bluuebunny/crossref_metadata_2025 huggingface dataset:
Settling the Unsettled: Roles for Belief
Authors: Jackson Elizabeth
Published: April 2021

In Unsettled Thoughts, Julia Staffel argues that non-ideal thinkers should seek to approximate ideal Bayesian rationality. She argues that the more rational you are, the more benefits of rationality you will enjoy. After summarizing Staffel's main results, this paper looks more closely at two issues that arise later in the book: the relationship between Bayesian rationality and other kinds of rationality, and the role that outright belief plays in addition to credence. Ultimately, I argue that there are several roles that outright belief might play, and I explore different ways that these roles for belief might fit together.
Transcutaneous Temperature-Controlled Radiofrequency Treatment: Improvement in Female Genital Appearance, Sexual Dysfunction, and Stress Urinary Incontinence
Authors: Desai Sejal Ajmera , Vakil Zahaan , Kroumpouzos George
Published: April 2021

Background

Transcutaneous temperature-controlled radiofrequency (TTCRF) treatment is an emerging modality for vulvovaginal rejuvenation. However, clinical experience with this modality is limited.

Objectives

The aim of this study was to examine the efficacy of TTCRF treatment in improving female genital appearance, sexual function, and stress urinary incontinence (SUI).

Methods

Forty-eight patients complaining of sexual dysfunction (SD; n = 41) and/or SUI (n = 37) were included. Most patients had ≤3 TTCRF sessions. To evaluate the aesthetic results, photographs of the genital area taken before treatment were compared to those taken 6 weeks posttreatment in a blinded manner. Prior to treatment and 6 weeks after the final session, the Female Sexual Function Index (FSFI) questionnaire was administered to participants complaining of SD and the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-UI-SF) to those with complaints/symptoms of SUI. Preprocedure scores were compared with postprocedure scores by paired t test.

Results

Aesthetic improvement was noted in all patients. Preprocedure mean total FSFI score was 21.77 vs the respective postprocedure score of 25.79 (P < 0.00001). Most FSFI domains improved (pre- vs post-TTCRF mean score): sexual desire (from 2.99 to 3.54), arousal (from 3.14 to 3.83), orgasm (from 3.14 to 4.39), pain (from 4.41 to 5.04) (P < 0.00001 for all) and satisfaction (from 3.75 to 4.42; P = 0.001). Mean preprocedure ICIQ-UI-SF score was 10.10 and decreased to 4.81 (P < 0.00001) postprocedure.

Conclusions

A substantial improvement in genital appearance was observed. Assessment based on validated instruments demonstrated significant improvements in sexual function and SUI. TTCRF is a safe and effective treatment for these conditions.

Level of Evidence: 4
The peripheral and core regions of virus-host network of COVID-19
Authors: Wang Bingbo , Dong Xianan , Hu Jie , Ma Xiujuan , Han Chao , Wang Yajun , Gao Lin
Published: April 2021

Two thousand nineteen novel coronavirus SARS-CoV-2, the pathogen of COVID-19, has caused a catastrophic pandemic, which has a profound and widespread impact on human lives and social economy globally. However, the molecular perturbations induced by the SARS-CoV-2 infection remain unknown. In this paper, from the perspective of omnigenic, we analyze the properties of the neighborhood perturbed by SARS-CoV-2 in the human interactome and disclose the peripheral and core regions of virus-host network (VHN). We find that the virus-host proteins (VHPs) form a significantly connected VHN, among which highly perturbed proteins aggregate into an observable core region. The non-core region of VHN forms a large scale but relatively low perturbed periphery. We further validate that the periphery is non-negligible and conducive to identifying comorbidities and detecting drug repurposing candidates for COVID-19. We particularly put forward a flower model for COVID-19, SARS and H1N1 based on their peripheral regions, and the flower model shows more correlations between COVID-19 and other two similar diseases in common functional pathways and candidate drugs. Overall, our periphery-core pattern can not only offer insights into interconnectivity of SARS-CoV-2 VHPs but also facilitate the research on therapeutic drugs.
MHCBI: a pipeline for calculating peptide-MHC binding energy using semi-empirical quantum mechanical methods with explicit/implicit solvent models
Authors: Ortiz-Mahecha Carlos A , Agudelo William A , Patarroyo Manuel A , Patarroyo Manuel E , Suárez Carlos F
Published: April 2021

Experimentally estimating peptide–major histocompatibility complex (pMHC) binding affinity has been quite challenging due to the many receptors and the many potential ligands implicated in it. We have thus proposed a straightforward computational methodology considering the different mechanisms involved in pMHC binding to facilitate studying such receptor–ligand interactions. We have developed a pipeline using semi-empirical quantum mechanical methods for calculating pMHC class I and II molecules’ binding energy (BE). This pipeline can systematize the methodology for calculating pMHC system BE, enabling the rational design of T-cell epitopes to be used as pharmaceuticals and vaccines.
A Framework for the Eltonian Niche of Humans
Authors: Moll Remington J , Killion Alexander K , Hayward Matt W , Montgomery Robert A
Published: April 2021

Recent research has highlighted several influential roles that humans play in ecosystems, including that of a superpredator, hyperkeystone species, and niche constructor. This work has begun to describe the Eltonian niche of humans, which encompasses humanity's cumulative ecological and evolutionary roles in trophic systems. However, we lack a unifying framework that brings together these strands of research, links them to ecoevolutionary and sociocultural theory, and identifies current research needs. In this article, we present such a framework in hope of facilitating a more holistic approach to operationalizing human roles in trophic systems across an increasingly anthropogenic biosphere. The framework underscores how humans play numerous nuanced roles in trophic systems, from top-down to bottom-up, that entail not only pernicious effects but also benefits for many nonhuman species. Such a nuanced view of the Eltonian niche of humans is important for understanding complex social–ecological system functioning and enacting effective policies and conservation measures.
Omitting completion axillary lymph node dissection after detection of sentinel node micrometastases in breast cancer: first results from the prospective SENOMIC trial
Authors: Andersson Y , Bergkvist L , Frisell J , de Boniface J
Published: April 2021

Background

Completion axillary lymph node dissection has been abandoned widely among patients with breast cancer and sentinel lymph node micrometastases, based on evidence from prospective RCTs. Inclusion in these trials has been subject to selection bias, with patients undergoing mastectomy being under-represented. The aim of the SENOMIC (omission of axillary lymph node dissection in SENtinel NOde MICrometases) trial was to confirm the safety of omission of axillary lymph node dissection in patients with breast cancer and sentinel lymph node micrometastases, and including patients undergoing mastectomy.

Methods

The prospective SENOMIC multicentre cohort trial enrolled patients with breast cancer and sentinel lymph node micrometastases who had breast-conserving surgery or mastectomy at one of 23 Swedish hospitals between October 2013 and March 2017. No completion axillary lymph node dissection was performed. The primary endpoint was event-free survival, with a trial accrual target of 452 patients. Survival proportions were based on Kaplan–Meier survival estimates.

Results

The trial included 566 patients. Median follow-up was 38 (range 7–67) months. The 3-year event-free survival rate was 96.2 per cent, based on 26 reported breast cancer recurrences, including five isolated axillary recurrences. The unadjusted 3-year event-free survival rate was higher than anticipated, but differed between patients who had mastectomy and those who underwent breast-conserving surgery (93.8 versus 97.8 per cent respectively; P = 0.011). Patients who underwent mastectomy had significantly worse tumour characteristics. On univariable Cox proportional hazards regression analysis, patients who had mastectomy without adjuvant radiotherapy had a significantly higher risk of recurrence than those who underwent breast-conserving surgery (hazard ratio 2.91, 95 per cent c.i. 1.25 to 6.75).

Conclusion

After 3 years, event-free survival was excellent in patients with breast cancer and sentinel node micrometastases despite omission of axillary lymph node dissection. Long-term follow-up and continued enrolment of patients having mastectomy, especially those not receiving adjuvant radiotherapy, are of utmost importance.
The role of gut dysbiosis in Parkinson’s disease: mechanistic insights and therapeutic options
Authors: Wang Qing , Luo Yuqi , Ray Chaudhuri K , Reynolds Richard , Tan Eng-King , Pettersson Sven
Published: April 2021

Parkinson’s disease is a common neurodegenerative disorder in which gastrointestinal symptoms may appear prior to motor symptoms. The gut microbiota of patients with Parkinson’s disease shows unique changes, which may be used as early biomarkers of disease. Alterations in the gut microbiota composition may be related to the cause or effect of motor or non-motor symptoms, but the specific pathogenic mechanisms are unclear. The gut microbiota and its metabolites have been suggested to be involved in the pathogenesis of Parkinson’s disease by regulating neuroinflammation, barrier function and neurotransmitter activity. There is bidirectional communication between the enteric nervous system and the CNS, and the microbiota-gut-brain axis may provide a pathway for the transmission of α-synuclein. We highlight recent discoveries about alterations to the gut microbiota in Parkinson’s disease and focus on current mechanistic insights into the microbiota-gut-brain axis in disease pathophysiology. Moreover, we discuss the interactions between the production and transmission of α-synuclein and gut inflammation and neuroinflammation. In addition, we draw attention to diet modification, the use of probiotics and prebiotics and faecal microbiota transplantation as potential therapeutic approaches that may lead to a new treatment paradigm for Parkinson’s disease.
Chemosensory Loss during a Traumatic Brain Injury Suggests a Central Pathway for the Rehabilitation of Anosmia
Authors: Laing David G , Epps Adrienne , Jinks Anthony L
Published: April 2021

Currently, no method has been developed for rehabilitating olfaction in anosmic patients following a traumatic brain injury (TBI). Here a method for rehabilitation is described which is based on a recent finding that the human posterior pyriform cortex (PPC) generates predictive odor “search images” in advance of an encounter with an olfactory stimulus. The search image enhances perceptual sensitivity and allows the odor it represents to be identified without input occurring from the olfactory receptors or bulbs. Furthermore, based on the finding here that anosmics with a TBI often have normal trigeminal and gustatory function, it is proposed that normality in these chemosensory systems may indicate that key cortical regions including the PPC are intact in anosmics and capable of processing olfactory information. In addition, the results of chemosensory tests of the olfactory, gustatory, and intranasal trigeminal systems of 18 patients with a TBI are given that identify which patients would most likely benefit from the rehabilitation procedure.
Frugal innovation in energy transitions: insights from solar energy cases in Brazil
Authors: Busch Hans-Christian
Published: April 2021

This article refines our understanding of frugal innovation in geographical energy transitions research. Frugal innovation represents a strategic approach to solving local problems with limited resources through complexity reduction. The article analyses three frugal innovation cases from São Paulo, Brazil. For each case, the analysis focuses on specific resource-constrained local context conditions, actors’ frugal approaches to overcoming these conditions and multi-scalar resource mobilisation strategies to scale frugal solutions. The article concludes by identifying three roles of frugality in energy transitions: (i) outcome complexity reduction enables scalable model solutions; (ii) process complexity reduction enables industrially scalable production; (iii) a philosophy of complexity reduction enables scalable dissemination strategies.
COVIDOUTCOME—estimating COVID severity based on mutation signatures in the SARS-CoV-2 genome
Authors: Nagy Ádám , Ligeti Balázs , Szebeni János , Pongor Sándor , Győrffy Balázs
Published: April 2021

Numerous studies demonstrate frequent mutations in the genome of SARS-CoV-2. Our goal was to statistically link mutations to severe disease outcome. We used an automated machine learning approach where 1594 viral genomes with available clinical follow-up data were used as the training set (797 ‘severe’ and 797 ‘mild’). The best algorithm, based on random forest classification combined with the LASSO feature selection algorithm, was employed to the training set to link mutation signatures and outcome. The performance of the final model was estimated by repeated, stratified, 10-fold cross validation (CV) and then adjusted for multiple testing with Bootstrap Bias Corrected CV. We identified 26 protein and Untranslated Region (UTR) mutations significantly linked to severe outcome. The best classification algorithm uses a mutation signature of 22 mutations as well as the patient’s age as the input and shows high classification efficiency with an area under the curve (AUC) of 0.94 [confidence interval (CI): [0.912, 0.962]] and a prediction accuracy of 87% (CI: [0.830, 0.903]). Finally, we established an online platform (https://covidoutcome.com/) that is capable to use a viral sequence and the patient’s age as the input and provides a percentage estimation of disease severity. We demonstrate a statistical association between mutation signatures of SARS-CoV-2 and severe outcome of COVID-19. The established analysis platform enables a real-time analysis of new viral genomes.
Mutations in GCR3, a Gene Involved in the Expression of Glycolytic Genes in Saccharomyces cerevisiae, Suppress the Temperature-Sensitive Growth of hpr1 Mutants
Authors: Uemura Hiroshi , Pandit Sunil , Jigami Yoshifumi , Sternglanz Rolf
Published: April 2021

To study the functions of DNA topoisomerase I and Hpr1 protein, a suppressor mutant of the temperature-sensitive growth of an hpr1 top1-5ts double mutant was isolated. The isolated triple mutant showed cold-sensitive growth. By complementation of this phenotype, the suppressor gene was cloned. DNA sequencing showed it to be GCR3, a gene involved in the expression of glycolytic genes. Further analysis showed that gcr3 mutations also suppressed the temperature-sensitive growth of hpr1 single mutants. Experiments with gcr3 truncation mutants also suggested a genetic interaction between GCR3 and HPR1. The fact that top1 suppressed the growth defect of gcr3 suggested an interaction between those two genes also. Plasmid DNA isolated from gcr3 mutants was significantly more negatively supercoiled than normal, suggesting that Gcr3 protein, like topoisomerase I and Hpr1p, affects chromatin structure, perhaps during transcription.
Genetic Architecture of Autosome-Mediated Hybrid Male Sterility in Drosophila
Authors: Marín Ignacio
Published: April 2021

Several estimators have been developed for assesing the number of sterility factors in a chromosome based on the sizes of fertile and sterile introgressed fragments. Assuming that two factors are required for producing sterility, simulations show that one of these, twice the inverse of the relative size of the largest fertile fragment, provides good average approximations when as few as five fertile fragments are analyzed. The estimators have been used for deducing the number of factors from previous data on several pairs of species. A particular result contrasts with the authors' interpretations: instead of the high number of sterility factors suggested, only a few per autosome are estimated in both reciprocal crosses involving Drosophila buzzatii and D. koepferae. It has been possible to map these factors, between three and six per chromosome, in the autosomes 3 and 4 of these species. Out of 203 introgressions of different fragments or combinations of fragments, the outcome of at least 192 is explained by the mapped zones. These results suggest that autosome-mediated sterility in the male hybrids of these species is mediated by a few epistatic factors, similarly to X-mediated sterility in the hybrids of other Drosophila species.
Functional Domains of Fused, a Serine-Threonine Kinase Required for Signaling in Drosophila
Authors: Thérond Pascal , Alves Georges , Limbourg-Bouchon Bernadette , Tricoire Hervé , Guillemet Elizabeth , Brissard-Zahraoui Jeanine , Lamour-Isnard Claudie , Busson Denise
Published: April 2021

fused (fu) is a segment-polarity gene encoding a putative serine-threonine kinase. In a wild-type context, all fu mutations display the same set of phenotypes. Nevertheless, mutations of the Suppressor of fused [Su(fu)] gene define three classes of alleles (fu0, fuI, fuII). Here, we report the molecular analysis of known fu mutations and the generation of new alleles by in vitro mutagenesis. We show that the Fused (Fu) protein functions in vivo as a kinase. The N-terminal kinase and the extreme C-terminal domains are necessary for Fu+ activity while a central region appears to be dispensable. We observe a striking correlation between the molecular lesions of fu mutations and the phenotype displayed in their interaction with Su(fu). Indeed, fuI alleles which are suppressed by Su(fu) mutations are defined by inframe alterations of the N-terminal catalytic domain whereas the C-terminal domain is missing or altered in all fuII alleles. An unregulated FuII protein, which can be limited to the 80 N-terminal amino acids of the kinase domain, would be responsible for the neomorphic costal-2 phenotype displayed by the fuII-Su(fu) interaction. We propose that the Fu C-terminal domain can differentially regulate the Fu catalytic domain according to cell position in the parasegment.
Quantitative Trait Loci for Murine Growth
Authors: Cheverud James M , Routman Eric J , Duarte F A M , van Swinderen Bruno , Cothran Kilinyaa , Perel Christy
Published: April 2021

Body size is an archetypal quantitative trait with variation due to the segregation of many gene loci, each of relatively minor effect, and the environment. We examine the effects of quantitative trait loci (QTLs) on age-specific body weights and growth in the F2 intercross of the LG/J and SM/J strains of inbred mice. Weekly weights (1-10 wk) and 75 microsatellite genotypes were obtained for 535 mice. Interval mapping was used to locate and measure the genotypic effects of QTLs on body weight and growth. QTL effects were detected on 16 of the 19 autosomes with several chromosomes carrying more than one QTL. The number of QTLs for age-specific weights varied from seven at 1 week to 17 at 10 wk. The QTLs were each of relatively minor, subequal effect. QTLs affecting early and late growth were generally distinct, mapping to different chromosomal locations indicating separate genetic and physiological systems for early and later murine growth.
Segregation and Recombination of Solanum brevidens Synteny Groups in Progeny of Somatic Hybrids With S. tuberosum: Intragenomic Equals or Exceeds Intergenomic Recombination
Authors: McGrath J Mitchell , Wielgus Susan M , Helgeson John P
Published: April 2021

The Solanum brmidens genome (2n = 2x = 24) was examined with randomly applied polymorphic DNA (RAPD) markers in a second backcross population derived from a S. brevidens + S. tuberosum somatic hybrid. RAPD markers cosegregated into 12 different S. brevidens synteny groups. Most synteny groups were nonrecombinant. However, nearly 40% of the S. brevidens synteny groups detected in this population were recombinant deletions that carried at least one, but not all, synteny group-specific RAPD markers. All S. brevidens synteny groups (except chromosome 5) were involved in recombination, and recombination occurred within most intervals between markers. About 20% of the recombinant S. brevidens synteny groups involved a single synteny group-specific marker. The inheritance of some single-marker representatives was followed in four BC3 families. At least nine changes in S. brevidens synteny groups had occurred during backcrossing. Six of the nine changes involved translocation of S. brevidens markers between nonhomologous S. brevidens chromosomes, and three S. brevidens markers may have been introgressed into the potato genome.
Mediterranean Diet and Changes in Frequency, Severity, and Localization of Pain in Older Adults: The Seniors-ENRICA Cohorts
Authors: Ortolá Rosario , García-Esquinas Esther , Sotos-Prieto Mercedes , Struijk Ellen A , Caballero Francisco Félix , Lopez-Garcia Esther , Rodríguez-Artalejo Fernando
Published: April 2021

Background

Although some components of the Mediterranean diet have shown benefits in pain risk through its anti-inflammatory/antioxidant properties, no population-based studies have investigated the effect of adherence to this diet on changes in pain over time.

Methods

We used data from 864 and 862 older adults recruited in the Seniors-ENRICA-1 and Seniors-ENRICA-2 cohorts and followed-up for 2.8 and 2.4 years, respectively. Adherence to the Mediterranean diet was assessed with the MEDAS score at baseline. Frequency, severity, and locations of pain obtained at baseline and follow-up were used to compute a pain scale. Analyses were performed using multinomial logistic regression models, and adjusted for the main confounders.

Results

Participants had a mean (SD) age of 71.5 (5.1) years, 36.8% were men, and 78.3% had chronic conditions. In the pooled cohorts, compared with participants in the lowest quartile of the MEDAS score (lowest adherence to the Mediterranean diet), those in the highest quartile showed a higher frequency of pain improvement versus worsening (relative risk ratio [95% confidence interval]: 1.43 [1.03, 1.99]). This association was also evidenced in 2 components of the pain scale: improvement in pain severity (1.43 [1.01, 2.04]) and reduction in pain locations (1.54 [1.08, 2.20]), but a tendency to pain frequency improvement (1.34 [0.92, 1.93]) was also observed. The main contributors to these associations were high consumption of fruit and vegetables, and low consumption of sugar-sweetened beverages.

Conclusions

A higher adherence to the Mediterranean diet was related to a subsequent improvement in pain characteristics in older adults, suggesting that improving diet quality may help reduce the high health impact of pain.
Pharmacist contributions to patient care and medical conditions present among recipients of Ontario primary care team pharmacist-led medication reviews: a qualitative analysis
Authors: Rezahi Sara , Mathers Annalise , Benny Gerard Nichelle , Mak Kei Cheng , Dolovich Lisa
Published: April 2021

Objectives

Family Health Teams (FHTs) in Ontario, Canada are interdisciplinary primary healthcare practices where pharmacists engage in patient care including medication and chronic disease management.

Methods

Descriptive content analysis was used to examine qualitative responses of FHT pharmacists on their most significant contribution to a patient’s medication management.

Key findings

Common roles described included medication management (70.2%), counselling and education (15.5%), monitoring and optimization (11.3%) and administration (3.1%). Chronic conditions addressed were diabetes (39.0%), cardiovascular (22.0%), pain (17.0%) and mental health (11.0%).

Conclusions

While FHT pharmacists primarily view themselves as medication management experts, larger roles in counselling, education and chronic disease management are key contributions.
A Model for Random Braiding in Graph Configuration Spaces
Authors: Levin David A , Ramos Eric , Young Benjamin
Published: April 2021

We define and study a model of winding for non-colliding particles in finite trees. We prove that the asymptotic behavior of this statistic satisfies a central limiting theorem, analogous to similar results on winding of bounded particles in the plane [ 42]. We also propose certain natural open questions and conjectures, whose confirmation would provide new insights on configuration spaces of trees.
Relative bioavailability of organic bis-glycinate bound copper relative to inorganic copper sulfate in beef steers fed a high antagonist growing diet
Authors: Deters Erin L , VanDerWal Allison J , VanValin Katherine R , Hansen Stephanie L
Published: April 2021

To assess the relative bioavailability of bis-glycinate bound Cu, 90 Angus-cross steers (265 ± 21 kg) were blocked by body weight (BW) to pens with GrowSafe bunks and randomly assigned to dietary treatments (14 to 18 steers/treatment): 0 mg supplemental Cu/kg dry matter (DM; CON), 5 or 10 mg supplemental Cu/kg DM as Cu sulfate (CS5; CS10) or bis-glycinate bound Cu (GLY5; GLY10). Steers received a high antagonist growing diet (analyzed 4.9 mg Cu/kg DM, 0.48% S, and 5.3 mg Mo/kg DM). Steers were weighed at the beginning (days 1 and 0) and end (days 125 and 126) of the trial to determine average daily gain (ADG) and gain:feed (G:F). Blood was collected from all steers on days 0, 28, 56, 84, and 126. Liver samples were collected on days −3 or −2 and day 123 or 124. Data were analyzed using ProcMixed of SAS (experimental unit = steer; fixed effect = treatment and block). Plasma Cu was analyzed as repeated measures (repeated effect = day). Plasma and liver Cu concentrations were regressed against total Cu intake using ProcGLM to calculate relative bioavailability of GLY. Final BW and overall ADG were greatest for CS5 and CS10 and least for CON and GLY5 (P = 0.01). Overall, DMI was not affected by treatment (P = 0.14), but overall G:F tended to be greatest for CS5, CS10, and GLY5 and least for CON (P = 0.08). Total and supplemental Cu intake was greatest for steers supplemented either source at 10 mg Cu/kg DM and least for CON (P < 0.01). However, total and supplemental Cu intake was greater for CS5 than GLY5 (P < 0.01). Final liver Cu concentrations were greatest for CS10, least for CON, CS5, and CS10, and intermediate for GLY10 (P < 0.01). Final plasma Cu was greatest for steers supplemented either source at 10 mg Cu/kg DM (P < 0.01). Relative bioavailability of GLY was 82% compared to CS based on liver Cu (P < 0.01) but did not differ based on plasma Cu (P = 0.60). The lesser bioavailability of GLY relative to CS could be due to a high concentration of dietary antagonists and lower solubility of GLY (68.9% relative to CS) in pH conditions (5.2) similar to the ruminal pH of a beef animal consuming a high concentrate diet. Future studies should examine the effects of bis-glycinate bound Cu fed in blended combination with inorganic Cu sulfate to determine the most effective blend of sources for feedlot cattle experiencing varying amounts of dietary Cu antagonists.
The Interplay Between ‘Peacetime’ Law and the Law of Armed Conflict: Consequences for Post-Conflict Peacebuilding
Authors: Fleck Dieter
Published: April 2021

Focussing on the interplay between rules of international law applicable in peacetime and rules applicable during armed conflicts, this contribution examines the impact on the jus post bellum. In this context certain specific legal obligations are discussed to answer the question whether and if so, how their application post-conflict may be affected by the peacebuilding process after the (former) armed conflict. Essential norms of the protection of victims during armed conflicts continue to be relevant for peace operations and post-conflict peacebuilding. This includes guiding principles and effective measures of control for operational detentions; law enforcement operations to secure the security and safety of peacekeepers; the protection of the environment and efforts to strengthen the role of States and international organizations as well as their accountability in post-conflict reconstruction. The author demonstrates that jus post bellum requires due diligence during military operations, responsible planning and precautions. He submits that post-conflict peacebuilding should be characterized by pragmatic limitation, conciliation and participation of the parties. This suggests certain deviations from peacetime principles and rules, deviations that may include certain limits of protection which will, however, be balanced out by the temporary nature of peacebuilding measures. While such interplay between the different branches of international law remains subject to changing situations, a few general principles are considered to be relevant for the jus post bellum. Even if codification remains difficult, further case-oriented research is encouraged to confirm general principles and rules of this important branch of international law.
Fabricating the past at Hammond Castle
Authors: Easton Martha
Published: April 2021

During the late nineteenth and early twentieth centuries, wealthy art collectors in the United States amassed extraordinary collections of medieval and early Renaissance art, and, on occasion, unscrupulous dealers fulfilled the demand for such objects by passing off fakes as originals. The story of one such object is instructive in understanding the way that collectors pursued, purchased and displayed their finds. A sculptural bas-relief of the Virgin and Child at Hammond Castle in Gloucester, Massachusetts, was purchased as an authentic Italian Renaissance piece, but the revelation of its true provenance as a modern work by Alceo Dossena ultimately connected it to one of the most notorious cases of art forgery in the early twentieth century. This article discusses the case of Dossena and his artistic fabrications, but also reconsiders the role such objects could play in the creation of an authentic atmosphere – the goal of revivalist monuments like Hammond Castle.
A honokiol-enriched Magnolia officinalis Rehder & E.H. Wilson. bark extract possesses anxiolytic-like activity with neuroprotective effect through the modulation of CB1 receptor
Authors: Borgonetti Vittoria , Governa Paolo , Manetti Fabrizio , Miraldi Elisabetta , Biagi Marco , Galeotti Nicoletta
Published: April 2021

Objectives

The exposure of neurons to an excessive excitatory stimulation induces the alteration of the normal neuronal function. Mood disorders are among the first signs of alterations in the central nervous system function. Magnolia officinalis bark extract has been extensively used in the traditional medicine systems of several countries, showing several pharmacological activities. Honokiol, the main constituent of M. officinalis, is a GABA modulator and a CB1 agonist, which is deeply investigated for its role in modulating mood disorders.

Methods

Thus, we evaluated the possible neuroprotective effect of a standardized M. officinalis bark extract (MOE), enriched in honokiol, and its effect on animal mood behavioural tests and in an in vitro model of excitotoxicity.

Key findings

MOE showed neuroprotective effect using SH-SY5Y cells, by normalizing brain-derived neurotrophic factor release. Then, we tested the effect of MOE in different behavioural tests evaluating anxiety and depression and we observed a selective anxiolytic-like effect. Finally, we confirmed the involvement of CB1 in the final effect of MOE by the co-administration of the CB1 antagonist, AM251.

Conclusion

These results suggest that MOE could be considered an effective and safe anxiolytic candidate with neuroprotective activity.
Warty (condylomatous) carcinoma of the back: a case report
Authors: Park Ilou , Koh Sung Hoon , Lee Hee Jeong
Published: April 2021

Warty carcinoma (WC), known as condylomatous carcinoma, generally derives from genito-urethral area. Its symbolic lesion is the exophytic and verruciform mass associated with human papillomavirus infection. A 90-year-old female presented with growing cauliflower-like mass in her back. A wide excision was performed for two masses. It was finally confirmed as WC throughout histopathological findings—arborescent papillomatosis, hyperkeratosis and acanthosis. The patient was an ordinary housewife and there was no recurrence and any postoperative complication 6 month after the surgery. Accordingly, careful physical examination and history-taking as well as wide-excision securing safety margin are essential, especially for senile patients.
Spinal cord monitoring using collateral network near-infrared spectroscopy during extended aortic arch surgery with a frozen elephant trunk
Authors: von Aspern Konstantin , Sgouropoulou Sophia , Davierwala Piroze , Borger Michael A , Etz Christian D
Published: April 2021

The true incidence of spinal cord injury associated with modern hybrid extended arch/descending aortic procedures utilizing a frozen elephant trunk (fET) remains unclear, and it is estimated with ~5–8%. Prolonged distal arrest without sufficient hypothermic protection as well as extended coverage of segmental arteries have been suggested to cause this complication, previously uncommon in open arch surgery. Recently, extensive clinical and experimental research led to the implementation of a new method of collateral network near-infrared spectroscopy (cnNIRS) to non-invasively monitor spinal cord oxygenation in the setting of extensive thoracoabdominal aortic repair. To date, limited experience with this method during arch procedures exists. Based on recent experiments regarding the optimal cnNIRS optode placement, we used this method for the first time during an fET procedure to document mid-thoracic paraspinous oxygenation levels.
The Musical Conductors’ Association: Collective Podium Power in Wartime Britain?
Authors: Palmer Fiona M
Published: April 2021

This article examines the impetus, aspirations, membership, propaganda, and impact of the Musical Conductors’ Association, founded 10 March 1916. A collective effort to resist foreign invasion of British orchestral life, the MCA provides a lens through which artistic struggles in and out of wartime are brought into sharper focus. During the decades preceding the First World War the function, status, and value of the conductor’s role in Britain had evolved in the thrall of foreign exemplars. This evaluation of the MCA provides new perspectives on a protectionist agenda shared among conductors whose working conditions were diverse. An exploration of unionization within the wider music profession underlines the value placed in the formation of professional societies in this period. Fresh insights emerge in respect of individual and collective agency, networks, collective bargaining, and authority among British conductors who sought to identify themselves as a separate and powerful branch of the music profession.
The impact of line-of-sight structures on measuring H0 with strong lensing time delays
Authors: Li Nan , Becker Christoph , Dye Simon
Published: April 2021

Measurements of the Hubble–Lemaitre constant from early- and local-Universe observations show a significant discrepancy. In an attempt to understand the origin of this mismatch, independent techniques to measure H0 are required. One such technique, strong lensing time delays, is set to become a leading contender amongst the myriad methods due to forthcoming large strong lens samples. It is therefore critical to understand the systematic effects inherent in this method. In this paper, we quantify the influence of additional structures along the line of sight by adopting realistic light-cones derived from the cosmoDC2 semi-analytical extragalactic catalogue. Using multiple-lens plane ray tracing to create a set of simulated strong lensing systems, we have investigated the impact of line-of-sight structures on time-delay measurements and in turn, on the inferred value of H0. We have also tested the reliability of existing procedures for correcting for line-of-sight effects. We find that if the integrated contribution of the line-of-sight structures is close to a uniform mass sheet, the bias in H0 can be adequately corrected by including a constant external convergence κext in the lens model. However, for realistic line-of-sight structures comprising many galaxies at different redshifts, this simple correction overestimates the bias by an amount that depends linearly on the median external convergence. We therefore conclude that lens modelling must incorporate multiple-lens planes to account for line-of-sight structures for accurate and precise inference of H0.
Recognizing and validating ligands with CheckMyBlob
Authors: Brzezinski Dariusz , Porebski Przemyslaw J , Kowiel Marcin , Macnar Joanna M , Minor Wladek
Published: April 2021

Structure-guided drug design depends on the correct identification of ligands in crystal structures of protein complexes. However, the interpretation of the electron density maps is challenging and often burdened with confirmation bias. Ligand identification can be aided by automatic methods such as CheckMyBlob, a machine learning algorithm that learns to generalize ligand descriptions from sets of moieties deposited in the Protein Data Bank. Here, we present the CheckMyBlob web server, a platform that can identify ligands in unmodeled fragments of electron density maps or validate ligands in existing models. The server processes PDB/mmCIF and MTZ files and returns a ranking of 10 most likely ligands for each detected electron density blob along with interactive 3D visualizations. Additionally, for each prediction/validation, a plugin script is generated that enables users to conduct a detailed analysis of the server results in Coot. The CheckMyBlob web server is available at https://checkmyblob.bioreproducibility.org.
Factors influencing fertility rates in Australian women receiving kidney replacement therapy: analysis of linked Australia and New Zealand Dialysis and Transplant Registry and perinatal data over 22 years
Authors: Hewawasam Erandi , Davies Christopher E , Gulyani Aarti , Li Zhuoyang , Clayton Philip A , Sullivan Elizabeth , McDonald Stephen P , Jesudason Shilpanjali
Published: April 2021

Background

Pregnancy in women receiving kidney replacement therapy (KRT) is uncommon, and trends and factors influencing fertility rates remain poorly defined.

Methods

The Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) was linked to mandatory perinatal data sets (all births from 1991 to 2013, ≥20 weeks’ gestation) in four Australian jurisdictions. Overall, age- and era-specific fertility rates were calculated based on general and KRT population denominators.

Results

From 2 948 084 births, 248 babies were born to 168 mothers receiving KRT (37 babies born to 31 dialysed mothers; 211 babies born to 137 transplanted mothers). Substantial agreement between ANZDATA and perinatal data sets was observed for birth events and outcomes. Transplanted women had higher fertility rates than dialysed women in all analyses, with 21.4 live births/1000 women/year [95% confidence interval (CI) 18.6–24.6] in transplanted women, 5.8 (95% CI 4.1–8.1) in dialysed women and 61.9 (95% CI 61.8–62.0) in the non-KRT cohort. Fertility rates for dialysed women rose in recent years. After adjusting for maternal age and treatment modality, Caucasian women had higher fertility rates, while women with pre-existing diabetes, or transplanted women with exposure to KRT for ≤3.0 years had lower rates. As expected, transplanted women with a pre-conception estimated glomerular filtration rate (eGFR) of <45 mL/min/1.73 m2 or transplant-to-pregnancy interval of <1.0 year had lower fertility rates. Geographical location, socioeconomic status and primary disease (glomerulonephritis versus other) did not affect fertility rates.

Conclusions

Reporting of births to ANZDATA is sufficiently accurate to justify ongoing data collection. Rising fertility rates in dialysed women may indicate permissive attitudes towards pregnancy. Treatment modality, ethnicity, diabetes, pre-conception eGFR, transplant-to-pregnancy interval and duration of KRT exposure were associated with fertility rates. These factors should be considered when counselling women with kidney disease about parenthood.
Evolution of the Neurosurgeon's Role in Clinical Trials for Glioblastoma: A Systematic Overview of the Clinicaltrials.Gov Database
Authors: Mansouri Alireza , Beyn Michelle E , Pancholi Aditya , Chow Clement T , Wang Ryan , Boutet Alexandre , Elias Gavin J B , Germann Jurgen , Loh Aaron , Voisin Mathew R , Lozano Andres M , Chiocca E Antonio , Vogelbaum Michael A , Zadeh Gelareh
Published: April 2021

BACKGROUND

The therapeutic challenge of glioblastoma (GBM) has catalyzed the development of clinical trials to evaluate novel interventions. With increased understanding of GBM biology and technological advances, the neurosurgeon's role in neuro-oncology has evolved.

OBJECTIVE

To evaluate the current landscape of procedure-based clinical trials for GBM to characterize this evolution, gain insight into past failures, and accordingly outline implications for future research and practice that may inform future studies.

METHODS

The ClinicalTrials.gov database was searched for surgical/procedural trials in individuals with GBM. Demographics, specific intervention, trial phase, and main outcome measures were abstracted.

RESULTS

A total of 224 of 2311 GBM trials (9.7%) were identified as procedural, with the majority being based in the United States (155/224, 69.2%), single-center (155/224, 69.2%), and not randomized (176/224, 78.6%). Primary and recurrent GBMs were evenly addressed. The leading interventions were local delivery of therapeutics (50.0%), surgical techniques (33.9%), such as image-guided surgery, and novel device applications (14.3%). Phase I designs predominated (82/224, 36.6%). The top primary outcome was safety/tolerability/feasibility (88/224, 39.3%), followed by survival (46/224, 20.5%). Approximately 17% of studies were terminated, withdrawn, or suspended. Fifty-two linked publications were identified, among which 42 were classified as having a positive result.

CONCLUSION

Procedural interventions comprised ∼10% of all registered GBM trials. Local delivery of therapeutics, use of surgical imaging techniques and novel device applications, predominantly through phase I designs, represent the evolved role of the neurosurgeon in neuro-oncology. Improved reporting of trial designs, outcomes, and results are needed to better inform the field and increase efficiency.
An economical business-cycle model
Authors: Michaillat Pascal , Saez Emmanuel
Published: April 2021

This article develops a new model of business cycles. The model is economical in that it is solved with an aggregate demand–aggregate supply diagram, and the effects of shocks and policies are obtained by comparative statics. The model builds on two unconventional assumptions. First, producers and consumers meet through a matching function. Thus, the model features unemployment, which fluctuates in response to aggregate demand and supply shocks. Secondly, wealth enters the utility function, so the model allows for permanent zero-lower-bound episodes. In the model, the optimal monetary policy is to set the interest rate at the level that eliminates the unemployment gap. This optimal interest rate is computed from the prevailing unemployment gap and monetary multiplier (the effect of the nominal interest rate on the unemployment rate). If the unemployment gap is exceedingly large, monetary policy cannot eliminate it before reaching the zero lower bound, but a wealth tax can.
Declining wintering shorebird populations at a temperate estuary in California: A 30-year perspective
Authors: Warnock Nils , Jennings Scott , Kelly John P , Condeso T Emiko , Lumpkin David
Published: April 2021

Worldwide, shorebird populations are declining. Our objectives were to examine abundance trends of shorebirds regularly wintering at Tomales Bay, Marin County, California, accounting for the local effects of rainfall, raptors, and the restoration of part of the bay to tidal wetlands. From November 1989 to February 2019, we conducted 177 comprehensive winter shorebird surveys of Tomales Bay; we averaged 5.7 ± 0.9 (mean ± SD) winter surveys per year. In 30 yr, we counted 1,215,821 shorebirds of 31 species. We used generalized linear models and multi-model inference to evaluate trends in shorebird abundance while accounting for local sources of variation. We conducted separate analyses for 14 species seen in at least 20 of the 30 yr of monitoring and for all shorebird species combined. During the study, the abundance of all species combined declined 66% (52% in the North Bay and 81% in the South Bay) with the most rapid decline in the first 10 yr of monitoring. Of 13 species for which year was in the top model, 10 species decreased in abundance and 3 species increased. Dunlin and Western Sandpiper accounted for the greatest losses in total numbers. The best-supported models to estimate trends in shorebirds included predictors for year and North Bay vs. South Bay. Of the local variables we considered, rainfall was included in 10 of the 15 best-supported models (including all species combined), negatively affecting the numbers of all species except Willets. The wetland restoration project was included in 5 top models, with a short-term positive impact. Raptor abundance was included in 3 top models with mixed results. Our results show that effective conservation and management of local shorebird populations must be linked with regional/global efforts if we are to reverse negative shorebird trends.
Breeding success in Southern Australian Little Penguins is negatively correlated with high wind speeds and sea surface temperatures
Authors: Johnson Bianca , Colombelli-Négrel Diane
Published: April 2021

As bio-indicators, seabirds across the globe help us understand how our environment is changing, and how this is affecting our wildlife. Little Penguins (Eudyptula minor) in Australia are a key species in understanding the changes to the Australian environment. However, studies generally focus on the effects of oceanic changes without always accounting for the potential interactions with the environmental conditions experienced on land during breeding. This study examined the relationships between both marine and terrestrial environmental variables and breeding success in South Australian Little Penguins, observing 10 colonies over a nonconsecutive 28-yr time period. Our results showed that South Australian Little Penguins had a lower breeding success (fewer fledglings produced per pair) when sea surface temperatures were higher in the 3 mo before breeding and when high winds occurred during the breeding season. We also observed local variation between the colonies: breeding success was only influenced by environmental variables for colonies located near open waters and not for colonies located in enclosed bays. These results confirm the idea that future oceanographic warming is expected to reduce the breeding success (and population size) of some Australian seabirds, including Little Penguins.