bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative study on static and dynamic characteristics of pumping-out and pumping-in herringbone grooved journal bearings
Authors: Lin Lepeng , Qiao Yahui , Li Hongjun , Zhou Chao
Published: May 2023

The aim of this paper is to compare the static and dynamic performances of two types of herringbone grooved journal bearings (HGJBs), that is, pumping-out HGJB and pumping-in HGJB. Firstly, based on finite control volume method and the principle of flow balance, an equivalent Reynolds equation considering the turbulence effect is derived. Then, the journal motion considering angular displacement is analyzed with linear perturbation method. The equivalent Reynolds equation is linearized into static-form one and perturbed-form ones. These equations are solved by finite difference method and their solutions are integrated on the bearing surface to determinate the static characteristics and dynamic coefficients of HGJB. Additionally, the critical mass and critical whirl frequency are defined for evaluating the stability and rigidity of bearing by solving a motion equation with four degree of freedoms (DOFs). Finally, the static and dynamic characteristics of two types of HGJBS are analyzed and compared symmetrically in consideration of effects of eccentricity ratio, length to diameter ratio, groove angle, groove depth, the width of sealing damp, tilting degree of journal, and rotation speed. The results show that, within the interested range of investigated parameters, static performances of pumping-out HGJB are superior to that of pumping-in HGJB generally. Stability of pumping-in HGJB is better than pumping-out HGJB but bearing rigidity of pumping-in HGJB is inferior to pumping-out HGJB.
RANKL inhibition: a new target of treating diabetes mellitus?
Authors: Xing Baodi , Yu Jie , Zhang Huabing , Li Yuxiu
Published: May 2023

Accumulating evidence demonstrates the link between glucose and bone metabolism. The receptor activator of nuclear factor-kB ligand (RANKL)/the receptor activator of NF-κB (RANK)/osteoprotegerin (OPG) axis is an essential signaling axis maintaining the balance between bone resorption and bone formation. In recent years, it has been found that RANKL and RANK are distributed not only in bone but also in the liver, muscle, adipose tissue, pancreas, and other tissues that may influence glucose metabolism. Some scholars have suggested that the blockage of the RANKL signaling may protect islet β-cell function and prevent diabetes; simultaneously, there also exist different views that RANKL can improve insulin resistance through inducing the beige adipocyte differentiation and increase energy expenditure. Currently, the results of the regulatory effect on glucose metabolism of RANKL remain conflicting. Denosumab (Dmab), a fully human monoclonal antibody that can bind to RANKL and prevent osteoclast formation, is a commonly used antiosteoporosis drug. Recent basic studies have found that Dmab seems to regulate glucose homeostasis and β-cell function in humanized mice or in vitro human β-cell models. Besides, some clinical data have also reported the glucometabolic effects of Dmab, however, with limited and inconsistent results. This review mainly describes the impact of the RANKL signaling pathway on glucose metabolism and summarizes clinical evidence that links Dmab and DM to seek a new therapeutic strategy for diabetes.
Antimicrobial resistance and virulence genes of invasive Salmonella enterica from children with bacteremia in north-central Nigeria
Authors: Uzairue Leonard I , Shittu Olufunke B , Ojo Olufemi E , Obuotor Tolulope M , Olanipekun Grace , Ajose Theresa , Arogbonlo Ronke , Medugu Nubwa , Ebruke Bernard , Obaro Stephen K
Published: May 2023

Objectives:

Bacteremia due to invasive Salmonella enterica has been reported earlier in children in Nigeria. This study aimed to detect the virulence and antibiotic resistance genes of invasive Salmonella enterica from children with bacteremia in north-central Nigeria.

Method:

From June 2015 to June 2018, 4163 blood cultures yielded 83 Salmonella isolates. This is a secondary cross-sectional analysis of the Salmonella isolates. The Salmonella enterica were isolated and identified using standard bacteriology protocol. Biochemical identifications of the Salmonella enterica were made by Phoenix MD 50 identification system. Further identification and confirmation were done with polyvalent antisera O and invA gene. Antimicrobial susceptibility testing was done following clinical and laboratory standard institute guidelines. Resistant genes and virulence genes were determined using a real-time polymerase chain reaction.

Result:

Salmonella typhi 51 (61.4%) was the most prevalent serovar, followed by Salmonella species 13 (15.7%), choleraesuis 8 (9.6%), enteritidis 6 (7.2%), and typhimurium 5 (6.1%). Fifty-one (61.4%) of 83 Salmonella enterica were typhoidal, while 32 (38.6%) were not. Sixty-five (78.3%) of the 83 Salmonella enterica isolates were resistant to ampicillin and trimethoprim-sulfamethoxazole, followed by chloramphenicol 39 (46.7%), tetracycline 41 (41.4%), piperacillin 33 (33.9%), amoxicillin-clavulanate, and streptomycin 21 (25.3%), while cephalothin was 19 (22.9%). Thirty-nine (46.9%) of the 83 Salmonella enterica isolates were multi-drug resistant, and none were extensive drug resistant or pan-drug resistant. A blaTEM 42 (50.6%), floR 32 (38.6%), qnrA 24 (28.9%), tetB 20 (20.1%), tetA 10 (10.0%), and tetG 5 (6.0%) were the antibiotic resistance genes detected. There were perfect agreement between phenotypic and genotypic detection of antimicrobial resistance in tetracycline, ciprofloxacin, and chloramphenicol, while beta-lactam showed κ = 0.60 agreement. All of the Salmonella enterica isolates had the virulence genes invA, sopB, mgtC, and sip4D, while 33 (39.8%), 45 (51.8%), and 2 (2.4%) had ssaQ, spvC, and ljsGI-1, respectively.

Conclusion:

Our findings showed multi-drug resistant Salmonella enterica in children with bacteremia in northern Nigeria. In addition, significant virulence and antimicrobial resistance genes were found in invasive Salmonella enterica in northern Nigeria. Thus, our study emphasizes the need to monitor antimicrobial resistance in Salmonella enterica from invasive sources in Nigeria and supports antibiotic prudence.
Spino-pelvic radiological parameters: Comparison of measurements obtained by radiologists using the traditional method versus spine surgeons using a semi-automated software (Surgimap)
Authors: Fleiderman Valenzuela José Gerardo , Cirillo Totera Juan Ignacio , Turkieltaub Diego Herreros , Echaurren Cristóbal Varela , Álvarez Lemos Facundo Lisandro , Arriagada Ramos Felipe Ignacio
Published: May 2023

Background

Spinopelvic balance measurement is a key point to get an appropriate diagnosis and treatment in a group of spine pathologies; thus, it seems necessary the evaluation of different methods for obtaining the most reliable values. For that reason, different automatic and semi-automatic computer-assisted tools have been developed, and one example of them is Surgimap.

Purpose

To demonstrate that the sagittal balance measurements with Surgimap are equal and more time-efficient than with Agfa-Enterprise.

Material and Methods

Retrospective-prospective study. Biased comparative analysis of radiographic measurements performed on two different occasions (96 h interval), between two spine surgeons using Surgimap and two radiologists using the traditional Cobb method (TCM) with the Agfa-Enterprise program in 36 full spine lateral X-ray, determining inter- and intra-observer reliability and the mean time required to obtain the measurements.

Results

Measurements with both methods demonstrated an excellent intra-observer correlation (Surgimap: PCC 0.95 [0.85–0.99]; TCM: PCC 0.90 [0.81–0.99]). Inter-observer correlation also demonstrated an excellent relationship (PCC >0.95). Thoracic kyphosis (TK) demonstrated the lowest levels of inter-observer correlation (PCC: 0.75). The average time in seconds with TCM was 154.6, while with the Surgimap it was 41.8 s.

Conclusion

Surgimap proved to be equally reliable and 3.5 times faster. Therefore, in consistency with the available literature, our results would allow us to promote the use of Surgimap as a clinical diagnostic tool considering precision and efficiency.
Japanese Professors’ Experiences in Teaching Sport for Development in Online English-Medium Courses
Authors: Sato Takahiro , Miller Ryan T. , Nagata Shinichi , Fuchikami Maho , Yamada Rie , Kitamura Takahiro , Shimizu Satoshi
Published: May 2023

This qualitative study examined professors’ experiences in teaching online courses in an English-medium graduate program at a Japanese university. Based on Andragogy Theory, data included in-depth, semi-structured interviews with six professors who were faculty in a graduate program in Sport for Development. Synchronous online and follow-up e-mail interviews were conducted. A constant comparative method was used to interpret the data and identify themes. The recurrent themes were: (a) positive experiences in teaching online sport for development courses, (b) learning how to become effective teachers in an English-medium program, and (c) the importance of faculty professional development. To better support Japanese professors’ online teaching, this study encourages academic departments, administrators, and faculty to better design professional development activities that enhance the quality of online education and the use of English as the medium of instruction.
Prioritizing Factors of Panic Buying Behaviour: A Neutrosophic Analytical Approach
Authors: Shri Charu , Verma Aastha , Gupta Garima , Kumra Rajeev
Published: May 2023

In a crisis, panic buying (PB) has negative ramifications for manufacturers, suppliers, retailers, consumers and the overall economy. There is a plethora of research in extant literature identifying the factors causing PB, but none has prioritized them so that firms can devise focused strategies to tackle the situation of PB. In this research, through extant literature and experts’ opinion, 18 PB factors (PBFs) are identified. The neutrosophic analytical hierarchy process is used for prioritizing the factors based on single-valued triangular neutrosophic numbers. From the 18 PBFs, on the basis of ranking received from results, top 50% most influencing factors are social media, fear of missing out, peer influence, social learning, product importance, cultural values, rumours, sense of security and government regulations. Thereafter, in close conjunction with these factors, most significant interventions/measures to curb PB are presented in the form of a PB prevention and control framework. The knowledge of the top influencing factors of PB is vital for policymakers, administrators, marketers, retailers and consumers so that they can devise appropriate interventions when required.
Social Support System and Old Age Vulnerability: An Investigation in India
Authors: Ghosh Dona
Published: May 2023

Population ageing is increasingly receiving attention in India. With economic development, a sustainable social support system during old age is essential to ensure life-long wellbeing. An accurate estimation of the problem and identification of appropriate vulnerable groups are indispensable for the success of any sustainable social support policy. However, such an attempt is lacking in the literature. Moreover, those, who tried to estimate the old-age vulnerability, mainly adopted the unidimensional vulnerability approach, and considered a single period. The present study, however, argues that vulnerability is a multi-dimensional phenomenon, and developed a comprehensive index. Furthermore, using quantitative and qualitative analyses, the study identified the extent of vulnerability among the elderly people across gender, socio-religion identity, household financial status, level of education and geographical residence. The findings have policy implications in presenting a comprehensive tool and identifying the vulnerable social groups to design a sustainable social support system for the older population.

JEL Classifications: D69, I31, J12, Z18
A Case of Cutaneous Vasculitis in the Setting of Systemic Lupus Erythematosus and Cocaine Use
Authors: Jaenke Chad M. , Moore Sara R. , Miller Matthew D. , Garg Anu
Published: May 2023

Cocaine, one of most prevalent illicit substances in the United States, affects a multitude of organ systems and precedes numerous negative health outcomes. Many of the consequences of cocaine are linked to induction of vasoconstriction. For this reason, cocaine users are placed at considerable risk of ischemic stroke, myocardial infarction, and cardiac arrhythmias. Furthermore, a prominent contaminant, levamisole, has been widely implicated in predisposing individuals to developing or exacerbating cutaneous vasculitides. This report details a 31-year-old woman with acute, localized necrotic skin lesions after cocaine use. Her clinical picture was complicated by a 17-year history of systemic lupus erythematosus (SLE) and Raynaud’s phenomenon. This case examines the challenge of forming a differential diagnosis, initiating an appropriate workup, and interpreting serologic-based and immunologic-based studies to differentiate between SLE and drug-based etiologies of skin necrosis. Finally, we discuss appropriate treatment plans to mitigate symptoms and reduce future instances of drug-induced vasculitis.
The COVID-19 Pandemic, Social Ties, and Psychosocial Well-Being of Middle-Aged Women in Rural Africa
Authors: Agadjanian Victor
Published: May 2023

The study contributes to the understanding of the societal impact of the coronavirus disease 2019 pandemic in the Global South by examining longer term implications of pandemic-induced disruptions and deprivations for social ties and psychosocial well-being. Using data from a survey of middle-aged women in rural Mozambique, the author finds a negative association between the pandemic-triggered household economic decline and perceived changes in the quality of relations with marital partners, non-coresident children, and relatives, but not with generally more distant actors, such as coreligionists and neighbors. In turn, multivariable analyses detect a positive association of changes in the quality of family and kin ties with participants’ life satisfaction, regardless of other factors. Yet women’s expectations for changes in their household living conditions in the near future show a significant association only with changes in the quality of relations with marital partners. The author situates these findings within the context of women’s enduring vulnerabilities in low-income patriarchal settings.
Politics, Planning and the Future of the Gauteng City-Region
Authors: Ebrahim Zayd , Everatt David
Published: May 2023

The Gauteng City-Region (GCR) incorporates the three major metropolitan municipalities of Johannesburg, Tshwane and Ekurhuleni and is the most important polycentric urban area in southern and South Africa. This article explores the interplay between the politics and planning of urban space in the post-apartheid context in which the GCR is located. This article applies theories of postcolonial and post-apartheid urbanism to analyse the dialectics of politics and planning in city-regions and in relation to their component cities, to help answer the key question: How is politics shaping planning in the GCR in the democratic period, and with what future impact?
Comparison between 5 extractions methods in either plasma or serum to determine the optimal extraction and matrix combination for human metabolomics
Authors: Lepoittevin Maryne , Blancart-Remaury Quentin , Kerforne Thomas , Pellerin Luc , Hauet Thierry , Thuillier Raphael
Published: May 2023

Background

Although metabolomics continues to expand in many domains of research, methodological issues such as sample type, extraction and analytical protocols have not been standardized, impeding proper comparison between studies and future research.

Methods

In the present study, five solvent-based and solid-phase extraction methods were investigated in both plasma and serum. All these extracts were analyzed using four liquid chromatography coupled with high resolution mass spectrometry (LC–MS) protocols, either in reversed or normal-phase and with both types of ionization. The performances of each method were compared according to putative metabolite coverage, method repeatability and also extraction parameters such as overlap, linearity and matrix effect; in both untargeted (global) and targeted approaches using fifty standard spiked analytes.

Results

Our results verified the broad specificity and outstanding accuracy of solvent precipitation, namely methanol and methanol/acetonitrile. We also reveal high orthogonality between methanol-based methods and SPE, providing the possibility of increased metabolome coverage, however we highlight that such potential benefits must be weighed against time constrains, sample consumption and the risk of low reproducibility of SPE method. Furthermore, we highlighted the careful consideration about matrix choice. Plasma showed the most suitable in this metabolomics approach combined with methanol-based methods.

Conclusions

Our work proposes to facilitate rational design of protocols towards standardization of these approaches to improve the impact of metabolomics research.
Early stage evaluation of cancer stem cells using platinum nanoparticles/CD133+ enhanced nanobiocomposite
Authors: Sadi Solmaz , Khalilzadeh Balal , Mahdipour Mahdi , Sokouti Nasimi Fatemeh , Isildak Ibrahim , Davaran Soodabeh , Rashidi Mohammad-Reza , Bani Farhad
Published: May 2023

Background

Cancer stem cells (CSCs) are of great diagnostic importance due to their involvement in tumorigenesis, therapeutic resistance, metastasis and relapse.

Method

In this work, a sensitive electrochemical cytosensor was successfully established to detect HT-29 colorectal cancer stem cells based on a nanocomposite composed of mesoporous silica nanoparticles (MSNs) and platinum nanoparticles (PtNPs) using a simple and fast electrodeposition technique on a glassy carbon electrode (GCE).

Results

According to SEM images, the PtNPs nanoparticles formed on the MSNs substrate are about 100 nm. As expected, high-rate porosity, increased surface-to-volume ratio, provides appropriate local electron transfer rate and suitable platform for the efficient formation of PtNPs. These features allow direct and stable binding of biotinylated monoclonal antibody of CD133to streptavidin (Strep) and the subsequent availability of active sites for CSCs identification. Differential pulse voltammetry (DPV) results show that close interaction of CD133+cells with monoclonal antibodies reduces charge transfer and electrical current, as confirmed by square wave voltammogram (SWV). Based on the recorded current versus number of CSCs, we noted that our developed system can sense CSCs from 5 to 20 cells/5 μL.

Conclusions

As a proof of concept, the designed nanobiocomposite was able to specifically detect CD133+cells compared to whole HT-29 cells before magnetic activated cell sorting (MACS) process.
Protective effect of L-pipecolic acid on constipation in C57BL/6 mice based on gut microbiome and serum metabolomic
Authors: Li Huan , Xiao Hong-yun , Yuan Li-ping , Yan Bo , Pan Ying , Tian Ping-ping , Zhang Wei-jie
Published: May 2023

Background

Functional constipation (FC) in children affects their growth, development and quality of life. L-pipecolic acid (L-PA) was decreased in FC children based on gut microbiome and serum metabolomic. In this study, loperamide-induced constipation in mice was used to evaluate the effects of L-PA on constipated mice.

Method

26 FC and 28 healthy children were recruited. Stool samples and serum samples were subjected to 16S rDNA sequencing and ultra-performance liquid chromatography/quadrupole time of flight (UPLC-Q/TOF-MS) approach, respectively. A loperamide-induced mouse constipation model was developed, and all mice were randomly divided into control (Con), loperamide (Lop) and L-PA (Lop + L-PA) treatment groups (6 mice per group). The mice in the Lop + L-PA group were given L-PA (250 mg/kg, once a day) and loperamide; the Lop group was given loperamide for 1 week, and the Con group was given saline. The fecal parameters and intestinal motility of mice in each group were detected. serum 5-HT levels and colon 5-HT expression were detected by ELISA and immunohistochemistry, respectively; qRT-PCR was used to detect the expression of AQP3 and 5-HT4R mRNA in each group.

Results

45 differential metabolites and 18 significantly different microbiota were found in FC children. The α and β diversity of gut microbiota in FC children was significantly reduced. Importantly, serum L-PA was significantly reduced in FC children. The KEGG pathway enrichment were mainly enriched in fatty acid biosynthesis, lysine degradation, and choline metabolism. L-PA was negatively associated with Ochrobactrum, and N6, N6, N6-trimethyl-l-lysine was positively associated with Phascolarcrobacterium. In addition, L-PA improved the fecal water content, intestinal transit rate, and increased the serum 5-HT levels in constipated mice. Moreover, L-PA increased the expression of 5-HT4R, reduced AQP3, and regulated constipation-associated genes.

Conclusions

Gut microbiota and serum metabolites were significantly altered in children with FC. The abundance of Phascolarctobacterium and Ochrobactrum and serum L-PA content were decreased in FC children. L-PA was found to alleviate the fecal water content, increase intestinal transit rate and the first black stool defecation time. L-PA improved constipation by increasing 5-HT and 5-HT4R expression while down-regulating AQP3 expression.
Comparative analyses and phylogenetic relationships of thirteen Pholidota species (Orchidaceae) inferred from complete chloroplast genomes
Authors: Li Lin , Wang Wanyao , Zhang Guoqiang , Wu Kunlin , Fang Lin , Li Mingzhi , Liu Zhongjian , Zeng Songjun
Published: May 2023

Background

The orchid genusPholidotaLindl. ex Hook. is economically important as some species has long been used in traditional medicine. However, the systematic status of the genus and intergeneric relationships inferred from previous molecular studies are unclear due to insufficient sampling and lack of informative sites. So far, only limited genomic information has been available. The taxonomy ofPholidotaremains unresolved and somewhat controversial. In this study, the complete chloroplast (cp.) genomes of thirteenPholidotaspecies were sequenced and analyzed to gain insight into the phylogeny ofPholidotaand mutation patterns in their cp. genomes.

Results

All examined thirteenPholidotacp. genomes exhibited typical quadripartite circular structures, with the size ranging from 158,786 to 159,781 bp. The annotation contained a total of 135 genes in each cp. genome, i.e., 89 protein-coding genes, 38 tRNA genes, and eight rRNA genes. The codon usage analysis indicated the preference of A/U-ending codons. Repeat sequence analysis identified 444 tandem repeats, 322 palindromic repeats and 189 dispersed repeats. A total of 525 SSRs, 13,834 SNPs and 8,630 InDels were detected. Six mutational hotspots were identified as potential molecular markers. These molecular markers and highly variable regions are expected to facilitate future genetic and genomic studies. Our phylogenetic analyses confirmed the polyphyletic status of the genusPholidota, with species grouped into four main clades:Pholidotas.s. was resolved as the sister to a clade containing species ofCoelogyne; the other two clades clustered together with species ofBulleyiaandPanisea, respectively; speciesP. ventricosawas placed at the basal position, deviated from all other species.

Conclusion

This is the first study to comprehensively examine the genetic variations and systematically analyze the phylogeny and evolution ofPholidotabased on plastid genomic data. These findings contribute to a better understanding of plastid genome evolution ofPholidotaand provide new insights into the phylogeny ofPholidotaand its closely related genera within the subtribe Coelogyninae. Our research has laid the foundation for future studies on the evolutionary mechanisms and classification of this economically and medicinally important genus.
Robotic magnetic navigation-guided pulmonary vein isolation in an atrial fibrillation patient with dextrocardia situs inversus: techniques and potential advantages
Authors: Luo Qingzhi , Xie Yun , Wu Liqun , Jin Qi
Published: May 2023

Background

Dextrocardia with situs inversus (DSI) is a very rare congenital anomaly. Catheter manipulation and ablation of atrial fibrillation (AF) in patients with this anatomical variant is challenging for the operators. This case report presents a safe and effective AF ablation guided by the robotic magnetic navigation (RMN) system in combination with intracardiac echocardiograhy (ICE) in a patient with DSI.

Case presentation

A 64-year-old male with DSI was referred for catheter ablation of symptomatic, drug-refractory paroxysmal AF. One transseptal access was achieved via the left femoral vein under the guidance of ICE. The three-dimensional reconstruction of the left atrium and the pulmonary veins (PVs) were performed by the magnetic catheter using the CARTO and the RMN system. Then, the electroanatomic map and pre-acquired CT images were merged. Finally, bilateral circumferential ablation lines were delivered around the ipsilateral PV ostia to achieve complete PV isolation (PVI).

Conclusions

This case demonstrates that AF catheter ablation under the guidance of the RMN system using ICE is feasible and safe in a patient with DSI. Moreover, the combination of these technologies broadly facilitates treatment of patients with complex anatomy, while reducing the risk of complications.
Neutral theory: applicability and neutrality of clinical study endpoints where a disease-specific instrument is available
Authors: Jandhyala Ravi
Published: May 2023

Background

There is a pressing need to improve the accuracy of rare disease clinical study endpoints. Neutral theory, first described here, can be used to assess the accuracy of endpoints and improve their selection in rare disease clinical studies, reducing the risk of patient misclassification.

Methods

Neutral theory was used to assess the accuracy of rare disease clinical study endpoints and the resulting probability of false positive and false negative classifications at different disease prevalence rates. Search strings were extracted from the Orphanet Register of Rare Diseases using a proprietary algorithm to conduct a systematic review of studies published until January 2021. Overall, 11 rare diseases with one disease-specific disease severity scale (133 studies) and 12 rare diseases with more than one disease-specific disease severity scale (483 studies) were included. All indicators from clinical studies were extracted, and Neutral theory was used to calculate their match to disease-specific disease severity scales, which were used as surrogates for the disease phenotype. For those with more than one disease-severity scale, endpoints were compared with the first disease-specific disease severity scale and a composite of all later scales. A Neutrality score of > 1.50 was considered acceptable.

Results

Around half the clinical studies for half the rare diseases with one disease-specific disease severity score (palmoplantar psoriasis, achalasia, systemic lupus erythematosus, systemic sclerosis and Fournier’s gangrene) met the threshold for an acceptable match to the disease phenotype, one rare disease (Guillain-Barré syndrome) had one study with an acceptable match, and four diseases (Behcet’s syndrome, Creutzfeldt-Jakob disease, atypical hemolytic uremic syndrome and Prader-Willi syndrome) had no studies. Clinical study endpoints in almost half the rare diseases with more than one disease-specific DSS (acromegaly, amyotrophic lateral sclerosis, cystic fibrosis, Fabry disease and juvenile rheumatoid arthritis) were a better match to the composite, while endpoints in the remaining rare diseases (Charcot Marie Tooth disease, Gaucher disease Type I, Huntington’s disease, Sjogren’s syndrome and Tourette syndrome) were a worse match. Misclassifications varied with increasing disease prevalence.

Conclusions

Neutral theory confirmed that disease-severity measurement needs improvement in rare disease clinical studies, especially for some diseases, and suggested that the potential for accuracy increases as the body of knowledge on a disease increases. Using Neutral theory to benchmark disease-severity measurement in rare disease clinical studies may reduce the risk of misclassification, ensuring that recruitment and treatment effect assessment optimise medicine adoption and benefit patients.
Peripheral CD4+CD25hiCD127low regulatory T cells are increased in patients with gastrointestinal cancer
Authors: Qiu Junlan , Shi Weiqiang , Zhang Jin , Gao Qinqin , Feng Lin , Zhuang Zhixiang
Published: May 2023

Background

Regulatory T cells (Tregs) play an important role in regulation of immune response and immunologic tolerance in cancer. Gastrointestinal cancer is still a leading cause of cancer-related death in the world. This study aimed to detect Tregs in patients with gastrointestinal cancer.

Methods

In this study, 45 gastric cancer patients, 50 colorectal cancer patients and 50 healthy controls were enrolled. Flow cytometry was used to detect CD4+CD25hiCD127low Tregs, CD4+CD25hi, and CD4+ cells in peripheral blood. Cytokine interleukin-10 (IL-10) and transforming growth factor-β1 (TGF-β1) in peripheral blood and in the supernatant of Tregs cultures were measured by enzyme linked immunosorbent assay.

Results

Compared with healthy controls, the levels of CD4+CD25hiCD127low Tregs and CD4+CD25hi cells increased significantly in patients with gastrointestinal cancer. Patients with gastrointestinal cancer also showed a significantly increased levels of IL-10 and TGF-β1 in both peripheral blood and CD4+CD25hiCD127low Tregs culture medium.

Conclusion

The present study firstly demonstrated that gastrointestinal patients have a compromised immune status where the CD4+CD25hiCD127low Tregs, as well as levels of IL-10 and TGF-β1 are elevated. The data offered new information for understanding the immunological features of gastrointestinal patients, as well as provided new insights into approaches to develop new immunotherapies for patients with gastrointestinal cancer.
Salmonella Durban meningitis: case report and genomics study
Authors: Diasi Christelle Nanga , Ceyssens Pieter-Jan , Vodolazkaia Alexandra , Mukovnikova Marina , Dorval Sarah , Bauraind Olivia , Mattheus Wesley
Published: May 2023

Background

Bacterial meningitis caused by non-typhoid Salmonella can be a fatal condition which is more common in low and middle-income countries.

Case presentation

We report the case of a Salmonella meningitis in a Belgian six-month old male infant. The first clinical examination was reassuring, but after a few hours, his general state deteriorated. A blood test and a lumbar puncture were therefore performed. The cerebrospinal fluid analysis was compatible with a bacterial meningitis which was later identified by the NRC (National Reference Center) as Salmonella enterica serovar Durban.

Conclusions

In this paper, we present the clinical presentation, genomic typing, and probable sources of infection for an unusually rare serovar of Salmonella. Through an extended genomic analysis, we established its relationship to historical cases with links to Guinea.
Effect of appropriate empirical antimicrobial therapy on mortality of patients with Gram-negative bloodstream infections: a retrospective cohort study
Authors: Xu Shanshan , Song Zhihui , Han Furong , Zhang Chao
Published: May 2023

Background

Little evidence exists regarding the prevalence of pathogens in bloodstream infections (BSIs), the mortality risk, and the benefit of combination therapy over monotherapy. This study aims to describe patterns of empiric antimicrobial therapy, and the epidemiology of Gram-negative pathogens, and to investigate the effect of appropriate therapy and appropriate combination therapy on the mortality of patients with BSIs.

Methods

This was a retrospective cohort study including all patients with BSIs of Gram-negative pathogens from January 2017 to December 2022 in a Chinese general hospital. The in-hospital mortality was compared between appropriate and inappropriate therapy, and between monotherapy and combination therapy for patients receiving appropriate therapy. We used Cox regression analysis to identify factors independently associated with in-hospital mortality.

Results

We included 205 patients in the study, of whom 147 (71.71%) patients received appropriate therapy compared with 58 (28.29%) who received inappropriate therapy. The most common Gram-negative pathogen was Escherichia coli (37.56%). 131 (63.90%) patients received monotherapy and 74 (36.10%) patients received combination therapy. The in-hospital mortality was significantly lower in patients administered appropriate therapy than inappropriate therapy (16.33% vs. 48.28%, p = 0.004); adjusted hazard ratio [HR] 0.55 [95% CI 0.35–0.84], p = 0.006). In-hospital mortality was also not different in combination therapy and monotherapy in the multivariate Cox regression analyses (adjusted HR 0.42 [95% CI 0.15–1.17], p = 0.096). However, combination therapy was associated with lower mortality than monotherapy in patients with sepsis or septic shock (adjusted HR 0.94 [95% CI 0.86–1.02], p = 0.047).

Conclusions

Appropriate therapy was associated with a protective effect on mortality among patients with BSIs due to Gram-negative pathogens. Combination therapy was associated with improved survival in patients with sepsis or septic shock. Clinicians need to choose optical empirical antimicrobials to improve survival outcomes in patients with BSIs.
Relationship between key continuous glucose monitoring-derived metrics and specific cognitive domains in patients with type 2 diabetes mellitus
Authors: Dong Shanshan , Wang Lina , Zhao Chenxu , Zhang Rui , Gao Zhaoyu , Jiang Lei , Guo Yingying , Zhou Huimin , Xu Shunjiang
Published: May 2023

Background

Continuous glucose monitoring (CGM)-derived time in range (TIR) is closely associated with micro- and macrovascular complications in type 2 diabetes mellitus (T2DM). This study was performed to investigate the relationship between key CGM-derived metrics and specific cognitive domains in patients with T2DM.

Methods

Outpatients with T2DM who were otherwise healthy were recruited for this study. A battery of neuropsychological tests was performed to evaluate cognitive function, including memory, executive functioning, visuospatial ability, attention, and language. Participants wore a blinded flash continuous glucose monitoring (FGM) system for 72 h. The key FGM-derived metrics were calculated, including TIR, time below range (TBR), time above range (TAR), glucose coefficient of variation (CV), and mean amplitude of glycemic excursions (MAGE). Furthermore, the glycemia risk index (GRI) was also calculated by the GRI formula. Binary logistic regression was used to assess risk factors for TBR, and we further analysed the associations between neuropsychological test results and key FGM-derived metrics with multiple linear regressions.

Results

A total of 96 outpatients with T2DM were recruited for this study, with 45.8% experiencing hypoglycemia (TBR< 3.9 mmol/L). Spearman analysis results revealed that a higher TBR< 3.9 mmol/L was correlated with worse performance on the Trail Making Test A (TMTA), Clock Drawing Test (CDT), and cued recall scores (P < 0.05). Logistic regression analysis results indicated that the TMTA (OR = 1.010, P = 0.036) and CDT (OR = 0.429, P = 0.016) scores were significant factors influencing the occurrence of TBR< 3.9 mmol/L. Multiple linear regressions further demonstrated that TBR< 3.9 mmol/L (β = -0.214, P = 0.033), TAR> 13.9 mmol/L (β = -0.216, P = 0.030) and TAR10.1–13.9 mmol/L (β = 0.206, P = 0.042) were significantly correlated with cued recall scores after adjusting for confounding factors. However, TIR, GRI, CV and MAGE showed no significant correlation with the results of neuropsychological tests (P > 0.05).

Conclusions

A higher TBR< 3.9 mmol/L and TAR> 13.9 mmol/L were associated with worse cognitive functions (memory, visuospatial ability, and executive functioning). Conversely, a higher TAR of 10.1–13.9 mmol/L was associated with better memory performance in memory tasks.
Association of chorioamnionitis with infertility treatment and subsequent neonatal outcomes in the US: a population-based cohort study
Authors: Ni Meng , Li Lijuan , Zhang Qianqian , Zhao Jiuru , Li Wei , Shen Qianwen , Yao Dongting , Wang Tao , Li Baihe , Ding Xiya , Qi Sudong , Liu Zhiwei
Published: May 2023

Background

Chorioamnionitis (CAM) is a common risk factor for preterm births, resulting in several adverse outcomes. The association between infertility treatment and CAM is unclear. Therefore, this study examined the association between infertility treatment and CAM and described subsequent neonatal outcomes.

Methods

This population-based cohort study used data from the National Vital Statistics System Database. We included women who had a singleton live birth from January 1, 2016 to December 31, 2018. Women-infant pairs were stratified by infertility treatment, and the main outcome was a reported diagnosis of CAM in a checkbox format: clinical CAM or maternal temperature of > 38 °C. Multivariate logistic regression was used to examine the association between infertility treatment and CAM and the effect of infertility treatment on neonatal outcomes in women diagnosed with CAM.

Results

The final sample comprised 10,900,495 woman-infant pairs, and 1.4% received infertility treatment. Compared with the natural conception group, women receiving infertility treatment had a significantly higher risk of CAM (adjusted odds ratio [aOR] 1.772 [95% confidence interval {CI}, 1.718–1.827]). Furthermore, newborns exposed to CAM had a higher risk of very low birth weight (VLBW) (aOR, 2.083 [95% CI, 1.664–2.606], P < .001), preterm birth (aOR, 1.497 [95% CI, 1.324–1.693]; P < .001), neonatal intensive care unit admission (aOR, 1.234 [95% CI, 1.156–1.317]; P < .001), and other adverse neonatal outcomes in the infertility treatment group compared with ones conceived naturally.

Conclusions

This study found that women who received infertility treatment had a higher risk of CAM. And CAM deteriorated neonatal outcomes in the infertility treatment group.
Real-world practice of conversion surgery for unresectable hepatocellular carcinoma - a single center data of 26 consecutive patients
Authors: Zhang Bo , Shi Xuetao , Cui Kai , Li Zhongchao , Li Lei , Liu Zhaogang , Zhang Chengsheng , Sun Pengfei , Zhong Jingtao , Sun Zhicheng , Chang Zhibin , Ma Zhao , Gordon-Weeks Alex , Li Mingming , Zhao Lei
Published: May 2023

Aim

To understand the proportion of uHCC (unresectable hepatocellular carcinoma) patients who achieve successful conversion resection in a high-volume setting with state of the art treatment options.

Methods

We retrospectively reviewed all HCC patients hospitalized to our center from June 1st, 2019 to June 1st, 2022. Conversion rate, clinicopathological features, response to systemic and/or loco-regional therapy and surgical outcomes were analyzed.

Results

A total of 1,904 HCC patients were identified, with 1672 patients receiving anti-HCC treatment. 328 patients were considered up-front resectable. Of the remaining 1344 uHCC patients, 311 received loco-regional treatment, 224 received systemic treatment, and the remainder (809) received combination systemic plus loco-regional treatment. Following treatment, one patient from the systemic group and 25 patients from the combination group were considered to have resectable disease. A high objective response rate (ORR) was observed in these converted patients (42.3% under RECIST v1.1 and 76.9% under mRECIST criteria). The disease control rate (DCR) reached 100%. 23 patients underwent curative hepatectomy. Major post-operative morbidity was equivalent in the both groups (P=0.76). Pathologic complete response (pCR) was 39.1%. During conversion treatment, grade 3 or higher treatment-related adverse events (TRAEs) were observed in 50% of patients. The median follow-up time was 12.9 months (range, 3.9~40.6) from index diagnosis and 11.4 months (range, 0.9~26.9) from resection. Three patients experienced disease recurrence following conversion surgery.

Conclusions

By intensive treatment, a small sub-group of uHCC patients (2%) may potentially be converted to curative resection. Loco-regional combined with systemic modality was relative safe and effective in the conversion therapy. Short-term outcomes are encouraging, but long-term follow-up in a larger patient population are required to fully understand the utility of this approach.
Long-term effectiveness and safety of lacosamide as adjunctive therapy in children and adolescents with refractory epilepsy: a real-world study
Authors: Zhao Ting , Yu Lu-hai , Zhang Hui-lan , Yu Jing , Feng Jie , Wang Ting-ting , Sun Yan , Li Hong-jian
Published: May 2023

Purpose

The effectiveness and tolerability of lacosamide (LCM) among Chinese children and adolescents with refractory epilepsy has not yet been established. Therefore, the objective of this study was to assess the effectiveness and tolerability of LCM among children and adolescents with refractory epilepsy in Xinjiang, Northwest China.

Methods

Effectiveness was assessed by measuring changes in seizure frequency at 3, 6 and 12 months compared with baseline. Patients that achieved ≥ 50% reduction in the frequency of all seizures per month, relative to baseline, were considered to be responders.

Results

105 children and adolescents with refractory epilepsy were enrolled in the study. The responder rates were 47.6%, 39.2%, and 31.9%, respectively at 3, 6, and 12 months. Seizure freedom rates were 32.4%, 28.9%, and 23.6% at 3, 6, and 12 months, respectively. The retention rates at 3, 6, and 12 months were 92.4%, 78.1%, and 69.5%, respectively. The maintenance dose of LCM within the responder group (8.2 ± 4.5 mg·kg− 1·d− 1) was significantly higher compared to the non-responder group (7.3 ± 2.3 mg·kg− 1·d− 1) (p < 0.05). At first follow-up, 44 patients (41.9%) reported experiencing at least one treatment-emergent adverse events.

Conclusion

This real-world study of children and adolescents validated that LCM was both an effective and well-tolerated treatment option for the treatment of refractory epilepsy.
Improved access to HIV diagnosis and linkage to antiretroviral therapy among children in Southern Nigeria: a before-after study
Authors: Nwanja Esther , Nwaokoro Pius , Akpan Uduak , Toyo Otoyo , Ezeh Golda , Elechi Iheanyichukwu , Idiong Helen , Badru Titilope , Sanwo Olusola , Idemudia Augustine , Pandey Satish Raj , Khamofu Hadiza , Bateganya Moses
Published: May 2023

Background

Globally, two out of five children living with HIV (CLHIV) are unaware of their HIV status, and a little more than 50% are receiving antiretroviral therapy (ART). This paper describes case-finding strategies and their contribution to identifying CLHIV and linking them to ART in Nigeria.

Methods

This before-after study used program data abstracted during the implementation of different paediatric-focused strategies (provider-initiated testing and counselling, orphans and vulnerable children testing, family-based index testing, early infant diagnosis (EID), community-driven EID, and community-based testing) delivered in health facilities and in communities to improve HIV case identification. Data were abstracted for children (0 to 14 years) who received HIV testing services and were initiated on ART in Akwa Ibom State, Nigeria during the pre-implementation period (April–June 2021) and during the implementation period (July–September 2021). Descriptive statistics were used to describe the testing coverage, positivity rate (proportion of tests that were positive for HIV), linkage to ART, and ART coverage, by age, sex, and testing modality. Interrupted time series analysis (ITSA) on STATA 14 was used to estimate the effect of the implementation of these strategies on HIV testing uptake and positivity rate at a 0.05 significance level.

Results

A total of 70,210 children were tested for HIV within the six-month period, and 1,012 CLHIV were identified. A total of 78% (n = 54,821) of the tests and 83.4% (n = 844) CLHIV were diagnosed during the implementation period. During implementation, the HIV positivity rate increased from 1.09% (168/15,389) to 1.54% (844/54,821), while linkage to ART increased from 99.4% (167/168) to 99.8% (842/844). The contribution from community-based modalities to CLHIV identified increased from 63% (106/168) to 84% (709/844) during the implementation, with the majority, 60.8% (431/709), from community-based index testing. Overall, ART coverage increased from 39.7 to 55.6% at the end of the intervention period.

Conclusion

The findings show that expanding differentiated HIV testing approaches provided mostly in the community significantly increased pediatric case identification. However, ART coverage remains low, especially for younger age groups, and requires further efforts.
Survival of children with trisomy 18 associated with the presence of congenital heart disease and intervention in the Republic of Korea
Authors: Song In Gyu , Shin Seung Han , Cho Yoon-Min , Lim Youna
Published: May 2023

Background

Trisomy 18 syndrome (T18) is the second most common autosomal trisomy and has a high risk of fetal loss and stillbirth. Aggressive surgical treatments for the respiratory, cardiac, or digestive systems of patients with T18 were previously futile, while the results of recent studies are controversial. Over the past decade, there have been approximately 300,000 to 400,000 births annually in the Republic of Korea; however, there have been no nationwide studies on T18. This nationwide retrospective cohort study aimed to determine the prevalence of T18 in Korea and its prognosis according to the presence of congenital heart disease and relevant interventions.

Methods

This study utilized NHIS-registered data between 2008 and 2017. A child was defined as having T18 if the ICD-10 revision code Q91.0–3 was reported. Subgroup analysis was performed for children with congenital heart diseases, and survival rates were compared based on the history of cardiac surgical or catheter interventions. The primary outcomes in this study were the survival rate during the first hospitalization period and the 1-year survival rate.

Results

Of the children born between 2008 and 2017, 193 were diagnosed with T18. Of these, 86 died, with a median survival of 127 days. The 1-year survival rate for children with T18 was 63.2%. The survival rate in the first admission of children with T18 who did and did not have congenital heart disease was 58.3% and 94.1%, respectively. Children with heart disease who underwent surgical or catheter intervention had a longer survival time than those who did not.

Conclusions

We suggest these data could be used in ante- and postnatal counseling. Ethical concerns about the prolonged survival of children with T18 remain; however, the potential benefits of interventions for congenital heart disease in this population need further study.