bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract SY37-01: Genomic instability and hypoxia as co-drivers of prostate cancer aggression
Authors: Bristow Robert G.
Published: July 2021

Understanding the mechanistic basis for transition to late stage aggressive disease is vital for both assigning patient risk status in the localised setting and also identifying novel treatment strategies to prevent progression. Sub-regions of intratumoral hypoxia are found in all solid tumours and are associated with many biologic drivers of tumour progression. Crucially, more recent findings show the co-presence of hypoxia and genomic instability can confer a uniquely adverse prognosis in prostate cancer. In-depth informatic and functional studies suggests a role for hypoxia in co-operating with oncogenic drivers (e.g. loss of PTEN) and suppressing DNA repair capacity. To delineate a direct relationship between hypoxia and PTEN loss, we interrogated the impact of chronic hypoxia (1% O2, 0.2% O2; 72 h) on PTEN oncogenic signalling and chromosome instability. Quantitative immunofluorescence of centrosome aberrations, using antibodies to phospho-Histone H3 and Centrin-1, show significant increases in centriole numbers (p < 0.05) in mitotic cells under chronic hypoxic conditions and an increase in the incidence of micronuclei (p < 0.005) specifically in chronic hypoxic cells with PTEN loss. Hypoxic suppression of homologous recombination represents a "contextual lethal" vulnerability in hypoxic prostate tumours which could extend the application of existing DNA repair targeting agents such as poly-ADP ribose polymerase inhibitors. Additional mechanistic studies using hTERT-immortalized, primary prostate epithelial cells isogenic for c-MYC, BRCA2, or TP53/RB (SV40-transduced) were studied as to the relationship between hypoxia, inherent versus acquired genetic instability and DNA repair capacity in-vitro and in-situ. Chronic hypoxia (20 generation doublings at 0.2% O2) was sufficient to drive increased copy number alterations (CNAs) in selected clones by up to 30% in TP53/RB null cells. This finding is now being quantitated with a clonal evolution model and genotype-phenotype associations are being validated using functional transformation and invasion assays. Further investigation is now required to assess this relationship on the background of existing genomic alterations relevant to prostate and other cancers and also characterise the role of hypoxia in driving early metastatic spread. Supported by core funding from Cancer Research UK Manchester Institute and grants within the Cancer Research UK Manchester RadNet Unit, NIHR Manchester Biomedical Research Centre and a Prostate Cancer UK-Movember Centre of Excellence award.

Citation Format: Robert G. Bristow. Genomic instability and hypoxia as co-drivers of prostate cancer aggression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr SY37-01.
Mobocertinib: A Potential Treatment for NSCLC with EGFR Exon 20 Insertions
Authors: Pacheco Jose M.
Published: July 2021

Amivantamab is the only FDA-approved therapy for non–small cell lung cancer (NSCLC) with EGFR exon 20 insertions. Unfortunately, patients eventually develop progression of disease on this therapy, and most do not respond to this treatment. In this issue of Cancer Discovery, Gonzalvez and colleagues and Riely and colleagues highlight preclinical and early clinical data supporting mobocertinib as a potentially efficacious agent for NSCLC with EGFR exon 20 insertions.

See related article by Riely et al., p. 1688.

See related article by Gonzalvez et al., p. 1672.
Retrospective Diagnosis of Ankylosing Spondylitis after Spinal Fractures: A Review of 3 Cases and Clinical Implication
Authors: Farooque Kamran , Kar Santanu , Siamwala Burhan Salim , Sharma Vijay
Published: July 2021

Ankylosing spondylitis (AS) is an underdiagnosed inflammatory condition in the initial stages of disease that can cause vertebral fractures in young adults after trivial trauma. Hence, low-energy spinal fractures in young patients must be carefully evaluated to exclude AS as the treatment protocol (fixation levels, period of immobilization) may change drastically if AS is diagnosed. Here, we present cases of 3 patients who presented at emergency after low-velocity spinal trauma and diagnosed as AS during workup for fracture management. This cases series indicates underdiagnosis of AS in general population as well as importance of strong suspicion of AS in low-energy spinal fractures in the younger age-group.
The Outcomes of Minimally Invasive Percutaneous Nephrolithotomy with Different Access Sizes for the Single Renal Stone ≤25 mm: A Randomized Prospective Study
Authors: Yu Weimin , Ruan Yuan , Xiong Zhuang , Zhang Yunlong , Rao Ting , Cheng Fan
Published: July 2021

Objectives: The aim of this study was to provide a randomized controlled trial comparing the outcomes of different access sizes used in the solo ultrasonic-guided minimally invasive percutaneous nephrolithotomy (mini-PCNL). Methods: From January 2018 to December 2019, a total of 160 cases with single renal stones of <25 mm were randomized to undergo mini-PCNLs with Fr16, Fr18, Fr20, or Fr22 accesses. All accesses were established with the axis of the target calyx as the marker for puncture location and then expanded to the desired size. Hemoglobin reduction, operative time, stone-free rate, complications, etc., were all recorded and assessed. Results: The demographic data were similar, and there were no significantly intergroup differences in stone-free rate, complications, and hospital stay time. The hemoglobin reduction was comparable and was 0.9 ± 0.6, 0.9 ± 0.7, 1.0 ± 0.5, and 1.1 ± 0.7 g/dL for the groups Fr16, Fr18, Fr20, and Fr22, respectively. The operative time was 53.4 ± 14.5, 48.5 ± 15.2, 42.8 ± 13.3, and 43.3 ± 13.1 min for the 4 groups, which decreased significantly from group Fr16 to Fr20, but there was no significant difference between Fr20 and Fr22 groups. Conclusions: The axis of target calyx is a reliable marker for establishment of percutaneous renal access under ultrasonic guidance. The surgical outcomes of different access sizes were comparable, but the operation time was significantly shortened with the increase of size. However, Fr22 was not more efficient than Fr20.
Axolotls’ and Mices’ Oral-Maxillofacial Trephining Wounds Heal Differently
Authors: Charbonneau Andre Marc , Åström Pirjo , Salo Tuula , Roy Stéphane , Tran Simon D.
Published: July 2021

The Ambystoma maxicanum (axolotl) regenerates strikingly from wounds and amputations. Comparing its healing ability to non-regenerative species such as the mouse should help narrow in on mechanisms to improve human wound healing. Here, the tongue and intermandibular soft tissues of both mice (C57BL/6NCrl) and axolotls were wounded with a 2–2.5 mm punch biopsy. The study aimed to compare the differences between these 2 species following surgical resection with regard to the macroscopic and histological characteristics. These include wound closure times, epithelial wound sealing and thickness as well as acute immune marker myeloperoxidase (MPO) response over 30 days. Post surgery, mice visually showed greater haemorrhage; their wounds immediately collapsed while it took 14 days for the axolotls mandibular void to close. The epithelium sealed the axolotls’ wound margins within 24 h with a maximal mean thickness of 0.42 ± 0.13-fold normalized to unwounded skin. In mice, the epithelium separately sealed the ventral and dorsal sides, respectively at 7 and 7–30 days with mean maximal epithelial thicknesses reaching 13 ± 5.6 and 3.0 ± 0.63-fold. Mean MPO-positive cell values peaked in axolotls at 14 ± 1.5-fold between hours 6–12; while in mice, it peaked at 8.7 ± 0.9-fold between hours 24–96. We conclude that axolotls form smaller blood clots, have a faster and thinner epithelial cell migrating front, and a shorter MPO-positive cell response in comparison to mice. These observations may help refine future oral and facial wound-healing research and treatment.
A Century in the Making: Receiving the Samaritan Pentecost (Acts 8:4–25) in the Pentecostal and Charismatic Traditions
Authors: Mittelstadt Martin W.
Published: July 2021

In this address, I outline a history of pentecostal/charismatic reception. I explore different ways that pentecostal/charismatic believers have received, appropriated, and used Acts 8 throughout our history. I propose that a reception of more than one hundred years of pentecostal musings over Acts 8 provides a snapshot of our extended pentecostal family. I suggest up front that this family history exposes pentecostal/charismatic notions about the nature of biblical interpretation. I conclude with general observations from my research and suggest further implications for students and scholars interested in reception history.
Skogler: Photography at the Service of Falangism (Zaragoza, July 1936)
Authors: Navarro-Bonilla Diego , Robledano-Arillo Jesús
Published: July 2021

This article analyses the role of ‘Skogler’ (Ángel Cortés Gracia), a photographer who worked for the insurgent Falangist forces in the city of Zaragoza, the capital of Aragón, from the beginning of the Spanish Civil War. Skogler’s strong and early ties to the fascist movement, going back years before the war, suggest a special profile of an individual who supported the Falangist party by means of visual propaganda and printed photographs. Most of the photographs selected for study here have never been published before. They were shot in the early days of the military uprising against the Republic and help give us a more accurate understanding of armed fascism in the Aragonese capital, which ultimately fell to the rebels. This paper is part of an ongoing research project and exhibition to analyse and describe the contents and physical characteristics of the Skogler Archive, composed of more than 3,500 negatives recovered in diverse chronological phases.
Fascism and (Transnational) Social Movements: A Reflection on Concepts and Theory in Comparative Fascist Studies
Authors: Dulić Tomislav
Published: July 2021

Scholars have recently begun advocating for the application of social movement theory in the analysis of the rise and development of fascist political entities. While representing a welcome effort to increase the theoretical depth in the analysis of fascism, the approach remains hampered by conceptual deficiencies. The author addresses some of these by the help of a critical discussion that problematises the often incoherent ways in which the concept of ‘movement’ is used when describing fascist political activity both within and across national borders. The analysis then turns to the application of social movement theory to the historical example of the Ustašas. While recent research on social movements has begun to explore the role and character of transnationalism, this case study analysis suggests that the lack of supra-national organisations during the period of ‘classic’ fascism prevented the emergence of a ‘transnational public space’ where fascist movements could have participated. The conclusion is that rather than acting and organising on a ‘transnational’ level, fascist entities appear to have limited themselves to state-based international ‘knowledge-transfer’ of a traditional type.
A new species of Albatrellus sensu stricto (Albatrellaceae, Russuales) from China
Authors: ZHOU HONG-MIN , WU YING-DA , DAI YU-CHENG
Published: July 2021

Based on morphological and molecular data, a new species of Albatrellus sensu stricto, A. alpinus sp. nov., is described from Yunnan Province of southwestern China. Albatrellus alpinus is characterized by a buff to pale yellow pileal surface, simple septate hyphae, yellow and shapeless oily substance present in all hyphae but seldom in tramal hyphae, and small amyloid basidiospores. Phylogenetic analyses based on the nuclear ribosomal internal transcribed spacer (nrITS) and the large subunit of the nuclear ribosomal RNA gene (nLSU) indicated that the new species is nested within Albatrellus sensu stricto. A key to the Chinese species of Albatrellus sensu stricto is provided.
Gilpinia hakonensis and similar species in Japan and ovipositors of five European Gilpinia species (Hymenoptera, Diprionidae)
Authors: HARA HIDEHO , SMITH DAVID R. , SHINOHARA AKIHIKO
Published: July 2021

The following three Japanese conifer sawflies are described or redescribed with figures of the ovipositors and male genitalia: Gilpinia hakonensis (Matsumura, 1912) from Honshu and Kyushu, Japan and Korea, G. amamiana Okutani, 1965, from Amami Oshima Island and Tokunoshima Island, Japan and G. okinawa sp. nov. from Okinawa Island, Japan. These three species are very similar and belong to the G. socia group. The lectotype for Lophyrus hakonensis Matsumura, 1912 is designated. The males of G. hakonensis and G. amamiana are described for the first time. Gilpinia fukudai (Togashi, 1964) from Honshu, Japan, is a new synonym of G. hakonensis. The host plant of G. hakonensis is Pinus densiflora Siebold et Zucc. Gilpinia amamiana is newly recorded from Tokunoshima Island. For comparison, ovipositors of five European species of the G. socia group, G. abieticola (Dalla Torre, 1894), G. frutetorum (Fabricius, 1793), G. laricis (Jurine, 1807), G. socia (Klug, 1812) and G. variegata (Hartig, 1834), are described and figured. The ovipositors of G. frutetorum, G. laricis and G. variegata are figured for the first time. Gilpinia laricis is newly recorded from Bulgaria.
Checklist of the infraorder Gryllidea (Orthoptera: Ensifera) from Yunnan province, China, with description of one new species
Authors: YUAN LI-LAN , XU FEI , WANG XIAO-XIAO , ZHANG DONG-XIAO , XIE GUANG-LIN , LIU HAO-YU
Published: July 2021

A checklist of 166 species and subspecies from 62 genera, 15 subfamilies, 5 families and 2 superfamilies of Gryllidea, is recorded from Yunnan Province of China, based on the published data and accumulated material. The detailed distribution of most species is provided in Yunnan Province. Mitius eryuanensis Yuan, Xie & Liu sp. nov. is described as new species.
A Variational Method for Filling in Missing Data in Doppler Velocity Fields
Authors: WOOD VINCENT T. , DAVIES-JONES ROBERT P. , SHAPIRO ALAN
Published: July 2021

Single-Doppler radar data are often missing in important regions of a severe storm due to low return power, low signal-to-noise ratio, ground clutter associated with normal and anomalous propagation, and missing radials associated with partial or total beam blockage. Missing data impact the ability of WSR-88D algorithms to detect severe weather. To aid the algorithms, we develop a variational technique that fills in Doppler velocity data voids smoothly by minimizing Doppler velocity gradients while not modifying good data. This method provides estimates of the analysed variable in data voids without creating extrema.

Actual single-Doppler radar data of four tornadoes are used to demonstrate the variational algorithm. In two cases, data are missing in the original data, and in the other two, data are voided artificially. The filled-in data match the voided data well in smoothly varying Doppler velocity fields. Near singularities such as tornadic vortex signatures, the match is poor as anticipated. The algorithm does not create any velocity peaks in the former data voids, thus preventing false triggering of tornado warnings. Doppler circulation is used herein as a far-field tornado detection and advance-warning parameter. In almost all cases, the measured circulation is quite insensitive to the data that have been voided and then filled. The tornado threat is still apparent.
Record-breaking summer rainfall in South Korea in 2020: Synoptic characteristics and the role of large-scale circulations
Authors: Park Chanil , Son Seok-Woo , Kim Hera , Ham Yoo-Geun , Kim Joowan , Cha Dong-Hyun , Chang Eun-Chul , Lee GyuWon , Kug Jong-Seong , Lee Woo-Seop , Lee Yun-Young , Lee Hee Choon , Lim Byunghwan
Published: July 2021

In the summer of 2020, South Korea experienced record-breaking rainfall due to 15 consecutive heavy rainfall events (HREs) from mid-June to early September. Among them, 11 HREs occurred in late June to mid-August with distinct synoptic characteristics depending on the occurrence period. All HREs from 29 June to 27 July (P1) were triggered by extratropical cyclones, while those from 28 July to 15 August (P2) mainly occurred along monsoon rainband. We argue that their transition is associated with atmospheric teleconnections. During P1, the western North Pacific subtropical high (WNPSH) anomalously extended westward, but its northward expansion was hindered by the meridional wave train from the suppressed convection over the South China Sea. This condition prevented a northward migration of the monsoon rainband but allowed more extratropical cyclones to pass over the Korean Peninsula, resulting in four HREs. During P2, the South China Sea convection was enhanced, and its circulation response prompted an abrupt northward expansion of the WNPSH with a large pressure gradient along its northern boundary. With intensified southwesterly moisture transport, a monsoon rainband was activated over the Korean Peninsula, producing six HREs. The opposite phases of the summer North Atlantic Oscillation, i.e., negative in P1 but positive in P2, further contributed to the anomalous monsoon circulation by modulating the mid-latitude circulation response to the South China Sea convection. This study demonstrates that the nature of summertime HREs in East Asia can be strongly modulated by remote forcings.
Predicting Physical Activity and Lifelong Health Through Personal Control and Educational Attainment
Authors: Zhou Jinyi , Ding Xuesong , Zhai Yuefan , Yi Qing
Published: July 2021

Prior studies have shown that physical activity (PA) is strongly associated with lifelong health and well-being. Thus, analyses of relationships among individual differences, PA, education, and health may provide important insights into the sustainability of PA-related personal development efforts. In this longitudinal study, we tested a proposed model in a data set of 12,686 participants from the National Longitudinal Survey of Youth 1979 (NLSY 79). We used hierarchical regressions and bootstrapping to test hypotheses concerning the main effect of personal control on lifetime health, the mediating effect of PA, and the moderating effect of educational achievement. We found that individuals’ self-reported PA was positively related to their health status. Additionally, there was a positive mediating effect of self-reported PA on the relationship between personal control and health when the individual’s educational level was high, and there was a negative mediating effect of self-reported PA when an individual’s educational level was low. Based on these results, we provide relevant government policy suggestions for increasing fitness participation, constructing sports facilities, and encouraging educational institutions to include health education in their efforts.
Chickpea shows genotype-specific nodulation responses across soil nitrogen environment and root disease resistance categories
Authors: Plett Krista L. , Bithell Sean L. , Dando Adrian , Plett Jonathan M.
Published: July 2021

Background

The ability of chickpea to obtain sufficient nitrogen via its symbiotic relationship with Mesorhizobium ciceri is of critical importance in supporting growth and grain production. A number of factors can affect this symbiotic relationship including abiotic conditions, plant genotype, and disruptions to host signalling/perception networks. In order to support improved nodule formation in chickpea, we investigated how plant genotype and soil nutrient availability affect chickpea nodule formation and nitrogen fixation. Further, using transcriptomic profiling, we sought to identify gene expression patterns that characterize highly nodulated genotypes.

Results

A study involving six chickpea varieties demonstrated large genotype by soil nitrogen interaction effects on nodulation and further identified agronomic traits of genotypes (such as shoot weight) associated with high nodulation. We broadened our scope to consider 29 varieties and breeding lines to examine the relationship between soilborne disease resistance and the number of nodules developed and real-time nitrogen fixation. Results of this larger study supported the earlier genotype specific findings, however, disease resistance did not explain differences in nodulation across genotypes. Transcriptional profiling of six chickpea genotypes indicates that genes associated with signalling, N transport and cellular localization, as opposed to genes associated with the classical nodulation pathway, are more likely to predict whether a given genotype will exhibit high levels of nodule formation.

Conclusions

This research identified a number of key abiotic and genetic factors affecting chickpea nodule development and nitrogen fixation. These findings indicate that an improved understanding of genotype-specific factors affecting chickpea nodule induction and function are key research areas necessary to improving the benefits of rhizobial symbiosis in chickpea.
Intestinal parasitic infections and associated factors among pregnant women in Ethiopia: a systematic review and meta-analysis
Authors: Animaw Zelalem , Melese Addisu , Demelash Habtamu , Seyoum Girma , Abebe Abiy
Published: July 2021

Background

Intestinal parasitic infections (IPIs) are public health problems widely distributed in the world and cause significant morbidity and mortality; many of which occur among women of reproductive age. IPIs caused by helminthes and protozoan parasites are common among pregnant women. Data on the national pooled prevalence of intestinal parasites and associated factors during pregnancy is not documented well in Ethiopia. This review aims at summarizing evidences on the burden of IPIs and associated factors among pregnant women in Ethiopia.

Methods

Published and unpublished studies were thoroughly searched at MEDLINE/PubMed, EMBASE, Google Scholar, CINAHL, Cochrane library and Science Direct. In addition, repositories of Addis Ababa, Gondar and Jimma Universities were searched. Eligible studies were selected following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guideline. The pooled prevalence of intestinal parasites and summary odds ratios (ORs) were determined with 95 % confidence intervals (CI). Sub-groups analyses were done based on study region, types of parasites, methods of stool examination and study setting. The statistical analyses were performed using STATA version 14.0 software.

Results

Among 168 retrieved studies, 31 studies with a total population of 12,118 pregnant women were included. The estimated pooled prevalence of IPIs among pregnant women in Ethiopia was 27.32 % (95 % CI: 20.61, 33.87 %). In the subgroup analysis, Oromia and Amhara regions had the highest prevalence with a 29.78 % (95 % CI: 15.97, 43.60) and 29.63 % (95 % CI: 15.37, 43.89); respectively. In addition, studies conducted in the community showed higher prevalence than institution based studies (49.93 % Vs 24.84 %; respectively). The most prevalent type of intestinal parasite identified wereHookwormfollowed byAscaris lumbricoideswith a pooled prevalence of 11.2 and 10.34 %, respectively. In our analysis; residence, being bare footed, lack of hand washing habit and eating uncooked/raw vegetables were significantly associated with IPIs among pregnant women in Ethiopia.

Conclusions

Prevalence of IPIs during pregnancy is relatively high in Ethiopia. Poor hygienic practices were identified as risk factors. Based on our finding, targeted preventive measures shall be considered so as to prevent morbidity and mortality due to IPIs.
Dual targeting of MEK and PI3K effectively controls the proliferation of human EGFR-TKI resistant non-small cell lung carcinoma cell lines with different genetic backgrounds
Authors: Qu Ge-Ping , Shi Min , Wang Dan , Wu Jiong-He , Wang Peng , Gong Mei-Liang , Zhang Zhi-Jian
Published: July 2021

Background

Molecular targeted therapy for non-small cell lung carcinoma (NSCLC) is restricted due to resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). This study evaluated the effects of dual targeting of MEK and PI3K in human EGFR-TKI resistant NSCLC cell lines.

Methods

EGFR-TKI resistant NSCLC cell lines H1975, H460, and A549, with different mutation and amplification status in EGFR, K-RAS, PIK3CA, and MET genes, were treated with a MEK162 (MEK inhibitor) and BKM120 (PI3K inhibitor) combination or a BIBW2992 (EGFR inhibitor) and ARQ197 (MET inhibitor) combination and assayed for cell proliferation, apoptosis, and cell cycle distribution.

Results

Dual targeting of MEK and PI3K efficiently inhibited the cell proliferation, induced apoptosis and the G0/G1 cell cycle, and decreased the phosphorylation of ERK1/2, AKT, S6, and 4E-BP1. H460 cells with K-RAS and PIK3CA mutation were most sensitive to MEK162 and BKM120 combinations. H1975 cells with EGFR and PIK3CA mutation and MET amplification were sensitive to BIBW2992 and ARQ197 combinations.

Conclusion

Dual targeting regulated the proliferation of EGFR-TKI-resistant NSCLC cells, especially mutants in K-RAS and PIK3CA that are promising for EGFR-TKI-resistant NSCLC therapeutics.
Magnification of fear and intention of avoidance in non-experienced versus experienced dental treatment in adults
Authors: Lin Chia-Shu , Lee Chen-Yi , Chen Li-Ling , Wu Long-Ting , Yang Shue-Fen , Wang Tze-Fang
Published: July 2021

Background

Dental fear is associated with the experience of prior dental treatment and avoidance of dental visits. It remains unclear if individuals show an intention of avoidance (IA) towards treatments that they have not received (i.e., non-experienced dental treatment). The study aims to investigated (a) if individuals showed an increased fear and IA to non-experienced, compared to experienced dental treatment, and (b) if fear and IA to non-experienced treatment is associated with dental anxiety.

Methods

Fear/IA of 12 common conditions of dental treatment of 402 adults were investigated. If subjects have experienced the condition, fear and IA were assessed based on subjects’ prior experience (i.e., ExpFear/ExpIA). If they have not experienced the condition, fear and IA were assessed based on their anticipation (i.e., NExpFear/NExpIA). Trait dental anxiety was assessed using the Index of Dental Anxiety and Fear (IDAF-4C+).

Results

(A) NExpFear and NExpIA were significantly higher than ExpFear and ExpIA, respectively. (B) The IDAF-4C+ scores are positively correlated with NExpFear/NExpIA and negatively correlated with the magnification of fear (i.e., the discrepancy in the fear/IA of non-experienced vs. experienced conditions). (C) The condition ‘extraction of a wisdom tooth’ and ‘root canal treatment’ showed the highest ratings on NExpFear.

Conclusions

Individuals may develop a high degree of fear and IA of the treatment they have not received. Trait dental anxiety plays a key role in the fear of non-experienced treatment.
Effect of epinephrine on the absorption of lidocaine following application to the oral mucosa in rats
Authors: Sasaki Rui , Sunada Katsuhisa
Published: July 2021

Background

We investigated the role of epinephrine in prolonging the localization of lidocaine on the oral mucosa and inhibiting its absorption in the blood of rats.

Methods

We used 7–8-week-old pathogen-free Wistar male rats (n = 128) for our study. We divided them into the control group administered with14C-labeled lidocaine hydrochloride gel only and the study group administered with14C-labeled lidocaine hydrochloride gel with epinephrine. The medications were administered in the palatal mucosa of the rats. The amount of mucosa, palatine bone, and serum lidocaine was measured by radioactivity using a liquid scintillation counter and was observed using autoradiograms.

Results

Initially, there was no significant difference in the lidocaine levels between the lidocaine and lidocaine with epinephrine groups in the palatal mucosa (751.9 ± 133.8 vs. 669.8 ± 101.6 ng/mg [2 min]). After 4 min, the values were significantly lower in the lidocaine with epinephrine group (1040.0 ± 142.8 vs. 701.2 ± 109.0 ng/mg [20 min]). After 40 min, the lidocaine level became significantly higher in the lidocaine with epinephrine group (586.8 ± 112.4 vs. 1131.3 ± 155.2 ng/mg [40 min]). Similar results were observed in the palatine bone and serum.

Conclusion

Epinephrine prolonged the localization of lidocaine applied to the mucosa and inhibited its absorption into the bloodstream of rats. Clinical studies are required to evaluate the use of epinephrine-containing topical anesthetics on the oral mucosa.
Metagenomic and phytochemical analyses of kefir water and its subchronic toxicity study in BALB/c mice
Authors: Kumar Muganti Rajah , Yeap Swee Keong , Mohamad Nurul Elyani , Abdullah Janna Ong , Masarudin Mas Jaffri , Khalid Melati , Leow Adam Thean Chor , Alitheen Noorjahan Banu
Published: July 2021

Background

In recent years, researchers are interested in the discovery of active compounds from traditional remedies and natural sources, as they reveal higher therapeutic efficacies and improved toxicological profiles. Among the various traditional treatments that have been widely studied and explored for their potential therapeutic benefits, kefir, a fermented beverage, demonstrates a broad spectrum of pharmacological properties, including antioxidant, anti-inflammation, and healing activities. These health-promoting properties of kefir vary among the kefir cultures found at the different part of the world as different media and culture conditions are used for kefir maintenance and fermentation.

Methods

This study investigated the microbial composition and readily found bioactive compounds in water kefir fermented in Malaysia using 16S rRNA microbiome and UHPLC sequencing approaches. The toxicity effects of the kefir water administration in BALB/c mice were analysed based on the mice survival, body weight index, biochemistry profile, and histopathological changes. The antioxidant activities were evaluated using SOD, FRAP, and NO assays.

Results

The 16S rRNA amplicon sequencing revealed the most abundant species found in the water kefir wasLactobacillus hilgardiifollowed byLactobacillus harbinensis,Acetobacter lovaniensis,Lactobacillus satsumensis,Acetobacter tropicalis,Lactobacillus zeae, andOenococcus oeni. The UHPLC screening showed flavonoid and phenolic acid derivatives as the most important bioactive compounds present in kefir water which has been responsible for its antioxidant activities. Subchronic toxicity study showed no toxicological signs, behavioural changes, or adverse effects by administrating 10 mL/kg/day and 2.5 mL/kg/day kefir water to the mice. Antioxidants assays demonstrated enhanced SOD and FRAP activities and reduced NO level, especially in the brain and kidney samples.

Conclusions

This study will help to intensify the knowledge on the water kefir microbial composition, available phytochemicals and its toxicological and antioxidant effects on BALB/c mice since there are very limited studies on the water kefir grain fermented in Malaysia.
Effect of in-vitro heat stress challenge on the function of blood mononuclear cells from dairy cattle ranked as high, average and low immune responders
Authors: Cartwright Shannon L. , McKechnie Marnie , Schmied Julie , Livernois Alexandra M. , Mallard Bonnie A.
Published: July 2021

Background

The warming climate is causing livestock to experience heat stress at an increasing frequency. Holstein cows are particularly susceptible to heat stress because of their high metabolic rate. Heat stress negatively affects immune function, particularly with respect to the cell-mediated immune response, which leads to increased susceptibility to disease. Cattle identified as having enhanced immune response have lower incidence of disease. Therefore, the objective of this study was to evaluate the impact of in vitro heat challenge on blood mononuclear cells from dairy cattle, that had previously been ranked for immune response, in terms of heat shock protein 70 concentration, nitric oxide production, and cell proliferation.

Results

Blood mononuclear cells from dairy cattle classified as high immune responders, based on their estimated breeding values for antibody and cell-mediated responses, produced a significantly greater concentration of heat shock protein 70 under most heat stress treatments compared to average and low responders, and greater cell-proliferation across all treatments. Similarly, a trend was observed where high responders displayed greater nitric oxide production compared to average and low responders across heat treatments.

Conclusion

Overall, these results suggest that blood mononuclear cells from high immune responder dairy cows are more thermotolerant compared to average and low immune responders.
Cementing technique for total knee arthroplasty in cadavers using a pastry bone cement
Authors: Bösebeck Hans , Holl Anna-Maria , Ochsner Peter , Groth Manuel , Stippich Kevin , Nowakowski Andrej M. , Egloff Christian , Hoechel Sebastian , Göpfert Beat , Vogt Sebastian
Published: July 2021

Background

In cemented primary total knee arthroplasty (TKA), aseptic loosening remains a major cause for failure. Cementing techniques and characteristics of a chosen cement play a key role for good fixation and implant survival. A pastry bone cement was developed to facilitate the cement preparation and to rule out most of preparation-associated application errors. The pastry bone cement was compared to a conventional polymethyl methacrylate cement in a TKA setting.

Methods

Standardized implantations of total knee endoprostheses were performed in bilateral knee cadavers to investigate handling properties, variables of cement application, working time, and temperature development. Mechanical aspects and cementation quality were assessed by pull-out trials and microscopic interface analysis.

Results

Both cements expressed similar characteristics during preparation and application, only the curing time of the pastry cement was about 3 min longer and the temperature peak was lower. Fractures of the conventional cement specimens differed from the pastry cement specimens in the tibial part, while no differences were found in the femoral part. Penetration depth of the pastry cement was similar (tibia) or deeper (femur) compared to the conventional cement.

Conclusions

The pastry cement facilitates the feasibility of cemented TKA. The pre-clinical tests indicate that the pastry bone cement fulfills the requirements for bone cement in the field of knee arthroplasty. A clinical trial is needed to further investigate the approach and ensure patient safety.
The effect of common variants in GDF5 gene on the susceptibility to chronic postsurgical pain
Authors: Yan Shaoyao , Nie Huiyong , Bu Gang , Yuan Weili , Wang Suoliang
Published: July 2021

Background

The growth differentiation factor 5 (GDF5) gene regulates the growth of neuronal axons and dendrites and plays a role in the inflammatory response and tissue damage. The gene may also be associated with chronic postsurgical pain. This study aimed to reveal the relationship between SNPs in the GDF5 gene and orthopedic chronic postsurgical pain in Han Chinese population based on a case-control study.

Methods

We genotyped 8 SNPs within GDF5 gene in 1048 surgical patients with chronic postsurgical pain as the case group and 2062 surgical patients who were pain free as the control group. SNP and haplotypic analyses were performed, and stratified analyses were conducted to determine the correlations between significant SNPs and clinical characteristics.

Results

Only rs143384 in the 5′UTR of GDF5 was identified as significantly associated with increased susceptibility to chronic postsurgical pain, and the risk of A allele carriers was increased approximately 1.35-fold compared with that of G allele carriers. Haplotypes AGG and GGG in the LD block rs143384-rs224335-rs739329 also showed similar association patterns. Furthermore, we found that rs143384 was significantly correlated with chronic postsurgical pain in the subgroup aged ≤ 61 years, subgroup with a BMI ≤ 26, subgroup with no-smoking or no pain history, and subgroup with a drinking history.

Conclusion

Our study provided supportive evidence that genetic variations in the GDF5 gene are potential genetic factors that can increase the risk of chronic postsurgical pain in the Han Chinese population, but further research is necessary to elucidate the underlying mechanism.
Stakeholders’ perspectives on integrating the management of depression into routine HIV care in Uganda: qualitative findings from a feasibility study
Authors: Rutakumwa Rwamahe , Ssebunnya Joshua , Mugisha James , Mpango Richard Steven , Tusiime Christine , Kyohangirwe Leticia , Taasi Geoffrey , Sentongo Hafsa , Kaleebu Pontiano , Patel Vikram , Kinyanda Eugene
Published: July 2021

Background

HIV/AIDS continues to be a major global public health problem with Eastern and Southern Africa being the regions most affected. With increased access to effective antiretroviral therapy, HIV has become a chronic and manageable disease, bringing to the fore issues of quality of life including mental wellbeing. Despite this, the majority of HIV care providers in sub-Saharan Africa, including Uganda’s Ministry of Health, do not routinely provide mental health care including depression management. The purpose of this paper is to explore stakeholders’ perspectives on the feasibility and acceptability of integrating depression management into routine adult HIV care. The paper addresses a specific objective of the formative phase of the HIV + D study aimed at developing and evaluating a model for integrating depression management into routine HIV care in Uganda.

Methods

This was a qualitative study. Data were collected through in-depth interviews with 11 patients at enrollment and follow-up in the pilot phase, and exit interviews with 11 adherent patients (those who completed their psychotherapy sessions) and six non-adherent patients (those missing at least two sessions) at the end of the pilot phase. Key informant interviews were held with four clinicians, five supervisors and one mental health specialist, as were three focus group discussions with lay health workers. These were purposively sampled at four public health facilities in Mpigi District. Data were analysed thematically.

Results

Patients highlighted the benefits of treating depression in the context of HIV care, including improved adherence to antiretroviral therapy, overcoming sleeplessness and suicidal ideation, and regaining a sense of self-efficacy. Although clinicians and other stakeholders reported benefits of treating depression, they cited challenges in managing depression with HIV care, which were organisational (increased workload) and patient related (extended waiting time and perceptions of preferential treatment). Stakeholders generally shared perspectives on how best to integrate, including recommendations for organisational level interventions–training, harmonisation in scheduling appointments and structural changes–and patient level interventions to enhance knowledge about depression.

Conclusions

Integrating depression management into routine HIV care in Uganda is acceptable among key stakeholders, but the technical and operational feasibility of integration would require changes both at the organisational and patient levels.
Inhibiting the redox function of APE1 suppresses cervical cancer metastasis via disengagement of ZEB1 from E-cadherin in EMT
Authors: Li Qing , Zhou Zhi-Wei , Duan Wei , Qian Cheng-Yuan , Wang Shu-Nan , Deng Meng-Sheng , Zi Dan , Wang Jian-Min , Mao Cheng-Yi , Song Guanbin , Wang Dong , Westover Kenneth D. , Xu Cheng-Xiong
Published: July 2021

Background

Metastasis is a major challenge in cervical cancer treatment. Previous studies have shown that the dual functional protein apurinic/apyrimidinic endonuclease 1 (APE1) promotes tumor metastasis and is overexpressed in cervical cancer. However, the biological role and mechanism of APE1 in cervical cancer metastasis have rarely been studied.

Methods

We used gene set enrichment analysis (GSEA) to determine the APE1-related signaling pathways in cervical cancer. To investigate the role and mechanism of APE1 in cervical cancer metastasis and invasion, immunohistochemistry, immunofluorescence, western blotting, secondary structure prediction, coimmunoprecipitation, luciferase reporter, and electrophoretic mobility shift assays were performed. The inhibitory effects of the APE1 redox function inhibitor APX3330 on cervical cancer metastasis were evaluated using animal models.

Results

Clinical data showed that high expression of APE1 was associated with lymph node metastasis in cervical cancer patients. GSEA results showed that APE1 was associated with epithelial to mesenchymal transition (EMT) in cervical cancer. Ectopic expression of APE1 promoted EMT and invasion of cervical cancer cells, whereas inhibition of APE1 suppressed EMT and invasion of cervical cancer cells in a redox function-dependent manner. Notably, APE1 redox function inhibitor APX3330 treatment dramatically suppressed cervical cancer cell lymph node and distant metastasis in vivo. Furthermore, we found that APE1 enhanced the interaction between ZEB1 and the E-cadherin promoter by binding to ZEB1, thereby suppressing the expression of E-cadherin, a negative regulator of EMT.

Conclusion

Our findings help to elucidate the role played by APE1 in cervical cancer metastasis and targeting APE1 redox function may be a novel strategy for inhibiting cervical cancer metastasis.
Massive hemobilia caused by rupture of gastroduodenal artery pseudoaneurysm, a delayed complication of laparoscopic cholecystectomy: a case report
Authors: Kurniawan Kurniawan , Wibawa I Dewa Nyoman , Somayana Gde , Mariadi I Ketut , Mulyawan I Made
Published: July 2021

Background

Hemobilia is a rare cause of upper gastrointestinal bleeding that originates from the biliary tract. It is infrequently considered in diagnosis, especially in the absence of abdominal trauma or history of hepatopancreatobiliary procedure, such as cholecystectomy, which can cause arterial pseudoaneurysm. Prompt diagnosis is crucial because its management strategy is distinct from other types of upper gastrointestinal bleeding. Here, we present a case of massive hemobilia caused by the rupture of a gastroduodenal artery pseudoaneurysm in a patient with a history of laparoscopic cholecystectomy 3 years prior to presentation.

Case presentation

A 44-year-old Indonesian female presented to the emergency department with complaint of hematemesis and melena accompanied by abdominal pain and icterus. History of an abdominal trauma was denied. However, she reported having undergone a laparoscopic cholecystectomy 3 years prior to presentation. On physical examination, we found anemic conjunctiva and icteric sclera. Nonvariceal bleeding was suspected, but esophagogastroduodenoscopy showed a blood clot at the ampulla of Vater. Angiography showed contrast extravasation from a gastroduodenal artery pseudoaneurysm. The patient underwent pseudoaneurysm ligation and excision surgery to stop the bleeding. After surgery, the patient’s vital signs were stable, and there was no sign of rebleeding.

Conclusion

Gastroduodenal artery pseudoaneurysm is a rare complication of laparoscopic cholecystectomy. The prolonged time interval, as compared with other postcholecystectomy hemobilia cases, resulted in hemobilia not being considered as an etiology of the gastrointestinal bleeding at presentation. Hemobilia should be considered as a possible etiology of gastrointestinal bleeding in patients with history of cholecystectomy, regardless of the time interval between the invasive procedure and onset of bleeding.
Bin2vec: learning representations of binary executable programs for security tasks
Authors: Arakelyan Shushan , Arasteh Sima , Hauser Christophe , Kline Erik , Galstyan Aram
Published: July 2021

Tackling binary program analysis problems has traditionally implied manually defining rules and heuristics, a tedious and time consuming task for human analysts. In order to improve automation and scalability, we propose an alternative direction based on distributed representations of binary programs with applicability to a number of downstream tasks. We introduce Bin2vec, a new approach leveraging Graph Convolutional Networks (GCN) along with computational program graphs in order to learn a high dimensional representation of binary executable programs. We demonstrate the versatility of this approach by using our representations to solve two semantically different binary analysis tasks – functional algorithm classification and vulnerability discovery. We compare the proposed approach to our own strong baseline as well as published results, and demonstrate improvement over state-of-the-art methods for both tasks. We evaluated Bin2vec on 49191 binaries for the functional algorithm classification task, and on 30 different CWE-IDs including at least 100 CVE entries each for the vulnerability discovery task. We set a new state-of-the-art result by reducing the classification error by 40% compared to the source-code based inst2vec approach, while working on binary code. For almost every vulnerability class in our dataset, our prediction accuracy is over 80% (and over 90% in multiple classes).
Radiation and Androgen Deprivation Therapy With or Without Docetaxel in the Management of Nonmetastatic Unfavorable-Risk Prostate Cancer: A Prospective Randomized Trial
Authors: D'Amico Anthony V. , Xie Wanling , McMahon Elizabeth , Loffredo Marian , Medeiros Shana , Joseph David , Denham Jim , Kumar Parvesh , Bubley Glenn , Sullivan Molly , Hellwig Richard , Carlos Vera Juan , Freter Rolf , Jeffrey Baker W. , Wong Jeffrey Y. , Renshaw Andrew A. , Kantoff Philip W.
Published: July 2021

PURPOSE

Although docetaxel is not recommended when managing men with unfavorable-risk prostate cancer (PC) given negative or inconclusive results from previous randomized trials, unstudied benefits may exist.

METHODS

Between September 21, 2005, and January 13, 2015, we randomly assigned 350 men 1:1 with T1c-4N0M0 unfavorable-risk PC to receive radiation therapy (RT) and androgen deprivation therapy (ADT) plus docetaxel (60 mg/m2once every 3 weeks for three cycles before RT and 20 mg/m2once weekly during RT) versus ADT + RT. We evaluated the treatment effect of adding docetaxel to ADT + RT on the primary end point of overall survival (OS) and the incidence of RT-induced cancers and explored whether the impact of the treatment effect on OS differed within prostate-specific antigen (PSA) subgroups (< 4, > 20 v 4-20 ng/mL) using the interaction test for heterogeneity adjusted for age and PC prognostic factors.

RESULTS

After a median follow-up of 10.2 years, 89 men died (25.43%); of these, 42 from PC (47.19%). Although OS was not significantly increased in the docetaxel arm (the restricted mean survival time over 10 years was 9.11 v 8.82 years; P = .22), significantly fewer RT-induced cancers were observed (10-year estimates: 0.61% v 4.90%; age-adjusted hazard ratio of 0.13; 95% CI, 0.02 to 0.97; P = .046). The treatment effect of adding docetaxel to ADT + RT on OS significantly differed in men with a PSA < 4 ng/mL versus 4-20 ng/mL (adjusted hazard ratio: 0.27 and 1.51, respectively) because of less PC-specific mortality on the docetaxel arm (0.00% v 28.57%) among men with PSA < 4 ng/mL.

CONCLUSION

Adding docetaxel to ADT + RT did not prolong OS in men with unfavorable-risk PC, but decreased RT-induced cancer incidence, and may prolong OS in the subgroup of men with a PSA < 4 ng/mL by reducing PC-specific mortality.