bluuebunny/crossref_metadata_2025 huggingface dataset:
Folklore, Animal Self-Medication, and Phytotherapy–Something Old, Something New, Something Borrowed, Some Things True
Authors: Huffman Michael A.
Published: October 2021

The use of medicines was long considered by Western schools of thought to be a a domain unique to humans; however, folklore/Traditional Ecological Knowledge (TEK) from around the world suggests that animals have also long provided inspiration for the discovery of some medicinal plants used to treat humans and their livestock. Searching for medicinal knowledge from animals depends on the recognition of their ability to select and effectively use medicinal plants to prevent or actively ameliorate disease and other homeostatic imbalances. The interdisciplinary field of animal self-medication is providing scientific evidence for this ability in species across the animal kingdom and lends support to animal-origin medicinal plant folklore and recent ethnomedicinal information. Here, 14 case studies of purported animal-inspired plant medicines used by cultures around the world are presented together with ethnomedicinal and pharmacological evidence. Based on this evidence, the
diversity and potential mode of self-medicative behaviors are considered. Over 20 animal species, including llama, sloth and jaguar in South America, reindeer and yak in Eurasia, langur and macaque in Asia, and chimpanzee, wild boar, porcupine and elephant in Africa, are linked to these case studies, representing a variety of potential preventative or therapeutic self-medicative behaviors. These examples provide an important perspective on what is likely to have been a much wider practice in the development of human traditional medicine. A role for animal self-medication research in the rejuvenation of old therapies and possible new discoveries of phytotherapies for human and livestock health is encouraged.
Gibt es eine „Kältekrankheit“ in der europäischen Naturheilkunde?
Authors: Stange Rainer
Published: October 2021

Der westlichen Welt entstammende Traditionelle Medizinen benutzen oft das Konzept der Konstitution. Sie kennen hier auch Anteile, die sich mit Wärme und Kälte beschäftigen. Später wurden diese Aspekte unter dem speziellen Begriff Thermokonstitution in allgemeinen Konstitutionslehren berücksichtigt. In der Regel signalisiert eine gesteigerte Kälteempfindlichkeit dabei eine eher schwache Konstitution, die den Träger sowohl für akute Infektionskrankheiten insbesondere der oberen Atemwege, aber auch für chronische Erkrankungen bis hin zu Krebs anfälliger werden lässt. Für die Praxis der Hydro-/Thermotherapie stellt sich die Frage nach der aktuellen Belastbarkeit. Wissenschaftlich sind alle diese wichtigen Fragen leider völlig unzureichend bearbeitet.
Menopause is more than Hot Flashes: What is Missing in Homeopathic Research? A Narrative Review
Authors: Macías-Cortés Emma
Published: October 2021

Background Menopausal complaints are frequently treated with homeopathy in daily practice worldwide. Recently, vasomotor symptoms have been understood to have implications as predictors of other important and long-term outcomes, causing increased risk of mortality and/or disability.

Methods A comprehensive search of the literature was conducted to investigate whether homeopathic treatments for menopausal women with vasomotor symptoms have a positive effect on other important health outcomes associated with menopause, such as cardiovascular disease, neurocognitive impairment, metabolic and mood disorders, or osteoporosis.

Results Though observational studies have shown encouraging results in reducing the severity and frequency of hot flashes in women treated with homeopathy, few randomized controlled trials have shown positive results. In most of the studies using homeopathy, the primary outcome is reduction in the frequency and severity of hot flashes, and other menopausal complaints are assessed secondarily as a part of the symptoms evaluated in the menopausal scales. Quality of life improves with homeopathic treatments for hot flashes, but there is scarce evidence of the effect of homeopathy on other health outcomes associated with menopause. Limited evidence exists in the case of menopausal women treated with individualized homeopathy for depression and metabolic disorders.

Conclusion A more comprehensive approach for treating menopause in routine homeopathic practice constitutes a valuable opportunity to increase knowledge and high-quality research in this field. Future homeopathic research for menopause should be focused on well-designed, double-blind, placebo-controlled, randomized trials as well as on pragmatic trials to show whether homeopathic treatments for vasomotor symptoms can also improve outcomes that are well-known to increase the risk of mortality and/or disability.
Chirurgische Universitätsklinik Heidelberg: Ein OP-Zentrum für die Zukunft
Authors: Lang Michael
Published: October 2021

Das Universitätsklinikum Heidelberg hat vor knapp einem Jahr die neue Chirurgische Klinik in Betrieb genommen. Mitarbeiterinnen und Mitarbeiter arbeiten im modernen OP-Zentrum seither erheblich effizienter.
Digitalisierung des Zentrallagers: Keine Papierlisten mehr
Authors: Szlamma Steffen
Published: October 2021

Die Alb Fils Kliniken digitalisierten in den vergangenen beiden Jahren ihr Zentrallager für Medizinprodukte und Wirtschaftsgüter. Die Abläufe im Lager basierten bisher zum großen Teil auf Papierausdrucken, händischen Notizen und aufwändigen Eingaben im Nachgang. Die Digitalisierung hat die Prozesse von Wareneingang bis Ausgabe erheblich beschleunigt.
Socio-Economic and Political Challenges of EU Member Countries: Grasping the Policy Direction of the European Semester
Authors: Casagrande Sara , Dallago Bruno
Published: October 2021

The European Semester (ES) and the country-specific recommendations (CSRs) have been introduced with the purpose to promote flexibility and adaptation to national circumstances in the governance of fiscal policies. To assess whether the ES has contributed to reconcile economic and social objectives, we measured, through the distance to frontier (DTF) score methodology, the distance of each member country from a benchmark based on EU aims and values defined in the EU treaties. Results show that EU member countries are far from the benchmark and CSRs have not prevented a progressive deterioration of stability and cohesion from an economic, political and social perspective. A content analysis of the CSRs issued from 2011 to 2018 and a comparison with the DTF scores reveal a weak connection between member countries’ performance and CSRs. Despite the social content of many CSRs, we actually observe a “commodification” of their goals. CSRs promote a society functional to flexible and competitive markets, and compatible with the requirements of fiscal discipline and sustainability. This neoliberal approach apparently played a role in the EU deterioration and makes the “socialization” of the ES a process with ambiguous implications for European citizens.
Velocity-tunable beam of continuously decelerated polar molecules for cold ion-molecule reaction studies
Authors: Greenberg James , Krohn O. A. , Bossert Jason A. , Shyur Yomay , Macaluso David , Fitch N. J. , Lewandowski H. J.
Published: October 2021

Producing high densities of molecules is a fundamental challenge for low-temperature, ion-molecule reaction studies. Traveling-wave Stark decelerators promise to deliver high density beams of cold, polar molecules but require non-trivial control of high-voltage potentials. We have overcome this experimental challenge and demonstrate continuous deceleration of ND3 from 385 to 10 m/s, while driving the decelerator electrodes with a 10 kV amplitude sinewave. In addition, we test an alternative slowing scheme, which increases the time delay between decelerated packets of ND3 and non-decelerated molecules, allowing for better energy resolution of subsequent reaction studies. We characterize this source of neutral, polar molecules suitable for energy-resolved reaction studies with trapped ions at cold translational temperatures. We also propose a combined apparatus consisting of the traveling-wave decelerator and a linear ion trap with a time-of-flight mass spectrometer and discuss to what extent it may achieve cold, energy-resolved, ion-neutral reactions.
Magnetic field sensors for detection of trapped flux in superconducting radio frequency cavities
Authors: Parajuli I. P. , Ciovati G. , Delayen J. R.
Published: October 2021

Superconducting radio frequency (SRF) cavities are fundamental building blocks of modern particle accelerators. They operate at liquid helium temperatures (2–4 K) to achieve very high quality factors (1010–1011). Trapping of magnetic flux within the superconductor is a significant contribution to the residual RF losses, which limit the achievable quality factor. Suitable diagnostic tools are in high demand to understand the mechanisms of flux trapping in technical superconductors, and the fundamental components of such diagnostic tools are magnetic field sensors. We have studied the performance of commercially available Hall probes, anisotropic magnetoresistive sensors, and flux-gate magnetometers with respect to their sensitivity and capability to detect localized, low magnetic flux amplitudes, of the order of a few tens of magnetic flux quantum at liquid helium temperatures. Although Hall probes have the lowest magnetic field sensitivity (∼96 nV/μT at 2 K), their physical dimensions are such that they have the ability to detect the lowest number of trapped vortices among the three types of sensors. Hall probes and anisotropic magnetoresistive sensors have been selected to be used in a setup to map regions of trapped flux on the surface of a single-cell SRF cavity.
Optimizing a rapid shutdown module for pre-polarization current in surface nuclear magnetic resonance
Authors: Zhou Kun , Chen Chao , Cao Yiming , Lin Tingting
Published: October 2021

Surface nuclear magnetic resonance (SNMR) technology is widely used for hydrological investigations. At high ambient noise levels, the use of a pre-polarization field can enhance the amplitude of the free induced decay (FID) signal. However, the spatial distribution of the pre-polarization field is inhomogeneous, and so it is vital to optimize the shutdown ramp and time for all combinations of the pre-polarization field amplitude and relative orientation. For this purpose, we designed a rapid and adiabatic shutdown circuit for pre-polarization surface nuclear magnetic resonance (PSNMR) systems. In the initial stage of the shutdown process, the magnetic field energy stored in the direct current transmitting coil is transferred to the capacitor by a semi-controlled full bridge circuit. At the end of the shutdown period, the pre-polarization current decays exponentially toward zero. The shutdown process can be controlled by adjusting the circuit parameters. The shutdown ramp and time of the designed circuit are verified through a series of simulations and experiments. As the initial voltage of the capacitor increases from 65 to 300 V, the initial amplitude of the exponential decay of the pre-polarization current increases from 15 to 48 A and the shutdown time decreases from 1.4 to 1 ms. Our design scheme provides a more reliable concept for the shutdown process in the case of multiple transmitting coils. This allows a larger gain of the FID signal to be obtained in specific PSNMR applications when pre-polarization currents with slightly different channel parameters need to be shutdown uniformly.
Semen quality, testosterone values, and testicular and accessory gland parameters in rams receiving sustained stimulation with low doses of buserelin
Authors: Gomes do Espírito Santo Caroline , Alvarez Balaro Mario Felipe , Dantas Rodrigues Santos Juliana , Francisco Leodido Correia Lucas , Vieira de Souza Clara , Ryonosuke Taira Augusto , Campos Pereira da Costa Marta Maria , da Silva Carvalho Ana Beatriz , Ungerfeld Rodolfo , Zandonadi Brandão Felipe
Published: October 2021

Context The use of buserelin, a gonadotropin-releasing hormone (GnRH) agonist, can improve semen quality. Nevertheless, the appropriate dosage, and frequency and time of application, remain to be established owing to the subsequent negative feedback on endogenous production of testosterone described so far. Aims This study aimed to propose a new buserelin application protocol for sperm improvement in Santa Inês rams. Methods Fifteen Santa Inês rams were divided into two experimental groups: the first group (n = 8) received 2.5 μg buserelin acetate; and the second group (n = 7) received saline solution. Treatments were applied for 21 days at intervals of 6 h, totalling four hormonal or saline applications per day. In all animals, macroscopic and microscopic seminal characteristics and freezability, plasma testosterone, pixels of testicular parenchyma, and biometric analysis of testicular and accessory sex glands by ultrasound were evaluated throughout the period of hormonal application and for a further 7 days. Key results Rams receiving buserelin showed a peak of testosterone after the first week (Day 7) of application, with a drop in values at Day 14, followed by negative feedback at Day 21 and return to basal concentrations at Day 28. They also showed improvement of kinetics parameters such as straight line velocity (μm/s: +buserelin 51.5 ± 1.5 > control 46.6 ± 1.6) and linearity coefficient (%: +buserelin 53.5 ± 1.8 > control 47.5 ± 1.9). Ultrasound parameters, pixels of testicular parenchyma, and freezability were not affected by treatment. Conclusions The administration of buserelin was able to improve some sperm kinetics parameters of Santa Inês rams. Implications Low doses of this GnRH analogue can be used; however, further adjustments to the hormonal protocol are needed to obtain an effective improvement in sperm quality.
Rapid cloud removal of dimethyl sulfide oxidation products limits SO
2
and cloud condensation nuclei production in the marine atmosphere
Authors: Novak Gordon A. , Fite Charles H. , Holmes Christopher D. , Veres Patrick R. , Neuman J. Andrew , Faloona Ian , Thornton Joel A. , Wolfe Glenn M. , Vermeuel Michael P. , Jernigan Christopher M. , Peischl Jeff , Ryerson Thomas B. , Thompson Chelsea R. , Bourgeois Ilann , Warneke Carsten , Gkatzelis Georgios I. , Coggon Mathew M. , Sekimoto Kanako , Bui T. Paul , Dean-Day Jonathan , Diskin Glenn S. , DiGangi Joshua P. , Nowak John B. , Moore Richard H. , Wiggins Elizabeth B. , Winstead Edward L. , Robinson Claire , Thornhill K. Lee , Sanchez Kevin J. , Hall Samuel R. , Ullmann Kirk , Dollner Maximilian , Weinzierl Bernadett , Blake Donald R. , Bertram Timothy H.
Published: October 2021

Significance

Ocean emissions of dimethyl sulfide (DMS) are a major precursor for the production and growth of aerosol particles, which can act as seeds for the formation of cloud droplets in the marine atmosphere with the subsequent impacts on Earth’s climate. Global aircraft observations indicate that DMS is efficiently oxidized to hydroperoxymethyl thioformate (HPMTF), a previously unrecognized molecule, which necessitates revisiting DMS oxidation chemistry in the marine atmosphere. We show through ambient observations and global modeling that a dominant loss pathway for HPMTF is uptake into cloud droplets. This loss process short circuits gas-phase oxidation and significantly alters the dynamics of aerosol production and growth in the marine atmosphere.
Semantic network of the German preposition hinter
Authors: Kermer Franka
Published: October 2021

The present study sets out to construct a semantic network for the German preposition hinter (‘behind’) based on the theoretical framework of “principled polysemy”. The analysis regarding the cognitive and pragmatic aspects motivating the meaning extensions of hinter attempts to highlight the importance of varying construal patterns and vantage points as well as the role of real-world knowledge. By means of corpus data, I intend to present six senses of the preposition hinter, hinting at the polysemous nature of prepositions more generally. Furthermore, the theory of conceptual metaphor is applied to account for metaphorical extensions of hinter to more abstract domains of embodied experience.
Grammatical metonymy and construal operations
Authors: Szymańska Monika
Published: October 2021

This article analyses the semantic features of two constructions characterised by the specific use of morphosyntactic indicators of the category of number. The constructions are based on unusual, unobvious ways of using singular and plural forms of NP. The singular (in the first construction) and plural (in the second) forms of NP give to the constructions a metonymic character. The constructions are described as two types of metonymy, representing two different ways of construal.
Natural-scalaron inflation
Authors: Salvio Alberto
Published: October 2021

A pseudo Nambu-Goldstone boson (such as an axion-like particle) is a theoretically well-motivated inflaton as it features a naturally flat potential (natural inflation). This is because Goldstone's theorem protects its potential from sizable quantum corrections. Such corrections, however, generically generates an R
2 term in the action, which leads to another inflaton candidate because of the equivalence between the R
2 term and a scalar field, the scalaron, with a quasi flat potential (Starobinsky inflation). Here it is investigated a new multifield scenario in which both the scalaron and a pseudo Nambu-Goldstone boson are active (natural-scalaron inflation). For generality, also a non-minimal coupling is included, which is shown to emerge from microscopic theories. It is demonstrated that a robust inflationary attractor is present even when the masses of the two inflatons are comparable. Moreover, the presence of the scalaron allows to satisfy all observational bounds in a large region of the parameter space, unlike what happens in pure-natural inflation.
Non-Abelian vector dark matter and lepton g-2
Authors: Chowdhury Talal Ahmed , Saad Shaikh
Published: October 2021

The mystery of dark matter remains an unsettled problem of particle physics. On top of that, experiments show a persistent contention of the muon anomalous magnetic moment (AMM) relative to the Standard Model (SM) prediction. In this work, we consider the possibility of extending the SM with a non-Abelian gauge symmetry SU(2)
X
, under which SM leptons transform non-trivially. SM leptons receive corrections to their AMMs of right order via one-loop processes mediated by beyond SM (BSM) fermions required to cancel anomalies, and BSM gauge bosons that play the role of dark matter. We show that simultaneous explanation of the muon AMM along with reproducing correct relic abundance allows rather a narrow range of 0.5–2 TeV dark matter mass, consistent with current experimental constraints. However, a concurrent description that also includes electron AMM is challenging in this set-up.
Stability, electronic structure, and optical properties of lead-free perovskite monolayer Cs3
B
2
X
9 (B = Sb, Bi; X = Cl, Br, I) and bilayer vertical heterostructure Cs3
B
2
X
9/Cs3

B2′

X
9(B,B′ = Sb, Bi; X = Cl, Br, I)
Authors: Long Yaowen , Zhang Hong , Cheng Xinlu
Published: October 2021

The lead-free perovskites Cs3
B
2
X
9 (B = Sb, Bi; X = Cl, Br, I) as the popular photoelectric materials have excellent optical properties with lower toxicity. In this study, we systematically investigate the stable monolayer Cs3
B
2
X
9 and bilayer vertical heterostructure Cs3
B
2
X
9/Cs3

B
2
′

X
9 (B,
B′ = Sb, Bi; X = Cl, Br, I) via first-principles simulations. By exploring the electrical structures and band edge positions, we find the band gap reduction and the band type transition in the heterostructure Cs3
B
2
X
9/Cs3

B
2
′

X
9 due to the charge transfer between layers. Furthermore, the results of optical properties reveal light absorption from the visible light to UV region, especially monolayer Cs3Sb2I9 and heterostructure Cs3Sb2I9/Cs3Bi2I9, which have absorption peaks in the visible light region, leading to the possibility of photocatalytic water splitting. These results provide insights for more two-dimensional semiconductors applied in the optoelectronic and photocatalytic fields.
Bandwidth-tunable silicon nitride microring resonators
Authors: Liu Jiacheng , Wu Chao , Xia Gongyu , Zheng Qilin , Zhu Zhihong , Xu() Ping
Published: October 2021

We designed a reconfigurable dual-interferometer coupled silicon nitride microring resonator. By tuning the integrated heater on interferometer’s arms, the “critical coupling” bandwidth of resonant mode is continuously adjustable whose quality factor varies from 7.9 × 104 to 1.9 × 105 with the extinction ratio keeping higher than 25 dB. Also a variety of coupling spanning from “under-coupling” to “over-coupling” were achieved, showing the ability to tune the quality factor from 6.0 × 103 to 2.3 × 105. Our design can provide an adjustable filtering method on silicon nitride photonic chip and contribute to optimize the nonlinear process for quantum photonics and all-optical signal processing.
Are fire refugia less predictable due to climate change?
Authors: Mackey Brendan , Lindenmayer David , Norman Patrick , Taylor Chris , Gould Susan
Published: October 2021

Fire refugia—unburnt habitat within a wildfire’s perimeter—play a key role in wildlife persistence and recovery. While studies have shown that the location of refugia is influenced by local topographic factors, growing evidence points to extreme fire weather becoming the dominant factor driving high-severity wildfires that result in the location of fire refugia being less predictable. Between September 2019 and February 2020, a series of mega-fires in eastern Australia burned largely in broadleaf forest. We assessed burned and unburned areas of forest in eastern Australia using Sentinel-2 satellite data, aggregated monthly over the fire season to calculate a fire severity layer at a 20 m pixel resolution. We found that fires burned 5.7 × 106 ha−1 of forest and woodland. The total percentage area of unburned forest within the wildfire footprint was approximately 10%. The majority (94%) of the unburnt forest and woodland patches within the fire perimeter occurred as patches <1 ha (n = 842 622 and 111 707 ha) with far fewer large unburnt patches (>100 ha) (n = 575 and 286 080 ha). Boosted regression tree analyses of the relationships between fire severity and potential explanatory variables revealed that 63%–78% of the variable importance in the models were climatic and weather-related factors. Fire weather index was the single most important variable for analyses, accounting for 40%–52% of modelled results. Our results reinforce mounting evidence that a shift is underway in the balance between deterministic and contingent factors in the occurrence of fire refugia with local topographic controls being increasingly overridden by severe fire weather conditions, and declining topographic effects as fire severity increases. Further studies are needed over a longer time frame, inclusive of prior forest management impacts, to confirm that the ability to predict fire refugia is permanently declining.
Pressure on the Health-Care System and Intensive Care Utilization During the COVID-19 Outbreak in the Lombardy Region of Italy: A Retrospective Observational Study in 43,538 Hospitalized Patients
Authors: Trentini Filippo , Marziano Valentina , Guzzetta Giorgio , Tirani Marcello , Cereda Danilo , Poletti Piero , Piccarreta Raffaella , Barone Antonio , Preziosi Giuseppe , Arduini Fabio , Della Valle Petra Giulia , Zanella Alberto , Grosso Francesca , del Castillo Gabriele , Castrofino Ambra , Grasselli Giacomo , Melegaro Alessia , Piatti Alessandra , Andreassi Aida , Gramegna Maria , Ajelli Marco , Merler Stefano
Published: October 2021

During the spring of 2020, the coronavirus disease 2019 (COVID-19) epidemic caused an unprecedented demand for intensive-care resources in the Lombardy region of Italy. Using data on 43,538 hospitalized patients admitted between February 21 and July 12, 2020, we evaluated variations in intensive care unit (ICU) admissions and mortality over the course of 3 periods: the early phase of the pandemic (February 21–March 13), the period of highest pressure on the health-care system (March 14–April 25, when numbers of COVID-19 patients exceeded prepandemic ICU bed capacity), and the declining phase (April 26–July 12). Compared with the early phase, patients aged 70 years or more were less often admitted to an ICU during the period of highest pressure on the health-care system (odds ratio (OR) = 0.47, 95% confidence interval (CI): 0.41, 0.54), with longer ICU delays (incidence rate ratio = 1.82, 95% CI: 1.52, 2.18) and lower chances of dying in the ICU (OR = 0.47, 95% CI: 0.34, 0.64). Patients under 56 years of age had more limited changes in the probability of (OR = 0.65, 95% CI: 0.56, 0.76) and delay to (incidence rate ratio = 1.16, 95% CI: 0.95, 1.42) ICU admission and increased mortality (OR = 1.43, 95% CI: 1.00, 2.07). In the declining phase, all quantities decreased for all age groups. These patterns may suggest that limited health-care resources during the peak phase of the epidemic in Lombardy forced a shift in ICU admission criteria to prioritize patients with higher chances of survival.
The Anticonvulsant Lamotrigine Reduces Bout-Like Alcohol Drinking in Rats
Authors: Poceviciute Ieva , Buisas Rokas , Danelius Tadas , Dulinskas Redas , Ruksenas Osvaldas , Vengeliene Valentina
Published: October 2021

We used an optical lickometer system to study drinking microstructure and effect of lamotrigine in voluntary alcohol-drinking rats. We showed that, similar to humans, animals differ by their drinking microstructure where some consume alcohol exclusively in a bout-like patterns. The study suggests that anticonvulsants, such as lamotrigine, may be one treatment strategy specifically affecting this type of drinking.
Transgenerational effects of temperature fluctuations inArabidopsis thaliana
Authors: Deng Ying , Bossdorf Oliver , Scheepens J F
Published: October 2021

Plant stress responses can extend into the following generations, a phenomenon called transgenerational effects. Heat stress, in particular, is known to affect plant offspring, but we do not know to what extent these effects depend on the temporal patterns of the stress, and whether transgenerational responses are adaptive and genetically variable within species. To address these questions, we carried out a two-generation experiment with nine Arabidopsis thaliana genotypes. We subjected the plants to heat stress regimes that varied in timing and frequency, but not in mean temperature, and we then grew the offspring of these plants under controlled conditions as well as under renewed heat stress. The stress treatments significantly carried over to the offspring generation, with timing having stronger effects on plant phenotypes than stress frequency. However, there was no evidence that transgenerational effects were adaptive. The magnitudes of transgenerational effects differed substantially among genotypes, and for some traits the strength of plant responses was significantly associated with the climatic variability at the sites of origin. In summary, timing of heat stress not only directly affects plants, but it can also cause transgenerational effects on offspring phenotypes. Genetic variation in transgenerational effects, as well as correlations between transgenerational effects and climatic variability, indicates that transgenerational effects can evolve, and have probably already done so in the past.
Volume Reduction of the Dorsal Lateral Prefrontal Cortex Prior to the Onset of Frank Psychosis in Individuals with an At-Risk Mental State
Authors: Takayanagi Yoichiro , Kulason Sue , Sasabayashi Daiki , Takahashi Tsutomu , Katagiri Naoyuki , Sakuma Atsushi , Ohmuro Noriyuki , Katsura Masahiro , Nishiyama Shimako , Kido Mikio , Furuichi Atsushi , Noguchi Kyo , Matsumoto Kazunori , Mizuno Masafumi , Ratnanather J Tilak , Suzuki Michio
Published: October 2021

Although some individuals with at-risk mental states (ARMS) develop overt psychosis, surrogate markers which can reliably predict a future onset of psychosis are not well established. The dorsal lateral prefrontal cortex (DLPFC) is thought to be involved in psychotic disorders such as schizophrenia. In this study, 73 ARMS patients and 74 healthy controls underwent 1.5-T 3D magnetic resonance imaging scans at three sites. Using labeled cortical distance mapping, cortical thickness, gray matter (GM) volume, and surface area of DLPFC were estimated. These measures were compared across the diagnostic groups. We also evaluated cognitive function among 36 ARMS subjects to clarify the relationships between the DLPFC morphology and cognitive performance. The GM volume of the right DLPFC was significantly reduced in ARMS subjects who later developed frank psychosis (ARMS-P) relative to those who did not (P = 0.042). There was a positive relationship between the right DLPFC volume and the duration prior to the onset of frank psychosis in ARMS-P subjects (r = 0.58, P = 0.018). Our data may suggest that GM reduction of the DLPFC might be a potential marker of future onset of psychosis in individuals with ARMS.
Risk stratification in cardiomyopathies (dilated, hypertrophic, and arrhythmogenic cardiomyopathy) by cardiac magnetic resonance imaging
Authors: Guglielmo Marco , Pontone Gianluca
Published: October 2021

Cardiac magnetic resonance imaging (CMR) is a non-invasive, multiplanar, and high spatial resolution imaging technique, which represents the current gold standard for the evaluation of biventricular volumes and function. Furthermore, unlike other methods, it has the great advantage of characterizing the myocardial tissue by identifying the presence of alterations, such as oedema and focal and diffuse fibrosis. In particular, the late gadolinium enhancement technique makes it possible to identify areas of focal fibrosis that often constitute the substrate for the triggering of threatening ventricular arrhythmias at the basis of sudden cardiac death. For this reason, the use of CMR in the study of cardiomyopathies has become of primary importance, both for the differential diagnosis and for patient risk stratification. In this brief review, the ability of CMR in prognostic stratification of patients with dilated, hypertrophic, and arrhythmogenic cardiomyopathy will be analysed. In particular, the role of CMR in the prediction of arrhythmic risk and in the decision-making process for the implantation of a cardiac defibrillator will be examined.
Certainties fading away: β-blockers do not worsen chronic obstructive pulmonary disease
Authors: Verdecchia Paolo , Cavallini Claudio , Coiro Stefano , Riccini Clara , Angeli Fabio
Published: October 2021

For many years, β-blockers have been considered contraindicated in patients with heart failure (HF) and in those with bronchial asthma or even chronic obstructive pulmonary disease (COPD) although without clear evidence of asthma. Today, despite overwhelming evidence of the usefulness of β-blockers, especially in HF with reduced left ventricular ejection fraction (HFrEF), and in ischaemic heart disease, some reluctance persists in using these drugs when COPD coexists. Such resistance is due to the fear that a possible worsening of bronchospasm induced by β-blockers could induce negative effects greater than the benefits. The Guidelines of the European Society of Cardiology clearly suggest that: (i) implantation of a cardiac defibrillator (ICD) are not contraindicated in COPD without clear evidence of bronchial asthma; (ii) β-blockers are only ‘relatively’ contraindicated when there is certainty of bronchial asthma with a documented bronchodilator response to the β2 stimulant. Therefore, bronchial asthma is not an absolute contraindication to β-blockers. The cardiologist should not limit the diagnosis of COPD to clinical suspicion, but should rely on a spirometry examination associated with any bronchodilation tests. In any case, selective β1 blockers are preferred, starting at a basic dose, which ensure a better dilator response to bronchodilators and in any case cause less bronchospasm than non-selective β-blockers. Unfortunately, there is still some reluctance to the use of β-blockers in patients with COPD associated with HF, which should be eliminated.
The ‘dreaded PFO’: anatomical and functional features of high risk for stroke
Authors: Radico Francesco , Foglietta Melissa , Di Fulvio Maria , Appignani Marianna , Rossi Serena , Angelis Maria Vittoria De , Gallina Sabina , Zimarino Marco
Published: October 2021

Patent foramen ovale (PFO) has a high prevalence in general population and can be implicated in cryptogenic stroke among young people. Recent trials have shown that transcatheter PFO closure is superior to medical treatment in the secondary prevention of ischaemic stroke. The benefit in the reduction of stroke recurrence is particularly evident in patients who have documentation of a PFO with high-risk characteristics. Therefore, after the assessment of a clear causal relationship with the event, a thoughtful documentation of anatomic (height, length, presence of an aneurysmatic or a floppy atrial septum, a prominent Eustachian valve or Chiari’s network, an acute angle with the inferior vena cava) and functional high-risk characteristics is mandatory.
Nitric Oxide Signals Through IRAG to Inhibit TRPM4 Channels and Dilate Cerebral Arteries
Authors: Ali Sher , Solano Alfredo Sanchez , Gonzales Albert L , Thakore Pratish , Krishnan Vivek , Yamasaki Evan , Earley Scott
Published: October 2021

Nitric oxide (NO) relaxes vascular smooth muscle cells (SMCs) and dilates blood vessels by increasing intracellular levels of cyclic guanosine monophosphate (cGMP), which stimulates the activity of cGMP-dependent protein kinase (PKG). However, the vasodilator mechanisms downstream of PKG remain incompletely understood. Here, we found that transient receptor potential melastatin 4 (TRPM4) cation channels, which are activated by Ca2+ released from the sarcoplasmic reticulum (SR) through inositol triphosphate receptors (IP3Rs) under native conditions, are essential for SMC membrane depolarization and vasoconstriction. We hypothesized that signaling via the NO/cGMP/PKG pathway causes vasodilation by inhibiting TRPM4. We found that TRPM4 currents activated by stretching the plasma membrane or directly activating IP3Rs were suppressed by exogenous NO or a membrane-permeable cGMP analog, the latter of which also impaired IP3R-mediated release of Ca2+ from the SR. The effects of NO on TRPM4 activity were blocked by inhibition of soluble guanylyl cyclase or PKG. Notably, upon phosphorylation by PKG, IRAG (IP3R-associated PKG substrate) inhibited IP3R-mediated Ca2+ release, and knockdown of IRAG expression diminished NO-mediated inhibition of TRPM4 activity and vasodilation. Using superresolution microscopy, we found that IRAG, PKG, and IP3Rs form a nanoscale signaling complex on the SR of SMCs. We conclude that NO/cGMP/PKG signaling through IRAG inhibits IP3R-dependent activation of TRPM4 channels in SMCs to dilate arteries.

Significance Statement

Nitric oxide is a gaseous vasodilator produced by endothelial cells that is essential for cardiovascular function. Although NO-mediated signaling pathways have been intensively studied, the mechanisms by which they relax SMCs to dilate blood vessels remain incompletely understood. In this study, we show that NO causes vasodilation by inhibiting the activity of Ca2+-dependent TRPM4 cation channels. Probing further, we found that NO does not act directly on TRPM4 but instead initiates a signaling cascade that inhibits its activation by blocking the release of Ca2+ from the SR. Thus, our findings reveal the essential molecular pathways of NO-induced vasodilation—a fundamental unresolved concept in cardiovascular physiology.
Translational control of lipogenesis links protein synthesis and phosphoinositide signaling with nuclear division inSaccharomyces cerevisiae
Authors: Maitra Nairita , Hammer Staci , Kjerfve Clara , Bankaitis Vytas A , Polymenis Michael
Published: October 2021

Continuously dividing cells coordinate their growth and division. How fast cells grow in mass determines how fast they will multiply. Yet, there are few, if any, examples of a metabolic pathway that actively drives a cell cycle event instead of just being required for it. Here, we show that translational upregulation of lipogenic enzymes in Saccharomyces cerevisiae increased the abundance of lipids and promoted nuclear elongation and division. Derepressing translation of acetyl-CoA carboxylase and fatty acid synthase also suppressed cell cycle-related phenotypes, including delayed nuclear division, associated with Sec14p phosphatidylinositol transfer protein deficiencies, and the irregular nuclear morphologies of mutants defective in phosphatidylinositol 4-OH kinase activities. Our results show that increased lipogenesis drives a critical cell cycle landmark and report a phosphoinositide signaling axis in control of nuclear division. The broad conservation of these lipid metabolic and signaling pathways raises the possibility these activities similarly govern nuclear division in other eukaryotes.
Differential effects of two catalytic mutations on full-length PRDM9 and its isolated PR/SET domain reveal a case of pseudomodularity
Authors: Powers Natalie R. , Billings Timothy , Paigen Kenneth , Petkov Petko M.
Published: October 2021

PRDM9 is a DNA-binding histone methyltransferase that designates and activates recombination hotspots in mammals by locally trimethylating lysines 4 and 36 of histone H3. In mice, we recently reported two independently produced point mutations at the same residue, Glu360Pro (Prdm9EP) and Glu360Lys (Prdm9EK), which severely reduce its H3K4 and H3K36 methyltransferase activities in vivo. Prdm9EP is slightly less hypomorphic than Prdm9EK, but both mutations reduce both the number and amplitude of PRDM9-dependent H3K4me3 and H3K36me3 peaks in spermatocytes. While both mutations cause infertility with complete meiotic arrest in males, Prdm9EP, but not Prdm9EK, is compatible with some female fertility. When we tested the effects of these mutations in vitro, both Prdm9EP and Prdm9EK abolished H3K4 and H3K36 methyltransferase activity in full-length PRDM9. However, in the isolated PRDM9 PR/SET domain, these mutations selectively compromised H3K36 methyltransferase activity, while leaving H3K4 methyltransferase activity intact. The difference in these effects on the PR/SET domain vs the full-length protein shows that PRDM9 is not an intrinsically modular enzyme; its catalytic domain is influenced by its tertiary structure and possibly by its interactions with DNA and other proteins in vivo. These two informative mutations illuminate the enzymatic chemistry of PRDM9, and potentially of PR/SET domains in general, reveal the minimal threshold of PRDM9-dependent catalytic activity for female fertility, and potentially have some practical utility for genetic mapping and genomics.
Establishment of a Reliable Model to Study the Failure of Fracture Healing in Aged Mice
Authors: Menger Maximilian M , Laschke Matthias W , Scheuer Claudia , Bauer David , Bleimehl Michelle , Später Thomas , Rollmann Mika F , Braun Benedikt J , Herath Steven C , Raza Ahsan , Menger Michael D , Histing Tina
Published: October 2021

The failure of fracture healing represents a substantial clinical problem. Moreover, aged patients demonstrate an elevated risk for failed bone healing. However, murine models to study the failure of fracture healing are established only in young adult animals. Therefore, the aim of this study was to develop a reliable model to study failed fracture healing in aged mice. After creation of a 1.8-mm segmental defect and periosteal resection, femora of aged mice (18–20 months) and young adult control mice (3–4 months) were stabilized by pin-clip fixation. Segmental defects were analyzed by means of biomechanics, x-ray, and micro-computed tomography, as well as histomorphometric, immunohistochemical, and Western blot analysis. After 10 weeks, all animals showed a complete lack of osseous bridging, resulting in fracture healing failure. Segmental defects in aged mice revealed a reduced bone formation and vascularization when compared to young adult mice. This was associated with a decreased expression of bone formation markers. In addition, we detected a reduced number of tartrate-resistant acid phosphatase-positive osteoclasts and an elevated osteoprotegerin/receptor activator of NF-ĸB ligand ratio in aged animals, indicating a reduced osteoclast activity. Moreover, aged animals showed also an enhanced inflammatory response, characterized by an increased infiltration of macrophages within the callus tissue. Taken together, we herein report for the first time a reliable model to study fracture healing failure in aged mice. In the future, the use of this model enables us to study novel therapeutic strategies and molecular mechanics of failed fracture healing during aging.
“We Closed the Ports to Protect Refugees.” Hygienic Borders and Deterrence Humanitarianism during Covid-19
Authors: Tazzioli Martina , Stierl Maurice
Published: October 2021

This article investigates how the security-humanitarian rationale that underpins migration governmentality has been restructured by and inflected in light of hygienic-sanitary borders which enforce racialised confinement in the name of both migrants' and citizens' safety from infection by Covid-19. Focusing on the politics of migration containment along EUrope's frontiers, examining in particular border reinforcements carried out by Italy, Malta and Greece, we interrogate how the pandemic has been exploited to enact deterrence through hygienic-sanitary border enforcements. These enforcements are underpinned by an ambivalent security-humanitarian narrative that crafts migrants as subjects who cannot be protected by EU member states from the pandemic if allowed inside, and, at once, as potential vehicles of contagion - ‘Corona spreaders’ - and thus as dangers on a bacterial-hygienic level. Our article demonstrates that these EUropean border measures are more than temporary responses to an unprecedented health crisis. Rather, the pandemic has been seized as an opportunity to strengthen existing deterrence measures and hamper migrants' access to asylum through biopolitical and spatial tactics that aim to restructure the border regime. While emphasising the historical trajectories and continuities underwriting these current developments, we contend that the pandemic functions as an accelerator of dynamics of migrant incarceration and containment.
Player Engagement with Games: Formal Reliefs and Representation Checks
Authors: Egerton Karl
Published: October 2021

Alongside the direct parallels and contrasts between traditional narrative fiction and games, there lie certain partial analogies that provide their own insights. This article begins by examining a direct parallel between narrative fiction and games—the role of fictional reliefs and reality checks in shaping aesthetic engagement—before arguing that from this a partial analogy can be developed stemming from a feature that distinguishes most games from most traditional fictions: the presence of rules. The relation between rules and fiction in games has heretofore been acknowledged but not examined in detail, giving an impression of a tension that is constant. However, the paired concepts of formal reliefs and representation checks, once introduced, allow us to explain how rules and fiction interact to alter the ways in which players engage with games in a dynamic but limited way.
Sepsis prediction, early detection, and identification using clinical text for machine learning: a systematic review
Authors: Yan Melissa Y , Gustad Lise Tuset , Nytrø Øystein
Published: October 2021

Objective

To determine the effects of using unstructured clinical text in machine learning (ML) for prediction, early detection, and identification of sepsis.

Materials and methods

PubMed, Scopus, ACM DL, dblp, and IEEE Xplore databases were searched. Articles utilizing clinical text for ML or natural language processing (NLP) to detect, identify, recognize, diagnose, or predict the onset, development, progress, or prognosis of systemic inflammatory response syndrome, sepsis, severe sepsis, or septic shock were included. Sepsis definition, dataset, types of data, ML models, NLP techniques, and evaluation metrics were extracted.

Results

The clinical text used in models include narrative notes written by nurses, physicians, and specialists in varying situations. This is often combined with common structured data such as demographics, vital signs, laboratory data, and medications. Area under the receiver operating characteristic curve (AUC) comparison of ML methods showed that utilizing both text and structured data predicts sepsis earlier and more accurately than structured data alone. No meta-analysis was performed because of incomparable measurements among the 9 included studies.

Discussion

Studies focused on sepsis identification or early detection before onset; no studies used patient histories beyond the current episode of care to predict sepsis. Sepsis definition affects reporting methods, outcomes, and results. Many methods rely on continuous vital sign measurements in intensive care, making them not easily transferable to general ward units.

Conclusions

Approaches were heterogeneous, but studies showed that utilizing both unstructured text and structured data in ML can improve identification and early detection of sepsis.
The significance of female dimorphic characters of primary freshwater crabs for the systematics of Eubrachyura (Crustacea: Decapoda: Brachyura)
Authors: Cumberlidge Neil , Johnson Emily C , Leever Ellen M , Soma Julia B , Ahles Kaitlyn M , Kamanli Seyit A , Clark Paul F
Published: October 2021

Male pleopods, pleon, and gonopods 1 and 2 of primary brachyuran freshwater crabs have been used for well over 100 years as important taxonomic characters to distinguish between species, genera, and families. In contrast, while there have been a number of studies of female dimorphic brachyuran characters, including two families of primary freshwater crabs, their pleopods have been virtually ignored and presumed to be uninformative with respect to systematics. Consequently, we provide for the first-time descriptions and images of the female pleon, pleopods, egg attachment sites, and telson of representatives of five primary freshwater crab families: Potamidae, Potamonautidae, Gecarcinucidae, Pseudothelphusidae, and Trichodactylidae. For preliminary comparative purposes, similar details are also presented for species representing two Heterotremata families, e.g., Epialtidae and Portunidae, and four Thoracotremata families e.g., Gecarcinidae, Grapsidae, Sesarmidae, and Varunidae. This morphological comparative study of female characters provides a new dataset for family-level comparisons of freshwater crabs. As a result, two groups of primary freshwater crabs are recognized: a revised Potamoidea Ortmann, 1896 for Potamidae, Potamonautidae, Deckeniidae, Gecarcinucidae, Pseudothelphusidae, and Epiloboceridae, and Trichodactyloidea comprising Trichodactylidae. Although all of the non-trichodactylid freshwater crab families are morphological heterotremes with male coxal gonopores and female sternal gonopores, their current Heterotremata assignment is here being questioned. From new evidence presented here, this group of primary freshwater Brachyura may be more properly positioned outside of Heterotremata, as a sister group of Thoracotremata. This use of novel female diagnostic characters, however, supports the continued assignment of Trichodactylidae to Heterotremata.