bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors Associated With Diagnostic Delay of Axial Spondyloarthritis in Colombian Patients
Authors: Parada-Arias Luisa , Vargas Juan F. , Ahcar Nassin S. , Rojas-Villarraga Adriana , Mantilla Rubén-Darío
Published: December 2021

Background/Objective

The diagnostic delay of axial spondyloarthritis (axSpA) is globally reported to be between 3 and 11 years. Early diagnosis and treatment have long-term benefits for patients and the health care system. Several international studies have evaluated some factors associated with diagnostic delay, but there are no known studies in the Colombian population. This study assesses the factors associated with diagnostic delay of axSpA in a rheumatology center in Bogota, Colombia.

Methods

This monocentric analytical cross-sectional study was done in a specialized rheumatology center. Patients who fulfilled the 2009 Assessment of Spondyloarthritis International Society (ASAS) classification criteria for axSpA were included. Information was obtained from medical records and a phone call. Bivariate and multivariate analyses were done to assess the associated factors with diagnostic delay.

Results

One hundred one patients were included, 54 were women (53.5%). The median diagnostic delay was 2 years (interquartile range, 1–7). The bivariate analysis showed that a younger age at diagnosis (p = 0.042) and previous diagnosis of lumbar degenerative disease (p = 0.029) were associated with a longer diagnostic delay. The logistical regression showed that previous lumbar degenerative disc disease (odds ratio, 2.8; 95% confidence interval, 1.09–7.53) and fibromyalgia (odds ratio, 4.0; 95% confidence interval, 1.2–13.1) diagnosis were both associated with a longer diagnostic delay.

Conclusions

Factors associated with a longer diagnostic delay were previous diagnosis of lumbar degenerative disc disease and fibromyalgia. Additional studies are needed so that the reasons for diagnostic delay are understood and early diagnosis and management of axSpA are enabled.
CT-Based Modeling of the Dentition for Craniomaxillofacial Surgical Planning
Authors: Abramson Zachary , Scoggins Matthew A. , Burton Christiane , Choudhri Asim F. , Holladay Chris , Briant Nancy Rose Pont , Sheyn Anthony , Susarla Srinivas
Published: December 2021

Historically, the accuracy of imaging teeth by computed tomography (CT) has been suboptimal and deemed inadequate for surgical planning of orthognathic procedures. However, recent advances in CT hardware and software have significantly improved the accuracy of imaging occlusal anatomy. This technical note describes a quantitative means of evaluating the accuracy of CT-based modeling of teeth. Three-dimensional models of the dentition were created from a CT scan obtained of a craniomaxillofacial skeleton. Multiple reconstruction algorithms and modeling parameters were applied. The dentition of the same skeleton was scanned using a handheld optical scanning device to serve as the “gold standard.” Semi-automated registrations of CT and optically acquired models were performed and deviation analysis was conducted. On average, the deviation of the CT model with the optical scan measured 0.19 to 0.25 mm across the various reconstruction and modeling parameters, with a mean of 0.22 mm. Computed tomography underestimated contours at cusp tips, while overestimating contours in occlusal groves. The use of bone reconstruction algorithms and decreased model smoothing resulted in more accurate models, though greater surface noise. Future studies evaluating the clinical effectiveness of CT-based occlusal splints should take this finding into account.
Patho-Mechanisms for Hemorrhage/Sepsis-Induced Indirect Acute Respiratory Distress Syndrome: A Role for Lung TIE1 and Its Regulation by Neutrophils
Authors: Zhu Jiali , Li Jinbao , Chung Chun-Shiang , Lomas-Neira Joanne L. , Ayala Alfred
Published: December 2021

Introduction:

Severe hemorrhage (Hem) has been shown to be causal for the development of extra-pulmonary/indirect acute respiratory distress syndrome (iARDS) and is associated with severe endothelial cell (EC) injury. EC growth factors, Angiopoietin (Ang)-1 and -2, maintain vascular homeostasis via tightly regulated competitive interaction with the tyrosine kinase receptor, Tie2, expressed on ECs.

Objective:

Since it has been reported that the orphan receptor, Tie1, may be able to play a role in Ang:Tie2 signaling; we chose to examine Tie1's capacity to alter the lung Ang:Tie2 interaction in response to the sequential insults of shock/sepsis (cecal ligation and puncture [CLP]), culminating in iARDS.

Methods:

Male mice were subjected to Hem alone or sequential Hem followed 24 hours later by CLP that induces iARDS. Changes in lung and/or plasma levels of Tie1, Tie2, Ang-1, Ang-2, various systemic cytokine/chemokines and indices of lung injury/inflammation were then determined. The role of Tie1 was established by intravenous administration of Tie1 specific or control siRNA at 1 h post-Hem. Alternatively, the contribution of neutrophils was assessed by pre-treating mice with anti-neutrophil antibody depletion 48 h prior to Hem.

Results:

Lung tissue levels of Tie1 expression elevated over the first 6 to 24 h post-Hem alone. Subsequently, we found that treatment of Hem/CLP mice with Tie1-specific siRNA not only decreased Tie1 expression in lung tissue compared to control siRNA, but, suppressed the rise in lung inflammatory cytokines, lung MPO and the rise in lung protein leak. Finally, much as we have previously shown that neutrophil interaction with resident pulmonary vascular ECs contribute significantly to Ang-2 release and EC dysfunction, central to the development of iARDS. Here, we report that depletion of neutrophils also decreased lung tissue Tie1 expression and increased Tie2 activation in Hem/CLP mice.

Conclusion:

Together, these data imply that shock-induced increased expression of Tie1 can contribute to EC activation by inhibiting Ang:Tie2 interaction, culminating in EC dysfunction and the development of iARDS.
The use of predefined scales and scores with eye-tracking devices for symptom identification in critically ill nonverbal patients
Authors: Ull Christopher , Hamsen Uwe , Weckwerth Christina , Schildhauer Thomas Armin , Gaschler Robert , Jansen Oliver , Waydhas Christian
Published: December 2021

BACKGROUND

Eye tracking (ET) may be a novel tool to enable nonverbal communication. We hypothesized that ET could be used successfully by intensive care unit (ICU) patients with artificial airways to express their levels of pain and mood, quality of life, and self-esteem with predefined scales and scores.

METHODS

Prospective, monocentric, observational study, including patients with an endotracheal tube or tracheostomy tube and a history of mechanical ventilation for more than 48 hours without delirium, and inadequate nonverbal communication skills. The ICU patients' pain was assessed with a numeric rating scale, their mood was tested with a smiley analog scale. Quality of life and self-esteem were measured with the European quality of life-5 dimensions-5 levels-score and the visual analog self-esteem scale.

RESULTS

A total of 75 patients with a mean age of 58.3 years were included. Main diagnoses for ICU admission were major trauma (45.3%), nonabdominal sepsis (22.6%), and acute abdomen (13.3%). Patients showed moderate levels of pain and sadness with a median of 4 (interquartile range, 3–5.5) on the numeric rating scale and a median of 4 (interquartile range, 3–4) on the smiley analog scale. The general health status on the European quality of life-5 dimensions-5 levels-score was rated as poor. Reporting on the visual analog self-esteem scale, most of the included patients felt trapped (90.7%) and not confident (72%), were frustrated (64%) or did not feel understood (56%). However, despite their severe illness, many patients classified themselves as intelligent (30.6%), not mixed up (38.6%), outgoing (38.6%), and optimistic (44%).

CONCLUSION

Eye tracking enables symptom identification in critically ill voiceless patients with impaired communication options. The results of our study may provide guidance for improvement measures in the care of voiceless ICU patients. We believe that ET is useful for symptom identification and therefore may be capable of improving patient-medical team interaction and patient satisfaction.

LEVEL OF EVIDENCE

Diagnostic Test or Criteria, Level III.
Epidemiology, patterns of care and outcomes of traumatic brain injury in deployed military settings: Implications for future military operations
Authors: Dengler Bradley A. , Agimi Yll , Stout Katharine , Caudle Krista L. , Curley Kenneth C. , Sanjakdar Sarah , Rone Malena , Dacanay Brian , Fruendt Jonathan C. , Phillips James B. , Meyer Ana-Claire L.
Published: December 2021

BACKGROUND

Traumatic brain injury (TBI) is prevalent and highly morbid among Service Members. A better understanding of TBI epidemiology, outcomes, and care patterns in deployed settings could inform potential approaches to improve TBI diagnosis and management.

METHODS

A retrospective cohort analysis of Service Members who sustained a TBI in deployed settings between 2001 and 2018 was conducted. Among individuals hospitalized with TBI, we compared the demographic characteristics, mechanism of injury, injury type, and severity between combat and noncombat injuries. We compared diagnostic tests and procedures, evacuation patterns, return to duty rates and days in care between individuals with concussion and those with severe TBI.

RESULTS

There were 46,309 service members with TBI and 9,412 who were hospitalized; of those hospitalized, 55% (4,343) had isolated concussion and 9% (796) had severe TBI, of whom 17% (132/796) had multiple injuries. Overall mortality was 2% and ranged from 0.1% for isolated concussion to 18% for severe TBI. The vast majority of TBI were evacuated by rotary wing to role 3 or higher, including those with isolated concussion. As compared with severe TBI, individuals with isolated concussion had fewer diagnostic or surgical procedures performed. Only 6% of service members with severe TBI were able to return to duty as compared with 54% of those with isolated concussion. Traumatic brain injury resulted in 123,677 lost duty days; individuals with isolated concussion spent a median of 2 days in care and those with severe TBI spent a median of 17 days in care and a median of 6 days in the intensive care unit.

CONCLUSION

While most TBI in the deployed setting are mild, TBI is frequently associated with hospitalization and multiple injuries. Overtriage of mild TBI is common. Improved TBI capabilities applicable to forward settings will be critical to the success of future multidomain operations with limitations in air superiority.

LEVEL OF EVIDENCE

Prognostic and Epidemiologic; Level III.
Au naturale: use of biologically derived cyclic di-nucleotides for cancer immunotherapy
Authors: Waters Christopher M.
Published: December 2021

Cyclic di-nucleotides (CDNs) are widespread second messenger signalling molecules that regulate fundamental biological processes across the tree of life. These molecules are also potent modulators of the immune system, inducing a Type I interferon response upon binding to the eukaryotic receptor STING. Such a response in tumours induces potent immune anti-cancer responses and thus CDNs are being developed as a novel cancer immunotherapy. In this review, I will highlight the use, challenges and advantages of using naturally occurring CDNs to treat cancer.
Football is becoming more predictable; network analysis of 88 thousand matches in 11 major leagues
Authors: Maimone Victor Martins , Yasseri Taha
Published: December 2021

In recent years, excessive monetization of football and professionalism among the players have been argued to have affected the quality of the match in different ways. On the one hand, playing football has become a high-income profession and the players are highly motivated; on the other hand, stronger teams have higher incomes and therefore afford better players leading to an even stronger appearance in tournaments that can make the game more imbalanced and hence predictable. To quantify and document this observation, in this work, we take a minimalist network science approach to measure the predictability of football over 26 years in major European leagues. We show that over time, the games in major leagues have indeed become more predictable. We provide further support for this observation by showing that inequality between teams has increased and the home-field advantage has been vanishing ubiquitously. We do not include any direct analysis on the effects of monetization on football’s predictability or therefore, lack of excitement; however, we propose several hypotheses which could be tested in future analyses.
Inhibitors of the Bub1 spindle assembly checkpoint kinase: synthesis of BAY-320 and comparison with 2OH-BNPP1
Authors: Amalina Ilma , Bennett Ailsa , Whalley Helen , Perera David , McGrail Joanne C. , Tighe Anthony , Procter David J. , Taylor Stephen S.
Published: December 2021

Bub1 is a serine/threonine kinase proposed to function centrally in mitotic chromosome alignment and the spindle assembly checkpoint (SAC); however, its role remains controversial. Although it is well documented that Bub1 phosphorylation of Histone 2A at T120 (H2ApT120) recruits Sgo1/2 to kinetochores, the requirement of its kinase activity for chromosome alignment and the SAC is debated. As small-molecule inhibitors are invaluable tools for investigating kinase function, we evaluated two potential Bub1 inhibitors: 2OH-BNPPI and BAY-320. After confirming that both inhibit Bub1
in vitro
, we developed a cell-based assay for Bub1 inhibition. We overexpressed a fusion of Histone 2B and Bub1 kinase region, tethering it in proximity to H2A to generate a strong ectopic H2ApT120 signal along chromosome arms. Ectopic signal was effectively inhibited by BAY-320, but not 2OH-BNPP1 at concentrations tested. In addition, only BAY-320 was able to inhibit endogenous Bub1-mediated Sgo1 localization. Preliminary experiments using BAY-320 suggest a minor role for Bub1 kinase activity in chromosome alignment and the SAC; however, BAY-320 may exhibit off-target effects at the concentration required. Thus, 2OH-BNPP1 may not be an effective Bub1 inhibitor
in cellulo
, and while BAY-320 can inhibit Bub1 in cells, off-target effects highlight the need for improved Bub1 inhibitors.
Light potentials of photosynthetic energy storage in the field: what limits the ability to use or dissipate rapidly increased light energy?
Authors: Kanazawa Atsuko , Chattopadhyay Abhijnan , Kuhlgert Sebastian , Tuitupou Hainite , Maiti Tapabrata , Kramer David M.
Published: December 2021

The responses of plant photosynthesis to rapid fluctuations in environmental conditions are critical for efficient conversion of light energy. These responses are not well-seen laboratory conditions and are difficult to probe in field environments. We demonstrate an open science approach to this problem that combines multifaceted measurements of photosynthesis and environmental conditions, and an unsupervised statistical clustering approach. In a selected set of data on mint (Menthasp.), we show that ‘light potentials’ for linear electron flow and non-photochemical quenching (NPQ) upon rapid light increases are strongly suppressed in leaves previously exposed to low ambient photosynthetically active radiation (PAR) or low leaf temperatures, factors that can act both independently and cooperatively. Further analyses allowed us to test specific mechanisms. With decreasing leaf temperature or PAR, limitations to photosynthesis during high light fluctuations shifted from rapidly induced NPQ to photosynthetic control of electron flow at the cytochromeb6fcomplex. At low temperatures, high light induced lumen acidification, but did not induce NPQ, leading to accumulation of reduced electron transfer intermediates, probably inducing photodamage, revealing a potential target for improving the efficiency and robustness of photosynthesis. We discuss the implications of the approach for open science efforts to understand and improve crop productivity.
What has
Royal Society Open Science
achieved in its first few years?
Authors: Sanders Jeremy K. M.
Published: December 2021

It has been a pleasure and a privilege to serve as the first Editor-in-Chief of
Royal Society Open Science
for the past 6 years. I step down at the end of December 2021, having completed two 3-year terms, and am taking the opportunity here to reflect on some of the successes and challenges that the journal has experienced and the innovations that we have introduced. When I was first approached back in 2015, the breadth of the journal, covering the whole of science, resonated with my own interests: my research career has ranged across the entire landscape of chemistry, while my leadership roles have embraced all of science, technology and medicine. The open access ethos, the objective refereeing policy that rejects the idea of only publishing what is in fashion, and the opportunities offered by a new venture that could transcend traditional disciplinary boundaries also all appealed to me. Among our successful innovations are Registered Reports, Replication Studies and the new ‘Science, Society and Policy' section. The challenges have included the transition to paid article processing charges (APCs), whether to resist pressure to retract a controversial paper, and bullying of young female authors by established senior males in the same field. I explore all of these below, provide some statistics on the journal's performance, also cover some of the notable papers we have published, and provide some concluding thoughts.
Sensitivity analysis of Wasserstein distributionally robust optimization problems
Authors: Bartl Daniel , Drapeau Samuel , Obłój Jan , Wiesel Johannes
Published: December 2021

We consider sensitivity of a generic stochastic optimization problem to model uncertainty. We take a non-parametric approach and capture model uncertainty using Wasserstein balls around the postulated model. We provide explicit formulae for the first-order correction to both the value function and the optimizer and further extend our results to optimization under linear constraints. We present applications to statistics, machine learning, mathematical finance and uncertainty quantification. In particular, we provide an explicit first-order approximation for square-root LASSO regression coefficients and deduce coefficient shrinkage compared to the ordinary least-squares regression. We consider robustness of call option pricing and deduce a new Black–Scholes sensitivity, a non-parametric version of the so-called Vega. We also compute sensitivities of optimized certainty equivalents in finance and propose measures to quantify robustness of neural networks to adversarial examples.
Honeybees use propolis as a natural pesticide against their major ectoparasite
Authors: Pusceddu Michelina , Annoscia Desiderato , Floris Ignazio , Frizzera Davide , Zanni Virginia , Angioni Alberto , Satta Alberto , Nazzi Francesco
Published: December 2021

Honeybees use propolis collected from plants for coating the inner walls of their nest. This substance is also used as a natural antibiotic against microbial pathogens, similarly to many other animals exploiting natural products for self-medication. We carried out chemical analyses and laboratory bioassays to test if honeybees use propolis for social medication against their major ectoparasite:Varroa destructor. We found that propolis is applied to brood cells where it can affect the reproducing parasites, with a positive effect on honeybees and a potential impact onVarroapopulation. We conclude that propolis can be regarded as a natural pesticide used by the honeybee to limit a dangerous parasite. These findings significantly enlarge our understanding of behavioural immunity in animals and may have important implications for the management of the most important threat to honeybees worldwide.
Demographic decline and lineage-specific adaptations characterize New Zealand kiwi
Authors: Bemmels Jordan B. , Mikkelsen Else K. , Haddrath Oliver , Colbourne Rogan M. , Robertson Hugh A. , Weir Jason T.
Published: December 2021

Small and fragmented populations may become rapidly differentiated due to genetic drift, making it difficult to distinguish whether neutral genetic structure is a signature of recent demographic events, or of long-term evolutionary processes that could have allowed populations to adaptively diverge. We sequenced 52 whole genomes to examine Holocene demographic history and patterns of adaptation in kiwi (
Apteryx
), and recovered 11 strongly differentiated genetic clusters corresponding to previously recognized lineages. Demographic models suggest that all 11 lineages experienced dramatic population crashes relative to early- or mid-Holocene levels. Small population size is associated with low genetic diversity and elevated genetic differentiation (
F
ST
), suggesting that population declines have strengthened genetic structure and led to the loss of genetic diversity. However, population size is not correlated with inbreeding rates. Eight lineages show signatures of lineage-specific selective sweeps (284 sweeps total) that are unlikely to have been caused by demographic stochasticity. Overall, these results suggest that despite strong genetic drift associated with recent bottlenecks, most kiwi lineages possess unique adaptations and should be recognized as separate adaptive units in conservation contexts. Our work highlights how whole-genome datasets can address longstanding uncertainty about the evolutionary and conservation significance of small and fragmented populations of threatened species.
Pseudomarimonas arenosa gen. nov., sp. nov. isolated from marine sand
Authors: Weerawongwiwat Veeraya , Kim Jong-Hwa , Yoon Jung-Hoon , Lee Jung-Sook , Sukhoom Ampaitip , Kim Wonyong
Published: December 2021

A novel Gram-negative, aerobic, non-motile, rod-shaped, bacterial strain (CAU 1598T) was isolated from marine sand. Strain CAU 1598T grew well at 30 °C, pH 6.5–7.0 and with 3 % NaCl (w/v). Phylogeny results based on 16S rRNA gene sequencing indicated that the identified strain had the highest similarity (94.3%) to

Pseudoxanthomonas putridarboris

, indicating that strain CAU 1598T belongs to the family

Xanthomonadaceae

. Further, the fatty acid profile of the strain was primarily composed of C16:0, iso-C15 : 0, iso-C16 : 0, summed feature 3 (consisting of C16 : 1
 ω7c/iso-C15 : 0 2-OH) and summed feature 9 (consisting of iso-C17 : 1
 ω9c and/or C16 : 0 10-methyl), with ubiquinone-8 as the major isoprenoid quinone. The polar lipid profile included diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphoglycolipid, an unidentified aminolipid and an unidentified lipid. The G+C content of the bacterial genome was 62.6 mol% and its 5.4 Mb length encompassed 144 contigs and 4236 protein-coding genes. These phenotypic, chemotaxonomic and phylogenetic data indicate that CAU 1598T belongs to a new genus and species, for which the name Pseudomarimonas arenosa gen. nov., sp. nov. is proposed. The type strain is CAU 1598T (=KCTC 82406T=MCCC 1K05673T).
Serum levels of specialised pro-resolving molecule pathways are greatly increased in SARS-CoV-2 patients and correlate with markers of the adaptive immune response
Authors: Turnbull James , Jha Rakesh , Ortori Catherine A. , Lunt Eleanor , Tighe Patrick J. , Irving William L. , Gohir Sameer A. , Kim Dong-Hyun , Valdes Ana M. , Tarr Alexander W. , Barrett David A. , Chapman Victoria
Published: December 2021

Background

Specialised pro-resolution molecules (SPMs) halt the transition to chronic pathogenic inflammation. We aimed to quantify serum levels of pro- and anti-inflammatory bioactive lipids in SARS-CoV-2 patients, and to identify potential relationships with innate responses and clinical outcome.

Methods

Serum from 50 hospital admitted inpatients (22 female, 28 male) with confirmed symptomatic SARS-CoV-2 infection and 94 age and sex matched cohort collected prior to the pandemic, were processed for quantification of bioactive lipids. Anti-nucleocapsid and anti-spike quantitative binding assays were performed.

Results

SARS-CoV-2 serum had significantly higher concentrations of omega-6 derived pro-inflammatory lipids and omega-6 and omega-3 derived SPMs, compared to age and sex matched controls. Levels of SPMs were not markedly altered by age. There were significant positive correlations between SPMs and other bioactive lipids and anti-spike antibody binding. Levels of some SPMs were significantly higher in patients with an anti-spike antibody value >0.5. Levels of linoleic acid (LA) and 5,6-dihydroxy-8Z,11Z,14Z-eicosatrienoic acid (5,6-DHET) were significantly lower in SARS-COV-2 patients who died.

Discussion

SARS-COV-2 infection was associated with a robust activation of the pathways that generate the specialised pro-resolution molecules and other anti-inflammatory bioactive lipids, supporting the future investigation of these pathways which may inform the development of novel treatments.
Cytokine release syndrome-like serum responses after COVID-19 vaccination are frequent but clinically inapparent in cancer patients under immune checkpoint therapy
Authors: Walle Thomas , Bajaj Sunanjay , Kraske Joscha A. , Rösner Thomas , Cussigh Christiane S. , Kälber Katharina A. , Müller Lisa Jasmin , Strobel Sophia Boyoung , Burghaus Jana , Kallenberger Stefan , Stein-Thöringer Christoph , Jenzer Maximilian , Schubert Antonia , Kahle Steffen , Williams Anja , Hoyler Birgit , Zielske Lin , Skatula Renate , Sawall Stefanie , Leber Mathias F. , Kunes Russell Z. , Krisam Johannes , Fremd Carlo , Schneeweiss Andreas , Krauss Jürgen , Berger Anne Katrin , Haag Georg M. , Zschäbitz Stefanie , Halama Niels , Springfeld Christoph , Kirsten Romy , Hassel Jessica C. , Jäger Dirk ,   NCT ANTICIPATE Investigators, Ungerechts Guy
Published: December 2021

Cancer patients frequently receive immune checkpoint therapies (ICT) which may modulate immune responses to COVID-19 vaccines. Recently, cytokine release syndrome (CRS) was observed in a cancer patient who received the BTN162b2 vaccine under ICT. Here, we analyzed adverse events (AEs) in patients of various solid tumor types undergoing (n=64) or not undergoing (n=26) COVID-19 vaccination under ICT as an exploratory endpoint of a prospectively planned cohort study. We did not observe clinically relevant CRS after vaccination (95% CI [0,0.056]). Short term (<4 weeks) serious AEs were rare (12.5%) and overall AEs under ICT were comparable to unvaccinated patients. Despite the absence of CRS symptoms, we observed a pairwise-correlated set of CRS-associated cytokines upregulated in 42% of patients after vaccination and ICT (>1.5fold). Hence, clinically meaningful CRS appears to be rare in cancer patients under ICT and elevated serum cytokine levels are common but not sufficient to establish CRS diagnosis.
Psychometric Properties of a New Stress-Related Personality Scale: The Virtual Inventory of Behavior and Emotions (VIBE)
Authors: Rettew David C. , Freckleton Dustin , Schork Nicholas , Graf Arnulf , Morrell Zoe , Lincoln Lucy , Smalley Susan , Hudziak James J.
Published: December 2021

Background

Personality traits are important factors with regard to the tendency to experience and response to stress. This study introduces and tests a new stress-related personality scale called the Virtual Inventory of Behavior and Emotions (VIBE).

Methods

Two samples totaling 5512 individuals (with 66% between the ages of 18 and 34) completed the VIBE along with other measures of personality, stress, mood, and well-being. Results: Exploratory factor analyses revealed a four-factor structure for the instrument with dimensions labelled: 1) stressed; 2) energetic; 3) social; and 4) disciplined. Confirmatory factor analytic procedures on the final 23-item version showed good psychometric properties and data fit while machine learning analyses demonstrated the VIBE’s ability to distinguish between groups with similar patterns of response. Strong convergent validity was suggested through robust correlations between the dimensions of the VIBE and other established rating scales.

Conclusion

Overall, the data suggest that the VIBE is a promising tool to help advance understanding of the relations between stress, personality, and related constructs.
Plasmodium vivax malaria serological exposure markers: assessing the degree and implications of cross-reactivity with P. knowlesi
Authors: Longley Rhea J , Grigg Matthew J , Schoffer Kael , Obadia Thomas , Hyslop Stephanie , Piera Kim A. , Nekkab Narimane , Mazhari Ramin , Takashima Eizo , Tsuboi Takafumi , Harbers Matthias , Tetteh Kevin , Drakeley Chris , Chitnis Chetan E. , Healer Julie , Tham Wai-Hong , Sattabongkot Jetsumon , White Michael T , Cooper Daniel J , Rajahram Giri S , Barber Bridget E. , William Timothy , Anstey Nicholas M , Mueller Ivo
Published: December 2021

Serological exposure markers are a promising tool for surveillance and targeted interventions for Plasmodium vivax malaria. P. vivax is closely related to the zoonotic parasite P. knowlesi, which also infects humans. P. vivax and P. knowlesi are co-endemic across much of South East Asia, making it important to design P. vivax serological markers that minimise cross-reactivity in this region. Our objective was to determine the degree of IgG antibody cross-reactivity against a panel of P. vivax serological markers in samples from human participants with P. knowlesi malaria. We observed higher levels of IgG antibody reactivity against P. vivax proteins that had high levels of sequence identity with their P. knowlesi ortholog. IgG reactivity peaked at 7 days post P. knowlesi infection and was short-lived, with minimal responses detected at 1-year post-infection. Using these data, we designed a panel of 8 P. vivax proteins with low-levels of cross-reactivity with P. knowlesi. This panel was able to accurately classify recent P. vivax infections whilst reducing misclassification of recent P. knowlesi infections.
(SARS-CoV-2) COVID 19: Genomic surveillance and evaluation of the impact on the population speaker of indigenous language in Mexico
Authors: Medel-Ramírez Carlos , Medel-López Hilario , Mérida Jennifer Lara
Published: December 2021

The importance of the working document is that it allows the analysis of information and cases associated with (SARS-CoV-2) COVID-19, based on the daily information generated by the Government of Mexico through the Secretariat of Health, responsible for the Epidemiological Surveillance System for Viral Respiratory Diseases (SVEERV). The information in the SVEERV is disseminated as open data, and the level of information is displayed at the municipal, state and national levels. On the other hand, the monitoring of the genomic surveillance of (SARS-CoV-2) COVID-19, through the identification of variants and mutations, is registered in the database of the Information System of the Global Initiative on Sharing All Influenza Data (GISAID) based in Germany. These two sources of information SVEERV and GISAID provide the information for the analysis of the impact of (SARS-CoV-2) COVID-19 on the population in Mexico. The first data source identifies information, at the national level, on patients according to age, sex, comorbidities and COVID-19 presence (SARS-CoV-2), among other characteristics. The data analysis is carried out by means of the design of an algorithm applying data mining techniques and methodology, to estimate the case fatality rate, positivity index and identify a typology according to the severity of the infection identified in patients who present a positive result. for (SARS-CoV-2) COVID-19. From the second data source, information is obtained worldwide on the new variants and mutations of COVID-19 (SARS-CoV-2), providing valuable information for timely genomic surveillance. This study analyzes the impact of (SARS-CoV-2) COVID-19 on the indigenous language-speaking population, it allows us to provide information, quickly and in a timely manner, to support the design of public policy on health.
Starting at the community: Treatment seeking pathways of children with suspected severe malaria in Uganda
Authors: Brunner Nina C. , Karim Aliya , Athieno Proscovia , Kimera Joseph , Tumukunde Gloria , Angiro Irene , Signorell Aita , Delvento Giulia , Lee Tristan T. , Lambiris Mark , Ogwal Alex , Nakiganda Juliet , Mpanga Flavia , Kagwire Fred , Amutuhaire Maureen , Burri Christian , Lengeler Christian , Awor Phyllis , Hetzel Manuel W.
Published: December 2021

Introduction

Community health workers (CHW) usually refer children with suspected severe malaria to the nearest public health facility or a designated public referral health facility (RHF). Caregivers do not always follow this recommendation. This study aimed at identifying post-referral treatment-seeking pathways that lead to appropriate antimalarial treatment for children less than five years with suspected severe malaria.

Methods

An observational study in Uganda enrolled children below five years presenting to CHWs with signs of severe malaria. Children were followed up 28 days after enrolment to assess their condition and treatment-seeking history, including referral advice and provision of antimalarial treatment from visited providers.

Results

Of 2211 children included in the analysis, 96% visited a second provider after attending a CHW. The majority of CHWs recommended caregivers to take their child to a designated RHF (65%); however, only 59% followed this recommendation. Many children were brought to a private clinic (33%), even though CHWs rarely recommended this type of provider (3%). Children who were brought to a private clinic were more likely to receive an injection than children brought to a RHF (78% vs 51%, p<0.001) and more likely to receive the second or third-line injectable antimalarial (artemether: 22% vs. 2%, p<0.001, quinine: 12% vs. 3%, p<0.001). Children who only went to non-RHF providers were less likely to receive an artemisinin-based combination therapy (ACT) than children who attended a RHF (odds ratio [OR] = 0.64, 95% CI 0.51–0.79, p<0.001). Children who did not go to any provider after seeing a CHW were the least likely to receive an ACT (OR = 0.21, 95% CI 0.14–0.34, p<0.001).

Conclusions

Health policies should recognise local treatment-seeking practices and ensure adequate quality of care at the various public and private sector providers where caregivers of children with suspected severe malaria actually seek care.
Comparing men who have sex with men and inject drugs and people who inject drugs who are men and have sex with men in San Francisco: Implications for HIV and hepatitis C virus prevention
Authors: Artenie Adelina , Facente Shelley N. , Patel Sheena , Stone Jack , Hecht Jennifer , Rhodes Perry , McFarland Willi , Wilson Erin , Vickerman Peter , Morris Meghan D.
Published: December 2021

Background

Men who have sex with men (MSM) and people who inject drugs (PWID) carry a disproportionate burden of HIV and hepatitis C virus (HCV) infections. We compared the demographic and risk profiles of MSM who inject drugs (MSM-IDU, i.e., men reached through affiliation with MSM) and PWID who are men and have sex with men (PWID-MSM, i.e., men reached through affiliation with PWID).

Methods

We used data from the most recent waves of the National HIV Behavioural Surveillance among MSM (2017) and PWID (2018) in San Francisco. Participants were recruited through venue-based (MSM) and peer-referral (PWID) sampling and completed standardised questionnaires. We compared the characteristics of MSM-IDU and PWID-MSM using bivariate tests.

Results

Of 504 participants completing the MSM survey, 6.2% reported past-year injection drug use (MSM-IDU). Among 311 male participants completing the PWID survey, 19.0% reported past-year sex with a male (PWID-MSM). Relative to MSM-IDU, more PWID-MSM were older, identified as bisexual, had lower income, a history of incarceration and were homeless. MSM-IDU had more male sexual partners (median: 10 vs 3) and fewer injected daily (29.0% vs 64.4%) than PWID-MSM. While more PWID-MSM sought sterile equipment from a syringe program (86.4% vs 35.5%), fewer reported using PrEP (15.0% vs 42.9%).

Conclusion

The sociodemographic, risk behaviour, and prevention access profiles of MSM-IDU and PWID-MSM in San Francisco suggest that they represent distinct populations who may require tailored HIV and HCV prevention strategies. MSM- and PWID-focused prevention programs should provide combined sexual health and harm reduction messages and services.
Emotional Distress, Stress, Anxiety and the Impact of the COVID-19 Pandemic on Early Career Women in Healthcare Sciences Research
Authors: Bittar Noor , Cohee Andrea A. , Savoy April , Ismail Heba M
Published: December 2021

Objectives

The main objective of this study was to report stress and anxiety levels during the early period of the pandemic on early career women researchers in health sciences research and determine the factors associated with increased stress and anxiety.

Methods

A 50-item self-administered internet questionnaire was developed using a mix of Likert-type scales and open-ended response questions. The survey was distributed via email and social media platforms June 10-August 3, 2020. Anxiety and stress associated with the demands of being in health sciences research as well as personal/family demands were assessed through validated measures (Patient Reported Outcomes Measurement Information System (PROMIS)-Anxiety Short Form and Perceived Stress Scale (PSS)) and open-ended responses.

Results

One hundred and fifty-one early career women in healthcare sciences research completed the survey. The mean respondent age was 37.3±5.2 years, all had a college degree or higher, 50.3% holding a PhD and 35.8%, M.D. Of the 151 respondents, 128 reported their race/ethnicity and the majority were Caucasian (74.0%). One-third (31.2%) reported being ‘very much’ concerned about reaching their research productivity goals, and 30.1% were ‘very much’ concerned about academic promotion and tenure. Fifty percent reported a ‘moderate’ PROMIS anxiety score and 72.1% reported a ‘moderate’ PSS score. For the open-ended responses, 65.6% reported a worry about their professional goals as a result of the COVID-19 pandemic. Major concerns revolved around finances, childcare and job security.

Conclusions

Throughout the pandemic, early career women investigators have reported high overall stress, anxiety and worries.
Machine Learning to Understand Genetic and Clinical Factors Associated with the Pulse Waveform Dicrotic Notch
Authors: Cunningham Jonathan W. , Achille Paolo Di , Morrill Valerie N. , Weng Lu-Chen , Choi Seung Hoan , Khurshid Shaan , Nauffal Victor , Pirruccello James P , Solomon Scott D. , Batra Puneet , Ho Jennifer E. , Philippakis Anthony A. , Ellinor Patrick T. , Lubitz Steven A.
Published: December 2021

Background

Absence of a dicrotic notch on finger photoplethysmography (PPG) is an easily ascertainable and inexpensive trait that has been associated with age and prevalent cardiovascular disease (CVD). However, the trait exists along a continuum, and little is known about its genetic underpinnings or prognostic value for incident CVD.

Methods

In 169,787 participants in the UK Biobank, we identified absent dicrotic notch on PPG and created a novel continuous trait reflecting notch smoothness using machine learning. Next, we determined the heritability, genetic basis, polygenic risk, and clinical relations for the binary absent notch trait and the newly derived continuous notch smoothness trait.

Results

Heritability of the continuous notch smoothness trait was 7.5%, compared with 5.6% for the binary absent notch trait. A genome wide association study of notch smoothness identified 15 significant loci, implicating genes including NT5C2 (P=1.2×10−26), IGFBP3 (P=4.8×10−18), and PHACTR1 (P=1.4×10−13), compared with 6 loci for the binary absent notch trait. Notch smoothness stratified risk of incident myocardial infarction or coronary artery disease, stroke, heart failure, and aortic stenosis. A polygenic risk score for notch smoothness was associated with incident CVD and all-cause death in UK Biobank participants without available PPG data.

Conclusion

We found that a machine learning derived continuous trait reflecting dicrotic notch smoothness on PPG was heritable and associated with genes involved in vascular stiffness. Greater notch smoothness was associated with greater risk of incident CVD. Raw digital phenotyping may identify individuals at risk for disease via specific genetic pathways.
Attributable is Preventable: Corrected and revised estimates of population attributable fraction of TB related to undernutrition in 30 high TB burden countries
Authors: Bhargava Anurag , Bhargava Madhavi , Beneditti Andrea , Kurpad Anura
Published: December 2021

Introduction

The Global TB Report 2020 estimated the population attributable fractions (PAF) for the major risk factors of TB. Undernourishment emerged as the leading risk factor accounting for 19% of the cases. The WHO however used the terms undernourishment and undernutrition interchangeably in its computation of PAF. Undernourishment is an indirect model derived estimate of decreased per capita energy availability, while undernutrition is defined by direct anthropometric measurements of nutritional status.

Methods

We re-estimated the PAF of undernutrition (instead of undernourishment) in 30 high TB burden countries, using the prevalence of undernutrition (age standardized estimate of BMI < 18.5 kg/m2 in adults for both sexes), and the relative risk (RR) of 3.2. Further, we revised PAF estimates of undernutrition with an RR of 4.49, in light of recent evidence.

Findings

Twenty four percent of TB in high burden countries is attributable to undernutrition. The PAF of undernutrition was highest in Asian countries, unlike the PAF of undernourishment that was highest in Africa. The corrected estimate led up to 65% increase in number of cases attributable to undernutrition in Asian countries. More than one-third to nearly half of TB cases in India could be attributable to undernutrition.

Interpretation

Estimation of the PAF of TB related to undernutrition is methodologically valid and operationally relevant, rather than PAF related to undernourishment. Addressing undernutrition, the leading driver of TB in high TB burden countries (especially Asia) could enable achievement of END TB milestones of TB incidence for 2025.
Mental health indicators in Sweden over a 12-month period during the COVID-19 pandemic
Authors: Lovik Anikó , González-Hijón Juan , Kähler Anna K. , Valdimarsdóttir Unnur A. , Frans Emma M. , Magnusson Patrik K. E. , Pedersen Nancy L. , Hall Per , Czene Kamila , Sullivan Patrick F. , Fang Fang
Published: December 2021

Background

The ongoing COVID-19 pandemic has had an unprecedented impact on the lives of people globally and is expected to have profound effects on mental health. Yet, self-reported large-scale online surveys on mental health are still relatively uncommon. Here we aim to describe the mental health burden experienced in Sweden using baseline data of the Omtanke2020 Study.

Method

Self-reported baseline data collected over a 12-month period (June 9, 2020-June 8, 2021) from the longitudinal online survey of the Omtanke2020 Study including 27,950 adults in Sweden. Participants were volunteers or actively recruited through existing cohorts and after providing informed consent responded to monthly online questionnaires on socio-demographics, mental and physical health, COVID-19 infection, and impact. Poisson regression was fitted to assess the relative risk of high mental health burden (depression, anxiety, and COVID-19 specific PTSD).

Result

The overall proportion of persons with high level of symptoms was 15.6%, 9.5% and 24.5% for depression, anxiety, and COVID-19 specific PTSD, respectively. Overall, 43.4% of the participants had significant, clinically relevant symptoms for at least one mental health outcome and 7.3% had significant symptoms for all three outcomes. We also observed differences in the prevalence of these symptoms across strata of sex, age, recruitment type, COVID-19 status, region, and seasonality.

Conclusion

While the proportion of persons with high mental health burden remains higher than in pre-pandemic publications, our estimates are lower than previously reported levels of depression, anxiety, and PTSD during the pandemic in Sweden and elsewhere.
A mechanistic investigation of enhanced nitrogen use efficiency in wheat seedlings after treatment with an Ascophyllum nodosum biostimulant
Authors: Łangowski Łukasz , Goñi Oscar , Ikuyinminu Elomofe , Feeney Ewan , O’Connell Shane
Published: December 2021

Reduction in the emissions of the greenhouse gas nitrous oxide and nitrogen (N) pollution of ground water by improving nitrogen use efficiency (NUE) in crops is urgently required in pursuit of a sustainable agricultural future. Utilising an engineered biostimulant (PSI-362) derived from the brown seaweed Ascophyllum nodosum, we examined its effect on wheat seedling growth dynamics and mechanistic spatiotemporal changes at transcriptional and biochemical levels in relation to N uptake, assimilation and NUE. PSI-362-mediated biomass increase was associated with increased nitrate uptake and N assimilation in the form of glutamate, glutamine, free amino acids, soluble proteins and total chlorophyll. Phenotypical and biochemical analysis were supported by evaluation of differential expression of genetic markers involved in nitrate perception and transport (TaNRT1.1/NPF6.3), and assimilation (TaNR1 and TaNiR1, TaGDH2, TaGoGAT, TaGS1). Finally, a comparative analysis of the PSI-362 and two generic Ascophyllum nodosum extracts (ANEs) demonstrated that the NUE effect greatly differs depending on the ANE biostimulant used. In the current context of climate warming the transition of agriculture to a more sustainable model is urgently required. Application and adoption of precision biostimulants creates an opportunity for sustainable crop management, reduced production cost and environmental pollution, while maintaining yields.
Leptin-mediated suppression of food intake by conserved Glp1r-expressing neurons prevents obesity
Authors: Rupp Alan C. , Tomlinson Abigail J. , Affinati Alison H. , True Cadence , Lindsley Sarah R. , Kirigiti Melissa A. , MacKenzie Alexander , Li Chien , Knudsen Lotte Bjerre , Olson David P. , Kievit Paul , Myers Martin G.
Published: December 2021

The adipose-derived hormone leptin acts via its receptor (LepRb) in the brain to control energy balance. A previously unidentified population of GABAergic hypothalamic LepRb neurons plays key roles in the restraint of food intake and body weight by leptin. To identify markers for candidate populations of LepRb neurons in an unbiased manner, we performed single-nucleus RNA-sequencing of enriched mouse hypothalamic LepRb cells, as well as with total hypothalamic cells from multiple mammalian species. In addition to identifying known LepRb neuron types, this analysis identified several previously unrecognized populations of hypothalamic LepRb neurons. Many of these populations display strong conservation across species, including GABAergic Glp1r-expressing LepRb (LepRbGlp1r) neurons that express more Lepr and respond more robustly to exogenous leptin than other LepRb populations. Ablating LepRb from these cells provoked hyperphagic obesity without impairing energy expenditure. Conversely, reactivating LepRb in Glp1r-expressing cells decreased food intake and body weight in otherwise LepRb-null mice. Furthermore, LepRb reactivation in GABA neurons improved energy balance in LepRb-null mice, and this effect required the expression of LepRb in GABAergic Glp1r-expressing neurons. Thus, the conserved GABAergic LepRbGlp1r neuron population plays crucial roles in the control of food intake and body weight by leptin.