bluuebunny/crossref_metadata_2025 huggingface dataset:
Gamma Glutamyl Transferase Activity Has Limited Utility in Assessment of Alkaline Phosphatase Elevations
Authors: Geno K Aaron , Poore Brad , Cervinski Mark A , Nerenz Robert D
Published: July 2021

Introduction

As part of an ongoing effort to improve healthcare value for patients, laboratories increasingly implement test utilization review. Alkaline phosphatase (ALP) isoenzymes (hereafter: isoenzymes) testing distinguishes the various ALP isoforms to explain elevations in total serum ALP. Gamma glutamyl transferase activity (GGT) has served as a proxy for total ALP elevations attributable to the hepatic isoform given that both are membrane-bound proteins with a shared mechanism of release. We assessed the utility of GGT in evaluating isoenzymes requests.

Methods

We obtained 8 years of isoenzymes results and identified same-patient GGT measurements obtained within 7 days. We assessed the ability of GGT to predict elevations in hepatic, bone, intestinal, and nonhepatic ALP isoforms overall. We generated ROC curves and calculated sensitivity and specificity using our in-house reference limits for GGT.

Results

GGT as a predictor of hepatic isoform elevation had an area under the ROC curve (AUC) of 0.68, and GGT activity above the upper reference limit was 46.6% sensitive and 85.0% specific for hepatic ALP elevation. GGT activity as a predictor of nonhepatic isoform elevation had an AUC of 0.52, and GGT within reference limits was 59.8% sensitive and 46.4% specific for elevation in a nonhepatic ALP isoform. In 133 individuals with hepatic isoform elevations, 93 had a concurrent elevation in a nonhepatic ALP isoform.

Conclusion

GGT was reasonably specific but insensitive for hepatic ALP isoform elevation and was a poor predictor of ALP isoform elevation overall, suggesting that its usefulness in evaluating isoenzymes orders is limited.
Shared clinical decision-making on vaccines: out of sight, out of mind
Authors: Shen Angela K , Michel Jeremey J , Langford Aisha T , Sobczyk Elizabeth A
Published: July 2021

Clinical decision support systems, which provide automated reminders in electronic health systems, are designed to provide physicians and other health professionals support in clinical decision-making. New clinical guidance from the Advisory Committee on Immunization Practices on a new category of recommendations referred to as “shared clinical decision-making” have left providers struggling to interpret how to best implement recommendations for adult vaccines. The issue at hand is how to ensure that a conversation between the patient and provider occurs. While traditional clinical decision support systems have driven immunization for years, these systems support a binary default opt-in process. The goal for shared decision-making is the discussion rather than the vaccination. The recommended provider–patient conversations need to be supported with both provider guidance as well as tools to ensure vaccines are not omitted from the conversations, particularly as future vaccine candidates progress through the vaccine development pipeline.
Nexobrid Treatment for Burn Injuries in Patients With Chronic Obstructive Pulmonary Disease and Home Oxygen Therapy
Authors: Daniels Marc , Stromps Jan Philipp , Heitzmann Wolfram , Schiefer Jennifer , Fuchs Paul Christian , Seyhan Harun
Published: July 2021

There is an increased risk for burn injuries associated with home oxygen therapy of patients with chronic obstructive pulmonary disease (COPD) since 10% to 50% of these patients continue to smoke. Enzymatic eschar removal of facial burns is gaining popularity but intubation of this specific patient group often leads to prolonged weaning and can require tracheostomy. This study dealt with the question if enzymatic debridement in these patients can also be performed in analgosedation. A selective review of the literature regarding burn trauma associated with home oxygen use in patients with COPD was performed, as well as a retrospective analysis of all patients with burn injuries associated with home oxygen use and COPD that were admitted to the study clinic. In the literature, 1746 patients with burns associated with home oxygen use are described, but none of them received enzymatic debridement. In this study, 17 patients were included. All three patients in this study with facial full-thickness burn injuries received enzymatic debridement. The mortality rate in this cohort was 17.6% (3/17). Up to date, there is limited experience performing regional anesthesia debridement in patients with COPD. This is the first manuscript describing the use of enzymatic debridement in patients with COPD and home oxygen therapy. We could confirm other studies that intubation of these patients leads to prolonged ventilation hours and increases the probability for poor prognosis. Therefore, we described the treatment of enzymatic debridement in analgosedation without intubation.
Subgroup analysis of the AFTER I-O study: a retrospective study on the efficacy and safety of subsequent molecular targeted therapy after immune-oncology therapy in Japanese patients with metastatic renal cell carcinoma
Authors: Tomita Yoshihiko , Kimura Go , Fukasawa Satoshi , Numakura Kazuyuki , Sugiyama Yutaka , Yamana Kazutoshi , Naito Sei , Kaneko Hirokazu , Tajima Yohei , Oya Mototsugu
Published: July 2021

Background

We performed subgroup analyses of the AFTER I-O study to clarify the association of time-to-treatment failure (TTF) and discontinuation reason of prior immune-oncology (I-O) therapy, and molecular targeted therapy (TT) regimen with the outcomes of TT after I-O.

Methods

The data of Japanese metastatic renal cell carcinoma patients treated with TT after nivolumab (NIVO) (CheckMate 025) or NIVO + ipilimumab (IPI) (CheckMate 214) were retrospectively analyzed. The objective response rates (ORRs), progression-free survival (PFS) and overall survival (OS) of TT after I-O were analyzed by subgroups: TTF (<6 or ≥6 months) and discontinuation reason of prior I-O (progression or adverse events), and TT regimen (sunitinib or axitinib). We also analyzed PFS2 of prior I-O and OS from first-line therapy.

Results

The ORR and median PFS of TT after NIVO and NIVO+IPI among the subgroups was 17–36% and 20–44%, and 7.1–11.6 months and 16.3-not reached (NR), respectively. The median OS of TT after NIVO was longer in patients with longer TTF of NIVO and treated with axitinib. Conversely, median OS of TT after NIVO+IPI was similar among subgroups. The median PFS2 of NIVO and NIVO+IPI was 36.7 and 32.0 months, respectively. The median OS from first-line therapy was 70.5 months for patients treated with NIVO and NR with NIVO+IPI. The safety profile of each TT after each I-O was similar to previous reports.

Conclusions

The efficacy of TT after NIVO or NIVO+IPI was favorable regardless of the TTF and discontinuation reason of prior I-O, and TT regimen.
Quasi circular orbits around prolate bodies
Authors: Ribeiro T , Winter O C , Mourão D , Boldrin L A G , Carvalho J P S
Published: July 2021

Recent observations of stellar occultations have revealed rings of particles around non-planetary bodies of the Solar system. These bodies are irregular and can be modelled by ellipsoids. In the context of numerical integrations for the study of studying the region close to these ellipsoidal bodies, it is known that the use of geometric initial conditions is necessary when the central object is significantly oblatened. In this paper, we show that for elongated bodies there is also a need for the adaptation of the initial velocity ($\nu _{C_{22}}$) so that equatorial periodic orbits of the first kind around this body have smaller radial variations since the circular Keplerian velocity produces a high oscillating eccentricity and radial variation. We describe an empirical method to obtain the velocity $\nu _{C_{22}}$ of a set of simulations where we vary the physical parameters of the central body. With the obtained data, developed empirical equations that allow the calculation of the orbital eccentricity, the initial velocity and an adapted Kepler’s Third Law as a function of the ellipticity coefficient and the semimajor axis. In addition, we identify an important change in the location of the primary body in relation to the elliptical orbit. In the cases of the orbits with minimal radial variation found in our study, the body starts to occupy the centre of the elliptical orbit. Finally, we include the rotation of the central body in the studied systems and analyse its implications for the dynamics of these orbits of low radial variation.
Determining our peculiar velocity from the aberration in the cosmic microwave background
Authors: Aurich R , Reinhardt D
Published: July 2021

The motion of our Solar system relative to the cosmic microwave background (CMB) rest frame leads to subtle distortions in the observed CMB sky map due to the aberration effect. Usually the corresponding peculiar velocity is determined from the CMB dipole but neglecting intrinsic dipole contributions. Here, it is investigated whether certain invariant scalar measures, which are derived from first and second order covariant derivatives on the sphere, can detect the distortions caused by the aberration effect at high multipoles. This would in principle allow to disentangle the Doppler from intrinsic dipole contributions providing an independent method for the determination of our peculiar velocity. It is found that the eigenvalues of the Hessian matrix of the temperature field are well suited for that task.
Flavors and Implied Reduced-Risk Descriptors in Cigar Ads at Stores Near Schools
Authors: Sterling Kymberle L , Vishwakarma Monika , Ababseh Kimberly , Henriksen Lisa
Published: July 2021

Introduction

Although the FDA prohibits using inaccurate, reduced-risk descriptors on tobacco product advertising, descriptors that imply reduced risk or an enhanced user experience may be present on cigar product advertising in retail outlets near schools. Therefore, to inform the development of federal labeling and advertising requirements that reduce youth appeal of cigars, we conducted a content analysis of cigar ads in retailers near schools to document the presence of implied health claims and other selling propositions that may convey enhanced smoking experience.

Aims and Methods

Up to four interior and exterior little cigar and cigarillo advertisements were photographed in a random sample of licensed tobacco retailers (n = 530) near California middle and high schools. Unique ads (n = 234) were coded for brand, flavor, and presence of implicit health claims, premium branding descriptors, and sensory descriptors. Logistic regressions assessed the association among flavored ads and presence of implicit health claims, premium branding, or sensory descriptors.

Results

Seventeen cigar brands were advertised near schools; Black & Mild (20.1%) and Swisher Sweets (20.1%) were most common. Flavor was featured in 64.5% of ads, with explicit flavor names (eg, grape) being more prevalent than ambiguous names (eg, Jazz) (49.6% vs. 34.2%). Compared to ads without flavors, ads with ambiguous flavors were more likely to feature implicit health claims (OR = 1.83, 95% CI = 1.06% to 3.19%) and sensory descriptors (OR = 2.64, 95% CI = 1.39% to 5.04%); ads with explicit flavors were more likely to feature premium branding (OR = 2.84, 95% CI = 1.53% to 5.41%).

Conclusions

Cigar ads that featured implicit health claims and premium branding, and sensory selling propositions are present at retailer stores near schools.

Implications

We document the presence of implied health claims, premium branding, and sensory descriptors on cigar ads found in retail settings near schools. This study adds to the body of evidence that supports the development of federal labeling and advertising requirements for cigar products to reduce their appeal among vulnerable groups.
Assessment of IQOS Marketing Strategies at Points-of-Sale in Israel at a Time of Regulatory Transition
Authors: Bar-Zeev Yael , Berg Carla J , Abroms Lorien C , Rodnay Maya , Elbaz Daniel , Khayat Amal , Levine Hagai
Published: July 2021

Introduction

IQOS, a tobacco heating system, and accompanying tobacco sticks (HEETS) entered the Israeli market in 2016, prior to rapid regulatory change. This study assessed IQOS marketing strategies and regulatory compliance at IQOS and/or HEETS point-of-sale (POS) in Israel in December 17, 2019 to January 7, 2020, after the ban on advertisement went into effect in March 8, 2019.

Aims and Methods

Research staff audited 80 randomly selected IQOS and/or HEETS POS in four cities using a structured form to assess store types, product placement, price, promotional strategies, and regulatory compliance. POS data were linked to neighborhood characteristics, including socioeconomic status, ethnicity, and proximity (under 300 m) to schools.

Results

Almost half of the stores (48.7%) were convenience stores. HEETS were visible to the customers in 46.1% of POS, 35% carried at least four HEETS colors, 20.0% had IQOS and/or HEETS special displays, and 13.8% displayed HEETS near youth-oriented merchandise. Mean HEETS pack price was US $8.7 (range: US $7.5–11.3), 27% more than the least expensive cigarette pack, and 39% less than the most expensive cigarette. HEETS promotions were uncommon. Compliance with the newly introduced advertisement ban was fairly high for HEETS (94.8%). Only one POS was located in a low-socioeconomic status area; 68.7% were near a school.

Conclusions

The relatively limited IQOS and/or HEETS marketing at POS suggests that, with regulatory changes, online or other forms of marketing might be prioritized. IQOS may be promoted to higher socioeconomic status populations, as indicated by pricing and POS neighborhood characteristics. Access near schools and placement near youth-oriented merchandise are potential concerns necessitating further research.

Implications

Globally, the POS is considered the least regulated channel for advertising and marketing of tobacco products. Assessing IQOS marketing strategies at the POS provides valuable findings that can inform regulatory efforts in Israel and other countries as well. Limited IQOS and/or HEETS marketing at POS suggests that primary marketing strategies may shift to online or other channels as regulatory contexts become more progressive and/or restrictive. Ongoing surveillance of IQOS via online marketing and POSs, specifically with regard to product placement and proximity to schools, is needed.
Ethical Implications of Preventive Medicine within Correctional Healthcare
Authors: Smith Molly
Published: July 2021

Incarcerated offenders are categorically high-risk patients who are disproportionately more likely to suffer from chronic illnesses than members of the general population. The conditions of confinement (e.g., overcrowding, poor nutrition, risky sexual practices) furthermore make them increasingly susceptible to acquiring an infectious disease. Past research has linked preventive care, including the early detection and treatment of such diseases, with better long-term health outcomes; however, such care is not universally provided to this population. The benefits and current availability of preventive care for incarcerated offenders is discussed and several questions are raised for future discussion within a global context. In particular, these questions include whether or not incarcerated offenders should receive preventive care, the underlying reason for such provision, who should advocate for and for be responsible for their access to preventive care, and the mechanisms through which access could be attained.
Whose Vote Counts for Crime Policy?
Authors: Duxbury Scott W
Published: July 2021

Policy responsiveness to public opinion is necessary for democratic governance, yet research on crime policy responsiveness has focused on the public at large, overlooking variation in policy support among demographic bodies and its heterogeneous effects on policy implementation. Creating new state-level measures of group opinion on punitive policy mood using 257,356 responses to 79 national surveys administered between 1970 and 2015, this study examines the effect of race, age, and gender-specific opinion on the incarceration rate. Consistent with prior studies, results reveal parallel trends in punitive policy support, with punitiveness increasing in tandem across demographic subgroups. Statistical findings from error correction models, however, reveal that not all groups had equal influence. Only the opinions of the most punitive groups—whites, men, and 30–44-year-olds—influenced the incarceration rate. Further, the largest divide in policy responsiveness to group opinion was between blacks and whites. In fact, estimates suggest that if whites’ punitive policy support had not risen, the current incarceration rate would be roughly the same as if violent crime had not risen during the 45 years of mass incarceration. The implications of these results are discussed for research on policy responsiveness, partisan politics, and for the “democracy at work” hypothesis of mass incarceration.
Concordance-Based Approaches for the Inference of Relationships and Molecular Rates with Phylogenomic Data Sets
Authors: Walker Joseph F , Smith Stephen A , Hodel Richard G J , Moyroud Edwige
Published: July 2021

Gene tree conflict is common and finding methods to analyze and alleviate the negative effects that conflict has on species tree analysis is a crucial part of phylogenomics. This study aims to expand the discussion of inferring species trees and molecular branch lengths when conflict is present. Conflict is typically examined in two ways: inferring its prevalence and inferring the influence of the individual genes (how strongly one gene supports any given topology compared to an alternative topology). Here, we examine a procedure for incorporating both conflict and the influence of genes in order to infer evolutionary relationships. All supported relationships in the gene trees are analyzed and the likelihood of the genes constrained to these relationships is summed to provide a likelihood for the relationship. Consensus tree assembly is conducted based on the sum of likelihoods for a given relationship and choosing relationships based on the most likely relationship assuming it does not conflict with a relationship that has a higher likelihood score. If it is not possible for all most likely relationships to be combined into a single bifurcating tree then multiple trees are produced and a consensus tree with a polytomy is created. This procedure allows for more influential genes to have a greater influence on an inferred relationship, does not assume conflict has arisen from any one source and does not force the data set to produce a single bifurcating tree. Using this approach, on three empirical data sets, we examine and discuss the relationship between influence and prevalence of gene tree conflict. We find that in one of the data sets, assembling a bifurcating consensus tree solely composed of the most likely relationships is impossible. To account for conflict in molecular rate analysis we also introduce a concordance-based approach to the summary and estimation of branch lengths suitable for downstream comparative analyses. We demonstrate through simulation that even under high levels of stochastic conflict, the mean and median of the concordant rates recapitulate the true molecular rate better than using a supermatrix approach. Using a large phylogenomic data set, we examine rate heterogeneity across concordant genes with a focus on the branch subtending crown angiosperms. Notably, we find highly variable rates of evolution along the branch subtending crown angiosperms. The approaches outlined here have several limitations, but they also represent some alternative methods for harnessing the complexity of phylogenomic data sets and enrich our inferences of both species relationships and evolutionary processes.[Branch length estimation; consensus tree; gene tree conflict; gene tree filtering; phylogenetics; phylogenomics.]
Lessons from the field: delivering trachoma mass drug administration safely in a COVID-19 context
Authors: Amanyi-Enegela Juliana A , Burn Nicholas , Dirisu Osasuyi , Ebenso Bassey , Sankar Girija , Ishaya Rinpan , Ogoshi Christopher , Kumbur Joseph , Ekweremadu Bright , Qureshi Babar M
Published: July 2021

The first coronavirus disease 2019 (COVID-19) interim guidance released by the World Health Organization recommended suspension of non-urgent community health interventions, including mass drug administration (MDA) for neglected tropical diseases. However, with no end in sight for the COVID-19 pandemic, it was crucial to find ways to restart MDA while testing measures to reduce the risk of COVID-19 transmission between health workers, volunteers and communities. Consequently, guidelines were developed for delivering MDA safely in a COVID-19 context and the training and implementation were assessed through an observation checklist. The study also gathered data on the feasibility of using the MDA platform to disseminate COVID-19 health education. The results suggest that delivering MDA safely in a COVID-19 context is possible but revealed significant challenges in using the MDA platform for COVID-19 education.
Marital Stability Over 10 Years Following Traumatic Brain Injury
Authors: Hammond Flora M. , Sevigny Mitch , Backhaus Samantha , Neumann Dawn , Corrigan John D. , Charles SherylKatta , Gazett Hannah
Published: July 2021

Objective:

To examine the stability of marriage from the time of traumatic brain injury (TBI) to 10 years postinjury.

Design:

Retrospective cohort.

Setting:

TBI Model Systems centers.

Participants:

In total, 1423 participants in the TBI Model Systems National Database who experienced TBI 10 years prior and were married at the time of injury.

Interventions:

Not applicable.

Main Outcome Measure:

Remaining married to the same partner from the time of injury to 10-year follow-up.

Results:

At 10 years, 66% (938) remained married to the same person. Significant associations were found with age at injury (P < .0001), sex (P = .0028), and preinjury problematic substance use (P = .0092). Marital stability over the 10-year period was higher for those who were older, were female, and had no problematic substance use history. Marital instability was greatest in the first year postinjury.

Conclusions:

Most married adults who received inpatient rehabilitation for TBI remained married to the same individual 10 years later. Those who were younger, were male, and had a history of problematic substance use were at a highest risk for relationship dissolution. Findings have implications for content, timing, and delivery of marital interventions. Substance use education and prevention appear to be important aspects of marital support.
Diagnosis and Treatment of Acne Inversa/Hidradenitis Suppurativa in China: An Expert Consensus Statement (2021 Version)#
Authors: Fang Hong , Gao Xing-Hua , Geng Song-Mei , Gu Heng , Gu Jun , He Li , Jiang Xian , Jin Hong-Zhong , Ju Qiang , Kang Xiao-Jing , Lai Wei , Li Cheng-Xin , Li Hang , Li Heng-Jin , Li Shan-Shan , Li Yu-Zhen , Sun Qing , Tao Juan , Wang Baoxi , Wang Gang , Wu Xin-Feng , Xiang Lei-Hong , Xie Hong-Fu , Xu Hao-Xiang , Xu Jin-Hua , Yan Yan , Zheng Zhi-Zhong
Published: July 2021

Acne inversa/hidradenitis suppurativa is a chronic, recurrent, inflammatory skin disease that affects the pilosebaceous units, causinfollicular occlusion. The etiology and pathogenesis of acne inversa/hidradenitis suppurativa involves internal and external factors such as genetic susceptibility, inflammation and immunity, microorganisms, obesity, and smoking. acne inversa/hidradenitis suppurativa is difficult to treat, and the current aim of treatment is to control the frequency and duration of disease flares and improve the quality of life. Treatment protocols for acne inversa/hidradenitis suppurativa should be selected based on the disease severity grade. Medical treatments include antibiotics, retinoids, biologics, immunosuppressive agents, and antiandrogen agents. Adjuvant treatments include surgery and laser/light therapies. This consensus aims to further standardize the diagnosis and treatment procedures of acne inversa/hidradenitis suppurativa in China to facilitate its diagnosis and treatment.
C-tactile touch perception in patients with chronic pain disorders
Authors: Gossrau Gudrun , Klimova Anna , Lapp Hanna Sophie , Frost Marie , Peschel Elisabeth , Weidner Kerstin , Koch Thea , Sabatowski Rainer , Croy Ilona
Published: July 2021

Introduction:

Slow brushing over the skin activates C-tactile nerve fibers that transmit pleasant tactile experiences in healthy subjects, leading to an inverted U-shaped velocity dependence of ratings: C-tactile optimal stroking stimulations are rated as more pleasant than slower or faster stimulations. Chronic pain diseases such as postherpetic neuralgia (PHN) and complex regional pain syndrome show altered C-fiber innervation density, sensory loss, and pain sensitization.

Objectives:

We aimed to investigate whether C-tactile function is affected in painful conditions.

Methods:

We assessed psychophysically C-tactile function and sensory perception thresholds in 16 patients with PHN, 19 patients with complex regional pain syndrome, and 22 healthy controls.

Results:

Assessment of C-tactile function showed a significantly altered perceived pleasantness of CT stimulation between healthy controls and patients with chronic pain. In specific, tactile stimulation was perceived less pleasant on the affected and contralateral side when compared with controls. In patients with PHN, velocity-dependent pleasantness ratings could not be obtained, suggesting highly impaired C-tactile function with functional loss of pleasant touch perception.

Conclusions:

In conclusion, this is the first report of impaired C-tactile function in patients with PHN. Reduced pleasantness resulting from gentle touch can reflect defective C-fiber function or result from central nervous system effects in a chronic pain state.
Streptomyces musisoli sp. nov., an actinomycete isolated from soil
Authors: Duangupama Thitikorn , Intaraudom Chakapong , Pittayakhajonwut Pattama , Suriyachadkun Chanwit , Tadtong Sarin , Sirirote Pramote , Tanasupawat Somboon , Thawai Chitti
Published: July 2021

An actinobacterium, strain CH5-8T, which formed spiral chains of spore arising from the aerial mycelium, was isolated from rhizosphere soil of Musa spp. The organism exhibited vivid greenish yellow substrate mycelium and easily produced the medium grey aerial spore mass on ISP2 medium. The typical chemotaxonomic properties of members of the genus

Streptomyces

were observed for strain CH5-8T, e.g. ll-diaminopimelic acid in cell peptidoglycan, MK-9(H8), MK-9(H6), and MK-9(H4) as major menaquinones and anteiso-C15 : 0, iso-C16 : 0, and anteiso-C17 : 0 as major fatty acids. Diphosphatidylglycerol, phosphatidylethanolamine, hydroxyphosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol and phosphatidylinositol mannoside were detected in the cells. A combination of morphological and chemotaxonomic data supported the assignment to the genus

Streptomyces

. The analysis result obtained for the 16S rRNA gene sequence confirmed the taxonomic affiliation at the genus level of this strain. The novel strain CH5-8T showed the highest 16S rRNA gene sequence values to

Streptomyces echinatus

NBRC 12763T (98.9 %), followed by

Streptomyces actinomycinicus

RCU-197T (98.9 %). The average nucleotide identity by blast (ANIb) and digital DNA–DNA hybridization values between CH5-8T and its closest relatives,

S. echinatus

CECT 3313T and

S. actinomycinicus

RCU-197T, were ≤91.6 % and ≤47.4 %, respectively. The digital DNA G+C content of genomic DNA was 72.1 mol%. On the basis of these phenotypic and genotypic data, strain CH5-8T represents a novel species, for which the name Streptomyces musisoli sp. nov. is proposed. The type strain is CH5-8T (=TBRC 9950T=NBRC 113997T).
A wolf in another wolf’s clothing: Post-genomic regulation dictates venom profiles of medically-important cryptic kraits in India
Authors: Sunagar Kartik , Khochare Suyog , Laxme R R Senji , Attarde Saurabh , Dam Paulomi , Suranse Vivek , Khaire Anil , Martin Gerard , Captain Ashok
Published: July 2021

The Common Krait (Bungarus caeruleus) shares a distribution range with many other ‘phenotypically-similar’ kraits across the Indian subcontinent. Despite several reports of fatal envenoming by otherBungarusspecies, commercial Indian antivenoms are only manufactured againstB. caeruleus. It is, therefore, imperative to understand the distribution of genetically-distinct lineages of kraits, compositional differences in their venoms, and the consequent impact of venom variation on the (pre)clinical effectiveness of antivenom therapy. To address this knowledge gap, we conducted phylogenetic and comparative venomics investigations of kraits in Southern and Western India. Phylogenetic reconstructions using mitochondrial markers revealed a new species of krait, Romulus’ krait (B. romulusi), in Southern India. Additionally, we find that kraits with 17 mid-body dorsal scale rows in Western India do not represent a subspecies of the Sind Krait (B. sindanus walli) as previously believed, but are genetically very similar toB. sindanusin Pakistan. Furthermore, venom proteomics and comparative transcriptomics revealed completely contrasting venom profiles. While the venom gland transcriptomes of all three species were highly similar, venom proteomes and toxicity profiles differed significantly, suggesting the prominent role of post-genomic regulatory mechanisms in shaping the venoms of these cryptic kraits.In vitrovenom recognition andin vivoneutralisation experiments revealed a strong negative impact of venom variability on the preclinical performance of commercial antivenoms. While the venom ofB. caeruleuswas neutralised as per the manufacturer’s claim, performance against the venoms ofB. sindanusandB. romulusiwas alarming, highlighting the need for regionally-effective antivenoms in India.
Glucan unmasking identifies regulators of temperature-induced translatome reprogramming inC. neoformans
Authors: Bloom Amanda L.M. , Goich David , Knowles Corey M. , Panepinto John C.
Published: July 2021

The cell walls of fungi are critical for cellular structure and rigidity, but also serve as a major communicator to alert the cell of the changing environment. In response to stresses encountered in human hosts pathogenic fungi remodel their cell walls. Masking the b-1,3-glucan component of the cell wall is critical to escape detection by innate immune cells. We previously demonstrated that b-1,3-glucan is unmasked in response to host temperature stress when translatome reprogramming is defective inC. neoformans. Here, we used b-1,3-glucan unmasking as an output to identify signaling modules involved both in masking and translatome reprogramming in response to host temperature stress. We reveal that the High Osmolarity Glycerol (HOG) MAPK pathway is involved in translatome reprogramming and that mutants in this pathway display moderate unmasking when grown at 37°C. Additionally, we show that mutants of the Cell Wall Integrity/Mpk1 MAPK pathway extensively unmask b-1,3-glucan. While the CWI pathway does not impact translatome reprogramming, our data suggest it may play a role in the post-translational regulation of transcription factors that govern masking.

Importance

Cryptococcus neoformans is a fungal pathogen that causes devastating morbidity and mortality in immunocompromised individuals. It possesses several virulence factors that aid in its evasion from the host immune system including a large polysaccharide capsule that cloaks the antigenic cell wall. Studies investigating how the cell wall is remodeled to keep this pathogen disguised in response to stress have been limited. We previously found that host temperature stress results in translatome reprogramming that is necessary for keeping the highly antigenic β-(1,3)-glucan component masked. Our data reveals signaling modules that trigger these responses and suggest the points of regulations at which these pathways act in achieving masking. Understanding these mechanisms may allow for therapeutic manipulation that could promote immune recognition and clearance of this fungal pathogen.
Impact of natural selection on global patterns of genetic variation, and association with clinical phenotypes, at genes involved in SARS-CoV-2 infection
Authors: Zhang Chao , Verma Anurag , Feng Yuanqing , Melo Marcelo C. R. , McQuillan Michael , Hansen Matthew , Lucas Anastasia , Park Joseph , Ranciaro Alessia , Thompson Simon , Rubel Meghan A. , Campbell Michael C. , Beggs William , Hirbo Jibril , Mpoloka Sununguko Wata , Mokone Gaonyadiwe George ,   Regeneron Genetic Center, Nyambo Thomas , Meskel Dawit Wolde , Belay Gurja , Fokunang Charles , Njamnshi Alfred K. , Omar Sabah A. , Williams Scott M. , Rader Daniel , Ritchie Marylyn D. , de la Fuente Nunez Cesar , Sirugo Giorgio , Tishkoff Sarah
Published: July 2021

We investigated global patterns of genetic variation and signatures of natural selection at host genes relevant to SARS-CoV-2 infection (ACE2, TMPRSS2, DPP4,andLY6E). We analyzed novel data from 2,012 ethnically diverse Africans and 15,997 individuals of European and African ancestry with electronic health records, and integrated with global data from the 1000GP. AtACE2,we identified 41 non-synonymous variants that were rare in most populations, several of which impact protein function. However, three non-synonymous variants were common among Central African hunter-gatherers from Cameroon and are on haplotypes that exhibit signatures of positive selection. We identify strong signatures of selection impacting variation at regulatory regions influencingACE2expression in multiple African populations. AtTMPRSS2, we identified 13 amino acid changes that are adaptive and specific to the human lineage. Genetic variants that are targets of natural selection are associated with clinical phenotypes common in patients with COVID-19.
The Evolution of Young People’s Mental Health during COVID-19: Evidence from four Low-and-Middle-Income-Countries
Authors: Porter Catherine , Hittmeyer Annina , Favara Marta , Scott Douglas , Sánchez Alan
Published: July 2021

Background

Though COVID-19 presents less risk to young people of serious morbidity or mortality, the resulting economic crisis has impacted their livelihoods. There is relatively little evidence on young people’s mental health in Low-and-Middle-Income-Countries (LMICs) as the pandemic has progressed.

Methods

Two consecutive phone-surveys (August/October and November/December 2020) in Ethiopia, India, Peru and Vietnam interviewed around 9,000 participants of a 20-year cohort study who grew up in poverty (now aged 19 and 26). We investigate how young people’s mental health has evolved in the four countries during the pandemic. Rates of (at least mild) anxiety (depression) measured by GAD-7 (PHQ-8) were compared across countries; between males/females, and food secure/food insecure households.

Results

Overall, rates of at least mild anxiety (depression) significantly decreased in all countries but Ethiopia as infection rates fell. However, young people in food insecure households report high rates of anxiety and depression and have not shown consistent improvements. Food insecure households are poorer, and have significantly more children (p<0.05) except in Ethiopia.

Conclusions

Food insecurity has increased during the COVID-19 pandemic and is negatively associated with young people’s mental health. Urgent support is needed for the most vulnerable.
Navigating sample overlap, winner’s curse and weak instrument bias in Mendelian randomization studies using the UK Biobank
Authors: Sadreev Ildar I , Elsworth Benjamin L , Mitchell Ruth E , Paternoster Lavinia , Sanderson Eleanor , Davies Neil M , Millard Louise AC , Smith George Davey , Haycock Philip C , Bowden Jack , Gaunt Tom R , Hemani Gibran
Published: July 2021

We performed GWAS on 2514 complex traits from the UK Biobank using a linear mixed model, identifying 40,620 independent significant associations (p<5×10−8). We estimate that winner’s curse incurs substantial overestimation of effect sizes in a mean of 35% of discovered associations per trait. We use these results to estimate that the polygenicity of most complex traits is below 10000 common causal variants. We evaluated the impact of winner’s curse on causal effect estimation and hypothesis testing in Mendelian randomization analyses. We show that winner’s curse substantially amplifies the magnitude of weak instrument bias, though any inflation of false discovery rates tends to be low or modest. We designed a process of pseudo-replication within the UK Biobank data to generate GWAS estimates that minimise bias in MR studies using these data. Our resource is integrated into the OpenGWAS platform and enables a convenient framework for researchers to minimise bias or maximise precision of causal effect estimates.
Chemosensory dysfunctions induced by COVID-19 can persist up to 7 months: A study of over 700 healthcare workers
Authors: Bussière Nicholas , Mei Jie , Lévesque-Boissonneault Cindy , Blais Mathieu , Carazo Sara , Gros-Louis Francois , De Serres Gaston , Dupré Nicolas , Frasnelli Johannes
Published: July 2021

Several studies have revealed either self-reported chemosensory alterations in large groups or objective quantified chemosensory impairments in smaller populations of patients diagnosed with COVID-19. However, due to the great variability in published results regarding COVID-19-induced chemosensory impairments and their follow-up, prognosis for chemosensory functions in patients with such complaints remains unclear. Our objective is to describe the various chemosensory alterations associated with COVID-19 and their prevalence and evolution after infection. A cross-sectional study of 704 healthcare workers with a RT-PCR confirmed SARS-CoV-2 infection between 28/2/2020 and 14/6/2020 was conducted 3 to 7 months after onset of symptoms. Data were collected with an online questionnaire. Outcomes included differences in reported chemosensory self-assessment of olfactory, gustatory, and trigeminal functions across time points and Chemosensory Perception Test scores from an easy-to-use at-home self-administered chemosensory test. Among the 704 participants, 593 (84.2%) were women, the mean (SD) age was 42 (12) years, and the questionnaire was answered on average 4.8 (0.8) months after COVID-19. During COVID-19, a decrease in olfactory, gustatory, and trigeminal sensitivities were reported by 81.3%, 81.5% and 48.0% respectively. Three to seven months later, reduced sensitivity was still reported by 52.0%, 41.9% and 23.3% respectively. Chemosensory Perception Test scores indicate that 19.5% of participants had objective olfactory impairment. These data suggest a significant proportion of COVID-19 cases have persistent chemosensory impairments at 3 to 7 months after their infection but the majority of those who had completely lost their olfactory, gustatory, and trigeminal sensitivity have improved.
The penetrance of age-related monogenic disease depends on ascertainment context
Authors: Mirshahi Uyenlinh L , Colclough Kevin , Wright Caroline F , Wood Andrew R , Beaumont Robin N , Tyrrell Jessica , Laver Thomas W , Stahl Richard , Golden Alicia , Goehringer Jessica M , Frayling Timothy F , Hattersley Andrew T , Carey David J , Weedon Michael N , Patel Kashyap A
Published: July 2021

BACKGROUND

Accurate penetrance of monogenic disorders is often unknown due to a phenotype-first approach to genetic testing. Here, we use a genotype-first approach in four large cohorts with different ascertainment contexts to accurately estimate penetrance of the three commonest causes of monogenic diabetes, Maturity Onset Diabetes of the Young (MODY). We contrastHNF1A-MODY /HNF4A-MODY which causes an age-related progressive diabetes andGCK-MODY, which causes life-long mild hyperglycaemia.

METHODS

We analysed clinical and genetic sequencing data from four different cohorts: 1742 probands referred for clinical MODY testing; 2194 family members of the MODY probands; 132,194 individuals from an American hospital-based cohort; and 198,748 individuals from a UK population-based cohort.

RESULTS

Age-related penetrance of diabetes for pathogenic variants inHNF1AandHNF4Awas substantially lower in the clinically unselected cohorts compared to clinically referred probands (ranging from 32% to 98% at age 40yrs forHNF1A, and 21% to 99% forHNF4A). The background rate of diabetes, but not clinical features or variant type, explained the reduced penetrance in the unselected cohorts. In contrast, penetrance of mild hyperglycaemia for pathogenicGCKvariants was similarly high across cohorts (ranging from 89 to 97%) despite substantial variation in the background rates of diabetes.

CONCLUSIONS

Ascertainment context is crucial when interpreting the consequences of monogenic variants for age-related variably penetrant disorders. This finding has important implications for opportunistic screening during genomic testing.
Post COVID-19 sequelae: A prospective observational study from Northern India
Authors: Naik Shivdas , Soneja Manish , Haldar Soumendra , Mundadan Netto George , Garg Prerna , Mittal Ankit , Desai Devashish , Trilangi Praveen Kumar , Chakraborty Sayan , Begam Nazneen Nahar , Bhattacharya Bisakh , Maher Ganesh , Kumar Swathi S , Kirthana J , Arunan Bharathi , Gupta Ankesh , Mahishi Niranjan , Rajanna Chaitra , Parsoon Prateek , Kumar Nikhil A , Maharatna Sayan , Bhattacharya Akashneel , Keri Vishakh C , Samed Sameer A , Adarsh AK , Shareef Imtiyaz , Ravela Neeren , Swain Satish , Sarda Radhika , Kadnur Harshith B , Dudhwal Ashok , Agarwal Ayush , Vedula Kartik , Gupta Ashish , Agarwal Shubham , Anand R , Lalikar Pratima , Jagtap Pallavi , Premjeet B , Kodan Parul , Sethi Prayas , Ray Animesh , Jorwal Pankaj , Kumar Arvind , Nischal Neeraj , Sinha Sanjeev , Biswas Ashutosh , Wig Naveet
Published: July 2021

Background

Long COVID, or post-COVID-19 sequelae, is being seen in a growing number of patients reporting a constellation of symptoms, both pulmonary and extrapulmonary. Studies on COVID-19 recovered patients are scarce. Thus, there is a need to add granularity to our existing knowledge about the course and long-term effects of the infection.

Aim

To describe the clinical details and risk factors of post-COVID sequelae in the North Indian population.

Method

This prospective observational study was conducted at a tertiary healthcare centre in Northern India between October 2020 to February 2021. Patients aged >18 years with a confirmed COVID-19 disease were recruited after at least two weeks of diagnosis and interviewed for any post-COVID-19 symptoms.

Results

Of 1234 patients recruited, who were followed up for a median duration of 91 days (IQR: 45-181 days), 495 (40.11%) patients had symptoms. In 223 (18.1%) patients, the symptoms resolved within four weeks, 150 (12.1%) patients had symptoms till twelve weeks, and 122 (9.9%) patients had symptoms beyond twelve weeks of diagnosis of COVID-19. Most common long COVID-19 symptoms included myalgia (10.9%), fatigue (5.5%), shortness of breath (6.1%), cough (2.1%), disturbed sleep (1.4%), mood disturbances (0.48%) and anxiety (0.6%). The major determinants of developing post-COVID-19 symptoms in the patients were hypothyroidism and the severity of the disease.

Conclusion

Most often, patients complain of myalgias, fatigue, dyspnoea, cough and disturbed sleep. Patients who are hypothyroid or have recovered from moderate to severe COVID-19 are at higher risk of developing post-COVID sequelae. Therefore, a multidisciplinary approach is required to diagnose and manage COVID-19 recovered patients.
Flying in the Face of Adversity: A Drosophila-based Virtual CURE Provides Semester-long Authentic Research Opportunity to the Flipped Classroom
Authors: Waddell Edward A. , Ruiz-Whalen Dara , O’Reilly Alana M. , Fried Nathan T.
Published: July 2021

A call for the integration of research experiences into all biology curricula has been a major goal for educational reform efforts nationally. Course-Based Undergraduate Research Experiences (CUREs) have been the predominant method of accomplishing this, but their associated costs and complex design can limit their wide adoption. In 2020, the COVID-19 pandemic forced programs to identify unique ways to still provide authentic research experiences while students were virtual. We report here a full guide for the successful implementation of a semester-long virtual CURE that uses Drosophila behavioral assays to explore the connection between pain and addiction with the use of a “lab-in-a-box” sent home to students. Individual components were piloted across three semesters and launched as a 100-level introductory course with 19 students. We found that this course increased science identity and successfully improved key research competencies as per the Undergraduate Research Student Self-Assessment (URSSA) survey. This course is ideal for flipped classrooms ranging from introductory biology to upper-level neuroscience courses and can be integrated directly into the lecture period without the need for building a new course. Given the low cost, recent comfort with virtual learning environments, and the current proliferation of flipped biology classrooms following the 2020 pandemic, this curriculum could serve as an ideal project-based active-learning tool for equitably increasing access to authentic research experiences.
A joint distribution framework to improve presence-only species distribution models by exploiting opportunistic surveys
Authors: Escamilla Molgora Juan M. , Sedda Luigi , Diggle Peter , Atkinson Peter M.
Published: July 2021

◦

Aim

We propose a Bayesian framework for modelling species distributions using presence-only biodiversity occurrences obtained from historical opportunistic surveys.

◦

Location

Global applicability with two case studies in south-east Mexico.

◦

Methods

The framework defines a bivariate spatial process separable into ecological and sampling effort processes that jointly generate occurrence observations of biodiversity records. Presence-only data are conceived as incomplete observations where some presences have been filtered out. A choosing principle is used to separate out presences, missing data and absences relative to the species of interest and the sampling observations. The framework provides three modelling alternatives for accounting the spatial autocorrelation structure: independent latent variables (model I); common latent spatial random effect (model II); and correlated latent spatial random effects (model III).

The framework was compared against the Maximum Entropy (MaxEnt) algorithm in two case studies: one for the prediction of pines (Class: Pinopsida), using botanical records as sampling observations and another for the prediction of Flycatchers (Family: Tyranidae), using bird sightings as sampling records.

◦

ăResults

In both case studies, at least one of the proposed models achieved higher predictive accuracy than MaxEnt. The model with correlated spatial effects fit best when the sampling effort was informative, while the one with a shared spatial effect was more suitable in cases with high proportion of non sampled sites.

◦

Main Conclusions

Our approach provides a flexible framework for presence-only SDMs aided by a sampling effort process informed by the accumulated observations of independent and heterogeneous surveys. For the two case studies, the framework provided a model with a higher predictive accuracy than an optimised version MaxEnt.