bluuebunny/crossref_metadata_2025 huggingface dataset:
Chlorogenic Acid Mitigates Ferroptosis by Activating the Nrf2/GPX4 Pathway through Keap1 Blockade in Vascular Dementia Rats
Authors: Shan Wen , Liu Guodong , Deng Chulei , Wei Yu , Ding Ke
Published: October 2024

Chlorogenic acid (CGA) is a dietary phenolic acid widely distributed in daily food and plants, but its role in vascular dementia (VaD) is still unclear. Hence, this study aimed to investigate whether CGA could rescue cognitive impairment in VaD, providing a new option for drug discovery. Novel object recognition and Morris water maze experiments revealed that CGA enhanced the learning and memory abilities in VaD rats. Nissl staining, Western blot, and transmission electron microscopy results demonstrated that CGA inhibited neuronal loss in the hippocampal CA1 region of VaD rats, increased the expression of synaptic‐related markers SYP and PSD95, thickened the postsynaptic density, and suppressed mitochondrial ridge rupture in neurons. GSH detection, MDA detection, and Western blot experiments indicated that CGA alleviated hippocampal GSH reduction and MDA elevation and increased the protein levels of GPX4 and SLC7A11. Cell activity, ROS detection, lipid peroxidation detection, intracellular Fe2+ level detection, GSH detection, and Western blot revealed that CGA inhibited the increase of intracellular Fe2+, ROS, and lipid peroxidation induced by OGD in PC12 cells, mitigated GSH reduction, and increased the protein levels of GPX4, SLC7A11, SYP, and PSD95. Western blot and immunofluorescence staining showed that CGA increased the expression of pSer40‐Nrf2 in the hippocampal tissue of VaD rats and PC12 cells, promoting Nrf2 nuclear translocation. Knockdown of Nrf2 prevented CGA from rescuing ferroptosis and synaptic damage induced by OGD in PC12 cells, as well as Nrf2 pathway activation. Molecular docking analysis suggested that CGA competitively bound to the Kelch domain of Keap1 with Nrf2 and then promoted Nrf2 release and activated downstream signaling pathways. In conclusion, our study suggests that CGA may activate the Nrf2 signaling pathway by disrupting the interaction between Nrf2 and Keap1 proteins, thereby inhibiting hippocampal neuronal ferroptosis and synaptic damage and ameliorating cognitive impairment in VaD. Practical Applications. Vascular dementia (VaD) stands as the second most prevalent type of dementia following Alzheimer’s disease. However, there is no effective clinical treatment drug available, and its pathogenic mechanisms remain elusive. This study proposed that CGA might activate the Nrf2‐GPX4 signaling pathway by competitively binding to Keap1, thereby attenuating hippocampal neuronal ferroptosis and synaptic damage and consequently ameliorating cognitive impairment in VaD. Our study may provide a novel option for drug research and development for VaD.
Effect of Fermentation by Penicillium nalgiovense and Geotrichum candidum on the Flavor Characteristics and Microbial Community Structure of Mianning Hams
Authors: Hao Mai , Li Ming , Wang Wei , Zhang Jiamin , Zhu Yan , Ji Lili , Chen Lin
Published: October 2024

In this study, the effect of the use of Penicillium nalgiovense (M600) or Penicillium nalgiovense + Geotrichum candidum (M800) on the physicochemical, microbiological, and flavor substances taking place during the manufacture of Mianning ham, a traditional Chinese ham, was studied. Three groups of hams were created and analysed during the manufacturing process (samples were taken and analysed at 30, 90, 150, and 210 days). At the end of fermentation, a total of 178 flavor substances were identified in the three groups of fermented hams, including 30 aldehydes, 29 alcohols, 14 ketones, 23 esters, 14 acids, 53 hydrocarbons, and 15 other substances. Compared with the control group, aldehydes, esters, and hydrocarbons were significantly increased (p < 0.05), acids were significantly decreased (p < 0.05), and ketones were not significantly changed in the M600 and M800 groups. The control group had the greatest bacterial and fungal abundance at the end of fermentation, with a higher degree of uniformity in fungal composition. M800 group had the highest degree of uniformity in bacterial and fungal composition. In this study, the microbial community changes and volatile flavor substances during the fermentation of Mianning ham were investigated, and the key microorganisms in the fermentation process were analysed. The results of this study indicate that the addition of Penicillium nalgiovense and Geotrichum candidum is an effective strategy to improve ham flavor and enhance ham quality. The results of the study provided a basis for the industrial production of Mianning ham.
Supplementary Figure 1 from Opening of the Blood–Brain Barrier Using Low-Intensity Pulsed Ultrasound Enhances Responses to Immunotherapy in Preclinical Glioma Models
Authors: Sabbagh Aria , Beccaria Kevin , Ling Xiaoyang , Marisetty Anantha , Ott Martina , Caruso Hillary , Barton Emily , Kong Ling-Yuan , Fang Dexing , Latha Khatri , Zhang Daniel Yang , Wei Jun , DeGroot John , Curran Michael A. , Rao Ganesh , Hu Jian , Desseaux Carole , Bouchoux Guillaume , Canney Michael , Carpentier Alexandre , Heimberger Amy B.
Published: October 2024

Supplement Figure 1. LIPU does not overcome immune checkpoint inhibitor resistance in a murine glioblastoma model.
Supplementary Table 2 from Steroid Ligands, the Forgotten Triggers of Nuclear Receptor Action; Implications for Acquired Resistance to Endocrine Therapy
Authors: Bleach Rachel , Madden Stephen F. , Hawley James , Charmsaz Sara , Selli Cigdem , Sheehan Katherine M. , Young Leonie S. , Sims Andrew H. , Souček Pavel , Hill Arnold D. , McIlroy Marie
Published: October 2024

Multivariate analysis of AR in relation to ER, PR, nodal status, tumour size, grade and patient age.
Supplementary Table 1 from Steroid Ligands, the Forgotten Triggers of Nuclear Receptor Action; Implications for Acquired Resistance to Endocrine Therapy
Authors: Bleach Rachel , Madden Stephen F. , Hawley James , Charmsaz Sara , Selli Cigdem , Sheehan Katherine M. , Young Leonie S. , Sims Andrew H. , Souček Pavel , Hill Arnold D. , McIlroy Marie
Published: October 2024

Univariate analysis of AR by subtypes
Supplementary Fig 4 from Steroid Ligands, the Forgotten Triggers of Nuclear Receptor Action; Implications for Acquired Resistance to Endocrine Therapy
Authors: Bleach Rachel , Madden Stephen F. , Hawley James , Charmsaz Sara , Selli Cigdem , Sheehan Katherine M. , Young Leonie S. , Sims Andrew H. , Souček Pavel , Hill Arnold D. , McIlroy Marie
Published: October 2024

Androstenedione driven gene changes post AI therapy (+ months)
Supplementary Fig 3 from Steroid Ligands, the Forgotten Triggers of Nuclear Receptor Action; Implications for Acquired Resistance to Endocrine Therapy
Authors: Bleach Rachel , Madden Stephen F. , Hawley James , Charmsaz Sara , Selli Cigdem , Sheehan Katherine M. , Young Leonie S. , Sims Andrew H. , Souček Pavel , Hill Arnold D. , McIlroy Marie
Published: October 2024

TMA images showing AR expression level by IHC in samples used in trasnscriptomic analysis
Supplementary Table S2 from Inhibition of DNA-PK with AZD7648 Sensitizes Tumor Cells to Radiotherapy and Induces Type I IFN-Dependent Durable Tumor Control
Authors: Nakamura Kyoko , Karmokar Ankur , Farrington Paul M. , James Neil H. , Ramos-Montoya Antonio , Bickerton Susan J. , Hughes Gareth D. , Illidge Timothy M. , Cadogan Elaine B. , Davies Barry R. , Dovedi Simon J. , Valge-Archer Viia
Published: October 2024

Growth Rate
Supplementary Table S1 from Inhibition of DNA-PK with AZD7648 Sensitizes Tumor Cells to Radiotherapy and Induces Type I IFN-Dependent Durable Tumor Control
Authors: Nakamura Kyoko , Karmokar Ankur , Farrington Paul M. , James Neil H. , Ramos-Montoya Antonio , Bickerton Susan J. , Hughes Gareth D. , Illidge Timothy M. , Cadogan Elaine B. , Davies Barry R. , Dovedi Simon J. , Valge-Archer Viia
Published: October 2024

Plating Efficiency
Supplementary Figure 4 from Identification of a Novel Inflamed Tumor Microenvironment Signature as a Predictive Biomarker of Bacillus Calmette-Guérin Immunotherapy in Non–Muscle-Invasive Bladder Cancer
Authors: Damrauer Jeffrey S. , Roell Kyle R. , Smith Markia A. , Sun Xuezheng , Kirk Erin L. , Hoadley Katherine A. , Benefield Halei C. , Iyer Gopakumar , Solit David B. , Milowsky Matthew I. , Kim William Y. , Nielsen Matthew E. , Wobker Sara E. , Dalbagni Guido , Al-Ahmadie Hikmat A. , Olshan Andrew F. , Bochner Bernard H. , Furberg Helena , Troester Melissa A. , Pietzak Eugene J.
Published: October 2024

Supplemental Figure 4 shows the relationship between Immune Signature score by Patient Cohort and UROMOL subtype.
Supplementary Figure 11 from Identification of a Novel Inflamed Tumor Microenvironment Signature as a Predictive Biomarker of Bacillus Calmette-Guérin Immunotherapy in Non–Muscle-Invasive Bladder Cancer
Authors: Damrauer Jeffrey S. , Roell Kyle R. , Smith Markia A. , Sun Xuezheng , Kirk Erin L. , Hoadley Katherine A. , Benefield Halei C. , Iyer Gopakumar , Solit David B. , Milowsky Matthew I. , Kim William Y. , Nielsen Matthew E. , Wobker Sara E. , Dalbagni Guido , Al-Ahmadie Hikmat A. , Olshan Andrew F. , Bochner Bernard H. , Furberg Helena , Troester Melissa A. , Pietzak Eugene J.
Published: October 2024

Supplemental Figure 11 shows the correlation between P53 Score by immune score, FOXM1 expression, Proliferation marker expression.
Supplementary Excel_nCounter PanCancer Human Pathways Panel Gene List from Pharmacodynamic Biomarkers Predictive of Survival Benefit with Lenvatinib in Unresectable Hepatocellular Carcinoma: From the Phase III REFLECT Study
Authors: Finn Richard S. , Kudo Masatoshi , Cheng Ann-Lii , Wyrwicz Lucjan , Ngan Roger K.C. , Blanc Jean-Frederic , Baron Ari D. , Vogel Arndt , Ikeda Masafumi , Piscaglia Fabio , Han Kwang-Hyub , Qin Shukui , Minoshima Yukinori , Kanekiyo Michio , Ren Min , Dairiki Ryo , Tamai Toshiyuki , Dutcus Corina E. , Ikezawa Hiroki , Funahashi Yasuhiro , Evans Thomas R. Jeffry
Published: October 2024

Supplementary Excel_nCounter PanCancer Human Pathways Panel Gene List
Supplementary Figure 1 from PELP1 Is a Novel Therapeutic Target in Hepatocellular Carcinoma
Authors: Nassar Khaled Mohamed , Yang Xue , Baker Adriana , Gopalam Rahul , Arnold William C. , Adeniran Timilehin T. , Hernandez Fernandez Marian H. , Mahajan Megharani , Lai Zhao , Chen Yidong , Sareddy Gangadhara R. , Viswanadhapalli Suryavathi , Sun Lu-Zhe , Vadlamudi Ratna K. , Pratap Uday P.
Published: October 2024

Figure S1. Levels of PELP1 expression in 6 HCC cell lines.
Figure 5 from PELP1 Is a Novel Therapeutic Target in Hepatocellular Carcinoma
Authors: Nassar Khaled Mohamed , Yang Xue , Baker Adriana , Gopalam Rahul , Arnold William C. , Adeniran Timilehin T. , Hernandez Fernandez Marian H. , Mahajan Megharani , Lai Zhao , Chen Yidong , Sareddy Gangadhara R. , Viswanadhapalli Suryavathi , Sun Lu-Zhe , Vadlamudi Ratna K. , Pratap Uday P.
Published: October 2024

PELP1-KD or SMIP34 treatment suppresses HCC xenograft tumor growth in vivo. Hep3B–control and Hep3B–PELP1-KD model cells were injected subcutaneously into female (A, D, and G) or male SCID mice (B, E, and H). Tumor volumes were assessed at 3 to 5 days of intervals. Tumor volume (A and B), tumor weights (D and E), and IHC analyses of Ki67 and PELP1 (G and H) for tumors are shown. Hep3B xenograft tumor fragments measuring 2 to 3 mm3 were implanted subcutaneously , and following tumor establishment (∼200 mm3), the mice were randomly assigned to receive either vehicle (control) or SMIP34 (20 mg/kg body weight) 5 days a week through i.p. injection (n = 5). Tumor volume (C), tumor weights (F) and IHC analyses of Ki67 and PELP1 (I) for tumors are shown. Scale bar, 100 μm. Data are represented as the mean ± SEM. P values are calculated using Student t test and two-way ANOVA, *, p < 0.05; **, p < 0.01; ***, p < 0.001; ****, p < 0.0001. Cont sh (Control short hairpin).
Figure S2 from The Tumor Microbiome as a Predictor of Outcomes in Patients with Metastatic Melanoma Treated with Immune Checkpoint Inhibitors
Authors: Dravillas Caroline E. , Coleman Samuel S. , Hoyd Rebecca , Caryotakis Griffin , Denko Louis , Chan Carlos H.F. , Churchman Michelle L. , Denko Nicholas , Dodd Rebecca D. , Eljilany Islam , Hardikar Sheetal , Husain Marium , Ikeguchi Alexandra P. , Jin Ning , Ma Qin , McCarter Martin D. , Osman Afaf E.G. , Robinson Lary A. , Singer Eric A. , Tinoco Gabriel , Ulrich Cornelia M. , Zakharia Yousef , Spakowicz Daniel , Tarhini Ahmad A. , Tan Aik Choon
Published: October 2024

16 gene signatures where high Z-scores are associated with ICI responsiveness in this cohort (FDR < 0.05)
Figure S1 from The Tumor Microbiome as a Predictor of Outcomes in Patients with Metastatic Melanoma Treated with Immune Checkpoint Inhibitors
Authors: Dravillas Caroline E. , Coleman Samuel S. , Hoyd Rebecca , Caryotakis Griffin , Denko Louis , Chan Carlos H.F. , Churchman Michelle L. , Denko Nicholas , Dodd Rebecca D. , Eljilany Islam , Hardikar Sheetal , Husain Marium , Ikeguchi Alexandra P. , Jin Ning , Ma Qin , McCarter Martin D. , Osman Afaf E.G. , Robinson Lary A. , Singer Eric A. , Tinoco Gabriel , Ulrich Cornelia M. , Zakharia Yousef , Spakowicz Daniel , Tarhini Ahmad A. , Tan Aik Choon
Published: October 2024

Association of CIBERSORT cell types with the response to ICIs
Data from PELP1 Is a Novel Therapeutic Target in Hepatocellular Carcinoma
Authors: Nassar Khaled Mohamed , Yang Xue , Baker Adriana , Gopalam Rahul , Arnold William C. , Adeniran Timilehin T. , Hernandez Fernandez Marian H. , Mahajan Megharani , Lai Zhao , Chen Yidong , Sareddy Gangadhara R. , Viswanadhapalli Suryavathi , Sun Lu-Zhe , Vadlamudi Ratna K. , Pratap Uday P.
Published: October 2024

Abstract
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths in the United States, with a median survival period of approximately 10 months. There is an urgent need for the development of effective targeted therapies for the treatment of HCC. Proline-, glutamic acid–, and leucine-rich protein 1 (PELP1) signaling is implicated in the progression of many cancers, although its specific contribution to the progression of HCC is not yet well understood. Analysis of The Cancer Genome Atlas HCC gene expression data sets and IHC analysis of HCC tissue microarray revealed that HCC tumors had elevated expression of PELP1 compared with normal tissues, and high expression of PELP1 is associated with unfavorable survival outcomes. Suppression of PELP1 expression using short hairpin RNA significantly reduced the cell viability, clonogenicity, and invasion of HCC cells. Importantly, SMIP34, a first-in-class small-molecule inhibitor targeting PELP1, effectively decreased the cell viability, clonogenic survival, and invasiveness of HCC cells. Gene expression analysis using RNA sequencing revealed that PELP1 knockdown cells exhibited a decrease in c-Myc, E2F, and other oncogenic pathways related to HCC. Mechanistic studies showed that SMIP34 treatment impaired the Rix complex, a critical component of ribosomal biogenesis, in HCC cells. Furthermore, the knockdown or pharmacologic inhibition of PELP1 significantly decelerated the HCC tumor growth in xenograft models. In summary, our study findings indicate that PELP1 could serve as a promising target for therapeutic intervention in HCC.
Significance:
HCC is one of the leading causes of cancer fatalities in the United States. Effective targeted therapeutics for HCC are urgently needed. In this study, we show that PELP1 proto-oncogene is crucial to HCC progression and that PELP1 inhibition reduced HCC cell proliferation in vitro and in vivo. Our results imply that PELP1-targeted drugs like SMIP34 may be useful as new therapeutic agents for HCC treatment.
Enhancing Conceptual Clarity regarding the Construct of Moral Injury
Authors: Frankfurt O'Brien Sheila , Baptista Isabelle , Szeszko Philip R.
Published: October 2024

Background: The construct of “moral injury” is used widely in the research literature and media to broadly describe the impact of events involving perceived violations of one’s sense of right and wrong (herein referred to as “potentially morally injurious events” [PMIEs]). Summary: In this theoretical review, we provided a brief overview of the “moral injury” construct and its limitations including the lack of consensus-drawn boundaries and operational definitions to guide hypothesis-driven research. We discussed whether this construct can be reliably distinguished from established psychiatric diagnoses and psychological constructs and the inherent challenges in separating or classifying the impact of high-magnitude stressful life events that likely form the majority of PMIEs. Assessments that purportedly measure “moral injury” are reviewed and limitations are discussed such as shared measurement variance with established psychological instruments. Key Messages: We identified conceptual strategies for investigating behavioral and neurobiological features of PMIEs that could be used to inform the field of traumatic stress. We concluded that the construct of “moral injury” may provide an interpretive framework for positing why someone may be beset by guilt, shame, and/or rage whereas existing psychiatric diagnoses such as post-traumatic stress disorder and depression provide comprehensive descriptions regarding what someone might experience following extremely stressful events. We proposed directions to better clarify the boundaries of “moral injury” versus established psychiatric categories that could be used to enhance the conceptualization and assessment of this construct.
The Kinomatics Australian Film Production Dataset: A Curated Dataset Describing Australian Feature Film Titles and Personnel 1975–2022
Authors: Jones Pete , Verhoeven Deb , Harvey Sophie Talalay , Kantoro Aigul , Martinez Garcia Juan , Vo Vi
Published: October 2024

This article presents a novel, extensive, and thoroughly documented dataset describing Australian feature films and the personnel filling ten key production roles on those films. The dataset is curated from public information in multiple sources and draws on further supplemental resources to verify, validate and consolidate this information. In total, the data describes 22,720 roles filled by 9,397 distinct people across 1,877 films, covering an important 47-year period in the Australian film industry. The authors outline how the dataset solves several problems for scholars interested in data that provides a historical record of the collaborative filmmaking process. In particular, to address concerns about known coverage problems with popular sources such as the Internet Movie Database, this dataset has undergone extensive manual checking to ensure that it is reliable as a source of information on a national film industry. Moreover, the authors have carefully and manually linked each person appearing in the dataset, which allows the dataset to provide a rich source of information for exploring the relationality of filmmaking collaborations. The inclusion of ten key filmmaking roles further expands the utility of the dataset beyond existing datasets which tend to focus on actors and/or directors, writers and producers.
A new broom Gonocytisus graecus (Genisteae, Leguminosae/Fabaceae), from Greece
Authors: ŞENTÜRK OZAN , Kenicer Gregory J. , YILDIRIM HASAN
Published: October 2024

Gonocytisus graecus Şentürk & Yıldırım is a new species of broom described from Greece. This taxon resembles G. dirmilensis that is endemic to Türkiye, but differs in its larger flowers and fruit, orbicular-reniform seeds and defined fine reticulate seed surface, as well as smaller subprolate pollen. However this species shares dehiscent fruits with G. dirmilensis, in contrast to the indehiscent fruits of G. angulatus and G. pterocladus, the other two species in the genus. In this study, morphological characters are presented in detail. A distribution map, detailed illustration, images and IUCN conservation status assessment are provided.
Four new species of Mesorhaga Schiner (Diptera: Dolichopodidae) from Northeastern Brazil, with an identification key to South American species of the genus
Authors: SANTOS EDNALDO BEZERRA DOS , CAPELLARI RENATO SOARES , OLIVEIRA FRANCISCO LIMEIRA-DE-
Published: October 2024

Four new species of the sciapodine genus Mesorhaga Schiner (Diptera: Dolichopodidae) are described from the states of Piauí and Maranhão (Northeastern Brazil): Mesorhaga danbickeli sp. nov., M. gomesi sp. nov., M. laetitia sp. nov. and M. parnasete sp. nov. All species are illustrated with photos of general habitus and genitalia of males, and an identification key to South American species is provided.
Multiple imputation using auxiliary imputation variables that only predict missingness can increase bias due to data missing not at random
Authors: Curnow Elinor , Cornish Rosie P. , Heron Jon E. , Carpenter James R. , Tilling Kate
Published: October 2024

Background

Epidemiological and clinical studies often have missing data, frequently analysed using multiple imputation (MI). In general, MI estimates will be biased if data are missing not at random (MNAR). Bias due to data MNAR can be reduced by including other variables (“auxiliary variables”) in imputation models, in addition to those required for the substantive analysis. Common advice is to take an inclusive approach to auxiliary variable selection (i.e. include all variables thought to be predictive of missingness and/or the missing values). There are no clear guidelines about the impact of this strategy when data may be MNAR.

Methods

We explore the impact of including an auxiliary variable predictive of missingness but, in truth, unrelated to the partially observed variable, when data are MNAR. We quantify, algebraically and by simulation, the magnitude of the additional bias of the MI estimator for the exposure coefficient (fitting either a linear or logistic regression model), when the (continuous or binary) partially observed variable is either the analysis outcome or the exposure. Here, “additional bias” refers to the difference in magnitude of the MI estimator when the imputation model includes (i) the auxiliary variable and the other analysis model variables; (ii) just the other analysis model variables, noting that both will be biased due to data MNAR. We illustrate the extent of this additional bias by re-analysing data from a birth cohort study.

Results

The additional bias can be relatively large when the outcome is partially observed and missingness is caused by the outcome itself, and even larger if missingness is caused by both the outcome and the exposure (when either the outcome or exposure is partially observed).

Conclusions

When using MI, the naïve and commonly used strategy of including all available auxiliary variables should be avoided. We recommend including the variables most predictive of the partially observed variable as auxiliary variables, where these can be identified through consideration of the plausible casual diagrams and missingness mechanisms, as well as data exploration (noting that associations with the partially observed variable in the complete records may be distorted due to selection bias).
Comparison of the effectiveness of open, laparoscopic, and robotic-assisted radical prostatectomies based on complication rates: a retrospective observational study with administrative data from Switzerland
Authors: von Ahlen Christine , Geissler Alexander , Vogel Justus
Published: October 2024

Background

Radical prostatectomies can be performed using open retropubic, laparoscopic, or robot-assisted laparoscopic surgery. The literature shows that short-term outcomes (in particular, inpatient complications) differ depending on the type of procedure. To date, these differences have only been examined and confirmed in isolated cases based on national routine data.

Methods

The data was based on the Swiss Medical Statistics from 2016 to 2018 from a national survey of administrative data from all Swiss hospitals. Cases with the coded main diseases neoplasm of the prostate (ICD C61) and the main treatments of laparoscopic (CHOP 60.5X.20) or retropubic (CHOP 60.5X.30) radical prostatectomies were included, resulting in a total sample size of 8,593 cases.

Results

A procedure-related complication occurred in 998 cases (11.6%). By surgical procedure, complication rates were 10.1% for robotic-assisted laparoscopic radical prostatectomy 9.0% for conventional laparoscopic radical prostatectomy and 17.1% for open retropubic radical prostatectomy (p < 0.001). Conventional and robotic-assisted laparoscopic radical prostatectomies had a significantly lower risk of complications than retropubic procedures. Moreover, the risk of a procedure-related complication was almost twice as high in cases operated on retropubically; however, no significant difference was found between conventional and robotic-assisted laparoscopic cases.

Discussion

The use of a surgical robot showed no advantages in radical prostatectomies regarding procedure-related during the hospital stay. However, both conventional and robotic-assisted laparoscopically operated radical prostatectomies show better results than open retropubic procedures. Further studies on the long-term course of patients based on claims data are needed to confirm the inherent benefits of surgical robots in tandem with them being increasingly employed in hospitals.
Experiences of harm and mental ill-health among gay, bisexual and other men-who-have-sex-with-men who use methamphetamine or GHB/GBL in different combinations: findings from the COMeT study in Taiwan
Authors: Hsu Jing-Hao , Huang Poyao , Li Chia-Wen , Bourne Adam , Strong Carol , Ku Stephane Wen-Wei
Published: October 2024

Introduction

Polydrug use in the context of chemsex is commonplace among gay, bisexual, and other men-who-have-sex-with-men (GBMSM). This study aimed to examine the differences in experiences of physical, social, and psychological harms, as well as mental ill-health among GBMSM who use different combinations of methamphetamine and gamma-hydroxybutyric acid/gamma-butyrolactone (GHB/GBL) during chemsex.

Method

Adult GBMSM participants who had experience of chemsex in the past 12 months participated in a cross-sectional online survey in Taiwan and self-reported their sociodemographic background, sexual behaviours, mental health, and experiences of harm following a chemsex session. We used univariable and multivariable logistic regression to assess the different experiences of harm and mental ill-health among GBMSM who engaged in chemsex without using methamphetamine, used methamphetamine but not GHB/GBL, and who used both drugs.

Results

Out of 510 participants who completed all items included in the analysis, 24.1% engaged in chemsex without using methamphetamine, 36.9% used methamphetamine but not GHB/GBL, and 39.0% used both drugs. Eighty five percent of men who used both methamphetamine and GHB/GBL reported at least one kind of social harm after a chemsex session, such as missing dates or appointments, or appearing “high” at work, followed by used methamphetamine but not GHB/GBL (69.7%) and those without using methamphetamine (37.4%). After controlling for polydrug and frequency of drug use in the multivariable logistic regression, those who used methamphetamine but not GHB/GBL and those who used both drugs were more likely to report experiencing physical and psychological harms compared to those who did not use methamphetamine (p < 0.003).

Conclusion

GBMSM who used both methamphetamine and GHB/GBL in a chemsex context were more likely to report experience of harms than those who only used a single chemsex drug or engaged in chemsex without methamphetamine or GHB/GBL. Harm reduction should focus on both preventing HIV and STI transmission and on minimising psychosocial harm to GBMSM, with varying impacts depending on drug use.
Deriving disability weights for the Netherlands: findings from the Dutch disability weights measurement study
Authors: Haagsma Juanita A. , Charalampous Periklis
Published: October 2024

Background

The aims of this study were to establish national disability weights based on the health state preferences of a Dutch general population sample, examine the relation between results and respondent’s characteristics, and compare disability weights with those estimated in the European disability weights study.

Methods

In this cross-sectional study, a web-based survey was administered to a general population 18–75 years from the Netherlands. The survey included paired comparison questions. Paired comparison data were analysed using probit regression and located results onto the 0-to-1 disability weight scale using non-parametric regression. Bootstrapping was used to estimate 95% uncertainty intervals (95%UI). Spearman’s correlation was used to investigate the relation of probit regression coefficients between respondent’s characteristics.

Results

3994 respondents completed the questionnaire. The disability weights ranged from 0.007 (95%UI: 0.003–0.012) for mild distance vision impairment to 0.741 (95% UI: 0.498–0.924) for intensive care unit admission. Spearman’s correlation of probit coefficients between sub-groups based on respondent’s characteristics were all above 0.95 (p < 0.001). Comparison of disability weights of 140 health states that were included in the Dutch and European disability weights study showed a high correlation (Spearman’s correlation: 0.942; p < 0.001); however, for 76 (54.3%) health states the point estimate of the Dutch disability weight fell outside of the 95%UI of the European disability weights.

Conclusions

Respondent’s characteristics had no influence on health state valuations with the paired comparison. However, comparison of the Dutch disability weights to the European disability weights indicates that health state preferences of the general population of the Netherlands differ from those of other European countries.
Minimizing human interference in an online fully automated daily adaptive radiotherapy workflow for bladder cancer
Authors: Azzarouali Sana , Goudschaal Karin , Visser Jorrit , Daniëls Laurien , Bel Arjan , den Boer Duncan
Published: October 2024

Purpose

The aim was to study the potential for an online fully automated daily adaptive radiotherapy (RT) workflow for bladder cancer, employing a focal boost and fiducial markers. The study focused on comparing the geometric and dosimetric aspects between the simulated automated online adaptive RT (oART) workflow and the clinically performed workflow.

Methods

Seventeen patients with muscle-invasive bladder cancer were treated with daily Cone Beam CT (CBCT)-guided oART. The bladder and pelvic lymph nodes (CTVelective) received a total dose of 40 Gy in 20 fractions and the tumor bed received an additional simultaneously integrated boost (SIB) of 15 Gy (CTVboost). During the online sessions a CBCT was acquired and used as input for the AI-network to automatically delineate the bladder and rectum, i.e. influencers. These influencers were employed to guide the algorithm utilized in the delineation process of the target. Manual adjustments to the generated contours are common during this clinical workflow prior to plan reoptimization and RT delivery. To study the potential for an online fully automated workflow, the oART workflow was repeated in a simulation environment without manual adjustments. A comparison was made between the clinical and automatic contours and between the treatment plans optimized on these clinical (Dclin) and automatic contours (Dauto).

Results

The bladder and rectum delineated by the AI-network differed from the clinical contours with a median Dice Similarity Coefficient of 0.99 and 0.92, a Mean Distance to Agreement of 1.9 mm and 1.3 mm and a relative volume of 100% and 95%, respectively. For the CTVboost these differences were larger, namely 0.71, 7 mm and 78%. For the CTVboost the median target coverage was 0.42% lower for Dauto compared to Dclin. For CTVelective this difference was 0.03%. The target coverage of Dauto met the clinical requirement of the CTV-coverage in 65% of the sessions for CTVboost and 95% of the sessions for the CTVelective.

Conclusions

While an online fully automated daily adaptive RT workflow shows promise for bladder treatment, its complexity becomes apparent when incorporating a focal boost, necessitating manual checks to prevent potential underdosage of the target.
Triheptanoin in patients with long-chain fatty acid oxidation disorders: clinical experience in Italy
Authors: Porta Francesco , Maiorana Arianna , Gragnaniello Vincenza , Procopio Elena , Gasperini Serena , Taurisano Roberta , Spada Marco , Dionisi-Vici Carlo , Burlina Alberto
Published: October 2024

Background

Long-chain fatty acid oxidation disorders (LC-FAOD) are rare and potentially life-threatening diseases that cause deficient energy production and accumulation of toxic metabolites. Despite dietary management, adherence to maximum fasting guidelines, restricted long-chain triglyceride intake and supplementation with medium-chain triglyceride (MCT) oil (current standard of care), most patients experience recurrent decompensation episodes that can require hospitalisation. Herein, we analysed the effectiveness and safety of triheptanoin (a highly purified, synthetic medium odd-chain triglyceride) treatment in a cohort of Italian patients with LC-FAOD.

Methods

This retrospective, nationwide study included nine patients with LC-FAOD who switched from standard therapy with MCT oil to triheptanoin oral liquid. Data were collected between 2018 and 2022. Clinical outcome measures were the number and duration of intercurrent catabolic episodes and number and duration of metabolic decompensation episodes requiring hospitalisation. Creatine kinase (CK) levels and treatment-related adverse effects were also reported.

Results

Patients were provided a mean ± standard deviation (SD) triheptanoin dose of 1.5 ± 0.9 g/kg/day in four divided administrations, which accounted for 23.9 ± 8.9% of patients’ total daily caloric intake. Triheptanoin treatment was started between 2.7 and 16 years of age and was continued for 2.2 ± 0.9 years. The number of intercurrent catabolic episodes during triheptanoin treatment was significantly lower than during MCT therapy (4.3 ± 5.3 vs 22.0 ± 22.2; p = 0.034), as were the number of metabolic decompensations requiring hospitalisation (mean ± SD: 2.0 ± 2.5 vs 18.3 ± 17.7; p = 0.014), and annualised hospitalisation rates and duration. Mean CK levels (outside metabolic decompensation episodes) were lower with triheptanoin treatment versus MCT oil for seven patients. No intensive care unit admissions were required during triheptanoin treatment. Epigastric pain and diarrhoea were recorded as adverse effects during both MCT and triheptanoin treatment.

Conclusions

The significant improvement in clinical outcome measures after the administration of triheptanoin highlights that this treatment approach can be more effective than MCT supplementation in patients with LC-FAOD. Triheptanoin was well tolerated and decreased the number of intercurrent catabolic episodes, metabolic decompensation episodes requiring hospitalisation, and the annualised rate and duration of hospitalisations.
Strategic nucleic acid detection approaches for diagnosing African swine fever (ASF): navigating disease dynamics
Authors: Zhu Yuanshou , Zhang Meng , Jie Zhijun , Guo Shujuan , Zhu Zhigang , Tao Sheng-ce
Published: October 2024

African swine fever (ASF) is a devastating disease caused by African swine fever virus (ASFV) and leads to significant economic losses in the pig farming industry. Given the absence of an effective vaccine or treatment, the mortality rate of ASF is alarmingly close to 100%. Consequently, the ability to rapidly and accurately detect ASFV on site and promptly identify infected pigs is critical for controlling the spread of this pandemic. The dynamics of the ASF virus load and antibody response necessitate the adoption of various detection strategies at different stages of infection, a topic that has received limited attention to date. This review offers detailed guidance for choosing appropriate ASF diagnostic techniques tailored to the clinical manifestations observed from the acute to chronic phases, including asymptomatic cases. We comprehensively summarize and evaluate the latest advancements in ASFV detection methods, such as CRISPR-based diagnostics, biosensors, and microfluidics. Additionally, we address the challenges of false negatives or positives due to ASF variants or the use of injected live attenuated vaccines. This review provides an exhaustive list of diagnostic tests suitable for detecting each stage of symptoms and potential target genes for developing new detection methods. In conclusion, we highlight the current challenges and future directions in ASFV detection, underscoring the need for continued research and innovation in this field.
Extensive Schmallenberg virus circulation in Germany, 2023
Authors: Wernike Kerstin , Fischer Luisa , Twietmeyer Sönke , Beer Martin
Published: October 2024

Schmallenberg virus (SBV) and bluetongue virus (BTV) are both transmitted by Culicoides biting midges and infect predominantly ruminants. To investigate the extent of virus spread in the 2022 and 2023 vector seasons, we serologically tested wild ruminants from western Germany. While antibodies against BTV were not detected in any animal, regardless of age or sampling time, numerous wild ruminants tested positive for antibodies to SBV. In 2022, a low seroprevalence of 4.92% was measured. In sharp contrast, 40.15% of the animals tested positive in 2023. Of the young animals, about 31.82% were seropositive, clearly indicating large-scale SBV circulation in summer and autumn 2023.
Safety and efficacy of oxycodone for refractory dyspnea in end-stage heart failure patients with chronic kidney disease: a case series of eight patients
Authors: Tanaka Masayuki , Maeba Hirofumi , Senoo Takeshi , Yoshimiya Nana , Ozaki Haruna , Uchitani Kazuki , Tanigawa Noboru , Okazaki Kazuichi
Published: October 2024

Background

Morphine is effective in palliative care for patients with end-stage heart failure; however, its use is avoided in patients with impaired renal function because it tends to induce adverse effects. Although oxycodone has been reported to be a useful alternative, the evidence is insufficient. Therefore, we investigated the safety and efficacy of oxycodone in eight patients with end-stage heart failure complicated by chronic kidney disease. 

Methods

This single-center retrospective study reviewed patients with end-stage heart failure who were referred to the heart failure multidisciplinary team at our institution and administered oxycodone for refractory dyspnea during hospitalization between January 2011 and December 2018. We examined the details of oxycodone usage, vital signs, and the Modified Borg Scale (MBS), which quantifies the symptoms of dyspnea and adverse events.

Results

Oxycodone was administered for refractory dyspnea in eight patients with end-stage heart failure [mean age: 81 years, men: 4, New York Heart Association functional class IV: 8, median left ventricular ejection fraction: < 40% (n = 6) and ≥ 50% (n = 2)]. Renal function was reduced in all patients; the estimated glomerular filtration rate (eGFR) in seven patients was < 30 mL/min/1.73 m2. The median initial intravenous dose of oxycodone was 7.05 mg/day (range: 5–10 mg/day), and the average duration of administration was 15.8 days. Significant decreases in MBS (before: median 9, range 7–10 vs. after: median 2.5, range 1–8; p < 0.01) were observed at a median of 2.0 days (range: 2 h to 7 days) after beginning oxycodone administration. Systolic blood pressure, heart rate, and respiratory rate were not significantly altered after treatment. Adverse events, including constipation, nausea, and tremors, were observed in three patients. However, no lethal adverse events related to oxycodone treatment occurred during treatment.

Conclusions

This study revealed the clinical practice of oxycodone treatment and suggested that it is an alternative therapy as a viable palliative for refractory dyspnea in patients with end-stage heart failure who should avoid the use of morphine.
Establishment of Z score reference of liver, spleen, and kidney parameters for Egyptian children and adolescents: a cross-sectional randomized study
Authors: El-Shafie Ali M. , Bahbah Wael A. , Zefzaf Heba M. S. El , Mousa Waleed A. , Abdellatif Hayam A. , EL-Hossary Rehab H. , Al Demerdash Amira H. , Hamza Mai N. , Omar Zein A.
Published: October 2024

Background

Among various growth parameters, liver and spleen size is an important parameter used for the evaluation of patients with certain disorders and abnormalities in these organs.

Aim

To determine the normal dimensions for the liver, spleen, and kidney in Egyptian infants, children, and adolescents from birth to 18 years.

Methods

This cross-sectional randomized study was conducted on 1861 Egyptian infants, children, and adolescents from birth to 18 years for the establishment of Z score reference of liver, spleen, and kidney parameters.

Results

Egyptian children of both sexes (51.5% boys and 48.5% girls) from birth to 18 years old were studied. Then Z scores reference for liver, spleen, and kidney parameters for both sexes were represented in detailed tables and graphs. There was no statistically significant difference between both sexes, so we used unisex tables and graphs (P > 0.05).

Conclusions

Determination of pathologic changes in the size of the liver, spleen, and kidney necessitates knowing the normal range of dimensions for these organs. So, our study established a Z score chart for normal values of liver, spleen, and kidney size for children and adolescents from birth to 18 years.
The use of interleukin-10 (IL-10) and phosphorus levels as predictors of the time to improvement in COVID-19 patients: a prospective study
Authors: Zidan Amira A. , Gad Ahmed Y. S. , Zakaria Nermine H. , El-Hariri Hazem M. , Elsharnouby Noha M. , Helmy Maged W. , El-Setouhy Maged
Published: October 2024

Early detection of COVID-19 improves the chance of recovery and helps identify high-risk patients. Our study aimed to statistically predict the time to improvement with the admission data of COVID-19 patients.

Methods: Our prospective cohort study occurred between January and September 2022 at Alexandria University Hospital’s outpatient clinic and isolation department. We enrolled 43 patients after assessing their eligibility and collecting their baseline data.

Results: The mean age was 34.8 years (± 12.3). Most of them were females (65.1%). The mean of oxygen saturation was 95.2% (± 2.8). We used linear regression to predict how long it would take to improve [time to improvement (days) = 1.186*P (mmol/L) + 0.010*IL-10 (pg/mL)]. Its diagnostic performance was 0.723 (95% CI: 0.552–0.894), and it was accurate at predicting improvement within a week but not at longer delays; additionally, its positive and negative predictive values were 56.3% and 85.2%, respectively.

Conclusion: We recommend monitoring phosphorus and interleukin-10 levels. The time-to-improvement delay negatively correlated with a reduction in baseline oxygen saturation upon admission. Additionally, for every 0.84 meq/L increase in phosphorus or 100 pg/mL increase in interleukin-10, there was a 1-day delay provided that the other was constant, with a coefficient of determination of 85.9%.
Air under pressure: a case report on tension pneumomediastinum arising from traumatic injury
Authors: Kotokey Udvass Kumar
Published: October 2024

Background

Tension pneumomediastinum (TPM) is a rare but critical condition characterized by the accumulation of air in the mediastinum, leading to increased intrathoracic pressure and cardiovascular compromise. This case report is novel due to the rarity of TPM arising from blunt chest trauma and the necessity for emergent surgical intervention after initial conservative management failed.

Case presentation

A 63-year-old male presented with severe chest pain and dyspnea following a high-impact motor vehicle collision. Initial assessment revealed tachypnea, tachycardia, and hypotension, along with extensive subcutaneous emphysema over the chest and neck. Imaging confirmed pneumomediastinum and bilateral pneumothoraxes, consistent with TPM. Despite initial management with high-flow oxygen and bilateral chest tube insertion, the patient’s condition deteriorated, necessitating emergent mediastinal decompression via an anterior subxiphoid incision. This intervention resulted in immediate hemodynamic improvement.

Conclusions

This case underscores the importance of recognizing TPM in patients with chest trauma and highlights the need for prompt surgical intervention in cases of hemodynamic instability. Early and accurate diagnosis and timely surgical management are crucial for improving patient outcomes in TPM.
A systematic review and meta-analysis of music interventions to improve sleep in adults with mental health problems
Authors: Zhao Nan , Lund Helle Nystrup , Jespersen Kira Vibe
Published: October 2024

Background

Music listening has been used as a sleep intervention among different populations. This systematic review and meta-analysis aimed to explore whether music is an effective sleep aid in adults with mental health problems.

Methods

We searched for studies investigating music interventions for sleep in adults with mental health problems. The primary outcome was subjective sleep quality; secondary outcomes were objective sleep outcomes, quality of life, and other mental health symptoms. Risk of bias assessment (RoB1) and random-effect model were used for the systematic review and meta-analyses.

Results

The initial screening (n = 1492) resulted in 15 studies in the systematic review. Further qualified studies led to the meta-analysis of sleep quality (n = 7), depression (n = 5), and anxiety (n = 5). We found that the music listening intervention showed a potential effect on subjective sleep quality improvement compared to treatment-as-usual or no-intervention groups. When excluding an outlier study with an extreme effect, the meta-analysis showed a moderate effect on sleep quality (Hedges’ g = −0.66, 95% CI [−1.19, −0.13], t = −3.21, p = 0.0236). The highest risk of bias was the blinding of participants and researchers due to the nature of the music intervention.

Conclusions

Our results suggest that music interventions could have the potential to improve sleep quality among individuals with mental health problems, even though more high-quality studies are needed to establish the effect fully.
Response to Crizotinib After Entrectinib Resistance in
ROS1
-Rearranged,
MET
-Amplified Lung Adenocarcinoma
Authors: Vaz Victor R. , Gandhi Malini M. , Ricciuti Biagio , Alessi Joao V. , Elkrief Arielle , Ladanyi Marc , Vanderbilt Chad , Pecci Federica , Aldea Mihaela , Barrichello Adriana , Saini Arushi , Sholl Lynette , Sands Jacob M. , Awad Mark M.
Published: October 2024

Crizotinib successfully overcomes MET amplification in ROS1-rearranged NSCLC after entrectinib failure.
Tracking and measuring local protein synthesis in vivo
Authors: Kays Ibrahim , Chen Brian E.
Published: October 2024

Detecting when and how much of a protein molecule is synthesized is important for understanding cell function, but current methods either cannot be performed in vivo or have poor temporal resolution. Here, we developed a technique to detect and quantify subcellular protein synthesis events in real time in vivo. This Protein Translation Reporting (PTR) technique uses a genetic tag that produces a stoichiometric ratio of a small peptide portion of a split fluorescent protein and the protein of interest during protein synthesis. We show that the split fluorescent protein peptide can generate fluorescence within milliseconds upon binding the larger portion of the fluorescent protein, and that the fluorescence intensity is directly proportional to the number of molecules of the protein of interest synthesized. Using PTR, we tracked and measured protein synthesis events in single cells over time in vivo. We use different color split fluorescent proteins to detect multiple genes or alleles in single cells simultaneously. We also split a photoswitchable fluorescent protein to photoconvert the reconstituted fluorescent protein to a different channel to continually reset the time of detection of synthesis events.