bluuebunny/crossref_metadata_2025 huggingface dataset:
Adenosine metabolized from extracellular ATP ameliorates organ injury by triggering A2BR signaling
Authors: Kelestemur Taha , Németh Zoltán H. , Pacher Pal , Beesley Jennet , Robson Simon C. , Eltzschig Holger K. , Haskó György
Published: July 2023

Background

Trauma and a subsequent hemorrhagic shock (T/HS) result in insufficient oxygen delivery to tissues and multiple organ failure. Extracellular adenosine, which is a product of the extracellular degradation of adenosine 5’ triphosphate (ATP) by the membrane-embedded enzymes CD39 and CD73, is organ protective, as it participates in signaling pathways, which promote cell survival and suppress inflammation through adenosine receptors including the A2BR. The aim of this study was to evaluate the role of CD39 and CD73 delivering adenosine to A2BRs in regulating the host’s response to T/HS.

Methods

T/HS shock was induced by blood withdrawal from the femoral artery in wild-type, global knockout (CD39, CD73, A2BR) and conditional knockout (intestinal epithelial cell-specific deficient VillinCre-A2BRfl/fl) mice. At 3 three hours after resuscitation, blood and tissue samples were collected to analyze organ injury.

Results

T/HS upregulated the expression of CD39, CD73, and the A2BR in organs. ATP and adenosine levels increased after T/HS in bronchoalveolar lavage fluid. CD39, CD73, and A2BR mimics/agonists alleviated lung and liver injury. Antagonists or the CD39, CD73, and A2BR knockout (KO) exacerbated lung injury, inflammatory cytokines, and chemokines as well as macrophage and neutrophil infiltration and accumulation in the lung. Agonists reduced the levels of the liver enzymes aspartate transferase and alanine transaminase in the blood, whereas antagonist administration or CD39, CD73, and A2BR KO enhanced enzyme levels. In addition, intestinal epithelial cell-specific deficient VillinCre-A2BRfl/fl mice showed increased intestinal injury compared to their wild-type VillinCre controls.

Conclusion

In conclusion, the CD39-CD73-A2BR axis protects against T/HS-induced multiple organ failure.
BID expression determines the apoptotic fate of cancer cells after abrogation of the spindle assembly checkpoint by AURKB or TTK inhibitors
Authors: Bertran-Alamillo Jordi , Giménez-Capitán Ana , Román Ruth , Talbot Sara , Whiteley Rebecca , Floc’h Nicolas , Martínez-Pérez Elizabeth , Martin Matthew J. , Smith Paul D. , Sullivan Ivana , Terp Mikkel G. , Saeh Jamal , Marino-Buslje Cristina , Fabbri Giulia , Guo Grace , Xu Man , Tornador Cristian , Aguilar-Hernández Andrés , Reguart Noemí , Ditzel Henrik J. , Martínez-Bueno Alejandro , Nabau-Moretó Núria , Gascó Amaya , Rosell Rafael , Pease J. Elizabeth , Polanska Urszula M. , Travers Jon , Urosevic Jelena , Molina-Vila Miguel A.
Published: July 2023

Background

Drugs targeting the spindle assembly checkpoint (SAC), such as inhibitors of Aurora kinase B (AURKB) and dual specific protein kinase TTK, are in different stages of clinical development. However, cell response to SAC abrogation is poorly understood and there are no markers for patient selection.

Methods

A panel of 53 tumor cell lines of different origins was used. The effects of drugs were analyzed by MTT and flow cytometry. Copy number status was determined by FISH and Q-PCR; mRNA expression by nCounter and RT-Q-PCR and protein expression by Western blotting. CRISPR-Cas9 technology was used for gene knock-out (KO) and a doxycycline-inducible pTRIPZ vector for ectopic expression. Finally, in vivo experiments were performed by implanting cultured cells or fragments of tumors into immunodeficient mice.

Results

Tumor cells and patient-derived xenografts (PDXs) sensitive to AURKB and TTK inhibitors consistently showed high expression levels of BH3-interacting domain death agonist (BID), while cell lines and PDXs with low BID were uniformly resistant. Gene silencing rendered BID-overexpressing cells insensitive to SAC abrogation while ectopic BID expression in BID-low cells significantly increased sensitivity. SAC abrogation induced activation of CASP-2, leading to cleavage of CASP-3 and extensive cell death only in presence of high levels of BID. Finally, a prevalence study revealed high BID mRNA in 6% of human solid tumors.

Conclusions

The fate of tumor cells after SAC abrogation is driven by an AURKB/ CASP-2 signaling mechanism, regulated by BID levels. Our results pave the way to clinically explore SAC-targeting drugs in tumors with high BID expression.
Biodegradable FePS3 nanoplatform for efficient treatment of osteosarcoma by combination of gene and NIR-II photothermal therapy
Authors: Luo Tingting , Jiang Mingyang , Cheng Ziqiang , Lin Yuntao , Chen Yuling , Zhang Zhenyu , Zhou Jian , Zhou Wenhua , Yu Xue-Feng , Li Shuchun , Geng Shengyong , Yang Hongyu
Published: July 2023

As a common tumor with high incidence, osteosarcoma possesses extremely poor prognosis and high mortality. Improving the survival of osteosarcoma patients is still a great challenge due to the precipice of advancement in treatment. In this study, a combination strategy of gene therapy and photothermal therapy (PTT) is developed for efficient treatment of osteosarcoma. Two-dimensional (2D) FePS3 nanosheets are synthesized and functionalized by poly-L-lysine-PEG-folic acid (PPF) to fabricate a multifunctional nanoplatform (FePS@PPF) for further loading microRNAs inhibitor, miR-19a inhibitor (anti-miR-19a). The photothermal conversion efficiency of FePS@PPF is up to 47.1% under irradiation by 1064 nm laser. In vitro study shows that anti-miR-19a can be efficiently internalized into osteosarcoma cells through the protection and delivery of FePS@PPF nanaocarrier, which induces up-regulation of PTEN protein and down-regulation p-AKT protein. After intravenous injection, the FePS@PPF nanoplatform specifically accumulates to tumor site of osteosarcoma-bearing mice. The in vitro and in vivo investigations reveal that the combined PTT-gene therapy displays most significant tumor ablation compared with monotherapy. More importantly, the good biodegradability promotes FePS@PPF to be cleared from body avoiding potential toxicity of long-term retention. Our work not only develops a combined strategy of NIR-II PTT and gene therapy mediated by anti-miR-19a/FePS@PPF but also provides insights into the design and applications of other nanotherapeutic platforms.
Advancing health through evidence assisted decisions with health policy and systems research program: a qualitative evaluation of a national health research grant management process in the Philippines
Authors: Sales Reneepearl Kim , Reyes-Ramos Gladys Kaye , de Veyra Chiqui , Gascon Gabrielle , Barraca Vianka , Garcia Gillian , Yap Maria Eufemia
Published: July 2023

Background

Health policy and systems research (HPSR) has influenced Philippine policies, including tobacco control, mental health, and COVID-19. The Department of Health (DOH) Philippines and Philippine Council for Health Research and Development (PCHRD) launched the Advancing Health through Evidence-Assisted Decisions (AHEAD) with HPSR program in 2017, aiming to build a community of researchers and decision-makers committed to evidence production and utilization. Research systems employ grant management processes for transparency and accountability in research funding, preventing waste, fraud, and misuse of funds.

Methods

This study evaluated AHEAD-HPSR's grant management using surveys, interviews, and focus groups to document (1) grant administration processes implemented by DOH and PCHRD, and (2) experiences of grantees, program managers, staff, and policymakers. Data were initially analyzed through the USA Grant Accountability Office’s Federal Grant Life Cycle, with new themes created as they emerged. The study identified processes and gaps in the research grant life cycle stages: design/redesign, pre-award, award, implementation, closeout, and research dissemination and utilization.

Results

Identification of research areas for the grant are identified using national and departmental research priorities. While Calls for Proposals are posted publicly, researchers that have previously worked with policymakers are contacted directly to submit proposals. The evaluation found that research is delayed by bureaucracies in grant administration, particularly in financial reporting and ethics review processes. Complying with the terminal financial report was identified as the most challenging part of the grant process due to immense auditing requirements. Grantees recommend the simplification of bureaucracy for fund release to enable them to focus on research work.

Conclusion

This study contributes to the limited literature on health research grant management in developing countries. Valuable information and recommendations were contributed by stakeholders in this evaluation. These are manifestations of a continuing interest and desire to make health policy and systems research in the Philippines more robust and relevant. It is imperative for the program to continually evolve and build systems most applicable to its multidisciplinary context.
Transfer of patient’s peripheral blood mononuclear cells (PBMCs) disrupts blood–brain barrier and induces anti-NMDAR encephalitis: a study of novel humanized PBMC mouse model
Authors: Shu Yaqing , Peng Fuhua , Zhao Bingchu , Liu Chunxin , Li Qihui , Li Huilu , Wang Yuge , Jiang Yanjun , Lu Tingting , Wang Qin , Sun Jian , Feng Huiyu , Lu Zhengqi , Liu Xiaodong , Wang Jie , Qiu Wei
Published: July 2023

Background

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a severe autoimmune neuropsychiatric disease. Brain access of anti-NMDAR autoantibody through the blood–brain barrier (BBB) is essential for pathogenesis. Most previous animal models limit the investigation of etiologies of BBB damage in patients.

Methods

In this study, we established a novel humanized mouse model of anti-NMDAR encephalitis by intraperitoneal injection of patients’ peripheral blood mononuclear cells (PBMCs) into BALB/c Rag2−/−Il2rg−/−SirpαNODFlk2−/− mice.

Results

We found that engraftment of patients’ PBMCs not only produced potent anti-GluN1 autoantibodies, but also disrupted BBB integrity to allow brain access of autoantibodies, resulting in a hyperactive locomotor phenotype, anxiety- and depressive-like behaviors, cognitive deficits, as well as functional changes in corresponding brain regions. Transcriptome analysis suggested an exaggerated immune response and impaired neurotransmission in the mouse model and highlighted Il-1β as a hub gene implicated in pathological changes. We further demonstrated that Il-1β was produced by endothelial cells and disrupted BBB by repressing tight junction proteins. Treatment with Anakinra, an Il-1 receptor antagonist, ameliorated BBB damage and neuropsychiatric behaviors.

Conclusions

Our study provided a novel and clinically more relevant humanized mouse model of anti-NMDAR encephalitis and revealed an intrinsic pathogenic property of the patient’s lymphocytes.
Chorionicity-associated variation in metabolic phenotype of cord blood in twin
Authors: Liu Xiaoyu , Yang Jing , Ran Rui , Long Fei , Yang Yang , Dong Xiaojing , Saffery Richard , Novakovic Boris , Mousa Hatem , Wei Yuan , Hu Lina , Han Ting-Li
Published: July 2023

Background

Monochorionic (MC) twins present a higher incidence of unfavorable clinical perinatal outcomes than dichorionic (DC) twins, often in association with placental vascular anastomosis. In this study, we profiled the umbilical cord plasma metabolomes of uncomplicated MC and DC twin pregnancies and related these to several offspring outcomes, previously associated with birthweight.

Methods

Umbilical vein blood samples were collected at birth from 25 pairs of uncomplicated MC twins and 24 pairs of uncomplicated DC twins. The samples were subjected to gas chromatography-mass spectrometry-based metabolomics. 152 metabolites were identified from the cord plasma samples of MC and DC twins. Partial least squares discriminant analysis and pathway analysis were performed to compare within DC/MC twin pairs and between DC and MC twins. A generalized estimating equation (GEE) model was utilized to explore the correlation between metabolic differences and birthweight discordance within and between twin pairs.

Results

Our study revealed clear differences between the metabolite profiles of umbilical cord plasma of MC and DC twins. Metabolite profiles in MC within twin pairs and DC within twin pairs were characterized by the differences in 2 − hydroxyglutaramic acid levels and nicotinamide levels, respectively. The metabolic pathways of GSH, tryptophan, and fatty acid metabolism, were significantly downregulated in MC twins compared to DC twins. In addition, the concentration of caffeine and decamethyl-cyclopentasiloxane (D5) was positively correlated with birthweight in MC and DC twins.

Conclusion

This study demonstrated that the altered metabolites in umbilical plasma made contributions to the different chorionicities between uncomplicated MC twins and DC twins. The chorionicity of twins seems to affect the metabolic cross-talk between co-twin pairs and be related to birthweight discordance of twins.
Pediatric unit spending in the North of Italy during the COVID-19 pandemic
Authors: Franceschi Roberto , Maines Evelina , Petrone Angelamaria , Bilato Simone , Trentini Ilaria , Di Spazio Lorenzo , Leonardi Luca , Soffiati Massimo , Francesconi Andrea
Published: July 2023

Background

During the COVID-19 pandemic, accesses to pediatric health care services decreased, as well as the consumption of traditional drugs, while the median cost per patient at the emergency department slightly increased and the cost of pediatric COVID-19 admissions to the pediatric ward too. Overall spending of a secondary level Pediatric Unit in the last two years has not been previously reported.

Methods

This is a retrospective study conducted by the Pediatric Unit of S. Chiara Hospital of Trento, North of Italy. We collected data on consumption and spending before and during the COVID-19 pandemic (between January 2018 and December 2022).

Results

The total spending ranged from 2.141.220 to 2.483.931 euros between 2018 and 2022. COVID-19 spending accounted only for 5–8% of the overall budget, while two macro-areas of spending were identified: (i) biologic drugs for inherited metabolic diseases (IMDs), that impacted for 35.4–41.3%, and (ii) technology devices for type 1 diabetes (T1D), that accounted for 41.6–32.8% of the overall budget, in 2021 and 2022, respectively. Analysis of costs along with the different health care services revealed that: (i) the spending for COVID-19 antigen tests and personal protective equipment had a major impact on the Emergency room budget (from 54 to 68% in the two years); (ii) biological drugs accounted mainly on the Pediatric Ward (for 57%), Day Hospital (for 74%) and rare disease center budget (for 95% of the spending); (iii) the cost for T1D devices was mainly due to continuous glucose monitoring, and impacted for the 97% of the outpatient clinic budget.

Conclusions

The main impact on the budget was not due to COVID-19 pandemic related costs, but to the costs for biologic drugs and T1D devices. Therefore, cost savings could be mainly achieved through generic and biosimilars introduction and with inter-regionals calls for technology devices. We emphasize how the control of spending in pediatric hospital care has probably moved from the bedside (savings on traditional drugs as antibiotics) to the bench of national or inter-regional round tables, to obtain discounts on the costs of biologic drugs and medical devices. Here we provide for the first-time in literature, data for bench-marking between secondary level Pediatric Units before and during the COVID-19 pandemic.
Association of air pollution with postmenopausal breast cancer risk in UK Biobank
Authors: Smotherman Carmen , Sprague Brian , Datta Susmita , Braithwaite Dejana , Qin Huaizhen , Yaghjyan Lusine
Published: July 2023

Background

We investigated the association of several air pollution measures with postmenopausal breast cancer (BCa) risk.

Methods

This study included 155,235 postmenopausal women (of which 6146 with BCa) from UK Biobank. Cancer diagnoses were ascertained through the linkage to the UK National Health Service Central Registers. Annual exposure averages were available from 2005, 2006, 2007, and 2010 for NO2, from 2007 and 2010 for PM10, and from 2010 for PM2.5, NOX, PM2.5–10 and PM2.5 absorbance. Information on BCa risk factors was collected at baseline. Cox proportional hazards regression was used to evaluate the associations of year-specific and cumulative average exposures with BCa risk, overall and with 2-year exposure lag, while adjusting for BCa risk factors.

Results

PM10 in 2007 and cumulative average PM10 were positively associated with BCa risk (2007 PM10: Hazard ratio [HR] per 10 µg/m3 = 1.18, 95% CI 1.08, 1.29; cumulative average PM10: HR per 10 µg/m3 = 1.99, 95% CI 1.75, 2.27). Compared to women with low exposure, women with higher 2007 PM10 and cumulative average PM10 had greater BCa risk (4th vs. 1st quartile HR = 1.15, 95% CI 1.07, 1.24, p-trend = 0.001 and HR = 1.35, 95% CI 1.25, 1.44, p-trend < 0.0001, respectively). No significant associations were found for any other exposure measures. In the analysis with 2-year exposure lag, both 2007 PM 10 and cumulative average PM10 were positively associated with BCa risk (4th vs. 1st quartile HR = 1.19, 95% CI 1.10, 1.28 and HR = 1.29, 95% CI 1.19, 1.39, respectively).

Conclusion

Our findings suggest a positive association of 2007 PM10 and cumulative average PM10 with postmenopausal BCa risk.
A quick, easy and efficient protocol for extracting high-quality RNA from Mycobacterium tuberculosis using a spin column commercial kit
Authors: Mvubu NE , Salig A. , Moopanar K. , Nyide ASG , Govender D. , Mankayi E.
Published: July 2023

RNA extraction from Mycobacterium tuberculosis has been a historically challenging task for researchers due to the thick lipids associated with the cell wall of this “notorious” pathogen that is responsible for Tuberculosis (TB) outbreaks. Several studies have successfully extracted RNA from M. tuberculosis using a Trizol reagent combined with organic solvents. Recently, our laboratory has successfully extracted high quality total RNA using a commercial kit from clinical strains belonging to F15/LAM4/KZN, Beijing and F11 strain families and H37Rv laboratory strain by exploiting high speed homogenizer for cell lysis and spin columns for RNA purification. The quality and integrity of the extracted RNA was analyzed and confirmed through the Nanodrop, Bioanalyzer and RNA 3-(N-morpholino) propanesulfonic acid (MOPS) gel electrophoresis. Furthermore, to confirm the integrity of small RNA (sRNA) molecules due to their vulnerability to degradation, the RNA samples were converted to cDNA and sRNAs were amplified and confirmed through PCR. This detailed RNA extraction protocol proposes to carve a new path into TB transcriptome research without the use of organic solvent for downstream purification steps while yielding high quality RNA that can be used to understand M. tuberculosis transcriptome regulation.
Bibliometric and visual analysis of diabetes mellitus and pyroptosis from 2011 to 2022
Authors: Li Xiaodong , Su Xiaojuan , Xia Fenglin , Qiu Jing , Zhang Jiaqi , Wu Haiyan , Xie Xuejun , Xu Mingchao
Published: July 2023

Objective

To visualize and analyze the published literature on diabetes mellitus and pyroptosis based on a bibliometric approach, so as to provide a comprehensive picture of the hot research directions and dynamic progress in this field.

Methods

This study was based on the web of science core collection database to conduct a comprehensive search of the published literature in the field of diabetes mellitus and Pyroptosis from January 1985 to August 2022, including the published research literature in this field, as well as a visual analysis of the number of citations, year of publication, journal, author, research institution, country, and research topic.

Results

A total of 139 literature on research related to diabetes mellitus and cellular scorch from 2011 to 2022 were retrieved, with a total of 3009 citations and a maximum of 255 citations for a single article, which had a first author Schmid-Burgk, JL The first author of this article is from Germany; among 20 publishing countries, China leads with 100 articles; among 222 publishing institutions, Harbin Medical University leads with 18 articles and 184 citations; among 980 authors, Chen, X from China tops the list of high-impact authors with 5 articles and 29 citations. Among the 98 journals, "CELL DEATH DISEASE" ranked first in both volume and high-impact journals with 4 articles and 29 citations. Among 349 keywords, "pyroptosis" ranked first with a cumulative frequency of 65 times. The cluster analysis was divided into three categories, chronic complications of diabetes mellitus and pyroptosis (67 articles), diabetes mellitus and pyroptosis (60 articles), and diabetes mellitus combined with other diseases and pyroptosis (12 articles), and the number of articles related to diabetes mellitus and its chronic complications increased rapidly from 2019, among which, diabetic cardiomyopathy (27 articles) had the highest number of articles.

Conclusions

Based on a comprehensive analysis of published literature in the field of diabetes mellitus and pyroptosis from 2011 to 2022, this study achieved a visual analysis of studies with significant and outstanding contributions to the field, thus framing a picture showing the development and changes in the field. At the same time, this study provides research information and direction for clinicians and investigators to conduct diabetes mellitus and pyroptosis-related research in the future.
Stereotactic radiotherapy for brain metastases: predictive factors of radionecrosis
Authors: Calderon Benoît , Vazquez Léa , Belkacemi Mohammed , Pourel Nicolas
Published: July 2023

Purpose

Stereotactic radiotherapy (SRT) is a highly effective approach and represents the current standard of treatment for patients with limited number of brain metastasis (BM). SRT is generally well tolerated but can sometimes lead to radionecrosis (RN). The aim of this study was to identify predictive factors of radionecrosis related to SRT for brain metastasis.

Methods

This retrospective observational cohort study included patients who underwent SRT in the Institut Sainte Catherine between January 1st, 2017 and December 31st, 2020 for the treatment of brain metastasis from any cancer. Individual data and particularly signs of radionecrosis (clinical, imaging, anatomopathological) were collected from electronic medical records. Radionecrosis was defined as the occurrence on MRI of contrast-enhancing necrotic lesions, surrounded by edema, occurring at least 6 months after SRT and localized within fields of irradiation.

Results

123 patients were included; median age was 66 years. 17 patients (11.8%) developed radionecrosis after a median follow up of 418.5 days [63;1498]. Predictive factors of radionecrosis in multivariate analysis were age under 66 years with a sensitivity of 77% and a specificity of 56%. No other factor as the presence of comorbidities, the number of irradiated metastases, the PTV volume or the volume of irradiated healthy brain were predictive of radionecrosis.

Conclusion

Age at treatment initiation and tumor location seems to be correlated with radionecrosis in patients with brain metastasis treated with SRT. These elements could be useful to adapted radiation therapy.
In-person and online sensory wellbeing workshop for eating disorders: updated case series
Authors: Li Zhuo , Holetic Victoria , Webb Jessica , Chubinidze Dimitri , Byford Sarah , Tchanturia Kate
Published: July 2023

Background

A one-off sensory wellbeing workshop has been developed to help patients with eating disorders (ED) manage sensory sensitivities. The aim of this study was to evaluate and compare the outcomes of the workshop in online versus face-to-face (F2F) formats among a sample of patients with ED.

Methods

Cumulative link models were applied to the outcome measures (awareness of sensory wellbeing, awareness of strategies to enhance sensory wellbeing, and confidence in managing sensory wellbeing) to test the differences between online and F2F workshops. Participants’ ratings of usefulness of the workshop were also compared between online and F2F workshops.

Results

A total of 14 workshops (4 online and 10 F2F) were run from 2020 to 2023. All participants reported significant and substantial improvements in all outcome measures. There was no significant difference in outcomes between online and F2F workshops. The majority of patients rated the workshops as useful.

Conclusions

Both online and face-to-face formats of the sensory workshop led to improvement in sensory wellbeing management for patients with ED. Future studies are warranted to test the impact of the workshop on ED treatment outcomes.
Nondestructive characterization and artificial intelligence recognition of acoustic identifiers of ancient ceramics
Authors: Jin Xiaoxue , Wang Xiufeng , Xue Chaohua
Published: July 2023

Cultural heritage identity management is the most basic and important work in the process of cultural heritage protection. It is of great significance to provide a unique and identifiable digital identity for ancient ceramics. At present, the identification information of ancient ceramics is mainly composed of external visual characteristics, and there is no report on feature identification method that can reflect the properties of ancient ceramics. Audible sound signals not only have advantages in non-destructive testing, but also can be used as voiceprint information to identify, monitor and analyze ancient ceramics. In this paper, seven ancient ceramics and 12 similar modern ceramic cups are taken as research objects, and an acoustic identifier (AID) is constructed. We put forward a reliable acoustic identification method for ancient ceramics, and established a digital code of acoustic characteristics of ancient ceramics. The results show that audible sound waves can reflect the attribute information of ancient ceramics. Sufficient acoustic data combined with deep learning can not only accurately match the identity of ancient ceramics, but also detect the real-time identity information of ancient ceramics, and make a comparative analysis of its cracks and whether it has caused damage. This method can provide a variety of practical applications for audible signal feature recognition technology in the exhibition, protection, trading, recognition and safety management of ancient ceramics and other cultural relics.
A macroscopic analysis of the demographic impacts of flood inundation in Thailand (2005–2019)
Authors: Tsuda Hinako , Tebakari Taichi
Published: July 2023

In Thailand, floods are occurring more frequently due to climate change, and recent economic development and population growth may have altered the way in which people interact with floods, including migration to other regions. In this study, we analyzed the relationship between flooding and population distribution across Thailand from 2005 to 2019 to improve measures for minimizing flood damage. We used population distribution point data from 2009 to 2019 produced by Oak Ridge National Laboratory to analyze trends in population movement and distribution, by examining whether population sizes were greater than, less than, or equal to estimated values in regions throughout Thailand. The results suggest that floods in 2011 and 2017 caused temporary migration to areas that were not inundated or to the metropolitan Bangkok area. Flood responses changed after the 2011 floods, which have been described as the worst flood in Thai history. Next, we examined the relationship between the number of regions with lower than estimated population and flood data for the previous year including precipitation, inundated area, and deaths caused by flooding. Inundation area had a significant impact on population decline, with correlation coefficients of 0.426 and 0.501 for the north and northeast, respectively. The number of deaths caused by flooding in a given year also led to a population decline in the following year. However, precipitation did not exhibit the same trend. Therefore, population demographics after floods have shown regional characteristics in recent years, with Thai people shifting from a flood-tolerance lifestyle to a flood-avoidance lifestyle, mainly in local urban areas and the metropolitan Bangkok area.
Polar microalgae extracts protect human HaCaT keratinocytes from damaging stimuli and ameliorate psoriatic skin inflammation in mice
Authors: Lim YoonHee , Park So-Hyun , Kim Eun Jae , Lim HeeJun , Jang Jinsun , Hong In-Sun , Kim Sanghee , Jung YunJae
Published: July 2023

Background

Polar microalgae contain unique compounds that enable them to adapt to extreme environments. As the skin barrier is our first line of defense against external threats, polar microalgae extracts may possess restorative properties for damaged skin, but the potential of microalgae extracts as skin protective agents remains unknown.

Purpose

This study aimed to analyze compound profiles from polar microalgae extracts, evaluate their potential as skin epithelial protective agents, and examine the underlying mechanisms.

Methods

Six different polar microalgae, Micractinium sp. (KSF0015 and KSF0041), Chlamydomonas sp. (KNM0029C, KSF0037, and KSF0134), and Chlorococcum sp. (KSF0003), were collected from the Antarctic or Arctic regions. Compound profiles of polar and non-polar microalgae extracts were analyzed using gas chromatography-mass spectrometry (GC-MS). The protective activities of polar microalgae extracts on human keratinocyte cell lines against oxidative stress, radiation, and psoriatic cytokine exposure were assessed. The potential anti-inflammatory mechanisms mediated by KSF0041, a polar microalga with protective properties against oxidative stress, ultraviolet (UV) B, and an inflammatory cytokine cocktail, were investigated using RNA-sequencing analysis. To evaluate the therapeutic activity of KSF0041, an imiquimod-induced murine model of psoriatic dermatitis was used.

Results

Polar microalgae contain components comparable to those of their non-polar counterparts, but also showed distinct differences, particularly in fatty acid composition. Polar microalgae extracts had a greater ability to scavenge free radicals than did non-polar microalgae and enhanced the viability of HaCaT cells, a human keratinocyte cell line, following exposure to UVB radiation or psoriatic cytokines. These extracts also reduced barrier integrity damage and decreased mRNA levels of inflammatory cytokines in psoriatic HaCaT cells. Treatment with KSF0041 extract altered the transcriptome of psoriatic HaCaT cells toward a more normal state. Furthermore, KSF0041 extract had a therapeutic effect in a mouse model of psoriasis.

Conclusions

Bioactive compounds from polar microalgae extracts could provide novel therapeutics for damaged and/or inflamed skin.
Recovery of memory retention after anesthesia with remimazolam: an exploratory, randomized, open, propofol-controlled, single-center clinical trial
Authors: Nobukuni Keiko , Shirozu Kazuhiro , Maeda Aiko , Funakoshi Kouta , Higashi Midoriko , Yamaura Ken
Published: July 2023

Purpose

Remimazolam, a newly developed ultra-short-acting benzodiazepine, provides early recovery of consciousness but its effects on memory recovery are unclear. This study examined memory recovery after emergence from general anesthesia using remimazolam.

Methods

Seventy-four patients undergoing breast surgery between October 2021 and March 2022 were enrolled and randomly assigned to receive propofol (control group) or remimazolam as general anesthetic during surgery. The primary endpoint was the number of posters patients remembered 24 h after surgery (among four posters shown after recovering from anesthesia) as an assessment of memory retention. The secondary endpoints were the recall of a numeric character patients had been shown just before anesthetic induction, as an assessment of retrograde amnesia 24 h after surgery.

Results

Sixty-six patients (propofol, 32; remimazolam, 34) were assessed. Patients in the remimazolam group remembered significantly fewer posters shown to them after surgery than those in the propofol group (0 [0 − 2] vs. 2 [1 − 3], p < 0.001). In the remimazolam group, the patients who received flumazenil remembered a higher number of posters than those who did not receive flumazenil (3 [1 − 4] vs. 0 [0 − 0], p < 0.001). All patients remembered all events that occurred during the preoperative period as well as the numeric character.

Conclusion

Patients recovering from remimazolam anesthesia without receiving flumazenil do not remember events after regaining consciousness.

IRB

Kyushu University School of Medicine Hospital Institutional Review Board (IRB) (approval number: 20212006).

Trial registration

This clinical trial was registered with the University Hospital Medical Information Network (UMIN) Center on September 28, 2021 (UMIN-CTR: UMIN000045593).

Implication statement

Memory recovery is slower following emergence from remimazolam than from propofol anesthesia.
A comparison of advertised versus actual cannabidiol (CBD) content of oils, aqueous tinctures, e-liquids and drinks purchased in the UK
Authors: Johnson Drusus A. , Hogan Megan , Marriot Ray , Heaney Liam M. , Bailey Stephen J. , Clifford Tom , James Lewis J.
Published: July 2023

Background

Cannabidiol (CBD)-containing products are sold widely in consumer stores, but concerns have been raised regarding their quality, with notable discrepancies between advertised and actual CBD content. Information is limited regarding how different types of CBD products may differ in their deviation from advertised CBD concentrations. Therefore, CBD concentrations were quantified and compared in aqueous tinctures, oils, e-liquids and drinks.

Methods

Products (13 aqueous tinctures, 29 oils, 10 e-liquids and 11 drinks) were purchased online in the UK. CBD concentrations were quantified in aqueous tinctures, oils and e-liquids via high performance liquid chromatography (HPLC), and in drinks via gas chromatograhy-mass spectrometry (GC-MS).

Results

Measured concentrations fell −25.7 ± 17.3, −6.1 ± 7.8, −6.9 ± 4.6 and − 0.03 ± 0.06 mg/mL below advertised concentrations for aqueous tinctures, oils, e-liquids and drinks, respectively (medians ± interquartile ranges; p < .05). Oils deviated relatively less (−19.0 ± 14.5%) from advertised concentrations than e-liquids (−29.2 ± 10.2%), aqueous tinctures (−51.4 ± 41.4%) and drinks (−65.6 ± 36.5%; p < .01), whilst e-liquids deviated less than aqueous tinctures and drinks (p < .05), and deviation was not different between aqueous tinctures and drinks (p = .19). Only 5/63 (8%) products had measured concentrations within 10% of advertised concentrations.

Discussion

Similarly to previous studies, few products had measured CBD concentrations within 10% of advertised concentrations, with most falling below advertised concentrations. All individual product types deviated from advertised concentrations, with oils deviating least. These findings may be indicative of poor manufacturing standards, or that CBD undergoes degradation in consumer products. This reinforces concerns over quality of CBD-containing consumer products and may highlight the need for improved regulation of such products.
Fire regimes over a 1070-m elevational gradient, San Francisco Peaks/Dook’o’oosłííd, Arizona, USA
Authors: Fulé Peter Z. , Barrett Molly Peige , Cocke Allison E. , Crouse Joseph E. , Roccaforte John P. , Normandin Donald P. , Covington W. Wallace , Moore Margaret M. , Heinlein Thomas A. , Stoddard Michael T. , Rodman Kyle C.
Published: July 2023

Background

Steep elevational gradients bring multiple forest types and fire regimes together in close proximity. The San Francisco Peaks/Dook’o’oosłííd in northern Arizona rise to 3851 m elevation with slopes that span many of the major forest types of the southwestern US mountains. To reconstruct past fire regimes across this broad elevational gradient, we sampled fire-scarred trees across the south face of the Peaks, complementing previous research on forest structure, composition, and origin of aspen stands.

Results

At the highest elevations, Rocky Mountain bristlecone pine forests had a mean fire interval (MFI) of 19.7 years prior to a modern fire exclusion period beginning after 1879. Other high-elevation (> 2800 m) mixed conifer forests had MFI = 5.7 years and low-elevation (< 2,800 m) pine forests had MFI = 4.0 years. After 1879, there were no large fires through the end of the twentieth century. Before 1879, fires occurred in the early to middle growing season, and fire event years were linked to climate across all elevations, with a stronger association to drought (i.e., the Palmer Drought Severity Index) than to El Niño-Southern Oscillation phase. Pulses of forest regeneration were associated with the fire regime, with the largest pulse occurring shortly after fire exclusion. In addition to fire exclusion, other factors such as post-fire sprouting and regeneration after tree harvesting likely contributed to the current dense forest structure on the Peaks.

Conclusions

Following over a century of fire exclusion, fire activity has increased on the Peaks over the past two decades, with large recent fires of uncharacteristic severity raising concerns about tree mortality, erosion, flooding, and infrastructure damage in surrounding human communities. Past fire regimes provide useful insight into fire-climate-forest interactions and the conditions under which existing forest communities were well adapted, but adaption to future conditions is likely to be challenging due to the rapid pace of projected environmental changes.
Prevalence and economic burden of dementia in the Arab world
Authors: Qassem Tarik , Itani Lynn , Nasr Walid , Al-Ayyat Dania , Javaid Syed Fahad , Al-Sinawi Hamed
Published: July 2023

Background

The growing prevalence of dementia is a global concern, especially in the Arab world, where updated economic impact data are scarce. Understanding its prevalence and cost is crucial for effective policies and support systems.

Aims

To estimate dementia prevalence and cost in Arab countries for 2021.

Method

United Nations population data and dementia prevalence estimates were used to calculate total cases. Direct costs were based on gross domestic product (GDP) per capita (purchasing power parity) and income classification. Indirect caregiver support costs were estimated using average monthly wages and two distinct scenarios.

Results

The highest dementia prevalence among those aged more than 60 years was in Lebanon (4.88%), Tunisia (4.43%) and Algeria (4.19%). The total direct cost in the Arab region was $8.18 billion for those over 50 years old. Indirect costs ranged from $2.25 billion (best case) to $5.67 billion (worst case), with a mean value of $3.98 billion. Total dementia care costs (direct and indirect) under the mean scenario for the entire Arab world amounted to $12.17 billion, with costs as a percentage of GDP ranging from 0.05% (Sudan) to 0.44% (Lebanon).

Conclusions

This study highlights dementia as a growing public health issue in the Arab world, with 1 329 729 individuals affected in 2021 and total costs between $10.43 billion and $13.90 billion. The findings emphasise the urgent need for investment in research and specialised services for older adults, particularly those with dementia.
Elevated Preoperative TPO Ab Titers Decrease Risk for DTC in a Linear Fashion: A Retrospective Analysis of 1635 Cases
Authors: Paparodis Rodis , Livadas Sarantis , Karvounis Evangelos , Bantouna Dimitra , Zoupas Ioannis , Angelopoulos Nicholaos , Imam Shahnawaz , Jaume Juan Carlos
Published: July 2023

Context

For some, chronic lymphocytic thyroiditis (Hashimoto thyroiditis) is an important risk factor for differentiated thyroid cancer (DTC). Surgical cohort studies even suggested a potential role for thyroid peroxidase antibodies (TPO-Abs) on that risk.

Objective

Our clinical observations argued against that possibility. We designed the present study to evaluate the relationship of TPO-Abs and DTC in a large patient population.

Methods

We recruited individuals who underwent thyroidectomies at 4 different clinical sites (USA: 1 clinic, 2000-2013, and Greece: 3 clinics, 2007-2021). We gathered data on TPO-Abs titers measured with commercially available chemiluminescence immunoassays, and reviewed patients’ data including surgical pathology. TPO-Abs of 34 IU/mL or greater was deemed positive (TPO+) and TPO-Abs less than 34 IU/mL was deemed negative (TPO–). Odds ratios (OR) for DTC were calculated with the Fisher exact test and P less than .05 was deemed significant.

Results

We reviewed data from 8461 consecutive thyroid surgery cases. TPO-Abs titers were available for 1635 individuals: DTC n = 716 (43.8%), benign pathology n = 919 (56.2%), TPO+ n = 540 (33.0%), and TPO− n = 1095 (67.0%). DTC was found at a lower frequency in TPO+ (198/540, 36.7%) compared to TPO− (518/1095, 47.3%) patients, OR 0.64 (0.52-0.80; P < .0001). Rising TPO-Abs titers conferred protection against DTC in a linear fashion: TPO-Abs less than 10 IU/mL: 59.3%, TPO-Abs less than 34 IU/mL: 47.4%, TPO-Abs 34 to 100 IU/mL: 42.6%, TPO-Abs 100 to 500 IU/mL: 32.0%, TPO-Abs greater than 1000 IU/mL: 19.4%; P less than .0001.

Conclusion

Higher TPO-Ab titers appear protective against DTC in our large multicenter cohort of patients who underwent thyroidectomies. Rising preoperative TPO-Abs titers conferred linearly increasing protection against DTC.
Growth Hormone Treatment for Non-GHD Disorders: Excitement Tempered by Biology
Authors: Grimberg Adda , Hawkes Colin P
Published: July 2023

The success of growth hormone (GH) replacement in children with classical GH deficiency has led to excitement that other causes of short stature may benefit similarly. However, clinical experience has shown less consistent and generally less dramatic effects on adult height, perhaps not surprising in light of increased understanding of GH and growth plate biology. Nonetheless, clinical demand for GH treatment continues to grow. Upon the 20th anniversary of the US Food and Drug Administration's approval of GH treatment for idiopathic short stature, this review will consider the factors underlying the expansion of GH treatment, the biological mechanisms of GH action, the non-GH–deficient uses of GH as a height-promoting agent, biological constraints to GH action, and future directions.
Mapping Pregnancy-dependent Sulfhydrome Unfolds Diverse Functions of Protein Sulfhydration in Human Uterine Artery
Authors: Bai Jin , Jiao Fenglong , Salmeron Alejandra Garcia , Xu Shi , Xian Ming , Huang Lan , Chen Dong-bao
Published: July 2023

Uterine artery (UA) hydrogen sulfide (H2S) production is augmented in pregnancy and, on stimulation by systemic/local vasodilators, contributes to pregnancy-dependent uterine vasodilation; however, how H2S exploits this role is largely unknown. S-sulfhydration converts free thiols to persulfides at reactive cysteine(s) on targeted proteins to affect the entire proteome posttranslationally, representing the main route for H2S to elicit its function. Here, we used Tag-Switch to quantify changes in sulfhydrated (SSH-) proteins (ie, sulfhydrome) in H2S-treated nonpregnant and pregnant human UA. We further used the low-pH quantitative thiol reactivity profiling platform by which paired sulfhydromes were subjected to liquid chromatography tandem mass spectrometry–based peptide sequencing to generate site (cysteine)-specific pregnancy-dependent H2S-responsive human UA sulfhydrome. Total levels of sulfhydrated proteins were significantly greater in pregnant vs nonpregnant human UA and further stimulated by treatment with sodium hydrosulfide. We identified a total of 360 and 1671 SSH-peptides from 480 and 1186 SSH-proteins in untreated and sodium hydrosulfide–treated human UA, respectively. Bioinformatics analyses identified pregnancy-dependent H2S-responsive human UA SSH peptides/proteins, which were categorized to various molecular functions, pathways, and biological processes, especially vascular smooth muscle contraction/relaxation. Pregnancy-dependent changes in these proteins were rectified by immunoblotting of the Tag-Switch labeled SSH proteins. Low-pH quantitative thiol reactivity profiling failed to identify low abundance SSH proteins such as KATP channels in human UA; however, immunoblotting of Tag-Switch–labeled SSH proteins identified pregnancy-dependent upregulation of SSH-KATP channels without altering their total proteins. Thus, comprehensive analyses of human UA sulfhydromes influenced by endogenous and exogenous H2S inform novel roles of protein sulfhydration in uterine hemodynamics regulation.
Vasopressin Expressed in Hypothalamic CRF Neurons Causes Impaired Water Diuresis in Secondary Adrenal Insufficiency
Authors: Yamagata Satoshi , Talukder Ashraf H , Murasawa Shingo , Niioka Kanako , Kumagai Naoya , Takagi Mao , Kawamura Meiko , Natsume Rie , Abe Manabu , Uchida Katsuya , Sato Tatsuya , Kurose Akira , Kageyama Kazunori , Daimon Makoto , Sakimura Kenji , Itoi Keiichi
Published: July 2023

Patients with secondary adrenal insufficiency can present with impaired free water excretion and hyponatremia, which is due to the enhanced secretion of vasopressin (AVP) despite increased total body water. AVP is produced in magnocellular neurons in the paraventricular nucleus of the hypothalamus (PVH) and supraoptic nucleus and in parvocellular corticotropin-releasing factor (CRF) neurons in the PVH. This study aimed to elucidate whether magnocellular AVP neurons or parvocellular CRF neurons coexpressing AVP are responsible for the pathogenesis of hyponatremia in secondary adrenal insufficiency. The number of CRF neurons expressing copeptin, an AVP gene product, was significantly higher in adrenalectomized AVP-floxed mice (AVPfl/fl) than in sham-operated controls. Adrenalectomized AVPfl/fl mice supplemented with aldosterone showed impaired water diuresis under ad libitum access to water or after acute water loading. They became hyponatremic after acute water loading, and it was revealed under such conditions that aquaporin-2 (AQP2) protein levels were increased in the kidney. Furthermore, translocation of AQP2 to the apical membrane was markedly enhanced in renal collecting duct epithelial cells. Remarkably, all these abnormalities observed in the mouse model for secondary adrenal insufficiency were ameliorated in CRF-AVP−/− mice that lacked AVP in CRF neurons. Our study demonstrates that CRF neurons in the PVH are responsible for the pathogenesis of impaired water excretion in secondary adrenal insufficiency.
A Book of Waves
Authors: Helmreich Stefan
Published: July 2023

In A Book of Waves Stefan Helmreich examines ocean waves as forms of media that carry ecological, geopolitical, and climatological news about our planet. Drawing on ethnographic work with oceanographers and coastal engineers in the Netherlands, the United States, Australia, Japan, and Bangladesh, Helmreich details how scientists at sea and in the lab apprehend waves' materiality through abstractions, seeking to capture in technical language these avatars of nature at once periodic and irreversible, wild and pacific, ephemeral and eternal. For researchers and their publics, the meanings of waves also reflect visions of the ocean as an environmental infrastructure fundamental to trade, travel, warfare, humanitarian rescue, recreation, and managing sea level rise. Interleaving ethnographic chapters with reflections on waves in mythology, surf culture, feminist theory, film, Indigenous Pacific activisms, Black Atlantic history, cosmology, and more, Helmreich demonstrates how waves mark out the wakes and breaks of social histories and futures.