bluuebunny/crossref_metadata_2025 huggingface dataset:
Why do patients with DR-TB do not complete their treatment? Findings of a qualitative study from Pakistan
Authors: Abubakar Muhammad , Ullah Matti , Shaheen Muhammad Aamir , Abdullah Orva
Published: February 2024

Background

One of the major reasons for unsuccessful treatment outcomes among patients with drug-resistant tuberculosis (DR-TB) is the high rate of loss to follow-up (LTFU). However, in Pakistan, no qualitative study has been conducted to explore the perceptions of LTFU patients with regard to DR-TB treatment, the problems they face and the reasons for LTFU in detail.

Methods

This was a qualitative study that involved semistructured, indepth, face-to-face interviews of 39 LTFU patients with DR-TB. All interviews were carried out in Pakistan’s national language ‘Urdu’ using an interview guide in two phases: the first phase was from December 2020 to February 2021 among patients with extensively drug-resistant tuberculosis and the second phase from July 2021 to September 2021 among patients with multidrug-resistant tuberculosis.

Results

The inductive thematic analysis of audio-recorded interviews generated the following four key themes, which were the major reasons reported by the participants of the current study to have led to LTFU: (1) patient-related factors, such as lack of awareness about the total duration of DR-TB treatment, fatigue from previous multiple failed episodes, lack of belief in treatment efficacy and perception of DR-TB as a non-curable disease; (2) medication-related factors, such as use of injectables, high pill burden, longer duration and adverse events; (3) socioeconomic factors, such as gender discrimination, poor socioeconomic conditions, non-supportive family members, social isolation and unemployment; and (4) service provider-related factors, such as distant treatment centres, non-availability of a qualified person, lack of adequate counselling and poor attitude of healthcare professionals.

Conclusion

In the current study, patients’ perceptions about DR-TB treatment, socioeconomic condition, medication and service provider-related factors emerged as barriers to the successful completion of DR-TB treatment. Increasing patients’ awareness about the duration of DR-TB treatment, interacting sessions with successfully treated patients, availability of rapid drug susceptibility testing facilities at treatment centres, decentralising treatment and using the recently recommended all-oral regimen may further decrease the rate of LTFU.
Randomised controlled trial assessing the effects of 6-week telerehabilitation exercise programme on chronic non-specific neck pain: a study protocol
Authors: Ahmed Zaina Zahur , Khan Mohammed Nayel , Bairapareddy Kalyana Chakravarthy
Published: February 2024

Chronic non-specific neck pain is one of the most common musculoskeletal conditions affecting the work and lifestyle of those suffering from it. Physiotherapy interventions, such as strength training and stretching, have positively influenced neck pain. Patient adherence to home-based exercises is a growing concern that could be easily improved through telerehabilitation exercise programmes. This can also be a cost-effective, time-efficient and patient-suitable service. Therefore, this study aims to establish the effectiveness of telerehabilitation exercise intervention by measuring patient adherence, pain score, disability index, cervical range of motion (CROM) and cervical muscle endurance. This randomised controlled trial will include n=60 participants, aged 18–45 years, in a 6-week home-based exercise programme delivered through telerehabilitation or paper-based instructions. Outcome measures from participants will be obtained at baseline and on completion of 6 weeks. These will include the Visual Analogue Scale for Pain, Neck Disability Index questionnaire, CROM by using the CROM instrument and cervical muscle endurance through the Craniocervical Flexion Test. For baseline differences between groups, an independent samples t-test will be used. Repeated measures analysis of variance will be used for within-group and between-group analyses at three different time points (0 weeks, 3 weeks, 6 weeks). Trial registration number:NCT06076174.
Window of opportunity in psoriatic arthritis: the earlier the better?
Authors: Snoeck Henkemans Selinde V J , de Jong Pascal H P , Luime Jolanda J , Kok Marc R , Tchetverikov Ilja , Korswagen Lindy-Anne , van der Kooij Sjoerd M , van Oosterhout Maikel , Baudoin Paul , Bijsterbosch Jessica , van der Kaap Jos H , van der Helm-van Mil Annette H M , Vis Marijn
Published: February 2024

Objectives

To investigate whether there is a window of opportunity for psoriatic arthritis (PsA) patients and to assess which patient characteristics are associated with a longer diagnostic delay.

Methods

All newly diagnosed, disease-modifying antirheumatic drug-naïve PsA patients who participated in the Dutch southwest Early PsA cohoRt and had ≥3 years of follow-up were studied. First, total delay was calculated as the time period between symptom onset and PsA diagnosis made by a rheumatologist and then split into patient and physician delays. The total delay was categorised into short (<12 weeks), intermediate (12 weeks to 1 year) or long (>1 year). These groups were compared on clinical (Minimal Disease Activity (MDA) and Disease Activity index for PSoriatic Arthritis (DAPSA) remission) and patient-reported outcomes during 3 years follow-up.

Results

708 PsA patients were studied of whom 136 (19%), 237 (33%) and 335 (47%) had a short, intermediate and long total delay, respectively. Patient delay was 1.0 month and physician delay was 4.5 months. Patients with a short delay were more likely to achieve MDA (OR 2.55, p=0.003) and DAPSA remission (OR 2.35,p=0.004) compared with PsA patients with a long delay. Patient-reported outcomes showed numerical but non-significant differences between the short and long delay groups. Female patients and those presenting with enthesitis, chronic back pain or normal C-reactive protein (CRP) had a longer delay.

Conclusions

In PsA, referral and diagnosis within 1 year is associated with better clinical outcomes, suggesting the presence of a window of opportunity. The most gain in referral could be obtained in physician delay and in females, patients with enthesitis, chronic back pain or normal CRP.
A unified empirical method for predicting both vertical and horizontal ground displacements induced by tunnel excavation
Authors: Lin Qingtao , Meng Xu , Lu Dechun , Miao Jinbo , Zhao Zhihong , Du Xiuli
Published: February 2024

An empirical model for describing the soil movements induced by tunneling is proposed, then the mathematical relationship between horizontal displacement and vertical displacement is obtained. By analyzing 25 sets of data from field engineering and 35 sets of data from model tests, the formula for the maximum settlement Sv, max( z) is optimized to adapt to different ground conditions. The Modified Gaussian function is developed by introducing the existing width coefficient of the settlement trough i( z) and the optimized Sv, max( z) to describe the surface and subsurface vertical displacement. Subsequently, the formula for the horizontal displacement is derived based on the Modified Gaussian function. H( z) representing the position of the oriented point of the soil movement is a variable in the formula for horizontal displacement. Based on measured results, a logarithmic function and a quadratic polynomial function are proposed to describe the variation of H( z) with depth in the clay stratum and sand stratum, respectively. Then, the rationality of the proposed method is validated by 4 sets of in-situ data and 4 sets of test data. Finally, the implementation process of the proposed method is illustrated, and the inversion results of the ground displacement field in Beijing Metro Line 12 are presented.
Multi-UAV networks for disaster monitoring: challenges and opportunities from a network perspective
Authors: Chandran Indu , Vipin Kizheppatt
Published: February 2024

Disasters, whether natural or man-made, demand rapid and comprehensive responses. Unmanned aerial vehicles (UAVs), or drones, have become essential in disaster scenarios, serving as crucial communication relays in areas with compromised infrastructure. They establish temporary networks, aiding coordination among emergency responders and facilitating timely assistance to survivors. Recent advancements in sensing technology have transformed emergency response by combining the collaborative power of these networks with real-time data processing. However, challenges remain to consider these networks for disaster monitoring applications, particularly in deployment strategies, data processing, routing, and security. Extensive research is crucial to refine ad hoc networking solutions, enhancing the agility and effectiveness of these systems. This article explores various aspects, including network architecture, formation strategies, communication protocols, and security concerns in multi-UAV networks for disaster monitoring. It also examines the potential of enabling technologies like edge computing and artificial intelligence to bolster network performance and security. Further, the article provides a detailed overview of the key challenges and open issues, outlining various research prospects in the evolving field of multi-UAV networks for disaster response.
Digital simulation of convex mixtures of Markovian and non-Markovian single qubit Pauli channels on NISQ devices
Authors: David I. J. , Sinayskiy I. , Petruccione F.
Published: February 2024

Quantum algorithms for simulating quantum systems provide a clear and provable advantage over classical algorithms in fault-tolerant settings. There is also interest in quantum algorithms and their implementation in Noisy Intermediate Scale Quantum (NISQ) settings. In these settings, various noise sources and errors must be accounted for when executing any experiments. Recently, NISQ devices have been verified as versatile testbeds for simulating open quantum systems and have been used to simulate simple quantum channels. Our goal is to solve the more complicated problem of simulating convex mixtures of single qubit Pauli channels on NISQ devices. We consider two specific cases: mixtures of Markovian channels that result in a non-Markovian channel (M + M = nM) and mixtures of non-Markovian channels that result in a Markovian channel (nM + nM = M). For the first case, we consider mixtures of Markovian single qubit Pauli channels; for the second case, we consider mixtures of Non-Markovian single qubit depolarising channels, which is a special case of the single qubit Pauli channel. We show that efficient circuits, which account for the topology of currently available devices and current levels of decoherence, can be constructed by heuristic approaches that reduce the number of CNOT gates used in our circuit. We also present a strategy for regularising the process matrix so that the process tomography yields a completely positive and trace-preserving (CPTP) channel.

Key points

This work simulates the convex mixtures of single qubit Markovian and non-Markovian quantum channels on NISQ devices provided by the IMBQE.

The circuits used to implement the channels take into account the topolgy of the quantum device used as well as the number of CNOT gates used.

We present a strategy for regularising the process matrix to ensure the quantum process tomography yields a CPTP channel. Something that is not correctly implemented in Qiskit.

A method is outlined for finding mixtures of non-Markovian depolarising channels that yield a Markovian depolarising channel. It is also shown that, one cannot convexly mix two Markovian depolarising channels that leads to a non-Markovian depolarising channel.
Numerical study of finite volume scheme for coagulation–fragmentation equations with singular rates
Authors: Bariwal Sanjiv Kumar , Barik Prasanta Kumar , Giri Ankik Kumar , Kumar Rajesh
Published: February 2024

This paper deals with the convergence of finite volume scheme (FVS) for solving coagulation and multiple fragmentation equations having locally bounded coagulation kernel but singularity near the origin due to fragmentation rates. Thanks to the Dunford–Pettis and De La Vall[Formula: see text]e-Poussin theorems, we establish that numerical solution is converging to the weak solution of the continuous model using a weak [Formula: see text] compactness argument. A suitable stable condition on time step is taken to achieve the result. Furthermore, when kernels are in [Formula: see text] space, first-order error approximation is demonstrated for a uniform mesh. It is numerically validated by taking four test problems of coupled coagulation–fragmentation models.
Magma mixing between rhyolite and pseudotachylite as the origin for the Glencoe ‘flinty crush rock’
Authors: Dobson David P. , Martinescu Viorela
Published: February 2024

The Glencoe caldera is a well-studied example of a caldera system exposed to intermediate depths along the glacially excavated glen. We present a first quantitative assessment of clast-size population and matrix chemistry from the flinty crush rock that occurs on the main ring faults. Size–shape metrics of clasts differ from those of a ‘normal’ pseudotachylite from the Outer Hebrides. Both samples display good power-law clast-size populations, once allowance is made for dissolution of a portion of clasts into the melt that contained them, with fractal dimensions of 2.7 and 4.0 for the Outer Hebrides and Glencoe samples respectively. Mass-balance calculations of flinty crush rock matrix chemistry imply an origin by mixing between rhyolite and pseudotachylite that was derived from semipelitic host rock. This means that the flinty crush rock was transported some distance from the point of frictional heating, as previously proposed, as semipelitic rocks are not present at the surface at Stob Mhic Mhartuin but are likely to be present at depth. This transport, and mixing with rhyolite magma, would have provided the time and thermal energy for clast dissolution beyond that possible during normal pseudotachylite generation and quenching on fault wall rocks.

Supplementary material:
Results of simulations, major element compositions of the matrix in the flinty crush rock sample and a supplementary figure are available at
https://doi.org/10.6084/m9.figshare.c.7084992
CACTUS: A Comprehensive Abstraction and Classification Tool for Uncovering Structures
Authors: Gherardini Luca , Varma Varun Ravi , Capała Karol , Woods Roger , Sousa Jose
Published: February 2024

The availability of large datasets is providing the impetus for driving many current artificial intelligent developments. However, specific challenges arise in developing solutions that exploit small datasets, mainly due to practical and cost-effective deployment issues, as well as the opacity of deep learning models. To address this, the Comprehensive Abstraction and Classification Tool for Uncovering Structures (CACTUS) is presented as a means of improving secure analytics by effectively employing explainable artificial intelligence. CACTUS achieves this by providing additional support for categorical attributes, preserving their original meaning, optimising memory usage, and speeding up the computation through parallelisation. It exposes to the user the frequency of the attributes in each class and ranks them by their discriminative power. Performance is assessed by applying it to various domains, including Wisconsin Diagnostic Breast Cancer, Thyroid0387, Mushroom, Cleveland Heart Disease, and Adult Income datasets.
Elotuzumab Enhances CD16‐Independent NK Cell‐Mediated Cytotoxicity against Myeloma Cells by Upregulating Several NK Cell‐Enhancing Genes
Authors: Wang Yan-Hua , Hagiwara Shotaro , Kazama Hiroshi , Iizuka Yuki , Tanaka Norina , Tanaka Junji
Published: February 2024

Multiple myeloma (MM) is an intractable hematological malignancy caused by abnormalities in plasma cells. Combination therapy using antibodies and natural killer (NK) effectors, which are innate immune cells with safe and potent antitumor activity, is a promising approach for cancer immunotherapy and can enhance antitumor effects. Elotuzumab (Elo) is an immune‐stimulatory antibody that targets the signaling lymphocytic activation molecule family 7 (SLAMF7) expressed on the surface of MM and NK cells. We confirmed that Elo strongly promoted NK cell‐mediated antibody‐dependent cellular cytotoxicity (ADCC) against SLAMF7‐positive MM cells in a CD16‐dependent NK cell line, and also activated expanded NK cells derived from peripheral blood mononuclear cells of healthy donors and patients with MM in the present study. However, the antitumor effects and genes involved in the direct promotion of NK cell‐mediated activation using Elo in CD16‐independent NK cells are not clearly known. In this study, we demonstrated that Elo pretreatment significantly enhanced CD16‐independent NK cell‐mediated cytotoxicity in both SLAMF7‐positive MM.1S and SLAMF7‐negative K562, U266, and RPMI 8226 tumor cells. Upon direct simulation of CD16‐independent NK cells with Elo, increased levels of CD107a degranulation and IFN‐γ secretion were observed along with the upregulation of granzyme B, TNF‐α, and IL‐1α gene expression. The enhanced NK cell function could also be attributed to the increased expression of the transcription factors T‐BET and EOMES. Furthermore, the augmentation of the antitumor effects of CD16‐independent NK cells upon pretreatment with Elo enhanced the expression of CRTAM, TNFRSF9, EAT‐2, and FOXP3 genes and reduced the expression of HSPA6. Our results suggest that Elo directly promotes the cytotoxic function of CD16‐independent NK cells against target cells, which is associated with the upregulation of the expression of several NK cell‐enhancing genes.
Sea Urchin-Like MnO2/Biomass Carbon Composite Electrode Material for High-Performance Supercapacitors
Authors: Zhao Xiaoyu , Wang Ning , Li Lei , Fang Zixun , Tang Shoufeng , Gu Jianmin
Published: February 2024

Manganese oxide materials for high-performance supercapacitors are as popular electrode materials of energy storage devices based on their high theoretical capacitance. However, its development is limited by its poor electrical conductivity and insufficient contact surface area, which causes the supercapacitor to fail to achieve its theoretical specific capacitance. In this paper, unique sea urchin-like MnO2/biomass carbon (BC) composite materials were prepared for supercapacitors, showing the lower resistance compared with pure MnO2, which possesses superior electrochemical performance due to the advances in outstanding electrical conductivity. The single electrode test results show that the composite material achieves a specific capacitance of 205.5 F·g−1 at the current density of 0.5 A·g−1; with the current density increasing by a factor of 20, the supercapacitor loaded with this composite still retained 63.2% of its initial capacitance, showing its high rate performance. Meanwhile, the constructed asymmetric supercapacitor can change the color of electrochromic devices and drive the light of electrochemiluminescent devices, indicating its promising application. This work provided a promising route for the rational construction of multiple dimensioned high-performance electrode materials for use in new energy storage devices.
The Development Strategy of Dual-Channel Supply Chain of Smart Elderly Care Service from the Perspective of Time Perception
Authors: Zhao Tong , Hou Qiaoming
Published: February 2024

The development of smart elderly industry is an inevitable way to cope with the aging of the population. This research takes the smart elderly care service supply chain as the object, combines the social emotional choice theory for the first time, and uses the time perception to refine the elderly care demand into future-orientation demand and present-orientation demand. This paper analyzes the coordination effect of suppliers’ efforts to meet the needs of the elderly under the two conditions of no contract and benefit-sharing contract on the dual-channel supply chain of smart elderly care services. The results show that the benefit-sharing contract is more conducive to maximizing the profit of the supply chain, and the segmentation of elderly demand is conducive to giving full play to the advantages of dual-channel differentiated services, which is conducive to forming a win-win situation of improving the service efficiency of the smart elderly service supply chain and increasing the happiness index of elderly users. The main contributions of this paper are: Using geriatric behavioral psychology to analyze the motivation of the elderly and designing the service effort level index considering the needs of the elderly. Match online and offline channels with personalized services to give full play to the “smart” effect. Based on the game method of Hotelling and Stackelberg, the coordination and optimization of the smart elderly care services dual-channel supply chain, considering the needs of the elderly are realized. This is of great research significance for maximizing the benefits of the smart elderly service supply chain and promoting the development of the smart elderly industry.
Primary Yolk Sac Tumor of the Liver: A Rare Cause of Bile Duct Obstruction
Authors: Patel Sahil M. , Sigman Kenneth M. , Dugum Mohannad F.
Published: February 2024

Primary yolk sac tumor (YST) of the liver is an extremely rare extragonadal germ cell tumor. Here, we present a case of a young man who developed primary YST of the liver which metastasized to periductal lymph nodes causing bile duct obstruction. A 32-year-old male was referred from an outside hospital for evaluation of painless jaundice. Initial investigation showed common bile duct compression from periductal lymph nodes. Inital biopsy results were concerning for adenocarcinoma. The patient was ultimately diganosed with primary YST of the liver. He was then started on a curative-intent chemotherapy regimen of bleomycin, etoposide, and cisplatin. This case highlights the importance of keeping the primary YST of the liver on the differential diagnosis as initial staining patterns are similar to adenocarcinoma which has a very different management.
Effects of Triazole Antifungal Agents on the Plasma Concentration and Dosage of Cyclosporin in Patients with Aplastic Anaemia
Authors: Tian Yangxiu , Song Yan , Qiao Yanan , Song Li , Zhao Qiang , Yin Donghong , Wang Shuyun , Hou Ruigang
Published: February 2024

Objectives. This study aimed to investigate the effects of different triazole antifungal agents on the blood concentration and dosage of cyclosporine (CsA) in patients with aplastic anaemia (AA). Methods. This retrospective study enrolled AA patients who received CsA and triazole antifungal agents simultaneously between January 2018 and December 2022. The ratio of CsA blood concentration (ng/mL) to dosage (mg/day) (C/D) co‐administration with and without azoles was compared. The effects of different triazole antifungal agents on blood concentrations and dosages of CsA were analysed. Results. The mean C/D ratio of CsA increased 1.97 times when co‐administered with posaconazole (POS), while the mean C/D ratio of CsA increased 1.76 times when co‐administered with fluconazole (FCZ). Compared with CsA monotherapy, there was a significant difference in CsA concentrations among patients with azoles (P < 0.05). The mean dose of CsA decreased was 0.26 (−0.25—1.05) mg/kg/day and 0.18 (−0.50—0.69) mg/kg/day when co‐administered with POS and FCZ, respectively. There is a wide interindividual variability in the magnitude of drug interaction between azoles and CsA. Conclusions. Although azoles increased CsA concentration, a wide individual variability was found in the patients with CsA C/D ratio. Therefore, the CsA dose should be adjusted by closely monitoring the blood levels of CsA co‐administered with triazole antifungal agents. In addition, we observed that POS had a greater effect on the blood concentration of CsA than FCZ. When adjusting the dose of CsA in clinical practice, the blood concentration of CsA and the type of co‐administered triazole antifungal agents should be considered.
Validation and Application of Screen-Printed Microchip for Potentiometric Determination of Metformin Hydrochloride in Tablet Dosage Form
Authors: Alqarni Mohammed , Alshehri Abdullah A. , Arida Hassan
Published: February 2024

Metformin is an oral biguanides hypoglycaemic agent, which used to lower the blood glucose levels in people with type 2 diabetes mellitus. Many analytical techniques have been used to quantify the drug in different pharmaceutical dosage forms; however, most of these methods have limited throughput in the quality control application. A disposable potentiometric microsensor responsive to metformin has recently been reported. For the first time, herein, this method of analysis has been validated according to IUPAC recommendations and successfully applied in the determination of metformin drug in some dosage form. Different drug formulations of metformin hydrochloride have been collected from the local pharmaceutical stores in Saudi Arabia and analysed using the validated microchip-based method of analysis. Subsequently, the results of this study showed that the validated method was linear, specific, precise, and accurate. The linear range was 1 × 10−1–1 × 10−5 mol L−1 and the correlation coefficient was 0.999. The limit of detection was 2.89 × 10−6 mol L−1, and the limit of quantification was 8.77 × 10−6 mol L−1. This method demonstrated high precision, with an RSD% of less than 2.22%. The accuracy of this method was obtained by comparing the recovery percentage with percentage values less than 5%. The results obtained showed that there was no significant difference between the references, label, and recovery of less than 5%.
Hygienic Practices of Vendors and Their Contribution to Coliform, Salmonella, and Shigella Bacteria of Raw Milk at Asella Town, Oromia, Ethiopia
Authors: Tusa Hirpo , Alemayehu Tsegaye , Subussa Bereket Wake , Ayalew Henok , Ali Musa Mohammed
Published: February 2024

Background. Coliform, Salmonella, and Shigella are among the most encountered bacteria in raw milk. This study is aimed at determining the extent of coliform, Salmonella, and Shigella bacteria in raw milk and vendor hygiene practices at Asella town, Oromia Regional State, Ethiopia, from March 1 to 30, 2022. Methods. In this study, 210 milk vendors were included; each vendor provided a 50 ml sample of raw milk. Bacteria were isolated and identified using standard bacteriological techniques. Data were entered and analyzed using EPI info version 7 and SPSS version 22, respectively. A binary logistic regression model was applied to determine the factors associated with bacterial contamination of raw milk. Results. The total contamination percentage of raw milk was 50 (23.8%) (95% CI: 18.1-29.5%). The predominant bacteria identified were coliform 43 (20.5%) followed by Salmonella species 7 (3.3%). Among coliforms, the predominant bacteria were Citrobacter species 15 (34.9%) followed by Enterobacter species 11 (25.6%), Escherichia coli and Serratia species each 6 (14%), and Klebsiella species 5 (11.6%). However, no Shigella was isolated in this study. Not having the habit of washing cow teats (p<0.0001), the habit of washing teats with tap water (p<0.0001), not having separate cloth during milking (p<0.0001), not having a practice of testing milk for bacterial contamination (p=0.027), and not having separate vending environment (p=0.039) were significantly associated with bacterial contamination of raw milk. Conclusions. The percentage of bacterial contamination of milk was found to be high. Participants without a habit of washing cow teats, a habit of washing milk utensils with only tap water, and not having separate vending environments were associated factors for bacterial contamination of raw milk. Milk vendors are advised to develop the habit of washing teats before milking, avoid washing teat/milk utensils only with tap water, and have a separate vending environment.
Video S1 from Cancer-associated Fibroblast–specific Expression of the Matricellular Protein CCN1 Coordinates Neovascularization and Stroma Deposition in Melanoma Metastasis
Authors: Hutchenreuther James , Nguyen John , Quesnel Katherine , Vincent Krista M. , Petitjean Louis , Bourgeois Sophia , Boyd Mark , Bou-Gharios George , Postovit Lynne-Marie , Leask Andrew
Published: February 2024

CCN1 +/+ stroma vasculature microct
FIGURE 7 from Cancer-associated Fibroblast–specific Expression of the Matricellular Protein CCN1 Coordinates Neovascularization and Stroma Deposition in Melanoma Metastasis
Authors: Hutchenreuther James , Nguyen John , Quesnel Katherine , Vincent Krista M. , Petitjean Louis , Bourgeois Sophia , Boyd Mark , Bou-Gharios George , Postovit Lynne-Marie , Leask Andrew
Published: February 2024

CCN1 expression by fibroblasts is associated with increased tumor penetration of CD4+ T cells and resistance to anti-PD1 checkpoint inhibitors. A, Tumors were subjected to flow cytometry with anti-CD4 anti-CD8 antibodies. Percentage of positive CD45-staining cells are indicated wild type (n = 3, CCN1f/f) and CCN1-deficient (n = 3, CCN1−/−) tumors (Student t test). Primary flow data of the median value is presented Tissue was examined after 14 days of tumor growth. B, Boxplot shows higher levels of CAF-specific CCN1 scores in patients on checkpoint inhibitors with progressive disease (GSE78220). A six-gene set of CAF-specific genes correlating with CCN1 (PDGFRA, COL1A1, DCN, TAGLN, COL6A3, and LPAR1), as described in Materials and Methods, was analyzed. P value (unpaired t test) displayed in top left corner. n = 14 in the responders and n = 12 in the progressive disease. C and D, Loss of CCN1 expression results in reduced MMP-9 expression in CCN1-deficient mice. Real-time PCR analysis of RNAs isolated from Ccn1+/+ and Ccn1−/− dermal fibroblasts from 3 different mice (N = 3; C) or skin (N = 4 Ccn1+/+, N = 8, Ccn1−/−; D) reveal that CCN1-deficient fibroblasts have reduced expression of the anti-PD1 resistance marker/effector MMP-9 (Student unpaired t test; *, P < 0.05). Please note that D was conducted on identical skin samples to those published previously (29).
Percutaneous Left Ventricular Unloading During High-Risk Coronary Intervention: Rationale and Design of the CHIP-BCIS3 Randomized Controlled Trial
Authors: Ryan Matthew , Ezad Saad M. , Webb Ian , O’Kane Peter D. , Dodd Matthew , Evans Richard , Laidlaw Lynn , Khan Sohail Q. , Weerackody Roshan , Bagnall Alan , Panoulas Vasileios F. , Rahman Haseeb , Strange Julian W. , Fath-Ordoubadi Farzin , Hoole Stephen P. , Stables Rod H. , Curzen Nick , Clayton Tim , Perera Divaka ,   on behalf of the CHIP-BCIS3 Investigators
Published: February 2024

INTRODUCTION:

Percutaneous coronary intervention for complex coronary disease is associated with a high risk of cardiogenic shock. This can cause harm and limit the quality of revascularization achieved, especially when left ventricular function is impaired at the outset. Elective percutaneous left ventricular unloading is increasingly used to mitigate adverse events in patients undergoing high-risk percutaneous coronary intervention, but this strategy has fiscal and clinical costs and is not supported by robust evidence.

METHODS:

CHIP-BCIS3 (Controlled Trial of High-Risk Coronary Intervention With Percutaneous Left Ventricular Unloading) is a prospective, multicenter, open-label randomized controlled trial that aims to determine whether a strategy of elective percutaneous left ventricular unloading is superior to standard care (no planned mechanical circulatory support) in patients undergoing nonemergent high-risk percutaneous coronary intervention. Patients are eligible for recruitment if they have severe left ventricular systolic dysfunction, extensive coronary artery disease, and are due to undergo complex percutaneous coronary intervention (to the left main stem with calcium modification or to a chronic total occlusion with a retrograde approach). Cardiogenic shock and acute ST-segment–elevation myocardial infarction are exclusions. The primary outcome is a hierarchical composite of all-cause death, stroke, spontaneous myocardial infarction, cardiovascular hospitalization, and periprocedural myocardial infarction, analyzed using the win ratio. Secondary outcomes include completeness of revascularization, major bleeding, vascular complications, health economic analyses, and health-related quality of life. A sample size of 250 patients will have in excess of 80% power to detect a hazard ratio of 0.62 at a minimum of 12 months, assuming 150 patients experience an event across all follow-up.

CONCLUSIONS:

To date, 169 patients have been recruited from 21 National Health Service hospitals in the United Kingdom, with recruitment expected to complete in 2024.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT05003817.
mPAP/CO Slope and Oxygen Uptake Add Prognostic Value in Aortic Stenosis
Authors: Hoedemakers Sarah , Pugliese Nicola Riccardo , Stassen Jan , Vanoppen Arnaud , Claessens Jade , Gojevic Tin , Bekhuis Youri , Falter Maarten , Moura Ferreira Sara , Dhont Sebastiaan , De Biase Nicolò , Del Punta Lavinia , Di Fiore Valerio , De Carlo Marco , Giannini Cristina , Colli Andrea , Dulgheru Raluca Elena , Geers Jolien , Yilmaz Alaaddin , Claessen Guido , Bertrand Philippe , Droogmans Steven , Lancellotti Patrizio , Cosyns Bernard , Verbrugge Frederik H. , Herbots Lieven , Masi Stefano , Verwerft Jan
Published: February 2024

BACKGROUND:

Recent guidelines redefined exercise pulmonary hypertension as a mean pulmonary artery pressure/cardiac output (mPAP/CO) slope >3 mm Hg·L
−1
·min
−1
. A peak systolic pulmonary artery pressure >60 mm Hg during exercise has been associated with an increased risk of cardiovascular death, heart failure rehospitalization, and aortic valve replacement in aortic valve stenosis. The prognostic value of the mPAP/CO slope in aortic valve stenosis remains unknown.

METHODS:

In this prospective cohort study, consecutive patients (n=143; age, 73±11 years) with an aortic valve area ≤1.5 cm
2
underwent cardiopulmonary exercise testing with echocardiography. They were subsequently evaluated for the occurrence of cardiovascular events (ie, cardiovascular death, heart failure hospitalization, new-onset atrial fibrillation, and aortic valve replacement) during a follow-up period of 1 year. Findings were externally validated (validation cohort, n=141).

RESULTS:

One cardiovascular death, 32 aortic valve replacements, 9 new-onset atrial fibrillation episodes, and 4 heart failure hospitalizations occurred in the derivation cohort, whereas 5 cardiovascular deaths, 32 aortic valve replacements, 1 new-onset atrial fibrillation episode, and 10 heart failure hospitalizations were observed in the validation cohort. Peak aortic velocity (odds ratio [OR] per SD, 1.48;
P
=0.036), indexed left atrial volume (OR per SD, 2.15;
P
=0.001), E/e’ at rest (OR per SD, 1.61;
P
=0.012), mPAP/CO slope (OR per SD, 2.01;
P
=0.002), and age-, sex-, and height-based predicted peak exercise oxygen uptake (OR per SD, 0.59;
P
=0.007) were independently associated with cardiovascular events at 1 year, whereas peak systolic pulmonary artery pressure was not (OR per SD, 1.28;
P
=0.219). Peak V
o
2
(percent) and mPAP/CO slope provided incremental prognostic value in addition to indexed left atrial volume and aortic valve area (
P
<0.001). These results were confirmed in the validation cohort.

CONCLUSIONS:

In moderate and severe aortic valve stenosis, mPAP/CO slope and percent-predicted peak V
o
2
were independent predictors of cardiovascular events, whereas peak systolic pulmonary artery pressure was not. In addition to aortic valve area and indexed left atrial volume, percent-predicted peak V
o
2
and mPAP/CO slope cumulatively improved risk stratification.
Association of Sex With Cardiovascular Outcomes in Heart Failure Patients With Obstructive or Central Sleep Apnea
Authors: Huang Boping , Huang Yan , Zhai Mei , Zhou Qiong , Ji Shiming , Liu Huihui , Zhuang Xiaofeng , Zhang Yuhui , Zhang Jian
Published: February 2024

Background

This study investigated the association of sex with cardiovascular outcomes in a prospective cohort of patients with heart failure (HF) with obstructive sleep apnea or central sleep apnea.

Methods and Results

Patients were screened for sleep apnea on admission using multichannel cardiopulmonary monitoring from May 2015 to July 2018. The primary outcome was a composite of cardiovascular death or unplanned hospitalization for worsening HF. Ultimately, 453 patients with HF with obstructive sleep apnea or central sleep apnea were included; 71 (15.7%) and 382 (84.3%) were women and men, respectively. During a median follow‐up of 2.33 years, 248 (54.7%) patients experienced the primary outcome. In the overall population, after adjusting for potential confounders, women had an increased risk of the primary outcome (66.2% versus 52.6%; hazard ratio [HR], 1.47 [95% CI, 1.05–2.04];
P
=0.024) and HF rehospitalization (62.0% versus 46.6%; HR, 1.55 [95% CI, 1.10–2.19];
P
=0.013) compared with men but a comparable risk of cardiovascular death (21.1% versus 23.3%; HR, 0.78 [95% CI, 0.44–1.37];
P
=0.383). Likewise, in patients with HF with obstructive sleep apnea, women had a higher risk of the primary outcome (81.8% versus 46.3%, HR, 2.37 [95% CI, 1.28–4.38];
P
=0.006) and HF rehospitalization (81.8% versus 44.7%, HR, 2.46 [95% CI, 1.32–4.56],
P
=0.004). However, in patients with HF with central sleep apnea, there was no statistically significant difference between women and men.

Conclusions

In hospitalized patients with HF, female sex was associated with an increased risk of the primary outcome and HF rehospitalization, especially in those with obstructive sleep apnea. Screening for sleep apnea should be emphasized to improve the prognosis.

Registration

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT02664818.
General dynamics of the URT microbiome and microbial signs of recovery in COVID-19 patients
Authors: Ignatyeva O. , Gostev V. , Taraskina A. , Tsvetkova I. , Pavlova P. , Sulian O. , Ageevets V. , Likholetova D. , Chulkova P. , Nikitina E. , Matkava L. , Terekhov M. , Lisovaya D. , Kashtanova D. , Ivanov M. , Kalinogorskaya O. , Avdeeva A. , Zhirkov A. , Goleva O. , Zakharenko S. , Zhdanov K. , Strizheletsky V. , Gomon Y. , Kruglov A. , Ni O. , Noskova T. , Gorbova I. , Cherenkova G. , Shlyk I. , Afanasyev A. , Yudin V. , Makarov V. , Sidorenko S. , Yudin S.
Published: February 2024

COVID-19 is caused by an airborne virus, SARS-CoV-2. The upper respiratory tract (URT) is, therefore, the first system to endure the attack. Inhabited by an assemblage of microbial communities, a healthy URT wards off the invasion. However, once invaded, it becomes destabilised, which could be crucial to the establishment and progression of the infection. We examined 696 URT samples collected from 285 COVID-19 patients at three time-points throughout their hospital stay and 100 URT samples from 100 healthy controls. We used 16S ribosomal RNA sequencing to evaluate the abundance of various bacterial taxa, α-diversity, and β-diversity of the URT microbiome. Ordinary least squares regression was used to establish associations between the variables, with age, sex, and antibiotics as covariates. The URT microbiome in the COVID-19 patients was distinctively different from that of healthy controls. In COVID-19 patients, the abundance of 16 genera was significantly reduced. A total of 47 genera were specific to patients, whereas only 2 were unique to controls. The URT samples collected at admission differed more from the control than from the samples collected at later stages of treatment. The following four genera originally depleted in the patients grew significantly by the end of treatment: Fusobacterium, Haemophilus, Neisseria, and Stenotrophomonas. Our findings strongly suggest that SARS-CoV-2 caused significant changes in the URT microbiome, including the emergence of numerous atypical taxa. These findings may indicate increased instability of the URT microbiome in COVID-19 patients. In the course of the treatment, the microbial composition of the URT of COVID-19 patients tended toward that of controls. These microbial changes may be interpreted as markers of recovery.
Diplomacy Within the Security Framework in Turkey and Romania During the Interwar Period
Authors: Emek Berk , Barlas Dilek
Published: February 2024

This article aims to highlight shifting diplomatic positions in Turkey and Romania and their stances towards the League of Nations collective security network during the interwar period. It takes a comparative approach to demonstrate the diplomatic activity and strategic decision-making mechanism employed by two strategically important Balkan and Black Sea countries vis-à-vis the fragile international system from the 1920s onwards. The rising threat of revisionism and declining belief in the League’s sanctioning power gradually led these countries to set their differences in foreign policy aside and strengthened the idea of joint regional action in the 1930s. Supported by primary sources from different archives, this comparative study proposes a new outlook, by demonstrating the contribution made by the notions of external threat and common aggressor to changing foreign policy perspectives in both countries.
How Much Lightning Actually Strikes the United States?
Authors: Vagasky Chris , Holle Ronald L. , Murphy Martin J. , Cramer John A. , Said Ryan K. , Guthrie Mitchell , Hietanen Jesse
Published: February 2024

The number of cloud-to-ground (CG) flashes over the contiguous United States (CONUS) has been estimated to be from as small as 25 million per year to as many as 40 million. In addition, many CG flashes contact the ground in more than one place. To clarify these values, recent data from the National Lightning Detection Network (NLDN) have been examined since the network is performing well enough to make precise updates to the number of CG flashes and their associated ground contact points. The average number of CG flashes is calculated to be about 23.4 million per year over the CONUS, and the average number of ground contact points is calculated as 36.8 million per year. Knowledge of these two parameters is critical to lightning protection standards, as well as better understanding of the effects of lightning on forest fire initiation, geophysical interactions, human safety, and applications that benefit from knowing that a single flash may transfer charge to the ground in multiple, widely spaced locations. Sensitivity tests to assess the effects of misclassification of CG and in-cloud (IC) lightning are also made to place bounds on these estimates, and the likely uncertainty is a few percent.
Temperature and Thermal Diffusivity Diagnostics in Laminar Methane Flames Using Infrared Four-Wave Mixing Techniques
Authors: Song Zihao , Chao Xing , Sahlberg Anna-Lena
Published: February 2024

Four-wave mixing techniques, such as coherent anti-Stokes Raman spectroscopy (CARS), laser-induced grating spectroscopy (LIGS), and degenerate four-wave mixing (DFWM), have been widely used in combustion diagnostics due to their advantages of high signal-to-noise ratio (S/N), coherent signal, and spatial resolution. In this work, a nano-second pulsed laser is utilized to generate mid-infrared (near 3 µm) pump beams, exciting the rovibrational transitions of nascent water in flames. Combined LIGS and DFWM measurements are demonstrated in premixed laminar CH4/O2/N2 flames with equivalence ratios from 0.6 to 1.5, to achieve precise thermometry in a wide range of flame conditions. The flame temperatures were also measured by thermocouple as a reference, and the results from LIGS and DFWM align well with the trends shown in the thermocouple measurements. In fuel-lean flames, where the mass-to-specific-heat ratio variation is minimal, LIGS provides temperature data with a precision better than 16 K (0.8%). In fuel-rich flames, where the increased H2 concentration in the flame introduces uncertainty in gas constants thus affecting the accuracy of LIGS thermometry, DFWM is instead employed for temperature measurement since it is less sensitive to the gas composition within the measured volume. The high-precision LIGS temperatures in lean flames serve as temperature reference during the DFWM calibration of the degree of saturation, and a precision better than 90 K (4.5%) is achieved for DFWM thermometry. In addition to temperature, a theoretical model is employed to fit LIGS signal time waveforms, extracting the local speed of sound and thermal diffusivity with precisions better than 0.5% and 1.3%, respectively. These high-precision measurements contribute additional data for flame research and simulation calculations. This way, the combined use of DFWM and LIGS proves the potential for accurate thermometry and diagnostics of other thermodynamic parameters across a wide range of flame conditions.
Improved model-free synergetic control of permanent magnet synchronous motor using unknown input observer
Authors: Wang Xiaodong , Wei Changyin , Chen Yong , Ma Qiang
Published: February 2024

Parametric uncertainties and inverter nonlinearity exist in the permanent magnet synchronous motor (PMSM) drive system, which may lead to performance degradation or failure of model-based control. This paper presents an enhanced model-free synergetic control method for PMSMs, addressing the limitations of relying on accurate motor models in existing speed control strategies. The proposed approach aims to achieve robust control performance in the presence of parameter perturbations without the need for an accurate motor model. Firstly, a new ultra-local model of the speed loop for the PMSM is established based on a newly developed ultra-local theory. Subsequently, a model-free synergetic controller is designed using the principles of synergetic control theory. To address the issue of output chattering in the sliding mode observer used to estimate the unknown part of the ultra-local model, a synergetic observer method is proposed. Simulation results are presented and compared with those obtained using a proportional-integral (PI) controller and a conventional model-free sliding mode controller. The results demonstrate that the model-free synergetic controller exhibits robust performance and provides accurate estimation of the unknown part without output chattering.