bluuebunny/crossref_metadata_2025 huggingface dataset:
Endovenous Thermal Ablation of Prominent Central Forehead Veins (Supratrochlear Veins)
Authors: Pereira Charles Esteves , Rover Carlos Alberto , Whiteley Mark Steven
Published: October 2020

BACKGROUND

Many patients complain of prominent vertical veins in the center of their forehead, worse when smiling, wrinkling the forehead in bright light, leaning forward, and when vasodilated in heat, when exercising, or with alcohol. Previous attempts to treat these with external laser, sclerotherapy, and phlebectomy have not been successful.

OBJECTIVE

To describe a new method of treating prominent vertical forehead veins and to report the early results.

MATERIALS AND METHODS

We used endovenous laser ablation with a 1470 nm diode laser in 15 patients (F:M 12:3; mean age 38.4 years range 24–69). A bare fiber was used once and a 400-μm single ring radial fiber (Biolitec, Vienna, Austria) in all other cases. Tumescence was placed around the vein and a power of 2 to 3 W with a pullback of 7 to 10 seconds per centimeter.

RESULTS

Twelve of the 15 patients (80%) ended up with a good cosmetic result and were satisfied, although 2 needed redo treatment. One patient had minor skin tethering, and 2 (13%) suffered burns—one was the only bare fiber case and the other, the only one where 4 W was used.

CONCLUSION

We present a novel technique to treat prominent vertical forehead veins, with apparently good early results.
Deep Anterior Lamellar Keratoplasty After Previous Anterior Lamellar Keratoplasty to Improve the Visual Outcomes
Authors: Sarnicola Caterina , Sarnicola Enrica , Cheung Albert Y. , Panico Edoardo , Panico Claudio , Sarnicola Vincenzo
Published: October 2020

Purpose:

To describe a series of patients who underwent deep anterior lamellar keratoplasty (DALK) after previous anterior lamellar keratoplasty (ALK) to improve their visual outcomes.

Methods:

This is a retrospective case series of 9 DALK eyes (9 patients) with a history of previous ALK and an unsatisfactory visual outcome. Surgery was performed in all cases at least 3 years after ALK. Cannula big bubble, air viscobubble, and manual dissection techniques were performed. Preoperative and postoperative best-corrected visual acuity, residual recipient bed thickness, and endothelial cell count were evaluated. Follow-up was at least 24 months for all eyes.

Results:

Two subtotal anterior lamellar keratoplasties (through 1 type 1 big bubble and 1 air viscobubble) and 7 manual dissection DALKs were achieved. A small rupture of the residual recipient bed occurred during 1 case, and it was managed without penetrating keratoplasty conversion. Mean best-corrected visual acuity improved from 0.64 to 0.09 logMAR. Postoperative residual recipient central bed thickness was less than 80 μm in all cases. No postoperative complications were recorded at the last follow-up (24–36 months postoperatively).

Conclusions:

Different DALK techniques can be successfully used to improve visual acuity in previous ALK eyes with an unsatisfactory visual outcome.
Validation of a Novel Confocal Microscopy Imaging Protocol With Assessment of Reproducibility and Comparison of Nerve Metrics in Dry Eye Disease Compared With Controls
Authors: Takhar Jaskirat S. , Joye Ashlin S. , Lopez Sarah E. , Marneris Athanasios G. , Tsui Edmund , Seitzman Gerami D. , Keenan Jeremy D. , Gonzales John A.
Published: October 2020

Purpose:

The purposes of this study were to assess the reproducibility of a novel standardized technique for capturing corneal subbasal nerve plexus images with in vivo corneal confocal microscopy and to compare nerve metrics captured with this method in participants with dry eye and control participants.

Methods:

Cases and controls were recruited based on their International Statistical Classification of Diseases and Related Health Problems (ICD-10) diagnoses. Participants completed the following 3 ocular symptom questionnaires: the Ocular Surface Disease Index, Neuropathic Pain Symptom Inventory, and Dry Eye Questionnaire 5. A novel eye fixation-grid system was used to capture 30 standardized confocal microscopy images of the central cornea. Each participant was imaged twice by different operators. Seven quantitative nerve metrics were analyzed using automated software (ACCmetrics, Manchester, United Kingdom) for all 30 images and a 6-image subset.

Results:

Forty-seven participants were recruited (25 classified as dry eye and 22 controls). The most reproducible nerve metrics were corneal nerve fiber length [intraclass correlation (ICC) = 0.86], corneal nerve fiber area (ICC = 0.86), and fractal dimension (ICC = 0.90). Although differences were not statistically significant, all mean nerve metrics were lower in those with dry eye compared with controls. Questionnaire scores did not significantly correlate with nerve metrics. Reproducibility of nerve metrics was similar when comparing the entire 30-image montage to a central 6-image subset.

Conclusions:

A standardized confocal imaging technique coupled with quantitative assessment of corneal nerves produced reproducible corneal nerve metrics even with different operators. No statistically significant differences in in vivo corneal confocal microscopy nerve metrics were observed between participants with dry eye and control participants.
Mongolian spots in GM1 gangliosidosis: a pictorial report
Authors: Mishra Shivani , Pai Pranita , Uttarilli Anusha , Girisha Katta Mohan
Published: October 2020

GM1 gangliosidosis is a lysosomal storage disorder, characterized by psychomotor deterioration, visceromegaly, facial coarseness, retinal cherry-red spots, and skeletal abnormalities. We report six unrelated patients with GM1 gangliosidosis with extensive Mongolian spots on the trunk and extremities that provided clue to clinical diagnosis. All patients exhibited psychomotor delay, coarse facies, hepatosplenomegaly, hypotonia, and dysostosis multiplex. Four patients had retinal cherry-red spots. The condition was confirmed by identification of very low activities of beta-galactosidase enzyme in peripheral leukocytes and biallelic pathogenic variants in the GLB1 gene. We identified one novel (c.1479G>T) and two known (c.75 + 2dup and c.1369C>T) pathogenic variants in homozygous state in them. Our work ascertains extensive Mongolian spots as a diagnostic handle for early recognition of GM1 gangliosidosis. Though a known feature of GM1 gangliosidosis, considerable variation in the prevalence and ethnic differences are observed. This report illustrates the Mongolian spots pictorially in Indian patients.
HIV-1 evades a Gag mutation that abrogates killer cell immunoglobulin-like receptor binding and disinhibits natural killer cells in infected individuals with KIR2DL2+/HLA-C∗03:04+ genotype
Authors: Ziegler Maja C. , Naidoo Kewreshini , Chapel Anais , Nkotwana Sindiswa , Mann Jaclyn , Mncube Zenele , Ismael Nasreen , Goulder Philip , Ndung’u Thumbi , Altfeld Marcus , Thobakgale Christina F.
Published: October 2020

HIV-1 sequence variations impact binding of inhibitory killer cell immunoglobulin-like receptors (KIRs) to human leukocyte antigen class I (HLA-I) molecules modulating natural killer cell function. HIV-1 strains encoding amino acids that mediate binding of inhibitory KIRs might therefore have a selective benefit in individuals expressing the respective KIR/HLA genotypes. Here, we demonstrate that HIV-1 clade C avoids a p24 Gag mutation that abolishes binding of KIR2DL2 to HLA-C∗03:04 and disinhibits natural killer cells in individual encoding for this genotype.
Odontogenic Cutaneous Fistula: A Case in Aged Patient With Delayed Diagnosis
Authors: Borbon Claudia , Gallesio Cesare , Ramieri Guglielmo
Published: October 2020

Odontogenic cutaneous fistula is a pathologic communication between the cutaneous surface of the face and the oral cavity and it is a rare entity frequently misdiagnosed.

Therefore, the lesion may persist for a long period before the correct diagnosis is made and odontogenic source is treated appropriately. Delay in diagnosis adds to the chronicity of the lesion and if not diagnosed in times fistula can even leave deforming scars.

Considering the scarceness and diagnostic predicament of odontogenic cutaneous fistulas, the authors report a significant case of 80 years old female.
A Patient With Traumatic Upper Eyelid Ectropion and Their Management by Canthopexy
Authors: Louca Milton , Dusseldorp Joseph R.
Published: October 2020

Upper eyelid ectropion is rare. When it does occur, the cicatricial subset of upper eyelid ectropion is its most common manifestation. Due to its rarity, little has been published regarding its treatment. Herein, we present the case of a 27-year-old patient who suffered significant left sided facial trauma in a high-velocity motor vehicle accident, resulting in a soft tissue defect in the left lateral supra-orbital region, including loss of the lateral half of the left eyebrow. The defect was left to heal by secondary intention causing severe cicatricial upper eyelid ectropion. Several reconstructive techniques were subsequently utilized including recreating the defect and replacing like with like tissues according to the facial sub-units. Right sided upper eyelid skin was used to replace the deficient left upper eyelid skin and a scalp composite graft was harvested to replace the deficient left lateral eyebrow. Temporary tarsorrhaphy, and steroid injections were used on multiple occasions to counteract the cicatricial forces. Ultimately, permanent lateral tarsorrhaphy and upper eyelid canthopexy was needed to obtain a satisfactory functional and cosmetic result.
A Rare Paranasal Sinus Abnormality: Maxillary Sinus Hypoplasia
Authors: Erdogan Banu Atalay
Published: October 2020

Maxillary sinus hypoplasia is a rare condition. The majority of patients are asymptomatic but in some cases, they suffer from headaches and facial pain. Awareness of this condition is important because of misdiagnosis and possible complications during endoscopic sinus surgery. This is a presentation of 24-year-old women with unilateral maxillary sinus hypoplasia who presented with headache and nasal blockage.
Women in Maxillofacial Surgery and Otolaryngology; Career Obstacles and Success Factors
Authors: Al Ryalat Nosaiba , Ryalat Soukaina , Al-Abdalla Mariam , Al-Shayyab Mohammad H. , Samara Osama , Taimeh Dina , Khreesha Lubna , Abu-Hammad Osama A. , Malkawi Ziad , Dar-Odeh Najla S.
Published: October 2020

Little is known on career factors and expectations for female oral and maxillofacial surgeons (OMFS) in developing countries. The study aimed to explore career perceptions of females in 2 related surgical specialties: oral and maxillofacial surgery and otolaryngology (ENT) with a focus on career obstacles and success factors. A structured questionnaire was distributed to female surgeons working in Jordan in the 2 surgical specialties. Questions addressed socio-professional characteristics and career-promoting and hindering factors. All surgeons registered in both specialties were invited. A total of 56 surgeons participated in the survey. Age range was 29 to 55 years (mean = 38.55 ± 5.799). Significantly more OMFS surgeons were single (P = 0.000) younger (P = 0.003), and had fewer years of experience (P = 0.01) than ENT surgeons. Significantly more ENT surgeons perceived the “hard working” attribute and “better communication skills” as career-promoting factors (P = 0.04, P = 0.015, respectively). Further, significantly more ENT surgeons believed that females in the surgical profession help in changing the traditional surgical stereotype linked with the male gender (93.8% ENT in contrast to 75% OMFS, P = 0.047), and expressed a preference for female mentors (48% ENT in contrast to 0% OMFS, P = 0.000). The results of this study indicate that female OMFS surgeons have different socio-professional characteristics and perceptions to their peers in ENT surgery, and this mainly manifested in professional experience, marital status, and important career perceptions. They seem to lack confidence in female participation and promotion of the surgical career, and they show preference for having exclusively male mentors.
Comparison of the Biomechanical Stiffness of Titanium and Sonic Weld RX Osteofixation Systems for Monoblock Zygomaticomaxillary Complex Fractures
Authors: Iwanaga Hiroyuki , Nuri Takashi , Ueda Koichi
Published: October 2020

Resorbable osteosynthesis systems are widely used for the fixation of zygomaticomaxillary complex (ZMC) fractures instead of titanium systems, because they do not have postoperative hardware-related complications. However, the strength of conventional resorbable systems is inferior to that of titanium systems. Recently, ultrasound-aided resorbable osteosynthesis systems, which have higher fixation than conventional resorbable osteosynthesis systems, have become available.

The purpose of this study was to compare the mechanical stiffness of the ultrasound-aided resorbable and titanium osteosynthesis systems in a cadaveric monoblock ZMC fracture model. Three human cadaveric monoblock ZMC fracture models (6 zygomas) were created. The fixation materials included the titanium (Level One Fixation; KLS Martin, Germany) and ultrasound-aided resorbable osteofixation systems (SonicWeld RX; KLS Martin). The fixation methods included the 3-point (zygomaticofrontal [ZF], zygomaticomaxillary buttress, and inferior orbital rim [Group I]) and the 2-point (ZF + inferior orbital rim [Group IIa] and ZF + zygomaticomaxillary buttress [Group IIb]) fixations. Each fixation model was mechanically tested with a load of up to 100 N, based on the previously reported postoperative masseter muscle strength, and the stiffness was calculated. Titanium was found to be stiffer than SonicWeld RX, though not significantly different. The fixation points in decreasing order of stiffness were Group I, Group IIa, and Group IIb, though the differences were not significant. In conclusion, the 2-point fixation, including the ZF fixation with SonicWeld RX, can be used as an alternative to the 3-point titanium fixation, which is considered to be stronger and stiffer.
Anesthesia-Associated Periodic Discharges
Authors: Husari Khalil S. , Ritzl Eva K.
Published: October 2020

Purpose:

Anesthetic agents have been widely used in the treatment of refractory status epilepticus and the medical management of increased intracranial pressure whenever the goal is therapeutic burst suppression. Periodic patterns typically consisting of generalized periodic discharges (GPDs) following emergence from anesthesia have been described in several case reports. However, their clinical significance and in particular whether these patterns are epileptiform remains unclear.

Methods:

This is a single-center, retrospective, observational study examining EEG patterns following emergence from pharmacologically induced burst suppression. Clinical and EEG data were collected. Patients who developed GPDs following anesthetic wean were compared with those who did not.

Results:

Over 4.5 years, 14 patients developed GPDs related to anesthetic withdrawal. The GPDs had a frequency between 0.5 and 2.5 Hz. Generalized periodic discharges related to anesthetic withdrawal were transient, with a median duration of 40 hours (interquartile range, 24–48 hours). Notably, in all patients, the pattern was stimulus dependent. When compared with a control group of 19 consecutive patients who did not develop a generalized periodic pattern in the context of the anesthetic wean, there was no significant difference in the status epilepticus relapse between the two groups (29% vs. 44%; P = 0.63). Patients in the GPD group were more likely to be on pentobarbital (93% vs. 58%; P = 0.05) and were more likely to have concomitant systemic infection treated with antibiotics compared with the control group (86% vs. 42%; P = 0.02).

Conclusions:

Generalized periodic patterns are common following the wean of intravenous anesthetics (particularly pentobarbital) and likely represent a transitional encephalopathic state in a subset of patients. Their morphology is distinct and can be differentiated from the reemergence of status epilepticus (if the latter was the indication for anesthetic treatment). Failure to recognize this pattern may lead to prolonged unnecessary treatments if it is mistaken for the emergence of seizure activity. The presence of concomitant systemic infection and associated antibiotic treatment may be risk factors for the development of this pattern.
Novosphingobium aquimarinum sp. nov., isolated from seawater
Authors: Le Ve Van , Ko So-Ra , Lee Sang-Ah , Jin Long , Ahn Chi-Yong , Oh Hee-Mock
Published: October 2020

A novel Gram-stain-negative, aerobic, and rod-shaped bacterial strain, M24A2MT, was isolated from seawater in the Republic of Korea. On the basis of the 16S rRNA gene phylogeny, strain M24A2MT was found to be closely related to

Novosphingobium pentaromativorans

US6-1T and

Novosphingobium mathurense

SM117T with pair-wise sequence similarities of 97.4 and 96.9 %, respectively. Phylogenetic analysis of 16S rRNA sequences indicated that M24A2MT formed a branch with

Novosphingobium pentaromativorans

US6-1T and represented a member of the genus

Novosphingobium

. The predominant cellular fatty acids were C14 : 0 2-OH, summed feature 3 (C16 : 1
ω7c and/or C16 : 1
ω6c), and summed feature 8 (C18 : 1
ω7c and/or C18 : 1
ω6c). The polar lipids of strain M24A2MT consisted mainly of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, one unidentified phospholipid, and two unidentified lipids. The respiratory quinone was ubiquinone Q-10. The genomic DNA G+C content was 63.9 %. Given the phenotypic characteristics along with the phylogenetic distinctness and chemotaxonomic features, strain M24A2MT is considered to represent a novel species within the genus

Novosphingobium

, for which the name Novosphingobium aquimarinum sp. nov. is proposed. The type strain of Novosphingobium aquimarinum sp. nov. is M24A2MT (=KCTC 72894T=JCM 33983T).
Effect of arsenite and growth in biofilm conditions on the evolution of Thiomonas sp. CB2
Authors: Freel Kelle C. , Fouteau Stephanie , Roche David , Farasin Julien , Huber Aline , Koechler Sandrine , Peres Martina , Chiboub Olfa , Varet Hugo , Proux Caroline , Deschamps Julien , Briandet Romain , Torchet Rachel , Cruveiller Stephane , Lièvremont Didier , Coppée Jean-Yves , Barbe Valérie , Arsène-Ploetze Florence
Published: October 2020

Thiomonas

bacteria are ubiquitous at acid mine drainage sites and play key roles in the remediation of water at these locations by oxidizing arsenite to arsenate, favouring the sorption of arsenic by iron oxides and their coprecipitation. Understanding the adaptive capacities of these bacteria is crucial to revealing how they persist and remain active in such extreme conditions. Interestingly, it was previously observed that after exposure to arsenite, when grown in a biofilm, some strains of

Thiomonas

bacteria develop variants that are more resistant to arsenic. Here, we identified the mechanisms involved in the emergence of such variants in biofilms. We found that the percentage of variants generated increased in the presence of high concentrations of arsenite (5.33 mM), especially in the detached cells after growth under biofilm-forming conditions. Analysis of gene expression in the parent strain CB2 revealed that genes involved in DNA repair were upregulated in the conditions where variants were observed. Finally, we assessed the phenotypes and genomes of the subsequent variants generated to evaluate the number of mutations compared to the parent strain. We determined that multiple point mutations accumulated after exposure to arsenite when cells were grown under biofilm conditions. Some of these mutations were found in what is referred to as ICE19, a genomic island (GI) carrying arsenic-resistance genes, also harbouring characteristics of an integrative and conjugative element (ICE). The mutations likely favoured the excision and duplication of this GI. This research aids in understanding how

Thiomonas

bacteria adapt to highly toxic environments, and, more generally, provides a window to bacterial genome evolution in extreme environments.
Exosome-LncPICALM-AU1 regulates endothelial–mesenchymal transition in hepatopulmonary syndrome
Authors: Yang Congwen , Yang Yihui , Chen Yang , Huang Jian , Li Yujie , Zhi Hongyu , Tang Xi , Wang Xiaobo , Belguise Karine , Xia Zhengyuan , Ning Jiaoling , Gu Jianteng , Yi Bin , Lu Kaizhi
Published: October 2020

As important mediators of intercellular communication, exosome have can modulate various cellular functions by transferring a variety of intracellular components to target cells. However, little is known about the role of exosome-mediated communication between distant organs. Hepatopulmonary syndrome (HPS) is a severe lung injury caused by chronic liver disease. A new long noncoding RNA (lncRNA) PICALM-AU1 was found and upregulated in the liver of HPS. It was located in the cholangiocytes of liver and then, secreted as exosome into the serum. PICALM-AU1 carrying serum exosomes induced endothelial-mesenchymal transition (EndMT) of PMVECs and promoted lung injury in vivo and in vitro. Furthermore, overexpression of PICALM-AU1 significantly suppressed miR144-3p and subsequently induced ZEB1 expression. Taken together, our findings identified cholangiocyte-derived exosomal lncRNA PICALM-AU1 plays a critical role in the EndMT of HPS lung. And PICALM-AU1 represents a noninvasive biomarker and potential therapeutic target for HPS.
Extra-cellular Matrix in cell aggregates is a proxy to mechanically control cell proliferation and motility
Authors: Dolega Monika E. , Monnier Sylvain , Brunel Benjamin , Joanny Jean-François , Recho Pierre , Cappello Giovanni
Published: October 2020

Imposed deformations play an important role in morphogenesis and tissue homeostasis, both in normal and pathological conditions. To perceive mechanical perturbations of different types and magnitudes, tissues need appropriate detectors, with a compliance that matches the perturbation amplitude. By comparing results of selective osmotic compressions of cells within multicellular aggregates with small osmolites and global aggregate compressions with big osmolites, we show that global compressions have a strong impact on the aggregates growth and internal cell motility, while selective compressions of same magnitude have almost no effect. Both compressions alter the volume of individual cells in the same way but, by draining the water out of the extracellular matrix, the global one imposes a residual compressive mechanical stress on the cells while the selective one does not. We conclude that, in aggregates, the extracellular matrix is as a sensor which mechanically regulates cell proliferation and migration in a 3D environment.
Two-tiered SARS-CoV-2 seroconversion screening in the Netherlands and stability of nucleocapsid, spike protein domain 1 and neutralizing antibodies
Authors: Garritsen Anja , Scholzen Anja , van den Nieuwenhof Daan W.A. , Smits Anke P.F. , Datema E. Suzan , van Galen Luc S. , Kouwijzer Milou L.C.E.
Published: October 2020

Serological testing in the COVID-19 pandemic is mainly implemented to gain sero-epidemiological data, but can also retrospectively inform about suspected SARS-CoV-2 infection. We verified and applied a two-tiered testing strategy combining a SARS-CoV-2 receptor-binding domain (RBD)-specific lateral flow assay (LFA) with a nucleocapsid protein (NCP) IgG ELISA to assess seroconversion in n=7241 individuals. The majority had experienced symptoms consistent with COVID-19, but had no access to RT-PCR testing. Longitudinal follow-up in n=97 LFA+ individuals was performed up to 20 weeks after initial infection using NCP and spike protein S1 domain (S1) IgG ELISAs and a surrogate virus neutralization test (sVNT). Individuals reporting symptoms from January 2020 onwards showed seroconversion, as did a considerable proportion of asymptomatic individuals. Seroconversion for symptomatic and asymptomatic individuals was higher in an area with a known infection cluster compared to a low incidence area. Overall, 94% of individuals with a positive IgG result by LFA were confirmed by NCP ELISA. The proportion of ELISA-confirmed LFA results declined over time, in line with contracting NCP IgG titers during longitudinal follow-up. Neutralizing antibody activity was considerably more stable than S1 and NCP IgG titers, and both reach a plateau after approximately 100 days. The sVNT proved to be not only highly specific, but also more sensitive than the specificity-focussed two-tiered serology approach. Our results demonstrate the high specificity of two-tiered serology testing and highlight the sVNT used as a valuable tool to support modelling of SARS-CoV-2 transmission dynamics, complement molecular testing and provide relevant information to individuals.
Distinct serum anti-Aβ antibody patterns in hemorrhagic and inflammatory cerebral amyloid angiopathy manifestations
Authors: Chantran Yannick , Capron Jean , Doukhi Diana , Felix Johanna , Féroul Mélanie , Kruse Florian , Chaigneau Thomas , Dorothée Guillaume , Allou Thibault , Ayrignac Xavier , Barrou Zina , de Broucker Thomas , Cret Corina , Turc Guillaume , Peres Roxane , Wacongne Anne , Sarazin Marie , Renard Dimitri , Cordonnier Charlotte , Alamowitch Sonia , Aucouturier Pierre
Published: October 2020

Objective

To study blood anti-Aβ antibodies in the context of spontaneous inflammatory or hemorrhagic CAA manifestations, which are similar to complications occurring after monoclonal anti-Aβ antibody immunotherapies.

Methods

In this case-control study, serum anti-Aβ antibody isotype, concentration, avidity, and reactivity toward soluble or fibrillary Aβ1-40 and Aβ1-42 isoforms were assessed using an ELISA-based multiplex analysis. Anti-Aβ serologic patterns were defined in CAA and CAA subgroups using multivariable logistic regression analyses.

Results

Fourty-one healthy aged controls and 64 CAA patients were recruited: 46 with hemorrhagic features (CAA-he) and 18 with CAA-related inflammation (CAA-ri). As compared to controls, the most striking features of CAA-related serological profiles were the following: i) both CAA-he and CAA-ri patients displayed lower binding diversity of anti-soluble Aβ1-40 IgM; ii) CAA-he patients displayed higher anti-soluble Aβ1-40 / fibrillary Aβ1-42 IgG4 concentrations ratio and higher anti-soluble Aβ1-42 IgG4 and IgA avidity; iii) CAA-ri patients displayed higher binding diversity of anti-soluble Aβ1-40 IgG3 and higher anti-fibrillary/soluble Aβ1-42 IgG4 dilution curve steepness ratio.

Conclusion

This proof-of-concept study revealed anti-Aβ antibody variations in CAA patients, some of which were associated to CAA clinical phenotypes, unveiling pathophysiological insights regarding CAA-hemorrhagic and inflammatory related events.
Optic nerve tortuosity and displacements during horizontal eye movements in healthy and highly myopic subjects
Authors: Wang Xiaofei , Chang Stanley , Grinband Jack , Yannuzzi Lawrence A. , Freund K. Bailey , Hoang Quan V. , Girard Michaël J. A.
Published: October 2020

Purpose

(1) To assess the morphology and 3D displacements of the eye globe and optic nerve (ON) in adduction/abduction using magnetic resonance imaging (MRI). (2) To assess differences between healthy emmetropic and highly myopic (HM) subjects.

Methods

MRI volumes of both eyes from 18 controls and 20 HM subjects in primary gaze, abduction and adduction (15°) were postprocessed. All ONs were manually-segmented and fitted to a 3D curve to assess ON tortuosity. ON displacements were evaluated in 4 quasicoronal planes which were perpendicular to the ON in primary gaze and 3 mm apart.

Results

Axial length was higher in the HM group (28.62±2.60 vs 22.84±0.89 mm; p<0.0001). Adjusted ON tortuosities (i.e., ON tortuosities estimated before myopia onset) were lower in HM eyes (0.9063±0.0591) versus controls (1.0152±0.02981) in primary gaze, adduction (0.9023±0.05538 versus 1.0137±0.0299) and abduction (0.9100±0.0594 versus 1.0182±0.0316); p<0.0001 for all cases. In all eyes, ON displacements in adduction were significantly different from those in abduction in the naso-temporal direction (p<0.0001 in all planes) but not in the supero-inferior direction. ON displacements in the posterior segments of the ON were smaller in the HM group in both gaze directions and were larger in the anterior-most ON segment in adduction only.

Conclusions

The adjusted tortuosity of the ON was significantly lower in HM eyes, suggesting that eyes destined toward HM exhibited higher ON traction forces during eye movements before the onset of myopia. Our ON metrics may be valuable to explore a potential link between eye movements and axial elongation.
Serological Analysis Reveals an Imbalanced IgG Subclass Composition Associated with COVID-19 Disease Severity
Authors: Yates Jennifer L. , Ehrbar Dylan J. , Hunt Danielle T. , Girardin Roxanne C. , Dupuis Alan , Payne Anne F. , Sowizral Mycroft , Varney Scott , Kulas Karen E. , Demarest Valerie L. , Howard Kelly M. , Carson Kyle , Hales Margaux , Ejemel Monir , Li Qi , Wang Yang , Mantis Nicholas J. , McDonough Kathleen A. , Lee William T.
Published: October 2020

COVID-19 is associated with a wide spectrum of disease severity, ranging from asymptomatic to acute respiratory distress syndrome (ARDS). Paradoxically, a direct relationship has been suggested between COVID-19 disease severity, and the levels of circulating SARS-CoV-2-specific antibodies, including virus neutralizing titers. Through a serological analysis of serum samples from 536 convalescent healthcare workers, we found that SARS-CoV-2-specific and virus-neutralizing antibody levels were indeed elevated in individuals that experienced severe disease. The severity-associated increase in SARS-CoV-2-specific antibody was dominated by IgG, with an IgG subclass ratio skewed towards elevated receptor binding domain (RBD)- and S1-specific IgG3. However, RBD- and S1-specific IgG1, rather than IgG3 were best correlated with virus-neutralizing titers.We propose that Spike-specific IgG3 subclass utilization contributes to COVID-19 disease severity through potent Fc-mediated effector functions. These results have significant implications for SARS-CoV-2 vaccine design, and convalescent plasma therapy.
When the ventral visual stream is not enough: A deep learning account of medial temporal lobe involvement in perception
Authors: Bonnen Tyler , Yamins Daniel L.K. , Wagner Anthony D.
Published: October 2020

The medial temporal lobe (MTL) supports a constellation of memory-related behaviors. Its involvement in perceptual processing, however, has been subject to enduring debate. This debate centers on perirhinal cortex (PRC), an MTL structure at the apex of the ventral visual stream (VVS). Here we leverage a deep learning framework that approximates visual behaviors supported by the VVS—i.e. lacking PRC. We first apply this approach retroactively, modeling 30 published visual discrimination experiments: Excluding non-diagnostic stimulus sets, there is a striking correspondence between VVS-modeled and PRC-lesioned behavior, while each are outperformed by PRC-intact participants. We corroborate and extend these results with a novel experiment, directly comparing PRC-intact human performance to electrophysiological recordings from the macaque VVS: PRC-intact participants outperform a linear readout of high-level visual cortex. By situating lesion, electrophysiological, and behavioral results within a shared computational framework, this work resolves decades of seemingly inconsistent findings surrounding PRC involvement in perception.
Ancestral dietary change alters development ofDrosophilalarvae through MAPK signalling
Authors: Towarnicki Samuel G. , Youngson Neil A. , Corley Susan M. , St John Jus C. , Turner Nigel , Morris Margaret J. , Ballard J. William O.
Published: October 2020

Increasing evidence in animal species ranging from mammals to insects has revealed phenotypes that are caused by ancestral life experiences including stress and diet. The descendent phenotypes themselves are wide ranging, and include changes to behaviour, disease risk, metabolism, and growth. Ancestral dietary macronutrient composition, and quantity (over- and under-nutrition) have been shown to alter descendent growth, metabolism and behaviour. Several studies have identified inherited molecules in gametes which are altered by ancestral diet and are required for the transgenerational effect. However, there is less understanding of the developmental pathways in the period between fertilisation and adulthood that are altered by the inherited molecules. Here we identify a key role of the MAPK signalling pathway in mediating changes toDrosophilalarval developmental timing due to variation in ancestral diet. We exposed grand-parental and great grand-parental generations to defined protein to carbohydrate (P:C) dietary ratios and measured developmental timing. Descendent developmental timing was consistently faster in the period between the embryonic and pupal stages when the ancestor had a higher P:C ratio diet. Transcriptional analysis of embryos, larvae and adults revealed extensive and long-lasting changes to the MAPK signalling pathway which controlled growth rate through regulation of ribosomal RNA transcription. The importance of these processes was supported by pharmacological inhibition of MAPK and rRNA proteins which reproduced the ancestral diet-induced developmental changes. This work provides insight into the role of developmental growth signalling networks in mediating non-genetic inheritance in the period between fertilisation and adult.

Summary statement

Ancestral, diet-induced descendent developmental timing changes are caused by alteration of MAPK signalling pathways in the period between the embryo and pupal stages inDrosophila.
Screening of Cultivars for Tissue Culture Response and Establishment of Genetic Transformation in a High-yielding and Disease-resistant Cultivar ofTheobroma cacao
Authors: Jones Jesse , Zhang Elaine , Tucker Dominick , Rietz Daniel , Dahlbeck Doug , Gomez Michael , Garcia Claudia , Marelli Jean-Philippe , Livingstone Donald , Schnell Ray , Staskawicz Brian , Cho Myeong-Je
Published: October 2020

A highly efficient transformation protocol is a prerequisite to developing genetically modified and genome-edited crops. A tissue culture system spanning the initiation of floral material to the regeneration of plantlets into soil has been tested and improved in cacao. Fourteen cultivars were screened for their tissue culture response and transfer DNA (T-DNA) delivery efficiency viaAgrobacterium. These key factors were used to determine the genetic transformability of various cultivars. The high-yielding, disease-resistant cultivar INIAPG-038 was selected for stable transformation and the method was further optimized. Multiple transgenic events were produced using two vectors containing both yellow fluorescent protein and neomycin phosphotransferase II genes. A two-fold strategy to improve both T-DNA delivery and secondary somatic embryogenesis rates was conducted to improve overall transformation frequency. The use ofAgrobacteriumstrain AGL1 and cotyledon tissue derived from immature somatic embryos ranging in size between 4-10 mm resulted in the highest T-DNA delivery efficiency. Furthermore, the use of higher concentrations of basal salts and cupric sulfate in secondary callus growth medium increased the percentage of explants producing greater than ten embryos by 504% and 443%, respectively. Consequently, an optimal combination of all these components resulted in a successful transformation of INIAPG-038 with 3.7% frequency at the T0plant level. Grafting transgenic scions with undeveloped roots to wild-type seedlings with strong, healthy roots helped make plantlets survive and facilitated quick transplantation to the soil. The present methods can be applied to improve tissue culture response and transformation frequency in other cacao cultivars.

Key message

Tissue culture and genetic transformation methods for a high-yielding, disease-resistant cultivar ofTheobroma cacaowere established while factors affecting T-DNA delivery and somatic embryogenesis were identified.
Permeabilization-freeen blocimmunohistochemistry for correlative microscopy
Authors: Fulton Kara A , Briggman Kevin L
Published: October 2020

A dense reconstruction of neuronal synaptic connectivity typically requires high-resolution 3D electron microscopy (EM) data, but EM data alone lacks functional information about neurons and synapses. One approach to augment structural EM datasets is with the fluorescent immunohistochemical (IHC) localization of functionally relevant proteins. We describe a protocol that obviates the requirement of tissue permeabilization in thick tissue sections, a major impediment for correlative pre-embedding IHC and EM. We demonstrate the permeabilization-free labeling of neuronal cell types, intracellular enzymes, and synaptic proteins in tissue sections hundreds of microns thick in multiple brain regions while simultaneously retaining the ultrastructural integrity of the tissue. Finally, we explore the utility of this protocol by performing proof-of-principle correlative experiments combining two-photon imaging of protein distributions and 3D electron microscopy.
Granger Causality Inference in EEG Source Connectivity Analysis: A State-Space Approach
Authors: Manomaisaowapak Parinthorn , Nartkulpat Anawat , Songsiri Jitkomut
Published: October 2020

This paper considers a problem of estimating brain effective connectivity from EEG signals using a Granger causality (GC) concept characterized on state-space models. We propose a state-space model for explaining coupled dynamics of the source and EEG signals where EEG is a linear combination of sources according to the characteristics of volume conduction. Our formulation has a sparsity prior on the source output matrix that can further classify active and inactive sources. The scheme is comprised of two main steps: model estimation and model inference to estimate brain connectivity. The model estimation consists of performing a subspace identification and the active source selection based on a group-norm regularized least-squares. The model inference relies on the concept of state-space GC that requires solving a discrete-time Riccati equation for the covariance of estimation error. We verify the performance on simulated data sets that represent realistic human brain activities under several conditions including percentages of active sources, a number of EEG electrodes and the location of active sources. The performance of estimating brain networks is compared with a two-stage approach using source reconstruction algorithms and VAR-based Granger analysis. Our method achieved better performances than the two-stage approach under the assumptions that the true source dynamics are sparse and generated from state-space models. The method is applied to a real EEG SSVEP data set and we found that the temporal lobe played a role of a mediator of connections between temporal and occipital areas, which agreed with findings in previous studies.
RIOK2 phosphorylation by RSK promotes synthesis of the human small ribosomal subunit
Authors: Cerezo Emilie L. , Houles Thibault , Lié Oriane , Sarthou Marie-Kerguelen , Audoynaud Charlotte , Lavoie Geneviève , Halladjian Maral , Cantaloube Sylvain , Froment Carine , Burlet-Schiltz Odile , Henry Yves , Roux Philippe P. , Henras Anthony K. , Romeo Yves
Published: October 2020

Ribosome biogenesis lies at the nexus of various signaling pathways coordinating protein synthesis with cell growth and proliferation. This process is regulated by well-described transcriptional mechanisms, but a growing body of evidence indicates that other levels of regulation exist. Here we show that the Ras/mitogen-activated protein kinase (MAPK) pathway stimulates post-transcriptional stages of human ribosome synthesis. We identify RIOK2, a pre-40S particle assembly factor, as a new target of the MAPK-activated kinase RSK. RIOK2 phosphorylation by RSK promotes cytoplasmic maturation of late pre-40S particles, which is required for optimal protein synthesis and cell proliferation. RIOK2 phosphorylation facilitates its release from pre-40S particles and its nuclear re-import, prior to completion of small ribosomal subunits. Our results bring a detailed mechanistic link between the Ras/MAPK pathway and the maturation of human pre-40S particles, which open a hitherto poorly explored area of ribosome biogenesis.
Global prevalence and phylogeny of hepatitis B virus (HBV) drug and vaccine resistance mutations
Authors: Mokaya Jolynne , Vasylyeva Tetyana I , Barnes Eleanor , Ansari M. Azim , Pybus Oliver G , Matthews Philippa C
Published: October 2020

Introduction

Vaccination and anti-viral therapy with nucleos(t)ide analogues (NAs) are key approaches to reducing the morbidity, mortality and transmission of hepatitis B virus (HBV) infection. However, the efficacy of these interventions may be reduced by the emergence of drug resistance-associated mutations (RAMs) and/or vaccine escape mutations (VEMs). We have assimilated data on the global prevalence and distribution of HBV RAMs/VEMs from publicly available data and explored the evolution of these mutations.

Methods

We analysed sequences downloaded from the Hepatitis B Virus Database, and calculated prevalence of 41 RAMs and 38 VEMs catalogued from published studies. We generated maximum likelihood phylogenetic trees and used treeBreaker to investigate the distribution of selected mutations across tree branches. We performed phylogenetic molecular clock analyses using BEAST to estimate the age of mutations.

Results

RAM M204I/V had the highest prevalence, occurring in 3.8% (109/2838) of all HBV sequences in our dataset, and a significantly higher rate in genotype C sequence at 5.4% (60/1102, p=0.0007). VEMs had an overall prevalence of 1.3% (37/2837) and had the highest prevalence in genotype C and in Asia at 2.2% (24/1102; p=0.002) and 1.6% (34/2109; p=0.009) respectively. Phylogenetic analysis suggested that most RAM/VEMs arose independently, however RAMs including A194T, M204V and L180M formed clusters in genotype B. We show evidence that polymorphisms associated with drug and vaccine resistance may have been present in the mid 20thcentury suggesting that they can arise independently of treatment/ vaccine exposure.

Discussion

HBV RAMs/VEMs have been found globally and across genotypes, with the highest prevalence observed in genotype C variants. Screening for the genotype and for resistant mutations may help to improve stratified patient treatment. As NAs and HBV vaccines are increasingly being deployed for HBV prevention and treatment, monitoring for resistance and advocating for better treatment regimens for HBV remains essential.
Leafminer attack induces plant-mediated facilitation of conspecific pupae in the soil
Authors: Escobar-Bravo Rocío , Schimmel Bernardus CJ , Glauser Gaétan , Klinkhamer Peter GL , Erb Matthias
Published: October 2020

Herbivore population dynamics are strongly influenced by the interactions established through their shared host. Such plant-mediated interactions can occur between different herbivore species and between different life developmental stages of the same herbivore. Yet, whether these interactions occur between leaf-feeding herbivores and their soil-dwelling pupae is unknown.

We studied whether tomato (Solanum lycopersicum) leaf-herbivory by the American serpentine leafminerLyriomiza trifoliiaffects the performance of conspecific pupae in the soil adjacent to the plant. To gain mechanistic insights, we performed insect bioassays with the jasmonate-deficient tomato mutantdef-1and its wild type, along with the analysis of phytohormones, gene expression and root volatiles.

Leafminer metamorphosis in the soil was accelerated when wild type plants were attacked aboveground by conspecifics, but the opposite was observed indef-1. Changes in pupal developmental rate were mediated by belowground volatiles. Accordingly, leafminer herbivory differentially modulated jasmonate and abscisic acid signaling and the accumulation of specific volatiles in the roots of wild type versusdef-1plants

Our results demonstrate that aboveground herbivores can facilitate their soil-dwelling pupae by inducingdef-1-dependent systemic responses. This study expands the repertoire of plant-herbivore interactions to herbivory-induced modulation of metamorphosis, with potentially important consequences for plant and herbivore community dynamics.
Transcranial Random Noise Stimulation acutely lowers the response threshold of human motor circuits
Authors: Potok Weronika , Bächinger Marc , van der Groen Onno , Cretu Andreea Loredana , Wenderoth Nicole
Published: October 2020

Abstract

Transcranial random noise stimulation (tRNS) over cortical areas has been shown to acutely improve performance in sensory detection tasks. One explanation for this behavioural effect is stochastic resonance, a mechanism that explains how signal processing in non-linear systems can benefit from added noise. While acute noise benefits of electrical random noise stimulation have been demonstrated at the behavioural level as well as inin vitropreparations of neural tissue, it is currently largely unknown whether similar effects can be shown at the neural population level using neurophysiological readouts of human cortex. Here we hypothesized that acute tRNS will increase the responsiveness of primary motor cortex (M1) when probed with transcranial magnetic stimulation. Neural responsiveness was operationalized via the well-known concept of the resting motor threshold (RMT). We showed that tRNS acutely decreases RMT. This effect was small, but it was consistently replicated across four experiments including different cohorts (total N=81, 46 females, 35 males), two tRNS electrode montages, and different control conditions. Our experiments provide critical neurophysiological evidence that tRNS can acutely generate noise benefits by enhancing the neural population response of human M1.

Significance statement

A hallmark feature of stochastic resonance is that signal processing can benefit from added noise. This has mainly been demonstrated at the single-cell levelin vitrowhere the neural response to weak input signals can be enhanced by simultaneously applying random noise. Our finding that tRNS acutely increases the excitability of corticomotor circuits extends the principle of noise benefits to the neural population level in human cortex. Our finding is in line with the notion that tRNS might affect cortical processing via the stochastic resonance phenomenon. It suggests that enhancing the response of cortical populations to an external stimulus might be one neurophysiological mechanism mediating performance improvements when tRNS is applied to sensory cortex during perception tasks.