bluuebunny/crossref_metadata_2025 huggingface dataset:
The journey to diagnosis of wild-type transthyretin-mediated (ATTRwt) amyloidosis: a path with multisystem involvement
Authors: Karam Chafic , Moffitt Colleen , Summers Catherine , Merkel Madeline P , Kochman Fran M , Weijers Laure , Puls Mathilde , Schurer Marieke , Jones Emily , Mason Nicola , Finkel Muriel , Schmitt Paula , Hanna Mazen
Published: November 2023

Background: Wild-type and hereditary transthyretin-mediated amyloidosis (ATTRwt and ATTRv amyloidosis, respectively) are progressive, fatal diseases with a broad range of clinical presentations and multisystem effects. Despite having a higher prevalence, ATTRwt amyloidosis is less well characterized due to its non-hereditary nature, and its relatively poorer disease awareness delays diagnosis. Understanding of its natural history has evolved in recent years, but this is largely based on physician-collected data rather than patients’ reports of their own experiences.
Results: Using a mixed-methods approach, we first conducted a US-based survey to explore how the journey of patients with ATTRwt amyloidosis differs from that of patients with ATTRv amyloidosis. The results revealed a high disease burden for patients with both conditions, with patients with ATTRwt reporting more diagnoses and procedures prior to their final diagnosis. Through further in-depth interviews with participants with ATTRwt amyloidosis, we present direct quotes from patients illustrating the paths they often take to diagnosis, through interactions with multiple physicians and specialists, and the opportunities for earlier diagnosis.
Conclusions: Our study provides insight into the overall impact of the patient journey on their quality of life and demonstrates how increased awareness of ATTRwt amyloidosis and more coordinated engagement with physicians could reduce the time to diagnosis.
The effect of single and combined microplastics with heavy metals Cu and Pb on digestive enzymes in Paphia undulata
Authors: Barus Beta Susanto , Purwiyanto Anna Ida Sunaryo , Suteja Yulianto , Dwinanti Sefti Heza
Published: November 2023

The contaminant most frequently found in aquatic habitats and potentially harms living things is called microplastic (MPs). MPs can also interact with other pollutants, such as heavy metals. This study aims to investigate the effects of PS particle of different sizes (20 and 150 µm) on the digestive enzymes (protease, amylase, and lipase) of the hard clam Paphia undulata, either alone or in combination with two distinct heavy metals (copper/Cu and lead/Pb). According to this study, clams' digestive enzyme responses often increased from days 5 to 7, then dropped the next day until the observation's completion. Greater enzyme activity results from exposure to larger particles (150 µm) than from smaller ones (20 µm). When heavy metals and MPs particles were exposed together, the peak phase of digestive enzyme activity was significantly higher (p < 0.05) than when only one particle or heavy metal was present. Hard clams exposed to MPs in combination with Pb increased digestive enzyme activity more than those exposed to MPs in combination with Cu. In addition, when PS particles were combined with Pb metal instead of Cu metal, the activity of digestive enzymes changed more quickly in the exposed clams. Clams exposed to PS in combination with Cu showed an increase in digestive enzyme activity on the seventh day of treatment, except for amylase. However, those treated with PS in combination with Pb metal showed an increase on the fifth day of exposure. This study demonstrates how these contaminants harm hard clams by disrupting their digestive systems, which can lead to growth inhibition and even death.
The impact of green credit on economic development quality - The mediating effect of firm innovation
Authors: Chen Jingpeng , Wu Yuqiang , Wan Yi , Cai Zigong
Published: November 2023

Implementing green credit is now a crucial step for nations looking to control social capital flows, improve environmental governance, and foster high-quality economic development in the context of the global low-carbon transition. This study analyzes the effects of green credit policy on high-quality economic development from the perspective of firm innovation using panel data from 30 Chinese provinces. The data is from the period between 2011 and 2020. The benchmark regression and mediation effect models are used to analyze the relationship between green credit and high-quality economic development. The research results show that (1) Green credit can directly and significantly raise the standard of economic growth. (2) Enterprise innovation mediates the relationship between green credit and high-quality economic growth. Green credit can promote high-quality economic development through enterprise technical innovation, human capital innovation, enterprise stock, and enterprise incremental innovation. (3) The most apparent mediating influence in enterprise innovation is played by human capital innovation. Our research provides policy implications for governments, banks and enterprises to promote green transformation and innovation, and ultimately achieve high-quality economic development.
Influence of alkaline on sodium sulfate activated slag: strength, phase assemblage and microstructure
Authors: Zhang Mingtao , Tang Han , Zhang Hua , Ye Jianxiong , Zhao Min , Wang Zeping , Li Xin
Published: November 2023

Alkali-activated slag (AAS) is gaining popularity as a low-carbon and energy-saving cementitious material. The use of Na2SO4 as an activator in AAS is a promising strategy that has yielded relatively favorable results. However, Na2SO4-activated slag have low compressive strength due to the low initial pH, which limits the consumption of AAS. In this study, the effect of Na2SO4 dosage and NaOH concentration on the compressive of Na2SO4-activated slag pastes were investigated. The phase assemblage and microstructure evolution of hardened pastes were analyzed by X-ray diffraction (XRD), thermogravimetric analysis (TGA) and scanning electronic microstructure (SEM). The results indicated that the 28 days compressive strength of AAS pastes developed progressively with the increase of Na2SO4 dosage, while the effect of NaOH on the compressive strength was related to the concentration of NaOH due to the changes of phase assemblage and microstructure. In the AAS pastes activated by sole Na2SO4, the main hydration products included C-(A)-S-H, ettringite and hydrotalcite-like phase. The addition of NaOH could promote the hydration of AAS, but inhibited the formation of ettringite, and the two mechanisms worked together to affect the compressive strength. When the NaOH concentration was less than 0.75 mol/L, the amount of ettringite decreased with the increase of NaOH concentration, and the amount of SO42− rich hydrotalcite-like phase gradually increased, which was much smaller in size, leading to a decrease of the compressive strengths of the pastes. After the NaOH concentration increased to more than 0.75 mol/L, the high concentration of OH− played a dominant role in promoting the hydration of AAS, leading to the improvement of compressive strength.
The probability of finding a z < 0.79 AGN changing-look optically is 0.0083?
Authors: Shen Yu-Fu
Published: November 2023

Active Galactic Nuclei (AGN) are characterized as supermassive black holes that accret matter, and are located at the center of a galaxy. AGNs are known to show flux variability, but some of them show much more dramatic changes, such as variations in their broad emission lines and X-ray cutoff frequencies, so-called changing-look AGNs (CL-AGNs). The causes of these changes are still unclear. The proportion of CL-AGN P could provide valuable insights into the underlying causes of CL-AGN, but it is hard to determine, since CL-AGN may have different timescales, so even if no CL event is observed, the possibility of it being a CL-AGN cannot be ruled out. In this work, P ∙ α, the probability of finding an AGN changing-look is defined, which is easier to determine, where α is the proportion of time an AGN exhibits changing. To obtain reliable P ∙ α, the two crucial steps are to acquire a sample with minimal selection biases and to minimize the Bayesian error. The Large Sky Area Multi-Object Fiber Spectroscopic Telescope data release 8 has observed a total of 1087 AGNs at least twice randomly, of which 486 have a redshift of less than 0.79. This is a sample with weak selection effect because it was not preselected based on conditions such as the amplitude of flux variation. By analyzing the OIII and Hβ flux ratios of these 486 AGNs, 6 CL-AGN candidates are identified, and several modes of changes in Hβ lines are found. Out of the 365 AGNs observed twice, there are 3 CL-AGN candidates; out of 82 AGNs observed thrice, there are 2; and out of 25 AGNs observed four times, there is one. These detailed data can constrain the range of P and α, resulting in P ∙ α ∼ 0.0083±0.0002. In addition, by combining WISE data, it seems that when the Hβ line itself enhances, the infrared band magnitude also significantly increases; However, when the Hβ line is enhanced due to the elevation of the continuous spectrum, there is no significant change in the infrared band, which may indicate that there are two independent regions contributing to the Hβ line.
Putative Identification of 12 Isomeric and 21 Non-isomeric Compounds from Leaves of Rubus Alceifolius Poir Using Database-affinity UHPLC-Q-Exactive-Qrbitrap-MS/MS
Authors: Li xican , Zeng Jingyuan , Ca Rongxin , Chen Shaoman , Li Chunhou , Jin Nana , Chen Tingshan , Lin Xiaohua , Khan Sunbal
Published: November 2023

This is the first article to report of the chemical profile of the leaves of Rubus alceifolius Poir, a widely distributed medicinal plant in the Eastern Hemisphere. Fresh leaves of R. alceifolius were treated by a set of experimental protocols to prepare a lyophilized aqueous extract. A novel strategy was used to analyze the extract, i.e., The extract was then analyzed using a new strategy, i.e., database-affinity ultra-high-performance liquid chromatography-quadrupole-Exactive-Orbitrap-tandem mass spectrometry (UHPLC-Q-Exactive-Orbitrap-MS/MS). Using MS/MS at full elucidation and comparison with the database, 33 compounds were putatively identified, including 12 flavonoid derivatives, 6 phenolic acid derivatives, 6 caffeoylquinic acids, two tea polyphenols, and others. Especially, 12 isomers have been strictly distinguished, including apigenin vs 2'-hydroxydaidzein, luteolin 7-O-glucuronide vs scutellarin, (+) catechin vs (-) epicatechin, 3-O-caffeoylquinic acid vs 4-O-caffeoylquinic acid vs 5-O-caffeoylquinic acid, and 3,4-O-dicaffeoylquinic acid vs 3,5-O-dicaffeoylquinic acid vs 4,5-O-dicaffeoylquinic acid. In addition, 21 non-isomeric compounds were also found under both negative and positive ion models, such as ellagic acid and gallic acid. Structural comparison suggested that there were biogenetic relationships among the flavonoid derivatives, such as glycosidation and hydroxylation. All these new findings will help to understand the substance basis of the traditional medicinal functions of R. Alceifolius. The structural comparison suggested biogenetic relationships between flavonoid derivatives, such as glycosidation and hydroxylation. These findings will allow the scientific community to better understand R. Alceifolius traditional medicinal functions.
In vitro micropropagation and hairy root induction for astragaloside IV production in Astragalus membranaceus var. mongholicus
Authors: Taghizadeh Siamak , Özzambak Mustafa Ercan , Zeybekoglu Emrah , Salehian Hamed , Azadi Pejman
Published: November 2023

Astragalus membranaceus var. mongholicus, is an important natural source of bioactive constituents. Pharmacological and clinical studies of secondary metabolites have confirmed that A. membranaceus has diverse biological functions. Plant tissue culture-based techniques and hairy root and adventitious root cultures are often used as practical platforms for the exploitation of biochemical compounds from medicinal plants. In this study, micropropagation of A. membranaceus was optimized for rapid proliferation, and hairy roots were induced by three strains of Agrobacterium rhizogenes (A4, A13, and MSU), on two leaf explant ages (10- and 20-day old), and three inoculation times (10, 20, and 30 min). In addition, the effects of three concentrations (100, 250, and 500 µM L− 1) of salicylic acid (SA) and methyl jasmonate (MJ) on astragaloside IV accumulation in A. membranaceus hairy roots were investigated. The highest number and length of branches were obtained on MS medium supplemented with 1 mg L− 1 BAP. Strain A13 caused the highest rate of induction of hairy root in leaf explants. In addition, since the age of explants had a significant effect on hairy root formation, the youngest explants obtained the highest number and longest hairy roots. Results showed that inducers of methyl jasmonate and salicylic acid elicitors could effectively stimulate the content of astragaloside. Our study showed that treating hairy root cultures with 250 µM MJ or 500 µM SA effectively increased astragaloside-IV accumulation in A. membranaceus hairy roots. Therefore, The findings provide valuable insights into optimal conditions for increasing large-scale production of astragaloside-IV such as industrial production in bioreactors.
Violence Against Healthcare Workers: ViSHWaS a Cross-Sectional Sub-analysis across the Kenya Region
Authors: Shah Reena , Shah Jasmit , Qasba Rakhtan K. , Qasba Ruman K. , Mbithi Annastacia , Njenga Erick , Banga Akshat , Kashyap Rahul , Surani Salim
Published: November 2023

Objective: Global concern exists for workplace violence against healthcare workers (HCWs), especially in low and middle-income nations. This violence includes physical, verbal, or sexual abuse and has a significant impact despite initiatives like Occupational Safety and Health Administration (OSHA) guidelines. We conducted a study in Kenya to address this issue.
Methods: We did a cross-sectional survey that collected responses during June 6th to August 9th, 2022, focused on healthcare professionals in Kenya within the global ViSHWaS study. Violence against healthcare professionals in multiple Kenyan counties was analysed, The study reached participants through social media, emails, and other channels using a snowball sampling technique.
Results: The survey included 1,458 HCWs, primarily females (66.5%), aged 36-45 (42.4%), and of African race, representing 40 counties, with the majority from Nairobi (28.9%) and working in government academic (35.5%) and private academic institutions (20.6%). Most had over 11 years of healthcare experience (64.4%), and registered nurses were the most common cadre (27.8%). Approximately half (49.9%) reported experiencing violence, with verbal violence (80.6%) and emotional abuse (78.6%) being common. Online harassment was reported by only 3.5%, mainly on Facebook (63.2%), involving hate speech (92.1%). Patients or their relatives were the most common aggressors (44.7%), while supervisors accounted for 12.5%. The frequency of violence varied, and 80.2% noted an increase after the COVID-19 pandemic. Only 41.2% of incidents were reported. Most were familiar with safety guidelines (93.6%). Self-violence was associated with familiarity with guidelines, concern about violence, preparedness, and night shifts, while colleague violence was associated with age, gender, race, work experience, training, preparedness, and night shifts.
Conclusion: Our Kenya-based cross-sectional sub-analysis highlights that a significant number of HCWs experienced violence, especially during the COVID-19 pandemic, which negatively affected job satisfaction. Although most HCWs were familiar with OSHA guidelines, there were difficulties in their practical implementation.
First molecular identification and subtyping of Blastocystis sp. in the most consumed edible marine fish of Iran: A foodborne concern
Authors: Asghari Ali , Banavand Shaghayegh , Akhlaghzadeh Maryam , Shamsi Laya , Hatam Golamreza
Published: November 2023

The presence of Blastocystis sp. is commonly observed in humans and different animals, displaying a wide range of genetic variations with the discovery of multiple subtypes (STs). However, the prevalence and distribution of these STs in edible marine fish and marine mammals remain uncertain. This study marks the first survey conducted in Iran and the second global molecular investigation to examine the occurrence and STs distribution of Blastocystis in various species of edible marine fish. This study screened 200 fresh intestinal contents from 10 well-known fish species (Narrow-barred mackerel, Indo-pacific king mackerel, Tigertooth croaker, Silver pomfret, Black pomfret, Longtail tuna, John's snapper, Blackspotted croaker, Four-finger threadfin, and Javelin grunter) in southern Iran, caught in the Persian Gulf. All collected samples were evaluated by microscopy and SSU-PCR methods. Based on both microscopy and PCR, the overall prevalence of Blastocystis sp. in evaluated fish species was [2% (4/200)]. In brief, Blastocystis sp. was reported from Narrow-barred mackerel [10% (2/20)], Silver pomfret [5% (1/20)], and Tigertooth croaker [5% (1/20)]. Interestingly, among infected fish species three zoonotic STs (ST1, ST2, and ST7) were identified. ST2 was the most predominant ST [50% (2/4)], followed by ST1 and ST7, one sample each [5% (1/20)]. Overall, the prevalence and STs distribution of Blastocystis in edible marine fish along with the possibility of its zoonotic transmission are still open to question and require extensive and more detailed studies.
The SOC of steppe grasslands is more sensitive to grazing than desert-steppe grasslands and is regulated by precipitation outside the growing season in the Mongolian Plateau
Authors: Quan Zhijia , Tsubo Mitsuru , Shinoda Masato , Cheng Yunxiang
Published: November 2023

Purpose
Soil organic carbon (SOC) predominates organic carbon pools in grassland. To address global climate change, it is essential to explore the soil organic carbon influencing factors and mechanisms.
Method
s We investigated the soil organic carbon (SOC) in 109 plots along the Mongolian Plateau grassland, which covers the desert-steppe and steppe. Specifically, we analyzed the SOC in the top 10 cm soil layer and its relationships with grazing intensity, climatic factors, soil properties, and vegetation diversity index.
Results
The average SOC of the desert-steppe (0.3%) was lower than that of the steppe (1.5%). In the desert-steppe, SOC did not vary with grazing intensity. In the steppe, SOC varied significantly with grazing pressure. Significant negative relationships were found between the SOC and growing season temperature (GST) and growing season aridity index (GSR) in the two regions. The responses of SOC to mean annual precipitation (MAP), growing season precipitation (GSP), and outside growing season precipitation (OGSP) in two types of grasslands were different. GST and soil EC were respectively identified as the major positive and negative factors influencing the SOC in the desert-steppe; the OGSP and soil PH were the major positive factors influencing the SOC in the steppe.
Conclusion
Out results proposed that soils of steppe grasslands have a large carbon sink potential but are more susceptible to grazing. These findings enhance our understanding of the different mechanisms of SOC in different grasslands along the Mongolian Plateau, which are crucial for predicting the effects and consequences of environmental change on carbon sequestration.
Iron oxide nanoparticle (Fe3O4-NP) elicitation of Artemisia annua L. in vitro toward enhancing artemisinin production through overexpression of key genes of terpenoids biosynthesis pathway and induction of oxidative stress
Authors: Ayoobi Akhtar , saboora azra , Asgarani Ezat , Efferth Thomas
Published: November 2023

An important phytochemical compound with bioactive properties is artemisinin, which is extracted from Artemisia annua L.. Frontline malaria treatments are artemisinin-based combination therapies (ACTs). The expression of key genes in the biosynthesis pathway of artemisinin can be regulated through metabolic engineering. In this study, we evaluated changes in the mRNA levels of the AaWRKY1, AaMYB2, HMGR, and CYP71A1 genes following the application of iron oxide nanoparticles (Fe3O4-NPs) after 0, 4, 8, 24, 48, and 96 h of spraying at concentrations of 0, 50, 100, and 200 mg L− 1 on the leaves of 6-week-old A. annua plants. The total protein contents and the activity of the CAT, POX, SOD, and PAL enzymes were increased by Fe3O4-NP, which triggered an enzymatic defense system associated with reactive oxygen species (ROS). This ROS-related defense mechanism was activated by Fe3O4-NPs, which significantly stimulated the expression of those target key genes and raised the artemisinin levels in A. annua. The artemisinin content increased after 96 h by 98.5%, 76.3%, and 77% in plants treated with the three Fe3O4-NP concentrations, respectively compared to the control. These findings can help the commercial production of this important medicinal compound both in vivo and in vitro.
In vitro Wound Healing Efficacy of Silver Nanoparticles Synthesized from Aqueous Extract of Turbinaria conoides.
Authors: Suresh Thirinavukkarasu Chitrikha , Poonguzhali Thinnaur Venugopal , Anuradha Venkatraman , Bharathi Selvaraj , Deepa Chokkalingam , Ramesh Balasubramanian , Kavitha Kuppusamy , Rajalakshmi Arumugam , Elumalai Perumal , Suresh Gopal
Published: November 2023

The wound healing potentials of brown algae Turbinaria conoides aqueous extract (TCAe) and silver nanoparticles synthesized utilizing T. conoides aqueous extract (TCAgNPs) were investigated in this study. TCAgNPs and TCAe were tested for cytotoxicity on human dermal fibroblast cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, which revealed that TCAgNPs and TCAe were not cytotoxic and may be tested for medicinal qualities. TCAgNPs and TCAe were tested for wound healing efficacy using a wound scratch assay on human dermal fibroblast cells. The damaged cells were subjected to TCAgNPs and TCAe, which demonstrated stronger wound repair activities than the control (Untreated). The cell cycle study of human dermal fibroblast primary cell lines treated with TCAgNPs and TCAe, as well as those not treated, was performed using flow cytometry to determine the DNA content of the nuclei. These findings show that TCAgNPs-treated cells proliferated more than TCAe and control-treated cells, implying that cell proliferation is boosted, which aids the wound-healing process. During immunoblot analysis, the TCAgNPs-treated group showed higher collagen and fibronectin expression than the TCAe-treated group. Our findings imply that TCAgNPs and TCAe can repair wounds in vitro and could be used as a source of wound healing agents.
Optimal Frequency for Biomedical Wireless Power Transfer
Authors: Nunen Tom van , Mestrom Rob , Visser Hubregt
Published: November 2023

When power is to be transferred to a mm-sized \gls{imd}, located multiple cm deep inside the human body, the main goal is often to maximize the received power, within the applicable \gls{sar} limits. It has been shown that, for equivalent homogeneous biological tissue, there is little difference between the received power using \gls{wpt} at (sub-)GHz frequencies compared to low MHz frequencies. However, it remains unclear whether the introduction of additional tissue layers, thus more accurately approximating the real environment, changes the optimal frequency for maximum received power. This paper presents an analytical model that can be used to calculate the \gls{em} fields, \gls{sar}, received power, and \gls{pte} in a planarly layered environment, consisting of an arbitrary number of layers with arbitrary thicknesses and arbitrary dielectric properties. The model is first validated by comparing it to CST Studio Suite\textregistered. It is then used to determine the optimal frequency for \gls{wpt} to a mm-sized implant, located multiple cm deep inside the human body. The optimal frequency is 10 kHz, and the received power is approximately constant up to 300 kHz. The same holds for the \gls{pte}.
Multiresistance of Escherichia coli and Salmonella spp Strains in chicken feces intended for consumption in open spaces of Ouagadougou, Burkina Faso
Authors: Bénao Stéphanie Lynseh Carine Sita , Mètuor Dabiré Amana , Ouattara Abdoul Karim , Tiemtoré Rahimatou Yasmine Wendkouni , Ouédraogo Blandine , Badini Rhaina Olivia , Bambara Lionel Eliada Benoit , Sougué Serge , Simporé Jacques
Published: November 2023

Background
Resistant bacteria can be transmitted to humans through feces or contaminated meat from chickens. Bacterial strains were isolated from the intestinal contents of 400 chicken samples from various sales sites. These strains were then characterized using bacteriological and biochemical methods to identify resistant strains.
Methods
In a study conducted in Ouagadougou, we systematically collected chicken fecal samples from 20 locations across the city, followed by isolation and identification of Salmonella spp using specific enrichment and culture methods, as well as Escherichia coli. Bacterial strains were characterized using the API 20E gallery method, and their antibiotic resistance profiles were determined through agar diffusion tests, revealing sensitivity or resistance to a range of antibiotics based on established scientific criteria.
Results
The results showed that out of the 400 samples collected, 81.25% and 63.5% contained isolates of Escherichia Coli and Salmonella spp, respectively. Among these, 86.15% of identified Escherichia Coli and 50.78% of Salmonella spp displayed resistance to at least one tested antibiotic. Among 280 Escherichia coli isolates identified resistant to at least one antibiotic, 31.07% were resistant to cefotaxide (CTX), 20.35% to ceftazidime (CAZ), 21.07% to ceftriaxone (CTR), 75% to amoxicillin + clavulanic acid (AMC), 23.57% aztreoname (TMJ) and 27.14% were resistant to imipenem (IMP). In the case of the 129 Salmonella spp isolates resistant to at least one tested antibiotic, 34.88% displayed resistance to CTX; 41.08% to CAZ; 35.65% to CTR, 92% to AMC, 39.53% to ATM and finally 47.28% were resistant to IMP.
Conclusions
Our study revealed high prevalence of resistance in bacterial strains isolated from chickens sold outdoors in Ouagadougou. These findings raise significant public health concerns, due to the possible transmission of these resistant strains to humans through the consumption of contaminated meat, thus complicating the treatment of bacterial infections.
Differentially expressed genes in ethanol extract of vanilla planifolia stem-induced cell death in glioblastoma cells
Authors: Chang Hui Hua , Chen Yu-Ju , Wu Sung-Ghun , Chen Li-Jyun , Tsai Bing-Chen , Hsueh Yuan-Shuo
Published: November 2023

Purpose
Glioblastoma multiforme (GBM) is a highly malignant brain tumor with poor prognosis after conventional treatment. Therefore, novel therapeutic targets and potential treatment strategies have gained increased attention. Vanilla planifolia is an original source for vanilla flavoring due to its high vanillin content. Several studies have proven the antitumor activity of vanillin in colon cancer.
Methods
In this study, three GBM cell lines, patient-derived temozolomide (TMZ)-resistant GBM P#5 TMZ-R cells, T98G cells, and U-87 MG cells, were used to evaluate the antitumor activity of extracts from vanilla planifolia.
Results
Our data showed that ethanol extract of vanilla planifolia stem (VAS) at 200 ng/µl significantly reduced cell viability and colony formation of GBM cells. Moreover, VAS induced MAP1LC3 cleavage, a marker of autophagy. Further RNA-seq analysis and MA plot showed 1972 upregulated differentially expressed genes (DEGs) and 2276 downregulated DEGs in 200 ng/µl VAS-treated P#5 TMZ-R cells compared to the control. Protein-protein interaction between fold change of DEGs less than − 3 and over 5 were further analyzed, and we found that 16 and 9 hub DEGs, respectively, were correlated with other DEGs. Further qPCR experiments showed that the mRNA expression of DHRS9, HOPX, AQP5, PCP4, RGS8, GNAT2, RLBP1, FA2H, TNMD, SKAP1, MATN1, IGFBP1, ELFN2, and C2CD4C was significantly downregulated. Moreover, the expression of IL36RN, CCL20, CCL5, CXCL10, HMOX1, MX2, RSAD2, IFI44L, and EGR1 was significantly upregulated.
Conclusion
These findings demonstrated that VAS reduced cell viability and colony formation, induced autophagy, and pinpointed some hub DEGs as potential therapeutic targets for GBM treatment.
Function rather than structure of phytoplankton community reveals changes of water quality in an ecological restored lake
Authors: Hu Caiqin , Xie Changxin , Yang Wanling , Liu Qianfu , Gao Yuan , Zeng Yanyi , Li Haiyan , Sun Jinhui , Wang Chao
Published: November 2023

Although phytoplankton are well known as robust bioindicators to aquatic environments, their indicating functions based on different community parameters remain to be understood. In order to filtering effective bioindicators to aquatic ecosystems, four phytoplankton community parameters including species richness (SR), total biomass (SBP), functional groups (FGBP) and size-fractionated chlorophyll-a (SC) were demonstrated and tested in a subtropical artificial lake with ecological restoration in South China. Our results indicated that all the above four parameters exhibited high sensitivity to environmental variations and illustrated distinct aspects of indicating functions to aquatic environments due to their individual biological characteristics. Based on FGBP, both spatial and temporal differences in phytoplankton community could be identified; SR and SBP only classified the spatial and temporal distributions, respectively; while SC could distinguish the sewage outfalls from other sites. In terms of ecological management, two parameters (SR and FGBP) could distinguish the restored waters from untreated environments as non-point source pollution, and another parameter SC could indicate the sewage outfalls as point source pollution. Therefore, the combination of the above two categories of phytoplankton community parameters could make the strongest indicating functions. Our study provided greater insight into indicating functions of phytoplankton community parameters in an ecological restored lake and enabled better managements in such artificial lakes.
Immune suppressive drugs negatively regulate the CD8+ T cells function by acetyltransferase p300 induced canonical and non-canonical autophagy
Authors: Ni Runfeng , Fan Liwei , Wang Haijin , Zhang Quan , Zhang Le , Yang Wuxia , Wang Aidi , Liu Baoshan
Published: November 2023

Macroautophagy is the mainly regulated form of autophagy that maintains the cellular homeostasis and degraded the transported cargoes. It is initiated by the protein kinase complex which initiation by receiving two signals pathway mTORC1-AMPK-ULK1 and ULK1-PI3K-PI3P. Currently, autolysosomes accumulate during in vitro CD8+ T cells aging and may participate in inducing death sensitization of senescent cells. Aplastic Anemia is a hyperimmune disease and mainly mechanism of AA is the T cells subsets imbalance such as CD8+ T cells abnormal activation and hyperfunction. Therefore, we focused on the role of autophagy in the CD8+ T cells and supposed whether some immunosuppress drugs induced the cells autophagic death to therapy the hyperimmune diseases. We found that the acetyltransferase p300 obviously increases in the AA patients and is related with the severity of illness. Previous studies have reported that canonical autophagy is regulated by the mTORC1-p300 axis. p300, which acetylation occurs on its substrates, is a critical bridge in the p300-VPS34 axis mediated non-canonical autophagy. We showed that there is autophagy deficiency and acetylation deficiency in the CD8+ T cells. We first researched the canonical autophagy in the CD8+ T cells, notably, the expression of p300 also decreased after the immunosuppressive drugs therapy. Our findings provide a framework for understanding how immunosuppressive drugs effect on the AA autophagy deficiency mechanism and we proved that CD8+ T cells was negatively regulated by immunosuppressive drugs by p300-mediated canonical autophagy pathway and non-canonical autophagy pathway.
Difference in impact of coinfections on antibiotic use in patients hospitalized with COVID- 19 between the Omicron-dominant period and the pre-Omicron period
Authors: Murakami Yasushi , Nozaki Yasuhiro , Morosawa Mika , Toyama Masanobu , Ogashiwa Hitoshi , Ueda Takashi , Nakajima Kazuhiko , Tanaka Ryoya , Takesue Yoshio
Published: November 2023

Background
Excessive antibiotic use in patients with coronavirus disease 2019 (COVID-19) can cause an increase in multidrug-resistant (MDR) organisms. This study evaluated antibiotic stewardship during the COVID-19 pandemic.
Methods
Antibiotic use in patients with COVID-19 was compared in a community hospital between 2022 when the Omicron variant was prevalent (n = 225) and 2021 when previous variants were prevalent (n = 257). Antibiotics were categorized as antibiotics predominantly used for community-acquired infections (CAIs) and antibiotics predominantly used for health care-associated infections (HAIs), and days of therapy per 100 bed days (DOT) was evaluated.
Results
Patients during the Omicron period were older and had more comorbidities. The rate of critically ill patients was around 10% in both periods. During the pre-Omicron period, > 90% of hospitalized patients were unvaccinated, whereas 41.8% of patients received a booster dose during the Omicron period. Ground-glass opacities, bilateral shadows, and a peripheral distribution on CT were observed in most patients in the pre-Omicron period and there were significant differences in comparison with the Omicron period. Although only 0.9% of patients had bacterial coinfection on admission in the pre-Omicron period, 38.9% of patients had the coinfection during the Omicron period and were less likely to receive COVID-19-directed therapy. Coinfection before /after admission was an independent risk factor for composite adverse events in both periods (odds ratio [OR] 3.77, 95% confidence interval [CI] 1.13–12.59, and OR 9.15, 95% CI 3.85–21.74). DOT in antibiotics for CAIs were significantly fewer in the COVID-19 ward than in general wards in the pre-Omicron period but increased in the Omicron period (from 3.60 ± 3.15 to 17.83 ± 10.00). Numerically lower DOT of antibiotics for HAIs was demonstrated in the COVID-19 ward than in the general wards (pre-Omicron, 3.33 ± 6.09 versus 6.37 ± 1.10; Omicron, 3.84 ± 2.93 versus 5.22 ± 0.79). No MDR gram-negative organisms were isolated in the COVID-19 ward.
Conclusions
Antibiotic use on admission was limited in the pre-Omicron period but increased in the Omicron period because of a high coinfection rate on admission. Excessive use of antibiotics for HAIs was avoided during both periods.
Altered dynamic and static brain activity and functional connectivity in COVID-19 patients: a preliminary study
Authors: Han Mingxing , He Chunni , Li Tianping , Li Qinglong , Chu Tongpeng , Wang Peiyuan , Li Jun
Published: November 2023

Background: Coronavirus disease 2019 (COVID-19) is a respiratory disease, but it also affects brain function. The use of resting-state functional MRI (rs_fMRI) technology to study COVID-19 patients has not been thoroughly explored. To investigate the effects of COVID-19 on brain functional activity and pave the way for a deeper understanding and future research.
Methods: fMRI scans were conducted on a cohort of 42 confirmed COVID-19-positive patients and 46 healthy controls (HCs) to assess brain functional activity. A combination of dynamic and static amplitude of low-frequency fluctuations (dALFF/sALFF) and functional connectivity (dFC/sFC) was used for evaluation. Abnormal brain regions identified were then used as feature inputs in the model to evaluate support vector machine (SVM) capability in recognizing COVID-19 patients. Moreover, the random forest (RF) model was employed to verify the stability of SVM diagnoses for COVID-19 patients.
Results: Compared to HCs, COVID-19 patients exhibited a decrease in sALFF in the right lingual gyrus and the left medial occipital gyrus, and an increase in dALFF in the right straight gyrus. Moreover, there was a decline in sFC between both lingual gyri and the right superior occipital gyrus and a reduction in dFC with the precentral gyrus. The dynamic and static combined ALFF and FC could distinguish between COVID-19 patients and the HCs with an accuracy of 0.885, a specificity of 0.818, a sensitivity of 0.933, and an AUC of 0.909.
Conclusion: The combination of dynamic and static ALFF and FC can provide information for detecting brain functional abnormalities in COVID-19 patients.
Status of the end-to-end demonstration readout chain for Athena/X-IFU
Authors: Roudil Gilles , Pajot François , Castellani Florent , Beaumont Sophie , Dupieux Michel , Murat David , Parot Yann , Ravera Laurent , Adams Joseph , Bandler Simon , Chervenak James , Cucchetti Edoardo , Daniel Christophe , Doriese William , Durking Malcolm , Geoffray Hervé , Hilton Gene , Mot Baptiste , Peille Philippe , Prêle Damien , Reintsema Carl , Sakai Kazuhiro , Ullom Joel , Wakeham Nicholas , Molin Alexei
Published: November 2023

The X-ray Integral Field Unit (X-IFU) of the Athena observatory, scheduled for launch in the mid 2030's, will provide X-ray imaging spectroscopy data with unprecedented spectral and spatial resolution. The detection chain, based on a ~ 1.5 kilo-pixel array of transition edge sensors (TESs) cooled down to 55 mK, is under development by a large international collaboration. In order to perform an end-to-end demonstration of the X-IFU readout chain, a 50 mK test bench (Elsa), is being developed at IRAP in collaboration with CNES. Based on a commercial ADR cryostat, it includes a 1024-pixel TES array provided by NASA/GSFC with its associated cold readout chain provided by NIST. The validation of the performance of the system was performed using a NIST and NASA/GSFC laboratory warm readout chain. These laboratory electronics will be replaced step by step by the demonstration models of the space qualified electronics designed for the X-IFU: the digital readout electronics by IRAP and the warm front-end electronics by APC. We present here the status of the 50 mK test bench, its performance budget, and the demonstration of a prototype of a first element of the flight electronics.
Causal association of sex hormones with osteoporosis: a two-sample Mendelian randomization study
Authors: zhang yu jun , Lian Qiufang , Nie Yanwu , Zhao Wei
Published: November 2023

Background
Epidemiologic studies have identified a correlation between sex hormones and osteoporosis(OP), yet the presence of a causal effect remains unverified. Confounding factors and reverse causal associations mean observational studies merely reflect this correlation, without clarifying the intricate causal relationships at play. This study, therefore, employed Mendelian randomization to thoroughly examine the causal link between sex hormones and osteoporosis.
Methods
Exposure variables for sex hormones, encompassing total testosterone (TT), bioavailable testosterone (BAT), sex hormone binding globulin (SHBG), and estradiol (E2), were derived from the IEU Open GWAS aggregated data. The outcome variable, osteoporosis, was sourced from the UK Biobank database. The Mendelian randomization analysis was conducted using the inverse variance weighted analysis (IVW) method, MR-Egger, and weighted median (WM) method to assess the causal relationship between sex hormones and osteoporosis. Outliers were identified via MR-PRESSO, the effect of individual SNPs on IVW analysis outcomes was investigated through leave-one-out sensitivity analysis, horizontal pleiotropy was detected using MR-Egger-intercept, heterogeneity among instrumental variables was evaluated with Cochran's Q-test, potential biases in findings were examined through funnel plots, and MR Steiger analysis was employed to explore any reverse causal associations.
Results
Mendelian randomization revealed that genetically predicted TT levels were inversely correlated with osteoporosis risk [IVW: OR (95% CI): 0.997 (0.995, 0.999), P = 0.004], while BAT exhibited a negative causal association with osteoporosis [IVW: OR (95% CI): 0.990 (0.987, 0.994), P = 4.83E-07]. Conversely, SHBG was positively correlated with osteoporosis [IVW: OR (95% CI): 1.008 (1.003, 1.012), P = 0.0004], and E2 demonstrated no causal effect [IVW: OR (95% CI): 0.981 (0.960, 1.002), P = 0.07129]. Cochran's Q-test indicated no heterogeneity in the instrumental variables (IVs) for BAT and E2(P > 0.05) and detected heterogeneity in the IVs for TT and SHBG (P < 0.05), thereby underscoring the relevance of the random-effects IVW model. Neither MR-Egger intercept nor MR- PRESSO analyses detected any level pleiotropy (P > 0.05). The IVW results remained robust after sequential omission of SNPs via the leave-one-out method.MR Steiger analysis confirmed the absence of reverse causality.
Conclusion
Our results indicate a causal relationship between sex hormones and osteoporosis, wherein TT and BAT decrease osteoporosis risk, whereas SHBG increases it. These findings suggest that sex hormones levels are significant in osteoporosis prevention and treatment strategies
Dairy consumption and vitamin D concentration in adolescents with challenge-confirmed cow's milk allergy during infancy
Authors: Piippo Sonja , Hauta-alus Helena , Viljanen Mirva , Savilahti Erkki , Kuitunen Mikael
Published: November 2023

Background/Objectives:
Milk is an important source of dietary calcium and, if fortified, vitamin D. Cow’s milk allergy (CMA) is treated with a milk elimination diet. Although most children become tolerant by age 3 years, some continue dairy avoidance. It remains unclear whether adolescents with a history of CMA adopt similar milk consumption as their peers. We assessed dairy consumption and concentration of serum 25-hydroxyvitamin D (25(OH)D) in adolescents with either confirmed CMA or a negative CMA challenge in infancy (CMA-refuted group) and age-matched controls.
Subjects/Methods:
This study is based on a previously reported randomized controlled trial from 1999 to 2002 on the treatment effect of probiotics on atopic eczema in participants aged < 12 months (n = 230) with data on CMA status. We followed up these participants, aged 15–18 years, in 2017 (n = 104). A 20-item food frequency questionnaire assessed dairy consumption. An automated immunoassay measured 25(OH)D concentration.
Results
Median dairy product consumption did not differ between adolescents with CMA (449 g/d, n = 40), the CMA-refuted group (566 g/d, n = 36), and controls (235 g/d, n = 51) (P = 0.117). Median 25(OH)D concentrations were 76.0, 79.3, and 80.8 nmol/l, respectively (P = 0.844). Among participants, 93% were vitamin D sufficient (25(OH)D ≥ 50 nmol/l), with no differences between groups (P = 0.914).
Conclusion
Among adolescents with a history of CMA during infancy, our study found no reintroduction failure of milk and no difference in vitamin D insufficiency rate compared with peers. Current management of CMA seems to adequately minimize later nutritional disadvantages associated with a cow’s milk elimination diet.
Association of weight loss strategies with all-cause and specific-cause mortality: a prospective cohort study
Authors: Diao Zhiquan , Zhu Yilin , Huang Wenqi , Wen Huiyan , Li Jiaxin , Qiu Jiamin , Niu Yingying , Yan Haoyu , Zhong Jianfeng , Bai Xuerui , Xu Zhitong , Liang Xiaofeng , Liu Dan
Published: November 2023

Background
The health effects of different weight loss strategies vary greatly, and the relationship between weight loss strategies, especially the application and combination of multiple strategies, and death is still unclear. We aimed to examine the associations of various numbers and combinations of weight loss strategies with all-cause and specific-cause mortality and to further evaluate the associations of different total weight loss volumes with mortality.
Methods
Using data from the NHANES (1999–2018) with 48,430 participants aged 20 and above, we collected fourteen self-reported weight loss strategies and identified five clusters using latent class analysis. Cox proportional hazards models were used to examine the association between the amounts and clusters of weight loss strategies and mortality.
Results
During a median follow-up of 9.1 years of 48,430 participants, 7,539 deaths were recorded (including 1,941 CVDs and 1,714 cancer). Participants who adopted 2, 3–4, and ≥ 5 weight loss strategies had a lower risk of all-cause mortality, with HRs of 0.88 (95% CI, 0.81 to 0.97), 0.89 (95% CI, 0.81 to 0.96) and 0.71 (95% CI, 0.61 to 0.82). Regardless of weight loss or weight gain categories, there was a significant trend toward reduced mortality as the number of weight loss strategies increased (P trend < 0.05). Participants who adopted weight loss strategies named cluster-1 (four strategies), cluster-2 (five strategies) and cluster-3 (three strategies) had a significantly lower risk of all-cause mortality, with HRs of 0.71 (95% CI, 0.60 to 0.84), 0.70 (95% CI, 0.55 to 0.89) and 0.81 (95% CI, 0.70 to 0.94). Among them, cluster-1 and cluster-2 are both characterized by exercising, drinking plenty of water, lowering calories and eating less fat. Conversely, cluster-4 (five strategies) and cluster-5 (five strategies) had marginally significant effects, and they both had actual higher total energy intakes. Similar associations were observed for CVDs and cancer mortality.
Conclusions
Employing two or more weight loss strategies was associated with a lower risk of death, even among those who gained weight. Exercising, drinking plenty of water, lowering calories and eating less fat is a better combination of strategies. On this basis, limiting the actual intake of total energy is necessary.
Is Ketamine Infusion an Effective Treatment for Post-Traumatic Stress Disorder? A Meta-Analysis
Authors: Mowdawalla Cyrus P. , Pradhan Basant K. , Mitrev Ludmil V. , Hunter Kystal , Saracco Benjamin , Kim Helen Wonjai , Helmond Noud van
Published: November 2023

Post-traumatic stress disorder (PTSD) affects ~ 6% of adolescents and adults in the US. Increased N-methyl-D-aspartate (NMDA) receptor activation leads to heightened intrusive memories and is associated with an increased risk of developing PTSD. Ketamine is an NMDA antagonist with ultra-rapid therapeutic action for treatment-resistant depression and suicide. In this meta-analysis, we assessed the effect of subanesthetic ketamine infusion on PTSD severity. Six databases were investigated according to PRISMA guidelines with quality assessments according to the NIH Quality Assessment tool. Eligible criteria included: 1) Randomized Control Trial (RCT) or cohort study 2) Used a single or multiple ketamine infusion(s) 3) Studies using another treatment for PTSD to which (2) is added 4) PTSD symptoms are measured at pre-infusion baseline and up to at least 40 minutes after infusion using a valid PTSD symptom measurement scale 5) Study included ≥ 5 patients. The primary outcome was the first measured value of PTSD symptoms after treatment completion. Meta-analysis using a random effects model was performed on pre-to-post changes in PTSD severity within ketamine treated patients and to compare ketamine to control outcomes. The search retrieved 526 articles. Nine articles met inclusion criteria: 5 RCTs and 4 cohort studies. Meta-analysis revealed that ketamine infusion reduced PTSD symptom severity (pre-post ketamine: standardized mean difference pre-to-post: 3.07, 95% confidence interval 1.54–4.60, P < 0.01). These results support ketamine infusions as an effective treatment modality for PTSD symptoms. Ketamine-assisted psychotherapy is shown to enhance ketamine effect and aid in prolonging remission. Further research is needed to provide effective and long-lasting PTSD treatment.