bluuebunny/crossref_metadata_2025 huggingface dataset:
Successful Free Bilamellar Eyelid Grafts for the Repair of Upper and Lower Eyelid Defects in Patients and Laser Speckle Contrast Imaging of Revascularization
Authors: Tenland Kajsa , Berggren Johanna , Engelsberg Karl , Bohman Elin , Dahlstrand Ulf , Castelo Nazia , Lindstedt Sandra , Sheikh Rafi , Malmsjö Malin
Published: May 2020

Purpose:

It is generally believed that large eyelid defects must be repaired using a vascularized flap for 1 lamella, while the other can be a free graft. Recent studies indicate that the pedicle of a tarsoconjunctival flap does not contribute to blood perfusion. The purpose of this study was to explore whether large eyelid defects can be repaired using a free bilamellar eyelid autograft alone.

Methods:

Ten large upper and lower eyelid defects resulting from tumor excision were reconstructed using bilamellar grafts harvested from the contralateral or opposing eyelid. Revascularization of the flap was monitored during healing using laser speckle contrast imaging, and the surgical outcome was assessed.

Results:

The functional and cosmetic results were excellent. All grafts survived and there was no tissue necrosis. Only 1 patient underwent revision after 4 days as the sutures came loose. Two patients developed minimal ectropion but needed no reoperation. All patients were satisfied with the surgical results. Perfusion monitoring showed that the grafts were gradually revascularized, exhibiting 50% perfusion after 4 weeks and 90% perfusion after 8 weeks.

Conclusions:

A free bilamellar eyelid graft appears to be an excellent alternative to the tarsoconjunctival flap procedure in the reconstruction of both upper and lower eyelid defects, especially in patients who cannot tolerate visual axis occlusion or the 2-stage procedure of the conventional staged flap procedure.
Injury Correlates Among a National Sample of Women in the US Fire Service
Authors: Hollerbach Brittany S. , Kaipust Christopher M. , Poston Walker S.C. , Haddock Christopher K. , Heinrich Katie M. , Jahnke Sara A.
Published: May 2020

Objective:

To examine occupational injuries among career women firefighters (FFs).

Methods:

A national cross-sectional survey assessed injury prevalence, types, frequencies, and predictors.

Results:

A total of 3012 women career FFs were enrolled in the study. Almost a third (31.7%) reported at least one occupational injury in the past 12 months. The most common injuries were dislocations, sprains, or strains (59.3%). Racial minority status, self-rated health, body composition, exercise habits, substance use, mental health, and job dissatisfaction were all significant injury correlates. Nearly 43% of injuries resulted in missed workdays. Additionally, 25% reported incurring chronic injuries.

Conclusions:

Women FFs reported a high prevalence of occupational injury and a significant percentage reported chronic injuries. These data can inform initiatives to curtail injuries in the fire service and better protect women FFs.
The impact of sarcopenia on patients undergoing treatment for pancreatic ductal adenocarcinoma
Authors: Amundson Julia R. , Williams Jelani K. , Benjamin Andrew J. , Witmer Hunter D.D. , Roggin Kevin K.
Published: May 2020

Introduction:

Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer that disproportionately affects geriatric patients. Combination therapy with surge. ry and chemotherapy is associated with longer survival than medical treatment or supportive care. Preoperative selection of patients for surgical treatment, based on patient-specific factors such as sarcopenia, may help risk-stratify patients and improve outcomes. This paper aims to review the current literature on the impact of sarcopenia and sarcopenic obesity on patients undergoing treatment for PDAC.

Outcomes:

The impact of sarcopenia and sarcopenia obesity on perioperative and long-term outcomes after treatment for PDAC is variable. Sarcopenia has been associated with high-grade complications, longer length of hospital, and intensive care unit stays, more frequent discharge to skilled nursing facilities and decreased utilization of adjuvant therapy in patients treated with curative intent surgery. Sarcopenic obesity has been associated with more complications, high-grade complications, and hematologic toxicities. Patients with sarcopenic obesity may have even lower overall survival than sarcopenic patients.

Discussion:

The effect of a pre-treatment diagnosis of sarcopenia or sarcopenic obesity on outcomes for patients undergoing treatment for PDAC remains unknown, in part due to the heterogeneity of studies and definitions. Prehabilitation programs including resistance exercise and nutritional supplementation have shown benefit in sarcopenic patients.

Conclusion:

PDAC remains a deadly disease and patient-specific factors such as sarcopenia and sarcopenic obesity identified at the time of cancer diagnosis offer potential as risk stratification measures and points of intervention. Currently, a paucity of standardized measurement tools, definitions, and prehabilitation regimens limits the clinical implementation of such knowledge.
Tympanoplasty With or Without Balloon Eustachian Tuboplasty for Chronic Suppurative Otitis Media With Obstructive Eustachian Tube Dysfunction
Authors: Hsieh Cheng-Yu , Chang Chan-Jung , Sun Chuan-Hung , Lee Chee-Yee , Gotamco Giselle L. , Hsu Chuan-Jen , Wu Hung-Pin
Published: May 2020

Objective:

To further elucidate the role of balloon Eustachian tuboplasty (BET) in tympanoplasty, we conducted a study to compare the outcomes of tympanoplasty with and without BET for the treatment of chronic suppurative otitis media (CSOM) with obstructive Eustachian tube dysfunction (OETD).

Study Design:

Case control study.

Setting:

Tertiary referral center.

Patients:

A total of 70 ears diagnosed with CSOM (tubotympanic type) and OETD were included in this study. Thirty-five patients were prospectively enrolled for BET and tympanomastoidectomy between February 2018 and June 2019. Thirty-five control subjects were matched by sex and age and retrospectively enrolled for tympanomastoidectomy between July 2016 and January 2018.

Interventions:

BET, tympanomastoidectomy.

Main Outcome Measures:

The graft take rate, hearing levels, and Eustachian tube function test results.

Results:

The graft take success rate was higher in the BET group (80.0%; 28/35) than in the control group (68.6%; 24/35). However, the difference was not statistically significant. The average air-bone gap (ABG) improvement was 10.93 ± 7.70 dB in the BET group and 7.11 ± 8.08 dB in the control group, with a statistically significant between-group difference (p = 0.033).

Conclusions:

Our findings suggest that BET can objectively and subjectively improve the Eustachian tube function, with a slight but significant improvement in ABG despite the lack of a clinically significant improvement overall. However, it does not affect the graft take rate. In summary, BET could be used as an adjunctive procedure in the treatment of CSOM with OETD.
The Application of a Venous Catheter for the Surgical Treatment of Punctal Occlusion
Authors: Meduri Alessandro , Inferrera Leandro , Tumminello Giuseppe , Delia Gabriele , Cicciù Marco , Aragona Pasquale
Published: May 2020

Purpose:

Presentation about advantages of a new surgical technique in 20 patients with punctal occlusion with a venous catheter during punctoplasty.

Methods:

The arrangement of a 30-mm venous catheter used during puncoplasty surgery was performed in 10 patients with punctal occlusion. The venous catheter was removed after 15 to 45 days after surgery.

Results:

The use of the venous catheter supports the recanalization of the lacrimal drainage system 15 days after surgery. The venous catheter is easy to find, not expensive, and easy to use.

Conclusion:

The technique is performed under regional anesthesia. Furthermore, after surgery, the recanalization of the lacrimal drainage system was observed with a significant reduction of the epiphora in 6 months after surgery.
Endoscopic Treatment of Huge Sinus Mucoceles Causing Orbital Symptoms
Authors: Kim Sangjun , Bae Woo Yong , Park Sang Hoo
Published: May 2020

Objective:

Paranasal sinus mucoceles are accumulation of mucoid secretions and desquamated epithelium within the sinus causing distension of its wall. They occur mostly in the frontal and ethmoid sinuses. Patients with giant frontal or ethmoidal sinus mucoceles suffer from orbital symptoms such as proptosis, visual disturbance, periorbital swelling, pain, or visual disturbance mostly, but they can also have rhinologic or neurologic symptoms. The purpose of this study is to evaluate the efficacy of endoscopic marsupialization for treating giant frontal and ethmoidal sinus mucoceles causing orbital symptoms.

Methods:

This study was a retrospective, consecutive clinical review of patients with giant frontal and ethmoidal sinus mucoceles with orbital symptoms, who were treated by endoscopic marsupialization between January 2012 and August 2019. Medical records including age, gender, nasal and orbital symptoms, imaging findings, and surgical methods were reviewed.

Results:

There were 15 patients with giant frontal and/or ethmoidal sinus mucoceles accompanied with orbital symptoms. The mean age of the patients was 50.5 years. One patient had previously undergone endoscopic sinus surgery for chronic rhinosinusitis. Within 15 patients, the main orbital symptoms were visual disturbance (6 patients), proptosis (8 patients), eyelid swelling (6 patients), and periorbital pain (1 patient). Other symptoms included nasal congestion, rhinorrhea, and headache. All patients underwent endoscopic marsupialization of the mucocele and had improvement in nasal and orbital signs and symptoms.

Conclusion:

Endoscopic marsupialization is an effective treatment for giant frontal and ethmoidal mucoceles with orbital symptoms.
Is a Final Splint Necessary in Bimaxillary Orthognathic Surgery?
Authors: Posnick Jeffrey C. , Kinard Brian E.
Published: May 2020

For bimaxillary orthognathic surgery, a splint is commonly used to achieve the final occlusion and is then maintained through initial skeletal healing. The purpose of this study is to document how often a final splint is used to achieve the planned intraoperative occlusion, and how often is the final splint retained after surgery to maintain the occlusion during the initial skeletal healing phase.

The investigators developed a retrospective case series. The study variables were demographic and operative. The outcome variables were the use of a final splint to achieve the desired intraoperative occlusion; the frequency and clinical indication for maintaining the final splint during the 5-weeks of initial skeletal healing; and the occlusion achieved after initial healing (5 weeks) compared to that planned from model surgery. Descriptive statistics were reported.

The study sample was composed of 41 consecutive subjects. The mean age at operation was 26.9 ± 11.8 years and 51% of the subjects were male. Twenty-five subjects required segmental maxillary surgery. The final splint was used in 39% of subjects to achieve final occlusion and maintained postoperatively in only 10%. No subjects developed transverse relapse during the initial healing phase (5-weeks). All subjects with planned immediate mid-arch open-bites (n = 8) showed vertical improvement or closure during the initial healing when the splint was not maintained.

The use of a final occlusal splint and then maintenance of the splint through initial skeletal healing is not required in the majority of bimaxillary orthognathic surgery cases to achieve the planned occlusion.
Comparison of the Efficiacy of Intra-Articular Injection of Liquid Platelet-Rich Fibrin and Hyaluronic Acid After in Conjunction With Arthrocentesis for the Treatment of Internal Temporomandibular Joint Derangements
Authors: Yuce Esra , Komerik Nurgul
Published: May 2020

The aim of this study was to evaluate the effectiveness of intra-articular injection of liquid platelet-rich fibrin (I-PRF) versus hyaluronic acid (HA) following arthrocentesis in patients suffering from temporomandibular joint (TMJ) pain and dysfunction. A total of 69 patients with internal TMJ derangement were enrolled in this retrospective, matched cohort study. A total of 47 included patients (67 joints) were divided into 3 groups as follows: 16 participants in the arthrocentesis-only group; 14 patients in the arthrocentesis plus HA injection group (A+HA); and 17 participants in the arthrocentesis plus I-PRF injection group (A+I-PRF). The 2 outcome variables were TMJ pain and maximal mouth opening (MMO) which were evaluated up to 12 months postoperatively. The data were analyzed using the Shapiro–Wilk test, Kruskal–Wallis test, Mann–Whitney U test, Wilcoxon sign test, Fisher exact test, and the χ
2 test. Statistically significant decreases in pain scores and increases in MMO values were observed in all 3 groups during the 12 months of follow-up. The significant decrease in pain values was shown in the A+I-PRF group as compared with the A+HA group at 9 months postoperatively. MMO values in the A+I-PRF group were significantly higher than in the A+HA group at 9 and 12 months postoperatively. All conventional treatment procedures can provide pain reduction and improvement to MMO. However, intraarticular injections of I-PRF in combination with arthrocentesis showed superior performance in terms of the gradual improvement in pain alleviation and range of mouth opening.
Modeling Medical Education: The Impact of Three-Dimensional Printed Models on Medical Student Education in Plastic Surgery
Authors: Lane Jaina C. , Black Jonathan S.
Published: May 2020

Purpose:

Trainee exposure to craniofacial pathology can be limited due to rare disease presentation, revealing a need for tools that assist in visualizing complex 3D pathologic anatomy. 3D-printed models show potential as a useful aid, allowing for physical manipulation and hands-on experience. This study investigates their educational value in teaching craniofacial pathology and surgical repair.

Methods:

Forty-four medical students randomly assigned to a control group or model group were given a PowerPoint presentation-based module on craniosynostosis and surgical repair. The model group was also provided with 3D-printed models of sagittal, metopic, and bicoronal synostosis, created using patient-specific preoperative computed tomography data. A survey using the Likert scale evaluated participants’ learning experience. Pre- and postmodule scores on a 10-question multiple choice quiz were recorded.

Results:

The survey showed that students in the model group reported better understanding of the anatomy (4.86 ± 0.15 versus 4.26 ± 0.22; P = 0.0001) and visualization of the pathology (4.76 ± 0.23 versus 4.26 ± 0.25; P = 0.0064), gaining an improved understanding of surgical approach (4.38 ± 0.37 versus 3.83 ± 0.29; P = 0.0266), which was more effectively taught (4.24 ± 0.33 versus 3.30 ± 0.38; P = 0.0007) with the 3D-printed models. The mean pre- and post-module quiz scores between groups were similar.

Conclusion:

3D-printed models demonstrated an improved learning experience for medical students as shown by survey. These findings suggest a potential use for 3D-printed models in medical education of craniofacial pathology and surgery.
Health-Related Quality of Life in Irritable Bowel Syndrome
Authors: Cassar Gillian E. , Youssef George J. , Knowles Simon , Moulding Richard , Austin David W.
Published: May 2020

Irritable bowel syndrome (IBS) affects up to 20% of the global population and is associated with impaired health-related quality of life (HRQoL). This systematic review and meta-analysis aimed to investigate differences in HRQoL of those with IBS compared with healthy controls and to examine whether HRQoL improves following psychological intervention. Online databases were searched for articles from 2002 to 2017. Studies were screened and data extracted according to predetermined criteria. A total of 4,154 citations were identified from which 36 were eligible for inclusion. Eight studies compared HRQoL of those with IBS (n = 822) with that of healthy individuals (n = 3,809). Those with IBS suffered significant impairment across all HRQoL domains compared with healthy individuals, with the majority of effects (Cohen's d) being moderate to large. Twenty-eight studies investigated HRQoL in IBS following psychological intervention (n = 1,308) relative to controls (n = 1,006). All HRQoL domains improved with large effects following treatment; however, maintenance of these effects was inconsistent. Those with IBS experience poorer HRQoL than the wider community; nevertheless, psychological interventions are associated with improved HRQoL across all domains. High-quality studies are needed to better inform gastroenterological nurses of which interventions are most efficacious in alleviating the burden of IBS, and which IBS subpopulations would benefit.
Cooperation between Caenorhabditis elegansCOMPASS and condensin in germline chromatin organization
Authors: Herbette M. , Robert V. , Bailly A. , Gely L. , Feil R. , Llères D. , Palladino F.
Published: May 2020

Deposition of histone H3 lysine 4 (H3K4) methylation at promoters by SET1/COMPASS is associated with context-dependent effects on gene expression and local changes in chromatin organization. Whether SET1/COMPASS also contributes to higher-order chromosome structure has not been investigated. Here, we address this question by quantitative FRET (Förster resonance energy transfer)-based fluorescence lifetime imaging microscopy (FLIM) onC. elegansgerm cells expressing histones H2B-eGFP and H2B-mCherry. We find that SET1/COMPASS subunits strongly influence meiotic chromosome organization, with marked effects on the close proximity between nucleosomes. We further show that inactivation of SET-2, theC. eleganshomologue of SET1, or CFP-1, the chromatin targeting subunit of COMPASS, strongly enhance chromosome organization defects and loss of fertility resulting from depletion of condensin-II. Defects in chromosome morphology resulting from conditional inactivation of topoisomerase II, another structural component of chromosomes, were also aggravated in the absence of SET-2. Combined, ourin vivofindings suggest a model in which the SET1/COMPASS histone methyltransferase complex plays a role in shaping meiotic chromosome in cooperation with the non-histone proteins condensin-II and topoisomerase.
Cortex cis-regulatory switches establish scale colour identity and pattern diversity inHeliconius
Authors: Livraghi Luca , Hanly Joseph J. , Van Belleghem Steven M. , Montejo-Kovacevich Gabriela , van der Heijden Eva S. M. , Loh Ling Sheng , Ren Anna , Warren Ian A. , Lewis James J. , Concha Carolina , López Laura H. , Wright Charlotte , Walker Jonah M. , Foley Jessica , Goldberg Zachary H. , Arenas-Castro Henry , Perry Michael W. , Papa Riccardo , Martin Arnaud , McMillan W. Owen , Jiggins Chris D.
Published: May 2020

InHeliconiusbutterflies, wing pattern diversity is controlled by a few genes of large effect that regulate colour pattern switches between morphs and species across a large mimetic radiation. One of these genes,cortex, has been repeatedly associated with colour pattern evolution in butterflies. Here we carried out CRISPR knock-outs in multipleHeliconiusspecies and show thatcortexis a major determinant of scale cell identity. Chromatin accessibility profiling and introgression scans identifiedcis-regulatory regions associated with discrete phenotypic switches. CRISPR perturbation of these regions in black hindwing genotypes recreated a yellow bar, revealing their spatially limited activity. In theH. melpomene/timaretalineage, the candidate CRE from yellow-barred phenotype morphs is interrupted by a transposable element, suggesting thatcis-regulatory structural variation underlies these mimetic adaptations. Our work shows thatcortexfunctionally controls scale colour fate and that itscis-regulatory regions control a phenotypic switch in a modular and pattern-specific fashion.
An efficient gene excision system in maize
Authors: Wang Ning , Arling Maren , Hoerster George , Ryan Larisa , Wu Emily , Lowe Keith , Gordon-Kamm Bill , Jones Todd J. , Chilcoat Nicholas Doane , Anand Ajith
Published: May 2020

Use of the morphogenic genesBaby Boom(Bbm) andWuschel2(Wus2), along with new ternary constructs, has increased the genotype range and the type of explants that can be used for maize transformation. In addition, altering the ectopic expression pattern forBbm/Wus2has resulted in rapid maize transformation methods that are faster and applicable to a broader range of inbreds. However, expression ofBbm/Wus2can compromise the quality of regenerated plants, leading to sterility. We reasoned excising morphogenic genes after transformation but before regeneration would increase production of fertile T0 plants. We developed a method that uses an inducible site-specific recombinase (Cre) to excise morphogenic genes. The use of developmentally regulated promoters, such asOle, Glb1, End2andLtp2, to driveCreenabled excision of morphogenic genes in early embryo development and produced excised events at a rate of 25%-100%. A different strategy utilizing an excision-activated selectable marker produced excised events at a rate of 53.3%-68.4%; however, the transformation frequency was lower (12.9%-49.9%). The use of inducible heat shock promoters (e.g.Hsp17.7, Hsp26) to express Cre, along with improvements in tissue culture conditions and construct design, resulted in high frequencies of T0 transformation (29%-69%), excision (50%-97%), usable quality events (3.6%-14%), and few escapes (non-transgenic; 14%-17%) in three elite maize inbreds. Transgenic events produced by this method are free of morphogenic and marker genes.
Robot-aided Training of Propulsion During Walking: Effects of Torque Pulses Applied to the Hip and Knee Joints During Stance
Authors: McGrath Robert , Bodt Barry , Sergi Fabrizio
Published: May 2020

The goal of this study is to evaluate the effects of the application of torque pulses to the hip and knee joint via a robotic exoskeleton in the context of training propulsion during walking. Based on our previous biomechanical study, we formulated a set of conditions of torque pulses applied to the hip and knee joint associated with changes in push-off posture, a component of propulsion. In this work, we quantified the effects of hip/knee torque pulses on metrics of propulsion, specifically hip extension (HE) and normalized propulsive impulse (NPI), in two experiments. In the first experiment, we exposed 16 participants to sixteen conditions of torque pulses during single strides to observe the immediate effects of pulse application. In the second experiment, we exposed 16 participants to a subset of those conditions to observe short-term adaptation effects.

During pulse application, NPI aligned with the expected modulation of push-off posture, while HE was modulated in the opposite direction. The timing of the applied pulses, early or late stance, was crucial, as the effects were often in the opposite direction when changing timing condition. Extension torque applied at late stance increased HE in both experiments range of change in HE: (1.6 ± 0.3 deg, 7.7 ± 0.9 deg),p< 0.001). The same conditions resulted in a negative change in NPI only in the single pulse experiment — change in NPI for knee torque: −2.9 ± 0.3 ms,p< 0.001, no significant change for hip torque. Also, knee extension and flexion torque during early and late stance, respectively, increased NPI during single pulse application — range of change in NPI: (3.4, 4.2) ± 0.3 ms,p< 0.001). During repeated pulse application, NPI increased for late stance flexion torque — range of change in NPI: (4.5, 4.8) ± 2 ms,p< 0.001), but not late stance extension torque. Upon pulse torque removal, we observed positive after-effects in HE in all conditions. While there were no after-effects in NPI significant at the group level, a responder analysis indicated that the majority of the group increased both NPI and HE after pulse application.
Physiological and molecular responses to combinatorial iron and phosphate deficiencies in hexaploid wheat seedlings
Authors: Kaur Gazaldeep , Shukla Vishnu , Meena Varsha , Kumar Anil , Tyagi Deepshikha , Singh Jagtar , Kandoth Pramod Kaitheri , Mantri Shrikant , Rouached Hatem , Pandey Ajay Kumar
Published: May 2020

Iron (Fe) and phosphorus (P) are the essential mineral nutrient for plant growth and development. However, the molecular interaction of the Fe and P pathways in crops remained largely obscure. In this study, we provide a comprehensive physiological and molecular analysis of hexaploid wheat response to single (Fe, P) and its combinatorial deficiencies. Our data showed that inhibition of the primary root growth occurs in response to Fe deficiency; however, growth was rescued when combinatorial deficiencies occurred. Analysis of RNAseq revealed that distinct molecular rearrangements during combined deficiencies with predominance for genes related to metabolic pathways and secondary metabolite biosynthesis primarily include genes for UDP-glycosyltransferase, cytochrome-P450s, and glutathione metabolism. Interestingly, the Fe-responsive cis-regulatory elements in the roots in Fe stress conditions were enriched compared to the combined stress. Our metabolome data also revealed the accumulation of distinct metabolites such as amino-isobutyric acid, arabinonic acid, and aconitic acid in the combined stress environment. Overall, these results are essential in developing new strategies to improve the resilience of crops in limited nutrients.

HIGHLIGHTS

This study was performed to understand the molecular changes occurring during the interaction of Phosphorus (P) and Iron (Fe) in hexaploid wheat roots.

P and Fe show cross-talk as Fe deficiency-induced phenotype that was restored by the withdrawal of P.

A total of 2780 differentially expressed genes were identified in the roots with the combined –Fe–P deficiencies with predominance for UDP-glycosyltransferases, cytochrome-450 and glutathione-S-transferases transcripts.

The metabolomic changes identified the importance of amino-isobutyric acid, arabinonic acid and aconitic acid during dual deficiency

This work provides a comprehensive insight to understand the molecular rearrangements occurring in wheat roots during Fe and P interaction.
Injectable hydrogels for sustained co-delivery of subunit vaccines enhance humoral immunity
Authors: Roth Gillie A. , Gale Emily C. , Alcántara-Hernández Marcela , Luo Wei , Axpe Eneko , Verma Rohit , Yin Qian , Yu Anthony C. , Hernandez Hector Lopez , Maikawa Caitlin L. , Smith Anton A. A. , Davis Mark M. , Pulendran Bali , Idoyaga Juliana , Appel Eric A.
Published: May 2020

Vaccines aim to elicit a robust, yet targeted, immune response. Failure of a vaccine to elicit such a response arises in part from inappropriate temporal control over antigen and adjuvant presentation to the immune system. In this work, we sought to exploit the immune system’s natural response to extended pathogen exposure during infection by designing an easily administered slow-delivery vaccine platform. We utilized an injectable and self-healing polymer-nanoparticle (PNP) hydrogel platform to prolong the co-delivery of vaccine components to the immune system. We demonstrated that these hydrogels exhibit unique delivery characteristics whereby physicochemically distinct compounds (such as antigen and adjuvant) could be co-delivered over the course of weeks. When administered in mice, hydrogel-based sustained vaccine exposure enhanced the magnitude, duration, and quality of the humoral immune response compared to standard PBS bolus administration of the same model vaccine. We report that the creation of a local inflammatory niche within the hydrogel, coupled with sustained release of vaccine cargo, enhanced the magnitude and duration of germinal center responses in the lymph nodes. This strengthened germinal center response promoted greater antibody affinity maturation, resulting in a more than 1000-fold increase in antigen-specific antibody affinity in comparison to bolus immunization. In summary, this work introduces a simple and effective vaccine delivery platform that increases the potency and durability of subunit vaccines.
Context matters: Situational stress impedes functional reorganization of intrinsic brain connectivity during problem solving
Authors: Liu Mengting , Backer Robert A. , Amey Rachel C. , Splan Eric E. , Magerman Adam , Forbes Chad E.
Published: May 2020

Extensive research has established the relationship between individual differences in brain activity in a resting state and individual differences in behavior. Conversely, when individuals are engaged in various tasks, certain task-evoked reorganization occurs in brain functional connectivity, which consequently can influence individuals’ performance as well. Here, we show that resting state and task-dependent state brain patterns interact as a function of contexts engendering stress. Findings revealed that when the resting state connectome was examined during performance, the relationship between connectome strength and performance only remained for participants under stress (who also performed worse than all other groups on the math task), suggesting stress preserved brain patterns indicative of underperformance whereas non-stressed individuals spontaneously transitioned out of brain patterns indicative of underperformance. These findings were subsequentially replicated in an independent sample set. Implications are discussed for network dynamics as a function of context.
Model-based fMRI reveals co-existing specific and generalized concept representations
Authors: Bowman Caitlin R. , Iwashita Takako , Zeithamova Dagmar
Published: May 2020

There has been a long-standing debate about whether categories are represented by individual category members (exemplars) or by the central tendency abstracted from individual members (prototypes). Across neuroimaging studies, there has been neural evidence for either exemplar representations or prototype representations, but not both. In the present study, we asked whether it is possible for individuals to form multiple types of category representations within a single task. We designed a categorization task to promote both exemplar and prototype representations, and we tracked their formation across learning. We found evidence for co-existing prototype and exemplar representations in brain in regions that aligned with previous studies: prototypes in ventromedial prefrontal cortex and anterior hippocampus and exemplars in inferior frontal gyrus and lateral parietal cortex. These findings show that, under the right circumstances, individuals may form representations at multiple levels of specificity, potentially facilitating a broad range of future memory-based decisions.
Cellular-scale silicon probes for high-density, precisely-localized neurophysiology
Authors: Egert Daniel , Pettibone Jeffrey R , Lemke Stefan , Patel Paras R. , Caldwell Ciara M. , Cai Dawen , Ganguly Karunesh , Chestek Cynthia A. , Berke Joshua D.
Published: May 2020

Neural implants with large numbers of electrodes have become an important tool for examining brain functions. However, these devices typically displace a large intracranial volume compared to the neurons they record. This large size limits the density of implants, provokes tissue reactions that degrade chronic performance, and impedes the ability to accurately visualize recording sites within intact circuits. Here we report next-generation silicon-based neural probes at cellular-scale (5×10µm cross-section), with ultra-high-density packing (as little as 66µm between shanks) and 64 or 256 closely-spaced recording sites per probe. We show that these probes can be inserted into superficial or deep brain structures and maintain high-quality spike recordings in freely behaving rats for many weeks. Finally, we demonstrate a slice-in-place approach for the precise registration of recording sites relative to nearby neurons and anatomical features, including striatal µ-opioid receptor patches. This scalable technology provides a valuable tool for examining information processing within neural circuits, and potentially for human brain-machine interfaces.
Sick of Eating: eco-evo-immuno dynamics of predators and their trophically acquired parasites
Authors: Fleischer Samuel R. , Bolnick Daniel I. , Schreiber Sebastian J.
Published: May 2020

When predators consume prey, they risk becoming infected with their prey’s parasites, which can then establish the predator as a secondary host. For example, stickleback in northern temperate lakes consume benthic or limnetic prey, which are intermediate hosts for distinct species of parasites (e.g.Eustrongylidesnematodes in benthic oligocheates andSchistocephalus soliduscopepods in limnetic copepods). These worms then establish the stickleback as a secondary host and can cause behavioral changes linked to increased predation by birds. In this study, we use a quantitative genetics framework to consider the simultaneous eco-evolutionary dynamics of predator ecomorphology and predator immunity when alternative prey may confer different parasite exposures. When evolutionary tradeoffs are sufficiently weak, predator ecomorphology and immunity are correclated among populations, potentially generating a negative correlation between parasite intake and infection.
Sparsely-Connected Autoencoder (SCA) for single cell RNAseq data mining
Authors: Alessandri L , Cordero F , Beccuti M , Licheri N , Arigoni M , Olivero M , Di Renzo F , Sapino A , Calogero RA
Published: May 2020

Single-cell RNA sequencing (scRNAseq) is an essential tool to investigate cellular heterogeneity. Although scRNAseq has some technical challenges, it would be of great interest being able to disclose biological information out of cell subpopulations, which can be defined by cluster analysis of scRNAseq data. In this manuscript, we evaluated the efficacy of sparsely-connected autoencoder (SCA) as tool for the functional mining of single cells clusters. We show that SCA can be uses as tool to uncover hidden features associated to scRNAseq data. Our approach is strengthened by two metrics, QCF and QCM, which respectively allow to evaluate the ability of SCA to reconstruct a cells cluster and to evaluate the overall quality of the neural network model. Our data indicate that SCA encoded spaces, derived by different experimentally validated data (TFs targets, miRNAs targets, Kinases targets, and cancer-related immune signatures), can be used to grasp single cell cluster-specific functional features. In our implementation, SCA efficacy comes from its ability to reconstruct only specific clusters, thus indicating only those clusters where the SCA encoding space is a key element for cells aggregation. SCA analysis is implemented as module in rCASC framework and it is supported by a GUI to simplify it usage for biologists and medical personnel.
Oncogenic mutation or overexpression of oncogenic KRAS or BRAF is not sufficient to confer oncogene addiction
Authors: Ito Reina E. , Oneyama Chitose , Aoki Kazuhiro
Published: May 2020

Oncogene addiction is a cellular property by which cancer cells become highly dependent on the expression of oncogenes for their survival. Oncogene addiction can be exploited to design molecularly targeted drugs that kill only cancer cells by inhibiting the specific oncogenes. Genes and cell lines exhibiting oncogene addiction, as well as the mechanisms by which cell death is induced when addicted oncogenes are suppressed, have been extensively studied. However, it is still not fully understood how oncogene addiction is acquired in cancer cells. Here, we take a synthetic biology approach to investigate whether oncogenic mutation or oncogene expression suffices to confer the property of oncogene addiction to cancer cells. We employed human mammary epithelium-derived MCF-10A cells expressing the oncogenic KRAS or BRAF. MCF-10A cells harboring an oncogenic mutation in a single-allele of KRAS or BRAF showed weak tumorigenic activity, but no characteristics of oncogene addiction. MCF-10A cells overexpressing oncogenic KRAS demonstrated the tumorigenic activity, but MCF-10A cells overexpressing oncogenic BRAF did not. Neither cell line exhibited any oncogene addiction properties. These results indicate that the introduction of oncogenic mutation or the overexpression of oncogenes is not sufficient for cancer cells to acquire oncogene addiction, and that oncogene addiction is not associated with tumorigenic potential.
Adolescent frontal top-down neurons receive heightened local drive to establish adult attentional behavior in mice
Authors: Nabel Elisa M , Garkun Yury , Koike Hiroyuki , Sadahiro Masato , Liang Ana , Norman Kevin J , Taccheri Giulia , Demars Michael P. , Im Susanna , Caro Keaven , Lopez Sarah , Bateh Julia , Hof Patrick R. , Clem Roger L. , Morishita Hirofumi
Published: May 2020

Frontal top-down cortical neurons projecting to sensory cortical regions are well-positioned to integrate long-range inputs with local circuitry in frontal cortex to implement top-down attentional control of sensory regions. How adolescence contributes to the maturation of top-down neurons and associated local/long-range input balance, and the establishment of attentional control is poorly understood. Here we combine projection-specific electrophysiological and rabies-mediated input mapping in mice to uncover adolescence as a developmental stage when frontal top-down neurons projecting from the anterior cingulate to visual cortex are highly functionally integrated into local excitatory circuitry and have heightened activity compared to adulthood. Chemogenetic suppression of top-down neuron activity selectively during adolescence, but not later periods, produces long-lasting visual attentional behavior deficits, and results in excessive loss of local excitatory inputs in adulthood. Our study reveals an adolescent sensitive period when top-down neurons integrate local circuits with long-range connectivity to produce attentional behavior.
Distinct Long-term Effects of Precision X-Radiation on Reflex Saliva Flow Rate and Tissue Integrity in a Preclinical Model of Chronic Hyposalivation
Authors: Aalam Syed Mohammed Musheer , Viringipurampeer Ishaq A. , Walb Matthew C. , Tryggestad Erik J. , Emperumal Chitra P. , Song Jianning , Xu Xuewen , Saini Rajan , Lombaert Isabelle M.A. , Sarkaria Jann N. , Garcia Joaquin , Janus Jeffrey R. , Kannan Nagarajan
Published: May 2020

Chronic salivary hypofunction and xerostomia are common side effects of radiation therapy which is an essential component in the curative management in patients with head & neck cancers. Over the years, improvements in delivery techniques such as image-guided intensity modulated radiation therapy have led to improvement in cancer management but chronic hyposalivation continues to be a challenge that causes long-term health implications resulting in compromised quality of life. Recent advances in salivary stem cell research promise new frontier in the treatment of radiation-induced hyposalivation by initiating regeneration of radiation-damaged salivary parenchymal cells. Lack of a standard preclinical immunodeficient model to assess radiation-induced changes objectively and quantitatively in salivary flow rates will impede rapid progress towards the development of cellular therapies for chronic salivary dysfunction and attendant xerostomia. Herein, we report the first fully characterized novel cone-beam computed tomography (CBCT)-guided precision ionizing radiation (IR) induced chronic hyposalivation model in radiosensitive, immunodeficient transgenic NSG-SGM3 mice expressing three human cytokines including c-KIT ligand/stem cell factor. Additionally, we also report a novel and instantaneous method to objectively assess the kinetics of pilocarpine-stimulated salivary flowrate. Comprehensive structural and functional characterization of salivary glands revealed previously unknown and highly complex gender, age, IR dose and salivary gland subtype-specific effects of salivary-ablative precision IR.
Subjective Beliefs In, Out, and About Control: A Quantitative Analysis
Authors: Mancinelli Federico , Roiser Jonathan , Dayan Peter
Published: May 2020

A critical facet of adjusting one’s behaviour after succeeding or failing at a task is assigning responsibility for the ultimate outcome. Humans have trait- and state-like tendencies to implicate aspects of their own behaviour (called ‘internal’ ascriptions) or facets of the particular task or Lady Luck (‘chance’). However, how these tendencies interact with actual performance is unclear. We designed a novel task in which subjects had to learn the likelihood of achieving their goals, and the extent to which this depended on their efforts. High internality (Levenson I-score) was associated with decision making patterns that are less vulnerable to failure, and at the same time less oriented to more rewarding achievements. Our computational analyses suggested that this depended heavily on the adjustment in the perceived achievability of riskier goals following failure. We found beliefs about chance not to be explanatory of choice behaviour in our task. Beliefs about powerful others were strong predictors of behaviour, but only when subjects lacked substantial influence over the outcome. Our results provide an evidentiary basis for heuristics and learning differences that underlie the formation and maintenance of control expectations by the self.
Complexity analysis of heartbeat-related signals in Brain MRI time series as a potential biomarker for ageing and cognitive performance
Authors: López Pérez David , Bokde Arun L. W. , Kerskens Christian M.
Published: May 2020

Getting older affects both the structure of the brain and some cognitive capabilities. Until now, magnetic resonance imaging (MRI) approaches have been unable to give a coherent reflection of the cognitive declines. It shows the limitation of the contrast mechanisms used in most MRI investigations, which are indirect measures of brain activities depending on multiple physiological and cognitive variables. However, MRI signals may contain information of brain activity beyond these commonly used signals caused by the neurovascular response. Here, we apply a zero-spin echo (ZSE) weighted MRI sequence, which can detect heartbeat evoked signals (HES). Remarkably, these MRI signals have properties only known from electrophysiology. We investigated the complexity of the HES arising from this sequence in two age groups; young (18-29 years) and old (over 65 years). While comparing young and old participants, we show that the complexity of the HES decreases with age, where the stability and chaoticity of these HES are particularly sensitive to age. However, we also found individual differences which were independent of age. Complexity measures were related to scores from different cognitive batteries and showed that higher complexity may be related to better cognitive performance. These findings underpin the affinity of the HES to electrophysiological signals. The profound sensitivity of these changes in complexity shows the potential of HES for understanding brain dynamics that need to be tested in more extensive and diverse populations with clinical relevance for all neurovascular diseases.
Host-dependent fungus-fungus competition suppresses fungal pathogenesis inArabidopsis thaliana
Authors: Pathompitaknukul Kuldanai , Hiruma Kei , Tanaka Hiroyuki , Kawamura Nanami , Toyoda Atsushi , Itoh Takehiko , Saijo Yusuke
Published: May 2020

Like animals, plants accommodate a rich diversity of microbes, typically without discernible disease symptoms. How their pathogenesis is prevented in the host remains obscure. Here, we show that the root-infecting fungusColletotrichum fructicolaof theC.gloeosporioidesclade (CgE), isolated from field-grown healthy Brassicaceae plants, inhibits growth of pathogenic fungi inArabidopsis thaliana, in a phosphate status-dependent manner. Loss of host ethylene signaling or phytoalexins, camalexin or indole glucosinolates, however, allows CgE to display pathogenesis, suggesting host contributions to endophytic CgE colonization and benefit. Compared to a closely-relatedC. gloeosporioidespathogen (CgP), CgE is characterized by genome expansion and >700 fungal genes (4.34%) specifically induced in the host roots when co-inoculated with CgP, including genes related to fungal secondary metabolism. This may underlie antimicrobial tolerance of CgE and its dominance over pathogenic fungi within the host, pointing to a role for fungus-fungus competition in asymptomatic fungal colonization in plants.
STX18-AS1is a Long Noncoding RNA predisposing to Atrial Septal Defect via downregulation ofNKX2-5in differentiating cardiomyocytes
Authors: Liu Yingjuan , Choy Mun-kit , Abraham Sabu , Tenin Gennadiy , Black Graeme C. , Keavney Bernard D.
Published: May 2020

Previous genome-wide association studies (GWAS) have identified a region of chromosome 4p16 associated with the risk of Atrial Septal Defect (ASD), which is among the commonest Congenital Heart Disease (CHD) phenotypes. Here, we identify the responsible gene in the region and elucidate disease mechanisms. Linkage disequilibrium in the region, eQTL analyses in human atrial tissues, and spatio-temporal gene expression studies in human embryonic hearts concordantly suggested the long noncoding RNA (lncRNA)STX18-AS1as the causative gene in the region. Using CRISPR/Cas9 knockdown in HepG2 cells,STX18-AS1was shown to regulate the expression of the key cardiac transcription factorNKX2-5via atrans-acting effect on promoter histone methylation. Furthermore,STX18-AS1knockdown depleted the potential of human embryonic stem cells (H9) to differentiate into cardiomyocytes, without affecting their viability and pluripotency, providing a mechanistic explanation for the clinical association.
A genomic footprint of a moving hybrid zone in marbled newts
Authors: Arntzen Jan W. , López-Delgado Julia , van Riemsdijk Isolde , Wielstra Ben
Published: May 2020

We developed a panel of 44 nuclear genetic markers and applied this to two species of marbled newts in the north (Triturus marmoratus) and the south (T. pygmaeus) of the Iberian Peninsula, to document pattern and process of interspecific gene flow. The northernmost occurrence ofT. pygmaeusgenetic material was in aT. marmoratuspopulation north of the Vouga river estuary. This suggested the past presence of a hybrid zone, possibly coinciding with a natural river outlet at ca. 1200 A.D. Since 1808, the species contact has moved back south to a by then completed, man-made Vouga channel. We also found evidence for aT. marmoratusgenomic footprint inT. pygmaeusfrom the Serra de Sintra, near Lisbon. In combination with a previously reported southern, relic occurrence ofT. marmoratusin between both areas, the data point to the superseding with hybridization ofT. marmoratusbyT. pygmaeus. We estimate that the species hybrid zone has moved over a distance of ca. 215 km.
Pharmacologically modified pluripotent stem cell-based cancer vaccines with anti-metastatic potential
Authors: Heront-Kishi Masae , Asgarova Afag , Desterke Christophe , Chaker Diana , de Goër de Herve Marie-Ghislaine , Turhan Ali G , Bennaceur-Griscelli Annelise , Griscelli Frank
Published: May 2020

Cancer is maintained by the activity of a rare population of self-renewing “cancer stem cells” (CSCs), which are resistant to conventional therapies. CSCs share several antigenic determinants with pluripotent stem cells (PSCs). We show here that PSCs, combined with a histone deacetylase inhibitor (HDACi), are able to elicit major anti-tumor responses in a model of highly aggressive breast cancer. This immunotherapy strategy was effective in preventing tumor establishment and efficiently targeted CSCs by inducing extensive modifications of the tumor microenvironment. The anti-tumor effect was correlated with a reduction in regulatory T and myeloid-derived suppressor cell populations and an increase in cytotoxic CD8+T cells within the tumor and the spleen along with a drastic reduction in metastatic dissemination and an improvement in the survival rate. These results demonstrate for the first time the possibility of using PSCs and HDACi as an allogeneic anticancer vaccine, in future universal immunotherapy strategies.