bluuebunny/crossref_metadata_2025 huggingface dataset:
S3V2-IDEAS: a package for normalizing, denoising and integrating epigenomic datasets across different cell types
Authors: Xiang Guanjue , Giardine Belinda M , Mahony Shaun , Zhang Yu , Hardison Ross C
Published: March 2021

Epigenetic modifications reflect key aspects of transcriptional regulation, and many epigenomic datasets have been generated under different biological contexts to provide insights into regulatory processes. However, the technical noise in epigenomic datasets and the many dimensions (features) examined make it challenging to effectively extract biologically meaningful inferences from these datasets. We developed a package that reduces noise while normalizing the epigenomic data by a novel normalization method, followed by integrative dimensional reduction by learning and assigning epigenetic states. This package, called S3V2-IDEAS, can be used to identify epigenetic states for multiple features, or identify discretized signal intensity levels and a master peak list across different cell types for a single feature. We illustrate the outputs and performance of S3V2-IDEAS using 137 epigenomics datasets from the VISION project that provides ValIdated Systematic IntegratiON of epigenomic data in hematopoiesis.

Availability and implementation

S3V2-IDEAS pipeline is freely available as open source software released under an MIT license at: https://github.com/guanjue/S3V2_IDEAS_ESMP.

Supplementary information

Supplementary data are available at Bioinformatics online.
Protein interaction interface region prediction by geometric deep learning
Authors: Dai Bowen , Bailey-Kellogg Chris
Published: March 2021

Motivation

Protein–protein interactions drive wide-ranging molecular processes, and characterizing at the atomic level how proteins interact (beyond just the fact that they interact) can provide key insights into understanding and controlling this machinery. Unfortunately, experimental determination of three-dimensional protein complex structures remains difficult and does not scale to the increasingly large sets of proteins whose interactions are of interest. Computational methods are thus required to meet the demands of large-scale, high-throughput prediction of how proteins interact, but unfortunately, both physical modeling and machine learning methods suffer from poor precision and/or recall.

Results

In order to improve performance in predicting protein interaction interfaces, we leverage the best properties of both data- and physics-driven methods to develop a unified Geometric Deep Neural Network, ‘PInet’ (Protein Interface Network). PInet consumes pairs of point clouds encoding the structures of two partner proteins, in order to predict their structural regions mediating interaction. To make such predictions, PInet learns and utilizes models capturing both geometrical and physicochemical molecular surface complementarity. In application to a set of benchmarks, PInet simultaneously predicts the interface regions on both interacting proteins, achieving performance equivalent to or even much better than the state-of-the-art predictor for each dataset. Furthermore, since PInet is based on joint segmentation of a representation of a protein surfaces, its predictions are meaningful in terms of the underlying physical complementarity driving molecular recognition.

Availability and implementation

PInet scripts and models are available at https://github.com/FTD007/PInet.

Supplementary information

Supplementary data are available at Bioinformatics online.
A Statistical-Based Light-Weight Anomaly Detection Framework for Wireless Body Area Networks
Authors: G S Smrithy , Balakrishnan Ramadoss
Published: March 2021

In healthcare scenario, the major challenge in anomaly detection for remote patient monitoring is to classify true medical conditions and false alarms. This paper proposes a light-weight anomaly detection (LWAD) framework for detecting anomalies in remote patient monitoring based on wireless body area networks. The proposed framework uses distance correlation for finding correlated (both linear and non-linear) physiological parameters. It also uses a statistical-based improvised dynamic sliding window algorithm for efficient short-range prediction of physiological parameters. Finally, the proposed LWAD framework detects anomalies using anomaly detection framework based on robust statistical techniques. The validation of LWAD framework is performed using three real time datasets with various statistical measures. The proposed LWAD framework outperforms existing methods.
Limits on performance and survival of juvenile sockeye salmon (Oncorhynchus nerka) during food deprivation: a laboratory-based study
Authors: Wilson Samantha M , Robinson Kendra A , Gutzmann Sarah , Moore Jonathan W , Patterson David A
Published: March 2021

Long-distance migrations can be energetically demanding and can represent phases of high mortality. Understanding relationships between body condition and migratory performance can help illuminate the challenges and vulnerabilities of migratory species. Juvenile anadromous sockeye salmon (Oncorhynchus nerka) may migrate over 1000 km from their freshwater nursery habitats to estuary and ocean feeding grounds. During the period corresponding to the seaward migration of sockeye salmon, we held smolts in the laboratory to ask the following: (i) Does non-feeding migration duration influence prolonged swim performance and survival? (ii) What are the relationships between individual body condition and swim performance and survival? Wild sockeye salmon were intercepted during their migration and held without food for up to 61 days to represent the non-feeding freshwater migration and the extremes of poor estuary habitat. We conducted 40 sets of prolonged swim trials on 319 fish from 3 treatment groups that represented entrance to the marine environment on (i) an average,(ii) a delayed and (iii) a severely delayed migration schedule. Experimentally controlled freshwater migration duration did not impact swim performance or survival. Swim performance decreased concomitant with condition factor, where smolts with a Fulton’s condition factor of <0.69 were less likely (<50% probability) to complete the swim test (90 min swim test, at ~0.50 m/s). Survival of salmon smolts in the laboratory was less likely at energy densities of less than 3.47 MJ/kg. Swim performance decreased much sooner than survival, suggesting that swim performance, and therefore condition factor, may be a good indicator of survival of migratory smolts, as fish with reduced swim performance will likely be predated. These two relationships, one more ecologically relevant and one more clinical, help reveal the limits of long-distance migration for juvenile salmon and can be used to determine population-specific starvation risk associated with various freshwater and marine habitat conditions.
Impact of the Coronavirus Lockdown on Older Adolescents Engaged in a School-Based Stress Management Program: Changes in Mental Health, Sleep, Social Support, and Routines
Authors: Marques Sara Schjølberg , Braidwood Ruth
Published: March 2021

The mental health effects of the coronavirus pandemic are likely to be significant and sustained, especially for those who experience adversity or preexisting mental health difficulties. This article examines the experiences of older adolescents during the United Kingdom government’s “lockdown” period (April 2020 to June 2020) on mental health, social support, sleep, and routines using both quantitative and qualitative methods. Participants were enrolled in DISCOVER, a school-based stress management program, in London (N = 107; 72 percent Black, Asian, or minority ethnicity). The Coping with COVID-19 questionnaire was developed and administered online. Changes in mental health, sleep, and routines were reported during the lockdown period as well as increased worry about family members’ physical and mental health. Positive experiences of the lockdown period included improvements in quality of relationships and increased time to spend on hobbies. Participants reported the use of cognitive–behavioral therapy techniques for coping. Results have implications for supporting older adolescents during the pandemic, including on their return to school.
Stem taper functions for white birch (Betula platyphylla) and costata birch (Betula costata) in the Xiaoxing’an Mountains, northeast China
Authors: Hussain Amna , Shahzad Muhammad Khurram , Burkhart Harold E , Jiang Lichun
Published: March 2021

White birch (Betula platyphylla Sukaczev) and costata birch (Betula costata Trautv.) are valuable hardwood tree species growing in northeast China. Several taper studies have analysed birch species in the countries harbouring the boreal forests. However, this study presents an initial attempt to develop stem taper models using the fixed- and mixed-effects modelling for white birch and costata birch in Xiaoxing’an Mountains, northeast China. Ten commonly used taper models were evaluated by using 228 destructively sampled trees of both tree species comprising of 4582 diameter and height measurements. The performance of these models was tested in predicting diameter at any height, total volume and merchantable volume (10 and 20 cm top diameters). We incorporated a second-order continuous-time error structure to adjust the inherent autocorrelation in the data. The segmented model of Clark best predicted the diameter and total or merchantable volume when the upper stem diameter at 5.3 m was available. When diameter measurements at 5.3 m were not available, the models of Kozak and Max and Burkhart were superior to other models for white birch and costata birch, respectively. After model comparison, the best model of Clark was refitted as the NLME model.
Utilization of Cobalamin Is Ubiquitous in Early-Branching Fungal Phyla
Authors: Orłowska Małgorzata , Steczkiewicz Kamil , Muszewska Anna
Published: March 2021

Cobalamin is a cofactor present in essential metabolic pathways in animals and one of the water-soluble vitamins. It is a complex compound synthesized solely by prokaryotes. Cobalamin dependence is scattered across the tree of life. In particular, fungi and plants were deemed devoid of cobalamin. We demonstrate that cobalamin is utilized by all non-Dikarya fungi lineages. This observation is supported by the genomic presence of both B12-dependent enzymes and cobalamin modifying enzymes. Fungal cobalamin-dependent enzymes are highly similar to their animal homologs. Phylogenetic analyses support a scenario of vertical inheritance of the cobalamin usage with several losses. Cobalamin usage was probably lost in Mucorinae and at the base of Dikarya which groups most of the model organisms and which hindered B12-dependent metabolism discovery in fungi. Our results indicate that cobalamin dependence was a widely distributed trait at least in Opisthokonta, across diverse microbial eukaryotes and was likely present in the LECA.
A Corpus Too Small: Uses of Text Data in a Hupa-English Bilingual Dictionary
Authors: Spence Justin
Published: March 2021

Although corpus-driven methods have led to a revolution in the way lexicographers of some languages approach their work, text corpora for many less-studied languages are too small for such methods to be used reliably. Hupa, a Native American language of northwestern California, is one such language. Nonetheless, the Hupa Online Dictionary and Texts website relies heavily on its small text corpus to support development of the dictionary component. The corpus is especially important as a way to address Hupa’s complex and productive polysynthetic morphology, both derivational and inflectional, with words attested in the corpus providing the empirical basis for creating new entries and expanding the coverage of existing ones. It also provides a ready source of example sentences in context, figurative uses of language that might not come to light through elicitation, and aspects of linguistic variation that dictionary normalization tends to obscure. Thus, while corpus-driven lexicography may not be a realistic possibility at this point, corpus-based lexicography (Tognini-Bonelli 2001) is certainly within reach.
The Validation of the SIMUL-qPCR Salmonella Assay for AOAC Research Institute Performance Tested MethodsSM Certification (Certificate No. 042001)
Authors: Lonczynski Thomas , Cowin Laura
Published: March 2021

Background

The Simultaneous Multiplex (SIMUL) Real-Time PCR (qPCR) Salmonella Assay is a quick, reliable method for detecting Salmonella species in environmental and food samples. The assay multiplexes several targets in one run to identify Salmonella species. For most matrixes, the assay uses buffered peptone water for enrichment purposes. However, the assay can be used in conjunction with the SIMUL-qPCR Top 7 STEC Assay for raw beef trim and raw ground beef when proprietary media (Enterohemorrhagic E. coli Recovery and Enrichment Broth or EREB) has been used. This media is optimized for single-step enrichment and recovery of enterohemorrhagic E. coli and Salmonella in those matrixes.

Objective

This report details the method validation study to validate raw beef trim, raw ground beef, fresh raw ground poultry, ready-to-eat cooked poultry, dry pet food, pasteurized liquid eggs, peanut butter, frankfurter/sausage, poultry carcass rinse, and environmental surface sponges and swabs for stainless steel, plastic, rubber, ceramic tile, and sealed concrete.

Method

Matrix studies, inclusivity/exclusivity, product consistency/stability, and robustness testing were conducted to assess the method’s performance.

Results

Inclusivity/exclusivity testing showed the SIMUL-qPCR Salmonella Assay was able to detect Salmonella strains while excluding the non-Salmonella isolates. There were no statistically significant differences found between the candidate and reference methods in the matrix studies. Small variations in critical test parameters (enrichment time, extraction reagent volume, and extracted sample volume) didn’t adversely affect the assay’s performance, and stability testing indicated consistent results for at least one year.

Conclusions

The data presented demonstrate the SIMUL-qPCR Salmonella Assay is a reliable method for detecting Salmonella.

Highlights

The SIMUL-qPCR Salmonella Assay is validated to detect Salmonella in a variety of matrices in as little as 16 hours in Buffered Peptone Water. The assay can also be used in conjunction with the SIMUL Top 7 Assay to test for both Salmonella and the Top 7 Shiga toxin producing E. coli using a single enrichment in EREB media.
Nondestructive Sampling for Spotted Lanternfly (Hemiptera: Fulgoridae) Egg Masses in Woodlands Based on Fixed-Radius Plots
Authors: Liu Houping , Hunter Matthew
Published: March 2021

A nondestructive sampling method was developed for Lycorma delicatula egg masses based on fixed-radius plot (100 m2) in 2020. All trees >1.0 cm DBH (diameter at breast height, 1.37 m in height) on each plot were visually inspected from the ground 4 m from the tree with binoculars. Egg masses found on trees were separated into six within-tree positions (lower trunk, middle trunk, upper trunk, first branch, second branch, above second branch) and recorded by cardinal directions, whereas those laid on shrubs/vines and stones were recorded without such separation. In total, 146 trees were inventoried at 28 plots over seven study sites (four plots per site). Egg masses were found on 19 tree species plus summer grape (Vitis aestivalis) and stone. Of the 421 total egg masses recorded, 31.1% were on Norway maple (Acer platanoides), followed by tree-of-heaven (Ailanthus altissima; 14.7%), black birch (Betula lenta; 12.6%), tuliptree (Liriodendron tulipifera; 11.9%), and American beech (Fagus grandifolia; 10.2%). Egg mass density per tree was positively correlated with tree diameter, and egg mass density per plot was positively correlated with plot basal area. Egg mass density after conversion ranged from 600 to 3,930 eggs masses/ha with no significant difference among study sites. Cardinal direction had no effect; however, significantly more egg masses were found on the first branches and upper trunks than other within-tree positions. Overall, branches were better than trunks in predicting egg mass number for the tree. The role of distance and late season adult aggregation on oviposition substrate selection are discussed.
Treatment of Disseminated Germ Cell Tumors With Cisplatin, Bleomycin, and Either Vinblastine or Etoposide
Authors: Risk Michael
Published: March 2021

This chapter reviews a landmark trial that randomized patients with disseminated testicular cancer to treatment with cisplatin, etoposide, and bleomycin (BEP) versus treatment with cisplatin, vinblastine, and bleomycin (PVB). This study demonstrated BEP to be superior to PVB in terms of adverse effects in this trial, with at least equivalent efficacy if not superiority in the setting of advanced disease. This study established BEP as the standard induction chemotherapy regimen used for the majority of patients with metastatic testicular cancer.
Characteristics of aquatic biospheres on temperate planets around Sun-like stars and M dwarfs
Authors: Lingam Manasvi , Loeb Abraham
Published: March 2021

Aquatic biospheres reliant on oxygenic photosynthesis are expected to play an important role on Earth-like planets endowed with large-scale oceans insofar as carbon fixation (i.e. biosynthesis of organic compounds) is concerned. We investigate the properties of aquatic biospheres comprising Earth-like biota for habitable rocky planets orbiting Sun-like stars and late-type M dwarfs such as TRAPPIST-1. In particular, we estimate how these characteristics evolve with the available flux of photosynthetically active radiation (PAR) and the ambient ocean temperature (TW), the latter of which constitutes a key environmental variable. We show that many salient properties, such as the depth of the photosynthesis zone and the net primary productivity (i.e. the effective rate of carbon fixation), are sensitive to PAR flux and TW and decline substantially when the former is decreased or the latter is increased. We conclude by exploring the implications of our analysis for exoplanets around Sun-like stars and M dwarfs.
A test of the planet–star unipolar inductor for magnetic white dwarfs
Authors: Walters N , Farihi J , Marsh T R , Bagnulo S , Landstreet J D , Hermes J J , Achilleos N , Wallach A , Hart M , Manser C J
Published: March 2021

Despite thousands of spectroscopic detections, only four isolated white dwarfs exhibit Balmer emission lines. The temperature inversion mechanism is a puzzle over 30 years old that has defied conventional explanations. One hypothesis is a unipolar inductor that achieves surface heating via ohmic dissipation of a current loop between a conducting planet and a magnetic white dwarf. To investigate this model, new time-resolved spectroscopy, spectropolarimetry, and photometry of the prototype GD 356 are studied. The emission features vary in strength on the rotational period, but in antiphase with the light curve, consistent with a cool surface spot beneath an optically thin chromosphere. Possible changes in the line profiles are observed at the same photometric phase, potentially suggesting modest evolution of the emission region, while the magnetic field varies by 10 per cent over a full rotation. These comprehensive data reveal neither changes to the photometric period, nor additional signals such as might be expected from an orbiting body. A closer examination of the unipolar inductor model finds points of potential failure: the observed rapid stellar rotation will inhibit current carriers due to the centrifugal force, there may be no supply of magnetospheric ions, and no antiphase flux changes are expected from ohmic surface heating. Together with the highly similar properties of the four cool, emission-line white dwarfs, these facts indicate that the chromospheric emission is intrinsic. A tantalizing possibility is that intrinsic chromospheres may manifest in (magnetic) white dwarfs, and in distinct parts of the Hertzsprung–Russell diagram based on structure and composition.
Hard X-ray selected giant radio galaxies – III. The LOFAR view
Authors: Bruni G , Brienza M , Panessa F , Bassani L , Dallacasa D , Venturi T , Baldi R D , Botteon A , Drabent A , Malizia A , Massaro F , Röttgering H J A , Ubertini P , Ursini F , van Weeren R J
Published: March 2021

Giant radio galaxies (GRGs), with extended structures reaching hundreds of kpc, are among the most spectacular examples of ejection of relativistic plasma from supermassive black holes. In this work, third of a series, we present Low-Frequency Array (LOFAR) images at 144 MHz, collected in the framework of the LOFAR Two-metre Sky Survey Data Release 2 (LoTSS DR2), for nine sources extracted from our sample of hard X-ray-selected GRGs (HXGRGs, i.e. from INTEGRAL/Imager on-Board the INTEGRAL Satellite and Swift/Burst Alert Telescope catalogues at >20 keV). Thanks to the resolution and sensitivity of LoTSS, we could probe the complex morphology of these GRGs, unveiling cases with diffuse (Mpc-scale) remnant emission, presence of faint off-axis wings, or a misaligned inner jet. In particular, for one source (B2 1144+35B), we could clearly detect a ∼300 kpc wide off-axis emission, in addition to an inner jet whose orientation is not aligned with the lobes axis. For another source (J1153.9+5848), a structure consistent with jet precession was revealed, appearing as an X-shaped morphology with relic lobes having an extension larger than the present ones, and with a different axis orientation. From an environment analysis, we found two sources showing an overdensity of cosmological neighbours, and a correspondent association with a galaxy cluster from catalogues. Finally, a comparison with radio-selected GRGs from LoTSS DR1 suggested that, on average, HXGRGs can grow to larger extents. These results highlight the importance of deep low-frequency observations to probe the evolution of radio galaxies, and ultimately estimate the duty cycle of their jets.
The probability distribution of 3D shapes of galaxy clusters from 2D X-ray images
Authors: Shankar Swapnil , Khatri Rishi
Published: March 2021

We present a new method to determine the probability distribution of the 3D shapes of galaxy clusters from the 2D images using stereology. In contrast to the conventional approach of combining different data sets (such as X-rays, Sunyaev–Zeldovich effect, and lensing) to fit a 3D model of a galaxy cluster for each cluster, our method requires only a single data set, such as X-ray observations or Sunyaev–Zeldovich effect observations, consisting of sufficiently large number of clusters. Instead of reconstructing the 3D shape of an individual object, we recover the probability distribution function (PDF) of the 3D shapes of the observed galaxy clusters. The shape PDF is the relevant statistical quantity, which can be compared with the theory and used to test the cosmological models. We apply this method to publicly available Chandra X-ray data of 89 well-resolved galaxy clusters. Assuming ellipsoidal shapes, we find that our sample of galaxy clusters is a mixture of prolate and oblate shapes, with a preference for oblateness with the most probable ratio of principle axes 1.4 : 1.3 : 1. The ellipsoidal assumption is not essential to our approach and our method is directly applicable to non-ellipsoidal shapes. Our method is insensitive to the radial density and temperature profiles of the cluster. Our method is sensitive to the changes in shape of the X-ray emitting gas from inner to outer regions and we find evidence for variation in the 3D shape of the X-ray emitting gas with distance from the centre.
Plecturocebus caquetensis(Primates: Pitheciidae)
Authors: Villota Johana , Ramírez-Chaves Héctor E , Defler Thomas R
Published: March 2021

Plecturocebus caquetensis (Defler, Bueno, and García, 2010) is a Neotropical primate commonly called the Caquetá titi monkey. It is small-sized with long, soft pelage of mixed coloration including grayish and buffy brown to agouti tones. It lacks the blackish or whitish band that is present on the forehead of closely related species. The tail is agouti-colored and slightly banded at its base. Endemic to the Amazonian region of Colombia with a distribution in areas near the eastern slopes of the Eastern and Central Cordillera of the Andes, P. caquetensis is confirmed in 104 localities in the departments of Cauca and Caquetá in Colombia. P. caquetensis is considered “Critically Endangered” (CR) by the International Union for Conservation of Nature and Natural Resources.
A Pilot Randomized Controlled Trial of Text Messaging to Increase Tobacco Treatment Reach in the Emergency Department
Authors: Abroms Lorien C , Wu Keng-Chieh , Krishnan Nandita , Long Michael , Belay Sarah , Sherman Scott , McCarthy Melissa
Published: March 2021

Introduction

Automated text messaging programs have been studied as a treatment tool, but have not been studied as an outreach tool to increase the reach of smoking cessation treatment.

Aims and Methods

Two distinct text messaging programs were developed. One was aimed at connecting smokers to quitline phone counseling via text message (Text4Coach [T4C]) and the other was aimed at connecting smokers to a smoking cessation text messaging program (Text&Quit [T&Q]). Adult daily smokers with Medicaid insurance (N = 80) were recruited from the Emergency Department at an urban hospital and randomized to T4C or T&Q. The primary outcome was program reach.

Results

Outreach text messages were found to have moderately high uptake, with the majority of participants (63.8%) opting into their assigned tobacco treatment program and younger and female participants more likely to opt in (p < .01). Receipt of the treatment portion of the program differed among the programs with 67.5% of T&Q receiving the treatment program and 27.5% of T4C receiving the program (p < .001). Most participants across both groups replied to at least one message (71.3%) and very few unsubscribed from the service over the 3-week trial. The majority of participants reported overall satisfaction with their program (63.8%), found it helpful for quitting smoking (60.0%) and would recommend the program to a friend (62.5%). Overall, 11 (13.8%) participants reported being abstinent from smoking for the past 7 days at follow-up, with no differences between groups.

Conclusions

Outreach text messages were found to have moderately high reach among Medicaid smokers. Larger trials are needed to evaluate the impact of such programs on helping low-income smokers quit.

Implications

Automated text messaging programs have been tested as a treatment tool, but have not been tested as an outreach tool to increase the reach of smoking cessation treatment. This study tests a new way of conducting outreach to smokers in a health system through text messages. It tests the effect of outreach on (1) rates of opting in and (2) successful treatment delivery. Results may inform new models of providing outreach for tobacco treatment in health systems.
Robotic-Assisted Tubular Transoral Parapharyngeal Approach to the Ventral Craniovertebral Junction
Authors: Basma Jaafar , Rangarajan Sanjeet V , Michael L Madison , Magnuson J Scott , Muhlbauer Michael S , Gleysteen John P
Published: March 2021

BACKGROUND

Transoral robotic surgery (TORS) has become a routine technique for treating benign and malignant lesions of the oropharynx with the advantage of reducing morbidity compared to open surgical techniques. However, TORS has not been used routinely for accessing lesions of the spine.

OBJECTIVE

To describe how TORS can be used to access spinal lesions.

METHODS

We describe our technique of accessing the parapharyngeal space using the robotic technique, and then dissecting the prevertebral muscles to expose the ventral craniovertebral junction. Tubular retraction with endoscopic visualization is then employed for surgical resection. We then report a case of a 14-yr-old competitive athlete who presented with an osseous lesion of C1, which underwent resection using this novel TORS approach.

RESULTS

Our patient underwent successful resection of a lateral C1 osteoid osteoma utilizing a combined TORS/endoscopic approach. She tolerated soft diet immediately and was discharged on postoperative day 2. Postoperative imaging revealed complete resection of the lesion, and she returned to competitive athletics within 6 wk.

CONCLUSION

Utilizing this novel, robotic-assisted approach can definitively treat osseous cervical spine lesions while reducing morbidity, allowing for early return to normal diet and minimizing overall length of hospital stay.
Two-Stage Double Petrosal Approach for the Total Resection of Petroclival-Cavernous Meningioma: 2-Dimensional Operative Video
Authors: Aboud Emad , Essayed Walid Ibn , Al-Mefty Ossama
Published: March 2021

The utilization of skull base approaches has markedly facilitated the safe surgical removal of challenging petroclival meningiomas.
1
The anterior petrosal approach has been utilized for tumors limited to the upper clivus, above the meatus, whereas the posterior petrosal approach has been the workhorse for the resection of larger tumors in the posterior fossa extending down the clivus.
2
Giant cases with extension in the middle fossa, cavernous sinus, and ventral to the brain stem would benefit from a wider exposure than each of these approaches provide. This could be achieved by total petrosectomy. However, in patients with serviceable hearing anterior and posterior petrosals can be combined while preserving the hearing apparatus.
2,3
This procedure is lengthy; hence, we tend to stage it in 2 subsequent days. The first stage is focused on the soft tissue and bone work including the mastoidectomy, sigmoid transverse sinus, and jugular bulb skeletonization, as well as anterior petrosectomy. The second stage is dedicated to tumor exposure through tentorial sectioning and microsurgical resection. We report the case of a 40-yr-old woman diagnosed with large left-sided petroclival meningioma with significant extension into the cavernous sinus and Meckel's cave. The patient had neurological deficits including cranial nerves, cerebellar dysfunction, and hydrocephalus, although her hearing was intact. Total tumor resection was achieved through the double petrosal approach in 2002. Extensive anatomic knowledge and thorough preoperative clinical and radiological evaluation, particularly the venous system, are key in the successful planning of this procedure. The patient consented for surgery and publication of their image.

 Figures at 2:40 and 3:47, ©Ossama Al-Mefty, used with permission.
Fight against hesitancy: public health concern towards COVID-19 vaccine
Authors: Punsalan Mairre Louie D
Published: March 2021

A recent correspondence revealed that medical students are hesitant of receiving vaccines. Recent studies revealed that the hesitancy was seen among other age groups. However, this challenge does not impede medical workers as they continue to care for patients infected with the virus. With proper education and guidance, hesitancy and fear will be replaced by trust to fight coronavirus disease 2019.
Toxicological assessment of CeO2 nanoparticles on early development of zebrafish
Authors: Roberta Pecoraro , Elena Maria Scalisi , Carmelo Iaria , Fabiano Capparucci , Maria Teresa Rizza , Sara Ignoto , Antonio Salvaggio , Roberto Fiorenza , Giuliana Impellizzeri , Maria Violetta Brundo
Published: March 2021

Nanomaterials involve an active research and a booming area including different fields (health, environment, electronics, manufacturing, drug delivery). Recently, new concerns are emerging about the risk from increased production and subsequent release into the environment, as they are largely present in consumer products and industrial applications. Our aim was to assess the effects of three different types of cerium oxide nanoparticles (CeO2 NPs) (type 1 defined “as prepared”; type 2 defined “modified”; type 3 defined “commercial”) on zebrafish embryos by Fish Embryo Toxicity test (Z-FET). Immunohistochemical analysis was also performed on treated larvae to evaluate the expression of the following biomarkers: Metallothionein, Heat Shock Protein 70 (HSP70) and 7-Ethoxyresorufin-O-Dietylase (EROD). After 96 h of exposure, there was no lethality, nor were there sub-lethal effects in embryonic development, when compared with the control. No particular positivity was found about Metallothionein and HSP70 expression, while an increased expression of EROD was observed in larvae exposed to the three types of CeO2 NPs compared with the controls. The analyze has confirmed a statistically significant difference (P < 0.001) to EROD biomarker between control group and treated larvae response, finding was higher at 1-mg/l concentration. Further investigations in order to solve conflicting views about potential effects of CeO2 NPs are necessary, also to evaluate its effectiveness in different fields as already reported in literature.
Surgical Management of Occipital Neuralgia
Authors: Robinson Isabel S. , Salibian Ara A. , Alfonso Allyson R. , Lin Lawrence J. , Janis Jeffrey E. , Chiu Ernest S.
Published: March 2021

Background

Occipital neuralgia (ON) is a primary headache disorder characterized by severe, paroxysmal, shooting or stabbing pain in the distribution of the greater occipital, lesser occipital, and/or third occipital nerves. Both medical and surgical options exist for treating headaches related to ON. The purposes of this study are to summarize the current state of surgical ON management through a systematic review of the literature and, in doing so, objectively identify future directions of investigation.

Methods

We performed a systematic review of primary literature on surgical management for ON of at least level IV evidence. Included studies were analyzed for level of evidence, therapeutic intervention, study design, sample size, follow-up duration, outcomes measured, results, and risk of bias.

Results

Twenty-two studies met the inclusion criteria. All 22 studies used patient-reported pain scores as an outcome metric. Other outcome metrics included complication rates (7 studies; 32%), patient satisfaction (7 studies; 32%), quality of life (7 studies; 18%), and analgesic usage (3 studies; 14%). Using the ROBINS-I tool for risk of bias in nonrandomized studies, 7 studies (32%) were found to be at critical risk of bias, whereas the remaining 15 studies (68%) were found to be at serious risk of bias.

Conclusions

Greater occipital nerve decompression seems to be a useful treatment modality for medically refractory ON, but further prospective, randomized data are required.
Sarcopenia and Myosteatosis Predict Adverse Outcomes After Emergency Laparotomy
Authors: Body Samantha , Ligthart Marjolein A. P. , Rahman Saqib , Ward James , May-Miller Peter , Pucher Philip H. , Curtis Nathan J. , West Malcolm A.
Published: March 2021

Objective:

To determine the relationship between BC, specifically low skeletal muscle mass (sarcopenia) and poor muscle quality (myosteatosis) and outcomes in emergency laparotomy patients.

Background:

Emergency laparotomy has one of the highest morbidity and mortality rates of all surgical interventions. BC objectively identifies patients at risk of adverse outcomes in elective cancer cohorts, however, evidence is lacking in emergency surgery.

Methods:

An observational cohort study of patients undergoing emergency laparotomy at ten English hospitals was performed. BC analyses were performed at the third lumbar vertebrae level using preoperative computed tomography images to quantify skeletal muscle index (SMI) and skeletal muscle radiation attenuation (SM-RA). Sex-specific SMI and SM-RA were determined, with the lower tertile splits defining sarcopenia (low SMI) and myosteatosis (low SM-RA). Accuracy of mortality risk prediction, incorporating SMI and SM-RA variables into risk models was assessed with regression modeling.

Results:

Six hundred ten patients were included. Sarcopenia and myosteatosis were both associated with increased risk of morbidity (52.1% vs 45.1%, P = 0.028; 57.5% vs 42.6%, P = 0.014), 30-day (9.5% vs 3.6%, P = 0.010; 14.9% vs 3.4%, P < 0.001), and 1-year mortality (27.4% vs 11.5%, P < 0.001; 29.7% vs 12.5%, P < 0.001). Risk-adjusted 30-day mortality was significantly increased by sarcopenia [OR 2.56 (95% CI 1.12-5.84), P = 0.026] and myosteatosis [OR 4.26 (2.01-9.06), P < 0.001], similarly at 1-year [OR 2.66 (95% CI 1.57-4.52), P < 0.001; OR2.08 (95%CI 1.26-3.41), P = 0.004]. BC data increased discrimination of an existing mortality risk-prediction model (AUC 0.838, 95% CI 0.835–0.84).

Conclusion:

Sarcopenia and myosteatosis are associated with increased adverse outcomes in emergency laparotomy patients.
Hemophagocytic lymphohistiocytosis associated with pembrolizumab therapy: a case report
Authors: Shankar Karthik , Shah Deep U. , Tetlay Maryam , Park Seon J. , Chen Jinyao E. , Bhagavatula Rama
Published: March 2021

Hemophagocytic lymphohistiocytosis, or HLH, is a rare, but life-threatening condition caused by over-activation of the immune system. Immunotherapy is a relatively new method of cancer treatment. We are still learning of the immunotherapy side effect profile. We present a case of Pembrolizumab-induced HLH. We report a case of an elderly man, with metastatic disease of unknown primary, who progressed through 2 lines of chemotherapy. He was started on third-line immunotherapy using Pembrolizumab. He remained persistently pancytopenic and febrile despite treatment for sepsis. Bone marrow biopsy showed results consistent with HLH. He was treated with Dexamethasone, then Etoposide without improvement. He eventually suffered from intracranial hemorrhage due to thrombocytopenia and was transitioned to hospice. He passed away soon after. HLH should be suspected when patients on immunotherapy present with pancytopenia and fever. Although rare, it is a life-threatening condition and early interventions may be able to halt the progression of disease. The diagnosis can have a large impact on patients both in the field of Oncology as well as in the field of Surgery.
Persistent SARS-CoV-2 infection and increasing viral variants in children and young adults with impaired humoral immunity
Authors: Truong Thao T. , Ryutov Alex , Pandey Utsav , Yee Rebecca , Goldberg Lior , Bhojwani Deepa , Aguayo-Hiraldo Paibel , Pinsky Benjamin A. , Pekosz Andrew , Shen Lishuang , Boyd Scott D. , Wirz Oliver F. , Röltgen Katharina , Bootwalla Moiz , Maglinte Dennis T. , Ostrow Dejerianne , Ruble David , Han Jennifer H. , Biegel Jaclyn A. , ScM Maggie Li , Huang ChunHong , Sahoo Mayala K. , Pannaraj Pia S. , O’Gorman Maurice , Judkins Alexander R. , Gai Xiaowu , Bard Jennifer Dien
Published: March 2021

Background

There is increasing concern that persistent infection of SARS-CoV-2 within immunocompromised hosts could serve as a reservoir for mutation accumulation and subsequent emergence of novel strains with the potential to evade immune responses.

Methods

We describe three patients with acute lymphoblastic leukemia who were persistently positive for SARS-CoV-2 by real-time polymerase chain reaction. Viral viability from longitudinally-collected specimens was assessed. Whole-genome sequencing and serological studies were performed to measure viral evolution and evidence of immune escape.

Findings

We found compelling evidence of ongoing replication and infectivity for up to 162 days from initial positive by subgenomic RNA, single-stranded RNA, and viral culture analysis. Our results reveal a broad spectrum of infectivity, host immune responses, and accumulation of mutations, some with the potential for immune escape.

Interpretation

Our results highlight the need to reassess infection control precautions in the management and care of immunocompromised patients. Routine surveillance of mutations and evaluation of their potential impact on viral transmission and immune escape should be considered.

Funding

The work was partially funded by The Saban Research Institute at Children’s Hospital Los Angeles intramural support for COVID-19 Directed Research (X.G. and J.D.B.), the Johns Hopkins Center of Excellence in Influenza Research and Surveillance HHSN272201400007C (A.P.), NIH/NIAID R01AI127877 (S.D.B.), NIH/NIAID R01AI130398 (S.D.B.), NIH 1U54CA260517 (S.D.B.), an endowment to S.D.B. from the Crown Family Foundation, an Early Postdoc.Mobility Fellowship Stipend to O.F.W. from the Swiss National Science Foundation (SNSF), and a Coulter COVID-19 Rapid Response Award to S.D.B. L.G. is a SHARE Research Fellow in Pediatric Hematology-Oncology.
Optimal mobility restriction minimizing COVID-19 and excess suicide deaths in Japan
Authors: Kurita Junko , Sugawara Tamie , Sugishita Yoshiyuki , Ohkusa Yasushi
Published: March 2021

Background

Strict countermeasures for COVID-19 outbreak such as lockdowns and voluntary restrictions against going out might have reduced mortality because of COVID-19 directly, but might have raised suicide rates.

Object

We examined best policies for minimizing overall mortality attributable to COVID-19 directly, and excess mortality by suicide because of COVID-19.

Method

We regressed the estimated excess mortality attributable to suicide deaths against mobility-restrictive measures. Mortality attributable to COVID-19 directly was estimated through association between the effective reproduction number and mobility. We sought the best mobility restriction for minimizing overall deaths.

Results

Significant association was found between mobility and suicide, but the data were very few. Results showed the best mobility level as 65.5, which represents a 34.5% reduction in mobility from the normal level.

Discussion and Conclusion

An overly restrictive policy inducing lower than optimal mobility led to higher total mortality.
Leveraging three-dimensional chromatin architecture for effective reconstruction of enhancer-target gene regulatory network
Authors: Salviato Elisa , Djordjilović Vera , Hariprakash Judith M. , Tagliaferri Ilario , Pal Koustav , Ferrari Francesco
Published: March 2021

A growing amount of evidence in literature suggests that germline sequence variants and somatic mutations in non-coding distal regulatory elements may be crucial for defining disease risk and prognostic stratification of patients, in genetic disorders as well as in cancer. Their functional interpretation is challenging because genome-wide enhancer-target gene (ETG) pairing is an open problem in genomics. The solutions proposed so far do not account for the most updated knowledge on chromatin three-dimensional (3D) architecture, which is organized in a hierarchy of structural domains.

Here we introduce a paradigm shift based on the definition of multi-scale structural chromatin domains, integrated in a statistical framework to define ETG pairs. In this worki) we develop a computational and statistical framework to reconstruct a comprehensive ETG regulatory network leveraging functional genomics data;ii) we demonstrate that the incorporation of chromatin 3D architecture information improves ETG pairing accuracy; andiii) we use multiple experimental datasets to extensively benchmark our method against previous solutions for the genome-wide reconstruction of ETG pairs. This solution will facilitate the annotation and interpretation of sequence variants in distal non-coding regulatory elements. We expect this to be especially helpful in clinically oriented applications of whole genome sequencing in cancer and undiagnosed genetic diseases research.
ISTDECO: In Situ Transcriptomics Decoding by Deconvolution
Authors: Andersson Axel , Diego Ferran , Hamprecht Fred A. , Wählby Carolina
Published: March 2021

In Situ Transcriptomics (IST) is a set of image-based transcriptomics approaches that enables localisation of gene expression directly in tissue samples. IST techniques produce multiplexed image series in which fluorescent spots are either present or absent across imaging rounds and colour channels. A spot’s presence and absence form a type of barcoded pattern that labels a particular type of mRNA. Therefore, the expression of a gene can be determined by localising the fluorescent spots and decode the barcode that they form. Existing IST algorithms usually do this in two separate steps: spot localisation and barcode decoding. Although these algorithms are efficient, they are limited by strictly separating the localisation and decoding steps. This limitation becomes apparent in regions with low signal-to-noise ratio or high spot densities. We argue that an improved gene expression decoding can be obtained by combining these two steps into a single algorithm. This allows for an efficient decoding that is less sensitive to noise and optical crowding.

We present IST Decoding by Deconvolution (ISTDECO), a principled decoding approach combining spectral and spatial deconvolution into a single algorithm. We evaluate ISTDECO on simulated data, as well as on two real IST datasets, and compare with state-of-the-art. ISTDECO achieves state-of-the-art performance despite high spot densities and low signal-to-noise ratios. It is easily implemented and runs efficiently using a GPU.

ISTDECO implementation, datasets and demos are available online at:github.com/axanderssonuu/istdeco
Influence of basal media composition on barrier fidelity within human pluripotent stem cell-derived blood-brain barrier models
Authors: Neal Emma H. , Katdare Ketaki A. , Shi Yajuan , Marinelli Nicholas A. , Hagerla Kameron A. , Lippmann Ethan S.
Published: March 2021

It is increasingly recognized that brain microvascular endothelial cells (BMECs), the principle component of the blood-brain barrier (BBB), are highly sensitive to soluble cues from both the bloodstream and the brain. This concept extendsin vitro, where the extracellular milieu can also influence BBB properties in cultured cells. However, the extent to which baseline culture conditions can affect BBB propertiesin vitroremains unclear, which has implications for model variability and reproducibility, as well as downstream assessments of molecular transport and disease phenotypes. Here, we explore this concept by examining BBB properties within human induced pluripotent stem cell (iPSC)-derived BMEC-like cells cultured under serum-free conditions in different basal media with fully defined compositions. We demonstrate notable differences in both passive and active BBB properties as a function of basal media composition. Further, RNA sequencing and phosphoproteome analyses revealed alterations to various signaling pathways in response to basal media differences. Overall, our results demonstrate that baseline culture conditions can have a profound influence on the performance ofin vitroBBB models, and these effects should be considered when designing experiments that utilize such models for basic research and preclinical assays.