bluuebunny/crossref_metadata_2025 huggingface dataset:
Influenza: clinical aspects, diagnosis, and treatment
Authors: Sukhdeo Sharon , Lee Nelson
Published: February 2022

Purpose of review

To review the clinico-epidemiological aspects of influenza in the context of the Coronavirus Disease 2019 (COVID-19) pandemic; the recent advances in point-of-care molecular diagnostics and co-detection of influenza and coronaviruses, and the development of new influenza therapeutics.

Recent findings

Rates of influenza have declined globally since the 2020–2021 season; waning population immunity and uncertainty in vaccine strains could pose a risk in its significant resurgence, especially where pandemic public health interventions start being lifted. As symptoms are similar for influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, accurate, rapid diagnostics are needed to guide management. In addition to neuraminidase inhibitors, newer class of antivirals including polymerase inhibitors show promise in treating influenza infections in adults, children, and high-risk individuals.

This review summarizes the most recent data on rapid molecular diagnostics, including point-of-care tests and co-detection of influenza and SARS-CoV-2 viruses. The implications to inform clinical and infection control practices, and detection of antiviral resistance are discussed. The latest clinical trial data on neuraminidase inhibitors and polymerase inhibitors, their efficacy, limitations, and resistance concerns are reviewed.
The role of social media in promoting vaccine hesitancy
Authors: Clark Shannon E. , Bledsoe Megan C. , Harrison Christopher J.
Published: February 2022

Purpose of review

To offer: (1) Insight into the antivaccine movement's use of social media negatively impacting vaccine hesitancy and disease outbreaks, (2) Examples via case observations, and (3) Selected resources to combat vaccine hesitancy.

Recent findings

For the past 25 years, daily social media usage has risen continually, allowing information to spread widely to a reading/listening/viewing audience via mostly unvetted social media sites. During a pandemic/epidemic (e.g., coronavirus disease 2019 pandemic), an overabundance of information from many sources, including social media, has led to what is now termed as an ’infodemic’. Infodemics arise from overwhelming amounts of both correct and incorrect information from experts and nonexperts alike. Differentiating correct from incorrect information is difficult for social media users who can be swayed by nonscientific ’influencers’ or fear-mongering more than by vetted expert scientific information. Consequently, vaccine misinformation is steadily increasing via social media, the use of which is often believed to be associated with vaccine hesitancy. Stopping the spread of misinformation has been a difficult task.

Vaccine misinformation on social media has been detrimental to public health. Vaccine advocates must increase the use of social media to the advantage of public health in the persistent struggle against vaccine hesitancy/refusal.
Toward greater nuance in delayed cord clamping
Authors: Marrs Laura , Niermeyer Susan
Published: February 2022

Purpose of review

For over a decade, the International Liaison Committee on Resuscitation has recommended delayed cord clamping (DCC), but implementation has been variable due to lack of consensus on details of technique and concerns for risks in certain patient populations. This review summarizes recent literature on the benefits and risks of DCC in term and preterm infants and examines alternative approaches such as physiologic-based cord clamping or intact cord resuscitation (ICR) and umbilical cord milking (UCM).

Recent findings

DCC improves hemoglobin/hematocrit among term infants and may promote improved neurodevelopment. In preterms, DCC improves survival compared to early cord clamping; however, UCM has been associated with severe intraventricular hemorrhage in extremely preterm infants. Infants of COVID-19 positive mothers, growth-restricted babies, multiples, and some infants with cardiopulmonary anomalies can also benefit from DCC. Large randomized trials of ICR will clarify safety and benefits in nonvigorous neonates. These have the potential to dramatically change the sequence of events during neonatal resuscitation.

Umbilical cord management has moved beyond simple time-based comparisons to nuances of technique and application in vulnerable sub-populations. Ongoing research highlights the importance of an individualized approach that recognizes the physiologic equilibrium when ventilation is established before cord clamping.
IgA vasculitis nephritis
Authors: Nüsken Eva , Weber Lutz T.
Published: February 2022

Purpose of review

The purpose of this update is to summarize current knowledge on the pathophysiology of immunglobulin A (IgA) vasculitis nephritis (IgAVN) as well as to critically review evidence for established therapeutic regimes and available biomarkers. An additional purpose is to raise the discussion what could be done to further improve our understanding of IgAVN, identify patients at risk for adverse outcome and increase the evidence for therapy recommendations.

Recent findings

Clinical and experimental studies have established the concept of a multilevel pathogenesis. Toll-like-receptor activation, B cell proliferation, micro-RNAs and complement activation have been identified or confirmed as potential therapeutic targets which can modify the course of the disease. Currently, kidney injury molecule-1, monocyte chemotactic protein-1, N-acetyl-β-glucosaminidase, and angiotensinogen are the most promising urinary biomarkers for early diagnosis of renal involvement in IgA vasculitis.

Close surveillance of all IgAV patients for renal involvement is recommended. Given the multilevel pathogenesis, early treatment of even mild cases should be initiated. Further therapeutic options should be considered in case first-line therapy (mostly corticosteroids) has no effect. The evidence supporting current therapeutic regimes is predominantly based on expert opinion. Prospective studies are needed and should involve substances inhibiting B cell proliferation and complement activation.
Derivation of the Pediatric Acute Gastroenteritis Risk Score to Predict Moderate‐to‐Severe Acute Gastroenteritis
Authors: Levine Adam C. , O'Connell Karen J. , Schnadower David , VanBuren T. John M. , Mahajan Prashant , Hurley Katrina F. , Tarr Phillip , Olsen Cody S. , Poonai Naveen , Schuh Suzanne , Powell Elizabeth C. , Farion Ken J. , Sapien Robert E. , Roskind Cindy G. , Rogers Alexander J. , Bhatt Seema , Gouin Serge , Vance Cheryl , Freedman Stephen B. ,   Pediatric Emergency Research Canada (PERC) the Pediatric Emergency Care Applied Research Network (PECARN)
Published: February 2022

Objectives:

Although most acute gastroenteritis (AGE) episodes in children rapidly self‐resolve, some children go on to experience more significant and prolonged illness. We sought to develop a prognostic score to identify children at risk of experiencing moderate‐to‐severe disease after an index emergency department (ED) visit.

Methods:

Data were collected from a cohort of children 3 to 48 months of age diagnosed with AGE in 16 North American pediatric EDs. Moderate‐to‐severe AGE was defined as a Modified Vesikari Scale (MVS) score ≥9 during the 14‐day post‐ED visit. A clinical prognostic model was derived using multivariable logistic regression and converted into a simple risk score. The model's accuracy was assessed for moderate‐to‐severe AGE and several secondary outcomes.

Results:

After their index ED visit, 19% (336/1770) of participants developed moderate‐to‐severe AGE. Patient age, number of vomiting episodes, dehydration status, prior ED visits, and intravenous rehydration were associated with MVS ≥9 in multivariable regression. Calibration of the prognostic model was strong with a P value of 0.77 by the Hosmer‐Lemenshow goodness‐of‐fit test, and discrimination was moderate with an area under the receiver operator characteristic curve of 0.68 (95% confidence interval [CI] 0.65–0.72). Similarly, the model was shown to have good calibration when fit to the secondary outcomes of subsequent ED revisit, intravenous rehydration, or hospitalization within 72 hours after the index visit.

Conclusions:

After external validation, this new risk score may provide clinicians with accurate prognostic insight into the likely disease course of children with AGE, informing disposition decisions, anticipatory guidance, and follow‐up care.
Pediatric Eosinophilic Esophagitis is Associated With Low Baseline Impedance
Authors: Eldredge Jessica A. , Omari Taher I. , Moore David J.
Published: February 2022

Background and Aims:

Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder that requires repeat endoscopic evaluation(s) to assess response to treatment. This results in high health care costs and a procedural burden in affected children. Noninvasive alternate modalities to reassess disease activity have not been established. Low baseline impedance measured by multichannel pH impedance (pH‐MII) is seen in adults with EoE, in keeping with poor mucosal integrity. We aimed to investigate the relationship between esophageal eosinophilia (or severity of eosinophilic infiltration) and baseline impedance in children with EoE.

Methods:

We retrospectively identified 15 children diagnosed with EoE at our institution who had undergone pH‐MII within 30 days of 3‐level esophageal biopsy. This group were not concurrently prescribed proton pump inhibitors and had negligible reflux parameters on pH‐MII. Average impedance baseline was calculated upper, mid, and lower esophageal segments via baseline impedance automated analysis (RIAA) and mean nocturnal baseline impedance (MNBI) methods. Eosinophil count data for upper, mid, and lower esophageal segments in the EoE group was collated.

Results:

A significantly lower baseline impedance was seen across the esophageal length in children with EoE, compared with 30 controls who had no differences in age or reflux burden on nonparametric testing. A relationship between baseline impedance and eosinophil number at corresponding esophageal segments was not established.

Conclusions:

Baseline impedance may be an important, less invasive adjunct in clinical practice to monitor treatment response in children with EoE. Larger prospective cohort studies should delineate optimally predictive baseline impedance thresholds for active and inactive disease.
Evaluation of Risk for Thromboembolic Events in Pediatric Inflammatory Bowel Disease
Authors: Dilillo Anna , Del Giudice Emanuela , Cucchiara Salvatore , Viola Franca , Maliardo Saverio , Isoldi Sara , lorfida Donatella , Bloise Silvia , Marcellino Alessia , Martucci Vanessa , Sanseviero Mariateresa , De Luca Enrica , Protano Carmela , Marotta Daniela , Ventriglia Flavia , Lubrano Riccardo
Published: February 2022

Objectives:

The occurrence of thrombotic events in adult patients with inflammatory bowel disease (IBD) is linked to multiple interactions between hereditary and acquired risk factors. There are few published data concerning children with iBD. The aim of this study was to investigate the presence of thromboembolic risk factors also in children with iBD.

Methods:

We enrolled three groups of children: one with Crohn disease (cD), one with ulcerative colitis (Uc), and a control group of healthy subjects. For all the participants the potential thromboembolic risk was evaluated clinically and with laboratory tests.

Results:

We studied: 30 children (25.6%) with CD, 28 (23.9%) with UC, and 59 (50.4%) healthy control subjects. Regarding Pediatric Crohn Disease Activity Index, no significant differences between thromboembolic risk factors and disease activity were detected. Instead, in the patients with UC, stratified with the Pediatric Ulcerative Colitis Activity Index, there was a statistically significant difference in serum fibrinogen levels between patients with mild and moderate/severe disease [3.8 (3.2–4.5) g/L vs 5.7 (4.8–6.2) g/L, P < 0.0032]. serum homocysteine levels were lower in healthy controls than in CD (P = 0.176) and UC (P = 0.026). An increased level ofhomocysteine in UC with a homozygous mutation in the methylene tetrahydrofolate reductase C677T gene was also observed.

Conclusions:

Our study showed that children with IBD have clinical features, acquired and congenital factors that can increase thrombotic risk, similarly to adults.
Neurogenin-3 Enteric Endocrinopathy: A Rare Case of Pediatric Congenital Diarrhea and Diabetes Mellitus
Authors: Francis Kendra L. , Verma Arushi , Pacheco M. Cristina , Wendel Danielle , Vue Padade M. , Hu Shannon J. , Scarlett Jarrad M.
Published: February 2022

Disorders of intestinal enteroendocrine cells (EEC) are a rare cause of congenital diarrhea and diabetes. The gene NEUROG3 is essential in EEC differentiation, and mutations in this gene lead to a paucity of EEC in the intestine and pancreas, often presenting clinically as congenital diarrhea and diabetes mellitus. We present the earliest known diagnosis of NEUROG3-associated enteric endocrinopathy, which was identified on a neonatal diabetes genetic panel sent at 4 weeks of age. Our patient presented with severe diarrhea, malnutrition, electrolyte derangements, and neonatal diabetes. He was started on parenteral nutrition at 3 months of age for nutritional and hydration support and required long-acting insulin for his diabetes. We demonstrate significant reduction in EEC, including cells expressing glucagon-like peptide-1, in intestinal biopsies from our patient, raising the possibility that loss of glucagon-like peptide-1 contributes to NEUROG3-associated diarrhea and diabetes mellitus. This case advances our understanding of the presentation, diagnosis, and management of this rare disease.
COVID-19 in Kidney Transplant Recipient and Waitlist Patients
Authors: Dong Yuchen , Dhingra Anant , Shamir Stephanie B. , Azzi Yorg A. , Ye Kenny , Greenstein Stuart M. , Haramati Linda B.
Published: February 2022

Purpose:

To evaluate the chest radiographic severity score (CXR-SS) for coronavirus disease 2019 (COVID-19) patients who are kidney transplant recipients compared with patients on the waitlist.

Study Design and Methods:

This retrospective cohort includes 78 kidney transplant recipients (50 men, mean age 59.9±11.9 y) and 59 kidney transplant waitlist patients (33 men, mean age 58.8±10.8 y) diagnosed with COVID-19 between March 15 and May 30, 2020 with reverse transcriptase-polymerase chain reaction. Patient chest radiographs were divided into 6 zones and examined for consolidation. Primary outcome was mortality. Secondary outcomes included hospital admission, intensive care unit (ICU) admission, and intubation. Predictors of our primary and secondary outcomes were identified by bivariate analysis and multivariate regression analysis.

Results:

No significant difference was found in CXR-SS between 2 groups (P=0.087). Transplant recipients had significantly higher rates of hospitalization (odds ratio, 6.8; 95% confidence interval: 1.7, 39.3; P<0.001), ICU admission (odds ratio, 6.5; 95% confidence interval [CI]: 1.8-35.9; P=0.002), intubation (odds ratio, 11; 95% CI: 2.4-96.9; P=0.001), and mortality (odds ratio, 17; 95% CI: 3.9-153.1; P<0.001). A higher CXR-SS was not predictive of mortality, intubation, or ICU admission. CXR-SS was associated with hospital admission overall (odds ratio, 1.613; 95% CI: 1.04-2.49; P=0.0314).

Conclusion:

The CXR-SS was not predictive of mortality, ICU admission or intubation in our population. Kidney transplant patients with COVID-19 had near universal hospital admission, more than one-third mortality and about a quarter were intubated and admitted to the ICU—all significantly worse outcomes than for patients on the transplant waitlist.
Atypical Causes of Dyspnea
Authors: Hoffman Ryan J. , Garner Hillary W. , Rojas Carlos A. , Grage Rolf A. , Sonavane Sushilkumar K. , Johnson Elizabeth M. , Mergo Patricia J. , Walker Christopher M. , Stowell Justin T.
Published: February 2022

Dyspnea is a common presenting symptom among patients with cardiopulmonary diseases. However, several neuromuscular and chest wall conditions are often overlooked and under-recognized causes of dyspnea. These disorders frequently adversely affect the structure and function of the ventilatory pump (diaphragm, accessory muscles of ventilation) and can precipitate respiratory failure despite normal lung parenchyma. Weakened musculature impairs clearance of airway secretions leading to aspiration and pneumonia, further compromising respiratory function. Radiologists should be aware of the pathophysiology and imaging manifestations of these conditions and might suggest them to be causes of dyspnea which otherwise may not have been considered by referring clinicians.
Burn Scar Ectropion Correction
Authors: Zucal Isabel , Waldner Matthias , Shojaati Golnar , Schweizer Riccardo , Klein Holger J. , Giovanoli Pietro , Plock Jan A.
Published: February 2022

Background

Eyelid scarring after severe burn injury of the face is a significant complication endangering vision in addition to the burn scar sequelae. Scar contraction leads to asymmetry and malposition of the eyelid axis, resulting in corneal exposure, eyelid retraction, and incomplete eyelid closure. In consequence, dryness and irritation of the cornea can lead to keratitis, corneal opacity, and vision impairment. In this study, we present our surgical technique for lateral canthopexy in combination with full-thickness skin grafting (FTSGing) in patients with eyelid axis distortion after scar contraction of the periorbital region after severe burn injuries of the face.

Methods

In this retrospective, single-center case study, we present 5 consecutive patients who experienced severe burn injuries to the face between 2014 and 2019. Patients were suffering from ectropion and malposition of the eyelid axis. In all cases, we performed lateral transosseous canthopexy and FTSGing.

Results

Improved symmetry and complete eyelid closure were restored in all 5 patients. The following ophthalmological examinations showed resolved corneal erosions, as well as reduction of chemosis and epiphora. Further vision impairment was successfully prohibited. Surgical revision with FTSGing was required in 2 patients because of recurrence of unilateral lower eyelid retraction.

Conclusions

Lateral transosseous canthopexy represents a suitable surgical method to durably correct eyelid malposition, ectropion, and incomplete lid closure in patients with severe scarring of the periorbital region after burns of the face. Early detection of patients at risk and timing of surgical intervention are of great importance.
A new stem-varanid lizard (Reptilia, Squamata) from the early Eocene of China
Authors: Dong Liping , Wang Yuan-Qing , Zhao Qi , Vasilyan Davit , Wang Yuan , Evans Susan E.
Published: February 2022

Monitor lizards (genusVaranus) are today distributed across Asia, Africa and Australasia and represent one of the most recognizable and successful lizard lineages. They include charismatic living species like the Komodo dragon of Indonesia and the even larger extinctVaranus prisca(Megalania) of Australia. The fossil record suggests that living varanids had their origins in a diverse assemblage of stem (varaniform) species known from the Late Cretaceous of China and Mongolia. However, determining the biogeographic origins of crown-varanids has proved problematic, with Asia, Africa and Australia each being proposed. The problem is complicated by the fragmentary nature of many attributed specimens, and the fact that the most widely accepted, and most complete, fossil of a stem-varanid, that ofSaniwa ensidens, is from North America. In this paper, we describe a well-preserved skull and skeleton of a new genus of stem-varanid from the Eocene of China. Phylogenetic analysis places the new genus as the sister taxon ofVaranus,suggesting that the transition from Cretaceous varaniform lizards toVaranusoccurred in East Asia before the origin and dispersal ofVaranusto other regions. The discovery of the new specimen thus fills an important gap in the fossil record of monitor lizards. The similar lengths of the fore- and hindlimbs in this new taxon are unusual among the total group Varanidae and suggest it may have had a different lifestyle, at least from the contemporaneous North AmericanS. ensidens.

This article is part of the theme issue ‘The impact of Chinese palaeontology on evolutionary research’.
Bovine rhinitis B virus is highly prevalent in acute bovine respiratory disease and causes upper respiratory tract infection in calves
Authors: Bhattarai Shaurav , Lin Chun-Ming , Temeeyasen Gun , Palinski Rachel , Li Feng , Kaushik Radhey S. , Hause Ben M.
Published: February 2022

Bovine respiratory disease (BRD) is the most significant cause of cattle morbidity and mortality worldwide. This multifactorial disease has a complex aetiology. Dogma posits a primary viral infection followed by secondary bacterial pneumonia. Bovine rhinitis B virus (BRBV) is an established aetiological agent of BRD, but little is known regarding its pathogenesis. Here, a BRD PCR panel identified 18/153 (11.8 %) lung samples and 20/49 (40.8 %) nasal swabs collected from cattle with respiratory signs as positive for BRBV, which was the most prevalent virus in nasal swabs. Primary bovine tracheal epithelial cells were used to isolate BRBV that was phylogenetically related to contemporary sequences from the USA and Mexico and genetically divergent from the previous sole BRBV isolate. To investigate virus pathogenesis, 1-week-old colostrum-deprived dairy calves were inoculated intranasally with 7.0 log10TCID50BRBV. Virus was isolated from nasal swabs, nasal turbinates, trachea and the brain of the challenged animals. Neutralizing antibodies were detected beginning 7 days post-inoculation and peaked at day 14.In situhybridization (ISH) localized BRBV infection in the upper respiratory ciliated epithelial and goblet cells, occasionally associated with small defects of the superficial cilia lining. Sporadically, pinpoint ISH signals were also detected in cells resembling glial cells in the cerebrum in one calf. Together, these results demonstrate the BRBV infection is highly prevalent in acute BRD samples and while the pathogenicity of BRBV is minimal with infection largely limited to the upper respiratory tract, further research is needed to elucidate a possible initiatory role in BRD.
Role of env gene and LTR sequence in the pathogenesis of subgroup K avian leukosis virus
Authors: Li Yang , Liu Yi , Lin Zhanye , Cui Shuai , Chang Shuang , Cui Zhizhong , Zhao Peng , Wang Yixin
Published: February 2022

Avian leukosis virus (ALV) is a retrovirus that induces tumours in infected birds; ALV is divided into different subgroups according to the env gene and cellular tropism. In general, ALV subgroup J (ALV-J) is considered to be the most pathogenic and prevalent subgroup while subgroup K (ALV-K), a newly identified subgroup, only causes mild symptoms. To illuminate the roles of the env viral gene and LTR sequence in pathogenic differences between ALV-J and ALV-K, rescued ALV-J strain rSDAU1005, rescued ALV-K strain rJS11C1, and recombinant strains rENV(J)-LTR(K) and rENV(K)-LTR(J) were characterized and investigated in this study. Among rescued viruses, rSDAU1005 had the highest replication efficiency while rJS11C1 replicated the slowest (replication efficiency rankings were rSDAU1005 >rENV(K)-LTR(J)>rENV(J)-LTR(K)>rJS11 C1). The luciferase reporter gene assay results showed that the promoter activity of ALV-K LTR was lower than that of the ALV-J LTR promoter, which may have accounted for the slower replication efficiency of ALV-K. Pathogenicity of the four rescued viruses was determined via inoculating the yolk sacs of specific-pathogen-free chickens. The results demonstrated that all four viruses were pathogenic; rSDAU1005 caused the most severe growth retardation and immunosuppression. rENV(J)-LTR(K) was more pathogenic when compared to rENV(K)-LTR(J), indicating that env and the LTR sequence play important roles in pathogenicity between ALV-K and ALV-J. Additionally, env seemed to especially play a role in ALV-K pathogenesis. This study provided scientific data and insight to improve detection methods and judgement criteria in ALV clearance and surveillance.
Reading instruction causes changes in category-selective visual cortex
Authors: Yeatman Jason D. , McCloy Daniel R. , Caffarra Sendy , Clarke Maggie D. , Ender Suzanne , Gijbels Liesbeth , Joo Sung Jun , Kubota Emily C. , Kuhl Patricia K. , Larson Eric , O’Brien Gabrielle , Peterson Erica R. , Takada Megumi E. , Taulu Samu
Published: February 2022

Education sculpts specialized neural circuits for skills like reading that are critical to success in modern society but were not anticipated by the selective pressures of evolution. Does the emergence of brain regions that selectively process novel visual stimuli like words occur at the expense of cortical representations of other stimuli like faces and objects? To answer this question we conducted a randomized controlled trial with pre-school children (five years of age). We found that being taught reading versus oral language skills induced different patterns of change in category-selective regions of visual cortex. Reading instruction enhanced the response to text but did not diminish the response to other categories. How these changes play out over a longer timescale is still unknown but, based on these data, we can surmise that high-level visual cortex undergoes rapid changes as children enter school and begin establishing new skills like literacy.
mcPBWT: Space-efficient Multi-column PBWT Scanning Algorithm for Composite Haplotype Matching
Authors: Shakya Pramesh , Naseri Ardalan , Zhi Degui , Zhang Shaojie
Published: February 2022

Positional Burrows-Wheeler Transform (PBWT) is a data structure that supports efficient algorithms for finding matching segments in a panel of haplotypes. It is of interest to study the composite patterns of multiple matching segments or blocks arranged contiguously along a same haplotype as they can indicate recombination crossover events, gene-conversion tracts, or, sometimes, errors of phasing algorithms. However, current PBWT algorithms do not support search of such composite patterns efficiently. Here, we present our algorithm, mcPBWT (multi-column PBWT), that uses multiple synchronized runs of PBWT at different variant sites providing a "look-ahead" information of matches at those variant sites. Such "look-ahead" information allows us to analyze multiple contiguous matching pairs in a single pass. We present two specific cases of mcPBWT, namely double-PBWT and triple-PBWT which utilize two and three columns of PBWT respectively. double-PBWT finds two matching pairs' combinations representative of crossover event or phasing error while triple-PBWT finds three matching pairs' combinations representative of gene-conversion tract.
Traveling waves in the monkey frontoparietal network predict recent reward memory
Authors: Zabeh E. , Foley N.C. , Jacobs J. , Gottlieb J.P.
Published: February 2022

Brain function depends on neural communication, but the mechanisms of this communication are not well understood. Recent studies suggest that one form of neural communication is through traveling waves (TWs)—patterns of neural oscillations that propagate within and between areas. We show that TWs appear robustly in microarray recordings in monkey frontal and parietal cortex and encode memory for recent rewards. While making saccades to obtain probabilistic rewards, monkeys were sensitive to the (statistically irrelevant) prior reward, which is consistent with behavioral biases produced by reward history. TWs in frontal and parietal areas were stronger in trials following a prior reward versus a lack of reward and, in the frontal lobe, correlated with the monkeys’ sensitivity to the prior reward. The findings suggest that neural communication across fronto-parietal areas, reflected by TWs, maintains default reward memories, while communication within the frontal lobe mediates the read out of the memories for prospective expectations.
Contact investigation of tuberculosis in Brunei Darussalam: Evaluation and risk factor analysis
Authors: Chaw Liling , Hamid Rafizah Abdul , Koh Kai Shing , Thu Kyaw
Published: February 2022

Introduction

We evaluated the yield of tuberculosis (TB) contact investigation in Brunei Darussalam, and identified the associated factors for latent TB infection (LTBI) diagnosis, as well as for initiating and completing LTBI treatment.

Methods

Data was extracted and digitalised for all close contacts of pulmonary TB cases at the National TB Coordinating Centre from January 2009 to December 2018. Generalising estimating equations (GEE) logistic regression models were used to determine the associated factors. Manual matching against electronic health records system was done to identify contacts who had progressed to active TB disease.

Results

Among 10,537 contacts, 9.9% (n= 1047) were diagnosed as LTBI, out of which 43.0% (n= 450) initiated LTBI treatment. Among those who initiated, 74.0% (n= 333) completed LTBI treatment. Contact factors associated with LTBI diagnosis include being male (adjusted Odds Ratio (aOR)= 1.18 [95%CI: 1.03,1.34]), local (aOR= 0.70 [95%CI: 0.56,0.88]), and a household contact (aOR= 1.59 [95%CI: 1.26,1.99]). Contacts of index cases who were <60 years old and diagnosed as smear positive PTB (aOR= 1.62 [95%CI: 1.19,2.20]) had higher odds of being diagnosed with LTBI. Local LTBI cases had higher odds of initiating LTBI treatment (aOR= 1.86 [95%CI: 1.26,2.73]). Also, LTBI cases detected from local (aOR= 2.32 [95%CI: 1.08,4.97]) and smear positive PTB index cases (aOR= 2.23 [95%CI: 1.09,4.55]) had higher odds of completing LTBI treatment. Among 1047 LTBI cases, 5 (0.5%) had progressed to active PTB within 1-8 years post-LTBI diagnosis.

Discussion

LTBI burden is disproportionately high towards foreign nationals, with higher odds of LTBI diagnosis but lower odds of treatment initiation. Determining the reasons of not initiating LTBI treatment will be useful to help improve LTBI treatment uptake. Establishing digital databases and building TB laboratory capacity for molecular typing would be useful to determine the contribution of LTBI or reactivation towards TB incidence in Brunei.

Key messages

What is already known on this topic

Brunei is an intermediate TB burden country with stagnating TB incidence since 2004, despite having an established national TB programme.

We undertook this study to evaluate the contact investigation process and also to understand the contribution of LTBI towards TB incidence in the country.

What this study adds

Among contacts of PTB index cases identified between 2009 and 2018, the proportions of LTBI diagnosis, treatment initiation and treatment completion were 9.9%, 43.0% and 74.0%, respectively.

The associated factors of LTBI diagnosis include being, male, foreign and a household contact. Local cases had higher odds of initiating LTBI treatment when compared to foreign nationals.

How this study might affect research, practice or policy

Strengthening LTBI screening and treatment uptake among foreign nationals could be an important step towards reducing TB incidence in Brunei.
Effects of cannabidiol on activated immune-inflammatory pathways in major depressive patients and healthy controls
Authors: Rachayon Muanpetch , Jirakran Ketsupar , Sodsai Pimpayao , Klinchanhom Siriwan , Sughondhabirom Atapol , Plaimas Kitiporn , Suratanee Apichat , Maes Michael
Published: February 2022

Background

Major depressive disorder and a major depressive episode (MDD/MDE) are characterized by activation of the immune-inflammatory response system (IRS) and the compensatory immune-regulatory system (CIRS). Cannabidiol (CBD) is a phytocannabinoid isolated from the cannabis plant which was reported to have antidepressant-like and anti- inflammatory effects. The aim of the present study is to examine the effects of CBD on IRS, CIRS, M1, T helper (Th)-1, Th-2, Th-17, T regulatory (Treg) profiles, and growth factors in depression and healthy controls.

Methods

Culture supernatant of stimulated (5 μg/mL of PHA and 25 μg/mL of LPS) whole blood of 30 depressed patients and 20 controls was assayed for cytokines using the LUMINEX assay. The effects of three CBD concentrations (0.1 µg/ml, 1 µg/mL, and 10 µg/mL) were examined.

Results

Depression was characterized by significantly increased Th-1, Th-2, Th-17, Treg, IRS, CIRS and neurotoxicity profiles. CBD 0.1 µg/mL did not have any immune effects. CBD 1.0 µg/mL decreased CIRS activities but increased growth factor production, while CBD 10.0 µg/mL suppressed Th-1, Th-17, IRS, CIRS, and a neurotoxicity profile and enhanced T cell growth and growth factor production. CBD 1.0 to 10.0 µg/mL dose-dependently decreased sIL- 1RA, IL-8, IL-9, IL-10, IL-13, CCL11, G-CSF, IFN-γ, CCL2, CCL4, and CCL5, and increased IL-1β, IL-4, IL-15, IL-17, GM-CSF, TNF-α, FGF, and VEGF.

Conclusion

CBD has very complex immunomodulatory effects which depend on the CBD dose. CBD does not normalize the activated immune profiles observed in depression while higher concentrations can worsen inflammatory processes.
Speech understanding oppositely affects acoustic and linguistic neural tracking in a speech rate manipulation paradigm
Authors: Verschueren Eline , Gillis Marlies , Decruy Lien , Vanthornhout Jonas , Francart Tom
Published: February 2022

When listening to continuous speech, the human brain can track features of the presented speech signal. It has been shown that neural tracking of acoustic features is a prerequisite for speech understanding and can predict speech understanding in controlled circumstances. However, the brain also tracks linguistic features of speech, which may be more directly related to speech understanding. We investigated acoustic and linguistic speech processing as a function of varying speech understanding by manipulating the speech rate. In this paradigm, acoustic and linguistic speech processing are affected simultaneously but in opposite directions: When the speech rate increases, more acoustic information per second is present. In contrast, the tracking of linguistic information becomes more challenging when speech is less intelligible at higher speech rates. We measured the EEG of 18 participants (4 male) who listened to speech at various speech rates. As expected and confirmed by the behavioral results, speech understanding decreased with increasing speech rate. Accordingly, linguistic neural tracking decreased with increasing speech rate, but acoustic neural tracking increased. This indicates that neural tracking of linguistic representations can capture the gradual effect of decreasing speech understanding. In addition, increased acoustic neural tracking does not necessarily imply better speech understanding. This suggests that, although more challenging to measure due to the low signal-to-noise ratio, linguistic neural tracking may be a more direct predictor of speech understanding.

Significance statement

An increasingly popular method to investigate neural speech processing is to measure neural tracking. Although much research has been done on how the brain tracks acoustic speech features, linguistic speech features have received less attention. In this study, we disentangled acoustic and linguistic characteristics of neural speech tracking via manipulating the speech rate. A proper way of objectively measuring auditory and language processing paves the way towards clinical applications: An objective measure of speech understanding would allow for behavioral-free evaluation of speech understanding, which allows to evaluate hearing loss and adjust hearing aids based on brain responses. This objective measure would benefit populations from whom obtaining behavioral measures may be complex, such as young children or people with cognitive impairments.
Local Extensional Flows Induce Long-Range Fiber Alignment in 3D Collagen Hydrogels
Authors: Ahmed Adeel , Joshi Indranil M. , Mansouri Mehran , Byerley Ann M. , Day Steven W. , Gaborski Thomas R. , Abhyankar Vinay V.
Published: February 2022

Randomly oriented type I collagen (COL1) fibers in the extracellular matrix (ECM) are reorganized by biophysical forces into aligned domains extending several millimeters and with varying degrees of fiber alignment. These aligned fibers can transmit traction forces, guide tumor cell migration, facilitate angiogenesis, and influence tissue morphogenesis. To create aligned COL1 domains in microfluidic cell culture models, shear flows have been used to align thin COL1 matrices (<50μm in height) in a microchannel. However, there has been limited investigation into the role of shear flows in aligning 3D hydrogels (>130μm). Here, we show that pure shear flows do not induce fiber alignment in 3D atelo COL1 hydrogels, but the simple addition of local extensional flow promotes alignment that is maintained across several millimeters, with a degree of alignment directly related to the extensional strain rate. We further advance experimental capabilities by addressing the practical challenge of accessing a 3D hydrogel formed within a microchannel by introducing a magnetically coupled modular platform that can be released to expose the microengineered hydrogel. We demonstrate the platform’s capability to pattern cells and fabricate multi-layered COL1 matrices using layer-by-layer fabrication and specialized modules. Our approach provides an easy-to-use fabrication method to achieve advanced hydrogel microengineering capabilities that combine fiber alignment with biofabrication capabilities.
Comparative study of immunogenicity and safety of Gam-COVID-Vac and Sinopharm BBIBP-CorV vaccines in Belarus
Authors: Stoma Igor , Korsak Katsiaryna , Voropaev Evgenii , Osipkina Olga , Kovalev Aleksey
Published: February 2022

Introduction

Lack of comparative studies on efficiency of a broad range of COVID19 vaccines leads to lower levels of adoption and subsequent lower total immunity in several regions, including Republic of Belarus. This clinical study captures and transparently demonstrates varying immunogenic responses to Sputnik V and Sinopharm vaccines.

Aim of this study was

to compare the immunogenicity and reactogenicity of Sputnik V (Gam-COVID-Vac), RF and Sinopharm (BBIBP-CorV), PRC vaccines in vaccinated individuals.

Materials and Methods

A total of 60 adults participated the study. The immune response after vaccination was assessed using enzyme immunoassay. IgG levels measured in all participants at three time points: before the vaccination, 42 days after the first vaccine dose, and 6 months after the first vaccine dose. The results of the SARS-CoV-2 antibody test is quantified according to the WHO First International Standard (NIBSC code:20/136) and expressed in international units (BAU/ml).

Results

The study participants were divided into two groups, where 30 people (50%) were vaccinated with Sputnik V (Gam-COVID-Vac), and 30 people were vaccinated with Sinopharm (BBIBP-CorV), with no gender differences in the groups. The IgG levels at 42 days after the first vaccine dose were: Sputnik V (Gam-COVID-Vac)(42 days): Me=650.4 (642.2-669.4); Sinopharm (BBIBP-CorV)(42 days): Me=376.5 (290.9-526.4); p<0,001). The IgG levels at 6 months after the first vaccine dose were: Sputnik V (Gam-COVID-Vac)(6 months) Me=608.7 (574.6-647.1); Sinopharm (BBIBP-CorV)(6 months): Me=106.3 (78.21-332.4); p<0,001). Reactions after vaccination appeared in 27 vaccinated individuals (45%).

Conclusion

The study showed that Sputnik V (Gam-COVID-Vac) vaccine was more immunogenic than Sinopharm (BBIBP-CorV) vaccine. IgG levels in vaccinated individuals who previously recovered from SARS-CoV-2 infection (“hybrid immunity”) were higher than in SARS-CoV-2 naïve individuals. Reactions after vaccines administration were mild to moderate.
Annelid functional genomics reveal the origins of bilaterian life cycles
Authors: Martín-Zamora Francisco M. , Liang Yan , Guynes Kero , Carrillo-Baltodano Allan M. , Davies Billie E. , Donnellan Rory D. , Tan Yongkai , Moggioli Giacomo , Seudre Océane , Tran Martin , Mortimer Kate , Luscombe Nicholas M. , Hejnol Andreas , Marlétaz Ferdinand , Martín-Durán José M.
Published: February 2022

Indirect development with an intermediate larva exists in all major animal lineages1, making larvae central to most scenarios of animal evolution2-12. Yet how larvae evolved remains disputed. Here we show that temporal shifts (i.e., heterochronies) in trunk formation underpin the diversification of larvae and bilaterian life cycles. Combining chromosome-scale genome sequencing in the slow-evolving annelidOwenia fusiformis13with transcriptomic and epigenomic profiling during the life cycles of this and two other annelids, we found that trunk development is deferred to pre-metamorphic stages in the feeding larva ofO. fusiformis, but starts after gastrulation in the non-feeding larva with gradual metamorphosis ofCapitella teletaand the direct developing embryo ofDimorphilus gyrociliatus. Accordingly, the embryos ofO. fusiformisdevelop first into an enlarged anterior domain that forms larval tissues and the adult head. Notably, this also occurs in the so-called “head larvae” of other bilaterians14,15, with whomO. fusiformislarva shows extensive transcriptomic similarities. Together, our findings suggest that the temporal decoupling of head and trunk formation, as maximally observed in “head larvae”, allowed larval evolution in Bilateria, thus diverging from prevailing scenarios that propose either co-option10,11or innovation12of gene regulatory programmes to explain larva and adult origins.
Equilibrium dynamics of the pre- and post-cleavage regions of SP1 are separately shifted by the HIV-1 maturation inhibitor Bevirimat
Authors: Xu Chaoyi , Perilla Juan R.
Published: February 2022

Human immunodeficiency virus type 1 (HIV-1) assembly and maturation proceeds in two distinct steps. During assembly, viral Gag oligomerizes into a hexagonal polyprotein lattice incorporating the capsid protein (CA) and spacer peptide 1 (SP1) domains, that constitute the immature Gag lattice. During maturation, CTD-SP1 hexamers formed in the previous step are cleaved by HIV-1 protease, causing a dramatic rearrangement of the immature virion to its mature, infectious form. The first-generation maturation inhibitor (MI) bevirimat (BVM) is reported to block the final cleavage between CA and SP1, thus blocking HIV maturation. In contrast, the host factor inositol hexakisphosphate (IP6) is a co-factor of Gag assembly and facilitates the formation of a quaternary arrangement of SP1 known as the six helix bundle (6HB). Here, starting from a MAS NMR structure and using atomistic free energy calculations, we establish that binding of BVM and IP6 to the immature lattice lacks any cooperativity or avidity. Furthermore, we rationalize the molecular origin of HIV resistance to BVM by determining the role of BVM on the stability of the 6HB and by revealing that SP1 shows independent dynamics for its pre- and post-cleavage regions. Finally, results from our simulations permit us to propose a novel chemical scaffold for the design of maturation inhibitors based on BVM and IP6.
Inhibition of a critical malaria host-pathogen interaction by a computationally designed inhibitor targeting Plasmodium vivax DBP
Authors: Tobin Autumn R , Crow Rachel , Urusova Darya V. , Klima Jason C. , Tolia Niraj H. , Strauch Eva-Maria
Published: February 2022

Malaria is a substantial global health burden with 229 million cases in 2019 and 450,000 deaths annually. Plasmodium vivax is the most widespread malaria-causing parasite putting 2.5 billion people at risk of infection. P. vivax has a dormant liver stage and therefore can exist for long periods undetected. Its blood-stage can cause severe reactions and hospitalization. Few treatment and detection options are available for this pathogen. To address this need, we developed nanomolar inhibitor that could serve as a therapeutic and a diagnostic. A unique characteristic of P. vivax is that it depends on the Duffy antigen/Receptor for chemokines (DARC) on the surface of host red blood cells for invasion. P. vivax employs the Duffy binding protein (DBP) to bind to DARC. We first de novo designed a three helical bundle scaffolding database which was screened via protease digestions for stability. Protease-resistant scaffolds highlighted thresholds for stability, which we utilized for selecting DARC mimetics that we subsequentially designed through grafting and redesign of these scaffolds. The optimized design small helical protein disrupts the DBP:DARC interaction. The inhibitor blocks the receptor binding site on DBP and thus forms a strong foundation for a therapeutic that will inhibit reticulocyte infection and prevent the pathogenesis of P. vivax malaria.

Teaser

De novo designed proteins present a new alternative for the development of therapeutics. They can be small, highly stable and easily manufactured. Here we designed a potential new therapeutic to inhibit entry of Plasmodium vivax into red blood cells by interfering its interactions of surface displayed DBP molecules with the host receptor DARC.
Ontological model for the acoustic management in a smart environment
Authors: Santiago Gabriela , Aguilar Jose
Published: February 2022

Purpose

The Reflective Middleware for Acoustic Management (ReM-AM), based on the Middleware for Cloud Learning Environments (AmICL), aims to improve the interaction between users and agents in a Smart Environment (SE) using acoustic services, in order to consider the unpredictable situations due to the sounds and vibrations. The middleware allows observing, analyzing, modifying and interacting in every state of a SE from the acoustics. This work details an extension of the ReM-AM using the ontology-driven architecture (ODA) paradigm for acoustic management.

Design/methodology/approach

This work details an extension of the ReM-AM using the ontology-driven architecture (ODA) paradigm for acoustic management. In this paper are defined the different domains of knowledge required for the management of the sounds in SEs, which are modeled using ontologies.

Findings

This work proposes an acoustics and sound ontology, a service-oriented architecture (SOA) ontology, and a data analytics and autonomic computing ontology, which work together. Finally, the paper presents three case studies in the context of smart workplace (SWP), ambient-assisted living (AAL) and Smart Cities (SC).

Research limitations/implications

Future works will be based on the development of algorithms for classification and analysis of sound events, to help with emotion recognition not only from speech but also from random and separate sound events. Also, other works will be about the definition of the implementation requirements, and the definition of the real context modeling requirements to develop a real prototype.

Practical implications

In the case studies is possible to observe the flexibility that the ReM-AM middleware based on the ODA paradigm has by being aware of different contexts and acquire information of each, using this information to adapt itself to the environment and improve it using the autonomic cycles. To achieve this, the middleware integrates the classes and relations in its ontologies naturally in the autonomic cycles.

Originality/value

The main contribution of this work is the description of the ontologies required for future works about acoustic management in SE, considering that what has been studied by other works is the utilization of ontologies for sound event recognition but not have been expanded like knowledge source in an SE middleware. Specifically, this paper presents the theoretical framework of this work composed of the AmICL middleware, ReM-AM middleware and the ODA paradigm.