bluuebunny/crossref_metadata_2025 huggingface dataset:
A human induced pluripotent stem cell-based modular platform to challenge sensorineural hearing loss
Authors: Zine Azel , Messat Yassine , Fritzsch Bernd
Published: November 2021

The sense of hearing depends on a specialized sensory organ in the inner ear, called the cochlea, which contains the auditory hair cells (HCs). Noise trauma, infections, genetic factors, side effects of ototoxic drugs (ie, some antibiotics and chemotherapeutics), or simply aging lead to the loss of HCs and their associated primary neurons. This results in irreversible sensorineural hearing loss (SNHL) as in mammals, including humans; the inner ear lacks the capacity to regenerate HCs and spiral ganglion neurons. SNHL is a major global health problem affecting millions of people worldwide and provides a growing concern in the aging population. To date, treatment options are limited to hearing aids and cochlear implants. A major bottleneck for development of new therapies for SNHL is associated to the lack of human otic cell bioassays. Human induced pluripotent stem cells (hiPSCs) can be induced in two-dimensional and three-dimensional otic cells in vitro models that can generate inner ear progenitors and sensory HCs and could be a promising preclinical platform from which to work toward restoring SNHL. We review the potential applications of hiPSCs in the various biological approaches, including disease modeling, bioengineering, drug testing, and autologous stem cell based-cell therapy, that offer opportunities to understand the pathogenic mechanisms of SNHL and identify novel therapeutic strategies.
Bedding system influences lying behaviour in dairy cows
Authors: Leach Katharine A. , Charlton Gemma L. , Green Martin J. , Lima Eliana , Gibbons Jenny , Black David , Bradley Andrew J.
Published: November 2021

Background

The nature and depth of bedding material have an important influence on cow lying behaviour and comfort. Increasing use of recycled manure solids (RMS) as bedding led to an investigation of the influence of this material on cow lying behaviour.

Methods

Leg mounted accelerometers were used to estimate daily lying time and number and duration of lying bouts in four groups of 40 cows. Each group spent two 2‐week periods on each of four bedding systems: deep sand, deep RMS, sawdust on mattresses and RMS on mattresses.

Results

Total daily lying times were significantly shorter on both RMS treatments than on sawdust. Number of lying bouts per day was greater on sawdust than any other treatment, while lying bouts were 2.6 min longer on deep RMS and 9.3 min longer on sand, than on sawdust.

Conclusions

Greater depth and apparent softness of bedding material does not necessarily result in longer total daily lying times. RMS may have some characteristics that reduce its attraction as a bedding material for cows. The influence of bedding system on number and duration of lying bouts and the resulting total lying time appear complex.
Effect of topical non‐steroidal anti‐inflammatory drugs on healing times and complications in dogs with spontaneous chronic corneal epithelial defects
Authors: Jost Haley E. , Keenan Alessandra V. , Keys Deborah A. , Myrna Kathern E. , Diehl Kathryn A.
Published: November 2021

Background

Little is published regarding topical NSAID effect on corneal healing in dogs. This retrospective cohort study aimed to compare healing times and complications in dogs with spontaneous chronic corneal epithelial defects (SCCED) treated with and without topical non‐steroidal anti‐inflammatory drugs (NSAID).

Methods

Medical records of 66 dogs (71 eyes) diagnosed with SCCED between 2008 and 2019 were included. Eyes were divided into: (1) those receiving topical NSAIDs (n = 33) versus (2) those not receiving topical NSAID (n = 38). Follow‐up until healed, such as comfortable eye, negative fluorescein stain was required. Use of topical or systemic anti‐inflammatories outside of NSAID or presence of ocular disorders or systemic endocrinopathies that may contribute to delayed healing resulted in study exclusion.

Results

Healing times were significantly longer in eyes that received topical NSAID (p = 0.008), however, the use of more topical medications for treatment was also associated with longer healing times (p = 0.001). The majority of eyes in the NSAID group received multiple medications, compared to the non‐NSAID group, so it was not possible to separate the effects of NSAID from a number of medications. Complications occurred in three eyes of three dogs within the NSAID group.

Conclusions

In these canine SCCED eyes, the use of more topical medications, including NSAID, was associated with significantly delayed healing time.
Atrial fibrillation secondary to ephedrine administration and responsive to lidocaine in a Shiloh shepherd dog
Authors: Martin‐Flores Manuel , Piscitell Lauren Marie , Kornreich Bruce Gordon
Published: November 2021

A 6‐year‐old, 43 kg, male Shiloh shepherd dog was anaesthetised for computed tomography to investigate the source of respiratory distress, lethargy and decreased appetite. Arterial hypotension during anaesthesia was treated with an infusion of phenylephrine and a bolus of ephedrine, 0.05 mg/kg intravenously (IV). Ephedrine resulted in increased blood pressure and reflexive bradycardia; atrial fibrillation developed immediately after. Approximately 10 minutes later, a bolus of lidocaine 2 mg/kg IV was administered, and normal sinus rhythm was restored within 1 minute. Lone atrial fibrillation may be triggered by agents or disease processes that increase vagal activity. While lidocaine has historically been used only to treat unstable ventricular dysrhythmias, it is effective for terminating this particular type of atrial fibrillation.
Soft gravitational radiation from multi-body collisions
Authors: Addazi Andrea , Zeng Kaiqiang Alan
Published: November 2021

Abstract

We derive a universal expression for the gravitational radiation energy spectrum dEGW/dω at sub-leading order emitted from a generic gravitational hard scattering of multi-particles or multi-bodies. Our result includes all $$ \mathcal{O} $$
O
(ω) corrections to the gravitational radiation flux from a generic 2 → N collision, in both the cases of massless and massive particles/bodies. We also show the dependence of the radiation energy flux by the quantum spin in case of particle collisions. Then, we consider the specific case of a gravitational elastic scattering of two massive bodies, i.e. m + M → m + M with m, M the masses of the two bodies respectively. We demonstrate that in this case all $$ \mathcal{O} $$
O
(ω) contributions to the energy flux exactly cancel each others. Nevertheless, we also show that, for a 2 → 2 inelastic scattering, the inclusion of sub-leading soft gravitons leads to a not zero radiation flux, having a simple expression in certain asymptotic regimes. Our results can be applied to the case of Black Hole collisions with possible testable implications in gravitational waves physics.
Classifying three-character RCFTs with Wronskian index equalling 0 or 2
Authors: Das Arpit , Gowdigere Chethan N. , Santara Jagannath
Published: November 2021

Abstract

In the modular linear differential equation (MLDE) approach to classifying rational conformal field theories (RCFTs) both the MLDE and the RCFT are identified by a pair of non-negative integers [n,l]. n is the number of characters of the RCFT as well as the order of the MLDE that the characters solve and l, the Wronskian index, is associated to the structure of the zeroes of the Wronskian of the characters. In this paper, we study [3,0] and [3,2] MLDEs in order to classify the corresponding CFTs. We reduce the problem to a “finite” problem: to classify CFTs with central charge 0 < c ≤ 96, we need to perform 6, 720 computations for the former and 20, 160 for the latter. Each computation involves (i) first finding a simultaneous solution to a pair of Diophantine equations and (ii) computing Fourier coefficients to a high order and checking for positivity.

In the [3,0] case, for 0 < c ≤ 96, we obtain many character-like solutions: two infinite classes and a discrete set of 303. After accounting for various categories of known solutions, including Virasoro minimal models, WZW CFTs, Franc-Mason vertex operator algebras and Gaberdiel-Hampapura-Mukhi novel coset CFTs, we seem to have seven hitherto unknown character-like solutions which could potentially give new CFTs. We also classify [3,2] CFTs for 0 < c ≤ 96: each CFT in this case is obtained by adjoining a constant character to a [2,0] CFT, whose classification was achieved by Mathur-Mukhi-Sen three decades ago.
The overlapping effect and fusion protocols of data augmentation techniques in iris PAD
Authors: Fang Meiling , Damer Naser , Boutros Fadi , Kirchbuchner Florian , Kuijper Arjan
Published: November 2021

Iris Presentation Attack Detection (PAD) algorithms address the vulnerability of iris recognition systems to presentation attacks. With the great success of deep learning methods in various computer vision fields, neural network-based iris PAD algorithms emerged. However, most PAD networks suffer from overfitting due to insufficient iris data variability. Therefore, we explore the impact of various data augmentation techniques on performance and the generalizability of iris PAD. We apply several data augmentation methods to generate variability, such as shift, rotation, and brightness. We provide in-depth analyses of the overlapping effect of these methods on performance. In addition to these widely used augmentation techniques, we also propose an augmentation selection protocol based on the assumption that various augmentation techniques contribute differently to the PAD performance. Moreover, two fusion methods are performed for more comparisons: the strategy-level and the score-level combination. We demonstrate experiments on two fine-tuned models and one trained from the scratch network and perform on the datasets in the Iris-LivDet-2017 competition designed for generalizability evaluation. Our experimental results show that augmentation methods improve iris PAD performance in many cases. Our least overlap-based augmentation selection protocol achieves the lower error rates for two networks. Besides, the shift augmentation strategy also exceeds state-of-the-art (SoTA) algorithms on the Clarkson and IIITD-WVU datasets.
Ionospheric corrections tailored to the Galileo High Accuracy Service
Authors: Rovira-Garcia A. , Timoté C. C. , Juan J. M. , Sanz J. , González-Casado G. , Fernández-Hernández I. , Orus-Perez R. , Blonski D.
Published: November 2021

The Galileo High Accuracy Service (HAS) is a new capability of the European Global Navigation Satellite System that is currently under development. The Galileo HAS will start providing satellite orbit and clock corrections (i.e. non-dispersive effects) and soon it will also correct dispersive effects such as inter-frequency biases and, in its full capability, ionospheric delay. We analyse here an ionospheric correction system based on the fast precise point positioning (Fast-PPP) and its potential application to the Galileo HAS. The aim of this contribution is to present some recent upgrades to the Fast-PPP model, with the emphasis on the model geometry and the data used. The results show the benefits of integer ambiguity resolution to obtain unambiguous carrier phase measurements as input to compute the Fast-PPP model. Seven permanent stations are used to assess the errors of the Fast-PPP ionospheric corrections, with baseline distances ranging from 100 to 1000 km from the reference receivers used to compute the Fast-PPP corrections. The 99% of the GPS and Galileo errors in well-sounded areas and in mid-latitude stations are below one total electron content unit. In addition, large errors are bounded by the error prediction of the Fast-PPP model, in the form of the variance of the estimation of the ionospheric corrections. Therefore, we conclude that Fast-PPP is able to provide ionospheric corrections with the required ionospheric accuracy, and realistic confidence bounds, for the Galileo HAS.
$$\infty $$-Operads via symmetric sequences
Authors: Haugseng Rune
Published: November 2021

We construct a generalization of the Day convolution tensor product of presheaves that works for certain double $$\infty $$
∞
-categories. Using this construction, we obtain an $$\infty $$
∞
-categorical version of the well-known description of (one-object) operads as associative algebras in symmetric sequences; more generally, we show that (enriched) $$\infty $$
∞
-operads with varying spaces of objects can be described as associative algebras in a double $$\infty $$
∞
-category of symmetric collections.
An experimental test of the Mocikat-Herwig theory of local turbulent heat transfer measurements on cold objects
Authors: Kapitz Marek , der Wiesche Stefan aus , Kadic Samir , Strehle Steffen
Published: November 2021

Experimental results are presented of a test of the theory of local turbulent heat transfer measurements proposed by Mocikat and Herwig in 2007. A miniaturized multi-layer heat transfer sensor was developed and employed in this study. The new heat transfer sensor was designed to work in air and liquids, and this capability enabled the simultaneous investigation of different Prandtl numbers. Two basic configurations, namely the flow past a blunt plate and the flow past an inclined square cylinder, were investigated in test sections of wind and water tunnels. Convective heat transfer coefficients were obtained through conventional testing (i.e., employing thoroughly heated test objects) and using the new miniaturized sensor approach (i.e., utilizing cold test objects without heating). The main prediction of the Mocikat-Herwig theory that a specific thermal adjustment coefficient of the employed actual miniaturized heat transfer sensor should exist in the fully turbulent flow regime was proven for developed two-dimensional flow. The observed effect of the Prandtl number on this coefficient was in good agreement with the prediction of the asymptotic expansion method. The square cylinder results indicated the inherent limits of the local turbulent heat transfer measurement approach, as suggested by Mocikat and Herwig.
Population pharmacokinetic and exposure–response analyses of elotuzumab plus pomalidomide and dexamethasone for relapsed and refractory multiple myeloma
Authors: Ide Takafumi , Osawa Mayu , Sanghavi Kinjal , Vezina Heather E.
Published: November 2021

Purpose

Elotuzumab plus pomalidomide/dexamethasone (E-Pd) demonstrated efficacy and safety in relapsed and refractory multiple myeloma (RRMM). The clinical pharmacology of elotuzumab [± lenalidomide/dexamethasone (Ld)] was characterized previously. These analyses describe elotuzumab population pharmacokinetics (PPK), the effect of Pd, and assess elotuzumab exposure–response relationships for efficacy and safety in patients with RRMM.

Methods

A previously established PPK model was updated with E-Pd data from the phase 2 ELOQUENT-3 study (NCT02654132). The dataset included 8180 serum concentrations from 440 patients with RRMM from 5 clinical trials. Elotuzumab PK parameter estimates were used to generate individual daily time-varying average concentrations (daily Cavg) for multi-variable time-to-event exposure–response analyses of progression-free survival (PFS) and time to the first occurrence of grade 3 + adverse events (AEs) in RRMM.

Results

Elotuzumab PK were well-described by a two-compartment model with parallel linear and Michaelis–Menten elimination from the central compartment (Vmax) and non-renewable target-mediated elimination from the peripheral compartment (Kint). Co-administration with Pd resulted in a 19% and 51% decrease in elotuzumab linear clearance and Kint, respectively, versus Ld; steady-state exposures were similar. Vmax increased with increasing serum M-protein. Hazard ratios (95% confidence intervals) for daily Cavg were 0.9983 (0.9969–0.9997) and 0.9981 (0.9964–0.9998) for PFS and grade 3 + AEs, respectively.

Conclusions

The PPK model adequately described the data and was appropriate for determining exposures for exposure–response analyses. There were no clinically relevant differences in elotuzumab exposures between Pd and Ld backbones. In ELOQUENT-3, increasing elotuzumab daily Cavg prolonged PFS without increasing grade 3 + AEs.
Video colposcopy versus headlight for large loop excision of the transformation zone (LLETZ): a randomised trial
Authors: Rezniczek Günther A. , Neghabian Nadja , Rehman Sadia , Tempfer Clemens B.
Published: November 2021

Purpose

To compare resected cone mass and resection margin status when performing Large Loop Excision of the Transformation Zone (LLETZ) using video colposcopy (LLETZ-VC) versus a headlight (LLETZ-HL) in women with cervical dysplasia.

Methods

Prospective, randomised trial (monocentric) at a specialised cervical dysplasia unit in a University Hospital. Women with a biopsy-proven CIN2 + or persisting CIN1 or diagnostic LLETZ were recruited and randomised. LLETZ was performed either under video colposcopic vision or using a standard surgical headlight. The primary endpoint was resected cone mass. Secondary endpoints were the rate of involved margins, fragmentation of the specimen, procedure time, time to complete haemostasis (TCH), blood loss, pain, intra- and postoperative complications, and surgeon preference.

Results

LLETZ-VC and LLETZ-HL (109 women each) had comparable cone masses (1.57 [0.98–2.37] vs. 1.67 [1.15–2.46] grams; P = 0.454). TCH was significantly shorter in the LLETZ-VC arm (60 [41–95.2] vs. 90 [47.2–130.2] seconds; P = 0.008). There was no statistically significant difference in involved resection margins (6/87 [6.5%] vs. 16/101 [13.7%], P = 0.068) and postoperative complications (13/82 [13.7%] vs. 22/72 [23.4%], P = 0.085). Patient-reported outcomes favoured LLETZ-VC with a lower use of analgesics (6/80 [7.0%] vs. 17/87 [16.3%]; P = 0.049). However, LLETZ-VC was more difficult to perform with significantly lower ratings for handling (7 [5–9] vs. 9 [8–10]; P < 0.001) and general satisfaction (7.5 [5–9] vs. 10 [8–10]; P < 0.001).

Conclusion

Intraoperative video colposcopy for LLETZ has minimal benefits at the cost of surgeons’ satisfaction.

Clinical trial registration

NCT04326049 (ClinicalTrials.gov).
Measuring in situ CO2 and H2O in apatite via ATR-FTIR
Authors: Hammerli Johannes , Hermann Jörg , Tollan Peter , Naab Fabian
Published: November 2021

We present a new approach to determine in situ CO2 and H2O concentrations in apatite via attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR). Absolute carbon and hydrogen measurements by nuclear reaction analysis (NRA) and elastic recoil detection (ERD) are used to calibrate ATR-FTIR spectra of CO2 and H2O in apatite. We show that CO2 and H2O contents in apatite can be determined via linear equations (r2 > 0.99) using the integrated area of CO2 and H2O IR absorption bands. The main benefits of this new approach are that ATR-FTIR analyses are non-destructive and can be conducted on polished sample material surfaces with a spatial resolution of ~ 35 μm. Furthermore, the wavenumber of the phosphate IR absorption band can be used to determine the crystallographic orientation of apatite, which allows for accurate quantification of CO2 and H2O in randomly orientated apatite grains. The limit of quantification of H2O in apatite is ~ 400 ppm and ~ 100 ppm for CO2. Via two examples, one from a carbonatite and one from a metasedimentary rock, we show that this new technique opens up new possibilities for determining volatile concentrations and behavior in a wide range of hydrothermal, igneous, and metamorphic systems.
The impact of musculoskeletal pain and strenuous work on self-reported physical work ability: a cohort study of Swedish men and women
Authors: Badarin Kathryn , Hemmingsson Tomas , Hillert Lena , Kjellberg Katarina
Published: November 2021

Objective

We investigated the separate and combined effects of musculoskeletal pain (MSP) and strenuous work (heavy physical workload (PWL)/low-decision authority) on poor physical work ability (WA).

Methods

This study uses baseline data from the 2010 Stockholm Public Health Questionnaire (SPHQ) including 9419 workers with good physical WA. Exposure to PWL and decision authority were estimated using sex-specific job-exposure matrices linked to occupations. Exposures (high/low) were combined with the presence of MSP. Follow-up data on physical WA were taken from the 2014 SPHQ and dichotomised (the responses: “moderate”, “rather poor” and “very poor” indicated poor WA). Logistic regression models calculated sex-specific odds ratios adjusting for age, education and health and lifestyle factors. Interaction between MSP and strenuous work was examined using the synergy index (SI). Analyses were conducted using SPSS.27.

Results

MSP, heavy PWL and low-decision authority were separately associated with poor WA. MSP was associated with higher odds of poor WA than strenuous work for women, the opposite for men. Combinations of MSP and strenuous work often resulted in higher risks of poor WA than when adding the effects of the single exposures (e.g., MSP and heavy PWL men: AOR 4.04 95% CI 2.00–8.15, women: AOR: 3.25 95% CI 1.81–5.83). The SI was non-significant for both sexes.

Conclusion

Workers with MSP and strenuous work often had higher risks of poor WA than would be expected from adding the effects of the single exposures. To decrease poor WA in this group, strenuous work should be lowered, and MSP addressed in workplaces.
Inducing low energy availability in trained endurance male athletes results in poorer explosive power
Authors: Jurov Iva , Keay Nicola , Spudić Darjan , Rauter Samo
Published: November 2021

Purpose

Low energy availability in males needs more original research to understand its health and performance consequences. The aim of the study was to induce low energy availability in previously healthy male endurance athletes by reducing energy availability by 25% for 14 consecutive days and measure any potential changes in performance, health, mental state or energy markers.

Methods

Energy availability was reduced in 12 trained, well-trained and elite endurance athletes by increasing energy expenditure and controlling energy intake. After intervention, health was assessed by blood draw, body composition was measured, energy markers by measuring resting energy expenditure, performance with three specific tests (measuring endurance, agility and explosive power) and two questionnaires were used for psychological assessment (the Three Factor Eating Questionnaire and Well-being questionnaire).

Results

Reduced energy availability (22.4 ± 6.3 kcal/kg FFM/day) caused significantly lower haemoglobin values (t(12) = 2.652, p = 0.022), there was a tendency for lower iron and IGF-1 (p = 0.066 and p = 0.077, respectively). Explosive power was reduced (t(12) = 4.570, p = 0.001), lactate metabolism was altered and athletes reported poorer well-being (t(12) = 2.385, p = 0.036). Cognitive restriction was correlated with energy availability (r = 0.528, p = 0.039).

Conclusion

This is the first research providing direct evidence that suboptimal energy availability negatively impacts explosive power before hormonal changes occur in male endurance athletes. It is also the first to show direct association of low energy availability and higher cognitive restriction. We also observed worse well-being and lower haemoglobin values. 25% of energy availability reduction as not enough to elicit changes in resting energy expenditure.
Real-time analysis and predictability of the health functional food market using big data
Authors: Kim Sang-Soon , Lim Seokwon , Kim Sangoh
Published: November 2021

This study conducted a real-time analysis of the health functional food market using big data. To assess the scope of big data in market analysis, big data of the health food category were compared and analyzed with actual market data. Data were first collected using a program to obtain data, through application programming interfaces, followed by SPSS to compare and analyze the actual market index and shopping search word data. The correlation between the online search data and the actual market was high, indicating that online search data can be used to predict the trend of the actual market. Various types of data, such as items and major functional ingredients, can be collected and analyzed through the program developed for this study, which is also used to predict the market trend. The results demonstrate how APIs can be used to predict market size in the food industry effectively.
CAF promotes chemoresistance through NRP2 in gastric cancer
Authors: Yang Yanpeng , Ma Yongchen , Yan Shen , Wang Pengyuan , Hu Jianwen , Chen Shanwen , Zhu Jing , Wang Jingui , Chen Guowei , Liu Yucun
Published: November 2021

Background

Fibroblasts are the predominant cell type in the stroma of tumor, and cancer-associated fibroblasts (CAFs) promote cancer chemoresistance by secreting various bioactive molecules. However, the differential expression between CAFs and normal fibroblasts (NFs) and how can CAFs uniquely impact cancer cells are still unexplored.

Methods

Primary CAFs and NFs were cultured from gastric cancer specimens, and their variant expression was analyzed by RNA-sequencing. Chemoresistance was evaluated by measuring cell viability, apoptosis, and 3D-coculture techniques.

Results

CAFs were isolated from gastric cancers and defined by specific cell-surface markers. CAFs decreased the sensitivity of gastric cancer cells to 5-FU. RNA-sequencing showed that CAFs expressed a higher level of NRP2 than NFs. And the high expression of NRP2 was correlated with worse oncological outcomes in gastric cancer patients. Further study showed that the knockdown of NRP2 eradicated the resistance to 5-FU. And the secretion of stromal cell-derived factor-1 (SDF-1) was reduced following NRP2 knockdown. Furthermore, we found that the increased sensitivity to 5-FU was induced by DNA damage. And this process was mediated by predominant effectors of the Hippo pathway, YAP/TAZ.

Conclusions

The present study indicated that CAFs within gastric cancers promote chemoresistance through the expression of NRP2. The secretion of SDF-1 that mediated by VEGF/NRP2 signaling in CAFs and the activation of Hippo pathway in cancer cells in large part participated in this project.
Stability of Einstein metrics on symmetric spaces of compact type
Authors: Schwahn Paul
Published: November 2021

We prove the linear stability with respect to the Einstein-Hilbert action of the symmetric spaces$${\text {SU}}(n)$$SU(n),$$n\ge 3$$n≥3, and$$E_6/F_4$$E6/F4. Combined with earlier results, this resolves the stability problem for irreducible symmetric spaces of compact type.
Systematic risk in the biopharmaceutical sector: a multiscale approach
Authors: Uddin Gazi Salah , Yahya Muhammad , Bekiros Stelios , Jayasekera Raanadeva , Kling Gerhard
Published: November 2021

It is well documented that the biopharmaceutical sector has exhibited weak financial returns, contributing to underinvestment. Innovations in the industry carry high risks; however, an analysis of systematic risk and return compared to other asset classes is missing. This paper investigates the time–frequency interconnectedness between stocks in the biotech sector and ten asset classes using daily cross-country data from 1995 to 2019. We capture investors' heterogeneous investment horizons by decomposing time series according to frequencies. Using a maximal overlap discrete wavelet transform (MODWT) and a dynamic conditional correlation (DCC)-Student-t copula, diversification potentials are revealed, helping investors to reap the benefits of investing in biotech. Our findings indicate that the underlying assets exhibit nonlinear asymmetric behavior that strengthens during periods of turmoil.
One in five patients with Duchenne muscular dystrophy dies from other causes than cardiac or respiratory failure
Authors: Wahlgren Lisa , Kroksmark Anna-Karin , Tulinius Mar , Sofou Kalliopi
Published: November 2021

Duchenne muscular dystrophy (DMD) is a severe neuromuscular disorder with increasing life expectancy from late teens to over 30 years of age. The aim of this nationwide study was to explore the prevalence, life expectancy and leading causes of death in patients with DMD in Sweden. Patients with DMD were identified through the National Quality Registry for Neuromuscular Diseases in Sweden, the Swedish Registry of Respiratory Failure, pathology laboratories, neurology and respiratory clinics, and the national network for neuromuscular diseases. Age and cause of death were retrieved from the Cause of Death Registry and cross-checked with medical records. 373 DMD patients born 1970–2019 were identified, of whom 129 patients deceased during the study period. Point prevalence of adult patients with DMD on December 31st 2019 was 3.2 per 100,000 adult males. Birth prevalence was 19.2 per 100,000 male births. Median survival was 29.9 years, the leading cause of death being cardiopulmonary in 79.9% of patients. Non-cardiopulmonary causes of death (20.1% of patients) mainly pertained to injury-related pulmonary embolism (1.3 per 1000 person-years), gastrointestinal complications (1.0 per 1000 person-years), stroke (0.6 per 1000 person-years) and unnatural deaths (1.6 per 1000 person-years). Death from non-cardiopulmonary causes occurred at younger ages (mean 21.0 years, SD 8.2; p = 0.004). Age at loss of independent ambulation did not have significant impact on overall survival (p = 0.26). We found that non-cardiopulmonary causes contribute to higher mortality among younger patients with DMD. We present novel epidemiological data on the increasing population of adult patients with DMD.
Natural and iatrogenic ocular manifestations of rheumatoid arthritis: a systematic review
Authors: Dammacco Rosanna , Guerriero Silvana , Alessio Giovanni , Dammacco Franco
Published: November 2021

Purpose

To provide an overview of the ocular features of rheumatoid arthritis (RA) and of the ophthalmic adverse drug reactions (ADRs) that may be associated with the administration of antirheumatic drugs.

Methods

A systematic literature search was performed using the PubMed, MEDLINE, and EMBASE databases. In addition, a cohort of 489 RA patients who attended the Authors’ departments were examined.

Results

Keratoconjunctivitis sicca, episcleritis, scleritis, peripheral ulcerative keratitis (PUK), and anterior uveitis were diagnosed in 29%, 6%, 5%, 2%, and 10%, respectively, of the mentioned cohort. Ocular ADRs to non-steroidal anti-inflammatory drugs are rarely reported and include subconjunctival hemorrhages and hemorrhagic retinopathy. In patients taking indomethacin, whorl-like corneal deposits and pigmentary retinopathy have been observed. Glucocorticoids are frequently responsible for posterior subcapsular cataracts and open-angle glaucoma. Methotrexate, the prototype of disease-modifying antirheumatic drugs (DMARDs), has been associated with the onset of ischemic optic neuropathy, retinal cotton-wool spots, and orbital non-Hodgkin’s lymphoma. Mild cystoid macular edema and punctate keratitis in patients treated with leflunomide have been occasionally reported. The most frequently occurring ADR of hydroxychloroquine is vortex keratopathy, which may progress to “bull’s eye” maculopathy. Patients taking tofacitinib, a synthetic DMARD, more frequently suffer herpes zoster virus (HZV) reactivation, including ophthalmic HZ. Tumor necrosis factor inhibitors have been associated with the paradoxical onset or recurrence of uveitis or sarcoidosis, as well as optic neuritis, demyelinating optic neuropathy, chiasmopathy, and oculomotor palsy. Recurrent episodes of PUK, multiple cotton-wool spots, and retinal hemorrhages have occasionally been reported in patients given tocilizumab, that may also be associated with HZV reactivation, possibly involving the eye. Finally, rituximab, an anti-CD20 monoclonal antibody, has rarely been associated with necrotizing scleritis, macular edema, and visual impairment.

Conclusion

The level of evidence for most of the drug reactions described herein is restricted to the “likely” or “possible” rather than to the “certain” category. However, the lack of biomarkers indicative of the potential risk of ocular ADRs hinders their prevention and emphasizes the need for an accurate risk vs. benefit assessment of these therapies for each patient.
Nonmonotonic Reasoning, Expectations Orderings, and Conceptual Spaces
Authors: Osta-Vélez Matías , Gärdenfors Peter
Published: November 2021

In Gärdenfors and Makinson (Artif Intell 65(2):197–245, 1994) and Gärdenfors (Knowledge representation and reasoning under uncertainty, Springer-Verlag, 1992) it was shown that it is possible to model nonmonotonic inference using a classical consequence relation plus an expectation-based ordering of formulas. In this article, we argue that this framework can be significantly enriched by adopting a conceptual spaces-based analysis of the role of expectations in reasoning. In particular, we show that this can solve various epistemological issues that surround nonmonotonic and default logics. We propose some formal criteria for constructing and updating expectation orderings based on conceptual spaces, and we explain how to apply them to nonmonotonic reasoning about objects and properties.
Development of 3H, 14C, 41Ca, 55Fe, 63Ni radiochemical analysis methods in activated concrete samples
Authors: Leskinen Anumaija , Salminen-Paatero Susanna
Published: November 2021

Development of 3H, 14C, 41Ca, 55Fe and 63Ni radiochemical analysis methods were carried out independently by two laboratories using both inactivate and activated concrete samples. Two preliminary radioanalytical procedures for the non-volatile radionuclides (41Ca, 55Fe, 63Ni) and one Thermal oxidation method for the volatile radionuclides (3H, 14C) were developed. The difficulties in the method development and analysis of results are discussed.
Atomism, Concepts, and Polysemy
Authors: Lemanek Kamil
Published: November 2021

The aim of this paper is to examine the theoretical architecture of semantic atomism and its consequences with respect to natural language. In particular, it looks to explore the notion of possible concepts using the fundamental distinction between simple and complex concepts and expressions in Jerry Fodor’s atomism. The distinction is exploited to produce an unusual type of concept referred to as a correlate, which effectively mirrors complex concepts while maintaining a distinct underlying structure. Though harmless in and of themselves, their presence in the context of polymorphemic expressions suggests that atomism harbors a tacit and unintuitive form of polysemy that is problematic in its own right and that leads to other complications, some of which may be demonstrated on the example of communication. These issues are tied to the way atomism is structured, and although they seem to have gone largely unnoticed, they appear to bear negatively on the adequacy of atomism where natural language is concerned.
Towards an Architecture of a Multi-purpose, User-Extendable Reference Human Brain Atlas
Authors: Nowinski Wieslaw L.
Published: November 2021

Human brain atlas development is predominantly research-oriented and the use of atlases in clinical practice is limited. Here I introduce a new definition of a reference human brain atlas that serves education, research and clinical applications, and is extendable by its user. Subsequently, an architecture of a multi-purpose, user-extendable reference human brain atlas is proposed and its implementation discussed. The human brain atlas is defined as a vehicle to gather, present, use, share, and discover knowledge about the human brain with highly organized content, tools enabling a wide range of its applications, massive and heterogeneous knowledge database, and means for content and knowledge growing by its users. The proposed architecture determines major components of the atlas, their mutual relationships, and functional roles. It contains four functional units, core cerebral models, knowledge database, research and clinical data input and conversion, and toolkit (supporting processing, content extension, atlas individualization, navigation, exploration, and display), all united by a user interface. Each unit is described in terms of its function, component modules and sub-modules, data handling, and implementation aspects. This novel architecture supports brain knowledge gathering, presentation, use, sharing, and discovery and is broadly applicable and useful in student- and educator-oriented neuroeducation for knowledge presentation and communication, research for knowledge acquisition, aggregation and discovery, and clinical applications in decision making support for prevention, diagnosis, treatment, monitoring, and prediction. It establishes a backbone for designing and developing new, multi-purpose and user-extendable brain atlas platforms, serving as a potential standard across labs, hospitals, and medical schools.
Biopharmaceutical Industry Capability Building in India: Report from a Symposium
Authors: Uppal Annu , Chakrabarti Ranjan , Chirmule Narendra , Rathore Anurag , Atouf Fouad
Published: November 2021

The biopharmaceutical industry is evolving with a shift in focus from recombinant proteins and antibodies towards more complex cell and gene therapies. To be competitive globally, biomanufacturers need to focus on aligning with global standards with regard to drug quality, reducing manufacturing failures and delivering drugs to market quickly. Building these capabilities requires a multifaceted approach that includes improvements in operations, quality compliance, and control strategies. To address these needs, the US Pharmacopeia (USP), the Department of Biotechnology (DBT) India, and the Confederation of Indian Industry (CII) held a symposium to discuss the requirements and gaps in the biotechnology and pharmaceutical sectors in India and other developing countries. A panel of experts from academia, manufacturing, and governmental agencies identified several drivers needed for capability building, including a skilled workforce, public–private partnerships, advanced manufacturing technologies, novel biologics, and favorable policies. This article summarizes the recommendations put forward by this panel.
Teaching scientific creativity through philosophy of science
Authors: Jaksland Rasmus
Published: November 2021

There is a demand to nurture scientific creativity in science education. This paper proposes that the relevant conceptual infrastructure with which to teach scientific creativity is often already included in philosophy of science courses, even those that do not cover scientific creativity explicitly. More precisely, it is shown how paradigm theory can serve as a framework with which to introduce the differences between combinational, exploratory, and transformational creativity in science. Moreover, the types of components given in Kuhn’s disciplinary matrix are argued to indicate a further subdivision within transformational creativity that makes explicit that this most radical type of creativity that aims to go beyond and thus to transform the current paradigm can take many different directions. More generally, it is argued that there are several synergies between the topic of scientific creativity and paradigm theory that can be utilized in most philosophy of science courses at relative ease. Doing so should promote the understanding of scientific creativity among students, provide another way to signify the relevance of paradigm theory, and more strategically be a way of reinforcing the place of philosophy of science in science education.
Fulvic acid isolation and characterisation from water of a Ramsar Lake Mansar, J&K, India
Authors: Sharma Arti , Anthal Ritika
Published: November 2021

The present study was undertaken with the aim to understand the chemical properties of aquatic fulvic acid in a clear water Lake Mansar. Along with that, the physical and chemical environment of the lake was also analysed. Fulvic acid was isolated from the water of Lake Mansar following IHSS recommended methodology and was subjected to characterisation, viz. elemental analysis, H-NMR and FTIR spectroscopy. The yield of fulvic acid from water of Lake Mansar was 0.22 mg/L that was far less than coloured aquatic systems. Elemental analysis revealed per cent carbon, hydrogen, nitrogen and oxygen content to be 53.6%, 5.04%, 6.3% and 35.06%, respectively. H-NMR and FTIR spectra revealed the presence of various functional groups like aliphatic, hydroxyl, amide, quinones, ketones, carbonyl, cellulose, etc. Based on the present studies, it was concluded that the origin of humic material in Lake Mansar is mostly from algae and non-vascular plants that have undergone less degree of humification.
The anisotropic mechanical characteristics of layered rocks under numerical simulation
Authors: Zhuo Xiao , Liu Xiangjun , Shi Xiangchao , Liang Lixi , Xiong Jian
Published: November 2021

Layered rocks pose the challenge of wellbore stability in drilling engineering because of the anisotropic mechanical properties caused by the distinct weak planes. To understand the significant anisotropy of layered rocks in real formation condition, true triaxial compression tests are conducted by numerical simulation in this study. It is revealed that the mechanical responses of layered rocks are either controlled by the rock matrix or dominated by the weak plane and exhibit three different types associated with the orientations of the weak plane (including the dip direction α and dip angle β). When the orientations of the weak plane are α = 0°–90° and β = 0°, 60°–90°, the failure and strength properties of layered rocks depend entirely on the rock matrix, classified to the first type. Whereas the layered rocks with angle α ≤ 45° and β = 15°–45° fail by slipping failure along the weak plane, the relationship curves of rock strength versus the intermediate principal stress (σ2) are downward convex parabolas. In the last type, the mechanical behaviors of layered rocks with α > 45° and β = 15°–45°, involved in the changes of failure mode and the strength curve, are complex. Besides, the limitation of the simulation is discussed, and further studies on layered rocks are essential.
Validation of copula-based weather generator for maintenance model of offshore wind farm
Authors: Skobiej Bartosz , Niemi Arto
Published: November 2021

This article discusses the aspect of modeling weather conditions in marine environment for implementation in the offshore wind farm domain. It is clear that harsh sea weather conditions influence many characteristics of any offshore installation. The accessibility to the infrastructure, maintenance procedures, failure ratios of components, energy provision levels, or utilization of vessels—are the examples of weather-related issues connected to the offshore wind industry. Regarding the growing popularity of digital twin methodology, authors present a novel view to generate weather data with copula-based method. The results obtained are compared to selected historical data and implemented into the maintenance model. The selected indicators of maintenance service are used for usability assessment of proposed copula-based method.
A pressure indicator for the impact of Iberian wild goat on moss and soils in a Mediterranean climate
Authors: García-Rodríguez Manuel , Vélez Javier Aroztegui , López-Sánchez Aida , Peláez Marta , Perea Ramón
Published: November 2021

In the Sierra de Guadarrama National Park (central Spain), the population of Iberian wild goat, also known as Spanish ibex (Capra pyrenaica) has grown strongly since its reintroduction three decades ago. The plant community is now under heavy browsing pressure due to this high population. A study of the presence of moss on rocks was used herein as the basis for the design of an indicator, named impact on mosses (im), to describe the environmental pressure exerted by the Iberian wild goat in terms of moss removal. Granite and gneiss zones at medium altitudes with continental Mediterranean climate are the most suitable areas for successful application of the indicator. The hypotheses to test are: (1) the indicator will discriminate between areas with different wild goat pressure levels, (2) wild goat pressure will explain a high proportion of moss loss variance, and (3) the im indicator will be useful to establish a mathematical model between wild goat pressure and moss loss. The proposed indicator was analyzed using both statistical and data science techniques. The results support the mentioned hypotheses. Specifically, statistically significant differences were found regarding the impact on mosses between areas with different levels of Iberian wild goat pressure. Thus, a high proportion of the variance was associated with wild goat pressure (80% for high-pressure areas, 56% for low-pressure areas). A modified parabolic function was fit to express the relationship between Iberian wild goat pressure and impact on mosses. In conclusion, the im indicator was shown to be a useful tool to assess pressure due to Iberian wild goat. Therefore, im can help assess and manage Iberian wild goat populations and determine their sustainable levels.
Tetrathiomolybdate Partially Alleviates Erectile Dysfunction of Type 1 Diabetic Rats Through Affecting Ceruloplasmin/eNOS and Inhibiting Corporal Fibrosis and Systemic Inflammation
Authors: Yin Yinghao , Peng Jingxuan , Zhou Jun , Chen Hanfei , Peng Dongyi , Li Dongjie , Gan Yu , Yin Guangming , Tang Yuxin
Published: November 2021

Introduction

Patients with erectile dysfunction induced by diabetes mellitus (DMED) show a poor effect rate for oral phosphodiesterase type 5 inhibitors (PDE5is). Therefore, the new therapeutic strategy is necessary in patients with DMED.

Aim

To investigate whether Tetrathiomolybdate (TM) supplementation could ameliorate DMED by activation of eNOS.

Methods

Twenty-four diabetic rats were induced by intraperitoneal injection of streptozotocin (STZ) and the other 6 normal rats constituted the control group. Eight weeks later, the erectile function of rats was assessed with an apomorphine test. Only some rats with DMED were treated with TM orally every day for 4 weeks; the other rats remained in the same condition for 4 weeks. After 1 week washout, the erectile function of rats in each group was evaluated. Then, the serum concentration of IL-6 and histologic changes of corpus cavernosum were measured.

Main Outcome Measure

Erectile function was measured after DMED rats treated with TM. The cavernosum level of Ceruloplasmin (Cp), eNOS, endothelial cell content, corporal fibrosis, apoptosis rate and the serum level of IL-6 were also assayed.

Results

Erectile function in the DMED group was significantly impaired compared with the control group and was partly, but significantly, improved in the DMED+TM group. The DMED group showed upregulation of Cp and inhibition of eNOS, but the inhibition was partly reversed in the DMED+TM group. The DMED group showed serious corporal fibrosis. However, TM supplementation partly increased the ratio of smooth muscle to collagen, decreased the ratio of apoptosis. What's more, gavage administration of TM profoundly decreased the serum level of IL-6 in DMED rats.

Conclusion

TM supplementation inhibits endothelial dysfunction, corporal fibrosis, and systemic inflammation, ultimately leading to partial improvement of DMED in rats.