bluuebunny/crossref_metadata_2025 huggingface dataset:
Value Based Perinatal Care
Authors:   , Depla Anne Louise
Published: April 2023

Our healthcare system is under increasing pressure, both in terms of financial and human capacity, which forces us into difficult choices. Value-based healthcare offers a theory in which the outcomes of care that matter to patients, relative to the costs incurred, are leading in these choices. Important principles of value-based healthcare are organizing care around the patient and gaining insight into care outcomes that matter to patients. In perinatal care, collaboration around the pregnant woman (integrated maternity care) is already underway, but relatively little insight exists into care results from the patient's perspective.

In this thesis, we investigated how structured questionnaires on patient-reported outcomes of perinatal care, such as breastfeeding or incontinence, and experiences, such as satisfaction or autonomy, can contribute to improved care. In clinic, we saw that discussing answers individually as part of regular care contacts helped to identify complaints and personalize care, provided that the questionnaires were properly aligned with the care path. At group level, the insight into outcome data gave healthcare providers motivation for quality improvement. Translating the data into recognizable personas helped to achieve substantive discussion and improvement actions. The network-wide approach to measuring and improving outcomes ensured patient-centeredness but hindered implementation. The iterative, context-specific approach of action research helped to achieve change. The findings in this thesis provide direction for the implementation and application of patient-reported measures around pregnancy and childbirth to strengthen the development towards a healthcare system driven by value for patients.
Regulation of signal transduction at M2 muscarinic receptor
Authors: Krejčí A , Michal P , Jakubík J , Říčný J , Doležal V
Published: April 2023

Muscarinic acetylcholine receptors mediate transmission of an extracellular signal represented by released acetylcholine to neuronal or effector cells. There are five subtypes of closely homologous muscarinic receptors which are coupled by means of heterotrimeric G-proteins to a variety of signaling pathways resulting in a multitude of target cell effects. Endogenous agonist acetylcholine does not discriminate among individual subtypes and due to the close homology of the orthosteric binding site the same holds true for most of exogenous agonists. In addition to the classical binding site muscarinic receptors have one or more allosteric binding sites at extracellular domains. Binding of allosteric modulators induces conformational changes in the receptor that result in subtype-specific changes in orthosteric binding site affinity for both muscarinic agonists and antagonists. This overview summarizes our recent experimental effort in investigating certain aspects of M2 muscarinic receptor functioning concerning i) the molecular determinants that contribute to the binding of allosteric modulators, ii) G-protein coupling specificity and subsequent cellular responses and iii) possible functional assays that exploit the unique properties of allosteric modulators for characterization of muscarinic receptor subtypes in intact tissue. A detailed knowledge of allosteric properties of muscarinic receptors is required to permit drug design that will modulate signal transmission strength of specific muscarinic receptor subtypes. Furthermore, allosteric modulation of signal transmission strength is determined by cooperativity rather than concentration of allosteric modulator and thus reduces the danger of overdose.
Biochemistry of transmembrane signaling mediated by trimeric G proteins
Authors: Svoboda P , Teisinger J , Novotný J , Bouřová L , Drmota T , Hejnová L , Moravcová Z , Lisý V , Rudajev V , Stöhr J , Vokurková A , Švandová I , Durchánková D
Published: April 2023

Many extracellular signals are at the cell surface received by specific receptors, which upon activation transduce information to the appropriate cellular effector molecules via trimeric G proteins. The G protein-mediated cascades ultimately lead to the highly refined regulation of systems such as sensory perception, cell growth, and hormonal regulation. Transmembrane signaling may be seriously deranged in various pathophysiological conditions. Over the last two decades the major experimental effort of our group has been devoted to better understanding the molecular mechanisms underlying transmembrane signaling regulated by G proteins and to the closely related process of desensitization of hormone response. This review provides general information about the basic principles of G protein-regulated transmembrane signaling as well as about our contribution to the current progress in the field.
Genetic analysis of “metabolic syndrome” in the spontaneously hypertensive rat
Authors: Pravenec M , Zídek V , Landa V , Šimáková M , Mlejnek P , Kazdová L , Bílá V , Křenová D , Křen V
Published: April 2023

In the current review, we summarize results of genetic analyses of "metabolic syndrome" in the spontaneously hypertensive rat (SHR). These results include (1) linkage analyses in the HXB/BXH recombinant inbred (RI) strains derived from SHR and Brown Norway (BN-Lx) strains which revealed quantitative trait loci (QTL) for hemodynamic and metabolic traits on several chromosomes, (2) genetic isolation of these putative QTL within differential chromosome segments of SHR.BN congenic strains, (3) detailed mapping of these QTL within limited chromosome segments of SHR.BN congenic sublines, (4) sequencing of selected positional candidate genes which revealed important mutations in the Cd36 and Srebp1 SHR genes, (5) functional tests of these candidate genes in SHR transgenic lines, and (6) integrated gene expression profiling and linkage mapping in RI strains which will be used to identify co-regulated genes and to determine co-segregation of transcriptional profiles with physiological and pathophysiological phenotypes.
Mitochondrial uncoupling proteins – facts and fantasies
Authors: Ježek P , Žáčková M , Růžička M , Škobisová E , Jabůrek M
Published: April 2023

Instead of a comprehensive review, we describe the basic undisputed facts and a modest contribution of our group to the fascinating area of the research on mitochondrial uncoupling proteins. After defining the terms uncoupling, leak, protein-mediated uncoupling, we discuss the assumption that due to their low abundance the novel mitochondrial uncoupling proteins (UCP2 to UCP5) can provide only a mild uncoupling, i.e. can decrease the proton motive force by several mV only. Contrary to this, the highly thermogenic role of UCP1 in brown adipose tissue is not given only by its high content (approximately 5 % of mitochondrial proteins) but also by the low ATP synthase content and high capacity respiratory chain. Fatty acid cycling mechanism as a plausible explanation for the protonophoretic function of all UCPs and some other mitochondrial carriers is described together with the experiments supporting it. The phylogenesis of all UCPs, estimated UCP2 content in several tissues, and details of UCP2 activation are described on the basis of our experiments. Functional activation of UCP2 is proposed to decrease reactive oxygen species (ROS) production. Moreover, reaction products of lipoperoxidation such as cleaved hydroperoxy-fatty acids and hydroxy-fatty acid can activate UCP2 and promote feedback down-regulation of mitochondrial ROS production.
Genetic defects of cytochrome c oxidase assembly
Authors: Pecina P , Houšťková H , Zeman J , Houštěk J
Published: April 2023

Cytochrome c oxidase (COX), the terminal enzyme of the mitochondrial respiratory chain, is one of the key functional and regulatory sites of the mammalian energy metabolism. Owing to the importance of the enzyme, pathogenetic mutations affecting COX frequently result in severe, often fatal metabolic disorders. No satisfactory therapy is currently available so that the treatment remains largely symptomatic and does not improve the course of the disease. While only few genetic defects of COX are caused by mutations in mitochondrial genome, during the last five years a large number of pathogenetic mutations in nuclear genes have been discovered. All these mutations are located in genes encoding COX-specific assembly proteins including SURF1, SCO1, SCO2, COX10, and COX15. Despite the identification of increasing number of mutations, their precise etiopathogenetic mechanisms, which are necessary for the development of future therapeutic protocols, still remain to be elucidated. This review summarizes recent developments, including our efforts in elucidation of the molecular basis of human mitochondrial diseases due to specific defects of COX with special focus on SURF1 assembly protein.
Molecular mechanisms of cardiac protection by adaptation to chronic hypoxia.
Authors: Kolář F , Ošťádal B
Published: April 2023

Effective protection of the heart against ischemia/reperfusion injury is one of the most important goals of experimental and clinical research in cardiology. Besides ischemic preconditioning as a powerful temporal protective phenomenon, adaptation to chronic hypoxia also increases cardiac tolerance to all major deleterious consequences of acute oxygen deprivation such as myocardial infarction, contractile dysfunction and ventricular arrhythmias. Although many factors have been proposed to play a potential role, the detailed mechanism of this long-term protection remains poorly understood. This review summarizes current limited evidence for the involvement of ATP-sensitive potassium channels, reactive oxygen species, nitric oxide and various protein kinases in cardioprotective effects of chronic hypoxia.
Confocal stereology and image analysis: methods for estimating geometrical characteristics of cells and tissues from three-dimensional confocal images
Authors: Kubínová L , Janáček J , Karen P , Radochová B , Difato F , Krekule I
Published: April 2023

A short review of confocal stereology and three-dimensional image analysis is presented, pointing out the achievements accomplished in this field by the Department of Biomathematics (Institute of Physiology, Prague). One of the methods of confocal stereology, the fakir method for surface area estimation, developed by this laboratory, is described. Methods for automatic measurement of geometrical characteristics of microscopical structures, based on 3-D image processing or surface triangulation, are discussed and compared with interactive stereological methods. Three-dimensional reconstruction programs and software implementation of stereological and digital methods as well as their practical applications are presented. The future trends are discussed.
Influence of thyroid status on the differentiation of slow and fast muscle phenotypes
Authors: Vadászová A , Zachařová G , Macháčová K , Jirmanová I , Soukup T
Published: April 2023

Muscle phenotype is determined by combined effects of intrinsic genetic and extrinsic factors like innervation, hormonal levels and mechanical factors or muscle activity. We have been studying the effect of altered thyroid hormone levels on the expression of myosin heavy chain (MyHC) isoforms in control and regenerating soleus and extensor digitorum longus muscles of euthyroid, hypothyroid or hyperthyroid female inbred Lewis rats. The fiber type composition has been determined according to the mATPase activity and immunocytochemical staining of MyHC isoforms, the content of MyHC isoforms has been determined by SDS-PAGE, the mRNA levels have been measured by RT-PCR and the ultrastructural transformation has been analyzed by electron-microscopy. Our results indicate that although the innervation plays a decisive role in the determination of muscle phenotype, levels of thyroid hormones contribute to the extent of muscle phenotype transformation.
Removal efficacy of fly ash composite filler on tailwater nitrogen and phosphorus and its application in constructed wetlands
Authors: Wang Shuhang , Yang Haoran , Che Feifei , Huang Wei , Yang Dianhai
Published: April 2023

Constructed wetlands (CWs) have been widely used in tailwater treatment. However, it is difficult to achieve considerable removal efficiency of nitrogen and phosphorus in tailwater solely by CWs—an efficient green wetland filler is also important. This study investigated 160 domestic sewage treatment facilities (DSTFs) in rural areas from two urban areas in Jiaxing for TP and NH3-N and found that TP and NH3-N concentrations in rural domestic sewage (RDS) in this plain river network are still high. Therefore, we selected a new synthetic filler (FA-SFe) to enhance nitrogen and phosphorus reduction, and we discuss the importance of filler in constructed wetlands. Experiments revealed the adsorption capacity of the new filler: the maximum adsorption amounts of TP and NH3-N reached 0.47 g m-2 d-1 and 0.91 g m-2 d-1, respectively. The application potential of FA-SFe was verified in actual wastewater treatment, with the removal rates of ammonia nitrogen and TP reaching 71.3% and 62.7%, respectively. This study provides a promising pathway for nitrogen and phosphorus removal from rural tailwaters.
Simultaneous effect of different chromatographic conditions on the chromatographic retention of pentapeptide derivatives (HGRFG and NPNPT)
Authors: Peng Huan , Yang Xiangrong , Fang Huanle , Zhang Zhongqi , Zhao Jinli , Zhao Te , Liu Jianli , Li Yan
Published: April 2023

Introduction: Oligopeptides exhibit great prospects for clinical application and its separation is of great importance in new drug development.

Methods: To accurately predict the retention of pentapeptides with analogous structures in chromatography, the retention times of 57 pentapeptide derivatives in seven buffers at three temperatures and four mobile phase compositions were measured via reversed-phase high-performance liquid chromatography. The parameters (kHA, kA, and pKa) of the acid–base equilibrium were obtained by fitting the data corresponding to a sigmoidal function. We then studied the dependence of these parameters on the temperature (T), organic modifier composition (φ, methanol volume fraction), and polarity (PmN parameter). Finally, we proposed two six-parameter models with (1) pH and T and (2) pH and φ or PmN as the independent variables. These models were validated for their prediction capacities by linearly fitting the predicted retention factor k-value and the experimental k-value.

Results: The results showed that logkHA and logkA exhibited linear relationships with 1/T, φ or PmN for all pentapeptides, especially for the acid pentapeptides. In the model of pH and T, the correlation coefficient (R2) of the acid pentapeptides was 0.8603, suggesting a certain prediction capability of chromatographic retention. Moreover, in the model of pH and φ or PmN, the R2 values of the acid and neutral pentapeptides were greater than 0.93, and the average root mean squared error was approximately 0.3, indicating that the k-values could be effectively predicted.

Discussion: In summary, the two six-parameter models were appropriate to characterize the chromatographic retention of amphoteric compounds, especially the acid or neutral pentapeptides, and could predict the chromatographic retention of pentapeptide compounds.
Emerging evidence on Monkeypox: resurgence, global burden, molecular insights, genomics and possible management
Authors: Sharma Ruchi , Chen Kow-Tong , Sharma Rohit
Published: April 2023

An outbreak of monkeypox (encoded enveloped double stranded DNA), resurgence and expansion has emerged in early 2022, posing a new threat to global health. Even though, many reports are available on monkeypox, still a comprehensive updated review is needed. Present updated review is focused to fill the research gaps pertaining to the monkeypox, and an extensive search was conducted in a number of databases, including Google Scholar, Scopus, Web of Science, and Science Direct. Although the disease usually progresses self-limiting, some patients require admission for kidney injury, pharyngitis, myocarditis, and soft tissue super infections. There is no well-known treatment available yet; still there has been a push for the use of antiviral therapy and tecovirimat as a promising option when dealing with co-morbidities. In this study, we mapped and discussed the updates and scientific developments surrounding monkeypox, including its potential molecular mechanisms, genomics, transmission, risk factors, diagnosis, prevention, vaccines, treatment, possible plant-based treatment along with their proposed mechanisms. Each day, a growing number of monkeypox cases are reported, and more cases are expected in the near future. As of now, monkeypox does not have a well-established and proven treatment, and several investigations are underway to find the best possible treatment from natural or synthetic drug sources. Multiple molecular mechanisms on pathophysiological cascades of monkeypox virus infection are discussed here along with updates on genomics, and possible preventive and therapeutic strategies.
Case report: Multiple arterial stenoses induced by autosomal-recessive hypophosphatemic rickets type 2 associated with mutation of ENPP1: a case study
Authors: Liu Jie , Song Xitao , Zhang Daming , Jiang Yan , Ma Mingsheng , Qiu Zhengqing , Xia Weibo , Chen Yuexin
Published: April 2023

Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1)-related multiple arterial stenoses is a rare clinical syndrome in which global arterial calcification begins in infancy, with a high probability of early mortality, and hypophosphatemic rickets develops later in childhood. The vascular status of an ENPP1-mutated patient when they enter the rickets phase has not been thoroughly explored. In this study, we presented a case of an adolescent with an ENPP1 mutation who complained of uncontrolled hypertension. Systematic radiography showed renal, carotid, cranial, and aortic stenoses as well as random calcification foci on arterial walls. The patient was incorrectly diagnosed with Takayasu’s arteritis, and cortisol therapy had little effect on reducing the vascular stenosis. As a result, phosphate replacement, calcitriol substitution, and antihypertensive medication were prescribed, and the patient was discharged for further examination. This research presented the vascular alterations of an ENPP1-mutanted patient, and while there is less calcification, intimal thickening may be the primary cause of arterial stenosis.
Impaired sensitivity to thyroid hormones is associated with hyperuricemia in a Chinese euthyroid population
Authors: Lu Yingning , Wang Jie , An Yu , Liu Jia , Wang Ying , Wang Guang , Leng Song
Published: April 2023

Objective

Impaired sensitivity to thyroid hormones has been reported as a common metabolic disorder, and it remains poorly understood whether it interplays with uric acid (UA) metabolism as an established risk factor for cardiovascular diseases (CVDs). We aimed to investigate the relationship between thyroid hormone sensitivity and elevated UA in a Chinese euthyroid population.

Methods

A total of 15,955 euthyroid subjects were included in this study. Thyroid hormone sensitivity indices were calculated, including the thyroid feedback quantile-based index (TFQI), the Chinese-referenced parametric TFQI (PTFQI), the TSH index (TSHI), and the thyrotropin thyroxine resistance index (TT4RI), and the FT3/FT4 ratio. Linear and logistic regression analyses were performed to detect the association between thyroid hormone sensitivity and elevated UA.

Results

Subjects with reduced sensitivity to thyroid hormones had increased UA levels in both genders (p for trend < 0.001). Logistic and linear regression analyses showed that higher TFQI, PTFQI, TSHI, and TT4RI were positively associated with elevated UA levels, but negatively associated with the FT3/FT4 ratio. The odds ratio (OR) of the highest versus the first quartile of TFQI was 1.20 (1.05, 1.38) in men and 1.80 (1.46, 2.23) in women (p < 0.001). PTHQI, TSHI, and TT4RI obtained similar results in both genders. Conversely, the highest quartile of the FT3/FT4 ratio was negatively correlated with elevated UA levels [men: OR 0.78 (0.68,0.89), women: OR 0.66 (0.53,0.81)].

Conclusion

Impaired sensitivity to thyroid hormones was associated with elevated UA levels in euthyroid subjects. Our findings shed light on the role of thyroid hormone sensitivity in UA metabolism.
Growth differentiation factor-15/adiponectin ratio as a potential biomarker for metabolic syndrome in Han Chinese
Authors: Zheng Shuai , Shen Min , Qian Yu , Li Shushu , Chen Yang , Jiang Hemin , Lv Hui , Chen Doudou , Zhao Ruiling , Zheng Xuqin , Sun Min , Yang Tao , Shi Yun , Fu Qi
Published: April 2023

Aims

Growth differentiation factor-15 (GDF-15) and adiponectin are adipokines that regulate metabolism. This study aimed to evaluate the roles of GDF-15, adiponectin, and GDF-15/adiponectin ratio (G/A ratio) as biomarkers for detecting metabolic syndrome (MS).

Materials and methods

This cross-sectional study included 676 participants aged 20–70 years in Jurong, China. The participants were divided into four groups based on sex and age (<40 and ≥40 years). MS was defined according to the modified National Cholesterol Education Program Adult Treatment Panel III criteria. Receiver operating characteristic curves were used to evaluate the performance of GDF-15, adiponectin, and the G/A ratio in predicting MS.

Results

The prevalence of MS was 22.0% (149/676). Logistic regression analysis indicated that the G/A ratio and adiponectin levels, but not GDF-15 levels, were correlated with MS [odds ratio; 95% CI 1.010 (1.006–1.013) and 0.798 (0.735–0.865), respectively] after adjusting for confounding factors. The G/A ratio displayed a significant relationship with MS in each subgroup and with each MS component in both men and women; however, adiponectin concentrations were significantly associated with MS and all its components only in men (all P <0.05). The area under the curve (AUC) of the G/A ratio and the adiponectin level for MS was 0.758 and 0.748, respectively. The highest AUC was 0.757 for the adiponectin level in men and 0.724 for the G/A ratio in women.

Conclusions

This study suggests that the G/A ratio and adiponectin are potential biomarkers for detecting MS in women and men, respectively.
Evaluation of predicted loss of different land use and land cover (LULC) due to coastal erosion in Bangladesh
Authors: Islam Md Sariful , Crawford Thomas W. , Shao Yang
Published: April 2023

Coastal erosion is one of the most significant environmental threats to coastal communities globally. In Bangladesh, coastal erosion is a regularly occurring and major destructive process, impacting both human and ecological systems at sea level. The Lower Meghna estuary, located in southern Bangladesh, is among the most vulnerable landscapes in the world to the impacts of coastal erosion. Erosion causes population displacement, loss of productive land area, loss of infrastructure and communication systems, and, most importantly, household livelihoods. With an aim to assess the impacts of historical and predicted shoreline change on different land use and land cover, this study estimated historical shoreline movement, predicted shoreline positions based on historical data, and quantified and assessed past land use and land cover change. Multi-temporal Landsat images from 1988–2021 were used to quantify historical shoreline movement and past land use and land cover. A time-series classification of historical land use and land cover (LULC) were produced to both quantify LULC change and to evaluate the utility of the future shoreline predictions for calculating amounts of lost or newly added land resources by LULC type. Our results suggest that the agricultural land is the most dominant land cover/use (76.04% of the total land loss) lost over the studied period. Our results concluded that the best performed model for predicting land loss was the 10-year time depth and 20-year time horizon model. The 10-year time depth and 20-year time horizon model was also most accurate for agricultural, forested, and inland waterbody land use/covers loss prediction. We strongly believe that our results will build a foundation for future research studying the dynamics of coastal and deltaic environments.
Tridepsides as potential bioactives: a review on their chemistry and the global distribution of their lichenic and non-lichenic natural sources
Authors: Norouzi Hooman , Sohrabi Mohammad , Yousefi Masoud , Boustie Joel
Published: April 2023

Tridepsides, as fully oxidized polyketides, have been known to exist in lichens for more than a century. Recent studies have showed that these possible defensive lichenochemicals possess various biological activities. Also, a candidate biosynthetic gene cluster was recently reported for gyrophoric acid (GA), an important tridepside. The present study focused on biosynthesis, natural sources, biological activities, and bioanalytical methods of tridepside molecules. Our survey shows that, so far, lichenic tridepsides have been reported from 37 families, 111 genera, and 526 species of lichen. Because many of their species contain tridepsides, the families Parmeliaceae, Lobariaceae, and Peltigeraceae can be considered critical lichenic sources of tridepsides. Furthermore, several species of Hypotrachyna in Parmeliaceae family showed lichenic tridepsides, suggesting that this genus is a viable source of tridepsides. This research also explored tridepsides from non-lichenic sources, such as non-lichenized fungi, lichenicolous fungi, endophytes, parasites, and liverworts, which offer substantial potential as biotechnological sources to produce tridepsides, which are produced in small amounts in lichen thalli. Two lichenic tridepsides have also been detected in non-lichenic sources: GA and tenuiorin (TE). Additionally, no significant correlation was found between tridepside biosynthesis and geographical distribution patterns for several potentially tridepside-producing lichens. We further showed that GA is the most studied tridepside with various reported biological activities, including anticancer, wound healing, photoprotection, anti-aging, antioxidant, cardiovascular effect, DNA interaction, anti-diabetes, anti-Alzheimer’s, anti-bacterial, and antifungal. Last but not least, this study provides an overview of some bioanalytical methods used to analyze tridepsides over the past few years.
Longitudinal analysis of SARS-CoV-2 infection and vaccination in the LA-SPARTA cohort reveals increased risk of infection in vaccinated Hispanic participants
Authors: Jenkins Meagan M. , Phan Tran Donna , Flores Evelyn A. , Kupferwasser Deborah , Pickering Harry , Zheng Ying , Gjertson David W. , Ross Ted M. , Schaenman Joanna M. , Miller Loren G. , Yeaman Michael R. , Reed Elaine F.
Published: April 2023

Introduction

SARS-CoV-2 is the etiologic agent of coronavirus disease 2019 (COVID-19). Questions remain regarding correlates of risk and immune protection against COVID-19.

Methods

We prospectively enrolled 200 participants with a high risk of SARS-CoV-2 occupational exposure at a U.S. medical center between December 2020 and April 2022. Participant exposure risks, vaccination/infection status, and symptoms were followed longitudinally at 3, 6, and 12 months, with blood and saliva collection. Serological response to the SARS-CoV-2 spike holoprotein (S), receptor binding domain (RBD) and nucleocapsid proteins (NP) were quantified by ELISA assay.

Results

Based on serology, 40 of 200 (20%) participants were infected. Healthcare and non-healthcare occupations had equivalent infection incidence. Only 79.5% of infected participants seroconverted for NP following infection, and 11.5% were unaware they had been infected. The antibody response to S was greater than to RBD. Hispanic ethnicity was associated with 2-fold greater incidence of infection despite vaccination in this cohort.

Discussion

Overall, our findings demonstrate: 1) variability in the antibody response to SARS-CoV-2 infection despite similar exposure risk; 2) the concentration of binding antibody to the SARS-CoV-2 S or RBD proteins is not directly correlated with protection against infection in vaccinated individuals; and 3) determinants of infection risk include Hispanic ethnicity despite vaccination and similar occupational exposure.
Effect of renin-angiotensin-aldosterone system inhibitors on survival outcomes in cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis
Authors: Shen Jinhai , Hou Hui , Liang Bowen , Guo Xiao , Chen Li , Yang Yong , Wang Yun
Published: April 2023

Background

Effect of renin-angiotensin-aldosterone system inhibitors (RAASIs) in combination with immune checkpoint inhibitors (ICIs) on prognoses in cancer patients remains controversial. This study systematically evaluated the effect of RAASIs on survival outcomes in cancer patients receiving ICIs treatment and provided an evidence-based reference for the rational use of RAASIs and ICIs combination therapy in clinical practice.

Methods

Studies evaluating the prognosis of RAASIs-used versus RAASIs-free in cancer patients receiving ICIs treatment from inception to 1 November 2022 were retrieved by searching PubMed, Cochrane Library, Web of Science, Embase, and major conference proceedings. Studies in English reporting hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS) and/or progression-free survival (PFS) were included. Statistical analyses were conducted using the software Stata 17.0.

Results

A total of 12 studies containing 11739 patients were included, comprising ~4861 patients in the RAASIs-used and ICIs-treated group and ~6878 patients in RAASIs-free and ICIs-treated group. The pooled HR was 0.85 (95%CI, 0.75–0.96; P = 0.009) for OS and 0.91 (95%CI, 0.76–1.09; P = 0.296) for PFS, indicating a positive effect of RAASIs concomitant with ICIs on cancer patients. This effect was observed especially in patients with urothelial carcinoma (HR, 0.53; 95%CI, 0.31-0.89; P = 0.018) and renal cell carcinoma (HR, 0.56; 95%CI, 0.37-0.84; P = 0.005) on OS.

Conclusion

Concomitant use of RAASIs and ICIs enhanced the efficacy of ICIs and this combination regimen was associated with significantly improved OS and a trend towards better PFS. RAASIs can be considered as adjuvant drugs when hypertensive patients receive ICIs treatment. Our results provide an evidence-based reference for the rational use of the RAASIs and ICIs combination therapy to improve the efficacy of ICIs in clinical practice.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42022372636; https://inplasy.com/, identifier INPLASY2022110136.
Proteomic profiling of eIF3a conditional knockout mice
Authors: Zhuo Wei , Chen Juan , Jiang Shilong , Zheng Juyan , Huang Hanxue , Xie Pan , Li Wei , Lei Mengrong , Yin Jiye , Gao Ying , Liu Zhaoqian
Published: April 2023

Eukaryotic translation initiation factor 3 subunit A (eIF3a) is the largest subunit of the eukaryotic translation initiation factor 3 (eIF3). eIF3a plays an integral role in protein biosynthesis, hence impacting the onset, development, and treatment of tumors. The proteins regulated by eIF3a are still being explored in vivo. In this study, a Cre-loxP system was used to generate eIF3a conditional knockout mice. Tandem mass tag (TMT) labeling with LC-MS/MS analysis was used to identify differentially expressed proteins (DEPs) in fat, lungs, skin, and spleen tissue of the eIF3a knockout mice and controls. Bioinformatics analysis was then used to explore the functions and molecular signaling pathways of these protein landscapes. It was observed that eIF3a is essential for life sustenance. Abnormal tissue pathology was found in the lungs, fat, skin, spleen, and thymus. In total, 588, 210, 324, and 944 DEPs were quantified in the lungs, fat, skin, and spleen, respectively, of the eIF3a knockout mice as compared to the control. The quantified differentially expressed proteins were tissue-specific, except for eight proteins shared by the four tissues. A broad range of functions for eIF3a, including cellular signaling pathway, immune response, metabolism, defense response, phagocytes, and DNA replication, has been revealed using bioinformatics analysis. Herein, several pathways related to oxidative stress in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, including nitrogen metabolism, peroxisome, cytochrome P450 drug metabolism, pyruvate metabolism, PPAR signaling pathway, phospholipase D signaling pathway, B-cell receptor signaling pathway, ferroptosis, and focal adhesion, have been identified. Collectively, this study shows that eIF3a is an essential gene for sustaining life, and its downstream proteins are involved in diverse novel functions beyond mRNA translational regulation.
The surge of HBsAb level in a HBsAg-negative ES-SCLC patient after anlotinib plus atezolizumab treatment: A case report
Authors: Chen Gangjun , Tian Tian , Cai Xingdong
Published: April 2023

Small-cell lung cancer (SCLC) is a poorly differentiated neuroendocrine tumor with endocrine function. For decades, chemotherapy and immune checkpoint inhibitors (ICIs) have been the first-line treatment options. Because of its ability to normalize tumor vessels, anlotinib is recommended as a novel therapy as a third-line treatment. A combination of anti-angiogenic drugs and ICIs can effectively and safely benefit advanced cancer patients. However, immune-related side effects caused by ICIs are common. Hepatitis B virus (HBV) reactivation and hepatitis are common during immunotherapy in patients with chronic HBV infection. A 62-year-old man with ES-SCLC who had brain metastasis was described in this case. It is unusual for a HBsAg-negative patient to develop an increase in HBsAb after receiving atezolizumab immunotherapy. Although some researchers have reported the functional cure of HBV by PD-L1 antibody, this is the first case that showed a sustained increased in HBsAb level after anti-PD-L1 therapy. It is related with CD4+ and CD8+ T cells activation and HBV infection microenvironment. Importantly, this could provide a solution to insufficient protective antibody production after vaccination as well as a therapeutic opportunity for HBV patients with cancers.
Zn-Co metal organic frameworks coated with chitosand and Au nanoparticles for chemo-photothermal-targeted combination therapy of liver cancer
Authors: Yang Congling , Tiwari Santosh K. , Guo Lianshan , An Guanghui , Zheng Heming , Huang JianFeng , Jiang Li , Bai Zhihao , Zhu Yanqiu , Wang Nannan
Published: April 2023

The toxic effects of chemotherapy drugs on normal tissues are still a major limiting factor in cancer treatment. In this paper, we report a metal-organic framework (Zn-Co ZIF) with chitosan-coated outer layer as a carrier for the drug adriamycin hydrochloride (DOX), a treatment for liver cancer, as a novel anti-cancer nanodrug-enhanced carrier. Gold nanoparticles, a good photothermal conversion agent, were combined with the target SH-RGD during surface functionalisation to prepare Zn-Co ZIF@DOX-CS-Au-RGD (ZD-CAR), a nanoplatform with good photothermal conversion properties and targeting for combined liver cancer therapy. ZD-CAR was developed after RGD accurately targeted the tumour and entered the tumour microenvironment (TME), it cleaves and releases the liver cancer therapeutic agent (DOX) in a weak acidic environment to effectively kill tumour cells. The metal skeleton cleavage releases Co2+, which catalyzes the production of oxygen from H2O2 to alleviate the tumour hypoxic environment. The dissolved oxygen could reach 14 mg/L after adding 80 mg/mL of ZD-CAR. Meanwhile, gold nanoparticles could convert light energy into heat energy under 808 NIR irradiation to induce local superheating and kill tumour cells. In summary, this study developed a nanoplatform that combines chemo-photothermal-targeted therapy. It has shown good therapeutic effeciency in cellular experiments and performance tests and has promising applications in anti-cancer therapy.
Case report: Favipiravir-induced bluish corneal discoloration in infant with COVID-19
Authors: Jiravisitkul Paveewan , Thonginnetra Saraiorn , Wongvisavavit Rintra
Published: April 2023

This report describes a case of a male infant diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who was prescribed favipiravir therapy. The mother noticed a discoloration of the child's eyes within 18 h of therapy, and the cornea returned to normal color within 5 days of medication cessation. This case report highlights the need for monitoring of favipiravir therapy in children due to the potential side effect of corneal discoloration, which has not yet had its long-term effects identified.
Assessing the role of lipid-lowering therapy on multi-cancer prevention: A mendelian randomization study
Authors: Min Yu , Wei Xiaoyuan , Liu Zheran , Wei Zhigong , Pei Yiyan , Li Ruidan , Jin Jing , Su Yongllin , Hu Xiaolin , Peng Xingchen
Published: April 2023

Background: Statin use for cancer prevention has raised wide attention but the conclusions are still controversial. Whether statins use have exact causal effects on cancer prevention remains unclear.

Methods: Based on the Genome-Wide Association Studies (GWAS) datasets from the large prospective UK Biobank and other consortium databases, two-sample mendelian randomization (MR) analysis was conducted to explore the causal effects of statins use on varied site-specific cancer risks. Five MR methods were applied to investigate the causality. The stability, heterogeneity, and pleiotropy of MR results were also evaluated.

Results: The atorvastatin use could increase the risk of colorectal cancer (odd ratio (OR) = 1.041, p = 0.035 by fixed-effects inverse variance weighted (IVW) method (IVWFE), OR = 1.086, p = 0.005 by weighted median; OR = 1.101, p = 0.048 by weighted mode, respectively). According to the weighted median and weighted mode, atorvastatin could modestly decrease the risk of liver cell cancer (OR = 0.989, p = 0.049, and OR = 0.984, p = 0.004, respectively) and head and neck cancer (OR = 0.972, p = 0.020). Besides, rosuvastatin use could reduce the bile duct cancer risk by 5.2% via IVWEF method (OR = 0.948, p = 0.031). No significant causality was determined in simvastatin use and pan-cancers via the IVWFE or multiplicative random-effects IVW (IVWMRE) method if applicable (p > 0.05). There was no horizontal pleiotropy observed in the MR analysis and the leave-one-out analysis proved the stability of the results.

Conclusion: The causalities between statin use and cancer risk were only observed in colorectal cancer and bile duct cancer in the European ancestry population. Future works are warranted to provide more robust evidence for supporting statin repurposing for cancer prevention.
Applying network and genetic analysis to the potato metabolome
Authors: Levina Anna V. , Hoekenga Owen A. , Gordin Mikhail , Broeckling Corey , De Jong Walter S.
Published: April 2023

Compositional traits in potato [Solanum tuberosum L.] are economically important but genetically complex, often controlled by many loci of small effect; new methods need to be developed to accelerate analysis and improvement of such traits, like chip quality. In this study, we used network analysis to organize hundreds of metabolic features detected by mass spectrometry into groups, as a precursor to genetic analysis. 981 features were condensed into 44 modules; module eigenvalues were used for genetic mapping and correlation analysis with phenotype data collected by the Solanaceae Coordinated Agricultural Project. Half of the modules were associated with at least one SNP according to GWAS; 11 of those modules were also significantly correlated with chip color. Within those modules features associated with chipping provide potential targets for selection in addition to selection for reduced glucose. Loci associated with module eigenvalues were not evenly distributed throughout the genome but were instead clustered on chromosomes 3, 7, and 8. Comparison of GWAS on single features and modules of clustered features often identified the same SNPs. However, features with related chemistries (for example, glycoalkaloids with precursor/product relationships) were not found to be near neighbors in the network analysis and did not share common SNPs from GWAS. Instead, the features within modules were often structurally disparate, suggesting that linkage disequilibrium complicates network analyses in potato. This result is consistent with recent genomic studies of potato showing that chromosomal rearrangements that create barriers to recombination are common in cultivated germplasm.
Plausible subjective experience versus fallible corroborative evidence: The formulation of insanity in Nigerian criminal courts
Authors: Ogunwale Adegboyega , Pienaar Letitia , Oluwaranti Oluwaseun
Published: April 2023

Insanity as a defence against criminal conduct has been known since antiquity. Going through significant reformulations across centuries, different jurisdictions across the globe, including Nigeria, have come to adopt various strains of the insanity defence, with the presence of mental disorder being the causative mechanism of the crime as their central theme. A critical ingredient in the Nigerian insanity plea is the presence of ‘mental disease’ or ‘natural mental infirmity’ as the basis for the lack of capacity in certain cognitive and behavioural domains resulting in the offence. Mental disorders, which are the biomedical formulations of this critical legal constituent are primarily subjective experiences with variable objective features. Using illustrative cases based on psycho-legal formulation as well as reform-oriented and fundamental legal research, it is shown that Nigerian courts have held that claims of insanity based on the accused person’s evidence alone should be regarded as “suspect” and not to be “taken seriously.” Thus, Nigerian judicial opinions rely on non-expert accounts of defendants’ apparent behavioural abnormalities and reported familial vulnerability to mental illness, amongst other facts while conventionally discountenancing the defendants’ plausible phenomenological experiences validated by expert psychiatric opinion in reaching a conclusion of legal insanity. While legal positivism would be supportive of the prevailing judicial attitude in entrenching the validity of the disposition in its tenuous precedential utility, legal realism invites the proponents of justice and fairness to interrogate the merit of such preferential views which are not supported by scientific evidence or philosophical reasoning. This paper argues that disregarding the subjective experience of the defendant, particularly in the presence of sustainable expert opinion when it stands unrebutted is not in the interest of justice. This judicial posturing towards mentally abnormal offenders should be reformed on the basis of current multidisciplinary knowledge. Learning from the South African legislation, formalising the involvement of mental health professionals in insanity plea cases, ensures that courts are guided by professional opinion and offers a model for reform.
Virtual self-conversation using motivational interviewing techniques to promote healthy eating and physical activity: A usability study
Authors: Anastasiadou Dimitra , Herrero Pol , Vázquez-De Sebastián Julia , Garcia-Royo Paula , Spanlang Bernhard , Álvarez de la Campa Elena , Slater Mel , Ciudin Andreea , Comas Marta , Ramos-Quiroga J. Antoni , Lusilla-Palacios Pilar
Published: April 2023

Introduction

We aim to examine the usability of a Virtual Reality (VR) platform, called ConVRSelf, which has been designed to address the needs of People Living With Obesity (PLWO).

Methods

Fourteen participants with a desire to eat healthier and exercise more (6 normal weight and 8 PLWO; Mean age = 41.86, SD = 13.89) were assigned to the experimental group (EG) or the control group (CG). EG participants, after being trained on motivational interviewing skills, engaged in a virtual self-conversation using embodiment and body swapping techniques, which aimed to normalize and resolve their ambivalence to change lifestyle habits. CG participants, embodied in their virtual bodies, participated in a pre-established discourse with a virtual counselor giving them psychoeducational advice about how to change lifestyle habits. A mixed-methods design was used, involving a semi-structured interview and self-report questionnaires, including readiness to change habits (Readiness Rulers), body ownership (Body Ownership Questionnaire, BOQ), and system usability (System Evaluation Questionnaire, SEQ). Thematic content analysis was carried out for qualitative data while statistical data analysis was carried out using SPSS 20.0.

Results

Participants from both groups showed high readiness to change lifestyle (Readiness Rulers) before engaging with the virtual experiences, which was maintained at the same level after the interventions and their scores on the SEQ and BOQ were satisfactory. Regarding qualitative information obtained from the interviews, almost all participants found the VR experience to be novel, interesting, and enjoyable. A higher acceptability was observed among PLWO from the EG than normal weight participants from the same group, a promising finding for the ConVRSelf platform, which had been specifically designed to address the needs of PLWO.

Conclusion

The ConVRSelf system is well-accepted by participants and is ready to be tested with PLWO in a clinical setting.
Sexual & reproductive health information on minor consent forms for pubertal suppression and gender affirming hormones
Authors: Taylor Julia , Vullikanti Meesha , Nelamangala Samhita L. , Boguszewski Katherine E. , Marshall Mary Faith
Published: April 2023

Introduction

Transgender and Nonbinary (TNB) youth need specialized sexual and reproductive health (SRH) information and counseling. One avenue for providing this information is the use of informed consent documents before initiating pubertal suppression (PS) and/or gender-affirming hormones (GAHs). This study aims to compare the type and amount of SRH information included on informed consent documents used across clinical sites providing PS and GAH to youth.

Methods

As part of a larger, IRB-approved survey on informed consent, providers of gender-related care to youth uploaded informed consent forms used in clinical practice. Publicly available forms were also included in analysis. Content analysis of these forms was undertaken using published clinical guidelines to inform coding and reflect the SRH implications of starting PS and GAH.

Results

21 unique consent documents were included in the content analysis (PS = 7, Masculinizing = 7, Feminizing = 7). SRH information on consent documents fell into 4 broad categories: (1) changes in sexual organs and functioning; (2) pregnancy and fertility information; (3) cancer risk; and (4) sexually transmitted infections. Forms varied considerably in the level of detail included about these SRH topics and most forms included implicit or explicit acknowledgement of the uncertainty that exists around certain SRH outcomes for TNB youth.

Conclusions

There was substantial variability in both SRH content and context across consent forms. The role of consent forms in fostering TNB youth's understanding of complex SHR information when initiating PS and GAHs needs further clarification and development. Future research should focus on ways to ensure provision of adequate SRH information for TNB youth.