bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical and epidemiological features of imported loiasis in Beijing: a report from patients returned from Africa
Authors: Li Xiaoli , Huang Minjun , Bi Kuo , Zou Yang , Wang Fei , Zheng Xiaoyan , Wang Lei
Published: July 2024

Background

Loiasis is one of the significant filarial diseases for people living in West and Central Africa with wide endemic area but is not seen in China. As economy booms and international traveling increase, China faces more and more imported parasitic diseases that are not endemic locally. Loiasis is one of the parasitic diseases that enter China by travelers infected in Africa. The better understanding of the clinical and laboratory features of loa loa infection will facilitate the diagnosis and treatment of loiasis in China.

Methods

The study targeted travelers who were infected with L. loa in endemic Africa regions and returned to Beijing between 2014 and 2023. Epidemiological, clinical, and biological data as well as treatment of these patients were collected.

Results

Total 21 cases were identified as L. loa infection based on their typical clinical manifestations and parasite finding. All cases had a history of travel to Africa for more than 6 months, most of them are the construction workers dispatched to West Africa with outdoor activities. Calabar swelling (n = 19; 90.5%) and pruritus (n = 11; 52.4%) were among the most common clinical symptoms followed by muscle pain (n = 7; 33.3%) and skin rash (n = 2; 9.5%). The adult worms were observed in the eyelid or subconjunctiva (n = 2; 9.5%) and subcutaneous tissues (n = 2; 9.5%). Although all patients presented with a high eosinophil count (> 0.52 × 109/L), only two cases displayed microfilariae in fresh venous blood and positive for filarial antigen. A cut section of adult worm was observed through biopsy on a skin nodule surrounded by lymphocytes, plasma cells and eosinophils. All subjects were positive in PCR targeting L. loa ITS-1. The constructed phylogenetic tree based on the amplified ITS-1 sequences identified their genetical relation to the L. Loa from Africa. All patients treated with albendazole and diethylcarbamazine were recovered without relapse.

Conclusion

This study provides useful information and guideline for physicians and researchers in non-endemic countries to diagnose and treat loiasis and L. loa infections acquired from endemic regions.
Intraoperative challenges and management of fibrovascular membrane with tractional retinoschisis in proliferative diabetic retinopathy
Authors: Shiraki Akihiko , Shiraki Nobuhiko , Sakimoto Susumu , Maruyama Kazuichi , Maeno Takatoshi , Nishida Kohji
Published: July 2024

Background

In severe Proliferative Diabetic Retinopathy (PDR), fibrovascular membrane (FVM) causes macular tractional retinal detachment (MTRD) which threatens vision and eventually leads to blindness. Here we present a case of separation between the inner and outer retina in tractional retinoschisis, induced during intraoperative FVM delamination.

Case presentation

A 68-year-old woman presented with PDR in the right eye, characterized by a combined FVM and retinal detachment, for which a vitrectomy was performed. Multiple holes, large retinal detachment extending to all quadrants, and white-lined blood vessels with FVM were found during the procedure. When membrane delamination was performed, it strayed into the space between the inner and outer retinal layers without being noticed due to retinoschisis and multiple retinal holes. After removing the FVM and detaching the separated inner retina, fluid-gas and photocoagulation were performed. Retinal reattachment was successfully achieved after surgery, and the postoperative visual acuity was improved and maintained for 26 months postoperatively.

Conclusions

When tractional retinoschisis due to FVM is combined with retinal holes in tractional retinal detachment (TRD), care must be taken to prevent delamination from straying into retinoschisis during separation.
Outcomes from Partner2Lose: a randomized controlled trial to evaluate 24-month weight loss in a partner-assisted intervention
Authors: Voils Corrine I. , Shaw Ryan J. , Gavin Kara L. , Hetzel Scott J. , Lewis Megan A. , Pabich Samantha , Johnson Heather M. , Elwert Felix , Mao Lu , Gray Kristen E. , Yuroff Alice , Garza Katya , Yancy William S. , Porter Laura S.
Published: July 2024

Background

Partner support is associated with better weight loss outcomes in observational studies, but randomized trials show mixed results for including partners. Unclear is whether teaching communication skills to couples will improve weight loss in a person attempting weight loss (index participant).

Purpose

To compare the efficacy of a partner-assisted intervention versus participant-only weight management program on 24-month weight loss.

Methods

This community-based study took place in Madison, WI. Index participants were eligible if they met obesity guideline criteria to receive weight loss counseling, were aged 18–74 years, lived with a partner, and had no medical contraindications to weight loss; partners were aged 18–74 years and not underweight. Couples were randomized 1:1 to a partner-assisted or participant-only intervention. Index participants in both arms received an evidence-based weight management program. In the partner-assisted arm, partners attended half of the intervention sessions, and couples were trained in communication skills. The primary outcome was index participant weight at 24 months, assessed by masked personnel; secondary outcomes were 24-month self-reported caloric intake and average daily steps assessed by an activity tracker. General linear mixed models were used to compare group differences in these outcomes following intent-to-treat principles.

Results

Among couples assigned to partner-assisted (n = 115) or participant-only intervention (n = 116), most index participants identified as female (67%) and non-Hispanic White (87%). Average baseline age was 47.27 years (SD 11.51 years) and weight was 106.55 kg (SD 19.41 kg). The estimated mean 24-month weight loss was similar in the partner-assisted (2.66 kg) and participant-only arms (2.89 kg) (estimated mean difference, 0.23 kg [95% CI, -1.58, 2.04 kg], p=0.80). There were no differences in 24-month average daily caloric intake (estimated mean difference 50 cal [95% CI: -233, 132 cal], p=0.59) or steps (estimated mean difference 806 steps [95% CI: -1675, 64 steps], p=0.07). The percentage of participants reporting an adverse event with at least possible attribution to the intervention did not differ by arm (partner-assisted: 9%, participant-only, 3%, p = 0.11).

Conclusions

Partner-assisted and individual weight management interventions led to similar outcomes in index participants.

Trial registration

Clinicaltrials.gov NCT03801174, January 11, 2019.
Depletion of b-series ganglioside prevents limb length discrepancy after growth plate injury
Authors: Hosokawa Yoshiaki , Matsuoka Masatake , Sakai Yuko , Fukuda Ryuichi , Matsugasaki Keizumi , Homan Kentaro , Furukawa Jun-ichi , Onodera Tomohiro , Iwasaki Norimasa
Published: July 2024

Introduction

Growth plate damage in long bones often results in progressive skeletal growth imbalance and deformity, leading to significant physical problems. Gangliosides, key glycosphingolipids in cartilage, are notably abundant in articular cartilage and regulate chondrocyte homeostasis. This suggests their significant roles in regulating growth plate cartilage repair.

Methods

Chondrocytes from 3 to 5 day-old C57BL/6 mice underwent glycoblotting and mass spectrometry. Based on the results of the glycoblotting analysis, we employed GD3 synthase knockout mice (GD3-/-), which lack b-series gangliosides. In 3-week-old mice, physeal injuries were induced in the left tibiae, with right tibiae sham operated. Tibiae were analyzed at 5 weeks postoperatively for length and micro-CT for growth plate height and bone volume at injury sites. Tibial shortening ratio and bone mineral density were measured by micro-CT.

Results

Glycoblotting analysis indicated that b-series gangliosides were the most prevalent in physeal chondrocytes among ganglioside series. At 3 weeks, GD3-/- exhibited reduced tibial shortening (14.7 ± 0.2 mm) compared to WT (15.0 ± 0.1 mm, P = 0.03). By 5 weeks, the tibial lengths in GD3-/- (16.0 ± 0.4 mm) closely aligned with sham-operated lengths (P = 0.70). Micro-CT showed delayed physeal bridge formation in GD3-/-, with bone volume measuring 168.9 ± 5.8 HU at 3 weeks (WT: 180.2 ± 3.2 HU, P = 0.09), but normalizing by 5 weeks.

Conclusion

This study highlights that GD3 synthase knockout mice inhibit physeal bridge formation after growth plate injury, proposing a new non-invasive approach for treating skeletal growth disorders.
The potential role of collagen type VII in breast cancer proliferation
Authors: Pérez-Díaz Sergio , Lindberg Jessica , Anerillas Luis Oliveros , Kingham Paul J. , Sund Malin , Rask Gunilla , Svensson Johan , Jansson Malin , Wiberg Rebecca
Published: July 2024

Background

Breast cancer is the most common cancer in women. Cancer cells can persist in a prolonged dormant state for years without any clinical evidence of disease creating an urgent need to better understand the molecular mechanisms leading to relapse. This study aimed to identify extracellular matrix (ECM) components associated with hypoxia-induced breast cancer dormancy. The effects of selected ECM proteins on breast cancer cell proliferation were analyzed, along with their correlation with established prognostic markers in human breast cancer tissue.

Materials and methods

Screening of extracellular matrix proteins was performed in hypoxia-induced dormant MCF-7 breast cancer cells. Proliferation of MCF-7 cells in vitro was subsequently determined in the presence of recombinant ColVII. Adipose tissue-derived mesenchymal stem cells (AdMSCs) subpopulation overexpressing ColVII were indirectly isolated by ColVII receptor integrin-α6 specific antibodies. AdMSCs- MCF-7 3D spheroid cultures were generated to model solid tumour conditions. In addition, the association between ColVII and various prognostic markers was evaluated in clinical samples of human breast cancer tissue.

Results

Dormant MCF-7 cells showed an elevated expression of ColVII while MCF-7 cells cultured on ColVII exhibited reduced proliferation in vitro. In AdMSCs-MCF-7 3D spheroids, a reduced proliferation of MCF-7 cells was observed in Int-α6+/ ColVIIhigh compared with Int-α6-/ ColVIIlow AdMSCs spheroids. In human tissue, high ColVII expression correlated to several positive prognostic markers. Staining for Cytokeratin-5 revealed that ColVIIhigh-expressing cells were predominantly myoepithelial cells.

Conclusion

ColVII is associated with reduced proliferation of breast cancer cells in vitro. ColVII is strongly expressed in myoepithelial cells and in breast cancer tissue the high ColVII expression correlates with several well-known positive prognostic markers, highlighting its potential as a prognostic marker in breast cancer.
USP13 ameliorates nonalcoholic fatty liver disease through inhibiting the activation of TAK1
Authors: Tang Min , Cao Han , Ma Yunqin , Yao Shuangshuang , Wei Xiaohui , Tan Yijiong , liu Fang , Peng Yongde , Fan Nengguang
Published: July 2024

Background

The molecular mechanisms underlying nonalcoholic fatty liver disease (NAFLD) remain to be fully elucidated. Ubiquitin specific protease 13 (USP13) is a critical participant in inflammation-related signaling pathways, which are linked to NAFLD. Herein, the roles of USP13 in NAFLD and the underlying mechanisms were investigated.

Methods

L02 cells and mouse primary hepatocytes were subjected to free fatty acid (FFA) to establish an in vitro model reflective of NAFLD. To prepare in vivo model of NAFLD, mice fed a high-fat diet (HFD) for 16 weeks and leptin-deficient (ob/ob) mice were used. USP13 overexpression and knockout (KO) strategies were employed to study the function of USP13 in NAFLD in mice.

Results

The expression of USP13 was markedly decreased in both in vitro and in vivo models of NAFLD. USP13 overexpression evidently inhibited lipid accumulation and inflammation in FFA-treated L02 cells in vitro. Consistently, the in vivo experiments showed that USP13 overexpression ameliorated hepatic steatosis and metabolic disorders in HFD-fed mice, while its deficiency led to contrary outcomes. Additionally, inflammation was similarly attenuated by USP13 overexpression and aggravated by its deficiency in HFD-fed mice. Notably, overexpressing of USP13 also markedly alleviated hepatic steatosis and inflammation in ob/ob mice. Mechanistically, USP13 bound to transforming growth factor β-activated kinase 1 (TAK1) and inhibited K63 ubiquitination and phosphorylation of TAK1, thereby dampening downstream inflammatory pathways and promoting insulin signaling pathways. Inhibition of TAK1 activation reversed the exacerbation of NAFLD caused by USP13 deficiency in mice.

Conclusions

Our findings indicate the protective role of USP13 in NAFLD progression through its interaction with TAK1 and inhibition the ubiquitination and phosphorylation of TAK1. Targeting the USP13-TAK1 axis emerges as a promising therapeutic strategy for NAFLD treatment.
Computing cell state discriminates the aberrant hematopoiesis and activated microenvironment in Myelodysplastic syndrome (MDS) through a single cell genomic study
Authors: Guo Xinyu , Jin Wenyan , Wen Yuchen , Wang Zhiqin , Ren Xiaotong , Liu Zhaoyun , Fu Rong , Cai Zhigang , Li Lijuan
Published: July 2024

Background

Myelodysplastic syndrome (MDS) is a complicated hematopoietic malignancy characterized by bone marrow (BM) dysplasia with symptoms like anemia, neutropenia, or thrombocytopenia. MDS exhibits considerable heterogeneity in prognosis, with approximately 30% of patients progressing to acute myeloid leukemia (AML). Single cell RNA-sequencing (scRNA-seq) is a new and powerful technique to profile disease landscapes. However, the current available scRNA-seq datasets for MDS are only focused on CD34+ hematopoietic progenitor cells. We argue that using entire BM cell for MDS studies probably will be more informative for understanding the pathophysiology of MDS.

Methods

Five MDS patients and four healthy donors were enrolled in the study. Unsorted cells from BM aspiration were collected for scRNA-seq analysis to profile overall alteration in hematopoiesis.

Results

Standard scRNA-seq analysis of unsorted BM cells successfully profiles deficient hematopoiesis in all five MDS patients, with three classified as high-risk and two as low-risk. While no significant increase in mutation burden was observed, high-risk MDS patients exhibited T-cell activation and abnormal myelogenesis at the stages between hematopoietic stem and progenitor cells (HSPC) and granulocyte–macrophage progenitors (GMP). Transcriptional factor analysis on the aberrant myelogenesis suggests that the epigenetic regulator chromatin structural protein-encoding gene HMGA1 is highly activated in the high-risk MDS group and moderately activated in the low-risk MDS group. Perturbation of HMGA1 by CellOracle simulated deficient hematopoiesis in mouse Lineage-negative (Lin-) BM cells. Projecting MDS and AML cells on a BM cell reference by our newly developed MarcoPolo pipeline intuitively visualizes a connection for myeloid leukemia development and abnormalities of hematopoietic hierarchy, indicating that it is technically feasible to integrate all diseased bone marrow cells on a common reference map even when the size of the cohort reaches to 1,000 patients or more.

Conclusion

Through scRNA-seq analysis on unsorted cells from BM aspiration samples of MDS patients, this study systematically profiled the development abnormalities in hematopoiesis, heterogeneity of risk, and T-cell microenvironment at the single cell level.
Microglial AKAP8L: a key mediator in diabetes-associated cognitive impairment via autophagy inhibition and neuroinflammation triggering
Authors: Zhang Wen-yuan , Wei Qian-qian , Zhang Tao , Wang Chang-shui , Chen Jing , Wang Jian-hua , Xie Xin , Jiang Pei
Published: July 2024

Background

Diabetes-associated cognitive impairment (DACI) poses a significant challenge to the self-management of diabetes, markedly elevating the risk of adverse complications. A burgeoning body of evidence implicates microglia as a central player in the pathogenesis of DACI.

Methods

We utilized proteomics to identify potential biomarkers in high glucose (HG)-treated microglia, followed by gene knockdown techniques for mechanistic validation in vitro and in vivo.

Results

Our proteomic analysis identified a significant upregulation of AKAP8L in HG-treated microglia, with concurrent dysregulation of autophagy and inflammation markers, making AKAP8L a novel biomarker of interest. Notably, the accumulation of AKAP8L was specific to HG-treated microglia, with no observed changes in co-cultured astrocytes or neurons, a pattern that was mirrored in streptozotocin (STZ)-induced diabetic mice. Further studies through co-immunoprecipitation and proximity ligation assay indicated that the elevated AKAP8L in HG-treated microglial cells interacts with the mTORC1. In the STZ mouse model, we demonstrated that both AKAP8L knockdown and rapamycin treatment significantly enhanced cognitive function, as evidenced by improved performance in the Morris water maze, and reduced microglial activation. Moreover, these interventions effectively suppressed mTORC1 signaling, normalized autophagic flux, mitigated neuroinflammation, and decreased pyroptosis.

Conclusions

Our findings highlight the critical role of AKAP8L in the development of DACI. By interacting with mTORC1, AKAP8L appears to obstruct autophagic processes and initiate a cascade of neuroinflammatory responses. The identification of AKAP8L as a key mediator in DACI opens up new avenues for potential therapeutic interventions.
Advanced screening methods for assessing motility and hatching in plant-parasitic nematodes
Authors: Kadlecová Alena , Hendrychová Romana , Jirsa Tomáš , Čermák Václav , Huang Mengmeng , Grundler Florian M.W. , Schleker A. Sylvia S.
Published: July 2024

Background

Plant-parasitic nematodes are economically important pests responsible for substantial losses in agriculture. Researchers focusing on plant-parasitic nematodes, especially on finding new ways of their control, often need to assess basic parameters such as their motility, viability, and reproduction. Traditionally, these assays involve visually counting juveniles and eggs under a dissecting microscope, making this investigation time-consuming and laborious.

Results

In this study, we established a procedure to efficiently determine the motility of two plant-parasitic nematode species, Heterodera schachtii and Ditylenchus destructor, using the WMicrotracker ONE platform. Additionally, we demonstrated that hatching of the cyst nematode H. schachtii can be evaluated using both the WMicrotracker ONE and by assessing the enzymatic activity of chitinase produced during hatching.

Conclusions

We present fast and straightforward protocols for studying nematode motility and hatching that allow us to draw conclusions about viability and survival. Thus, these methods are useful tools for facilitating fast and efficient evaluation in various fields of research focused on plant-parasitic nematodes.
Feasibility of epicardial implantation of medtronic 3830 lead in a pediatric patient : case report
Authors: Yuan Dou , Lin Ke , Xu Yuanning
Published: July 2024

Background

High-grade atrioventricular block is the primary reason for epicardial permanent pacemaker implantation during the perioperative period in patients with congenital heart disease. Due to the smaller diameter of venous vessels in children, epicardial permanent pacemaker implantation is usually a preferred choice, we report one pediatric patient who received epicardial permanent pacemaker implantation using a new approach.

Case presentation

We present the case of a 2-year-old girl who underwent the modified Konno procedure and Pulmonary valvuloplasty surgery and presented after surgery with a High-grade atrioventricular block. At over 20 days after the patient underwent a redo-sternotomy which epicardial permanent pacemaker implantation. Medtronic Model 4965 Capsure Epi ® steroid-eluting unipolar epicardial pacing lead was immobilized on the surface of the right ear. The Medtronic 3830 pacing lead was screwed obliquely and clockwise under direct view from the surface of the right ventricle to the endocardium near the interventricular septum. The patient’s recovery was uneventful.

Conclusion

In this case report, we demonstrate the feasibility and potential benefits of using the Medtronic 3830 lead for epicardial pacing in a pediatric patient with severe cardiac complications following surgery for congenital heart disease. This approach offers a viable alternative to traditional epicardial pacing methods, particularly in complex cases where conventional leads fail to provide stable pacing thresholds.
Early treatment for children with mental health problems and genetic conditions through a parenting intervention (The GAP): study protocol for a pragmatic randomized controlled trial
Authors: Serrano Mercedes , Elias Maria , Llorens Marta , Bolasell Mercè , Vall-Roqué Helena , Villalta Laia
Published: July 2024

Background

Children with genetic conditions are at increased risk for mental health and neurodevelopmental problems, often accompanied by significant parental distress. Genetic and family factors can impact children and parents’ mental health. Early parenting interventions, like the Incredible Years® programs, have demonstrated to improve parental distress and children’s mental health. The recent version for young children with language delays or autism spectrum disorder (IY-ASLD®) has shown to be feasible and effective to support parents in their children’s developmental trajectories. The effectiveness of treatments for children with genetic conditions and neurodevelopmental problems is largely unexplored, leaving significant gaps in evidence-based options. Clinicians lack guidance, especially when patients exhibit language or social communication impairments but do not meet diagnostic criteria for a full-blown autism spectrum disorder (ASD). We aim to fill this gap, providing evidence on the feasibility and effectiveness of the IY-ASLD® intervention for such patients.

Methods

We designed a prospective multicenter pragmatic randomized controlled trial including approximately 68 children aged 3 to 7 years, recruited from three tertiary care reference hospitals. Inclusion criteria will necessitate genetic confirmation of a neurodevelopmental disorder along with language, communication, or socialization difficulties. Individuals with an ASD diagnosis will be excluded. All subjects are included in a territorial register for rare conditions (ReMin, Registre de Malalties Minoritàries de Catalunya). Families will randomly be assigned to the intervention or the control group. The intervention will be held online by clinical psychologists and child and adolescent psychiatrists.

Discussion

Our group has recently piloted the online implementation of the IY-ASLD® intervention for the first time in Spain, for parents of children with language delays, socialization difficulties, or ASD, but not genetically determined. Our multicenter research consortium is well-positioned to recruit patients with rare conditions and implement efficient treatment pathways within the National Health System. Given the geographical dispersion of families affected by rare conditions, the online format offers logistical advantages and improved therapy access, enhancing homogeneity across all patients. The results of this study will inform clinicians and policymakers about evidence-based treatment options for this vulnerable and overlooked group of young children.

Trial registration

ClinicalTrials.gov NCT06125093. Date of registration: first submitted 2023–10-23; first posted 2023–11-09. URL of trial registry record.
Protocol update for a multi-centre randomised controlled trial of exercise rehabilitation for people with pulmonary hypertension: the SPHERe trial
Authors: Ennis Stuart , Bruce Julie , Sandhu Harbinder , Ratna Mariam , Lall Ranjit , Ji Chen , Mason James , Kandiyali Rebecca , Seers Kate , Banerjee Prithwish , Taylor Stephanie J. C. , Robertson Elizabeth , Underwood Martin , McGregor Gordon
Published: July 2024

Background

The SPHERe (Supervised Pulmonary Hypertension Exercise Rehabilitation) trial is a multi-centre, pragmatic, randomised controlled trial assessing the clinical and cost-effectiveness of supervised exercise rehabilitation with psychosocial and motivational support compared to best-practice usual care for people with pulmonary hypertension (PH). The original protocol was published in BMC Pulmonary Medicine (accessible online). We randomised our first participant in January 2020. In response to the COVID-19 pandemic, the trial was stopped in March 2020. In person delivery of the SPHERe intervention to a vulnerable population was not possible during the COVID-19 pandemic. We describe here how trial procedures and intervention delivery were adapted in response to the COVID-19 pandemic.

Methods

Restrictions imposed by the COVID-19 pandemic on the clinically vulnerable PH population meant that trial delivery was changed from a centre-based rehabilitation programme to remotely delivered group online sessions. This led to minor alterations to the eligibility criteria. These changes followed a consultation process with stakeholders and people with PH and were approved by the funder and independent trial committees.

Conclusions

We describe the modified SPHERe trial protocol in response to restrictions imposed by the COVID-19 pandemic. SPHERe is the first randomised controlled trial to assess the clinical and cost-effectiveness of an online group rehabilitation programme for people with PH compared to usual care.

Trial registration

ISRCTN no. 10608766. Prospectively registered on 18th March 2019, updated 16th August 2023.
CUT&Tag applied to zebrafish adult tail fins reveals a return of embryonic H3K4me3 patterns during regeneration
Authors: Duong Phu , Rodriguez-Parks Anjelica , Kang Junsu , Murphy Patrick J.
Published: July 2024

Regenerative potential is governed by a complex process of transcriptional reprogramming, involving chromatin reorganization and dynamics in transcription factor binding patterns throughout the genome. The degree to which chromatin and epigenetic changes contribute to this process remains only partially understood. Here we provide a modified CUT&Tag protocol suitable for improved characterization and interrogation of changes in chromatin modifications during adult fin regeneration in zebrafish. Our protocol generates data that recapitulates results from previously published ChIP-Seq methods, requires far fewer cells as input, and significantly improves signal to noise ratios. We deliver high-resolution enrichment maps for H3K4me3 of uninjured and regenerating fin tissues. During regeneration, we find that H3K4me3 levels increase over gene promoters which become transcriptionally active and genes which lose H3K4me3 become silenced. Interestingly, these reprogramming events recapitulate the H3K4me3 patterns observed in developing fin folds of 24-h old zebrafish embryos. Our results indicate that changes in genomic H3K4me3 patterns during fin regeneration occur in a manner consistent with reactivation of developmental programs, demonstrating CUT&Tag to be an effective tool for profiling chromatin landscapes in regenerating tissues.
Anticandidal activity of a wild Bacillus subtilis NAM against clinical isolates of pathogenic Candida albicans
Authors: Gharieb Mohamed M. , Rizk Aya , Elfeky Nora
Published: July 2024

Background

Resistance to antifungal medications poses a significant obstacle in combating fungal infections. The development of novel therapeutics for Candida albicans is necessary due to the increasing resistance of candidiasis to the existing medications. The utilization of biological control is seen as a more advantageous and less hazardous strategy therefore the objective of this study is to identify the antifungal properties of Bacillus subtilis against pathogenic C. albicans.

Results

We conducted a study to evaluate the antifungal properties of three bacterial isolates against the human pathogen Candida albicans. One of the bacterial isolates exhibited a potent antifungal activity against this fungal pathogen. This bacterium was identified as Bacillus subtilis based on the 16Sr RNA gene sequence. It exhibited inhibitory efficacy ranging from 33.5 to 44.4% against 15 Candida isolates. The optimal incubation duration for achieving the maximum antifungal activity was determined to be 48 h, resulting in a mean inhibition zone diameter of 29 ± 0.39 mm. The Potato Dextrose agar (PDA) medium was the best medium for the most effective antifungal activity. Incubation temperature of 25oC and medium pH value of 8.0 were the most favorable conditions for maximum antagonistic activity that resulted fungal growth inhibition of 40 ± 0.16 and 36 ± 0.94 mm respectively. Furthermore, the addition of 10.5 mg/ml of bacterial filtrate to C. albicans colonies resulted in 86.51%. decrease in the number of germinated cells. The fungal cell ultrastructural responses due to exposure to B. subtilis filtrate after 48 h were investigated using transmission electron microscopy (TEM). It revealed primary a drastic abnormality that lead to cellular disintegration including folding and lysis of the cell wall, total collapse of the yeast cells, and malformed germ tube following the exposure to the filtrate. However, the control culture treatment had a characteristic morphology of the normal fungal cells featuring a consistently dense central region, a well-organized nucleus, and a cytoplasm containing several components of the endomembrane system. The cells were surrounded by a uniform and intact cell wall.

Conclusion

The current study demonstrates a notable antifungal properties of B. subtilis against C. albicans as a result of production of bioactive components of the bacterial exudate. This finding could be a promising natural antifungal agent that could be utilized to combat C. albicans.
Radiotherapy for subependymal giant cell astrocytoma: time to challenge a historical ban? A case report and review of the literature
Authors: Kamel Randa , Van den Berge Dirk
Published: July 2024

Background

Subependymal giant cell astrocytoma is a benign brain tumor that occurs in patients with tuberous sclerosis complex. Surgical removal is the traditional treatment, and expert opinion is strongly against the use of radiotherapy. Recently, success has been reported with the mTor inhibitor everolimus in reducing tumor volume, but regrowth has been observed after dose reduction or cessation.

Case report

We present the case of a 40-year-old Asian female patient treated successfully for growing bilateral subependymal giant cell astrocytoma with fractionated stereotactic radiotherapy before everolimus became available. After a follow-up of 8 years, everolimus was administered for renal angiomyolipoma and the patient was followed up until 13 years after radiotherapy. Successive magnetic resonance imaging demonstrated an 80% volume reduction after radiotherapy that increased to 90% with everolimus. A review of the literature was done leveraging Medline via PubMed, and we assembled a database of 1298 article references and 780 full-text articles in search of evidence for contraindicating radiotherapy in subependymal giant cell astrocytoma. Varying results of single-fraction radiosurgery were described in a total of 13 cases. Only in two published cases was the radiation dose of fractionated radiotherapy mentioned. One single publication mentions an induced secondary brain tumor 8 years after whole-brain radiotherapy.

Conclusion

There is no evidence of contraindication and exclusion of fractionated radiotherapy in treating subependymal giant cell astrocytoma. Our experience demonstrates that subependymal giant cell astrocytoma, as other benign intracranial tumors, responds slowly but progressively to radiotherapy and suggests that fractionated stereotactic radiotherapy holds promise to consolidate responses obtained with mTor inhibitors avoiding regrowth after cessation.
The influence of vesicularity on grain morphology in basaltic pyroclasts from Mauna Loa and Kīlauea volcanoes
Authors: van Helden Kira M. , Schmith Johanne , Downs Drew T.
Published: July 2024

Vesicularity of individual pyroclasts from airfall tephra deposits is an important parameter that is commonly measured at basaltic volcanoes. Conventional methods used to determine pyroclast vesicularity on a large number of clasts has the potential to be time consuming, particularly when rapid analysis is required. Here we propose dynamic image analysis on two-dimensional (2D) projection shapes of crushed pyroclasts from tephra deposits as a new method to estimate vesicularity. This method relies on the influence of vesicles and uses grain morphology as a proxy for vesicle size and abundance. Pyroclasts from a variety of basaltic tephra deposits from the volcanoes of Mauna Loa and Kīlauea were analyzed. Vesicularities between 52–98% were measured via nitrogen-gas pycnometry. The same pyroclasts were then crushed and sieved, and their grain shapes measured using dynamic image analysis on a CAMSIZER®. This yields values for the mean sphericity, elongation, compactness, and Krumbein roundness of the grains. Our data show that grains become increasingly irregular with increasing vesicularity, with the degree of correlation between shape parameters and vesicularity depending on the size of measured grains. Shape irregularities in small grains (60–250 µm) are mostly area-based, with elongation being the best vesicularity indicator, whereas shape irregularities in large grains (250–700 µm) are mostly perimeter-based, with Krumbein roundness as the best vesicularity indicator. Using mean shape parameter values with all grain sizes included, grain elongation is the most well-correlated shape parameter with vesicularity, with the best fitted model explaining 76% of variation in the observations. Microscope images of thin sections of intact pyroclasts, as well as from crushed pyroclasts, were analyzed using CSDCorrections 1.6 software in ImageJ to find local vesicularity, vesicle size, grain size, grain elongation, and vesicle spatial distribution by stereological conversion. Observed correlation between grain shape and vesicularity can be explained by the local effect of vesicles on the shape of the solid structure in between those vesicles. Grain shape depends not only on vesicularity, but also on vesicle to grain size ratio and the spatial distribution of vesicles. The influence of vesicles on grain shape is best captured by grains with the size of the solid structure in between vesicles, which generally increases with decreasing vesicularity. Dynamic image analysis is a useful tool to quickly gauge vesicularity, which could be used in near-real-time during an eruption response. However, this method is best suited for highly vesicular (> 80%) basaltic pyroclasts from tephra deposits with few microlites and phenocrysts. Further research on crushing techniques, optimum grain size for shape measurements, and Krumbein roundness measurements for the grain size range of 250–700 µm might enable application of this method to lower vesicularity pyroclasts.
Time-series metagenomics reveals changing protistan ecology of a temperate dimictic lake
Authors: Krinos Arianna I. , Bowers Robert M. , Rohwer Robin R. , McMahon Katherine D. , Woyke Tanja , Schulz Frederik
Published: July 2024

Background

Protists, single-celled eukaryotic organisms, are critical to food web ecology, contributing to primary productivity and connecting small bacteria and archaea to higher trophic levels. Lake Mendota is a large, eutrophic natural lake that is a Long-Term Ecological Research site and among the world’s best-studied freshwater systems. Metagenomic samples have been collected and shotgun sequenced from Lake Mendota for the last 20 years. Here, we analyze this comprehensive time series to infer changes to the structure and function of the protistan community and to hypothesize about their interactions with bacteria.

Results

Based on small subunit rRNA genes extracted from the metagenomes and metagenome-assembled genomes of microeukaryotes, we identify shifts in the eukaryotic phytoplankton community over time, which we predict to be a consequence of reduced zooplankton grazing pressures after the invasion of a invasive predator (the spiny water flea) to the lake. The metagenomic data also reveal the presence of the spiny water flea and the zebra mussel, a second invasive species to Lake Mendota, prior to their visual identification during routine monitoring. Furthermore, we use species co-occurrence and co-abundance analysis to connect the protistan community with bacterial taxa. Correlation analysis suggests that protists and bacteria may interact or respond similarly to environmental conditions. Cryptophytes declined in the second decade of the timeseries, while many alveolate groups (e.g., ciliates and dinoflagellates) and diatoms increased in abundance, changes that have implications for food web efficiency in Lake Mendota.

Conclusions

We demonstrate that metagenomic sequence-based community analysis can complement existing efforts to monitor protists in Lake Mendota based on microscopy-based count surveys. We observed patterns of seasonal abundance in microeukaryotes in Lake Mendota that corroborated expectations from other systems, including high abundance of cryptophytes in winter and diatoms in fall and spring, but with much higher resolution than previous surveys. Our study identified long-term changes in the abundance of eukaryotic microbes and provided context for the known establishment of an invasive species that catalyzes a trophic cascade involving protists. Our findings are important for decoding potential long-term consequences of human interventions, including invasive species introduction.
Qualitative insights into mental health treatment through telemedicine during the COVID-19 crisis: a natural experiment in community mental health centers
Authors: Hood Brittany J.
Published: July 2024

Background

The COVID-19 pandemic exacerbated existing mental health challenges and introduced new ones, particularly among vulnerable populations such as individuals within the criminal justice system, who disproportionately experienced employment, financial, and housing issues. As mandatory lockdowns and social distancing mandates were implemented, the United States saw unprecedented interruptions to treatment. Telemedicine emerged as a transformative tool in alleviating new and existing treatment barriers. Yet, limited empirical research has examined the impact and implications of telemedicine on mental health treatment in criminal justice populations.

Methods

The timing of this study’s data collection overlapped with the spread of COVID-19 in the United States and provided a unique opportunity to examine the impact of telemedicine as part of a natural experiment. Utilizing interviews with 61 community mental health center service providers, this study qualitatively examined service providers’ experiences in treating criminal justice-involved individuals with serious mental illness who were receiving mental health treatment through telemedicine.

Results

Service providers expressed satisfaction with telemedicine in addressing client transportation and childcare barriers while increasing engagement. Service providers voiced new concerns regarding clients’ confidentiality, digital literacy, and limitations to gathering non-verbal client information during virtual treatment.

Conclusions

Mental health treatment offered through telemedicine mitigates barriers to treatment that disproportionately affect criminal justice clients. Despite its benefits, challenges like access to reliable internet and to internet-enabled devices, confidentiality concerns, and information gathering must be addressed to achieve optimal and equitable mental health treatment through telemedicine. The findings support the continued use of telemedicine in mental health treatment delivery for this population.
An experimental study on the curing of desert sand using bio-cement
Authors: Fu Xiao , Ye Wan-jun
Published: July 2024

In order to promote the development and utilization of desert sand, this study is based on researching the most suitable ratio of bio-cement, analyzing the shear strength and permeability of improved desert sand by combining bio-cement and fly ash, and clarifying the applicability of tap water in bio-cement. The relationship between the two and the microstructural properties was investigated using the results of the straight shear test and the permeability test. The results showed that the urease solution prepared with tap water had a more pronounced temperature resistance. The urea concentration and the corresponding pH environment had a direct effect on the urease activity. The calcium carbonate yield was positively correlated with the calcium concentration, and the urea concentration was higher in the ranges of 1.0–1.5 mol/L. As the enzyme-to-gel ratio decreased, the calcium carbonate precipitate produced per unit volume of urease solution gradually converged to a certain value. The shear strength (increased by 37.9%) and permeability (decreased by about 8.9–68.5%) of the modified desert sand peaked with the increase in fly ash content. The microscopic test results indicated that the fly ash could provide nucleation sites for the bio-cement, effectively improving the mechanical properties of the desert sand. The crystal types of calcium carbonate in the modified desert sand were calcite and aragonite, which were the most stable crystal types. This study provides innovative ideas for interdisciplinary research in the fields of bioengineering, ecology and civil engineering.
Transcatheter embolization for duodenal ulcer bleeding originating from cystic artery erosion
Authors: Hu Peng , Chen Guangwen , Wei Jingpeng , Huang Rengui , Luo Yaochang
Published: July 2024

Background

Ulcer erosion into the cystic artery is a rare cause of bleeding in duodenal ulcers, with only a limited number of cases described in the literature. Historically, treatment has predominantly involved surgical intervention. We present three cases of duodenal ulcer bleeding due to cystic artery erosion, which were successfully managed with cystic artery embolization.

Case presentation

This case series includes three male patients with duodenal ulcer bleeding, aged 90, 81, and 82 years, respectively, and no prior history of biliary system disorders. The ulcer locations were identified as two in the post-bulbar region and one in the anterior bulb. After the failure of medical and endoscopic treatment, transcatheter arterial embolization was adopted. Initial angiography did not reveal any contrast medium extravasation. Empirical embolization of the gastroduodenal artery using gelatin sponge particles and coils failed to achieve hemostasis. Super-selective cystic artery angiography confirmed the source of bleeding as the cystic artery. One patient was embolized with gelatin sponge particles and coils, while the other two patients were embolized with N-butyl-cyanoacrylate. All patients achieved successful hemostasis without gallbladder infraction.

Conclusions

Cystic artery embolization proved to be a minimally invasive technique for achieving hemostasis in these cases, indicating that it may be a safe and effective alternative to surgery for this uncommon cause of upper gastrointestinal bleeding. Validation through further studies is warranted.
Progesterone Receptor Signaling Promotes Cancer Associated Fibroblast Mediated Tumorigenicity in ER+ Breast Cancer
Authors: Diep Caroline H , Spartz Angela , Truong Thu H , Dwyer Amy R , El-Ashry Dorraya , Lange Carol A
Published: July 2024

Breast cancer progression involves intricate interactions between cancer cells and the tumor microenvironment (TME). This study elucidates the critical role of progesterone receptor (PR) signaling in mediating the protumorigenic effects of cancer-associated fibroblasts (CAFs) on estrogen receptor–positive (ER+) luminal breast cancer cells. We demonstrate that CAFs produce physiologically relevant levels of estrogen and progesterone, which significantly contribute to breast cancer tumorigenicity. Specifically, CAF conditioned media (CM) promoted PR-dependent anchorage-independent growth, tumorsphere formation/stem cell expansion, and CD44 upregulation. CAF cells formed co-clusters more frequently with PR+ breast cancer cells relative to PR-null models. While both PR isoforms mediated these actions, PR-A was a dominant driver of tumorsphere formation/stemness, while PR-B induced robust CD44 expression and CAF/tumor cell co-cluster formation. CD44 knockdown impaired CAF/tumor cell co-clustering. Fibroblast growth factor 2 (FGF2), also secreted by CAFs, phosphorylated PR (Ser294) in a MAPK-dependent manner and activated PR to enhance CD44 expression and breast cancer tumorigenicity. The FGF receptor (FGFR) inhibitor PD173074 diminished CAF– and FGF2–dependent PR activation, tumorsphere formation, and co-clustering. In summary, this study reveals a novel mechanism through which stromal CAFs orchestrate elevated PR signaling in ER+ luminal breast cancer via secretion of both progesterone and FGF2, a potent activator of ERK1/2. Understanding tumor cell/TME interactions provides insights into potential therapeutic strategies aimed at disrupting PR– and/or FGF2/FGFR-dependent signaling pathways to prevent early metastasis in patients with ER+ breast cancer.
Implementation of Choosing Wisely® Recommendations for Lymph Node Surgery in Male Breast Cancer
Authors: Pratt Catherine G. , Whitrock Jenna N. , Carter Michela M. , Long Szu-Aun , Lewis Jaime D. , Heelan Alicia A.
Published: July 2024

Background

The Choosing Wisely® (CW) campaign recommended de-implementation of surgical management of axillary nodes in specified patients. This study aimed to assess trends in the application of CW guidelines for lymph node (LN) surgery in males with breast cancer.

Methods

The National Cancer Database was queried for males diagnosed with breast cancer from 2017 to 2020. Patients were categorized into two cohorts based on CW criteria. Cohort 1 included all T1-2, clinically node-negative patients who underwent breast-conserving therapy and with ≤ 2 positive nodes, and Cohort 2 included all T1-2, node-negative, hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative patients aged ≥ 70 years. In Cohort 1, patients who underwent sentinel LN biopsy (SLNB) alone were compared with axillary LN dissection (ALND) or no LN surgery, while in Cohort 2, patients who underwent LN surgery were compared with those with no LN surgery.

Results

Of 617 patients who met the criteria for Cohort 1, 73.1% underwent SLNB alone compared with ALND (11.8%) or no LN surgery (15.1%). Those who received SLNB alone were younger (65 vs. 68 vs. 73 years; p < 0.001). The annual proportion of males who underwent SLNB alone remained stable from 2017 to 2020. Overall, 1565 patients met the criteria for Cohort 2, and 84.9% received LN surgery. LN surgery was omitted in older patients (81 vs. 77; p < 0.001). The proportion of elderly males with early-stage breast cancer who underwent LN surgery increased from 2017 to 2020.

Conclusion

This study demonstrates that CW recommendations are not being routinely applied to males. These findings reinforce the need for additional studies and subsequent recommendations for optimal application of axillary surgery de-implementation for males diagnosed with breast cancer.