bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Drug Approval Pathways for Paediatric Inflammatory Bowel Disease
Authors: Crowley Eileen , Ma Christopher , Andic Marija , Feagan Brian G , Griffiths Anne M , Jairath Vipul
Published: August 2021

Background and Aims

Timely access to approved medications is a priority in paediatric inflammatory bowel disease [IBD]. To date, the timing of drug studies in paediatric IBD has been suboptimal, with most studies conducted long after approval has been granted for adult IBD. This delay in approval leads to extensive off-label prescribing of medications in children, often without clear guidance on optimal dosing. The European Medicines Agency [EMA] and U.S. Food and Drug Administration [FDA] have implemented drug development frameworks in an attempt to address these challenges. However, access to information on these regulatory pathways in paediatric IBD is limited. We summarised the time from adult to paediatric approval of IBD therapies, outlining the regulatory approval pathway between the EMA and FDA, with the goal of identifying areas for improvement.

Methods

We reviewed publicly accessible data from the EMA and the FDA to identify therapeutic agents approved over 2005–2021 for paediatric IBD.

Results and Conclusions

Five drugs are currently approved for use in the paediatric IBD population, with long interval delays after adult approval. The impact of these drug development processes in paediatric IBD is awaited. Further consideration needs to be given to the age of enrolment along with novel, more efficient trial designs in an effort to improve access for paediatric IBD patients to newer therapies.
Clinical significance of the N-terminal pro-brain natriuretic peptide and B-type natriuretic peptide ratio in the acute phase of acute heart failure
Authors: Sawatani Tomofumi , Shirakabe Akihiro , Okazaki Hirotake , Matsushita Masato , Shibata Yusaku , Shigihara Shota , Otsuka Yusuke , Kiuchi Kazutaka , Kobayashi Nobuaki , Hata Noritake , Shimizu Wataru , Asai Kuniya
Published: August 2021

Aims

Serum N-terminal pro-brain natriuretic peptide (NT-proBNP) and B-type natriuretic peptide (BNP) levels are rarely evaluated simultaneously in the acute phase of acute heart failure (AHF).

Method and results

A total of 1207 AHF patients were enrolled, and 1002 patients were analysed. Blood samples were collected within 15 min of admission. Patients were divided into two groups according to the median value of the NT-proBNP/BNP ratio [low-NT-proBNP/BNP group (Group L) vs. high-NT-proBNP/BNP group (Group H)]. A multivariate logistic regression model showed that the C-reactive protein level (per 1-mg/dL increase), Controlling Nutrition Status score (per 1-point increase), and estimated glomerular filtration rate (eGFR, per 10-mL/min/1.73 m2 increase) were independently associated with Group H [odds ratio (OR) 1.049, 95% confidence interval (CI) 1.009–1.090, OR 1.219, 95% CI 1.140–1.304, and OR 1.543, 95% CI 1.401–1.698, respectively]. A Kaplan–Meier curve analysis showed that the prognosis was significantly poorer in Group H than in Group L, and a multivariate Cox regression model revealed Group H to be an independent predictor of 180-day mortality [hazard ratio (HR) 3.084, 95% CI 1.838–5.175] and HF events (HR 1.963, 95% CI 1.340–2.876). The same trend in the prognostic impact was significantly observed in the low-BNP (<810 pg/mL, n = 501), high-BNP (≥810 pg/mL, n = 501), and low-eGFR (<60 mL/min/1.73 m2, n = 765) cohorts, and tended to be observed in normal-eGFR (≥60 mL/min/1.73 m2, n = 237) cohort.

Conclusion

A high NT-proBNP/BNP ratio was associated with a non-cardiac condition (e.g. inflammatory reaction, nutritional status, and renal dysfunction) and is independently associated with adverse outcomes in AHF.
A stent for branch pulmonary artery stenosis after double-lung transplantation in a patient with COVID-19: a case report
Authors: Zheng Qiang , Shang Xiaoke , Dong Nianguo , Shi Jiawei
Published: August 2021

Background

Coronavirus disease 2019 (COVID-19) continues to be a pandemic worldwide. Lung transplantation is the last option to increase life expectancy of end-stage COVID-19 patients. Branch pulmonary artery stenosis (PAS) is a rare complication after lung transplantation with an extremely poor prognosis. The current trend in the management of branch PAS is percutaneous balloon angioplasty and/or stent implantation, rather than high-risk reoperation with a lower success rate.

Case summary

The subject was a 54-year-old male with severe acute respiratory syndrome coronavirus 2 infection who underwent a double-lung transplantation. He suffered hypoxaemia and right heart dysfunction following the operation. Right cardiac catheterization and pulmonary angiography examination revealed severe stenosis of the right branch pulmonary artery. Due to immunosuppression and reduced coagulation function, the patient underwent pulmonary artery balloon dilatation and stent implantation, and ultimately recovered well.

Discussion

The combination of balloon dilatation and stent implantation is a good alternative to reoperation for patients with COVID-19.
A kinetic analysis of the aflatoxin detoxification potential of lactic acid bacteria in Terxine (a cereal-based food)
Authors: Pourmohammadi Kiana , Sohrabi Maryam , Hashemi Seyed Mohammad Bagher , Amiri Mohammad Javad
Published: August 2021

Aflatoxin B1 (AFB1) is a hazardous component that can seriously threaten the public health. Terxine is a component used in traditional soup and found in the western mountainous regions of Iran. Several microorganisms have been reported to bind or degrade aflatoxins (AFs) in foods and feeds. This research aimed to investigate the effect of Terxine fermentation by Lactobacillus plantarum strains AF1 and LU5 on AFB1. Fermentation was carried out, and pH, lactic acid and AFB1 amount and microbial count were further determined. In addition, the kinetic experimental data of AFB1 by L. plantarum AF1 and LU5 (obtained at 37°C) were fitted to the zero-order, first-order and parabolic diffusion models. According to the coefficient of determination (R2) and root mean square of errors (RMSE), the zero-order model best described AF degradation. The growth of Lactobacillus strains was increased by the rise in the fermentation time; in this regard, the number of L. plantarum AF1 increased from 4.2 to 5.1 log cfu/g and that of L. plantarum LU5 increased from 4.1 to 5.2 log cfu/g in the first 8 h, reaching 7.2 and 7.4 log cfu/g in the next 8 h, respectively. The results also showed that the amount of lactic acid increased whereas the pH value decreased during the 24 h fermentation. Both microorganisms reduced the amount of AFB1 while L. plantarum AF1 was more effective. Therefore, L. plantarum strains AF1 and LU5 can be effectively used to reduce AFB1 in fermented foods.
A catalogue of signal molecules that interact with sensor kinases, chemoreceptors and transcriptional regulators
Authors: Matilla Miguel A , Velando Félix , Martín-Mora David , Monteagudo-Cascales Elizabet , Krell Tino
Published: August 2021

Bacteria have evolved many different signal transduction systems that sense signals and generate a variety of responses. Generally, most abundant are transcriptional regulators, sensor histidine kinases and chemoreceptors. Typically, these systems recognize their signal molecules with dedicated ligand-binding domains (LBDs), which, in turn, generate a molecular stimulus that modulates the activity of the output module. There are an enormous number of different LBDs that recognize a similarly diverse set of signals. To give a global perspective of the signals that interact with transcriptional regulators, sensor kinases and chemoreceptors, we manually retrieved information on the protein-ligand interaction from about 1,200 publications and 3D structures. The resulting 811 proteins were classified according to the Pfam family into 127 groups. These data permit a delineation of the signal profiles of individual LBD families as well as distinguishing between families that recognize signals in a promiscuous manner and those that possess a well-defined ligand range. A major bottleneck in the field is the fact that the signal input of many signaling systems is unknown. The signal repertoire reported here will help the scientific community design experimental strategies to identify the signaling molecules for uncharacterised sensor proteins.
A functional genomic screen in Saccharomyces cerevisiae reveals divergent mechanisms of resistance to different alkylphosphocholine chemotherapeutic agents
Authors: Garcia Jaquelin M , Schwabe Michael J , Voelker Dennis R , Riekhof Wayne R
Published: August 2021

The alkylphosphocholine (APC) class of antineoplastic and antiprotozoal drugs, such as edelfosine and miltefosine, are structural mimics of lyso-phosphatidylcholine (lyso-PC), and are inhibitory to the yeast Saccharomyces cerevisiae at low micromolar concentrations. Cytotoxic effects related to inhibition of phospholipid synthesis, induction of an unfolded protein response, inhibition of oxidative phosphorylation, and disruption of lipid rafts have been attributed to members of this drug class, however, the molecular mechanisms of action of these drugs remain incompletely understood. Cytostatic and cytotoxic effects of the APCs exhibit variability with regard to chemical structure, leading to differences in effectiveness against different organisms or cell types. We now report the comprehensive identification of S. cerevisiae titratable-essential gene and haploid nonessential gene deletion mutants that are resistant to the APC drug miltefosine (hexadecyl-O-phosphocholine). Fifty-eight strains out of ∼5600 tested displayed robust and reproducible resistance to miltefosine. This gene set was heavily enriched in functions associated with vesicular transport steps, especially those involving endocytosis and retrograde transport of endosome derived vesicles to the Golgi or vacuole, suggesting a role for these trafficking pathways in transport of miltefosine to potential sites of action in the endoplasmic reticulum and mitochondrion. In addition, we identified mutants with defects in phosphatidylinositol-4-phosphate synthesis (TetO::STT4) and hydrolysis (sac1Δ), an oxysterol binding protein homolog (osh2Δ), a number of ER-resident proteins, and multiple components of the eisosome. These findings suggest that ER-plasma membrane contact sites and retrograde vesicle transport are involved in the interorganelle transport of lyso-PtdCho and related lyso-phospholipid-like analogs to their intracellular sites of cytotoxic activity.
Modeling in yeast how rDNA introns slow growth and increase desiccation tolerance in lichens
Authors: Armaleo Daniele , Chiou Lilly
Published: August 2021

We connect ribosome biogenesis to desiccation tolerance in lichens, widespread symbioses between specialized fungi (mycobionts) and unicellular phototrophs. We test whether the introns present in the nuclear ribosomal DNA of lichen mycobionts contribute to their anhydrobiosis. Self-splicing introns are found in the rDNA of several eukaryotic microorganisms, but most introns populating lichen rDNA are unable to self-splice, being either catalytically impaired group I introns, or spliceosomal introns ectopically present in rDNA. Although the mycobiont’s splicing machinery removes all introns from rRNA, Northern analysis indicates delayed post-transcriptional removal during rRNA processing, suggesting interference with ribosome assembly. To study the effects of lichen introns in a model system, we used CRISPR to introduce a spliceosomal rDNA intron from the lichen fungus Cladonia grayi into all nuclear rDNA copies of Saccharomyces cerevisiae, which lacks rDNA introns. Three intron-bearing yeast mutants were constructed with the intron inserted either in the 18S rRNA genes, the 25S rRNA genes, or in both. The mutants removed the introns correctly but had half the rDNA genes of the wildtype, grew 4.4–6 times slower, and were 40–1700 times more desiccation tolerant depending on intron position and number. Intracellular trehalose, a disaccharide implicated in desiccation tolerance, was detected at low concentration. Our data suggest that the interference of the splicing machinery with ribosome assembly leads to fewer ribosomes and proteins and to slow growth and increased desiccation tolerance in the yeast mutants. The relevance of these findings for slow growth and desiccation tolerance in lichens is discussed.
Development of a Predictive Score for Mortality at 3 and 12 Months After Discharge From an Acute Geriatric Unit as a Trigger for Advanced Care Planning
Authors: Deschasse Guillaume , Bloch Frédéric , Drumez Elodie , Charpentier Anne , Visade Fabien , Delecluse Celine , Loggia Gilles , Lescure Pascale , Attier-Żmudka Jadwiga , Bloch Jennifer , Gaxatte Cedric , Van Den Berghe William’s , Puisieux François , Beuscart Jean-Baptiste
Published: August 2021

Background

There is a need for a mortality score that can be used to trigger advanced care planning among older patients discharged from acute geriatric units (AGUs).

Objective

We developed a prognostic score for 3- and 12-month mortality after discharge from an AGU, based on a comprehensive geriatric assessment, in-hospital events, and the exclusion of patients already receiving palliative care.

Methods

Devenir Après la Médecine Aigue Gériatrique (DAMAGE) is a French multicenter, prospective, cohort study. The broad inclusion criteria ensured that the cohort is representative of patients treated in an AGU. The DAMAGE participants underwent a comprehensive geriatric assessment, a daily clinical checkup, and follow-up visits 3 and 12 months after discharge. Multivariable logistic regression models were used to develop a prognostic score for the derivation and validation subsets.

Results

A total of 3 509 patients were assessed and 3 112 were included. The patient population was very old and frail or dependant, with a high proportion of deaths at 3 months (n = 455, 14.8%) and at 12 months (n = 1 014, 33%). The score predicted an individual risk of mortality ranging from 1% to 80% at 3 months and between 5% and 93% at 12 months, with an area under the receiving operator characteristic curve in the validation cohort of 0.728 at 3 months and 0.733 at 12 months.

Conclusions

Our score predicted a broad range of risks of death after discharge from the AGU. Having this information at the time of hospital discharge might trigger a discussion on advanced care planning and end-of-life care with very old, frail patients.

Clinical Trials Registration Number: NCT02949635
Sensitivity analysis of the frozen soil nonlinear latent heat and its precise transformation method
Authors: Chen Zhixiang , Guo Xiaoxia , Shao Longtan , Li Shunqun , Gao Lingxia
Published: August 2021

Latent heat of soil water phase transition is an important parameter affecting the prediction of the temperature field in a frozen soil. With the nonlinear change of unfrozen water content in freezing soil, the latent heat appears nonlinearly in a frozen soil. To evaluate the influence of the estimation of phase quantity and phase change interval on the formation of the temperature field in a frozen soil, the thermal parameters at different temperatures are measured, and a soil freezing model test is carried out. Meanwhile, based on the evolutionary trend of the unfrozen water content, a precise method of transforming the latent heat of phase change into specific heat and a segment processing method of latent heat in a frozen soil are proposed. Also, these methods are used in the ABAQUS to simulate the temperature of the soil freezing model. The sensitivity of the estimation of phase quantity and phase change interval on the formation of the temperature field in a frozen soil is analysed based on the numerical calculation values and model test values. The results show that the estimation accuracy of phase change interval greatly affects the prediction accuracy of the temperature field in the warm temperature stage, and the method of transforming latent heat into apparent specific heat can improve the prediction accuracy of the temperature field.
Efficient numerical Bloch solutions for multipulse surface NMR
Authors: Griffiths Matthew P , Grombacher Denys J , Larsen Jakob Juul
Published: August 2021

Simplified solutions of the Bloch equation can lead to inaccurate estimates of hydrogeological parameters from surface nuclear magnetic resonance measurements. Even for single pulse measurements, using simplified forward models is common practice because of the computational intensity of obtaining the full-Bloch solution. These challenges are exacerbated for multipulse sequences. We show parallelizing the full-Bloch solver on a Graphics Processing Unit reduces the solve time by three orders of magnitude. Further optimizations by numerical, analytical and hybrid solutions yield an additional 3× speed up. We simulate the full-Bloch physics for free-induction decay, spin-echo and pseudo-saturation recovery excitation schemes for an unprecedented range of physical scenarios. We explore the time-dependence and relaxation time sensitivity in these solution spaces. Characterizing the solution spaces with polynomials of the relaxation times, the solutions can be rapidly reproduced; a technique known as fast-mapping. By fitting these higher dimensional solution ensembles with polynomials, the original fast-mapping technique is extended to include T1 at arbitrary times. Accuracy of the 7th order polynomial is such that a minimum 96 per cent of the models are within a ±3 per cent relative error. This permits the rapid reproduction of full-Bloch solutions with a matrix multiplication and opens up surface NMR to time-series based inversion of single and multipulse data.
The Impact of NAFLD on Hospitalization Outcomes in Patients With Inflammatory Bowel Diseases: Nationwide Analysis
Authors: Noorian Shaya , Jeon Yejoo , Nguyen Minh T , Sauk Jenny , Limketkai Berkeley N
Published: August 2021

Background

Nonalcoholic fatty liver disease (NAFLD) is highly prevalent in patients with inflammatory bowel diseases (IBD). Yet, the impact of NAFLD on outcomes, along with the contribution of nonmetabolic factors to NAFLD development, is unclear. To investigate these topics, we conducted a nationwide study examining the impact of NAFLD on hospitalization outcomes in IBD patients after adjusting for metabolic factors.

Methods

Patients with IBD-related hospitalizations were identified using the Nationwide Readmissions Database from 2016 to 2018. Inflammatory bowel disease patients with and without NAFLD were matched based on IBD type, age, sex, metabolic syndrome, and diabetes mellitus. Primary outcomes were IBD-related readmission, IBD-related surgery, and death. Secondary outcomes were length of stay (LOS) and cost of care (COC). The primary multivariable model adjusted for obesity, dyslipidemia, Charlson-Deyo comorbidity index, hospital characteristics, payer, patient income, and elective status of admissions.

Results

Nonalcoholic fatty liver disease was associated with a higher risk of IBD-related readmission (adjusted hazard ratio, 1.90; P < .01) and death (adjusted hazard ratio, 2.73; P < .01), 0.71-day longer LOS (P < .01), and $7312 higher COC (P < .01) in those with Crohn’s disease. Nonalcoholic fatty liver disease was also associated with a higher risk of IBD-related readmission (adjusted hazard ratio, 1.65; P < .01), 0.64-day longer LOS (P < .01), and $9392 (P < .01) higher COC, but there was no difference in death in those with UC. No differences in risk of IBD-related surgery were observed.

Conclusions

Nonalcoholic fatty liver disease is associated with worse hospitalization outcomes in IBD patients after adjusting for metabolic factors. These data suggest nonmetabolic factors may be implicated in the pathogenesis of NAFLD in IBD patients and may contribute to worsened clinical outcomes.
ISDS Reform: The Long View
Authors: Alvarez José E
Published: August 2021

This lecture surveys the criticisms directed at international investment agreements (IIAs) and their reliance on investor-State dispute settlement (ISDS), as well as the leading reform venues that have been addressing such criticisms: UNCTAD, ICSID, and UNCITRAL. It argues that despite these ambitious efforts, the international investment regime’s reliance on investor-State arbitration will not be wholly displaced by any of the alternatives under active discussion – from national courts to mediation to a Multilateral Investment Court. In the long run, current reform efforts are likely to produce an ever more complex regime, governed by more diverse substantive rules interpreted by more complex options for dispute resolution. The focus on reforming the ways investor-State disputes are resolved fails to respond to doubts about the need for IIAs, undermines aspirations to harmonize international investment law, and ignores dire needs for stimulating (and protecting) foreign capital flows to achieve the goals of the Sustainable Development Goals – from mitigating climate change to preventing the next pandemic.
Minimal Gap in the Spectrum of the Sierpiński Gasket
Authors: Alonso Ruiz Patricia
Published: August 2021

This paper studies the size of the minimal gap between any two consecutive eigenvalues in the Dirichlet and in the Neumann spectrum of the standard Laplace operator on the Sierpiński gasket. The main result shows the remarkable fact that this minimal gap is achieved and coincides with the spectral gap. The Dirichlet case is more challenging and requires some key observations in the behavior of the dynamical system that describes the spectrum.
Increasing Viscosity Helps Explain Locomotor Control in Swimming Polypterus senegalus
Authors: Lutek K , Standen E M
Published: August 2021

Synopsis

Locomotion relies on the successful integration of sensory information to adjust brain commands and basic motor rhythms created by central pattern generators. It is not clearly understood how altering the sensory environment impacts control of locomotion. In an aquatic environment, mechanical sensory feedback to the animal can be readily altered by adjusting water viscosity. Computer modeling of fish swimming systems shows that, without sensory feedback, high viscosity systems dampen kinematic output despite similar motor control input. We recorded muscle activity and kinematics of six Polypterus senegalus in four different viscosities of water from 1 cP (normal water) to 40 cP. In high viscosity, P. senegalus exhibit increased body curvature, body wave speed, and body and pectoral fin frequency during swimming. These changes are the result of increased muscle activation intensity and maintain voluntary swimming speed. Unlike the sensory-deprived model, intact sensory feedback allows fish to adjust swimming motor control and kinematic output in high viscous water but maintain typical swimming coordination.
Termite Pest Identification Method Based on Deep Convolution Neural Networks
Authors: Huang Jia-Hsin , Liu Yu-Ting , Ni Hung Chih , Chen Bo-Ye , Huang Shih-Ying , Tsai Huai-Kuang , Li Hou-Feng
Published: August 2021

Several species of drywood termites, subterranean termites, and fungus-growing termites cause extensive economic losses annually worldwide. Because no universal method is available for controlling all termites, correct species identification is crucial for termite management. Despite deep neural network technologies’ promising performance in pest recognition, a method for automatic termite recognition remains lacking. To develop an automated deep learning classifier for termite image recognition suitable for mobile applications, we used smartphones to acquire 18,000 original images each of four termite pest species: Kalotermitidae: Cryptotermes domesticus (Haviland); Rhinotermitidae: Coptotermes formosanus Shiraki and Reticulitermes flaviceps (Oshima); and Termitidae: Odontotermes formosanus (Shiraki). Each original image included multiple individuals, and we applied five image segmentation techniques for capturing individual termites. We used 24,000 individual-termite images (4 species × 2 castes × 3 groups × 1,000 images) for model development and testing. We implemented a termite classification system by using a deep learning–based model, MobileNetV2. Our models achieved high accuracy scores of 0.947, 0.946, and 0.929 for identifying soldiers, workers, and both castes, respectively, which is not significantly different from human expert performance. We further applied image augmentation techniques, including geometrical transformations and intensity transformations, to individual-termite images. The results revealed that the same classification accuracy can be achieved by using 1,000 augmented images derived from only 200 individual-termite images, thus facilitating further model development on the basis of many fewer original images. Our image-based identification system can enable the selection of termite control tools for pest management professionals or homeowners.
Forgotten Conflicts: Producing Knowledge and Ignorance in Security Studies
Authors: Brenner David , Han Enze
Published: August 2021

Security studies privileges the study of civil wars in some contexts over others. The field's leading journals mostly publish studies of armed conflicts in Africa, Eastern Europe, and the Middle East. Armed conflicts in Asia receive comparatively little attention, despite their prevalence and protracted nature. Against the background of our own empirical archive—the decades-old but largely ignored civil war in Myanmar—we ask why some conflicts draw more scholarly interest than others and why this uneven attention matters. In doing so, we argue that the empirical selectivity bias in the study of civil war and armed conflict reflects (1) institutional entanglements between the field of security studies and Western foreign policy; and (2) sociological factors that shape the formation of scholarly subjectivities and pertain to methodological challenges. This uneven empirical landscape shapes our conceptual understanding of civil wars. In fact, prominent debates within leading security studies journals surrounding the nature of civil war and armed conflict are inseparable from the empirical contexts in which they emerged. Leveling such an uneven empirical landscape thus generates opportunities for discussing conflict, insecurity, and violence in a different light. In shedding light on this issue, we urge closer attention to questions of place, time, and power in the scholarly production of knowledge and ignorance.
Moving on from Dutch to English: Young Refugees Feeling Betrayed by the Dutch Language Integration Policy and Seeking for More Inclusive Environments
Authors: Pozzo Moos
Published: August 2021

This article explores the linguistic strategies of young refugees (ages 12–23) in the Netherlands. The study takes place within a societal context in which new migrants and refugees are increasingly pressured to learn Dutch as key to their integration, but English is becoming more and more dominant, and in which learning Dutch is not considered necessary for other newcomer groups such as exchange students and expats. It starts from a puzzling finding in participants’ use of languages within their personal networks (collected 2016–18): their decreasing use of Dutch and increasing use of English while integrating into Dutch society. Participants’ ‘network stories’ reveal that they shifted from Dutch to English to distance themselves from the identities ascribed to them by the Dutch dominant negative discourse and to imagine their futures and belonging in more inclusive environments.
A universal relation between the properties of supermassive black holes, galaxies, and dark matter haloes
Authors: Marasco A , Cresci G , Posti L , Fraternali F , Mannucci F , Marconi A , Belfiore F , Fall S M
Published: August 2021

We study the relations between the mass of the central black hole (BH) MBH, the dark matter halo mass Mh, and the stellar-to-halo mass fraction f⋆∝M⋆/Mh in a sample of 55 nearby galaxies with dynamically measured $M_{\rm BH}\gt 10^6\, {\rm M}_\odot$ and $M_{\rm h}\gt 5\times 10^{11}\, {\rm M}_\odot$. The main improvement with respect to previous studies is that we consider both early- and late-type systems for which Mh is determined either from globular cluster dynamics or from spatially resolved rotation curves. Independently of their structural properties, galaxies in our sample build a well defined sequence in the MBH–Mh–f⋆ space. We find that: (i) Mh and MBH strongly correlate with each other and anticorrelate with f⋆; (ii) there is a break in the slope of the MBH–Mh relation at Mh of $10^{12}\, {\rm M}_\odot$, and in the f⋆–MBH relation at MBH of $\sim 10^7\!-\!10^8\, {\rm M}_\odot$; (iii) at a fixed MBH, galaxies with a larger f⋆ tend to occupy lighter haloes and to have later morphological types. We show that the observed trends can be reproduced by a simple equilibrium model in the ΛCDM framework where galaxies smoothly accrete dark and baryonic matter at a cosmological rate, having their stellar and BH build-up regulated both by the cooling of the available gas reservoir and by the negative feedback from star formation and active galactic nuclei (AGNs). Feature (ii) arises as the BH population transits from a rapidly accreting phase to a more gentle and self-regulated growth, while scatter in the AGN feedback efficiency can account for feature (iii).
Uncovering fossils of the distant Milky Way with UNIONS: NGC 5466 and its stellar stream
Authors: Jensen Jaclyn , Thomas Guillaume , McConnachie Alan W , Starkenburg Else , Malhan Khyati , Navarro Julio , Martin Nicolas , Famaey Benoit , Ibata Rodrigo , Chapman Scott , Cuillandre Jean-Charles , Gwyn Stephen
Published: August 2021

We examine the spatial clustering of blue horizontal branch (BHB) stars from the u-band of the Canada–France Imaging Survey (CFIS, a component of the Ultraviolet Near-Infrared Optical Northern Survey, or UNIONS). All major groupings of stars are associated with previously known satellites, and among these is NGC 5466, a distant (16 kpc) globular cluster. NGC 5466 reportedly possesses a long stellar stream, although no individual members of the stream have previously been identified. Using both BHBs and more numerous red giant branch stars cross-matched to Gaia Data Release 2, we identify extended tidal tails from NGC 5466 that are both spatially and kinematically coherent. Interestingly, we find that this stream does not follow the same path as the previous detection at large distances from the cluster. We trace the stream across 31° of sky and show that it exhibits a very strong distance gradient in the range 10 < Rhelio < 30 kpc. We compare our observations to simple dynamical models of the stream and find that they are able to broadly reproduce the overall path and kinematics. The fact that NGC 5466 is so distant, traces a wide range of Galactic distances, has an identified progenitor, and appears to have recently had an interaction with the Galaxy’s disc makes it a unique test-case for dynamical modelling of the Milky Way.
Evolutionary innovations driving abiotic stress tolerance in C4 grasses and cereals
Authors: Pardo Jeremy , VanBuren Robert
Published: August 2021

Grasslands dominate the terrestrial landscape, and grasses have evolved complex and elegant strategies to overcome abiotic stresses. The C4 grasses are particularly stress tolerant and thrive in tropical and dry temperate ecosystems. Growing evidence suggests that the presence of C4 photosynthesis alone is insufficient to account for drought resilience in grasses, pointing to other adaptations as contributing to tolerance traits. The majority of grasses from the Chloridoideae subfamily are tolerant to drought, salt, and desiccation, making this subfamily a hub of resilience. Here, we discuss the evolutionary innovations that make C4 grasses so resilient, with a particular emphasis on grasses from the Chloridoideae (chloridoid) and Panicoideae (panicoid) subfamilies. We propose that a baseline level of resilience in chloridoid ancestors allowed them to colonize harsh habitats, and these environments drove selective pressure that enabled the repeated evolution of abiotic stress tolerance traits. Furthermore, we suggest that a lack of evolutionary access to stressful environments is partially responsible for the relatively poor stress resilience of major C4 crops compared to their wild relatives. We propose that chloridoid crops and the subfamily more broadly represent an untapped reservoir for improving resilience to drought and other abiotic stresses in cereals.
Resolving the Hubble tension in a U(1)$_{L_\mu-L_\tau}$ model with the Majoron
Authors: Araki Takeshi , Asai Kento , Honda Kei , Kasuya Ryuta , Sato Joe , Shimomura Takashi , Yang Masaki J S
Published: August 2021

We explore the possibility of resolving the Hubble tension and $(g-2)_{\mu}$ anomaly simultaneously in a U(1)$_{L_\mu - L_\tau}$ model with Majoron. We only focus on the case where the Majoron $\phi$ does not exist at the beginning of the universe and is created by neutrino inverse decay $\nu\nu\to \phi$ after electron–positron annihilation. In this case, the contributions of the new gauge boson $Z'$ and the Majoron $\phi$ to the effective number of neutrino species $N_{\rm eff}$ can be calculated in separate periods. These contributions are labelled $N'_{\rm eff}$ for the U(1)$_{L_\mu - L_\tau}$ gauge boson and $\Delta N_{\rm eff}^\prime$ for the Majoron. The effective number $N_{\rm eff} = N'_{\rm eff} + \Delta N_{\rm eff}^\prime$ is evaluated by the evolution equations of the temperatures and the chemical potentials of light particles in each period. As a result, we find that the heavier $Z'$ mass $m_{Z^\prime}$ results in a smaller $N_{\mathrm{eff}}^\prime$ and requires a larger $\Delta N_{\mathrm{eff}}^\prime$ to resolve the Hubble tension. Therefore, compared to previous studies, the parameter region where the Hubble tension can be resolved is slightly shifted toward the larger value of $m_{Z^\prime}$.
Do Sex and Pain Characteristics Influence the Effectiveness of Pain Neuroscience Education in People Scheduled for Total Knee Arthroplasty? Secondary Analysis of a Randomized Controlled Trial
Authors: Huysmans Eva , Baeyens Jean-Pierre , Dueñas Lirios , Falla Deborah , Meeus Mira , Roose Eva , Nijs Jo , Lluch Girbés Enrique
Published: August 2021

Objective

This explorative study investigates the moderating effect of sex and baseline pain characteristics on the effectiveness of preoperative pain neuroscience education (PNE) plus knee joint mobilization versus biomedical education plus knee joint mobilization in patients who have knee osteoarthritis and are scheduled to undergo total knee arthroplasty (TKA).

Methods

After baseline assessment of self-reported questionnaires (pain intensity, disability, symptoms of central sensitization and pain cognitions) and quantitative sensory testing, 44 participants with knee osteoarthritis were randomized into the PNE plus knee joint mobilization or biomedical education plus knee joint mobilization group. The questionnaires were retaken directly after and 1 month after 4 sessions of treatment and at 3 months after surgery. Based on baseline quantitative sensory testing results, the sample was subdivided into a high (showing high experimental pain levels and low pressure pain thresholds) and low pain cluster using principal components analysis and cluster analysis. Therapy effects over time were evaluated using 3-way analysis of variance, with time as the within factor and treatment, sex, and baseline pain cluster as between factors.

Results

Women benefited significantly more from the PNE intervention compared with the control intervention in terms of self-reported symptoms of central sensitization. For both pain clusters, differences in therapeutic effects concerning pain intensity and pain cognitions were found, with higher superiority of the PNE intervention in the high-pain cluster subgroup compared with the low-pain cluster.

Conclusion

Based on these explorative analyses, it can be concluded that sex and preoperative pain measures may influence the effectiveness of preoperative PNE for some specific outcome measures in people scheduled to undergo TKA.

Impact

Although further research on this topic is needed, the potential influence of sex and preoperative pain measures on the effectiveness of preoperative PNE should be considered when implementing this intervention in people undergoing TKA.
paraSBOLv: a foundation for standard-compliant genetic design visualization tools
Authors: Clark Charlie J , Scott-Brown James , Gorochowski Thomas E
Published: August 2021

Diagrams constructed from standardized glyphs are central to communicating complex design information in many engineering fields. For example, circuit diagrams are commonplace in electronics and allow for a suitable abstraction of the physical system that helps support the design process. With the development of the Synthetic Biology Open Language Visual (SBOLv), bioengineers are now positioned to better describe and share their biological designs visually. However, the development of computational tools to support the creation of these diagrams is currently hampered by an excessive burden in maintenance due to the large and expanding number of glyphs present in the standard. Here, we present a Python package called paraSBOLv that enables access to the full suite of SBOLv glyphs through the use of machine-readable parametric glyph definitions. These greatly simplify the rendering process while allowing extensive customization of the resulting diagrams. We demonstrate how the adoption of paraSBOLv can accelerate the development of highly specialized biodesign visualization tools or even form the basis for more complex software by removing the burden of maintaining glyph-specific rendering code. Looking forward, we suggest that incorporation of machine-readable parametric glyph definitions into the SBOLv standard could further simplify the development of tools to produce standard-compliant diagrams and the integration of visual standards across fields.
Temephos Decreases Sperm Quality and Fertilization Rate and Is Metabolized in Rat Reproductive Tissues at Low-Dose Exposure
Authors: Ramos-Flores Ángel , Camacho-Hernández Israel , Sierra-Santoyo Adolfo , Solís-Heredia María de Jesús , Verdín-Betancourt Francisco Alberto , Parra-Forero Lyda Yuliana , López-González Ma de Lourdes , Hernández-Ochoa Isabel , Quintanilla-Vega Betzabet
Published: August 2021

Temephos is an organophosphorus pesticide used in control campaigns against vectors that transmit diseases, including dengue, a public health concern. The WHO classifies temephos in category III and its safe concentration (low-observable-adverse-effect level) in male rats is 100 mg/kg/day for up to 44 days. Temephos inhibits acetylcholinesterase (AChE) and is metabolized in different tissues, probably by mixed-function oxidases; one of its metabolites is bisphenol S (BPS), which is considered an endocrine disruptor. The aim of this study was to evaluate the effects of temephos on sperm function and its biotransformation in the testis, epididymis, and other tissues to explore its toxicity in rats treated with 100 mg/kg/day/5 or 7 days (gavage). AChE activity was inhibited 70% starting on day 3 and 13 or 41% mortality was observed at 5 or 7 days, respectively. After 7 days, temephos significantly decreased sperm motility (30%) and viability (10%) and increased (10%) lipoperoxidation, and the sperm DNA exhibited no damage. Temephos was distributed and metabolized in all tissues, with the highest levels observed in the adipose tissue and temephos levels were 16-fold higher in the epididymis than in the testis. Notably, BPS was observed in the testis. At 5 days, decreased sperm motility (12.5%) and viability (5.7%) were observed and sperm fertilization decreased (30%). These results suggest that temephos decreases sperm quality and fertilization capacity at recommended safe concentrations and that it is metabolized in male reproductive tissues. This pesticide places the reproductive health of exposed people at risk, suggesting the need to reevaluate its toxicity.
A Clinical Trial to Assess the Role of Repetitive Transcranial Magnetic Stimulation in Smoking Cessation in an Egyptian Sample
Authors: Nawara Mayar , Abd El Moneam Mohamed H.E. , Elkholy Hussien , Elhabiby Mahmoud , Rabie Menan A. , ELNahas Gihan
Published: August 2021

Objective:

The objective of this study was to assess whether repetitive transcranial magnetic stimulation (rTMS) increases the likelihood of smoking cessation after 6 months of treatment

Methods:

A randomized, double-blind controlled clinical trial is conducted by enrolling 54 tobacco users divided into 2 equal groups; one group receiving active rTMS and the other group receiving a sham rTMS. Both groups were followed up for 24 weeks after treatment for abstinence using the Nicotine Use Inventory, cigarette consumption, cravings by Arabic Tobacco Craving Questionnaire-12.

Results:

Fifty-four subjects received the full intervention and were analyzed. Carbon monoxide was significantly less in the study group after the last treatment session. At week 24, the percentage of point prevalence abstinent subjects was 25.9% in the active group and 18.5% in the sham group, however, the difference was not statistically significant. Arabic Tobacco Craving Questionnaire-12 measures at different time points showed a statistically significant decrease in emotionality, expectancy, and purposefulness measures. However, this appears to be due to the effect of time, not treatment. Treatment response was higher in the study group, yet the difference was statistically insignificant.

Conclusions:

In a study that simulates real-life conditions in Egyptian smokers, 6 sessions of high-frequency active rTMS over the left dorsolateral prefrontal cortex did not produce a statistically significant increase in abstinence over sham rTMS at the same site. However, an effect on carbon monoxide measures and treatment response warrants further research.
Preeclampsia and cancer risk in women in later life: a systematic review and meta-analysis of cohort studies
Authors: Wang Fengxia , Zhang Wenyan , Cheng Wenke , Huo Nana , Zhang Shenfeng
Published: August 2021

Importance:

Results of this work may provide some guidance for subsequent ovarian cancer screening in women with preeclampsia and provide new directions for future studies.

Objective:

This study investigated the difference in cancer risk between women with preeclampsia and women with a normal pregnancy.

Evidence Review:

Electronic databases, namely PubMed, Embase, and the Cochrane Library, were searched for relevant studies from database inception to February 4, 2021. The results are expressed as risk ratios (RRs).

Findings:

The study included 13 cohort studies comprising 5,254,150 participants. The difference in the total cancer risk between the control and preeclampsia groups was statistically nonsignificant. However, breast cancer (BC) risk was lower in the preeclampsia group (RR = 0.88, 95% confidence interval (CI) = 0.83-0.93; I2 = 57.2%). A subgroup analysis stratified by reproductive factors demonstrated that BC risk in the preeclampsia population decreased in parous women (RR = 0.79, 95% CI = 0.72-0.87; I2 = 0%), women with full-term pregnancies (RR = 0.79, 95% CI = 0.75-0.84; I2 = 0%), and women with increasing parity. Furthermore, BC risk reduced in women with preeclampsia regardless of their menopausal status and the sex of their offspring.

Conclusions and Relevance:

Overall, women with preeclampsia have a decreased BC risk and increased ovarian cancer risk compared with the normal population. A subgroup analysis stratified by reproductive factors demonstrated that BC risk decreased in the preeclampsia population in parous women, women with full-term pregnancies, and women with increasing parity regardless of their menopausal status and the sex of their offspring.
Vaginal CO2 laser therapy versus sham for genitourinary syndrome of menopause management: a systematic review and meta-analysis of randomized controlled trials
Authors: Khamis Yasser , Abdelhakim Ahmed Mohamed , Labib Kareem , Islam Bassem Aly , Nassar Salma Ashraf , Motaal Ahmed Osama Abdel , Saleh Doaa M. , Abdou Hossam , Abbas Ahmed M. , Mojahed Eman M.
Published: August 2021

Importance:

The research of new therapeutic modalities, especially with energy-based devices, has been increasing nowadays for genitourinary syndrome of menopause (GSM) management. Microablative fractional CO2 laser has been used for pelvic floor dysfunction management.

Objective:

To conduct a systematic review and meta-analysis of randomized controlled trials to compare fractional CO2 laser therapy versus sham therapy for GSM management.

Evidence Review:

We searched for the available randomized clinical trials in Cochrane Library, PubMed, ISI web of science, and Scopus during March 2021. We included randomized clinical trials that compared CO2 laser to sham among postmenopausal women with GSM diagnosis. We extracted the available data from included studies and pooled them in a meta-analysis model using RevMan software. Our main outcomes were total vaginal score assessment using the Vaginal Assessment Scale, sexual function using the Female Sexual Function Index, urinary symptoms using the Urogenital Distress Inventory-6, and satisfaction.

Findings:

Three studies met our inclusion criteria with a total number of 164 women. The CO2 laser was linked to a significant reduction in Vaginal Assessment Scale score when compared with the sham group (mean difference [MD] = −0.49, 95% CI [−0.75 to −0.22], P = 0.004). The CO2 laser was associated with a significant improvement in Female Sexual Function Index score in comparison with sham group (MD = 9.37, 95% CI [6.59-12.14], P < 0.001). In addition, a significant reduction in Urogenital Distress Inventory-6 score was reported among the CO2 laser group (MD = −6.95, 95% CI [−13.24 to −0.67], P = 0.03). More women were significantly satisfied among the CO2 laser group (risk ratio  = 1.98, 95% CI [1.36-2.89], P = 0.004).

Conclusions and Relevance:

CO2 laser therapy is a promising alternative for GSM management. Further randomized trials with larger sample sizes are required to confirm our findings.
Long-term changes in manifest refraction subsequent to cataract surgery
Authors: Hayashi Ken , Yoshida Motoaki , Manabe Shin-ichi , Yoshimura Koichi
Published: August 2021

Purpose:

To examine the long-term refractive changes after stabilization of surgically induced changes (SICs) subsequent to cataract surgery.

Setting:

Private hospital.

Design:

Case–control study.

Methods:

Manifest refraction of 300 eyes of 300 patients who underwent phacoemulsification and 300 eyes of 300 age-matched and sex-matched patients without surgery was examined the day on which SICs stabilized (baseline) and ≥7 years postbaseline using an autorefractometer. Refraction was divided into 3 components: spherical power (M), vertical/horizontal astigmatism (J0), and oblique astigmatism (J45) using power vector analysis, and the components were compared between the 2 timepoints and between groups.

Results:

Data of All 600 eyes were collected. In the surgery group, the mean M and J45 did not change significantly between baseline and ≥7 years postbaseline, but the J0 significantly decreased between the 2 timepoints (P < .001), indicating an against-the-rule (ATR) shift. In the nonsurgery group, the mean M significantly increased and J0 significantly decreased between the timepoints (P < .001), whereas J45 did not change significantly. The mean change in M between the 2 timepoints was significantly smaller in the surgery group (P < .001), whereas the changes in J0 and J45 did not differ significantly between the timepoints.

Conclusions:

Spherical power did not change and refractive astigmatism significantly changed toward ATR astigmatism during the more than 7-year follow-up after stabilization of SICs in pseudophakic eyes, whereas hyperopic and ATR shifts occurred in phakic eyes, and the astigmatic changes were comparable between pseudophakic and phakic eyes.