused by maternal alloantibodies directed against paternally inherited human platelet alloantigens (HPAs) present on the surface of fetal and neonatal platelets. There are currently no approved therapies for the prevention of FNAIT. We report herein the ability of 2 human HPA-1a–specific therapeutic candidates, one a polyclonal, and the other a monoclonal antibody, to prevent alloimmunization in a novel preclinical mouse model of FNAIT. Both antibody preparations effected the rapid and complete elimination of HPA-1a+ platelets from circulation and prevented the development of HPA-1a alloantibodies. HPA-1a− female mice treated prophylactically with anti–HPA-1a antibody prior to exposure to HPA-1a+ platelets gave birth to HPA-1a+/− pups with significantly improved platelet counts and no bleeding symptoms. These preclinical data establish both the potential and threshold exposure targets for prophylactic treatment with HPA-1a–specific antibodies for the prevention of FNAIT in humans.
Loss of sphingosine kinase 2 promotes the expansion of hematopoietic stem cells by improving their metabolic fitness
Authors: Li Changzheng , Wu Binghuo , Li Yishan , Liu Yaxi , Wang Jin , Xie Jiayi , Xu Xi , Tian Xiaobin , Ye Zhitao , Guan Jingjing , Chen Jie , Xie Siyu , Zhang Baolin , Cai Boyong , Wang Qianhao , Yu Haopeng , Lan Tian , Man Cheuk Him , Kang Xunlei , Qian Pengxu , Perry John M. , He Aibin , Jiang Linjia , Zhao Meng
Published: July 2022

Hematopoietic stem cells (HSCs) have reduced capacities to properly maintain and replenish the hematopoietic system during myelosuppressive injury or aging. Expanding and rejuvenating HSCs for therapeutic purposes has been a long-sought goal with limited progress. Here, we show that the enzyme Sphk2 (sphingosine kinase 2), which generates the lipid metabolite sphingosine-1-phosphate, is highly expressed in HSCs. The deletion of Sphk2 markedly promotes self-renewal and increases the regenerative potential of HSCs. More importantly, Sphk2 deletion globally preserves the young HSC gene expression pattern, improves the function, and sustains the multilineage potential of HSCs during aging. Mechanistically, Sphk2 interacts with prolyl hydroxylase 2 and the Von Hippel-Lindau protein to facilitate HIF1α ubiquitination in the nucleus independent of the Sphk2 catalytic activity. Deletion of Sphk2 increases hypoxic responses by stabilizing the HIF1α protein to upregulate PDK3, a glycolysis checkpoint protein for HSC quiescence, which subsequently enhances the function of HSCs by improving their metabolic fitness; specifically, it enhances anaerobic glycolysis but suppresses mitochondrial oxidative phosphorylation and generation of reactive oxygen species. Overall, targeting Sphk2 to enhance the metabolic fitness of HSCs is a promising strategy to expand and rejuvenate functional HSCs.
Quercetin as a JAK–STAT inhibitor: a potential role in solid tumors and neurodegenerative diseases
Authors: Zalpoor Hamidreza , Nabi-Afjadi Mohsen , Forghaniesfidvajani Razieh , Tavakol Chanour , Farahighasreaboonasr Faranak , Pakizeh Farid , Dana Vahid Ghobadi , Seif Farhad
Published: July 2022

The Janus kinase–signal transducer and activator of transcription (JAK–STAT) pathway is involved in many immunological processes, including cell growth, proliferation, differentiation, apoptosis, and inflammatory responses. Some of these processes can contribute to cancer progression and neurodegeneration. Owing to the complexity of this pathway and its potential crosstalk with alternative pathways, monotherapy as targeted therapy has usually limited long-term efficacy. Currently, the majority of JAK–STAT-targeting drugs are still at preclinical stages. Meanwhile, a variety of plant polyphenols, especially quercetin, exert their inhibitory effects on the JAK–STAT pathway through known and unknown mechanisms. Quercetin has shown prominent inhibitory effects on the JAK–STAT pathway in terms of anti-inflammatory and antitumor activity, as well as control of neurodegenerative diseases. This review discusses the pharmacological effects of quercetin on the JAK–STAT signaling pathway in solid tumors and neurodegenerative diseases.
DNA methylation-mediated differential expression of DLX4 isoforms has opposing roles in leukemogenesis
Authors: Zhou Jing-dong , Zhao Yang-jing , Leng Jia-yan , Gu Yu , Xu Zi-jun , Ma Ji-chun , Wen Xiang-mei , Lin Jiang , Zhang Ting-juan , Qian Jun
Published: July 2022

Background

Previously, we reported the expression ofDLX4isoforms (BP1andDLX7) in myeloid leukemia, but the functional role ofDLX4isoforms remains poorly understood. In the work described herein, we further determined the underlying role ofDLX4isoforms in chronic myeloid leukemia (CML) leukemogenesis.

Methods

The expression and methylation ofDLX4isoforms were detected by real-time quantitative PCR (RT-qPCR) and real-time quantitative methylation-specific PCR (RT-qMSP) in patients with CML. The functional role ofDLX4isoforms was determined in vitro and in vivo. The molecular mechanism ofDLX4isoforms in leukemogenesis was identified based on chromatin immunoprecipitation with high-throughput sequencing (ChIP-Seq)/assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-Seq) and RNA sequencing (RNA-Seq).

Results

BP1expression was increased in patients with CML with unmethylated promoter, butDLX7expression was decreased with hypermethylated promoter. Functionally, overexpression ofBP1increased the proliferation rate of K562 cells with S/G2 promotion, whereasDLX7overexpression reduced the proliferation rate of K562 cells with G1 arrest. Moreover, K562 cells withBP1overexpression increased the tumorigenicity in NCG mice, whereas K562 cells withDLX7overexpression decreased the tumorigenicity. Mechanistically, a total of 91 genes including 79 messenger RNAs (mRNAs) and 12 long noncoding RNAs (lncRNAs) were discovered by ChIP-Seq and RNA-Seq as direct downstream targets ofBP1. Among the downstream genes, knockdown ofRREB1andSGMS1-AS1partially revived the proliferation caused byBP1overexpression in K562 cells. Similarly, using ATAC-Seq and RNA-Seq, a total of 282 genes including 151 mRNA and 131 lncRNAs were identified as direct downstream targets ofDLX7. Knockdown of downstream genesPTPRBandNEAT1partially revived the proliferation caused byDLX7overexpression in K562 cells. Finally, we also identified and validated aSGMS1-AS1/miR-181d-5p/SRPK2competing endogenous RNA (ceRNA) network caused byBP1overexpression in K562 cells.

Conclusions

The current findings reveal that DNA methylation-mediated differential expression ofDLX4isoformsBP1andDLX7plays opposite functions in leukemogenesis.BP1plays an oncogenic role in leukemia development, whereasDLX7acts as a tumor suppressor gene. These results suggestDLX4as a therapeutic target for antileukemia therapy.
A novel biomarker selection method combining graph neural network and gene relationships applied to microarray data
Authors: Xie Weidong , Li Wei , Zhang Shoujia , Wang Linjie , Yang Jinzhu , Zhao Dazhe
Published: July 2022

Background

The discovery of critical biomarkers is significant for clinical diagnosis, drug research and development. Researchers usually obtain biomarkers from microarray data, which comes from the dimensional curse. Feature selection in machine learning is usually used to solve this problem. However, most methods do not fully consider feature dependence, especially the real pathway relationship of genes.

Results

Experimental results show that the proposed method is superior to classical algorithms and advanced methods in feature number and accuracy, and the selected features have more significance.

Method

This paper proposes a feature selection method based on a graph neural network. The proposed method uses the actual dependencies between features and the Pearson correlation coefficient to construct graph-structured data. The information dissemination and aggregation operations based on graph neural network are applied to fuse node information on graph structured data. The redundant features are clustered by the spectral clustering method. Then, the feature ranking aggregation model using eight feature evaluation methods acts on each clustering sub-cluster for different feature selection.

Conclusion

The proposed method can effectively remove redundant features. The algorithm’s output has high stability and classification accuracy, which can potentially select potential biomarkers.
IDPsBind: a repository of binding sites for intrinsically disordered proteins complexes with known 3D structures
Authors: Sun CanZhuang , Feng YongE , Fan GuoLiang
Published: July 2022

Background

Intrinsically disordered proteins (IDPs) lack a stable three-dimensional structure under physiological conditions but play crucial roles in many biological processes. Intrinsically disordered proteins perform various biological functions by interacting with other ligands.

Results

Here, we present a database, IDPsBind, which displays interacting sites between IDPs and interacting ligands by using the distance threshold method in known 3D structure IDPs complexes from the PDB database. IDPsBind contains 9626 IDPs complexes and 880 intrinsically disordered proteins verified by experiments. The current release of the IDPsBind database is defined as version 1.0. IDPsBind is freely accessible at http://www.s-bioinformatics.cn/idpsbind/home/.

Conclusions

IDPsBind provides more comprehensive interaction sites for IDPs complexes of known 3D structures. It can not only help the subsequent studies of the interaction mechanism of intrinsically disordered proteins but also provides a suitable background for developing the algorithms for predicting the interaction sites of intrinsically disordered proteins.
Artemisia argyi allelopathy: a generalist compromises hormone balance, element absorption, and photosynthesis of receptor plants
Authors: Li Jinxin , Zhao Tingting , Chen Le , Chen Hong , Luo Dandan , Chen Changjie , Miao Yuhuan , Liu Dahui
Published: July 2022

Background

Allelopathy is expressed through the release of plant chemicals and is considered a natural alternative for sustainable weed management. Artemisia argyi (A. argyi) is widely distributed throughout Asia, and often dominates fields due to its strong allelopathy. However, the mechanism of A. argyi allelopathy is largely unknown and need to be elucidated at the physiological and molecular levels.

Results

In this study, we used electron microscopy, ionomics analysis, phytohormone profiling, and transcriptome analysis to investigate the physiological and molecular mechanisms of A. argyi allelopathy using the model plant rice (Oryza sativa) as receptor plants. A. argyi water extract (AAWE)-treated rice plants grow poorly and display root morphological anomalies and leaf yellowing. We found that AAWE significantly inhibits rice growth by destroying the root and leaf system in multiple ways, including the integrity of ultrastructure, reactive oxygen species (ROS) homeostasis, and the accumulation of soluble sugar and chlorophyll synthesis. Further detection of the hormone contents suggests that AAWE leads to indole-3-acetic acid (IAA) accumulation in roots. Moreover, ionomics analysis shows that AAWE inhibits the absorption and transportation of photosynthesis-essential mineral elements, especially Mg, Fe, and Mn. In addition, the results of transcriptome analysis revealed that AAWE affects a series of crucial primary metabolic processes comprising photosynthesis in rice plants.

Conclusions

This study indicates that A. argyi realizes its strongly allelopathy through comprehensive effects on recipient plants including large-scale IAA synthesis and accumulation, ROS explosion, damaging the membrane system and organelles, and obstructing ion absorption and transport, photosynthesis and other pivotal primary metabolic processes of plants. Therefore, AAWE could potentially be developed as an environmentally friendly botanical herbicide due to its strong allelopathic effects.
Adaptive responses of carbon and nitrogen metabolisms to nitrogen-deficiency in Citrus sinensis seedlings
Authors: Huang Wei-Tao , Zheng Zhi-Chao , Hua Dan , Chen Xu-Feng , Zhang Jiang , Chen Huan-Huan , Ye Xin , Guo Jiu-Xin , Yang Lin-Tong , Chen Li-Song
Published: July 2022

Background

In China, nitrogen (N)-deficiency often occurs in Citrus orchards, which is one of the main causes of yield loss and fruit quality decline. Little information is known about the adaptive responses of Citrus carbon (C) and N metabolisms to N-deficiency. Seedlings of ‘Xuegan’ (Citrus sinensis (L.) Osbeck) were supplied with nutrient solution at an N concentration of 0 (N-deficiency), 5, 10, 15 or 20 mM for 10 weeks. Thereafter, we examined the effects of N supply on the levels of C and N in roots, stems and leaves, and the levels of organic acids, nonstructural carbohydrates, NH4+-N, NO3−-N, total soluble proteins, free amino acids (FAAs) and derivatives (FAADs), and the activities of key enzymes related to N assimilation and organic acid metabolism in roots and leaves.

Results

N-deficiency elevated sucrose export from leaves to roots, C and N distributions in roots and C/N ratio in roots, stems and leaves, thus enhancing root dry weight/shoot dry weight ratio and N use efficiency. N-deficient leaves displayed decreased accumulation of starch and total nonstructural carbohydrates (TNC) and increased sucrose/starch ratio as well as a partitioning trend of assimilated C toward to sucrose, but N-deficient roots displayed elevated accumulation of starch and TNC and reduced sucrose/starch ratio as well as a partitioning trend of assimilated C toward to starch. N-deficiency reduced the concentrations of most FAADs and the ratios of total FAADs (TFAADs)/N in leaves and roots. N-deficiency reduced the demand for C skeleton precursors for amino acid biosynthesis, thus lowering TFAADs/C ratio in leaves and roots. N-deficiency increased (decreased) the relative amounts of C-rich (N-rich) FAADs, thus increasing the molar ratio of C/N in TFAADs in leaves and roots.

Conclusions

Our findings corroborated our hypothesis that C and N metabolisms displayed adaptive responses to N-deficiency in C. sinensis seedlings, and that some differences existed between roots and leaves in N-deficiency-induced alterations of and C and N metabolisms.
Early and midterm results of frozen elephant trunk operation with Evita open stent-graft in patients with Marfan syndrome: results of a multicentre study
Authors: Widenka Kazimierz Jan , Kosiorowska Monika , Jakob Heinz , Pacini Davide , Hemmer Wolfgang , Grabenwoeger Martin , Sioris Thanos , Moritz Anton , Tsagakis Konstantinos
Published: July 2022

Background

Endovascular treatment of patients with Marfan syndrome (MFS) is not recommended. Hybrid procedures such as frozen elephant trunk (FET), which combines stent-graft deployment with an integrated non-stented fabric graft for proximal grafting and suturing, have not been previously evaluated. The aim of this study was to assess the safety and feasibility of FET operation in patients with MFS.

Methods

Patients enrolled in the International E-vita Open Registry (IEOR) who underwent FET procedure between January 2001 and February 2020 meeting Ghent criteria for MFS were included in the study. Early and midterm results were retrospectively analyzed. Preoperative, postoperative and follow-up computed tomography angiography scans were analysed.

Results

We analyzed 37 patients [mean age 38 ± 11 years, 65% men]. Acute or chronic aortic dissection was present in 35 (95%) patients (14 and 21 patients respectively). Two (5%) patients had an aneurysm without dissection. Malperfusion syndrome was present in 4 patients. Twenty-nine (78%) patients had history of aortic surgical interventions. The 30-day and in-hospital mortality amounted to 8 and 14% respectively. False lumen exclusion was present in 73% in stented segment in last postoperative CT. The overall 5-year survival was 71% and freedom from reintervention downstream was 58% at 5 years. Of the nine patients who required reintervention for distal aortic disease, one patient died.

Conclusions

FET operation for patients with MFS can be performed with acceptable mortality and morbidity. In long-term follow-up no reinterventions on the aortic arch were required. FET allows for easier second stage operations providing platform for surgical and endovascular reinterventions.
Survival prediction models: an introduction to discrete-time modeling
Authors: Suresh Krithika , Severn Cameron , Ghosh Debashis
Published: July 2022

Background

Prediction models for time-to-event outcomes are commonly used in biomedical research to obtain subject-specific probabilities that aid in making important clinical care decisions. There are several regression and machine learning methods for building these models that have been designed or modified to account for the censoring that occurs in time-to-event data. Discrete-time survival models, which have often been overlooked in the literature, provide an alternative approach for predictive modeling in the presence of censoring with limited loss in predictive accuracy. These models can take advantage of the range of nonparametric machine learning classification algorithms and their available software to predict survival outcomes.

Methods

Discrete-time survival models are applied to a person-period data set to predict the hazard of experiencing the failure event in pre-specified time intervals. This framework allows for any binary classification method to be applied to predict these conditional survival probabilities. Using time-dependent performance metrics that account for censoring, we compare the predictions from parametric and machine learning classification approaches applied within the discrete time-to-event framework to those from continuous-time survival prediction models. We outline the process for training and validating discrete-time prediction models, and demonstrate its application using the open-source R statistical programming environment.

Results

Using publicly available data sets, we show that some discrete-time prediction models achieve better prediction performance than the continuous-time Cox proportional hazards model. Random survival forests, a machine learning algorithm adapted to survival data, also had improved performance compared to the Cox model, but was sometimes outperformed by the discrete-time approaches. In comparing the binary classification methods in the discrete time-to-event framework, the relative performance of the different methods varied depending on the data set.

Conclusions

We present a guide for developing survival prediction models using discrete-time methods and assessing their predictive performance with the aim of encouraging their use in medical research settings. These methods can be applied to data sets that have continuous time-to-event outcomes and multiple clinical predictors. They can also be extended to accommodate new binary classification algorithms as they become available. We provide R code for fitting discrete-time survival prediction models in a github repository.
The effects of family-centered empowerment model on depression, anxiety, and stress of the family caregivers of patients with COVID-19: a randomized clinical trial
Authors: Nia Mohammad Namazi , Mohajer Samira , Bagheri Nasser , Sarboozi-hoseinabadi Tahere
Published: July 2022

Background

Taking care of patients with Covid-19 is regarded as a challenging task for family caregivers. Hence, a Family-Centered Empowerment Model (FCEM) should help them achieve greater psychological strength throughout the home healthcare process.

Methods

This study is a randomized clinical trial with two groups; besides, pre-test and post-test designs were conducted based on the CONSORT checklist from April to July 2020, in Iran. Seventy family caregivers were randomly assigned to FCEM (n = 35) and control (n = 35) groups. Then, four stages of FCEM in four online sessions were provided to the participants of the intervention group via WhatsApp messenger. The procedure started at the patient's discharge and continued for two weeks. The demographic information questionnaire and Depression Anxiety Stress Scale (DASS-21) were employed before and five days after the FCEM sessions to gather the required data.

Results

The sample was made up of 55.8% women and 44.2% men caregivers, with a mean age of 42.5 years. The results demonstrated a substantial difference in the average score of stress (p = 0.023), anxiety (p = 0.003), and depression (p = 0.012).

Conclusions

The combination of a face-to-face orientation session and online methods of FCEM is likely to lower stress, anxiety, and depression in family caregivers, which can be contributed to the practicability, simplicity, and effectiveness of this home health intervention.

Trial registration

This study (no. IRCT20180429039463N2) was registered in the Iranian Registry of Clinical Trials on 10/04/2020.
Prediction of the therapeutic efficacy of epirubicin combined with ifosfamide in patients with lung metastases from soft tissue sarcoma based on contrast-enhanced CT radiomics features
Authors: Miao Lei , Ma Shu-Tao , Jiang Xu , Zhang Huan-Huan , Wang Yan-Mei , Li Meng
Published: July 2022

Objective

To investigate the value of contrast-enhanced computed tomography (CECT) radiomics features in predicting the efficacy of epirubicin combined with ifosfamide in patients with pulmonary metastases from soft tissue sarcoma.

Methods

A retrospective analysis of 51 patients with pulmonary metastases from soft tissue sarcoma who received the chemotherapy regimen of epirubicin combined with ifosfamide was performed, and efficacy was evaluated by Recist1.1. ROIs (1 or 2) were selected for each patient. Lung metastases were used as target lesions (86 target lesions total), and the patients were divided into a progression group (n = 29) and a non-progressive group (n = 57); the latter included a stable group (n = 34) and a partial response group (n = 23). Information on lung metastases was extracted from CECT images before chemotherapy, and all lesions were delineated by ITK-SNAP software manually or semiautomatically. The decision tree classifier had a better performance in all radiomics models. A receiver operating characteristic curve was plotted to evaluate the predictive performance of the radiomics model.

Results

In total, 851 CECT radiomics features were extracted for each target lesion and finally reduced to 2 radiomics features, which were then used to construct a radiomics model. Areas under the curves of the model for predicting lesion progression were 0.917 and 0.856 in training and testing groups, respectively.

Conclusion

The model established based on the radiomics features of CECT before treatment has certain predictive value for assessing the efficacy of chemotherapy for patients with soft tissue sarcoma lung metastases.
A case of Gitelman syndrome with membranous nephropathy
Authors: Guo Xiafei , Yu Shanshen , Sun Jia , Mou Lijun
Published: July 2022

Background

Gitelman syndrome (GS) is a rare autosomal recessive inherited salt-losing tubulopathy (SLT). Here, we report, for the first time, a case of GS overlapping nephrotic syndrome (NS) related to PLA2R-associated membranous nephropathy (MN).

Case presentation

We described a male patient had a 4-year history of recurrent fatigue. Serum biochemistry revealed hypokalemia with renal potassium wasting, hypomagnesemia, metabolic alkalosis, hyperreninemia, hypocalciuria, as well as nephrotic-range proteinuria, hypoalbuminemia, and elevated serum anti-phospholipase A2 receptor (PLA2R) antibody. Gene sequencing identified compound heterozygous mutations in SLC12A3 [c.536T > A(p.V179D) and c.1456G > A(p.D486N)]. The unusual association of SLTs and nephrotic-range glomerular proteinuria prompted us to perform a renal biopsy. Renal biopsy showed idiopathic MN. Due to the potential to activate the sodium-chloride co-transporter (NCC) and cause hyperkalemia, tacrolimus was selected to treat NS. Following treatment with potassium chloride, magnesium oxide, low-dose glucocorticoid combined with tacrolimus, the fatigue significantly improved, and concurrently hypokalemia, hypomagnesemia were corrected and NS was remitted.

Conclusions

Renal biopsy should be warranted for GS patients with moderate to nephrotic-range proteinuria. Tacrolimus was preferred to the management of GS patients with NS.
Effect of breast milk with or without bacteria on infant gut microbiota
Authors: Huang Ting , Zeng Zichun , Liang Xinyuan , Tang Xiaomei , Luo Huijuan , Wang Dongju , Zhou Juan , Xiao Xiaomin
Published: July 2022

Background

The breast milk microbiome could be a source of infant intestinal microbiota. Several studies have found that some breast milk is extremely low in bacteria or is even sterile. There are limited studies on the effect of milk without bacteria on the infant gut microbiota. The purpose of this study was to investigate the gut microbiota of infants fed with bacterial milk or sterile milk. Meanwhile, we attempted to find the cause of undetectable bacteria in milk.

Methods

A total of 17 healthy pregnant women and 17 infants were enrolled in this study. Fecal samples were collected from full-term pregnant women. Milk samples and infant fecal samples were collected on the 14th postnatal day. Breast milk and fecal samples were examined using 16S rRNA sequencing technology. Pregnant women and infants were grouped according to milk with or without bacteria. To compare the differences in gut microbiota and clinical characteristics between groups.

Results

Bacteria were detected in 11 breast milk samples, and the bacterial detection rate was 64.7%. Infants fed with bacterial milk showed higher Shannon index and Simpson index (P = 0.020,P = 0.048), and their relative abundance ofLachnospirales,LachnospiraceaeandEggerthellaceaewas markedly higher. In addition, there were more bacterial associations in the co-occurrence network of infants fed with bacterial milk. Pregnant women with sterile and bacterial breast milk showed no significant differences in their clinical characteristics, and microbial composition and diversity.

Conclusions

Some breast milk from healthy postpartum women failed to be sequenced due to low microbial DNA quantities or is sterile. Research is needed to explore the reasons for this phenomenon. Infants fed with bacterial milk had higher Alpha diversity and more complex microbiota networks. These findings provide novel insight into milk microbiota and infant gut microbiota.
Design of and outcomes in a student-run free mental health clinic serving the uninsured in East Harlem
Authors: Powell Samuel K. , Saali Alexandra , Frere Justin , Magill Elizabeth , Krystal Hannah , Serafini Randal A. , Sultana Syeda , Dale Brandon , Ali Muhammad , Kumar Vedika , Datta Debjyoti , Hernandez-Antonio Josimar , Aronson Anne , Meah Yasmin S. , Gluhoski Vicki , Katz Craig L.
Published: July 2022

Background

Safety-net clinics are an important source of low-cost or free mental healthcare to those with limited financial resources. Such clinics are often staffed by trainees in early stages of their career. Only limited data exist on best practices in treatment-implementation and on clinical outcomes attained in such clinics. The primary purpose of this article is to describe the design of an outpatient psychiatry student-run free clinic (SRFC) serving uninsured individuals in New York City’s East Harlem neighborhood and to analyze the quality of services provided and the clinical outcomes attained.

Methods

The authors conducted a retrospective chart review ofn = 69 patients treated in the EHHOP Mental Health Clinic (E-MHC) to describe the demographic and clinical characteristics of the study population. Utilizing Health Effectiveness Data and Information Set metrics, they estimated the likelihoods of patients meeting metric quality criteria compared to those in other New York State (NYS) insurance groups. The authors derived linear mixed effect and logistic regression models to ascertain factors associated with clinical outcomes. Finally, the authors collected patient feedback on the clinical services received using a customized survey.

Results

Almost all patients were of Hispanic ethnicity, and about half of patients had more than one psychiatric disorder. The clinical service performance of the E-MHC was non-inferior on most measures examined. Factors associated with symptom improvement were the number of treatment sessions and certain demographic and clinical variables. Patients provided highly positive feedback on the mental healthcare services they received.

Conclusions

SRFCs can provide quality care to vulnerable patients that leads to clinically meaningful reductions in psychiatric symptoms and is well-received by patients.
The influence of diverse bone cement distribution patterns for metastatic vertebral lesions after bilateral percutaneous kyphoplasty
Authors: Wu Wence , Zhang Xinxin , Li Xiaoyang , Yu Shengji
Published: July 2022

Objective

To investigate the influence of diverse bone cement distribution patterns in patients with metastatic vertebral lesions after bilateral percutaneous kyphoplasty (PKP).

Methods

Fifty-nine patients with single-level metastatic vertebral lesions who received bilateral PKP were retrospectively reviewed. According to the different bone cement distribution patterns, patients were divided into confluent (n = 35, CF) and separated (n = 24, SP) groups. Indicators including visual analogue scale (VAS), Oswestry Disability Index (ODI), vertebral body height (VBH) variation, quality of life (QoL), and related complications were reviewed and compared between the two groups.

Results

No statistically significant differences were observed between the two groups in age, sex, types of lesions, locations of lesions, posterior vertebral body and/or pedicle involvement, percentage of vertebral invasion, procedure duration or cement volume (p > 0.05). There was significant improvement in VAS, ODI, VBH and QoL at any follow-up examination (p < 0.05) compared with those preoperatively. The CF group exhibited better pain relief in VAS scores than did the SP group just at 3 days and 1 month after PKP (p < 0.05). There were no significant differences between the two groups in VAS scores at 3 months or 1 year after PKP (p > 0.05). No statistically significant differences were observed between the two groups in terms of ODI, VBH or QoL (p > 0.05). There was no statistically significant difference in the incidence of complications between the two groups (p > 0.05).

Conclusions

More rapid pain relief was achieved with confluent rather than separated bone cement distribution patterns in PKP for patients with metastatic vertebral lesions.
Psychosocial burden in nurses working in nursing homes during the Covid-19 pandemic: a cross-sectional study with quantitative and qualitative data
Authors: Schulze Susanne , Merz Sibille , Thier Anne , Tallarek Marie , König Franziska , Uhlenbrock Greta , Nübling Matthias , Lincke Hans-Joachim , Rapp Michael A. , Spallek Jacob , Holmberg Christine
Published: July 2022

Background

The Covid-19 pandemic led to increased work-related strain and psychosocial burden in nurses worldwide, resulting in high prevalences of mental health problems. Nurses in long-term care facilities seem to be especially affected by the pandemic. Nevertheless, there are few findings indicating possible positive changes for health care workers. Therefore, we investigated which psychosocial burdens and potential positive aspects nurses working in long-term care facilities experience during the Covid-19 pandemic.

Methods

We conducted a mixed-methods study among nurses and nursing assistants working in nursing homes in Germany. The survey contained the third German version of the Copenhagen Psychosocial Questionnaire (COPSOQ III). Using Welch’s t-tests, we compared the COPSOQ results of our sample against a pre-pandemic reference group of geriatric nurses from Germany. Additionally, we conducted semi-structured interviews with geriatric nurses with a special focus on psychosocial stress, to reach a deeper understanding of their experiences on work-related changes and burdens during the pandemic. Data were analysed using thematic coding (Braun and Clarke).

Results

Our survey sample (n = 177) differed significantly from the pre-pandemic reference group in 14 out of 31 COPSOQ scales. Almost all of these differences indicated negative changes. Our sample scored significantly worse regarding the scales ‘quantitative demands’, ‘hiding emotions’, ‘work-privacy conflicts’, ‘role conflicts’, ‘quality of leadership’, ‘support at work’, ‘recognition’, ‘physical demands’, ‘intention to leave profession’, ‘burnout’, ‘presenteeism’ and ‘inability to relax’. The interviews (n = 15) revealed six main themes related to nurses’ psychosocial stress: ‘overall working conditions’, ‘concern for residents’, ‘management of relatives’, ‘inability to provide terminal care‘, ‘tensions between being infected and infecting others’ and ‘technicisation of care’. ‘Enhanced community cohesion’ (interviews), ‘meaning of work’ and ‘quantity of social relations’ (COPSOQ III) were identified as positive effects of the pandemic.

Conclusions

Results clearly illustrate an aggravation of geriatric nurses’ situation and psychosocial burden and only few positive changes due to the Covid-19 pandemic. Pre-existing hardships seem to have further deteriorated and new stressors added to nurses’ strain. The perceived erosion of care, due to an overemphasis of the technical in relation to the social and emotional dimensions of care, seems to be especially burdensome to geriatric nurses.
X-linked recessive ichthyosis in 8 Tunisian patients: awareness of misdiagnosis due to the technical trap of the STS pseudogene
Authors: Chouk Hamza , Saad Sarra , Dimassi Sarra , Fetoui Nadia Ghariani , Bennour Ayda , Gammoudi Rima , Elmabrouk Haifa , Saad Ali , Denguezli Mohamed , H’mida Dorra
Published: July 2022

Introduction

X-linked recessive ichthyosis (XLI) is a genodermatosis, caused by a deficiency of the steroid sulphatase enzyme encoded by the STS gene (OMIM # 300,747). Adopted XLI molecular diagnosis approaches differ from one laboratory to another depending on available technical facilities. Our work aims to figure out a sound diagnostic strategy for XLI.

Patients and methods

We collected 8 patients with XLI, all males, from 3 unrelated Tunisian families from central Tunisia. Genetic diagnosis was conducted through a large panel of genetic techniques including: Sanger Sequencing, haplotype analysis of STR markers, MLPA analysis, FISH and array CGH.

Results

Direct Sanger sequencing of the STS gene showed the same deletion of 13 base pairs within the exon 4 in all patients resulting in a premature stop codon. However, all patients’ mothers were not carriers of this variant and no common haplotype flanking STS gene was shared between affected patients. Sequence alignment with reference human genome revealed an unprocessed pseudogene of the STS gene located on the Y chromosome, on which the 13 bp deletion was actually located. STS MLPA analysis identified a deletion of the entire STS gene on X chromosome for all affected patients. This deletion was confirmed by FISH and delineated by array CGH.

Conclusion

All our patients shared a deletion of the entire STS gene revealed by MLPA, confirmed by FISH and improved by array CGH. Geneticists must be aware of the presence of pseudogenes that can lead to XLI genetic misdiagnosis.
Induction of apoptosis and cell cycle arrest in colorectal cancer cells by novel anticancer metabolites of Streptomyces sp. 801
Authors: Kouroshnia Arghavan , Zeinali Sirous , Irani Shiva , Sadeghi Akram
Published: July 2022

Background

Colorectal cancer is the third and most significant cause of death and fourth most common cancer in the world. Chemotherapy can be introduced in the cases of locally or distantly invasive colorectal cancer. In recent years Actinomycetes, especially the genus Streptomyces, contain numerous bioactive compounds, some of which are known as important anti-tumor chemotherapy drugs. In this research, we aimed to explore the anti-cancer mode of action of Streptomyces sp. 801 on colorectal cancer cells in vitro conditions.

Methods

Fermented supernatant of strain Streptomyces sp. 801 isolated from soil showed maximum growth inhibition on human colorectal cancer cells. The cytotoxic effects of various concentrations of EtOAc extract from bacterial culture supernatant on HT-29, HCT 116 and SW480 cancer cells were surveyed using the MTT assay. Moreover, flow cytometry assays and Bax, Bcl-2, Cyclin D1 and P21 gene expressions were carried out to assess the apoptotic and cell cycle effects. Also, the scratch assay was performed to measure migration. Finally, Ethyl acetate (EtOAc) extract was analyzed by LC–MS to identify anti-cancer compounds.

Results

The cell viability of all three cell lines were decreased in a dose-dependent manner. The successful induction of apoptosis and cell cycle arrest at IC50 values, were confirmed by flow cytometry as well as by the mRNA expression levels of the genes involved in these processes. Scratch assays indicated the inhibition of cell migration in the cancer cell lines treated by Streptomyces sp. 801. Nine anti-cancer compounds of Streptomyces sp. 801 were detected by liquid chromatography–mass spectrometry (LC–MS) analysis.

Conclusions

These findings suggest that Streptomyces sp. 801 can be a source of promising anticancer metabolites.

Graphical Abstract
DSF/Cu induces antitumor effect against diffuse large B-cell lymphoma through suppressing NF-κB/BCL6 pathways
Authors: Zhu Yunying , Lei Chenshuang , Jiang Qian , Yu Qinhua , Qiu Liannv
Published: July 2022

Background

The B-cell lymphoma 6 (BCL6) oncogene is required for the survival of diffuse large B-cell lymphoma (DLBCL), which is incurable using conventional chemotherapy. Thus, it is imperative to improve the survival of patients with DLBCL. Disulfide (DSF) has been shown to have anticancer effects, but its effect on DLBCL remains unclear.

Methods

Four DLBCL cell lines (OCI-LY1, OCI-LY7, OCI-LY10 and U2932) and primary DLBCL cells from eight newly diagnosed DLBCL patients were pretreated with DSF alone or in combination with Cu. Cell morphology was observed under microscope. Flow cytometry was performed to evaluate the cell apoptosis, cell cycle, the mitochondrial membrane potential and the intracellular accumulation of reactive oxygen species (ROS). The protein expression was respectively measured by flow cytometry and western blotting.

Results

DSF or DSF/Cu exhibited a marked inhibitory effect on the growth of DLBCL cells, accompanied by cell cycle arrest at the G0/G1 phase. Meanwhile, DSF or DSF/Cu significantly induced DLBCL cells apoptosis. Further study revealed that DSF or DSF/Cu promoted apoptosis by inhibiting NF-κB signaling pathway. Interestingly, DSF/Cu significantly reduced BCL6 and AIP levels. In addition, DSF significantly up-regulate p53 protein in OCI-LY7 and OCI-LY10 while down-regulate p53 protein in OCI-LY1 and U2932.

Conclusion

These results provided evidence for the anti-lymphoma effects of DSF on DLBCL and suggested that DSF has therapeutic potential to DLBCL.
Population replacement gene drive characteristics for malaria elimination in a range of seasonal transmission settings: a modelling study
Authors: Leung Shirley , Windbichler Nikolai , Wenger Edward A , Bever Caitlin A , Selvaraj Prashanth
Published: July 2022

Background

Gene drives are a genetic engineering method where a suite of genes is inherited at higher than Mendelian rates and has been proposed as a promising new vector control strategy to reinvigorate the fight against malaria in sub-Saharan Africa.

Methods

Using an agent-based model of malaria transmission with vector genetics, the impacts of releasing population-replacement gene drive mosquitoes on malaria transmission are examined and the population replacement gene drive system parameters required to achieve local elimination within a spatially-resolved, seasonal Sahelian setting are quantified. The performance of two different gene drive systems—“classic” and “integral”—are evaluated. Various transmission regimes (low, moderate, and high—corresponding to annual entomological inoculation rates of 10, 30, and 80 infectious bites per person) and other simultaneous interventions, including deployment of insecticide-treated nets (ITNs) and passive healthcare-seeking, are also simulated.

Results

Local elimination probabilities decreased with pre-existing population target site resistance frequency, increased with transmission-blocking effectiveness of the introduced antiparasitic gene and drive efficiency, and were context dependent with respect to fitness costs associated with the introduced gene. Of the four parameters, transmission-blocking effectiveness may be the most important to focus on for improvements to future gene drive strains because a single release of classic gene drive mosquitoes is likely to locally eliminate malaria in low to moderate transmission settings only when transmission-blocking effectiveness is very high (above ~ 80–90%). However, simultaneously deploying ITNs and releasing integral rather than classic gene drive mosquitoes significantly boosts elimination probabilities, such that elimination remains highly likely in low to moderate transmission regimes down to transmission-blocking effectiveness values as low as ~ 50% and in high transmission regimes with transmission-blocking effectiveness values above ~ 80–90%.

Conclusion

A single release of currently achievable population replacement gene drive mosquitoes, in combination with traditional forms of vector control, can likely locally eliminate malaria in low to moderate transmission regimes within the Sahel. In a high transmission regime, higher levels of transmission-blocking effectiveness than are currently available may be required.
Self-adjuvanting cancer nanovaccines
Authors: Liao Zhiyun , Huang Jing , Lo Pui-Chi , Lovell Jonathan F. , Jin Honglin , Yang Kunyu
Published: July 2022

Nanovaccines, a new generation of vaccines that use nanoparticles as carriers and/or adjuvants, have been widely used in the prevention and treatment of various diseases, including cancer. Nanovaccines have sparked considerable interest in cancer therapy due to a variety of advantages, including improved access to lymph nodes (LN), optimal packing and presentation of antigens, and induction of a persistent anti-tumor immune response. As a delivery system for cancer vaccines, various types of nanoparticles have been designed to facilitate the delivery of antigens and adjuvants to lymphoid organs and antigen-presenting cells (APCs). Particularly, some types of nanoparticles are able to confer an immune-enhancing capability and can themselves be utilized for adjuvant-like effect for vaccines, suggesting a direction for a better use of nanomaterials and the optimization of cancer vaccines. However, this role of nanoparticles in vaccines has not been well studied. To further elucidate the role of self-adjuvanting nanovaccines in cancer therapy, we review the mechanisms of antitumor vaccine adjuvants with respect to nanovaccines with self-adjuvanting properties, including enhancing cross-presentation, targeting signaling pathways, biomimicking of the natural invasion process of pathogens, and further unknown mechanisms. We surveyed self-adjuvanting cancer nanovaccines in clinical research and discussed their advantages and challenges. In this review, we classified self-adjuvanting cancer nanovaccines according to the underlying immunomodulatory mechanism, which may provide mechanistic insights into the design of nanovaccines in the future.

Graphical Abstract
Hyaluronic acid-coated Bi:Cu2O: an H2S-responsive agent for colon cancer with targeted delivery and enhanced photothermal performance
Authors: Cheng Yuying , Bo Haiji , Qin Ruomeng , Chen Fulai , Xue Fengfeng , An Lu , Huang Gang , Tian Qiwei
Published: July 2022

Background

Endogenous hydrogen sulfide (H2S)-responsive theranostic agents have attracted extensive attention due to their specificity for colon cancer. However, the development of such agents with high enrichment in tumors and excellent photothermal performance remains challenging.

Results

We prepared hyaluronic acid (HA)-coated Bi-doped cuprous oxide (Bi:Cu2O@HA) via a one-pot method. The HA specifically targets colon cancer tumor cells to improve the enrichment of Bi:Cu2O@HA at tumor sites, while the doped Bi both enhances the photothermal performance of the H2S-triggered Cu2O and serves as an agent for tumor imaging. The results in this work demonstrated that the Bi:Cu2O@HA nanoparticles exhibit good biocompatibility, target colon cancer tumor cells, facilitate computed tomography imaging, and enhanced H2S-responsive photothermal therapy performance, resulting in an excellent therapeutic effect in colon cancer.

Conclusions

The novel Bi:Cu2O@HA nanoparticles exhibit excellent tumor targeting and photothermal therapeutic effects, which provide new strategies and insights for colon cancer therapy.

Graphical Abstract