bluuebunny/crossref_metadata_2025 huggingface dataset:
Sulfur Isotope and Trace Element Systematics in Arc Magmas: Seeing through the Degassing via a Melt Inclusion Study of Kyushu Island Volcanoes, Japan
Authors: Kawaguchi Masataka , Koga Kenneth T , Rose-Koga Estelle F , Shimizu Kenji , Ushikubo Takayuki , Yoshiasa Akira
Published: July 2022

Sulfur is a minor element in magmas but one of the major volatile elements released in volcanic systems, from the magma to the fluid phase upon ascent. Not only are sulfur gasses potentially toxic for humans and plants, they are also involved in causing drastic climate changes after major volcanic eruptions. Therefore, studies are carried out by the geoscience community to assess the magmatic sulfur flux by looking at the sulfur content and isotopes in erupted products, with the ultimate aim of improving understanding of the sulfur cycle in subduction zones. Kyushu Island in Japan hosts 25 volcanoes, among which 11 are active and represent a natural hazard for the local population. It is perhaps the most suitable site for the study of the sulfur cycle for its availability of recent volcanic deposits and its many highly monitored volcanoes. We investigated sulfur and sulfur isotope compositions of the magma source of Kyushu Island arc using olivine-hosted melt inclusions in mafic tephras and lavas, from eight volcanoes (nine Holocene samples) going from Northern Kyushu with Oninomi, Yufu, Kuju, and Aso, to Southern Kyushu volcanoes such as Kirishima-Ohachidake, Kirishima-Shinmoedake, Sumiyoshi-ike, and Kaimondake, and one back arc volcano, Fukue-Onidake. We measured major, trace and volatile elements and S isotopes (δ34S) in melt inclusions. Magma composition recorded in the inclusions ranges from basalt to andesite (SiO2 ranging from 40.3 to 60.7 wt%). For each edifice, we identified the least degassed and least differentiated compositions based on volatile and trace element systematics and selected the melt inclusions closest to their primitive melts. Comparing these primitive magmas, Sr/Y underlines a compositional dichotomy between volcanoes from northern (Sr/Y > 20) and southern Kyushu (Sr/Y < 20), separated by a non-volcanic area corresponding to the subduction of the Kyushu-Palau ridge. The δ34S in melt inclusions range from −0.32 ± 0.79‰ to +9.43 ± 0.47‰ (2σ) and trace the source of the magma from the different volcanoes, rather than degassing or crustal fractionation processes. δ34S is not fractionated by the nature of the fluid (aqueous or melt) metasomatizing the mantle wedge, therefore it is not the first-order factor controlling the sulfur isotope variations. Instead, this study illustrates the need for a heavy δ34S component, likely sulfate from seawater, contained in the agent that metasomatized the mantle beneath the arc. If such an observation is confirmed in other subduction zones, sulfur isotopes in melt inclusions may be an effective way to trace seawater input into the mantle beneath
Modeling pandemic to endemic patterns of SARS-CoV-2 transmission using parameters estimated from animal model data
Authors: Mullin Sarah , Wyk Brent Vander , Asher Jennifer L , Compton Susan R , Allore Heather G , Zeiss Caroline J
Published: July 2022

The contours of endemic coronaviral disease in humans and other animals are shaped by the tendency of coronaviruses to generate new variants superimposed upon nonsterilizing immunity. Consequently, patterns of coronaviral reinfection in animals can inform the emerging endemic state of the SARS-CoV-2 pandemic. We generated controlled reinfection data after high and low risk natural exposure or heterologous vaccination to sialodacryoadenitis virus (SDAV) in rats. Using deterministic compartmental models, we utilized in vivo estimates from these experiments to model the combined effects of variable transmission rates, variable duration of immunity, successive waves of variants, and vaccination on patterns of viral transmission. Using rat experiment-derived estimates, an endemic state achieved by natural infection alone occurred after a median of 724 days with approximately 41.3% of the population susceptible to reinfection. After accounting for translationally altered parameters between rat-derived data and human SARS-CoV-2 transmission, and after introducing vaccination, we arrived at a median time to endemic stability of 1437 (IQR = 749.25) days with a median 15.4% of the population remaining susceptible. We extended the models to introduce successive variants with increasing transmissibility and included the effect of varying duration of immunity. As seen with endemic coronaviral infections in other animals, transmission states are altered by introduction of new variants, even with vaccination. However, vaccination combined with natural immunity maintains a lower prevalence of infection than natural infection alone and provides greater resilience against the effects of transmissible variants.
Economic Agents as Imperfect Problem Solvers
Authors: Ilut Cosmin , Valchev Rosen
Published: July 2022

We develop a novel bounded rationality model of imperfect reasoning as the interaction between automatic (System 1) and analytical (System 2) thinking. In doing so, we formalize the empirical consensus of cognitive psychology using a structural, constrained-optimal economic framework of mental information acquisition about the unknown optimal policy function. A key result is that agents reason less (more) when facing usual (unusual) states of the world, producing state- and history-dependent behavior. Our application is an otherwise standard incomplete-markets model with no a priori behavioral biases. The ergodic distribution of actions and beliefs is characterized by endogenous learning traps, where locally stable state dynamics generate familiar regions of the state space within which behavior appears to follow memory-based heuristics. This results in endogenous behavioral biases that have many empirically desirable properties: the marginal propensity to consume is high even for unconstrained agents, hand-to-mouth status is more frequent and persistent, and there is more wealth inequality than in the standard model.
Homotopy Motions of Surfaces in 3-Manifolds
Authors: Koda Yuya , Sakuma Makoto
Published: July 2022

We introduce the concept of a homotopy motion of a subset in a manifold and give a systematic study of homotopy motions of surfaces in closed orientable 3-manifolds. This notion arises from various natural problems in 3-manifold theory such as domination of manifold pairs, homotopical behavior of simple loops on a Heegaard surface and monodromies of virtual branched covering surface bundles associated with a Heegaard splitting.
The natural history of insomnia: high sleep reactivity interacts with greater life stress to predict the onset of acute insomnia
Authors: Walker Jamie L , Vargas Ivan , Drake Christopher L , Ellis Jason G , Muench Alexandria , Perlis Michael L
Published: July 2022

Study Objectives

Prior research suggests that some individuals have a predisposition to experience insomnia following acute stressors (i.e. sleep reactivity). The present study was a proof of concept and specifically aimed to provide additional empirical evidence that the link between stressful life events and the onset of acute insomnia is moderated by sleep reactivity.

Methods

About 1,225 adults with a history of good sleep (Mage = 53.2 years, 68% female, 83% white) were recruited nationwide for an online study on sleep health. Participants completed surveys to assess sleep reactivity (baseline), sleep patterns (daily sleep diary), and stressful life events (weekly survey). All daily and weekly measures were completed for a one-year period. Sleep diary data were used to identify sleep initiation/maintenance difficulties, including whether they met criteria for acute insomnia at any point during the one-year interval.

Results

Participants with high sleep reactivity compared to low sleep reactivity were at 76% increased odds of developing acute insomnia during the one-year interval. In general, greater weekly stressful life events were associated with greater insomnia during the subsequent week. Those participants with high sleep reactivity demonstrated a stronger relationship between weekly stressful life events and insomnia, such that they reported the greatest levels of insomnia following weeks where they experienced a greater number of stressful life events.

Conclusions

These results further support the sleep reactivity model of insomnia, and specifically, provide evidence that sleep reactivity predicts the incidence of acute insomnia in a sample of participants with no history of insomnia.
Religion, Race, and Perceptions of Police Harassment
Authors: Ferguson Jauhara , Scheitle Christopher P , Ecklund Elaine Howard
Published: July 2022

Research examining how race and ethnic locations shape perceptions of the police is well-established. Yet there is little research examining how religion shapes individuals’ experiences with police. This study examines the influence of race and religion on U.S. adults’ reported experiences with police harassment due to their religion. We find that, independent of race and ethnicity, Muslim adults are significantly more likely to report police harassment due to their religion. Race and ethnicity moderate this effect, with Muslim adults identifying as Black or as Middle Eastern-Arab-North African (MENA) significantly more likely than White Muslim adults to report religion-based police harassment. We find that, independent of religion, adults identifying as Black or as MENA are significantly more likely to report religion-based police harassment when compared to White individuals, a finding that is explained by these individuals’ greater reports of race-based police harassment. That is, exposure to police harassment based on race is more likely to make an individual perceive harassment based on their religion as well. These findings highlight the intersectional nature of individuals’ social locations more broadly and the importance of addressing these multiple locations if we are to address the social problem of police harassment and victimization.
Childhood Adversity Among Adults With Chronic Pain
Authors: Craner Julia R. , Lake Eric S. , Barr Aex C. , Kirby Krissa E. , O’Neill Mariceli
Published: July 2022

Objectives:

Adverse childhood experiences (ACEs) have been linked to the development and impact of chronic pain in adulthood. The goal of this study was to investigate the prevalence of ACEs in a treatment-seeking sample of adults with chronic pain and the relationship between number and type(s) of ACEs and pain-related outcomes.

Methods:

Adults (N=1794) presenting for treatment at a multidisciplinary pain management center completed self-report measures of childhood adversity, pain, functioning, emotional distress, and adjustment to pain.

Results:

Participants endorsing ≥4 ACEs had significantly worse pain-related outcomes and lower quality of life compared with individuals reporting fewer ACEs. Having ≥3 ACEs was associated with higher anxiety and depression levels. Experiences of childhood neglect negatively affected mental health–related outcomes independent of the number of ACEs. Significant sex differences were found in the number and type of ACEs reported but not in the relationship between ACEs and outcome variables.

Conclusion:

Findings suggest that the number and the type of self-reported ACE(s) are associated with pain-related variables and psychosocial functioning in adults with chronic pain. The results highlight the importance of assessment of ACEs and trauma-informed care with patients with chronic pain.
Do Patients With Chronic Diabetes Have Worse Motor Outcomes After Cervical ASIA C Traumatic Spinal Cord Injury?
Authors: Moon Tyler J. , Furdock Ryan , Ahn Nicholas
Published: July 2022

Study Design:

This was a level IV retrospective prognostic study.

Objective:

The objective of this study was to determine if patients with chronic diabetes have worse functional outcomes and motor recovery after cervical traumatic spinal cord injury (TSCI).

Summary of Background Data:

Diabetes mellitus has multiple deleterious neurological effects and has been shown to worsen elective cervical spine surgery outcomes. Prior literature has scarcely characterized the impact of chronic diabetes on motor and functional outcomes after TSCI.

Methods:

The National Spinal Cord Injury Statistical Center (NSCISC) database was utilized to retrospectively collect data on cervical American Spinal Injury Association (ASIA) C TSCI between 2011 and 2016. Patients were divided into diabetes and nondiabetes groups. Primary outcomes included wheelchair requirement and ambulatory status 1 year after injury. Secondary outcomes were motor score collected at the time of rehab admission, rehab discharge, and 1-year follow-up. All outcome variables were analyzed using univariate and multivariate regression to assess for differences between diabetes and nondiabetes groups and possible confounders.

Results:

A total of 219 patients met the inclusion criteria for the study: 193 without diabetes and 26 with diabetes (12.0%). After controlling for confounders, patients with diabetes had had significantly increased wheelchair requirement (83.3% vs. 51.8%, relative risk=1.63, 95% confidence interval: 1.20–1.83, P=0.009 multivariate) and decreased ambulatory rates (50% vs. 67.9%, relative risk=0.55, 95% confidence interval: 0.25–0.98, P=0.042 multivariate) at 1 year. They also had no difference in average total motor scores at rehab admission but significantly worse total motor scores at rehab discharge (50.6±23.3 vs. 60.3±21.4, P=0.033 univariate, P=0.002 multivariate).

Conclusions:

Patients with diabetes have increased wheelchair requirement and decreased ambulatory ability at 1 year after the injury as well as diminished recovery in motor scores after motor-incomplete cervical TSCI. These patients may be targets for aggressive diabetic screening and intervention to minimize negative outcomes.
Duchenne muscular dystrophy and dilated cardiomyopathy with deletion of exon 45 and 49
Authors: Zhuang Xin-Yu , Luo Su-Shan , Fan Hui-Hua , Zhang Jin-Jin , Chen Hua , Yan Ping-Ping , Bao Li-Wen
Published: July 2022

A 26-year-old young man presented with paroxysmal chest pain and systemic edema that started 2 years earlier and worsened during the past 2 months. Echocardiogram indicated total heart enlargement as well as severe left and right ventricular systolic dysfunction. MRI revealed atrophy of most muscles in the thigh and calf on both sides. EMG suggested myogenic damage to myoelectrical changes and early recruitment changes. A diagnosis of Duchenne muscular dystrophy (DMD) was established on biopsy and genetic testing showing deletion of exons 45 and 49 of the dystrophin gene. He had no family history of major cardiovascular diseases. The patient disclosed later that muscle weakening started at 7 years of age. Symptoms improved after treatment with a variety of agents to manage heart failure and complications, and was discharged. He survived for 2 years, during which the general condition and heart failure deteriorated progressively. In summary, skeletal muscle weakness is typically the first sign of DMD, but heart involvement is commonly seen later. With the current treatment options, prognosis is poor. Gene therapy might be warranted.
The Effects of Progressive Relaxation Exercises on COVID-19-Related Fear, Anxiety, and Sleep Quality in Emergency Aid Station Employees
Authors: Gündoğan Reva , Kaplan Serin Emine
Published: July 2022

This study aimed to investigate the effects of progressive relaxation exercises on emergency aid station employees' COVID-19-related fear, anxiety, and sleep quality levels. This study was conducted as a randomized, controlled, and experimental design and included 30 emergency aid station employees (emergency medical technicians and paramedics). The descriptive information form, Generalized Anxiety Disorder Test, COVID-19 Fear Scale, and Pittsburgh Sleep Quality Index (PSQI) were used for data collection. There was no significant difference between the groups in terms of their scale scores before the intervention (P > .05). After the intervention, there was a significant difference between the groups only in the sleep duration dimension of the PSQI. In the intervention group, on the other hand, there were significant differences in the anxiety, economic dimension of the Fear scale and the total sleep quality, and subjective sleep quality, sleep latency and daytime dysfunction dimensions after the intervention (P < .05). In this study, in comparison to the control group, the intervention group lowered their anxiety and fear levels and improved their sleep quality at the end of the 5 days. It was determined that anxiety and fear had a 35% cumulative effect on sleep quality (P > .05). According to the results of this study, progressive muscle relaxation exercises had a positive effect in improving the sleep quality and reducing the anxiety and fear levels of the emergency aid station employees.
Bridging the LatinX community care gap
Authors: Gonzalez Andrea Gerard
Published: July 2022

Purpose of review

To summarize current developments aimed at improving diabetes care utilizing novel and culturally sensitive strategies to bridge the care gap in the LatinX community.

Recent findings

There is more than a decade of literature describing disparities in diabetes care and outcomes particularly involving ethnic and racial minorities leading to higher incidence of acute and long-term complications. Social determinants of health including language and cultural barriers in the LatinX community are important determining factors. We found three novel strategies reported in the current literature aimed at closing the diabetes care gap in LatinX patients: community-based efforts: community health workers (CHWs) and peer-led; shared medical and educational models; and adapting telehealth group appointments.

Here we review relevant but limited published articles found in the literature addressing the diabetes care gap in the LatinX community utilizing cost effective, novel and culturally sensitive strategies and reinforce the importance of continued work and publications on this very important field.
Selective progesterone receptor modulators and reproductive health
Authors: Nieman Lynnette K.
Published: July 2022

Purpose of review

This review is intended to provide perspective on the history of selective progesterone receptor modulators (SPRMs) and progesterone antagonists, their current availability, therapeutic promise and safety concerns.

Recent findings

Despite keen interest in synthesis of these compounds, only a handful have had clinical test results allowing for commercialization. Mifepristone is well tolerated and effective for single dose first trimester at-home pregnancy termination and is available in much of the world. Ulipristal acetate, at single doses, is well tolerated and effective for emergency contraception, with less availability. Chronic use of these agents has been associated with abnormal liver enzymes, and rarely, with hepatic failure; causality is not understood.

SPRMs and progesterone antagonists have great therapeutic promise for use in other reproductive disorders, including breast cancer, endometriosis, adenomyosis, estrogen-free contraception and cervical ripening but require additional study. Alternative formulations, whether local (topical breast or intrauterine) or extended-release may reduce the incidence of liver function abnormalities and should be explored.
Factors affecting short-term functional gain following total knee arthroplasty in patients aged from 75 years at a postacute rehabilitation setting
Authors: Kawaguchi Kenichi , Kuwakado So , Ohtsuka Hiroshi , Sakugawa Akemi , Takahashi Masanori , Oda Taiji , Shimamoto Nobuto , Hamai Satoshi , Nakashima Yasuharu
Published: July 2022

The intensive rehabilitation of older patients after total knee arthroplasty (TKA) is vital for short-term improvement in mobility and daily living activities. We aimed to investigate the effectiveness of multidisciplinary rehabilitation and assess the early postoperative predictors that are associated with functional gain in TKA patients aged from 75 years in a postacute care setting. This study included 190 patients following primary TKA who were admitted at the postacute rehabilitation hospital. The main outcome measures were the motor component of functional independence measure (M-FIM), M-FIM effectiveness, numerical rating scale, knee extension strength and range of motion, 10-m walk test, Berg balance scale (BBS), and mini-mental state examination (MMSE). The functional gain between patient age groups of ≥75 (n = 105) and <75 (n = 85) years were compared. Although patients aged ≥75 years showed lower improvement in BBS score compared with <75 years, the M-FIM gains and other physical functions were similar in both age groups. In multivariate analysis, the results for M-FIM at admission (β: −0.703; P = 0.001), BBS (β: 0.342; P = 0.032) and MMSE (β: 0.446; P = 0.021) were independently associated with functional gain in the patients following TKA aged ≥75 years. Multidisciplinary inpatient rehabilitation was beneficial for basic functional gain except for improvement in balance ability in patients after TKA aged ≥75 years. Functional level, balance ability and cognitive status in the early postoperative period can be useful predictors for short-term functional gain in the postacute care phase.
Reliability and validity of the Neck Disability Index among patients undergoing cervical surgery
Authors: Widbom-Kolhanen Sara , Pernaa Katri I. , Saltychev Mikhail
Published: July 2022

To explore the internal consistency and factor structure of the Neck Disability Index (NDI) among patients undergoing surgery on the cervical spine. This was an observational retrospective cohort study among 392 patients undergoing cervical surgery of any kind in a university hospital between 2018 and 2021. The patients responded to repeated surveys preoperatively, and 3, 12 and 24 months postoperatively. The reliability and validity of the NDI were investigated using Cronbach’s alpha and factor analysis. The internal consistency of the NDI was found to be good at 0.86. The exploratory factor analysis demonstrated unidimensionality. The correlations between the main factor ‘disability’ and all the individual items of the NDI were at least moderate. The highest correlations were observed for pain intensity, reading, driving and recreation. The NDI is an internally consistent and unidimensional scale when applied to a population of patients undergoing cervical surgery.
Characteristics of sit-to-stand movement are associated with trunk and lower extremity selective control in children with cerebral palsy: a cross-sectional study
Authors: Gunes Dilara , Karadag-Saygi Evrim , Giray Esra , Kurt Sefa
Published: July 2022

Even though the effect of several factors on sit-to-stand (STS) performance of children with CP has been previously explored, the potential role of lower extremity selective control, trunk control and sitting function on the performance of STS has not been examined. This study aimed to investigate the association of trunk control and lower extremity selective motor control with STS performance in children with CP. We recruited 28 children with CP aged between 4 and 10 years whose Gross Motor Function Classification System levels were I and II and 32 age-matched typically developing (TP) children. Trunk control, sitting function, selective control of the lower extremities and STS were evaluated with Trunk Control Measurement Scale (TCMS), sitting section of Gross Motor Function Measure-88 (GMFM-88), Selective Control Assessment of the Lower Extremity (SCALE) and the STS outcomes of a force platform [weight transfer time, rising index, and center of gravity (COG) sway velocity], respectively. In all evaluations, children with CP demonstrated lower scores than TD children. A moderate correlation was found between total scores of TCMS, GMFM-88 sitting section scores and COG sway velocity during STS and a fair correlation between SCALE total scores and COG sway velocity in the CP group (r = −0.51, r = −0.52, r = −0.39, respectively). A fair correlation was found between SCALE total scores and the weight transfer time during STS in children with CP (r = −0.39). Based on these results, improving trunk and lower extremity selective control may enhance STS performance in children with CP.
Analysis of the Effects of Melanin Depigmentation on Immunohistochemical Staining
Authors: de Pablo Velasco David , Fernández Aceñero María J. , Cortés Toro José A. , González Morales María L. , Latorre García Esthefania , Acedo Jimenez Virginia , García Martínez Ricardo , Ortega Medina Luís
Published: July 2022

Heavily pigmented lesions are difficult to evaluate histologically, as melanin obscures cellular details. Several classic laboratory techniques aim to clear melanin and allow evaluation. Most of them are old and appeared before immunohistochemistry (IHC) use. Many laboratories perform IHC with aminoethylcarbazole instead of diaminobenzidine (DAB) in heavily pigmented lesions, as red-stained is easy to interpret despite pigmentation. Nevertheless, many laboratories lack alternatives to DAB. The aim of this study is to compare 6 different tissue bleaching techniques and evaluate which is the best for immunohistochemical staining with DAB. In the present study we have selected a case with gross pigmentation because of the high grade of melanin deposition. We have performed 6 different bleaching techniques and subsequently performed 2 different IHC stains, frequently used in melanoma: SOX10 (nuclear) and Melan-A (cytoplasmic). Five different pathologists, 2 of them with expertise in dermatopathology, have blindly reviewed and scored the staining quality. Our results indicate a high grade of interobserver concordance in the evaluation of IHC results between pathologists. All the bleaching techniques that included a sulfuric acid led to tissue detachment from the slide. The best method for SOX10 was that based in potassium permanganate, with a high quality of staining (4 over 5), while the best method for Melan-A was the 1 based in peroxide hydrogen (4 over 5). We consider this study can be quite useful for those laboratories lacking aminoethylcarbazole for IHC techniques, allowing the use of DAB for IHC of heavily pigmented lesions.
DICER1-associated Tumors in the Female Genital Tract: Molecular Basis, Clinicopathologic Features, and Differential Diagnosis
Authors: Han Lucy M. , Weiel Julianna J. , Longacre Teri A. , Folkins Ann K.
Published: July 2022

DICER1 syndrome is a tumor predisposition syndrome in which patients are at an increased risk of developing a wide variety of benign and malignant neoplasms with a hallmark constellation of pediatric pleuropulmonary blastoma, cystic nephroma, and thyroid lesions. DICER1 encodes an RNA endoribonuclease that is crucial to the processing of microRNA and may play a role in the maturation of Müllerian tissue. Within the gynecologic tract, germline mutations in DICER1 are associated with an array of rare tumors, including Sertoli-Leydig cell tumor, embryonal rhabdomyosarcoma of the cervix, gynandroblastoma, and juvenile granulosa cell tumor, which typically present in childhood, adolescence, or early adulthood. In addition, somatic DICER1 mutations have been described in rare gynecologic tumors such as adenosarcoma, Sertoli cell tumor, ovarian fibrosarcoma, cervical primitive neuroectodermal tumor, carcinosarcoma, and germ cell tumors. In light of the significant association with multiple neoplasms, genetic counseling should be considered for patients who present with a personal or family history of these rare DICER1-associated gynecologic tumors. This review highlights the most current understanding of DICER1 genetic alterations and describes the clinical, histopathologic, and immunohistochemical features and differential diagnoses for gynecologic tumors associated with DICER1 mutation.
Primary Hepatic Angiosarcoma Having FDG Uptake at the Similar Level of the Normal Liver Parenchyma
Authors: Wang Peipei , Li Fang
Published: July 2022

Primary hepatic angiosarcoma is a rare but aggressive malignancy. A 60-year-old woman presented with multiple liver lesions with progressive enhancement detected with multiphasic CT. FDG PET did not show any FDG-avid lesions, and the uptake of hepatic lesions was similar to that of the normal liver parenchyma. Subsequently, pathological examination revealed hepatic angiosarcoma.
Myoclonus as a Manifestation of Reflex Seizures
Authors: Szabo Charles Akos , Kasteleijn Dorothee
Published: July 2022

Myoclonus is a motor symptom commonly associated with reflex seizures in people with idiopathic generalized epilepsies. The most frequently observed triggers of myoclonus are related to visual stimuli, including flashing lights or patterns; nonetheless, myoclonus can also be activated by movement, speech or reading, calculations, and praxis. Reflex myoclonic seizures may be the hallmark of a reflex epilepsy, but it may lead to the diagnosis of generalized epilepsy syndromes. In the setting of idiopathic generalized epilepsies, reflex myoclonus can persist despite optimal medical therapies and may be a marker for active, even medically intractable, epilepsy. In this article, the clinical significance, diagnosis, and treatment of myoclonus, associated with visual stimulation, movement, and praxis, will be reviewed.
ActinoBase: tools and protocols for researchers working on Streptomyces and other filamentous actinobacteria
Authors: Feeney Morgan Anne , Newitt Jake Terry , Addington Emily , Algora-Gallardo Lis , Allan Craig , Balis Lucas , Birke Anna S. , Castaño-Espriu Laia , Charkoudian Louise K. , Devine Rebecca , Gayrard Damien , Hamilton Jacob , Hennrich Oliver , Hoskisson Paul A. , Keith-Baker Molly , Klein Joshua G. , Kruasuwan Worarat , Mark David R. , Mast Yvonne , McHugh Rebecca E. , McLean Thomas C. , Mohit Elmira , Munnoch John T. , Murray Jordan , Noble Katie , Otani Hiroshi , Parra Jonathan , Pereira Camila F. , Perry Louisa , Pintor-Escobar Linamaria , Pritchard Leighton , Prudence Samuel M. M. , Russell Alicia H. , Schniete Jana K. , Seipke Ryan F. , Sélem-Mojica Nelly , Undabarrena Agustina , Vind Kristiina , van Wezel Gilles P. , Wilkinson Barrie , Worsley Sarah F. , Duncan Katherine R. , Fernández-Martínez Lorena T. , Hutchings Matthew I.
Published: July 2022

Actinobacteria is an ancient phylum of Gram-positive bacteria with a characteristic high GC content to their DNA. The ActinoBase Wiki is focused on the filamentous actinobacteria, such as

Streptomyces

species, and the techniques and growth conditions used to study them. These organisms are studied because of their complex developmental life cycles and diverse specialised metabolism which produces many of the antibiotics currently used in the clinic. ActinoBase is a community effort that provides valuable and freely accessible resources, including protocols and practical information about filamentous actinobacteria. It is aimed at enabling knowledge exchange between members of the international research community working with these fascinating bacteria. ActinoBase is an anchor platform that underpins worldwide efforts to understand the ecology, biology and metabolic potential of these organisms. There are two key differences that set ActinoBase apart from other Wiki-based platforms: [] ActinoBase is specifically aimed at researchers working on filamentous actinobacteria and is tailored to help users overcome challenges working with these bacteria and [] it provides a freely accessible resource with global networking opportunities for researchers with a broad range of experience in this field.
Machine Learning Identifies Signatures of Macrophage Reactivity and Tolerance that Predict Disease Outcomes
Authors: Ghosh Pradipta , Sinha Saptarshi , Katkar Gajanan D. , Vo Daniella , Taheri Sahar , Dang Dharanidhar , Das Soumita , Sahoo Debashis
Published: July 2022

Single-cell transcriptomic studies have greatly improved organ-specific insights into macrophage polarization states are essential for the initiation and resolution of inflammation in all tissues; however, such insights are yet to translate into therapies that can predictably alter macrophage fate. Using machine learning algorithms on human macrophages, here we reveal the continuum of polarization states that is shared across diverse contexts. A path, comprised of 338 genes accurately identified both physiologic and pathologic spectra of “reactivity” and “tolerance”, and remained relevant across tissues, organs, species and immune cells (> 12,500 diverse datasets). This 338-gene signature identified macrophage polarization states at single-cell resolution, in physiology and across diverse human diseases, and in murine pre-clinical disease models. The signature consistently outperformed conventional signatures in the degree of transcriptome-proteome overlap, and in detecting disease states; it also prognosticated outcomes across diverse acute and chronic diseases, e.g., sepsis, liver fibrosis, aging and cancers. Crowd-sourced genetic and pharmacologic studies confirmed that model-rationalized interventions trigger predictable macrophage fates. These findings provide a formal and universally relevant definition of macrophage states and a predictive framework (http://hegemon.ucsd.edu/SMaRT) for the scientific community to develop macrophage-targeted precision diagnostics and therapeutics.

One Sentence Summary

Signatures ofmacrophagereactivity andtolerance (SMaRT) predict disease outcomes
Honey Bees Find the Shortest Path: A Collective Flow-Mediated Approach
Authors: Nguyen Dieu My T , Fard Golnar Gharooni , Iuzzolino Michael , Peleg Orit
Published: July 2022

Honey bees (Apis mellifera L.) are social insects that makes frequent use of volatile pheromone signals to collectively navigate unpredictable and unknown environments. Ants have been shown to effectively use pheromone trails to find the shortest path between two points, the nest and the food source. The ant pheromone trails are accomplished by depositing of pheromones which are then diffused passively, creating isotropic (i.e., non-directional and axi-symmetric) signals. In this study, we report the first instance of the honey bees’ ability to solve the shortest path problem to localize the queen and aggregate around her by using a collective flow-mediated scenting strategy. In this strategy, individual bees not only emit pheromones, but also fan their wings to actively direct the flow of the signals, providing colony members with directional messages to the queen’s location. We use computer vision and deep learning approaches to perform automatic and accurate image analysis. As a result, we quantify the number of bees in the short and long paths, and show that the short path is frequented by significantly more bees over time. We also reconstruct attractive surfaces using the positions and directions of scenting bees, and show that this surface is more “attractive” along the short path and around the queen as scenting bees send out directional messages and the swarm makes their way to the queen. Overall, we show that the honey bees can effectively use the collective scenting behavior to overcome local and volatile pheromone communication and find the shortest path to the queen.
Deciphering the involvement of the Hippo pathway co-regulators, YAP/TAZ in invadopodia formation and matrix degradation
Authors: Venghateri Jubina Balan , Dassa Bareket , Morgenstern David , Shreberk-Shaked Michal , Oren Moshe , Geiger Benjamin
Published: July 2022

Invadopodia are adhesive, actin-rich protrusions, formed by metastatic cancer cells that degrade the extracellular matrix and facilitate invasion. They support the metastatic cascade by a spatially and temporally coordinated process whereby invading cells bind to the matrix, degrade it by specific metalloproteinases, and mechanically penetrate diverse tissue barriers by forming actin-rich extensions. However, despite the apparent involvement of invadopodia in the metastatic process, the molecular mechanisms that regulate invadopodia formation and function are still largely unclear. In this study, we have explored the involvement of the key Hippo pathway co-regulators, namely YAP, and TAZ, in invadopodia formation and matrix degradation. Towards that goal, we tested the effect of depletion of YAP, TAZ, or both on invadopodia formation and activity in multiple human cancer cell lines. We report that knockdown of YAP and TAZ or their inhibition by verteporfin induce a significant elevation in matrix degradation and invadopodia formation in several cancer cell lines. Conversely, overexpression of these proteins strongly suppresses invadopodia formation and matrix degradation. Proteomic and transcriptomic profiling of MDA-MB-231 cells, following co-knockdown of YAP and TAZ, revealed a significant change in the levels of key invadopodia-associated proteins, including the crucial proteins Tks5 and MT1-MMP (MMP14). Collectively, our findings show that YAP and TAZ act as negative regulators of invadopodia formation in diverse cancer lines, most likely by reducing the levels of essential invadopodia components. Dissecting the molecular mechanisms of invadopodia formation in cancer invasion may eventually reveal novel targets for therapeutic applications against invasive cancer.
Variola virus is as old as the earliest historical lines of evidence suggest
Authors: Forni Diego , Molteni Cristian , Cagliani Rachele , Clerici Mario , Sironi Manuela
Published: July 2022

Archaeovirology efforts provided a rich portrait of the evolutionary history of variola virus (VARV), the causative agent of smallpox. These studies revealed frequent viral lineage extinction and a relatively recent origin of VARV as a human pathogen (∼ 1,700 years ago, ya). This contrasts with historical records suggesting the presence of smallpox as early as 3,500 ya. By performing an analysis of ancestry components in modern, historic, and ancient VARV genomes, we unveil the progressive drifting of VARV lineages from a common ancestral population and we show that a small proportion of Viking-Age ancestry persisted until the 18th century. After the split of the P-I and P-II lineages, which occurred before the onset of smallpox vaccination, the former (but not the latter) experienced a severe bottleneck. We suggest this was due to the distinct epidemiology of the two lineages, which display remarkably different disease severity. As for the emergence of VARV, we corrected time estimates by accounting for the time-dependent rate phenomenon. Using this approach, we estimate that VARV emerged earlier than 3,800 ya, thus supporting its presence in ancient societies, including Egypt, as pockmarked mummies suggest.

Importance

Now eradicated, smallpox was one of the most devastating human diseases, causing the death of at least 300 million people in the 20th century. Humans were the only known host of variola virus, but the time-frame of its emergence in our species has been a matter of debate. Specifically, molecular dating suggested a relatively recent origin, whereas historical sources indicated the presence of VARV in ancient societies. By applying population genetic methods, we analyzed the ancestry components in modern and historic VARV genomes, and we found a progressive drifting of VARV lineages from a common ancestral population. By accounting for the common observation that rates of viral evolution scale negatively with the time-frame of measurement, we estimated that VARV emerged earlier than 3800 years ago. Thus, out data settle a controversy and provide novel insight into the origin and evolution of one of the most historically relevant human pathogens.
MRSL: A phenome-wide causal discovery algorithm based on GWAS summary data
Authors: Hou Lei , Geng Zhi , Shi Xu , Wang Chuan , Li Hongkai , Xue Fuzhong
Published: July 2022

Causal discovery is a powerful tool to disclose underlying structures by analyzing purely observational data. Genetic variants can provide useful complementary information for structure learning. Here, we propose a novel algorithm MRSL (Mendelian Randomization (MR)-based Structure Learning algorithm), which combines the graph theory with univariable and multivariable MR to learn the true structure using only GWAS summary statistics. Specifically, MRSL also utilizes topological sorting to improve the precision of structure learning and provides three adjusting categories for multivariable MR. Results of simulation reveal that MRSL has up to two-fold higher F1 score than other eight competitive methods. Additionally, the computing time of MRSL is 100 times faster than other methods. Furthermore, we apply MRSL to 26 biomarkers and 44 ICD10-defined diseases from UK Biobank. The results cover most of expected causal links which have biological interpretations and several new links supported by clinical case reports or previous observational literatures.
CASP4/11 contributes to pulmonary inflammation and disease exacerbation in COVID-19
Authors: Rodrigues Tamara S. , Caetano Camila C.S. , de Sá Keyla S.G. , Almeida Leticia , Becerra Amanda , Gonçalves Augusto V. , de Sousa Lopes Leticia , Oliveira Samuel , Mascarenhas Danielle P.A. , Batah Sabrina S. , Silva Bruna M. , Gomes Giovanni F. , Castro Ricardo , Martins Ronaldo B. , Avila Jonathan , Frantz Fabiani G. , Cunha Thiago M. , Arruda Eurico , Cunha Fernando Q , Nakaya Helder , Cunha Larissa D. , Fabro Alexandre T , Louzada-Junior Paulo , de Oliveira Renê D.R. , Zamboni Dario S.
Published: July 2022

Infection with SARS-CoV-2 induces COVID-19, an inflammatory disease that is usually self-limited, but depending on patient conditions may culminate with critical illness and patient death. The virus triggers activation of intracellular sensors, such as the NLRP3 inflammasome, which promotes inflammation and aggravates the disease. Thus, identification of host components associated with NLRP3 inflammasome is key for understanding the physiopathology of the disease. Here, we reported that SARS-CoV-2 induces upregulation and activation of human Caspase-4/CASP4 (mouse Caspase-11/CASP11) and this process contributes to inflammasome activation in response to SARS-CoV-2. CASP4 was expressed in lung autopsy of lethal cases of COVID-19 and CASP4 expression correlates with expression of inflammasome components and inflammatory mediators such asCASP1,IL1B,IL18andIL6. In vivo infections performed in transgenic hACE2 humanized mouse, deficient or sufficient forCasp11, indicate that hACE2Casp11−/−mice were protected from disease development, with reduced body weight loss, reduced temperature variation, increased pulmonary parenchymal area, reduced clinical score of the disease and reduced mortality. Collectively, our data establishes that CASP4/11 contributes to disease pathology and contributes for future immunomodulatory therapeutic interventions to COVID-19.
Sofosbuvir and its tri-phosphate metabolite inhibit the RNA-dependent RNA polymerase activity of non-Structural protein 5 from the Kyasanur forest disease virus
Authors: Malik Mansi , Vijayan Parvathy , Jagannath Deepak K , Mishra Rakesh K , Lakshminarasimhan Anirudha
Published: July 2022

Kyasanur forest disease is a neglected zoonotic disease caused by a single-stranded RNA-based flavivirus, the incidence of which was first recorded in 1957 in the Southern part of India. Kyasanur forest disease virus is transmitted to monkeys and humans through the infected tick bite ofHaemophysalis spinigera. Kyasanur forest disease is a febrile illness, which in severe cases, results in neurological complications leading to mortality. The current treatment regimens are symptomatic and supportive, and no targeted therapies are available for this disease. In this study, we evaluated the ability of FDA-approved drugs sofosbuvir (and its active metabolite) and Dasabuvir to inhibit the RNA-dependent RNA polymerase activity of NS5 protein from the Kyasanur forest disease virus. NS5 protein containing the N-terminal methyl transferase domain and C-terminal RNA-dependent RNA polymerase domain was expressed inEscherichia coli, and RNA-dependent RNA polymerase activity was demonstrated with the purified protein. The RNA-dependent RNA polymerase assay conditions were optimized, followed by the determination of apparent Km,ATPto validate the enzyme preparation. Half maximal-inhibitory concentrations against RNA-dependent RNA polymerase activity were determined for Sofosbuvir and its active metabolite. Dasabuvir did not show detectable inhibition with the tested conditions. This is the first demonstration of the inhibition of RNA-dependent RNA polymerase activity of NS5 protein from the Kyasanur forest disease virus with small molecule inhibitors. These initial findings can potentially facilitate the discovery and development of targeted therapies for treating Kyasanur forest disease.
Denoising sparse microbial signals from single-cell sequencing of mammalian host tissues
Authors: Ghaddar Bassel , Blaser Martin J. , De Subhajyoti
Published: July 2022

We developed SAHMI, a computational resource to identify truly present microbial nucleic acids and filter contaminants and spurious false-positive taxonomic assignments from standard transcriptomic sequencing of mammalian tissues. In benchmark studies, SAHMI correctly identifies known microbial infections present in diverse tissues. The application of SAHMI to single-cell and spatial genomic data enables co-detection of somatic cells and microorganisms and joint analysis of host-microbiome ecosystems.
Tradeoff between speed and reproductive number in pathogen evolution
Authors: Eilersen Andreas , Nielsen Bjarke Frost , Sneppen Kim
Published: July 2022

The rapid succession of new variants of SARS-CoV-2 emphasizes the need to understand the factors driving pathogen evolution. Here, we investigate a possible tradeoff between the rate of progression of a disease and its reproductive number. Using an SEIR framework, we show that in the exponential growth phase of an epidemic, there is an optimal disease duration that balances the advantage of a fast disease progression with that of causing many secondary infections. This result offers one possible explanation for the ever shorter generation times of novel variants of SARS-CoV-2, as it progressed from the original strain to the Alpha, Delta, and, from late 2021 onwards, to several Omicron variant subtypes. In the endemic state, the optimum disappears and longer disease duration becomes advantageous for the pathogen. However, selection pressures depend on context: mitigation strategies such as quarantine of infected individuals may slow down the evolution towards longer-lasting, more infectious variants. This work then suggests that, in the future, the trend towards shorter generation times may reverse, and SARS-CoV-2 may instead evolve towards longer-lasting variants.
Genome-wide association study of ACE inhibitor-induced cough implicates neuropeptides and shows genetic overlap with chronic dry cough
Authors: Coley Kayesha , Shepherd David J. , Packer Richard , John Catherine , Free Robert C. , Hollox Edward J. , Wain Louise V. , Tobin Martin D. , Batini Chiara
Published: July 2022

ACE inhibitors (ACEIs) are commonly prescribed for hypertension, a global risk factor for cardiovascular disease. Their primary side effect is a dry cough which affects 5-35% of users. As clinical guidelines recommend switching those experiencing cough to an angiotensin-II receptor blocker, we have used this switch as a proxy for ACEI-induced cough. Through a two-stage multi-ancestry genome-wide association study, including up to 7,030 cases and 39,921 controls, we identify five independent genome-wide significant associations implicating six protein-coding genes, includingINHBC, KCNIP4, NTSR1andPREPwhich encode proteins involved in the nervous system. We also observe genetic overlap between ACEI-induced cough and chronic dry cough through genetic correlation and phenome-wide association studies. In line with existing hypotheses, our findings suggest a neurological basis for the pathology of ACEI-induced cough, particularly the role of proinflammatory mediators in sensory airway sensitivity and cough reflex modulation, and shared biological mechanisms with chronic dry cough.