bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficient creation and characterization of multi-kilobase knockins by CRISPR/Cas9 and multiple rAAVs
Authors: Sentmanat Monica F. , Wang Zi Teng , Kouranova Evguenia , Peters Samuel , Chan Wan Ching , Lin Jed , Miao Yong , Ritchey Julie , O’Neal Julie , Dipersio John , White J. Michael , Wallace Mia , Cui Xiaoxia
Published: November 2024

We report the successful creation of multi-kilobase knockin mice and cell lines using three rAAV donors and CRISPR/Cas9 via consecutive homology-directed repair and reliable generation of over 120 KI mice with rAAV donors. For comprehensive analysis of the post-edit genome, we combined target capture and long-read sequencing for a multiplexable and high-throughput, all-in-one method to detect on-target insertion and as importantly, various undesired editing outcomes in the genome. Together, the two novel methods greatly improve the efficiency and accuracy of challenging large KI mouse and cell models.
Charge screening and hydrophobicity drive progressive assembly and liquid-liquid phase separation of reflectin protein
Authors: Gordon Reid , Levenson Robert , Malady Brandon , Al Sabeh Yahya , Nguyen Alan , Morse Daniel E.
Published: November 2024

The intrinsically disordered reflectin proteins drive tunable reflectivity for dynamic camouflage and communication in the recently evolvedLoliginidaefamily of squid. Previous work revealed that reflectin A1 forms discrete assemblies whose size is precisely predicted by protein net charge density (NCD) and charge screening by the local anion concentration. Using dynamic light scattering (DLS), Forster resonant energy transfer (FRET) and confocal microscopy, we show that these assemblies, of which 95-99% of bulk protein in solution is partitioned into, are dynamic intermediates to liquid protein-dense condensates formed by liquid-liquid phase separation (LLPS). Increasing salt concentration drives this progression by anionic screening of the cationic protein’s Coulombic repulsion, and by increasing the hydrophobic effect which tips the balance between short-range attraction and long-range repulsion (SALR) to drive protein assembly and ultimately LLPS. Measuring fluorescence recovery after photobleaching (FRAP) and droplet fusion dynamics, we demonstrate that reflectin diffusivity in condensates is tuned by salt concentration and protein NCD. These results illuminate the physical processes governing reflectin A1 assembly and LLPS, and demonstrate the potential for reflectin A1 condensate-based tunable biomaterials. They also compliment previous observations of liquid phase separation in the Bragg lamellae of activated iridocytes and suggest that LLPS behavior may serve a critical role in governing the tunable and reversible dehydration of the membrane-bounded Bragg lamellae and vesicles containing reflectin in biophotonically active cells.
Effects of chemotherapy on skeletal muscle mitochondrial oxidative capacity using Near-Infrared Spectroscopy (NIRS): Protocol paper for an observational mixed model repeated measures design in patients with breast and gynecological cancer
Authors: Hutchison Randolph , Smith Shannon , Caudell Chloe , Biddle Sara , Gluck W. Larry , Trilk Jennifer
Published: November 2024

Chemotherapy-associated cachexia results in significant metabolic disturbances and loss of skeletal muscle. These physiologic effects increase fatigue, reduce physical functioning, and decrease quality of life in patients undergoing treatment for cancer. Mitochondrial dysfunction, a hallmark of metabolic disturbances in the skeletal muscle, has previously been studied in health participants using invasive muscle biopsy and/or time consuming, high-cost magnetic resonance spectroscopy. However, less is understood regarding mitochondrial dysfunction in patients with cancer. Near infrared spectroscopy (NIRS) is a non-invasive and cost-effective approach to assessing mitochondrial function of skeletal muscle by measuring oxygenated and deoxygenated hemoglobin and calculating the resulting tissue saturation index. NIRS has not yet been utilized to evaluate skeletal muscle change in cancer patients throughout chemotherapy. Therefore, we plan to conduct a single center clinical trial, using an observational mixed model repeated measures design to evaluate the change in mitochondrial oxidative capacity from baseline and throughout progression of an oncologist-prescribed chemotherapy regimen. Evaluation of mitochondrial function will be performed by taking real-time, NIRS in-situ measurements within the working muscle during stationary cycling exercise and subsequent recovery periods (e.g. “on” kinetics and “off” kinetics). We also plan to observe if there is a difference in mitochondrial oxidative capacity between different chemotherapy regimens across different patients. This pilot study will provide information on the feasibility of capturing on/off kinetics mitochondrial function data longitudinally using NIRS in patients newly diagnosed with breast or gynecological cancer, provide preliminary data for future extramural funding, as well as inform the scientific community of results through dissemination via conferences and peer-reviewed publications.
Investigation of locomotive syndrome improvement by total hip arthroplasty in patients with hip osteoarthritis: a before-after comparative study focusing on 25-question geriatric locomotive function scale
Authors: Miyazaki Shigeaki , Tsuruta Kurumi , Yoshinaga Saori , Fujii Yoshinori , Hombu Amy , Funamoto Taro , Sakamoto Takero , Tajima Takuya , Nakamura Yoshihiro , Arakawa Hideki , Nakatake Jun , Chosa Etsuo
Published: November 2024

Background

The 25-Question Geriatric Locomotive Function Scale (GLFS-25) is one of the tests used to assess the risk of locomotive syndrome (LS). It is a comprehensive tool to measure LS improvement after total hip arthroplasty (THA) and provides beneficial information for rehabilitation after THA. This study aims to investigate the effectiveness of LS improvement three months after THA in patients who underwent THA for hip osteoarthritis (OA) by using the total clinical decision limits (CDL) 3-stage scale to identify specific trends in LS improvement based on the GLFS-25.

Methods

The participants of this study were 273 patients who underwent primary THA for hip OA. LS was evaluated using the stand-up test, two-step test, and GLFS-25 before receiving THA and three months after THA.

Results

The total CDL was improved by THA in 132 patients (improvement rate: 48.4%). There were 15 questions out of 25 in the GLFS-25 showed improvements in more than 60% of the patients. The question Q13, “To what extent has it been difficult to walk briskly?” revealed the highest improvement rate, followed by Q12, “To what extent has it been difficult to go up and down stairs?”, and Q3, “Did you have any pain (including numbness) in your lower limbs?”.

Conclusions

At three months after THA, approximately half of the patients showed improvement in LS. Furthermore, improvement in locomotion movements was identified as the most significant area of progress among motor functions.
Bioinformatics and machine learning-based identification of cell cycle-related genes and molecular subtypes in endometrial cancer
Authors: Pan Jingying , Huang Shuhan , Fu Bidong , Zhang Ruiyu , Zhou Minqin , Yu Zichuan , Zeng Hong , Geng Xitong , Zhu Yanting , Zheng Hao , Wan Hao , Qu Xiaoyu , Tang Shengwei , Zhong Yanying
Published: November 2024

Endometrial cancer is a common malignant tumor in women, with rising incidence rates and an unoptimistic prognosis. DSN1 is a kinetochore protein-coding gene that affects centromere assembly and progression in cell cycles, which is associated with adverse predictions for many cancers. However, the role of DSN1 in UCEC has not yet been reported. We identified the UCEC-related gene module and obtained the differential genes. Then we constructed a diagnostic model and identified the subtype of the molecule and its association with predictions. Subsequently, we identified DSN1 as the core gene and predicted its predictive value. Furthermore, using bioinformatics methods, we found DSN1 was associated with certain clinical characteristics and experimentally validated the expression in cancer tissues of DSN1. Pathway enrichment analysis identified DSN1 as a cell cycle-associated protein, which was validated by WB. The protein interaction network also revealed DSN1 was significantly associated with NDC80. Then we explored the correlation of DSN1 and immune cells and immune cell infiltration and found that DSN1 may affect Th2 enrichment by affecting CCL7 and CCL8. Drug susceptibility analysis showed DSN1 was sensitive to cisplatin and resistant to sunitinib. In conclusion, DSN1 was a novel biomarker that contributes to prognosis and treatment.
A comparison of core temperature at different sites during cytoreductive surgery with hyperthermic intraperitoneal chemotherapy: A prospective observational study
Authors: Kim Jung–Won , Kim Jin Ho , Oh Soojeong , Ahn So Woon
Published: November 2024

Background

During cytoreductive surgery with hyperthermic intraperitoneal chemotherapy, body temperature rapidly changes due to the hyperthermic agent. Depending on the method used, obtained values may vary, particularly during localized heating of the abdominal cavity. The primary aim of our study was to compare the effectiveness of core temperature monitoring techniques, nasopharyngeal temperature, zero-heat flux cutaneous thermometer device, and esophageal temperature, during hyperthermic intraperitoneal chemotherapy with cytoreductive surgery.

Methods

Body temperature was measured using a zero-heat flux cutaneous thermometer device on the forehead and esophageal and nasopharyngeal probes throughout the surgery. Temperature differences were then calculated for each pair of measurements. We conducted an agreement analysis between the nasopharyngeal temperature and reference core temperature measurements using the 95% Bland–Altman limits of agreement for repeated measurement data. The proportion of all differences that were within 0.5 °C and repeated measures Lin’s concordance correlation coefficient were estimated.

Results

The mean overall difference between nasopharyngeal and forehead temperature was -0.04 ± 0.33 °C (95% limits of agreement: -0.69–0.62), and esophageal temperature was 0.02 ± 0.35°C (95% limits of agreement: -0.66–0.71). The proportion of differences within 0.5 °C of TSpotOn was 0.03 (95% CI 0.01–0.04) and that of esophageal temperature was -0.06 (95% CI -0.08 to -0.05). The Lin’s concordance correlation coefficient of both were 0.94 (95% CI 0.93–0.94). After the hyperthermic intraperitoneal chemotherapy period, the temperatures rapidly decreased, followed by a noticeable rebound increase, particularly nasopharyngeal and forehead temperatures. The maximum difference between esophageal temperature and other temperatures was 1.5 °C.

Conclusions

Our results reveal a strong correlation between nasopharyngeal, zero-heat flux cutaneous, and esophageal temperatures during surgery. However, consistent temperature differences with the esophageal thermometer were not observed. Post-hyperthermic intraperitoneal chemotherapy, rebound heating occurred at all sites, notably in the nasopharyngeal and zero-heat flux cutaneous areas.
Help-Seeking Behavior and Its Associated Factors Among 18– 24 years Victims of Intimate Partner Violence in Kenya: Insights from a Respondent-Driven Survey
Authors: Felix Humwa , Daniel Onguru , Peter Memiah , Amolo Asito S.
Published: November 2024

Background

Intimate partner violence (IPV) is a pervasive issue with significant mental health implications. Understanding the factors that influence help-seeking behavior among IPV survivors is crucial for developing effective interventions.

Objective

This study aims to identify the demographic, educational, behavioral, mental health, and social network characteristics associated with help-seeking behavior among IPV survivors aged between 18-24 years.

Methods

This was a cross-sectional respondent-driven survey conducted within three cities of Kisumu, Mombasa, and Nairobi in Kenya among individuals aged 18-24 years. Data was analyzed using univariate and multivariable logistic regression to identify factors associated with help-seeking behavior.

Results

Data was analyzed from 351 (58% females) participants who were exposed to IPV. Residency, educational attainment, mental health status, social networks, and health status significantly impact the likelihood of seeking help (p < .05).

Conclusion

The study highlights the complex interplay of various factors influencing help-seeking behavior among IPV survivors. These findings underscore the need for targeted interventions that address specific barriers and facilitators of help-seeking behavior, particularly in urban settings.
Adult patients with autoinflammation of unknown origin partially phenocopy the immune presentation of Still’s disease
Authors: Veiga Rafael , Vuyst Leana De , Neumann Julika , Bücken Leoni , Prezzemolo Teresa , Willemsen Mathijs , Vanderschueren Steven , Matthys Patrick ,   Immunome Project Consortium for Autoinflammatory Disorders (ImmunAID), Wouters Carine , Humblet-Baron Stephanie , Liston Adrian
Published: November 2024

Autoinflammation of unknown origin remains amongst the most enigmatic of systemic autoinflammatory disorders (SAIDs), immunological disorders characterized by inappropriate activation of the innate immune response. Recent clinical research has identified multiple distinct disorders, although overlap in clinical characteristics and genetic drivers impede rapid and precise diagnosis, and the immunological underpinning of disease is poorly understood. Here we aimed to understand the immunological process behind patients with autoinflammation of unknown origin. In a multi-center European trial, we collected samples from 36 treatment-naïve patients with active disease, and used deep immunophenotyping to compare to 58 healthy controls and an additional demographically-similar 93 SAID patients. Key immunological changes were upregulation of CD38 and HLA across T cell subsets of autoinflammation of unknown origin patients, a trait which partially phenocopied the Still’s disease in adult patients. Together this study identifies potential biomarkers and disease-mediators in autoinflammation of unknown origin.
Sex differences in the rates and association of cerebral blood flow and glucose metabolism in normative ageing
Authors: Deery Hamish A. , Moran Chris , Liang Emma X. , Gurvich Caroline , Egan Gary F. , Jamadar Sharna D.
Published: November 2024

Although dysfunction in cerebral blood flow and glucose metabolism is linked to neurodegeneration, it is currently unclear if there are sex and age differences in their rates and association. Seventeen younger males (mean age 27.5 years), 20 younger females (28.4), 22 older males (76.6) and 20 older females (75.3) completed a MR/PET scan and cognitive battery. Females had higher CBF and CMRGLCthan males, regardless of age. CBF was lower in ageing. As CMRGLCincreased, the positive effect of higher CBF on working memory, cognitive flexibility, and processing speed also increased. Individuals with the highest CBF had the highest CMRGLC. However, this association was moderated by sex and age, with significant negative associations across older females, possibly reflecting a compensatory response to a loss of blood flow and metabolism. We conclude that there are sex differences in the rates and association of cerebral blood flow and glucose metabolism in normative ageing and that high rates of blood flow and metabolism combine to support cognition.
Alterations in the plasma metabolome associated with maternal smoking during the first trimester
Authors: Masvosva Wadzanai , Voutilainen Taija , Lehtonen Marko , Haikonen Retu , Auriola Seppo , Keski-Nisula Leea , Rysä Jaana , Kärkkäinen Olli
Published: November 2024

Tobacco smoking during pregnancy has been associated with an increased risk of adverse outcomes like low birth weight. This study determined changes in the circulating metabolome linked to maternal smoking in the first trimester and correlated these changes to the growth of the fetus. The circulating metabolome was examined from first trimester plasma samples by non-targeted liquid chromatography mass spectrometry based metabolite profiling of 227 pregnant women (99 smokers and 117 non-smokers) from the Kuopio Birth Cohort Study. Tobacco smoking was self-reported through a questionnaire and verified with cotinine measurements from plasma samples. In summary, 64 significant differences were observed between the groups after correction for multiple testing e.g. in metabolites indicating endocrine disruption (e.g., dehydroepiandrosterone sulfate [DHEA-S], VIP=2.70, d=0.68, p<0.0001), metabolites associated with oxidative stress (e.g., bilirubin, VIP=2.00, d=0.50, p<0.0001) and lipid metabolism (e.g., LysoPC 16:1, VIP=2.07, d=0.51, p<0.0001). Some of these metabolites, e.g., DHEA-S and bilirubin, correlated with low birth weight, and some, e.g. LysoPC 16:1, correlated with small head circumference at birth. In conclusion, maternal smoking during the first trimester of pregnancy was associated with an altered metabolite profile linked to endocrine disruption and increased oxidative stress.

Plain language summary

Tobacco smoking during pregnancy has been associated with an increased risk of adverse outcomes like low birth weight. In this study, we measured changes in the circulating metabolome linked to maternal smoking in the first trimester and correlated these changes to the growth of the fetus. Maternal smoking during the first trimester of pregnancy was associated with an altered metabolite profile linked to endocrine disruption and increased oxidative stress. Furthermore, some these changes were associated with reduced growth of the fetus.
Self-reported health, neuropsychological tests and biomarkers in fully recovered COVID-19 patients vs patients with post-COVID cognitive symptoms: a pilot study
Authors: Lawrence Michael R. , Arnetz Judith E. , Counts Scott E. , Ahmed Aiesha , Arnetz Bengt B.
Published: November 2024

Objective

Substantial numbers of individuals who contract COVID-19 experience long-lasting cognitive symptoms such as brain fog. Yet research to date has not compared these patients with healthy controls with a history of laboratory-confirmed COVID-19 infection, making it difficult to understand why certain COVID patients develop post-COVID cognitive symptoms while others do not. The objective of this pilot study was to compare two groups of laboratory-confirmed post-COVID patients, with and without cognitive symptoms, on measures of cognitive and psychological functioning, self-reported perceptions of functional status and quality of life, and biomarkers of stress, inflammation, and neuroplasticity.

Methods

Using a case-control design, 17 participants were recruited from a healthcare system in western Michigan, USA in 2022 through 2024. All participants were aged 25-65 and had a positive polymerase chain reaction (PCR) test confirming previous COVID-19 infection. Ten participants reported cognitive symptoms (long COVID group) while seven were fully recovered with no residual symptoms (controls). All participants underwent an interview on their self-rated health and quality of life, a battery of neurocognitive tests, and blood draw for biomarker analysis.

Results

No group differences were detected for neuropsychological test measures except for letter fluency where the long COVID group scored significantly lower (p<.05). The long COVID group had significantly lower ratings than controls on quality of life, physical health, emotional functioning, and psychological well-being. Serum levels of nerve growth factor (NGF), a biomarker of brain plasticity, were significantly lower in the long COVID group, which was significantly more likely than controls to have serum levels of inflammatory marker (interleukin (IL)-10) values greater than or equal to the median (p=0.015).

Conclusion

Biomarker analyses suggest possible prolonged inflammatory processes in long COVID patients compared to fully recovered patients. Results of decreased neuroplastic functioning give credence to patients’ reports of post-COVID changes in brain function.
Seasonal variation in SARS-CoV-2 transmission in the Netherlands, 2020-2022: statistical evidence for a negative association with temperature
Authors: Klinkenberg Don , Backer Jantien , Reusken Chantal , Wallinga Jacco
Published: November 2024

In temperate regions, respiratory viruses such as SARS-CoV-2 are better transmitted in Winter than in Summer. Understanding how temperature and humidity affect SARS-CoV-2 transmissibility can enhance projections of COVID-19 incidence and improve estimation of the effectiveness of control measures. During the pandemic, transmissibility was tracked by the reproduction numberRt. This study aims to determine whether information about the daily temperature and absolute humidity improves predictions ofRtin the Netherlands from 2020 to 2022, and to quantify the relationship betweenRt, daily temperature and absolute humidity. We conducted a regression analysis, accounting for immunity from vaccination and previous infection, higher transmissibility of new variants, and changes in contact behaviour due to control measures. Results show a linear association between logRtand daily temperature, indicating a ratio ofRtin Winter versus Summer of 1.5 (95% CI, 1.2-1.8). Including absolute humidity in the model did not improve predictions. The possibility that this association arises from unrelated seasonal patterns was dismissed, as weather data from earlier years provided poorer fits, and incorporating mobility data did not affect results. This suggests a causal relationship between temperature and SARS-CoV-2 transmissibility, enhancing confidence in using this relationship for short-term predictions and other epidemiological analyses.
The piRNA pathway mediates transcriptional silencing of LTR retrotransposons in the soma and germline ofAedesmosquitoes
Authors: Taşköprü Ezgi , Bacchi Marianna , Overheul Gijs J. , Linthout Charlotte , Koenraadt Constantianus J. M. , Qu Jieqiong , Miesen Pascal , Halbach Rebecca , van Rij Ronald P
Published: November 2024

The PIWI-interacting RNA (piRNA) pathway is crucial for maintaining genomic integrity by suppressing transposable elements in animal germlines. Despite its well-established function in the animal germline, piRNAs and PIWI proteins are expressed in somatic tissues across arthropod species, raising questions about piRNA functions outside the gonads. For example,Aedes albopictusmosquitoes express four PIWI genes,Piwi4,Piwi5,Piwi6andAgo3,in both germline and somatic tissues. We generatedPiwi6knockoutAe. albopictuscell lines and observed a substantial upregulation of Long Terminal Repeat (LTR)-retrotransposons, among which a full-length endogenous retrovirus that we namedAalERV1. We found that Piwi6 silencesAalERV1at the transcriptional level by guiding the deposition of the repressive H3K9me3 histone mark. Importantly, the control ofAalERV1is recapitulatedin vivoasPiwi6knockdown increasedAalERV1expression in both somatic and germline tissues ofAe. albopictusmosquitoes. These results establishAedesmosquitoes as a model to study nuclear PIWI functions and suggest that somatic piRNA-mediated transposon silencing is evolutionarily conserved across arthropod species.
An investigation of carbapenemase-encoding genes inBurkholderia cepaciaandAeromonas sobrianosocomial infections among Iraqi patients
Authors: Al-Ouqaili Mushtak T. S. , Hussein Rawaa A. , Kanaan Bushra A. , Al-Neda Ahmed T.S.
Published: November 2024

Burkholderia cepaciaandAeromonas sobriaare difficult to eradicate due to their innate resistance to a variety of medications, and cause various diseases. The aim of this study was to investigate the occurrence of carbapenemase genes and patterns of antibiotic resistance in isolates ofB. cepaciaandA. sobria.A cross-sectional study was conducted in the Ramadi Teaching Hospitals in the Al-Anbar Governorate in 2024. Various study samples, were used to collect the studied bacteria. The antibiotic resistance was detected by the VITEK®2 System. The presence of carbapenemase genes was confirmed via PCR technique. In this investigation, seventy-five (75) isolates ofA. sobriaandB. cepaciawere assessed. Of these,A. sobriamade up 16.6% (n = 20) whileB. cepaciaaccounted for 45.8% (n = 55). The study isolates showed highest antimicrobial resistance to piperacillin, cefepime, ceftriaxone (100%), ceftazidime (97.3%), and lowest antimicrobial resistance to imipenem (36%). The result showed 55/57recAgene positive for differentiatedB. cepacia complexfrom other Burkholderia spp. The overall prevalence of carbapenemase genes was 92.8%% (52/56) withblaKPCaccounting for 80.8% (42/52) andblaGESfor 19.2% (10/52) of the total. The 42B. cepaciaisolates that tested positive for carbapenem resistance were constituted of 38blaKPC(n = 38) and twoblaGES(n = 2); in contrast, fourblaKPC(n = 4) and eightblaGES(n = 8) were present in theA. sobriaisolates that tested positive for carbapenems resistance. None of isolates studied tested positive for theblaIMPgene. The recent study concluded thatrecAgene identification was more sensitive and specific technique for detectionB. cepacia complexisolates. There was a notable predominance ofblaKPCandblaGEScarbapenemase producers among the isolates under investigation. TheblaIMPgene was not found in any of the research isolates.
More or fewer latent variables in the high-dimensional data space? That is the question
Authors: Vaccari Francesco Edoardo , Diomedi Stefano , Bettazzi Edoardo , Filippini Matteo , De Vitis Marina , Hadjidimitrakis Kostas , Fattori Patrizia
Published: November 2024

Dimensionality reduction is widely used in modern Neuro-science to process massive neural recordings data. Despite the development of complex non-linear techniques, linear algorithms, in particular Principal Component Analysis (PCA), are still the gold standard. However, there is no consensus on how to estimate the optimal number of latent variables to retain. In this study, we addressed this issue by testing different criteria on simulated data. Parallel analysis and cross validation proved to be the best methods, being largely unaffected by the number of units and the amount of noise. Parallel analysis was quite conservative and tended to underestimate the number of dimensions especially in low-noise regimes, whereas in these conditions cross validation provided slightly better estimates. Both criteria consistently estimate the ground truth when 100+ units were available. As an exemplary application to real data, we estimated the dimensionality of the spiking activity in two macaque parietal areas during different phases of a delayed reaching task. We show that different criteria can lead to different trends in the estimated dimensionality. These apparently contrasting results are reconciled when the implicit definition of dimensionality underlying the different criteria is considered. Our findings suggest that the term ‘dimensionality’ needs to be defined carefully and, more importantly, that the most robust criteria for choosing the number of dimensions should be adopted in future works. To help other researchers with the implementation of such an approach on their data, we provide a simple software package, and we present the results of our simulations through a simple Web based app to guide the choice of latent variables in a variety of new studies.

Key points

Parallel analysis and cross-validation are the most effective criteria for principal components retention, with parallel analysis being slightly more conservative in low-noise conditions, but being more robust with larger noise.

The size of data matrix as well as the decay rate of the explained variance decreasing curve strongly limit the number of latent components that should be considered.

When analyzing real spiking data, the estimated dimensionality depends dramatically on the criterion used, leading to apparently different results. However, these differences stem, in large part, from the implicit definitions of ‘dimensionality’ underlying each criterion.

This study emphasizes the need for careful definition of dimensionality in population spiking activity and suggests the use of parallel analysis and cross-validation methods for future research.
Combining Glycosidases and Nanopore Technology for Glycan Sequencing
Authors: Yao Guangda , Xia Bingqing , Wei Fangyu , Wang Jiahong , Yang Yuting , Ma Shengzhou , Ke Wenjun , Li Tiehai , cheng Xi , Wen Liuqing , Long Yi-tao , Gao Zhaobing
Published: November 2024

The efficient characterization of glycan structures remains a critical challenge. Direct glycan sequencing technologies with improved sensitivity and throughput are still needed. Here, we propose a glycan sequencing strategy based on glycosidase -assisted nanopore sensing. We used engineered nanopore α-hemolysin (M113R/T115A), which provided high-resolution discrimination of monosaccharide volume differences and sensitivity to variations in glycan chain length. By utilizing the specificity of glycosidases, we sequentially hydrolyzed the terminal residues of the glycan chains and detected the characteristic shifts in electrical signals generated by the translocation of hydrolysis products. The accuracy of recognition of hydrolysis fragments achieved over 90 % using machine learning. This allowed us to efficiently and conveniently determine the sequence of consecutive monosaccharide units in the glycan chains. Based on this principle, we conducted a proof-of-concept demonstration on actual samples and verified the accuracy via HPLC-MS. We achieved the sequencing of consecutive units in glycan chains, confirming the theoretical feasibility of glycosidase -assisted nanopore glycan sequencing. With future optimization, the development of arrayed nanopore glycan sequencing technology based on hydrolysis strategy will provide an innovative approach for rapid decoding of glycans, which could promote the progress of glycomics research and glycobiology.
The effect of urbanization and local environmental heterogeneity on phenotypic variability in a tropical frog
Authors: Provete Diogo B. , Severgnini Marcos Rafael
Published: November 2024

Urbanisation reduces species richness and change community composition. However, little is known on how the phenotype of organisms with low dispersal ability respond to environmental changes associated with urbanisation in fast urbanizing centres, such as those in the Global South. Here, we tested how urbanisation rate, local environmental heterogeneity, land surface temperature, and spatial gradients affect phenotypic traits associated with dispersal, resource acquisition, and performance, namely: body size, head shape, and leg length of the Dwarf Treefrog (Dendropsophus nanus) using a space-for-time substitution approach. We took linear measurements from 768 individuals in 21 ponds along an urban gradient in central Brazil. We also measured local environmental variables and summarized them using Hill-Smith Principal Component Analysis. The spatial arrangement of ponds at multiple scales was described using Moran Eigenvector Maps. Those variables were then entered into a Structural Equation Model to test their direct and indirect effects on the mean and coefficient of variation (CV) of phenotypic traits. Additionally, we calculated the Scaled Mass Index as a proxy for fitness and estimated the adaptive landscape for body size, size-free leg length, and head shape. We also tested for spatial autocorrelation in traits. Body size decreased from the periphery to the urban centre, whereas CV of body size and head shape had the opposite pattern. Body size increased, whereas CV of body size and head shape decreased in man-made ponds. The CV of leg length decreased with increasing land surface temperature. The remaining traits were not affected by any predictor variable. None of the traits were spatially autocorrelated. Both body size and head shape were under weak directional selection, but in opposite directions. Our results suggest that the lack of a clear spatial variation in phenotypic traits can be due to a weak selection, due to a recent, although intense, urbanisation process. In conclusion, eco-evolutionary dynamics in tropical cities seem to have a different pace compared to temperate ones. Our results can contribute to building urban ecological theory that explicitly includes city age, their development, growth rate, and history.
A meta-analysis of age-dependent changes in extracellular vesicle proteins inC. elegans
Authors: Bhunia Prasun Kumar , Kasturi Prasad
Published: November 2024

Extracellular vesicles (EVs) contribute to the maintenance of organism-wide proteostasis by mediating intercellular communication. Loss of proteostasis and altered intercellular communication are associated with aging and age-related diseases, suggesting key roles for EVs. However, it is unclear how the proteome of the EVs changes with age. To identify EV-associated proteins and their fate with age, we curated publicly available proteome data from C.elegans model organism. Our analysis reveals that EVs carry proteins that involve protein quality control. We found that abundance of the EV proteins changes significantly with age. Many of these EV proteins also aggregate with age and overlap with Aβ driven protein aggregates. Further, we find that a subset of proteins that alter their abundance in response to heat stress and pathogen infections are also associated with the EVs. This meta-analysis highlights EVs proteome composition, their abundance changes, and aggregation during aging and stress conditions. Overall, this study provides new insights into the dynamics of EV proteins during and aging and may possibly help in identifying potential biomarkers for age-related diseases.
A cost analysis comparing Seasonal Malaria Chemoprevention with and without Vitamin A Supplementation among under-5 children in Nigeria
Authors: Oresanya Olusola , Arije Olujide , Fadipe Jesujuwonlo , Rotimi Kunle , Phillips Abimbola , Maxwell Kolawole , Shekarau Emmanuel , Onwu Nneka , Bazant Eva S.
Published: December 2024

Background

Child mortality in Nigeria, significantly affected by malaria and malnutrition, remains a public health concern in the country. Seasonal Malaria Chemoprevention (SMC) and Vitamin A supplementation (VAS) are effective interventions that can be delivered through integrated health campaigns to reduce this mortality. This study assesses the cost implications of integrating these two interventions among under-5 children in Northeast Nigeria.

Methods

A cost analysis compared standalone SMC (Cycle 1 in July 2021) with SMC-VAS integrated campaign (Cycle 4 in October 2023) in two Local Government Areas (LGAs) in Bauchi State. The number of children reached by the SMC-only campaign was 168,820 and for the SMC+Vit A campaign, the number was 170,681. Data collection utilized a mixed-methods approach, drawing from primary and secondary sources, including programmatic, financial, and coverage records. Costs were categorized into distribution, Sulphadoxine-Pyrimethamine plus Amodaiquine (SPAQ) for SMC, Vitamin A, training, supplies, meetings, labor, supervision, and social mobilization costs. Sensitivity analyses evaluated the effect of a 10% fluctuation in the costs of distribution, labor, SPAQ, and supplies on the cost per child.

Results

The total cost for the SMC standalone campaign was US$158,934, and the SMC-VAS integration was US$186,426. Distribution and drug costs were the largest contributors in the integrated and SMC-only campaign. The SMC-only cost per child was $0.94 and $1.18 when eligible children received both SMC and VAS. The integration of VAS into the SMC campaign cycle incurred an additional US$27,492 over Cycle 1 cost (US$186,426 - US$158,934). Fluctuations in distribution costs were the most influential component of the cost per child.

Conclusion

Integrating VAS with SMC campaigns increases the cost by US$0.24 per child, a modest increment considering the potential health benefits. The results support the feasibility of this integration, in terms of cost, to combat child mortality from malaria and malnutrition in Nigeria. Further research is recommended to explore the cost-effectiveness of this integrated distribution model.
Diabetic Retinopathy: Knowledge, Staging and Barriers to Early Presentation in a Tertiary Eye Care Centre in Ghana
Authors: Appiagyei Emmanuel , Essuman Yaw Akye , Ahmed Akwasi Agyeman
Published: December 2024

Background

Diabetic retinopathy is the most common microvascular complication of diabetes mellitus and a leading cause of new-onset blindness in populations of working age. Late presentation of patients to eye care facilities has been associated with the development of vision-threatening complications. The study sought to determine the clinical profile, knowledge and factors influencing late presentation of diabetic retinopathy among diabetics at the Eye Centre of the Komfo Anokye Teaching Hospital in Ghana.

Methods

This descriptive cross-sectional study was conducted between the periods of February 2022 to April 2022. All diabetic patients referred to the retina clinic were examined for diabetic retinopathy. Both eyes of participants were examined and the eye with the most severe form of diabetic retinopathy was used for the staging. A structured questionnaire was employed to collect patients’ socio-economic factors and knowledge on diabetic retinopathy. Data was analysed using the SPSS ver. 23 software. Statistical significance was set at p<0.05.

Results

A total of 78 diabetic patients were included in the study. Thirty-six (36, 46.2%) were males and 42 (53.8%) females. Mean age of the study population was 49.9±11.4 years. The mean (+SD) knowledge score of study participants on diabetic retinopathy was 5.3 (±3.2) with a maximum possible score of 12. Majority of the participants (65%) were aware that uncontrolled diabetes mellitus affects the eyes; 7.7% had mild NPDR, 16.7%) had moderate NPDR, 10.3%; severe NPDR, 19.2%; very severe NPDR, 9.0%; high risk PDR and 37.2% showed signs of advanced PDR. Fifty-four participants (69.2%) highlighted a lack of knowledge about the condition as the main reason for late presentation.

Conclusion

Most diabetic patients who presented to the eye clinic had advanced PDR stage of the condition. The major factor to late presentation of diabetic retinopathy cases was lack of knowledge about the condition.
A mixed methods evaluation of 99DOTS digital adherence technology uptake among adolescents treated for pulmonary tuberculosis in Uganda.
Authors: Wambi Peter , West Nora , Nabugoomu Josephine , Kityamuwesi Alex , Crowder Rebecca , Kunihira Lyn , Wobudeya Eric , Adithya Cattamanchi , Jaganath Devan , Katamba Achilles
Published: December 2024

Introduction: Adolescents and young adults are at risk of poor adherence to tuberculosis (TB) treatment and subsequently worse TB treatment outcomes. Digital adherence technologies, including the mobile phone-based 99DOTS platform, can support TB treatment, but there is limited data on their use among adolescents. Objective: To evaluate factors associated with the uptake of 99DOTS among adolescents with TB. Methods: We conducted an explanatory sequential mixed methods study that utilized quantitative data from adolescents collected during the scale-up of 99DOTS at 30 health facilities in Uganda, and qualitative in-depth and key informant interviews with a subset of adolescents with pulmonary TB offered 99DOTS and healthcare providers at participating facilities. Findings were further mapped onto the Capability, Opportunity, Motivation, and Behavior (COM-B) model. Results: Overall, 299/410 (73%) eligible adolescents were enrolled in 99DOTS. Older adolescents 15 to 19 years old were more likely to enroll in 99DOTS than younger adolescents 10 to 14 years [aPR= 0.56, 95% CI: (0.42-0.73)]. Conversely, adolescents treated at Health Center IV and General Hospitals were less likely to be enrolled compared to Health Center III (aPR= 0.8, 95% CI, 0.67-0.94, and aPR=0.71, 95% CI 0.58-0.85, respectively). Technological savviness among older adolescents, access to training, caregiver or treatment supporter involvement, and desire for wellness facilitated the uptake of 99DOTS. In contrast, variable mobile phone access, concerns about TB status disclosure, and health worker workload in hospitals were barriers to the uptake of 99DOTS. Conclusion: 99DOTS uptake was high among adolescents with TB. Increased access to mobile phones, health worker training on adolescent communication, and more involvement of caregivers could facilitate greater use of 99DOTS and similar technologies.
A low-abundance class of Dicer-dependent siRNAs produced from a variety of features inC. elegans
Authors: Knittel Thiago L. , Montgomery Brooke E. , Tate Alex J. , Deihl Ennis W. , Nawrocki Anastasia S. , Hoerndli Frederic J. , Montgomery Taiowa A.
Published: December 2024

Canonical small interfering RNAs (siRNAs) are processed from double-stranded RNA (dsRNA) by Dicer and associate with Argonautes to direct RNA silencing. InCaenorhabditis elegans, 22G-RNAs and 26G-RNAs are often referred to as siRNAs but display distinct characteristics. For example, 22G-RNAs do not originate from dsRNA and do not depend on Dicer, whereas 26G-RNAs require Dicer but derive from an atypical RNA duplex and are produced exclusively antisense to their messenger RNA (mRNA) templates. To identify canonical siRNAs inC. elegans, we first characterized the siRNAs produced via the exogenous RNA interference (RNAi) pathway. During RNAi, dsRNA is processed into ∼23 nt duplexes with ∼2 nt, 3′-overhangs, ultimately yielding siRNAs devoid of 5′G-containing sequences that bind with high affinity to the Argonaute RDE-1, but also to the microRNA (miRNA) pathway Argonaute, ALG-1. Using these characteristics, we searched for their endogenous counterparts and identified thousands of endogenous loci representing dozens of unique elements that give rise to mostly low to moderate levels of siRNAs, called 23H-RNAs. These loci include repetitive elements, putative coding genes, pseudogenes, noncoding RNAs, and unannotated features, many of which adopt hairpin (hp) structures reminiscent of the hpRNA/RNAi pathway in flies and mice. RDE-1 competes with other Argonautes for binding to 23H-RNAs. When RDE-1 is depleted, these siRNAs are enriched in ALG-1 and ALG-2 complexes. Our results expand the known repertoire ofC. eleganssmall RNAs and their Argonaute interactors, and demonstrate that key features of the endogenous siRNA pathway are relatively unchanged in animals.
Quasi-Nambu-Goldstone modes in many-body scar models
Authors: Ren Jie , Wang Yu-Peng , Fang Chen
Published: December 2024

From the quasisymmetry-group perspective [J. Ren , ], we show the universal existence of collective, coherent modes of excitations in many-body scar models in the degenerate limit, where the energy spacing in the scar tower vanishes. The number of these modes, as well as the quantum numbers carried by them, are given, not by the symmetry of the Hamiltonian, but by the quasisymmetry of the scar tower: hence the name quasi-Nambu-Goldstone modes. Based on this, we draw a concrete analogy between the paradigm of spontaneous symmetry breaking and the many-body scar physics in the degenerate limit.

Published by the American Physical Society
2024
New method to clarify the contribution of the chiral magnetic effect in small collision systems
p↑+A
involving a transversely polarized proton
Authors: Wu Gui-Zhen , Zhang Zong-Wei , Gao Chen , Xu Yi , Deng Wei-Tian
Published: December 2024

In this Letter, we propose a new experimental method to check the contribution of the chiral magnetic effect (CME). With experimental data of deep inelastic scattering (DIS) involving transversely polarized proton, we have calculated the three-dimensional charge density inside the polarized proton, which is found to have a significant violation to spherical symmetry. Then we have calculated the property of electromagnetic field (EM field) generated by a single transversely polarized proton (p↑). Based on them, the EM fields generated in small collision system p↑+A are studied. We find that the orientation of this EM field has a significant dependence on the polarization direction of the proton, and the correlator (Δγ) has also significant dependence on the angle between the reaction plane and polarization direction. As background contributions are canceled comparing two collision geometry schemes, only the contribution of CME remains.

Published by the American Physical Society
2024
Probing radiative electroweak symmetry breaking with colliders and gravitational waves
Authors: Liu Wei , Xie Ke-Pan
Published: December 2024

Radiative symmetry breaking provides an appealing explanation for electroweak symmetry breaking and addresses the hierarchy problem. We present a comprehensive phenomenological study of this scenario, focusing on its key feature: the logarithmic-shaped potential. This potential gives rise to a relatively light scalar boson that mixes with the Higgs boson and leads to first-order phase transitions (FOPTs) in the early Universe. Our study includes providing exact and analytical solutions for the vacuum structure and scalar interactions, classifying four patterns of cosmic thermal history, and calculating the supercooled FOPT and gravitational waves (GWs). A detailed treatment of the FOPT dynamics reveals that an ultra-supercooled FOPT does not always imply strong GW signals, due to its short duration. By combining future collider and GW experiments, we can probe the conformal symmetry breaking scales up to 105–108  GeV.

Published by the American Physical Society
2024
Structure constants in
N=4
supersymmetric Yang-Mills theory and separation of variables
Authors: Bercini Carlos , Homrich Alexandre , Vieira Pedro
Published: December 2024

We propose a new framework for computing three-point functions in planar N=4 super Yang-Mills theory where these correlators take the form of multiple integrals of separation of variables type. We test this formalism at weak coupling at leading and next-to-leading orders in a noncompact SL(2) sector of the theory and all the way to next-to-next-to-leading orders for a compact SU(2) sector. We find evidence that wrapping effects can also be incorporated.

Published by the American Physical Society
2024
Predictive evaluation of hydrogen diffusion coefficient on Pd(111) surface by path integral simulations using neural network potential
Authors: Kataoka Yuta , Haruyama Jun , Sugino Osamu , Shiga Motoyuki
Published: December 2024

Quantum diffusion of hydrogen (H) on palladium (Pd) (111) was studied using two types of path integral simulations: quantum transition state theory (QTST) and ring polymer molecular dynamics (RPMD). The use of an artificial neural network potential trained by density functional theory calculations has made it feasible to perform path integral simulations considering nuclear quantum effects (NQEs) of a many-body Pd-H system with accuracy. The QTST result has shown a clear non-Arrhenius behavior in the diffusion coefficient (D) of H below the temperature of 150–200 K due to the NQEs. Comparing the D on Pd surface and bulk Pd, it was found that surface and bulk diffusion are competitive at high temperature. Consistent with this, it was observed in the RPMD simulation at 800 K that a part of the quantum trajectories of H on the surface bifurcates to the Pd subsurface. As the temperature decreases, the surface diffusion becomes much faster than the bulk diffusion. Furthermore, distinct quantum behaviors of H were identified at the surface and within the bulk. The D values obtained from this study using a “flexible” Pd surface model differed considerably from those previously reported using “frozen” Pd surface models, indicating an important contribution from Pd vibrations coupled with H diffusion.

Published by the American Physical Society
2024