bluuebunny/crossref_metadata_2025 huggingface dataset:
Sulfur dioxide derivatives aggravated ovalbumin-induced asthma through targeting TRPV1 and tight junctions
Authors: Zhou Liping , Lao Zishan , Fan Xinsheng , Hao Mengyang , Yang Yubing
Published: April 2023

This study aimed to investigate the effects of sulfur dioxide (SO2) derivatives on asthma induced by ovalbumin (OVA). Sprague Dawley rats were sensitized to and challenged with OVA and SO2 derivatives (NaHSO3 and Na2SO3, 1:3 M/M) to establish 28-day (short-term) and 42-day (long-term) asthma models. Exposure to SO2 derivatives aggravated asthma and hence, promoted lung injury in OVA-induced asthma. In addition, it upregulated the protein expression of TRPV1 and downregulated the expression of tight junctions (TJs). These changes were dose-dependent and were more pronounced in the presence of a high concentration of SO2 derivatives. In vitro, SO2 derivatives also increased the calcium influx and TRPV1 protein expression, and decreased TJ expression. Besides, no significant difference in the TJ expression was found between the WT and TRPV1−/- mice. The underlying mechanism might be related to regulating the effects of TRPV1 and TJs.
PyHMMER: a Python library binding to HMMER for efficient sequence analysis
Authors: Larralde Martin , Zeller Georg
Published: April 2023

PyHMMER provides Python integration of the popular profile Hidden Markov Model software HMMER via Cython bindings. This allows the annotation of protein sequences with profile HMMs and building new ones directly with Python. PyHMMER increases flexibility of use, allowing creating queries directly from Python code, launching searches, and obtaining results without I/O, or accessing previously unavailable statistics like uncorrected P-values. A new parallelization model greatly improves performance when running multithreaded searches, while producing the exact same results as HMMER.

Availability and implementation

PyHMMER supports all modern Python versions (Python 3.6+) and similar platforms as HMMER (x86 or PowerPC UNIX systems). Pre-compiled packages are released via PyPI (https://pypi.org/project/pyhmmer/) and Bioconda (https://anaconda.org/bioconda/pyhmmer). The PyHMMER source code is available under the terms of the open-source MIT licence and hosted on GitHub (https://github.com/althonos/pyhmmer); its documentation is available on ReadTheDocs (https://pyhmmer.readthedocs.io).
ConsAlign: simultaneous RNA structural aligner based on rich transfer learning and thermodynamic ensemble model of alignment scoring
Authors: Tagashira Masaki
Published: April 2023

Motivation

To capture structural homology in RNAs, alignment and folding (AF) of RNA homologs has been a fundamental framework around RNA science. Learning sufficient scoring parameters for simultaneous AF (SAF) is an undeveloped subject because evaluating them is computationally expensive.

Results

We developed ConsTrain—a gradient-based machine learning method for rich SAF scoring. We also implemented ConsAlign—a SAF tool composed of ConsTrain’s learned scoring parameters. To aim for better AF quality, ConsAlign employs (1) transfer learning from well-defined scoring models and (2) the ensemble model between the ConsTrain model and a well-established thermodynamic scoring model. Keeping comparable running time, ConsAlign demonstrated competitive AF prediction quality among current AF tools.

Availability and implementation

Our code and our data are freely available at https://github.com/heartsh/consalign and https://github.com/heartsh/consprob-trained.
Exploring Survey-Based Water, Sanitation, and Animal Associations With Enteric Pathogen Carriage: Comparing Results in a Cohort of Cases With Moderate-to-Severe Diarrhea to Those in Controls in the Vaccine Impact on Diarrhea in Africa (VIDA) Study, 2015–2018
Authors: Berendes David M , Omore Richard , Prentice-Mott Graeme , Fagerli Kirsten , Kim Sunkyung , Nasrin Dilruba , Powell Helen , Jahangir Hossain M , Sow Samba O , Doh Sanogo , Jones Joquina Chiquita M , Ochieng John B , Juma Jane , Awuor Alex O , Ogwel Billy , Verani Jennifer R , Widdowson Marc-Alain , Kasumba Irene N , Tennant Sharon M , Roose Anna , Zaman Syed M A , Liu Jie , Sugerman Ciara E , Platts-Mills James A , Houpt Eric R , Kotloff Karen L , Mintz Eric D
Published: April 2023

Background

The magnitude of pediatric enteric pathogen exposures in low-income settings necessitates substantive water and sanitation interventions, including animal feces management. We assessed associations between pediatric enteric pathogen detection and survey-based water, sanitation, and animal characteristics within the Vaccine Impact on Diarrhea in Africa case-control study.

Methods

In The Gambia, Kenya, and Mali, we assessed enteric pathogens in stool of children aged <5 years with moderate-to-severe diarrhea and their matched controls (diarrhea-free in prior 7 days) via the TaqMan Array Card and surveyed caregivers about household drinking water and sanitation conditions and animals living in the compound. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using modified Poisson regression models, stratified for cases and controls and adjusted for age, sex, site, and demographics.

Results

Bacterial (cases, 93%; controls, 72%), viral (63%, 56%), and protozoal (50%, 38%) pathogens were commonly detected (cycle threshold <35) in the 4840 cases and 6213 controls. In cases, unimproved sanitation (RR, 1.56; 95% CI, 1.12–2.17), as well as cows (RR, 1.61; 95% CI, 1.16–2.24) and sheep (RR, 1.48; 95% CI, 1.11–1.96) living in the compound, were associated with Shiga toxin–producing Escherichia coli. In controls, fowl (RR, 1.30; 95% CI, 1.15–1.47) were associated with Campylobacter spp. In controls, surface water sources were associated with Cryptosporidium spp., Shigella spp., heat-stable toxin-producing enterotoxigenic E. coli, and Giardia spp.

Conclusions

Findings underscore the importance of enteric pathogen exposure risks from animals alongside more broadly recognized water and sanitation risk factors in children.
Exploration of a Potential Desirability of Outcome Ranking Endpoint for Complicated Intra-Abdominal Infections Using 9 Registrational Trials for Antibacterial Drugs
Authors: Kinamon Tori , Gopinath Ramya , Waack Ursula , Needles Mark , Rubin Daniel , Collyar Deborah , Doernberg Sarah B , Evans Scott , Hamasaki Toshimitsu , Holland Thomas L , Howard-Anderson Jessica , Chambers Henry , Fowler Vance G , Nambiar Sumati , Kim Peter , Boucher Helen W
Published: April 2023

Background

Desirability of outcome ranking (DOOR) is a novel approach to clinical trial design that incorporates safety and efficacy assessments into an ordinal ranking system to evaluate overall outcomes of clinical trial participants. Here, we derived and applied a disease-specific DOOR endpoint to registrational trials for complicated intra-abdominal infection (cIAI).

Methods

Initially, we applied an a priori DOOR prototype to electronic patient-level data from 9 phase 3 noninferiority trials for cIAI submitted to the US Food and Drug Administration between 2005 and 2019. We derived a cIAI-specific DOOR endpoint based on clinically meaningful events that trial participants experienced. Next, we applied the cIAI-specific DOOR endpoint to the same datasets and, for each trial, estimated the probability that a participant assigned to the study treatment would have a more desirable DOOR or component outcome than if assigned to the comparator.

Results

Three key findings informed the cIAI-specific DOOR endpoint: (1) a significant proportion of participants underwent additional surgical procedures related to their baseline infection; (2) infectious complications of cIAI were diverse; and (3) participants with worse outcomes experienced more infectious complications, more serious adverse events, and underwent more procedures. DOOR distributions between treatment arms were similar in all trials. DOOR probability estimates ranged from 47.4% to 50.3% and were not significantly different. Component analyses depicted risk-benefit assessments of study treatment versus comparator.

Conclusions

We designed and evaluated a potential DOOR endpoint for cIAI trials to further characterize overall clinical experiences of participants. Similar data-driven approaches can be utilized to create other infectious disease–specific DOOR endpoints.
Targeted Community Merging provides an efficient comparison between collaboration clusters and departmental partitions
Authors: Bauza F J , Ruiz-Manzanares G , Gómez-Gardeñes J , Tarancón A , Íñiguez D
Published: April 2023

Community detection theory is vital for the structural analysis of many types of complex networks, especially for human-like collaboration networks. In this work, we present a new community detection algorithm, the Targeted Community Merging algorithm, based on the well-known Girvan–Newman algorithm, which allows obtaining community partitions with high values of modularity and a small number of communities. We then perform an analysis and comparison between the departmental and community structure of scientific collaboration networks within the University of Zaragoza. Thus, we draw valuable conclusions from the inter- and intra-departmental collaboration structure that could be useful to take decisions on an eventual departmental restructuring.
Development of a new ‘human cyber-resilience scale’
Authors: Joinson Adam N , Dixon Matt , Coventry Lynne , Briggs Pam
Published: April 2023

While there has been an upsurge in interest in cyber resilience in organizations, we know little about the resilience of individuals to cyber attacks. Cyber resilience in a domestic or non-work setting is important because we know that the majority of people will face cyber threats in their use of technology across a range of contexts, and the ability to resist a cyber attack, or quickly recover and learn from a successful attack, is as important for individuals’ wellbeing as it is for organizations. There is, unfortunately, a dearth of studies on the cyber resilience of people, in part because it is not clear how such a construct could be defined and then measured. In the present work, we present a series of five studies—with a total sample of n = 1503—that sought to develop and validate a theoretically based measure of cyber resilience for individuals. The final scale, comprising 16 items and 4 subscales (self-efficacy, learning and growth, social support, and helplessness), demonstrates good internal reliability and validity.
Successful treatment of refractory chylothorax with MEK inhibitor trametinib in a child with Noonan syndrome: case report
Authors: Hribernik Ines , Brooks Teresa , Dunlop-Jones Alix , Bentham James R
Published: April 2023

Background

Refractory chylous effusions due to lymphatic dysplasia related to Noonan syndrome cause significant morbidity and mortality due to protein and immunoglobulin losses. Very few cases have been published reporting successful treatment of patients with trametinib where all conventional treatments had failed.

Case summary

We present a girl with Noonan syndrome and hypertrophic cardiomyopathy who presented with life-threatening refractory chylothorax where all conventional treatment options failed. She was successfully treated with mitogen-activated extracellular signal-regulated kinase inhibitor trametinib.

Discussion

MEK inhibition with trametinib is emerging as a possible salvage treatment option for a subset of patients with Noonan syndrome and severe pulmonary lymphangiectasia. More experience is required to establish optimal treatment regimen and long-term outcomes.
Shared patterns of segment size development in trilobites and vertebrates
Authors: Nikolic Mark C , Hopkins Melanie J , Evans Alistair R
Published: April 2023

The relative sizes of body segments are a major determinant of the shape and functionality of an animal. Developmental biases affecting this trait can therefore have major evolutionary implications. In vertebrates, a molecular activator/inhibitor mechanism, known as the inhibitory cascade (IC), produces a simple and predictable pattern of linear relative size along successive segments. The IC model is considered the default mode of vertebrate segment development and has produced long-term biases in the evolution of serially homologous structures such as teeth, vertebrae, limbs, and digits. Here we investigate whether the IC model or an IC-like model also has controls on segment size development in an ancient and hyperdiverse group of extinct arthropods, the trilobites. We examined segment size patterning in 128 trilobite species, and during ontogenetic growth in three trilobite species. Linear relative segment size patterning is prominent throughout the trunk of trilobites in the adult form, and there is strict regulation of this patterning in newly developing segments in the pygidium. Extending the analysis to select stem and modern arthropods suggests that the IC is a common default mode of segment development capable of producing long-term biases in morphological evolution across arthropods as it does in vertebrates.
Body size and substrate use affect ventral, but not dorsal, brightness evolution in lizards
Authors: Goldenberg Jonathan , Massetti Federico , D’Alba Liliana , Shawkey Matthew D
Published: April 2023

Substrate properties can affect the thermal balance of organisms, and the colored integument, alongside other factors, may influence heat transfer via differential absorption and reflection. Dark coloration may lead to higher heat absorption and could be advantageous when substrates are cool (and vice versa for bright coloration), but these effects are rarely investigated. Here, we examined the effect of substrate reflectance, specific heat capacity (cp), and body size on the dorso-ventral brightness using 276 samples from 12 species of cordylid lizards distributed across 26 sites in South Africa. We predicted, and found, that bright ventral colors occur more frequently in low cp (i.e., drier, with little energy needed for temperature change) substrates, especially in larger body-sized individuals, possibly to better modulate heat transfer with the surrounding environment. By contrast, dorsal brightness was not associated with body size nor any substrate thermal property, suggesting selection pressures other than thermoregulation. Ancestral estimation and evolutionary rate analyses suggest that ventral brightness rapidly differentiated within the Cordylinae starting 25 Mya, coinciding with an aridification period, further hinting at a thermoregulatory role for ventral colors. Our study indicates that substrate properties can have a direct role in shaping the evolution of ventral brightness in ectotherms.
Continuity of care and mortality for patients with chronic disease: an observational study using Norwegian registry data
Authors: Pahlavanyali Sahar , Hetlevik Øystein , Baste Valborg , Blinkenberg Jesper , Hunskaar Steinar
Published: April 2023

Background

Research on continuity of care (CoC) is mainly conducted in primary care and has received little acknowledgment in other levels of care. This study sought to investigate CoC across care levels for patients with selected chronic diseases, along with its association with mortality.

Methods

In a registry-based cohort study, patients with ≥1 consultation in primary or specialist healthcare or hospital admission with asthma, chronic obstructive pulmonary disease (COPD), diabetes mellitus, or heart failure in 2012 were linked to disease-related consultation data in 2013–2016. CoC was measured by Usual Provider of Care index (UPC) and Bice–Boxermann continuity of care score (COCI). Values equal to one were categorized into one group and the rest into three equal groups (tertiles). The association with mortality was determined by Cox regression models.

Results

The highest mean UPCtotal was measured for patients with diabetes mellitus (0.58) and the lowest for those with asthma (0.46). The population with heart failure had the highest death rate (26.5). In adjusted Cox regression analyses for COPD, mortality was 2.6 times higher (95% CI 2.25–3.04) for patients in the lowest tertile of continuity compared to those with UPCtotal = 1. Patients with diabetes mellitus and heart failure showed similar results.

Conclusion

CoC was moderate to high for disease-related contacts across care levels. A higher mortality associated with lower CoC was observed for patients with COPD, diabetes mellitus, and heart failure. A similar, but not statistically significant trend was found for patients with asthma. This study suggests that higher CoC across levels of care can decrease mortality.
Lymphatic contractile dysfunction in mouse models of Cantú Syndrome with KATP channel gain-of-function
Authors: Davis Michael J , Castorena-Gonzalez Jorge A , Kim Hae Jin , Li Min , Remedi Maria , Nichols Colin G
Published: April 2023

Cantú Syndrome (CS) is an autosomal dominant disorder caused by gain-of-function (GoF) mutations in the Kir6.1 and SUR2 subunits of KATP channels. KATP overactivity results in a chronic reduction in arterial tone and hypotension, leading to other systemic cardiovascular complications. However, the underlying mechanism of lymphedema, developed by >50% of CS patients, is unknown. We investigated whether lymphatic contractile dysfunction occurs in mice expressing CS mutations in Kir6.1 (Kir6.1[V65M]) or SUR2 (SUR2[A478V], SUR2[R1154Q]). Pressure myograph tests of contractile function of popliteal lymphatic vessels over the physiological pressure range revealed significantly impaired contractile strength and reduced frequency of spontaneous contractions at all pressures in heterozygous Kir6.1[V65M] vessels, compared to control littermates. Contractile dysfunction of intact popliteal lymphatics in vivo was confirmed using near-infrared fluorescence microscopy. Homozygous SUR2[A478V] vessels exhibited profound contractile dysfunction ex vivo, but heterozygous SUR2[A478V] vessels showed essentially normal contractile function. However, further investigation of vessels from all three GoF mouse strains revealed significant disruption in contraction wave entrainment, decreased conduction speed and distance, multiple pacemaker sites, and reversing wave direction. Tests of 2-valve lymphatic vessels forced to pump against an adverse pressure gradient revealed that all CS-associated genotypes were essentially incapable of pumping under an imposed outflow load. Our results show that varying degrees of lymphatic contractile dysfunction occur in proportion to the degree of molecular GoF in Kir6.1 or SUR2. This is the first example of lymphatic contractile dysfunction caused by a smooth muscle ion channel mutation and potentially explains the susceptibility of CS patients to lymphedema.
A novel ubiquitin–proteasome system regulation of Sgf73/ataxin-7 that maintains the integrity of the coactivator SAGA in orchestrating transcription
Authors: Barman Priyanka , Kaja Amala , Chakraborty Pritam , Guha Shalini , Roy Arpan , Ferdoush Jannatul , Bhaumik Sukesh R
Published: April 2023

Ataxin-7 maintains the integrity of Spt-Ada-Gcn5-Acetyltransferase (SAGA), an evolutionarily conserved coactivator in stimulating preinitiation complex (PIC) formation for transcription initiation, and thus, its upregulation or downregulation is associated with various diseases. However, it remains unknown how ataxin-7 is regulated that could provide new insights into disease pathogenesis and therapeutic interventions. Here, we show that ataxin-7's yeast homologue, Sgf73, undergoes ubiquitylation and proteasomal degradation. Impairment of such regulation increases Sgf73's abundance, which enhances recruitment of TATA box-binding protein (TBP) (that nucleates PIC formation) to the promoter but impairs transcription elongation. Further, decreased Sgf73 level reduces PIC formation and transcription. Thus, Sgf73 is fine-tuned by ubiquitin–proteasome system (UPS) in orchestrating transcription. Likewise, ataxin-7 undergoes ubiquitylation and proteasomal degradation, alteration of which changes ataxin-7's abundance that is associated with altered transcription and cellular pathologies/diseases. Collectively, our results unveil a novel UPS regulation of Sgf73/ataxin-7 for normal cellular health and implicate alteration of such regulation in diseases.
Homogenization of magnitudes of the ISC Bulletin
Authors: Lolli Barbara , Randazzo Daniele , Vannucci Gianfranco , Biondini Emanuele , Gasperini Paolo
Published: April 2023

We implemented an automatic procedure to download the hypocentral data of the online Bulletin of the International Seismological Centre (ISC) in order to produce in near real-time a homogeneous catalogue of the Global and EuroMediterranean instrumental seismicity to be used for forecasting experiments and other statistical analyses. For the interval covered by the reviewed ISC Bulletin, we adopt the ISC locations and convert the surface wave magnitude (Ms) and short-period body-wave magnitude (mb) as computed by the ISC to moment magnitude (Mw), using empirical relations. We merge the so obtained proxies with real Mw provided by global and EuroMediterranean moment tensor catalogues. For the most recent time interval (about 2 yr) for which the reviewed ISC Bulletin is not available, we do the same but using the preferred (prime) location provided by the ISC Bulletin and converting to Mw the Ms and mb provided by some authoritative agencies. For computing magnitude conversion equations, we use curvilinear relations defined in a previous work and the chi-square regression method that accounts for the uncertainties of both x and y variables.
Observation site selection for physical model parameter estimation towards process-driven seismic wavefield reconstruction
Authors: Nakai K , Nagata T , Yamada K , Saito Y , Nonomura T , Kano M , Ito S , Nagao H
Published: April 2023

The ‘big’ seismic data not only acquired by seismometers but also acquired by vibrometers installed in buildings and infrastructure and accelerometers installed in smartphones will be certainly utilized for seismic research in the near future. Since it is impractical to utilize all the seismic big data in terms of the computational cost, methods which can select observation sites depending on the purpose are indispensable. We propose an observation site selection method for the accurate reconstruction of the seismic wavefield by process-driven approaches. The proposed method selects observation sites suitable for accurately estimating physical model parameters such as subsurface structures and source information to be input into a numerical simulation of the seismic wavefield. The seismic wavefield is reconstructed by the numerical simulation using the parameters estimated based on the observed signals at only observation sites selected by the proposed method. The observation site selection in the proposed method is based on the sensitivity of each observation site candidate to the physical model parameters; the matrix corresponding to the sensitivity is constructed by approximately calculating the derivatives based on the simulations, and then, observation sites are selected by evaluating the quantity of the sensitivity matrix based on the D-optimality criterion proposed in the optimal design of experiments. In this study, physical knowledge on the sensitivity to the parameters such as seismic velocity, layer thickness, and hypocentre location was obtained by investigating the characteristics of the sensitivity matrix. Furthermore, the effectiveness of the proposed method was shown by verifying the accuracy of seismic wavefield reconstruction using the observation sites selected by the proposed method.
Genomic features of meiotic crossovers in diploid potato
Authors: Jiang Xiuhan , Li Dawei , Du Hui , Wang Pei , Guo Liang , Zhu Guangtao , Zhang Chunzhi
Published: April 2023

Meiotic recombination plays an important role in genome evolution and crop improvement. Potato (Solanum tuberosum L.) is the most important tuber crop in the world, but research about meiotic recombination in potato is limited. Here, we resequenced 2163 F2 clones derived from five different genetic backgrounds and identified 41 945 meiotic crossovers. Some recombination suppression in euchromatin regions was associated with large structural variants. We also detected five shared crossover hotspots. The number of crossovers in each F2 individual from the accession Upotato 1 varied from 9 to 27, with an average of 15.5, 78.25% of which were mapped within 5 kb of their presumed location. We show that 57.1% of the crossovers occurred in gene regions, with poly-A/T, poly-AG, AT-rich, and CCN repeats enriched in the crossover intervals. The recombination rate is positively related with gene density, SNP density, Class II transposon, and negatively related with GC density, repeat sequence density and Class I transposon. This study deepens our understanding of meiotic crossovers in potato and provides useful information for diploid potato breeding.
Creation of a watermelon haploid inducer line via ClDMP3-mediated single fertilization of the central cell
Authors: Chen Xiner , Li Yuxiu , Ai Gongli , Chen Jinfan , Guo Dalong , Zhu Zhonghou , Zhu Xuejie , Tian Shujuan , Wang Jiafa , Liu Man , Yuan Li
Published: April 2023

The use of doubled haploids is one of the most efficient breeding methods in modern agriculture. Irradiation of pollen grains has been shown to induce haploids in cucurbit crops, possibly because it causes preferential fertilization of the central cell over the egg cell. Disruption of the DMP gene is known to induce single fertilization of the central cell, which can lead to the formation of haploids. In the present study, a detailed method of creating a watermelon haploid inducer line via ClDMP3 mutation is described. The cldmp3 mutant induced haploids in multiple watermelon genotypes at rates of up to 1.12%. These haploids were confirmed via fluorescent markers, flow cytometry, molecular markers, and immuno-staining. The haploid inducer created by this method has the potential to greatly advance watermelon breeding in the future.
Density of Biopsy Sampling Required to Ensure Accurate Histological Assessment of Inflammation in Active Ulcerative Colitis
Authors: McBride Russell B , Suarez-Farinas Mayte , Ko Huaibin M , Chen Xiuxu , Liu Qingqing , Harpaz Noam
Published: April 2023

Background

Histological response to treatment is an important outcome in patients with ulcerative colitis (UC). The accuracy of biopsy-based measurements of inflammation may be limited by error imposed by natural microscopic heterogeneity on the scale of individual biopsies. We determined the magnitude of this error, its histological correlates, and the density of biopsy sampling within mucosal regions of interest required to meet specified benchmarks for accuracy.

Methods

A total of 994 sequential 1-mm digital microscopic images (virtual biopsies) from consecutive colectomies from patients with clinically severe UC were scored by 2 pathologists. Agreement statistics for Geboes subscores and Nancy (NHI) and Robarts Histological Indices (RHI) between random samples from 1 to 10 biopsies and a reference mean score across a 2-cm region of mucosa were calculated using bootstrapping with 2500 iterations.

Results

The agreement statistics improved across all indices as the biopsy density increased, with the largest proportional gains occurring with addition of the second and third biopsies. One biopsy achieved moderate to good agreement with 95% confidence for NHI and RHI corresponding to scale-specific errors of 0.40 (0.25-0.66) and 3.02 (2.08-5.36), respectively; and 3 biopsies achieved good agreement with 95% confidence corresponding to scale-specific errors of 0.22 (0.14-0.39) and 1.87 (1.19-3.25), respectively. Of the individual histological features, erosions and ulcers had the greatest impact on the agreement statistics.

Conclusions

In the setting of active colitis, up to 3 biopsy samples per region of interest may be required to overcome microscopic heterogeneity and ensure accurate histological grading.
“The Evil Spirits Are Always Trying to Bring You Down”: Righteousness and Spirit Harassment Among Latter-day Saints in Northern Utah
Authors: Stiles Erin E
Published: April 2023

This article explores contemporary Latter-day Saint conceptions of evil in northern Utah through considering both the lived experiences of spirits and the didactic tales of spirits that are a rich part of local folklore. Latter-day Saints are visited by both benevolent and malevolent spirits. These encounters with spirits are connected with local conceptions of “righteousness,” a moral framework that is centered on positive action. Malevolent spirit visits are typically understood as the consequence of “unrighteous” actions or as impediments to exceptionally righteous activity; indeed, the most righteous actions are perhaps the most spiritually dangerous. Negative visitations reflect a cultural framework of evil as a human phenomenon that results from the temptations and distractions of an aggressive, external cosmological force—Satan. Righteous and unrighteous actions both attract the interest of Satan, and therefore invite the possibility of evil to disrupt the moral order.
Cost analysis of dalbavancin versus standard of care for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) in two Italian hospitals
Authors: Bai Francesca , Mazzitelli Maria , Silvola Sofia , Raumer Francesca , Restelli Umberto , Croce Davide , Marchetti Giulia , Cattelan Anna Maria
Published: April 2023

Objectives

Thanks to its long half-life, dalbavancin qualifies as an optimal drug for saving costs. We aimed to assess the cost and effectiveness of dalbavancin versus the standard of care (SoC).

Patients and methods

We conducted a multicentre retrospective study, including all hospitalized or outpatients diagnosed with ABSSSIs at Padua University Hospital, Padua and San Paolo Hospital, Milan (1 January 2016 to 31 July 2020). We compared patients according to antibiotic treatment (dalbavancin versus SoC), the number of lines of dalbavancin treatment, and monotherapy or combination (dalbavancin in association with other antibiotics). Primary endpoints were direct medical costs and length of hospital stay (LOS) associated with ABSSSI management; Student’s t-test, chi-squared test and one-way ANOVA were used.

Results

One hundred and twenty-six of 228 (55.3%) patients received SoC, while 102/228 (44.7%) received dalbavancin. Twenty-seven of the 102 (26.5%) patients received dalbavancin as first-line treatment, 46 (45.1%) as second-line, and 29 (28.4%) as third- or higher-line treatment. Most patients received dalbavancin as monotherapy (62/102; 60.8%). Compared with SoC, dalbavancin was associated with a significant reduction of LOS (5 ± 7.47 days for dalbavancin, 9.2 ± 5.59 days for SoC; P < 0.00001) and with lower mean direct medical costs (3470 ± 2768€ for dalbavancin; 3493 ± 1901€ for SoC; P = 0.9401). LOS was also reduced for first-line dalbavancin, in comparison with second-, third- or higher-line groups, and for dalbavancin monotherapy versus combination therapy. Mean direct medical costs were significantly lower in first-line dalbavancin compared with higher lines, but no cost difference was observed between monotherapy and combination therapy.

Conclusions

Monotherapy with first-line dalbavancin was confirmed as a promising strategy for ABSSSIs in real-life settings, thanks to its property in reducing LOS and saving direct medical costs.
Alternations of ensiling performance and bacterial community in response to different native grassland in Mongolian Plateau
Authors: Bao Jian , Wang Zhijun , Sun Lin , Zhao Muqier , Bai Baochao , Hao Junfeng , Jia Yushan , Du Shuai
Published: April 2023

Aims

The aim of this study was to investigate the dynamics of bacterial communities and natural fermentation quality in three steppe types [meadow steppe (MS); typical steppe (TS); and desert steppe (DS)] on the Mongolian Plateau.

Methods and results

PacBio single molecule with real-time sequencing technology was applied to provide insights into the dynamics of the physicochemical characteristics and the complex microbiome of native grass after 1, 7, 15, and 30 days of fermentation process. The dry matter, crude protein, and water soluble carbohydrate (WSC) contents of the three groups slowly decreased after 1 day of fermentation process, and the lowest WSC concentration after 30 days of ensiling was detected in the DS group compared to that in the MS and TS groups. There was no significant effect of steppe types on lactic acid and butyric acid content (P > 0.05). The pH was higher in the early stages of fermentation. After 30 days of fermentation, the pH of MS and DS dropped to ∼5.60, while TS was as high as 5.94. At different ensiling days, the pH of TS was significantly higher than that of MS (P < 0.05). The ammonia nitrogen content of MS was significantly higher than TS and DS (P < 0.05). During the whole fermentation process, Leuconostoc mesenteroides and Pseudocitrobacter faecalis were the main species of DS, while Enterobacter roggenkampii and Faecalibacterium prausnitzii dominated the fermentation process in MS and TS, respectively.

Conclusions

The fermentation quality of native grass silage of different steppe types was less satisfactory, with the silage quality ranging from DS, MS, and TS in descending order. The epiphytic bacteria dominating the fermentation process differed between steppe types of silage. Leuconostoc mesenteroides as the main strain of DS had a modulating effect on pH and LA content, while the main strains of MS and TS (Enterobacter roggenkampii and Faecalibacterium prausnitzii) dominated the silage without significant effect on improving fermentation characteristics and nutritional quality.
Amicus Curiae Applications in Malawi—Reflections of a South African Practitioner
Authors: Swemmer Sheena
Published: April 2023

Amicus curiae applications are important as they aim to raise awareness for the court around aspects of a case that might otherwise be overlooked. This is especially significant in cases dealing with the intersection of various rights of vulnerable individuals such as women and children. In this practice note, I discuss the amicus intervention of the South African non-profit organization, the Centre of Applied Legal Studies, in the Malawian Constitutional Court case of AJ and TS v State and Others. The case deals with the constitutionality of section 138(1) of the Malawian Penal Code, which makes it an offence for anyone to engage in intercourse with a female child under the age of 16. Although this section was undoubtedly aimed to protect female children from sexual violence and rape it casts the net too wide by including consensual intercourse between minor children. In this case, both minor children were under the age of 15 at the time of their arrests. They had both engaged in consensual intercourse with their female partners (also minors) at the time and both faced a prison sentence of up to 14 years.

In this note I proceed to explore the importance of the amici submissions in the case, the process of applying to be admitted as an amicus curiae in Malawi, as well as the challenges associated with being a foreign amici before the Malawian Constitutional Court.
Cancer mortality rates by racial and ethnic groups in the United States, 2018-2020
Authors: Haque Anika T , Berrington de González Amy , Chen Yingxi , Haozous Emily A , Inoue-Choi Maki , Lawrence Wayne R , McGee-Avila Jennifer K , Nápoles Anna M , Pérez-Stable Eliseo J , Taparra Kekoa , Vo Jacqueline B , Freedman Neal D , Shiels Meredith S
Published: April 2023

Background

Starting in 2018, national death certificates included a new racial classification system that accounts for multiple-race decedents and separates Native Hawaiian and Pacific Islander (NHPI) individuals from Asian individuals. We estimated cancer death rates across updated racial and ethnic categories, sex, and age.

Methods

Age-standardized US cancer mortality rates and rate ratios from 2018 to 2020 among individuals aged 20 years and older were estimated with national death certificate data by race and ethnicity, sex, age, and cancer site.

Results

In 2018, there were approximately 597 000 cancer deaths, 598 000 in 2019, and 601 000 in 2020. Among men, cancer death rates were highest in Black men (298.2 per 100 000; n = 105 632), followed by White (250.8; n = 736 319), American Indian/Alaska Native (AI/AN; 249.2; n = 3376), NHPI (205.6; n = 1080), Latino (177.2; n = 66 167), and Asian (147.9; n = 26 591) men. Among women, Black women had the highest cancer death rates (206.5 per 100 000; n = 104 437), followed by NHPI (192.1; n = 1141), AI/AN (189.9; n = 3239), White (183.0; n = 646 865), Latina (128.4; n = 61 579), and Asian (111.4; n = 26 396) women. The highest death rates by age group occurred among NHPI individuals aged 20-49 years and Black individuals aged 50-69 and 70 years and older. Asian individuals had the lowest cancer death rates across age groups. Compared with Asian individuals, total cancer death rates were 39% higher in NHPI men and 73% higher in NHPI women.

Conclusions

There were striking racial and ethnic disparities in cancer death rates during 2018-2020. Separating NHPI and Asian individuals revealed large differences in cancer mortality between 2 groups that were previously combined in vital statistics data.
Septic retrocalcaneal bursitis in a young soccer player treated with hindfoot endoscopic bursectomy: a case report
Authors: Shota Morimoto , Toshiya Tachibana , Tomoya Iseki
Published: April 2023

Septic retrocalcaneal bursitis (RB) is extremely rare with no reports on surgical treatment. Here, we describe a rare case of septic RB in a 14-year-old male soccer player who was treated with hindfoot endoscopic bursectomy. A 14-year-old male soccer player complained of right heel pain without trauma histories when he was playing a soccer. Based on physical examination, radiological findings and laboratory results, we diagnosed the patient with septic RB and started to treat with conservative treatment including a non-weightbearing splint and intravenous antibiotics therapy. However, his symptoms and laboratory results did not improve at 4 days after starting intravenous antibiotics therapy, and so we applied hindfoot endoscopic bursectomy for him. At 4 weeks after the surgery, he could return to the original sport at preinjury level without symptoms and complications. Septic RB in a 14-year-old male soccer player was successfully treated with hindfoot endoscopic bursectomy.
Single-port transoral robotic surgery for a rare tonsil mass
Authors: Allen David Z , Gorelik Daniel , Butler Edward B , Zhang Jun , Kain Joshua J
Published: April 2023

Squamous cell carcinoma predominates as the most common malignant lesion of the oropharynx with human papilloma virus-associated disease now predominant over tobacco-related oropharynx cancer. Other rare malignant pathologies can manifest as visible neoplasms in these anatomic sites with varying degrees of symptoms such as dysphagia, odynophagia, otalgia, aspiration, hemorrhage, weight loss and dyspnea. We present a case of a rarely encountered primary oropharyngeal sarcoma managed by single-port transoral robotic resection and a selective cervical lymph node dissection followed by adjuvant radiotherapy.
Cost-effectiveness of treatment strategies for populations from strongyloidiasis high-risk areas globally who will initiate corticosteroid treatment in the USA
Authors: Joo Heesoo , Maskery Brian A , Alpern Jonathan D , Weinberg Michelle , Stauffer William M
Published: April 2023

Background

The risk of developing strongyloidiasis hyperinfection syndrome appears to be elevated among individuals who initiate corticosteroid treatment. Presumptive treatment or treatment after screening for populations from Strongyloides stercoralis-endemic areas has been suggested before initiating corticosteroids. However, potential clinical and economic impacts of preventative strategies have not been evaluated.

Methods

Using a decision tree model for a hypothetical cohort of 1000 individuals from S. stercoralis-endemic areas globally initiating corticosteroid treatment, we evaluated the clinical and economic impacts of two interventions, ‘Screen and Treat’ (i.e. screening and ivermectin treatment after a positive test), and ‘Presumptively Treat’, compared to current practice (i.e. ‘No Intervention’). We evaluated the cost-effectiveness (net cost per death averted) of each strategy using broad ranges of pre-intervention prevalence and hospitalization rates for chronic strongyloidiasis patients initiating corticosteroid treatment.

Results

For the baseline parameter estimates, ‘Presumptively Treat’ was cost-effective (i.e. clinically superior with cost per death averted less than a threshold of $10.6 million per life) compared to ‘No Intervention’ ($532 000 per death averted) or ‘Screen and Treat’ ($39 000 per death averted). The two parameters contributing the most uncertainty to the analysis were the hospitalization rate for individuals with chronic strongyloidiasis who initiate corticosteroids (baseline 0.166%) and prevalence of chronic strongyloidiasis (baseline 17.3%) according to a series of one-way sensitivity analyses. For hospitalization rates ≥0.022%, ‘Presumptively Treat’ would remain cost-effective. Similarly, ‘Presumptively Treat’ remained preferred at prevalence rates of ≥4%; ‘Screen and Treat’ was preferred for prevalence between 2 and 4% and ‘No Intervention’ was preferred for prevalence <2%.

Conclusions

The findings support decision-making for interventions for populations from S. stercoralis-endemic areas before initiating corticosteroid treatment. Although some input parameters are highly uncertain and prevalence varies across endemic countries, ‘Presumptively Treat’ would likely be preferred across a range for many populations, given plausible parameters.
An evo-devo view of the gynoecium
Authors: Reyes-Olalde J Irepan , Aida Mitsuhiro , de Folter Stefan
Published: April 2023

The appearance of the flower marks a key event in the evolutionary history of plants. Among the four types of floral organs, the gynoecium represents the major adaptive advantage of the flower. The gynoecium is an enclosing structure that protects and facilitates the fertilization of the ovules, which then mature as seeds. Upon fertilization, in many species, the gynoecium itself eventually becomes the fruit, which contributes to the dispersal of the seeds. However, despite its importance and the recent advances in our understanding of the genetic regulatory network guiding early gynoecium development, many questions remain to be resolved regarding the extent of the conservation of the molecular mechanisms for gynoecium development among different taxa, and how these mechanisms give origin and diversification to the gynoecium. In this review, we compile the existing knowledge about the evolution, development, and molecular mechanisms involved in the origin and evolution of the gynoecium.
Web archive analytics: Blind spots and silences in distant readings of the archived web
Authors: Donig Simon , Eckl Markus , Gassner Sebastian , Rehbein Malte
Published: April 2023

In this article, we discuss epistemological and methodological aspects of web archive analytics, a recent development towards more data-centred access to web archives. More specifically, we suggest understanding both the process of archiving and subsequent steps of analysis at scale as acts of observation that can be questioned for their epistemological priori. Therefore, we propose the concepts of ‘blind spots’ (features of the live web not included upon creation in the archive) and ‘silences’ (latent features present in the archive but requiring a particular method to be made articulate). In particular, we address two forms of silences playing a structural role in web archive analytics, crucial to both historians and social scientists alike: abundance (or scale) and time. We trace epistemological implications of web archive analytics across an exemplary case study workflow and suggest methodological answers to the issues raised in this process. On the data extraction side, we introduce warc2corpus (w2c), a new tool for extracting granular, structured data, especially temporal information related to the creation, modification, and publication specifically of webpages. For data analysis, we demonstrate how distant reading techniques—more specifically structural topic modelling (STM)—can contribute to providing a rich, temporally structured representation of textual web archive content that in turn can be subjected to scholarly inquiry, interpretation, and re-contextualization.
Striking up a Conversation: Exploring Advising in Graduate Programs in Health Professions Education
Authors: Elliott Shelby Ann , Schermerhorn Janse , Durning Steven , Costello Joseph , Norton Candace , Meyer Holly
Published: April 2023

Introduction

Advising is happening across the medical education continuum, within non-medical graduate education programs, and is central to the advancement of said learners. This suggests that advising should play a role in graduate health progressions education (HPE) programs.

Materials and Methods

To explore advising curricula among HPE programs, we conducted a website review of all published HPE programs on the Foundation for Advancement of International Medical Education and Research’s website.

Results

We recognized the lack of information published on advisory roles in graduate HPE programs. This prompted a literature review, which revealed a similar gap.

Conclusions

Advising serves to benefit a student, advisor, and program thus carrying importance and need for discussion. This article is intended to kick-start a scholarly discussion about advising within graduate HPE programs.
A direct N-body integrator for modelling the chaotic, tidal dynamics of multibody extrasolar systems: TIDYMESS
Authors: Boekholt Tjarda C N , Correia Alexandre C M
Published: April 2023

Tidal dissipation plays an important role in the dynamical evolution of moons, planets, stars, and compact remnants. The interesting complexity originates from the interplay between the internal structure and external tidal forcing. Recent and upcoming observing missions of exoplanets and stars in the galaxy help to provide constraints on the physics of tidal dissipation. It is timely to develop new N-body codes, which allow for experimentation with various tidal models and numerical implementations. We present the open-source N-body code TIDYMESS, which stands for ‘TIdal DYnamics of Multibody ExtraSolar Systems’. This code implements a Creep deformation law for the bodies, parametrized by their fluid Love numbers and fluid relaxation times. Due to tidal and centrifugal deformations, we approximate the general shape of a body to be an ellipsoid. We calculate the associated gravitational field to quadruple order, from which we derive the gravitational accelerations and torques. The equations of motion for the orbits, spins and deformations are integrated directly using a fourth-order integration method based on a symplectic composition. We implement a novel integration method for the deformations, which allows for a time-step solely dependent on the orbits, and not on the spin periods or fluid relaxation times. This feature greatly speeds up the calculations, while also improving the consistency when comparing different tidal regimes. We demonstrate the capabilities and performance of TIDYMESS, particularly in the niche regime of parameter space where orbits are chaotic and tides become non-linear.