bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplementary Figure Legend from Rapamycin Regulates Stearoyl CoA Desaturase 1 Expression in Breast Cancer
Authors: Luyimbazi David , Akcakanat Argun , McAuliffe Priscilla F. , Zhang Li , Singh Gopal , Gonzalez-Angulo Ana Maria , Chen Huiqin , Do Kim-Anh , Zheng Yuhuan , Hung Mien-Chie , Mills Gordon B. , Meric-Bernstam Funda
Published: April 2023

Supplementary Figure Legend from Rapamycin Regulates Stearoyl CoA Desaturase 1 Expression in Breast Cancer
Supplementary Fig. S4 from In vivo target-specific activatable near-infrared optical labeling of humanized monoclonal antibodies
Authors: Ogawa Mikako , Regino Celeste A.S. , Choyke Peter L. , Kobayashi Hisataka
Published: April 2023

Supplementary Fig. S4 from In vivo target-specific activatable near-infrared optical labeling of humanized monoclonal antibodies
Supplementary Fig. S3 from In vivo target-specific activatable near-infrared optical labeling of humanized monoclonal antibodies
Authors: Ogawa Mikako , Regino Celeste A.S. , Choyke Peter L. , Kobayashi Hisataka
Published: April 2023

Supplementary Fig. S3 from In vivo target-specific activatable near-infrared optical labeling of humanized monoclonal antibodies
Supplementary Fig. S2 from In vivo target-specific activatable near-infrared optical labeling of humanized monoclonal antibodies
Authors: Ogawa Mikako , Regino Celeste A.S. , Choyke Peter L. , Kobayashi Hisataka
Published: April 2023

Supplementary Fig. S2 from In vivo target-specific activatable near-infrared optical labeling of humanized monoclonal antibodies
Supplementary Fig. from Regulation of leukemic cell differentiation and retinoid-induced gene expression by statins
Authors: Sassano Antonella , Lo Iacono Marco , Antico Giovanni , Jordan Alison , Uddin Shahab , Calogero Raffaele A. , Platanias Leonidas C.
Published: April 2023

Supplementary Fig. from Regulation of leukemic cell differentiation and retinoid-induced gene expression by statins
Supplementary Table S5 from Profiling SLCO and SLC22 genes in the NCI-60 cancer cell lines to identify drug uptake transporters
Authors: Okabe Mitsunori , Szakács Gergely , Reimers Mark A. , Suzuki Toshihiro , Hall Matthew D. , Abe Takaaki , Weinstein John N. , Gottesman Michael M.
Published: April 2023

Supplementary Table S5 from Profiling SLCO and SLC22 genes in the NCI-60 cancer cell lines to identify drug uptake transporters
Supplementary Table S3 from Profiling SLCO and SLC22 genes in the NCI-60 cancer cell lines to identify drug uptake transporters
Authors: Okabe Mitsunori , Szakács Gergely , Reimers Mark A. , Suzuki Toshihiro , Hall Matthew D. , Abe Takaaki , Weinstein John N. , Gottesman Michael M.
Published: April 2023

Supplementary Table S3 from Profiling SLCO and SLC22 genes in the NCI-60 cancer cell lines to identify drug uptake transporters
Supplementary Figure 4 from Identification of LIV1, a Putative Zinc Transporter Gene Responsible for HDACi-Induced Apoptosis, Using a Functional Gene Screen Approach
Authors: Ma Xiaoli , Ma Quanfu , Liu Jia , Tian Yuan , Wang Beibei , Taylor Kathryn M. , Wu Peng , Wang Daowen , Xu Gang , Meng Li , Wang Shixuan , Ma Ding , Zhou Jianfeng
Published: April 2023

Supplementary Figure 4 from Identification of LIV1, a Putative Zinc Transporter Gene Responsible for HDACi-Induced Apoptosis, Using a Functional Gene Screen Approach
Supplementary Table S1 from Profiling SLCO and SLC22 genes in the NCI-60 cancer cell lines to identify drug uptake transporters
Authors: Okabe Mitsunori , Szakács Gergely , Reimers Mark A. , Suzuki Toshihiro , Hall Matthew D. , Abe Takaaki , Weinstein John N. , Gottesman Michael M.
Published: April 2023

Supplementary Table S1 from Profiling SLCO and SLC22 genes in the NCI-60 cancer cell lines to identify drug uptake transporters
Supplementary Figure 2 from Identification of LIV1, a Putative Zinc Transporter Gene Responsible for HDACi-Induced Apoptosis, Using a Functional Gene Screen Approach
Authors: Ma Xiaoli , Ma Quanfu , Liu Jia , Tian Yuan , Wang Beibei , Taylor Kathryn M. , Wu Peng , Wang Daowen , Xu Gang , Meng Li , Wang Shixuan , Ma Ding , Zhou Jianfeng
Published: April 2023

Supplementary Figure 2 from Identification of LIV1, a Putative Zinc Transporter Gene Responsible for HDACi-Induced Apoptosis, Using a Functional Gene Screen Approach
Supplementary Data from A Genetically Encoded Multifunctional TRAIL Trimer Facilitates Cell-Specific Targeting and Tumor Cell Killing
Authors: Spitzer Dirk , McDunn Jonathan E. , Plambeck-Suess Stacey , Goedegebuure Peter S. , Hotchkiss Richard S. , Hawkins William G.
Published: April 2023

Supplementary Data from A Genetically Encoded Multifunctional TRAIL Trimer Facilitates Cell-Specific Targeting and Tumor Cell Killing
Supplementary Table S2 from Reversine, a novel Aurora kinases inhibitor, inhibits colony formation of human acute myeloid leukemia cells
Authors: D'Alise Anna Morena , Amabile Giovanni , Iovino Mariangela , Di Giorgio Francesco Paolo , Bartiromo Marta , Sessa Fabio , Villa Fabrizio , Musacchio Andrea , Cortese Riccardo
Published: April 2023

Supplementary Table S2 from Reversine, a novel Aurora kinases inhibitor, inhibits colony formation of human acute myeloid leukemia cells
Supplementary Figure 2 from Response prediction to a multitargeted kinase inhibitor in cancer cell lines and xenograft tumors using high-content tyrosine peptide arrays with a kinetic readout
Authors: Versele Matthias , Talloen Willem , Rockx Cindy , Geerts Tamara , Janssen Boud , Lavrijssen Tom , King Peter , Göhlmann Hinrich W.H. , Page Martin , Perera Tim
Published: April 2023

Supplementary Figure 2 from Response prediction to a multitargeted kinase inhibitor in cancer cell lines and xenograft tumors using high-content tyrosine peptide arrays with a kinetic readout
Supplementary Fig. S1 legend from Nuclear factor-κB activation: a molecular therapeutic target for estrogen receptor–negative and epidermal growth factor receptor family receptor–positive human breast cancer
Authors: Singh Sindhu , Shi Qian , Bailey Shannon T. , Palczewski Marek J. , Pardee Arthur B. , Iglehart J. Dirk , Biswas Debajit K.
Published: April 2023

Supplementary Fig. S1 legend from Nuclear factor-κB activation: a molecular therapeutic target for estrogen receptor–negative and epidermal growth factor receptor family receptor–positive human breast cancer
Supplementary Fig. S4 from Multiple signaling pathways must be targeted to overcome drug resistance in cell lines derived from melanoma metastases
Authors: Smalley Keiran S.M. , Haass Nikolas K. , Brafford Patricia A. , Lioni Mercedes , Flaherty Keith T. , Herlyn Meenhard
Published: April 2023

Supplementary Fig. S4 from Multiple signaling pathways must be targeted to overcome drug resistance in cell lines derived from melanoma metastases
Integrating Theory with Education about Genetic Risk for Alcohol Use Disorder: The Effects of a Brief Online Educational Tool on Elements of the Health Belief Model
Authors: Driver Morgan N , Kuo Sally I-Chun , Austin Jehannine , Dick Danielle M.
Published: March 2023

Introduction: The utility of genetic risk information relies on the assumption that individuals will use the information to change behavior to reduce risk of developing health problems. Educational interventions designed to target elements of the Health Belief Model have shown to be effective in promoting behaviors for positive outcomes. Methods: A randomized controlled trial (RCT) was conducted in 325 college students to assess whether a brief, online educational intervention altered elements of the Health Belief Model that are known to be associated with motivations and intentions to change behavior. The RCT included a control condition, an intervention condition that received information about alcohol use disorder (AUD), and an intervention condition that received information about polygenic risk scores and AUD. We used t tests and ANOVA methods to compare differences in beliefs related to the Health Belief Model across study conditions and demographic characteristics. Results: Providing educational information did not impact worry about developing AUD, perceived susceptibility and severity of developing alcohol problems, or perceived benefits and barriers of risk-reducing actions. Individuals in the condition that received educational information about polygenic risk scores and AUD reported higher perceived chance of developing AUD than individuals in the control condition (adj. p < 0.01). Sex, race/ethnicity, family history, and drinking status were associated with several components of the Health Belief Model. Conclusion: Findings from this study demonstrate the need to better design and refine the educational information intended to accompany the return of genetic feedback for AUD to better promote risk-reducing behaviors.
Sobre alguns generos e espécies de heptapsogastridae (mallophaga) III
Authors: Guimarães Lindolpho R.
Published: March 2023

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Stroke Severity Mediates the Association Between Socioeconomic Disadvantage and Poor Outcomes Among Patients With Acute Ischemic Stroke
Authors: Pan Alan P. , Potter Thomas , Bako Abdulaziz T. , Tannous Jonika , McCane Charles D. , Garg Tanu , Gadhia Rajan , Misra Vivek , Volpi John , Chiu David , Vahidy Farhaan S.
Published: March 2023

Background

Impact of mediating factors on the relationship between socioeconomic disadvantage and outcomes among patients with acute ischemic stroke has not been well characterized.

Methods

Data on patients with acute ischemic stroke were extracted from electronic medical records, and 90‐day modified Rankin scale (mRS) scores were collected as part of a prospective stroke registry. Exact patient addresses were geocoded and characterized using Area Deprivation Index (ADI) ranks. The 90‐day modified Rankin scale scores ≥3 were categorized as poor outcomes. Logistic regression models (adjusted for treatment with intravenous tissue plasminogen activator or intraarterial therapy, sociodemographics, and comorbidities) were fitted to compute adjusted odds ratios (aORs) and 95% CIs for total effect of high ADI on poor outcomes. In‐hospital mortality (versus survived) and unfavorable (versus favorable) discharge disposition were also evaluated as outcomes. Structural equation modeling was used to report the average causal mediation effects of stroke severity (National Institutes of Health Stroke Scale [NIHSS]) and treatment (intravenous tissue plasminogen activator or intraarterial therapy).

Results

Between May 2016 and December 2021, 13 641 patients with acute ischemic stroke (median age, 69 years; 50.1% women) were included. Among 3002 patients with functional outcomes data, a high ADI was significantly associated with poor 90‐day modified Rankin scale score (aOR, 1.16 [95% CI, 1.04–1.29]). Patients in higher ADI neighborhoods had increased odds of having higher NIHSS scores (aOR, 1.19 [95% CI, 1.07–1.32]). Likewise, a higher NIHSS score was associated with poor 90‐day modified Rankin scale score (aOR, 9.34 [95% CI, 7.64–11.5]). The effect of neighborhood disadvantage on poor 90‐day modified Rankin scale score was 59% mediated by NIHSS score (average causal mediation effects:
P
<0.001). NIHSS score also accounted for 93% of the pathway for unfavorable discharges. In‐hospital mortality was not associated with ADI, and treatment did not significantly mediate any outcomes.

Conclusions

Neighborhood disadvantage leads to unfavorable hospital discharges and worse 90‐day disability, mediated via stroke severity. Tracking social determinants of health may identify opportunities for reducing the onset of severe strokes and poor outcomes.
Permutation Inference with a Finite Number of Heterogeneous Clusters
Authors: Hagemann Andreas
Published: March 2023

I introduce a simple permutation procedure to test conventional (non-sharp) hypotheses about the effect of a binary treatment in the presence of a finite number of large, heterogeneous clusters when the treatment effect is identified by comparisons across clusters. The procedure asymptotically controls size by applying a level-adjusted permutation test to a suitable statistic. The adjusted permutation test is easy to implement in practice and performs well at conventional levels of significance with at least four treated clusters and a similar number of control clusters. It is particularly robust to situations where some clusters are much more variable than others.
Trust, Happiness, and Pro-Social Behavior
Authors: Carattini Stefano , Roesti Matthias
Published: March 2023

This paper combines several large-scale surveys and empirical strategies to shed new light on the determinants of cooperative behavior. We provide evidence indicating that the level of trust maximizing subjective well-being tends to be above the income maximizing level. Higher trust is also linked to more cooperative and pro-social behaviors, including the private provision of global public goods such as climate change mitigation. Consistent with “warm glow” theories of pro-social behavior, our results indicate that individuals may enjoy being more cooperative than what would lead them to maximize income, which can be reflected in higher levels of subjective well-being.
Voicing Disagreement in Science: Missing Women
Authors: Klinowski David
Published: March 2023

This paper examines the authorship of post-publication criticisms in the scientific literature, with a focus on gender differences. Bibliometrics from journals in the natural and social sciences show that comments that criticize or correct a published study are 20-40% less likely than regular papers to have a female author. In preprints in the life sciences, prior to peer review, women are missing by 20-40% in failed replications compared to regular papers, but are not missing in successful replications. In an experiment, I then find large gender differences in willingness to point out and penalize a mistake in someone's work.
A Note on the Structure of Hebrews 10:11–13
Authors: Akagi Kai
Published: March 2023

Lexical, syntactical, and semantic correspondence demonstrates that Heb 10:11–13 consists of a concentric structure not discussed in the commentary literature. Obser‑ vation of this structure clarifies the number of contrasts that appear in the sentence spanning these verses and provides additional data informing the debated question of whether the phrase εἰς τὸ διηνεκές in Heb 10:12 modifies the preceding participle προσενέγκας or the following verb ἐκάθισεν. This structure furthermore serves as one more example of the emphasis on the singularity of Jesus’s sacrifice in Hebrews.
The Role of Islam in Realizing the Goals of Climate Change Law: From Theory to Practice?
Authors: Salimi Turkamani Hojjat
Published: March 2023

As the second-largest followed religion, Islam traditionally has general teachings about protecting the environment. In the context of climate change these traditional teachings have crystallized in the form of non-binding declarations. These traditional and new perceptions have been manifested as promotive force in the behavior of Islamic actors, including Muslims, Islamic ngo s, Islamic stats, and international Islamic organizations to combat climate change. The question is, have Islamic teachings been able to be effective in the practice of Islamic countries in achieving the goals of the climate change law? Analyzing of the latest report of oic (2021) indicates that, despite the increasing vulnerability of Islamic countries to the effects of greenhouse gas emissions, their greenhouse gas emissions have increased. It is concluded that despite the extensive participation of Islamic countries in international climate change meetings and documents, due to the economic problems, secularity of the government and the continuous effects of colonialism on them, Islam has had an ineffective role on the final result; Because, their approach to climate change is subject to economic and political considerations and not Islamic teachings. Therefore, to create a promotive role for Islam in realizing the goals of climate change law, more attention should be paid to the economic and political considerations of Islamic countries.
Local rarity of vascular plants in a human-dominated landscape of Northern Ethiopia
Authors: Gebrehiwot Kflay , Woldu Zerihun , Demissew Sebsebe
Published: March 2023

Understanding species rarity is crucial in developing conservation priorities by reasonably allocating limited funds effectively. The local rarity of vascular plants in the Abune Yosef mountain range in Ethiopia was assessed using Rabinowitz’s seven forms of rarity. Of the 199 vascular species analyzed for rarity, 171 species (86%) were rare. On the contrary, only 28 species (14%) were found to be common in the study area. The rarity index (rr) ranged from 0.46 to 1. On the other hand, species range (gri), total density of mature individuals (psi), and Habitat specificity (hsi) ranges were 0.99–1, 0–1, and 0.04–1, respectively. Land transformation was identified as likely the main driver for rarity in the study area. The characterization of the plant species of the Abune Yosef mountain range provided here can be used in the management of this threatened landscape and provide a basis for broader national-level conservation efforts of plants within the biodiverse landscapes of Ethiopia.
The Student as Broker: Friedrich Wilhelm Roloff and the Translation of Early Modern Biblical Scholarship
Authors: Schmid Philippe Bernhard
Published: March 2023

Translation supplied early modern students with a first output for their academic career, while introducing them to the workings of the printing trade. This article shows that through translation students could also become information brokers in the Republic of Letters. I focus on Friedrich Wilhelm Roloff (1714–1741) in Berlin, who translated a single chapter from the Histoire critique de Manichée et de manichéisme (1734) by the Huguenot theologian Isaac de Beausobre (1659–1738). Highlighting the paratexts of Roloff’s publication, I argue that print enabled students to play the role of mediators in theological disputes. Translating Beausobre’s chapter into the material format of a printed dissertation, Roloff dedicated his book to Siegmund Jakob Baumgarten (1706–1757), commemorating Baumgarten’s appointment as professor at Halle. As the translation and its collaborative production formed part of a larger network of Wolffianism, my article reveals that Roloff was made into a broker by accident.
Taxonomic review of the genus Tarika Moore with descriptions of six new species from Nepal, China and Indochina (Lepidoptera: Erebidae: Arctiinae)
Authors: VOLYNKIN ANTON V. , SALDAITIS AIDAS , ČERNÝ KAREL , HUANG SI-YAO
Published: March 2023

The Asiatic footman moth genus Tarika Moore, 1878, which used to be considered as monotypic is reviewed. Six new species are described: T. annapurna sp. n. (Сentral Nepal), T. erlanga sp. n. (China: Sichuan), T. reducta sp. n. (North Thailand), T. danieli sp. n. (China: Yunnan, Sichuan, Fujian, Shandong), T. kinha sp. n. (North Vietnam and China: Yunnan), and T. biserratula sp. n. (China: Hunan). Lectotypes are designated for Lithosia varana Moore, 1865 and Tarika nivea Moore, 1878. Adults, male and female genitalia are illustrated.
Sinolethrus, a new subgenus of the genus Lethrus Scopoli, 1777 from China (Coleoptera: Geotrupidae: Lethrinae) and new synonymy of the subgenus Paralethrus Nikolajev, 2003
Authors: BAGATUROV MIKHAIL F. , HILLERT OLIVER
Published: March 2023

Sinolethrus Bagaturov & Hillert, new subgenus is described as a monotypical subgenus for Lethrus serpentifer Semenov & Medvedev, 1935. The new subgenus is distributed in the north-central part of China. An identification key for the subgenera of the genus Lethrus Scopoli, 1777 is provided, diagnostic characters are illustrated. Furthermore, Lethrus mediocris Fairmaire, 1892 is synonymized with Lethrus (Paralethrus) bituberculatus impressifrons Ballion, 1870, and its lectotype is designated.
The Protective Role of Dispositional Mindfulness on Cyber Dating Abuse: A 6-Month Longitudinal Study
Authors: Fernández-González Liria , Orue Izaskun , González-Cabrera Joaquín , Machimbarrena Juan Manuel , Calvete Esther
Published: March 2023

Dispositional mindfulness has been related to a decreased propensity to aggressive behaviors toward others, including dating partners. Nevertheless, research in the context of romantic relationships is scarce, based on cross-sectional designs and offline (face to face) aggression. Thus, this 6-month longitudinal study seeks to fill a gap in the literature by examining the predictive role of dispositional mindfulness facets (observing, describing, acting with awareness, non-judging, and non-reacting) in the perpetration of cyber dating abuse (CDA) behaviors in adolescents. The moderator role of the dispositional mindfulness facets in the perpetuation over time of cyber aggression toward the partner was also explored. Participants were 501 high school students (54.1% girls; mean age: 14.17 years, SD = 1.39) from different regions of Spain who completed self-report measures about CDA and dispositional mindfulness at two time points with a 6-month interval between them. Path analysis showed that the acting with awareness mindfulness facet predicted a decrease in the perpetration of CDA 6 months later. Moreover, non-reacting showed a moderator role in the perpetuation over time of CDA. In particular, adolescents with higher scores on non-reacting, evidenced a lower perpetuation of CDA. Mindfulness-based interventions can be a valuable tool in preventing cyber aggression that occurs in adolescent dating relationships.
Phytochemical Constituents from the Aerial Parts of Acanthus ebracteatus Vahl. and Their Cytotoxic Activity
Authors: Anh Bui Thi Mai , Nga Tran Thi Thuy , Lan Hoang Thi Tuyet , Mai Nguyen Thi , Huong Phan Thi Thanh , Tai Bui Huu , Nhiem Nguyen Xuan , Van Kiem Phan
Published: March 2023

Objective

Acanthus ebracteatus Vahl. (family Acanthaceae) is distributed in the mangrove areas of northern Vietnam. The whole plant has the effect of dissolving blood stasis, reducing swelling, relieving pain, dissolving phlegm, and is often used to treat back pain, numbness, cough, and asthma. In our screening program for seeking cytotoxic active compounds, the methanol extract of this plant significantly showed activity and was selected for further study. In this paper we report the chemical constituents of A. ebracteatus and their cytotoxic activity towards two cancer cell lines, HepG2 and SK-LU1 in vitro.

Methods

The dried and powdered aerial parts of A. ebracteatus were ultrasonically extracted with methanol. This extract was suspended in water and successively partitioned with n-hexane, dichloromethane, and ethyl acetate to give n-hexane, dichloromethane, ethyl acetate, and water-soluble extracts. These extracts were fractionated and purified by column and HPLC chromatographic methods. The chemical structures of the isolates were determined by analysis of HRESIMS, and 1D and 2D NMR, and CD spectra. The isolates were screened for their in vitro cytotoxic activity by SRB assay.

Results

One new flavone glycoside (1) and ten known compounds (2-11), including five flavones (2-6), three alkaloids (7-9), and two phenolic glycosides (10 and 11), were isolated from the aerial parts of A. ebracteatus. Compounds 7–9 showed moderate cytotoxic activity against HepG2 and SK-LU1 cell lines with IC50 values ranging from 28.2 to 31.1 µM. Compounds 2–6, 8, 9, and 11 are reported herein from A. ebracteatus for the first time.

Conclusion

One new (1) and five known flavonoids (2-6), together with three alkaloids (7-9) and two phenolic glycosides (10 and 11) were recorded from A. ebracteatus. Our results preliminarily revealed that alkaloids may be cytotoxic ingredients of A. ebracteatus.
STAT5 activation promotes progression and chemotherapy-resistance in early T-cell precursor acute lymphoblastic leukemia
Authors: Tremblay Cedric S. , Saw Jesslyn , Boyle Jacqueline A , Haigh Katharina , Litalien Veronique , McCalmont Hannah Ruth , Evans Kathryn , Lock Richard B , Jane Stephen M , Haigh Jody J , Curtis David J
Published: March 2023

IL-7 supports the growth and chemoresistance of T-cell acute lymphoblastic leukemia (T-ALL), particularly the early T-cell precursor subtype (ETP-ALL), which frequently has activating mutations of IL-7 signaling. STAT5 is an attractive therapeutic target because it is almost universally activated in ETP-ALL, even in the absence of mutations of upstream activators such as the IL-7R, JAK and FLT3. To examine the role of activated STAT5 in ETP-ALL, we have used a Lmo2-transgenic (Lmo2Tg) mouse model in which we can monitor chemoresistant pre-leukemia (pre-LSCs) and leukemia stem cells (LSCs) that drive T-ALL development and relapse following chemotherapy. Using IL-7R-deficient Lmo2Tg mice, we show that IL-7 signaling was not required for the formation of pre-LSCs but essential for their expansion and clonal evolution into LSCs to generate T-ALL. Activated STAT5B was sufficient for the development of T-ALL in IL-7R; Lmo2Tg mice, indicating that inhibition of STAT5 is required to block the supportive signals provided by IL-7. To further understand the role of activated STAT5 in LSCs of ETP-ALL, we developed a new transgenic mouse that enables T-cell specific and doxycycline-inducible expression of the constitutively activated STAT5B1*6 mutant. Expression of STAT5B1*6 in T-cells had no effect alone but promoted expansion and chemoresistance of LSCs in Lmo2Tg mice. Pharmacologic inhibition of STAT5 with Pimozide induced differentiation and loss of LSCs, whilst enhancing response to chemotherapy. Furthermore, Pimozide significantly reduced leukemia burden in vivo and overcame chemoresistance of patient-derived ETP-ALL xenografts. Overall, our results demonstrate that STAT5 is an attractive therapeutic target for eradicating LSCs in ETP-ALL.
Differential bumble bee gene expression associated with pathogen infection and pollen diet
Authors: Giacomini Jonathan J. , Adler Lynn S. , Reading Benjamin J. , Irwin Rebecca E.
Published: March 2023

Background

Diet and parasitism can have powerful effects on host gene expression. However, how specific dietary components affect host gene expression that could feed back to affect parasitism is relatively unexplored in many wild species. Recently, it was discovered that consumption of sunflower (Helianthus annuus) pollen reduced severity of gut protozoan pathogen Crithidia bombi infection in Bombus impatiens bumble bees. Despite the dramatic and consistent medicinal effect of sunflower pollen, very little is known about the mechanism(s) underlying this effect. However, sunflower pollen extract increases rather than suppresses C. bombi growth in vitro, suggesting that sunflower pollen reduces C. bombi infection indirectly via changes in the host. Here, we analyzed whole transcriptomes of B. impatiens workers to characterize the physiological response to sunflower pollen consumption and C. bombi infection to isolate the mechanisms underlying the medicinal effect. B. impatiens workers were inoculated with either C. bombi cells (infected) or a sham control (un-infected) and fed either sunflower or wildflower pollen ad libitum. Whole abdominal gene expression profiles were then sequenced with Illumina NextSeq 500 technology.

Results

Among infected bees, sunflower pollen upregulated immune transcripts, including the anti-microbial peptide hymenoptaecin, Toll receptors and serine proteases. In both infected and un-infected bees, sunflower pollen upregulated putative detoxification transcripts and transcripts associated with the repair and maintenance of gut epithelial cells. Among wildflower-fed bees, infected bees downregulated immune transcripts associated with phagocytosis and the phenoloxidase cascade.

Conclusions

Taken together, these results indicate dissimilar immune responses between sunflower- and wildflower-fed bumble bees infected with C. bombi, a response to physical damage to gut epithelial cells caused by sunflower pollen, and a strong detoxification response to sunflower pollen consumption. Identifying host responses that drive the medicinal effect of sunflower pollen in infected bumble bees may broaden our understanding of plant-pollinator interactions and provide opportunities for effective management of bee pathogens.
Understanding host response to infectious salmon anaemia virus in an Atlantic salmon cell line using single-cell RNA sequencing
Authors: Gervais Ophélie , Peñaloza Carolina , Gratacap Remi , Papadopoulou Athina , Beltrán Mariana , Henderson Neil C. , Houston Ross D. , Hassan Musa A. , Robledo Diego
Published: March 2023

Background

Infectious Salmon Anaemia Virus (ISAV) is an Orthomixovirus that represents a large problem for salmonid aquaculture worldwide. Current prevention and treatment methods are only partially effective. Genetic selection and genome engineering have the potential to develop ISAV resistant salmon stocks. Both strategies can benefit from an improved understanding of the genomic regulation of ISAV pathogenesis. Here, we used single-cell RNA sequencing of an Atlantic salmon cell line to provide the first high dimensional insight into the transcriptional landscape that underpins host-virus interaction during early ISAV infection.

Results

Salmon head kidney (SHK-1) cells were single-cell RNA sequenced at 24, 48 and 96 h post-ISAV challenge. At 24 h post infection, cells showed expression signatures consistent with viral entry, with genes such as PI3K, FAK or JNK being upregulated relative to uninfected cells. At 48 and 96 h, infected cells showed a clear anti-viral response, characterised by the expression of IFNA2 or IRF2. Uninfected bystander cells at 48 and 96 h also showed clear transcriptional differences, potentially suggesting paracrine signalling from infected cells. These bystander cells expressed pathways such as mRNA sensing, RNA degradation, ubiquitination or proteasome; and up-regulation of mitochondrial ribosome genes also seemed to play a role in the host response to the infection. Correlation between viral and host genes revealed novel genes potentially key for this fish-virus interaction.

Conclusions

This study has increased our understanding of the cellular response of Atlantic salmon during ISAV infection and revealed host-virus interactions at the cellular level. Our results highlight various potential key genes in this host-virus interaction, which can be manipulated in future functional studies to increase the resistance of Atlantic salmon to ISAV.
The prevalence of permanent pacemaker implantation after open-heart surgeries; eight years of experience in Tehran heart center
Authors: Yazdani Kaveh Oraii , Shafiee Akbar , Heidari Amirhossein , Ahmadi-Tafti Hossein , Yaminisharif Ahmad
Published: March 2023

Background

We aimed to evaluate the prevalence of permanent pacemaker implantation (PPI) among open-heart surgery patients.

Methods

We reviewed data from 23 461 patients undergoing open-heart surgeries between 2009 and 2016 in our heart center in Iran. A total of 18 070 patients (77%) had coronary artery bypass grafting (CABG), 3 598 (15.3%) valvular surgeries, and 1 793 (7.6%) congenital repair procedures. Finally, 125 patients who received PPI following open-heart surgeries were enrolled in our study. We defined the demographic and clinical characteristics of all these patients.

Results

PPI was required in 125 (0.53%) patients with an average age of 58 ± 15.3 years. The average hospitalization time after surgery and waiting time for PPI were 19.7 ± 10.2 and 11.4 ± 6.5 days, respectively. Atrial fibrillation was the dominant pre-operative cardiac conduction abnormality (29.6%). Also, the primary indication for PPI was complete heart block in 72 patients (57.6%). Patients in the CABG group were significantly older (P = 0.002) and were more likely to be male (P = 0.030). The valvular group longer bypass and cross-clamp times and had more left atrial abnormalities. In addition, the congenital defect group was younger and had longer ICU stay times.

Conclusions

Based on our study findings, PPI was required in 0.53% of patients following open-heart surgery due to damage to the cardiac conduction system. The current study paves the way for future investigations to identify possible predictors of PPI in patients undergoing open-heart surgeries.
Intermittent versus continuous esketamine infusions for long-term pain modulation in complex regional pain syndrome: protocol of a randomized controlled non-inferiority study (KetCRPS-2)
Authors: Mangnus Thomas J. P. , Dirckx Maaike , Bharwani Krishna D. , Baart Sara J. , Siepman Theodora A. M. , Redekop Ken , Dik Willem A. , de Vos Cecile C. , Huygen Frank J. P. M.
Published: March 2023

Background

Complex regional pain syndrome (CRPS) is a chronic pain condition of an extremity. While achieving pain relief in CRPS is challenging, esketamine infusions can accomplish pain relief for several weeks post-infusion in a subgroup of CRPS patients. Unfortunately, CRPS esketamine protocols are very heterogeneous in advice on dosage, administration and treatment setting. Currently, no trials are available that study differences between intermittent and continuous esketamine infusions for CRPS. With the current situation of bed shortages, it is difficult to admit patients for several consecutive days for inpatient esketamine treatments. In this study, we investigate whether 6 intermittent outpatient esketamine treatments are not inferior to a continuous 6-day inpatient esketamine treatment in establishing pain relief. In addition, several secondary study parameters will be assessed in order to investigate mechanisms responsible for pain relief by esketamine infusions. Furthermore, the cost-effectiveness will be analyzed.

Methods

In this RCT, the primary objective is to demonstrate that an intermittent esketamine dosing regimen is non-inferior to a continuous esketamine dosing regimen at 3 months follow-up. We will include 60 adult CRPS patients. The inpatient treatment group receives a continuous intravenous esketamine infusion for 6 consecutive days. The outpatient treatment group receives a 6-hour intravenous esketamine infusion every 2 weeks for 3 months. Esketamine dose will be individually tailored and is started at 0.05 mg/kg/h and can be increased to a maximum of 0.2 mg/kg/h. Each patient will be followed for 6 months. The primary study parameter is perceived pain intensity, measured by an 11-point Numerical Rating Scale. Secondary study parameters are conditioned pain modulation, quantitative sensory testing, adverse events, thermography, blood inflammatory parameter, questionnaires about functionality, quality of life and mood and costs per patient.

Discussion

If our study reveals non-inferiority between intermittent and continuous esketamine infusions, these findings can be beneficial to increase the availability and flexibility of esketamine infusions through outpatient treatments. Furthermore, the costs of outpatient esketamine infusions could be lower than inpatient esketamine infusions. In addition, secondary parameters may predict response to esketamine treatment.

Trial registration

ClinicalTrials.gov Identifier NCT05212571, date of registration 01-28-2022.

Protocol version: Version 3, February 2022.
‘I can feel myself coming out of the rut’: a brief intervention for supporting behaviour change is acceptable to patients with chronic musculoskeletal conditions
Authors: Parchment Amelia , Lawrence Wendy , Rahman Em , Townsend Nick , Wainwright Elaine , Wainwright David
Published: March 2023

Aim

To a) understand the perceptions and experiences of patients with musculoskeletal (MSK) conditions in relation to their physiotherapy care and their acceptability of ‘Making Every Contact Count Healthy Conversation Skills’ (MECC HCS) as a brief intervention within this care and, b) explore the mechanisms through which MECC HCS might facilitate behaviour change and enhance self-management in patients with MSK conditions.

Methods

This study adopted an exploratory qualitative design, in which individual, semi-structured interviews with participants were conducted. Eight participants were interviewed. Five had been engaging with physiotherapists trained in and delivering MECC HCS within their routine physiotherapy appointments and three had been engaging with physiotherapists who had not received this training and were instead delivering usual care. MECC HCS is a person-centred approach to behaviour change that aims to empower individuals to take control of their health behaviours by building self-efficacy. The MECC HCS training programme helps healthcare professionals to develop skills in i) using ‘open discovery’ questions to explore context and allow patients to identify barriers and generate solutions; ii) listening more than giving information/ making suggestions; iii) reflecting on practice and iv) supporting Specific, Measurable, Action-oriented, Realistic, Timed, Evaluated, Reviewed (SMARTER) goal setting.

Results

Those who had engaged with MECC HCS trained physiotherapists found their physiotherapy care highly acceptable and felt that their physiotherapist listened to them, tried to understand their context and world, and helped them plan for change. These individuals experienced increases in self-efficacy and motivation for self-managing their MSK conditions. A need for continued support following physiotherapy treatment was, however, emphasised for long-term self-management.

Conclusions

MECC HCS is highly acceptable to patients with MSK conditions and pain and may successfully facilitate health-promoting behaviour change and enhance self-management. Providing opportunities to join support groups following physiotherapy treatment may promote long-term self-management and provide social and emotional benefits for individuals. The positive findings of this small qualitative study warrant further investigation on the differences in experiences and outcomes between patients engaging with MECC HCS physiotherapists and those receiving treatment as usual during routine physiotherapy care.
Experience of a modified chest tube suture-fixation technique in uniportal thoracoscopic pulmonary resection
Authors: Shi Wensong , Hu Yuzhui , Wang Cuimei , Chang Guotao , Zheng Huiyu , Yang Zhiqiang , Yang Yulun , Zhao Xiaogang , Li Xiangnan
Published: March 2023

Objective

This study aimed to explore the feasibility and advantages of a modified chest tube suture-fixation technique in uniportal video-assisted thoracic surgery for pulmonary resection.

Methods

A retrospective analysis was conducted on 116 patients who underwent uniportal video-assisted thoracic surgery (U-VATS) for lung diseases in Zhengzhou People’s Hospital between October 2019 and October 2021. Patients were stratified into two groups based on the applied suture-fixation methods, i.e., 72 patients in the active group and 44 patients in the control group. The two groups were subsequently compared in the terms of gender, age, operation method, indwelling time of chest tube, postoperative pain score, chest tube removal time, wound healing grade, length of hospital stay, incision healing grade, and patient satisfaction.

Results

There was no significant difference between the two groups in terms of gender, age, operation method, indwelling time of chest tube, postoperative pain score, and length of hospital stay (P = 0.167, 0.185, 0.085, 0.051, 0.927, and 0.362, respectively). However, the chest tube removal time, incision healing grade, and incision scar satisfaction in the active group were significantly better compared with those of the control group (P = < 0.001, 0.033, and < 0.001, respectively).

Conclusion

In summary, the new suture-fixation approach can minimize the number of stitches, and time necessary for chest tube removal process, and avoid the pain experienced when removing the drainage tube. This method is more feasible, has better incision conditions, and provides a convenient tube removal, making it more suitable to patients.
A population-based cross-sectional study on the situation of cervical cancer screening in Liaoning, China
Authors: Zhu Bo , Yu Huihui , Ni Ping , Chen Xi , Zhang Jing , Wang Danbo
Published: March 2023

Background

Cervical cancer (CC) screening is currently recognized as an effective intervention for CC. Previous studies found that the proportion of screening was low in China, especially in Liaoning. Therefore, we performed a population-based cross-sectional survey to investigate the situation of cervical cancer screening and analyze their related factors for providing a decision-making basis for sustainable and effective development of cervical cancer screening.

Methods

This population-based cross-sectional study involved aged 30 to 69 years in nine counties/districts in Liaoning from 2018 to 2019. Data were collected using the quantitative data collection methods, and analyzed in SPSS version 22.0.

Results

Overall, only 22.37% of 5334 respondents reported having ever been screened for cervical cancer in past 3 years, and 38.41% of respondents reported having the willingness for cervical cancer screening in next 3 years. In the rate of CC screening, multilevel analysis indicated that age, marital status, education level, type of occupation, medical insurance, family income, place of residence and regional economic level had a significant impact on proportion of screening. In the rate of CC screening willingness, multilevel analysis indicated that age, family income, health status, place of residence, regional economic level and CC screening still had a significant impact, but marital status, education level and medical insurance type had no significant impact. There was no significant difference in marital status, education level and medical insurance type after the factors of CC screening were added in the model.

Conclusion

Our study found both proportion of screening and willingness were at a low level, and age, economic and regional factors were the main factors for implementation of CC screening in China. In the future, targeted policies should be formulated according to the characteristics of different groups of people, and reduce the gap in the current health service capacity between different regions.
Mapping ethical issues in the use of smart home health technologies to care for older persons: a systematic review
Authors: Felber Nadine Andrea , Tian Yi Jiao , Pageau Félix , Elger Bernice Simone , Wangmo Tenzin
Published: March 2023

Background

The worldwide increase in older persons demands technological solutions to combat the shortage of caregiving and to enable aging in place. Smart home health technologies (SHHTs) are promoted and implemented as a possible solution from an economic and practical perspective. However, ethical considerations are equally important and need to be investigated.

Methods

We conducted a systematic review according to the PRISMA guidelines to investigate if and how ethical questions are discussed in the field of SHHTs in caregiving for older persons.

Results

156 peer-reviewed articles published in English, German and French were retrieved and analyzed across 10 electronic databases. Using narrative analysis, 7 ethical categories were mapped: privacy, autonomy, responsibility, human vs. artificial interactions, trust, ageism and stigma, and other concerns.

Conclusion

The findings of our systematic review show the (lack of) ethical consideration when it comes to the development and implementation of SHHTs for older persons. Our analysis is useful to promote careful ethical consideration when carrying out technology development, research and deployment to care for older persons.

Registration

We registered our systematic review in the PROSPERO network under CRD42021248543.
Bioinformatics screening of colorectal-cancer causing molecular signatures through gene expression profiles to discover therapeutic targets and candidate agents
Authors: Horaira Md Abu , Islam Md. Ariful , Kibria Md. Kaderi , Alam Md. Jahangir , Kabir Syed Rashel , Mollah Md. Nurul Haque
Published: March 2023

Background

Detection of appropriate receptor proteins and drug agents are equally important in the case of drug discovery and development for any disease. In this study, an attempt was made to explore colorectal cancer (CRC) causing molecular signatures as receptors and drug agents as inhibitors by using integrated statistics and bioinformatics approaches.

Methods

To identify the important genes that are involved in the initiation and progression of CRC, four microarray datasets (GSE9348, GSE110224, GSE23878, and GSE35279) and an RNA_Seq profiles (GSE50760) were downloaded from the Gene Expression Omnibus database. The datasets were analyzed by a statistical r-package of LIMMA to identify common differentially expressed genes (cDEGs). The key genes (KGs) of cDEGs were detected by using the five topological measures in the protein–protein interaction network analysis. Then we performed in-silico validation for CRC-causing KGs by using different web-tools and independent databases. We also disclosed the transcriptional and post-transcriptional regulatory factors of KGs by interaction network analysis of KGs with transcription factors (TFs) and micro-RNAs. Finally, we suggested our proposed KGs-guided computationally more effective candidate drug molecules compared to other published drugs by cross-validation with the state-of-the-art alternatives of top-ranked independent receptor proteins.

Results

We identified 50 common differentially expressed genes (cDEGs) from five gene expression profile datasets, where 31 cDEGs were downregulated, and the rest 19 were up-regulated. Then we identified 11 cDEGs (CXCL8, CEMIP, MMP7, CA4, ADH1C, GUCA2A, GUCA2B, ZG16, CLCA4, MS4A12 and CLDN1) as the KGs. Different pertinent bioinformatic analyses (box plot, survival probability curves, DNA methylation, correlation with immune infiltration levels, diseases-KGs interaction, GO and KEGG pathways) based on independent databases directly or indirectly showed that these KGs are significantly associated with CRC progression. We also detected four TFs proteins (FOXC1, YY1, GATA2 and NFKB) and eight microRNAs (hsa-mir-16-5p, hsa-mir-195-5p, hsa-mir-203a-3p, hsa-mir-34a-5p, hsa-mir-107, hsa-mir-27a-3p, hsa-mir-429, and hsa-mir-335-5p) as the key transcriptional and post-transcriptional regulators of KGs. Finally, our proposed 15 molecular signatures including 11 KGs and 4 key TFs-proteins guided 9 small molecules (Cyclosporin A, Manzamine A, Cardidigin, Staurosporine, Benzo[A]Pyrene, Sitosterol, Nocardiopsis Sp, Troglitazone, and Riccardin D) were recommended as the top-ranked candidate therapeutic agents for the treatment against CRC.

Conclusion

The findings of this study recommended that our proposed target proteins and agents might be considered as the potential diagnostic, prognostic and therapeutic signatures for CRC.