bluuebunny/crossref_metadata_2025 huggingface dataset:
Penyebab Pengembalian Berkas Klaim Pelayanan Kesehatan JKN di Rumah Sakit Ibu Dan Anak Mutiara Bunda Padang
Authors: Ahdinur Rahmi Yanti , Semiarty Rima , Fahmy Rahmi
Published: June 2023

Permasalahan pengembalian berkas klaim disebabkan oleh ketidaklengkapan dan ketidaksesuaian dokumen berkas klaim mulai dari pelayanan administrasi, pengisian resume medis, pengkodean dan entri data, verifikasi berkas klaim, serta pengajuan klaim. RS Mutiara Bunda merupakan rumah sakit Ibu Anak yang bekerjasama dengan BPJS Kesehatan, kasus pending cukup tinggi dibandingkan dari seluruh klaim yang ditagihkan tahun 2021 pada RSIAyaitu sebanyak 2%. Tujuan penelitian ini adalah diketahuinya informasi mendalam terkait pengembalian berkas klaim pelayanan kesehatan JKN di RSIA Mutiara Bunda. Penelitian ini menggunakan desain kualitatif dengan teknik pengumpulan data melalui wawancara mendalam, observasi, dan telaah dokumen, serta analisis data melalui tahapan triangulasi sumber dan metode. Adapun hasil penelitian dari sisi pelayanan admission, belum lengkapnya dokumen klaim yang dipersyaratkan, dari sisi pengkodean dan entri data klaim belum sesuai dengan aturan koding, dari sisi verifikasi berkas klaim masih terjadi pending dikarenakan terlewatnya pada saat verifikasi terkait ketidaklengkapan berkas klaim, adanya formulir yang tidak terscan dan kesalahan pengkodean. Harapannya perlu pembuatan SOP dan uraian tugas pelayanan admission dan pengisian resume medis oleh dokter, pendidikan dan pelatihan koding bagi tenaga koder sehingga mengurangi kekeliruan dalam kodifikasi, memenuhi kelengkapan sarana prasarana penunjang diantaranya mesin scan dan printer untuk dapat mempercepat proses kerja koder.
Activated biocarbons derived from molasses as new tailored CO2 adsorbents
Authors: Kiełbasa Karolina
Published: June 2023

An innovative and cost-effective method for enhancing CO2 capture by modifying the textural properties of derived activated biocarbons was explored. A molasses solution was prepared with a sucrose concentration of 1 mol/dm3. A two-step synthesis process was involved, which includes the hydrothermal synthesis of spherical carbonaceous materials from molasses followed by chemical activation. The carbonaceous material to activation agent ratio was studied from 1 to 4. The CO2 adsorption of all activated biocarbons was tested at 0, 10, and 20°C and a pressure of up to 1 bar. The results showed a significant correlation between CO2 adsorption and the textural properties of the activated biocarbons. The activated biocarbon with the highest CO2 adsorption of 7.1 mmol/g at 1 bar and 0°C was successfully produced by modifying with KOH. The selectivity of CO2 over N2 calculated on the basis of the Ideal Adsorbed Solution Theory was excellent (16.5). The Sips model was found to be the most suitable, and the isosteric heats of adsorption were also specified.
Recent advances in genetic systems in obligate intracellular human-pathogenic bacteria
Authors: Fisher Derek J. , Beare Paul A.
Published: June 2023

The ability to genetically manipulate a pathogen is fundamental to discovering factors governing host–pathogen interactions at the molecular level and is critical for devising treatment and prevention strategies. While the genetic “toolbox” for many important bacterial pathogens is extensive, approaches for modifying obligate intracellular bacterial pathogens were classically limited due in part to the uniqueness of their obligatory lifestyles. Many researchers have confronted these challenges over the past two and a half decades leading to the development of multiple approaches to construct plasmid-bearing recombinant strains and chromosomal gene inactivation and deletion mutants, along with gene-silencing methods enabling the study of essential genes. This review will highlight seminal genetic achievements and recent developments (past 5 years) for Anaplasma spp., Rickettsia spp., Chlamydia spp., and Coxiella burnetii including progress being made for the still intractable Orientia tsutsugamushi. Alongside commentary of the strengths and weaknesses of the various approaches, future research directions will be discussed to include methods for C. burnetii that should have utility in the other obligate intracellular bacteria. Collectively, the future appears bright for unraveling the molecular pathogenic mechanisms of these significant pathogens.
The coherent organization of dynamic visual images
Authors: Lappin Joseph S. , Bell Herbert H.
Published: June 2023

Biological vision relies on the intrinsic spatiotemporal structure of a continuously flowing image stream. We review converging psychophysical and physiological evidence about the structure and precision of the perceived spatiotemporal organization of dynamic images. Visual acuity, temporal resolution, and contrast sensitivity have been found to involve (a) motion-produced increases in image contrast, (b) coherent phase relations among temporally varying retinal signals, and (c) physiological preservation of spatiotemporal structure from retina to cortex. Moreover, psychophysical theory and evidence show that the spatiotemporal structure of dynamic retinal images carries precise information for perceiving surfaces and motions—consistent with the corresponding differential structures of spatiotemporal images and environmental surfaces.
Association of gamma-tocopherol serum concentrations and blood pressure among adults in the United States: a cross-sectional study
Authors: Wu Zhijian , Xie Feng , Li Kai , Feng Jie , Han Leilei , Wu Yanqing
Published: June 2023

Background

hypertension is one of the major preventable risk factors for numerous diseases. The role of vitamin E in blood pressure (BP) has been controversial. We aimed to investigate the relationship between gamma-tocopherol serum concentration (GTSC) and BP

Methods

Data from 15,687 US adults from the National Health and Nutrition Examination Survey (NHANES) were analyzed. The correlations of GTSC with systolic BP (SBP), diastolic BP (DBP), and prevalence of hypertension were investigated by multivariate logistic regression models, generalized summation models, and fitted smoothing curves. Subgroup analyses were performed to investigate possible effect modifiers between them.

Results

With each natural log increase in GTSC, SBP, and DBP increased by 1.28 mmHg (β 1.28, 95% CI 0.71–1.84) and 1.15 mmHg (β 1.15, 95% CI 0.72–1.57), respectively, both P for trend < 0.001; the prevalence of hypertension increased by 12% (OR 1.12, 95% CI 1.03–1.22), P for trend 0.008. In subgroup analysis, in drinkers, with each natural log increase in GTSC, SBP, and DBP increased by 1.77 mmHg (β 1.77,95% CI 1.13–2.41) and 1.37 mmHg (β 1.37,95% CI 0.9–1.85), respectively, whereas they were not correlated in non-drinkers.

Conclusion

GTSC was linearly and positively associated with SBP, DBP, and the prevalence of hypertension, and alcohol consumption may modify the relationship of GTSC with SBP and DBP.
Left atrial appendage volume is an independent predictor of atrial arrhythmia recurrence following cryoballoon pulmonary vein isolation in persistent atrial fibrillation
Authors: Pongratz J. , Riess L. , Hartl S. , Brueck B. , Tesche C. , Ebersberger U. , Helmberger T. , Crispin A. , Wankerl M. , Dorwarth U. , Hoffmann E. , Straube F.
Published: June 2023

Purpose

Pulmonary vein isolation (PVI) is the cornerstone of atrial fibrillation (AF) ablation in persistent AF (persAF), and cryoballoon PVI emerged as an initial ablation strategy. Symptomatic atrial arrhythmia recurrence following successful PVI in persAF is observed more frequently than in paroxysmal AF. Predictors for arrhythmia recurrence following cryoballoon PVI for persAF are not well described, and the role of left atrial appendage (LAA) anatomy is uncertain.

Methods

Patients with symptomatic persAF and pre-procedural cardiac computed tomography angiography (CCTA) images undergoing initial second-generation cryoballoon (CBG2) were enrolled. Left atrial (LA), pulmonary vein (PV) and LAA anatomical data were assessed. Clinical outcome and predictors for atrial arrhythmia recurrence were evaluated by univariate and multivariate regression analysis.

Results

From May 2012 to September 2016, 488 consecutive persAF patients underwent CBG2-PVI. CCTA with sufficient quality for measurements was available in 196 (60.4%) patients. Mean age was 65.7 ± 9.5 years. Freedom from arrhythmia was 58.2% after a median follow-up of 19 (13; 29) months. No major complications occurred. Independent predictors for arrhythmia recurrence were LAA volume (HR 1.082; 95% CI, 1.032 to 1.134; p = 0.001) and mitral regurgitation ≥ grade 2 (HR, 2.49; 95% CI 1.207 to 5.126; p = 0.013). LA volumes ≥110.35 ml [sensitivity: 0.81, specificity: 0.40, area under the curve (AUC) = 0.62] and LAA volumes ≥9.75 ml (sensitivity: 0.56, specificity 0.70, AUC = 0.64) were associated with recurrence. LAA-morphology, classified as chicken-wing (21.9%), windsock (52.6%), cactus (10.2%) and cauliflower (15.3%), did not predict outcome (log-rank, p = 0.832).

Conclusion

LAA volume and mitral regurgitation were independent predictors for arrhythmia recurrence following cryoballoon ablation in persAF. LA volume was less predictive and correlated with LAA volume. LAA morphology did not predict the clinical outcome. To improve outcomes in persAF ablation, further studies should focus on treatment strategies for persAF patients with large LAA and mitral regurgitation.
Sex differences in the renin-angiotensin-aldosterone system and its roles in hypertension, cardiovascular, and kidney diseases
Authors: Nwia Sarah M. , Leite Ana Paula O. , Li Xiao Chun , Zhuo Jia Long
Published: June 2023

Cardiovascular disease is a pathology that exhibits well-researched biological sex differences, making it possible for physicians to tailor preventative and therapeutic approaches for various diseases. Hypertension, which is defined as blood pressure greater than 130/80 mmHg, is the primary risk factor for developing coronary artery disease, stroke, and renal failure. Approximately 48% of American men and 43% of American women suffer from hypertension. Epidemiological data suggests that during reproductive years, women have much lower rates of hypertension than men. However, this protective effect disappears after the onset of menopause. Treatment-resistant hypertension affects approximately 10.3 million US adults and is unable to be controlled even after implementing ≥3 antihypertensives with complementary mechanisms. This indicates that other mechanisms responsible for modulating blood pressure are still unclear. Understanding the differences in genetic and hormonal mechanisms that lead to hypertension would allow for sex-specific treatment and an opportunity to improve patient outcomes. Therefore, this invited review will review and discuss recent advances in studying the sex-specific physiological mechanisms that affect the renin-angiotensin system and contribute to blood pressure control. It will also discuss research on sex differences in hypertension management, treatment, and outcomes.
Availability and trend of dissemination of cardiac rehabilitation in China: report from the multicenter national registration platform between 2012 and 2021
Authors: Zhang Sisi , Ding Rongjing , Chen Sikun , Meng Xiaoping , Jianchao Li , Wang Dao Wen , Hu Dayi
Published: June 2023

The study aimed to evaluate the current status of cardiac rehabilitation programs in China by registering and tracking patients undergoing CR programs in the database. Data were extracted from the online registry platform of the China Society of Cardiopulmonary Prevention and Rehabilitation from February 2012 to December 2021. Overall, data on 19,896 patients with cardiovascular diseases (CVDs) from 159 hospitals in 34 provinces of China were extracted. From a time point of view, the number of patients who had undergone CR and institutions that perform CR showed the first decline in 2009 and then increased until 2021. From a geographic point of view, the degree of participation varied greatly among regions, most of which were concentrated in eastern parts of China. A higher population of patients who underwent CR were male, aged less than 60 years, with low-a risk for coronary heart disease (CHD), and tended to choose the hospital-based CR program among all cases registered in the database. The top three diseases in the patients who participated in CR were CHD, hypertension, and metabolic syndrome (MS). Centers with CR were more likely to be tertiary-level hospitals. After adjusting for baseline values, there were significant differences in post-CR exercise capacity among the three groups (home-based CR group, hospital-based CR group, and hybrid CR group), which were in favor of the hybrid CR group compared with other groups. The underutilization of CR is a global issue, not just in China. Despite the number of CR programs showing an increasing trend in the past years, CR in China is still in the preliminary stage of development. Furthermore, the participation of CR in China shows wide diversity across geography, disease, age, sex, risk stratification, and hospital-level factors. These findings reinforce the importance of the implementation of effective measures to improve the participation, enrollment in, and uptake of cardiac rehabilitation.
Myosteatosis and bone marrow adiposity are not associated among postmenopausal women with fragility fractures
Authors: Badr Sammy , Dapvril Héloïse , Lombardo Daniela , Khizindar Huda , Martin Claire , Cortet Bernard , Cotten Anne , Paccou Julien
Published: June 2023

Objectives

Although paravertebral intramuscular fatty infiltration (known as myosteatosis) following a vertebral fracture is well-known, scarce data are available regarding interactions between muscle, bone, and other fat depots. Based on a homogeneous cohort comprising postmenopausal women with or without a history of fragility fracture, we aimed to better depict the interrelationship between myosteatosis and bone marrow adiposity (BMA).

Methods

102 postmenopausal women were included, 56 of whom had a fragility fracture. Mean proton density fat fraction (PDFF) was measured in the psoas (PDFFPsoas) and paravertebral (PDFFParavertebral) muscles at the lumbar level, as well as in the lumbar spine and non-dominant hip using chemical shift encoding-based water-fat imaging. Visceral adipose tissue (VAT) and total body fat (TBF) were assessed using dual X-ray absorptiometry. Statistical models were adjusted for age, weight, height (all comparisons), and bone mineral density (when considering BMA).

Results

PDFF in the psoas and paravertebral muscles was higher in the fracture group compared to controls even after adjustment for age, weight, and height (PDFFPsoas = 17.1 ± 6.1% versus 13.5 ± 4.9%, p=0.004; PDFFParavertebral = 34.4 ± 13.6% versus 24.9 ± 8.8%, p=0.002). Higher PDFFParavertebral was associated with lower PDFF at the lumbar spine (β = -6.80 ± 2.85, p=0.022) among controls but not in the fracture group. In both groups, a significant relationship between higher PDFFPsoas and higher VAT was observed (β = 20.27 ± 9.62, p=0.040 in the fracture group, and β = 37.49 ± 8.65, p<0.001 in the control group). Although solely observed among controls, a similar relationship was observed between PDFFParavertebral and TBF (β = 6.57 ± 1.80, p<0.001). No significant association was observed between BMA and other fat depots.

Conclusion

Myosteatosis is not associated with BMA among postmenopausal women with fragility fractures. Whereas myosteatosis was associated with other fat depots, BMA appears uniquely regulated.
Predicting nutritional status during pregnancy by women's empowerment in West Shewa Zone, Ethiopia
Authors: Etea Tizita Dengia , Yalew Alemayehu Worku , Sisay Mitike Molla , Shiferaw Solomon
Published: June 2023

Background

Considerable proportions of pregnant women are affected by poor nutrition outcomes in Ethiopia. Women's empowerment, on the other hand, is highly recognized as a means to achieve better maternal nutrition outcomes. However, the role of pregnant women's empowerment in nutritional status during pregnancy has not been empirically examined in Ethiopia. This study aimed to address this gap.

Objective

To assess the association of individual and composite women's empowerment dimensions with pregnant women's nutrition outcomes in West Shewa Zone, Ethiopia.

Methods

A health facility-based cross-sectional study was performed on 1,453 pregnant women living in West Shewa Zone, Ethiopia, in 2021. Exploratory and confirmatory factor analyses were conducted on half of the samples to identify and validate dimensions of pregnant women's empowerment. The associations between pregnant women's empowerment dimensions and anemia status and mid upper arm circumference levels were examined by logistic regressions.

Results

Composite pregnant women's empowerment was positively associated with both anemia status and mid-upper-arm circumference level. The odds of not being anemic were higher among pregnant women empowered in economic [adjusted odds ratio (AOR) = 1.7, 95% confidence interval (CI): 1.26, 2.22] and assertiveness (AOR = 1.9, 95% CI: 1.46, 2.38) dimensions than those not empowered in these dimensions. Empowered pregnant women in household decision-making (AOR = 1.6, 95% CI: 1.19, 2.22) and psychological (AOR = 1.4, 95% CI: 1.04, 1.85) dimensions had higher odds of having normal mid-upper-arm circumference measures than those not empowered in the respective dimensions. Communication and time dimensions were not significantly associated with any of the nutrition outcomes.

Conclusions

This study suggests that empowered pregnant women are nutritionally better off than their less empowered counterparts. This is also important in child health outcomes. Policies and programs that aim to improve maternal and child health in the study area need to consider interventions that promote the decision-making power, economic, psychological, and assertiveness dimensions of pregnant women.
A tale of two conditions: when people living with HIV meet three doses of inactivated COVID-19 vaccines
Authors: Tan Yuting , Zou Shi , Ming Fangzhao , Wu Songjie , Guo Wei , Wu Mengmeng , Tang Weiming , Liang Ke
Published: June 2023

Background

Currently, data on long-term immune responses to a homogenous booster dose of the inactivated COVID-19 vaccine are still limited among people living with HIV (PLWH).

Methods

A prospective cohort study with a 13-month follow-up was conducted in China between March 2021 and August 2022 to evaluate the dynamics of SARS-CoV-2 specific humoral and cellular immunity against three doses of the inactivated COVID-19 vaccine from before the first dose until 6 months after the booster dose vaccination among PLWH in comparison to healthy controls (HC).

Results

43 PLWH on antiretroviral therapy (ART) and 23 HC were enrolled. Compared with HC, the neutralizing antibodies (nAbs) levels among PLWH were significantly lower on days 14, 30, 60, 90, and 120 after the booster dose vaccination. Among PLWH, the nAbs titers on days 14, 30, and 60 after the booster dose were significantly higher than the peak of the second dose. However, on day 180 after the booster dose, the nAbs titers were similar to the peak of the second dose vaccination. Compared with HC, the frequencies of IFN-γ-secreting and TNF-α-secreting CD4+ and CD8+ T cells among PLWH were lower on days 14 and 180 after the booster dose vaccination. Among PLWH, increased T cell immunity was induced by the booster dose of the vaccine and kept stable on day 180 after the booster dose vaccination.

Conclusion

Although a homogenous booster dose following two doses of the inactivated COVID-19 vaccine among PLWH could elicit higher nAb titers, reduce antibody decay, and maintain T cell responses even 6 months after vaccination, the overall immunogenicity of the booster dose was found to be lower among PLWH than among healthy controls. Further strategies are needed to improve immunogenicity to the inactivated COVID-19 vaccine among PLWH.
Breast cancer associated CD169+ macrophages possess broad immunosuppressive functions but enhance antibody secretion by activated B cells
Authors: Gunnarsdottir Frida Björk , Briem Oscar , Lindgren Aida Yifter , Källberg Eva , Andersen Cajsa , Grenthe Robert , Rosenqvist Cassandra , Millrud Camilla Rydberg , Wallgren Mika , Viklund Hannah , Bexell Daniel , Johansson Martin E. , Hedenfalk Ingrid , Hagerling Catharina , Leandersson Karin
Published: June 2023

CD169+ resident macrophages in lymph nodes of breast cancer patients are for unknown reasons associated with a beneficial prognosis. This contrasts CD169+ macrophages present in primary breast tumors (CD169+ TAMs), that correlate with a worse prognosis. We recently showed that these CD169+ TAMs were associated with tertiary lymphoid structures (TLSs) and Tregs in breast cancer. Here, we show that CD169+ TAMs can be monocyte-derived and express a unique mediator profile characterized by type I IFNs, CXCL10, PGE2 and inhibitory co-receptor expression pattern. The CD169+ monocyte-derived macrophages (CD169+ Mo-M) possessed an immunosuppressive function in vitro inhibiting NK, T and B cell proliferation, but enhanced antibody and IL6 secretion in activated B cells. Our findings indicate that CD169+ Mo-M in the primary breast tumor microenvironment are linked to both immunosuppression and TLS functions, with implications for future targeted Mo-M therapy.
ITPKC polymorphism (rs7251246 T > C), coronary artery aneurysms, and thrombosis in patients with Kawasaki disease in a Southern Han Chinese population
Authors: Liu Jie , Yuan Piaoliu , Pang Yusheng , Su Danyan
Published: June 2023

Objectives

Kawasaki disease (KD) is a commonly acquired pediatric systemic vasculitis disease resulting in coronary artery aneurysm (CAA). The relationship between the ITPKC polymorphism (rs7251246) and the severity and susceptibility to KD in the Han Chinese population in Southern China remains unclear.

Methods

We enrolled 262 children as controls and 221 children with KD (46 [20.8%] with intravenous immunoglobulin resistance and 82 [37.1%] with CAA). The relationship between the ITPKC rs7251246 polymorphism, KD susceptibility, and CAA formation was investigated.

Results

While the ITPKC rs7251246 T>C polymorphism was not significantly associated with KD susceptibility, it was significantly related to the CAA risk in children with KD [CC/CT vs. TT: adjusted odds ratio [OR] 2.089, 95% confidence interval [CI] 1.085–4.020]. Male children with the rs7251246 CT/TT genotype had a significantly lower risk of thrombosis [CT/TT vs. CC: adjusted OR 0.251, 95% CI 0.068–0.923]. Children with KD, especially those with CAA, had significantly downregulated ITPKC mRNA compared to healthy children. ITPKC mRNA levels were lower in children with CAA who developed thrombosis (P=0.039). In children with KD, the CC genotype showed lower mRNA levels of ITPKC (P=0.035).

Conclusion

The ITPKC rs7251246 T>C polymorphism may be a risk factor for CAA and thrombosis in children with KD in the Han Chinese population, likely due to differences in mature mRNA levels caused by interference of RNA splicing. Dual antiplatelet therapy for thrombosis is recommended for male children with the rs7251246 CC genotype.
SARS-CoV-2 and the host-immune response
Authors: Maison David P. , Deng Youping , Gerschenson Mariana
Published: June 2023

The SARS-CoV-2 pandemic and the COVID-19 disease have affected everyone globally, leading to one of recorded history’s most significant research surges. As our knowledge evolves, our approaches to the virus and treatments must also evolve. The evaluation of future research approaches to SARS-CoV-2 will necessitate reviewing the host immune response and viral antagonism of that response. This review provides an overview of the current knowledge on SARS-CoV-2 by summarizing the virus and human response. The focuses are on the viral genome, replication cycle, host immune activation, response, signaling, and antagonism. To effectively fight the pandemic, efforts must focus on the current state of research to help develop treatments and prepare for future outbreaks.
Severe and fatal adverse events of immune checkpoint inhibitor combination therapy in patients with metastatic renal cell carcinoma: a systematic review and meta-analysis
Authors: Feng Yao-Ning , Xie Guang-Yu , Xiao Li , Mo Dun-Chang , Huang Jian-Feng , Luo Peng-Hui , Liang Xiu-Juan
Published: June 2023

Introduction

Immune checkpoint inhibitor (ICI) combination therapy has changed the treatment landscape for metastatic renal cell carcinoma (mRCC). However, little evidence exists on the treatment-related severe adverse events (SAEs) and fatal adverse events (FAEs) of ICI combination therapy in mRCC.

Method

We searched PubMed, Embase, and Cochrane Library databases to evaluate randomized controlled trials (RCTs) of ICI combination therapy versus conventional tyrosine kinase inhibitor (TKI)-targeted therapy in mRCC. Data on SAEs and FAEs were analyzed using revman5.4 software.

Results

Eight RCTs (n=5380) were identified. The analysis showed no differences in SAEs (60.5% vs. 64.5%) and FAEs (1.2% vs. 0.8%) between the ICI and TKI groups (odds ratio [OR], 0.83; 95%CI 0.58−1.19, p=0.300 and OR, 1.54; 95%CI 0.89−2.69, p=0.120, respectively). ICI-combination therapy was associated with less risk of hematotoxicities, including anemia (OR, 0.24, 95%CI 0.15–0.38, p<0.001), neutropenia (OR, 0.07, 95%CI 0.03–0.14, p<0.001), and thrombocytopenia (OR, 0.05, 95%CI 0.02−0.12, p<0.001), but with increased risks of hepatotoxicities (ALT increase [OR, 3.39, 95%CI 2.39–4.81, p<0.001] and AST increase [OR, 2.71, 95%CI 1.81−4.07, p<0.001]), gastrointestinal toxicities (amylase level increase [OR, 2.32, 95%CI 1.33–4.05, p=0.003] and decreased appetite [OR, 1.77, 95%CI 1.08–2.92, p=0.020]), endocrine toxicity (adrenal insufficiency [OR, 11.27, 95%CI 1.55–81.87, p=0.020]) and nephrotoxicity of proteinuria (OR, 2.21, 95%CI 1.06−4.61, p=0.030).

Conclusions

Compared with TKI, ICI combination therapy has less hematotoxicity in mRCC but more specific hepatotoxicity, gastrointestinal toxicity, endocrine toxicity, and nephrotoxicity, with a similar severe toxicity profile.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42023412669.
Energy metabolism and maternal-fetal tolerance working in decidualization
Authors: Meng Xinhang , Chen Chunqin , Qian Jinfeng , Cui Liyuan , Wang Songcun
Published: June 2023

One pivotal aspect of early pregnancy is decidualization. The decidualization process includes two components: the differentiation of endometrial stromal cells to decidual stromal cells (DSCs), as well as the recruitment and education of decidual immune cells (DICs). At the maternal-fetal interface, stromal cells undergo morphological and phenotypic changes and interact with trophoblasts and DICs to provide an appropriate decidual bed and tolerogenic immune environment to maintain the survival of the semi-allogeneic fetus without causing immunological rejection. Despite classic endocrine mechanism by 17 β-estradiol and progesterone, metabolic regulations do take part in this process according to recent studies. And based on our previous research in maternal-fetal crosstalk, in this review, we elaborate mechanisms of decidualization, with a special focus on DSC profiles from aspects of metabolism and maternal-fetal tolerance to provide some new insights into endometrial decidualization in early pregnancy.
Activation of ryanodine-sensitive calcium store drives pseudo-allergic dermatitis via Mas-related G protein-coupled receptor X2 in mast cells
Authors: Wang Zhao , Zhao Xi , Zhou Hongmei , Che Delu , Du Xiaojie , Ye Dan , Zeng Weihui , Geng Songmei
Published: June 2023

Mast cell (MC) activation is implicated in the pathogenesis of multiple immunodysregulatory skin disorders. Activation of an IgE-independent pseudo-allergic route has been recently found to be mainly mediated via Mas-Related G protein-coupled receptor X2 (MRGPRX2). Ryanodine receptor (RYR) regulates intracellular calcium liberation. Calcium mobilization is critical in the regulation of MC functional programs. However, the role of RYR in MRGPRX2-mediated pseudo-allergic skin reaction has not been fully addressed. To study the role of RYR in vivo, we established a murine skin pseudo-allergic reaction model. RYR inhibitor attenuated MRGPRX2 ligand substance P (SP)-induced vascular permeability and neutrophil recruitment. Then, we confirmed the role of RYR in an MC line (LAD2 cells) and primary human skin-derived MCs. In LAD2 cells, RYR inhibitor pretreatment dampened MC degranulation (detected by β-hexosaminidase retlease), calcium mobilization, IL-13, TNF-α, CCL-1, CCL-2 mRNA, and protein expression activated by MRGPRX2 ligands, namely, compound 48/80 (c48/80) and SP. Moreover, the inhibition effect of c48/80 by RYR inhibitor was verified in skin MCs. After the confirmation of RYR2 and RYR3 expression, the isoforms were silenced by siRNA-mediated knockdown. MRGPRX2-induced LAD2 cell exocytosis and cytokine generation were substantially inhibited by RYR3 knockdown, while RYR2 had less contribution. Collectively, our finding suggests that RYR activation contributes to MRGPRX2-triggered pseudo-allergic dermatitis, and provides a potential approach for MRGPRX2-mediated disorders.
The good and the bad of T cell cross-reactivity: challenges and opportunities for novel therapeutics in autoimmunity and cancer
Authors: Gouttefangeas Cécile , Klein Reinhild , Maia Ana
Published: June 2023

T cells are main actors of the immune system with an essential role in protection against pathogens and cancer. The molecular key event involved in this absolutely central task is the interaction of membrane-bound specific T cell receptors with peptide-MHC complexes which initiates T cell priming, activation and recall, and thus controls a range of downstream functions. While textbooks teach us that the repertoire of mature T cells is highly diverse, it is clear that this diversity cannot possibly cover all potential foreign peptides that might be encountered during life. TCR cross-reactivity, i.e. the ability of a single TCR to recognise different peptides, offers the best solution to this biological challenge. Reports have shown that indeed, TCR cross-reactivity is surprisingly high. Hence, the T cell dilemma is the following: be as specific as possible to target foreign danger and spare self, while being able to react to a large spectrum of body-threatening situations. This has major consequences for both autoimmune diseases and cancer, and significant implications for the development of T cell-based therapies. In this review, we will present essential experimental evidence of T cell cross-reactivity, implications for two opposite immune conditions, i.e. autoimmunity vs cancer, and how this can be differently exploited for immunotherapy approaches. Finally, we will discuss the tools available for predicting cross-reactivity and how improvements in this field might boost translational approaches.
Calibration and experiment of discrete element model parameters of Zanthoxylum bungeanum
Authors: Wang Jian , Chen Lin , Tang Yingwen , Chen Zhifan , Wu Qingsong , Han Dandan
Published: June 2023

Zanthoxylum bungeanum is a characteristic spice in culinary culture. This article focuses on the lack of intrinsic and contact parameters for Zanthoxylum bungeanum and studies the intrinsic parameters of the discrete element for tribute pepper from Hanyuan. This is to provide support for the mechanized harvesting of Zanthoxylum bungeanum. The EDEM software was used to establish a discrete element model for Zanthoxylum bungeanum granules. The intrinsic parameters of Zanthoxylum bungeanum granules, such as Three-dimensional dimension, density, Poisson’s ratio, and elastic modulus, were measured through experiments. The elastic recovery coefficient, static friction coefficient, and rolling friction coefficient between Zanthoxylum bungeanum granules and Dragon Skin 30 silicone sheets were also measured. Subsequently, the elastic recovery coefficient, static friction coefficient, and rolling friction coefficient between Zanthoxylum bungeanum granules and materials, as well as between Zanthoxylum bungeanum granules were obtained through discrete element simulation experiments, steepest climb test, and Quadratic regression orthogonal rotation combination test. Finally, the Angle of repose was used for verification experiments. The results showed that the elastic recovery coefficient, static friction coefficient, and rolling friction coefficient between Zanthoxylum bungeanum granules and materials were 0.437, 0.758, and 0.0136, respectively, while those between Zanthoxylum bungeanum granules were 0.378, 0.56, and 0.0143, respectively. The error between the simulation angle of repose and the measured angle of repose was 0.204%, verifying the reliability of the discrete element model for Zanthoxylum bungeanum granules. This method is of great significance for the design and optimization of Zanthoxylum bungeanum harvesters.
The ethical challenges of personalized digital health
Authors: Maeckelberghe Els , Zdunek Kinga , Marceglia Sara , Farsides Bobbie , Rigby Michael
Published: June 2023

Personalized digital health systems (pHealth) bring together in sharp juxtaposition very different yet hopefully complementary moral principles in the shared objectives of optimizing health care and the health status of individual citizens while maximizing the application of robust clinical evidence through harnessing powerful and often complex modern data-handling technologies. Principles brought together include respecting the confidentiality of the patient–clinician relationship, the need for controlled information sharing in teamwork and shared care, benefitting from healthcare knowledge obtained from real-world population-level outcomes, and the recognition of different cultures and care settings. This paper outlines the clinical process as enhanced through digital health, reports on the examination of the new issues raised by the computerization of health data, outlines initiatives and policies to balance the harnessing of innovation with control of adverse effects, and emphasizes the importance of the context of use and citizen and user acceptance. The importance of addressing ethical issues throughout the life cycle of design, provision, and use of a pHealth system is explained, and a variety of situation-relevant frameworks are presented to enable a philosophy of responsible innovation, matching the best use of enabling technology with the creation of a culture and context of trustworthiness.
Discordance of global assessment between the patients and physicians predicts 9-year pain-related outcomes in rheumatoid arthritis patients
Authors: Hayashi Kazuhiro , Miki Kenji , Shi Kenrin , Yukioka Masao , Hirayama Takehiro , Tsujimoto Kohei , Takeuchi Takao , Hayaishi Yasuhisa , Hayaishi Masahiro
Published: June 2023

Introduction

Perspectives regarding the disease state often differ between patients with rheumatoid arthritis (RA) and physicians. The aim of the present longitudinal cohort study was to investigate the impact of the discordance in global assessments between patients and physicians on 9-year pain-related outcomes in patients with rheumatoid arthritis.

Method

Sixty-eight consecutive outpatients with rheumatoid arthritis on their first visit to a tertiary center were included. Baseline measurements included demographic data, drugs used, disease activity, and a modified Health Assessment Questionnaire (mHAQ). Discordance in global assessment between patients and physicians at baseline was defined as 10 mm higher in the patient global assessment (PGA) than in the physician global assessment. A 9-year follow-up assessment included pain intensity, the European Quality of Life 5 Dimensions 3 Level (EQ-5D-3L) scale, Pain Catastrophizing Scale (PCS), Hospital Anxiety and Depression Scale (HADS), Pain Disability Assessment Scale (PDAS), and Pain Self-Efficacy Questionnaire (PSEQ).

Results

The number of patients with discordance was 26 (38%) in 68 patients. Patients with a 10 mm higher PGA than the physician global assessment at baseline measurements had significantly worse pain intensity, PCS score, PSEQ score, and EQ-5D-3L score measurements at the 9-year follow-up than those with concordance. A higher mHAQ score and 10 mm higher PGA at baseline were significantly independently associated with the EQ-5D-3L scale score and pain intensity at the 9-year follow-up.

Conclusion

This longitudinal cohort study suggested that discordance in global assessment between patients and physicians modestly predicted worse 9-year pain-related outcomes in patients with rheumatoid arthritis.
Novel cost-effective design for bio-volatilization studies in photosynthetic microalgae exposed to arsenic with emphasis on growth and glutathione modulation
Authors: Upadhyay Atul K. , Mallick Shekhar , Singh Ranjan , Singh Lav , Singh Nitesh , Mandotra S. K. , Singh Arpit , Srivastava Ravi Prakash , Pandey Shivaraman , Saxena Gauri
Published: June 2023

A novel laboratory model was designed to study the arsenic (As) biotransformation potential of the microalgaeChlorella vulgarisandNannochloropsissp. and the cyanobacteriumAnabaena doliolum. The Algae were treated under different concentrations of As(III) to check their growth, toxicity optimization, and volatilization potential. The results revealed that the algaNannochloropsissp. was better adopted in term of growth rate and biomass thanC. vulgarisandA. doliolum.Algae grown under an As(III) environment can tolerate up to 200 μM As(III) with moderate toxicity impact. Further, the present study revealed the biotransformation capacity of the algaeA. doliolum,Nannochloropsissp., andChlorella vulgaris. The microalgaNannochloropsissp. volatilized a large maximum amount of As (4,393 ng), followed byC. vulgaris(4382.75 ng) andA. doliolum(2687.21 ng) after 21 days. The present study showed that As(III) stressed algae-conferred resistance and provided tolerance through high production of glutathione content and As-GSH chemistry inside cells. Thus, the biotransformation potential of algae may contribute to As reduction, biogeochemistry, and detoxification at a large scale.
Reconstruction of engineered yeast factory for high yield production of ginsenosides Rg3 and Rd
Authors: Lin Yuan , Wang Yi Na , Zhang Guang Hui , Chen Geng , Yang Qing Hui , Hao Bing , Yang Sheng Chao
Published: June 2023

Panax notoginseng is one of the most valuable traditional Chinese herbs. The main active ingredients, dammarane-type ginsenosides, show multiple pharmacological activities. Recently, the key UDP-dependent glycosyltransferases (UGTs) involved in the biosynthesis of common ginsenosides have been widely studied. However, only a few UGTs that catalyze ginsenoside formation have been reported. This study further investigated the new catalytic function of 10 characterized UGTs from the public database. PnUGT31(PnUGT94B2) and PnUGT53 (PnUGT71B8)exhibited promiscuous sugar-donor specificity of UDP-glucose and UDP-xylose, which could catalyze the glycosylation of C20-OH sites and elongation of the sugar chain at the C3 and/or C20 sites. We further analyzed the expression patterns in P. notoginseng and predicted the catalytic mechanisms of PnUGT31 and PnUGT53 using molecular docking simulations. Moreover, different gene modules were built to increase the yield of ginsenosides in engineered yeast. The metabolic flow of the proginsenediol (PPD) synthetic pathway was enhanced by LPPDS gene modules based on the engineered strain. The resulting yeast was constructed to produce 1.72 g/L PPD in a shaking flask, but cell growth was significantly inhibited. EGH and LKG gene modules were constructed to achieve high-level production of dammarane-type ginsenosides. The production of G-Rg3 controlled by LKG modules increased 3.84 times (254.07 mg/ L), whereas the G-Rd titer reached 56.68 mg/L after 96 h in shaking flask culture under the control of all modules, both of which yielded the highest values for known microbes.
The transportome of the endophyte Serendipita indica in free life and symbiosis with Arabidopsis and its expression in moderate salinity
Authors: Haro Rosario , Lanza Mónica , Aguilella Marcos , Sanz-García Eugenio , Benito Begoña
Published: June 2023

Serendipita indica is an endophytic root symbiont fungus that enhances the growth of various plants under different stress conditions, including salinity. Here, the functional characterization of two fungal Na+/H+ antiporters, SiNHA1 and SiNHX1 has been carried out to study their putative role in saline tolerance. Although their gene expression does not respond specifically to saline conditions, they could contribute, together with the previously characterized Na+ efflux systems SiENA1 and SiENA5, to relieve Na+ from the S. indica cytosol under this stressed condition. In parallel, an in-silico study has been carried out to define its complete transportome. To further investigate the repertoire of transporters expressed in free-living cells of S. indica and during plant infection under saline conditions, a comprehensive RNA-seq approach was taken. Interestingly, SiENA5 was the only gene significantly induced under free-living conditions in response to moderate salinity at all the tested time points, revealing that it is one of the main salt-responsive genes of S. indica. In addition, the symbiosis with Arabidopsis thaliana also induced SiENA5 gene expression, but significant changes were only detected after long periods of infection, indicating that the association with the plant somehow buffers and protects the fungus against the external stress. Moreover, the significant and strongest induction of the homologous gene SiENA1 occurred during symbiosis, regardless the exposure to salinity. The obtained results suggest a novel and relevant role of these two proteins during the establishment and maintenance of fungus-plant interaction.
Genotyping of Mycoplasma pneumoniae strains isolated in Japan during 2019 and 2020: spread of p1 gene type 2c and 2j variant strains
Authors: Kenri Tsuyoshi , Yamazaki Tsutomu , Ohya Hitomi , Jinnai Michio , Oda Yoichiro , Asai Sadasaburo , Sato Rikako , Ishiguro Nobuhisa , Oishi Tomohiro , Horino Atsuko , Fujii Hiroyuki , Hashimoto Toru , Nakajima Hiroshi , Shibayama Keigo
Published: June 2023

We characterized 118 Mycoplasma pneumoniae strains isolated from three areas of Japan (Saitama, Kanagawa, and Osaka) during the period of 2019 and 2020. Genotyping of the p1 gene in these strains revealed that 29 of them were type 1 lineage (29/118, 24.6%), while 89 were type 2 lineage (89/118, 75.4%), thereby indicating that type 2 lineage was dominant in this period. The most prevalent variant of type 2 lineage was type 2c (57/89, 64%), while the second-most was type 2j, a novel variant identified in this study (30/89, 33.7%). Type 2j p1 is similar to type 2 g p1, but cannot be distinguished from reference type 2 (classical type 2) using the standard polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP) with HaeIII digestion. Thus, we used MboI digestion in the PCR-RFLP analysis and re-examined the data from previous genotyping studies as well. This revealed that most strains reported as classical type 2 after 2010 in our studies were actually type 2j. The revised genotyping data showed that the type 2c and 2j strains have been spreading in recent years and were the most prevalent variants in Japan during the time-period of 2019 and 2020. We also analyzed the macrolide-resistance (MR) mutations in the 118 strains. MR mutations in the 23S rRNA gene were detected in 29 of these strains (29/118, 24.6%). The MR rate of type 1 lineage (14/29, 48.3%) was still higher than that of type 2 lineage (15/89, 16.9%); however, the MR rate of type 1 lineage was lower than that found in previous reports published in the 2010s, while that of type 2 lineage strains was slightly higher. Thus, there is a need for continuous surveillance of the p1 genotype and MR rate of M. pneumoniae clinical strains, to better understand the epidemiology and variant evolution of this pathogen, although M. pneumoniae pneumonia cases have decreased significantly since the COVID-19 pandemic.
Psoriasis immunometabolism: progress on metabolic biomarkers and targeted therapy
Authors: Sarandi Evangelia , Krueger-Krasagakis Sabine , Tsoukalas Dimitris , Sidiropoulou Polytimi , Evangelou George , Sifaki Maria , Rudofsky Gottfried , Drakoulis Nikolaos , Tsatsakis Aristidis
Published: June 2023

Psoriasis is a common inflammatory disease that affects mainly the skin. However, the moderate to severe forms have been associated with several comorbidities, such as psoriatic arthritis, Crohn’s disease, metabolic syndrome and cardiovascular disease. Keratinocytes and T helper cells are the dominant cell types involved in psoriasis development via a complex crosstalk between epithelial cells, peripheral immune cells and immune cells residing in the skin. Immunometabolism has emerged as a potent mechanism elucidating the aetiopathogenesis of psoriasis, offering novel specific targets to diagnose and treat psoriasis early. The present article discusses the metabolic reprogramming of activated T cells, tissue-resident memory T cells and keratinocytes in psoriatic skin, presenting associated metabolic biomarkers and therapeutic targets. In psoriatic phenotype, keratinocytes and activated T cells are glycolysis dependent and are characterized by disruptions in the TCA cycle, the amino acid metabolism and the fatty acid metabolism. Upregulation of the mammalian target of rapamycin (mTOR) results in hyperproliferation and cytokine secretion by immune cells and keratinocytes. Metabolic reprogramming through the inhibition of affected metabolic pathways and the dietary restoration of metabolic imbalances may thus present a potent therapeutic opportunity to achieve long-term management of psoriasis and improved quality of life with minimum adverse effects.