bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of fungus-growing termite-associated halogenated-PKS maduralactomycin a as a potential inhibitor of MurF protein of multidrug-resistant Acinetobacter baumannii
Authors: Shoaib Muhammad , Shehzadi Iram , Asif Muhammad Umair , Shen Yulong , Ni Jinfeng
Published: April 2023

Multidrug-resistant Acinetobacter baumannii infections have become a major public health concern globally. Inhibition of its essential MurF protein has been proposed as a potential target for broad-spectrum drugs. This study aimed to evaluate the potential of a novel ecological niche of 374 fungus-growing termite associated Natural Products (NPs). The molecular docking and computational pharmacokinetics screened four compounds, i.e., Termstrin B, Fridamycin A, Maduralactomycin A, and Natalenamide C, as potential compounds that have higher binding affinities and favourable protein-ligand interactions. The compound Maduralactomycin A induced more stability based on its lowest average RMSD value (2.31 Å) and low standard deviation (0.35) supported by the consistent flexibility and β-factor during the protein’s time-dependent motion. While hydrogen bond analysis indicated that Termstrin B has formed the strongest intra-protein interaction, solvent accessibility was in good agreement with Maduralactomycin A compactness. Maduralactomycin A has the strongest binding energy among all the compounds (−348.48 kcal/mol) followed by Termstrin B (−321.19 kcal/mol). Since these findings suggest Maduralactomycin A and Termstrin B as promising candidates for inhibition of MurF protein, the favourable binding energies of Maduralactomycin A make it a more important compound to warrant further investigation. However, experimental validation using animal models and clinical trials is recommended before reaching any final conclusions.
The cumulative effect of the combined action of miR-101 and curcumin in a liposome on a model of Alzheimer’s disease in mononuclear cells
Authors: Sokolik Victoria Vasilevna , Berchenko Olga Grigorievna
Published: April 2023

The leading pathological mechanisms of Alzheimer’s disease (AD) are amyloidosis and chronic inflammation. The study of new therapeutic drugs of the corresponding action, in particular miRNAs and curcominoids, as well as methods for their packaging, is topical. The aim of the work was to study the effect of miR-101 + curcumin in a single liposome in a cellular AD model. AD model was made by incubating a suspension of mononuclear cells with aggregates of beta-amyloid peptide 1–40 (Aβ40) for 1 h. The effect of the subsequent application of liposomal (L) preparations miR-101, curcumin (CUR), and miR-101 + CUR was analyzed over time of 1, 3, 6, and 12 h. A decrease in the level of endogenous Aβ42 under the influence of L(miR-101 + CUR) was revealed during the entire incubation period (1–12 h), the first part of which was overlapped due to inhibition of mRNAAPP translation by miR-101 (1–3 h), and the second-by inhibition of mRNAAPP transcription by curcumin (3–12 h), the minimum concentration of Aβ42 was recorded at 6 h. The cumulative effect of the combination drug L(miR-101 + CUR) was manifested in the suppression of the increase in the concentration of TNFα and IL-10 and a decrease in the concentration of IL-6 during the entire incubation period (1–12 h). Thus, miR-101 + CUR in one liposome enhanced each other’s antiamyloidogenic and anti- inflammatory effects in a cellular AD model.
Combined open revascularization and endovascular treatment of complex intracranial aneurysms: case series
Authors: Rennert Robert C. , Nguyen Vincent N. , Abedi Aidin , Atai Nadia A. , Carey Joseph N. , Tenser Matthew , Amar Arun , Mack William J. , Russin Jonathan J.
Published: April 2023

Background and purpose

The treatment of complex intracranial aneurysms can be challenging with stand-alone open or endovascular techniques, particularly after rupture. A combined open and endovascular strategy can potentially limit the risk of extensive dissections with open-only techniques, and allow for aggressive definitive endovascular treatments with minimized downstream ischemic risk.

Materials and methods

Retrospective, single-institution review of consecutive patients undergoing combined open revascularization and endovascular embolization/occlusion for complex intracranial aneurysms from 1/2016 to 6/2022.

Results

Ten patients (4 male [40%]; mean age 51.9 ± 8.7 years) underwent combined open revascularization and endovascular treatment of intracranial aneurysms. The majority of aneurysms, 9/10 (90%), were ruptured and 8/10 (80%) were fusiform in morphology. Aneurysms of the posterior circulation represented 8/10 (80%) of the cases (vertebral artery [VA] involving the posterior inferior cerebellar artery [PICA] origin, proximal PICA or anterior inferior cerebellar artery/PICA complex, or proximal posterior cerebral artery). Revascularization strategies included intracranial-to-intracranial (IC-IC; 7/10 [70%]) and extracranial-to-intracranial (EC-IC; 3/10 [30%]) constructs, with 100% postoperative patency. Initial endovascular procedures (consisting of aneurysm/vessel sacrifice in 9/10 patients) were performed early after surgery (0.7 ± 1.5 days). In one patient, secondary endovascular vessel sacrifice was performed after an initial sub-occlusive embolization. Treatment related strokes were diagnosed in 3/10 patients (30%), largely from involved or nearby perforators. All bypasses with follow-up were patent (median 14.0, range 4–72 months). Good outcomes (defined as a Glasgow Outcomes Scale ≥4 and modified Rankin Scale ≤2) occurred in 6/10 patients (60%).

Conclusion

A variety of complex aneurysms not amenable to stand-alone open or endovascular techniques can be successfully treated with combined open and endovascular approaches. Recognition and preservation of perforators is critical to treatment success.
Boost event-driven tactile learning with location spiking neurons
Authors: Kang Peng , Banerjee Srutarshi , Chopp Henry , Katsaggelos Aggelos , Cossairt Oliver
Published: April 2023

Tactile sensing is essential for a variety of daily tasks. Inspired by the event-driven nature and sparse spiking communication of the biological systems, recent advances in event-driven tactile sensors and Spiking Neural Networks (SNNs) spur the research in related fields. However, SNN-enabled event-driven tactile learning is still in its infancy due to the limited representation abilities of existing spiking neurons and high spatio-temporal complexity in the event-driven tactile data. In this paper, to improve the representation capability of existing spiking neurons, we propose a novel neuron model called “location spiking neuron,” which enables us to extract features of event-based data in a novel way. Specifically, based on the classical Time Spike Response Model (TSRM), we develop the Location Spike Response Model (LSRM). In addition, based on the most commonly-used Time Leaky Integrate-and-Fire (TLIF) model, we develop the Location Leaky Integrate-and-Fire (LLIF) model. Moreover, to demonstrate the representation effectiveness of our proposed neurons and capture the complex spatio-temporal dependencies in the event-driven tactile data, we exploit the location spiking neurons to propose two hybrid models for event-driven tactile learning. Specifically, the first hybrid model combines a fully-connected SNN with TSRM neurons and a fully-connected SNN with LSRM neurons. And the second hybrid model fuses the spatial spiking graph neural network with TLIF neurons and the temporal spiking graph neural network with LLIF neurons. Extensive experiments demonstrate the significant improvements of our models over the state-of-the-art methods on event-driven tactile learning, including event-driven tactile object recognition and event-driven slip detection. Moreover, compared to the counterpart artificial neural networks (ANNs), our SNN models are 10× to 100× energy-efficient, which shows the superior energy efficiency of our models and may bring new opportunities to the spike-based learning community and neuromorphic engineering. Finally, we thoroughly examine the advantages and limitations of various spiking neurons and discuss the broad applicability and potential impact of this work on other spike-based learning applications.
Circulating metabolites and depression: a bidirectional Mendelian randomization
Authors: Dong Yankai , Zou Zengxiao , Deng Pin , Fan Xiaoping , Li Chunlin
Published: April 2023

Background

Studies have shown an association between depression and circulating metabolites, but the causal relationship between them has not been elucidated. The purpose of this study was to elucidate the causal relationship between circulating metabolites and depression and to explore the role of circulating metabolites in depression.

Methods

In this study, the top single-nucleotide polymorphisms (SNPs) associated with circulating metabolites (n = 24,925) and depression (n = 322,580) were obtained based on the publicly available genome-wide association study using two-sample Mendelian randomization (MR). SNP estimates were summarized through inverse variance weighted, MR Egger, weighted median, MR pleiotropy residual sum and outlier, and “leave-one-out” methods.

Results

Apolipoprotein A-I (OR 0.990, 95% CI 981–0.999) and glutamine (OR 0.985, 95% CI 0.972–0.997) had protective causal effects on depression, whereas acetoacetate (OR 1.021, 95% CI 1.009–1.034), glycoproteins (OR 1.005, 95% CI 1.000–1.009), isoleucine (OR 1.013, 95% CI 1.002–1.024), and urea (OR 1.020, 95% CI 1.000–1.039) had an anti-protective effect on depression. Reversed MR showed no effect of depression on the seven circulating metabolites.

Conclusion

In this study, MR analysis showed that apolipoprotein A-I and glutamine had a protective effect on depression, and acetoacetate, glycoprotein, isoleucine, glucose, and urea may be risk factors for depression. Therefore, further research must be conducted to translate the findings into practice.
Potential novel therapeutic strategies for neuropathic pain
Authors: Du Zelu , Zhang Jian , Han Xu , Yu Weifeng , Gu Xiyao
Published: April 2023

Purpose

To explore the potential therapeutic strategies of different types of neuropathic pain (NP) and to summarize the cutting-edge novel approaches for NP treatment based on the clinical trials registered on ClinicalTrials.gov.

Methods

The relevant clinical trials were searched using ClinicalTrials.gov Dec 08, 2022. NP is defined as a painful condition caused by neurological lesions or diseases. All data were obtained and reviewed by the investigators to confirm whether they were related to the current topic.

Results

A total of 914 trials were included in this study. They were divided into painful diabetic neuropathy (PDN), postherpetic neuralgia (PHN), sciatica (SC), peripheral nerve injury-related NP (PNI), trigeminal neuralgia (TN), chemotherapy-induced NP (CINP), general peripheral NP (GPNP) and spinal cord injury NP (SCI-NP). Potential novel therapeutic strategies, such as novel drug targets and physical means, were discussed for each type of NP.

Conclusion

NP treatment is mainly dominated by drug therapy, and physical means have become increasingly popular. It is worth noting that novel drug targets, new implications of conventional medicine, and novel physical means can serve as promising strategies for the treatment of NP. However, more attention needs to be paid to the challenges of translating research findings into clinical practice.
The decision to reimage following extravasation in diagnostic nuclear medicine
Authors: Kiser Jackson W.
Published: April 2023

The primary goal of diagnostic nuclear medicine is to provide complete and accurate reports without equivocation or disclaimers. If specific clinical questions cannot be answered because of radiopharmaceutical extravasation, the imaging study may have to be repeated. The decision to reimage is based on several factors including the diagnostic quality of the images, additional patient radiation dose, patient burden, and administrative constraints. Through process improvement efforts, nuclear medicine departments can significantly reduce the frequency of extravasation and thereby also the need for reimaging. Communication with the patient is important any time extravasation may impact their immediate or future care. The circumstances and potential ramifications should be explained, and patient concerns should be addressed. Although recent arguments have been made in favor of investigating and addressing only those extravasations which result in serious patient injury, patients and their referring physicians deserve to know any time their nuclear medicine study may have been impacted.
Necroptosis-related lncRNAs: establishment of a gene module and distinction between the cold and hot tumors in glioma
Authors: Cao Kangxi , Su Fengbo , Shan Xuchun , Jiang Xingyu , Ni Zhaohui , Chen Yan
Published: April 2023

Background

Gliomas are the most common primary tumors of the central nervous system and portend a poor prognosis. The efficacy of emerging and promising immunotherapies varies significantly among individuals. Distinction and transformation of cold and hot tumors may improve the antitumor efficacy of immunotherapy.

Methods and Results

In this study, we constructed a necroptosis-related lncRNA module based on public databases. The association of this module with survival was assessed using the Cox regression, Kaplan-Meier survival analysis, and nomogram, external validation was also conducted in another public database. Furthermore, we performed gene set enrichment analysis (GSEA), immune checkpoint and tumor microenvironment analysis, and in vitro qRT-PCR validation. Finally, we clustered all samples into 2 clusters based on the expression of model lncRNAs and identified cluster 1 as cold tumors with fewer infiltrating T cells.

Conclusions

Identifying cold and hot tumors by necroptosis-related lncRNAs can help available immunotherapeutic strategies to achieve efficacy in the precise treatment of individuals. Prior treatment failure can be overcome by targeting necroptosis-related lncRNAs.
Targeted locus amplification to develop robust patient-specific assays for liquid biopsies in pediatric solid tumors
Authors: van Zogchel Lieke M. J. , Lak Nathalie S. M. , Gelineau Nina U. , Sergeeva Irina , Stelloo Ellen , Swennenhuis Joost , Feitsma Harma , van Min Max , Splinter Erik , Bleijs Margit , Groot Koerkamp Marian , Breunis Willemijn , Meister Michael Torsten , Kholossy Waleed Hassan , Holstege Frank C. P. , Molenaar Jan J. , de Leng Wendy W. J. , Stutterheim Janine , van der Schoot C. Ellen , Tytgat Godelieve A. M.
Published: April 2023

Background

Liquid biopsies combine minimally invasive sample collection with sensitive detection of residual disease. Pediatric malignancies harbor tumor-driving copy number alterations or fusion genes, rather than recurrent point mutations. These regions contain tumor-specific DNA breakpoint sequences. We investigated the feasibility to use these breakpoints to design patient-specific markers to detect tumor-derived cell-free DNA (cfDNA) in plasma from patients with pediatric solid tumors.

Materials and methods

Regions of interest (ROI) were identified through standard clinical diagnostic pipelines, using SNP array for CNAs, and FISH or RT-qPCR for fusion genes. Using targeted locus amplification (TLA) on tumor organoids grown from tumor material or targeted locus capture (TLC) on FFPE material, ROI-specific primers and probes were designed, which were used to design droplet digital PCR (ddPCR) assays. cfDNA from patient plasma at diagnosis and during therapy was analyzed.

Results

TLA was performed on material from 2 rhabdomyosarcoma, 1 Ewing sarcoma and 3 neuroblastoma. FFPE-TLC was performed on 8 neuroblastoma tumors. For all patients, at least one patient-specific ddPCR was successfully designed and in all diagnostic plasma samples the patient-specific markers were detected. In the rhabdomyosarcoma and Ewing sarcoma patients, all samples after start of therapy were negative. In neuroblastoma patients, presence of patient-specific markers in cfDNA tracked tumor burden, decreasing during induction therapy, disappearing at complete remission and re-appearing at relapse.

Conclusion

We demonstrate the feasibility to determine tumor-specific breakpoints using TLA/TLC in different pediatric solid tumors and use these for analysis of cfDNA from plasma. Considering the high prevalence of CNAs and fusion genes in pediatric solid tumors, this approach holds great promise and deserves further study in a larger cohort with standardized plasma sampling protocols.
AI diagnostic performance based on multiple imaging modalities for ovarian tumor: A systematic review and meta-analysis
Authors: Ma Lin , Huang Liqiong , Chen Yan , Zhang Lei , Nie Dunli , He Wenjing , Qi Xiaoxue
Published: April 2023

Background

In recent years, AI has been applied to disease diagnosis in many medical and engineering researches. We aimed to explore the diagnostic performance of the models based on different imaging modalities for ovarian cancer.

Methods

PubMed, EMBASE, Web of Science, and Wanfang Database were searched. The search scope was all published Chinese and English literatures about AI diagnosis of benign and malignant ovarian tumors. The literature was screened and data extracted according to inclusion and exclusion criteria. Quadas-2 was used to evaluate the quality of the included literature, STATA 17.0. was used for statistical analysis, and forest plots and funnel plots were drawn to visualize the study results.

Results

A total of 11 studies were included, 3 of them were modeled based on ultrasound, 6 based on MRI, and 2 based on CT. The pooled AUROCs of studies based on ultrasound, MRI and CT were 0.94 (95% CI 0.88-1.00), 0.82 (95% CI 0.71-0.93) and 0.82 (95% Cl 0.78-0.86), respectively. The values of I2 were 99.92%, 99.91% and 92.64% based on ultrasound, MRI and CT. Funnel plot suggested no publication bias.

Conclusion

The models based on ultrasound have the best performance in diagnostic of ovarian cancer.
Squamous cell lung carcinoma with gastrointestinal metastasis: a case report and review of literature
Authors: Li Feifei , Liu Yiqiang , Xu Ke , Yao Quan , Li Qiang , Wu Hong
Published: April 2023

Squamous cell lung carcinoma (LUSC) originates from squamous cells and has a high rate of metastasis and recurrence. The lack of effective genetic targets and specific therapies has resulted in a poor prognosis for patients with LUSC. Gastrointestinal metastasis of LUSC is a rare occurrence in clinical practice. Patients with gastrointestinal metastasis usually have worse overall survival and the process of diagnosis is more complicated than those with metastasis elsewhere. What’s more, there are no helpful guidelines for treating patients with a clinically confirmed diagnosis of gastrointestinal metastasis, which means the treatment method is limited. Here, we review the clinical features, diagnosis, and treatment of LUSC patients with gastrointestinal metastasis and report a rare case of LUSC accompanied by gastrointestinal metastasis. The patient was admitted to the hospital with coughing and hemoptysis. A tumor was found in his lung, and lesions were initially controlled with standard treatment. The patient’s tumor re-occurred again shortly for which treatment was lacking. Without effective treatment methods, the disease was difficult to control. Our learnings from the case demonstrate that LUSC metastasizes to secondary lymphoid organs of the gastrointestinal tract, usually with a poor prognosis.
Coexistence of a novel STRN-ALK, NBEA-ALK double-fusion in an ovarian malignant mesothelioma patient: a case report and review
Authors: Wu Xiao , Wang Qi , Xu Xiaohu
Published: April 2023

Primary ovarian mesothelioma (POM) is a rare malignant tumor with poor prognosis. Although anaplastic lymphoma kinase gene (ALK) double-fusion partners have been found in various tumors, it is rarely reported in mesothelioma. In this article, we describe the coexistence of a novel STRN-ALK, neurobeachin (NBEA)-ALK double-fusion in a patient with primary ovarian mesothelioma. A 30-year-old woman was found to have pelvic masses for more than a year. Color Doppler ultrasound showed mixed mass in the left ovary and multiple solid masses in the right ovary. the patient underwent laparoscopic surgery, including total hysterectomy, bilateral salpingo-oopherectomy, pelvic lymph node and abdominal aortic lymph node resection, omentum resection and abdominal focus resection. Pathologic examination revealed bilateral ovarian malignant mesothelioma and no evidence of malignancy in the resected bilateral round/broad ligaments, bilateral parametrial tissues, vaginal stump, bilateral fallopian tubes, pelvic and paraaortic lymph nodes. Immunohistochemistry showed that it was positive for Calretinin, VIM, WT1, PAX8, mesothelin, CK5/6, PCK, CK7, MLH1, PMS2, MSH2, MSH6, weakly positive for BAP1, while being negative for Napsin A, P504S, CEA, D2-40, GATA3. The sequencing analysis identified STRN-ALK (intron3:intron19) and NBEA-ALK (intron1:intron16) double-ALK fusion. To the best of our knowledge, this is the first report that a novel NBEA-ALK and EML4-ALK coexist in one patient with POM. The patient has completed 6 cycles of continuous chemotherapy and is in stable condition. Whether ALK inhibitors can bring promising benefits to POM patients in the future deserves further study.
Case Report: Co-existence of a novel EXOC4‐TRHDE gene fusion with PML-RARA in acute promyelocytic leukemia
Authors: Liu Xiaodong , Li Wanting , Xiao Jian , Zhong Huixiu , Yang Kun
Published: April 2023

Acute promyelocytic leukemia (APL) is a type of myeloid leukemia with a specific chromosomal translocation t(15;17)(q22; q12) forming the PML-RARA fusion gene. However, approximately one third of newly diagnosed patients with APL have additional chromosomal abnormalities. Here, we report a case of APL with co-existence of a novel translocation t(7;12)(q32;q13) involving an out-of-frame fusion between EXOC4 and TRHDE, together with PML-RARA. The patient achieved complete remission after treatment with conventional therapy with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). Although the causative link between EXOC4‐TRHDE and PML-RARA has yet to be established, the patient had a good response to therapy, suggesting that the EXOC4‐TRHDE fusion does not affect the efficacy of combined treatment with ATRA and ATO.
“A source of empowerment and well-being”: Experiences of a dance and yoga intervention for young girls with functional abdominal pain disorders
Authors: Högström Sofie , Eriksson Mats , Mörelius Evalotte , Duberg Anna
Published: April 2023

Background

Functional abdominal pain disorders are common among children and adolescents worldwide and effective treatments are needed to alleviate suffering for these children and their families. This study aimed to explore the experience of participating in a combined dance and yoga intervention from the perspectives of girls aged 9–13 years with functional abdominal pain disorders.

Materials and Methods

A randomized controlled trial called Just in TIME (Try, Identify, Move and Enjoy) recruited 121 girls aged 9–13 years with functional abdominal pain disorders. The eight-month intervention combined dance and yoga twice a week, focusing on enjoyment, socialization and playful creativity in an undemanding and non-judgemental environment. The intervention group comprised 64 girls, of whom 25 were purposefully selected for this qualitative interview study. Semi-structured interviews were conducted and analysed using qualitative content analysis with an inductive approach.

Results

The girls' experiences of the Just in TIME intervention can be described as “A source of empowerment and well-being which facilitated personal growth and new ways of engaging in life”. The main category was derived from six generic categories: “A sense of belonging”, “Joy and emotional expression through movement”, “Relief from pain”, “More self-confident”, “More active in daily life” and “A sense of calm.”

Conclusions

Regular participation in an eight-month intervention with combined dance and yoga in a supportive and non-judgemental atmosphere can ease pain and strengthen inner resources, resulting in empowerment, well-being and a more active life for girls with functional abdominal pain disorders.

Trial registration

The Just in TIME study is available online at clinicaltrials.gov, ID: NCT02920268.
The deadly impact of COVID-19 among children from Latin America: The case of Ecuador
Authors: Ortiz-Prado Esteban , Izquierdo-Condoy Juan S. , Fernandez-Naranjo Raul , Vasconez Jorge , Dávila Rosero María Gabriela , Revelo-Bastidas Doménica , Herrería-Quiñonez Diva , Rubio-Neira Mario
Published: April 2023

Background

The SARS-CoV-2 pandemic remains a critical global health concern, with older adults being the most vulnerable group. Nonetheless, it is crucial to recognize that COVID-19 has caused numerous deaths in children worldwide. Emerging evidence indicates that infants and breastfeeding children, particularly those aged below one year, face a greater risk of hospitalization and mortality than older children with COVID-19.

Objective

This study aimed to describe the epidemiology of COVID-19 among children during the early phase of the pandemic in Ecuador.

Methods

We conducted a country-wide population-based analysis of the epidemiology of COVID-19, using incidence and mortality data reported from Ecuador between February 15, 2020 and May 14 2021. Measurements of frequency, central tendency, dispersion, and absolute differences were calculated for all categorical and continuous variables.

Results

At least 34,001 cases (23,587 confirmed cases, 5,315 probable and 5,099 suspected) and 258 COVID-19 related deaths have been reported among children in Ecuador during the first 16 months of the pandemic. The overall incidence rate was 612 cases per 100,000 children, the mortality rate was 3 per 100,000, while the case fatality rate was 0.76%. The highest risk group for infection was children and adolescents between 15 and 19 years of age; however, the highest mortality rate occurred in children under one year of age. The largest provinces, such as Pichincha, Guavas and Manabí, were the ones that reported the highest number of cases, 27%, 12.1% and 10.8%, respectively.

Conclusions

This study is the first to report on COVID-19 epidemics among children in Ecuador. Our findings reveal that younger children have a lower risk of SARS-CoV-2 infection, but a higher risk of mortality compared to older children and adolescents. Additionally, we observed significant disparities in infection rates and outcomes among children living in rural areas, those with comorbidities, and those from indigenous ethnic groups.
Adverse events related to central venous catheters (CVC) and the influence of CVC characteristics on peripheral blood hematopoietic progenitor cell collection in children
Authors: Zubicaray Josune , Martin-Consuegra Sofía , Nieto Monserrat , Albi Gustavo , Iriondo June , Sebastian Elena , Gálvez Eva , Molina Blanca , González-Vicent Marta , de Pablo Jesus Gonzalez , Castillo Ana , Ramírez Manuel , Madero Luis , Díaz Miguel Angel , Sevilla Julián
Published: April 2023

Introduction

The use of peripheral blood progenitor cells (PBPCs) as a source for hematopoietic stem cell transplantation (HSCT) in pediatric healthy donors is still under debate. The risk of a central venous catheter (CVC) placement and catheter-related complications continue to be the main arguments to discourage its use.

Methods

we present a retrospective analysis of 140 PBPC collections in pediatric patients and donors, describing adverse events (AE) related to CVCs as well as the influence of catheterrelated variables on the efficiency of the leukapheresis.

Results

14 CVC-related AEs were recorded (10%). The most common was fever in 5 patients, 4 of which had a catheter-related bacteriemia. Thrombotic events were only observed in 3 patients with active malignancy. A healthy donor presented a moderate bleeding after catheter withdrawal that resolved with local measures, and none of the rest presented any AE. Regarding variables related to the development of AEs, the subject group (patient or donor) was the only one significantly associated (p < 0.0001). Of interest, efficiency was also related to catheter location, being worse in those located in the femoral vein than in into the jugular or the subclavian veins (p < 0.05). In a multivariate analysis, the only variable significantly associated was catheter size (beta 0.238, p < 0.01).

Discussion

Placing a CVC for PBPC collection in pediatric subjects is overall safe; CVC-related complications in pediatric healthy donors are very rare. Furthermore, we should try to place catheters of the largest caliber possible, since the efficiency of the collection is related to this variable.
Prevention, diagnosis, and management of donor derived infections in pediatric kidney transplant recipients
Authors: Epperson Katrina , Crane Clarkson , Ingulli Elizabeth
Published: April 2023

Donor derived infections (DDIs) in pediatric kidney transplant recipients remain challenging to diagnose and can result in serious morbidity and mortality. This review summarizes the current guidelines and recommendations for prevention, diagnosis, and treatment of unexpected DDIs in pediatric kidney transplant recipients. We provide a contemporary overview of DDI terminology, surveillance, epidemiology, and recommended approaches for assessing these rare events with an emphasis on the pediatric recipient. To address prevention and risk mitigation, important aspects of donor and pediatric candidate evaluations are reviewed, including current Organ Procurement and Transplantation Network (OPTN) and American Society of Transplantation (AST) recommendations. Common unexpected DDI encountered by pediatric transplant teams including multi-drug resistant organisms, tuberculosis, syphilis, West Nile Virus, toxoplasmosis, Chagas disease, strongyloidiasis, candidiasis, histoplasmosis, coccidioidomycosis, and emerging infections such as COVID-19 are discussed in detail. Finally, we consider the general challenges with management of DDIs and share our experience with a novel application of next generation sequencing (NGS) of microbial cell-free DNA that will likely define a future direction in this field.
Lenvatinib resistance mechanism and potential ways to conquer
Authors: Bo Wentao , Chen Yan
Published: April 2023

Graphical Abstract

In this review, we summerized the absorption, distribution, metabolism, excretion of lenvatinib in clinic. The lastest mechanism and potential approches to overcome resistance caused by lenvatinib were supplied.
Olaparib and advanced ovarian cancer: Summary of the past and looking into the future
Authors: Maiorano Brigida Anna , Maiorano Mauro Francesco Pio , Maiello Evaristo
Published: April 2023

Ovarian cancer (OC) is women’s eighth most common cancer, bearing the highest mortality rates of all female reproductive system malignancies. Poly (ADP-ribose) polymerase inhibitors (PARPis) have reshaped the treatment scenario of metastatic OC as a maintenance post platinum-based chemotherapy. Olaparib is the first PARPi developed for this disease. Results from Study 42, Study 19, SOLO2, OPINION, SOLO1, and PAOLA-1 clinical trials, led to the FDA and EMA approval of olaparib for the maintenance treatment of women with high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer without platinum progression: in the platinum-sensitive recurrent OC; in the newly diagnosed setting in case Breast Cancer (BRCA) mutations and, in combination with bevacizumab, in case of BRCA mutation or deficiency of homologous recombination genes. In this review, we synthetized olaparib’s pharmacokinetic and pharmacodynamic properties and its use in special populations. We summarized the efficacy and safety of the studies leading to the current approvals and discussed the future developments of this agent.
P2X7 receptor contributes to long-term neuroinflammation and cognitive impairment in sepsis-surviving mice
Authors: Alves Vinícius Santos , Silva Joyce Pereira da , Rodrigues Fabiana Cristina , Araújo Suzana Maria Bernardino , Gouvêa André Luiz , Leite-Aguiar Raíssa , Santos Stephanie Alexia Cristina Silva , Silva Milla Souza Pessoa da , Ferreira Fernanda Silva , Marques Eduardo Peil , Passos Beatriz Amanda Barbosa Rangel dos , Maron-Gutierrez Tatiana , Kurtenbach Eleonora , da Costa Robson , Figueiredo Cláudia Pinto , Wyse Angela T. S. , Coutinho-Silva Robson , Savio Luiz Eduardo Baggio
Published: April 2023

Introduction: Sepsis is defined as a multifactorial debilitating condition with high risks of death. The intense inflammatory response causes deleterious effects on the brain, a condition called sepsis-associated encephalopathy. Neuroinflammation or pathogen recognition are able to stress cells, resulting in ATP (Adenosine Triphosphate) release and P2X7 receptor activation, which is abundantly expressed in the brain. The P2X7 receptor contributes to chronic neurodegenerative and neuroinflammatory diseases; however, its function in long-term neurological impairment caused by sepsis remains unclear. Therefore, we sought to evaluate the effects of P2X7 receptor activation in neuroinflammatory and behavioral changes in sepsis-surviving mice.

Methods: Sepsis was induced in wild-type (WT), P2X7−/−, and BBG (Brilliant Blue G)-treated mice by cecal ligation and perforation (CLP). On the thirteenth day after the surgery, the cognitive function of mice was assessed using the novel recognition object and Water T-maze tests. Acetylcholinesterase (AChE) activity, microglial and astrocytic activation markers, and cytokine production were also evaluated.

Results: Initially, we observed that both WT and P2X7−/− sepsis-surviving mice showed memory impairment 13 days after surgery, once they did not differentiate between novel and familiar objects. Both groups of animals presented increased AChE activity in the hippocampus and cerebral cortex. However, the absence of P2X7 prevented partly this increase in the cerebral cortex. Likewise, P2X7 absence decreased ionized calcium-binding protein 1 (Iba−1) and glial fibrillary acidic protein (GFAP) upregulation in the cerebral cortex of sepsis-surviving animals. There was an increase in GFAP protein levels in the cerebral cortex but not in the hippocampus of both WT and P2X7−/− sepsis-surviving animals. Pharmacological inhibition or genetic deletion of P2X7 receptor attenuated the production of Interleukin-1β (IL-1β), Tumor necrosis factor-α (TNF-α), and Interleukin-10 (IL-10).

Conclusion: The modulation of the P2X7 receptor in sepsis-surviving animals may reduce neuroinflammation and prevent cognitive impairment due to sepsis-associated encephalopathy, being considered an important therapeutic target.
Efficient modeling of sharp-edge acoustofluidics
Authors: Pavlic Alen , Roth Lukas , Harshbarger Cooper Lars , Dual Jürg
Published: April 2023

Sharp-edge structures exposed to acoustic fields are known to produce a strong non-linear response, mainly in the form of acoustic streaming and acoustic radiation force. The two phenomena are useful for various processes at the microscale, such as fluid mixing, pumping, or trapping of microparticles and biological cells. Numerical simulations are essential in order to improve the performance of sharp-edge-based devices. However, simulation of sharp-edge structures in the scope of whole acoustofluidic devices is challenging due to the thin viscous boundary layer that needs to be resolved. Existing efficient modeling techniques that substitute the need for discretization of the thin viscous boundary layer through analytically derived limiting velocity fail due to large curvatures of sharp edges. Here, we combine the Fully Viscous modeling approach that accurately resolves the viscous boundary layer near sharp edges with an existing efficient modeling method in the rest of a device. We validate our Hybrid method on several 2D configurations, revealing its potential to significantly reduce the required degrees of freedom compared to using the Fully Viscous approach for the whole system, while retaining the relevant physics. Furthermore, we demonstrate the ability of the presented modeling approach to model high-frequency 3D acoustofluidic devices featuring sharp edges, which will hopefully facilitate a new generation of sharp-edge-based acoustofluidic devices.
Transcriptomic dissection of termite gut microbiota following entomopathogenic fungal infection
Authors: Tang Ya-ling , Kong Yun-hui , Qin Sheng , Merchant Austin , Shi Ji-zhe , Zhou Xu-guo , Li Mu-wang , Wang Qian
Published: April 2023

Termites are social insects that live in the soil or in decaying wood, where exposure to pathogens should be common. However, these pathogens rarely cause mortality in established colonies. In addition to social immunity, the gut symbionts of termites are expected to assist in protecting their hosts, though the specific contributions are unclear. In this study, we examined this hypothesis in Odontotermes formosanus, a fungus-growing termite in the family Termitidae, by 1) disrupting its gut microbiota with the antibiotic kanamycin, 2) challenging O. formosanus with the entomopathogenic fungus Metarhizium robertsii, and finally 3) sequencing the resultant gut transcriptomes. As a result, 142531 transcripts and 73608 unigenes were obtained, and unigenes were annotated following NR, NT, KO, Swiss-Prot, PFAM, GO, and KOG databases. Among them, a total of 3,814 differentially expressed genes (DEGs) were identified between M. robertsii infected termites with or without antibiotics treatment. Given the lack of annotated genes in O. formosanus transcriptomes, we examined the expression profiles of the top 20 most significantly differentially expressed genes using qRT-PCR. Several of these genes, including APOA2, Calpain-5, and Hsp70, were downregulated in termites exposed to both antibiotics and pathogen but upregulated in those exposed only to the pathogen, suggesting that gut microbiota might buffer/facilitate their hosts against infection by finetuning physiological and biochemical processes, including innate immunity, protein folding, and ATP synthesis. Overall, our combined results imply that stabilization of gut microbiota can assist termites in maintaining physiological and biochemical homeostasis when foreign pathogenic fungi invade.
Resistance screening and in silico characterization of cloned novel RGA from multi-race resistant lentil germplasm against Fusarium wilt (Fusarium oxysporum f. sp. lentis)
Authors: Nishmitha K. , Singh Rakesh , Dubey Sunil C. , Akthar Jameel , Tripathi Kuldeep , Kamil Deeba
Published: April 2023

Fusarium wilt caused by Fusarium oxysporum f. sp. lentis (Fol) is the most devastating disease of lentil present worldwide. Identification of multi-race fusarium wilt resistance genes and their incorporation into existing cultivars will help to reduce yield losses. In the present study, 100 lentil germplasms belonging to seven lentil species were screened against seven prevalent races of Fol, and accessions IC201561 (Lens culinaris subsp. culinaris), EC714243 (L. c. subsp. odemensis), and EC718238 (L. nigricans) were identified as resistant. The typical R gene codes for the nucleotide-binding site and leucine-rich repeats (NBS-LRR) at the C terminal are linked to either the Toll/interleukin 1-like receptor (TIR) or coiled coil (CC) at the N terminal. In the present study, degenerate primers, designed from the NBS region amplifying the P-loop to the GLPLA motif, isolated forty-five resistance gene analogues (RGAs) from identified resistant accessions. The sequence alignment identified both classes of RGAs, TIR and non-TIR, based on the presence of aspartate (D) and tryptophan (W) at the end of the kinase motif, respectively. The phylogenetic analysis grouped the RGAs into six classes, from LRGA1 to LRGA6, which determined the diversity of the RGAs present in the host. Grouping of the RGAs identified from Lens nigricans, LnRGA 2, 9, 13 with I2 revealed the structural similarity with the fusarium resistance gene. The similarity index ranged from 27.85% to 86.98% among the RGAs and from 26.83% to 49.41% among the known R genes, I2, Gpa2, M, and L6. The active binding sites present along the conserved motifs grouped the RGAs into 13 groups. ADP/ATP, being the potential ligand, determines the ATP binding and ATP hydrolysis activity of the RGAs. The isolated RGAs can be used to develop markers linked to the functional R gene. Furthermore, expression analysis and full-length gene isolation pave the path to identifying the molecular mechanism involved in resistance.
Identification of QTL, QTL-by-environment interactions, and their candidate genes for resistance HG Type 0 and HG Type 1.2.3.5.7 in soybean using 3VmrMLM
Authors: Jiang Haipeng , Lv Suchen , Zhou Changjun , Qu Shuo , Liu Fang , Sun Haowen , Zhao Xue , Han Yingpeng
Published: April 2023

Introduction

Soybean cyst nematode (SCN, Heterodera glycines Ichinohe) is an important disease affecting soybean yield in the world. Potential SCN-related QTLs and QTL-by-environment interactions (QEIs) have been used in SCN-resistant breeding.

Methods

In this study, a compressed variance component mixed model, 3VmrMLM, in genome-wide association studies was used to detect QTLs and QEIs for resistance to SCN HG Type 0 and HG Type 1.2.3.5.7 in 156 different soybean cultivars materials.

Results and discussion

The results showed that 53 QTLs were detected in single environment analysis; 36 QTLs and 9 QEIs were detected in multi-environment analysis. Based on the statistical screening of the obtained QTLs, we obtained 10 novel QTLs and one QEI which were different from the previous studies. Based on previous studies, we identified 101 known genes around the significant/suggested QTLs and QEIs. Furthermore, used the transcriptome data of SCN-resistant (Dongnong L-10) and SCN-susceptible (Suinong 14) cultivars, 10 candidate genes related to SCN resistance were identified and verified by Quantitative real time polymerase chain reaction (qRT-PCR) analysis. Haplotype difference analysis showed that Glyma.03G005600 was associated with SCN HG Type 0 and HG Type 1.2.3.5.7 resistance and had a haplotype beneficial to multi-SCN-race resistance. These results provide a new idea for accelerating SCN disease resistance breeding.
Schema therapy for Dissociative Identity Disorder: a case report
Authors: Bachrach Nathan , Rijkeboer Marleen M. , Arntz Arnoud , Huntjens Rafaële J. C.
Published: April 2023

Treatment for Dissociative Identity Disorder (DID) often follows a practice-based psychodynamic psychotherapy approach that is conducted in three phases: symptom stabilization, trauma processing, and identity integration and rehabilitation. The percentage of patients that reach the third phase is relatively low, treatment duration is long, and the effects of this treatment on the core DID symptoms have been found to be small or absent, leaving room for improvement in the treatment of DID. Schema Therapy (ST) is an integrative psychotherapy that has been proposed as a treatment for DID. This approach is currently being investigated in several studies and has the potential to become an evidence-based treatment for DID. This case report presents an overview of the protocol adaptations for DID ST treatment. The presented case concerns a 43-year-old female patient with DID, depressive disorder (recurrent type), PTSD, cannabis use disorder, and BPD. Functioning was very low. She received 220 sessions of ST, which included direct trauma processing through Imagery Rescripting (ImRs). The patient improved in several domains: she experienced a reduction of PTSD symptoms, as well as dissociative symptoms, there were structural changes in the beliefs about the self, and loss of suicidal behaviors. After treatment she was able to stop her punitive mode, to express her feelings and needs to others, and to participate adequately in social interaction. This case report indicates that ST might be a viable treatment for DID, adding to a broader scope of treatment options for this patient group.
Pregnant individual’s lived experience of cannabis use during the COVID-19 pandemic: a qualitative study
Authors: Young-Wolff Kelly C. , Foti Tara R. , Green Andrea , Iturralde Esti , Jackson-Morris Melanie , Does Monique B. , Adams Sara R. , Goler Nancy , Conway Amy , Ansley Deborah , Altschuler Andrea
Published: April 2023

Introduction

Quantitative studies indicate that the COVID-19 pandemic has contributed to increased rates of prenatal cannabis use. However, little is known about how the pandemic has impacted cannabis use from the perspective of pregnant individuals themselves. Our objective was to characterize COVID-19-related changes in cannabis use among pregnant individuals who used cannabis during the pandemic.

Methods

We conducted 18 focus groups (from 11/17/2021 to 12/17/2021) with Black and White pregnant individuals aged 18+ who self-reported prenatal cannabis use during universal screening at entrance to prenatal care (at ~8 weeks gestation) in Kaiser Permanente Northern California. Virtual focus groups were transcribed and analyzed using thematic analysis.

Results

The sample of 53 pregnant individuals (23 Black, 30 White) was 30.3  years old (SD = 5.2) on average, and most (70%) self-reported daily versus weekly or monthly prenatal cannabis use. Major themes regarding the impact of the pandemic on cannabis use included increases in use (resulting from depression, anxiety, stress, boredom), and changes in social use (less sharing of smoked cannabis products), modes of use (from smoking to other modes due to respiratory concerns) and source (from storefront retailers to delivery).

Conclusion

Coping with mental health symptoms and stress were identified drivers of perceived pandemic-related increases in prenatal cannabis use in 2021. Pregnant individuals adapted their use in ways consistent with public health recommendations to decrease social contact and reduce or quit smoking to mitigate COVID-19 transmission and harms. Proactive, mental health outreach for pregnant individuals during future pandemic waves may reduce prenatal cannabis use.