bluuebunny/crossref_metadata_2025 huggingface dataset:
Systemic Inflammatory Response Syndrome, a Form of Cytokine Storm Associated with Adult-onset Still's Disease
Authors: pan zhou , Zhang Lei , Liu Shengyun
Published: November 2023

Objective
This study aimed to analyse data regarding the clinical characteristics and outcomes of adult-onset Still's disease (AOSD) patients with systemic inflammatory response syndrome (SIRS).
Methods
A retrospective analysis of 72 AOSD patients at the First Affiliated Hospital of Zhengzhou University was conducted comparing the clinical characteristics, treatment protocols, and outcomes of patients with SIRS and macrophage activation syndrome (MAS).
Results
This study included 15 AOSD patients with SIRS (12 women) and 57 with MAS (47 women). The mean (SD) age of the patients with SIRS was 30.1 (14.2) years, and that of patients with MAS was 34.6 (14.9) years. Clinical features of these patients included fever, hepatosplenomegaly, polyserositis, and shock. There were statistically significant differences in leukocyte counts, platelets, albumin, lactate dehydrogenase, ferritin, erythrocyte sedimentation rate, and C-reactive protein values between the two groups. Patients with SIRS had lower HScore scores than patients with MAS (171 [156, 192] vs. 216 [178, 248], P = 0.02). Patients were treated with glucocorticoids (13 SIRS, 55 MAS), cyclosporine (7 SIRS, 49 MAS), intravenous immunoglobulin (8 SIRS, 30MAS), etoposide (5 SIRS, 34 MAS), and tocilizumab (2 SIRS, 21 MAS). The mortality rate of patients with SIRS (40%) was higher than that of patients with MAS (1.8%, P < 0.001).
Conclusions
SIRS is a rare but often fatal form of cytokine storm caused by persistent AOSD activity. Early treatment with immunosuppressants, etoposide, and IL-1 and IL-6 inhibitors is necessary for these patients.
Scalable Atomic Arrays for Spin-Based Quantum Computers in Silicon
Authors: Jakob Alexander , Robson Simon , Firgau Hannes , Mourik Vincent , Schmitt Vivien , Holmes Danielle , Posselt Matthias , Mayes Edwin , Spemann Daniel , Morello Andrea , Jamieson David
Published: November 2023

Semiconductor spin qubits combine excellent quantum performance with the prospect of manufacturing quantum devices using industry-standard metal-oxide-semiconductor (MOS) processes. This applies also to ion-implanted donor spins, which further afford exceptional coherence times and large Hilbert space dimension in their nuclear spin. Here we demonstrate and integrate multiple strategies to manufacture scale-up donor-based quantum computers. We use 31PF2 molecule implants to triple the placement certainty compared to 31P ions, while attaining 99.99% confidence in detecting the implant. Similar confidence is retained by implanting heavier atoms such as 123Sb and 209Bi, which represent high-dimensional qudits for quantum information processing, while Sb2 molecules enable deterministic formation of closely spaced qudits. We demonstrate the deterministic formation of regular arrays of donor atoms with 300nm spacing, using step-and-repeat implantation through a nano aperture. These methods cover the full gamut of technological requirements for the construction of donor-based quantum computers in silicon.
Dose Escalation of Total Marrow and Lymphoid Irradiation Prior to Allogeneic Stem Cell Transplantation treating for Acute Leukemia and Lymphoma
Authors: Xiong Yu , Liu Weicheng , Jiang Dazhen , Shen Jiuling , Wang Xiaoyong , Deng Di , Liu Yu
Published: November 2023

Purpose
Hematopoietic stem cell transplantation (HSCT) is a curative option for various hematologic malignancies (HM), however, the risk of relapse hampers favorable HSCT outcomes. Augmentation of irradiation to sites of disease is one potential strategy to overcome this risk. This study evaluated the feasibility of radiation dose escalation of total marrow and lymphoid irradiation (TMLI) as part of the conditioning regimen prior to HSCT.
Methods and Materials
53 patients (5 acute myelogenous leukemia (AML), 29 acute lymphoblastic leukemia (ALL), 17 non-Hodgkin’s lymphoma (NHL), 2 mixed acute leukemia (MAL)) received conditioning radiation treatment with TMLI 10 Gy (8 Gy to bone marrow (BM), 10 Gy to involved lymphatic sanctuary sites in 2 fractions per day). 36 patients (5 AML, 26 ALL, 2 NHL, 3 MAL) underwent the radiation treatment with TMLI 12 Gy (8 Gy to BM, 12 Gy to involved lymphatic sanctuary sites in 2 fractions per day) before HSCT.
Results
The median age of patients receiving TMLI 10 Gy and 12 Gy was 24 (4–47) and 27 (8–55) years old, respectively. Median dose of organs at risk (OARs) was down-regulated by 27% − 79% and 11% − 83% of the prescription dose at TMLI 10 Gy and 12 Gy compared to standard total body irradiation (TBI). Grade 1–2 acute toxicities were primarily observed. The 2 years progression-free survival (PFS) was 73.6% at TMLI 10 Gy and 84.8% at TMLI 12 Gy (95% CI: 0.15, 1.33) and, and the 2 years overall survival (OS) was 79.1% and 65.7% respectively (95% CI: 0.28, 2.15). The 2-year relapse rate was 19% and 11%, and the non-relapse mortality was 9% and 22% at TMLI 10 Gy and 12 Gy, respectively.
Conclusions
This study suggests that the relapse rate and 2 years PFS of HM are considerably improved when TMLI is performed prior to HSCT, which will offer an effective strategy for treating these diseases.
Viability of Medicines Regulatory Harmonization (MRH) Regional Programs in advancing medicines Access – Case of New Drug Applications for East Africa Community (EAC) MRH
Authors: Mwangi John M , Makokha Teresa N.
Published: November 2023

Access to essential medicines remains a significant challenge for patients in Africa. This is attributable to, among other factors, overreliance on imports from other countries for essential medicines, poor healthcare infrastructure, and weak regulatory systems. This is more apparent in the case of communicable diseases of Malaria, HIV, and TB in addition to the rising non-communicable diseases burden whose medicines access has been affected by the inefficient regulatory systems. Realizing this need, African countries through the support of WHO and the donor community started initiatives to strengthen regulatory systems over the last decade with the view to bring Africa towards being at par with other countries and regions of the world. An example has been the 2009 Africa Medicines Regulatory Harmonization (AMRH) program started with the goal of harmonizing regulatory requirements across Africa through regional economic communities as interim building blocks. In East Africa, such an initiative was launched in 2012 resulting in multiple regulatory milestones being fulfilled to date. Past studies have assessed the utility of the process from a regulator’s perspective. The current study assessed the impact of EAC MRH from an industry perspective as a tool to accelerate medicines access. The study looked at retrospective data covering fifteen years in the company regulatory database showing approval timelines for new drug applications using the traditional/national procedures in comparison to the EAC MRH procedure. From the results, there was a reported reduction in regulatory timelines for new drug application authorizations among the member countries from a high of up to 17 months to 12 months on average. Additionally, the EAC MRH process was found to be predictable, transparent, and a platform to practice regulatory reliance, therefore, facilitating quicker access to health products and medicines for patients. From the findings, applicants are encouraged to explore the EAC MRH route as an alternative to the national regulatory procedures as one way to guarantee faster access to health products and medicines. It is also recommended to address the gaps in the national procedures that have been shown to delay regulatory decisions in the East Africa region. This report however did not cover other regulatory aspects such as the sustainability of the program, post-approval changes, GMP inspection, and vigilance which are not as well developed and which should be a focus for future work by industry and regulators.
Double-walled Al-based MOF with large microporous specific surface area for trace benzene adsorption
Authors: Yang Kun , Hu Laigang , Wu Wenhao , Hu Min , Jiang Ling , Lin Daohui , Wu Jian
Published: November 2023

Double-walled metal-organic frameworks (MOFs), synthesized using Zn and Co, are potential porous materials for trace benzene adsorption. Aluminum is with low-toxicity and abundance in nature, in comparison with Zn and Co. Therefore, a novel double-walled Al-based MOF, named as ZJU-520(Al), with large microporous specific surface area of 2235 m2/g, pore size distribution in the range of 9.26 – 12.99 Å and excellent thermal-chemical stability, was synthesized in this study. ZJU-520(Al) is consisted by helical chain of AlO6 clusters and 4,6-Di(4-carboxyphenyl)pyrimidine ligands. It exhibits unprecedented trace benzene adsorption up to 5.98 mmol/g at 298 K and P/P0 = 0.01. Adsorbed benzene molecules are trapped on two types of sites. One (site I) is near the AlO6 clusters, another (site II) is near the N atom of ligands, using Grand Canonical Monte Carlo (GCMC) simulations. ZJU-520(Al) also can effectively separate trace benzene from mixed vapor flow of benzene and cyclohexane, due to the adsorption affinity of benzene higher than that of cyclohexane. Therefore, ZJU-520(Al) is a potential adsorbent for trace benzene adsorption and benzene/cyclohexane separation.
Identification of Diagnostic Model in Heart Failure with Myocardial Fibrosis and Conduction Block by Integrated Gene Co-expression Network Analysis
Authors: yuan yonghua , Niu Yiwei , Ye Jiajun , Xu Yuejuan , He Xuehua , Chen Sun
Published: November 2023

Background: Despite the advancements in heart failure(HF) research, the early diagnosis of HF continues to be a challenging issue in clinical practice. This study aims to investigate the genes related to myocardial fibrosis and conduction block, with the goal of developing a diagnostic model for early treatment of HF in patients.
Method: The gene expression profiles of GSE57345, GSE16499, and GSE9128 were obtained from the Gene Expression Omnibus (GEO) database. After merging the expression profile data and adjusting for batch effects, differentially expressed genes (DEGs) associated with conduction block and myocardial fibrosis were identified. Gene Ontology (GO) resources, Kyoto Encyclopedia of Genes and Genomes (KEGG) resources, and gene set enrichment analysis (GSEA) were utilized for functional enrichment analysis. A protein-protein interaction network (PPI) was constructed using a string database. Potential key genes were selected based on the bioinformatics information mentioned above. SVM and LASSO were employed to identify hub genes and construct the module associated with HF. The mRNA levels of TAC mice and external datasets (GSE141910 and GSE59867) are utilized for validating the diagnostic model. Additionally, the study explores the relationship between the diagnostic model and immune cell infiltration.
Results: A total of 395 genes exhibiting differential expression were identified. Functional enrichment analysis revealed that these specific genes primarily participate in biological processes and pathways associated with the constituents of the extracellular matrix (ECM), immune system processes, and inflammatory responses. We identified a diagnostic model consisting of 16 hub genes, and its predictive performance was validated using external data sets and a transverse aortic coarctation (TAC) mouse model. In addition, we observed significant differences in mRNA expression of 7 genes in the TAC mouse model. Interestingly, our study also unveiled a correlation between these model genes and immune cell infiltration.
Conclusions: We identified sixteen key genes associated with myocardial fibrosis and conduction block, as well as diagnostic models for heart failure. Our findings have significant implications for the intensive management of individuals with potential genetic variants associated with heart failure, especially in the context of advancing cell-targeted therapy for myocardial fibrosis.
A Pseudorandom Bit Generator Based onBose-type Sidon Sets
Authors: Osorio Rigo Julian , Trujullo Carlos Alberto , Ruiz Diego Fernando
Published: November 2023

Sidon sets have a variety of applications in mathematics and in real-world problems, such as error-correcting codes, the signal compression in telecommunications, and cryptography. In particular, pseudorandom number (bit) generators with good randomness qualities is critical in the development of secure applications. Based on the construction of Bose-type Sidon sets, in this paper we present the construction of a new pseudorandom bit generator (PRBG) with large period, high degree of entropy and good randomness properties.
MSC Classification: 43A46 , 12E20 , 94A55
In vitro replicative potential of an HIV-1/MO intergroup recombinant virus compared to HIV-1/M and HIV-1/O parental viruses
Authors: Moisan Alice , Tombette Fabienne , Vautrin Manon , Alessandri-Gradt Elodie , Mourez Thomas , Plantier Jean-Christophe
Published: November 2023

Genetic recombination is one of the major evolution processes of HIV-1. Despite their great genetic divergence, HIV-1 groups M and O can generate HIV-1/MO intergroup recombinants. The current description of 20 HIV-1/MO unique recombinant forms suggests a possibl e benefit of the recombination.
The aim of this work was to study in vitro the replicative potential of HIV-1/MO recombinant forms.
This analysis was based on a simple recombination pattern, [Ogag/pol-Menv], harboring a breakpoint in Vpr. A chimeric infectious molecular clone, pOM-TB-2016 was synthesized from HIV-1/M subtype B and HIV-1/O subgroup T and recombinant viruses were obtained by transfection/co-culture. To compare the replicative potential of these viruses, two markers were monitored in culture supernatants: Reverse Transcriptase (RT) activity and P24 antigen concentration. The results showed a superiority of the group M parental virus compared to group O for both markers. In contrast, for the recombinant virus, RT activity data did not overlap with the concentration of P24 antigen, suggesting a hybrid behavior of the recombinant, in terms of enzyme activity and P24 production.
These results highlighted many hypotheses about the impact of recombination on replicative potential and demonstrated gain the significant plasticity of HIV genomes and their infinite possibility of evolution.
Importance :
HIV-1/M and HIV-1/O can generate HIV-1/MO intergroup recombinants. The current description of 19 URF_MO raises the question of a possible benefit of recombination in terms of emergence. The objectives of this work were to study in vitro the replicative potential of HIV-1/MO recombinant viruses. For this, a chimeric infectious molecular clone (IMC) generated from HIV-1/M subtype B and HIV-1/O subgroup T and recombinant viruses were obtained by transfection and co-culture. To compare the replicative potential of recombinant viruses with HIV-1/M and HIV-1/O parental viruses, RT activity and P24 antigen concentration were monitored in culture supernatants. A superiority of the group M parental virus compared to group O was observed for both markers whereas a hybrid behavior in terms of enzyme activity and P24 production was found for the recombinant virus. These results demonstrated once again the significant plasticity of HIV genomes and their infinite possibility of evolution.
Fecal microbiome associations with age, body condition score, and stool consistency in domestic cats (Felis catus) living in an animal shelter
Authors: Kittson Molly A. , Tanprasertsuk Jirayu , Burnham Christina M. , Honaker Ryan W. , Jones Roshonda B. , Trivedi Shweta , Strong Sandra , Heugten Kimberly Ange-van
Published: November 2023

Background: Few studies delve into the gut microbiome of domestic cats, and many feline-specific studies are hampered by small sample population sizes. We investigated the fecal microbiome as a proxy for gut microbiome within a large shelter cat population (n=288) in Raleigh, NC, USA from February to July 2021. Single stool samples were collected from cats of various age groups that lived in one of four rooms (adoption, n=117; feral, n=113; quarantine, n=37; isolation, n=20; no room, n=1) at the shelter during the sampling period. The fecal microbiome was characterized by shotgun sequencing. Statistical differences in α- and β-diversity were assessed based on assigned shelter room as well as cat age group, body condition score (BCS; scale 1-9), and stool consistency (Bristol fecal scale). Enrichment of composition (as characterized by microbial taxa) and functional potential (as characterized by Kyoto Encyclopedia of Genes and Genomes (KEGG) orthology (KO) terms) based on subject characteristics were evaluated.
Results:
Analyses consistently indicated significant (p<0.05) differences in β-diversity based on assigned shelter room, age, body condition score, and stool consistency. The β-diversity within samples from cats housed within the adoption room was different from that of the other rooms. In KO terms, samples from the isolation room were also different from the adoption and feral room but not the quarantine room. Regarding age, kittens differed significantly in β-diversity from mature adults in post-hoc comparisons, and mature adults were abundant in much fewer microbiome species and KO terms when compared to kittens and young adults. Underweight and normal weight cats had different microbial profiles, and underweight cats were deficient in a KO term related to microbial lysine biosynthesis. Microbial taxa enriched in felines with overly dense stool or diarrhea were reported, with felines producing dense stools abundant in members of the genera Desulfovibrio and Alistipes and deficient in probiotic Lactobacillus spp. and diarrhetic cats abundant in members of the families Lachnospiraceae and Streptococcaceae. There were no significant differences among α-diversity metrics.
Conclusions:
To our knowledge, this research utilizes the largest feline microbiome dataset to date and validates previously reported differences in gut microbiome diversity due to age, BCS, and stool consistency while illuminating novel differences associated with the shelter setting. Gaining insight into the diverse microbial populations within the feline gut microbiome is essential for future research into enhancing host health and quality of life.
Impact of COVID-19 Among College Students Academic, Financial and Physical Matters in Kerala
Authors: Panicker Rani Oomman , Navas Sana S , Jose Rose Mary , J Mary Jaya V
Published: November 2023

Closure of schools and colleges due to the COVID-19 pandemic has brought significant disruption to the educational systems worldwide. According to the UNESCO report, COVID-19 affected about 800 million students worldwide. This paper aims to study the impact of the COVID-19 pandemic among college students in Kerala, one of the states in India. Through this quantitative study, we investigate the impact of the COVID-19 pandemic on education matters, physical health, and financial matters for Kerala college students. For that, we sent an online questionnaire form via WhatsApp to college students, and 406 of them filled out the questionnaire. Through this study, we concluded that, 62.31% of students have lost their concentration in studies, 42.11% of respondents have decreased their interaction with teachers, 45.06% of respondents have decreased their interaction among classmates, 50% of the students have become worse at time management during offline exams, 54.3% of respondents agreed that their interest in participating in extracurricular activities has reduced, and 66.9% of respondents agreed that their financial status is badly affected by the COVID-19 pandemic. In the case of physical matters, 73.89% of respondents revealed that they are affected by irregular sleep, and 45.97% of females are affected by irregularities in their menstrual cycles. Also, females are more affected by muscle pain (50.93%), breathing disorders (38.58%), cholesterol (12.65%), stroke (19.13%), fainting (23.45%), and blood pressure (19.13%) than males. Overall, the pandemic of COVID-19 negatively impacted the education, physical health, and financial matters of college students greatly.
Multi-night cortico-basal recordings reveal mechanisms of NREM slow wave suppression and spontaneous awakenings at high-temporal resolution in Parkinson’s disease
Authors: Anjum Md Fahim , Smyth Clay , Dijk Derk-Jan , Starr Philip , Denison Timothy , Little Simon
Published: November 2023

Background
Sleep disturbance is a prevalent and highly disabling comorbidity in individuals with Parkinson's disease (PD) that leads to worsening of daytime symptoms, reduced quality of life and accelerated disease progression.
Objectives
We aimed to record naturalistic overnight cortico-basal neural activity in people with PD, in order to determine the neurophysiology of spontaneous awakenings and slow wave suppression in non-rapid eye movement (NREM) sleep, towards the development of novel sleep-targeted neurostimulation therapies.
Methods
Multi-night (n=58) intracranial recordings were performed at-home, from chronic electrocorticography and subcortical electrodes, with sensing-enabled Deep Brain Stimulation (DBS), paired with portable polysomnography. Four participants with PD and one participant with cervical dystonia were evaluated to determine the neural structures, signals and functional connectivity modulated during NREM sleep and prior to spontaneous awakenings. Intracranial recordings were performed both ON and OFF DBS to evaluate the impact of stimulation. Sleep staging was then classified with machine-learning models using intracranial cortico-basal signals on classical (30 s) and rapid (5 s) timescales.
Results
We demonstrate an increase in cortico-basal slow wave delta (1-4 Hz) activity and a decrease in beta (13-31 Hz) activity during NREM (N2 and N3) versus wakefulness in PD. Cortical-basal ganglia coherence was also found to be higher in the delta range and lower in the beta range during NREM. DBS stimulation resulted in a further elevation in cortical delta and a decrease in alpha (8-13 Hz) and low beta (13-15 Hz) power compared to the OFF stimulation state. Within NREM sleep, we observed a strong inverse interaction between subcortical beta and cortical slow wave activity and found that subcortical beta increases prior to spontaneous awakenings at high-temporal resolution (5s). Our machine-learning models trained on intracranial cortical or subcortical power features achieved high accuracy in both traditional (30s) and rapid (5s) time windows for NREM vs. wakefulness classification (30s: 92.6±1.7%; 5s: 88.3±2.1%).
Conclusions
Chronic, multi-night recordings in PD reveal increased cortico-basal slow wave, decreased beta activity, and changes in functional connectivity in NREM vs wakefulness, effects that are enhanced in the presence of DBS. Within NREM, subcortical beta and cortical delta are strongly inversely correlated and subcortical beta power increases prior to spontaneous awakenings. Our findings elucidate the network-level neurophysiology of sleep dysfunction in PD and the mechanistic impact of conventional DBS. Additionally, through accurate machine-learning classification of spontaneous awakenings, this study also provides a foundation for future personalized adaptive DBS therapies for sleep dysfunction in PD.
Saposin-related gene function as tumor suppressor in tracheal system of Drosophila larvae via Hippo signaling pathway: Novel gene to gene network prediction with GeneMANIA
Authors: El-Kholy Samar , Fathy Mai , Salem Maha M.
Published: November 2023

Saposin-related (Sap-R) proteins promote the hydrolases of sphingolipids in lysosomes. Disrupted human Sap-R functions may lead to death at an early age. More worse, effective therapeutics are not available due to poorly understood molecular underlying mechanisms. To gain more insights about these mechanisms, we utilized Drosophila melanogaster as a simple invertebrate model with available genetic tools, with special focus on larval stage to simulate the stage of infancy in human. We found that Sap-R localizes in inka cells of larval tracheal system. Down regulation of Sap-R using inka cells driver reduces the expression level of ecdyson triggering hormone without significant effect on ecdysis. Sap-R mutant larvae have reduced lysosomal function, disrupted tracheal cell-to-cell junctions, huge number of tracheal cells nuclei because of observed cell divisions. Moreover, reduced expression of Hippo signal transduction pathway key genes in Sap-R mutant trachea was confirmed theoretically and practically which may indicate the development of cancer. This initial study showed a relevant role of Sap-R signaling for suppressing airway cancer. Interfering with theoretically predicted pathways may provide novel therapeutic options in the future.
Hepatoprotective effect of selenium nanoparticles coated with Spirulina polysaccharides against anti-tuberculosis drugs induced apoptosis
Authors: Afifi Safaa , Hamza Refaat G , Boraei Ibrahim H , Abdel-Ghaffar Abdel-Rahman B , Hamdy Germine M
Published: November 2023

This study aims to evaluate the ameliorating effect of selenium nanoparticles (SeNPs) coated withSpirulinapolysaccharides(SPs-SeNPs) against anti-tuberculosis drugs (ATDs) induced hepatotoxicity and apoptosis in a trial to enhance the drug efficacy and tolerance, as well as to improve the chance of recovery of tuberculosis patients. The results revealed that utilizing SPs as a capping agent resulted in size-controlled, highly stable, and monodispersed spherical SeNPs with an average diameter < 50 nm. When compared to ATDs-treated animals, co-administration of either SPs (0.5mg /kg bw/day/8 weeks), SeNPs (0.5mg /kg bw/day/8 weeks) or SPs-SeNPs (0.5mg /kg bw/day/8 weeks) together with the ATDs[ ((Isoniazid (INH; 50 mg/kg) + Rifampicin (RIF;100 mg/kg) + Pyrazinamide (PZA;350 mg/kg)) /day/8 weeks ] for to rats modulated ATDs-induced side effects as evidenced by reductions in CYP2E1, CASPASE-3, malondialdehyde (MDA) concentration, liver function enzymes, levels of total bilirubin with elevation in total antioxidant capacity (TAC) and glutathione content (GSH) levels. These findings also demonstrated that treatment with SPs-SeNPs had a greater significant effect on ATDs-induced damage than treating with SPs or SeNPs alone. The results suggested that SPs–SeNPs could be a promising anti-toxic and antioxidant agent, and the strategy of using SPs as a surface decorator could be a very effective way to enhance the efficacy of nanomaterials.
Human-Robot Harmonious Coexistence: A Robot Navigation Framework Follows Social Norms in Dynamic Scenarios
Authors: LingliYu  , JiaweiLuo  , WeiweiZhu  , ZhengTan  , JianzhiZhou
Published: November 2023

Designing a path planner that provides humans with a comfortable experience is a crucial step in enabling robots to seamlessly integrate into human environments. In this paper, we propose a comprehensive framework that equips robots with the ability to navigate in human environments by taking into account social norms and predicting human trajectories. Firstly, we propose a generalized social space modeling method based on Gaussian Mixture Model (GMM). This model is used to constrain the robot's adherence to social norms and incorporates factors such as human posture, velocity, and group distribution. Secondly, to achieve collision-free navigation, we introduce a trajectory prediction method using a four-parameter logistic curve. This method considers human historical trajectory information, velocity constraints, and incorporates confidence weights. Finally, we use piecewise high-order polynomials to optimize robot's local trajectory spatiotemporally. The collision avoidance constraints between the robot and humans are carefully designed to maximize human comfort and robot sociability. To validate the effectiveness of our approach, we compare it with existing methods, and the results demonstrate a significant improvement in human comfort.
Human sterile immunity to Plasmodium vivax malaria correlates with specific antibody response elicited by immunization with radiation-attenuated sporozoites
Authors: Lopez-Perez Mary , Jain Aarti , Davies D. Huw , Vásquez-Jiménez Juan M. , Herrera Sonia M , Oñate José , Felgner Philip L. , Herrera Sócrates , Arévalo-Herrera Myriam
Published: November 2023

Malaria sterile immunity has been reproducibly induced by immunization with Plasmodium radiation-attenuated sporozoites (RAS). Analyses of sera from RAS-immunized individuals allowed the identification of P. falciparum antigens, such as the circumsporozoite protein (CSP), the basis for the RTS, S vaccine. Similar advances in P. vivax (Pv) vaccination have been elusive. We previously reported 42% (5/12) of sterile protection in malaria-unexposed, Duffy-positive (Fy+) volunteers immunized with PvRAS followed by a controlled human malaria infection (CHMI). Using a custom protein microarray displaying 515 Pv antigens, we found that PvRAS group seroreactivity was lower in protected than non-protected volunteers. Nevertheless, protected volunteers showed higher reactivity to PvCSP and other antigens. In Fy- volunteers immunized with non-irradiated Pv-infected mosquitoes, parasite reactivity increased throughout immunizations. Mock-vaccinated Fy + volunteers developed a vigorous response to CHMI. These findings allowed the identification of novel parasite antigens currently being pursued as vaccine candidates.
RETRACTED: Microglial elimination and repopulation ameliorates surgery-induced cognitive impairment in an ZEB1-dependent manner
Authors: Zhang Xinyue , Cui Xiaotong , Wu Xinyi , Sun Huanan , Jin Jiahui , Pan Xue , Liu Sidan , Zhou Yongjian , Wang Renyi , Liu Fang , Cao Xuezhao
Published: November 2023

The authors have requested that this preprint be removed from Research Square.
Enabling Magnetic Pulse Welding for dissimilar tubular arrester cable joints
Authors: Graß Markus , Sommer Niklas , Böhm Stefan
Published: November 2023

Climate change exacerbates the need for resource-efficient and cost-effective production processes across manifold industries, including the field of electrical connections. This specific field is characterized by a conflict of objectives, i.e., weight reductions while maintaining joint strength and electrical conductivity. From a materials point of view, the use of aluminum as a conductor material is suitable for this application, as it is lighter than copper, a classical conductor material. Electrical conductors are often used in the form of flexible cables, so-called stranded wires. This type of conductor as well as the fact that the sole use of aluminum in electrical systems not feasible, e.g., because the predetermined connection terminals of power electronic components are made of copper, creates a substantial demand for dissimilar aluminum-copper cable arrester joints. However, traditional fusion-based welding processes have proved incapable of reliably producing these dissimilar aluminum-copper joints because of thermophysical effects and chemical incompabilities, the latter eventually leading to the formation of intermetallic phases. These phases adversely affect the quality of the joint in terms of both mechanical and electrical performance. Yet, magnetic pulse welding, a pressure welding process, is ideally suited for producing dissimilar metal joints on basis of a low energy input during the welding process. Consequently, the formation of intermetallic phases is restrained. However, magnetic pulse welding has not been sufficiently investigated for the reliable contacting of stranded cables to tubular arresters. As a result, this paper focuses on the fabrication of tubular stranded cable arrester joints using magnetic pulse welding. To shed light on possible material combinations, aluminum to aluminum and copper to copper joints as well as their dissimilar counterparts are welded. Subsequently, the joints are characterized with regard to their microstructure and quasi-static material strength. Electrical characterization comprises the four-wire Kelvin measurement method to evaluate the resistance of the electrical joints. The results demonstrate that magnetic pulse welding is ideally suited to join the aforementioned material combination and joint configuration due to its process characteristics eventually leading to material continuity. As a result, the stranded wires are welded to the tubular arresters rather than crimped. Consequently, a comparative analysis of the joint properties with those of the joining partners shows that the measured electrical resistances and mechanical tensile forces may be considered very good.
Drug shortages in Israel, revisited - a bitter pill to swallow
Authors: Schwartzberg Eyal , Marom Eli , Vishkautzan Alla , Gorelik Einat , Shani Segev
Published: November 2023

Background: In 2017, we published an article addressing drug shortages (DS) in Israel, exploring regulatory perspectives, challenges, and potential solutions. Since then, DS remain a significant concern for patients, healthcare providers, and policymakers globally. In this updated article, we revisit the topic, providing new insights, data, and analysis on the current DS landscape in Israel, efforts to mitigate them, and propose strategies to combat this escalating issue.
Methods: We conducted a comprehensive search of the Israeli Ministry of Health (MOH) DS database, spanning from 2013 to the present. We extracted DS numbers and reasons. Further searches on the Israeli MOH website, pharmaceutical division archives, and the internet yielded official MOH publications and correspondence regarding regulatory responses to DS from 2017 onwards. Additionally, two specific cases of DS were examined to analyze their handling. Recent activities and publications from the Israeli MOH aimed at reducing DS were also reviewed.
Results: Between 2014 and 2022, marketing discontinuations surged 2.66-fold. Total discontinuations were 3,228; 672 due to commercial reasons, and 2,556 to operational reasons (20.5% and 79.5% respectively). The average duration of intermittent marketing discontinuations increased 1.56-fold, from 85 to 133 days. Manufacturers informed the MOH 22 days prior to discontinuation on average. Analyzing 2022's discontinued medicines (640) by ATC groups, prominent categories included nervous system drugs (18%), drugs acting on the alimentary tract and metabolism (14%), and dermatologicals (11%). Operational DS in 2022 (n=564) were primarily due to stock delivery delays (38%), stock over-utilization (12%), and raw material shortages (9%). Sixteen official MOH publications on DS were identified from 2017 onwards. Moreover, two high-impact DS case studies were examined.
Conclusion: Despite routine monitoring by the Israeli MOH and updating the DS policy throughout this period, DS persist, intensifying annually and posing serious health risks. This trend mirrors international patterns, affecting countries globally. In Israel's uniquely structured healthcare system, with its swift stakeholder cooperation and implementation capabilities, more effective DS management is conceivable. We propose ten universally applicable rules to address DS challenges.
Proteomic insights into the pathophysiology of hypertension-associated albuminuria: Pilot study in a South African cohort
Authors: Govender Melanie A. , Stoychev Stoyan H. , Brandenburg Jean-Tristan , Ramsay Michèle , Fabian June , Govender Ireshyn S.
Published: November 2023

Background: Hypertension is an important public health priority with a high prevalence in Africa. It is also an independent risk factor for kidney outcomes. We aimed to identify potential proteins and pathways involved in hypertension-associated albuminuria by assessing urinary proteomic profiles in black South African participants with combined hypertension and albuminuria compared to those who have neither condition.
Methods: The study included 24 South African cases with both hypertension and albuminuria and 49 control participants who had neither condition. Protein was extracted from urine samples and analysed using ultra-high-performance liquid chromatography coupled with mass spectrometry. Data was generated using data-independent acquisition (DIA) and processed using Spectronaut™ 15. Statistical and functional data annotation were performed on Perseus and Cytoscape to identify and annotate differentially abundant proteins. Machine learning was applied to the dataset using the OmicLearn platform.
Results: Overall, a mean of 1,225 and 915 proteins were quantified in the control and case groups, respectively. Three hundred and thirty-two differentially abundant proteins were constructed into a network. Pathways associated with these differentially abundant proteins included the immune system (q-value [false discovery rate]=1.4x10-45), innate immune system (q=1.1x10-32), extracellular matrix (ECM) organisation (q=0.03) and activation of matrix metalloproteinases (q=0.04). Proteins with high disease scores (76–100% confidence) for both hypertension and CKD included angiotensinogen (AGT), albumin (ALB), apolipoprotein L1 (APOL1), and uromodulin (UMOD). A machine learning approach was able to identify a set of 20 proteins, differentiating between cases and controls.
Conclusions: The urinary proteomic data combined with the machine learning approach was able to classify disease status and identify proteins and pathways associated with hypertension and albuminuria.
Identification and molecular mapping of a major gene conferring resistance to Phytophthora sansomeana in soybean ‘Colfax’
Authors: Wang Dechun , Lin Feng , Salman Muhammad , Zhang Zhanguo , McCoy Austin G , Li Wenlong , Magar Raju Thada , Mitchell Drew , Zhao Meixia , Gu Cuihua , Chilvers Martin I
Published: November 2023

Phytophthora root rot (PRR) is one of the most important diseases in soybean (Glycine max). PRR is mainly caused by Phytophthora sojae, but recent studies showed that P. sansomeana is another causal agent of PRR with more aggressive symptoms, especially in seeds and seedlings. Unlike P. sojae which can be effectively managed by Rps genes, no known resistance genes have yet been reported for P. sansomeana. Our previous study screened 470 soybean germplasm for resistance to P. sansomeana and found that soybean ‘Colfax’ (PI 573008) carries major resistance to the pathogen. In this study, we crossed ‘Colfax’ with a susceptible parent ‘Senaki’ and developed three mapping populations with a total of 234 F2:3 families. Inheritance pattern analysis indicated a 1:2:1 ratio for resistant: segregating: susceptible lines among all the three populations, indicating a single dominant gene conferring the resistance in ‘Colfax’ (designated Rpsan1). Linkage analysis using extreme phenotypes anchored Rpsan1 to a 30Mb region on chromosome 3. By selecting 9 polymorphic SNP markers within the region, Rpsan1 was genetically delimited into a 21.3 cM region between Gm03_4487138_A_C and Gm03_5451606_A_C, which corresponds to a 1.06 Mb genomic region containing 9 NBS-LRR genes based on Gmax2.0 assembly. The mapping results were then validated using two breeding populations derived from ‘E12076T-03’ × ‘Colfax’ and ‘E16099’ × ‘Colfax’. Marker-assisted resistance spectrum analyses with 9 more isolates of P. sansomeana indicated that Rpsan1 carries a broad resistance to P. sansomeana isolates and has strong merit in protecting soybean from PRR in the future.
Efficacy and safety of artemether-lumefantrine for the treatment of uncomplicated falciparum malaria in mainland Tanzania, 2018
Authors: Ngasala Billy , Chiduo Mercy G. , Bushukatale Samwel , Mmbando Bruno P. , Makene Twilumba , Kamugisha Erasmus , Ahmed Maimuna , Mandara Celine I. , Francis Filbert , Mahende Muhidin K. , Kavishe Reginald A. , Muro Florida , Ishengoma Deus S. , Mandike Renata , Molteni Fabrizio , Chacky Frank , Kitojo Chonge , Greer George , Bishanga Dunstan , Njau Ritha , Warsame Marian , Kabula Bilali , Nyinondi Ssanyu S. , Reaves Erik , Mohamed Ally
Published: November 2023

Background: Use of artemisinin combination therapy (ACT) is recommended by the World Health Organization (WHO) for the treatment of uncomplicated falciparum malaria. Artemether-lumefantrine (AL) is the most widely adopted first-line ACT for uncomplicated malaria in sub-Saharan Africa (SSA), including mainland Tanzania, where it was introduced in December 2006. The WHO recommends regular assessment to monitor the efficacy of the first-line treatment specifically considering that artemisinin partial resistance was reported in Greater Mekong sub-region and has been confirmed in East Africa (Rwanda and Uganda). The main aim of this study was to assess the efficacy and safety of AL for the treatment of uncomplicated falciparum malaria in mainland Tanzania.
Methods: A single-arm prospective antimalarial drug efficacy trial was conducted in Kibaha, Mlimba, Mkuzi, and Ujiji (in Pwani, Morogoro, Tanga, and Kigoma regions, respectively) in 2018. The sample size of 88 patients per site was determined based on WHO 2009 standard protocol. Participants were febrile patients (documented axillary temperature ≥37.5 °C and/or history of fever during the past 24 hours) aged 6 months to 10 years.Patients received a 6-dose AL regimen by weight twice a day for 3 days. Clinical and parasitological parameters were monitored during 28 days of follow-up to evaluate the drug effi­cacy and safety.
Results: A total of 653 children were screened for uncomplicated malaria and 349 (53.7%) were enrolled between April and August 2018. Of the enrolled children, 345 (98.9%) completed the 28 days of follow-up or attained the treatment outcomes. There were no early treatment failures, but recurrent infections were higher in Mkuzi (35.2%) and Ujiji (23%). By Kaplan–Meier analysis analysis of polymerase chain reaction (PCR) uncorrected adequate clinical and parasitological response (ACPR) ranged from 63.4% in Mkuzi to 85.9% in Mlimba, while PCR-corrected ACPR on day 28 varied from 97.6% in Ujiji to 100% in Mlimba. The drug was well tolerated; the commonly reported adverse events were cough, runny nose, and abdominal pain. No serious adverse event was reported.
Conclusion: This study showed that AL had adequate efficacy and safety for the treatment of uncomplicated falciparum malaria. The high number of recurrent infections were mainly due to new infections, indicating the necessity of utilizing alternative ACTs such as artesunate amodiaquine, which provide a significantly longer post-treatment prophylactic effect.
Study of Short-term and Long-term Outcomes between Esophagogastrostomy and Double-Tract Reconstruction after Proximal Gastrectomy.
Authors: Hasegawa Tsuyoshi , Kubo Naoshi , Sakurai Katsunobu , Nishimura Junya , Iseki Yasuhito , Nishii Takafumi , Shimizu Sadatoshi , Inoue Toru , Nishiguchi Yukio , Maeda Kiyoshi
Published: November 2023

Background.
As the opportunities for proximal gastrectomy (PG) for early gastric cancer in the upper third stomach have been increasing, the safety and feasibility of PG has been a great concern in recent years. This study aimed to compare to the short-term and long-term outcomes between patients who underwent esophagogastrostomy (EG) and those who underwent the double-tract reconstruction (DTR) after PG.
Methods.
We retrospectively reviewed the medical records of 34 patients who underwent EG and 39 who underwent DTR at our hospital between 2011 and 2022. We compared the procedure data and postoperative complications including anastomotic complications within 1 year after surgery as short-term outcomes, and the rates of change in nutritional status, skeletal muscle mass, and 3-year survival as long-term outcomes.
Results.
Although operation time of DTR group was significantly longer than that of EG group, there were not significantly differences in postoperative complications between 2 groups. Regarding the endoscopic findings, the incidence of anastomotic stenosis and reflux esophagitis was significantly higher in the EG group than in the DTR group (26.5% vs 0%; p < 0.001, 15.2% vs 0%; p = 0.020). In long-term outcomes, there were no significant differences in body weight, BMI, laboratory data, and skeletal muscle mass index between 2 groups for 3 years. The 3-year overall survival rates of 2 groups were similar.
Conclusion.
DTR after PG could prevent the occurrence of anastomotic complications in comparison to EG. The long-term outcomes were similar between these 2 types of reconstruction.
The Impact of an Integrated Early Palliative Care Telehealth Intervention on the Quality of Life of Heart Failure Patients: A Randomized Controlled Feasibility Study
Authors: Mirshahi Arvin , Bakitas Marie , Khoshavi Meysam , khanipour-kencha Ali , Riahi Seyed Mohammad , Wells Rachel , Odom J. Nicholas , Ghiyasvandian Shahrzad , Zakerimoghadam Masoumeh
Published: November 2023

Background: While palliative care for patients with heart failure has gained global attention, in Iran most palliative care interventions have focused only on cancer patients. The purpose of this study is to determine the feasibility and acceptability of a telehealth palliative care intervention to improve the quality of life in patients with heart failure in Iran.
Methods: This single-site, pilot randomized clinical trial of a telehealth palliative care intervention versus usual care was conducted on patients with New York Heart Association class II/III heart failure recruited from a heart failure clinic in Iran. Under the supervision of a nurse interventionist, intervention participants received 6 weekly educational webinars and concurrent WhatsApp® group activities, with 6 weeks of follow-up. Feasibility was assessed by measuring recruitment, attrition, and questionnaire completion rates; acceptability was assessed via telephone interviews asking about satisfaction and attitudes. Secondary outcomes measured at baseline and 6 weeks included quality of life (PKCCQ and FACIT-Pal-14), anxiety and depression (HADS), and emergency department visits.
Results: We recruited and randomized 50 patients (mean age 47.5 years, 60% men). Among those approached for consent, 65% of patients agreed to participate and total study attrition was 10%. Also 68% of patients successfully completed at least 4 out of the 6 webinar sessions. Acceptability: 78% of patient participants expressed willingness to participate in the present study again or recommend other patients to participate. There was preliminary evidence for improvements in quality of life but not for anxiety, depression, and emergency department visits.
Conclusion: This nurse-led, early telehealth-palliative care intervention demonstrated evidence of acceptability and feasibility.
Trial registration: The study was registered at the Iranian Registry of Clinical Trials (IRCT) at 14 November, 2021, and can be found on the Iranian Registry of Clinical Trials Platform.
IRCT registration number: IRCT20100725004443N29