bluuebunny/crossref_metadata_2025 huggingface dataset:
Habitat complexity and complex signal function – exploring the role of ornamentation
Authors: Wilgers Dustin J , Colton Watts J , Hebets Eileen A
Published: November 2021

Animals often communicate in complex, heterogeneous environments, leading to hypothesized selection for increased detectability or discriminability in signaling traits. The extent to which secondary sexual ornaments have evolved to overcome the challenges of signaling in complex environments, however, remains understudied, especially in comparison to their role as indicator traits. This study tested the hypothesis that the condition-dependent secondary sexual ornamentation in the wolf spider Rabidosa rabida functions to increase detectability/discriminability in visually complex environments. We predicted that male ornamentation would interact with the complexity of the signaling environment to affect male mating success. In particular, we expected ornaments to confer a greater mating advantage when males courted in visually complex environments. To test this, we artificially manipulated male foreleg ornamentation (present/absent) and ran repeated-measures mating trials across laboratory microcosms that represented simple versus complex visual signaling environments. Microcosm visual complexity differed in their background pattern, grass stem color, and grass stem placement. We found that ornamented males mated more often and more quickly than unornamented males across both environments, but we found no support for an ornament-by-environment interaction. Male courtship rate, however, did interact with the signaling environment. Despite achieving the same level of mating success across signaling environments, ornamented males courted less rapidly in complex versus simple environments, although environmental complexity had no influence on unornamented male courtship rates. Our results suggest that the visual complexity of the signaling environment influences the interactive influence of ornamentation and dynamic visual courtship on female mate choice.
Convergent developmental patterns underlie the repeated evolution of adhesive toe pads among lizards
Authors: Griffing Aaron H , Gamble Tony , Cohn Martin J , Sanger Thomas J
Published: November 2021

How developmental modifications produce key innovations, which subsequently allow for rapid diversification of a clade into new adaptive zones, has received much attention. However, few studies have used a robust comparative framework to investigate the influence of evolutionary and developmental constraints on the origin of key innovations, such as the adhesive toe pad of lizards. Adhesive toe pads evolved independently at least 16 times in lizards, allowing us to examine whether the patterns observed are general evolutionary phenomena or unique, lineage-specific events. We performed a high-resolution comparison of plantar scale development in 14 lizard species in Anolis and geckos, encompassing five independent origins of toe pads (one in Anolis, four in geckos). Despite substantial evolutionary divergence between Anolis and geckos, we find that these clades have undergone similar developmental modifications to generate their adhesive toe pads. Relative to the ancestral plantar scale development, in which scale ridges form synchronously along the digit, both padded geckos and Anolis exhibit scansor formation in a distal-to-proximal direction. Both clades have undergone developmental repatterning and, following their origin, modifications in toe pad morphology occurred through relatively minor developmental modifications, suggesting that developmental constraints governed the diversification of the adhesive toe pad in lizards.
Iffy Endorsements
Authors: Kaufmann Magdalena , Kaufmann Stefan
Published: November 2021

Theories of imperatives differ in how they aim to derive the distributional and functional properties of this clause type. One point of divergence is how to capture the fact that imperative utterances convey the speaker’s endorsement for the course of events described. Condoravdi & Lauer (2017) observe that conditionals with imperative consequents (conditionalized imperatives, CIs) are infelicitous as motivations of advice against doing something and take this as evidence for an analysis of imperatives as encoding speaker endorsement. We investigate CIs in further contexts and argue that their account in terms of preferential conflicts fails to capture the more general infelicity of CIs as motivations for or against doing something. We develop an alternative in which imperatives do not directly encode speaker preferences, but express modalized propositions and impose restrictions on the discourse structure (along the lines of Kaufmann, 2012). We show how this carries over to conditionalized imperatives to derive the behavior of CIs, and conclude with a discussion of more general problems regarding an implementation of conditional preferential commitments, an issue that can be avoided on our account of imperatives.
A case of splenic rupture a week after appendectomy
Authors: Deleuze Catherine , Rasmont Celine , Ivanov Todor , Brassart Nicolas , Ghaddab Malek , Romero Stoca Laura , Hossey Didier , Choy Tsy-Yeng , Lemaitre Jean
Published: November 2021

A 52-year-old woman developed atraumatic splenic rupture 1 week after appendectomy for perforated appendicitis. The emergency computed tomography (CT) revealed abscessed appendicitis. We performed a laparoscopic appendectomy and meticulous peritoneal lavage of the right lower quadrant peritonitis. Intravenous antibiotics were prolonged after surgery. Six days after appendectomy, she presented acute signs of hypotensive shock associated with abdominal pain and blood in the pelvic drain. Emergency CT scan revealed splenic rupture with major hemoperitoneum and active splenic bleeding. Embolization of the splenic artery was initially successful, but she relapsed into shock a few hours later. We proceeded to splenectomy. Pathological examination only found inflammation. She was discharged 1 month after the initial operation. Spontaneous splenic rupture is a rare but life-threatening complication of appendicitis with major peritonitis. It must be identified and treated immediately. Colic microbiota could be responsible of acute splenitis and congestion after a bacteremia.
IMGT® databases, related tools and web resources through three main axes of research and development
Authors: Manso Taciana , Folch Géraldine , Giudicelli Véronique , Jabado-Michaloud Joumana , Kushwaha Anjana , Nguefack Ngoune Viviane , Georga Maria , Papadaki Ariadni , Debbagh Chahrazed , Pégorier Perrine , Bertignac Morgane , Hadi-Saljoqi Saida , Chentli Imène , Cherouali Karima , Aouinti Safa , El Hamwi Amar , Albani Alexandre , Elazami Elhassani Merouane , Viart Benjamin , Goret Agathe , Tran Anna , Sanou Gaoussou , Rollin Maël , Duroux Patrice , Kossida Sofia
Published: November 2021

IMGT®, the international ImMunoGeneTics information system®, http://www.imgt.org/, is at the forefront of the immunogenetics and immunoinformatics fields with more than 30 years of experience. IMGT® makes available databases and tools to the scientific community pertaining to the adaptive immune response, based on the IMGT-ONTOLOGY. We focus on the recent features of the IMGT® databases, tools, reference directories and web resources, within the three main axes of IMGT® research and development. Axis I consists in understanding the adaptive immune response, by deciphering the identification and characterization of the immunoglobulin (IG) and T cell receptor (TR) genes in jawed vertebrates. It is the starting point of the two other axes, namely the analysis and exploration of the expressed IG and TR repertoires based on comparison with IMGT reference directories in normal and pathological situations (Axis II) and the analysis of amino acid changes and functions of 2D and 3D structures of antibody and TR engineering (Axis III).
Coronavirus disease 2019 and cardiovascular diseases: collateral damage?
Authors: Pillai Ajay , Lawson Barbara
Published: November 2021

Purpose of review

Cardiovascular involvement in coronavirus disease 2019 (COVID-19) is relatively common and portends an increased risk of morbidity and mortality. Manifestations of myocardial injury may exhibit significant overlap and result in diagnostic uncertainty. This review will summarize recent literature around cardiovascular complications of COVID-19.

Recent findings

Venous thromboembolism, atrial fibrillation, and type II myocardial infarction are observed commonly in COVID-19, while severe acute respiratory syndrome coronavirus 2 viral myocarditis remains quite rare. Although infrequent, COVID-19 vaccination has been associated with myocarditis and pericarditis in young individuals.

Various forms of COVID-19-related myocardial injury have been associated with increased utilization of mechanical ventilation, hemodynamic deterioration, and mortality. Manifestations of myocardial injury in COVID-19 are varied, but share common drivers of illness including sequelae of sepsis, immune-mediated factors, and a prothrombotic state. Understanding the forms of myocardial injury in COVID-19 may aid in rapid diagnosis and treatment.
A Virtual Clinic for DDH Pavlik Harness Monitoring
Authors: Merchant Rajiv M. , Khan Shehzaad A. , Douglas Christine , Edel Penina , Khan Tahir , Eastwood Deborah M.
Published: November 2021

Background:

Pavlik harness (PH) treatment is successful in treating over 90% of newborns with developmental dysplasia of the hip (DDH). There is a need for close supervision, frequent adjustments, size changes, and monitoring of complications. This paper aims to provide a safe criterion for remote follow-up of DDH patients treated in a PH to reduce the risk of COVID-19 (coronavirus disease 2019) exposure to patients, parents, and health practitioners.

Methods:

All infants with stable hips (Graf I, IIa/b/c/d, treated III/IV) with consenting parents after appropriate counseling were enrolled in a virtual clinic. Clinics were conducted using the NHS “Attend anywhere” virtual link service by an extended scope practitioner-specialist physiotherapist and a clinical nurse specialist. The virtual clinic group was compared with a matched cohort of patients from 2018/2019.

Results:

A total of 141 patients were referred to the neonatal hip clinic; 45 patients were eligible for harness treatment and 20 patients were selected for virtual clinics. In total, there were 35 virtual clinic appointments. Each of the patients had an average of 1.7 virtual appointments ranging from 1 to 3 (26.3% of total number of clinics). Age at presentation of the treated group was 7±4.2 weeks and control group 5.7±5.5 weeks (P=0.59). PH duration of the study group was 9±2.6 weeks and the control group, 7.8±2.5 weeks (P=0.12). There were no missed complications at the follow-up face-to-face appointment. Patients saved an average of 76 km total travel distance.

Conclusions:

This study demonstrates adequate evidence that children requiring routine follow-up appointments involving PH adjustment, skincare, and identification of clinical anomalies, can be treated and followed up safely using virtual clinics. Clinical triage of suitable patients for virtual clinic provision must always be made by experienced clinicians. Children presenting with Graf IIa, IIb, IIc, IId, as well as those with stable and improving Graf III at initial diagnoses, had successful treatment with virtual clinic follow-up appointments in this study.

Level of Evidence:

Level IV.
Attitudes and Perceptions Toward the Use of Medical Marijuana by Glaucoma Specialists
Authors: Bergman Zachary , Douglas John , Wang Jiangxia , Idowu Omolola , Kaleem Mona
Published: November 2021

Précis:

With expanding legality of medical marijuana (MMJ) in the United States, it is important for ophthalmologists to have greater understanding of the implications of MMJ and glaucoma treatment and how it can impact their patients.

Purpose:

Previous work has demonstrated that inhaled tetrahydrocannabinol can lower intraocular pressure. The stance of the American Glaucoma Society (AGS) is that MMJ is not an acceptable treatment for glaucoma. The purpose of this study is to evaluate the glaucoma specialists’ perceptions and attitudes toward the use of MMJ for glaucoma.

Methods:

An electronic survey was sent to members of the AGS which addressed attitudes and perceptions on the use of MMJ in the management of glaucoma. Study questions included practitioner demographics, previous experiences with patients discussing the topic, prescribing patterns, and knowledge regarding the use of MMJ for the treatment of glaucoma.

Results:

Thirty-seven percent of respondents reported having patients who cited using MMJ for their glaucoma, and 38% of respondents were asked about MMJ by their patients at least once per week. Fifty-five percent of respondents had patients who asked them for MMJ prescriptions. When asked if they felt if there was a possible role for marijuana in the management of glaucoma patients, 27% of survey takers responded yes. Fourteen percent of survey respondents kept information on MMJ in their office. Finally, 76% of participants responded they would be interested in additional education on the topic.

Conclusions:

Over 25% of the glaucoma specialists responded that MMJ had a role in the treatment of glaucoma, despite the recommendation of the professional society. This group was least likely to have received education on the topic. Given the expanding legality and curiosity of patients with regards to marijuana in the United States, it is important for ophthalmologists to have a greater understanding of the implications of marijuana in glaucoma.
Changes in Nursing Students' Attitudes and Perceptions After Receipt of Enhanced Substance Use-Related Curricular Content
Authors: Finnell Deborah S. , Sanchez Michael , Hansen Bryan R. , Stevens Alicia , Savage Christine L. , Seale J. Paul , Johnson J. Aaron
Published: November 2021

Background

Negative attitudes toward persons who use alcohol and other drugs contribute to suboptimal care. Nurses are in key roles to address the needs of this population, yet they lack the education needed to identify persons who may be at risk because of substance use and intervene accordingly. The purpose of this study was to evaluate the impact of a substance-use-related curriculum on nursing students' attitudes and therapeutic commitment for working with patients with alcohol- and drug-use-related problems.

Methods

Data were collected for four cohorts of 169 nursing students enrolled in a Master's Entry into Nursing program. Questionnaires included the Person-Centered Alcohol and Alcohol Problems Perception Questionnaire and the Drug and Drug Problems Perception Questionnaire, completed before and after completing the curriculum. Paired samples t test were used to examine pre/post differences for each measure's subscale.

Results

Four of the seven Person-Centered Alcohol and Alcohol Problems Perception Questionnaire subscales showing significant increases were role adequacy, role support, role legitimacy, and general perceptions. Four of the five Drug and Drug Problems Perception Questionnaire subscales showing significant increases were role adequacy, role support, job satisfaction, and role legitimacy; there was a significant change in role-related self-esteem, however, in a negative direction.

Conclusions

This study adds to the growing evidence of the positive impact of providing evidence-based information and skill development, which enhance alcohol- and drug-related knowledge and competence for nurses entering professional practice.
Pilot Test of a Definitive Prosthetic Socket Made with 3D Printing Technology
Authors: Nickel Eric , Cataldo Alana , Walker Nicole , Santa Ana Christine , Barrons Kyle , Gravely Amy , Hand Barry , Hansen Andrew
Published: November 2021

Introduction

Additive manufacturing (also known as 3D printing) as a fabrication method is ideally suited to merging the organic shapes of human anatomy with engineered components. Many early adopters are exploring the application of these technologies for the fabrication of 3D-printed sockets, but questions remain regarding the ability to fabricate strong, well-fitting definitive sockets. The goal of the present study was to examine the real-world effect of using 3D-printed sockets with regards to mobility, comfort, balance confidence, and user acceptance.

Materials and Methods

Nine veterans with transtibial amputations participated in the study, three each using pin, sealing sleeve, or seal-in liner for suspension. Participants had their conventional definitive socket duplicated using 3D printing. When the 3D-printed socket was ready, using their conventional socket, participants performed a 2-minute walk test, followed by socket comfort score and rating of perceived exertion (10-point scale), Prosthetic Limb Users Survey of Mobility, Activities-Specific Balance Confidence, select subscales of the Prosthesis Evaluation Questionnaire, and the Amputee Body Image Scale–Revised. After completing the baseline data, participants were fitted with the 3D-printed socket and, after using it for 2 weeks, we repeated the data collection.

Results

Three participants were not able to complete the study. No large differences were observed for any of the measures. Participants were generally satisfied with the fit of the 3D-printed sockets, but there were challenges with getting the 3D-printed sockets to support elevated vacuum with the sealing sleeve and seal-in liner suspension methods.

Conclusions

No differences in performance or user acceptance were identified for pin suspension, but the 3D-printed sockets were not able to reliably support suction or elevated vacuum; further development will be needed before they are ready for clinical application.

Clinical Relevance

The present study has demonstrated the ability to achieve satisfactory fit and outcomes using 3D printing to fabricate definitive prosthetic sockets, but the printing method was unable to deliver consistent air-tight sealing for suction or elevated vacuum suspension. Other 3D printing methods and some secondary processing steps may be able to correct this deficiency.
An Update on Vitamin D Deficiency in the twenty-first century: nature and nurture
Authors: Stoffers Ashley J. , Weber David R. , Levine Michael A.
Published: November 2021

Purpose of review

Here, we review the most up-to-date understanding of the pathogenesis, prevention and treatment of vitamin D deficient rickets in children. This will include recent advances in the genetic determinants of abnormal vitamin D metabolism, with the intention of aiding clinicians with establishing the diagnosis and implementing treatment plans for children presenting with vitamin D deficiency rickets.

Recent findings

Vitamin D deficiency rickets is a frequently encountered, but entirely preventable, disorder of bone mineral metabolism. Risk factors for developing vitamin D deficiency rickets include inadequate exposure to sunlight, exclusive breast feeding without vitamin D supplementation and inadequate intake of vitamin D, calcium or phosphorus. Other factors that may influence the development of vitamin D deficiency and/or rickets include genetic alterations or medications that alter vitamin D metabolism.

Vitamin D levels in individuals are influenced by environmental factors, as well as genetic factors. A thorough understanding of these factors is critical for the evaluation and treatment of a child presenting with rickets. There remains a great need for additional research to determine ideal vitamin D status across diverse populations, and to better understand how vitamin D status affects overall health.
How many is too many? Polyposis syndromes and what to do next
Authors: Gupta Nina , Drogan Christine , Kupfer Sonia S.
Published: November 2021

Purpose of review

The goal of this review is to help providers recognize, diagnose and manage gastrointestinal (GI) polyposis syndromes.

Recent findings

Intestinal polyps include a number of histological sub-types such as adenomas, serrated, hamartomas among others. Over a quarter of individuals undergoing screening colonoscopy are expected to have colonic adenomas. Although it is not uncommon for adults to have a few GI polyps in their lifetime, some individuals are found to have multiple polyps of varying histology throughout the GI tract. In these individuals, depending on polyp histology, number, location and size as well as extra-intestinal features and/or family history, a polyposis syndrome should be considered with appropriate testing and management.

Diagnosis and management of polyposis syndromes has evolved with advent of multigene panel testing and new data on optimal surveillance strategies. Evidence-based recommendations and current practice guidelines for polyposis syndromes are reviewed here. Areas of uncertainty and future research are also highlighted.
Effect of vagus nerve stimulation paired with rehabilitation for upper limb function improvement after stroke: a systematic review and meta-analysis of randomized controlled trials
Authors: Zhao Kehong , Yang Jiaen , Huang Jiapeng , Zhao Ziqi , Qu Yun
Published: November 2021

Vagus nerve stimulation (VNS) could potentially facilitate arm function recovery after stroke. The aim of this review was to evaluate the effect of VNS paired with rehabilitation on upper limb function recovery after stroke. We considered randomized controlled trials (RCTs) that used VNS paired with rehabilitation for the improvement of upper limb function after stroke and were published in English. Eligible RCTs were identified by searching electronic databases, including MEDLINE, Web of Science, Embase, CENTRAL and PEDro, from their inception until June 2021. Quality of included studies was assessed using PEDro score and Cochrane’s risk of bias assessment. A meta-analysis was performed on the collected data. Five studies with a total of 178 participants met the inclusion criteria. Overall, the present meta-analysis revealed a significant effect of VNS on Fugl–Meyer Assessment for Upper Extremity (FMA-UE, MD = 3.59; 95% CI, 2.55–4.63; P < 0.01) when compared with the control group. However, no significant difference was observed in adverse events associated with device implantation between the invasive VNS and control groups (RR = 1.10; 95% CI, 0.92–1.32; P = 0.29). No adverse events associated with device use were reported in invasive VNS, and one was reported in transcutaneous VNS. This study revealed that VNS paired with rehabilitation can facilitate the recovery of upper limb function in patients with stroke on the basis of FMA-UE scores, but the long-term effects remain to be demonstrated.
Repeatability and Reproducibility of ADC Measurements and MRI Signal Intensity Measurements of Bone Marrow in Monoclonal Plasma Cell Disorders
Authors: Wennmann Markus , Thierjung Heidi , Bauer Fabian , Weru Vivienn , Hielscher Thomas , Grözinger Martin , Gnirs Regula , Sauer Sandra , Goldschmidt Hartmut , Weinhold Niels , Bonekamp David , Schlemmer Heinz-Peter , Weber Tim Frederik , Delorme Stefan , Rotkopf Lukas Thomas
Published: November 2021

Background/Objectives

Apparent diffusion coefficient (ADC) and signal intensity (SI) measurements play an increasing role in magnetic resonance imaging (MRI) of monoclonal plasma cell disorders. The purpose of this study was to assess interrater variability, repeatability, and reproducibility of ADC and SI measurements from bone marrow (BM) under variation of MRI protocols and scanners.

Patients and Methods

Fifty-five patients with suspected or confirmed monoclonal plasma cell disorder were prospectively included in this institutional review board–approved study and underwent several measurements after the standard clinical whole-body MR scan, including repeated scan after repositioning, scan with a second MRI protocol, scan at a second 1.5 T scanner with a harmonized MRI protocol, and scan at a 3 T scanner. For T1-weighted, T2-weighted STIR, B800 images, and ADC maps, regions of interest were placed in the BM of the iliac crest and sacral bone, and in muscle tissue for image normalization. Bland-Altman plots were constructed, and absolute bias, relative bias to mean, limits of agreement, and coefficients of variation were calculated.

Results

Interrater variability and repeatability experiments showed a maximal relative bias of −0.077 and a maximal coefficient of variation of 16.2% for all sequences. Although the deviations at the second 1.5 T scanner with harmonized MRI protocol to the first 1.5 T scanner showed a maximal relative bias of 0.124 for all sequences, the variation of the MRI protocol and scan at the 3 T scanner led to large relative biases of up to −0.357 and −0.526, respectively. When comparing the 3 T scanner to the 1.5 T scanner, normalization to muscle reduced the bias of T1-weighted and T2-weighted sequences, but not of ADC maps.

Conclusions

The MRI scanners with identical field strength and harmonized MRI protocols can provide relatively stable quantitative measurements of BM ADC and SI. Deviations in MRI field strength and MRI protocol should be avoided when applying ADC cutoff values, which were established at other scanners or when performing multicentric imaging trials.
Guiding, Intermediating, Facilitating, and Teaching (GIFT)
Authors: Roze des Ordons Amanda L. , Eppich Walter , Lockyer Jocelyn , Wilkie Ryan D. , Grant Vincent , Cheng Adam
Published: November 2021

Introduction

Use of frameworks for simulation debriefing represents best practice, although available frameworks provide only general guidance. Debriefers may experience difficulties implementing broad recommendations, especially in challenging debriefing situations that require more specific strategies. This study describes how debriefers approach challenges in postsimulation debriefing.

Methods

Ten experienced simulation educators participated in 3 simulated debriefings. Think-aloud interviews before and after the simulations were used to explore roles that debriefers adopted and the associated strategies they used to achieve specific goals. All data were audio recorded and transcribed, and a constructivist grounded theory approach was used for analysis.

Results

4 roles in debriefing were identified: guiding, (inter)mediating, facilitating integration, and teaching. Each role was associated with specific goals and strategies that were adopted to achieve these goals. The goal of creating and maintaining a psychologically safe learning environment was common across all roles. These findings were conceptualized as the GIFT debriefing framework.

Conclusions

Our findings highlight the multiple roles debriefers play and how these roles are enacted in postsimulation debriefing. These results may inform future professional development and mentorship programs for debriefing in both simulation-based education and healthcare settings.
Single-cell mtDNA heteroplasmy in colorectal cancer
Authors: Almeida João , Pérez-Figueroa Andrés , Alves João M. , Valecha Monica , Prado-López Sonia , Alvariño Pilar , Cameselle-Teijeiro Jose Manuel , Chantada Debora , Fonseca Miguel M. , Posada David
Published: November 2021

Human mitochondria can be genetically distinct within the same individual, a phenomenon known as heteroplasmy. In cancer, this phenomenon seems exacerbated, and most mitochondrial mutations seem to be heteroplasmic. How this genetic variation is arranged within and among normal and tumor cells is not well understood. To address this question, here we sequenced single-cell mitochondrial genomes from multiple normal and tumoral locations in four colorectal cancer patients. Our results suggest that single cells, both normal and tumoral, can carry various mitochondrial haplotypes. Remarkably, this intra-cell heteroplasmy can arise before tumor development and be maintained afterward in specific tumoral cell subpopulations. At least in the colorectal patients studied here, the somatic mutations in the single-cells do not seem to have a prominent role in tumorigenesis.
Management and containment of a SARS-CoV-2 Beta variant outbreak at the Malawi University of Science and Technology
Authors: Bandawe Gama , Chigwechokha Petros , Kunyenje Precious , Kazembe Yohane , Mwale Jeverson , Kamaliza Madalitso , Mpakati Mtisunge , Nyakanyaka Yanjanani , Makamo Charles , Kimu Saizi , Madanitsa Mwayiwawo , Bangoh Joseph Bitilinyu , Nyirenda Tonney , Luhanga Richard , Sambani Martha , Mvula Benard , Giandhari Jennifer , Pillay Sureshnee , Naidoo Yeshnee , Ramphal Upasana , San James Emmanuel , Tegally Houriiyah , Wilkinson Eduan , de Oliveira Tulio , Malata Address
Published: November 2021

Outbreaks of COVID at university campuses can spread rapidly and threaten the broader community. We describe the management of an outbreak at a Malawian university in April-May 2021 during Malawi’s second wave. Classes were suspended following detection of infections by routine testing and campus-wide PCR mass testing was conducted. Fifty seven cases were recorded, 55 among students, two among staff. Classes resumed 28 days after suspension following two weeks without cases. Just 6.3% of full-time staff and 87.4% of outsourced staff tested while 65% of students at the main campus and 74% at the extension campus were tested. Final year students had significantly higher positivity and lower testing coverage compared to freshmen. All viruses sequenced were beta variant and at least four separate virus introductions onto campus were observed. These findings are useful for development of campus outbreak responses and indicate the need to emphasize staff, males and senior students in testing.

Article Summary Line

Successful management of a campus outbreak using test trace and isolate approach with resumption within a month following suspension of all in-person classes. Trends in voluntary testing by gender, age and year of study that can help in formation of future management approaches.
A fourth dose of the mRNA-1273 SARS-CoV-2 vaccine improves serum neutralization against the delta variant in kidney transplant recipients
Authors: Benotmane Ilies , Bruel Timothée , Planas Delphine , Fafi-Kremer Samira , Schwartz Olivier , Caillard Sophie
Published: November 2021

In immunocompetent subjects, the effectiveness of SARS-CoV-2 vaccines against the delta variant appears three- to five-fold lower than that observed against the alpha variant. Additionally, three doses of SARS-CoV-2 mRNA-based vaccines might be unable to elicit a sufficient immune response against any variant in immunocompromised kidney transplant recipients. This study describes the kinetics of the neutralizing antibody (NAbs) response against the delta strain before and after a fourth dose of a mRNA vaccine in 67 kidney transplant recipients who had experienced a weak antibody response after three doses. While only 16% of patients harbored NAbs against the delta strain prior to the fourth injection – this percentage raised to 66% afterwards. We also found that, after the fourth dose, the NAbs titer increased significantly (p=0.0001) from <7.5 (IQR : <7.5−15.1) to 47.1 (IQR <7.5−284.2). Collectively, our data indicate that a fourth dose of the mRNA-1273 vaccine in kidney transplant recipients with a weak antibody response after three previous doses improves serum neutralization against the delta variant.
Seven chain adaptive immune receptor repertoire analysis in rheumatoid arthritis: association to disease and clinically relevant phenotypes
Authors: Aterido Adrià , López-Lasanta María , Blanco Francisco , Juan-Mas Antonio , García-Vivar María Luz , Erra Alba , Pérez-García Carolina , Sánchez-Fernández Simón Ángel , Sanmartí Raimon , Fernández-Nebro Antonio , Alperi-López Mercedes , Tornero Jesús , Ortiz Ana María , Fernández-Cid Carlos Marras , Palau Núria , Pan Wenjing , Byrne-Steele Miranda , Starenki Dmytro , Weber Daniel , Rodriguez-Nunez Ivan , Han Jian , Myers Richard M. , Marsal Sara , Julià Antonio
Published: November 2021

Rheumatoid arthritis (RA) is an immune-mediated inflammatory disease characterized by a defective adaptive immune receptor repertoire (AIRR) that fails to distinguish self from non-self antigens. The AIRR is vast, encompassing four T cell receptor (TCR) and three B cell receptor (BCR) chains, each of which displays an extraordinary amino acid sequence variability in the antigen-binding site. How the concerted action of T and B cell clones is associated with the development and clinical evolution of immune-mediated diseases is still not known. Using a new immunosequencing technology that allows the unbiased amplification of the seven receptor chains, we conducted an in-depth quantitative analysis of the seven-receptor chain variability in RA. Compared to healthy controls, the AIRR in RA was found to be characterized by a lower BCR diversity, the depletion of highly similar BCR clones, an isotype-specific signature as well as a skewed IGL chain and gene segment usage. A predictor based on quantitative multi-chain AIRR information was able to accurately predict disease, including the elusive seronegative subset of RA patients. AIRR features of the seven immune receptor chains were also different between patients with distinct clinically relevant phenotypes. Incorporating HLA variation data, we were able to identify the TCR clones that are specifically associated with the main disease risk variants. The longitudinal analysis of the AIRR revealed that treatment with Tumor Necrosis Factor (TNF) inhibitors selectively restores the diversity of B cell clones in RA patients by reducing the frequency of clones with a similar biochemical profile. The biochemical properties of the TNFi-modulated clones were also found to differ between responders and non-responders, supporting a different antigenic reactivity in the B cell compartment of these two groups of RA patients. Our comprehensive analysis of the TCR and BCR repertoire reveals a complex T and B cell architecture in RA, and provides the basis for precision medicine strategies based on the highly informative features of the adaptive immune response.
Evaluation of Mycobacterium tuberculosis-specific IFN-γ, TNF-α, CXCL10, IL2, CCL2, CCL7 and CCL4 levels for active tuberculosis diagnosis
Authors: Fries Anastasia , Mandagere Vinayak , Parker Robert , Tolosa-Wright Mica , Berrocal-Almanza Luis C. , Hoang Long , Boakye Aime , Halliday Alice , Lalvani Ajit
Published: November 2021

Our study evaluates seven previously reported biomarkers for active tuberculosis (ATB) diagnosis. We compared Mycobacterium tuberculosis-specific IFN-γ, TNF-α, CXCL10, IL2, CCL2, CCL7 and CCL4 levels in patients with ATB and non-tuberculosis respiratory diseases. Our ATB group included equal numbers of patients with positive and negative QuantiFERON-TB Gold In-Tube (QFT-GIT) results, to assess whether any biomarker offered superior diagnostic accuracy to IFN-γ. No biomarker achieved higher sensitivity than QFT-GIT for ATB diagnosis without significant loss of specificity. Our study design provides an efficient strategy for rapidly gating future biomarkers by using clinically relevant and representative patient groups in whom current QFT-GIT tests fail.
Modelling the interplay of SARS-CoV-2 variants in the United Kingdom
Authors: Barreiro N. L. , Govezensky T. , Ventura C. I. , Núñez M. , Bolcatto P. G. , Barrio R. A.
Published: November 2021

Most COVID-19 vaccines have proved to be effective to combat the pandemic and to prevent severe disease but their distribution proceeds in a context of global vaccine shortage Their uneven distribution favors the appearance of new variants of concern, as the highly transmissible Delta variant, affecting especially non-vaccinated people. We consider that devising reliable models to analyse the spread of the different variants is crucial. These models should include the effects of vaccination as well as non-pharmaceutical measures used to contain the pandemic by modifying social behaviour. In this work, we present a stochastic geographical model that fulfills these requirements. It consists of an extended compartmental model that includes various strains and vaccination strategies, allowing to study the emergence and dynamics of the new COVID-19 variants. The models conveniently separates the parameters related to the disease from the ones related to social behavior and mobility restrictions. The geographical spread of the virus is modeled taking into account the actual population distribution in any given country of interest. Here we choose the UK as model system, taking advantage of the reliable available data, in order to fit the recurrence of the currently prevalent variants. Our computer simulations allow to describe some global features observed in the daily number of cases, as the appearance of periodic waves and the features that determine the prevalence of certain variants. They also provide useful predictions aiming to help planning future vaccination boosters. We stress that the model could be applied to any other country of interest.
Persistent racial/ethnic associated disparity in anti-tumor effectiveness of immune checkpoint inhibitors despite equal access
Authors: Florez M.A. , Kemnade J.O. , Chen N. , Du W. , Sabichi A. L. , Wang D.Y. , Huang Q. , Miller-Chism C.N. , Jotwani A , Chen A.C. , Hernandez D. , Sandulache V.C.
Published: November 2021

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of both lung cancer and head and neck squamous cell carcinoma demonstrating clear benefit over traditional chemotherapy alone in the metastatic setting. While the overwhelming majority of ICI trial participants have been White patients, results of these trials have been broadly applied to patients of all ethnic/racial backgrounds. It has, therefore, not been well defined if response to ICIs differs between ethnic/racial populations or socio-economic groups.

We reviewed response to ICI of 208 patients with diagnoses of lung or head and neck cancers treated with ICI between 2015 and 2020 at one of three clinical pavilions associated with the Dan L. Duncan Comprehensive Cancer Center at Baylor College of Medicine in Houston, TX. Two of these pavilions (Harris Health System and the Michael E. DeBakey Veterans Affairs Medical Center) serve large minority patient populations and provide equal access of care to patients regardless of means. Of the 208 patients, 175 had a diagnosis of lung cancer [non-small cell lung carcinoma (NSCLC) or small cell lung cancer (SCLC)] and 33 had a diagnosis of head and neck squamous cell carcinoma (HNSCC); 38% self-identified as Black, 45% as non-Hispanic White, and 18% as Hispanic. The objective response rate (ORR) was similar for lung cancer (31.4%) and HNSCC patients (27.3%) (p=0.894). Statistically, the ORR for Hispanic and Black patients did not differ compared to non-Hispanic White patients (H 23.7%, B 28.6%, W 35.5%; H vs. W p=0.189; B vs. W p=0.338). When considering patients treated with ICI monotherapy, the ORR for Hispanic patients dropped to 13.3% and was significantly lower than the ORR of the non-Hispanic White patients while the ORR of Black and non-Hispanic White patients remained about the same (B 29.3% and W 34.6%, H vs. W p=0.0285; B vs. W p=0.5131). Immune related adverse events (irAEs) were the lowest in the Hispanic population occurring in only 30% of patients compared to 50% of patients exhibiting irAEs in the Black and non-Hispanic white cohorts.

ICIs demonstrate comparable anti-tumor effects in lung cancer (NSCLC + SCLC) and HNSCC during routine clinical practice regardless of race or ethnicity. The significantly lower ORR observed in our cohort for Hispanic patients, particularly when used as monotherapy, is an unexpected finding and will require additional study to identify potential biological and non-biological confounders which could contribute to reduced ICI effectiveness in this patient population.
The subcortical morphology correlates of autistic traits in school-age children: a population-based neuroimaging study
Authors: Sharp T.H. , Elsabbagh M. , Pickles A. , Bedford R.
Published: November 2021

Background

There is emerging evidence that the neuroanatomy of autism forms a spectrum which extends into the general population. However, whilst several studies have identified cortical morphology correlates of autistic traits, it is not established whether morphological differences are present in the subcortical structures of the brain. Additionally, it is not clear to what extent previously reported structural associations may be confounded by co-occurring psychopathology. To address these questions, we utilised neuroimaging data from the Adolescent Brain Cognitive Development Study to assess whether a measure of autistic traits was associated with differences in child subcortical morphology, and if any observed differences persisted after adjustment for child internalising and externalising symptoms.

Methods

Our analyses included data from 7,005 children aged 9-10 years (female: 47.19%) participating in the Adolescent Brain Cognitive Development Study. Autistic traits were assessed using scores from the Social Responsiveness Scale. Volumes of subcortical regions-of-interest were derived from structural magnetic resonance imaging data.

Results

Overall, we did not find strong evidence for an association of autistic traits with differences in subcortical morphology in this sample of school-aged children. Whilst lower absolute volumes of the nucleus accumbens and putamen were associated with higher scores of autistic traits, these differences did not persist once a global measure of brain size was accounted for.

Conclusions

These findings from our well-powered study suggest that other metrics of brain morphology, such as cortical morphology or shape-based phenotypes, may be stronger candidates to prioritise when attempting to identify robust neuromarkers of autistic traits.
A generic method and software to estimate the transmission advantage of pathogen variants in real-time : SARS-CoV-2 as a case-study
Authors: Bhatia Sangeeta , Wardle Jack , Nash Rebecca K , Nouvellet Pierre , Cori Anne
Published: November 2021

Recent months have demonstrated that emerging variants may set back the global COVID-19 response. The ability to rapidly assess the threat of new variants in real-time is critical for timely optimisation of control strategies.

We extend the EpiEstim R package, designed to estimate the time-varying reproduction number (Rt), to estimate in real-time the effective transmission advantage of a new variant compared to a reference variant. Our method can combine information across multiple locations and over time and was validated using an extensive simulation study, designed to mimic a variety of real-time epidemic contexts.

We estimate that the SARS-CoV-2 Alpha variant is 1.46 (95% Credible Interval 1.44-1.47) and 1.29, (95% CrI 1.29-1.30) times more transmissible than the wild type, using data from England and France respectively. We further estimate that Beta and Gamma combined are 1.25 (95% CrI 1.24-1.27) times more transmissible than the wildtype (France data). All results are in line with previous estimates from literature, but could have been obtained earlier and more easily with our off-the-shelf open-source tool.

Our tool can be used as an important first step towards quantifying the threat of new variants in real-time. Given the popularity of EpiEstim, this extension will likely be used widely to monitor the co-circulation and/or emergence of multiple variants of infectious pathogens.

Significance Statement

Early assessment of the transmissibility of new variants of an infectious pathogen is critical for anticipating their impact and designing appropriate interventions. However, this often requires complex and bespoke analyses relying on multiple data streams, including genomic data. Here we present a novel method and software to rapidly quantify the transmission advantage of new variants. Our method is fast and requires only routinely collected disease surveillance data, making it easy to use in real-time. The ongoing high level of SARS-CoV-2 circulation in a number of countries makes the emergence of new variants highly likely. Our work offers a powerful tool to help public health bodies monitor such emerging variants and rapidly detect those with increased transmissibility.
It Takes Two to Tango: Combining Conventional Culture with Molecular Diagnostics Enhances Accuracy of Streptococcus pneumoniae Detection and Pneumococcal Serogroup/Serotype determination in Carriage
Authors: Miellet Willem R. , van Veldhuizen Janieke , Litt David , Mariman Rob , Wijmenga-Monsuur Alienke J. , Badoux Paul , Nieuwenhuijsen Tessa , Thombre Rebecca , Mayet Sanaa , Eletu Seyi , Sheppard Carmen , van Houten Marlies A. , Rots Nynke Y. , Miller Elizabeth , Fry Norman K. , Sanders Elisabeth A.M. , Trzciński Krzysztof
Published: November 2021

Background

The specificity of molecular methods for the detection of Streptococcus pneumoniae carriage is under debate. We propose a procedure that increases the accuracy of molecular detection of live pneumococci in polymicrobial respiratory samples.

Methods

Culture and qPCR methods were applied to detect S. pneumoniae and pneumococcal serotypes in 1549 nasopharyngeal samples collected in the Netherlands (n=972) and England (n=577) from 946 toddlers and 603 adults, and in paired oropharyngeal samples collected exclusively from 319 Dutch adults. Samples with no live pneumococci isolated at primary diagnostic culture yet generating pneumococcus-specific signal in qPCRs were re-examined with a second, qPCR-guided culture. Optimal Cq cut-offs for positivity in qPCRs were determined via receiver operating characteristic (ROC) curve analysis using isolation of live pneumococci from the primary and qPCR-guided cultures as reference.

Results

Detection of S. pneumoniae and pneumococcal serotypes with qPCRs in cultured (culture-enriched) nasopharyngeal samples exhibited near-perfect agreement with conventional culture (Cohen’s kappa: 0.95). Molecular methods also displayed increased sensitivity of detection for multiple serotype carriage. Among paired samples from adults, the sensitivity of S. pneumoniae detection in primary nasopharyngeal plus oropharyngeal cultures was significantly lower compared with molecular detection in both culture-enriched samples together (p<0.0001) and also in culture-enriched oropharyngeal samples alone (p<0.05).

Conclusions

The sensitivity of S. pneumoniae carriage surveillance can be greatly improved by complementing conventional culture with qPCR and vice versa. The specificity of molecular methods for the detection of live pneumococci can be enhanced by incorporating statistical procedures based on ROC curve analysis. The procedure we propose improves detection of S. pneumoniae carriage in adults in particular and enhances specificity of serotype carriage detection.