bluuebunny/crossref_metadata_2025 huggingface dataset:
Neurofilament light-associated connectivity in young-adult Huntington’s disease is related to neuronal genes
Authors: McColgan Peter , Gregory Sarah , Zeun Paul , Zarkali Angeliki , Johnson Eileanoir B , Parker Christopher , Fayer Kate , Lowe Jessica , Nair Akshay , Estevez-Fraga Carlos , Papoutsi Marina , Zhang Hui , Scahill Rachael I , Tabrizi Sarah J , Rees Geraint
Published: June 2022

Upregulation of functional network connectivity in the presence of structural degeneration is seen in the premanifest stages of Huntington’s disease (preHD) 10–15 years from clinical diagnosis. However, whether widespread network connectivity changes are seen in gene carriers much further from onset has yet to be explored.

We characterized functional network connectivity throughout the brain and related it to a measure of disease pathology burden (CSF neurofilament light, NfL) and measures of structural connectivity in asymptomatic gene carriers, on average 24 years from onset. We related these measurements to estimates of cortical and subcortical gene expression.

We found no overall differences in functional (or structural) connectivity anywhere in the brain comparing control and preHD participants. However, increased functional connectivity, particularly between posterior cortical areas, correlated with increasing CSF NfL level in preHD participants. Using the Allen Human Brain Atlas and expression-weighted cell-type enrichment analysis, we demonstrated that this functional connectivity upregulation occurred in cortical regions associated with regional expression of genes specific to neuronal cells. This relationship was validated using single-nucleus RNAseq data from post-mortem Huntington’s disease and control brains showing enrichment of neuronal-specific genes that are differentially expressed in Huntington’s disease.

Functional brain networks in asymptomatic preHD gene carriers very far from disease onset show evidence of upregulated connectivity correlating with increased disease burden. These changes occur among brain areas that show regional expression of genes specific to neuronal GABAergic and glutamatergic cells.
Sustainable development of community-supported STEM-learning ecosystems in rural areas of the United States
Authors: Timko Gary , Harris Maren , Hayde Dolly , Peterman Karen
Published: June 2022

The Rural Activation & Innovation Network (RAIN) project was funded by the National Science Foundation (NSF) (DRL#: 161255) from 2017 through 2021. The purpose of the project was to engage, support, and better understand rural communities in changing perceptions of the importance of Science, Technology, Engineering, Math (STEM) learning to public education and the local economy, as well as leveraging local resources and expertise to support STEM learning. The literature indicates that STEM thinking and science literacy helps people to logically, systematically, and critically identify and solve problems and issues facing their communities. Using science and evidence-based facts and information helps to empower communities to engage in civic action, to organize, and to influence policies that help improve the human condition. This article is a case study of four rural regions located in the southwest region of the United States. It presents key stages of the RAIN project that have contributed toward sustaining the development of informal STEM learning opportunities in these regions. It brings together research and evaluation efforts that include survey data collected from community members and Regional Innovation Councils (RICs) in each of the four RAIN project regions, as well as interviews with key stakeholders and document review. The findings and discussion provide insights and strategies for development of sustainable community-supported STEM learning ecosystems in rural areas of the United States that meet their unique needs and identities.
Harnessing the Power of Health Systems and Networks for Antimicrobial Stewardship
Authors: Buckel Whitney R , Stenehjem Edward A , Hersh Adam L , Hyun David Y , Zetts Rachel M
Published: June 2022

Twenty of 21 health systems and network-based antimicrobial stewardship programs (ASPs) who were invited participated in a questionnaire, a webinar, and focus groups to understand implementation strategies for system-wide antimicrobial stewardship. Four centralized ASPs structures emerged. Of participating organizations, 3 (15%) confirmed classification as collaborative, 3 (15%) as centrally coordinated, 3 (15%) as in between or in transition between centrally coordinated and centrally led, 8 (40%) as centrally led, 2 (10%) as collaborative, consultative network. One (5%) organization considered themselves to be a hybrid. System-level stewardship responsibilities varied across sites and generally fell into 6 major categories: building and leading a stewardship community, strategic planning and goal setting, development of validated data streams, leveraging tools and technology for stewardship interventions, provision of subject-matter expertise, and communication/education. Centralized ASPs included in this study most commonly took a centrally led approach and engaged in activities tailored to system-wide goals.
Size specific boldness associated with differences in resource requirements and habitat use: a cross-sectional study in hermit crabs
Authors: Briffa Mark , Archer Rose
Published: June 2022

Animal personality is often studied within compressed periods of observation that represent narrow windows in comparison to animal lifespans. Although much is known about the relations between repeatable personality traits and cross-situational behavioral plasticity, less is known about how such traits might differ across age classes or life history transitions. We conducted a cross-sectional study of startle response duration in 3 size classes of Pagurus bernhardus, the common European hermit crab. We defined size classes using transitions in the preferred species of gastropod shells that accompany growth, and this change in preference is in turn associated with a transition from intertidal to subtidal habitats. Compared with small- and medium-sized intertidal individuals the larger subtidal hermit crabs behaved cautiously by showing startle responses of greater duration following disturbance. Startle responses were also repeatable within all 3 size classes, confirming the presence of animal personality in intertidal hermit crabs and demonstrating that this pattern is retained within the largest size classes, which have undergone the transition from intertidal to subtidal habitat. Interestingly, there was a trend for the pattern of repeatable startle response durations to increase with size class, with the highest value for repeatability and the greatest range of startle response durations being present within the large subtidal population. The greater range of startle responses indicates that the longer startle response durations in some larger individuals are more likely due to developmental changes with age and habitat use than reflecting selection against the boldest individuals during earlier stages of life.
Treatment strategies for thromboembolism-in-transit with pulmonary embolism
Authors: Sakai Hiroki , Uchida Takayuki , Matsumoto Takashi
Published: June 2022

A 46-year-old obese woman undergoing treatment for bipolar disorder presented with acute shortness of breath, chest pain and palpitations. She was tachypnoea and tachycardia, but blood pressure was stable. Computed tomography angiogram revealed bilateral pulmonary embolism. Echocardiogram revealed thrombus-in-transit. She underwent surgical embolectomy only for thrombus-in-transit and closure of the patent foramen ovale. However, pulmonary hypertension worsened, haemodynamical instability prolonged and hepatic congestion progressed. After veno-arterial extracorporeal membrane oxygenation insertion, we performed thrombectomy by catheter and anticoagulation therapy. One month later, the patient was transferred to another hospital for rehabilitation.
Nanaomycin E inhibits NLRP3 inflammasome activation by preventing mitochondrial dysfunction
Authors: Matsui Yudai , Takemura Naoki , Shirasaki Yoshitaka , Takahama Michihiro , Noguchi Yoshihiko , Ikoma Kenta , Pan Yixi , Nishida Shuhei , Taura Manabu , Nakayama Akiyoshi , Funatsu Takashi , Misawa Takuma , Harada Yoshie , Sunazuka Toshiaki , Saitoh Tatsuya
Published: June 2022

Nod-like receptor family pyrin domain-containing 3 (NLRP3) is a cytosolic innate immune receptor that senses organelle dysfunction induced by various stimuli, such as infectious, environmental, metabolic and drug stresses. Upon activation, NLRP3 forms an inflammasome with its adaptor protein apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and caspase-1, to trigger the release of inflammatory cytokines. The development of effective anti-inflammatory drugs targeting the NLRP3 inflammasome is in high demand as its aberrant activation often causes inflammatory diseases. Here, we found that nanaomycin A (NNM-A), a quinone-based antibiotic isolated from Streptomyces, effectively inhibited NLRP3 inflammasome-mediated inflammatory responses induced by imidazoquinolines, including imiquimod. Interestingly, its epoxy derivative nanaomycin E (NNM-E) showed a comparable inhibitory effect against the NLRP3 inflammasome-induced release of interleukin (IL)-1β and IL-18 from macrophages, with a much lower toxicity than NNM-A. NNM-E inhibited ASC oligomerization and caspase-1 cleavage, both of which are hallmarks of NLRP3 inflammasome activation. NNM-E reduced mitochondrial damage and the production of reactive oxygen species, thereby preventing the activation of the NLRP3 inflammasome. NNM-E treatment markedly alleviated psoriasis-like skin inflammation induced by imiquimod. Collectively, NNM-E inhibits NLRP3 inflammasome activation by preventing mitochondrial dysfunction with little toxicity and showed an anti-inflammatory effect in vivo. Thus, NNM-E could be a potential lead compound for developing effective and safe anti-inflammatory agents for the treatment of NLRP3 inflammasome-mediated inflammatory diseases.
Development and validation of a deep learning model to predict the survival of patients in ICU
Authors: Tang Hai , Jin Zhuochen , Deng Jiajun , She Yunlang , Zhong Yifan , Sun Weiyan , Ren Yijiu , Cao Nan , Chen Chang
Published: June 2022

Background

Patients in the intensive care unit (ICU) are often in critical condition and have a high mortality rate. Accurately predicting the survival probability of ICU patients is beneficial to timely care and prioritizing medical resources to improve the overall patient population survival. Models developed by deep learning (DL) algorithms show good performance on many models. However, few DL algorithms have been validated in the dimension of survival time or compared with traditional algorithms.

Methods

Variables from the Early Warning Score, Sequential Organ Failure Assessment Score, Simplified Acute Physiology Score II, Acute Physiology and Chronic Health Evaluation (APACHE) II, and APACHE IV models were selected for model development. The Cox regression, random survival forest (RSF), and DL methods were used to develop prediction models for the survival probability of ICU patients. The prediction performance was independently evaluated in the MIMIC-III Clinical Database (MIMIC-III), the eICU Collaborative Research Database (eICU), and Shanghai Pulmonary Hospital Database (SPH).

Results

Forty variables were collected in total for model development. 83 943 participants from 3 databases were included in the study. The New-DL model accurately stratified patients into different survival probability groups with a C-index of >0.7 in the MIMIC-III, eICU, and SPH, performing better than the other models. The calibration curves of the models at 3 and 10 days indicated that the prediction performance was good. A user-friendly interface was developed to enable the model’s convenience.

Conclusions

Compared with traditional algorithms, DL algorithms are more accurate in predicting the survival probability during ICU hospitalization. This novel model can provide reliable, individualized survival probability prediction.
Survey of United States Mosquito Control Programs Reveals Opportunities to Improve the Operational Value of Centers for Disease Control and Prevention Bottle Bioassays
Authors: Richards Stephanie L , Byrd Brian D , Breidenbaugh Mark , Vandock Kurt
Published: June 2022

Mosquito control programs have increasingly used Centers for Disease Control and Prevention bottle bioassays (BB) to evaluate insecticide resistance (IR). The reported utility, benefits, and limitations of BB and other methods were assessed via electronic survey of U.S. mosquito control professionals to identify potential areas for improvement, future study, and professional training. Opportunities were identified to improve BB operational value and IR detection.
Vertical evolution of exocometary gas – I. How vertical diffusion shortens the CO lifetime
Authors: Marino S , Cataldi G , Jankovic M R , Matrà L , Wyatt M C
Published: June 2022

Bright debris discs can contain large amounts of CO gas. This gas was thought to be a protoplanetary remnant until it was recently shown that it could be released in collisions of volatile-rich solids. As CO is released, interstellar UV radiation photodissociates CO producing CI, which can shield CO allowing a large CO mass to accumulate. However, this picture was challenged because CI is inefficient at shielding if CO and CI are vertically mixed. Here, we study for the first time the vertical evolution of gas to determine how vertical mixing affects the efficiency of shielding by CI. We present a 1D model that accounts for gas release, photodissociation, ionization, viscous evolution, and vertical mixing due to turbulent diffusion. We find that if the gas surface density is high and the vertical diffusion weak (αv/α < [H/r]2) CO photodissociates high above the mid-plane, forming an optically thick CI layer that shields the CO underneath. Conversely, if diffusion is strong (αv/α > [H/r]2) CI and CO become well mixed, shortening the CO lifetime. Moreover, diffusion could also limit the amount of dust settling. High-resolution ALMA observations could resolve the vertical distribution of CO and CI, and thus constrain vertical mixing and the efficiency of CI shielding. We also find that the CO and CI scale heights may not be good probes of the mean molecular weight, and thus composition, of the gas. Finally, we show that if mixing is strong the CO lifetime might not be long enough for CO to spread interior to the planetesimal belt where gas is produced.
Beat Synchronization and Reading: The Feasibility of Music and Video Game Trainings
Authors: Chen Yu-Ling , Khoo Didier
Published: June 2022

The prevalence of reading disabilities ranges from 5% to 12%, making it important to support reading programs. More specifically, children with reading disabilities show difficulties in beat synchronization that requires fine audio-motor synchrony. This synchrony, which demonstrates temporal processing skills, is linked to reading development. The purpose of the present study was to establish the feasibility of 2 music training programs for reading through practicing beat synchronization and to explore the preliminary efficacy of these programs for third graders identified as having reading challenges. Two participants attended the rhythmic music exercise group where they performed musical tasks set to a metronome beat. Two other participants attended the video game playing group where they played Donkey Konga. Each group attended a 30-minute session twice a week for 4 weeks. The Gray Oral Reading Test Fifth Edition (GORT-5) was used to assess reading ability. Selected subtests from the Comprehensive Test of Phonological Awareness Second Edition (CTOPP-2) were used to assess phonological processing. Feasibility data indicated that both programs were successfully implemented and well received by the participants. While preliminary-efficacy analysis demonstrated positive trends in the reading and phonological awareness tests for the rhythmic music exercise group and mixed results for the video game playing group, a large, controlled pilot study is needed to determine the effects of these training programs. Music therapists may potentially apply the proposed rhythmic music exercises to address reading-related goals.
Guiding the folding of G-quadruplexes through loop residue interactions
Authors: Jana Jagannath , Vianney Yoanes Maria , Schröder Nina , Weisz Klaus
Published: June 2022

A G-rich sequence was designed to allow folding into either a stable parallel or hybrid-type topology. With the parent sequence featuring coexisting species, various related sequences with single and double mutations and with a shortened central propeller loop affected the topological equilibrium. Two simple modifications, likewise introduced separately to all sequences, were employed to lock folds into one of the topologies without noticeable structural alterations. The unique combination of sequence mutations, high-resolution NMR structural information, and the thermodynamic stability for both topological competitors identified critical loop residue interactions. In contrast to first loop residues, which are mostly disordered and exposed to solvent in both propeller and lateral loops bridging a narrow groove, the last loop residue in a lateral three-nucleotide loop is engaged in stabilizing stacking interactions. The propensity of single-nucleotide loops to favor all-parallel topologies by enforcing a propeller-like conformation of an additional longer loop is shown to result from their preference in linking two outer tetrads of the same tetrad polarity. Taken together, the present studies contribute to a better structural and thermodynamic understanding of delicate loop interactions in genomic and artificially designed quadruplexes, e.g. when employed as therapeutics or in other biotechnological applications.
Polymer formulated self-amplifying RNA vaccine is partially protective against influenza virus infection in ferrets
Authors: McKay P F , Zhou J , Frise R , Blakney A K , Bouton C R , Wang Z , Hu K , Samnuan K , Brown J C , Kugathasan R , Yeow J , Stevens M M , Barclay W S , Tregoning J S , Shattock R J
Published: June 2022

COVID-19 has demonstrated the power of RNA vaccines as part of a pandemic response toolkit. Another virus with pandemic potential is influenza. Further development of RNA vaccines in advance of a future influenza pandemic will save time and lives. As RNA vaccines require formulation to enter cells and induce antigen expression, the aim of this study was to investigate the impact of a recently developed bioreducible cationic polymer, pABOL for the delivery of a self-amplifying RNA (saRNA) vaccine for seasonal influenza virus in mice and ferrets. Mice and ferrets were immunized with pABOL formulated saRNA vaccines expressing either haemagglutinin (HA) from H1N1 or H3N2 influenza virus in a prime boost regime. Antibody responses, both binding and functional were measured in serum after immunization. Animals were then challenged with a matched influenza virus either directly by intranasal inoculation or in a contact transmission model. While highly immunogenic in mice, pABOL-formulated saRNA led to variable responses in ferrets. Animals that responded to the vaccine with higher levels of influenza virus-specific neutralizing antibodies were more protected against influenza virus infection. pABOL-formulated saRNA is immunogenic in ferrets, but further optimization of RNA vaccine formulation and constructs is required to increase the quality and quantity of the antibody response to the vaccine.
Characterization of regulatory modules controlling leaf angle in maize
Authors: Wang Xiaokun , Wang Xianglan , Sun Shilei , Tu Xiaoyu , Lin Kande , Qin Lei , Wang Xingyun , Li Gang , Zhong Silin , Li Pinghua
Published: June 2022

Leaf angle is an important agronomic trait determining maize (Zea mays) planting density and light penetration into the canopy and contributes to the yield gain in modern maize hybrids. However, little is known about the molecular mechanisms underlying leaf angle beyond the ZmLG1 (liguleless1) and ZmLG2 (Liguleless2) genes. In this study, we found that the transcription factor (TF) ZmBEH1 (BZR1/BES1 homolog gene 1) is targeted by ZmLG2 and regulates leaf angle formation by influencing sclerenchyma cell layers on the adaxial side. ZmBEH1 interacted with the TF ZmBZR1 (Brassinazole Resistant 1), whose gene expression was also directly activated by ZmLG2. Both ZmBEH1 and ZmBZR1 are bound to the promoter of ZmSCL28 (SCARECROW-LIKE 28), a third TF that influences leaf angle. Our study demonstrates regulatory modules controlling leaf angle and provides gene editing targets for creating optimal maize architecture suitable for dense planting.
Seesaw mechanism in the R-parity-violating supersymmetric standard model with the gauged flavor U(1)X symmetry
Authors: Hinata Atsushi
Published: June 2022

We study the seesaw mechanism in the supersymmetric standard model (SSM) with the ${\mathbb {Z}}_3$ symmetry called matter triality (M3). The Abelian discrete symmetry prohibits the baryon number violation operators at the (non-)renormalizable level, which ensures proton longevity. The cubic coupling by right-handed neutrinos generates the Majorana mass term after the right-handed sneutrinos develop into the vacuum expectation values. Due to the R-parity violation, the active neutrino masses can be generated not only from the mixings with the right-handed neutrinos but also from those with the minimal SSM neutralinos. We propose a model where M3 is embedded in the gauged flavor symmetry. The flavor charges are constrained by the anomaly cancellation conditions and the requirements to realize the fermion masses and mixing angles in the quark and lepton sectors. We analyze the assignments of the flavor charge, and show that the sterile neutrino mass is allowed to be below the soft supersymmetry-breaking scale, which is constrained by the half-lifetime of the neutrinoless double beta decay.
Elevated highly sensitive C-reactive protein in fibromyalgia associates with symptom severity
Authors: Zetterman Teemu , Markkula Ritva , Kalso Eija
Published: June 2022

Objectives

Fibromyalgia (FM), a common pain syndrome, is thought to be a non-inflammatory, nociplastic condition, but evidence implicating neuroinflammation has been increasing. Systemic inflammation may be associated with more severe symptoms in some FM patients. We studied healthy controls and FM patients with and without systemic inflammation detectable using high-sensitivity CRP (hsCRP) measurement.

Methods

We measured hsCRP levels and gathered clinical and questionnaire data [including the Fibromyalgia Impact Questionnaire (FIQ)] from 40 female FM patients and 30 age-matched healthy women. An hsCRP level >3 mg/l was considered elevated.

Results

FM patients had significantly higher mean hsCRP levels than controls, explained by overweight and lower leisure-time physical activity. Eight FM patients had elevated hsCRP levels and 29 had normal hsCRP levels. Levels of hsCRP were significantly correlated with FIQ scores. Patients with elevated hsCRP had higher FIQ scores, with worse physical functioning and greater pain and were less likely to be employed than patients with normal hsCRP. These patient groups did not differ by blood count, liver function or lipid profiles, nor by education, psychological measures, sleep disturbance, smoking or comorbidities.

Conclusion

Some FM patients have elevated hsCRP, mostly due to overweight and physical inactivity. They have worse symptoms and their ability to work is impaired. Measurement of hsCRP may help to identify FM patients in greatest need of interventions supporting working ability.

Trial registration

ClinicalTrials.gov (https://clinicaltrials.gov), NCT03300635
Mainstreaming Gender in Policy Narratives: Childcare Policies during Latin America’s Left Turn
Authors: Marcondes Mariana Mazzini , Farah Marta Ferreira Santos
Published: June 2022

During Latin America’s left turn, women and children benefited from the expansion of social policies. This expansion, however, was not followed by the homogeneous incorporation of a gender equality perspective in childcare policies, with different processes occurring in similar countries. What might explain these differences? To address this question, we conducted qualitative and comparative research on Argentina, Brazil, and Uruguay. We found greater progress in mainstreaming childcare policies when a broad discourse coalition gathered around a master frame that was simultaneously mainstreamed by feminist perspectives.
Staffing models in the cardiac intensive care unit
Authors: Quien Mary , Thomas Alexander , Ludmir Jonathan , Miller P. Elliott
Published: June 2022

Purpose of review

The modern cardiac intensive care unit (CICU) has evolved into a high-intensity unit that cares for critically ill patients. Despite this transformation, changes to the staffing model and organizational structure in these specialized units have only recently begun to meet these challenges. We describe the most recent evidence which will inform future CICU staffing models.

Recent findings

In the United States, the majority of CICUs are open as opposed to closed units, yet recent data suggests that transition to a closed staffing model is associated with a decrease in mortality. These reductions in mortality in closed CICUs are most pronounced in the most critically ill populations, such as patients with mechanical circulatory support, cardiac arrest, and respiratory failure. In addition, one study has shown that transition to a cardiac intensivist staffed CICU was associated with a reduction in mortality. Finally, multidisciplinary and protocolized teams imbedded within the CICU, specifically 'shock teams,’ have recently been developed and may reduce mortality in this particularly sick patient population.

Although the preponderance of data suggests improved outcomes with a closed, intensivist staffed CICU model, future multicenter studies are needed to better define the ideal staffing models for the contemporary CICU.
Prevalence and comorbidities of bronchiolitis in adults
Authors: Jeong Jae Seok , Kim Jong Seung , Yeom Sang Woo , Lee Min Gyu , You Yeon Seok , Lee Yong Chul
Published: June 2022

Bronchiolitis generally refers to inflammation and/or fibrosis of the non-cartilaginous small airways located approximately from the 8th airway generation down to the terminal and respiratory bronchioles. In contrast to young children, the frequency of small airway infection in adult bronchiolitis appears less frequent and a number of other pathophysiological conditions have been implicated in adult bronchiolitis. However, little information is available on the exact medical burden of bronchiolitis such as its prevalence and comorbidities in the adult population. The aim of this study is to elucidate the prevalence and comorbidities of bronchiolitis. We used the Korea National Health Insurance Service-National Sample Cohort, which provides data for 1,000,000 individuals out of the entire population by 2% stratified random sampling according to age, sex, residential area, and level of household income. We defined the cause of bronchiolitis other than acute infection as a patient with diagnostic code J448 or J684 and over 20 years of age who visited a clinic or hospital in South Korea. Then, 1:1 propensity score matching was performed to define a non-bronchiolitis (control) group to compare the comorbidities and mortality in the 2 groups. The overall prevalence of bronchiolitis was 688 cases/1,000,000 population during the study period (95% confidence interval, 625–751). The most common comorbid clinical condition in adults with bronchiolitis was rhinitis (52.3%), followed by bronchial asthma (52.23%), hypertension (43.69%), gastroesophageal reflux disease (30.56%), sinusitis (28.72%), diabetes (22.77%), and osteoporosis (17.85%). Other common bronchiolitis-associated comorbidities were cerebrovascular disease (16.86%), angina (14.37%), peripheral vascular disease (13.42%), congestive heart failure (11.9%), and malignancy in any organ (10.6%). Healthcare costs for bronchiolitis increased steeply during the same period. Malignancy in any organ was the leading cause of mortality in the patient group, followed by bronchiolitis itself. Further larger prospective multiethnic cohort studies should be carried out in the near future.
Stairway to Heaven
Authors: Singh Swaran P.
Published: June 2022

Mystical and spiritual experiences have been reported throughout human history. Causal explanations for these range from psychopathology of mental illness, drugs such as hallucinogens, neurological disorders including temporal lobe epilepsy, and genuine mystical or spiritual awakening. There is a common core of phenomena in such experiences, as described both in historical accounts and recent research, but also evidence of cultural specificity. This article is a personal account of such an experience, which occurred in a postanesthetic state. A striking feature of the experience was noesis: a sense of revelation and complete understanding. I argue that while there must be a neural basis to these phenomena, it is difficult to reduce the subjective meaning of the experience purely to a brain dysfunction. Reconciling mechanism and meaning of such experiences remains a challenge for both neuroscience and philosophy.
Oculofacial Prosthetic Rehabilitation Complemented With Temporary Fillers and Neurotoxin
Authors: Schnorr Nathalia Gusmão Prado , Salazar-Gamarra Rodrigo , Latuff Daniela Cortizo , Dib Luciano Lauria
Published: June 2022

Surgical treatment of head and neck cancer causes severe tissue loss, therefore, deformities and psychosocial consequences. In cases involving orbit exenteration, satisfactory reconstruction can only be achieved with prosthetic replacement, despite successful reconstructive plastic surgery. Extraoral implants, 3D scanning, and prototyping technologies have contributed to increase satisfactory aesthetic results of oculofacial prosthesis. However, to achieve prosthetic rehabilitation refinement, patients' biological tissues have been treated with injectable cosmetic adjuncts methods as complements to results. This study aimed to describe the use of botulinum toxin type A, hyaluronic acid, and calcium hydroxyapatite previously to oculofacial prostheses manufacturing, in 5 oncologic patients of a rehabilitation unit. Outcomes produced by additional cosmetic methods on tissues, prostheses planning, and overall facial rehabilitation were observed and registered by photographs. Botulinum toxin type A, hyaluronic acid, and calcium hydroxyapatite has shown to be useful in improving asymmetries, volumizing surgical depressions and dissembling atrophic scars. Presenting an additional resource to improve overall results, enabling the manufacturing of smaller, thinner, and better-fitting oculofacial prostheses. Limitations as chronic infection and necrosis episodes, related to filler injection into previously irradiated sites, were described. The temporary effect of the materials used generates a need for reapplications but increases the safety of such procedures and enables patients' cancer treatment follow-up.
Premature Fusion of the Posterior Intraoccipital Synchondrosis, A Minor Suture Mimic of Lambdoid Craniosynostosis
Authors: Aguilo-Seara Gabriela , Tang Jason H. , Couture Daniel E. , Runyan Christopher M.
Published: June 2022

The posterior intraoccipital synchondrosis (PIOS) is a cartilaginous division separating the exoccipital and supraoccipital bones, allowing for flexibility of the cranial base at birth and which later ossifies in adolescence. The authors report a case of right PIOS synostosis that resembled right lambdoid synostosis, with left occipital bossing in a healthy, six-month-old female with an unremarkable birth history and no antecedent trauma. An initial referral was made from the pediatrician to oncology because of a concern over the presence and growth of a possible mass at the left occiput. Over 8 months, this mass grew and became more firm, accompanied by left occipital bossing and right occipital flattening. A computed tomography was obtained, which demonstrated the fusion of the PIOS, prompting a referral to plastic surgery. Cranial vault remodeling with switch cranioplasty was performed at age 14 months, complicated only by a superficial infection along the suture line. There are exceedingly few reports of PIOS synostosis, with occipital osteodiastasis related to birth trauma as the only prior explanation for this condition. With no birth trauma and delayed onset, our case likely represents idiopathic PIOS synostosis. With the many similarities in presentation, the surgical approaches commonly used for lambdoid synostosis, particularly switch cranioplasty, are suitable solutions to PIO synchondrosis with optimal functional and aesthetic outcomes.
Exosomal Transfer of DNA Methyl-Transferase mRNA Induces an Immunosuppressive Phenotype in Human Monocytes
Authors: Wisler Jon R. , Singh Kanhaiya , McCarty Adara , Harkless Ryan , Karpurapu Manjula , Hernandez Edward , Mukherjee Debasmita , Abouhashem Ahmed S. , Christman John W. , Sen Chandan K.
Published: June 2022

Introduction:

Survivors of sepsis exhibit persistent immunosuppression. Epigenetic events may be responsible for some of these immunosuppressive changes. During sepsis circulating exosomes contain large quantities of DNA methyltransferase (DNMT) mRNAs. We hypothesized that exosomes directly transfer DNMT mRNAs to recipient monocytes with resultant methylation events and immunosuppression.

Methods:

Exosomes containing DNMT mRNA were generated by stimulating monocytes with LPS. Confocal microscopy was used to determine uptake kinetics in the presence of pharmacologic inhibition. Expression and packaging of specific DNMT mRNA was controlled using DNMT siRNAs. Whole genome and gene specific methylation was assessed using bisulfite sequencing. Ingenuity pathway analysis was performed to determine the biological function of significance of differentially methylated regions.

Results:

Exosomes effectively transferred DNMT mRNA to recipient monocytes. Pharmacologic inhibition of exosome uptake prevented this increase in DNMT mRNA expression. Recipient monocytes exhibited hypermethylation changes and gene suppression. siRNAs decreased the packaging of DNMT mRNAs and prevented TNFα gene suppression, restoring immunocompetence.

Conclusion:

These data support a role for exosome-mediated transfer of DNMT mRNA with resultant methylation and gene silencing. Pharmacologic uptake inhibition or targeted siRNA mediated DNMT gene silencing prevented DNMT mRNA transfer and maintained the cell's ability to express TNFα in response to LPS. This highlights the potential therapeutic value of targeting these exosome-mediated epigenetic events to maintain the host immune response during sepsis.
A Limited Role for AMD3100 Induced Stem Cell Mobilization for Modulation of Thoracic Trauma Outcome
Authors: Vogel Mona , Möhrle Bettina , Sakk Vadim , Brown Andreas , Palmer Annette , Braumüller Sonja , Huber-Lang Markus , Allgöwer Andreas , Cancelas Jose A. , Geiger Hartmut
Published: June 2022

Thoracic trauma is a major cause of mortality due to the associated inflammatory acute respiratory distress syndrome and morbidity due to impaired tissue regeneration. Trauma-induced lung inflammation is characterized by the early recruitment of cells with pro- or anti-inflammatory activity to the lung. Therapeutic interventions reducing the level of tissue inflammation may result in decreased tissue damage and improved healing and recovery. Stem cells might be able to improve trauma outcome via immunomodulation or by enhancing tissue regeneration.

Here, we describe the migratory dynamics of murine mesenchymal, hematopoietic and endothelial stem and progenitor cells (SPCs) as well as mature inflammatory cells (monocytes, neutrophils, lymphocytes) to peripheral blood (PB) and lung tissue between 0.2 and 48 h post-blunt chest trauma (TXT). We demonstrate that the kinetics of immune cell and SPC distribution upon trauma are both cell-type and tissue-dependent. We identified a transient, early increase in the number of inflammatory cells in PB and lung at 2 h post-TXT and a second wave of infiltrating SPCs in lungs by 48 h after TXT induction, suggesting a role for SPCs in tissue remodeling after the initial inflammatory phase. Cxcl12/Cxcr4 blockade by AMD3100 within the first 6 h after TXT, while inducing a strong and coordinated mobilization of SPCs and leukocytes to PB and lung tissue, did not significantly affect TXT associated inflammation or tissue damage as determined by inflammatory cytokine levels, plasma markers for organ function, lung cell proliferation and survival, and myofibroblast/fibroblast ratio in the lung. Further understanding the dynamics of the distribution of endogenous SPCs and inflammatory cells will therefore be indispensable for stem cell-based or immunomodulation therapies in trauma.
Translational Epidemiology: An Integrative Approach to Determine the Interplay Between Genetic Ancestry and Neighborhood Socioeconomic Status on Triple Negative Breast Cancer
Authors: Goel Neha , Yadegarynia Sina , Kwon Deukwoo , Kesmodel Susan B. , Harbour James W. , Kobetz Erin , Merchant Nipun , Rodriguez Daniel A.
Published: June 2022

Objective:

To investigate the impact of global and local genetic ancestry and neighborhood socioeconomic status (nSES), on breast cancer (BC) subtype, and gene expression.

Background:

Higher rates of aggressive BC subtypes [triple negative breast cancer (TNBC)] and worse overall BC survival are seen in black women [Hispanic Black (HB) and non-Hispanic Black (NHB)] and women from low nSES. However, the complex relationship between genetic ancestry, nSES, and BC subtype etiology remains unknown.

Methods:

Genomic analysis was performed on the peripheral blood from a cohort of 308 stage I to IV non-Hispanic White (NHW), Hispanic White (HW), HB, and NHB women with BC. Patient and tumor characteristics were collected. Global and local ancestral estimates were calculated. Multinomial logistic regression was performed to determine associations between age, stage, genetic ancestry, and nSES on rates of TNBC compared to estrogen receptor (ER+)/epidermal growth factor receptor 2 (HER2−), ER+/HER2+, and ER−/HER2+ disease.

Results:

Among 308 women, we identified a significant association between increasing West African (WA) ancestry and odds of TNBC [odds ratio (OR): 1.06, 95% confidence interval (95% CI): 1.001–1.126, P=0.046] as well as an inverse relationship between higher nSES and TNBC (OR: 0.343, 95% CI: 0.151–0.781, P=0.011). WA ancestry remained significantly associated with TNBC when adjusting for patient age and tumor stage, but not when adjusting for nSES (OR: 1.049, 95% CI: −0.987–1.116, P=0.120). Local ancestry analysis, however, still revealed nSES-independent enriched WA ancestral segment centered at χ2=42004914 (p=3.70×10−5) in patients with TNBC.

Conclusions:

In this translational epidemiologic study of genetic ancestry and nSES on BC subtype, we discovered associations between increasing WA ancestry, low nSES, and higher rates of TNBC compared to other BC subtypes. Moreover, on admixture mapping, specific chromosomal segments were associated with WA ancestry and TNBC, independent of nSES. However, on multinomial logistic regression adjusting for WA ancestry, women from low nSES were more likely to have TNBC, independent of genetic ancestry. These findings highlight the complex nature of TNBC and the importance of studying potential gene-environment interactions as drivers of TNBC.
Preemptive Infiltration of Local Anesthetics During Vaginal Hysterectomy: A Systematic Review and Meta-analysis of Randomized Controlled Trials
Authors: Zacharakis Dimitrios , Prodromidou Anastasia , Douligeris Athanasios , Athanasiou Stavros , Hadzilia Sophia , Kathopoulis Nikolaos , Athanasiou Veatriki , Grigoriadis Themos
Published: June 2022

Importance

Vaginal hysterectomy (VH) is the preferred route of choice for women desiring hysterectomy to treat uterine pathology, including premalignant conditions and fibroids.

Objective

The aim of this study was to evaluate the impact of the use of preemptive local analgesia (LA) on postoperative pain and perioperative outcomes for women undergoing VH.

Study Design

A systematic search of 4 electronic databases (MEDLINE, Scopus, Cochrane CENTRAL Register of Controlled Trials, and Clinicaltrials.gov) was performed for articles published up to January 2021. All randomized controlled trials that presented outcomes of patients who underwent VH due to pelvic floor disorders or other benign gynecological disorders and received local infiltration analgesia were finally included.

Results

A total of 5 studies with 277 women (138 LA group vs 199 no-LA group) who underwent a VH were included in the present meta-analysis. Mean pain scores at both 30 minutes to 2 hours and 3 to 6 hours postoperatively were significantly lower in the LA group compared with the non-LA group (220 patients: mean difference [MD], −1.75; 95% confidence interval [CI], −2.77 to −0.74; P = 0.0007; and 220 patients: MD, −1.68; 95% CI, −2.28 to 1.09; P < 0.00001, respectively). Morphine/narcotic opioid-based consumption up to 24 hours postoperatively was significantly reduced in the LA group compared with the non-LA group (197 patients MD, −9.47 mg; 95% CI, −16.51 to −2.43; P = 0.008).

Conclusions

The use of preemptive LA during VH seems to be beneficial especially with regard to short-term postoperative pain and opioid use. However, further studies are needed to identify the optimal anesthetic regimen, the dosage, and sites of application aiming to achieve the optimal benefit in the postoperative management.
How the living world evolved and where it's headed now
Authors: Raven Peter H.
Published: June 2022

The growth of life on Earth over more than 4 billion years has experienced five major extinction events, each followed by a period of rapid increase in species number. When organisms first invaded the land about 480 million years ago, another explosive proliferation of species followed. Our species,
Homo sapiens
, appeared some 300 000 years ago, developed agriculture about 11 000 years ago and grew rapidly to some 7.8 billion people, who are currently consuming about 175% of the sustainable productivity available worldwide. By mid-century (2050), we will have grown to about 9.9 billion. Wealth is very unequally distributed. Meanwhile, the Earth's mean temperature has increased by 1.1°C above pre-industrial levels, and we are on track for a total increase of 2.6 to 3.9°C. We are driving species to extinction at a rate unprecedented for the past 66 million years. These changes promise to be disastrous for the maintenance of civilization. Indeed, our only hope for a sustainable future will be for us to find a way to overcome our unremitting greed at all levels and to love one another while building social justice.

This article is part of the theme issue ‘Ecological complexity and the biosphere: the next 30 years’.
From coral reefs to Joshua trees: What ecological interactions teach us about the adaptive capacity of biodiversity in the Anthropocene
Authors: Lagerstrom Katherine M. , Vance Summer , Cornwell Brendan H. , Ruffley Megan , Bellagio Tatiana , Exposito-Alonso Moi , Palumbi Stephen R. , Hadly Elizabeth A.
Published: June 2022

The pervasive loss of biodiversity in the Anthropocene necessitates rapid assessments of ecosystems to understand how they will respond to anthropogenic environmental change. Many studies have sought to describe the adaptive capacity (AC) of individual species, a measure that encompasses a species’ ability to respond and adapt to change. Only those adaptive mechanisms that can be used over the next few decades (e.g. via novel interactions, behavioural changes, hybridization, migration, etc.) are relevant to the timescale set by the rapid changes of the Anthropocene. The impacts of species loss cascade through ecosystems, yet few studies integrate the capacity of ecological networks to adapt to change with the ACs of its species. Here, we discuss three ecosystems and how their ecological networks impact the AC of species and vice versa. A more holistic perspective that considers the AC of species with respect to their ecological interactions and functions will provide more predictive power and a deeper understanding of what factors are most important to a species’ survival. We contend that the AC of a species, combined with its role in ecosystem function and stability, must guide decisions in assigning ‘risk’ and triaging biodiversity loss in the Anthropocene.

This article is part of the theme issue ‘Ecological complexity and the biosphere: the next 30 years’.
Environmental Galenics: large-scale fortification of extant microbiomes with engineered bioremediation agents
Authors: de Lorenzo Víctor
Published: June 2022

Contemporary synthetic biology-based biotechnologies are generating tools and strategies for reprogramming genomes for specific purposes, including improvement and/or creation of microbial processes for tackling climate change. While such activities typically work well at a laboratory or bioreactor scale, the challenge of their extensive delivery to multiple spatio-temporal dimensions has hardly been tackled thus far. This state of affairs creates a research niche for what could be called
Environmental Galenics
(EG), i.e. the science and technology of releasing designed biological agents into deteriorated ecosystems for the sake of their safe and effective recovery. Such endeavour asks not just for an optimal performance of the biological activity at stake, but also the material form and formulation of the agents, their propagation and their interplay with the physico-chemical scenario where they are expected to perform. EG also encompasses adopting available physical carriers of microorganisms and channels of horizontal gene transfer as potential paths for spreading beneficial activities through environmental microbiomes. While some of these propositions may sound unsettling to anti-genetically modified organisms sensitivities, they may also fall under the tag of TINA (there is no alternative) technologies in the cases where a mere reduction of emissions will not help the revitalization of irreversibly lost ecosystems.

This article is part of the theme issue ‘Ecological complexity and the biosphere: the next 30 years’.
Network-level containment of single-species bioengineering
Authors: Maull Victor , Solé Ricard
Published: June 2022

Ecological systems are facing major diversity losses in this century owing to Anthropogenic effects. Habitat loss, overexploitation of resources, invasion and pollution are rapidly jeopardizing the survival of whole communities. It has been recently suggested that a potential approach to flatten the curve of species extinction and prevent catastrophic shifts would involve the engineering of one selected species within one of these communities. Such possibility has started to become part of potential intervention scenarios to preserve biodiversity. Despite its potential, very little is known about the actual dynamic responses of complex ecological networks to the introduction of a synthetic strains derived from a resident species. In this paper, we address this problem by modelling the response of a community to the addition of a synthetic strain derived from a member of a stable ecosystem. We show that the community interaction matrix largely limits the spread of the engineered strain, thus suggesting that species diversity acts as an ecological firewall. The implications for future scenarios of ecosystem engineering are outlined.

This article is part of the theme issue ‘Ecological complexity and the biosphere: the next 30 years’.