bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Stroke Alert With Unexpected Outcome
Authors: Gritsch David , Harahsheh Ehab , Mbonde Amir , Mangipudi Kartik , Dawit Sara , Noe Katherine H. , Demaerschalk Bart M. 
Published: December 2021

Introduction:
Observational studies have suggested that intravenous (IV) thrombolysis may be unfavorable in patients with high-grade gliomas. However, current literature on thrombolysis outcomes in patients with primary brain tumors is largely limited to case reports and may be influenced by publication bias.

Case Report:
A 69-year-old male presented with acute left hemiplegia, left hemisensory loss, neglect, dysarthria and right gaze preference (National Institutes of Health Stroke Scale 22). An emergent noncontrast head computerized tomography showed hypoattenuation in the right parietal lobe of unclear chronicity and IV thrombolysis with tissue plasminogen activator was administered within the 4.5 hour window. Following IV thrombolysis, a computerized tomography angiogram of the head and neck revealed no large vessel occlusion. However, a marginally enhancing, and centrally nonenhancing mass within the right parietal lobe associated with vasogenic edema was elucidated. Subsequently, the patient developed abnormal left hemibody tonic-clonic motor activity, left gaze preference and left-beating nystagmus concerning for focal motor status epilepticus. An emergent electroencephalogram, following administration of IV levetiracetam, showed right hemispheric electrographic seizures and right hemispheric periodic lateralized epileptiform discharges. Brain magnetic resonance imaging with gadolinium revealed 2.5 cm ring-enhancing mass in the right parietal lobe. The patient underwent right sided craniotomy with resection of the mass and pathology revealed Glioblastoma.

Conclusion:
We report a case of thrombolysis administered in a patient with high-grade glioma with no apparent complications.
Split Buccal Fat Flap in Modified Furlow Palatoplasty: Surgical Technique and Early Result
Authors: Denadai Rafael , Lo Lun-Jou 
Published: December 2021

Summary:
Encouraging results have been described for the use of pedicled buccal fat pad flap in primary cleft palate repair. This retrospective study describes the surgical technique and early results of a technical innovation utilizing the split buccal fat flaps in modified Furlow palatoplasty with small double-opposing Z-plasty. This technique introduces buccal fat tissue for coverage of lateral denuded palate surfaces to reduce the bone exposure and scar formation to potentially attenuate maxillary growth interference and for reinforcement of the palatal areas of high tension or with incomplete closure to decrease the risk of postoperative dehiscence and oronasal fistula formation. Consecutive nonsyndromic patients (n = 56) with cleft palate were treated with this method, all of whom demonstrated fast mucosalization of lateral palatal recipient regions within 3 weeks postoperatively and showed no fistula with 12 months’ follow-up. Of 19 patients (33.9 percent) who underwent auditory-perceptual assessment, 15 (78.9 percent) had normal resonance. Surgeons could add this alternative surgical maneuver to their armamentarium during the primary palatoplasty, in which coverage of lateral surfaces and reinforcement with fat tissue in the anterior soft palate space are of paramount relevance.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, IV.
Quantitative Morphologic Analysis of Cranial Vault in Twist1 +/− Mice: Implications in Craniosynostosis
Authors: Nuri Takashi , Ota Masato , Ueda Koichi , Iseki Sachiko 
Published: December 2021

Background:
The haploinsufficiency in the TWIST1 gene encoding a basic helix-loop-helix transcription factor is a cause of one of the craniosynostosis syndromes, Saethre-Chotzen syndrome. Patients with craniosynostosis usually require operative release of affected sutures, which makes it difficult to observe the long-term consequence of suture fusion on craniofacial growth.

Methods:
In this study, we performed quantitative analysis of morphologic changes of the skull in Twist1 heterozygously–deleted mice (Twist1
+/−) with micro–computed tomographic images.

Results:
In Twist1
+/− mice, fusion of the coronal suture began before postnatal day 14 and progressed until postnatal day 56, during which morphologic changes occurred. The growth of the skull was not achieved by a constant increase in the measured distances in wild type mice; some distances in the top-basal axis were decreased during the observation period. In the Twist1
+/− mouse, growth in the top-basal axis was accelerated and that of the frontal cranium was reduced. In the unicoronal suture fusion mouse, the length of the zygomatic arch of affected side was shorter in the Twist1
+/− mouse. In one postnatal day 56 Twist1
+/− mouse with bilateral coronal suture fusion, asymmetric zygomatic arch length was identified.

Conclusion:
The authors’results suggest that measuring the length of the left and right zygomatic arches may be useful for early diagnosis of coronal suture fusion and for estimation of the timing of synostosis, and that more detailed study on the growth pattern of the normal and the synostosed skull could provide prediction of the risk of resynostosis.

Clinical Relevance Statement:
The data from this study can be useful to better understand the cranial growth pattern in patients with craniosynostosis.
Stress-Related Inflammation and Social Withdrawal in Mothers of a Child With Cancer: A 1-Year Follow-Up Study
Authors: Lindsay Emily K. , Inagaki Tristen K. , Walsh Catherine P. , Messay Berhane , Ewing Linda J. , Marsland Anna L. 
Published: December 2021

ABSTRACT

Objective
Acute inflammation-induced sickness behavior involves changes in social behavior that are believed to promote recovery. Whether chronic inflammation can influence social behaviors in ways that promote recovery is unknown. In a sample of mothers of a child with cancer, this report explores the relationship between inflammation that accompanies the stress of diagnosis and changes in social network, cancer-related stress, and inflammation across 1 year. Three hypotheses tested whether a) initial levels of stress associate with initial levels of inflammation, b) initial levels of inflammation predict social network changes over time, and c) social network changes over time buffer changes in stress and inflammation over time.

Methods
Cancer-related stress (Impact of Events Scale), social network (social roles and contacts from the Social Network Inventory), and systemic inflammation (circulating interleukin [IL]-6) were assessed in 120 mothers three times after their child’s cancer diagnosis: after diagnosis (T1), 6-month follow-up (T2), and 12-month follow-up (T3).

Results
Consistent with predictions, greater cancer-related stress after diagnosis (T1) was associated with higher IL-6 after diagnosis (T1; b = 0.014, standard error [SE] = 0.01, p = .008). In turn, higher IL-6 after diagnosis (T1) was associated with a decrease in social roles over time (T1 ➔ T3; B = −0.030, SE = 0.01, p = .041). Finally, dropping social roles over time (T1 ➔ T3) was associated with decreases in cancer-related stress (B = 25.44, SE = 12.31, p = .039) and slower increases in IL-6 (B = 1.06, SE = 0.52, p = .040) over time.

Conclusions
This study provides a first indication that chronic stress–related systemic inflammation may predict changes in social behavior that associate with stress recovery and slower increases in inflammation in the year after a major life stressor.
Deep learning based models to study the effect of glaucoma genes on angle dysgenesis in-vivo
Authors: Gupta Viney , Birla Shweta , Varshney Toshit , Somarajan Bindu I , Gupta Shikha , Gupta Mrinalini , Mahalingam Karthikeyan , Singh Abhishek , Gupta Dinesh 
Published: December 2021

AbstractObjectiveTo predict the presence of Angle Dysgenesis on Anterior Segment Optical Coherence Tomography (ADoA) using deep learning and to correlate ADoA with mutations in known glaucoma genes.DesignA cross-sectional observational study.ParticipantsEight hundred, high definition anterior segment optical coherence tomography (ASOCT) B-scans were included, out of which 340 images (One scan per eye) were used to build the machine learning (ML) model and the rest were used for validation of ADoA. Out of 340 images, 170 scans included PCG (n=27), JOAG (n=86) and POAG (n=57) eyes and the rest were controls. The genetic validation dataset consisted of another 393 images of patients with known mutations compared with 320 images of healthy controlsMethodsADoA was defined as the absence of Schlemm’s canal(SC), the presence of extensive hyper-reflectivity over the region of trabecular meshwork or a hyper-reflective membrane (HM) over the region of the trabecular meshwork. Deep learning was used to classify a given ASOCT image as either having angle dysgenesis or not. ADoA was then specifically looked for, on ASOCT images of patients with mutations in the known genes for glaucoma (MYOC, CYP1B1, FOXC1andLTBP2).Main Outcome measuresUsing Deep learning to identify ADoA in patients with known gene mutations.ResultsOur three optimized deep learning models showed an accuracy > 95%, specificity >97% and sensitivity >96% in detecting angle dysgenesis on ASOCT in the internal test dataset. The area under receiver operating characteristic (AUROC) curve, based on the external validation cohort were 0.91 (95% CI, 0.88 to 0.95), 0.80 (95% CI, 0.75 to 0.86) and 0.86 (95% CI, 0.80 to 0.91) for the three models. Amongst the patients with known gene mutations, ADoA was observed among all the patients withMYOCmutations, as it was also observed among those withCYP1B1, FOXC1and withLTBP2mutations compared to only 5% of those healthy controls (with no glaucoma mutations).ConclusionsThree deep learning models were developed for a consensus-based outcome to objectively identify ADoA among glaucoma patients. All patients withMYOCmutations had ADoA as predicted by the models.
Antibodies to ILT3 abrogate myeloid immunosuppression and enable tumor killing
Authors: Brandish Philip E. , Palmieri Anthony , Ayanoglu Gulesi , Baker Jeanne , Bueno Raphael , Byford Alan , Caniga Michael , Chappell Craig , Cherwinski Holly , Cua Daniel J. , Du Xiaoyan , Fayadat-Dilman Laurence , Hall Brian E. , Issafras Hassan , Joyce-Shaikh Barbara , Juan Veronica , Levy Rachel D. , Loboda Andrey , Lunceford Jared , Mieczkowski Carl , Meehl Michael , Qu Yujie , Rosenzweig Michael , Singh Latika , Stivers Peter , Tramontozzi Peter J. , Vermilya Kimberly , Vroom Karin , Wilson Douglas C. , Zhang Chungsheng , Zhang-Hoover Jie 
Published: December 2021

ABSTRACTTumor myeloid suppressor cells impede response to T cell checkpoint immunotherapy. Immunoglobulin-like transcript 3 (ILT3, gene name, LILRB4) expressed on dendritic cells (DCs) promotes antigen-specific tolerance. Circulating monocytic MDSCs that express ILT3 have been linked to clinical outcomes and a soluble form of ILT3 is elevated in certain cancers. We find that LILRB4 expression is correlated with Gene Expression Profile of T-cell inflamed tumor microenvironment shown to be significantly associated with response to the anti-PD1 antibody pembrolizumab across several tumor types. A potent and selective anti-ILT3 mAb effectively antagonized IL-10 polarization of DCs and enabled T cell priming. In an MLR assay anti-ILT3 combined with pembrolizumab afforded greater CD8+ T cell activation compared to either agent alone. Anti-ILT3 antibodies impaired the acquisition of a suppressive phenotype of monocytes co-cultured with SK-MEL-5 cancer cells, accompanied by a reduction in surface detection of peptidase inhibitor 16, a cis interaction candidate for ILT3. Growth of myeloid cell-abundant SK-MEL-5 tumors was abrogated by ILT3 blockade and remodeling of the immune tumor microenvironment was evident by CyTOF. These data support the testing of anti-ILT3 antibodies for the treatment of a wide range of solid tumors replete with myeloid cells.
Functional Network Connectivity Imprint In Febrile Seizures
Authors: Acharya Ullas V , Kulanthaivelu Karthik , Panda Rajanikant , Saini Jitender , Gupta Arun K , Sankaran Bindu Parayil , Raghavendra Kenchaiah , Mundlamuri Ravindranath Chowdary , Sinha Sanjib , Keshavamurthy ML , Bharath Rose Dawn 
Published: December 2021

AbstractComplex febrile seizures (CFS), a subset of paediatric febrile seizures (FS), have been studied for their prognosis, epileptogenic potential and neurocognitive outcome. We evaluated their functional connectivity differences with simple febrile seizures (SFS) in children with recent-onset FS. Resting-state fMRI (rs-fMRI) datasets of 24 children with recently diagnosed FS (SFS-n=11; CFS-n=13) were analysed. Functional connectivity (FC) was estimated using time series correlation of seed region–to-whole-brain-voxels and network topology was assessed using graph theory measures. Regional connectivity differences were correlated with clinical characteristics (FDR correctedp <0.05). CFS patients demonstrated increased FC of the bilateral middle temporal pole (MTP), and bilateral thalami when compared to SFS. Network topology study revealed increased clustering coefficient and decreased participation coefficient in basal ganglia and thalamus suggesting an inefficient-unbalanced network topology in patients with CFS. The number of seizure recurrences negatively correlated with the integration of Left Thalamus (r= −0.58) and FC measures of Left MTP to ‘Right Supplementary Motor and left Precentral’ connectivity (r=−0.53). The FC of Right MTP to Left Amygdala, Putamen, Parahippocampal, and Orbital Frontal Cortex (r=0.61) and FC of Left Thalamus to left Putamen, Pallidum, Caudate, Thalamus Hippocampus and Insula (r 0.55) showed a positive correlation to the duration of the longest seizure. The findings of the current study report altered connectivity in children with CFS proportional to the seizure recurrence and duration. Regardless of the causal/consequential nature, such observations demonstrate the imprint of these disease-defining variables of febrile seizures on the developing brain.
Multi T1-weighted contrast imaging and T1 mapping with Compressed sensing FLAWS at 3T
Authors: Beaumont J. , Fripp J. , Raniga P. , Acosta O. , Ferre J.C. , McMahon K. L. , Trinder J. , Kober T. , Gambarota G. 
Published: December 2021

AbstractThe Fluid And White matter Suppression (FLAWS) MRI sequence allows for the acquisition of multiple T1-weighted contrasts in a single sequence acquisition. However, its acquisition time is prohibitive for use in clinical practice when the k-space is linearly downsampled and reconstructed using the Generalized Autocalibrating Partially Parallel Acquisition (GRAPPA) technique. This study proposes a FLAWS sequence optimization tailored to allow for the acquisition of FLAWS images with a Cartesian phyllotaxis k-space undersampling and compressed sensing (CS) reconstruction at 3T. The CS FLAWS sequence parameters were determined using a method previously employed to optimize FLAWS imaging at 1.5T and 7T. In-vivo experiments show that the proposed CS FLAWS optimization allows to reduce the FLAWS sequence acquisition time from 8 mins to 6 mins without decreasing the FLAWS image quality. In addition, this study demonstrates for the first time that T1-weighted imaging with low B1 sensitivity and T1 mapping can be performed with the FLAWS sequence at 3T for both GRAPPA and CS reconstructions. The FLAWS T1 mapping was validated using in-silico, in-vitro and in-vivo experiments with comparison against the inversion recovery turbo spin echo and MP2RAGE T1 mappings. These new results suggest that the recent advances in FLAWS imaging allow to combine the MP2RAGE imaging benefits (T1-weigthed imaging with low B1 sensitivity and T1 mapping) and with the previous version of FLAWS imaging benefits (multi T1-weighted contrast imaging) in a single 6 mins sequence acquisition.Graphical abstract
An exploration of linkage fine-mapping on sequences from case-control studies
Authors: Nickchi Payman , Karunarathna Charith , Graham Jinko 
Published: December 2021

AbstractLinkage analysis maps genetic loci for a heritable trait by identifying genomic regions with excess relatedness among individuals with similar trait values. Analysis may be conducted on related individuals from families, or on samples of unrelated individuals from a population. For allelically heterogeneous traits, population-based linkage analysis can be more powerful than genotypic-association analysis. Here, we focus on linkage analysis in a population sample, but use sequences rather than individuals as our unit of observation. Earlier investigations of sequence-based linkage mapping relied on known sequence relatedness, whereas we infer relatedness from the sequence data. We propose two ways to associate similarity in relatedness of sequences with similarity in their trait values and compare the resulting linkage methods to two genotypic-association methods. We also introduce a procedure to label case sequences as potential carriers or non-carriers of causal variants after an association has been found. This post-hoc labeling of case sequences is based on inferred relatedness to other case sequences. Our simulation results indicate that methods based on sequence-relatedness improve localization and perform as well as genotypic-association methods for detecting rare causal variants. Sequence-based linkage analysis therefore has potential to fine-map allelically heterogeneous disease traits.
Protection following BNT162b2 booster substantially exceeds that of a fresh 2-dose vaccine: a quasi-experimental study
Authors: Amir Ofra , Goldberg Yair , Mandel Micha , Bar-On Yinon M. , Bodenheimer Omri , Ash Nachman , Alroy-Preis Sharon , Huppert Amit , Milo Ron 
Published: December 2021

AbstractIsrael began administering a BNT162b2 booster dose to restore protection following the waning of the 2-dose vaccine. Biological studies have shown that a fresh booster leads to increased antibody levels compared to a fresh 2-dose vaccine, which may suggest increased effectiveness. To compare the real-world effectiveness of a fresh booster dose with that of a fresh 2-dose vaccine, we conduct a quasi-experimental study that compares populations that were eligible to receive the vaccine at different times due to age cutoff policies. Our analysis shows that a fresh booster increases protection against confirmed infection by 3.7 (95% CI: 2.7 to 5.2) fold compared to a fresh 2-dose vaccine.
Notch inhibition promotes regeneration and immunosuppression supports cone survival in a zebrafish model of inherited retinal dystrophy
Authors: Fogerty Joseph , Song Ping , Boyd Patrick , Grabinski Sarah , Hoang Thanh , Reich Adrian , Cianciolo Lauren T. , Blackshaw Seth , Mumm Jeff S. , Hyde David R. , Perkins Brian D. 
Published: December 2021

AbstractPhotoreceptor degeneration leads to irreversible vision loss in humans with retinal dystrophies such as Retinitis Pigmentosa. Whereas photoreceptor loss is permanent in mammals, zebrafish possesses the ability to regenerate retinal neurons and restore visual function. Following acute damage, Müller glia (MG) re-enter the cell cycle and produce multipotent progenitors whose progeny differentiate into mature neurons. Both MG reprogramming and proliferation of retinal progenitor cells require reactive microglia and associated inflammatory signaling. Paradoxically, MG in zebrafish models of photoreceptor degeneration fail to re-enter the cell cycle and regenerate lost cells. Here, we used the zebrafish cep290 mutant to demonstrate that progressive cone degeneration generates an immune response but does not stimulate MG proliferation. Acute light damage triggered photoreceptor regeneration in cep290 mutants but cones were only restored to pre-lesion densities. Using irf8 mutant zebrafish, we found that the chronic absence of microglia reduced inflammation and rescued cone degeneration in cep290 mutants. Finally, single-cell RNA-sequencing revealed sustained expression of notch3 in MG of cep290 mutants and inhibition of Notch signaling induced MG to re-enter the cell cycle. Our findings provide new insights on the requirements for MG to proliferate and the potential for immunosuppression to prolong photoreceptor survival.
A transcriptomic atlas ofAedes aegyptireveals detailed functional organization of major body parts and gut regional specializations in sugar-fed and blood-fed adult females
Authors: Hixson Bretta , Bing Xiao-Li , Yang Xiaowei , Bonfini Alessandro , Nagy Peter , Buchon Nicolas 
Published: December 2021

AbstractMosquito vectors transmit numerous pathogens, but large gaps remain in our understanding of their physiology. To facilitate future explorations of mosquito biology, with specific attention to the major vectorAedes aegypti, we have created Aegypti-Atlas (http://aegyptiatlas.buchonlab.com/), an online resource hosting RNAseq profiles ofAe. Aegyptibody parts (head, thorax, abdomen, gut, Malpighian tubules, and ovaries), gut regions (crop, proventriculus, anterior and posterior midgut, and hindgut), and a time course of blood meal digestion in the gut. Using Aegypti-Atlas, we provide new insights into the regionalization of gut function, blood feeding response, and immune defenses. We find that the anterior and posterior regions of the mosquito midgut possess clearly delineated digestive specializations which are preserved in the blood-fed state. Blood feeding initiates the sequential transcriptional induction and repression/depletion of multiple cohorts of peptidases throughout blood meal digestion. With respect to defense, immune signaling components, but not recognition or effector molecules, show enrichment in ovaries. Basal expression of antimicrobial peptides is dominated by two genes, holotricin and gambicin, that are expressed in the carcass and the digestive tissues, respectively, in a near mutually exclusive manner. In the midgut, gambicin and other immune effector genes are almost exclusively expressed in the anterior regions, while the posterior midgut exhibits the hallmarks of immune tolerance. Finally, in a cross-species comparison between the midguts ofAe. aegyptiandAnopheles gambiae, we observe that regional digestive and immune specializations are closely conserved, indicating that our data may yield inferences that are broadly relevant to multiple mosquito vector species. We further demonstrate that the expression of orthologous genes is highly correlated, with the exception of a ‘species signature’ comprising a small number of highly/disparately expressed genes. With this work, we show the potential of Aegypti-Atlas to unlock a more complete understanding of mosquito biology.