bluuebunny/crossref_metadata_2025 huggingface dataset:
Choice, Selection, and Learning
Authors: Levinthal Daniel A.
Published: July 2021

The chapter examines the relationship among processes of choice, selection, and learning. The notions of choice and selection differ with respect to the degree of intentionality that they suggest. However, if “choice” is viewed as the identification of preferential action over some set of latent alternatives, then processes of choice and selection can be seen as differing primarily by their level of analysis. Another critical distinction among these processes is their temporal orientation. In the case of rational choice, selection is driven by a projection of the future consequences of alternative actions. In contrast, evolutionary selection processes are driven by the contemporaneous relative fitness of alternatives. A third perspective is that of learning. Here, the preferential attraction to different alternatives is backward looking, with actions that are perceived to have been associated with more successful outcomes more likely to be enacted than those associated with less successful outcomes.
Exploration and Exploitation
Authors: Levinthal Daniel A.
Published: July 2021

While traditionally processes of exploration and exploitation have been understood with respect to the novelty of the associated behavior and the a priori beliefs of the promise of these behaviors, the perspective developed here highlights the possible contestation regarding the merit and promise of a given action or initiative. An action may be viewed as exploratory from an observer’s perspective, while that same action may be considered exploitive from the perspective of the focal actor. The argument highlights the alternative beliefs and cognitive schemas by which promising behaviors and initiatives are evaluated. Validating actions to others, either ex ante or ex post, requires either the validation of particular dimensions of performance or the casting of “shadows” on the dimension of performance valued by others.
Punctuated Change
Authors: Levinthal Daniel A.
Published: July 2021

The pace of change is a central question regarding evolutionary dynamics. Some management theorists have pointed to processes of punctuated change; however, it is argued here that such accounts have generally under-attended to the multi-level nature of these processes and in particular to the critical role of speciation. By recognizing the multi-level nature of these dynamics, we can reconcile our often conflicting sense of organizations and technologies as undergoing periods of rapid change, while still conforming to a gradualist perspective with regard to the underlying elements of organizational capabilities and technologies. This argument is developed to consider change processes in three different contexts: the pace of technological change, shifts in organizational strategy and capabilities, and changes in the scope of firms.
A fundamental plane in X-ray binary activity of external galaxies
Authors: Inoue Yoshiyuki , Yabe Kiyoto , Ueda Yoshihiro
Published: July 2021

We construct a new catalog of extragalactic X-ray binaries (XRBs) by matching the latest Chandra source catalog with local galaxy catalogs. Our XRB catalog contains 4430 XRBs hosted by 237 galaxies within ∼130 Mpc. As XRBs dominate the X-ray activity in galaxies, the catalog enables us to study the correlations between the total X-ray luminosity of a galaxy LX,tot, star formation rate $\dot{\rho }_\star$, and stellar mass M⋆. As previously reported, LX,tot is correlated with $\dot{\rho }_\star$ and M⋆. In particular, we find that there is a fundamental plane in those three parameters; $\log L_{\rm X,tot}={38.80^{+0.09}_{-0.12}}+\log (\dot{\rho }_\star + \alpha M_\star )$, where α = (3.36 ± 1.40) × 10−11 yr−1. In order to investigate this relation, we construct a phenomenological binary population synthesis model. We find that the high-mass XRB and low-mass XRB fraction in formed compact object binary systems is $\sim\! 9\%$ and ${0.04}\%$, respectively. Utilizing the latest XMM-Newton and Swift X-ray source catalog data sets, additional XRB candidates are also found, resulting in a total of 5757 XRBs hosted by 311 galaxies.
The co-chaperone HOP3 participates in jasmonic acid signaling by regulating CORONATINE-INSENSITIVE 1 activity
Authors: Muñoz Alfonso , Santamaria M Estrella , Fernández-Bautista Nuria , Mangano Silvina , Toribio René , Martínez Manuel , Berrocal-Lobo Marta , Diaz Isabel , Castellano M Mar
Published: July 2021

HOPs (HSP70–HSP90 organizing proteins) are a highly conserved family of HSP70 and HSP90 co-chaperones whose role in assisting the folding of various hormonal receptors has been extensively studied in mammals. In plants, HOPs are mainly associated with stress response, but their potential involvement in hormonal networks remains completely unexplored. In this article we describe that a member of the HOP family, HOP3, is involved in the jasmonic acid (JA) pathway and is linked to plant defense responses not only to pathogens, but also to a generalist herbivore. The JA pathway regulates responses to Botrytis cinerea infection and to Tetranychus urticae feeding; our data demonstrate that the Arabidopsis (Arabidopsis thaliana) hop3-1 mutant shows an increased susceptibility to both. The hop3-1 mutant exhibits reduced sensitivity to JA derivatives in root growth assays and downregulation of different JA-responsive genes in response to methyl jasmonate, further revealing the relevance of HOP3 in the JA pathway. Interestingly, yeast two-hybrid assays and in planta co-immunoprecipitation assays found that HOP3 interacts with COI1, suggesting that COI1 is a target of HOP3. Consistent with this observation, COI1 activity is reduced in the hop3-1 mutant. All these data strongly suggest that, specifically among HOPs, HOP3 plays a relevant role in the JA pathway by regulating COI1 activity in response to JA and, consequently, participating in defense signaling to biotic stresses.
Weighting gates in circuit complexity and holography
Authors: Akal I
Published: July 2021

Motivated by recent studies of quantum computational complexity in quantum field theory and holography, we discuss how weighting certain classes of gates building up a quantum circuit more heavily than others affects the complexity. Utilizing Nielsen’s geometric approach to circuit complexity, we investigate the effects for a regulated field theory for which the optimal circuit is a representation of $GL(N,\mathbb{R})$. More precisely, we work out how a uniformly chosen weighting factor acting on the entangling gates affects the complexity and, particularly, its divergent behavior. We show that assigning a higher cost to the entangling gates increases the complexity. Employing penalized and unpenalized complexities for the $\mathcal{F}_{\kappa=2}$ cost, we further find an interesting relation between the latter and that based on the unpenalized $\mathcal{F}_{\kappa=1}$ cost. In addition, we exhibit how imposing such penalties modifies the leading-order UV divergence in the complexity. We show that appropriately tuning the gate weighting eliminates the additional logarithmic factor, thus resulting in a simple power-law scaling. We also compare the circuit complexity with holographic predictions, specifically based on the complexity=action conjecture, and relate the weighting factor to certain bulk quantities. Finally, we comment on certain expectations concerning the role of gate penalties in defining complexity in field theory and also speculate on possible implications for holography.
An examination of housing interventions among youth experiencing homelessness: an investigation into racial/ethnic and sexual minority status
Authors: Hill C , Hsu H , Holguin M , Morton M , Winetrobe H , Rice E
Published: July 2021

Objectives

The purpose of this study is to explore main and interaction effects of minority and multiple minority statuses on exits from homelessness and the stability of homelessness exits overtime.

Methods

This study utilized the Homeless Management Information System administrative data of 10 922 youth experiencing homelessness collected from a convenience sample of 16 geographically diverse communities across the USA between 2015–17. Using multinomial logistic regression analyses and logistic regression, main effects and interaction effects of racial/ethnic minority identity and sexual/gender minority identity were examined on various homelessness exits (n = 9957) and housing sustainability (n = 5836).

Results

Black youth, relative to White youth, were disproportionately exiting homelessness through incarceration (P < 0.001). Black and Latinx youth were less likely to successfully self-resolve their homelessness (both P < 0.05). Black heterosexual and Black and Latinx non-heterosexual youth were most frequently lost to the homeless system (all P < 0.01). Black youth, relative to White youth, were approximately half as likely to remain stably housed after returning to family (P < 0.01).

Conclusions

With respect to housing exits and exit stability, Black and Latinx heterosexual youth are consistently at a disadvantage. Homelessness/housing systems and programs need to conduct a deeper investigation into how they implement and develop equitable outreach and engagement practices.
Incidence and course of COVID-19 hospitalizations among patients with familial Mediterranean fever
Authors: Kharouf Fadi , Ishay Yuval , Kenig Ariel , Bitan Menachem , Ben-Chetrit Eldad
Published: July 2021

Objectives

To evaluate the incidence of hospitalization for coronavirus disease 2019 (COVID-19) in patients with FMF, as compared with the general population, and to compare the disease course between FMF inpatients, and age-, sex-, ethnicity- and comorbidity-matched non-FMF COVID-19 inpatients.

Methods

We used electronic medical records to obtain data about the total number of the insured population and the number of FMF patients in the two largest health management organizations in Jerusalem, Clalit and Meuhedet. The total number of COVID-19 inpatients at the Hadassah Medical Center, including those with FMF, for the period between 1 February 2020 and 10March 2021, was retrieved from the electronic medical records of Hadassah. COVID-19 course was compared between the FMF inpatient group and age-, sex-, ethnicity- and comorbidity-matched non-FMF COVID-19 inpatients. Each FMF inpatient was matched with two non-FMF controls.

Results

We found no statistically significant difference in the odds of hospitalization for COVID-19 between FMF patients and the non-FMF population (0.46% vs 0.41%, P = 0.73). Furthermore, we found similar disease severity and therapeutic approach in FMF COVID-19 inpatients and matched non-FMF COVID-19 inpatients.

Conclusions

Neither FMF nor baseline colchicine therapy, appear to affect the incidence of hospitalization for COVID-19 or the disease course, in terms of severity and therapeutic approach.
DOSIMETRIC CHARACTERISATION OF A SUB-NATURAL BACKGROUND RADIATION ENVIRONMENT FOR RADIOBIOLOGY INVESTIGATIONS
Authors: Kennedy Konnor J , LeBlanc Alexandre , Pirkkanen Jake , Thome Christopher , Tai T C , LeClair Robert , Boreham Douglas R
Published: July 2021

Living systems have evolved in the presence of naturally occurring ionising radiation. REPAIR is a research project investigating the biological effects of sub-natural background radiation exposure in SNOLAB, a deep-underground laboratory. Biological systems are being cultured within a sub-background environment as well as two control locations (underground and surface). A comprehensive dosimetric analysis was performed. GEANT4 simulation was used to characterise the contribution from gamma, muons and neutrons. Additionally, dose rates from radon, 40K and 14C were calculated based on measured activity concentrations. The total absorbed dose rate in the sub-background environment was 27 times lower than the surface control, at 2.48 ± 0.20 nGy hr−1, including a >400-fold reduction in the high linear energy transfer components. This modelling quantitatively confirms that the environment within SNOLAB provides a substantially reduced background radiation dose rate, thereby setting the stage for future sub-background biological studies using a variety of model organisms.
The (temporary) end of the Fundatio Europaea (FE)
Authors: Jung Stefanie
Published: July 2021

In 2012, the European Commission presented a draft regulation proposing the establishment of a European Foundation (called Fundatio Europaea). This article concisely retraces the legislative process of the project, which—unfortunately—was not successful in the end. The project is not expected to be revived in the short or medium term. Concrete alternatives to the FE have not yet been considered either. Nevertheless, regarding social enterprises, the European Union could potentially consider measures partially addressing similar issues.
Is Oral Food Challenge as Safe Enough as It Seems?
Authors: Sengul Emeksiz Zeynep , Ertugrul Aysegul , Ozmen Serap , Cavkaytar Ozlem , Ercan Nazlı , Bostancı İlknur Birol
Published: July 2021

Background

Oral food challenges (OFCs) assist in the diagnosis of food allergies and are essential to determine whether an allergy has been outgrown. During the OFC, a medical procedure e introduces foods suspected to be allergenic orally in increasing doses. Mild skin reactions such as urticaria or rarely serious life-threatening reactions such as anaphylaxis may develop.

Objective

In this study, we aimed to retrospectively evaluate the clinical and laboratory characteristics of patients who experienced anaphylaxis during open OFCs in a tertiary care children’s hospital.

Methods

Patients who underwent OFCs to confirm the presence of a food allergy or to assess tolerance status at the University of Health Sciences, Ankara, Dr. Sami Ulus Maternity and Children Training and Research Hospital, Pediatric Allergy and Immunology Outpatient Clinic between 1 January 2013 and 1 February 2016, were included in the study. Patients’ data were obtained retrospectively from electronic medical records and challenge chart reviews.

Results

A total of 623 OFCs were performed during the period studied. Nine patients (1.4%) between 13 and 67 months of age (mean age: 38.3 months) developed anaphylaxis during their OFC.

Conclusion

OFCs should be performed in a hospital or outpatient office under medical supervision that is adequate for anaphylaxis intervention by an allergy specialist. Close observation of objective and subjective symptoms is essential during the challenge because there are no laboratory tests that can predict an anaphylactic diagnosis or the severity of the reaction.
Acetabular volume and femoral coverage change following Dega-like osteotomy in treatment of developmental dysplasia of the hip
Authors: Gigi Roy , Lawniczak Dominik , Kurian Binu , Madan Sanjeev , Fernandes James
Published: July 2021

Although Dega’s acetabuloplasty has become a commonly used osteotomy, there is still an ongoing debate regarding its impact on the volume and depth of the acetabulum. The purpose of our study was to assess the postoperative images of the transverse acetabular plane and version obtained from developmental dysplasia of the hip (DDH) patients after a modified Dega osteotomy. We performed a retrospective study of the morphologic indices obtained from the pelvic X-rays and computer tomography (CT) scans of patients with DDH, who were operated in our institution between July 2005 and October 2013, using the modified Dega osteotomy. Preoperative and postoperative pelvic X-rays were used to measure the acetabular index and the acetabular (ACM) angle. The postoperative CT scans were used to measure the acetabular anteversion angle (AAA), acetabular depth and depth of acetabular coverage [total acetabular index (TAI)]. The contralateral unaffected hips served as control. The postoperative acetabular indices and ACMs showed a significant improvement, with near-normal values measured 1 year after the surgery. Comparing the CT scan parameters (AAA, TAI and the depth of acetabulum) showed that TAI and the depth of acetabulum were not significantly different between the groups (TAI: P = 0.423; depth of acetabulum: P = 0.132), whereas AAA comparison implied a slight advantage of the DDH hips (17.6° DDH vs. 13.3° contralateral, P = 0.001). On the basis of images set of acetabular morphometric parameters, our study substantiates previous reports on an increase of acetabular volume and a significant improvement of femoral head coverage for patients with DDH who underwent Dega acetabuloplasty. Level of evidence: Level III – retrospective comparative study.
Extension toward the Trapezius in a Transversely Oriented Latissimus Dorsi Flap for Breast Reconstruction
Authors: Numajiri Toshiaki , Morita Daiki , Tsujiko Shoko , Moriguchi Yoshio
Published: July 2021

Background:

A transverse paddle latissimus dorsi (LD) flap has the advantage that if the skin paddle is placed in the transverse bra line, the donor site scar is well hidden by underwear. With this transfer, medial back tissues are usually moved to the medial area of the reconstructed breast following 180 degree rotation. Because these tissues are thinner than the lateral thoracic area, the medial part of the reconstructed breast sometimes becomes flatter than expected.

Methods:

To add bulk in the medial lower quadrant for giving an impression of an outward-expanding breast, we modified the LD flap by adding a part of the trapezius muscle. Seven patients underwent mastectomy and simultaneously received a modified LD flap. To hide the donor site scar beneath underwear, the skin paddle needed to be oriented transversely. The additional harvested tissues were tested for vascularity by fluorescence following intravascular injections of indocyanine green. If this was negative, the tissue was not used for breast reconstruction. Postoperatively, another surgeon judged whether this modification had contributed favorably to the reconstructed medial lower quadrant.

Results:

Indocyanine green testing was positive in six cases. The shape of the lower medial quadrant was judged as good in five of the seven cases. Complications included an animation deformity of the LD muscle, donor site seroma, and donor site wound dehiscence.

Conclusion:

This transversely oriented LD flap with extension to the trapezius muscle placed at the bra-line is one option to add bulk to the medial lower quadrant of the reconstructed breast when an additional scar is not desired for cosmetic reasons.
Activation of the intestinal tissue renin-angiotensin system by transient sodium loading in salt-sensitive rats
Authors: Ryuzaki Masaki , Miyashita Kazutoshi , Sato Masaaki , Inoue Hiroyuki , Fujii Kentaro , Hagiwara Aika , Uto Asuka , Endo Sho , Oshida Takuma , Kinouchi Kenichiro , Itoh Hiroshi
Published: July 2021

Background:

The renal tissue renin-angiotensin system is known to be activated by salt loading in salt-sensitive rats; however, the response in other organs remains unclear.

Method:

Spontaneously hypertensive rats were subjected to normal tap water or transient high-salt-concentration water from 6 to 14 weeks of age and were thereafter given normal tap water. From 18 to 20 weeks of age, rats given water with a high salt concentration were treated with an angiotensin II type 1 receptor blocker, valsartan.

Results:

Sustained blood pressure elevation by transient salt loading coincided with a persistent decrease in the fecal sodium content and sustained excess of the circulating volume in spontaneously hypertensive rats. Administration of valsartan sustainably reduced the blood pressure and normalized the fecal sodium levels. Notably, transient salt loading persistently induced the intestinal tissue renin-angiotensin system and enhanced sodium transporter expression exclusively in the small intestine of salt-sensitive rats, suggesting the potential connection of intestinal sodium absorption to salt sensitivity.

Conclusion:

These results reveal the previously unappreciated contribution of the intestinal tissue renin-angiotensin system to sodium homeostasis and blood pressure regulation in the pathophysiology of salt-sensitive hypertension.
The Effect of Spinal Orthoses on Immobilizing the Cervical Spine: A Systematic Review of Research Methodologies
Authors: Eddison Nicola , Benyahia Salma , Chockalingam Nachiappan
Published: July 2021

Introduction

The purpose of this article is to review the literature on the effect of immobilization of the cervical spine using orthotic devices. The review focused on the methodologies of the studies to see if this might be a contributing factor to the lack of available clinical guidelines on spinal immobilization using orthoses.

Methods

This review was conducted using PRISMA guidelines (PLoS Med. 2009;6:e1000097). The search was conducted in August 2019 within all major databases using relevant phrases. No date restrictions were applied, but the search was restricted to full manuscripts published in English. These searches were then supplemented by tracking all key references from the appropriate articles identified. Articles were selected according to a priori–defined criteria. Initially, data were extracted regarding publication details, orthosis name and group, spinal level studied, and whether cervical range of motion was measured.

Results

A total of 52 articles fulfilled the inclusion criteria. This article discusses the methodology of the included studies.

Conclusions

There is a clear paucity of well-designed research on immobilization of the cervical spine using orthotic devices. Comparing the results of studies using different types of orthoses is difficult due to the type and age of the participants involved (healthy, pathological, cadaver) and the different techniques of measurement used. This lack of standardization prevents meta-analyses from being performed and may be a contributing factor to the lack of available clinical guidelines. An agreed structured methodology is required to enable meta-analyses and determine clinical guidelines for the prescription of spinal orthoses for cervical spine pathology.
Determinants of functional outcome following ankle fracture
Authors: Audet Megan A. , Benedick Alex , Breslin Mary A. , Schmidt Tegan , Vallier Heather A.
Published: July 2021

Objectives:

To assess the patient and injury characteristics that impact functional outcomes after ankle fracture.

Design:

Retrospective study.

Setting:

Urban level I trauma center.

Patients/Participants:

One thousand patients underwent fixation of ankle fracture (AO/OTA 44) between 2006 and 2015. Four hundred sixteen completed functional outcome surveys by telephone or mail at a mean of 5.9 years after injury.

Intervention:

Open reduction internal fixation.

Main outcome measure:

Foot Function Index (FFI) and Short Musculoskeletal Function Assessment (SMFA).

Results:

Mean age was 46.7 years, with 46.2% male. Higher (worse) FFI scores were seen in tobacco users (38.9 vs 30.1), recreational drug users (45.9 vs 32.7), and the morbidly obese (52.0 vs 30.6), all P < .005. Higher (worse) SMFA dysfunction and bothersome scores were also seen in these groups, and in females and alcohol users. Multiple regression analysis identified female gender, obesity, tobacco and alcohol use, complications, secondary procedures, and multiple additional injuries as independent predictors of higher scores (all P < .04). Fracture patterns, open fracture, and development of arthritis had no impact on FFI or SMFA scores.

Conclusion:

Patient characteristics, not under surgeon-control, such as female sex, obesity, and substance use, appear to contribute to patient-reported functional outcome scores more than injury characteristics.

Level of Evidence:

Level 3, prognostic
Brief Report: Pharmacokinetics of Bictegravir and Tenofovir in Combination With Darunavir/Cobicistat in Treatment-Experienced Persons With HIV
Authors: Salama Engie , Hill Lucas , Patel Nimish , Best Brookie M. , Momper Jeremiah D.
Published: July 2021

Background:

Bictegravir coformulated with emtricitabine and tenofovir alafenamide as a fixed-dose combination (BIC/FTC/TAF 50/200/25 mg) is recommended as an initial regimen in patients who are antiretroviral (ARV)-naïve or virologically suppressed on a stable ARV regimen. However, no real-world pharmacokinetic (PK) data are available in treatment-experienced patients with antiretroviral resistance receiving BIC/FTC/TAF plus a boosted protease inhibitor.

Setting/methods:

This prospective, single-center, nonrandomized pharmacokinetic study enrolled adult treatment-experienced persons with HIV and creatinine clearance >30 mL/min receiving BIC/FTC/TAF + DRV/c as part of routine clinical care. Steady-state PK profiles of BIC, TAF, tenofovir (TFV), and DRV after daily dosing of BIC/FTC/TAF + darunavir/cobicistat (DRV/c) were obtained with samples at predose and 0.5, 1, 2, and 4 hours postdose. The AUC0–24 at steady state was extrapolated by imputing C0 for C24 for each participant (AUC0-tau,exp).

Results:

Nine participants were enrolled with a median age of 59 years (range 54–67) and median number of years on ART of 19 (range 5.8–30). The median (interquartile range [IQR]) BIC AUC0-tau,exp and Cmax values were 128.9 µg*h/mL (78.1–159.5) and 6.9 µg/mL (5.1–9.8), respectively. The median (IQR) TAF AUC0-tau,exp and Cmax values were 0.376 µg*h/mL (0.199–0.430) and 0.276 µg/mL (0.149–0.543), respectively. Predose concentrations of TFV and DRV were comparable with historical data.

Conclusion:

Treatment-experienced persons with HIV receiving BIC/FTC/TAF + darunavir/cobicistat (DRV/c) had BIC exposures (AUC0-tau) that were increased by approximately 26% compared with historical PK data. Although TAF exposures were substantially increased, plasma TFV was only modestly higher. These results suggest that BIC/TAF/FTC + DRV/c is a viable antiviral regimen option for treatment-experienced persons.
Dermatomyositis on 68Ga-FAPI PET/CT in a Patient With Nasopharyngeal Carcinoma
Authors: Wu Junhao , Qiu Lin , Wang Yingwei , Zhang Chunyin
Published: July 2021

Dermatomyositis is an idiopathic inflammatory myopathy often associated with malignancies. 68Ga-FAPI PET/CT was performed on a 58-year-old man with newly diagnosed dermatomyositis. 68Ga-FAPI PET/CT showed multiple increased FAPI activity in whole-body muscles and nasopharyngeal lesion. A biopsy of the nasopharyngeal lesion confirmed nasopharyngeal carcinoma. 68Ga-FAPI PET/CT can provide a “1-stop” imaging method for patients with dermatomyositis.
Maternal spatial training before fertilization improves the spatial learning process in female offspring
Authors: Riyahi Javad , Abdoli Behrouz , Gelfo Francesca , Petrosini Laura , Rezaei Rasoul , Haghparast Abbas
Published: July 2021

Recent results of our team showed that parental spatial training before fertilization improves the offspring’s spatial memory. However, the process of spatial learning (short-term/working and long-term memories, mnesic consolidation and procedures) in the offspring has not been fully clarified yet. Therefore, this study aimed at specifically analyzing whether maternal learning of a spatial task before fertilization can impact on the process of spatial learning in the female offspring. In the present study, 8-week-old female Wistar rats that had been spatially trained (or not) in the Morris Water Maze (MWM) were mated with conspecific standard-reared male rats, and their 4-week-old female offspring were spatially tested in the same MWM to evaluate their learning and memory processes. Results showed that the female offspring of trained mothers significantly displayed lower escape latencies, higher swimming speed, shorter total distance swum, longer percentage of time spent in the target quadrant and better localization memory in comparison to the female offspring of not trained mothers. Further, MWM performances of mothers trained and their female offspring significantly correlated. These findings indicate that the maternal spatial training before fertilization improves the spatial learning and memory consolidation process of the female offspring.
Simultaneous treatment with pentoxifylline does not adversely affect the neurotrophic effects of brain-derived neurotrophic factor on spiral ganglion neurons
Authors: Geissler Christin , Blumenstock Miriam , Gabrielpillai Jennis , Guchlerner Leon , Stöver Timo , Diensthuber Marc
Published: July 2021

The hemorheologic drug pentoxifylline is applied for the treatment of sudden sensorineural hearing loss and tinnitus to improve cochlear microcirculation. Recent studies also suggest protective and trophic effects on neuronal cells. Because the preservation of sensorineural structures of the inner ear is fundamental for normal hearing and hearing restoration with auditory prostheses, pentoxifylline and neurotrophic factors such as brain-derived neurotrophic factor (BDNF) are promising candidates to treat degenerative disorders of the inner ear. We used an in-vitro model to determine the neurotrophic effects of these factors on spiral ganglion cells from postnatal rats. Pentoxifylline, alone and in combination with BDNF, was added at various concentrations to the cultured cells. Cells were immunolabeled and analyzed to determine neuronal survival, neurite length, neuronal branching and morphology. Pentoxifylline did not significantly increase or decrease neuronal survival, neurite length and neuronal branching compared to control cultures. Analysis of cellular morphology showed that diverse neuronal subtypes developed in the presence of pentoxifylline. Our data revealed that pentoxifylline did not interfere with the robust neurotrophic effects of BDNF on spiral ganglion neurons when cultured cells were treated with pentoxifylline and BDNF simultaneously. The results of our study do not suggest major neurotrophic effects of pentoxifylline on cultured spiral ganglion neurons. Because pentoxifylline has no detrimental effects on spiral ganglion neurons and does not reduce the effects of BDNF, both agents could be combined to treat diseases of the inner ear provided that future in vivo experiments and clinical studies support these findings.
Neurovascular protection of salvianolic acid B and ginsenoside Rg1 combination against acute ischemic stroke in rats
Authors: Fu Yao , Xing Rongrong , Wang Linlin , Yang Li , Jiang Baohong
Published: July 2021

Ischemic stroke continues to be a major global health problem associated with considerable mortality and morbidity. Thus, it is still targeted by researchers for developing new strategies or drugs to alleviate the lesion of stroke. In the present study, both the permanent occlusion of the middle cerebral artery (MCAO) model and the restoration of cerebral blood flow after middle cerebral artery occlusion (CI/R) model were set up for evaluating the efficiency of salvianolic acid B and ginsenoside Rg1 combination (SalB-Rg1). SalB-Rg1 decreased infarct area through 3,5-triphenyltetrazolium chloride stain and improved neurological behavior through Longa Score or Left-Biased Swings on both MCAO rats and CI/R rats. Neural protection of SalB-Rg1 against ischemia or ischemic reperfusion injury was evidenced by the inhibition of nucleus pyknosis, liquefaction necrosis through H&E stain and Nissl stain. Furthermore, protection of SalB-Rg1 on blood-brain barrier (BBB) was more significant on CI/R rats, accompanying with the downregulation of matrix metalloproteinase-2 and matrix metalloproteinase-9, and recovery of zonula occludens-1 expression. These results provide compelling evidence that SalB-Rg1 holds the potential to be developed as an optimal therapeutic strategy to alleviate the injury of ischemia or ischemic reperfusion.
Structural identifiability of the generalized Lotka–Volterra model for microbiome studies
Authors: Remien Christopher H. , Eckwright Mariah J. , Ridenhour Benjamin J.
Published: July 2021

Population dynamic models can be used in conjunction with time series of species abundances to infer interactions. Understanding microbial interactions is a prerequisite for numerous goals in microbiome research, including predicting how populations change over time, determining how manipulations of microbiomes affect dynamics and designing synthetic microbiomes to perform tasks. As such, there is great interest in adapting population dynamic theory for microbial systems. Despite the appeal, numerous hurdles exist. One hurdle is that the data commonly obtained from DNA sequencing yield estimates of relative abundances, while population dynamic models such as the generalized Lotka–Volterra model track absolute abundances or densities. It is not clear whether relative abundance data alone can be used to infer parameters of population dynamic models such as the Lotka–Volterra model. We used structural identifiability analyses to determine the extent to which a time series of relative abundances can be used to parametrize the generalized Lotka–Volterra model. We found that only with absolute abundance data to accompany relative abundance estimates from sequencing can all parameters be uniquely identified. However, relative abundance data alone do contain information on relative interaction strengths, which is sufficient for many studies where the goal is to estimate key interactions and their effects on dynamics. Using synthetic data of a simple community for which we know the underlying structure, local practical identifiability analysis showed that modest amounts of both process and measurement error do not fundamentally affect these identifiability properties.
The anatomy and palaeobiology of the early armoured dinosaur
Scutellosaurus lawleri
(Ornithischia: Thyreophora) from the Kayenta Formation (Lower Jurassic) of Arizona
Authors: Breeden Benjamin T. , Raven Thomas J. , Butler Richard J. , Rowe Timothy B. , Maidment Susannah C. R.
Published: July 2021

The armoured dinosaurs, Thyreophora, were a diverse clade of ornithischians known from the Early Jurassic to the end of the Cretaceous. During the Middle and Late Jurassic, the thyreophorans radiated to evolve large body size, quadrupedality, and complex chewing mechanisms, and members of the group include some of the most iconic dinosaurs, including the plated
Stegosaurus
and the club-tailed
Ankylosaurus
; however, the early stages of thyreophoran evolution are poorly understood due to a paucity of relatively complete remains from early diverging thyreophoran taxa.
Scutellosaurus lawleri
is generally reconstructed as the earliest-diverging thyreophoran and is known from over 70 specimens from the Lower Jurassic Kayenta Formation of Arizona, USA. Whereas
Scutellosaurus lawleri
is pivotal to our understanding of character-state changes at the base of Thyreophora that can shed light on the early evolution of the armoured dinosaurs, the taxon has received limited study. Herein, we provide a detailed account of the osteology of
Scutellosaurus lawleri
, figuring many elements for the first time.
Scutellosaurus lawleri
was the only definitive bipedal thyreophoran. Histological studies indicate that it grew slowly throughout its life, possessing lamellar-zonal tissue that was a consequence neither of its small size nor phylogenetic position, but may instead be autapomorphic, and supporting other studies that suggest thyreophorans had lower basal metabolic rates than other ornithischian dinosaurs. Faunal diversity of the Kayenta Formation in comparison with other well-known Early Jurassic-aged dinosaur-bearing formations indicates that there was considerable spatial and/or environmental variation in Early Jurassic dinosaur faunas.
Interindividual plasticity in metabolic and thermal tolerance traits from populations subjected to recent anthropogenic heating
Authors: Drown Melissa K. , DeLiberto Amanda N. , Ehrlich Moritz A. , Crawford Douglas L. , Oleksiak Marjorie F.
Published: July 2021

To better understand temperature's role in the interaction between local evolutionary adaptation and physiological plasticity, we investigated acclimation effects on metabolic performance and thermal tolerance among naturalFundulus heteroclitus(small estuarine fish) populations from different thermal environments.Fundulus heteroclituspopulations experience large daily and seasonal temperature variations, as well as local mean temperature differences across their large geographical cline. In this study, we use three populations: one locally heated (32°C) by thermal effluence (TE) from the Oyster Creek Nuclear Generating Station, NJ, and two nearby reference populations that do not experience local heating (28°C). After acclimation to 12 or 28°C, we quantified whole-animal metabolic (WAM) rate, critical thermal maximum (CTmax) and substrate-specific cardiac metabolic rate (CaM, substrates: glucose, fatty acids, lactate plus ketones plus ethanol, and endogenous (i.e. no added substrates)) in approximately 160 individuals from these three populations. Populations showed few significant differences due to large interindividual variation within populations. In general, for WAM and CTmax, the interindividual variation in acclimation response (log2ratio 28/12°C) was a function of performance at 12°C and order of acclimation (12–28°C versus 28–12°C). CTmaxand WAM were greater at 28°C than 12°C, although WAM had a small change (2.32-fold) compared with the expectation for a 16°C increase in temperature (expect 3- to 4.4-fold). By contrast, for CaM, the rates when acclimatized and assayed at 12 or 28°C were nearly identical. The small differences in CaM between 12 and 28°C temperature were partially explained by cardiac remodeling where individuals acclimatized to 12°C had larger hearts than individuals acclimatized to 28°C. Correlation among physiological traits was dependent on acclimation temperature. For example, WAM was negatively correlated with CTmaxat 12°C but positively correlated at 28°C. Additionally, glucose substrate supported higher CaM than fatty acid, and fatty acid supported higher CaM than lactate, ketones and alcohol (LKA) or endogenous. However, these responses were highly variable with some individuals using much more FA than glucose. These findings suggest interindividual variation in physiological responses to temperature acclimation and indicate that additional research investigating interindividual may be relevant for global climate change responses in many species.
Quality characteristics of lotus root (Nelumbo
nucifera G.) snacks according to heat treatment methods and
conditions
Authors: Choi Ji-Young , Park Junghoon , Kim Jiyoon , Kim Jungsoo , Jeong Saeul , Kim Minhyun , Park Sanghyeok , Moon Kwang-Deog
Published: July 2021

This work investigated the effects of various heating methods and conditions on
the quality characteristics of lotus root (Nelumbo nucifera G.)
snack. The lotus root snacks were processed using the following heating methods:
oven heating (OV), microwave heating (MW), air frying (AF), and oil frying (FR).
Twenty four samples were prepared based on the various temperatures and time
durations used for heating. Based on the results of color and hardness analyses,
OV (180°C, 9 min), MW (850 W, 8 min), AF (120°C, 10 min) and FR
(180°C, 70 sec) were selected as appropriate conditions for producing the
lotus root snacks. AF resulted in low carbohydrate content, crude fat content,
and neural detergent fiber content and the highest moisture content. There were
no significant differences in hardness among four methods. AF (120°C, 10
min) showed significantly higher L* values, total phenolics
contents, and 2,2-dipheny-1-picrylhydrazyl,
2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid radical scavenging
activity than other methods. In addition, water absorption and water solubility
indexes were the lowest in AF. Therefore, AF (120°C, 10 min) was
considered as an appropriate heating condition for the manufacturing of lotus
root snacks.
Antimicrobial activity and stability of Prunus
mume fruit extract against Streptococcus
mutans KCCM 40105 strain
Authors: Kim Bok-Seon , Kim So-Mang , Jeong Jae-Hee , Han Hong-Bi , Lee Hui-Won , Kim Cheol-Min , Woo Hyo-Gyeong , Hwang Dae-Sub , Park Myung-Won , Huh Chang-Ki
Published: July 2021

In this study, natural materials with antibacterial activity against the
Streptococcus mutans KCCM 40105 strain were selected, and
the most efficient extraction conditions were observed. The active substance was
stable under various treatment conditions. Of the 10 food materials groups, only
Prunus mume fruit showed antibacterial activity against
S. mutans strains. The antimicrobial activity by the
various extraction solvents was 18.66 mm (clear zone diameter) in the ethanol
extract and 20.18 mm in the water extract. Measurements of the antibacterial
activity according to the mixing ratio of the two solvents revealed the 30%
ethanol extract to have the highest activity (20.49 mm). Measurements of the
minimum inhibitory concentration (MIC) showed activity at a concentration of 3.0
mg/mL. The stability to heat was observed, but the extract was not active at pH
6.0 or higher. The antimicrobial activity of the 30% ethanol extract of
P. mume treated with enzymes was the same with both 10 ppm
and 100 ppm of the nine enzymes. On the other hand, the activity tended to
decrease slightly at 1,000 ppm. The activity of the catazyme enzyme and hydrogen
peroxide treatment decreased at the treatment concentration of 100 ppm.
Modeling shield immunity to reduce COVID-19 transmission in long-term care facilities
Authors: Lucia-Sanz Adriana , Magalie Andreea , Rodriguez-Gonzalez Rogelio , Leung Chung-Yin , Weitz Joshua S.
Published: July 2021

Nursing homes and other long-term care facilities in the United States have experienced severe COVID-19 outbreaks and elevated mortality rates, often following upon the inadvertent introduction of SARS-CoV-2. Following FDA emergency use approval, widespread distribution of vaccines has resulted in rapid reduction in COVID-19 cases in vulnerable, older populations. Yet, vaccination coverage remains incomplete amongst residents and healthcare workers. As such, mitigation and prevention strategies are needed to reduce the ongoing risk of transmission and mortality amongst vulnerable, nursing home populations. One such strategy is that of ‘shield immunity’, in which recovered individuals increase their contact rates and therefore shield individuals who remain susceptible to infection. Here, we adapt recent population-scale shield immunity models to a network context. To do so, we evaluate network-based shield immunity by evaluating how restructured interactions in a bipartite network (e.g., between healthcare workers and long-term care residents) affects SARS-CoV-2 epidemic dynamics. First, we identify a series of rewiring principles that leverage viral testing, antibody testing, and vaccination information to reassign immunized healthcare workers to care for infected residents while retaining workload balance amidst an outbreak. We find a significant reduction in outbreak size when using infection and immune-based cohorting as a weekly intervention. Second, we also identify a preventative strategy using shield-immunity rewiring principles, by assigning susceptible healthcare workers to care for cohorts of immunized residents; this strategy reduces the risk that an inadvertent introduction of SARS-CoV-2 into the facility via a healthcare worker spreads to susceptible residents. Network-based epidemic modeling reveals that preventative rewiring can control the size of outbreaks at levels similar to that of isolation of infectious healthcare workers. Overall, this assessment of shield immunity provides further support for leveraging infection and immune status in network-based interventions to control and prevent the spread of COVID-19.
Senescence of stromal cells contributes to endometrium dysfunction and embryo implantation failure
Authors: Deryabin Pavel I. , Ivanova Julia S. , Borodkina Aleksandra V.
Published: July 2021

Successful implantation requires two-sided interaction between genetically normal embryo and properly prepared endometrium. At the cellular level the latter means hormone-regulated differentiation of endometrial stromal cells (ESCs) into decidual ones that create appropriate microenvironment for invading embryo. Impaired decidualization is proved to mediate implantation failures. Here we elicited ESCs’ senescence as the cause for disturbed decidualization of endometrial stroma and impaired blastocyst implantation. Ability to decidualize and to accept modeled blastocysts inversely correlated with senescence in patients’ ESCs lines. Reduced hormonal responsiveness of senescent ESCs led to inappropriate decidualization dynamics resulting in altered receptivity, disturbed ligand-receptor interaction with trophoblasts and modified architecture of extracellular matrix what hindered blastocysts’ invasion. Furthermore, senescent ESCs caused ‘bystander’ quenching of decidual reaction in adjacent cells reinforcing dysfunction of stromal compartment. Implementation of senomorphics reducing senescence phenotype diminished adverse effects of senescent ESCs on decidualization and implantation using both in vitro models and patients’ lines, what suggests a promising strategy to increase in vitro fertilization efficacy.
Diverse human astrocyte and microglial transcriptional responses to Alzheimer’s pathology
Authors: Smith Amy M. , Davey Karen , Tsartsalis Stergios , Khozoie Combiz , Fancy Nurun , Tang See Swee , Liaptsi Eirini , Weinert Maria , McGarry Aisling , Muirhead Robert C. J. , Gentleman Steve , Owen David R. , Matthews Paul M.
Published: July 2021

To better define roles that astrocytes and microglia play in Alzheimer’s disease (AD), we used single-nuclei RNA sequencing to comprehensively characterize transcriptomes in astrocyte and microglia nuclei isolated post mortem from neuropathologically-defined AD and control brains with a range of amyloid-beta and phospho-tau (pTau) pathology. Significant differences in glial gene expression (including AD risk genes expressed in astrocytes [CLU, MEF2C, IQCK] and microglia [APOE, MS4A6A, PILRA]) were correlated with tissue amyloid and pTau expression. Astrocytes were enriched for proteostatic, inflammatory and metal ion homeostasis pathways. Pathways for phagocytosis, proteostasis and autophagy were highly enriched in microglia and perivascular macrophages. Gene co-expression analyses revealed potential functional associations of soluble biomarkers of AD in astrocytes (CLU) and microglia (GPNMB). Our work highlights responses of both astrocytes and microglia for pathological protein clearance and inflammation, as well as glial transcriptional diversity in AD.
Effects of four antibiotics on the diversity of the intestinal microbiota
Authors: Huang Ce , Feng Shengyu , Huo Fengjiao , Liu Hailiang
Published: July 2021

Oral antibiotics remain the therapy of choice for severe bacterial infections; however, antibiotic use disrupts the intestinal microbiota, which increases the risk of colonization with intestinal pathogens. Currently, our understanding of antibiotic-mediated disturbances of the microbiota remains at the level of bacterial families or specific species, and little is known about the effect of antibiotics on potentially beneficial and potentially pathogenic bacteria under conditions of gut microbiota dysbiosis. Additionally, it is controversial whether the effects of antibiotics on the gut microbiota are temporary or permanent. In this study, we used 16S rRNA gene sequencing to evaluate the short-term and long-term effects of ampicillin, vancomycin, metronidazole, and neomycin on the murine intestinal microbiota by analyzing changes in the relative numbers of potentially beneficial and potentially pathogenic bacteria. We found that the changes in the intestinal microbiota reflected the antibiotics’ mechanisms of action and that dysbiosis of the intestinal microbiota led to competition between the different bacterial communities. Thus, destruction of bacteria with beneficial potential increased the abundance of bacteria with pathogenic potential. In addition, we found that these oral antibiotics had long-term negative effects on the intestinal microbiota and promoted the development of antibiotic-resistant bacterial strains. These results indicate that ampicillin, vancomycin, metronidazole, and neomycin have long-term negative effects and can cause irreversible changes in the diversity of the intestinal microbiota and the relative proportions of bacteria with beneficial potential and bacteria with pathogenic potential, thereby increasing the risk of host disease.