bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coronavirus Disease 2019 (COVID-19) Vaccination and Assisted Reproduction Outcomes
Authors: Chamani Isaac J. , Taylor Lauren L. , Dadoun Simon E. , McKenzie Laurie J. , Detti Laura , Ouellette Lara , McCulloh David H. , Licciardi Frederick L. 
Published: July 2023

OBJECTIVE:
To assess the association between coronavirus disease 2019 (COVID-19) vaccination and female assisted reproduction outcomes through a systematic review and meta-analysis.

DATA SOURCES:
We searched Medline (OVID), EMBASE, Web of Science, Cochrane Library, and ClinicalTrials.gov on January 11, 2023, for original articles on assisted reproduction outcomes after COVID-19 vaccination. The primary outcome was rates of clinical pregnancy; secondary outcomes included number of oocytes retrieved, number of mature oocytes retrieved, fertilization rate, implantation rate, ongoing pregnancy rate, and live-birth rate.

METHODS OF STUDY SELECTION:
Two reviewers independently screened citations for relevance, extracted pertinent data, and rated study quality. Only peer-reviewed published studies were included.

TABULATION, INTEGRATION, AND RESULTS:
Our query retrieved 216 citations, of which 25 were studies with original, relevant data. Nineteen studies reported embryo transfer outcomes, with a total of 4,899 vaccinated and 13,491 unvaccinated patients. Eighteen studies reported data on ovarian stimulation outcomes, with a total of 1,878 vaccinated and 3,174 unvaccinated patients. There were no statistically significant results among our pooled data for any of the primary or secondary outcomes: clinical pregnancy rate (odds ratio [OR] 0.94, 95% CI 0.88–1.01, P=.10), number of oocytes retrieved (mean difference −0.26, 95% CI −0.68 to 0.15, P=.21), number of mature oocytes retrieved (mean difference 0.31, 95% CI −0.14 to 0.75, P=.18), fertilization rate (OR 0.99, 95% CI 0.87–1.11, P=.83), implantation rate (OR 0.92, 95% CI 0.84–1.00, P=.06), ongoing pregnancy rate (OR 0.95, 95% CI 0.86–1.06, P=.40), or live-birth rate (OR 0.95, 95% CI 0.78–1.17, P=.63). A subanalysis based on country of origin and vaccine type was also performed for the primary and secondary outcomes and did not change the study results.

CONCLUSION:
Vaccination against COVID-19 is not associated with different fertility outcomes in patients undergoing assisted reproductive technologies.

SYSTEMATIC REVIEW REGISTRATION:
PROSPERO, CRD42023400023.
Evaluation of the Recommended 30 cc/kg Fluid Dose for Patients With Septic Shock and Hypoperfusion With Lactate Greater Than 4 mmol/L
Authors: Yohannes Seife , Serafim Laura Piccolo , Slavinsky Victoria , O’Connor Timothy , Cabrera Mathew , Chin Meghan K. , Pratt Alexandra 
Published: July 2023

OBJECTIVES:
The Surviving Sepsis Campaign Guidelines recommend fluid administration of 30 cc/kg ideal body weight (IBW) for patients with sepsis and lactate greater than 4 mmol/L within 3 hours of identification. In this study, we explore the impact of fluid dose on lactate normalization, treatment cost, length of stay, and mortality in patients with lactate greater than 4.

DESIGN:
Multicenter retrospective observational study.

SETTING:
Eight-hospital urban healthcare system in Northeastern United States.

PATIENTS:
Patients with sepsis, initial lactate value greater than 4 mmol/L, and received appropriate antibiotics within 3 hours.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
We stratified patients into five groups based on the dose of fluid administered within 3 hours after sepsis identification. The groupings were less than 15 cc/kg IBW, 15.1–25 cc/kg IBW, 25.1–35 cc/kg IBW, 35.1–50 cc/kg IBW, and greater than 50 cc/kg IBW. We used the group that received a fluid dose of 25.1–35 cc/kg IBW, as a reference group. The mean age was 66 years, and 56% were male. Three hundred seventy-one (25%) received less than 15 cc/kg of IBW of crystalloid fluid, 278 (17%) received 15–25 cc/kg of IBW, 316 (21%) received 25.1–35 cc/kg of IBW, 319 (21%) received 35.1–50 cc/kg of IBW, and 207 (14%) received greater than 50 cc/kg of IBW. After multilinear regression, there was no significant difference in lactate normalization between the reference group and any of the other fluid groups. We also found no statistically significant difference in the observed/expected cost, or observed/expected length of stay, between the reference group and any of the other fluid groups. Mortality was higher among patients who received greater than 50 cc/kg IBW when compared to the recommended dose.

CONCLUSIONS:
In patients with sepsis and lactate value greater than 4 mmol/L, high or low fluid doses were not associated with better lactate clearance or patient outcomes. Greater than 50 cc/kg IBW dose of fluids within 3 hours is associated with higher mortality.
Developing a Machine Learning Risk-adjustment Method for Hospitalizations and Emergency Department Visits of Nursing Home Residents With Dementia
Authors: Xu Huiwen , Bowblis John R. , Becerra Adan Z. , Intrator Orna 
Published: July 2023

Background:
Long-stay nursing home (NH) residents with Alzheimer disease and related dementias (ADRD) are at high risk of hospital transfers. Machine learning might improve risk-adjustment methods for NHs.

Objectives:
The objective of this study was to develop and compare NH risk-adjusted rates of hospitalizations and emergency department (ED) visits among long-stay residents with ADRD using Extreme Gradient Boosting (XGBoost) and logistic regression.

Research Design:
Secondary analysis of national Medicare claims and NH assessment data in 2012 Q3. Data were equally split into the training and test sets. Both XGBoost and logistic regression predicted any hospitalization and ED visit using 58 predictors. NH-level risk-adjusted rates from XGBoost and logistic regression were constructed and compared. Multivariate regressions examined NH and market factors associated with rates of hospitalization and ED visits.

Subjects:
Long-stay Medicare residents with ADRD (N=413,557) from 14,057 NHs.

Results:
A total of 8.1% and 8.9% residents experienced any hospitalization and ED visit in a quarter, respectively. XGBoost slightly outperformed logistic regression in area under the curve (0.88 vs. 0.86 for hospitalization; 0.85 vs. 0.83 for ED visit). NH-level risk-adjusted rates from XGBoost were slightly lower than logistic regression (hospitalization=8.3% and 8.4%; ED=8.9% and 9.0%, respectively), but were highly correlated. Facility and market factors associated with the XGBoost and logistic regression-adjusted hospitalization and ED rates were similar. NHs serving more residents with ADRD and having a higher registered nurse-to-total nursing staff ratio had lower rates.

Conclusions:
XGBoost and logistic regression provide comparable estimates of risk-adjusted hospitalization and ED rates.
Optimal Duration of High-Fidelity Simulator Training for Bronchoscope-Guided Intubation
Authors: Jiang Luyang , Yang Qingmei , Li Qingyue , Jiang Bailin , Laba Ciren , Feng Yi 
Published: July 2023

Introduction
The optimal simulator training duration for flexible optical bronchoscopic (FOB) intubation is unknown. This study aimed to determine whether a learning curve-based training modality was noninferior to a fixed training time modality in terms of clinical FOB intubation time.

Methods
This multicenter, randomized, noninferiority study was conducted from May to August 2022. Anesthesiology residents or interns were enrolled. Eligible participants were randomized in a 1:1 ratio to receive new learning curve-based simulator training (individualized training time based on performance, group New) or reference fixed training time simulator training (1 hour, group Reference). The primary outcome was the time to complete FOB intubation in patients, which was defined as the time from the introduction of the FOB into the mouth until the first capnography visualization. The margin for detecting clinical significance was defined as 10 seconds.

Results
A total of 32 participants were included in the analysis (16 in each group). All trainees successfully intubated the patients. The mean intubation time (95% confidence interval [CI]) was 81.9 (65.7–98.1) seconds in group New and 97.0 (77.4–116.6) seconds in group Reference. The upper bound of the 1-sided 97.5% CI for the mean difference of clinical intubation time between groups was 9.3 seconds. Noninferiority was claimed. The mean duration of the training in group New was 28.4 (95% CI, 23.5–33.4) minutes. The total number of training procedures on simulators in group New was significantly less than that in group Reference (P < 0.01).

Conclusions
The clinical FOB intubation time in group New was noninferior to that in group Reference.
Epidemiology of Autism Spectrum Disorder in Buenos Aires, Argentina: Insights from Unique Disability ID Issuance Trends
Authors: Aragón-Daud Agustina , Vetere Giselle , Argañaraz Marina , Musich Francisco 
Published: July 2023

AbstractPurposeAutism Spectrum Disorder (ASD) prevalence rates vary greatly across regions and studies. Some countries, such as Argentina, have unknown rates. Due to this high heterogeneity in ASD prevalence worldwide, it is important to study its prevalence and characteristics in such countries to develop effective policies.Methodswe analyzed official data from the Unique Disability IDs (UDIDs) issued for individuals with ASD in the Autonomous City of Buenos Aires from 2016 to 2021, examining age, gender, and diagnosis.Resultsmost UDIDs were issued for males, for Pervasive Developmental Disorders, and almost half to individuals over 8 years old, with these trends remaining stable over these years. However, UDID issuance abruptly dropped in 2020.Conclusionsour findings highlight epidemiological aspects of the autism population in Argentina, including challenges such as delayed diagnosis and high prevalence of broad diagnosis categories. Addressing these challenges requires further research and intervention to improve the quality of life of individuals with ASD.
Long-read Transcriptome Landscapes of Primary and Metastatic Liver Cancers at Transcript Resolution
Authors: Chen Zhiao , Shi Qili , Zhao Yiming , Xu Midie , Liu Yizhe , Li Xinrong , Liu Li , Sun Menghong , Wu Xiaohua , Shao Zhimin , Xu Ye , Wang Lu , He Xianghuo 
Published: July 2023

AbstractBackgroundThe liver is the sixth most common site of primary cancer in humans and is frequently colonized by metastases from cancers of other organs. Few studies have investigated the transcriptomic profiles of matched primary tumor and hepatic metastases of patients. Moreover, the read length of 100-200 bases in conventional short-read RNA sequencing is too short, which makes it difficult to directly infer the full-length transcript structure. To help develop effective treatments and improve survival, it is crucial to understand the complex and diverse molecular mechanisms of primary and metastatic liver cancers.MethodsNinety-five primary and secondary liver cancer patients who underwent hepatic resection were included with long-read sequencing isoform-sequencing and short-read RNA sequencing. We compared the transcriptome landscapes of primary and metastatic liver cancers and systematically investigated HCC, paired primary tumors and liver metastases, and matched non-tumor liver tissues.ResultsWe defined the full-length isoform-level transcriptome of human primary and metastatic liver cancers and identified isoform-level diversity in HCC and metastasis-associated transcriptome variations in metastatic liver cancers. Specific RNA transcripts and isoform switching events with clinical implications were profoundly discovered in liver cancer. Metastasis-specific transcripts that can predict the metastatic risk and identify the primary sites of cancers of unknown primary liver metastasis patients were defined. Additionally, we found that adjacent paracancerous liver tissues are abnormal and characterized the premetastatic immunological and metabolic alterations in the liver that favor the spread of cancer metastases.ConclusionsOur findings strongly highlight the powerfulness of full-length transcriptome profiling to yield novel biological insights into understanding the molecular basis of tumorigenesis and will further benefit the treatment of primary and metastatic liver cancers.
The Auxin and Cytokinin Balance Influence the in Vitro Regeneration ofPhalaenopsisShoots (Orchidaceae)
Authors: Cruz Kaliane Zaira Camacho Maximiano , Alencar Antonio André Silva , Santana Josefa Grasiela Silva , Oliveira Alves Laura Eliza 
Published: July 2023

AbstractOrchids (Phalaenopsis) are considerably appreciated or their high and durable flowering rate and exotic appearance. The optimization of in vitro cultivation begins with an understanding of hormonal balance and its implications in production. This work aimed to regenerate shoots from seeds germination of thePhalaenopsisGolden Peoker ‘BL’ HCC / AOS’ under exogenous auxin and cytokinin influence. To do so, naphthalene acetic acid (NAA), 6-benzyladenine (BA), and Kinetin (Kin) were added to the culture medium to induce organogenesis, totaling 17 treatments with eight replications per treatment. The variables number of shoots (NS), shoot length (SL), and presence of root primordia (RP) were evaluated. A non-parametric test (the Friedman test), followed by the Bonferroni procedure, was used to compare the different groups. Hence, the MS medium provided 610 complete plants after 90 days of cultivation. The T6 treatment had the highest median NS (1.5 shoots per plant at 15 days) and SL. At 30 days, the highest NS was for the T16, with 6.15 shoots per plant; for SL, the one that stood out was the T9. Regarding RP in shoots, the best treatments were T2, T3, T9, T10, and T17, with the formation of RP at 15 days, remaining these treatments at 30 days. In conclusion, the T9 is the most suitable for an efficient protocol reproduction, as it showed the best plant development.HIGHLIGHTS (MANDATORY)The auxin and cytokinin balance promoted shoot regeneration.The BA and NAA combined promoted the shoot formation ofPhalaenopsisGolden Peoker ‘BL’ HCC/AOS’.The use of KIN isolated showed hyperhydricity and malformation in shoots ofPhalaenopsis.
The unique properties of Big tau in the visual system
Authors: Fischer Itzhak , Connors Theresa , Bouyer Julien , Jin Ying 
Published: July 2023

AbstractTau is a microtubule associated protein that plays important roles in regulating the properties of microtubules and axonal transport, as well as tauopathies associated with toxic aggregates leading to neurodegenerative diseases. It is encoded by the MAPT gene forming multiple isoforms by alternative splicing of exons 2/3 at the N-terminal and exon 10 which determines the numbers of microtubule binding repeats (3R or 4R). The high molecular weight (MW) tau isoform termed Big tau contains an additional large exon 4a generating a long projecting domain and expressed as a 110 kDa protein. Big tau was originally discovered in the peripheral nervous system but later found in selective CNS areas that project to the periphery as well as in the cerebellum and the visual system. However, there is a gap of knowledge in understanding the expression patterns and the role of Big tau during normal neuronal development and pathological conditions relative to the common low MW isoforms. Here we investigated the properties of Big tau in the retina and optic nerve and in particular its unique isoform structure as a middle MW of 90kDa and its distribution in retinal ganglion cells and axons of the optic nerve. We discovered that Big tau expresses the 4a exon as well as exons 6 and 10 (4R), lacking exons 2/3 but sharing the extensive phosphorylation characteristic of other tau isoforms. Importantly, early in development the visual system expresses only the low MW isoform (3R) switching to both the low and middle MW isoforms (4R) in adult retinal ganglion neurons and their corresponding axons. This is a unique structure and expression pattern of Big tau likely associated with different properties than what has been previously described, requiring more research to elucidate the detailed roles of Big tau in the visual system.
Distinguishing word identity and sequence context in DNA language models
Authors: Sanabria Melissa , Hirsch Jonas , Poetsch Anna R. 
Published: July 2023

AbstractTransformer-based large language models (LLMs) are very suited for biological sequence data, because the structure of protein and nucleic acid sequences show many analogies to natural language. Complex relationships in biological sequence can be learned, although there may not be a clear concept of words, because they can be generated through tokenization. Training is subsequently performed for masked token prediction. With this strategy, the models learn both the token sequence identity and a larger sequence context. We developed a framework to interrogate what a model learns, which is both relevant for the interpretability of the model and to evaluate its potential for specific tasks.We used a DNA language model, which is trained on the human reference genome with a Bidirectional Encoder Representations from Transformers (BERT) model. In this model, tokens are defined with overlapping k-mers. To gain insight into the model’s learning, we interrogated how the model performs predictions, extracted token embeddings, and defined a fine-tuning benchmarking task to predict the next tokens of different sizes without overlaps. This task is very suited to evaluate different pretrained DNA language models, also called foundation models, since it does not interrogate specific genome biology, does not depend on the tokenization strategy, the size of the vocabulary, the dictionary, or the number of parameters used to train the model. Lastly, the task performs without leakage of information from token identity into the prediction task, which makes it particularly useful to evaluate the learning of sequence context.Through this assessment we discovered that the model with overlapping k-mers struggles to learn larger sequence context. Instead, the learned embeddings largely represent token sequence. Still, good performance is achieved for genome biology inspired fine-tuning tasks. Models with overlapping tokens may be used for tasks where a larger sequence context is of less relevance, but the token sequence directly represents the desired learning feature. This emphasizes the need to interrogate knowledge representation in biological large language models. Transparency is particularly important for biomedical use cases and an understanding of what the models are learning can be used to match the model to the desired task.
Faster action reprogramming, but not stopping, with proactive cues: Combining EMG and computational modelling in response-selective stop signal tasks
Authors: Salomoni Sauro E. , Gronau Quentin F. , Heathcote Andrew , Matzke Dora , Hinder Mark R. 
Published: July 2023

AbstractThe ability to stop simple ongoing actions has been extensively studied using the stop signal task, but less is known about inhibition in more complex scenarios. Here we used a task requiring bimanual responses to go stimuli, but selective inhibition of only one of those responses following a stop signal. We assessed how proactive cues affect the nature of both the responding and stopping processes, and the well-documented “stopping delay” in the continuing action following successful stopping. In this task, estimates of the speed of inhibition based on a simple-stopping model are inappropriate, and have produced inconsistent findings about the effects of proactive control on motor inhibition. We instead used a multi-modal approach, based on improved methods of detecting and interpreting partial electromyographical (EMG) responses and the recently proposed SIS (simultaneously inhibit and start) model of selective stopping behaviour. Our results provide clear and converging evidence that proactive cues reduce the stopping delay effect by slowing bimanual responses and speeding unimanual responses, with a negligible effect on the speed of the stopping process.
Increased collective migration correlates with germline stem cell competition in a basal chordate
Authors: Fentress Megan K. , De Tomaso Anthony W. 
Published: July 2023

AbstractCell competition is a process that compares the relative fitness of progenitor cells, resulting in ‘winners’, which contribute further to development, and ‘losers’, which are excluded, and is likely a universal quality control process that contributes to the fitness of an individual. Cell competition also has pathological consequences, and can create super-competitor cells responsible for tumor progression. We are studying cell competition during germline regeneration in the colonial ascidian,Botryllus schlosseri. Germline regeneration is due to the presence of germline stem cells (GSCs) which have a unique property: a competitive phenotype. When GSCs from one individual are transplanted into another, the donor and recipient cells compete for germline development. Often the donor GSCs win, and completely replace the gametes of the recipient-a process called germ cell parasitism (gcp). gcp is a heritable trait, and winner and loser genotypes can be found in nature and reared in the lab. However, the molecular and cellular mechanisms underlying gcp are unknown. Using an ex vivo migration assay, we show that GSCs isolated from winner genotypes migrate faster and in larger clusters than losers, and that cluster size correlates with expression of the Notch ligand, Jagged. Both cluster size and jagged expression can be manipulated simultaneously in a genotype dependent manner: treatment of loser GSCs with hepatocyte growth factor increases both jagged expression and cluster size, while inhibitors of the MAPK pathway decrease jagged expression and cluster size in winner GSCs. Live imaging in individuals transplanted with labeled winner and loser GSCs reveal that they migrate to the niche, some as small clusters, with the winners having a slight advantage in niche occupancy. Together, this suggests that the basis of GSC competition resides in a combination in homing ability and niche occupancy, and may be controlled by differential utilization of the Notch pathway.
Sensitivity and validation of porous membrane electrical cell substrate impedance spectroscopy (PM-ECIS) for measuring endothelial barrier properties
Authors: Ugodnikov Alisa , Chebotarev Oleg , Persson Henrik , Simmons Craig A. 
Published: July 2023

ABSTRACTConventional trans-endothelial electrical resistance (TEER) setups are invasive and cannot directly measure monolayer integrity in co-culture. These limitations are addressed by porous membrane electrical cell-substrate impedance sensing (PM-ECIS), which measures barrier integrity in cell monolayers grown directly on permeable membranes patterned with electrodes. Here we advance the design and utility of PM-ECIS by investigating its sensitivity to working electrode size and correlation to TEER. Gold electrodes were fabricated on porous membrane inserts using hot embossing and UV lithography, with working electrode diameters of 250, 500, and 750 µm within the same insert. Frequency scans of confluent primary endothelial monolayers showed normalized resistance peaking at 4 kHz, consistent with traditional solid substrate ECIS. Sensitivity to resistance changes (4 kHz) during endothelial barrier formation was inversely proportional to electrode size, with the smallest electrodes being the most sensitive (p<0.001). Similarly, smaller electrodes were most sensitive to changes in impedance (40 kHz) corresponding to cell spreading and proliferation (p<0.001). Barrier disruption with EGTA was detectable by 250 and 750 µm (p<0.01), and 500 µm electrodes (p=0.058). Resistances measured by PM-ECIS vs. TEER for sodium chloride solutions were positively and significantly correlated for all electrode sizes (r>0.9; p<0.0001), but only with 750 µm electrodes for endothelial monolayers (r=0.71; p=0.058). These data inform design and selection of PM-ECIS electrodes for specific applications, and support PM-ECIS as a promising alternative to conventional TEER due to its capacity for direct, non-invasive, and real-time assessment of cells cultured on porous membranes.