bluuebunny/crossref_metadata_2025_split huggingface dataset:
Towards generalizable prediction of antibody thermostability using machine learning on sequence and structure features
Authors: Harmalkar Ameya , Rao Roshan , Honer Jonas , Deisting Wibke , Anlahr Jonas , Hoenig Anja , Czwikla Julia , Sienz-Widmann Eva , Rau Doris , Rice Austin , Riley Timothy P. , Li Danqing , Catterall Hannah B. , Tinberg Christine E. , Gray Jeffrey J. , Wei Kathy Y. 
Published: June 2022

AbstractOver the last three decades, the appeal for monoclonal antibodies (mAbs) as therapeutics has been steadily increasing as evident with FDA’s recent landmark approval of the 100th mAb. Unlike mAbs that bind to single targets, multispecific biologics (bsAbs) with their single-chain variable fragment (scFv) modules have garnered particular interest owing to the advantage of engaging distinct targets. Despite their exquisite specificity and affinity, the relatively poor thermostability of these scFv modules often hampers their development as a potential therapeutic drug. In recent years, engineering antibody sequences to enhance their stability by mutations has gained considerable momentum. As experimental methods for antibody engineering are time-intensive, laborious, and expensive, computational methods serve as a fast and inexpensive alternative to conventional routes. In this work, we show two machine learning methods - one with pre-trained language models (PTLM) capturing functional effects of sequence variation, and second, a supervised convolutional neural network (CNN) trained with Rosetta energetic features - to better classify thermostable scFv variants from sequence. Both these models are trained over temperature-specific data (TS50 measurements) derived from multiple libraries of scFv sequences. In this work, we show that a sufficiently simple CNN model trained with energetic features generalizes better than a pre-trained language model on out-of-distribution (blind) sequences (average Spearman correlation coefficient of 0.4 as opposed to 0.15). Further, we demonstrate that for an independent mAb with available thermal melting temperatures for 20 experimentally characterized thermostable mutations, these models trained on TS50 data could identify 18 residue positions and 5 identical amino-acid mutations showing remarkable generalizability. Our results suggest that such models can be broadly applicable for improving the biological characteristics of antibodies. Further, transferring such models for alternative physico-chemical properties of scFvs can have potential applications in optimizing large-scale production and delivery of mAbs or bsAbs.
Processing UMI Datasets at High Accuracy and Efficiency with the Sentieon ctDNA Analysis Pipeline
Authors: Hu Jinnan , Jiang Cai , Huang Yu S. , Chen Haodong , Feng Hanying , Freed Donald , Qu Yan , Fan Rui , Su Zhencheng , Chen Weizhi 
Published: June 2022

AbstractLiquid biopsy enables identification of low allele frequency (AF) tumor variants and novel clinical applications such as minimum residual disease (MRD) monitoring. However, challenges remain, primarily due to limited sample volume and low read count of low-AF variants. Because of the low AFs, some clinically significant variants are difficult to distinguish from errors introduced by PCR amplification and sequencing. Unique Molecular Identifiers (UMIs) have been developed to further reduce base error rates and improve the variant calling accuracy, which enables better discrimination between background errors and real somatic variants. While multiple UMI-aware ctDNA analysis pipelines have been published and adopted, their accuracy and runtime efficiency could be improved.In this study, we present the Sentieon ctDNA pipeline, a fast and accurate solution for small somatic variant calling from ctDNA sequencing data. The pipeline consists of four core modules: alignment, consensus generation, variant calling, and variant filtering. We benchmarked the ctDNA pipeline using both simulated and real datasets, and found that the Sentieon ctDNA pipeline is more accurate than alternatives.
Cortical-brainstem interplay during speech perception in older adults with and without hearing loss
Authors: Lai Jesyin , Alain Claude , Bidelman Gavin M. 
Published: June 2022

AbstractReal-time modulation of brainstem frequency-following responses (FFRs) by online changes in cortical arousal state via the corticofugal (top-down) pathway has been demonstrated previously in young adults and is more prominent in the presence of background noise. FFRs during high cortical arousal states also have a stronger relationship with speech perception. Aging is associated with increased auditory brain responses, which might reflect degraded inhibitory processing within the peripheral and ascending pathways, or changes in attentional control regulation via descending auditory pathways. Here, we tested the hypothesis that online corticofugal interplay is impacted by age-related hearing loss. We measured EEG in older adults with normal-hearing (NH) and mild to moderate hearing-loss (HL) while they performed speech identification tasks in different noise backgrounds. We measured α power to index online cortical arousal states during task engagement. Subsequently, we split brainstem speech-FFRs, on a trial-by-trial basis, according to fluctuations in concomitant cortical α power into low or high α FFRs to index cortical-brainstem modulation. We found cortical α power was smaller in the HL than NH group. In NH listeners, α-FFRs modulation for clear speech (i.e., without noise) also resembled that previously observed in younger adults for speech in noise. Cortical-brainstem modulation was further diminished in HL older adults in the clear condition and by noise in NH older adults. Machine learning classification showed low α FFR frequency spectra yielded higher accuracy for classifying listeners’ perceptual performance in both NH and HL participants. Moreover, low α FFRs decreased with increased hearing thresholds at 0.5-2 kHz for clear speech but noise generally reduced low α FFRs in the HL group. Collectively, our study reveals cortical arousal state actively shapes brainstem speech representations and provides a potential new mechanism for older listeners’ difficulties perceiving speech in cocktail party-like listening situations in the form of a miss-coordination between cortical and subcortical levels of auditory processing.
Consuming Royal Jelly Causes Mosquitoes to Shift Into and Out of Their Overwintering Dormancy
Authors: Bianco Olivia E. , Abdi Aisha , Klein Matthias S. , Meuti Megan E. 
Published: June 2022

AbstractFemales of the Northern house mosquito,Culex pipiens, enter an overwintering dormancy, or diapause, in response to short day lengths and low environmental temperatures. Diapausing female mosquitoes feed exclusively on sugar-rich products rather than human or animal blood, thereby reducing disease transmission. During diapause, Major Royal Jelly Protein 1 (MRJP1) is upregulated in females ofCx. pipiens. This protein is highly abundant in royal jelly, a substance produced by honey bees (Apis mellifera), that is fed to future queens throughout larval development and stimulates longevity and fecundity. However, the role of MRJP1 inCx. pipiensis unknown. We investigated how supplementing the diets of both diapausing and nondiapausing females ofCx. pipienswith royal jelly affects gene expression, egg follicle length, fat content, protein content, longevity, and metabolic profile. We found that feeding royal jelly to long day-reared females significantly reduced the egg follicle lengths of females and switched their metabolic profiles to be similar to diapausing females. In contrast, feeding royal jelly to short day-reared females significantly reduced lifespan and switched their metabolic profile to be similar nondiapausing mosquitoes. Moreover, RNAi directed againstMRJPIsignificantly increased egg follicle length of short day-reared females, suggesting that these females averted diapause, although RNAi againstMRJP1also extended the lifespan of short day-reared females. Taken together, our data show that consuming royal jelly reverses the seasonal responses ofCx. pipiensand that these responses are likely mediated in part by MRJP1.Summary StatementConsuming royal jelly reversed seasonal differences in physiological states, lifespan and metabolic profiles in females of the Northern house mosquito, a major vector of West Nile virus.
Flying honeybees adjust their reaction times to enable group cohesion
Authors: Islam Md. Saiful , Faruque Imraan A. 
Published: June 2022

AbstractFlying insects routinely demonstrate coordinated flight in groups. How they achieve this with very limited communication, vision, and neural systems remains an open question. We measured the visual reaction time in flying honeybees while they chased a moving target, and compared in-flight reaction times for solo animals with those flying in groups. Across 425 insects, the solo honeybees show diverse reaction times (an average of 30ms and a standard deviation of 50ms). The reaction times in groups are significantly more uniform (an average of 15ms and a standard deviation of only 7ms), indicating that honeybees in group flight adjust their reaction times to match their neighbors. To investigate the role of this adjustment, we curve fit the reaction time distributions and analyzed them in a mathematical model of swarming, finding that the reaction time increases the stable region of a cohesive swarm. To verify the stabilizing effect was not an artifact of curve fitting, we then inserted the measured delays in a swarm simulation, which breaks apart under the solo reaction times and achieves stable formations for the group reaction times. Together, our findings highlight how flying animals can synchronize their reaction times in group flights to improve group cohesion.
Proteomic Dynamics of Breast Cancers Identifies Potential Therapeutic Protein Targets
Authors: Sun Rui , Zhu Yi , Sayad Azin , Ge Weigang , Luna Augustin , Liang Shuang , Segura Luis Tobalina , Rajapakse Vinodh N. , Yu Chenhuan , Zhang Huanhuan , Fang Jie , Wu Fang , Xie Hui , Saez-Rodriguez Julio , Ying Huazhong , Reinhold William C. , Sander Chris , Pommier Yves , Neel Benjamin G. , Guo Tiannan , Aebersold Ruedi 
Published: June 2022

AbstractTreatment and relevant targets for breast cancer (BC) remain limited, especially for triple-negative BC (TNBC). We quantified the proteomes of 76 human BC cell lines using data independent acquisition (DIA) based proteomics, identifying 6091 proteins. We then established a 24-protein panel distinguishing TNBC from other BC types. Integrating prior multi-omics datasets with the present proteomic results to predict the sensitivity of 90 drugs, we found that proteomics data improved drug sensitivity predictions. The sensitivity of the 90 drugs was mainly associated with cell cytoskeleton, signal transduction and mitochondrial function. We next profiled the proteome changes of nine cell lines (five TNBC cell lines, four non-TNBC cell lines) perturbated by EGFR/AKT/mTOR inhibitors. In the TNBC cell lines, metabolism pathways were dysregulated after EGFR/mTOR inhibitors treatment, while RNA modification and cell cycle pathways were dysregulated after AKT inhibitor treatment. Our study presents a systematic multi-omics and in-depth analysis of the proteome of BC cells. This work aims to aid in prioritization of potential therapeutic targets for TNBC as well as to provide insight into adaptive drug resistance in TNBC.
Predictors of second COVID-19 booster dose or new COVID-19 vaccine hesitancy among nurses: a cross-sectional study
Authors: Galanis Petros , Vraka Irene , Katsiroumpa Aglaia , Siskou Olga , Konstantakopoulou Olympia , Katsoulas Theodoros , Mariolis-Sapsakos Theodoros , Kaitelidou Daphne 
Published: June 2022

AbstractAims and objectivesTo assess the levels of second COVID-19 booster dose or new COVID-19 vaccine hesitancy among nurses and explore the potential predictors of vaccine hesitancy.BackgroundCOVID-19 full vaccination seems to be highly effective against highly contagious variants of SARS-CoV-2. Healthcare workers are a high-risk group since they have experienced high levels of COVID-19-associated morbidity and mortality.MethodsAn on-line cross-sectional study was carried out in Greece in May 2022, using a self-administered questionnaire. The study population included nurses in healthcare services who were fully vaccinated against COVID-19 at the time of study. We considered socio-demographic characteristics, COVID-19-related variables, and attitudes toward COVID-19 vaccination and pandemic as potential predictors of vaccine hesitancy.ResultsAmong 795 nurses, 30.9% were hesitant toward a second booster dose or a new COVID-19 vaccine. Independent predictors of hesitancy included lower educational level, absence of a chronic condition, good/very good self-perceived physical health, lack of flu vaccination during 2021, front-line nurses that provided healthcare to COVID-19 patients during the pandemic, nurses that had not been diagnosed with COVID-19 during the pandemic, and nurses that had at least one relative/friend that has died from COVID-19. Moreover, increased compliance with hygiene measures, increased fear of a second booster dose/new COVID-19 vaccine, and decreased trust in COVID-19 vaccination were associated with increased hesitancy.ConclusionsOur study shows that a significant percentage of nurses are hesitant toward a second booster dose/new COVID-19 vaccine. This initial hesitancy could be a barrier to efforts to control the COVID-19 pandemic. There is a need to communicate COVID-19 vaccine science in a way that is accessible to nurses in order to decrease COVID-19 vaccine hesitancy.
Host preference and survivorship ofEuschistus heros(Hemiptera: Pentatomidae) strains on cotton and soybean
Authors: Hickmann Frederico , Cordeiro Erick M. G. , Aurélio Mateus Souza L. , Saldanha Alan Valdir , Corrêa Alberto Soares 
Published: June 2022

AbstractThe Neotropical brown stink bugEuschistus heros(Fabricius) (Hemiptera: Pentatomidae) is a key pest of soybeans,Glycine max, and recently became an economically important pest of cotton,Gossypium hirsutum. This stink bug has two allopatric strains, one prevalent in southern Brazil (SS), and another in the north (NS). The two strains hybridize in central Brazil. Knowledge of host preferences and host suitability of these strains can clarify the contribution of the different gene pools to contemporary adaptive features such as the ability to harm cotton crops. We tested the attraction of theE. herosstrains and reciprocal hybrids [♀N × ♂S (HNS) and ♀S × ♂N (HSN)] to soybean and cotton plants and evaluated the nymph development and survivorship of the two strains and reciprocal hybrids fed on soybean or cotton. We conducted host-choice experiments with 4th instars and adult females and evaluated the survival of immatures on soybean and cotton plants in laboratory conditions. The SS strain preferred soybean over cotton. NS and hybrid strains chose randomly between soybean and cotton plants. All strains developed on soybean, with similar survival rates. On cotton, the pure strains did not reach adulthood; however, the hybrids developed on cotton but with a survival rate less than 1%. Our results showed thatE. herosSS was more attracted to soybeans, and NS and hybrid strains had a polyphagous choice behavior, suggesting that current host selection has been mediated by historical and, mainly, contemporary relationships ofE. herosstrains with these hosts.
Super-resolution stimulated Raman Scattering microscopy with A-PoD
Authors: Jang Hongje , Li Yajuan , Fung Anthony A. , Bagheri Pegah , Hoang Khang , Skowronska-Krawczyk Dorota , Chen Xiaoping , Wu Jane Y. , Bintu Bogdan , Shi Lingyan 
Published: June 2022

ABSTRACTUnlike traditionally-mapped Raman imaging, stimulated Raman scattering (SRS) imaging achieved the capability of imaging metabolic dynamics and a greatly improved signal-noise-ratio. However, its spatial resolution is still limited by the numerical aperture or scattering cross-section. To achieve super-resolved SRS imaging, we developed a new deconvolution algorithm – Adam optimization-based Pointillism Deconvolution (A-PoD) – for SRS imaging, and demonstrated a spatial resolution of 52 nm on polystyrene beads. By changing the genetic algorithm to A-PoD, the image deconvolution process was shortened by more than 3 orders of magnitude, from a few hours to a few seconds. By applying A-PoD to spatially correlated multi-photon fluorescence (MPF) imaging and deuterium oxide (D2O)-probed SRS (DO-SRS) imaging data from diverse samples, we compared nanoscopic distributions of proteins and lipids in cells and subcellular organelles. We successfully differentiated newly synthesized lipids in lipid droplets using A-PoD coupled with DO-SRS. The A-PoD-enhanced DO-SRS imaging method was also applied to reveal the metabolic change in brain samples from Drosophila on different diets. This new approach allows us to quantitatively measure the nanoscopic co-localization of biomolecules and metabolic dynamics in organelles. We expect that the A-PoD algorithm will have a wide range of applications, from nano-scale measurements of biomolecules to processing astronomical images.
Sleeve gastrectomy promotes colitis-associated colorectal cancer in a murine model via a modified gut microbiome
Authors: Luo James N. , Haridas Renuka S. , Lo Tammy , Tavakkoli Ali , Yoo James , Sheu Eric G. 
Published: June 2022

ABSTRACTColorectal cancer (CRC) remains the third leading cause of cancer death in the United States with an alarming rise among young (<50-years-old) patients.1Epidemiologically, obesity appears to be a risk factor for CRC.1Although bariatric surgery has been shown to be associated with decreased risk for most cancers, studies to date on bariatric surgery and CRC continue to yield conflicting results.2One possible explanation for this seeming irreconcilability is the inherent heterogeneity of CRC with its varied mechanisms. This is likely compounded by the differing bariatric operations currently employed. Here, we sharpen our focus and investigate how the most performed bariatric operation, sleeve gastrectomy (SG), affects colitis-associated CRC. Using a murine model, we found that SG significantly exacerbates both colitis and colitis-associated CRC. Using a germ-free (GF) microbiota transplant model, we found that the post-SG microbiota, when transplanted into GF mice, is capable of independently recapitulating the tumor-promoting phenotype of SG. Our results suggest that the postsurgical microbiome plays a key causal role in the increased risk for CRC after SG. This finding represents the first step in our understanding of this complex relationship that is at the intersection of two rising public health threats.
Age-dependent Aedes mosquito resistance profiling and mortality rate to repeated insecticides exposure in Western region, Saudi Arabia
Authors: Al Nazawi Ashwaq M , Weetman David 
Published: June 2022

AbstractBackgroundLittle is documented on Aedes aegypti age-dependent role on different resistance mechanisms to repeated insecticides exposures. The study examined the age-dependence of mortality rate and genetic resistance in two mechanistically pyrethroid resistant mosquito strains exposed once or repeatedly at different ages.MethodsWHO bioassays and real time polymerase chain reaction (qPCR) were performed to ascertain their association between age-dependent exposures related mortality rate and single/repeated resistance in the Jeddah and Makkah. Candidate genes of interest (CYP9J7, CYP9J27, CYP9J26, AAEL006953, CYP9P450, AAEL006013) were assessment.ResultsAge dependent and exposure duration had a significant effect on the survival of the Jeddah and resistant Cayman. Our results showed that in a single exposure assays, age had no significant effect on mortality in the Cayman strain (χ2=2.76, df=1, P=0.097), but there was significantly increased mortality in the Jeddah strain younger age (χ2=5.46, df=1, P=0.02), but not statistically significant at older age. In the multiple exposure assay, GLiM analysis showed a significant strain, day and strain*day interaction indicating mortality rate is influenced by the strain or day (which also corresponds to age).The Jeddah strain showed generally lower survival,, there was a highly significant association of survival with repeated exposures in the Jeddah strain (χ2=43.6, df=1, P=4.1×10E-11) and the Cayman strain (χ2=12.5, df=1, P=0.0004). Mortality rate correlated statistically and significantly with the number of days of exposure in the Cayman strain (Spearman rank correlation ρ=-0.77, P=0.01), but in the Jeddah strain it was not statistically significant (ρ= -0.42, P=0.23). After repeated insecticide exposure, the AAEL006013 was statistically and significantly over-expressed compared to the control (P=0.03).ConclusionTo the best of our knowledge, this is one of the first research on age and exposure linked genomic and bioassay on field Ae. aegypti in Jeddah, KSA. The study showed that repeated exposure to pyrethroids reduced the Aedes mosquito population mortality rate. This suggests that there is indeed increasing age-dependent resistance or survival with multiple exposure high-doses of same or repeated insecticide, thus indicating the need to rethink on integrated vector control policy and interventions and technical assistance in the Kingdom.
Development of a mouse model for spontaneous oral squamous cell carcinoma in Fanconi anemia
Authors: Errazquin Ricardo , Page Angustias , Suñol Anna , Segrelles Carmen , Carrasco Estela , Peral Jorge , Garrido-Aranda Alicia , Del Marro Sonia , Ortiz Jessica , Lorz Corina , Minguillon Jordi , Surralles Jordi , Belendez Cristina , Alvarez Martina , Balmaña Judith , Bravo Ana , Ramirez Angel , Garcia-Escudero Ramon 
Published: June 2022

ABSTRACTFanconi anemia (FA) patients frequently develop oral squamous cell carcinoma (OSCC). This cancer in FA patients is diagnosed within the first 3-4 decades of life, very often preceded by lesions that suffer a malignant transformation. In addition, they respond poorly to current treatments due to toxicity or multiple recurrences.Translational research of new chemopreventive agents and therapeutic strategies has been unsuccessful partly due to scarcity of disease models or failure to fully reproduce the disease. Here we report that Fanca gene knockout mice (Fanca-/-) frequently display pre-malignant lesions in the oral cavity. Moreover, when these animals were crossed with animals having conditional deletion of Trp53 gene in oral mucosa (K14cre;Trp53F2-10/F2-10), they spontaneously developed OSCC with a high penetrance and a median latency of less than ten months. Tumors were well differentiated and expressed markers of squamous differentiation, such as keratins K5 and K10. In conclusion, Fanca and Trp53 genes cooperate to suppress oral cancer in mice, and Fanca-/-;K14cre;Trp53F2-10/F2-10 mice constitute the first animal model of spontaneous OSCC in FA.