bluuebunny/crossref_metadata_2025 huggingface dataset:
Drug interaction potential of high-dose rifampicin in patients with pulmonary tuberculosis
Authors: Stemkens Ralf , Jager Veronique de , Dawson Rodney , Diacon Andreas H. , Narunsky Kim , Padayachee Sherman D. , Boeree Martin J. , van Beek Stijn W. , Colbers Angela , Coenen Marieke J. H. , Svensson Elin M. , Fuhr Uwe , Phillips Patrick P. J. , te Brake Lindsey H. M. , Aarnoutse Rob E. ,   on behalf of the PanACEA consortium
Published: September 2023

Accumulating evidence supports the use of higher doses of rifampicin for tuberculosis (TB) treatment. Rifampicin is a potent inducer of metabolic enzymes and drug transporters, resulting in clinically relevant drug interactions. To assess the drug interaction potential of higher doses of rifampicin, we compared the effect of high-dose rifampicin (40 mg/kg daily, RIF40) and standard-dose rifampicin (10 mg/kg daily, RIF10) on the activities of major cytochrome P450 (CYP) enzymes and P-glycoprotein (P-gp). In this open-label, single-arm, two-period, fixed-order phenotyping cocktail study, adult participants with pulmonary TB received RIF10 (days 1–15), followed by RIF40 (days 16–30). A single dose of selective substrates (probe drugs) was administered orally on days 15 and 30: caffeine (CYP1A2), tolbutamide (CYP2C9), omeprazole (CYP2C19), dextromethorphan (CYP2D6), midazolam (CYP3A), and digoxin (P-gp). Intensive pharmacokinetic blood sampling was performed over 24 hours after probe drug intake. In all, 25 participants completed the study. Geometric mean ratios (90% confidence interval) of the total exposure (area under the concentration versus time curve, RIF40 versus RIF10) for each of the probe drugs were as follows: caffeine, 105% (96%–115%); tolbutamide, 80% (74%–86%); omeprazole, 55% (47%–65%); dextromethorphan, 77% (68%–86%); midazolam, 62% (49%–78%), and 117% (105%–130%) for digoxin. In summary, high-dose rifampicin resulted in no additional effect on CYP1A2, mild additional induction of CYP2C9, CYP2C19, CYP2D6, and CYP3A, and marginal inhibition of P-gp. Existing recommendations on managing drug interactions with rifampicin can remain unchanged for the majority of co-administered drugs when using high-dose rifampicin. Clinical Trials registration number
NCT04525235
.
Biofilm formation stabilizes metabolism in a
Roseobacteraceae
bacterium under temperature increase
Authors: Wang Meng , Lu Jie , Qin Peng , Wang Shuaitao , Ding Wei , Fu Hui-Hui , Zhang Yu-Zhong , Zhang Weipeng
Published: September 2023

Ocean warming profoundly impacts microbes in marine environments; yet, how lifestyle (e.g., free living versus biofilm associated) affects the bacterial response to rising temperature is not clear. Here, we compared transcriptional, enzymatic, and physiological responses of free-living and biofilm-associated
Leisingera aquaemixtae
M597, a member of the
Roseobacteraceae
family isolated from marine biofilms, to the increase in temperature from 25℃ to 31℃. Complete genome sequencing and metagenomics revealed the prevalence of M597 in global ocean biofilms. Transcriptomics suggested a significant effect on the expression of genes related to carbohydrate metabolism, nitrogen and sulfur metabolism, and phosphorus utilization of free-living M597 cells due to temperature increase, but such drastic alterations were not observed in its biofilms. In the free-living state, the transcription of the key enzyme participating in the Embden-Meyerhof-Parnas pathway was significantly increased due to the increase in temperature, accompanied by a substantial decrease in the Entner-Doudoroff pathway, but transcripts of these glycolytic enzymes in biofilm-forming strains were independent of the temperature variation. The correlation between the growth condition and the shift in glycolytic pathways under temperature change was confirmed by enzymatic activity assays. Furthermore, the rising temperature affected the growth rate and the production of intracellular reactive oxygen species when M597 cells were free living rather than in biofilms. Thus, biofilm formation stabilizes metabolism in M597 when grown under high temperature and this homeostasis is probably related to the glycolytic pathways.

IMPORTANCE

Biofilm formation is one of the most successful strategies employed by microbes against environmental fluctuations. In this study, using a marine Roseobacteraceae bacterium, we studied how biofilm formation affects the response of marine bacteria to the increase in temperature. This study enhances our understanding of the function of bacterial biofilms and the microbe-environment interactions in the framework of global climate change.
IL-9 promotes methicillin-resistant
Staphylococcus aureus
pneumonia by regulating the polarization and phagocytosis of macrophages
Authors: Xu Weihua , Tian Keyin , Hu Shaowen , Chen Mingxiao , Zhang Meng
Published: September 2023

In this study, we examined the effect of
Il9
deletion on macrophages in methicillin-resistant
Staphylococcus aureus
(MRSA) infection. MRSA-infected mice were employed for the
in vivo
experiments, and RAW264.7 cells were stimulated with MRSA for the
in vitro
experiments. Macrophage polarization was determined by flow cytometry and quantitative real-time PCR; macrophage phagocytosis was assessed by flow cytometry and laser scanning confocal microscopy; cell apoptosis was assessed by flow cytometry and western blotting.
Il9
deletion markedly elevated macrophage phagocytosis and M2 macrophages in MRSA infection, which was accompanied by elevated expression of
Il10
and
Arg1
and reduced expression of
Inos
, tumor necrosis factor-α (
Tnfα)
, and
Il6. Il9
deletion also inhibited macrophage apoptosis in MRSA infection, which was manifested by elevated B-cell lymphoma 2 (BCL-2) protein level and reduced protein levels of cleaved cysteine protease 3 (CASPASE-3) and BCL2-Associated X (BAX). Both the
in vivo
and
in vitro
experiments further showed the activation of phosphoinositide 3-kinase (PI3K)/AKT (also known as protein kinase B, PKB) signaling pathway in MRSA infection and that the regulation of
Il9
expression may be dependent on Toll-like receptor (TLR) 2/PI3K pathway. The above results showed that
Il9
deletion exhibited a protective role against MRSA infection by promoting M2 polarization and phagocytosis of macrophages and the regulation of
Il9
partly owing to the activation of TLR2/PI3K pathway, proposing a novel therapeutic strategy for MRSA-infected pneumonia.
Transcriptome screening identifies TIPARP as an antiviral host factor against the Getah virus
Authors: Jiao Houqi , Yan Ziqing , Zhai Xiaofeng , Yang Yichen , Wang Ningning , Li Xiaoling , Jiang Zhiwen , Su Shuo
Published: September 2023

Alphaviruses are emerging and re-emerging viruses that cause severe disease and threaten public health worldwide. To advance the understanding of the underlying mechanisms of alphavirus replication and identify new host restriction factors, we performed RNA-seq and identified antiviral host factors on the Getah virus (GETV), a re-emerging alphavirus. We identified tetrachlorodibenzo-p-dioxin-inducible poly(ADP ribose) polymerase (TIPARP) as a host antiviral factor. TIPARP is downregulated in GETV-infected Vero cells, and its overexpression significantly inhibits GETV replication, while TIPARP deficiency results in significantly increased viral titers. We demonstrated that TIPARP interacts with the viral E2 glycoprotein, inducing k48-linked ubiquitination and subsequent proteasomal degradation. Additionally, we found that TIPARP recruits the E3 ubiquitin ligase membrane-associated RING-CH 8 (MARCH8) to modify the ubiquitination, leading to the degradation of E2. Lys253 in E2 was identified as the TIPARP-facilitated ubiquitination site. A mutation in Lys253 resulted in the loss of TIPARP’s anti-GETV effect. Our study demonstrated for the first time that host TIPARP is a restricting factor against GETV replication. Investigating the underlying mechanisms and understanding TIPARP for GETV will be essential to fully understanding viral pathogenesis and developing novel broad-spectrum therapeutic strategies against alphavirus infection.

IMPORTANCE

Alphaviruses threaten public health continuously, and Getah virus (GETV) is a re-emerging alphavirus that can potentially infect humans. Approved antiviral drugs and vaccines against alphaviruses are few available, but several host antiviral factors have been reported. Here, we used GETV as a model of alphaviruses to screen for additional host factors. Tetrachlorodibenzo-p-dioxin-inducible poly(ADP ribose) polymerase was identified to inhibit GETV replication by inducing ubiquitination of the glycoprotein E2, causing its degradation by recruiting the E3 ubiquitin ligase membrane-associated RING-CH8 (MARCH8). Using GETV as a model virus, focusing on the relationship between viral structural proteins and host factors to screen antiviral host factors provides new insights for antiviral studies on alphaviruses.
Inhalation of vaccines and antiviral drugs to fight respiratory virus infections: reasons to prioritize the pulmonary route of administration
Authors: Heida Rick , Frijlink Henderik W. , Hinrichs Wouter L. J.
Published: September 2023

Many of the current pandemic threats are caused by viruses that infect the respiratory tract. Remarkably though, the majority of vaccines and antiviral drugs are administered via alternative routes. In this perspective, we argue that the pulmonary route of administration deserves more attention in the search for novel therapeutic strategies against respiratory virus infections. Firstly, vaccines administered at the viral portal of entry can induce a broader immune response, employing the mucosal arm of the immune system; secondly, direct administration of antiviral drugs at the target site leads to superior bioavailability, enabling lower dosing and reducing the chance of side effects. We further elaborate on why the pulmonary route may induce a superior effect compared to the intranasal route of administration and provide reasons why dry powder formulations for inhalation have significant advantages over standard liquid formulations.
The VBNC state: a fundamental survival strategy of
Acinetobacter baumannii
Authors: König Patricia , Wilhelm Alexander , Schaudinn Christoph , Poehlein Anja , Daniel Rolf , Widera Marek , Averhoff Beate , Müller Volker
Published: September 2023

The viable but non-culturable (VBNC) state is a persistence strategy adopted by bacteria to withstand long-lasting periods of unfavorable conditions. VBNC cells evade classical detection methods and are therefore easily transmitted in the hospital causing relapsing infections. The opportunistic human pathogen
Acinetobacter baumannii
has become a major threat in health care institutions and the food industry due to multiple antibiotic resistances and its ability to quickly adapt to very different ecological niches. Here, we report an additional, novel survival strategy of
A. baumannii
. Upon prolonged incubation in high-salt media, cells became unculturable. However, LIVE/DEAD staining followed by flow cytometry, respiratory activity assays, and resuscitation experiments revealed that these cells were viable but non-culturable. VBNC cells underwent large morphological changes. Entry into the VBNC state was also induced by pH and temperature stress, as well as by desiccation and anaerobiosis. The VBNC state was found in several strains of
A. baumannii
. Genome-wide expression profiling revealed a plethora of genes differentially regulated upon entry into the VBNC state. In summary, this study presents unequivocal evidence for a dormancy state in
A. baumannii
that has important consequences for detection of this pathogen and recurrent outbreaks.

IMPORTANCE

Currently, the viable but non-culturable (VBNC) state is an underappreciated niche for pathogenic bacteria which provides a continuous source for recurrent infections and transmission. We propose the VBNC state to be a global persistence mechanism used by various
A. baumannii
strains to cope with many stresses it is confronted with in the clinical environment and in the host. This requires a novel strategy to detect viable cells of this pathogen that is not only based on plating assays.
Dissociative episodes characterised by hair-pulling in a late adolescent woman
Authors: Healey Danielle Nicole , Lee Jessica J , Getzoff Testa Elizabeth , Gautam Rishi
Published: September 2023

A woman in late adolescence with a history of sickle cell disease, moyamoya disease, cerebrovascular accident, mild intellectual disability, post-traumatic stress disorder, functional seizures, generalised anxiety disorder and transient psychosis was referred for a psychiatry consultation. She presented with worsening episodes of dissociation characterised by compulsory hair-pulling. Limited research exists regarding patients engaging in activities of automated behaviour during episodes of dissociation. Thus, we aim to describe a case of a patient with episodes of hair-pulling during dissociative events to discuss the aetiology and treatment. We are describing the aetiology and treatment of a patient with episodes of hair-pulling during dissociative events.
Focal CNS vasculitis masquerading as new-onset focal aware seizures
Authors: Vibha Deepti , Singh Rajesh kumar , Garg Ajay , Tripathi Manjari
Published: September 2023

Primary angiitis of the central nervous system (PACNS) is an autoimmune disease with myriad presentations in the form of headache, focal neurological deficits, seizures and rapid cognitive decline. Predilection or isolated and recurrent involvement of one hemisphere is rarely described in literature. This leads to low clinical suspicion and often delayed diagnosis of PACNS, if clinical and radiological involvement is focal. We describe the case of a young man presenting with new-onset focal seizures with imaging suggestive of focal involvement and the brain biopsy clinched an early diagnosis. The 1-year follow-up showed clinical and radiological resolution.
Immunosuppressive CD29+Treg accumulation in the liver in mice on checkpoint inhibitor therapy
Authors: Green Benjamin L , Myojin Yuta , Ma Chi , Ruf Benjamin , Ma Lichun , Zhang Qianfei , Rosato Umberto , Qi Jonathan , Revsine Mahler , Wabitsch Simon , Bauer Kylynda , Benmebarek Mohamed-Reda , McCallen Justin , Nur Amran , Wang Xin , Sehra Vivek , Gupta Revant , Claassen Manfred , Wang Xin Wei , Korangy Firouzeh , Greten Tim F
Published: September 2023

Objective

Liver metastases are often resistant to immune checkpoint inhibitor therapy (ICI) and portend a worse prognosis compared with metastases to other locations. Regulatory T cells (Tregs) are one of several immunosuppressive cells implicated in ICI resistance of liver tumours, but the role played by Tregs residing within the liver surrounding a tumour is unknown.

Design

Flow cytometry and single-cell RNA sequencing were used to characterise hepatic Tregs before and after ICI therapy.

Results

We found that the murine liver houses a Treg population that, unlike those found in other organs, is both highly proliferative and apoptotic at baseline. On administration of αPD-1, αPD-L1 or αCTLA4, the liver Treg population doubled regardless of the presence of an intrahepatic tumour. Remarkably, this change was not due to the preferential expansion of the subpopulation of Tregs that express PD-1. Instead, a subpopulation of CD29+(Itgb1, integrin β1) Tregs, that were highly proliferative at baseline, doubled its size in response to αPD-1. Partial and full depletion of Tregs identified CD29+Tregs as the prominent niche-filling subpopulation in the liver, and CD29+Tregs demonstrated enhanced suppressionin vitrowhen derived from the liver but not the spleen. We identified IL2 as a critical modulator of both CD29+and CD29−hepatic Tregs, but expansion of the liver Treg population with αPD-1 driven by CD29+Tregs was in part IL2-independent.

Conclusion

We propose that CD29+Tregs constitute a unique subpopulation of hepatic Tregs that are primed to respond to ICI agents and mediate resistance.
Indigenous protected and conserved areas (IPCAs): Canada's new path forward for biological and cultural conservation and Indigenous well-being
Authors: Mansuy Nicolas , Staley Diana , Alook Sharlene , Parlee Brenda , Thomson Alexandra , Littlechild Danika Billie , Munson Matthew , Didzena Fred
Published: September 2023

Wilderness and national parks play a fundamental role in defining Canadian identity, yet Indigenous Peoples have historically been excluded from conservation decisions, resulting in systematic dispossession and oppression. In this article, we collaborate with Dene Tha'First Nation to discuss the recent paradigm shift towards Indigenous-led conservation and propose guiding principles to advance and assert the critical role of Indigenous Peoples in conservation. We begin with a brief history of Indigenous Peoples in conservation, followed by the concept of Indigenous protected and conserved areas (IPCAs). Our analyses show that IPCAs have gained momentum recently, driven by the Truth and Reconciliation Commission and Canada's commitment to global conservation goals. With one of the largest landmasses and Indigenous populations in the world, IPCAs in Canada have the potential to make immense contributions to environmental and cultural conservation rooted in an intrinsic relationship to the land. Despite this biocultural diversity, as of 2022, less than 1% of Canada's landmass is declared as Indigenous-led protected areas. However, more than 50 Indigenous communities across the country have currently received funding to establish IPCAs or to undertake early planning and engagement that could position Canada as a global leader in Indigenous-led conservation. As the Government of Canada aims to designate 25% of the territory as protected space by 2025 and 30% by 2030, embedding Indigenous rights, knowledge, and values in the national conservation strategy will be essential to simultaneously honoring the commitments to reconciliation and meeting the ambitious targets stipulated in the Kunming–Montreal Global Biodiversity Framework.
Toward extracting $$\gamma $$ from $$B\rightarrow DK$$ without binning
Authors: Backus Jeffrey V. , Freytsis Marat , Grossman Yuval , Schacht Stefan , Zupan Jure
Published: September 2023

$$B^\pm \rightarrow DK^\pm $$

B
±

→
D

K
±

transitions are known to provide theoretically clean information about the CKM angle $$\gamma $$
γ
, with the most precise available methods exploiting the cascade decay of the neutral D into CP self-conjugate states. Such analyses currently require binning in the D decay Dalitz plot, while a recently proposed method replaces this binning with the truncation of a Fourier series expansion. In this paper, we present a proof of principle of a novel alternative to these two methods, in which no approximations at the level of the data representation are required. In particular, our new strategy makes no assumptions about the amplitude and strong phase variation over the Dalitz plot. This comes at the cost of a degree of ambiguity in the choice of test statistic quantifying the compatibility of the data with a given value of $$\gamma $$
γ
, with improved choices of test statistic yielding higher sensitivity. While our current proof-of-principle implementation does not demonstrate optimal sensitivity to $$\gamma $$
γ
, its conceptually novel approach opens the door to new strategies for $$\gamma $$
γ
extraction. More studies are required to see if these can be competitive with the existing methods.
Sol–gel synthesis, electromagnetic properties and microwave absorption behavior of strontium Co2Z hexaferrites
Authors: Gu Z. F. , Yu Z. C. , Hong B. , Xu J. C. , Han Y. B. , Peng X. L. , Ge H. L. , Wang X. Q.
Published: September 2023

Owing to the special planar structure and very high resistivity, [Formula: see text]-type hexaferrites possess the high initial permeability and cut-off frequency, indicating great application potential in high-frequency devices. Strontium Co2Z hexaferrites (Sr3Co2Fe[Formula: see text]O[Formula: see text]) were successfully prepared by the sol–gel method and calcined at the different temperatures from [Formula: see text]C to [Formula: see text]C. The influence of the calcined temperatures on the microstructure, phase structures, magnetic properties and microwave absorption behavior of all samples was investigated in detail. All results indicated that strontium hexaferrites go through the [Formula: see text]-, [Formula: see text]-, [Formula: see text]-, and [Formula: see text]-phase transformation process from [Formula: see text]C to [Formula: see text]C, and S-1200 (calcined at [Formula: see text]C) is confirmed to be Co2Z-type hexaferrites. S-1200 showed the highest imaginary permeability while the imaginary permittivity of all samples is close to zero, indicating the excellent microwave adsorption behavior of strontium Co2Z hexaferrites. The reflection loss results indicate that S-1200 exhibits the best microwave absorption performance with the RL value of −32.4 dB for 4.0 mm thickness at 4.72 GHz, according to the impedance matching and quarter-wavelength theory.
A Simple and Cost-effective Approach to Make a Modified Suture Anchor in Orthopaedics
Authors: KAMATH B. N. Jagannath , NAYAK U. Keerthan Ranga , KAMATH K. Ramachandra , JAYASHEELAN Nikil
Published: September 2023

The purpose of this study is to describe a technique of using an affordable suture anchor for various soft tissue repairs of both upper and lower limb surgeries in our series of patients. Eighteen patients with minimum 1-year follow-up after various upper limb surgeries using modified suture anchor were assessed both clinically and radiographically. In all 18 cases, the purpose of the suture anchor was served in terms of attachment of ligament or the tendon. There was no incidence of breakage of suture material or loosening of the implant seen during the insertion. There were no complications related to the implant noted. This novel technique turns a simple screw and suture material into an efficient suture anchor while saving time, being quick, easy, affordable and repeatable.

Level of Evidence: Level V (Therapeutic)
Experimental Study on the Effect of Operating Conditions on the Efficiency of Vanadium Redox Flow Battery
Authors: Huang Zebo , Liu Yilin , Xie Xing , Huang Qian , Huang Cao
Published: September 2023

The operating conditions can have a negative impact on the efficiency of a vanadium redox flow battery (VRFB), and it is therefore important to systematically study how these conditions affect battery efficiency. In the experiment, various operating parameters such as charge/discharge cut-off voltage, flow rate, membrane thickness, current density, and shelving time are selected to evaluate their impact on battery efficiency. The experimental results indicate that increasing the range of the cut-off voltage reduces the battery’s energy efficiency. Additionally, both coulomb efficiency and energy efficiency improve as flow rate increases, but these efficiencies decline after reaching a critical value. Increasing the thickness of the ion conduction membrane enhances its effectiveness in preventing the crossing of vanadium ions, resulting in lower capacity loss. Furthermore, an increase in current density intensifies ohmic polarization and concentration polarization, leading to a decrease in energy efficiency.
Study on the Electrochemical Properties of Mg1−xYxCO3@2MnCO3 Doped at Magnesium Site and the Effect of Manganese Carbonate and Magnesium Carbonate Composite Material Modified by Zn Doping
Authors: Li Ling , Zhou Jiyao , Pei Xinbin
Published: September 2023

Mangan-based zinc ion batteries have received increasing attention due to their high theoretical capacity and environmental friendly properties. However, the capacity attenuation of manganese-based materials during the charge-discharge cycle seriously affects the improvement of electrochemical performance. In order to solve the problem of capacity attenuation, magnesium carbonate material was combined with manganese carbonate material, and the magnesium site was doped and modified. In this paper, the Mg0.98Zn0.02CO3@2MnCO3 material was selected out from all the synthesized materials due to its stable electrochemical performance, its capacity is as high as 283.65 mAh g−1 under the current density of 100 mA g−1. Subsequently, the characterization test was carried out to further discover the composition of the material. It can be observed from SEM that the material has two main structures: cube shape and spheroid shape, and nanowires grow on the surface of the cube structure. Moreover, the EDS and XPS tests were conducted which could prove the elements contained in Mg0.98Zn0.02CO3@2MnCO3 material were consistent with the valence states of the elements in manganese carbonate and magnesium carbonate. The further infrared and Raman tests showed that the functional groups in the material were also consistent with the molecular formula. According to the XRD test result, no obvious impurity peak can be oberved, indicating the electrochemical performance of Mg0.98Zn0.02CO3@2MnCO3 composite material synthesized by hydrothermal method is relatively stable.
Molecular Dynamics Simulations of Ammonium-Based Acrylate Polymerized Ionic Liquids
Authors: Luo Xubo , Paddison Stephen J.
Published: September 2023

Polymerized ionic liquids (polyILs) are interesting materials that may find application as the electrolyte in electrochemical devices provided that they can be made with sufficiently high ion conductivities. The continuous optimization requires the understanding of the ion transport in available materials. In this work, a group of ammonium-based acrylate polyILs were examined as the candidates with engineered side chains containing long linker and various alkyl tails. Classical molecular dynamics simulations were performed to investigate the mechanism of ion transport. For all simulated systems, the diffusion coefficients were higher than previously investigated polyILs with imidazolium vinyl cations directly bonded to the backbones. Diffusivity was further improved when the tail length increased from methyl to propyl, but this trend did not persist for butyl and longer tails. The higher diffusion coefficient generally coexisted with less ion pair association, lower dynamical heterogeneity, and suppressed string-like cooperative motion. It was affirmed that only a few counterions were fast-moving for effective hopping, and the counterions exhibited smoother motion in acrylate polyILs than the imidazolium-based polyIL with a shorter side chain. For better ion transport, this work suggested that long linker and intermediate tails in the polymerized ions appeared to be the attractive candidates.
Real-Time Observation of Multiphysics Coupling Fields in the Electrochemical Trepanning of Vibrating Cathodes
Authors: Wang Penghui , Zhu Dong , Li Zhengyin , Jiao Erhao
Published: September 2023

Electrochemical trepanning (ECTr) with a vibrating cathode is widely used to manufacture blisk as a typical electrochemical machining (ECM) technology. The inter-electrode gap (IEG) distribution is very important for the accuracy of ECTr. An ECTr processing system with an observable IEG is designed to study the effects of vibrating cathodes on the IEG distribution. A multiphysics coupled field model for a vibrating cathode ECTr with electric, gas-liquid two-phase flow, and temperature fields is developed based on this system. The distribution laws of the current density, bubble volume fraction, and temperature in the IEG are obtained via multiphysics simulations of the coupled fields. Compared to conventional ECTr, the current density within the IEG increases, the end-gap current density percentage grows by 3%, and the electrolyte renewal within the IEG is promoted. An experimental study of a vibrating cathode ECTr verifies the validity of the simulations. A distinct white bubble layer appeared at the transition corner of the end gap near the cathode side. The bubbles were gradually increasing as the cathode was fed to the workpiece during a cycle. No obvious white bubble layer is seen at the side gap. The observations verify the multiphysics field simulations to study the gas volume fraction distribution law. The experimental results show that the vibrating cathode improves the integrity of the blade profile and surface quality. The rounded corners at the top and root of the workpiece are reduced by 0.33 and 0.59 mm, respectively, and the blade width improves by 0.62 mm. The surface roughness of the sidewalls reduces from Ra 1.385 μm to Ra 0.912 μm and the surface roughness of the runner surface is reduced from 4.925 to 2.187 μm.
Maternal cardiorespiratory coupling: differences between pregnant and nonpregnant women are further amplified by sleep-stage stratification
Authors: Bester Maretha , Perciballi Giulia , Fonseca Pedro , van Gilst Merel M. , Mischi Massimo , van Laar Judith OEH , Vullings Rik , Joshi Rohan
Published: September 2023

We compare CRC, i.e., the reciprocal interaction between the cardiac and respiratory systems, between healthy pregnant and nonpregnant women for the first time. Although CRC is present in both groups, CRC is reduced during healthy pregnancy; there is less synchronization between maternal cardiac and respiratory activity and a smaller response in maternal heart rate to respiratory inhalations and exhalations. Stratifying this analysis by sleep stages reveals that differences are most prominent during deep sleep.
Prognostic Value of Endothelial Progenitor Cells in Acute Myocardial Infarction Patients
Authors: Ye Gongjie , Chen Xiaodan , Zhou Yinchao , Zhou Jianqing , Song Yongfei , Yang Xiaoyong , Yang Lei
Published: September 2023

Objective. To determine prognostic role of endothelial progenitor cells (EPCs) in intensive care patients with acute myocardial infarction (AMI). Materials and Methods. From December 2018 to July 2021, a total of 91 eligible patients with AMI were consecutively examined in a single intensive care unit (ICU) in China. Patients with a history of acute coronary artery disease were excluded from the study. Samples were collected within 24 hr of onset of symptoms. EPCs, defined as coexpression of CD34+/CD133+ cells or CD133+/CD34+/KDR+, were studied using flow cytometry and categorized by quartiles. Based on the 28-days mortality outcome, the patients were further divided into two groups: death and survival. The study incorporated various variables, including cardiovascular risk factors such as body mass index, hypertension, diabetes, hypercholesterolemia, atherosclerotic burden, and medication history, as well as clinical characteristics such as APACHEⅡscore, central venous-arterial carbon dioxide difference (GAP), homocysteine, creatinine, C-reactive protein, HbAlc, and cardiac index. Cox regression analysis was employed to conduct a multivariate analysis. Results. A total of 91 patients with AMI who were admitted to the ICU were deemed eligible for inclusion in the study. Among these patients, 23 (25.3%) died from various causes during the follow-up period. The counts of EPCs were found to be significantly higher in the survival group compared to the death group (

P
<
0.05

). In the univariate analysis, it was observed that the 28-days mortality rate was associated with the several factors, including the APACHEⅡscore (

P
=
0.00

), vasoactive inotropic score (

P
=
0.03

), GAP (

P
=
0.00

), HCY (

P
=
0.00

), creatinine (

P
=
0.00

), C-reactive protein (

P
=
0.00

), HbAlc (

P
=
0.00

), CI (

P
=
0.01

), quartiles of CD34+/CD133+ cells (

P
=
0.00

), and quartiles of CD34+/CD133+/KDR+ cells (

P
=
0.00

). CD34+/CD133+/KDR+ cells retained statistical significance in Cox regression models even after controlling for clinical variables (HR: 6.258 × 10−10 and

P
=
0.001

). Nevertheless, no significant correlation was observed between CD34+/CD133+ cells and all-cause mortality. Conclusions. The decreased EPCs levels, especially for CD34+/CD133+/KDR+ cells subsets, were an independent risk factor for 28-days mortality in AMI patients.
Production Forecasting of Unruly Geoenergy Extraction Wells Using Gaussian Decline Curve Analysis
Authors: Weijermars Ruud
Published: September 2023

Fast and rigorous well performance evaluation is made possible by new solutions of the pressure diffusion equation. The derived Gaussian pressure transient (GPT) solutions can be practically formulated as a decline curve analysis (DCA) equation for history matching of historic well rates to then forecast the future well performance and estimate the remaining reserves. Application in rate transient analysis (RTA) mode is also possible to estimate fracture half-lengths. Because GPT solutions are physics-based, these can be used for production forecasting as well as in reservoir simulation mode (by computing the spatial and temporal pressure gradients everywhere in the reservoir section drained by either an existing or a planned well). The present paper focuses on the physics-based production forecasting of so-called “unruly” wells, which at first seem to have production behavior noncompliant with any DCA curve. Four shale wells (one from the Utica, Ohio; one from the Eagle Ford Formation, East Texas; and two from the Wolfcamp Formation, West Texas) are analyzed in detail. Physics-based adjustments are made to the Gaussian DCA history matching process, showing how the production rate of these wells is fully compliant with the rate implied by the hydraulic diffusivity of the reservoir sections where these wells drain from.
Adsorption of Hydrogen Sulfide on Reduced Graphene Oxide-Wrapped Titanium Dioxide Nanofibers
Authors: Kamlangkla Kanchit , Phongphala Aphichard , Pakdee Udomdej
Published: September 2023

This work presents a fabrication of room-temperature gas sensor for hydrogen sulfide (H2S) adsorption. Pristine titanium dioxide (TiO2) nanofibers, reduced graphene oxide (rGO) sheets, and reduced graphene oxide-wrapped titanium dioxide (rGO-wrapped TiO2) nanofibers were presented in the form of integrated suspension used for a gas-sensing layer. The TiO2 nanofibers were firstly synthesized by using an electrospinning method with a polyvinylpyrrolidone (PVP) polymer. The rGO sheets were then wrapped around TiO2 nanofibers by a hydrothermal method. Scanning electron microscope, transmission electron microscope, X-ray diffractometer, and Raman spectrometer confirmed the presence of rGO sheets onto the surface of TiO2 nanofibers. Ultraviolet-visible spectrophotometer was also considered and displayed to calculate the band gap of TiO2 and rGO-wrapped TiO2 nanofibers. After preparing the gas-sensing suspensions, they were dropped onto the polyethylene terephthalate substrates with silver-interdigitated electrodes. The gas-sensing properties of sensors were evaluated for H2S adsorption at room temperature. Based on the results, the rGO-wrapped TiO2 nanofiber gas sensor exhibited higher H2S sensitivity and selectivity than pristine TiO2 nanofiber and pure rGO gas sensors. The H2S-sensing mechanism of rGO-wrapped TiO2 nanofiber gas sensor was discussed based on a formation of p-n heterojunctions between p-type rGO sheets and n-type TiO2 nanofibers. Furthermore, a direct charge-transfer process by physisorption was also highlighted as a second H2S-sensing mechanism.
Helicobacter pylori Exposure in Nausea and Vomiting of Pregnancy Increases Risk of Preterm Delivery
Authors: Masaadeh Amr H. , Mathias Patrick C. , Ford Bradley A. , Bosch Dustin E.
Published: September 2023

Background. Hyperemesis gravidarum (HG), a severe form of nausea and vomiting in pregnancy (NVP), is a leading indication for hospitalization in the first trimester. NVP and HG are associated with Helicobacter pylori (HP) infection in non-United States cohorts. How HP exposure and NVP interact to affect metabolic disturbance and pregnancy outcomes is not known. Materials and Methods. We designed a retrospective cohort study relating HP and NVP to serum electrolyte laboratory results, preterm delivery, and infant birth weight. Single academic institution discovery and independent multi-institutional validation cohorts included pregnant subjects with an HP test result. Associations of HP, NVP, and pregnancy outcomes were assessed with odds ratio calculations, Student’s

t

-tests, and multivariate logistic regression. Results. Among subjects with positive HP test results, the prevalence of hyperemesis gravidarum (HG) was 0.025 (66 of 2671) and NVP was 0.27 (710 of 2671). Subjects with negative HP had prevalence of HG 0.015 (165 of 10,960) and NVP 0.22 (2392 of 10,960). History of HP exposure increased risk of NVP, including HG (odds ratio 1.3, 95% CI 1.1-1.4). Patients with HP exposure had lower serum potassium (mean difference 0.1 mEq/L) and bicarbonate (mean difference 0.3 mEq/L) during pregnancy than HP-negative patients (

p
<
0.01

). Serum potassium was lowest in subjects with both NVP and HP exposure (mean 3.5 mEq/L [3.4-3.6],

p
<
0.0001

). HP exposure alone carried increased risk for preterm delivery (OR 1.3 [1.1-1.4]). NVP alone increased risk of preterm delivery (OR 2.8 [2.5-3.1]) including second trimester delivery (OR 2.2 [1.7-2.8]). In multivariate analysis, HP exposure in the setting of NVP further increased risk of preterm delivery (adjusted OR 1.4 [1.0-1.9],

p
=
0.03

). Conclusions. H. pylori exposure and diagnosis of NVP are individually associated with metabolic disturbances and adverse pregnancy outcomes such as preterm labor and delivery, and their combination further increases risk in US populations.
Incidence, Clinical Features, and Outcomes of the Confirmed Neonatal COVID-19 Infection in the Southwest Iran
Authors: Maharlouei Najmeh , Khojasteh Zonoozi Arash , Noeizad Zaynab , Erami Atila , Parsa Hamidreza , Kootahi Zahra Eskandari , Raji Sara , Lankarani Kamran B.
Published: September 2023

Background. The impact of COVID-19 on the neonatal population is still mysterious. This study is aimed at reporting the prevalence of COVID-19 and its clinical characteristics and outcomes among neonates in Iran. Methods. We conducted a retrospective cohort including 25 neonates who had COVID-19 infection confirmed by reverse transcription polymerase chain reaction (RT-PCR). Based on neonates’ hospitalization records, data regarding neonatal and maternal characteristics and clinical and paraclinical findings were extracted. Results. In Fars Province, the incidence of COVID-19 among neonates was 47.5 per 100000 living births in one year. From 25 neonates, 20 cases (80%) were recovered, while five cases (20%) died, and all of them were symptomatic. Nine cases (37.5%) were preterm, and two cases (22.2%) belonged to deceased neonates. Four out of five deceased neonates (80%) suffered from congenital abnormalities, and all required respiratory support in the course of their disease progression. Also, 18 neonates (72%) were admitted to NICU. Moreover, the COVID-19 RT-PCR test of nine mothers (43.7%) became positive. Conclusions. This study showed that the incidence of confirmed and symptomatic SARS-CoV-2 infection among neonates in the Fars Province of Iran over one year was 47.5 per 100000 living births. Thoroughly evaluating the epidemiological factors associated with COVID-19, such as underlying health conditions and family history of COVID-19, is crucial in properly managing neonates during the pandemic and increasing awareness.
Modification of Metal Oxide Semiconductor Gas Sensors Using Conducting Polymer Materials
Authors: Wuloh Jonah , Agorku Eric Selorm , Boadi Nathaniel Owusu
Published: September 2023

Conducting polymers have shown great potential in detecting gases at room temperature. This has caused the rapid development of these materials for gas sensing because their conductivity can be altered when exposed to oxidant or reductant molecules at room temperature. Nevertheless, due to their relatively high attraction to volatile organic and water molecules and low conductivity, they show low sensitivity, selectivity, and thermal instability that impede their practical applications as sensors. Moreover, semiconducting inorganic (metal oxide) sensors show distinct advantages in sensing gases, including high sensitivity, rapid response to low‐concentration analytes, versatile exterior or surface chemistry, and high‐surface area. However, their high‐temperature operation has limited their sensing applications while performing excellently at room temperature. Combining these two sensitive materials brings synergistic effects. The hybrid increases sensitivity, selectivity, long‐term stability, and low‐temperature operation, which has concerned extensive interest in their use as sensors. This review summarizes the use of semiconducting metal oxides, conducting polymers, and the recent advancement in metal oxide‐conducting polymer composites for their gas‐sensing applications. Moreover, in this review, the advantages and limitations of these sensor materials are presented, and why the composites give an excellent synergistic effect by increasing sensing performance have been highlighted.
Haematopoietic Stem Cell Transplant Trends in Pakistan: Activity Survey from Pakistan Bone Marrow Transplant Group
Authors: Ali Natasha , Iftikhar Raheel , Ayaz Mir Muhammad , Bokhari Syed Waqas , Rehman Jehanzeb Ur , Zaidi Uzma , Nasir Shahzad , Adil Salman Naseem , Satti Tariq , Nisa Chaudhry Qamar Un , Farhan Muhammad , Farzana Tasneem , Ghafoor Tariq , Ahsan Bushra , Khan Azhar S. , Khan Farrukh Ali , Fatima Syeda Itrat , Samad Shafaq Abdul , Batool Aliya , Nadeem Hafiz Muhammad , Abbas Bukhari Syed Nasir , Ansari Saqib Hussain , Ahmed Parvez
Published: September 2023

Pakistan is the fifth most populous country with a population of 225 million and has health expenditure accounting for only 2.8 percent of gross domestic product (GDP). Accordingly, there are a limited number of haematology-oncology and transplant centers in the country. The Pakistan Blood and Marrow Transplant (PBMT) group was established in 2020, and this report is the first activity survey from January 2021 to December 2022 focusing on the trends of matched-related donor, haploidentical, and autologous transplants in a developing country. A total of 12 transplant centers contributed data on the modified PBMT survey form retrospectively and 806 haematopoietic stem cell transplants (HSCTs) were carried out during the study duration. Allogeneic HSCT constituted 595 (73.8%) of all the transplants; this is in stark contrast to Western data, where autologous HSCT accounts for the majority of transplants. ß-thalassemia major and aplastic anemia were the commonest indications for allogeneic HSCT, in contrast to Western data, where acute leukemia is the leading transplant indication. Autologous transplants were more frequently performed for Hodgkin’s lymphoma as compared to non-Hodgkin’s lymphoma and multiple myeloma. The use of peripheral and bone marrow stem cells was comparable. A myeloablative conditioning regimen was routinely used in patients with acute leukemia. This report provides an insight of HSCT trends in Pakistan which are different from those of Western centers contributing to transplant data from South Asia.
Organoides de origen humano como modelo fisiopatológico de evaluación terapéutica de fármacos en COVID-19
Authors: Weinstein Caroline , González-López Emilio , Bahamondez-Canas Tania , Campos-Estrada Carolina , Moraga-Espinoza Daniel
Published: September 2023

Introducción: La pandemia causada por SARS-CoV-2 ha impactado al mundo gravemente en diversos ámbitos y con ello ha surgido la necesidad de contar con herramientas con mayor relevancia fisiológica para investigar patologías complejas como el COVID-19. Los organoides son un modelo experimental con características únicas como la capacidad de autoformar una estructura tridimensional utilizando células en cultivo. Sobre esta base, surge la siguiente pregunta ¿son los organoides un modelo experimental factible para reflejar la fisiopatología del COVID-19 y evaluar la eficacia de fármacos que limiten su progresión?
Metodología: Para abordar esta interrogante, esta revisión plantea el analizar la validez de los organoides como modelo experimental y verificar su utilidad en la evaluación de fármacos para el COVID-19. Para cumplir estos objetivos se realizó una revisión sistemática cualitativa de la literatura, a través de una búsqueda en PubMed con el término ‘COVID-19 and stem cells and organoids’ y también en un número especial de la revista Cell. Resultados: Se organizaron los resultados relevantes por sistema fisiológico y en la evaluación de fármacos. Los organoides más empleados para estudios de COVID-19 correspondieron a tejido respiratorio, nervioso y digestivo. Algunos resultados encontrados en la revisión fueron similares a aquellos obtenidos a partir de tejidos de pacientes COVID-19 o autopsias, encontrándose hallazgos relevantes como la posible disrupción de la barrera epitelial del sistema nervioso por infección del plexo coroideo. También se logró observar efectividad de fármacos que posteriormente pasaron a ser aprobados y utilizados exitosamente en pacientes. Conclusión: Los organoides se pueden componer a partir de diferentes tipos celulares y bajo diferentes protocolos experimentales, siendo relevante la lectura crítica de los artículos científicos para decidir si sus resultados son extrapolables a la fisiopatología de la enfermedad.
Supplementary Fig. S1 from Cellular Senescence Is Immunogenic and Promotes Antitumor Immunity
Authors: Marin Ines , Boix Olga , Garcia-Garijo Andrea , Sirois Isabelle , Caballe Adrià , Zarzuela Eduardo , Ruano Irene , Attolini Camille Stephan-Otto , Prats Neus , López-Domínguez José A , Kovatcheva Marta , Garralda Elena , Muñoz Javier , Caron Etienne , Abad María , Gros Alena , Pietrocola Federico , Serrano Manuel
Published: September 2023

Senescent cells upregulate MHC-I antigen presentation
Data from Universal Viral Screening of Patients with Newly Diagnosed Cancer in the United States: A Cost-efficiency Evaluation
Authors: Vaidya Riha , Unger Joseph M. , Loomba Rohit , Hwang Jessica P. , Chugh Rashmi , Tincopa Monica A. , Arnold Kathryn B. , Hershman Dawn L. , Ramsey Scott D.
Published: September 2023

Recommendations for universal screening of patients with cancer for hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) are inconsistent. A recent multisite screening study (S1204) from the SWOG Cancer Research Network found that a substantial number of patients with newly diagnosed cancer had previously unknown viral infections. The objective of this study was to determine the cost-efficiency of universal screening of patients with newly diagnosed cancer. We estimated the cost-efficiency of universal screening of new cancer cases for HBV, HCV, or HIV, expressed as cost per virus detected, from the health care payer perspective. The prevalence of each virus among this cohort was derived from S1204. Direct medical expenditures included costs associated with laboratory screening tests. Costs per case detected were estimated for each screening strategy. Secondary analysis examined the cost-efficiency of screening patients whose viral status at cancer diagnosis was unknown. Among the possible options for universal screening, screening for HBV alone ($581), HCV alone ($782), HBV and HCV ($631) and HBV, HCV, and HIV ($841) were most efficient in terms of cost per case detected. When screening was restricted to patients with unknown viral status, screening for HBV alone ($684), HBV and HCV ($872), HBV and HIV ($1,157), and all three viruses ($1,291) were most efficient in terms of cost per newly detected case. Efficient viral testing strategies represent a relatively modest addition to the overall cost of managing a patient with cancer. Screening for HBV, HCV, and HIV infections may be reasonable from both a budget and clinical standpoint.
Significance:
Screening patients with cancer for HBV, HCV, and HIV is inconsistent in clinical practice despite national recommendations and known risks of complications from viral infection. Our study shows that while costs of viral screening strategies vary by choice of tests, they present a modest addition to the cost of managing a patient with cancer.