bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of CYP2C19 gene polymorphism and influencing factors of pharmacological response of clopidogrel in patients with cerebral infarction in Zhejiang, China
Authors: Mo Yijun , Lu Yao , Guo Fei , Wu Aihua , Weng Yuesong
Published: February 2023

Background

Certain genetic and non-genetic factors may cause damaged platelet inhibition by clopidogrel. We aimed to determine the effect of cytochrome P4502C19 (CYP2C19) polymorphism, along with other clinical factors, on the platelet response to clopidogrel in patients with acute ischemic stroke (AIS).

Methods

A total of 214 patients with AIS receiving clopidogrel at a maintenance dose of 75 mg daily admitted to the Ningbo First Hospital between 1 January 2020, and 31 December 2021, were enrolled. Platelet aggregation analysis was performed to determine clopidogrel resistance. Quantitative real-time polymerase chain reaction (QRT-PCR) was used to determine CYP2C19 genotype. Other laboratory data on complete blood count and biochemical parameters were taken from patient medical files.

Results

Among the 214 AIS patients treated with clopidogrel in the Ningbo population, the incidence of clopidogrel resistance was approximately 43.9%, and the distribution of CYP2C19 genotypes was highest for CYP2C19(*1/*2) (43.0%), followed by CYP2C19 (*1/*1) (38.8%). The distribution of alleles *1, *2, *3, and *17 was 62.1, 32.5, 4.9, and 0.5%, respectively. A chi-squared test showed that the gene frequencies of alleles *2 and *3 were significantly higher in the clopidogrel-resistant group than in the clopidogrel-sensitive group (p < 0.001), and a Mann–Whitney U-test showed that high HCY levels were significantly correlated with clopidogrel resistance (p < 0.001). Multi-factor logistic regression analysis demonstrated that mutant heterozygous genotype [OR 2.893; 95% confidence interval (CI) 1.456–5.748; p = 0.002], mutant homozygous genotype (OR 4.741; 95% CI 1.828–12.298; p = 0.001), and high HCY levels (OR 1.209; 95% CI 1.072–1.362; p = 0.002) were significantly associated with clopidogrel resistance.

Conclusion

According to our results, carrying the CYP2C19*2/*3 allele and high HCY levels are independent risk factors for clopidogrel resistance after clopidogrel therapy in patients with AIS. These two factors should be considered prior to clopidogrel administration.
Impact of coronary computed tomography angiography-derived fractional flow reserve based on deep learning on clinical management
Authors: Pan Yueying , Zhu Tingting , Wang Yujijn , Deng Yan , Guan Hanxiong
Published: February 2023

Background

To examine the value of coronary computed tomography angiography (CCTA)-derived fractional flow reserve based on deep learning (DL-FFRCT) on clinical practice and analyze the limitations of the application of DL-FFRCT.

Methods

This is an observational, retrospective, single-center study. Patients with suspected coronary artery disease (CAD) were enrolled. The patients underwent invasive coronary angiography (ICA) examination within 1 months after CCTA examination. And quantitative coronary angiography (QCA) was performed to evaluate the area stenosis rate. The CCTA data of these patients were retrospectively analyzed to calculate the FFRCT value.

Results

A total of 485 lesions of coronary arteries in 229 patients were included in the analysis. Of the lesions, 275 (56.7%) were ICA-positive, and 210 (43.3%) were FFRCT-positive. The discordance rate of the risk stratification of FFRCT for ICA-positive lesions was 33.1% (91) and that for ICA-negative lesions was 12.4% (26). 14.6% (7/48) patients with mild to moderate coronary stenosis in ICA have functional ischemia according to FFRCT positive indications. In addition, hemodynamic analysis of severely calcified, occluded, or small (< 2 mm in diameter) coronary arteries by DL-FFRCT is not so reliable.

Conclusion

This study revealed that most patients with ICA negative did not require further invasive FFR. Besides, some patients with mild to moderate coronary stenosis in ICA may also have functional ischemia. However, for severely calcified, occluded, or small coronary arteries, treatment strategy should be selected based on ICA in combination with clinical practice.
A new approach to analyzing wellbore pressure dynamically in well-killing
Authors: Liu Pu , Wang Zhiping , Wang ChenLong , Tang Zhengqiang , Yu Hao , Liu Huixin , Li Kaixuan
Published: February 2023

Casing pressure during well-killing is both an unknown variable that must be addressed and a time-dependent function. Therefore, the calculation of the dynamic reaction of wellbore pressure during well-killing is a dynamic indeterminate boundary problem. Due to the intricacy of the analytical solution technique, finding an analytical solution for the dynamic issue of uncertain boundaries is nearly impossible. Current numerical simulation software is only capable of resolving problems with defined bounds (such as flow or pressure) and is incapable of continuously calculating the wellbore pressure, which varies dynamically with well-killing time. Developing a dynamic reaction computation method for wellbore pressure during well-killing can solve this issue. Based on the mathematical model and definite solution conditions of the wellbore pressure dynamic response under well-killing conditions, this paper applies the finite difference principle and constructs the calculation method of choke and kill wellbore pressure dynamic response through reasonable mesh division of wellbore and gradual iteration of the calculation process. The resultsdemonstrate that the maximum wellhead casing pressure value and the time node of peak value are both highly congruent with the measured data, indicating the method’s high reliability and highlighting its significance for the progress of oil and gas well control safety.
The proto-type basin and tectono-paleogeographic evolution of the Tarim basin in the Late Paleozoic
Authors: Xia Jinkai , Zhong Ziqi , Huang Shaoying , Luo Caiming , Lou Hong , Chang Haining , Li Xiang , Wei Lunyan
Published: February 2023

The Tarim basin is a large composite and superimposed sedimentary basin that has undergone complex multi-period and polycyclic tectonic movements. Understanding the proto-type basin and tectono-paleogeographic evolution of this complex superimposed basin is important for understanding the basin-mountain coupling and dynamical mechanisms of the Paleo-Asian and Tethys tectonic systems as well as hydrocarbon exploration and development. Based on previous works, together with the recent exploration, and geological evidences, three global plate tectonic pattern maps, four Tarim proto-type basin maps (in present-day geographic coordinates) and four regional tectono-paleogeography maps (in paleogeographic coordinates) during the Late Paleozoic are provided in this paper. Based on these maps, the proto-type basin and tectono-paleogeographic features of the Tarim basin during the Late Paleozoic are illustrated. The Devonian to Permian is an important period of terranes/island-arcs accretion and oceanic closure along the periphery of the Tarim block, and a critical period when the polarity of Tarim basin (orientation of basin long-axis) rotated at the maximum angle clockwise. During the Late Paleozoic, the periphery of the Tarim block was first collisional orogeny on its northern margin, followed by continuous collisional accretion of island arcs on its southern margin: on the Northern margin, the North and South Tianshan Oceans closed from East to West; on the South-Western margin, the Tianshuihai Island Arc gradually collided and accreted. These tectonic events reduced the extent of the seawater channel of the passive continental margin in the Western part of the basin until its complete closure at the end of the Permian. The Tarim basin was thus completely transformed into an inland basin. This is a process of regression and uplift. The Southwest of the Tarim basin changed from a passive to an active continental margin, through back-arc downwarping and eventually complete closure to foreland setting. The intra-basin lithofacies range from shelf-littoral to platform-tidal flat to alluvial plain-lacustrine facies. The tectonic-sedimentary evolution of the Tarim basin is strongly controlled by peripheral geotectonic setting.
Experiences of childhood play among different generations in Estonia
Authors: Ugaste Aino
Published: February 2023

Play is an important part of child development, learning and the lives of children; however, access to the space and time necessary for play has dramatically changed in recent years. The aim of this study is to examine memories about childhood play from three generations of people in Estonia. Individual interviews were used to retrospectively explore perceptions of play with 98 respondents. The respondents mainly associated play memories with outdoor games that involved joy, fun, and excitement. The findings identified that freedom and a variety of options for play were important for children. The results highlighted the wide repertoire of play across generations and the difference between play for urban and rural children. The findings were compared with earlier studies and considered in light of educational and political changes in Estonian society.
Empirical evaluation of ethical practices and digitalization of agricultural system with the mediation of user behavior: A case study of Pakistan
Authors: Manzoor Faiza , Wei Longbao , Chen Jingyuan
Published: February 2023

Pakistan is one developing country and 70% of the population is depending on Agriculture and faces a lack of innovation in the agriculture sector overall. the main objectives of our study were to i) identify ethical practices (knowledge-sharing, trustworthiness in loan providing, loyalty in professionalism, responsibility of actions, and accountability) of the agriculture departments and institutions or government towards improving digital technology in the agriculture sector. ii) Quantify the user behavior in the digitalization of the agricultural system. iii) Identify the intervening role of user behavior in the relation to ethical practices and agricultural technology development. The study examined 490 users of farming technologies who work in the agriculture sector in two provinces of Pakistan. Using the Baron and Kenny framework, this research confirmed the prediction that user behavior mediated the relationship between ethical practices and agricultural technology in a four-step process. The main outcomes of the study have revealed a positive and significant impact of ethical practices on the development of the digitalization of the agricultural system. Specifically, the study indicated that “user behavior” significantly mediates the association between ethical practices and agricultural technology development. Furthermore, this study proposes that it is essential for Pakistan’s agriculture sector to nurture circumstances dedicated to better practices as it will not only attract more residents to agricultural growth but also help the agriculture sector achieve its eventual goal of increased productivity. Implications of this research study are deliberated and provide directions for future research in the area.
Campylobacter in aquatic and terrestrial mammals is driven by life traits: A systematic review and meta-analysis
Authors: Brooks Michael R. , Medley Sarah , Ponder Monica , Alexander Kathleen A.
Published: February 2023

Introduction

Campylobacter spp. infections are responsible for significant diarrheal disease burden across the globe, with prevalence thought to be increasing. Although wild avian species have been studied as reservoirs of Campylobacter spp., our understanding of the role of wild mammalian species in disease transmission and persistence is limited. Host factors influencing infection dynamics in wild mammals have been neglected, particularly life traits, and the role of these factors in zoonotic spillover risk is largely unknown.

Methods

Here, we conducted a systematic literature review, identifying mammalian species that had been tested for Campylobacter spp. infections (molecular and culture based). We used logistic regression to evaluate the relationship between the detection of Campylobacter spp. in feces and host life traits (urban association, trophic level, and sociality).

Results

Our analysis suggest that C. jejuni transmission is associated with urban living and trophic level. The probability of carriage was highest in urban-associated species (p = 0.02793) and the most informative model included trophic level. In contrast, C. coli carriage appears to be strongly influenced by sociality (p = 0.0113) with trophic level still being important. Detection of Campylobacter organisms at the genus level, however, was only associated with trophic level (p = 0.0156), highlighting the importance of this trait in exposure dynamics across host and Campylobacter pathogen systems.

Discussion

While many challenges remain in the detection and characterization of Camploybacter spp., these results suggest that host life traits may have important influence on pathogen exposure and transmission dynamics, providing a useful starting point for more directed surveillance approaches.
Preemptive interferon-α therapy could prevent relapse of acute myeloid leukemia following allogeneic hematopoietic stem cell transplantation: A real-world analysis
Authors: Fan Shuang , Pan Tian-Zhong , Dou Li-Ping , Zhao Yan-Min , Zhang Xiao-Hui , Xu Lan-Ping , Wang Yu , Huang Xiao-Jun , Mo Xiao-Dong
Published: February 2023

Introduction

Measurable residual disease (MRD)-directed interferon-a treatment (i.e. preemptive IFN-α treatment) can eliminate the MRD in patients with acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Therefore, this study aimed to further assess its efficacy in a multicenter retrospective study in a real-world setting.

Methods

A total of 247 patientswho received preemptive IFN-α treatment were recruited from 4 hospitals in China. The protocols for MRD monitoring mainly based on quantitative polymerase chain reaction [qPCR] and multiparameter flow cytometry [MFC].

Results

The median duration of IFN-α treatment was 56 days (range, 1–1211 days). The cumulative incidences of all grades acute graft-versus-host disease (aGVHD), all grades chronic graft-versus-host disease (cGVHD), and severe cGVHD at 3 years after IFN-α therapy were 2.0% (95% confidence interval [CI], 0.3–3.8%), 53.2% (95% CI, 46.8–59.7%), and 6.2% (95% CI, 3.1–9.2%), respectively. The cumulative incidence of achieving MRD negative state at 2 years after IFN-α treatment was 78.2% (95% CI, 72.6–83.7%). The 3-year cumulative incidences of relapse and non-relapse mortality following IFN-α therapy were 20.9% (95% CI, 15.5–26.3%) and 4.9% (95%CI, 2.0–7.7%), respectively. The probabilities of leukemia-free survival and overall survival at 3 years following IFN-α therapy were 76.9% (95% CI, 71.5–82.7%) and 84.2% (95% CI, 78.7–90.1%), respectively. Multivariable analysis showed that MRD positive state by qPCR and MFC before IFN-α treatment, high-risk disease risk index before allo-HSCT, and receiving identical sibling donor HSCT were associated with a higher risk of relapse and a poorer leukemia-free survival. Severe cGVHD was associated with an increased risk of non-relapse mortality.

Discussion

Thus, real-world data suggest that preemptive IFN-α is effective for treating patients with AML with MRD after allo-HSCT.
The role of thymus- and extrathymus-derived regulatory T cells in maternal-fetal tolerance
Authors: Li Zhengjuan , Liang Xinyuan , Chen Xiaowen , Chen Yuying , Wang Fang , Wang Shuoshi , Liao Yihong , Li Liping
Published: February 2023

Regulatory T (Treg) cells could be divided into thymus-derived Treg (tTreg) cells and peripherally derived Treg (pTreg) cells, and in vitro induced Treg (iTreg) cells. To date, the functions of tTreg versus pTreg and their relative contributions to maternal-fetal immune tolerance remain insufficiently defined due to a lack of a specific marker to distinguish tTreg cells from pTreg cells. In this study, we investigated the role of thymus- and extrathymus-derived Treg cells in pregnancy tolerance using transgenic ACT-mOVA, Foxp3DTR and Foxp3GFP mice, and Treg cell adoptive transfer, etc. We found that the frequencies of Treg cells in the thymus, spleen and lymph nodes (LNs) in either syngeneically- or allogeneically-mated pregnant mice were not different from non-pregnant mice. However, percentages of blood Treg cells in pregnant mice increased at mid-gestation, and percentages of decidua Treg cells in pregnant mice increased as the pregnancy progressed compared with non-pregnant mice, and were significantly higher in allogeneic mice than those in syngeneic group. Compared with syngeneic mice, levels of CCR2 and CCR6 on blood and decidua Treg cells and CCL12 in the decidua significantly increased in allogeneic mice. A surrogate fetal antigen mOVA that was recognized by naïve T cells from OT-IIFoxp3GFP mice induced the generation of pTreg cells in vivo. Transfusion of thymus and spleen Treg cells significantly decreased diphtheria toxin (DT)-increased embryo resorption rates (ERRs) and IFN-γ levels in the blood and decidua. iTreg cells also decreased ERRs and IFN-γ levels in the blood and decidua to an extent lower than thymus and spleen Treg cells. In conclusion, increased blood and decidua Treg cells in pregnancy and increased ERRs in DT-treated Foxp3DTR mice suggest an important immunosuppressive role of Treg cells in pregnancy. Elevated decidua Treg cells in pregnancy could be derived from the recruitment of tTreg cells to the decidua, or from the transformation of naïve T cells in the decidua to pTreg cells. While the immune-suppression effects of thymus and spleen Treg cells are comparable, iTreg cells might play a weaker role in maternal-fetal tolerance.
Effects of the Kuroshio on internal tides in the Luzon Strait: A model study
Authors: Tang Guoqin , Deng Zengan , Chen Ru , Xiu Fangrui
Published: February 2023

Internal tides have a great impact on the meridional overturning circulation and climate variability through contributing to diapycnal mixing. The Luzon Strait (LS) is one of the most important sites of internal tide generation in the global ocean. In this study, we evaluate the effect of the Kuroshio on the M2 and K1 internal tides in both summer and winter seasons in the South China Sea (SCS), particularly within the LS. High-resolution ocean numerical simulations with the Kuroshio Current were compared with those without. We found that the Kuroshio has negligible impact on the generation site of internal tides. Compared to seasonal variability in the total barotropic to baroclinic conversion rate over the LS, the Kuroshio has relatively little influence. However, the Kuroshio flow strongly guides the propagating direction of the internal tides from the LS into the SCS. The Kuroshio also substantially decreases the southward energy fluxes going out of the LS. For both M2 and K1 tides, turning off the Kuroshio leads to a weaker energy exchange between the background shear and internal tides. Turning off the Kuroshio also weakens the divergence of internal tide energy due to the advection of background flow. Thus, our results reveal a non-negligible effect of the Kuroshio on the internal tides in the LS. If one aims to realistically simulate, or better understand, internal tides, these results indicate that one should include realistic oceanic circulation fields.
Impact of upstream variability on the Loop Current dynamics in numerical simulations of the Gulf of Mexico
Authors: Laxenaire Rémi , Chassignet Eric P. , Dukhovskoy Dmitry S. , Morey Steven L.
Published: February 2023

The Loop Current (LC), which is the main mesoscale dynamic feature of the Gulf of Mexico (GoM), has a major impact on the circulation and its variability in the interior Gulf. The LC is a highly variable and dynamic feature. It changes shape from a short jet connecting the two openings of the GoM in an almost straight line ("retracted phase") to a long loop invading most of the eastern part of the GoM ("extended phase"). When it is in the extended phase, it can shed large anticyclonic eddies, called Loop Current Eddies, which then migrate to the western GoM. In this study, the processes controlling the LC dynamics are investigated using two multi-decadal simulations of the Gulf of Mexico HYbrid Coordinate Ocean Model differing in their open boundary conditions (BCs) and altimetry-derived gridded fields. The LC in the simulation with BCs derived from monthly climatology state variables frequently remains in its retracted phase significantly longer than observed. In contrast, the duration of the retracted phase is notably shorter in the simulation in which the BCs have realistic daily variability. By examining the flow properties through the Yucatan Channel from which the LC originates, we find that increased intensity of this current and a westward shift of the mean core is associated with the LC transitions from the retracted to the extended phase. This transition is accompanied by an increase of both cyclonicity of the flow in the west and anticyclonicity in the east of the core of this jet. Moreover, the number of anticyclonic eddies entering in the GoM through the Yucatan Channel is significantly higher when the LC extends in the GoM. Consequently, this study demonstrates the importance of realistic flow variability at the lateral boundaries for accurate simulation of the LC system in a model, and reveals characteristics of the upstream flow associated with different LC behavior that can potentially aid in forecasting the LC system.
Planktic foraminifera iodine/calcium ratios from plankton tows
Authors: Winkelbauer Helge A. , Hoogakker Babette A. A. , Chance Rosie J. , Davis Catherine V. , Anthony Christopher J. , Bischoff Juliane , Carpenter Lucy J. , Chenery Simon R. N. , Hamilton Elliott M. , Holdship Philip , Peck Victoria L. , Poulton Alex J. , Stinchcombe Mark C. , Wishner Karen F.
Published: February 2023

Planktic foraminifera test iodine to calcium ratios represent an emerging proxy method to assess subsurface seawater oxygenation states. Several core-top studies show lower planktic foraminifera I/Ca in locations with oxygen depleted subsurface waters compared to well oxygenated environments. The reasoning behind this trend is that only the oxidized species of iodine, iodate, is incorporated in foraminiferal calcite. The I/Ca of foraminiferal calcite is thought to reflect iodate contents in seawater. To test this hypothesis, we compare planktic foraminifera I/Ca ratios, obtained from plankton tows, with published and new seawater iodate concentrations from 1) the Eastern North Pacific with extensive oxygen depletion, 2) the Benguela Current System with moderately depleted oxygen concentrations, and 3) the well oxygenated North and South Atlantic. We find the lowest I/Ca ratios (0.07 µmol/mol) in planktic foraminifera retrieved from the Eastern North Pacific, and higher values for samples (up to 0.72 µmol/mol) obtained from the Benguela Current System and North and South Atlantic. The I/Ca ratios of plankton tow foraminifera from environments with well oxygenated subsurface waters, however, are an order of magnitude lower compared to core-tops from similarly well-oxygenated regions. This would suggest that planktic foraminifera gain iodine post-mortem, either when sinking through the water column, or during burial.
Underwater noise characteristics of offshore exploratory drilling and its impact on marine mammals
Authors: Huang Long-Fei , Xu Xiao-Mei , Yang Liang-Liang , Huang Shen-Qin , Zhang Xin-Hai , Zhou Yang-Liang
Published: February 2023

Geotechnical survey is an important prerequisite to the construction of offshore wind farms. However, the impact of underwater survey noises has not yet been studied in details. In this paper, we studied transmission of underwater noises from offshore exploratory drilling (OED) at the Xiamen port. The noises were categorized into three types: hammering noises (hammering down of casings, which were 180-mm diameter steel pipes), vibrating noises (vibration of casings that had been hammered down), and drilling noises (generated during the borehole drilling process). We considered the variation in intensity of these three noise types, and set up two fixed and one movable stations to measure and analyze the source and propagation characteristics of these noises. The results indicate that hammering noise is an impulsive sound with a dominant frequency below 10 kHz, and source levels (SLs) of 197.1 dB re 1μPa @ 1 m (rms over 95% energy duration. 1–64,000 Hz) and 212.9 dB re 1μPa @ 1 m (peak). Vibrating and drilling noises are non-impulsive sounds with the fundamental frequencies of 41 Hz and 45 Hz, and SLs of 158.9 dB re 1μPa rms @ 1 m and 155.9 dB re 1μPa rms @ 1 m, respectively. The impact assessment of OED noises on five groups of marine mammals with different audible frequency ranges (Low (LF), High (HF), and Very High (VHF) frequency cetaceans, sirenians (SI), and phocid pinnipeds (PW)) demonstrates that hammering noise can induce a high risk of hearing damage to their hearing, at as far as 300 meters for VHF group, while drilling noise can only induce hearing damage at about 40 meters. Marine mammals are susceptible to behavior alteration, with a detectable distance of 1.9 km from the source, and it is recommended to set a warning zone with a radius of 1.9 km during OED construction.
A hybrid deep learning model for predicting the Kuroshio path south of Japan
Authors: Wu Xiaobo , Han Guijun , Li Wei , Ji Zenghua , Cao Lige , Dong Wanqiu
Published: February 2023

At present, many prediction models based on deep learning methods have been widely used in ocean prediction with satisfactory results. However, few deep learning models are used to predict the Kuroshio path south of Japan. In this study, a hybrid deep learning prediction model is constructed based on the long short-term memory (LSTM) neural network, combined with the complex empirical orthogonal function (CEOF) and bivariate empirical mode decomposition (BEMD), called CEOF-BEMD-LSTM. We train the model by using a 50-year (1958-2007) long time series of daily mean positions of the Kuroshio path south of Japan extracted from a regional ocean reanalysis dataset. During the test period of 15 years (2008-2022) by using daily altimetry dataset, our model shows a good performance for the Kuroshio path prediction with the lead time of 120 days, with 0.44° root-mean-square error (RMSE) and 0.75 anomaly correlation coefficient (ACC). This model also has good prediction skill score (SS). Moreover, the CEOF-BEMD-LSTM model successfully hindcasts the formation of the latest Kuroshio large meander since the summer of 2017. Predictions of the Kuroshio path for the coming 120 days (from January1 to April 30, 2023) indicate that the Kuroshio will continue to remain in the state of the large meander. Besides, predictor(s) of the Kuroshio path south of Japan need to be sought and added in future research.
The local stratification preconditions the marine heatwaves in the Yellow Sea
Authors: Lee Eun Young , Lee Dong Eun , Park Young-Gyu , Kang Hyunjin , Baek Haedo
Published: February 2023

Vertical stratification preconditions marine heat wave (MHW) events in marginal seas. The major events since 1982 in the marginal sea area west and south of the Korean Peninsula have been led by abnormally strong stratification in the vicinity, which was detected at least two months in advance. This robust coincidence provides substantial control over mid-summer events through local stratification in early summer. Such heatwave-leading stratification can be attributed to various oceanic factors during early summers, including anomalous sea surface temperature, freshwater flux, and wind mixing. Knockout-style experiments using a 1-dimensional ocean model revealed that the upper ocean stratification in the preceding months, mostly through wind mixing, is capable of regulating MHWs. Meanwhile, in the longer historical records, gradual decreases in the intensity and frequency of the daily wind gusts were found, possibly as a mixed result of anthropogenically induced climate change and strong natural variability of the midlatitudes. This might have dominated in enhancing the occurrence of MHWs, combined with the rising background surface temperature.
Chidamide as maintenance after chemotherapy or hematopoietic stem cell transplantation in 27 children with T-cell lymphoblastic leukemia: A real-world prospective study
Authors: Li Xin-Yu , Han Xia-Wei , Huang Ke , Zhang Ya-Ting , Xu Hong-Gui , Zhou Dun-Hua , Xu Lu-Hong , Fang Jian-Pei
Published: February 2023

Background

The long-term overall survival of children with T-cell acute lymphoblastic leukemia (T-ALL) is limited to approximately 80–85% because of a high incidence of relapse after achieving remission with intensive chemotherapy and hematopoietic stem cell transplantation (HSCT). Novel treatment strategies inducing long-term remission are needed to improve the outcome. Histone deacetylase inhibitors (HDACis) have been reported to be effective in a series of T-ALL cases. Preclinical studies suggested that T-ALL cells are sensitive to Chidamide, which is a selective HDACi.

Methods

This preliminary clinical study evaluated the efficacy and safety of Chidamide in combination with chemotherapy or post-HSCT for children with T-ALL at a dose of 0.5 mg/kg weight of patient twice per week for at least 6 months.

Results

In total, 27 children with a mean age of 7.88 years were included. The high-risk proportion was 66.7%. After a median follow-up period of 37.8 months (9.5–67.9 months), the overall survival and event-free survival in the patients treated with Chidamide were 94.1 and 95.2%, respectively. All patients except two maintained persistent remission with <0.01% blast cells in minimal residual disease.

Conclusion

The combination therapy with Chidamide in a case series of T-ALL shows the promising clinical efficacy and good safety in children.

Clinical trial registration

https://www.chictr.org.cn/, identifier ChiCTR2000030357.
Histopathological evaluation of Onchocerca volvulus nodules by microscopy and by digital image analysis for the study of macrofilaricidal drug efficacy
Authors: Fischer Kerstin , Dubben Bettina , Debrah Linda B. , Kuehlwein Janina M. , Ricchiuto Arcangelo , Debrah Alexander Y. , Hoerauf Achim , Weil Gary J. , Fischer Peter U. , Klarmann-Schulz Ute
Published: February 2023

Background

Novel drugs or drug combinations that kill or permanently sterilize adult Onchocerca volvulus worms would be very helpful for treatment and elimination of onchocerciasis. In absence of a reliable biomarker for viable adult worms, histopathological assessment of worms within onchocercal nodules is a standard method to determine macrofilaricidal activity. The goal of the present study was to determine the agreement between two independent experts in the analysis of nodule sections and to assess the value of digital imaging as a means of standardizing the analysis.

Material and methods

Two expert microscopists independently assessed 605 nodules by direct microscopy. At least two sections with two different stains hematoxylin & eosin (H&E, APR immunostain) of paraffin-embedded, ethanol-fixed whole-nodule cross-sections were analyzed. After variables were identified prone to observer discrepancies, we performed a second study to compare consolidated results for 100 nodules obtained by the two readers by microscopy and by analysis of scanned, high resolution digital images (20x magnification). The last data set analyzed was a quality panel of 100 nodules that has been previously examined by microscopy, and included additional immunostains for Wolbachia endobacteria. These slides were digitalized, read by the two assessors and results were compared with original microscopy results.

Results

The degree of agreement between assessors varied for different parameters. Agreement for female worm counts in nodules was approximately 80%, while agreement regarding female worm viability was 98%. There were no major differences observed between results obtained by microscopy or digital images. Good agreement for important parameters was also observed for the nodules of the quality panel.

Conclusion

Nodule analysis by experienced microscopists was reproducible with regard to important parameters such as identification of living female worms or detection of normal embryogenesis. Assessments varied more for other parameters, and we recommend continued use of two independent readers for detailed analyzes. Analysis of scanned images provided similar results to direct microscopy. This facilitates training and comparison of nodule findings by readers in different locations. Analysis of high quality digital images that can be viewed remotely should improve the quality and availability of nodule assessments that are primary endpoints for onchocerciasis clinical trials.
Boletaceae in China: Taxonomy and phylogeny reveal a new genus, two new species, and a new record
Authors: Wang Yang , Wang Li-Ying , Dai Dan , Qi Zheng-Xiang , Zhang Zhen-Hao , Liu Ya-Jie , Hu Jia-Jun , Zhang Peng , Li Yu , Zhang Bo
Published: February 2023

Boletaceae, the largest family in Boletales, has been attracted by mycologists in the world due to its diverse morphology and complex history of evolution. Although considerable work has been done in the past decades, novel taxa are continually described. The current study aimed to introduce three new taxa and one new record of Boletaceae from China. The morphological descriptions, color photographs, phylogenetic trees to show the positions of the taxa, and comparisons with allied taxa are provided. The new genus Hemilanmaoa is unique in the Pulveroboletus group, and Hemilanmaoa retistipitatus was introduced as the type species. It can be distinguished by its bluing basidioma when injured, a decurrent hymenophore, a stipe covered with distinct reticulations, and a fertile stipitipellis. Porphyrellus pseudocyaneotinctus is characterized by its pileipellis consisting of broadly concatenated cells and thin-walled caulocystidia in Porphyrellus. In Phylloporus, Phylloporus biyangensis can be distinguished by its hymenophores that change to blue when injured and yellow basal mycelium. Lanmaoa angustispora, as a new record, is first reported in Northern China. Internal transcribed spacer (ITS), 28S rDNA (28S), translation elongation factor 1-alpha (tef1-α), RNA polymerase II subunit 1 (rpb1), and RNA polymerase II subunit 2 (rpb2) were employed to execute phylogenetic analyses.
Investigation of probing repeatability inside a micro-hole by changing probe approach direction for a local surface interaction force detection type microprobe
Authors: Aruga Masakazu , Ito So , Kato Daichi , Matsumoto Kimihisa , Kamiya Kazuhide
Published: February 2023

The inner diameter measurement of the micro-hole was performed by a tactile microprobing system using a method of the local surface interaction force detection. The inner diameter of the micro-hole was calculated by the least square method based on the probing coordinates obtained by a custom-made micro-coordinate measuring machine. The dispersion of the probing coordinates was investigated by changing the probe approaching direction with respect to the normal direction of the inner side of the micro-hole. During the probing inside the micro-hole, it was confirmed that the dispersion of the probing coordinates increased when the disagreement between the probe approaching direction and the normal direction of the micro-hole at the measured point became large. The influence of the dispersion of the probing coordinates was evaluated through the uncertainty analysis of the inner diameter measurement. It was revealed that the uncertainty of the inner diameter measurement could be improved when limiting the disagreement between the probe approaching direction and the normal direction of the micro-hole to within ±pi/4 rad.
Imaging of glutamate in acute carbon monoxide poisoning using chemical exchange saturation transfer
Authors: Zheng Hongyi , Zheng Wenbin , Liu Hongkun , Zhang Gengbiao , Li Weijia , Zhuang Jiayan , Guo Yuelin
Published: February 2023

Aims

This study adopted the Glutamate Chemical Exchange Saturation Transfer (GluCEST) imaging technique to quantitatively analyze cranial glutamate and discussed the effectiveness of GluCEST values in identifying the pathogenesis of encephalopathy after CO poisoning.

Methods

The routine MRI and functional MRI scans of two cohorts of subjects (CO group, n = 29; Control group, n = 21) were performed. Between-group comparisons were conducted for GluCEST% in regions of interest (ROI), including the basal ganglia, the thalamus, the frontal lobe, the occipital lobe, the genu of corpus callosum, the cingulate gyrus, and the cuneus. Moreover, an age-stratified subgroup analysis was devised, and a correlational analysis was performed for GluCEST% in each ROI, including the time in coma, Simple Mini-Mental State Examination Scale (MMSE) score, Hamilton Anxiety Scale score, and blood COHb%.

Results

As compared to the healthy control, the CO group led to significantly increasing GluCEST% in the basal ganglia, the occipital lobe, the genu of the corpus callosum, the cingulate gyrus, and the cuneus (p < 0.05). In the subgroup analysis for age, adult patients had higher GluCEST% in the basal ganglia, the thalamus, the occipital lobe, the cingulate gyrus, and the cuneus compared to healthy adults (p < 0.05). In addition, the correlational analysis of CO-poisoned patients revealed a statistical association between the GluCEST% and the MMSE in the thalamus and the genu of the corpus callosum.

Conclusion

The GluCEST technique is superior to routine MRI in that it can identify the cerebral biochemical changes sooner after acute CO poisoning, which is significant for our understanding of the role of neurotransmitters in the pathological basis of this disease. Brain injury caused by CO poisoning may be different in adults and children.
Age differences and brain maturation provide insight into heterogeneous results in autism spectrum disorder
Authors: O’Hearn Kirsten , Lynn Andrew
Published: February 2023

Studies comparing individuals with autism spectrum disorder (ASD) to typically developing (TD) individuals have yielded inconsistent results. These inconsistencies reflect, in part, atypical trajectories of development in children and young adults with ASD compared to TD peers. These different trajectories alter group differences between children with and without ASD as they age. This paper first summarizes the disparate trajectories evident in our studies and, upon further investigation, laboratories using the same recruiting source. These studies indicated that cognition improves into adulthood typically, and is associated with the maturation of striatal, frontal, and temporal lobes, but these age-related improvements did not emerge in the young adults with ASD. This pattern – of improvement into adulthood in the TD group but not in the group with ASD – occurred in both social and non-social tasks. However, the difference between TD and ASD trajectories was most robust on a social task, face recognition. While tempting to ascribe this uneven deficit to the social differences in ASD, it may also reflect the prolonged typical development of social cognitive tasks such as face recognition into adulthood. This paper then reviews the evidence on age-related and developmental changes from other studies on ASD. The broader literature also suggests that individuals with ASD do not exhibit the typical improvements during adolescence on skills important for navigating the transition to adulthood. These skills include execution function, social cognition and communication, and emotional recognition and self-awareness. Relatedly, neuroimaging studies indicate arrested or atypical brain maturation in striatal, frontal, and temporal regions during adolescence in ASD. This review not only highlights the importance of a developmental framework and explicit consideration of age and/or stage when studying ASD, but also the potential importance of adolescence on outcomes in ASD.
Multimodal processing in face-to-face interactions: A bridging link between psycholinguistics and sensory neuroscience
Authors: Benetti Stefania , Ferrari Ambra , Pavani Francesco
Published: February 2023

In face-to-face communication, humans are faced with multiple layers of discontinuous multimodal signals, such as head, face, hand gestures, speech and non-speech sounds, which need to be interpreted as coherent and unified communicative actions. This implies a fundamental computational challenge: optimally binding only signals belonging to the same communicative action while segregating signals that are not connected by the communicative content. How do we achieve such an extraordinary feat, reliably, and efficiently? To address this question, we need to further move the study of human communication beyond speech-centred perspectives and promote a multimodal approach combined with interdisciplinary cooperation. Accordingly, we seek to reconcile two explanatory frameworks recently proposed in psycholinguistics and sensory neuroscience into a neurocognitive model of multimodal face-to-face communication. First, we introduce a psycholinguistic framework that characterises face-to-face communication at three parallel processing levels: multiplex signals, multimodal gestalts and multilevel predictions. Second, we consider the recent proposal of a lateral neural visual pathway specifically dedicated to the dynamic aspects of social perception and reconceive it from a multimodal perspective (“lateral processing pathway”). Third, we reconcile the two frameworks into a neurocognitive model that proposes how multiplex signals, multimodal gestalts, and multilevel predictions may be implemented along the lateral processing pathway. Finally, we advocate a multimodal and multidisciplinary research approach, combining state-of-the-art imaging techniques, computational modelling and artificial intelligence for future empirical testing of our model.
Investigating the attentional focus to workplace-related soundscapes in a complex audio-visual-motor task using EEG
Authors: Rosenkranz Marc , Cetin Timur , Uslar Verena N. , Bleichner Martin G.
Published: February 2023

Introduction

In demanding work situations (e.g., during a surgery), the processing of complex soundscapes varies over time and can be a burden for medical personnel. Here we study, using mobile electroencephalography (EEG), how humans process workplace-related soundscapes while performing a complex audio-visual-motor task (3D Tetris). Specifically, we wanted to know how the attentional focus changes the processing of the soundscape as a whole.

Method

Participants played a game of 3D Tetris in which they had to use both hands to control falling blocks. At the same time, participants listened to a complex soundscape, similar to what is found in an operating room (i.e., the sound of machinery, people talking in the background, alarm sounds, and instructions). In this within-subject design, participants had to react to instructions (e.g., “place the next block in the upper left corner”) and to sounds depending on the experimental condition, either to a specific alarm sound originating from a fixed location or to a beep sound that originated from varying locations. Attention to the alarm reflected a narrow attentional focus, as it was easy to detect and most of the soundscape could be ignored. Attention to the beep reflected a wide attentional focus, as it required the participants to monitor multiple different sound streams.

Results and discussion

Results show the robustness of the N1 and P3 event related potential response during this dynamic task with a complex auditory soundscape. Furthermore, we used temporal response functions to study auditory processing to the whole soundscape. This work is a step toward studying workplace-related sound processing in the operating room using mobile EEG.
Allium sativum: A potential natural compound for NAFLD prevention and treatment
Authors: Mardi Parham , Kargar Reza , Fazeli Ramina , Qorbani Mostafa
Published: February 2023

Introduction

Non-alcoholic fatty liver disease (NAFLD) results from an excessive accumulation of fat particles that causes liver inflammation, which ultimately causes liver damage. There is still considerable uncertainty about the effects of any nutritional supplements compared to no additional intervention. This review aimed to evaluate the efficacy of Allium sativum (A. sativum), known as garlic, in preventing and treating NAFLD.

Methods

A systematic search based on a search strategy consisting of two components of “NAFLD” and “Allium sativum” in databases including PubMed, Web of Science (WoS), and SCOPUS was conducted on papers evaluating the effects of A. sativum on NAFLD treatment and prevention. We obtained studies from inception until 20 September 2022, followed by study selection and data extraction based on our eligibility criteria. Consequently, qualitative and quantitative synthesis was conducted.

Results

Our qualitative analysis reveals that A. sativum consumption is linked to the prevention of NAFLD, especially in males, although qualitative data in this study regarding the therapeutic properties of NAFLD was controversial. Our meta-analysis showed that NAFLD patients treated with A. sativum have significantly declined aminotransferase levels. That is to say, our meta-analysis revealed a lower alanine transaminase (ALT) (SMD = −0.580, 95%CI = −0.822 to −0.338), and aspartate transaminase (AST(SMD = −0.526, 95%CI = −0.767 to −0.284) in NAFLD patients treated with A. sativum compared to the placebo group. Also, pooling data from case-control studies showed that A. sativum consumption decreases the odds of being diagnosed with NAFLD by 46% (OR = 0.538, 95%CI = 0.451–0.625).

Conclusion

A. sativum consumption is not merely associated with NAFLD prevention but also results in a considerable decline in blood aminotransferase levels in patients diagnosed with NAFLD. To put it simply, A. sativum is linked to a decline in AST and ALT, which are considered reliable biomarkers of NAFLD response to treatment. Nevertheless, A. sativum is insufficient to improve NAFLD independent of other dietary amendments and lifestyle modifications.