bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physical Activity Spaces Not Effective against Socioeconomic Inequalities in Myopia Incidence: The Generation R Study
Authors: Enthoven Clair A. , Mölenberg Famke J. M. , Tideman J. Willem L. , Polling Jan Roelof , Labrecque Jeremy A. , Raat Hein , van Lenthe Frank J. , Klaver Caroline C. W. 
Published: November 2021

SIGNIFICANCE
Our findings show that non-Dutch background, lower maternal education, and lower net household income level may be new risk factors for myopia development in the Netherlands. Newly introduced physical activity spaces may not be effective enough in increasing outdoor exposure in children to reduce eye growth.

PURPOSE
The aims of this study were to evaluate socioeconomic inequalities in myopia incidence, eye growth, outdoor exposure, and computer use and to investigate if newly introduced physical activity spaces can reduce eye growth in school-aged children.

METHODS
Participants (N = 2643) from the Dutch population–based birth cohort Generation R were examined at ages 6 and 9 years. Socioeconomic inequalities in myopia incidence, eye growth, and lifestyle were determined using regression analyses. Information on physical activity spaces located in Rotterdam was obtained. Differences in eye growth between those who became exposed to new physical activity spaces (n = 230) and those nonexposed (n = 1866) were evaluated with individual-level fixed-effects models.

RESULTS
Myopia prevalence was 2.2% at age 6 years and 12.2% at age 9 years. Outdoor exposure was 11.4 h/wk at age 6 years and 7.4 h/wk at age 9 years. Computer use was 2.1 h/wk at age 6 years and 5.2 h/wk at age 9 years. Myopia incidence was higher in children with non-Dutch background, and families with lower household income and lower maternal education (odds ratio [OR], 1.081 [95% confidence interval, 1.052 to 1.112]; OR, 1.035 [95% confidence interval, 1.008 to 1.063]; OR, 1.028 [95% confidence interval, 1.001 to 1.055], respectively). Children living <600 m of a physical activity space did not have increased outdoor exposure, except those from families with lower maternal education (β = 1.33 h/wk; 95% confidence interval, 0.15 to 2.51 h/wk). Newly introduced physical activity spaces were not associated with reduction of eye growth.

CONCLUSIONS
Children from socioeconomically disadvantaged families became more often myopic than those from socioeconomically advantaged families. We did not find evidence that physical activity spaces protect against myopia for the population at large, but subgroups may benefit.
Feasibility of Aortic Annular Measurements Using Noncontrast-Enhanced Cardiac Computed Tomography in Preprocedural Evaluation of Transcatheter Aortic Valve Replacement: A Comparison With Contrast-Enhanced Computed Tomography
Authors: Suh Young Joo , Lee Sak , Hong Geu-Ru , Ko Young-Guk , Hong Myeong-Ki , Kim Young Jin 
Published: November 2021

Objective
Noncontrast-enhanced (NCE) cross-sectional images other than contrast-enhanced (CE)-computed tomography (CT) may be necessary for annular sizing before transcatheter aortic valve replacement (TAVR), because of the risk of contrast-induced nephropathy. We aimed to investigate the feasibility of aortic annular measurements using NCE-CT in TAVR candidates by comparing them with CE-CT measurements.

Methods
We retrospectively enrolled 46 patients who underwent CT for the purpose of pre-TAVR evaluation (17 men; mean age, 82.3 ± 5.0 years). On CE and NCE examination, measurements of the average diameter and perimeter of aortic annulus were performed by 2 observers, and coronary ostial heights were measured. Differences in annular parameters and coronary ostial heights between NCE and CE examinations were assessed using Bland-Altman analysis and intraclass correlation coefficients (ICCs).

Results
Aortic annulus measurement values were significantly larger in the NCE examinations compared with those in the CE examinations according to both readers (mean differences of 0.8 mm for the average diameter and 2.1 mm for the perimeter according to observer 1, and 1.1 mm for the average diameter and 3.4 mm for the perimeter according to observer 2; ICC, 0.771–0.923). The mean difference between coronary ostial height measurement on NCE and CE examination was 0.6 mm for left coronary ostium (ICC, 0.795) and 0.7 mm for right coronary ostium (ICC, 0.802). No case showed disagreement between NCE and CE examinations for hypothetical valve sizing.

Conclusions
Noncontrast-enhanced cardiac CT examination may be feasible for aortic annular measurements before TAVR and provides comparable measurement values to CE examination.
Temporomandibular Disorder Patients Benefit From Intramuscular Botulinum Toxin Type a Injections
Authors: Oksanen Erkka , Männistö Ville , Kormi Eeva , Vallioniemi Hanna , Suojanen Juho 
Published: November 2021

Purpose:
The aim of this study was to analyze the clinical outcome of the use of botulinum toxin type A (BTX) intramuscular injections to the head and neck, particularly the masticatory muscles of patients with temporomandibular disorder (TMD).

Methods:
The medical records of all patients who had received intramuscular BTX injections between 2005 and 2018 at Päijät- Häme Central Hospital, Lahti, Finland were analyzed retrospectively. Gender, age, previous medical history, number of injections, injection areas, and therapeutic results were collected and analyzed. The outcome was divided into three categories based on the patients’ subjective reports: not beneficial, beneficial, and highly beneficial.

Results:
A total of 68 patients had received intramuscular BTX injections in our unit for TMD symptoms. Clinical effectiveness could be analyzed from 63 patients. Overall, 87% of them reported fävorable outcomes. 8 (13%) reported BTX injections as not beneficial, 15 (24%) as beneficial, and 40 patients (63%) as highly beneficial.
Most patients had already received conventional treatment with an occlusal splint (93%) combined with pain medication (60%) in the primary care units before they were referred to our hospital.
There were 59 (83%) female patients, and they responded better to BTX therapy than the male patients: 91% versus 57% (P value = 0.04). Average age at the first BTX injection visit was 44.6 years (range 17.8–77.2). Most commonly (65%), BTX was divided bilaterally to the masseter and temporalis muscles.

Conclusions:
BTX injections had good therapeutic outcomes for our TMD patients. However, most patients require multiple injection visits.
A Novel Method for Correction of the Tethered and Contracted Facial Scars: The Three-Dimensional Subcutaneous Z-Plasty
Authors: Demir Can Ilker , Yaşar Emrah Kağan , Alagöz Murat Şahin 
Published: November 2021

Objective:
Scar revision is 1 of the basic surgery in the field of plastic and reconstructive surgery. The classic treatment of the scar is excision scarless tissue, wide undermining and suture by planes. This method has had unsatisfying results on contracted and tethered scars. The aim of this study is to present the three-dimensional subcutaneous z-plasty technique for correction of tethered facial scars without scar lengthening.

Materials and Methods:
Twenty tethered scars were corrected using this technique. All scars were located on the face. Objectively, the final result was evaluated by using the Stony Brook Scar Evaluation Scale. Subjectively, patients’ overall satisfaction was assessed 1 year after the surgical operation. In addition, the information on the age, gender, etiology, scar location, scar length, type of anesthesia, and follow-up period were examined.

Results:
This procedure was used in nineteen patients (8 males and eleven females). The mean follow-up period was 15.3 months. There was a mean increase of 2.85 points increase in the Stony Brook Scar Evaluation Scale value. The overall success rates for the procedure, as assessed by the patients, were: very satisfied in 12 patients, satisfied in 5 patients, and slightly satisfied in 2 patients. One patient had minimal wound dehiscence. No complications including hypertrophic scar, infection, hematoma, and suture reaction were observed in any patients.

Conclusions:
The three-dimensional subcutaneous z-plasty technique is a procedure that uses only basic plastic surgery principles. It offers a good solution for the correction of tethered and contracted scars without recurrence. This technique combines the advantages of elliptical excision and z-plasty by enabling the augmentation of the depressed area without extending the scar length.
Difference in the ascending reticular activating system between vegetative and minimally conscious states following traumatic brain injury
Authors: Jang Sung Ho , Kim Seong Ho , Kim Jae Woon , Lee Han Do , Cho Min Kyeong 
Published: November 2021

Objectives
We investigated differences in the ascending reticular activating system (ARAS) between vegetative state (VS) and minimally conscious state (MCS) in patients with traumatic brain injury (TBI) by using diffusion tensor tractography.

Methods
We recruited TBI patients and normal subjects. We reconstructed the lower ARAS and five parts of upper ARAS [prefrontal cortex (PFC), premotor cortex, primary motor cortex, primary somatosensory cortex, and posterior parietal cortex].

Results
Significant differences were observed in the fractional anisotropy (FA) and fiber number (FN) values of the five parts of upper ARAS between the VS and control groups and between the MCS and control groups (P < 0.05), but no differences were detected in the lower ARAS (P > 0.05). The FA and FN values of the PFC in the upper ARAS were significantly different between the VS and MCS groups (P < 0.05). No other significant differences in FA and FN values were detected among the other segments of the upper ARAS or in the lower ARAS (P > 0.05).

Conclusion
The results indicate that the prefrontal portion of the upper ARAS is the critical area for distinguishing between VS and MCS in patients with TBI.
Parent-of-origin effects in the UK Biobank
Authors: Hofmeister R. J. , Rubinacci S. , Ribeiro D. M. , Kutalik Z. , Buil A. , Delaneau O. 
Published: November 2021

AbstractIdentical genetic variations can have different phenotypic effects depending on their parent of origin (PofO). Yet, studies focussing on PofO effects have been largely limited in terms of sample size due to the need of parental genomes or known genealogies. Here, we used a novel probabilistic approach to infer PofO of individual alleles in the UK Biobank that does not require parental genomes nor prior knowledge of genealogy. Our model uses Identity-By-Descent (IBD) sharing with second- and third-degree relatives to assign alleles to parental groups and leverages chromosome X data in males to distinguish maternal from paternal groups. When combined with robust haplotype inference and haploid imputation, this allowed us to infer the PofO at 5.4 million variants genome-wide for 26,393 UK Biobank individuals. We used this large dataset to systematically screen 59 biomarkers and 38 anthropomorphic phenotypes for PofO effects and discovered 101 significant associations, demonstrating that this type of effects contributes to the genetics of complex traits. Notably, we retrieved well known PofO effects, such as the MEG3/DLK1 locus on platelet count, and we discovered many new ones at loci often unsuspected of being imprinted and, in some cases, previously thought to harbour additive associations.
Octopamine drives honeybee thermogenesis
Authors: Kaya-Zeeb Sinan , Engelmayer Lorenz , Bayer Jasmin , Bähre Heike , Seifert Roland , Scherf-Clavel Oliver , Thamm Markus 
Published: November 2021

AbstractIn times of environmental change species have two options to survive: they either relocate to a new habitat or they adapt to the altered environment. Adaptation requires physiological plasticity and provides a selection benefit. In this regard, the Western honeybee (Apis mellifera) protrudes with its thermoregulatory capabilities, which enables a nearly worldwide distribution. Especially in the cold, shivering thermogenesis enables foraging as well as proper brood development and thus survival. In this study, we present octopamine signaling as a neurochemical prerequisite for honeybee thermogenesis: we were able to induce hypothermia by depleting octopamine in the flight muscles. Additionally, we could restore the ability to increase body temperature by administering octopamine. Thus we conclude, that octopamine is necessary and sufficient for thermogenesis. Moreover, we show that these effects are mediated by β octopamine receptors. The significance of our results is highlighted by the fact the respective receptor genes underlie enormous selective pressure due to adaptation to cold climates. Finally, octopamine signaling in the service of thermogenesis might be a key strategy to survive in a changing environment.
GAPDH cooperativity mediates drug resistance and metabolism in Plasmodium fal-ciparum malaria parasites
Authors: Jezewski Andrew J. , Guggisberg Ann M. , Hodge Dana M. , Ghebremichael Naomi , McLellan Lisa K. , Odom John Audrey R. 
Published: November 2021

ABSTRACTEfforts to control the global malaria health crisis are undermined by antimalarial resistance. Iden-tifying mechanisms of resistance will uncover the underlying biology of the Plasmodium falciparum malaria parasites that allow evasion of our most promising therapeutics and may reveal new drug targets. We utilized fosmidomycin (FSM) as a chemical inhibitor of plastidial isoprenoid biosynthesis through the methylerythritol phosphate (MEP) pathway. We have thus identified an unusual metabolic regulation scheme in the malaria parasite through the essential glycolytic enzyme, glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Two parallel genetic screens converged on independent but functionally analogous resistance alleles in GAPDH. Metabolic profiling of FSM-resistant gapdh mutant parasites indicates that neither of these mutations disrupt overall glycolytic output. While FSM-resistant GAPDH variant proteins are catalytically active, they have reduced assembly into the homotetrameric state favored by wild-type GAPDH. Disrupted oligomerization of FSM-resistant GAPDH variant proteins is accompanied by altered enzymatic cooperativity and reduced susceptibility to inhibition by free heme. Together, our data identifies a new genetic biomarker of FSM-resistance and reveals the central role of GAPDH cooperativity in MEP pathway control and antimalarial sensitivity.
Efficient transformation and genome editing of watermelon assisted by genes that encode developmental regulators
Authors: Pan Wenbo , Cheng Zhentao , Han Zhiguo , Yang Hong , Zhang Wanggen , Zhang Huawei 
Published: November 2021

AbstructThe Cucurbitaceae contains multiple species of important food plants. But most of them are difficult to be genetically transformed. Watermelon is one of the most important fruit species of Cucurbitaceae, and it is a model horticulture crops. Its low transgenic efficiency is the major bottleneck in functional genome research and genome editing-based breeding. Here, with the help of genes that encode developmental regulators (DRs), in particular AtGRF5, and an appropriate Agrobacterium strain (GV3101), we have significantly increased the transformation efficiency of watermelon to about 25%, which is a 40-fold increase compared with a traditional vector. AtGRF5-mediated transformation increased the number of transformable watermelon genotypes without causing obvious side effects. Moreover, when applying this strategy to CRISPR/Cas9-mediated genome editing, clpds knockout mutants were generated in the T0 generation. Our results show that AtGRF5 is a powerful and robust tool to effectively create transgenic plants or knockout mutations in watermelon. Similar strategies using DRs might also be able to overcome the transformation barriers in many other Cucurbitaceae species.
Discrete-to-analog signal conversion in human pluripotent stem cells
Authors: Prochazka Laura , Michaels Yale S. , Lau Charles , Siu Mona , Yin Ting , Wu Diana , Jang Esther , Jones Ross D. , Vázquez-Cantú Mercedes , Gilbert Penney M. , Kaul Himanshu , Benenson Yaakov , Zandstra Peter W. 
Published: November 2021

AbstractDuring development, state transitions are coordinated through changes in the identity of molecular regulators in a cell state- and dose specific manner. The ability to rationally engineer such functions in human pluripotent stem cells (hPSC) will enable numerous applications in regenerative medicine. Herein we report the generation of synthetic gene circuits that can detect a discrete cell state, and upon state detection, produce fine-tuned effector proteins in a programmable manner. Effectively, these gene circuits convert a discrete (digital-like) cell state into an analog signal by merging AND-like logic integration of endogenous miRNAs (classifiers) with a miRNA-mediated output fine-tuning technology (miSFITs). Using an automated miRNA identification and model-guided circuit optimization approach, we were able to produce robust cell state specific and graded output production in undifferentiated hPSC. We further finely controlled the levels of endogenous BMP4 secretion, which allowed us to document the effect of endogenous factor secretion in comparison to exogenous factor addition on early tissue development using the hPSC-derived gastruloid system. Our work provides the first demonstration of a discrete-to-analog signal conversion circuit operating in living hPSC, and a platform for customized cell state-specific control of desired physiological factors, laying the foundation for programming cell compositions in hPSC-derived tissues and beyond.Graphical Abstract
Differential ion dehydration energetics explains selectivity in the non-canonical lysosomal K+ channel TMEM175
Authors: Oh SeCheol , Marinelli Fabrizio , Zhou Wenchang , Lee Jooyeon , Choi Ho Jeong , Kim Min , Faraldo-Gómez José D. , Hite Richard K. 
Published: November 2021

AbstractStructures of the human lysosomal K+ channel TMEM175 in open and closed states revealed a novel architecture lacking the canonical K+ selectivity filter motif present in previously known K+ channel structures. A hydrophobic constriction composed of four isoleucine residues was resolved in the pore and proposed to serve as the gate in the closed state, and to confer ion selectivity in the open state. Here, we achieve higher-resolution structures of the open and closed states and employ molecular dynamics simulations to analyze the conducting properties of the putative open state, demonstrating that it is capable of permeating K+ ions at the expected rate. Monovalent cations must dehydrate significantly to penetrate the narrow hydrophobic constriction, but ion flow is assisted by a favorable electrostatic field generated by the protein that spans the length of the pore. The balance of these opposing energetic factors explains why permeation is feasible, and why TMEM175 is selective for K+ over Na+, despite the absence of the canonical selectivity filter. Accordingly, mutagenesis experiments reveal an exquisite sensitivity of the channel to perturbations that mitigate the constriction. Together, these data reveal a novel mechanism for selective permeation of ions by TMEM175 that is unlike that of other K+ channels.
Transcriptional regulation of sphingolipid metabolism in budding yeast
Authors: Komatsu Nao , Ishino Yuko , Shirai Rina , Sakata Ken-taro , Tani Motohiro , Maeda Tatsuya , Tanaka Naotaka , Tabuchi Mitsuaki 
Published: November 2021

AbstractGlobal control for the synthesis of lipids constituting a bilayer of cell membranes is known to be with a small number of transcription factors called master transcriptional regulators, which target a wide range of genes encoding lipid metabolism enzymes and/or their regulators. Although master transcriptional regulators of glycerophospholipids and sterols have been identified in both yeast and mammals, this aspect of sphingolipid metabolism is not yet understood. In the present study, we identified the C2H2-type zinc finger transcription factor, Com2, as a master transcriptional regulator of sphingolipid metabolism in the budding yeast, Saccharomyces cerevisiae. The target of rapamycin complex 2 (TORC2)-activated protein kinase Ypk1 is known to regulate sphingolipid metabolism. Activated Ypk1 stimulates the activity of serine palmitoyl transferase (SPT), the first-step enzyme in sphingolipid biosynthesis, by phosphorylating and inhibiting Orm1/2, a negative regulator of SPT. This regulation of SPT activity is thought to be a major pathway in the regulation of sphingolipid metabolism. In the present study, we found that inhibition of sphingolipid synthesis upregulates the expression of Com2, which in turn leads to the concomitant expression of Ypk1. The upregulation of Ypk1 expression was found to be dependent on a putative Com2-binding site in the YPK1 promoter. Our results also suggested that Com2 senses intracellular sphingolipid levels through a pathway independent of TORC2-Ypk1-mediated sensing of sphingolipids. Our results revealed an additional layer of mechanistic regulation that allows cells to maintain appropriate levels of sphingolipid biosynthesis and to rapidly induce this process in response to environmental stresses.Significance StatementOne of the major regulatory mechanisms involved in the control of lipid metabolism in bilayers of biological membranes is regulation at the transcriptional level by master transcriptional regulators that control the transcription of genes encoding lipid metabolism enzymes and/or their regulators. In the present study, we identified the C2H2-type zinc finger transcription factor Com2 as a master transcriptional regulator in sphingolipid metabolism. We found that Com2 regulates sphingolipid metabolism by transcriptionally controlling the expression of Ypk1, which regulates Orm1/2, a negative regulator of serine palmitoyl transferase, the first-step enzyme in sphingolipid biosynthesis, through phosphorylation. Our study revealed a new layer of regulation that allows the maintenance of an appropriate level of sphingolipid biosynthesis for a rapid response to environmental stresses.