bluuebunny/crossref_metadata_2025 huggingface dataset:
MORC proteins regulate transcription factor binding by mediating chromatin compaction in active chromatin regions
Authors: Zhong Zhenhui , Xue Yan , Harris C. Jake , Wang Ming , Li Zheng , Ke Yunqing , Liu Mukun , Zhou Jessica , Jami-Alahmadi Yasaman , Feng Suhua , Wohlschlegel James A. , Jacobsen Steven E.
Published: April 2023

Background

The microrchidia (MORC) proteins are a family of evolutionarily conserved GHKL-type ATPases involved in chromatin compaction and gene silencing. Arabidopsis MORC proteins act in the RNA-directed DNA methylation (RdDM) pathway, where they act as molecular tethers to ensure the efficient establishment of RdDM and de novo gene silencing. However, MORC proteins also have RdDM-independent functions although their underlying mechanisms are unknown.

Results

In this study, we examine MORC binding regions where RdDM does not occur in order to shed light on the RdDM-independent functions of MORC proteins. We find that MORC proteins compact chromatin and reduce DNA accessibility to transcription factors, thereby repressing gene expression. We also find that MORC-mediated repression of gene expression is particularly important under conditions of stress. MORC-regulated transcription factors can in some cases regulate their own transcription, resulting in feedback loops.

Conclusions

Our findings provide insights into the molecular mechanisms of MORC-mediated chromatin compaction and transcription regulation.
Longitudinal associations between physical activity and five risk factors of metabolic syndrome in middle-aged adults in Germany
Authors: Cleven Laura , Dziuba Anna , Krell-Roesch Janina , Schmidt Steffen C. E. , Bös Klaus , Jekauc Darko , Woll Alexander
Published: April 2023

Background

We examined the longitudinal association between (change in) physical activity (PA) with new onset of five risk factors of metabolic syndrome among 657 middle-aged adults (mean age 44.1 (standard deviation (SD) 8.6) years) who were free of the respective outcome at baseline, in a longitudinal cohort study spanning over 29 years.

Methods

Levels of habitual PA and sports-related PA were assessed by a self-reported questionnaire. Incident elevated waist circumference (WC), elevated triglycerides (TG), reduced high-density lipoprotein cholesterols (HDL), elevated blood pressure (BP), and elevated blood-glucose (BG) were assessed by physicians and by self-reported questionnaires. We calculated Cox proportional hazard ratio regressions and 95% confidence intervals.

Results

Over time, participants developed (cases of incident risk factor; mean (SD) follow-up time) elevated WC (234 cases; 12.3 (8.2) years), elevated TG (292 cases; 11.1 (7.8) years), reduced HDL (139 cases; 12.4 (8.1) years), elevated BP (185 cases; 11.4 (7.5) years), or elevated BG (47 cases; 14.2 (8.5) years). For PA variables at baseline, risk reductions ranging between 37 and 42% for reduced HDL levels were detected. Furthermore, higher levels of PA (≥ 16.6 METh per week) were associated with a 49% elevated risk for incident elevated BP. Participants who increased PA levels over time, had risk reductions ranging between 38 and 57% for elevated WC, elevated TG and reduced HDL. Participants with stable high amounts of PA from baseline to follow-up had risk reductions ranging between 45 and 87% for incident reduced HDL and elevated BG.

Conclusions

PA at baseline, starting PA engagement, maintaining and increasing PA level over time are associated with favorable metabolic health outcomes.
Alagille-like syndrome with surprising karyotype: a case report
Authors: Amimoto S. , Ishii M. , Tanaka K. , Araki S. , Kuwamura M. , Suga S. , Kondo E. , Shibata E. , Kusuhara K. , Yoshino K.
Published: April 2023

Background

Chromosome 5p partial monosomy (5p-syndrome) and chromosome 6p partial trisomy are chromosomal abnormalities that result in a variety of symptoms, but liver dysfunction is not normally one of them. Alagille syndrome (OMIM #118450) is a multisystem disorder that is defined clinically by hepatic bile duct paucity and cholestasis, in association with cardiac, skeletal, and ophthalmologic manifestations, and characteristic facial features. Alagille syndrome is caused by mutations in JAG1 on chromosome 20 or NOTCH2 on chromosome 1. Here, we report a preterm infant with karyotype 46,XX,der(5)t(5,6)(p15.2;p22.3) and hepatic dysfunction, who was diagnosed as having incomplete Alagille syndrome.

Case presentation

The Japanese infant was diagnosed based on the cardiac abnormalities, ocular abnormalities, characteristic facial features, and liver pathological findings. Analysis of the JAG1 and NOTCH sequences failed to detect any mutations in these genes.

Conclusions

These results suggest that, besides the genes that are known to be responsible for Alagille syndrome, other genetic mutations also may cause Alagille syndrome.
Genetic associations between circulating metabolic biomarkers and lung cancer in East Asians and Europeans
Authors: Liu Kai , Wang Shangshang , Zhou Yuhan , Huang Sha , Liu Yifan , Song Lijiang , He Zhengfu
Published: April 2023

Background

Metabolic biomarkers are reported to be associated with the risk of lung cancer (LC). However, the observed associations from epidemiological studies are either inconsistent or inconclusive.

Methods

The genetic summary data of high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), total cholesterol (TC), triglyceride (TG), fasting plasma glucose (FPG), and glycated hemoglobin (HbA1c) and those of the LC and its histological subtypes were retrieved from previous GWASs. We performed two-sample Mendelian randomization (MR) and multivariable MR analyses to examine the associations between genetically predicted metabolic biomarkers and LC in East Asians and Europeans.

Results

In East Asians, the inverse-variance weighted (IVW) method suggests that LDL (odds ratio [OR] = 0.799, 95% CI 0.712–0.897), TC (OR = 0.713, 95% CI 0.638–0.797), and TG (OR = 0.702, 95% CI 0.613–0.804) were significantly associated with LC after correction for multiple testing. For the remaining three biomarkers, we did not detect significant association with LC by any MR method. Multivariable MR (MVMR) analysis yielded an OR of 0.958 (95% CI 0.748–1.172) for HDL, 0.839 (95% CI 0.738–0.931) for LDL, 0.942 (95% CI 0.742–1.133) for TC, 1.161 (95% CI 1.070–1.252) for TG, 1.079 (95% CI 0.851–1.219) for FPG, and 1.101 (95% CI 0.922–1.191) for HbA1c. In Europeans, the univariate MR analyses did not detect significant association between exposures and outcomes. However, in MVMR analysis integrating circulating lipids and lifestyle risk factors (smoking, alcohol drinking, and body mass index), we found that TG was positively associated with LC in Europeans (OR = 1.660, 95% CI 1.060–2.260). Subgroup and sensitivity analysis yielded similar results to the main analyses.

Conclusions

Our study provides genetic evidence that circulating levels of LDL was negatively associated with LC in East Asians, whereas TG was positively associated with LC in both populations.
Meta-organism gene expression reveals that the impact of nitrate enrichment on coral larvae is mediated by their associated Symbiodiniaceae and prokaryotic assemblages
Authors: Tong Haoya , Zhang Fang , Sun Jin , McIlroy Shelby E. , Zhang Weipeng , Wang Yan , Huang Hui , Zhou Guowei , Qian Pei-Yuan
Published: April 2023

Background

Coral meta-organisms consist of the coral, and its associated Symbiodiniaceae (dinoflagellate algae), bacteria, and other microbes. Corals can acquire photosynthates from Symbiodiniaceae, whilst Symbiodiniaceae uses metabolites from corals. Prokaryotic microbes provide Symbiodiniaceae with nutrients and support the resilience of corals as meta-organisms. Eutrophication is a major cause of coral reef degradation; however, its effects on the transcriptomic response of coral meta-organisms remain unclear, particularly for prokaryotic microbes associated with corals in the larval stage. To understand acclimation of the coral meta-organism to elevated nitrate conditions, we analyzed the physiological and transcriptomic responses of Pocillopora damicornis larvae, an ecologically important scleractinian coral, after 5 days of exposure to elevated nitrate levels (5, 10, 20, and 40 µM).

Results

The major differentially expressed transcripts in coral, Symbiodiniaceae, and prokaryotic microbes included those related to development, stress response, and transport. The development of Symbiodiniaceae was not affected in the 5 and 20 µM groups but was downregulated in the 10 and 40 µM groups. In contrast, prokaryotic microbe development was upregulated in the 10 and 40 µM groups and downregulated in the 5 and 20 µM groups. Meanwhile, coral larval development was less downregulated in the 10 and 40 µM groups than in the 5 and 20 µM groups. In addition, multiple larval, Symbiodiniaceae, and prokaryotic transcripts were significantly correlated with each other. The core transcripts in correlation networks were related to development, nutrient metabolism, and transport. A generalized linear mixed model, using least absolute shrinkage and selection operator, demonstrated that the Symbiodiniaceae could both benefit and cost coral larval development. Furthermore, the most significantly correlated prokaryotic transcripts maintained negative correlations with the physiological functions of Symbiodiniaceae.

Conclusions

Results suggested that Symbiodiniaceae tended to retain more nutrients under elevated nitrate concentrations, thereby shifting the coral-algal association from mutualism towards parasitism. Prokaryotic microbes provided Symbiodiniaceae with essential nutrients and may control Symbiodiniaceae growth through competition, whereby prokaryotes can also restore coral larval development inhibited by Symbiodiniaceae overgrowth.
Accurate detection of early-stage lung cancer using a panel of circulating cell-free DNA methylation biomarkers
Authors: Hu Shuo , Tao Jinsheng , Peng Minhua , Ye Zhujia , Chen Zhiwei , Chen Haisheng , Yu Haifeng , Wang Bo , Fan Jian-Bing , Ni Bin
Published: April 2023

Background

Lung cancer remains the leading cause of cancer mortality worldwide. Early detection of lung cancer helps improve treatment and survival. Numerous aberrant DNA methylations have been reported in early-stage lung cancer. Here, we sought to identify novel DNA methylation biomarkers that could potentially be used for noninvasive early diagnosis of lung cancers.

Methods

This prospective-specimen collection and retrospective-blinded-evaluation trial enrolled a total of 317 participants (198 tissues and 119 plasmas) comprising healthy controls, patients with lung cancer and benign disease between January 2020 and December 2021. Tissue and plasma samples were subjected to targeted bisulfite sequencing with a lung cancer specific panel targeting 9,307 differential methylation regions (DMRs). DMRs associated with lung cancer were identified by comparing the methylation profiles of tissue samples from patients with lung cancer and benign disease. Markers were selected with minimum redundancy and maximum relevance algorithm. A prediction model for lung cancer diagnosis was built through logistic regression algorithm and validated independently in tissue samples. Furthermore, the performance of this developed model was evaluated in a set of plasma cell-free DNA (cfDNA) samples.

Results

We identified 7 DMRs corresponding to 7 differentially methylated genes (DMGs) including HOXB4, HOXA7, HOXD8, ITGA4, ZNF808, PTGER4, and B3GNTL1 that were highly associated with lung cancer by comparing the methylation profiles of lung cancer and benign nodule tissue. Based on the 7-DMR biomarker panel, we developed a new diagnostic model in tissue samples, termed “7-DMR model”, to distinguish lung cancers from benign diseases, achieving AUCs of 0.97 (95%CI: 0.93-1.00)/0.96 (0.92-1.00), sensitivities of 0.89 (0.82–0.95)/0.92 (0.86–0.98), specificities of 0.94 (0.89–0.99)/1.00 (1.00–1.00), and accuracies of 0.90 (0.84–0.96)/0.94 (0.89–0.99) in the discovery cohort (n = 96) and the independent validation cohort (n = 81), respectively. Furthermore, the 7-DMR model was applied to noninvasive discrimination of lung cancers and non-lung cancers including benign lung diseases and healthy controls in an independent validation cohort of plasma samples (n = 106), yielding an AUC of 0.94 (0.86-1.00), sensitivity of 0.81 (0.73–0.88), specificity of 0.98 (0.95-1.00), and accuracy of 0.93 (0.89–0.98).

Conclusion

The 7 novel DMRs could be promising methylation biomarkers that merits further development as a noninvasive test for early detection of lung cancer.

Graphical abstract
Laser-based techniques for the non-invasive characterisation of grisaille paints on stained-glass windows
Authors: Machado Carla , Oujja Mohamed , Cerqueira Alves Luís , Martínez-Weinbaum Marina , Maestro-Guijarro Laura , Carmona-Quiroga Paula María , Castillejo Marta , Vilarigues Márcia , Palomar Teresa
Published: April 2023

Grisaille was the first paint applied on stained-glass panels, used in Europe since the twelfth century. Historical written sources described the use of iron and copper together with a high lead-silica base glass in the grisailles production. This project aims to study the evolution of the grisaille paint composition throughout time and the changes in the raw materials used in their production using non-destructive and non-invasive techniques. To achieve this objective, 23 grisaille samples dated from the 13th to the twentieth centuries from nine different countries (Portugal, Poland, United Kingdom, Sweden, Norway, Belgium, Low Countries, Germany, and France) were studied by means of micro particle-induced X-ray emission (μ-PIXE), micro energy dispersive X-ray fluorescence (μ-EDXRF), laser-induced breakdown spectroscopy (LIBS), laser-induced fluorescence (LIF), non-linear optical microscopy (NLOM) in the modality of multiphoton excitation fluorescence (MPEF) and optical microscopy (OM). The results showed that it was possible to identify compositional differences and patterns throughout the samples when compared with literature results. The preference for using copper in central and south-central European countries and the addition of new compounds (CoO, Cr2O3, MnO) as colouring agents since the nineteenth century was verified. The LIBS analyses allow the identification of boron on two samples, confirming the change of base glass components since the seventeenth century. The NLOM-MPEF showed the capability of this technique to measure the grisaille paint layers’ thickness. This non-invasive multi-analytical and complementary approach proves itself efficient in identifying changes in the grisaille’s composition throughout time, which can be interpreted as changes in the raw materials and manufacture used in the production of these paint materials.
Fake news detection on social media: the predictive role of university students’ critical thinking dispositions and new media literacy
Authors: Orhan Ali
Published: April 2023

This study aimed to investigate the predictive role of critical thinking dispositions and new media literacies on the ability to detect fake news on social media. The sample group of the study consisted of 157 university students. Sosu Critical Thinking Dispositions Scale, New Media Literacy Scale, and fake news detection task were employed to gather the data. It was found that university students possess high critical thinking dispositions and new media literacies as well as high fake news detection abilities and there is a positive and moderate relationship among these variables. Also, this study revealed that critical thinking dispositions and new media literacies significantly predicted university students’ abilities to detect fake news on social media and they together explained 18% of the total variance on fake news detection. Besides, university students’ critical thinking dispositions presented a larger effect on their abilities to detect fake news than new media literacies.
Posterior cruciate ligament repair seems safe with low failure rates but more high level evidence is needed: a systematic review
Authors: Vandenrijt Jasper , Callenaere Sofie , Van der Auwera Dries , Michielsen Jozef , Van Dyck Pieter , Heusdens Christiaan H. W.
Published: April 2023

Purpose

To discuss recent literature on posterior cruciate ligament (PCL) repair and report on the clinical and radiological outcomes.

Methods

A systematic review was conducted according to the PRISMA guidelines. In August 2022, three databases (PubMed, Scopus, and Cochrane Library) were searched for studies on PCL repair by two independent reviewers. Articles published between January 2000 and August 2022 focussing on the clinical and/or radiological outcomes, following PCL repair, were included. Patient demographic data, clinical evaluations, patient‑reported outcome measures, post‐operative complications and radiological outcomes were extracted.

Results

Nine studies met the inclusion criteria, covering 226 patients with a mean age ranging from 22.4 to 38.8 years and mean follow‐up periods ranging from 14 to 78.6 months. Seven studies (77.8%) were level IV and two studies (22.2%) were level III. Arthroscopic PCL repair was performed in four studies (44.4%) while the remaining five studies (55.6%) described open PCL repair. In four studies (44.4%) additional suture augmentation was applied. Arthrofibrosis affected a combined total of 24 patients (11.7%; range 0–21.0%) making it the most common complication and the overall failure rate was 5.6%, ranging from 0 to 15.8%. Two studies (22.2%) performed post‐operative MRI and confirmed PCL healing.

Conclusion

This systematic review indicates that PCL repair can be a safe procedure with an overall failure rate of 5.6%, ranging from 0% to 15.8%. However, more high quality research is necessary before widespread clinical implementation is warranted.

Level of Evidence

IV.
Omental arteriovenous fistula after splenectomy treated with transarterial embolization
Authors: Sanomura Takayuki , Norikane Takashi , Uchinomura Satoshi , Takami Yasukage , Ensako Toshiya , Nagao Mina , Deguchi Akihiro , Okano Keiichi , Nishiyama Yoshihiro
Published: April 2023

Background

Laparoscopic splenectomy for patients with portal hypertension is associated with a high risk of bleeding. The use of vessel-sealing devices and automatic sutures is important for bleeding control. However, a rare complication of abdominal surgery is the direct communication between the arterial and portal circulation related to surgical procedures such as simultaneous ligature of an artery and adjacent vein. We describe a rare case of omental arteriovenous fistula (AVF) after laparoscopic splenectomy treated with transarterial embolization.

Case presentation

We report a case of a 46-year-old male patient with an omental AVF after a laparoscopic splenectomy 6 years ago for splenomegaly associated with alcoholic cirrhosis. Follow-up abdominal dynamic computed tomography accidentally revealed a vascular sac (25 mm in the major axis) that formed an omental AVF with anastomosis to the left colonic vein. The communication was considered to be caused by using a vessel-sealing device. No symptoms related to the AVF were observed. The AVF was embolized with microcoils using the transarterial approach. A 4-axis catheter system was used for accurate embolization due to the long and tortuous distance from the celiac artery. No recurrence or symptoms were observed after 6 months.

Conclusions

Treatment of arterioportal fistula is mandatory, even in asymptomatic patients. Embolization is a less invasive alternative to surgical approaches. The 4-axis catheter system was useful for accurate embolization via a long and tortuous artery.
Interference with sex expression, estimation of yield and bioactive compounds in bitter gourd under PGRs-induced conditions
Authors: Islam Md. Rafikul , Siddiquee Shafiquzzaman , Rahman Md. Mofizur , Muhammad Noor , Uddain Jasim , Sarkar Md. Dulal
Published: April 2023

Background

The bitter gourd fruit yields are not at a desirable level due to maleness. Maleness is one of the biggest difficulties with bitter gourd, reducing fruit yields substantially. On the other hand, plant stages are the most important consideration for PGR application because of their sensitive responsiveness. Therefore, it is necessary to determine how bitter gourd plants respond to plant growth regulators, namely PGR0 (control: application of water as control treatment), PGR1 (GA3-Gibberellic acid, 100 mgL−1), PGR2 (NAA-Naphthalene acetic acid, 100 mgL−1), and PGR3 (MH- Maleic hydrazide, 100 mgL−1) at three application phases, S1: soaking of seeds; S2: four-leaf; and S3: flower bud in terms of vegetative development, male–female flower sex alteration, and fruit features including bioactive compounds.

Results

Physiological, floral and yield characteristics of bitter gourd exposed significant changes by GA3 and MH at various stages. The number of leaves plant−1, the fresh mass of the plant, and the fresh mass of fruit and fruit dry matter content were enhanced remarkably for MH application at the seed soaking stage except for plant height and the number of branches plant−1. MH increased the number of female flowers plant−1, the number of fruits plant−1 and the yield at the 4-leaf stage of application. PGRs substantially influenced the quantity of sugar, chlorophyll, total carotenoids, protein, and water content at various phases of their application but not on ascorbic acid, TSS, or total phenol concentration.

Conclusions

For sex expression and yield attributes, 100 mgL−1 MH at the 4-leaf stage would be effective in bitter gourd. Exogenous NAA showed a considerable dual influence on plant development and antioxidant enzyme activity in bitter gourd fruits.
Effect of resistive exercise on insomnia and sleep quality in postmenopausal women: a randomized controlled trial
Authors: Massoud Esraa F. , ElDeeb Abeer M. , Samir Sameh H. , Shehata Mai M. A.
Published: April 2023

Background

Sleep disorders are common in postmenopausal women and are linked to poor physical and mental health, which affect quality of life. Therefore, this study aimed to investigate the effect of resistive exercise on insomnia and sleep quality in postmenopausal women. Fifty-six postmenopausal women suffering from sleep disturbance and insomnia participated in this study. Their age ranged from 50–65 years, and their body mass index (BMI) was 25–29.5 kg/m2. They were randomly distributed into two groups of an equal number. Control group received self-care and lifestyle advice, while study group received the same advice in addition to resistive exercises for 20–30 min per session for 4 weeks. Plasma estradiol levels were assessed, as well as the Pittsburgh Sleep Quality Index and Insomnia Severity Index, which were used to evaluate sleep quality and insomnia pre- and post-treatment.

Results

Control group revealed a significant decrease (p < 0.001) in Pittsburgh sleep quality index and insomnia severity index and a non-significant difference (p = 0.059) in plasma estradiol level post-treatment. However, study group showed a significant decrease (p < 0.001) in Pittsburgh sleep quality index and insomnia severity index, as well as a significant increase (p = 0.001) in plasma estradiol level. Compared to control group, study group showed a significant decrease (p = 0.000) in insomnia and sleep quality, as well as a non-significant difference (p = 0.179) in estradiol level post-treatment. Also, there was a negative correlation between plasma estradiol level and insomnia severity score in the study group post-treatment.

Conclusion

Resistive exercise is an effective modality for postmenopausal women suffering from sleep disorders as it improves insomnia, sleep quality, which in turn affects the quality of life. Increased estradiol level is an important factor that helps improve insomnia in postmenopausal women.
Physiological and electrophysiological evaluation of the hearing system in low birth weight neonates treated with cholestin: a cohort study
Authors: Khosravi Nastaran , Mazaheryazdi Malihah , Kalani Majid , Khalesi Nasrin , Shakeri Zinat , Archang Saeedeh , Archang Maryam
Published: April 2023

Background

Infections in neonates are mainly caused by sepsis and are the most important complications of low birth weight. In the treatment of these infections, it is common to use broad-spectrum antibiotics such as cholestin. Cholestin can cause changes in the latency of brainstem-evoked response waves. The current cohort study tried to investigate the probability of changes caused by cholestin in LBW neonates and benefiting from two common tests to identify the hearing system in neonates after treatment by cholestin and compared them with a control group.

Methods

The study was an exposure-based cohort, during which hearing damage caused by receiving cholestin was evaluated in 104 low birth weight neonates, in two groups (52 exposure and 52 no-exposure to cholestin). OAE and ABR tests were performed at the age of 3 months to identify complications in two groups and their results were compared.

Results

The absolute latency of waves I, III, and V in the brainstem evoked response test with an intensity of 80 dB Hl showed a significant difference in the exposure group with the control group. The interpeak latency of the waves as well as the effect of the drug on the gender of the infants did not show significant differences with the control group.

Conclusion

Cholestin did not affect the axonal or synaptic transmission time of the auditory nerve to the brainstem. It is possible that the simultaneous presence of risk factors, such as the use of cholestin, low birth weight, noises in the intensive care unit, and other unknown factors, can be effective in the change of the absolute latency of waves.
Epistemology Normalized
Authors: Goodman Jeremy , Salow Bernhard
Published: April 2023

We offer a general framework for theorizing about the structure of knowledge and belief in terms of the comparative normality of situations compatible with one’s evidence. The guiding idea is that, if a possibility is sufficiently less normal than one’s actual situation, then one can know that that possibility does not obtain. This explains how people can have inductive knowledge that goes beyond what is strictly entailed by their evidence. We motivate the framework by showing how it illuminates knowledge about the future, knowledge of lawful regularities, knowledge about parameters measured using imperfect instruments, the connection between knowledge, belief, and probability, and the dynamics of knowledge and belief in response to new evidence.
Ultrasound-stimulated microbubbles enhanced vascular disruption in fractionated radiotherapy-treated tumours via ASMase activation
Authors: Leong Kai Xuan , Yang Wenyi , Sharma Deepa , Liu Stanley , Czarnota Gregory J.
Published: April 2023

Recent studies have indicated that radiotherapy affects tumour vasculature as well as tumour cells. The use of ultrasound-stimulated microbubbles (USMB) can potentially enhance the effects of radiotherapy through the activation of the acid sphingomyelinase [ASMase or sphingomyelin phosphodiesterase 1 (SMPD1)]-ceramide pathway. ASMase knockout (ASMase−/−) and wild-type (WT) mice bearing fibrosarcoma (MCA/129 tumour line) were treated with 10 Gy or 20 Gy in five fractions alongside or independently of USMB treatments. The results indicated that tumour responses to fractionated radiotherapy (fXRT) were enhanced when fXRT was coupled with USMB as part of the treatment regimen. Sphingosine-1-phosphate (S1P)-treated mice and ASMase−/− mice demonstrated radioresistance against fXRT alone, whereas only ASMase−/− mice showed radioresistance against fXRT treatment alone and when combined with USMB. Results indicated that in WT and S1P-treated cohorts, the use of USMB with fXRT enhanced the tumour response compared to use of USMB or fXRT alone. Although in WT and S1P-treated cohorts, there was enhanced vascular disruption, ASMase−/− cohorts demonstrated no significant vascular disruption, indicating the importance of ASMase in facilitating vascular changes in response to fXRT and USMB treatment.
Relative Wealth Concerns, Executive Compensation, and Managerial Risk-Taking
Authors: Liu Qi , Sun Bo
Published: April 2023

This paper theoretically examines how relative wealth concerns affect equilibrium contracting and systemic risk-taking. We find that such externalities can generate pay for luck as an equilibrium strategy. In expectation of pay for luck in other firms, tying managerial pay to luck provides insurance to managers against a compensation shortfall relative to executive peers. We also show that an effort-inducing mechanism exists: managers have additional incentives to exert effort in utilizing investment opportunities, which helps them keep up with their peers during industry movements; however, pay for luck that is efficient within firms can nonetheless exacerbate aggregate fluctuations, especially during periods of heightened market risk. (JEL D81, D82, D86, G51, M12, M52)
Too Good to Be True? Retention Rules for Noisy Agents
Authors: Espinosa Francisco , Ray Debraj
Published: April 2023

An agent who privately knows his type seeks to be retained by a principal. Agents signal their type with some ambient noise, but can alter this noise, perhaps at some cost. Our main finding is that in equilibrium, the principal treats extreme signals in either direction with suspicion, and retains the agent if and only if the signal falls in some intermediate bounded set. In short, she follows the maxim: “if it seems too good to be true, it probably is.” We consider extensions and applications, including non-normal signal structures, dynamics with term limits, risky portfolio management, and political risk-taking. (JEL D72, D82, G11, G41)
Optimal Task Scheduling under Adverse Selection and Hidden Actions
Authors: Agastya Murali , Birulin Oleksii
Published: April 2023

A Principal owns a project consisting of several tasks. Tasks differ, both in their innate success probabilities and their incremental benefits. Moreover, only specialists can perform these tasks. Subject to moral hazard and adverse selection, in what order should the Principal commission the tasks, and when should she terminate the project? What investments into changing tasks’ characteristics yield the highest marginal profit? These are typical issues that arise in sequencing R&D activities and other sequential production processes. We show that, despite informational constraints, a simple index—a task’s effective marginal contribution—determines the optimal schedule/mechanism. (JEL D82, L23, L24, L65, M11, O31)
Raising the Bar: Certification Thresholds and Market Outcomes
Authors: Hui Xiang , Saeedi Maryam , Spagnolo Giancarlo , Tadelis Steven
Published: April 2023

Certification of sellers by trusted third parties helps alleviate information asymmetries in markets, yet little is known about the impact of a certification’s threshold on market outcomes. Exploiting a policy change on eBay, we study how a more selective certification threshold affects the distribution of quality and incumbent behavior. We develop a stylized model that shows how changes in selectivity change the distribution of quality and prices in markets. Using rich data from hundreds of online categories on eBay.com , we find support for the model’s hypotheses. Our results help inform the design of certification selectivity in electronic and other markets. (JEL D82, L11, L15, L86)
Ultrasound assessment of the inferior glenohumeral capsule in normal shoulders—a study of measurement variables and reliability
Authors: Shrestha-Taylor Sumi , Ginn Karen , Poulos Ann , Clarke Jillian L
Published: April 2023

Objectives:

To establish the reliability of a standardised ultrasound protocol to measure normal inferior glenohumeral capsule (IGHC) thickness and to investigate the effects of age, sex, hand dominance and angles of abduction on the thickness.

Methods:

IGHC images were obtained at 60o, 90o and 180o abduction angles of 151 asymptomatic shoulders in supine position. Following the proposed guidelines, three sonographers blindly measured the IGHC thicknesses for intra- and interrater reliability assessments.

Results:

The intrarater reliability was excellent (intraclass correlation coefficient value = 0.95; 95% CI = 0.92–0.97). The interrater reliability was moderate (intraclass correlation coefficient value = 0.74; 95% CI = 0.60–0.83). The mean IGHC thickness values in mm ± SD at 60o, 90o and 180o abduction angles for males were 3.3 ± 0.93, 3.0 ± 0.80 and 2.6 ± 0.55 and those for females were 2.7 ± 0.86, 2.4 ± 0.7 and 2.0 ± 0.56 respectively. Although males had thicker IGHC, the rate at which the thickness reduced with increased abduction was same in both males and females. Age and hand dominance had no effect.

Conclusion:

The normal IGHC thickness varies with sex and the abduction angle of the arm at which it is measured. A large variation of IGHC thickness exists in the normal population.

Advances in knowledge:

The results of this study discourage the use of a single value of IGHC thickness and emphasise the importance of comparing the thickness of the symptomatic side to that of the asymptomatic side of the same subject at the same abduction level. The guidelines provided in this study can be used in clinical practice and in future research studies.
Clinical applications of artificial intelligence in radiology
Authors: Mello-Thoms Claudia , Mello Carlos A B
Published: April 2023

The rapid growth of medical imaging has placed increasing demands on radiologists. In this scenario, artificial intelligence (AI) has become an attractive partner, one that may complement case interpretation and may aid in various non-interpretive aspects of the work in the radiological clinic. In this review, we discuss interpretative and non-interpretative uses of AI in the clinical practice, as well as report on the barriers to AI’s adoption in the clinic. We show that AI currently has a modest to moderate penetration in the clinical practice, with many radiologists still being unconvinced of its value and the return on its investment. Moreover, we discuss the radiologists’ liabilities regarding the AI decisions, and explain how we currently do not have regulation to guide the implementation of explainable AI or of self-learning algorithms.
Ex vivo comparative investigation of suprachiasmatic nucleus excitotoxic resiliency
Authors: Acharyya Debalina , Cooper Joanna , Prosser Rebecca A.
Published: April 2023

Background: Glutamate signaling in the brain is regulated by release, reuptake, and receptor responsiveness. In diseased conditions, glutamate signaling can exceed normal regulatory processes, giving rise to a condition called excitotoxicity. Although regional differences in the excitotoxic effects of glutamate in the brain have been reported, the extent and characteristics of these potential differences are not clear.  Here we compared the excitotoxic resiliency of the suprachiasmatic nucleus (SCN), anterior hypothalamus (AH) and cortex. 

Methods: We treated acute brain slices containing either the SCN and AH or the cortex from adult male mice at different times across the diurnal cycle with varying concentrations of N-methyl-D-aspartate (NMDA), NMDA+ α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) or control medium. The extent of cell damage was assessed using propidium iodide (PI), a cell death marker.

Results: The results indicate that all three brain regions exhibited increasing cell damage/death when treated with increasing concentrations of NMDA. However, higher concentrations of NMDA were needed to significantly increase cell damage in the SCN compared to the cortex and AH.  All three brain regions also exhibited greater cell death/damage when treated in the nighttime compared to the daytime, although the SCN exhibited increased cell death during a more restricted time interval compared to the AH and cortex. 

Conclusions: Together, these data confirm previous studies showing excitotoxic resiliency in the SCN, while extending them in two ways.  First, we demonstrate a dose-dependency in excitotoxic susceptibility that differentiates the SCN from the surrounding AH and the cortex using a brain slice preparation. Second, we demonstrate a diurnal rhythm in excitotoxic susceptibility with a broadly similar phase across all three brain regions. These data increase our understanding of the extent and nature of the SCN excitotoxic resiliency, which will inform future studies on the cellular mechanisms underlying this phenomenon.
Enhanced human periodontal ligament stem cell viability and osteogenic differentiation on two implant materials: An experimental in vitro study
Authors: El Shafei Sara F. , Raafat Shereen N. , Farag Engy A.
Published: April 2023

Background: Surface roughness of dental implants impacts the survival of adult periodontal stem cells and rate of differentiation. This research was conducted to test how human periodontal ligament stem cells behaved on yttria stabilized tetragonal zirconia polycrystals and polyetheretherketone (PEEK) discs with different surface topographies.

Methods: Discs roughening was prepared by sandblasting. Stem cells were cultivated on zirconia discs with a polished surface, PEEK discs with a polished surface, sandblasted zirconia discs and sandblasted PEEK discs. Cells viability was assessed after 24, 48, 72 hours. Scanning electron microscopy was used to examine the adherence and attachment of cells. Osteoblastic differentiation capacity was studied by checking the mineralization clusters development through alizarin red S staining and alkaline phosphatase assay. ANOVA and the Tukey post hoc test were used for the statistical analysis.

Results: Polished PEEK discs showed lower cell viability, whereas roughened sandblasted zirconia and PEEK discs showed the highest proliferation rates and cell viability percent. The osteogenic differentiation was enhanced for rough surfaces in comparison to polished surfaces. Sandblasted zirconia and PEEK discs showed a markedly increased mineralized nodule development and ALP enzyme activity compared to the polished surface and control.

Conclusions: Micro- topographies creation on the PEEK implant surface enhances stem cell attachment, viability, and osteogenic differentiation.
An Insight into developmental changes in reasoning skills among Indian Preschoolers: A cross-sectional study using a story-based approach
Authors: Prasanna Aparna , Bajaj Gagan , Anakkathil Anil Malavika , Bhat Jayashree S
Published: April 2023

Background: Considering the importance of exploring the development of reasoning skills during preschool period and the suitability of using a culturally linguistically relevant story-based approach for the same, the present research intended to profile the reasoning skills in typically developing Indian preschool children between 36 and 72 months using a story-based approach. The specific objectives were to develop explanation, prediction, and inference based reasoning tasks around a story and assess the reasoning skills in typically developing Indian preschool children using the same.

Method: Reasoning tasks across explanation, prediction, and inference domains were developed based on a story and evaluated for its psychometric properties. The developed tasks were then administered to 63 typically developing Indian preschool children attending English medium schools in Mangalore. The preschoolers were equally divided into three age groups, and the responses obtained across the age groups were analyzed quantitatively and qualitatively. 

Results: The developed tasks were confirmed to have good psychometric properties like content validity and reliability. The age comparisons of reasoning abilities using one-way ANOVA suggested an increase in reasoning abilities with age during the preschool period.  The qualitative analysis further suggested that with increasing age, the nature of reasoning changed from content-based reasoning to reasoning based on prior knowledge which was integrated with the story content.

Conclusion: The study describes reasoning skill development using a story-based task in Indian preschoolers. The study findings further provide clinical and educational implications to assess and foster reasoning abilities among preschoolers.
Virtual screening of zinc compounds similar to NSAIDS with better pharmacodynamic and pharmacokinetic profiles
Authors: Kamakia Faith , Ouma Stephen , Kagia Richard
Published: April 2023

BACKGROUND: Pain is a common symptom that is managed in both outpatients and inpatients. There are many side effects associated with opioids such as respiratory depression, constipation, hyperalgesia, and tolerance. Non- steroidal anti-inflammatory drugs cause gastrointestinal tract (GIT) irritation and may be a risk factor for developing peptic ulcer disease. This study aimed to generate active analgesic agents from known analgesics, determine the docking scores of these agents to their receptors, determine the pharmacokinetic properties of these agents, and evaluate their toxicity profiles.

METHODS: PubChem was used to download smiles for ibuprofen, aspirin and celecoxib. Avogadro optimized the ligands. The smiles were copied to SwissSimilarity and were used as query compounds to generate zinc compounds. DrugBank and Protein Data Bank were used to download cyclooxygenase 1 and 2. Molecular docking was done using Chimera and Autodock Vina. Smiles for both query compounds and generated zinc compounds were pasted onto the Protox II webserver and SwissADME for toxicity and pharmacokinetics properties determination. The data was presented in tabular forms with textual descriptions of the contents in the tables.

RESULTS: Aspirin, ibuprofen and celecoxib’s zinc compounds were generated and the first 20 compounds were docked to COX-1 and COX-2 enzymes. Seven, one, and four of the docked compounds showed better binding energies to COX-2 than COX-1. The zinc compounds were analyzed for toxicity profiles. ZINC01680731 and ZINC33823423 were predicted to have LD50 of 1240 mg/kg as compared to aspirin’s 250mg/kg. Ibuprofen and ZINC39120409 showed LD50 of 299mg/kg and they were hepatoactive. Celecoxib and four of its zinc compounds showed LD50 of 1400mg/kg. All compounds had high GIT absorption and they conformed with Lipinski rule of five.

CONCLUSIONS: ZINC01680731 0.994 and ZINC00600558 0.988 were identified as the best compounds as they showed better binding affinities, toxicities and pharmacokinetics properties compared to standard compounds.
Instruments used to assess gender-affirming healthcare access: a scoping review protocol
Authors: Kearns Seán , Hardie Philip , O'Shea Donal , Neff Karl
Published: April 2023

Background: Internationally, the demand for gender-affirming care has increased exponentially in recent years. The clinical presentation of those seeking care has changed with an increase in transmasculine and non-binary identities and a decrease in the average age of those seeking care. Healthcare navigation remains complicated for this population and warrants further investigation in light of ongoing changes in the field. This paper presents a protocol for a methodological scoping review that aims to systematically map and synthesise the extent and nature of the peer-reviewed, published academic literature on the instruments used to assess factors relating to healthcare navigation and healthcare access for transgender and non-binary individuals seeking gender-affirming healthcare. 

Methods: This review will search databases (PsychINFO, CINAHL, Medline, and Embase.) and grey literature sources. In line with the methodological framework for scoping reviews, the following six stages will be undertaken: (1) identifying the research question, (2) identifying relevant studies, (3) study selection, (4) charting the data, (5) collating, summarising and reporting results and (6) consultation. The PRISMA Extension for Scoping Reviews (PRISMA-ScR): checklist and explanation will be utilised and reported. The research team will undertake the study as outlined in this protocol and an expert panel of young transgender and non-binary youth will oversee the project through patient and public involvement. 

Conclusions: This scoping review has the potential to inform policy, practice, and future research through enhanced understanding of the complex interplay of factors that impact healthcare navigation for transgender and non-binary people seeking gender-affirming care. The results from this study will inform further research into healthcare navigation considerations generally and will inform a research project entitled “Navigating access to gender care in Ireland—a mixed-method study on the experiences of transgender and non-binary youth”.
A microwave cavity design and optimisation for a homogeneous and faster drying process inside an industrial Agitated Nutsche Filter
Authors: Schütz Sebastiano , Di Domenico Mauro , Poretti Samuel , Monleone Ricardo
Published: April 2023

Background: Nowadays the disposal or recycling of polyethylene terephthalate (PET) material is a real-world problem. The European Union’s DEM3TO project aims at recycling PET to return it to the main chemical components with which it was produced. In a specific reactor, microwave radiation is used to quickly depolymerise the initial polymer. At the end of the de-polymerization process, a filtering and drying process through an agitated Nutsche filter (ANF) is necessary.

Methods: This study aims to design and develop a High Frequency (HF) cavity inside the ANF (plugin “HF-ANF”) to speed up and improve the drying process. The effects studied are the efficiency of the HF cavity as a function of the heating process, the evaporation/drying process, and the mechanical mixing (due to the blades) of the mixture.

Results: During these studies it was possible to improve the efficiency of the HF plugin and allowing to absorb more than the 95% of the microwave energy into the mixture to increase the drying speed and the drying homogeneity of the ANF. In addition, the mixture was characterised to obtain the dielectric proprieties as a function of the temperature of the ANF and the concentration of the residual water.

Conclusions: The study allowed us to develop some important methodology that usually cannot to be simulated in a non-multi physics simulator. The careful modelling of certain aspects that are not normally available in EM (Electro-Magnetic) simulators, like variable geometries, mixed material, heating effect and the dielectrics characterization process are difficult and critical process but are very important steps to be undertaken in order to obtain results that can be compared with real measurements.
Automated staging of zebrafish embryos using machine learning
Authors: Jones Rebecca A. , Renshaw Matthew J. , Barry David J. , Smith James C.
Published: April 2023

The zebrafish (Danio rerio), is an important biomedical model organism used in many disciplines, including development, disease modeling and toxicology, to better understand vertebrate biology. The phenomenon of developmental delay in zebrafish embryos has been widely reported as part of a mutant or treatment-induced phenotype, and accurate characterization of such delays is imperative. Despite this, the only way at present to identify and quantify these delays is through manual observation, which is both time-consuming and subjective. Machine learning approaches in biology are rapidly becoming part of the toolkit used by researchers to address complex questions. In this work, we introduce a machine learning-based classifier that has been trained to detect temporal developmental differences across groups of zebrafish embryos. Our classifier is capable of rapidly analyzing thousands of images, allowing comparisons of developmental temporal rates to be assessed across and between experimental groups of embryos. Finally, as our classifier uses images obtained from a standard live-imaging widefield microscope and camera set-up, we envisage it will be readily accessible to the zebrafish community, and prove to be a valuable resource.