bluuebunny/crossref_metadata_2025 huggingface dataset:
Bone healing study of alendronate combined with enoxaparin sodium bone cement in rabbits with bone defects
Authors: Xiao Zhihang , Fu Dehao , Zhang Li , Fan Weiye , Shen Xiaoyu , Qi Xiangbei
Published: September 2022

Background

To observe the effect of enoxaparin sodium-polymethyl methacrylate (ES-PMMA) bone cement supplemented with alendronate (AN) on bone repair of bone defects in New Zealand rabbits.

Methods

Twenty-seven New Zealand rabbits were randomly divided into ES/AN, ES-PMMA and PMMA groups, with a total of 27 New Zealand rabbits. The drugs loaded in 40 g bone cement powder were as follows: ES/AN group 8000 AxaIU enoxaparin (ES) and 200 mg alendronate (AN), ES-PMMA group 8000 AxaIU enoxaparin (ES), PMMA group without drugs. A bone defect model with a length of 10 mm and a diameter of 5 mm was made from the left tibia of rabbits, and the prepared bone cement was placed in the tibia defect. At 4 weeks, 8 weeks and 12 weeks after the operation, 3 rabbits in each group were sacrificed, and left tibia samples were collected for histological scoring, HE staining and Masson staining. Bone mineral density and new bone volume were measured by imaging, and the related data were processed by one-way ANOVA and least significance difference (LSD) post hoc test.

Results

(1) Bone mineral density (BMD, mg/mm3) around the bone defect: at the 4th week, BMD in the ES/AN group was higher than that in the PMMA group; at the 8th week, the BMD in the ES/AN group was significantly higher than that in the other two groups; and at the 12th week, the BMD in the ES/AN group was significantly higher than that in the other two groups. (2) New bone volume (BV, mm3): at the 4th week, BV in the ES/AN group was significantly higher than that in the other two groups, BV in the ES/AN group was significantly higher than that in the other two groups at the 8th and 12th weeks, and BV in the ES-PMMA group was higher than that in the PMMA group. (3) Histological score: at the 4th and 8th weeks, the histological score of the ES/AN group was higher than that of the PMMA group, and at the 12th week, the histological score of the ES/AN group was higher than that of the other two groups. (4) Cortical bone thickness (μm): at the 4th, 8th and 12th weeks, the cortical bone thickness in the ES/AN group was higher than that in the other two groups, and the cortical bone thickness in the ES-PMMA group was higher than that in the PMMA group. (5) The percentage of mature area of new bone in the ES/AN group was higher than that in the other two groups at the 4th week, and at the 8th and 12th weeks, the percentage of mature area of new bone in the ES/AN group and ES-PMMA group was significantly higher than that in the PMMA group.

Conclusion

(1) Enoxaparin sodium bone cement supplemented with alendronate was superior to enoxaparin sodium bone cement and PMMA bone cement in promoting bone repair of tibial bone defects in New Zealand rabbits. (2) Enoxaparin sodium bone cement is superior to PMMA bone cement in promoting bone repair, showing a certain osteogenic potential.
Impact of hyperbilirubinemia associated acute kidney injury on chronic kidney disease after aortic arch surgery: a retrospective study with follow-up of 1-year
Authors: Lyu Lin , Song Haicheng , Gao Guodong , Dong He , Liao Pingping , Shen Ziying , Liu Hui , Chu Haichen , Yuan Li
Published: September 2022

Background

Hyperbilirubinemia (HB) is a serious complication in aortic arch surgery, which is associated with acute kidney injury (AKI). The association between HB and chronic kidney disease (CKD) is unknown. The aim of this study was to investigate the impact of HB associated AKI on CKD after aortic arch surgery.

Methods

We reviewed 284 patients who underwent aortic arch surgery from 2016 to 2020 in our hospital. AKI was defined as a 50% increase in sCr from baseline value within the first 7 postoperative days. HB was defined as total bilirubin > 51.3 μmol/L. Patients were divided into 3 groups based on AKI and HB: HB associated AKI (HB-AKI) group (AKI patients suffered HB within the first 7 postoperative days); AKI without HB group and Non-AKI group.

Results

Follow-up for 204 patients ranged from 3 to 12 months. Kaplan–Meier analysis showed that the 1-year cumulative incidence of CKD was highest in HB-AKI (32.6%) than AKI without HB (17.8%) and Non-AKI (7.4%, log-rank test, p < 0.001), and the incidence of CKD was higher in HB group than that in Non-HB group (26.7% vs. 13.9%, log-rank test, p = 0.015). Preoperative sCr (HR 1.010, 95% CI 1.004–1.016, p = 0.001), AKI without HB (HR 2.887, 95% CI 1.133–7.354, p = 0.026) and HB-AKI (HR 4.490, 95% CI 1.59–12.933, p = 0.005) were associated with CKD during 1-year follow-up.

Conclusions

Patients suffering HB associated AKI were at more increased odds of CKD than patients suffering AKI without HB after aortic arch surgery.
Polygenic risk modeling of tumor stage and survival in bladder cancer
Authors: Nascimben Mauro , Rimondini Lia , Corà Davide , Venturin Manolo
Published: September 2022

Introduction

Bladder cancer assessment with non-invasive gene expression signatures facilitates the detection of patients at risk and surveillance of their status, bypassing the discomforts given by cystoscopy. To achieve accurate cancer estimation, analysis pipelines for gene expression data (GED) may integrate a sequence of several machine learning and bio-statistical techniques to model complex characteristics of pathological patterns.

Methods

Numerical experiments tested the combination of GED preprocessing by discretization with tree ensemble embeddings and nonlinear dimensionality reductions to categorize oncological patients comprehensively. Modeling aimed to identify tumor stage and distinguish survival outcomes in two situations: complete and partial data embedding. This latter experimental condition simulates the addition of new patients to an existing model for rapid monitoring of disease progression. Machine learning procedures were employed to identify the most relevant genes involved in patient prognosis and test the performance of preprocessed GED compared to untransformed data in predicting patient conditions.

Results

Data embedding paired with dimensionality reduction produced prognostic maps with well-defined clusters of patients, suitable for medical decision support. A second experiment simulated the addition of new patients to an existing model (partial data embedding): Uniform Manifold Approximation and Projection (UMAP) methodology with uniform data discretization led to better outcomes than other analyzed pipelines. Further exploration of parameter space for UMAP and t-distributed stochastic neighbor embedding (t-SNE) underlined the importance of tuning a higher number of parameters for UMAP rather than t-SNE. Moreover, two different machine learning experiments identified a group of genes valuable for partitioning patients (gene relevance analysis) and showed the higher precision obtained by preprocessed data in predicting tumor outcomes for cancer stage and survival rate (six classes prediction).

Conclusions

The present investigation proposed new analysis pipelines for disease outcome modeling from bladder cancer-related biomarkers. Complete and partial data embedding experiments suggested that pipelines employing UMAP had a more accurate predictive ability, supporting the recent literature trends on this methodology. However, it was also found that several UMAP parameters influence experimental results, therefore deriving a recommendation for researchers to pay attention to this aspect of the UMAP technique. Machine learning procedures further demonstrated the effectiveness of the proposed preprocessing in predicting patients’ conditions and determined a sub-group of biomarkers significant for forecasting bladder cancer prognosis.
Peptide-based PROTAC degrader of FOXM1 suppresses cancer and decreases GLUT1 and PD-L1 expression
Authors: Wang Kun , Dai Xiaoyong , Yu Albert , Feng Chunyan , Liu Kewei , Huang Laiqiang
Published: September 2022

Background

Peptide proteolysis-targeting chimeras (p-PROTACs) with advantages of high specificity and low toxicity have emerged as a powerful technology of targeted protein degradation for biomedical applications. FOXM1, a proliferation-associated transcription factor, is overexpressed in a variety of human tumors as a key driver of tumorigenesis and cancer progression, and is a potential anticancer therapeutic target. However, FOXM1-targeting p-PROTACs has not been researched.

Methods

Here, we first analyzed the expression of FOXM1, GLUT1 and PD-L1 in liver cancer through database and clinical samples of patients. FOXM1-targeting peptides, selected by screening phage display library, are verified its targeting effect by immunofluorescence and CCK-8 test. The novel p-PROTAC degrader of FOXM1 is chemically synthesis, named FOXM1-PROTAC, by linking a FOXM1-binding antagonistic peptide, with the E3 ubiquitin ligase recruitment ligand Pomalidomide and with the cell membrane penetrating peptide TAT. Its degradation effect on FOXM1 was detected by Western blotting, qPCR, and we verified its effect on the behavior of cancer cells by flow cytometry, scratch assay, and Transwell in vitro. The tumor xenografted mice model was used for evaluating FOXM1-PROTAC therapeutic response in vivo. Finally, we detected the expression of GLUT1 and PD-L1 after FOXM1-PROTAC degraded FOXM1 by using Western Blotting and hippocampal detectors and dual immunofluorescence.

Results

We found that the novel FOXM1-PROTAC efficiently entered cells and induced degradation of FOXM1 protein, which strongly inhibits viability as well as migration and invasion in various cancer cell lines, and suppressed tumor growth in HepG2 and MDA-MB-231 cells xenograft mouse models, without detected toxicity in normal tissues. Meanwhile, FOXM1-PROTAC decreased the cancer cells glucose metabolism via downregulating the protein expression levels of glucose transporter GLUT1 and the immune checkpoint PD-L1, which suggests involvement of FOXM1 in cancer cell metabolism and immune regulation.

Conclusions

Our results indicate that biologically targeted degradation of FOXM1 is an attractive therapeutic strategy, and antagonist peptide-containing FOXM1-PROTACs as both degrader and inhibitor of FOXM1 could be developed as a safe and promising drug for FOXM1-overexpressed cancer therapy.
LncRNA FAM83H-AS1 promotes the malignant progression of pancreatic ductal adenocarcinoma by stabilizing FAM83H mRNA to protect β-catenin from degradation
Authors: Zhou Min , Pan Shutao , Qin Tingting , Zhao Chunle , Yin Taoyuan , Gao Yang , Liu Yuhui , Zhang Zhenxiong , Shi Yongkang , Bai Yu , Gong Jun , Guo Xingjun , Wang Min , Qin Renyi
Published: September 2022

Background

Pancreatic ductal adenocarcinoma is prone to metastasis, resulting in short survival and low quality of life. LncRNAs are pivotal orchestrators that participate in various tumor progress. The underlying role and mechanism of lncRNA FAM83H-AS1 is still unknown in PDAC progression.

Methods

To address this issue, firstly, we profiled and analyzed the aberrant lncRNA expression in TCGA database and identified FAM83H-AS1 as the most effective one in promoting the migration of pancreatic cancer cells. Then, the expression levels of FAM83H-AS1 in patient’s serum, tumor tissues and PDAC cells were detected using RT-qPCR, and FAM83H-AS1 distribution in PDAC cells was determined by performing FISH and RT-qPCR. Next, a series of in vivo and in vitro functional assays were conducted to elucidate the role of FAM83H-AS1 in cell growth and metastasis in PDAC. The regulatory relationship between FAM83H-AS1 and FAM83H (the homologous gene of FAM83H-AS1) was verified by performing protein and RNA degradation assays respectively. Co-IP assays were performed to explore the potential regulatory mechanism of FAM83H to β-catenin. Rescue assays were performed to validate the regulation of the FAM83H-AS1/FAM83H/β-catenin axis in PDAC progression.

Results

FAM83H-AS1 was highly expressed in the tumor tissues and serum of patients with PDAC, and was correlated with shorter survival. FAM83H-AS1 significantly promoted the proliferation, invasion and metastasis of PDAC cells, by protecting FAM83H mRNA from degradation. Importantly, FAM83H protein manifested the similar malignant functions as that of FAM83H-AS1 in PDAC cells, and could bind to β-catenin. Specifically, FAM83H could decrease the ubiquitylation of β-catenin, and accordingly activated the effector genes of Wnt/β-catenin signaling.

Conclusions

Collectively, FAM83H-AS1 could promote FAM83H expression by stabilizing its mRNA, allowing FAM83H to decrease the ubiquitylation of β-catenin, thus resulted in an amplified FAM83H-AS1/FAM83H/β-catenin signal axis to promote PDAC progression. FAM83H-AS1 might be a novel prognostic and therapeutic target for combating PDAC.
Integrated mental health care and vocational rehabilitation intervention to improve return to work rates for people on sick leave due to common mental and functional disorders (IBBIS-II)—a study protocol for a randomized clinical trial
Authors: Christensen Thomas Nordahl , Poulsen Chalotte Heinsvig , Ebersbach Bea Kolbe , Eplov Lene Falgaard
Published: September 2022

Background

Mental illness has an estimated financial burden on the Danish economy of 3.4% of the gross national product every year due to lost productivity, social benefits, and healthcare costs, and approximately 50% of people receiving long-term sickness benefits have a common mental illness. Furthermore, a significant treatment gap exists where less than 30% are treated for their mental illness. The primary objective of the randomized trial is to examine whether people on sick leave with a diagnosis of anxiety, depression, stress, personality disorders, or functional disorders return to work faster and have higher job retention if they receive an integrated and optimized vocational rehabilitation and mental health care intervention, compared to people who receive the standard mental health care and vocational rehabilitation service.

Methods

The trial is designed as an investigator-initiated, randomized, two-group parallel, assessor-blinded, superior trial. A total of 900 participants with a common mental illness will randomly be assigned into two groups: (1) IBBIS-II, consisting of integrated mental health care and vocational rehabilitation, or (2) service as usual (SAU), at two sites in Denmark. The primary outcome is the difference between the two groups in time to return to work (RTW) at 12 months using data from the Danish Register for Evaluation of Marginalization (DREAM) database.

Discussion

This study will contribute with new knowledge on vocational recovery and integrated vocational and health care interventions in a Scandinavian context.

Trial registration

ClinicalTrials.govNCT04432129. Registered on June 16, 2020
Effectiveness of the Unified Barlow Protocol (UP) and neuropsychological treatment in cancer survivors for cognitive impairments: study protocol for a randomized controlled trial
Authors: García-Torres Francisco , Tejero-Perea Adrián , Gómez-Solís Ángel , Castillo-Mayén Rosario , Jaén-Moreno Maria José , Luque Bárbara , Gálvez-Lara Mario , Sánchez-Raya Araceli , Jablonski Marcin , Rodríguez-Alonso Beatriz , Aranda Enrique
Published: September 2022

Background

Cancer survivors frequently develop cognitive impairment, which negatively affects their quality of life and emotional well-being. This study compares the effectiveness of a well-established treatment (neuropsychological treatment) with the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders (UP) to reduce these cognitive deficits and evaluate the effect of both treatments on anxiety-depressive symptoms and the quality of life of cancer survivors.

Methods

A three-arm, randomized superiority clinical trial with a pre-post and repeated follow-up measures intergroup design using a 1:1:1 allocation ratio will be performed. One hundred and twenty-three cancer survivors with mild to moderate cognitive impairment will be randomly assigned to one of the study interventions: a cognitive rehabilitation intervention group, an intervention group with UP intervention, or a control group on the waiting list. The primary outcome is to observe a significant improvement in cognitive function in both intervention groups and a significant decrease in emotional impairments in comparison with the waitlist group. Improvements in anxiety, depression, and quality of life are also expected as secondary outcomes. These results will be maintained at 6 months of follow-up.

Discussion

The aim of this trial is to test the efficacy of the UP intervention in reducing cognitive deficits in breast cancer survivors. The results of this trial may be useful in reducing the presence of cognitive problems in cancer survivors and improving their emotional state and quality of life.

Trial registration

ClinicalTrials.gov NCT05289258. Registered 12 March 2022, v01.
Observation on the effectiveness and safety of sodium bicarbonate Ringer’s solution in the early resuscitation of traumatic hemorrhagic shock: a clinical single-center prospective randomized controlled trial
Authors: Zhang Jizhe , Han Dong , Zhang Kun , Guan Weiqiang , Li Li , Gu Zhengtao
Published: September 2022

Background

Traumatic hemorrhagic shock (THS) is the main cause of death in trauma patients with high mortality. Rapid control of the source of bleeding and early resuscitation are crucial to clinical treatment. Guidelines recommend isotonic crystal resuscitation when blood products are not immediately available. However, the selection of isotonic crystals has been controversial. Sodium bicarbonate Ringer solutions (BRS), containing sodium bicarbonate, electrolyte levels, and osmotic pressures closer to plasma, are ideal. Therefore, in this study, we will focus on the effects of BRS on the first 6 h of resuscitation, complications, and 7-day survival in patients with THS.

Methods

/design.

This single-center, prospective, randomized controlled trial will focus on the efficacy and safety of BRS in early THS resuscitation. A total of 400 adults THS patients will be enrolled in this study. In addition to providing standard care, enrolled patients will be randomized in a 1:1 ratio to receive resuscitation with BRS (test group) or sodium lactate Ringer’s solution (control group) until successful resuscitation from THS. Lactate clearance at different time points (0.5, 1, 1.5, 3, and 6 h) and shock duration after drug administration will be compared between the two groups as primary end points. Secondary end points will compare coagulation function, temperature, acidosis, inflammatory mediator levels, recurrence of shock, complications, medication use, and 7-day mortality between the two groups. Patients will be followed up until discharge or 7 days after discharge.

Discussion

At present, there are still great differences in the selection of resuscitation fluids, and there is a lack of systematic and detailed studies to compare and observe the effects of various resuscitation fluids on the effectiveness and safety of early resuscitation in THS patients. This trial will provide important clinical data for resuscitation fluid selection and exploration of safe dose of BRS in THS patients.

Trial registration.

Chinese Clinical Trial Registry (ChiCTR), ChiCTR2100045044. Registered on 4 April 2021.
Fusarium proliferatum-induced chronic lip ulcer: successful treatment with itraconazole: a case report
Authors: Mohaghegh Fatemeh , Abtahi-Naeini Bahareh , Nasri Elahe , Badiee Parisa , Morovati Hamid , Fakhim Hamed , Farmani Aida , Meidani Mohsen , Ranjbar-Mobarake Maryam , Mohammadi Rasoul
Published: September 2022

Background

Fusarium species are saprophytic fungi with a worldwide distribution. These fungi cause various infections among immunocompromised patients; however, they can also involve immunocompetent individuals.

Case presentation

We report a case of a 41-year-old Iranian woman who presented with ulcerative lesions on her lips 10 months ago. She had a long history of anxiety but had no history of classical risk factors such as trauma, cosmetic lip tattoo, burning in her lips, smoking or use of alcohol and opium. A skin biopsy from the lower lip was performed and sent for microbiological examinations. Hyaline septate hyphae were seen on direct microscopy with potassium hydroxide. The clinical specimen was subcultured on sabouraud dextrose agar with chloramphenicol and prepared for antifungal susceptibility testing and molecular identification. Considering the minimum inhibitory concentrations (MIC) for antifungals, itraconazole (100 mg orally twice a day) was started for her, and after 2 months, the lesions were treated. She followed up for 3 months, and no signs of disease recurrence were observed.

Conclusions

Selecting an appropriate treatment strategy according to the laboratory assessments is essential in clinical practice and the management of rare infections to prevent related mortality and morbidity of opportunistic fungal infections.
Runx2 and Nell-1 in dental follicle progenitor cells regulate bone remodeling and tooth eruption
Authors: Zeng Li , He Hong , Sun Mingjie , Gong Xinyi , Zhou Mengqi , Hong Yaya , Wu Yongjia , Chen Xuepeng , Chen Qianming
Published: September 2022

Dental follicles are necessary for tooth eruption, surround the enamel organ and dental papilla, and regulate both the formation and resorption of alveolar bone. Dental follicle progenitor cells (DFPCs), which are stem cells found in dental follicles, differentiate into different kinds of cells that are necessary for tooth formation and eruption. Runt‐related transcription factor 2 (Runx2) is a transcription factor that is essential for osteoblasts and osteoclasts differentiation, as well as bone remodeling. Mutation of Runx2 causing cleidocranial dysplasia negatively affects osteogenesis and the osteoclastic ability of dental follicles, resulting in tooth eruption difficulties. Among a variety of cells and molecules, Nel-like molecule type 1 (Nell-1) plays an important role in neural crest-derived tissues and is strongly expressed in dental follicles. Nell-1 was originally identified in pathologically fused and fusing sutures of patients with unilateral coronal synostosis, and it plays indispensable roles in bone remodeling, including roles in osteoblast differentiation, bone formation and regeneration, craniofacial skeleton development, and the differentiation of many kinds of stem cells. Runx2 was proven to directly target the Nell-1 gene and regulate its expression. These studies suggested that Runx2/Nell-1 axis may play an important role in the process of tooth eruption by affecting DFPCs. Studies on short and long regulatory noncoding RNAs have revealed the complexity of RNA-mediated regulation of gene expression at the posttranscriptional level. This ceRNA network participates in the regulation of Runx2 and Nell-1 gene expression in a complex way. However, non-study indicated the potential connection between Runx2 and Nell-1, and further researches are still needed.
Gesture recognition method based on misalignment mean absolute deviation and KL divergence
Authors: Tian Yong , Zhuang Chuanzhen , Cui Jiadong , Qiao Runjie , Ding Xuejun
Published: September 2022

At present, it has become very convenient to collect channel state information (CSI) from ubiquitous commercial WiFi network cards, and the location or activity of a human who affects the CSI can be recognized by analyzing the change of the CSI. Therefore, wireless sensing technology based on the CSI has received widespread attention. However, the existing CSI-based gesture recognition methods still have some problems, which include that subcarrier selection is not optimized and motion interval extraction is not accurate enough, so the accuracy of gesture recognition methods still needs to be further improved. In response to the above problems, a gesture recognition method based on misalignment mean absolute deviation (MMAD) and KL divergence is proposed in the paper, which is called MMAD-KL-GR method. This method uses the proposed MMAD algorithm to extract the CSI amplitude intervals containing gesture information, then selects subcarriers by comparing the KL divergence of the CSI amplitude, and finally uses the subspace K-nearest neighbor (KNN) algorithm to recognize the gestures. Several experiments show that the MMAD-KL-GR method can effectively improve the accuracy of the gesture recognition.
MF-GCN-LSTM: a cloud-edge distributed framework for key positions prediction in grid projects
Authors: Huang Shaoyuan , Zhang Yuxi , Peng Guozheng , Zhao Juan , Zhu Keping , Zhang Heng , Wang Xiaofei
Published: September 2022

In this article, we solve the key positions prediction problem of engineering projects in smart grid, which pays more attention to the spatial-temporal distribution of projects. Many studies show that the projects are affected by multi-dimensional features such as time, space, correlation etc. However, few work can accurately predict the key positions of projects based on multi-dimensional features. In order to solve this problem, we propose the idea of multi-feature extraction, and make use of the real-world records trace to conduct multi-dimensional modeling. Then we introduce a multi-dimensional features extraction model: Multi-Feature-based GCN-LSTM (MF-GCN-LSTM) to take the effect of time, space and correlation for predicting the key positions of projects. Experiments on different datasets with various project types have proved that our model can complete the key positions prediction task efficiently. Compared with the other traditional method and non-linear models, our model shows higher prediction accuracy and robustness. Moreover, we show that the whole prediction framework MF-GCN-LSTM can be split and deployed in a distributed manner to accelerate the inference of the model under the cloud edge system.
CD7-directed CAR T-cell therapy: a potential immunotherapy strategy for relapsed/refractory acute myeloid leukemia
Authors: Cao Xuanqi , Dai Haiping , Cui Qingya , Li Zheng , Shen Wenhong , Pan Jinlan , Shen Hongjie , Ma Qinfen , Li Mengyun , Chen Sifan , Chen Juncheng , Zhu Xiaming , Meng Huimin , Yang Lin , Wu Depei , Tang Xiaowen
Published: September 2022

Relapsed/refractory acute myeloid leukemia (AML) patients generally have a dismal prognosis and the treatment remains challenging. Due to the expression of CD7 on 30% AML and not on normal myeloid and erythroid cells, CD7 is an attractive target for immunotherapy of AML. CD7-targeted CAR T-cells had demonstrated encouraging efficacy in xenograft models of AML. We report here on the use of autologous CD7 CAR T-cells in the treatment of a relapsed/refractory AML patient with complex karyotype, TP53 deletion, FLT3-ITD mutation, and SKAP2-RUNX1 fusion gene. Before the CAR T-cell therapy, the patient achieved partial remission with IA regimen and attained complete remission after reinduction therapy (decitabine and venentoclax). Relapse occurred after consolidation (CLAG regimen). Then she failed CLIA regimen combined with venetoclax and exhibited resistance to FLT3 inhibitors. Bone marrow showed 20% blasts (CD7+ 95.6%). A total dose of 5 × 106/kg CD7 CAR T-cells was administered after the decitabine +FC regimen. Seventeen days after CAR T-cells infusion, she achieved morphologic leukemia-free state. The patient developed grade 3 cytokine release syndrome. No severe organ toxicity or immune effector cell-associated neurotoxicity syndrome was observed. In summary, the autologous CD7 CAR T-cell therapy could be considered a potential approach for AML with CD7 expression (NCT04762485).

Trial registration Clinical Trials.gov, NCT04762485. Registered on February 21, 2021, prospectively registered
Assessment of deep geothermal research and development in the Upper Rhine Graben
Authors: Frey Matthis , Bär Kristian , Stober Ingrid , Reinecker John , van der Vaart Jeroen , Sass Ingo
Published: September 2022

Deep geothermal energy represents a key element of future renewable energy production due to its base load capability and the almost inexhaustible resource base. Especially with regard to heat supply, this technology offers a huge potential for carbon saving. One of the main targets of geothermal projects in Central Europe is the Upper Rhine Graben, which exhibits elevated subsurface temperatures and reservoirs with favorable hydraulic properties. Several decades of intensive research in the region resulted in a comprehensive understanding of the geological situation. This review study summarizes the findings relevant to deep geothermal projects and thus provides a useful working and decision-making basis for stakeholders. A total of nine geological units have been identified that are suitable for deep geothermal exploitation, comprising the crystalline basement, various sandstone formations and Mesozoic carbonates. An extensive lithostratigraphic, structural, geochemical, hydraulic and petrophysical characterization is given for each of these potential reservoirs. This paper furthermore provides an overview of the available data and geological as well as temperature models.
Influence of management practice on the microbiota of a critically endangered species: a longitudinal study of kākāpō chick faeces and associated nest litter
Authors: West Annie G. , Digby Andrew , Lear Gavin ,   Kākāpō Recovery Team,   Kākāpō Aspergillosis Research Consortium, Digby Andrew , Armstrong Doug , Armstrong-James Darius , Bromley Mike , Buckley Elizabeth , Chatterton James , Cox Murray P. , Cramer Robert A. , Crane Jodie , Dearden Peter K. , Eason Daryl , Fisher Matthew C. , Gago Sara , Gartrell Brett , Gemmell Neil J. , Glare Travis R. , Guhlin Joseph , Howard Jason , Lacap-Bugler Donnabella , Le Lec Marissa , Lin Xiao Xiao , Lofgren Lotus , Mackay John , Meis Jacques , Morelli Kaesi A. , Perrott John , Petterson Megan , Quinones-Mateu Miguel , Rhodes Johanna , Roberts Joanna , Stajich Jason , Taylor Michael W. , Tebbutt Scott J. , Truter-Meyer Amber , Uddstrom Lydia , Urban Lara , van Rhijn Norman , Vercoe Deidre , Vesely Elisa , Weir Bevan S. , West Annie G. , Winter David J. , Yeung Juliana , Taylor Michael W.
Published: September 2022

Background

The critically endangered kākāpō is a flightless, nocturnal parrot endemic to Aotearoa New Zealand. Recent efforts to describe the gastrointestinal microbial community of this threatened herbivore revealed a low-diversity microbiota that is often dominated by Escherichia-Shigella bacteria. Given the importance of associated microbial communities to animal health, and increasing appreciation of their potential relevance to threatened species conservation, we sought to better understand the development of this unusual gut microbiota profile. To this end, we conducted a longitudinal analysis of faecal material collected from kākāpō chicks during the 2019 breeding season, in addition to associated nest litter material.

Results

Using an experimental approach rarely seen in studies of threatened species microbiota, we evaluated the impact of a regular conservation practice on the developing kākāpō microbiota, namely the removal of faecal material from nests. Artificially removing chick faeces from nests had negligible impact on bacterial community diversity for either chicks or nests (p > 0.05). However, the gut microbiota did change significantly over time as chick age increased (p < 0.01), with an increasing relative abundance of Escherichia-Shigella coli over the study period and similar observations for the associated nest litter microbiota (p < 0.01). Supplementary feeding substantially altered gut bacterial diversity of kākāpō chicks (p < 0.01), characterised by a significant increase in Lactobacillus bacteria.

Conclusions

Overall, chick age and hand rearing conditions had the most marked impact on faecal bacterial communities. Similarly, the surrounding nest litter microbiota changed significantly over time since a kākāpō chick was first placed in the nest, though we found no evidence that removal of faecal material influenced the bacterial communities of either litter or faecal samples. Taken together, these observations will inform ongoing conservation and management of this most enigmatic of bird species.
A one health approach to plant health
Authors: Hoffmann Vivian , Paul Birthe , Falade Titilayo , Moodley Arshnee , Ramankutty Navin , Olawoye Janice , Djouaka Rousseau , Lekei Elikana , de Haan Nicoline , Ballantyne Peter , Waage Jeff
Published: September 2022

One Health has been defined as an approach to the pursuit of public health and well-being that recognizes the interconnections between people, animals, plants, and their shared environment. In this opinion piece, based on a webinar of the same name, we argue that a One Health perspective can help optimize net benefits from plant protection, realizing food security and nutrition gains while minimizing unintentional negative impacts of plant health practices on people, animals and ecosystems. We focus on two primary trade-offs that lie at the interface of plant health with animal, ecosystem, and human health: protecting plant health through use of agrochemicals versus minimizing risks to human health and antimicrobial and insecticide resistance; and ensuring food security by prioritizing the health of crops to maximize agricultural production versus protecting environmental systems critical for human health. We discuss challenges and opportunities for advancement associated with each of these, taking into account how the priorities and constraints of stakeholders may vary by gender, and argue that building the capacity of regulatory bodies in low- and middle-income countries to conduct cost–benefit analysis has the potential to improve decision-making in the context of these and other multi-dimensional trade-offs.
Minding the Bathwater: Fertility and Reproductive Toxicity in the Age of Immuno-Oncology
Authors: Kim Anne E. , Nelson Ariel , Stimpert Kyle , Flyckt Rebecca L. , Thirumavalavan Nannan , Baker Karen C. , Weinmann Sophia C. , Hoimes Christopher J.
Published: September 2022

Immune checkpoint inhibition has resulted in significant efficacy across many cancer types, including melanoma. Melanoma is the second most common cancer among those of reproductive age, yet the reproductive toxicities of adjuvant and first-line immunotherapy are largely unknown.The normal innate and adaptive immune systems play a vital role in reproductive organ homeostasis of men and women and are essential for implantation, fertility, and a successful pregnancy. The programmed cell death-1 receptor/programmed cell death receptor ligand-1 (PD-1/PD-L1) pathway is essential in several aspects of fertility and pregnancy. Recent studies have largely focused on the role of the PD-1/PD-L1 pathway in fetomaternal tolerance, highlighting the importance of intact immune regulation in promoting a successful pregnancy.In this review, we describe a case of a reproductive-aged female with stage IIIC melanoma who sought guidance on family planning after pembrolizumab therapy. We discuss the known fertility-related toxicities of immune checkpoint inhibitors, the potential targets for reproductive toxicity in males and nonpregnant females, and the implications of anti–PD-1 therapy in relation to fetomaternal tolerance. Informed decision making will benefit from data and consensus.
Entrenching Inequity, Eroding Democracy: State Preemption of Local Housing Policy
Authors: Michener Jamila
Published: September 2022

Housing is a fundamental right and a vital determinant of health. Health equity is not possible without widespread access to safe, affordable, high-quality housing. Local housing policy is a central conduit for advancing such ends. However, preemption of local law is a powerful institutional mechanism that state legislatures sometimes deploy to inhibit or nullify municipal efforts to address housing-based inequities. Local housing policies often have high stakes, are ideologically laden, and are politically salient. This makes them a clear target for preemptive action. Political science research to date has focused on broadly explaining the causes of preemption, with scant emphasis on its consequences and minimal attention to the implications for racial and economic equity. This article highlights the political repercussions of state preemption. Drawing on in-depth qualitative interviews, the article examines how local tenant organizations that work to build power within racially and economically marginalized communities perceive and respond to state preemption. The findings demonstrate how both the reality and the threat of state preemption prompt tenant organizations to adjust (and often minimize) their policy goals and to adapt their political strategies in ways that strain their capacity. By burdening local organizations that are crucial power resources in marginalized communities, state preemption of local housing policy risks entrenching inequity and eroding democracy.
County-Level Segregation and Racial Disparities in COVID-19 Outcomes
Authors: Trounstine Jessica , Goldman-Mellor Sidra
Published: September 2022

Context: Segregation has been linked to unequal life chances. Individuals from marginalized communities experience more crime, higher levels of poverty, poorer health, and less civic engagement. In addition, segregated metropolitan regions have been found to display inequality in access to basic services. This article builds on these findings by linking segregation to infection and deaths from COVID-19.

Methods: Using census data matched to COVID infection and death statistics at the county level, this article offers a theoretical basis for the researchers' choice of segregation measures and predictions for different racial groups. It analyzes the relationship between two dimensions of segregation—racial isolation and racial unevenness—and COVID outcomes for different racial and ethnic groups.

Findings: In counties where Black and Latino residents lived in more racially isolated neighborhoods, they were much more likely to contract COVID-19. This pattern was exacerbated in counties with a high proportion of frontline workers. In addition, racial segregation increased COVID-19 death rates for Black, Latino, and white residents.

Conclusions: These findings suggest that devastating outcomes of the coronavirus pandemic were linked to a long history of racial marginalization and entrenched discrimination produced by structural inequalities embedded in our geographies. This knowledge should be used to inform public health planning.
The Political Economy of Market Power in Pharmaceuticals
Authors: Kapczynski Amy
Published: September 2022

The pharmaceutical industry is among the most politically powerful business sectors in the United States today. This article describes how this industry has successfully entrenched its power, with attention to four sources of power: property power, vertical power over politics, ideational power, and material power. Attempts to reform the industry must grapple with these forms of power, which are not easily separated and which, in the current environment, tend to reinforce one another.
Study of bypassing Microsoft Windows Security using the MITRE CALDERA Framework
Authors: Mohamed Nachaat
Published: September 2022

Background: Microsoft Windows Security is a recently implemented safeguard for the Windows operating systems, including the latest versions of Windows10 and 11. However, there is a major shortcoming in this system to stop Advanced Persistent Threat (APT). These are government-financed groups that are funded to attack other government entities. Following the initial security breach, the hacked Windows device is used to access the rest of the network devices in order to transfer data to external storage (Exfiltration).

Methods: In this work, we have tested the Microsoft Windows Security system using MITRE CALDERA and ATT&CK frameworks and explain how APT groups are able to bypass Windows Security.

Results: In this study we used "54ndc47" agent through GoLang feature in MITRE CALDERA platform to test and bypass Microsoft Windows Security systems (MS Windows 10). Through it, we were able to bypass the Windows Security system and display entire files in the victim's device.

Conclusions: In this paper, we have provided recommendations to Microsoft to improve their Windows Security tool through the use of Artificial intelligence (AI).
Parents’ perceptions on policies of early childhood care and education programmes in selected states of Malaysia
Authors: Tang Dandan , Peng Chew Fong , Abdul Rahman MohdNazri , Dhamotharan Mogana
Published: September 2022

Background:

The 2030 agenda for sustainable development proposed global equitable quality education and lifelong learning opportunities for all children. The quality of early childhood care and education (ECCE) programs helps shape children’s minds, attitudes and behaviors, and has short and long-term effects on a child, a family and a country. In Malaysia, the government has formulated some policies and laws to protect children’s rights. However, ECCE is facing some challenges. The purpose of this study is to investigate parents’ perceptions of the quality of ECCE programs implemented by Malaysian government.

Methods: A mixed method was used to collect data on parents’ perceptions of ECCE policies in selected states in Malaysia. The questionnaires, (P1/POL) from the research project “Development of a Comprehensive and Integrated Model of Quality Malaysian ECCE”, were distributed among 629 respondents who have a child in a preschool, and 22 participants were randomly selected to take part in five focus group interviews

Results: The key findings of the study revealed 68% parents were not familiar with ECCE Malaysian government policy, however 84.3% stressed it is important for the government to educate them about ECCE. Thus findings indicated that the majority of parents lack awareness of the ECCE policies and quality of early childhood care and education programs related to the policies remain the issue. While interviewing the focus group ,most of them were not aware of ECCE and pointed out parents are stressing children’s academic learning in particular preschools.

Conclusions: It is concluded that parents’ awareness regarding the ECCE program must be part of the policies and needs to improve. It is recommended that the government of Malaysia should supply more information on ECCE policies to parents and focus on policy implementation. Moreover, the quality of ECCE programs should be improved based on the parents’ perceptions.
Machine learning-based heart attack prediction: A symptomatic heart attack prediction method and exploratory analysis
Authors: Nandal Neha , Goel Lipika , TANWAR ROHIT
Published: September 2022

Background; Heart attack prediction is one of the serious causes of morbidity in the world’s population. The clinical data analysis includes a very crucial disease i.e., cardiovascular disease as one of the most important sections for the prediction. Data Science and machine learning (ML) can be very helpful in the prediction of heart attacks in which different risk factors like high blood pressure, high cholesterol, abnormal pulse rate, diabetes, etc... can be considered. The objective of this study is to optimize the prediction of heart disease using ML.

Methods: In this paper, we are presenting a machine learning-based heart attack prediction (ML-HAP) method in which the analysis of different risk factors and prediction for heart attacks is done using ML approaches of Support Vector Machines, Logistic Regression, Naïve Bayes and XGBoost. The data of heart disease  symptoms has been collected from the UCI ML Repository and analysis has been performed on the data using ML methods. The focus has been on optimizing the prediction on the basis of different parameters.

Results: XGBoost provided the best prediction among the four. The Area under the curve achieved with XGBoost is .94 and Logistic Regression is .92. The prediction with ML models in identifying heart attack symptoms is highly efficient, especially with boosting algorithms. The prediction was done to evaluate accuracy, precision, recall, and area under the curve. ML models are being trained to perform optimized predictions.

Conclusions: This prediction can help clinically in analyzing the risk factors of the disease and interpretation of the patient scenario. Boosting the algorithm provided promising results to predict symptoms of heart disease. It can further be optimized by working further on risk factors associated with this condition.
Prevalence and correlates of neurocognitive impairment and psychiatric disorders among schoolchildren in Wakiso District, Uganda: a cross-sectional study
Authors: Nampijja Margaret , Sembajjwe Wilber , Mpairwe Harriet , Mpango Richard , Kinyanda Eugene
Published: September 2022

Background: There is limited data on the burden of mental disorders among children in the general population in Africa. We examined the prevalence and correlates of neurocognitive and psychiatric disorders among schoolchildren in Uganda.

Methods: This cross-sectional study enrolled 322 schoolchildren aged 5-17years in Wakiso, Uganda. We assessed for neurocognitive impairment using the Kaufmann-Assessment-Battery, and psychiatric disorders (major-depressive-disorder (MDD), attention-deficit-hyperactivity-disorder (ADHD), generalised-anxiety-disorder (GAD), and substance-use-disorder (SUD)) using the parent version of the Child and Adolescent Symptom Inventory-5, and Youth Inventory-4R Self Report. Prevalence and risk factors were determined using respectively descriptive statistics, and univariable and  multivariable logistic regression.

Results: Twenty-five participants (8%) had neurocognitive impairment. Nineteen (5.9%) participants had MDD, nine (2.8%) had ADHD, seven (2.2%) had GAD, 14 (8.6%) had SUD; and 30 (9.3%) had any psychiatric disorder. Among the exposure variables examined in this study, including asthma, age, sex, grade of schooling, type of school and maternal and father’s education and family socio-economic status, only asthma was associated with the disorders (MDD).

Conclusions: The relatively high burden of mental disorders in this general population of children warrants targeted screening of those at risk, and treatment of those affected. Further, future studies should extensively investigate the factors that underlie the identified psychiatric disorders in this and similar general populations.
Chemical and physico-chemical methods of wastewater and man-made water treatment
Authors: Ksenofontov Boris , Lukanin Aleksandr , Pirogov Evgeniy
Published: September 2022

The monograph discusses issues related to chemical and physico-chemical methods of wastewater and man-made water treatment, including oxidation and sorption of pollutants, as well as their coagulation and flocculation and other processes of wastewater and man-made water treatment. At the same time, individual tasks are considered for the first time both in domestic and in the world practice of water treatment. First of all, this applies to the use of strong oxidizing agents in the practice of water purification, as well as neutralizing substances. In addition, the issues of intensification of chemical reactions occurring during wastewater treatment using various reagents are considered. At the same time, water treatment using ultraviolet light, electromagnetic fields, etc. is considered as an intensifying effect. As a result of the complex effect on the treated water, a high technological effect of purification is achieved.
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