bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic compensation of triacylglycerol biosynthesis in the green microalga Chlamydomonas reinhardtii
Authors: Lee Yi‐Ying , Park Rudolph , Miller Stephen M. , Li Yantao 
Published: June 2022

SUMMARYGenetic compensation has been proposed to explain phenotypic differences between gene knockouts and knockdowns in several metazoan and plant model systems. With the rapid development of reverse genetic tools such as CRISPR/Cas9 and RNAi in microalgae, it is increasingly important to assess whether genetic compensation affects the phenotype of engineered algal mutants. While exploring triacylglycerol (TAG) biosynthesis pathways in the model alga Chlamydomonas reinhardtii, it was discovered that knockout of certain genes catalyzing rate‐limiting steps of TAG biosynthesis, type‐2 diacylglycerol acyltransferase genes (DGTTs), triggered genetic compensation under abiotic stress conditions. Genetic compensation of a DGTT1 null mutation by a related PDAT gene was observed regardless of the strain background or mutagenesis approach, for example, CRISPR/Cas 9 or insertional mutagenesis. However, no compensation was found in the PDAT knockout mutant. The effect of PDAT knockout was evaluated in a Δvtc1 mutant, in which PDAT was upregulated under stress, resulting in a 90% increase in TAG content. Knockout of PDAT in the Δvtc1 background induced a 12.8‐fold upregulation of DGTT1 and a 272.3% increase in TAG content in Δvtc1/pdat1 cells, while remaining viable. These data suggest that genetic compensation contributes to the genetic robustness of microalgal TAG biosynthetic pathways, maintaining lipid and redox homeostasis in the knockout mutants under abiotic stress. This work demonstrates examples of genetic compensation in microalgae, implies the physiological relevance of genetic compensation in TAG biosynthesis under stress, and provides guidance for future genetic engineering and mutant characterization efforts.
SUBANG RADAR CAPPI DATA PROCESSING AND Z-R OPTIMIZATION FOR QUANTITATIVE PRECIPITATION ESTIMATES (QPE) OVER LANGAT RIVER BASIN
Authors: Tahir Wardah , Ramli Suzana , Abdullah Jazuri , Muhammad Nur Shazwani , M Rahim Nur Farhana Hairine 
Published: June 2022

The main advantage of radar data over point gauge rainfall is its ability to provide continuous spatial and temporal resolution of rainfall details over a large area. Weather radar transmits electromagnetic wave, interacts with raindrops and reflects some of the intercepted power (backscattering) that is subsequently converted into rainfall intensity. Despite its advantages, indirect rainfall estimation using radar reflectivity factor suffers from various sources of error such as ground clutter, partial beam occultation, beam blockage and attenuation effects. Literatures on the use of radar quantitative precipitation estimates (QPE) in Malaysia have been increasing since the past 15 years ago. However, none of the previous work have detailed out the sources of radar data used and its processing for rainfall rate conversion. This paper will discuss the fundamentals in radar data acquisition and processing for rainfall input to a case study of Langat river basin, Malaysia. The methodology in raw radar data processing is decribed in details and the use of CAPPI data for rainfall estimation over Langat river basin is discussed. The findings indicate a good performance of the radar CAPPI data as an alternative source to the rainfall measurement for Langat river basin with correlation coefficient between radar rainfall and gauged rainfall ranging from 0.69 to 0.75. Improvement on radar rainfall estimates is also recommended by newly derived optimized Z-R equations based on monsoon season. The results presented in this study are encouraging, especially for the application of water resources management for the river basin.
Mobilization With Movement as Therapy to Reduce Knee Pain and Increase Knee Range of Motion
Authors: Plummer Steve , Leonard Julie 
Published: June 2022

Clinical Scenario: Knee pain and limited knee range of motion (ROM) are among the most common conditions found in individuals who report lower body health-related issues. Factors such as weight gain, lack of mobility, balance issues, and pain can lead to a more sedentary lifestyle, which, in turn, causes knee stiffness or knee limited ROM. As a result, the patient will be at higher risk of osteoporosis, patellofemoral pain syndrome, reduced quadriceps strength, heart disease, and even depression. Clinical Question: Is mobilization with movement (MWM) an effective method of treatment for reducing knee pain and increasing knee ROM in individuals being treated for knee pain and limited knee ROM? Summary of Key Findings: (1) The literature searched were peer-reviewed articles that investigated the effects of MWM as a therapy to reduce knee pain and increase knee ROM. (2) MWM was shown to be an effective treatment for reducing knee pain and increasing knee ROM. Clinical Bottom Line: There is conclusive evidence that MWM is an effective method of treatment for reducing knee pain and increasing knee ROM in individuals who experience knee pain and knee limited ROM. Strength of Recommendation: Grade (“A”) evidence exists showing that MWM therapy results are greater when performed either alone or in combination with a current conventional therapy for decreasing knee pain and increasing knee ROM.
L-5-hydroxytryptophan promotes antitumor immunity by inhibiting PD-L1 inducible expression
Authors: Huang Jing , Wang Xiaobo , Li Bing , Shen Shiyu , Wang Ruina , Tao Hongru , Hu Junchi , Yu Jin , Jiang Hualiang , Chen Kaixian , Luo Cheng , Dang Yongjun , Zhang Yuanyuan 
Published: June 2022

BackgroundThe repression or downregulation of programmed death-ligand 1 (PD-L1) can release its inhibition of T cells and activate antitumor immune responses. Although PD-1 and PD-L1 antibodies are promising treatments for diverse tumor types, their inherent disadvantages and immune-related adverse events remain significant issues. The development of small molecule inhibitors targeting the interaction surface of PD-1 and PD-L1 has been reviving, yet many challenges remain. To address these issues, we aimed to find small molecules with durable efficacy and favorable biosafety that alter PD-L1 surface expression and can be developed into a promising alternative and complementary therapy for existing anti-PD-1/PD-L1 therapies.MethodsCell-based screen of 200 metabolic molecules using a high-throughput flow cytometry assay of PD-L1 surface expression was conducted, and L-5-hydroxytryptophan (L-5-HTP) was found to suppress PD-L1 expression induced by interferon gamma (IFN-γ). Inhibition of PD-L1 induction and antitumor effect of L-5-HTP were evaluated in two syngeneic mouse tumor models. Flow cytometry was performed to investigate the change in the tumor microenvironment caused by L-5-HTP treatment.ResultsWe discovered that L-5-HTP suppressed IFN-γ-induced PD-L1 expression in tumor cells transcriptionally, and this effect was directly due to itself. Mechanistically, L-5-HTP inhibited IFN-γ-induced expression of RTK ligands and thus suppressed phosphorylation-mediated activation of RTK receptors and the downstream MEK/ERK/c-JUN signaling cascade, leading to decreased PD-L1 induction. In syngeneic mouse tumor models, treatment with 100 mg/kg L-5-HTP (intraperitoneal) inhibited PD-L1 expression and exhibited antitumor effect. L-5-HTP upregulated the ratio of granzyme B+ CD8+ activated cytotoxic T cells. An intact immune system and PD-L1 expression was critical for L-5-HTP to exert its antitumor effects. Furthermore, L-5-HTP acted synergistically with PD-1 antibody to improve anticancer effect.ConclusionOur study illustrated L-5-HTP’s inhibitory effect on PD-L1 induction stimulated by IFN-γ in tumor cells and also provided insight into repurposing L-5-HTP for use in tumor immunotherapy.
Cancer cells resist antibody-mediated destruction by neutrophils through activation of the exocyst complex
Authors: van Rees Dieke J , Bouti Panagiota , Klein Bart , Verkuijlen Paul J H , van Houdt Michel , Schornagel Karin , Tool Anton T J , Venet David , Sotiriou Christos , El-Abed Sarra , Izquierdo Miguel , Guillaume Sébastien , Saura Cristina , Di Cosimo Serena , Huober Jens , Roylance Rebecca , Kim Sung-Bae , Kuijpers Taco W , van Bruggen Robin , K van den Berg Timo , Matlung Hanke L 
Published: June 2022

BackgroundNeutrophils kill antibody-opsonized tumor cells using trogocytosis, a unique mechanism of destruction of the target plasma. This previously unknown cytotoxic process of neutrophils is dependent on antibody opsonization, Fcγ receptors and CD11b/CD18 integrins. Here, we demonstrate that tumor cells can escape neutrophil-mediated cytotoxicity by calcium (Ca2+)-dependent and exocyst complex-dependent plasma membrane repair.MethodsWe knocked down EXOC7 or EXOC4, two exocyst components, to evaluate their involvement in tumor cell membrane repair after neutrophil-induced trogocytosis. We used live cell microscopy and flow cytometry for visualization of the host and tumor cell interaction and tumor cell membrane repair. Last, we reported the mRNA levels of exocyst in breast cancer tumors in correlation to the response in trastuzumab-treated patients.ResultsWe found that tumor cells can evade neutrophil antibody-dependent cellular cytotoxicity (ADCC) by Ca2+-dependent cell membrane repair, a process induced upon neutrophil trogocytosis. Absence of exocyst components EXOC7 or EXOC4 rendered tumor cells vulnerable to neutrophil-mediated ADCC (but not natural killer cell-mediated killing), while neutrophil trogocytosis remained unaltered. Finally, mRNA levels of exocyst components in trastuzumab-treated patients were inversely correlated to complete response to therapy.ConclusionsOur results support that neutrophil attack towards antibody-opsonized cancer cells by trogocytosis induces an active repair process by the exocyst complex in vitro. Our findings provide insight to the possible contribution of neutrophils in current antibody therapies and the tolerance mechanism of tumor cells and support further studies for potential use of the exocyst components as clinical biomarkers.
Improving visualization of three-dimensional aneurysm features via segmentation with upsampled resolution and gradient enhancement (SURGE)
Authors: MacDonald Daniel E , Cancelliere Nicole M , Rustici Arianna , Pereira Vitor M , Steinman David A 
Published: June 2022

BackgroundIntracranial aneurysm neck width tends to be overestimated when measured with three-dimensional rotational angiography (3DRA) compared with two-dimensional digital subtraction angiography (2D-DSA), owing to high curvature at the neck. This may affect morphological and hemodynamic analysis in support of treatment planning. We present and validate a method for extracting high curvature features, such as aneurysm ostia, during segmentation of 3DRA images.MethodsIn our novel SURGE (segmentation with upsampled resolution and gradient enhancement) approach, the gradient of an upsampled image is sharpened before gradient-based watershed segmentation. Neck measurements were performed for both standard and SURGE segmentations of 3DRA for 60 consecutive patients and compared with those from 2D-DSA. Those segmentations were also qualitatively compared for surface topology and morphology.ResultsCompared with the standard watershed method, SURGE reduced neck measurement error relative to 2D-DSA by >60%: median error was 0.49 mm versus 0.17 mm for SURGE, which is less than the average pixel resolution (~0.33 mm) of the 3DRA dataset. SURGE reduced neck width overestimations >1 mm from 13/60 to 5/60 cases. Relative to 2D-DSA, standard segmentations were overestimated by 16% and 93% at median and 95th percentiles, respectively, compared with only 6% and 37%, respectively, for SURGE.ConclusionSURGE provides operators with high-level control of the image gradient, allowing recovery of high-curvature features such as aneurysm ostia from 3DRA where conventional algorithms may fail. Compared with standard segmentation and tedious manual editing, SURGE provides a faster, easier, and more objective method for assessing aneurysm ostia and morphology.
Early versus delayed complete revascularisation in patients presenting with ST-segment elevation myocardial infarction and multivessel disease: a systematic review and meta-analysis of randomised controlled trials
Authors: Abouelmagd Khaled , Tayel Hesham , Atta Ashraf , Ladwiniec Andrew , Ibrahim Mokhtar 
Published: June 2022

BackgroundSeveral studies have demonstrated that complete revascularisation improves clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary disease. However, the optimal timing of non-culprit lesion revascularisation remains controversial.ObjectiveThe aim of this systematic review and meta-analysis was to assess the effect of timing of complete revascularisation on cardiovascular outcomes in patients with STEMI and multivessel coronary artery disease.MethodsSearches of PubMed, the Cochrane Library, ClinicalTrials.gov and the reference lists of relevant papers were conducted covering the period from 2004 to 2019. A pairwise analysis was performed to compare the difference in clinical outcome between early complete revascularisation (index procedure or index hospitalisation) and delayed complete revascularisation (after discharge) in patients with STEMI.The primary endpoint was the incidence of major adverse cardiac events (MACE), which was defined as the composite of all-cause mortality, recurrent myocardial infarction, unplanned repeated revascularisation and cardiovascular death.ResultsTwelve studies including a total of 7596 patients were identified. The MACE rate was 10.37% in early complete revascularisation compared with 18.17% in culprit only (p=0.01). When complete revascularisation was delayed, the MACE rate was 11.81% after complete revascularisation compared with 17.21% in culprit-only percutaneous coronary intervention (PCI) (p=0.01). A meta-regression analysis demonstrated no relationship between timing of complete revascularisation and reduction in MACE relative to culprit-only PCI (p=0.862).ConclusionIn patients with STEMI treated by primary PCI and multivessel disease, there is a benefit of complete revascularisation over culprit-only PCI whether non-culprit revascularisation is performed early in hospital or delayed as an elective procedure. We have not demonstrated a relationship between timing of complete revascularisation and MACE.PROSPERO registration numberCRD42021226789.
Extremal charged black holes and superradiantly unstable quasinormal modes
Authors: Mai Zhan-Feng , Yang Run-Qiu , Lü H. 
Published: June 2022

AbstractIt was recently shown that the extremal charged black holes in STU supergravity suffer from superradiant instability owing to the existence of the unstable (low-frequency) quasibound states associated with a charged massive scalar field. In this paper, we show numerically that for some charge configurations, these black holes can also excite the (higher-frequency) superradiantly unstable quasinormal modes. We find empirically that the unstable modes are closely related to having a volcano-shaped effective potential in the Schrödinger-like wave equation.
Deterministic Response Threshold Models of Reproductive Division of Labor Are More Robust Than Probabilistic Models in Artificial Ants
Authors: Marriott Chris , Bae Peter , Chebib Jobran 
Published: June 2022

Abstract
We implement an agent-based simulation of the response threshold model of reproductive division of labor. Ants in our simulation must perform two tasks in their environment: forage and reproduce. The colony is capable of allocating ant resources to these roles using different division of labor strategies via genetic architectures and plasticity mechanisms. We find that the deterministic allocation strategy of the response threshold model is more robust than the probabilistic allocation strategy. The deterministic allocation strategy is also capable of evolving complex solutions to colony problems like niche construction and recovery from the loss of the breeding caste. In addition, plasticity mechanisms had both positive and negative influence on the emergence of reproductive division of labor. The combination of plasticity mechanisms has an additive and sometimes emergent impact.
Heterogeneous Supervised Topic Models
Authors: Sridhar Dhanya , Daumé Hal , Blei David 
Published: June 2022

AbstractResearchers in the social sciences are often interested in the relationship between text and an outcome of interest, where the goal is to both uncover latent patterns in the text and predict outcomes for unseen texts. To this end, this paper develops the heterogeneous supervised topic model (HSTM), a probabilistic approach to text analysis and prediction. HSTMs posit a joint model of text and outcomes to find heterogeneous patterns that help with both text analysis and prediction. The main benefit of HSTMs is that they capture heterogeneity in the relationship between text and the outcome across latent topics. To fit HSTMs, we develop a variational inference algorithm based on the auto-encoding variational Bayes framework. We study the performance of HSTMs on eight datasets and find that they consistently outperform related methods, including fine-tuned black-box models. Finally, we apply HSTMs to analyze news articles labeled with pro- or anti-tone. We find evidence of differing language used to signal a pro- and anti-tone.
Children’s Right to Participation: How Do Students See It?
Authors: Trbojević Aleksandra , Gajić Milica , Španović Svetlana , Gajić Olivera 
Published: June 2022

Abstract
This paper aims to present the perspective of 10- and 11-year-old students on the right to participate in school (Convention on the Rights of the Child, Article 12). Data were obtained via focus group interviews with 60 students (Serbia). The interviews revealed that students perceive only the rhetoric of their rights, that they most often participate in matters related to extracurricular activities and never in teaching-related matters. Students experience participation as being occasionally asked about their opinion by adults. Findings suggest that achieving the most participation in school depends on the support and encouragement of adults.
Biochip array technology for new psychoactive substances detection in biological samples: Evaluation of the specificity of the Randox Evidence Investigator®
Authors: Deville Marine , Bailly Ronald , Gauthier Nicolas , Pitti Pauline , Wachtelaer Audrey , Charlier Corinne 
Published: June 2022

Background The need to detect new psychoactive substances in biological samples is of crucial interest. In this paper, the specificity of a benchtop immunoanalyzer commercialized by Randox was evaluated on real patient samples. Method The Evidence Investigator was assessed to screen for NPS on 80 serum and urine samples coming from patients admitted to the emergency department. Targeted NPS were included in various categories such as synthetic cannabinoids, opioids and benzodiazepines. Results were compared with a chromatographic technique coupled with mass spectrometry. Results No NPS was detected by the reference technique. Concerning immunoanalysis, some piperazines were positive, caused by the presence of medicine containing this chemical structure. Clonazepam and fentanyl derivatives were confirmed in some cases, but sometimes the positivity was explained by other opiates or benzodiazepines, which also explained two samples falsely positive for etizolam. Conclusions The Randox Evidence Investigator was rapid and easy to use. It can be used as a first intention but always followed by a more specific technique in order to detect false positive result.
Lifestyle choices following head and neck cancer treatment: A qualitative study
Authors: Hanika Claire , Porter Nicola , Blick Kate , Mendis Jeewaka 
Published: June 2022

Background The benefits of a healthy lifestyle in reducing risk of cancer and chronic disease are well-documented. Many individuals who have had head and neck cancer (HNC) report complex social situations with a history of poor dietary habits, smoking and alcohol abuse. Survivorship can be a strong motivator to make positive lifestyle changes, reducing risk of cancer recurrence and ill-health. Research investigating whether HNC survivors adopt healthy lifestyle recommendations is lacking. Aim To explore the health-related practices of post-treatment HNC patients, seeking to identify barriers and motivators to following recommended health guidelines. Methods Tape-recorded interviews were conducted with 20 HNC survivors, and comparisons made to Department of Health recommendations. Results 80% of participants made lifestyle changes following HNC treatment. The most prevalent changes were to diet and alcohol intake. Key motivators were reducing cancer risk and ill-health; barriers included lack of motivation, support and misinformation. Treatment side-effects presented both motivators and barriers. There was widespread recognition of the “5 a day” message, and harm caused by smoking. Other public health recommendations were less well-known; 98% were unaware of current alcohol guidelines, physical activity was overestimated, and only one participant took vitamin D. Conclusion In this study HNC survivors were highly motivated to make healthy lifestyle changes. Further work is required to increase awareness of Government guidelines, as health messages are not always reaching the public or are misinterpreted.
MDMA-assisted therapy for posttraumatic stress disorder: A pooled analysis of ethnoracial differences in efficacy and safety from two Phase 2 open-label lead-in trials and a Phase 3 randomized, blinded placebo-controlled trial
Authors: Ching Terence HW , Williams Monnica T , Wang Julie B , Jerome Lisa , Yazar-Klosinski Berra , Emerson Amy , Doblin Rick 
Published: June 2022

Background: Limited ethnoracial diversity in previous ±3,4-methylenedioxymethamphetamine-assisted therapy (MDMA-AT) trials for posttraumatic stress disorder (PTSD) has prompted questions concerning whether Black, Indigenous, and People of Color (BIPOC) also benefit from this treatment. Methods: Secondary analysis was conducted using a modified intent-to-treat sample pooled from two Phase 2 open-label trials and a Phase 3 randomized, blinded placebo-controlled trial to compare efficacy and safety of MDMA-AT for PTSD between BIPOC and non-Hispanic White participants. Four subgroups were of interest: MDMA-AT, BIPOC ( n = 20); MDMA-AT, non-Hispanic White ( n = 63); Placebo-assisted therapy (Placebo-AT), BIPOC ( n = 17); and Placebo-AT, non-Hispanic White ( n = 27). Planned comparisons tested subgroup differences in changes in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) scores from baseline to primary endpoint, controlling for study type and baseline scores. Adverse events (AEs) on the day of (day 0) to 2 days post-dosing were reported for each subgroup. Results: In the MDMA-AT group, no significant ethnoracial difference in CAPS-5 change scores was observed. In the Placebo-AT group, BIPOC participants trended toward greater reductions in CAPS-5 scores than non-Hispanic Whites. Among non-Hispanic Whites, MDMA-AT was accompanied by significantly greater reductions in CAPS-5 scores than Placebo-AT. No treatment difference emerged among BIPOC participants. AEs were mostly rated as mild or moderate across subgroups. Conclusions: These findings provide preliminary support for the efficacy and safety of MDMA-AT for treating PTSD across ethnoracial groups. There was also a trend toward greater efficacy with Placebo-AT among BIPOC participants. There was an imbalance in subgroups, highlighting the need for culturally responsive recruitment strategies to diversify future studies.