bluuebunny/crossref_metadata_2025 huggingface dataset:
PrEP Indications and PrEP Knowledge, Access, and Interest Among Individuals With HCV
Authors: Hill Kristi C , Kattakuzhy Sarah M , Silk Rachel , Eyasu Rahwa , Ogbumbadiugha Onyinyechi , Ebah Emade , Cover Amelia A , Davis Ashley , Gayle Britt , Sternberg David , Bijole Phyllis , Sun Junfeng , Masur Henry , Kottilil Shyam , Solomon Daniel , Rosenthal Elana S
Published: September 2022

Background

Individuals with hepatitis C (HCV) represent a population that may benefit from pre-exposure prophylaxis (PrEP), given the overlapping risk factors and transmission networks of HCV and HIV. This analysis assesses the prevalence of PrEP indications among individuals with HCV monoinfection and PrEP awareness, interest, and access in this population.

Methods

GRAVITY was an observational study for the collection of epidemiologic data from individuals with HCV and/or HIV in Washington DC and Baltimore, with the present analysis limited to HCV-monoinfected patients. The prevalence of PrEP indications was determined using epidemiologic survey responses. Bivariate and multivariable analyses assessed for associations between PrEP indications and PrEP awareness, access, and interest.

Results

Among 314 HCV-monoinfected participants, 109 (35%) had an indication for PrEP. Forty-eight (44%) had a drug use indication alone, 40 (37%) had a sexual indication alone, and 21 (19%) had both drug use and sexual indications. Eighty-five (27%) participants had heard of PrEP, 32 (10%) had been offered PrEP by a provider, 114 (38%) were interested or maybe interested in PrEP, and 6 (2%) were currently taking PrEP. On bivariate analysis, PrEP awareness was significantly associated with study site (P < .0001), race (P = .0003), age (P < .0001), and sexual PrEP indication (P = .04). However, only study site remained significant (P = .0002) on regression analysis.

Conclusions

Though indications for PrEP were prevalent among individuals with HCV in this cohort, most patients were unaware of PrEP, had never been offered PrEP, and were not using PrEP. These data support the need for improved PrEP implementation among people with HCV.
Introduction to Effective Field Theories
Authors: Manohar Aneesh V.
Published: September 2022

Introductory lectures on effective field theory (EFT) methods as used in high-energy physics to compute experimentally observable quantities. Topics covered in this chapter, which is based on these lectures, include power counting, loop corrections, field redefinitions and their relation to the equations of motion, decoupling of heavy particles, naive dimensional analysis, and the standard model effective field theory (SMEFT). It also discusses naturalness and the hiearchy problem in an appendix. There are many exercises with detailed solutions (written up by the students) included to aid understanding of the topic.
The economic and fiscal effects on the United States from reduced numbers of refugees and asylum seekers
Authors: Clemens Michael A
Published: September 2022

International migrants who seek protection also participate in the economy. Thus the policy of the United States to drastically reduce refugee and asylum-seeker arrivals from 2017 to 2020 might have substantial and ongoing economic consequences. This paper places conservative bounds on those effects by critically reviewing the research literature. It goes beyond prior estimates by including ripple effects beyond the wages earned or taxes paid directly by migrants. The sharp reduction in US refugee admissions starting in 2017 costs the overall US economy today over $9.1 billion per year ($30,962 per missing refugee per year, on average) and costs public coffers at all levels of government over $2.0 billion per year ($6,844 per missing refugee per year, on average) net of public expenses. Large reductions in the presence of asylum seekers during the same period likewise carry ongoing costs in the billions of dollars per year. These estimates imply that barriers to migrants seeking protection, beyond humanitarian policy concerns, carry substantial economic costs.
Carm1 and the Epigenetic Control of Stem Cell Function
Authors: Saber John , Rudnicki Michael A
Published: September 2022

Coactivator-associated arginine methyltransferase 1 (CARM1) is a methyltransferase whose function has been highly studied in the context of nuclear receptor signaling. However, CARM1 is known to epigenetically regulate expression of several myogenic genes involved in differentiation such as Myog and MEF2C. CARM1 also acts to regulate myogenesis through its influence on various cellular processes from embryonic to adult myogenesis. First, CARM1 has a crucial role in establishing polarity-regulated gene expression during an asymmetric satellite cell division by methylating PAX7, leading to the expression of Myf5. Second, satellite cells express the CARM1-FL and CARM1-ΔE15 isoforms. The former has been shown to promote pre-mRNA splicing through its interaction with CA150 and U1C, leading to their methylation and increased activity, while the latter displays a reduction in both metrics, thus, modulating alternative pre-mRNA splice forms in muscle cells. Third, CARM1 is a regulator of autophagy through its positive reinforcement of AMPK activity and gene expression. Autophagy already has known implications in ageing and disease, and CARM1 could follow suite. Thus, CARM1 is a central regulator of several important processes impacting muscle stem cell function and myogenesis.
Thirty-day Treatment Continuation After Audio-only Buprenorphine Telehealth Initiation
Authors: Wunsch Caroline , Wightman Rachel , Pratty Claire , Jacka Brendan , Hallowell Benjamin D. , Clark Seth , Davis Corey S. , Samuels Elizabeth A.
Published: September 2022

Objectives

Before the coronavirus disease 2019 pandemic, federal law required in-person evaluation before buprenorphine initiation. Regulatory changes during the pandemic allow for buprenorphine initiation by audio-only or audiovisual telehealth. Little is known about treatment engagement after buprenorphine initiation conducted via audio-only telehealth.

Methods

A retrospective cohort study of 94 individuals who received initial treatment through an audio-only encounter between April 2020 and February 2021 was performed. Participant demographics, substance use history, withdrawal symptoms, 30-day treatment engagement, and adverse outcomes were determined by an electronic chart and REDcap database review. Subsequent buprenorphine prescriptions filled within 30 days of the initial encounter were tracked through the Rhode Island Prescription Drug Monitoring Program.

Results

Buprenorphine was prescribed for 94 individuals. Most (92 of 94 [97.9%]) filled their prescription within 30 days. Most had previously taken buprenorphine, including prescribed (42 of 92 [45.7%]) and nonprescribed (58 of 92 [63.0%]). Two thirds were in opioid withdrawal at the time of the call (61 of 92 [66.3%]) with a mean Subjective Opioid Withdrawal Scale of 26.8 (range, 4–57). Four individuals experienced precipitated withdrawal (4 of 94 [4.3%]), and 2 reported persistent withdrawal at their follow-up visit (2 of 94 [2.1%]). More than 70% filled a subsequent prescription for buprenorphine within 30 days of the end of their hotline prescription (65 of 92 [70.7%]), on average of 5.88 days (range, 0–28) after completion of their telehealth prescription.

Conclusions

Expanding telehealth-delivered buprenorphine care has the potential to address treatment gaps and facilitate delivery of on-demand services during peak motivation. This evaluation of audio-only buprenorphine initiation found high rates of unobserved buprenorphine initiation and treatment continuation with low rates of complications.
Health and Vaccination Status of Unaccompanied Minors After Arrival in a European Border Country: A Cross-sectional Study (2017–2020)
Authors: Carreras-Abad Clara , Oliveira-Souto Inés , Pou-Ciruelo Diana , Pujol-Morro Joan Miquel , Soler-Palacín Pere , Soriano-Arandes Antoni , Sulleiro Elena , Treviño-Maruri Begoña , Broto-Cortés Claudia , Esperalba Juliana , García-Salgado Guadalupe , Zarzuela Francesc , Serre-Delcor Núria , Espiau María
Published: September 2022

Background:

Unaccompanied and separated children (UASC) are a high-risk group for infectious diseases and information on their vaccination status is scarce. Different approaches are used to screen newly arrived minors in Europe. The aim of this study was to describe the health status and serological protection against different vaccine-preventable diseases among UASC to inform public health decision-making.

Methods:

Retrospective study of all UASC seen at an international health reference center in Barcelona (Spain) between January 2017 and February 2020. Screening results were analyzed using binary logistic regression with adjustment for symptoms, geographic origin, and time since arrival.

Results:

We studied 289 UASC (88.9% males; median age, 17 years). At least one infection was diagnosed in 136 minors (47.1%). There was a high prevalence of intestinal parasites (22.8%), latent tuberculosis infection (22.5%), and hepatitis B (5.2%), even in asymptomatic individuals, and especially among UASC from sub-Saharan Africa (odds ratio, 2.5; 95% confidence interval, 1.5–4.0, P < 0.001). We did not observe a significant association between clinical symptoms and the presence of infection or differences in the prevalence of different infections according to number of months since arrival. Protection against hepatitis B virus (36%), measles (80%), and varicella (83%) was suboptimal.

Conclusions:

Our results highlight the importance of screening and vaccination programs for UASC arriving in Europe, especially border countries. Protocols should be adjusted according to geographic origin. Absence of symptoms does not necessarily rule out infection, highlighting the importance of screening in asymptomatic minors. These programs are a public health priority and should not be neglected during the current COVID-19 pandemic.
Mycobacterium abscessus Pneumonia in an Immunonormal Infant
Authors: Sands Ashley , Klepper Emily , Bolton Michael
Published: September 2022

A 2-month-old male with failure to thrive and respiratory symptoms was found to have bilateral pneumonia secondary to Mycobacterium abscessus. M. abscessus pulmonary infections have mainly been noted in immunocompromised children; prior reports presented similarly, though our patient is unique given the young age of presentation and lack of diagnosed immunodeficiency or underlying disease.
Fatigue in Heart Failure
Authors: Hoch Christine R. , Klinedinst N. Jennifer , Larimer Karen , Renn Cynthia , Fiskum Gary , Gottlieb Stephen S.
Published: September 2022

Background

Fatigue in heart failure (HF) is a burdensome symptom with profoundly negative effects on quality of life and an association with worsening prognosis and mortality. Despite its deleterious outcomes, HF-related fatigue remains poorly understood with limited treatment modalities.

Objective

The objective of this study was to identify correlates of HF-related fatigue.

Methods

A scoping review was completed using the Arksey and O'Malley framework. The theory of unpleasant symptoms was used as a basis for organizing key findings into concepts related to HF-related fatigue. Published, primary studies in English that explored correlates or predictors of fatigue in adult patients with HF were included.

Results

The search identified 655 articles, of which 38 were retained. An additional 4 articles were included for final review (N = 42). Nineteen concepts were identified as having a relationship with HF-related fatigue: age, sex, disease severity, inflammation, anemia, volume status, dyspnea, pain, body weight, depression, anxiety, perception of symptoms/health, sleep disturbances, poor social support, poor self-care, polypharmacy, reduced quality of life, risk for hospitalization, and mortality. Concepts were grouped into 4 categories: physiologic, psychologic, situational, and outcome.

Conclusions

Heart failure–related fatigue is a complex symptom that has physiologic, psychologic, and situational antecedents that influence the symptom and patient outcomes, all of which should be addressed when developing treatment modalities. Cultural and societal norms, racial disparities, and the co-occurrence of multiple symptoms should also be considered. Inconsistent or weak relationships with multiple physiologic correlates suggest the presence of unrecognized influencing factors.
The Impact of Resilience, Health Literacy, and Social Support on Medication Adherence and Self-care Among Adults With Heart Failure
Authors: Meraz Rebecca , McGee Jocelyn , Caldwell Elizabeth Perry , Ke Weiming , Osteen Kathryn
Published: September 2022

Background

Personal and psychological factors, such as depression, have a considerable influence on nonadherence to medications and self-care in those with heart failure. More evidence is needed about positive personal factors that motivate adherence to medications and self-care in those with heart failure.

Objective

The purpose of this study was to investigate whether there was a relationship between the personal resources of resilience, hope, health literacy, social support, and self-care activation and adherence to HF self-care and medications and whether race impacts adherence.

Methods

This study used a cross-sectional, correlational design. Stepwise regression was used to test whether resilience, hope, health literacy, self-care activation, and race significantly predicted medication adherence and self-care. A diverse sample was recruited for this study.

Results

Of the 174 participants, 51% were female, 51.7% were White, and the mean age was 62 years. After adjustment for differences in age and depressive symptoms, a predictive relationship remained between resilience, health literacy, and medication adherence. Hope, activation, and race were not selected in the final regression model. A high level of perceived social support was the only predictor of better HF self-care.

Conclusion

Persons with heart failure may have better medication adherence and overall self-care if sufficiently resilient, health literate, and supported regardless of their degree of hope or activation. Race and age may be important factors to consider. More research is needed to understand the connection between resilience and medication adherence.
More than sleepiness: prevalence and relevance of nonclassical symptoms of obstructive sleep apnea
Authors: Verbraecken Johan
Published: September 2022

Purpose of review

The purpose of this review is to describe the nonclassical symptoms and manifestations occurring in patients with obstructive sleep apnea (OSA), both from a standpoint of prevalence and in terms of clinical relevance. Particular emphasis will be given to nightmares, comorbid insomnia, restless legs syndrome and periodic limb movement disorder, bruxism, morning headache, nocturia, acid reflux, chronic cough and dysphagia.

Recent findings

A review of the recent literature suggests that nonclassical symptoms have a high prevalence, are underestimated, and can interact with quality of life. Although these disturbances may occur together by mere coincidence, they may interact reciprocally. However, the degree of symptoms is not always correlated with OSA severity.

OSA is a heterogeneous disease with variable clinical manifestations. This review highlights the need for detailed evaluation of patients with OSA to diagnose other important sleep disorders and clinical manifestations, given their frequent association.
Progress and challenges in fungal lung disease in cystic fibrosis
Authors: Hong Gina
Published: September 2022

Purpose of review

This review is an overview of the recent progress made for the diagnosis and understanding of fungal lung disease in people with cystic fibrosis (CF), with a focus on Aspergillus fumigatus, the most common filamentous fungus in the CF airway. Currently, the longstanding question of the clinical significance of Aspergillus fumigatus and other fungi in CF respiratory cultures, in the absence of allergy, remains. Clinical criteria and biomarkers are needed to classify fungal lung disease and determine who may warrant therapy.

Recent findings

Several retrospective and prospective studies have described the prevalence of A. fumigatus and other fungi in the CF lung and factors contributing to the changes in fungal epidemiology. Selective fungus culture testing for the detection of fungi in CF sputa has been well studied, yet a standardized fungus culture protocol has yet to be defined. Culture-independent molecular studies and other fungal diagnostic testing have been conducted in the CF population, leading to efforts to better understand the clinical role of these tests. Recent works have aimed to determine whether chronic A. fumigatus colonization is associated with lung disease progression measured by FEV1 percentage predicted, structural lung disease, lung clearance index and respiratory quality-of-life. However, the existing knowledge gaps remain: definition of a fungal respiratory infection, the association between fungal infection and clinical outcomes, and indications for antifungal therapy.

Significant progress has been made for the detection and diagnosis of fungal lung disease. Yet, the role and impact of A. fumigatus and other fungal infections on respiratory health in people with CF remains to be determined.
Risk Factors Associated with Severe Macromastia among Adolescents and Young Women
Authors: Massey Gabrielle G. , Firriolo Joseph M. , Nuzzi Laura C. , Pramanick Tannishtha , Malloy Shannon M. , DiVasta Amy D. , Labow Brian I.
Published: September 2022

Background:

Macromastia is common among adolescents and young women with well-documented, negative physical and psychosocial impacts. The pathogenesis of idiopathic macromastia has been attributed to increased end organ sensitivity to circulating gonadal hormones. Despite the known negative effects of macromastia, there is a paucity of literature examining the clinical risk factors associated with macromastia severity in this age group.

Methods:

In this cross-sectional study, standardized clinical forms were administered to patients between the ages of 12-21 years undergoing reduction mammaplasty. Data were collected pertaining to patient demographics, biometrics, breast symptomology, medical/family history, and breast tissue resection mass at the time of reduction. Resection mass was normalized to patient body surface area in analyses.

Results:

A total of 375 subjects were included in analyses; mean surgical age was 18.1 years. The following risk factors were positively associated macromastia severity in both univariate and multivariate logistic regression models: overweight/obesity, racial/ethnic minority status, patient-reported gynecological/endocrine complaints, and early menarche (P < .05, all). More severe cases of macromastia were associated with approximately three times the odds of being overweight or obese or achieving menarche before 11 years old.

Conclusions:

In our sample, overweight/obesity, racial/ethnic minority status, early menarche, and patient-reported gynecological/endocrine complaints were all positively associated with macromastia severity. Awareness of these factors can empower physicians to identify and address modifiable risk factors to prevent progression to more severe disease. Macromastia itself should prompt screening for gynecological/endocrine complaints with referral as indicated.
Optimization of Patient Positioning for the Sonographic Evaluation of Gallstone Impaction: Analysis of Gallbladder Orientation Based on Computed Tomography
Authors: Zulfiqar Maria , Calhoun Brendan , Shetty Anup , Jyoti Arora , Middleton William
Published: September 2022

An important sonographic sign of cholecystitis is stone impaction in the gallbladder neck. Demonstration of stone mobility excludes impaction. The purpose of this study is to analyze the orientation of the gallbladder on computed tomography and determine the patient position most likely to facilitate stone mobility. ImageJ processing software was used to determine the x (transverse), y (anterior-posterior), and z (craniocaudal) coordinates for the gallbladder neck and fundus in 544 consecutive computed tomography examinations. The differences in the fundal and neck coordinates were used to determine the likelihood of moving a stone from the neck to the fundus for the left and right lateral decubitus positions (x coordinates), the prone position (y coordinates), and the upright position (z coordinates). The coordinate with the largest difference was considered to predict the position most likely to facilitate stone motion. The difference in position of the fundus and neck was greatest in the y-, z-, and x-axis in 232 (42.6%), 194 (35.7%), and 118 (21.7%) of patients, respectively. For body mass index (BMI) less than 25 kg/m2, the difference was greatest in the z-axis (59.8%). For BMI greater than 25 kg/m2, the difference was greatest in the y-axis (47.1%). Based on their relative location, the optimal position to facilitate gallstone mobility from the gallbladder neck to fundus was most often prone (especially in high BMI patients), followed by upright (especially in low BMI patients), followed by right lateral decubitus. The left lateral decubitus position was never optimal.
Lighting the Way with Fluorescent Cholangiography in Laparoscopic Cholecystectomy: Reviewing 7 Years of Experience
Authors: Broderick Ryan C , Li Jonathan Z , Huang Estella Y , Blitzer Rachel R , Lee Arielle M , Serra Joaquin L , Bouvet Michael , Sandler Bryan J , Jacobsen Garth R , Horgan Santiago
Published: September 2022

BACKGROUND:

Laparoscopic cholecystectomy with fluorescent cholangiography using indocyanine green dye (FC) identifies extrahepatic biliary structures, potentially augmenting the critical view of safety. We aim to describe trends for the largest single-center cohort of patients undergoing FC in laparoscopic cholecystectomy.

STUDY DESIGN:

A retrospective review of a prospectively maintained database identified patients undergoing laparoscopic cholecystectomy with FC at a single academic institution. Patient factors included age, sex, BMI, and American Society of Anesthesiologists score. Outcomes included operative time, conversion to open procedure, biliary injury, length of stay, and complications.

RESULTS:

A total of 828 patients underwent FC. Of these, 74.3% were female, the mean age was 50.4 years, and the average BMI 28.8 kg/m2. Mean operating room time was 68.6 minutes. There were no mortalities or common bile duct injuries. Morbidities included 4 bile leaks and 1 retained stone. Six patients required conversion to an open approach. Operative time, length of stay, and open conversion significantly decreased after a standard indocyanine green protocol (p < 0.05). Compared with white light, FC demonstrated lower operative times (99 vs 68 minutes), length of stay (1.4 vs 0.4 days), open conversions (8% vs 0.7%), emergency department visits (13% vs 8%) and drain placements (12% vs 3%) (all p < 0.05). Patients with BMI greater than 30 saw elevated operative times and length of stay.

CONCLUSIONS:

In conclusion, this paper demonstrates improved operative outcomes with the use of FC through the consistent ability to delineate biliary anatomy, even in the setting of complex anatomy. No common bile duct injuries have occurred in our 7-year experience with FC. We recommend FC as the standard of care when performing laparoscopic cholecystectomies.
Lighting the Way for Necrosis Excision Through Indocyanine Green Fluorescence–Guided Surgery
Authors: Zajac Jocelyn C , Liu Aiping , Uselmann Adam J , Lin Christie , Hassan Sameeha E , Faucher Lee D , Gibson Angela LF
Published: September 2022

BACKGROUND:

No objective technique exists to distinguish necrotic from viable tissue, risking over-excision in burns and loss of wound healing potential. Second window indocyanine green (SWIG) is a novel fluorescence-imaging modality being studied to identify residual solid tumors during oncological surgery. SWIG has also been shown to have avidity for necrosis in animal models, but translation of these findings to humans is lacking. The objective of this study was to evaluate SWIG in the identification of burn wound necrosis and compare it with previously published indocyanine green angiography (ICGA) techniques.

STUDY DESIGN:

This study used mouse, human skin xenograft and human patient burn models. Brightfield and SWIG near-infrared imaging were performed on macroscopic tissue samples, which were then cryopreserved, sectioned, and analyzed for microscopic fluorescence. SWIG fluorescence findings were correlated to visual assessment of the burn wound as well as histological markers of necrosis using hematoxylin and eosin and lactate dehydrogenase stains.

RESULTS:

We found that SWIG identified burn necrosis in a manner dependent on the dose and timing of indocyanine green (ICG) administration and had an inverse fluorescence signal compared with ICGA. Furthermore, SWIG fluorescence identified the interface of viable and nonviable tissue.

CONCLUSION:

Our study confirmed that ICGA is an inconsistent and nonstandardized modality to evaluate burn injuries. In contrast, SWIG imaging is a potential imaging modality to objectively prognosticate burn wound healing potential and guide intraoperative burn excision. Further studies are needed to define ratios of fluorescence intensity values to guide surgical decision-making in burn excision and to better define how ICG is retained in necrotic tissue to enhance utility of SWIG in other disease processes.
Long-Term, Prospective, Multicenter Study of Poly-4-Hydroxybutyrate Mesh (Phasix Mesh) for Hernia Repair in Cohort at Risk for Complication: 60-Month Follow-Up
Authors: Roth John Scott , Anthone Gary J , Selzer Don J , Poulose Benjamin K , Pierce Richard A , Bittner James G , Hope William W , Dunn Raymond M , Martindale Robert G , Goldblatt Matthew I , Earle David B , Romanelli John R , Mancini Gregory J , Greenberg Jacob A , Linn John G , Parra-Davila Eduardo , Sandler Bryan J , Deeken Corey R , Badhwar Amit , Salluzzo Jennifer L , Voeller Guy R
Published: September 2022

BACKGROUND:

Long-term resorbable mesh represents a promising technology for ventral and incisional hernia repair (VIHR). This study evaluates poly-4-hydroxybutyrate mesh (P4HB; Phasix Mesh) among comorbid patients with CDC class I wounds.

STUDY DESIGN:

This prospective, multi-institutional study evaluated P4HB VIHR in comorbid patients with CDC class I wounds. Primary outcomes included hernia recurrence and surgical site infection. Secondary outcomes included pain, device-related adverse events, quality of life, reoperation, procedure time, and length of stay. Evaluations were scheduled at 1, 3, 6, 12, 18, 24, 30, 36, and 60 months. A time-to-event analysis (Kaplan-Meier) was performed for primary outcomes; secondary outcomes were reported as descriptive statistics.

RESULTS:

A total of 121 patients (46 male, 75 female) 54.7 ± 12.0 years old with a BMI of 32.2 ± 4.5 kg/m2 underwent VIHR with P4HB Mesh (mean ± SD). Fifty-four patients (44.6%) completed the 60-month follow-up. Primary outcomes (Kaplan-Meier estimates at 60 months) included recurrence (22.0 ± 4.5%; 95% CI 11.7% to 29.4%) and surgical site infection (10.1 ± 2.8%; 95% CI 3.3 to 14.0). Secondary outcomes included seroma requiring intervention (n = 9), procedure time (167.9 ± 82.5 minutes), length of stay (5.3 ± 5.3 days), reoperation (18 of 121, 14.9%), visual analogue scale–pain (change from baseline –3.16 ± 3.35 cm at 60 months; n = 52), and Carolinas Comfort Total Score (change from baseline –24.3 ± 21.4 at 60 months; n = 52).

CONCLUSIONS:

Five-year outcomes after VIHR with P4HB mesh were associated with infrequent complications and durable hernia repair outcomes. This study provides a framework for anticipated long-term hernia repair outcomes when using P4HB mesh.
High throughput Bioluminescent assay to characterize and monitor the activity of SARS-CoV-2 Methyltransferases
Authors: Hsiao Kevin , Zegzouti Hicham , Goueli Said
Published: September 2022

The fast rate of viral mutations of SARS CoV-2 result in decrease in the efficacy of the vaccines that have been developed before the emergence of these mutations. Thus, it is believed that using additional measures to combat the virus is not only advisable but also beneficial. Two antiviral drugs were authorized for emergency use by the FDA, namely Pfizer’s two-drug regimen sold under the brand name Paxlovid, and Merck’s drug Lagevrio. Pfizer’s two-drug combination consists of nirmatrelvir, a protease inhibitor that blocks coronavirus ability to multiply and another antiviral, ritonavir, that lowers the rate of drug clearance to boost the longevity and activity of the protease inhibitor. Merck’s drug Lagevrio (molnupiravir) is a nucleoside analogue with a mechanism of action that aims to introduce errors into the genetic code of the virus. We believe the armament against the virus can be augmented by the addition of another class of enzyme inhibitors that are required for viral survival and its ability to replicate. Enzymes like nsp14 and nsp10/16 methyltransferases represent another class of drug targets since they are required for viral RNA translation and evading the host immune system. In this communication, we have successfully verified that the Methyltransferase Glo, which is universal and homogeneous methyltransferase assay can be used to screen for inhibitors of the two pivotal enzymes nsp14 and nsp16 of SARS CoV-2. Furthermore, we have carried out extensive studies on those enzymes using different RNA substrates and tested their activity using various inhibitors and verified the utility of this assay for use in drug screening programs. We anticipate our work will be pursued further to screen for large libraries to discover new and selective inhibitors for the viral enzymes particularly that these enzymes are structurally different from their mammalian counterparts.
Functional impairment of the Lateral Geniculate Nucleus in Multiple Sclerosis
Authors: Sardaripour Neda , Asadi Mehrdad , Moghaddam Hamid Abrishami , Khadem Ali , Rajimehr Reza
Published: September 2022

Visual impairment is one of the early symptoms of Multiple sclerosis (MS) disease. The objective of this study is evaluating function of Lateral geniculate nucleus, which bridges visual information from retina to other higher order visual processing areas. We collected BOLD fMRI data from 19 MS and 19 control subjects by employing selective visual stimulation tasks to provoke the whole LGN, Magnocellular, Parvocellular, and Koniocellular pathways as part of LGN multilayer structure. Through statistical analysis, we observed a significant reduction (p<0.05) of the average BOLD signal from the whole LGN structure in MS group. Further investigations showed a significant reduction of BOLD signal (p<0.05) in response to Magno and Parvo stimuli compared to healthy controls that suggested a selective functional impairment emerging in primary visual pathways in MS. In summary, we showed functional abnormalities in LGN structure and its M and P subdivisions based on functional MRI.
Pea-adapted biotype of the aphid Acyrthosiphon pisum induces susceptibility of pea to non-adapted biotype enabling improved feeding and performance
Authors: Shih Po-Yuan , Ollivier Rémi , Cherqui Anas , Ameline Arnaud , Morlière Stéphanie , Outreman Yannick , Simon Jean-Christophe , Sugio Akiko
Published: September 2022

Most insect herbivores are adapted to feed on a few host plants only, but the mechanisms underlying plant specialization are poorly understood. One of the dominant hypotheses is that insects inject an oral secretion into the plant that manipulates the plant’s defences resulting in induced susceptibility. We tested this hypothesis on the pea aphid (Acyrthosiphon pisum), which forms multiple biotypes, each specialized on specific legume hosts. In particular, we tested whether a pea-adapted biotype can induce host susceptibility on pea, which should positively affect the fitness of a non-pea-adapted biotype. We found that survival and fecundity of an alfalfa-adapted biotype on pea were enhanced by co-infestation but not pre-infestation with a pea-adapted biotype. The electrical penetration graph (EPG) method was then used to dissect the components of alfalfa biotype feeding behaviour on pea with and without co-infestation by the pea biotype. While probing time did not differ between these two conditions, differences were observed in most other EPG parameters. When co-infested with the pea-adapted biotype, the alfalfa-adapted biotype was more likely to establish a phloem feeding and exhibited a longer ingestion time on pea. Our results clearly indicated that the pea-adapted biotype induced pea susceptibility by increasing the accessibility of non-pea-adapted aphids to the host phloem sap, and as a result, the alfalfa biotype increased its survival rate and fecundity. These results contribute to understanding how aphids manipulate their specific host plants.
Effect of Nitrogen Fertilizer Rate on Yield and Quality Parameters of Malt Barley Varieties for Beer Production in South Gonder, Ethiopia
Authors: Abebe Admas Alemu , Hagos Fikre
Published: September 2022

The objective of this study was to examine the effect of different nitrogen rates on the yield and malt barley quality parameters of two malting barley varieties (Holker and miskal-21). The experiment was carried out during 2013 cropping season at three locations, namely Ebnat, Estie and Farta. The following nitrogen rates were applied: 0, 60, 120and 180 kg ha-1 and a factorial experiment arranged in RCBD was applied to conduct the research. The result of this study indicated that nitrogen significantly increased the grain yield (648.2 to 1657.4and 666.7 to 1851.8 kg ha-1for Holker and Miskal-21 respectively). Malt quality was decreased by increasing nitrogen rates (1.28 to 2.34%). Apart from nitrogen rates, the varieties also affected the yield and nature of the protein content levels. As indicated in this result Holker variety gave optimum grain yield and lowest protein content, therefore, this variety is advisable to be used by malt brewers to satisfy their requirements. The optimal malt quality and yield was achieved by applying between 60-120 kg N ha-1 beyond this rate, grain yield might be significantly increased but malt qualities at the same time significantly decreased therefore it is recommended to obtain optimum yield as well as high malt qualities
Understanding changes in genetic literacy over time and in genetic research participants
Authors: Little India D. , Koehly Laura M. , Gunter Chris
Published: September 2022

As genomic and personalized medicine becomes mainstream, assessing and understanding the public’s genetic literacy is paramount. Because genetic research drives innovation in this area and involves much of the public, it is equally important to assess its impact on genetic literacy. We designed a survey to assess genetic literacy in three ways (familiarity, knowledge, and skills) and distributed it to two distinct samples: 2050 members of the general population, and 2023 individuals currently enrolled in a large-scale genetic research study. We compared these data to a similar survey implemented in 2013. The results indicate that familiarity with basic genetic terms in 2021 (M = 5.36, p<.001) and knowledge of genetic concepts in 2021 (M = 9.06, p = 0.002) is significantly higher compared to 2013 (M = 5.08; M = 8.72). Those currently enrolled in a genetic study were also significantly more familiar with genetic terms (M = 5.79, p<.001), more knowledgeable of genetic concepts (M = 10.27, p<.001), and scored higher in skills (M = 3.57, p<.001) than the general population (M = 4.98; M = 9.06; M = 2.65).The results suggest that genetic literacy is improving over time, though there is room for improvement. The data also suggest that participating in genetic research is one avenue for improving genetic literacy. We conclude that educational interventions are needed to ensure familiarity with and comprehension of basic genetic concepts. We also suggest further exploration of the impact of genetic research participation on genetic literacy to determine mechanisms for potential interventions.
Predicting 3D genome architecture directly from the nucleotide sequence with DNA-DDA
Authors: Lainscsek Xenia , Taher Leila
Published: September 2022

3D genome architecture is characterized by multi-scale patterns and plays an essential role in gene regulation. Chromatin conformation capturing experiments have revealed many properties underlying 3D genome architecture such as the compartmentalization of chromatin based on transcriptional states. However, they are complex, costly, and time consuming, and therefore only a limited number of cell types have been examined using these techniques. Increasing effort is being directed towards deriving computational methods that can predict chromatin conformation and associated structures. Here we present DNA-DDA, a purely sequence-based method based on chaos theory to predict genome-wide A and B compartments. We show that DNA-DDA models derived from a 20 Mb sequence are sufficient to predict genome wide compartmentalization at the scale of 100 kb in four different cell types. Although this is a proof-of-concept study, our method shows promise in elucidating the mechanisms responsible for genome folding as well as modeling the impact of genetic variation on 3D genome architecture and the processes regulated thereby.
Mangroves deviate from other angiosperms in their genome size, leaf cell size, and cell packing density relationships
Authors: Jiang Guo-Feng , Li Su-Yuan , Dinnage Russell , Cao Kun-Fang , Simonin Kevin A. , Roddy Adam B.
Published: September 2022

Background and Aims

While genome size limits the minimum sizes and maximum numbers of cells that can be packed into a given leaf volume, mature cell sizes can be substantially larger than their meristematic precursors and vary in response to abiotic conditions. Mangroves are iconic examples of how abiotic conditions can influence the evolution of plant phenotypes.

Methods

Here, we examined the coordination between genome size, leaf cell sizes, and cell packing densities, and leaf size in 13 mangrove species across four sites. Four of these species occurred at more than one site, allowing us to test the effect of climate on leaf anatomy.

Results

We found that genome sizes of mangroves were very small compared to other angiosperms, and, like other angiosperms, mangrove cells were always larger than the minimum size defined by genome size. Increasing mean annual temperature of a growth site led to higher packing densities of veins (Dv) and stomata (Ds) and smaller epidermal cells but had no effect on stomatal size. Contrary to other angiosperms, mangroves exhibited (1) a negative relationship between guard cell size and genome size; (2) epidermal cells that were smaller than stomata, and (3) coordination between Dv and Ds that was not mediated by epidermal cell size. Furthermore, mangrove epidermal cell sizes and packing densities covaried with leaf size.

Conclusions

While mangroves exhibited coordination between veins and stomata and attained a maximum theoretical stomatal conductance similar to other angiosperms, the tissue-level tradeoffs underlying these similar relationships across species and environments was markedly different, perhaps indicative of the unique structural and physiological adaptations of mangroves to their stressful environments.
Function of cell adhesion molecules in differentiation of ray sensory neurons in C. elegans
Authors: Sakai Naoko , Sun Peter , Kim Byunghyuk , Emmons Scott W.
Published: September 2022

For proper functioning of the nervous system, it is crucial that neurons find their appropriate partners and build the correct neural connection patterns. Although cell adhesion molecules (CAMs) have been studied for many years as essential players in neural connections, we have yet to unravel the code by which CAMs encode synaptic specificity. We analyzed the effects of mutations in CAM genes on the morphology and synapses of a set of sensory neurons in the C. elegans male tail. B-type ray sensory neurons express ten genes encoding CAMs. We examined the effect on axon trajectory and localization of presynaptic components in viable mutants of nine of these. We found axon trajectory defects in mutants of UNC-40/DCC, SAX-3/ROBO, and FMI-1/Flamingo/Celsr1. In none of the mutants was presence of presynaptic components in axons lost, and in several the level appeared to increase, suggesting possible accumulation. B-type sensory neurons fasciculate with a second type of ray sensory neuron, the A-type, in axon commissures. We found cell non-autonomous effects consistent with each promoting the trajectory of the other. Overall, single and multiple mutants of CAM genes had limited effects on ray neuron trajectories and accumulation of synaptic components.
Identifying the engagement of a brain network during a targeted tDCS-fMRI experiment using a machine learning approach
Authors: Shinde A. B. , Mohapatra S. , Schlaug G.
Published: September 2022

Transcranial direct current stimulation (tDCS) can noninvasively modulate behavior, cognition, and physiologic brain functions depending on polarity and dose of stimulation as well as montage of electrodes. Concurrent tDCS-fMRI presents a novel way to explore the parameter space of non-invasive brain stimulation and to inform the experimenter as well as the participant if a targeted brain region or a network of spatially separate brain regions has been engaged and modulated. We compared a multi-electrode (ME) with a single electrode (SE) montage and both active conditions with a no-stimulation (NS) control condition to assess the engagement of a brain network and the ability of different electrode montages to modulate network activity. The multi-electrode montage targeted nodal regions of the right Arcuate Fasciculus Network (AFN) with anodal electrodes placed over the skull position of the posterior superior temporal/middle temporal gyrus (STG/MTG), supramarginal gyrus (SMG), posterior inferior frontal gyrus (IFG) and a return cathodal electrode over the left supraorbital region. In comparison, the single electrode montage used only one anodal electrode over a nodal brain region of the AFN, but varied the location between STG/MTG, SMG, and posterior IFG for different participants. Whole-brain rs-fMRI was obtained every three seconds. The tDCS-stimulator was turned on at 3 minutes after the scanning started. A 4D rs-fMRI data set was converted to dynamic functional connectivity (DFC) matrices using a set of ROI pairs belonging to the AFN as well as other unrelated brain networks. In this study, we evaluated the performance of five algorithms to classify the DFC matrices from the three conditions (ME, SE, NS) into three different categories. The highest accuracy of 0.92 was obtained for the classification of the ME condition using the K Nearest Neighbor (KNN) algorithm. In other words, applying the classification algorithm allowed us to identify the engagement of the AFN and the ME condition was the best montage to achieve such an engagement. The top 5 ROI pairs that made a major contribution to the classification of participant’s rs-fMRI data were identified using model performance parameters; ROI pairs were mainly located within the right AFN. This proof-of-concept study using a classification algorithm approach can be expanded to create a real-time feedback system at a participant level to detect the engagement and modulation of a brain network that spans multiple brain lobes.
Meggie – easy-to-use graphical user interface for M/EEG analysis based on MNE-python
Authors: Heinilä Erkka , Parviainen Tiina
Published: September 2022

Background

In the last decades, electrophysiological imaging methodology has seen many advances and the computational power in the neuroscience laboratories has steadily increased. Still, the new methodologies are unavailable for many. There is a need for more versatile analysis approaches for neuroscience specialists without a programming background.

New method

Using a software which provides standard pipelines, provides good default values for parameters, has a good multi-subject support, and stores the used analysis steps with the parameters in one place for reporting, is efficient and fast. In addition to enabling analysis for people without background in programming, it enables analysis for people with background in programming but a limited background in neuroscience. When constructed with care, the GUI may guide the researcher to apply analysis steps in correct order with reasonable default parameters.

Comparison to existing methods

Two existing software, EEGLAB and Brainstorm, both provide an easy-to-use graphical user interface for end-to-end analysis for multiple subjects. The key difference to work presented here is the choice of language. The scientific community is moving en masse towards the python programming language, thus making it an ideal platform for extendable software. Another problem with Matlab is that it is not free - both from the perspective of open source and concrete monetary resources. Within the current trend towards increasing open science, covering data, analysis and reporting, the need for open source software is imperative.

Results

Meggie is an open source software for running MEG and EEG analysis with easy-to-use graphical user interface. It is written in Python 3, runs on Linux, macOS and Windows, and uses the MNE-python library under the hood to do heavy lifting. It is designed to allow end-to-end analysis of MEG and EEG datasets from multiple subjects with common sensor-level analysis steps such as preprocessing, epoching and averaging, spectral analysis and time-frequency analysis. Most of the analysis steps can be run for all the subjects in one go, and combining the results across subjects is made possible with grand averages. We have emphasized the extendibility of Meggie by implementing most of the Meggie itself as plugins, thus ensuring that new plugins have access to all necessary core features.

Conclusion

Meggie answers the demand for easy-to-use and extendable python-based graphical user interface that provides an end-to-end analysis environment for M/EEG data analysis. It is freely available at https://github.com/cibr-jyu/meggie under the BSD license. Installation instructions, documentation and tutorials are found on that website.

Highlights

- MNE-python-based graphical user interface for M/EEG analysis

- Easy to use even without programming background

- Has good support for multiple subjects

- Written in python, and can be easily extended with plugins

- Free and open source with BSD license