bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficient bending and lifting patterns in snake locomotion
Authors: Alben S.
Published: October 2022

We optimize three-dimensional snake kinematics for locomotor efficiency. We assume a general space-curve representation of the snake backbone with small-to-moderate lifting off the ground and negligible body inertia. The cost of locomotion includes work against friction and internal viscous dissipation. When restricted to planar kinematics, our population-based optimization method finds the same types of optima as a previous Newton-based method. With lifting, a few types of optimal motions prevail. We have an s-shaped body with alternating lifting of the middle and ends at small-to-moderate transverse friction. With large transverse friction, curling and sliding motions are typical at small viscous dissipation, replaced by large-amplitude bending at large viscous dissipation. With small viscous dissipation, we find local optima that resemble sidewinding motions across friction coefficient space. They are always suboptimal to alternating lifting motions, with average input power 10–100% higher.
Impact of a rigid sphere onto an elastic membrane
Authors: Agüero Elvis A. , Alventosa Luke , Harris Daniel M. , Galeano-Rios Carlos A.
Published: October 2022

We study the axisymmetric impact of a rigid sphere onto an elastic membrane theoretically and experimentally. We derive governing equations from first principles and impose natural kinematic and geometric constraints for the coupled motion of the sphere and the membrane during contact. The free-boundary problem of finding the contact surface, over which forces caused by the collision act, is solved by an iterative method. This results in a model that produces detailed predictions of the trajectory of the sphere, the deflection of the membrane, and the pressure distribution during contact. Our model predictions are validated against our direct experimental measurements. Moreover, we identify new phenomena regarding the behaviour of the coefficient of restitution for low impact velocities, the possibility of multiple contacts during a single rebound, and energy recovery on subsequent bounces. Insight obtained from this model problem in contact mechanics can inform ongoing efforts towards the development of predictive models for contact problems that arise naturally in multiple engineering applications.
The power of vision: calibration of auditory space after sight restoration from congenital cataracts
Authors: Senna Irene , Piller Sophia , Gori Monica , Ernst Marc
Published: October 2022

Early visual deprivation typically results in spatial impairments in other sensory modalities. It has been suggested that, since vision provides the most accurate spatial information, it is used for calibrating space in the other senses. Here we investigated whether sight restoration after prolonged early onset visual impairment can lead to the development of more accurate auditory space perception. We tested participants who were surgically treated for congenital dense bilateral cataracts several years after birth. In Experiment 1 we assessed participants' ability to understand spatial relationships among sounds, by asking them to spatially bisect three consecutive, laterally separated sounds. Participants performed better after surgery than participants tested before. However, they still performed worse than sighted controls. In Experiment 2, we demonstrated that single sound localization in the two-dimensional frontal plane improves quickly after surgery, approaching performance levels of sighted controls. Such recovery seems to be mediated by visual acuity, as participants gaining higher post-surgical visual acuity performed better in both experiments. These findings provide strong support for the hypothesis that vision calibrates auditory space perception. Importantly, this also demonstrates that this process can occur even when vision is restored after years of visual deprivation.
A rare and fatal case of puerperal sepsis due to Burkholderia pseudomallei

Authors: Bhaskar M Maanasa , Rajamanikam Soundarya , Raj Sruthi , Sistla Sujatha , Nichanahalli Kubera Siddappa
Published: October 2022

Introduction : Melioidosis is an emerging life threatening  infectious disease caused by Gram negative bacilli  Burkholderia pseudomallei  found in contaminated soil and surface ground water .  It often presents with varied clinical manifestations and has a high mortality if left untreated due to lack of clinical suspicion. Here we report a rare and fatal case of puerperal sepsis due to  Burkholderia pseudomallei  in a young woman.
Case report:  A 25-year-old female comes to a medical consultation at day 43 post partum with complains of fever on and off for the past 40 days associated with vomiting. On per speculum examination, greenish discharge from the cervix was seen and a right adnexal mass was felt which was cystic in consistency, non-tender and pushing cervix to the left side. Exploratory laparotomy was carried out and pus was drained from below the rectus sheath, and from right tubo-ovarian mass. Peripheral blood sample and the pus samples collected intraoperatively grew  Burkholderia pseudomallei . The patient expired on the 5 th  post operative day due to septic shock with disseminated intravascular coagulation  secondary to puerperal sepsis. 
Conclusion:  Melioidosis is a fatal but treatable disease when it is promptly diagnosed. In a country like India, where tuberculosis is highly endemic, underdiagnosis of melioidosis can be a common consequence. Clinicians and Microbiologists should have high index of suspicion especially in individuals with underlying illness.
A Multi-Center, Controlled Human Infection Study of Influenza A (H1N1)pdm09 in Healthy Adults
Authors: Ortiz Justin R. , Bernstein David I. , Hoft Daniel F. , Woods Christopher W. , McClain Micah T. , Frey Sharon E. , Brady Rebecca C. , Bryant Christopher , Wegel Ashley , Frenck Robert W , Walter Emmanuel B. , Abate Getahun , Williams Sarah R. , Atmar Robert L. , Keitel Wendy A. , Rouphael Nadine , Memoli Mathew J. , Makhene Mamodikoe K. , Roberts Paul C. , Neuzil Kathleen M.
Published: October 2022

Background

Influenza controlled human infection model (CHIM) studies can advance development of vaccines and therapeutics. Our objective was to evaluate the associations between baseline challenge virus-specific hemagglutination inhibition (HAI) and microneutralization (MN) titers and subsequent symptomatic influenza virus infection.

Methods

We enrolled healthy adults aged 18 through 49 years in a multisite CHIM study using influenza A/Bethesda/MM2/H1N1, an A/California/04/2009/H1N1pdm-like virus (NCT04044352). We excluded persons vaccinated against influenza within the previous six months. We collected serial safety labs, serum for HAI and MN, and nasopharyngeal swabs for RT-PCR testing. Analyses used the putative seroprotective titer of ≥40 for HAI and MN. The primary clinical outcome was mild-to-moderate influenza disease (MMID), defined as ≥1 post-challenge positive qualitative RT-PCR test with a qualifying symptom/clinical finding.

Findings

Of 76 participants given influenza virus challenge, 54 (71.1%) experienced MMID. Clinical illness post-challenge was generally very mild. MMID attack rates among participants with baseline titers ≥40 by HAI and MN were 64.9% and 67.9%, respectively, while MMID attack rates among participants with baseline titers <40 by HAI and MN were 76.9% and 78.3%, respectively. The estimated odds of developing MMID decreased by 19% (odds ratio=0.81; 95% CI: 0.62, 1.06; p=0.126) for every two-fold increase in baseline HAI. There were no deaths, serious adverse events, or other significant adverse events.

Interpretation

In a multi-site influenza CHIM study, we assured the safety of our participants and achieved a 71.1% attack rate of MMID. High baseline HAI and MN were associated with protection from illness.
Evaluating the Evidence Quality Supporting the Role of Acupuncture for Herpes Zoster Pain: An Umbrella Review of Systematic Reviews and Meta-analyses
Authors: Li Jianhong , Liu Kun , Ruan Wenjia , Lin Guohua
Published: October 2022

Objective

Acupuncture is one of the most effective means to treat herpes zoster, especially during the acute stage. It can shorten the duration of pain, with a low incidence of residual neuralgia. The aim of this review was to assess the methodological and evidence quality of systematic reviews and meta-analyses on acupuncture for herpes zoster pain and provide clinical suggestions.

Methods

Eight databases were searched from their inception to Feb 2022. Methodological quality was evaluated by using the Assessment of Multiple Systematic Reviews 2, and the Grading of Recommendations Assessment Development and Evaluation was applied to evaluate the quality of the evidence.

Results

Nineteen SRs/MAs were included according to the inclusion criteria. Assessment of Multiple Systematic Reviews 2 results showed that the methodological quality was low for 16 studies and very low for 3 studies. According to the Grading of Recommendations Assessment Development and Evaluation, 43 outcome indicators were evaluated in this review, and the results showed that the evidence quality was high in three, medium in twelve, low in twenty-three, and very low in five. Compared with drugs for herpes zoster, acupuncture can reduce pain and the incidence of postherpetic neuralgia. Acupuncture at Jia ji acupoint was generally one of the most effective methods.

Conclusions

Our study showed that fire needle, acupuncture at Jia ji, pricking collaterals and bloodletting are beneficial therapies for the clinical practice of herpes zoster. However, the methodological and evidence quality of the included studies were low. More rigorous design and comprehensive investigations by systematic reviews and meta-analyses are needed.

Strengths and limitations of this study

This study is a comprehensive review to assess the methodological and evidence quality of recent SRs/MAs on acupuncture for herpes zoster pain, we mainly focused on pain symptoms, for example VAS score, time for pain relief, incidence of PHN, with qualitative analysis of efficiency. Only systematic reviews published in Chinese and English were included, so the conclusions of this study may not be generalizable. Some gray documents may be omitted. Subjective factors could not be completely eliminated during screening and evaluation.

PROSPERO registration number CRD42022304247.
The Long-term Mediation Role of Cytokines on the Causal Pathway from Maternal Gestational Age to Offspring Visual System: Lifecourse-Network Mendelian Randomization
Authors: Hou Lei , Li Yunxia , Kang Lili , Li Xiaoying , Li Hongkai , Xue Fuzhong
Published: October 2022

Background

Gestational duration has a non-negligible impact on eye diseases. However, the long-term role of cytokines on the causal relationship of maternal gestational age on offspring visual impairment remains unclear.

Methods

We perform a lifecourse-network Mendelian randomization (MR) to explore the causal relationships among maternal gestational duration (from EGG and iPSYCH, N=84,689), neonatal/adult cytokines (from the NHGRI-EBI Catalog, N=764/4,618) and adult eye diseases (from FinnGen consotium, N=309,154) using summary-level data from large genome-wide association studies. Multiplicative random effects inverse variance weighted (IVW) and multivariable-IVW method are the main analysis methods and the other 15 pleiotropy-robust methods, weak IV-robust methods and outliers-robust methods are performed as auxiliary methods.

Results

We find that maternal gestational age (early preterm birth, preterm birth, gestational duration and postterm birth) has causal relationships with 42 eye diseases. Specially, four neonatal cytokines: TNF-α, IL10, GROA and CTACK, as well as four adult cytokines: CTACK, IL10, IL12p70 and IL6.26 are mediators in the causal relationships between early preterm birth and preterm birth to 8 eye diseases. However, after adjusting for these mediators, null direct causal effect of early preterm birth and preterm birth on 8 eye diseases can be found. In addition, there is no mediator in the causal relationships from gestational duration and postterm birth to eye diseases.

Conclusion

The influences of maternal gestational duration on the offspring eye diseases through cytokines are long-term and lifecourse.
Genetic, demographic and clinical variables act synergistically to impact neurodevelopmental outcomes in children with single ventricle heart disease
Authors: Miller Thomas A. , Hernandez Edgar J. , Gaynor J. William , Russell Mark W. , Newburger Jane W. , Chung Wendy , Goldmuntz Elizabeth , Cnota James F. , Zyblewski Sinai C. , Mahle William T. , Zak Victor , Ravishankar Chitra , Kaltman Jonathan R. , McCrindle Brian W. , Clarke Shanelle , Votava-Smith Jodie K. , Graham Eric M. , Seed Mike , Rudd Nancy , Bernstein Daniel , Lee Teresa M. , Yandell Mark , Tristani-Firouzi Martin
Published: October 2022

Recent large-scale sequencing efforts have shed light on the genetic contribution to the etiology of congenital heart defects (CHD); however, the relative impact of genetics on clinical outcomes remains less understood. Outcomes analyses using genetic data are complicated by the intrinsic severity of the CHD lesion and by interactions with conditionally dependent clinical variables. Here we apply Bayesian Networks, an explainable Artificial Intelligence solution, to describe the intertwined relationships between clinical variables, demography, and genetics in a cohort of children with single ventricle CHD. As isolated variables, a damaging genetic variant in a gene related to abnormal heart morphology and prolonged ventilator support following stage I palliative surgery increased the probability of having a low Mental Developmental Index (MDI) score at 14 months of age by 1.9- and 5.8-fold, respectively. However, in combination, these variables acted synergistically to further increase the probability of a low MDI score by 10-fold. Likewise, genetic information was predictive of a favorable neurodevelopmental outcome. For example, the absence of a damaging variant in a known syndromic CHD gene and a shorter post-operative ventilator support increased the probability of a normal MDI score 1.7- and 2.4-fold, respectively, but in combination increased the probability of a good outcome by 59-fold. Our analyses suggest a modest genetic contribution to neurodevelopmental and growth outcomes as isolated variables, similar to known clinical predictors. By contrast, genetic, demographic, and clinical variables interact synergistically to markedly impact clinical outcomes. These findings underscore the importance of capturing and quantifying the impact of damaging genomic variants in the context of multiple, conditionally dependent variables, such as pre- and post-operative factors, and demography.
Gene expression profiling and protein-protein network analysis revealed prognostic hub biomarkers linking cancer risk in type 2 diabetic patients
Authors: Kasera Harshita , Shekhawat Rajveer Singh , Yadav Pankaj , Singh Priyanka
Published: October 2022

Type 2 diabetes mellitus (T2DM) and cancer are highly prevalent diseases imposing major health burden globally. Several epidemiological studies indicate increased susceptibility to cancer in T2DM patients. However, genetic factors linking T2DM with cancer are poorly studied so far. We used computational approach on the raw gene expression data of peripheral blood mononuclear cells of Homo sapiens available at the gene expression omnibus (GEO) database, to identify shared differentially expressed genes (DEGs) in T2DM and three common cancer types namely, pancreatic (PC), liver (LC) and breast cancer (BC). Additional functional and pathway enrichment analysis of identified common DEGs highlighted involvement of important biological pathways including cell cycle events, immune system process, cell morphogenesis, gene expression and metabolism. Furthermore, we retrieved the PPI network for crucial DEGs obtained from above analysis to deduce molecular level interactions. Based on the result of network analysis, we found 8, 5 and 9 common hub genes in T2DM vs PC, T2DM vs LC and T2DM vs BC, respectively. Overall, our analysis identified important genetic markers potentially able to predict the chances of pancreatic, liver and breast cancer onset in T2DM patients.
Evaluating the potential of marine invertebrate and insect protein hydrolysates to reduce fetal bovine serum in cell culture media for cultivated fish production
Authors: Batish Inayat , Zarei Mohammad , Nitin Nitin , Ovissipour Reza
Published: October 2022

The use of fetal bovine serum (FBS) and the price of the cell culture media are the key constraints for developing serum-free cost-effective media. This study aims to replace or reduce the typical 10% serum application in fish cell culture media by applying protein hydrolysates from insects and marine invertebrate species for the growth of Zebrafish embryonic stem cells (ESC) as the model organism. Protein hydrolysates were produced from Black soldier fly (BSF), cricket, oyster, mussel, and lugworm with high protein content, suitable functional properties, adequate amino acids composition, and the degree of hydrolysis from 18.24 to 33.52%. Protein hydrolysates at low concentrations from 0.001 to 0.1 mg/mL in combination with 1 and 2.5% serum significantly increased cell growth compared to the control groups (5 and 10% serum) (P < 0.05). All protein hydrolysates with concentrations of 1 and 10 mg/mL were found to be toxic to cells and significantly reduced cell growth and performance (P < 0.05). However, except for cricket, all hydrolysates were able to restore or significantly increase cell growth and viability with 50% less serum at a concentration of 0.001, 0.01, and 0.1 mg/mL. Although cell growth was enhanced at lower concentrations of protein hydrolysates, cell morphology was altered due to the lack of serum. Lactate dehydrogenase (LDH) activity results indicated that BSF and lugworm hydrolysates did not alter the cell membrane. In addition, light and fluorescence imaging revealed that cell morphological features were comparable to the 10% serum control group. Overall, lugworm and BSF hydrolysates reduced serum by up to 90% while preserving excellent cell health.
Topological incongruence between Median-Joining Networks and Bayesian inference phylogenies
Authors: Kong Sungsik , Sánchez-Pacheco Santiago J. , Murphy Robert W.
Published: October 2022

1

Inferring phylogenies among intraspecific individuals often yields unresolved relationships (i.e., polytomies). Consequently, methods that compute distance-based abstract networks, like Median-Joining Networks (MJNs), are thought to be more appropriate tools for reconstructing such relationships than traditional trees. MJNs visualize all routes of relationships in the form of cycles, if needed, when traditional approaches cannot resolve them. However, the MJN method is a distance-based phenetic approach that does not involve character transformations and makes no reference to ancestor–descendant relationships. Although philosophical and theoretical arguments challenging the implication that MJNs reflect phylogenetic signal in the traditional sense have been presented elsewhere, an empirical comparison with a character-based approach is needed given the increasing popularity of MJN analysis in evolutionary biology. Here, we use the conservative Approximately Unbiased (AU) test to compare 85 cases of branching patterns of cycle-free MJNs and Bayesian Inference (BI) phylogenies using datasets from 55 empirical studies. By rooting the MJN analyses to provide directionality, analyses find substantial disagreement between computed MJNs and posterior distributions on BI phylogenies. The branching patterns in MJNs and BI phylogenies show significantly different relationships in 37.6% of cases. Among the relationships that were not significantly different, 96.2% show different sets of relationships. Our results indicate that the two methods provide different measures of relatedness in a phylogenetic sense. Finally, our analyses also support previous observations of the statistical hypothesis testing by reconfirming the over-conservativeness of the Shimodaira–Hasegawa test versus the AU test.
Tunable image-mapping optical coherence tomography
Authors: Lee Jaeyul , Du Xiaoxi , Park Jongchan , Cui Qi , Iyer Rishyashring R. , Boppart Stephen A. , Gao Liang
Published: October 2022

We present tunable image-mapping optical coherence tomography (TIM-OCT), which can provide optimized imaging performance for a given application by using a programmable phase-only spatial light modulator in a low-coherence full-field spectral-domain interferometer. The resultant system can provide either a high lateral resolution or a high axial resolution in a snapshot without moving parts. Alternatively, the system can achieve a high resolution along all dimensions through a multiple-shot acquisition. We evaluated TIM-OCT in imaging both standard targets and biological samples. Additionally, we demonstrated the integration of TIM-OCT with computational adaptive optics in correcting sample-induced optical aberrations.
Assessing a multivariate model of brain-mediated genetic influences on disordered eating in the ABCD cohort
Authors: Westwater Margaret L. , Mallard Travis T. , Warrier Varun , Bethlehem Richard A.I. , Scheinost Dustin , Grillon Christian , Fletcher Paul C. , Seidlitz Jakob , Ernst Monique
Published: October 2022

Eating disorders (EDs) are complex psychiatric conditions that often emerge during adolescence, and affected individuals frequently demonstrate high rates of psychiatric comorbidity, particularly with depressive and anxiety disorders. Although risk for EDs reflects both genetic and neurobiological factors, knowledge of how genetic risk for EDs relates to neurobiology and psychiatric symptoms during critical developmental periods remains limited. We therefore implemented a novel multivariate framework, which sought to advance knowledge of the etiology of EDs by simultaneously estimating associations between genetic risk, brain structure and ED-related psychopathology symptoms in over 4,500 adolescents of European ancestry from the Adolescent Brain and Cognitive Development study (M(SD)age=119.29(7.49) months). Polygenic scores for anorexia nervosa (AN PGS) and body mass index (BMI PGS) were generated and related to three morphometric brain features— cortical thickness, surface area and subcortical grey matter volume—and to latent psychopathology factors using structural equation modeling. We identified a three-factor structure of ED-related psychopathology symptoms: eating, distress and fear factors. Increased BMI PGS were uniquely associated with greater eating factor scores, whereas AN PGS were unrelated to psychopathology factors. Moreover, genetic risk for high BMI and for AN had distinct neural correlates, where greater BMI PGS predicted widespread increases in cortical thickness and reductions in surface area while AN PGS were nominally related to reduced caudate volume. Altered default mode and visual network thickness was associated with greater eating factor scores, whereas distress and fear factor scores reflected a shared reduction in somatomotor network thickness. Our novel findings indicate that greater genetic risk for high BMI and altered cortical thickness of canonical brain networks underpin ED symptomatology in early adolescence. As neurobiological factors appear to shape disordered eating earlier in the life course than previously thought, these results underscore the need for early detection and intervention efforts for EDs.
Fatal cases after Omicron BA.1 and BA.2 infection: Diffuse alveolar damage occurs only in a minority – results of an autopsy study
Authors: Märkl Bruno , Dintner Sebastian , Schaller Tina , Sipos Eva , Kling Elisabeth , Miller Silvia , Farfan Francisco , Grochowski Przemyslaw , Reitsam Nic , Waidhauser Johanna , Hirschbühl Klaus , Spring Oliver , Fuchs Andre , Wibmer Thomas , Boor Peter , Beer Martin , Wylezich Claudia
Published: October 2022

Compared with previously prevalent variants of SARS-CoV-2, the Omicron lineages BA.1 and BA.2 are known to be associated with mild clinical courses. In addition, well-established animal models do not develop severe diseases.

To address whether the supposedly fatal cases after Omicron-BA.1/2 infection show the known COVID-19 organ alterations, especially in the lungs, 23 full and 3 partial autopsies in the deceased with known Omicron BA.1/2 infections have been consecutively performed. Viral RNA was determined by RT-qPCR and RNA-in situ hybridization. The lineages were analyzed by whole genome sequencing or S-gene analysis.

Despite high viral loads in almost all nasopharyngeal swabs and in 13 lung tissue samples, death caused by COVID-19-associated diffuse alveolar damage (DAD) in the acute and organizing stages was found in only eight cases (31%). This rate is significantly lower compared to previous studies, including non-Omicron variants, where rates of 92% and 69% for non-vaccinated and fully vaccinated vaccines were observed. It is of special interest that neither vaccination status nor known risk factors (i.e., age, comorbidities, obesity, immuno-suppression) were significantly associated with a direct cause of death by COVID-19. Only the reason for the hospital admission of the patients due to COVID-19-related symptoms showed a significant correlation with directly COVID-19-caused deaths (P < 0.001).

DAD still occurred in the Omicron BA.1/BA.2 era of the SARS-CoV-2 pandemic but at a considerably lower frequency than seen with previous variants of concern. In our study, none of the known risk factors discriminated the cases with COVID-19-caused death from those that had COVID-19 infections but died due to a different disease. Therefore, the host’s genomics might play a key role in this regard. Further studies are urgently needed to elucidate the existence of a genomic mechanism as a risk factor for a fatal course.
Predicting congenital syphilis cases: a performance evaluation of different machine learning models
Authors: Teixeira Igor Vitor , Silva Leite Morgana Thalita da , de Morais Melo Flávio Leandro , Silva Rocha Élisson da , Sadok Sara , da Costa Carrarine Ana Sofia Pessoa , Santana Marília , Rodrigues Cristina Pinheiro , de Lima Oliveira Ana Maria , Gadelha Keduly Vieira , de Morais Cleber Matos , Kelner Judith , Endo Patricia Takako
Published: October 2022

Background

Communicable diseases represent a huge economic burden for healthcare systems and for society. Sexually transmitted infections (STIs) are a concerning issue, especially in developing and underdeveloped countries, in which environmental factors and other determinants of health play a role in contributing to its fast spread. In light of this situation, machine learning techniques have been explored to assess the incidence of syphilis and contribute to the epidemiological surveillance in this scenario.

Objective

The main goal of this work is to evaluate the performance of different machine learning models on predicting undesirable outcomes of congenital syphilis in order to assist resources allocation and optimize the healthcare actions, especially in a constrained health environment.

Method

We use clinical and sociodemographic data from pregnant women that were assisted by a social program in Pernambuco, Brazil, named Mãe Coruja Pernambucana Program (PMCP). Based on a rigorous methodology, we propose six experiments using three feature selection techniques to select the most relevant attributes, pre-process and clean the data, apply hyperparameter optimization to tune the machine learning models, and train and test models to have a fair evaluation and discussion.

Results

The AdaBoost-BODS-Expert model, an Adaptive Boosting (AdaBoost) model that used attributes selected by health experts, presented the best results in terms of evaluation metrics and acceptance by health experts from PMCP. By using this model, the results are more reliable and allows adoption on a daily usage to classify possible outcomes of congenital syphilis using clinical and sociodemographic data.
Social and structural determinants of injection drug use-associated bacterial and fungal infections: a qualitative systematic review and thematic synthesis
Authors: Brothers Thomas D. , Bonn Matthew , Lewer Dan , Comeau Emilie , Kim Inhwa , Webster Duncan , Hayward Andrew , Harris Magdalena
Published: October 2022

Background

Injection drug use-associated bacterial and fungal infections are increasingly common, and social contexts shape individuals’ injecting practices and treatment experiences. We sought to synthesize qualitative studies of social-structural factors influencing incidence and treatment of injecting-related infections.

Methods

We searched PubMed, EMBASE, Scopus, CINAHL, and PsycINFO from January 1, 2000, to February 18, 2021. Informed by Rhodes’ “risk environment” framework, we performed thematic synthesis in three stages: (1) line-by-line coding; (2) organizing codes into descriptive themes, reflecting interpretations of study authors; (3) consolidating descriptive themes into conceptual categories to identify higher-order analytic themes.

Results

We screened 4,841 abstracts and included 26 qualitative studies on experiences of injecting-related bacterial and fungal infections. We identified six descriptive themes organized into two analytic themes. The first analytic theme, social production of risk, considered macro-environmental influences. Four descriptive themes highlighted pathways through which this occurs: (1) unregulated drug supply, leading to poor drug quality and solubility; (2) unsafe spaces, influenced by policing practices and insecure housing; (3) health care policies and practices, leading to negative experiences that discourage access to care; and (4) harm reduction programs, including structural barriers to effective service provision. The second analytic theme, practices of care among people who inject drugs, addresses protective strategies that people who inject drugs employ within infection risk environments. Associated descriptive themes were: (5) mutual care, including assisted-injecting and sharing sterile equipment; and (6) self-care, including vein health and self-treatment. Within constraining risk environments, some protective strategies for bacterial infections precipitated other health risks (e.g., HIV transmission).

Conclusions

Injecting-related bacterial and fungal infections are shaped by modifiable social-structural factors, including unregulated drug quality, criminalization, insufficient housing, limited harm reduction services, and harmful health care practices. Enabling environment interventions that address these factors could further empower people who inject drugs to protect themselves and their community.
Dynamics of Vaccine-Hesitant Parents’ Considerations Regarding Covid-19 Vaccination
Authors: Atad Erga , Netzer Itamar , Peleg Orr , Landsman Keren , Dalyot Keren , Reuven Shanny Edan , Nitzany Eyal , Baram-Tsabari Ayelet
Published: October 2022

Introduction

Most studies present a snapshot of hesitant parents’ decisions and thinking concerning COVID-19 vaccination, but for many it is a dynamic rather than a stable process. We examined the considerations of a group of vaccine hesitant parents (VHPs) with respect to COVID-19 vaccinations for their children before, during and after the main vaccination campaign for the 12 to15-year-old age group in Israel, over a six-month period.

Methods

Digital surveys were administered to 1118 Israeli parents. After VHPs were identified, three surveys were conducted to evaluate considerations that discourage or encourage vaccination. A logistic regression was carried out on sixteen models; of these, six were found to be statistically significant.

Results

456 parents’ data were analyzed. Parents’ intentions to vaccinate prior to the vaccination campaign were a good predictor of their actual behavior, (rp=.497, p<.001). We divided the parents into four groups: consistently pro-vaccine (39.4%), consistently anti-vaccine (15.2%), pro-vaccine parents who did not vaccinate (17.6%), and anti-vaccine parents who did vaccinate (27.9%). We identified eight considerations that were significant in VHPs’ vaccination behavior: trust in scientists, doctors and drug companies, children’s preferences, spread of COVID, social responsibility, children’s characteristics, the vaccine’s speed of development and its side effects.

Discussion

Greater vaccine uptake for teenagers may depend on the attitudes and perceptions of their parents. We identified encouraging and discouraging considerations that may make potential targets for public health officials when communicating about vaccines.

Article Summary

Encouraging and discouraging considerations re COVID-19 vaccination are explored and identified in vaccine hesitant parents.

What’s known on this subject

Most studies found that vaccine uptake is improved among well-to-do or highly educated parents. Severity of the disease and safety of the vaccination are the main factors influencing the decision.

What this study adds

The dynamics of attitude change toward vaccination among VHPs may be affected by several different factors. Chief are children’s preferences and individual health characteristics, side effects and speed of vaccine development
TACCO: Unified annotation transfer and decomposition of cell identities for single-cell and spatial omics
Authors: Mages Simon , Moriel Noa , Avraham-Davidi Inbal , Murray Evan , Chen Fei , Rozenblatt-Rosen Orit , Klughammer Johanna , Regev Aviv , Nitzan Mor
Published: October 2022

Rapid advances in single-cell-, spatial-, and multi-omics, allow us to profile cellular ecosystems in tissues at unprecedented resolution, scale, and depth. However, both technical limitations, such as low spatial resolution and biological variations, such as continuous spectra of cell states, often render these data imperfect representations of cellular systems, best captured as continuous mixtures over cells or molecules. Based on this conceptual insight, we build a versatile framework, TACCO (Transfer of Annotations to Cells and their COmbinations) that extends an Optimal Transport-based core by different wrappers or boosters to annotate a wide variety of data. We apply TACCO to identify cell types and states, decipher spatio-molecular tissue structure at the cell and molecular level, and resolve differentiation trajectories. TACCO excels in speed, scalability, and adaptability, while successfully outperforming benchmarks across diverse synthetic and biological datasets. Along with highly optimized visualization and analysis functions, TACCO forms a comprehensive integrated framework for studies of high-dimensional, high-resolution biology.
Exploring causal effects of smoking and alcohol related lifestyle factors on self-report tiredness: a Mendelian randomization study
Authors: Li Heshan , Zhao Junru , Liang Jing , Song Xiaoyu
Published: October 2022

Self-reported tiredness or low energy, often referred to as fatigue, has been linked to lifestyle factors, although data from randomized–controlled trials are lacking. We investigate whether modifiable lifestyle factors including smoking and alcohol intake related exposures (SAIEs) are causal factors for fatigue using Mendelian randomization (MR). A two-sample MR study was performed by using genome-wide association summary results from UK Biobank (UKBB), and each of the sample size is more than 100,000. We used the inverse variance weighted method, and sensitivity analyses (MR Egger, weighted median and penalized median estimators) to account for pleiotropy. The two-sample MR analyses showed inverse causal effect of never-smoking status and positive effect of current smoking status on the risk of fatigue. Similarly, genetically predicted alcoholic intake was positively associated with fatigue. The results were consistent across the different MR methods. Our Mendelian randomization analyses do support that the cessation of smoking and alcohol can decrease the risk of fatigue, and limit alcohol intake frequency can also reduce the risk.

Author summary

Many lifestyle factors have been associated with the risk of fatigue, but we cannot ascertain the causality between lifestyle factors and the risk of fatigue; whether the modification of lifestyles will reduce the risk. Another challenge is that fatigue is usually caused by various physiological and pathological factors, so most epidemiological data which examined risk factor modification have not studied the relationship between modifiable risk factors and self-reported tiredness in extensive conditions. SAIEs are the ones of the most influential lifestyle factors for human health and wellbeing. We performed MR analyses to estimate the causal effect of SAIEs on fatigue. In our study, we initially identified genetic variants which are significantly associated with SAIEs. We found SAIEs are causally involved in fatigue. The results could be extremely useful in the context of lifestyle - health relationships.
The Crux toolkit for analysis of bottom-up tandem mass spectrometry proteomics data
Authors: Kertesz-Farkas Attila , Adoquaye Acquaye Frank Lawrence Nii , Bhimani Kishankumar , Eng Jimmy K. , Fondrie William E. , Grant Charles , Hoopmann Michael R. , Lin Andy , Lu Yang Y. , Moritz Robert L. , MacCoss Michael J. , Noble William Stafford
Published: October 2022

The Crux tandem mass spectrometry data analysis toolkit provides a collection of algorithms for analyzing bottom-up proteomics tandem mass spectrometry data. Many publications have described various individual components of Crux, but a comprehensive summary has not been published since 2014. The goal of this work is to summarize the functionality of Crux, focusing on developments since 2014. We begin with empirical results demonstrating our recently implemented speedups to the Tide search engine. Other new features include a new score function in Tide, two new confidence estimation procedures, as well as three new tools: Param-medic for estimating search parameters directly from mass spectrometry data, Kojak for searching cross-linked mass spectra, and DIAmeter for searching data independent acquisition data against a sequence database.
Environmental and genetic predictors of human cardiovascular ageing
Authors: Shah Mit , Inácio Marco H. de A. , Lu Chang , Schiratti Pierre-Raphaël , Zheng Sean L. , Clement Adam , Bai Wenjia , King Andrew P. , Ware James S. , Wilkins Martin R. , Mielke Johanna , Elci Eren , Kryukov Ivan , McGurk Kathryn A. , Bender Christian , Freitag Daniel F. , O’Regan Declan P.
Published: October 2022

Cardiovascular ageing is a process that begins early in life and leads to a progressive change in structure and decline in function due to accumulated damage across diverse cell types, tissues and organs contributing to multi-morbidity. Damaging biophysical, metabolic and immunological factors exceed endogenous repair mechanisms resulting in a pro-fibrotic state, cellular senescence and end-organ damage, however the genetic architecture of cardiovascular ageing is not known. Here we used machine learning approaches to quantify cardiovascular age from image-derived traits of vascular function, cardiac motion and myocardial fibrosis, as well as conduction traits from electrocardiograms, in 39,559 participants of UK Biobank. Cardiovascular ageing was found to be significantly associated with common or rare variants in genes regulating sarcomere homeostasis, myocardial immunomodulation, and tissue responses to biophysical stress. Ageing is accelerated by cardiometabolic risk factors and we also identified prescribed medications that were potential modifiers of ageing. Through large-scale modelling of ageing across multiple traits our results reveal insights into the mechanisms driving premature cardiovascular ageing and reveal potential molecular targets to attenuate age-related processes.
Role of anti-polyethylene glycol (PEG) antibodies in the allergic reactions and immunogenicity of PEG-containing Covid-19 vaccines
Authors: Kozma Gergely Tibor , Mészáros Tamás , Berényi Petra , Facskó Réka , Patkó Zsófia , Oláh Csaba Zs. , Nagy Adrienne , Fülöp Tamás Gyula , Glatter Kathryn Anne , Radovits Tamás , Merkely Béla , Szebeni János
Published: October 2022

The polyethylene-glycol (PEG)-containing Covid-19 vaccines can cause hypersensitivity reactions (HSRs), or rarely, life-threatening anaphylaxis. A causal role of anti-PEG antibodies (Abs) has been proposed, but not yet proven in humans. The 191 blood donors in this study included 10 women and 5 men who displayed HSRs to Comirnaty or Spikevax Covid-19 vaccines with 3 anaphylaxis. 118 donors had pre-vaccination anti-PEG IgG/IgM values as measured by ELISA, of which >98% were over background regardless of age, indicating the presence of these Abs in almost everyone. Their values varied over 2-3 orders of magnitude and displayed strong left-skewed distribution with 3-4% of subjects having >15-30-fold higher values than the respective median. First, or booster injections with both vaccines led to significant rises of anti-PEG IgG/IgM with >10-fold rises in about ∼10% of Comirnaty, and all Spikevax recipients, measured at different times after the injections. The anti-PEG Ab levels measured within 4-months after the HSRs were significantly higher than those in nonreactors. Serial testing of plasma (n=361 tests) showed the SARS-CoV-2 neutralization IgG to vary over a broad range, with a trend for biphasic dose dependence on anti-PEG Abs. The highest prevalence of anti-PEG Ab positivity in human blood reported to date represents new information which can most easily be rationalized by daily exposure to common PEG-containing medications and/or household items. The significantly higher, HSR-non-coincidental blood level of anti-PEG Abs in hypersensitivity reactor vs. non-reactors, taken together with relevant clinical and experimental data in the literature, suggest that anti-PEG Ab supercarrier people might be at increased risk for HSRs to PEG-containing vaccines, which themselves can induce these Abs via bystander immunogenicity. Our data also raise the possibility that anti-PEG Abs might also contribute to the reduction of these vaccines’ virus neutralization efficacy. Thus, screening for anti-PEG Ab supercarriers may identify people at risk for HSRs or reduced vaccine effectiveness.
Non-specific effects of Bacillus Calmette-Guérin - a systematic review and meta-analysis of randomized controlled trials
Authors: Trunk Gerhard , Davidović Maša , Bohlius Julia
Published: October 2022

Vaccines induce antigen-specific immunity which provides long-lived protection from the target pathogen. Trials especially from high infectious disease areas indicated that the tuberculosis vaccine Bacillus Calmette-Guérin (BCG) induces in addition non-specific immunity against various pathogens and thereby reduces overall mortality. Although recent trials produced conflicting results, it was suggested that BCG might protect from non-tuberculosis respiratory infections and could be used to bridge time until a specific vaccine against novel respiratory diseases like COVID-19 is available. We performed a systematic search for randomized controlled trials (RCT) published between 2011 and August 5th, 2022 providing evidence about non-specific effects after BCG vaccination, assessed their potential for bias, and meta-analyzed relevant clinical outcomes. We excluded RCTs investigating vaccination with an additional vaccine, unless outcomes from a follow-up period before the second vaccination were reported. Our search identified 15 RCTs including 32160 participants. Vaccination with BCG caused an estimated 49% decrease in risk for respiratory infections (HR 0.51, 95% CI 0.33-0.80) with substantial heterogeneity between trials (I2=80%; p<0.00001). There was evidence for a protective effect on all-cause mortality of 22% if follow-up was restricted to one year (HR 0.78, 95% CI 0.63-0.96); we did not find evidence for an effect when we considered longer follow-up (HR 0.87, 95% CI 0.75-1.02). Infection-related mortality after BCG-vaccination was reduced by 33% (HR 0.67; 95% CI 0.46-0.99), mortality for sepsis by 38% (HR 0.62, 95% CI 0.41-0.93). There was no evidence for a protective effect of BCG vaccination on infections of any origin (HR 0.84, 95% CI 0.71-1.00), COVID-19 (HR 0.83, 95% CI 0.61-1.14), sepsis (HR 0.82, 95% CI 0.62-1.07) or hospitalization (HR 1.02, 95% CI 0.92-1.14). According to these results, depending on the setting, vaccination with BCG provides time-limited partial protection against non-tuberculosis respiratory infections and may reduce mortality. These findings underline BCG’s potential 1) in pandemic preparedness against novel pathogens especially in developing countries with established BCG-vaccination programs but limited access to specific vaccines; 2) in reducing microbial infections, antimicrobial prescriptions and thus the development of antimicrobial resistance. There is a need for additional RCTs to clarify the circumstances under which BCG’s non-specific protective effects are mediated.
Glaucoma Detection and Staging from Visual Field Images using Machine Learning Techniques
Authors: Akter Nahida , Gordon Jack , Li Sherry , Poon Mikki , Perry Stuart , Fletcher John , Chan Thomas , White Andrew , Roy Maitreyee
Published: October 2022

Purpose

In this study, we investigated the performance of deep learning (DL) models to differentiate between normal and glaucomatous visual fields (VFs) and classify glaucoma from early to the advanced stage to observe if the DL model can stage glaucoma as Mills criteria using only the pattern deviation (PD) plots. The DL model results were compared with a machine learning (ML) classifier trained on conventional VF parameters.

Methods

A total of 265 PD plots and 265 numerical datasets of Humphrey 24-2 VF images were collected from 119 normal and 146 glaucomatous eyes to train the DL models to classify the images into four groups: normal, early glaucoma, moderate glaucoma, and advanced glaucoma. The two popular pre-trained DL models: ResNet18 and VGG16, were used to train the PD images using five-fold cross-validation (CV) and observed the performance using balanced, pre-augmented data (n= 476 images), imbalanced original data (n=265) and feature extraction. The trained images were further investigated using the Grad-CAM visualization technique. Moreover, four ML models were trained from the global indices: mean deviation (MD), pattern standard deviation (PSD) and visual field index (VFI), using five-fold CV to compare the classification performance with the DL model’s result.

Results

The DL model, ResNet18 trained from balanced, pre-augmented PD images, achieved high accuracy in classifying the groups with an overall F1-score: 96.8%, precision: 97.0%, recall: 96.9%, and specificity: 99.0%. The highest F1 score was 87.8% for ResNet18 with the original dataset and 88.7% for VGG16 with feature extraction. The DL models successfully localized the affected VF loss in PD plots. Among the ML models, the random forest (RF) classifier performed best with an F1 score of 96%.

Conclusion

The DL model trained from PD plots was promising in differentiating normal and glaucomatous groups and performed similarly to conventional global indices. Hence, the evidence-based DL model trained from PD images demonstrated that the DL model could stage glaucoma using only PD plots like Mills criteria. This automated DL model will assist clinicians in precision glaucoma detection and progression management during extensive glaucoma screening.