bluuebunny/crossref_metadata_2025 huggingface dataset:
The chimeric GaaR-XlnR transcription factor induces pectinolytic activities in the presence of D-xylose in Aspergillus niger
Authors: Kun Roland S. , Garrigues Sandra , Di Falco Marcos , Tsang Adrian , de Vries Ronald P.
Published: July 2021

Aspergillus niger is a filamentous fungus well known for its ability to produce a wide variety of pectinolytic enzymes, which have many applications in the industry. The transcriptional activator GaaR is induced by 2-keto-3-deoxy-L-galactonate, a compound derived from D-galacturonic acid, and plays a major role in the regulation of pectinolytic genes. The requirement for inducer molecules can be a limiting factor for the production of enzymes. Therefore, the generation of chimeric transcription factors able to activate the expression of pectinolytic genes by using underutilized agricultural residues would be highly valuable for industrial applications. In this study, we used the CRISPR/Cas9 system to generate three chimeric GaaR-XlnR transcription factors expressed by the xlnR promoter by swapping the N-terminal region of the xylanolytic regulator XlnR to that of the GaaR in A. niger. As a test case, we constructed a PpgaX-hph reporter strain to evaluate the alteration of transcription factor specificity in the chimeric mutants. Our results showed that the chimeric GaaR-XlnR transcription factor was induced in the presence of D-xylose. Additionally, we generated a constitutively active GaaR-XlnR V756F version of the most efficient chimeric transcription factor to better assess its activity. Proteomics analysis confirmed the production of several pectinolytic enzymes by ΔgaaR mutants carrying the chimeric transcription factor. This correlates with the improved release of D-galacturonic acid from pectin by the GaaR-XlnR V756F mutant, as well as by the increased L-arabinose release from the pectin side chains by both chimeric mutants under inducing condition, which is required for efficient degradation of pectin.

Key points

• Chimeric transcription factors were generated by on-site mutations using CRISPR/Cas9.

• PpgaX-hph reporter strain allowed for the screening of functional GaaR-XlnR mutants.

• Chimeric GaaR-XlnR induced pectinolytic activities in the presence of D-xylose.
Male aggressiveness and risk-taking during reproduction are repeatable but not correlated in a wild bird population
Authors: Salazar Stephen M. , García Julia I. Camacho , Kuspiel Miriam , Fokkema Rienk W. , Komdeur Jan , Korsten Peter
Published: July 2021

The existence of among-individual variation in behaviour within populations is poorly understood. Recent theory suggests that fine-scale individual differences in investment into current versus future reproduction may lead to a ‘slow-fast’-pace-of-life continuum, also referred to as the ‘pace-of-life-syndrome’ (POLS) hypothesis. According to this idea, individuals are predicted to differ in their level of risk-taking, which may drive among-individual variation and covariation of behaviours. Consistent individual differences in aggression, an ecologically relevant and potentially risky behaviour, have been reported across the animal kingdom. Here we test whether such individual differences in aggression are a manifestation of underlying differences in risk-taking. In a wild blue tit (Cyanistes caeruleus) population, we used standard behavioural tests to investigate if male territorial aggressiveness and risk-taking during breeding are positively related. At the start of breeding, we simulated conspecific territorial intrusions to obtain repeated measures of male aggressiveness. Subsequently, we measured male risk-taking as their latency to resume brood provisioning after presenting two different predators at their nest: human and sparrowhawk, a common predator of adult songbirds. First, we found substantial repeatability for male aggressiveness (R = 0.56 ± 0.08 SE). Second, while males took longer to resume provisioning after presentation of a sparrowhawk mount as compared to a human observer, risk-taking was repeatable across these two predator contexts (R = 0.51 ± 0.13 SE). Finally, we found no evidence for a correlation between male aggressiveness and risk-taking, thereby providing little support to a main prediction of the POLS hypothesis.

Significance statement

Consistent, and often correlated, individual differences in basal behaviours, such as aggression, exploration and sociability, are found across the animal kingdom. Why individuals consistently differ in their behaviour is poorly understood, as behavioural traits would seem inherently flexible. The ‘pace-of-life syndrome’ (POLS) hypothesis proposes observed behavioural variation to reflect differences in risk-taking associated with individual reproductive strategies. We tested this idea in a wild blue tit population by investigating whether individual males that were more aggressive toward territorial intruders also took more risk when provisioning their nestlings under a threat of predation. While we found consistent individual differences in both aggressiveness and risk-taking, these behaviours were not significantly correlated. Therefore, our study demonstrates among-individual variation in ecologically relevant behaviours in wild blue tits but provides little support for the POLS hypothesis.
Role of bile acids in inflammatory liver diseases
Authors: Evangelakos Ioannis , Heeren Joerg , Verkade Esther , Kuipers Folkert
Published: July 2021

Bile acids and their signaling pathways are increasingly recognized as potential therapeutic targets for cholestatic and metabolic liver diseases. This review summarizes new insights in bile acid physiology, focusing on regulatory roles of bile acids in the control of immune regulation and on effects of pharmacological modulators of bile acid signaling pathways in human liver disease. Recent mouse studies have highlighted the importance of the interactions between bile acids and gut microbiome. Interfering with microbiome composition may be beneficial for cholestatic and metabolic liver diseases by modulating formation of secondary bile acids, as different bile acid species have different signaling functions. Bile acid receptors such as FXR, VDR, and TGR5 are expressed in a variety of cells involved in innate as well as adaptive immunity, and specific microbial bile acid metabolites positively modulate immune responses of the host. Identification of Cyp2c70 as the enzyme responsible for the generation of hydrophilic mouse/rat-specific muricholic acids has allowed the generation of murine models with a human-like bile acid composition. These novel mouse models will aid to accelerate translational research on the (patho)physiological roles of bile acids in human liver diseases .
Wilhelm His Sr. and the development of paraffin embedding
Authors: van der Lem Tim , de Bakker Merijn , Keuck Gerhard , Richardson Michael K.
Published: July 2021

Paraffin histology is one of the most important and commonly-used laboratory techniques in diagnostic histopathology. The discovery of paraffin embedding is often attributed to the pathologist Edwin Klebs. Klebs was following the lead of Stricker, who embedded embryos in a mixture of hot stearin and white beeswax. We show that Klebs experimented with paraffin wax for embedding tumour tissue. But he quickly rejected it as unsuitable because paraffin wax did not infiltrate the tissue. One of Klebs’ correspondents, embryologist Wilhelm His, Sr., learned of Klebs’ experiments and decided to try paraffin embedding. His dehydrated chicken embryos in alcohol, cleared them in lavender oil, and dripped hot paraffin wax onto them. This process allowed His to cut good sections. Here, we have replicated His’s paraffin embedding protocol in order to determine whether His had indeed made the landmark discovery of infiltration embedding with paraffin wax. We followed the protocol that he gives in his 1868 monograph on the early development of the chicken. The protocol described by His failed, in our hands, to yield sections of the quality that he illustrates in his monograph. Typically, the tissue disintegrated when sectioned due to poor infiltration of the wax. Usable sections could only be obtained if His’s protocol was modified by melting the embedded embryos in fresh paraffin wax. One explanation for our findings is that we failed to faithfully replicate His’s protocol. Another is that his protocol was incomplete. We suggest that His is likely to have discovered and perfected infiltration embedding with paraffin wax but did not publish a complete protocol.
Axial spondyloarthritis and inflammatory bowel disease: association between disease activity and endothelial dysfunction markers
Authors: Przepiera-Będzak Hanna , Fischer Katarzyna , Brzosko Marek
Published: July 2021

Objective

We aimed to assess patients with axial spondyloarthritis (axSpA) and inflammatory bowel disease (IBD) for disease activity and serum markers of endothelial dysfunction.

Methods

We studied 161 patients (123 males, 38 females) with axSpA: 153 with ankylosing spondylitis and 8 with non-radiographic axSpA, and 30 healthy controls (HC). We collected: age; sex; disease duration; extra-articular symptoms (IBD and acute anterior uveitis), comorbidities; human leukocyte antigen B27 status; and treatment. We measured serum interleukin (IL)-6, interleukin-18, IL-23, vascular endothelial growth factor (VEGF) epidermal growth factor (EGF), asymmetric dimethylarginine (ADMA), endothelin-1 (ET-1), and fetuin-A levels.

Results

IBD was diagnosed in 19 (11.8%) patients with axSpA. Compared to patients with axSpA without IBD, those with IBD had higher serum C-reactive protein (CRP) level (p = 0.05), erythrocyte sedimentation rate (ESR) (p = 0.005), and serum ET-1 levels (p = 0.01). In patients with axSpA and IBD, ET-1 levels correlated positively with CRP level (p = 0.006) and ESR (p = 0.02), and ADMA levels with visual analog scale scores (p = 0.01). Patients with axSpA and IBD had higher serum levels of IL-6 (p = 0.01), IL-18 (p = 0.005), and ADMA (p = 0.01) and lower serum levels of fetuin-A (p = 0.01) than did controls.

Conclusions

Patients with axSpA and IBD had higher levels of disease activity, as assessed by ESR and CRP and ET-1 levels, than did patients with axSpA without IBD. Compared to HC, patients with axSpA and IBD had increased IL-18, ADMA levels and decreased fetuin-A level.
Results after primary reverse shoulder arthroplasty with and without subscapularis repair: a prospective-randomized trial
Authors: Engel Nina Myline , Holschen Malte , Schorn Domink , Witt Kai-Axel , Steinbeck Jörn
Published: July 2021

Introduction

Indications for reverse shoulder arthroplasties (rTSA) have increased since their development by Paul Grammont in 1985. Prosthesis design was enhanced over time, but the management of the tendon of the M. subscapularis (SSC-tendon) in primary rTSA is still a controversial subject with regard to perform a refixation or not.

Methods

50 patients were randomized in a refixation group (A) and a non-refixation-group (B) of the SSC-tendon in a double-blinded fashion. SSC-function was assessed at baseline before surgery, such as 3 and 12 months after surgery. Constant–Murley-Shoulder Score (CS), American Shoulder and Elbow Surgeons Score (ASES), strength, range of motion (ROM), and pain on numeric rating scale (NRS) were measured in all examinations. An ultrasound examination of the shoulder was performed for evaluation of subscapularis tendon integrity at 3 and 12 month follow-up visits. Pain was evaluated on NRS via phone 5 days after surgery. Surgery was performed by a single experienced senior surgeon in all patients.

Results

Patients with a refixation of the SSC-tendon and primary rTSA had improved internal rotation [40° (20°–60°) vs. 32° (20°–45°); p = 0.03] at 12 months of follow-up. Additionally, the A-group had increased CS [74 (13–90) vs. 69.5 (40–79); p = 0.029] 1 year after surgery. Results were strengthened by subgroup analysis of successful refixation in ultrasound examination vs. no refixation. No differences were seen in ASES and NRS 1 year after rTSA.

Conclusion

SSC-tendon repair in rTSA improves CS and internal rotation 12 months after surgery.
A structured group intervention (TüTASS) with focus on self-perception and mindfulness for children with autism spectrum disorder, ASD. A pilot study
Authors: Drüsedau Laura , Schoba Anja , Conzelmann Annette , Sokolov Alexander , Hautzinger Martin , Renner Tobias J. , Barth Gottfried M.
Published: July 2021

Autism spectrum disorders (ASD) represent a set of long-lasting severe neurodevelopmental conditions and effective therapeutic interventions are needed. Recent research points to the importance of including mindfulness-based elements to improve emotion and body perception in the psychotherapy of patients with ASD. Therefore, we developed a structured group psychotherapy program The Tübinger Training for Autism Spectrum Disorders (Tübinger Training für Autismus-Spektrum-Störungen; TüTASS) which focuses on mindfulness-based training elements. This pilot study accompanying the TüTASS reports the first results on the feasibility of the program with a pre-post comparison of 25 treated children with ASD. The psychometric assessment comprised five standardized questionnaires/ scales evaluating on the basis of parents and patients self-reports the child’s social responsiveness, behavior, strengths and difficulties, quality of life, and depressive symptoms before and after training completion. The results indicated that upon training completion, symptoms with respect to emotional and social problems, externalizing behavior, and attentional and schizoid-compulsive behavior substantially declined. In a questionnaire assessing feasibility and quality of the group training, patients and parents found the therapy highly beneficial, especially as to the focus on emotions and body, and strengths and failures. This training program was developed to bridge the gap of lacking mindfulness-based interventions with the aim to optimize the course of ASD, especially with respect to behavioral disturbances and social-emotional problems.
The angiographic presentation of European Moyamoya angiopathy
Authors: Pilgram-Pastor Sara , Chapot René , Kraemer Markus
Published: July 2021

Background and purpose

Little is known about the angiographic presentation of Moyamoya angiopathy (MMA) in non-Asian patients.

Methods

Conventional cerebral angiograms from 155 Caucasian patients diagnosed as MMA were analyzed with respect to extracranial champagne bottle neck sign, Suzuki stages, collateral status, as well as presence of aneurysms and posterior cerebral artery stenosis.

Results

In 84 of 155 angiograms, the extracranial carotid artery was visualized, in 65 of them (77.4%), a champagne bottle neck sign was noted. Of the 278 analyzable hemispheres, 13.7%,11.2%, 37.8%, 27.3%, 8.6%, and 1.4% were classified as Suzuki stage I, stage II, stage III, stage IV, stage V, and stage VI, respectively. Among 280 hemispheres, in 53 hemispheres (18.9%) isolated basal collaterals (pathway I) and in 104 hemispheres (37.1%) choroidal and pericallosal collaterals (including basal collaterals, pathway II) were found. In 74 hemispheres (26.4%) ethmoidal collaterals (pathways III), and in 17 hemispheres (6.1%) vault collaterals were visualized. Patients with higher Suzuki stages IV–VI (p = 0.008) and ethmoidal collaterals (p < 0.001) suffered more often from cerebral hemorrhage. Transient ischemic attacks occurred more frequently in patients with Suzuki stage I to III (p < 0.001). In 10 of 155 patients (6.5%), the angiogram revealed a cerebral aneurysm. In 13 patients (8.4%), a stenotic P1 segment of the posterior cerebral artery was found.

Conclusions

This is so far the largest observational study about angiography in Caucasian European MMA patients. A comparison with Asian data indicates similarity of disease in Caucasian and Asian patients.
The Castrop formula for calculation of toric intraocular lenses
Authors: Langenbucher Achim , Szentmáry Nóra , Cayless Alan , Weisensee Johannes , Wendelstein Jascha , Hoffmann Peter
Published: July 2021

Purpose

To explain the concept behind the Castrop toric lens (tIOL) power calculation formula and demonstrate its application in clinical examples.

Methods

The Castrop vergence formula is based on a pseudophakic model eye with four refractive surfaces and three formula constants. All four surfaces (spectacle correction, corneal front and back surface, and toric lens implant) are expressed as spherocylindrical vergences. With tomographic data for the corneal front and back surface, these data are considered to define the thick lens model for the cornea exactly. With front surface data only, the back surface is defined from the front surface and a fixed ratio of radii and corneal thickness as preset. Spectacle correction can be predicted with an inverse calculation.

Results

Three clinical examples are presented to show the applicability of this calculation concept. In the 1st example, we derived the tIOL power for a spherocylindrical target refraction and corneal tomography data of corneal front and back surface. In the 2nd example, we calculated the tIOL power with keratometric data from corneal front surface measurements, and considered a surgically induced astigmatism and a correction for the corneal back surface astigmatism. In the 3rd example, we predicted the spherocylindrical power of spectacle refraction after implantation of any toric lens with an inverse calculation.

Conclusions

The Castrop formula for toric lenses is a generalization of the Castrop formula based on spherocylindrical vergences. The application in clinical studies is needed to prove the potential of this new concept.
The effect of the menstrual cycle and hyperglycaemia on hormonal and metabolic responses during exercise
Authors: Hulton A. T. , Malone J. J. , Campbell I. T. , MacLaren D. P. M.
Published: July 2021

Purpose

Variations in substrate metabolism have been identified in women during continuous steady-state aerobic exercise performed at the same relative intensity throughout discrete phases of the menstrual cycle, although some evidence exists that this is abolished when carbohydrate is ingested. This investigation examined the effects of a supraphysiologic exogenous glucose infusion protocol, administered during two phases of the menstrual cycle (follicular and luteal) in eumenorrheic women to identify differences between metabolic, hormonal and substrate oxidative responses.

Methods

During the experimental conditions, blood glucose was infused intravenously at rates to “clamp” blood glucose at 10 mM in seven healthy females (age 20 ± 1 y, mass 55.0 ± 4.1 kg, $$\dot V{O_{2peak}}$$

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40.0 ± 1.8 ml/kg/min). Following 30 min of seated rest, participants exercised on a cycle ergometer for 90 min at 60% $$\dot V{O_{2peak}}$$

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. During the rest period and throughout exercise, blood metabolites and hormones were collected at regular intervals, in addition to expired air for the measurement of substrate oxidation.

Results

Significant differences between ovarian hormones and menstrual phase were identified, with estrogen significantly higher during the luteal phase compared to the follicular phase (213.28 ± 30.70 pmol/l vs 103.86 ± 13.85 pmol/l; p = 0.016), and for progesterone (14.23 ± 4.88 vs 2.11 ± 0.36 nmol/l; p = 0.042). However, no further significance was identified in any of the hormonal, metabolite or substrate utilisation patterns between phases.

Conclusion

These data demonstrate that the infusion of a supraphysiological glucose dose curtails any likely metabolic influence employed by the fluctuation of ovarian hormones in eumenorrheic women during moderate exercise.
Sudden cessation of fluoxetine before alcohol drinking reinstatement alters microglial morphology and TLR4/inflammatory neuroadaptation in the rat brain
Authors: Aranda Jesús , Fernández-Arjona María del Mar , Alén Francisco , Rivera Patricia , Rubio Leticia , Smith-Fernández Inés , Pavón Francisco Javier , Serrano Antonia , Serrano-Castro Pedro J. , Rodríguez de Fonseca Fernando , Suárez Juan
Published: July 2021

Preclinical studies on the effects of abrupt cessation of selective serotonin reuptake inhibitors (SSRIs), a medication often prescribed in alcohol use disorder (AUD) patients with depression, results in alcohol consumption escalation after resuming drinking. However, a potential neuroinflammatory component on this escalation remains unexplored despite the immunomodulatory role of serotonin. Here, we utilized a rat model of 14-daily administration of the SSRI fluoxetine (10 mg/kg/day) along alcohol self-administration deprivation to study the effects of fluoxetine cessation on neuroinflammation after resuming alcohol drinking. Microglial morphology and inflammatory gene expression were analyzed in prelimbic cortex, striatum, basolateral amygdala and dorsal hippocampus. Results indicated that alcohol drinking reinstatement increased microglial IBA1 immunoreactivity and altered morphometric features of activated microglia (fractal dimension, lacunarity, density, roughness, and cell area, perimeter and circularity). Despite alcohol reinstatement, fluoxetine cessation modified microglial morphology in a brain region-specific manner, resulting in hyper-ramified (spatial complexity of branching), reactive (lower heterogeneity and circularity)-like microglia. We also found that microglial cell area correlated with changes in mRNA expression of chemokines (Cx3cl1/fractalkine, Cxcl12/SDF1α, Ccl2/MCP1), cytokines (IL1β, IL6, IL10) and the innate immune toll-like receptor 4 (TLR4) in dorsal hippocampus. Specifically, TLR4 correlated with microglial spatial complexity assessed by fractal dimension in striatum, suggesting a role in process branching. These findings suggest that alcohol drinking reinstatement after fluoxetine treatment cessation disturbs microglial morphology and reactive phenotype associated with a TLR4/inflammatory response to alcohol in a brain region-specific manner, facts that might contribute to alcohol-induced damage through the promotion of escalation of alcohol drinking behavior.
Cortical visual area CSv as a cingulate motor area: a sensorimotor interface for the control of locomotion
Authors: Smith Andrew T.
Published: July 2021

The response properties, connectivity and function of the cingulate sulcus visual area (CSv) are reviewed. Cortical area CSv has been identified in both human and macaque brains. It has similar response properties and connectivity in the two species. It is situated bilaterally in the cingulate sulcus close to an established group of medial motor/premotor areas. It has strong connectivity with these areas, particularly the cingulate motor areas and the supplementary motor area, suggesting that it is involved in motor control. CSv is active during visual stimulation but only if that stimulation is indicative of self-motion. It is also active during vestibular stimulation and connectivity data suggest that it receives proprioceptive input. Connectivity with topographically organized somatosensory and motor regions strongly emphasizes the legs over the arms. Together these properties suggest that CSv provides a key interface between the sensory and motor systems in the control of locomotion. It is likely that its role involves online control and adjustment of ongoing locomotory movements, including obstacle avoidance and maintaining the intended trajectory. It is proposed that CSv is best seen as part of the cingulate motor complex. In the human case, a modification of the influential scheme of Picard and Strick (Picard and Strick, Cereb Cortex 6:342–353, 1996) is proposed to reflect this.
Wrist and finger motor representations embedded in the cerebral and cerebellar resting-state activation
Authors: Kusano Toshiki , Kurashige Hiroki , Nambu Isao , Moriguchi Yoshiya , Hanakawa Takashi , Wada Yasuhiro , Osu Rieko
Published: July 2021

Several functional magnetic resonance imaging (fMRI) studies have demonstrated that resting-state brain activity consists of multiple components, each corresponding to the spatial pattern of brain activity induced by performing a task. Especially in a movement task, such components have been shown to correspond to the brain activity pattern of the relevant anatomical region, meaning that the voxels of pattern that are cooperatively activated while using a body part (e.g., foot, hand, and tongue) also behave cooperatively in the resting state. However, it is unclear whether the components involved in resting-state brain activity correspond to those induced by the movement of discrete body parts. To address this issue, in the present study, we focused on wrist and finger movements in the hand, and a cross-decoding technique trained to discriminate between the multi-voxel patterns induced by wrist and finger movement was applied to the resting-state fMRI. We found that the multi-voxel pattern in resting-state brain activity corresponds to either wrist or finger movements in the motor-related areas of each hemisphere of the cerebrum and cerebellum. These results suggest that resting-state brain activity in the motor-related areas consists of the components corresponding to the elementary movements of individual body parts. Therefore, the resting-state brain activity possibly has a finer structure than considered previously.
Convergence results for an averaged LQR problem with applications to reinforcement learning
Authors: Pesare Andrea , Palladino Michele , Falcone Maurizio
Published: July 2021

In this paper, we will deal with a linear quadratic optimal control problem with unknown dynamics. As a modeling assumption, we will suppose that the knowledge that an agent has on the current system is represented by a probability distribution $$\pi $$
π
on the space of matrices. Furthermore, we will assume that such a probability measure is opportunely updated to take into account the increased experience that the agent obtains while exploring the environment, approximating with increasing accuracy the underlying dynamics. Under these assumptions, we will show that the optimal control obtained by solving the “average” linear quadratic optimal control problem with respect to a certain $$\pi $$
π
converges to the optimal control driven related to the linear quadratic optimal control problem governed by the actual, underlying dynamics. This approach is closely related to model-based reinforcement learning algorithms where prior and posterior probability distributions describing the knowledge on the uncertain system are recursively updated. In the last section, we will show a numerical test that confirms the theoretical results.
Disparities in access to mobile devices and e-health literacy among breast cancer survivors
Authors: Moon Zoe , Zuchowski Mira , Moss-Morris Rona , Hunter Myra S. , Norton Sam , Hughes Lyndsay D.
Published: July 2021

Background

The number of e-health interventions developed for breast cancer survivors continues to increase. However, issues with engagement and retention are common. This study aimed to explore e-health literacy rates and access to smartphones and tablets in a large sample of breast cancer survivors.

Methods

In study 1, women were recruited from outpatient breast clinics across England and Wales. Eligible women were asked to complete a questionnaire pack to assess their access to devices and their e-health literacy. Multiple regression analyses were run to assess the relationship between technology access and e-health literacy with sociodemographic variables such as age, social deprivation, and education. Study 2 presents a smaller sample recruited through social media who answered a questionnaire relating to use of mobile devices and e-health, and apps.

Results

Two thousand nine women participated in the study. Seventy-one percent had access to a smartphone, 54% had access to a tablet, and 20% did not have access to either device. Multiple logistic regressions showed that women who were younger, had higher levels of education, and who were from less deprived areas were more likely to have access to either device. Poorer e-health literacy was associated with being older, having less education, and not having access to a mobile device.

Conclusions

Whilst the results show relatively widespread access to mobile devices, there is evidence of a digital divide across some groups. Online interventions should be developed with consideration of individuals who are less e-health-literate and less technologically adept in order to increase the likelihood of engagement.
Upper limb dysfunction and activities in daily living in idiopathic normal pressure hydrocephalus
Authors: Sirkka Jani , Parviainen Marita , Jyrkkänen Henna-Kaisa , Koivisto Anne M. , Säisänen Laura , Rauramaa Tuomas , Leinonen Ville , Danner Nils
Published: July 2021

Background

Idiopathic normal pressure hydrocephalus (iNPH) is a neurodegenerative disease with a characteristic symptom triad of gait disturbance, cognitive decline, and incontinence. Recently, also dysfunctions in upper limbs have been described in iNPH and reported to improve after shunt surgery. We aim to describe the role of upper limb motor function in the clinical assessment of iNPH patients and its influence on activities of daily living (ADL).

Methods

Seventy-five consecutive patients with probable iNPH were studied pre-operatively and at 3 and 12 months after shunt surgery. The pre-operative evaluation included lumbar drainage of cerebrospinal fluid (tap test). Motor functions were assessed in upper and lower limbs with Grooved Pegboard Test (GPT), Box & Block Test (BBT), Total Score of Gait (TSG), and balance test. ADL was assessed with Barthel’s index and cognition in accordance with the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD).

Results

Patients showed improvement in all motor tests and ADL at 3 months after shunt surgery. The improvement remained stable during the 12-month post-operative follow-up. The motor function tests correlated with each other and with ADL.

Conclusions

A 3-month follow-up period after shunt surgery is adequate to show improvement in motor tasks, and a positive outcome will last for at least 12 months. A shunt-responsive dysfunction of upper limb motor performance plays a major role in ADL of iNPH patients. Therefore, we suggest an evaluation of upper limb motor performance to be included in routine evaluation of iNPH patients.
Prediction of the layered ink layout for 3D printers considering a desired skin color and line spread function
Authors: Nagasawa Kazuki , Yoshii Junki , Yamamoto Shoji , Arai Wataru , Kaneko Satoshi , Hirai Keita , Tsumura Norimichi
Published: July 2021

We propose a layout estimation method for multi-layered ink using a measurement of the line spread function (LSF) and machine learning. The three-dimensional printing market for general consumers focuses on the reproduction of realistic appearance. In particular, for the reproduction of human skin, it is important to control translucency by adopting a multilayer structure. Traditionally, layer design has depended on the experience of designers. We, therefore, developed an efficient layout estimation to provide arbitrary skin color and translucency. In our method, we create multi-layered color patches of human skin and measure the LSF as a metric of translucency, and we employ a neural network trained with the data to estimate the layout. As an evaluation, we measured the LSF from the computer-graphics-created skin and fabricate skin using the estimated layout; evaluation with root-mean-square error showed that we can obtain color and translucency that are close to the target.
Differential Privacy and the Accuracy of County-Level Net Migration Estimates
Authors: Winkler Richelle L. , Butler Jaclyn L. , Curtis Katherine J. , Egan-Robertson David
Published: July 2021

Each decade since the 1950s, demographers have generated high-quality net migration estimates by age, sex, and race for US counties using decennial census data as starting and ending populations. The estimates have been downloaded tens of thousands of times and widely used for planning, diverse applications, and research. Census 2020 should allow the series to extend through the 2010–2020 decade. The accuracy of new estimates, however, could be challenged by differentially private (DP) disclosure avoidance techniques in Census 2020 data products. This research brief estimates the impact of DP implementation on the accuracy of county-level net migration estimates. Using differentially private Census 2010 demonstration data, we construct a hypothetical set of DP migration estimates for 2000–2010 and compare them to published estimates, using common accuracy metrics and spatial analysis. Findings show that based on demonstration data released in 2020, net migration estimates by five-year age groups would only be accurate enough for use in about half of counties. Inaccuracies are larger in counties with populations less than 50,000, among age groups 65 and over, and among Hispanics. These problems are not fully resolved by grouping into broader age groups. Moreover, errors tend to cluster spatially in some regions of the country. Ultimately, the ability to generate accurate net migration estimates at the same level of detail as in the past will depend on the Census Bureau’s allocation of the privacy loss budget.
Synergistic effects in cross-linked blends of ion-conducting PEO-/PPO-based unsaturated polyesters
Authors: Sassmann Pia B. , Weichold Oliver
Published: July 2021

Ion-conductive unsaturated polyesters (UP) were synthesised from poly(ethylene oxide) (Xn = 9, 13, 22, 90) or poly(propylene oxide) (Xn = 7, 13, 20, 34, 68) and maleic anhydride. Subsequently, the polyesters were doped with LiClO4 and cross-linked with styrene using a redox initiator. For PEO-based polyesters, the minimum resistivity is found at an O/Li+ molar ratio of 50/1. In contrast, more lithium is required to reach the minimum when using PPO (O/Li+ = 10/1). Unlike the PEO-based polyesters, cross-linking of the PPO types gives rise to decreasing resistivities at increasing molecular weight. This correlates well with the transverse proton relaxation time determined by single-sided NMR, which is an indicator of the chain mobility. The cross-linking reaction of these UP with styrene exactly follows the predictions based on the copolymerisation parameters and is, therefore, not dependent on the ratio of styrene to UP double bonds as previously reported. Due to the opposing effects of the molecular weight on the ion conductivity of PEO- and PPO-based UP, 1:1 blends of short-chain PPO and long-chain PEO polyesters were cross-linked with styrene. The resulting networks showed a resistivity of 4 kΩ m (σ = 2.5∙10−4 S∙m−1), which is 5 times lower than the pure PEO and 3 times lower than the pure PPO materials.
Is There More to Within-plant Variation in Seed Size than Developmental Noise?
Authors: Pélabon Christophe , De Giorgi Francesca , Opedal Øystein H. , Bolstad Geir H. , Raunsgard Astrid , Scott Armbruster W.
Published: July 2021

Within-plant variation in seed size may merely reflect developmental instability, or it may be adaptive in facilitating diversifying bet-hedging, that is, production of phenotypically diverse offspring when future environments are unpredictable. To test the latter hypothesis, we analyzed patterns of variation in seed size in 11 populations of the perennial vineDalechampia scandensgrown in a common greenhouse environment. We tested whether population differences in the mean and variation of seed size covaried with environmental predictability at two different timescales. We also tested whether within-plant variation in seed size was correlated with independent measures of floral developmental instability and increased under stressful conditions. Populations differed genetically in the amount of seed-size variation occurring among plants, among infructescences within plants, and among seeds within infructescences. Within-individual variation was not detectably correlated with measures of developmental instability and did not increase under stress, but it increased weakly with short-term environmental unpredictability of precipitation at the source-population site. These results support the hypothesis that greater variation in seed size is adaptive when environmental predictability is low.
Mathematical Modeling and Numerical Simulation of Atherosclerosis Based on a Novel Surgeon’s View
Authors: Soleimani Meisam , Haverich Axel , Wriggers Peter
Published: July 2021

This paper deals with the mathematical modeling of atherosclerosis based on a novel hypothesis proposed by a surgeon, Prof. Dr. Axel Haverich (Circulation 135(3):205–207, 2017). Atherosclerosis is referred as the thickening of the artery walls. Currently, there are two schools of thoughts for explaining the root of such phenomenon: thickening due to substance deposition and thickening as a result of inflammatory overgrowth. The hypothesis favored here is the second paradigm stating that the atherosclerosis is nothing else than the inflammatory response of of the wall tissues as a result of disruption in wall nourishment. It is known that a network of capillaries called vasa vasorum (VV) accounts for the nourishment of the wall in addition to the natural diffusion of nutrient from the blood passing through the lumen. Disruption of nutrient flow to the wall tissues may take place due to the occlusion of vasa vasorums with viruses, bacteria and very fine dust particles such as air pollutants referred to as PM 2.5. They can enter the body through the respiratory system at the first place and then reach the circulatory system. Hence in the new hypothesis, the root of atherosclerotic vessel is perceived as the malfunction of microvessels that nourish the vessel. A large number of clinical observation support this hypothesis. Recently and highly related to this work, and after the COVID-19 pandemic, one of the most prevalent disease in the lungs are attributed to the atherosclerotic pulmonary arteries, see Boyle and Haverich (Eur J Cardio Thorac Surg 58(6):1109–1110, 2020). In this work, a general framework is developed based on a multiphysics mathematical model to capture the wall deformation, nutrient availability and the inflammatory response. For the mechanical response an anisotropic constitutive relation is invoked in order to account for the presence of collagen fibers in the artery wall. A diffusion–reaction equation governs the transport of the nutrient within the wall. The inflammation (overgrowth) is described using a phase-field type equation with a double well potential which captures a sharp interface between two regions of the tissues, namely the healthy and the overgrowing part. The kinematics of the growth is treated by classical multiplicative decomposition of the gradient deformation. The inflammation is represented by means of a phase-field variable. A novel driving mechanism for the phase field is proposed for modeling the progression of the pathology. The model is 3D and fully based on the continuum description of the problem. The numerical implementation is carried out using FEM. Predictions of the model are compared with the clinical observations. The versatility and applicability of the model and the numerical tool allow.
Therapies to Restore Consciousness in Patients with Severe Brain Injuries: A Gap Analysis and Future Directions
Authors: Edlow Brian L. , Sanz Leandro R. D. , Polizzotto Len , Pouratian Nader , Rolston John D. , Snider Samuel B. , Thibaut Aurore , Stevens Robert D. , Gosseries Olivia ,   the Curing Coma Campaign and its contributing members, Akbari Yama , Bleck Thomas P. , Diringer Michael N. , Foreman Brandon , Hartings Jed A. , Helbok Raimund , Hemphill J. Claude , Ling Geoffrey S. F. , Mayer Stephan A. , McNett Molly , Monti Martin M. , Olson DaiWai M. , Owen Adrian M. , Park Soojin , Provencio J. Javier , Puybasset Louis , Vespa Paul , Wagner Amy , Whyte John , Ziai Wendy
Published: July 2021

Background/Objective

For patients with disorders of consciousness (DoC) and their families, the search for new therapies has been a source of hope and frustration. Almost all clinical trials in patients with DoC have been limited by small sample sizes, lack of placebo groups, and use of heterogeneous outcome measures. As a result, few therapies have strong evidence to support their use; amantadine is the only therapy recommended by current clinical guidelines, specifically for patients with DoC caused by severe traumatic brain injury. To foster and advance development of consciousness-promoting therapies for patients with DoC, the Curing Coma Campaign convened a Coma Science Work Group to perform a gap analysis.

Methods

We consider five classes of therapies: (1) pharmacologic; (2) electromagnetic; (3) mechanical; (4) sensory; and (5) regenerative. For each class of therapy, we summarize the state of the science, identify gaps in knowledge, and suggest future directions for therapy development.

Results

Knowledge gaps in all five therapeutic classes can be attributed to the lack of: (1) a unifying conceptual framework for evaluating therapeutic mechanisms of action; (2) large-scale randomized controlled trials; and (3) pharmacodynamic biomarkers that measure subclinical therapeutic effects in early-phase trials. To address these gaps, we propose a precision medicine approach in which clinical trials selectively enroll patients based upon their physiological receptivity to targeted therapies, and therapeutic effects are measured by complementary behavioral, neuroimaging, and electrophysiologic endpoints.

Conclusions

This personalized approach can be realized through rigorous clinical trial design and international collaboration, both of which will be essential for advancing the development of new therapies and ultimately improving the lives of patients with DoC.
Flavor Enhancement in Daily Life of Patients with Olfactory Dysfunction
Authors: Koenighofer Martin , Niebauer Verena , Liu David Tianxiang , Renner Bertold , Besser Gerold , Mueller Christian A.
Published: July 2021

Introduction

Patients with olfactory dysfunction report deterioration of taste due to loss of flavor, leading to less food enjoyment, alterations in dietary behaviors and stress. The aim of this study was to introduce flavor enhancement to investigate its acceptance and possible effects on quality of life.

Methods

In this prospective, controlled, randomized, single-blinded, cross-over pilot study, we recruited 30 olfactory dysfunction patients, of which 16 were hyposmic and 14 anosmic. After single-blinded triangle flavor discrimination test, flavor drops were randomized either in high or low concentration for 14 days and vice versa for another 14 days. Records included a daily diary and the questionnaire of olfactory disorders.

Results

Usage rates were excellent with 82.2% of all days, while drops were mainly used for breakfast (44.6%, p < 0.05). Hyposmics used flavor enhancement on significantly more days (median = 14) compared to anosmics (median = 11, p = 0.0094). QOD improved in 12 patients to a meaningful extent.

Conclusions

In this pilot study, we show that flavor enhancement is feasible accompanied by high compliance and acceptance in olfactory dysfunction patients. Flavor drops were used regardless of low or high concentrations with no adverse events noted.

Implications

Our findings give rise to further studies illuminating the possible advantages of flavor enhancement in patients with olfactory disorders.
Comeback als demokratische Führungsmacht?
Authors: Ruß-Sattar Sabine , Riecke Henning
Published: July 2021

Joe Biden stellt die US-Außenpolitik unter ein demokratisches Paradigma, will demokratische Allianzen festigen und hat einen „Gipfel für die Demokratie“ versprochen. Ziel ist es, das Gewicht freiheitlicher Staaten im Systemkonflikt mit Autokratien zu erhöhen. Bündnispartner in Europa und Asien reagieren skeptisch, fürchten eine Verhärtung der Konflikte mit China und Russland und den Verlust der Handlungsfreiheit. Wir plädieren für eine Allianz der Demokratien, mit Blick auf die Resilienz ihrer politischen Systeme und eingebettet in andere Formate multilateraler Kooperation.
Geochemical study of the early cretaceous Fahliyan oil reservoir in the northwest Persian Gulf
Authors: Manshad Abbas Khaksar , Pashaki Reza Sedighi , Ali Jagar A. , Iglauer Stefan , Memariani M. , Akbari Majid , Keshavarz Alireza
Published: July 2021

Three crude oil samples from the Fahliyan Formation in ‘KG’ and ‘F’ fields in the northwest Persian Gulf, namely KG-031, F9A-3H and F15-3H for the geochemical study. In this study, the physicochemical properties, gas chromatography (GC, GC Mass) and (Detailed Hydrocarbon Analysis) DHA analyses for the collected Fahliyan oils were carried out. The API, Trace Element (Ni, V) and S% parameters indicated that the Fahliyan oil was generated from a source rock which deposited in reducing environment condition with a carbonate-shale compound lithology. Moreover, low pour point, higher S% and low viscosity parameters of “KG” sample confirmed the existence of medium oil characteristics in this field. In addition, the geochemical outcomes of GC, GC–MS and DHA analyses indicated that the ‘KG’ oils are more aromatic compared with ‘F’ oil; while biomarkers revealed that Fahliyan reservoir oil is highly mature and was formed from a carbonate source rock containing types II, III kerogen. Thus, sterane/hopane biomarkers (C24/C23 and C22/C21 ratios) revealed that Fahliyan oil originated from carbonate source rocks deposited in an anoxic to dysoxic environment, which is consistent with the above analyses. It was identified that the source rock age is early Cretaceous to late Jurassic. It can be reported that the Fahliyan oils from both fields were generated in the same source rock and have almost the same physical properties, and will have the same production strategy.
Rotary steerable systems: mathematical modeling and their case study
Authors: Andrade Caetano P. S. , Saavedra J. Luis , Tunkiel Andrzej , Sui Dan
Published: July 2021

Directional drilling is a common and essential procedure of major extended reach drilling operations. With the development of directional drilling technologies, the percentage of recoverable oil production has increased. However, its challenges, like real-time bit steering, directional drilling tools selection and control, are main barriers leading to low drilling efficiency and high nonproductive time. The fact inspires this study. Our work aims to contribute to the better understanding of directional drilling, more specifically regarding rotary steerable system (RSS) technology. For instance, finding the solutions of the technological challenges involved in RSSs, such as bit steering control, bit position calculation and bit speed estimation, is the main considerations of our study. Classical definitions from fundamental physics including Newton’s third law, beam bending analysis, bit force analysis, rate of penetration (ROP) modeling are employed to estimate bit position and then conduct RSS control to steer the bit accordingly. The results are illustrated in case study with the consideration of the 2D and 3D wellbore scenarios.