bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term Functional Outcomes Among Older Adults Undergoing Video-assisted Versus Open Surgery for Lung Cancer
Authors: Hallet Julie , Rousseau Mathieu , Gupta Vaibhav , Hirpara Dhruvin , Zhao Haoyu , Coburn Natalie , Darling Gail , Kidane Biniam ,   Members of the REcovery After Surgical Therapy for Older Adults Research – Cancer (RESTORE-Cancer) Group
Published: January 2022

Objective:
To examine the long-term healthcare dependency outcomes of older adults undergoing VATS compared to open lung cancer resection.

Summary of Background Data:
Although the benefits of VATS for lung cancer resection have been reported, there is a knowledge gap related to long-term functional outcomes central to decision-making for older adults.

Methods:
We conducted a population-based retrospective comparative cohort study of patients ≥70 years old undergoing lung cancer resection between 2010 and 2017 using linked administrative health databases. VATS was compared to open surgery for lung cancer resection. Outcomes were receipt of homecare and high time-at-home, defined as <14 institution-days within 1 year, in 5 years after surgery. We used time-to-event analyses. Homecare was analyzed as recurrent dichotomous outcome with Andersen-Gill multivariable models, and high time-at-home with Cox multivariable models.

Results:
Of 4974 patients, 2951 had VATS (59.3%). In the first three months postoperatively, homecare use ranged from 17.5% to 34.4% for VATS and 23.0% to 36.6% for open surgery. VATS was independently associated with lower need for postoperative homecare over 5 years (hazard ratio 0.82, 95% confidence interval 0.74-0.92). 1- and 5-year probability of high “time-at-home” were superior for VATS (74.4% vs 66.7% and 55.6% vs 45.4%, p < 0.001). VATS was independently associated with higher probability of high “time-at-home” (hazard ratio 0.81, 95% confidence interval 0.74-0.89) compared to open surgery.

Conclusions:
Compared to open surgery, VATS was associated with lower homecare needs and higher probability of high “time-at-home,” indicating reduced long-term functional dependence. Those important patient-centered endpoints reflect the overall long-term treatment burden on mortality and morbidity that can inform surgical decision-making.
Postoperative Opioid Prescribing and New Persistent Opioid Use
Authors: Howard Ryan , Brown Craig S. , Lai Yen-Ling , Gunaseelan Vidhya , Brummett Chad M. , Englesbe Michael , Waljee Jennifer , Bicket Mark C. 
Published: January 2022

Objective:
Evaluate the association between postoperative opioid prescribing and new persistent opioid use.

Summary Background Data:
Opioid-nave patients who develop new persistent opioid use after surgery are at increased risk of opioid-related morbidity and mortality. However, the extent to which postoperative opioid prescribing is associated with persistent postoperative opioid use is unclear.

Methods:
Retrospective study of opioid-naïve adults undergoing surgery in Michigan from 1/1/2017 to 10/31/2019. Postoperative opioid prescriptions were identified using a statewide clinical registry and prescription fills were identified using Michigan's prescription drug monitoring program. The primary outcome was new persistent opioid use, defined as filling at least 1 opioid prescription between post-discharge days 4 to 90 and filling at least 1 opioid prescription between post-discharge days 91 to 180.

Results:
A total of 37,654 patients underwent surgery with a mean age of 52.2 (16.7) years and 20,923 (55.6%) female patients. A total of 31,920 (84.8%) patients were prescribed opioids at discharge. Six hundred twenty-two (1.7%) patients developed new persistent opioid use after surgery. Being prescribed an opioid at discharge was not associated with new persistent opioid use [adjusted odds ratio (aOR) 0.88 (95% confidence interval (CI) 0.71-1.09)]. However, among patients prescribed an opioid, patients prescribed the second largest [12 (interquartile range (IQR) 3) pills] and largest [20 (IQR 7) pills] quartiles of prescription size had higher odds of new persistent opioid use compared to patients prescribed the smallest quartile [7 (IQR 1) pills] of prescription size [aOR 1.39 (95% CI 1.04-1.86) andaOR 1.97 (95% CI 1.442.70), respectively].

Conclusions:
In a cohort of opioid-naïve patients undergoing common surgical procedures, the risk of new persistent opioid use increased with the size of the prescription. This suggests that while opioid prescriptions in and of themselves may not place patients at risk of long-term opioid use, excessive prescribing does. Consequently, these findings support ongoing efforts to mitigate excessive opioid prescribing after surgery to reduce opioid-related harms.
Into the wild—a field study on the evolutionary and ecological importance of thermal plasticity in ectotherms across temperate and tropical regions
Authors: Noer Natasja K. , Ørsted Michael , Schiffer Michele , Hoffmann Ary A. , Bahrndorff Simon , Kristensen Torsten N. 
Published: January 2022

Understanding how environmental factors affect the thermal tolerance of species is crucial for predicting the impact of thermal stress on species abundance and distribution. To date, species' responses to thermal stress are typically assessed on laboratory-reared individuals and using coarse, low-resolution, climate data that may not reflect microhabitat dynamics at a relevant scale. Here, we examine the daily temporal variation in heat tolerance in a range of species in their natural environments across temperate and tropical Australia. Individuals were collected in their habitats throughout the day and tested for heat tolerance immediately thereafter, while local microclimates were recorded at the collection sites. We found high levels of plasticity in heat tolerance across all the tested species. Both short- and long-term variability of temperature and humidity affected plastic adjustments of heat tolerance within and across days, but with species differences. Our results reveal that plastic changes in heat tolerance occur rapidly at a daily scale and that environmental factors on a relatively short timescale are important drivers of the observed variation in thermal tolerance. Ignoring such fine-scale physiological processes in distribution models might obscure conclusions about species' range shifts with global climate change.
This article is part of the theme issue ‘Species’ ranges in the face of changing environments (part 1)’.
Gene surfing of underdominant alleles promotes formation of hybrid zones
Authors: Gilbert Kimberly J. , Moinet Antoine , Peischl Stephan 
Published: January 2022

The distribution of genetic diversity over geographical space has long been investigated in population genetics and serves as a useful tool to understand evolution and history of populations. Within some species or across regions of contact between two species, there are instances where there is no apparent ecological determinant of sharp changes in allele frequencies or divergence. To further understand these patterns of spatial genetic structure and potential species divergence, we model the establishment of clines that occur due to the surfing of underdominant alleles during range expansions. We provide analytical approximations for the fixation probability of underdominant alleles at expansion fronts and demonstrate that gene surfing can lead to clines in one-dimensional range expansions. We extend these results to multiple loci via a mixture of analytical theory and individual-based simulations. We study the interaction between the strength of selection against heterozygotes, migration rates, and local recombination rates on the formation of stable hybrid zones. Clines created by surfing at different loci can attract each other and align after expansion, if they are sufficiently close in space and in terms of recombination distance. Our findings suggest that range expansions can set the stage for parapatric speciation due to the alignment of multiple selective clines, even in the absence of ecologically divergent selection.This article is part of the theme issue ‘Species' ranges in the face of changing environments (part I)’.
Shorter serial intervals in SARS-CoV-2 cases with Omicron BA.1 variant compared to Delta variant in the Netherlands, 13 – 26 December 2021
Authors: Backer Jantien A. , Eggink Dirk , Andeweg Stijn P. , Veldhuijzen Irene K. , van Maarseveen Noortje , Vermaas Klaas , Vlaemynck Boris , Schepers Raf , van den Hof Susan , Reusken Chantal B.E.M. , Wallinga Jacco 
Published: January 2022

AbstractThe SARS-CoV-2 Omicron variant has a growth advantage over the Delta variant, due to higher transmissibility, immune evasion, or a shorter serial interval. Using S-gene target failure (SGTF) as indication for Omicron BA.1, we identify 908 SGTF and 1621 non-SGTF serial intervals in the same period. Within households, we find that the mean serial interval for SGTF cases is 0.2-0.6 days shorter than for non-SGTF cases. This suggests that the growth advantage of Omicron is partly due to a shorter serial interval.
An expanded high throughput RT-PCR assay to rapidly identify all known SARS-CoV-2 variants of concern using melting temperature coding
Authors: Banada Padmapriya P , Green Raquel , Banik Sukalyani , Streck Deanna , Montalvan Ibsen , Reiss Robert , Jones Robert , Marras Salvatore A. E. , Chakravorty Soumitesh , Alland David 
Published: January 2022

AbstractBackgroundThe rapid emergence of new vaccine-resistant SARS-CoV-2 variants of concern (VOC) requires an equally rapid deployment of diagnostic tests to specifically identify each VOC as soon as it arises. Here, we report an expanded version of our previously described sloppy molecular beacon (SMB) Alpha/Beta/Gamma RT-PCR melting temperature (Tm) signature-based assay, which now includes modifications that allow specific detection of Delta (B.1.617.2) and Omicron (B.1.529) VOCs.MethodsWe developed a dual SMB assay (SMB-452), which targeted the T22917G (L452R) mutation in the SARS-CoV-2 spike protein to specifically detect the Delta VOC. We also identified a Tm profile in our existing SMB-501 and SMB-484 assays (which detect mutations in codons 501 and 484 of the SARS-CoV-2 spike protein, respectively) that differentiate the Omicron-specific N501Y (A23063T) and E484A (A23013C) mutations from both wild type (WT) and other VOCs. The entire six SMB three-codon assay was tested using reference SARS-CoV-2 RNAs. The assay was then validated using clinical samples from COVID-19 patients tested with a LightCycler 480 (LC480) (74 samples), Bio-Rad CFX96 (34 samples), Rotor-Gene Q (Qiagen) (34 samples) and an ABI-7500 (34 samples) RT-PCR instruments. Six SMB Tm results were then inputted into an Excel Analysis tool to generate specific VOC identifications.ResultsThe limit of detection (LOD) for the new SMB-452 assay, which specifically identified the Delta variant was 1 genomic equivalent (GE) per reaction. The LODs of the SMB-501 and SMB-484 assays, which detect Omicron were 100 and 103 GE respectively. Clinical validation of the 3-codon assay in the LC480 instrument showed the assay detected 94% of the samples as WT or VOCs in clinical samples and 6% of the tests producing indeterminate results. None of the samples were incorrectly identified as WT or as a different VOC. Thus, excluding samples with indeterminant results, the assay was 100% sensitive and 100% specific compared to sequencing. There was also 100% concordance between the LC480, BioRad, ABI and Qiagen results, excluding negative or indeterminate results; however, the Qiagen assay had significantly more indeterminates than the other assays.ConclusionThis new assay can serve as a robust diagnostic tool for selecting appropriate monoclonal antibody therapy and rapid VOC surveillance.
Asthma treatment outcome and factors associated with uncontrolled asthma among adult asthmatic patients in Addis Ababa, Ethiopia
Authors: Tsegaye Tesfaye , Gebretekle Gebremedhin Beedemariam , Ahmed Mohammedjud Hassen , Bayissa Tola , Habte Bruck Messele 
Published: January 2022

AbstractBackgroundAsthma is a major public health challenge in the world resulting in significant health and economic burden. The modifiable and non-modifiable risk factors could have considerable impact on Asthma control and medical care. Our goal was to evaluate the treatment outcome and identify risk factors for poor asthma control among asthmatic patients in Addis Ababa, Ethiopia.MethodA multicentre cross-sectional study using interview and chart review was conducted among asthmatic patients attending ambulatory care of two large public hospitals in Addis Ababa, Ethiopia between March and June 2018. The Global Initiative for Asthma Guideline was used to determine treatment outcomes. The variables of interest were described using descriptive statistics such as frequencies, percentages, mean, and standard deviations. Multivariable logistic regression was used to determine factors associated with uncontrolled asthma. All statistical significance level was determined at p<0.05.ResultA total of 230 asthmatic patients were interviewed. More than half (65.2%) of patients were females and their mean age was 54±15.1 years. Overall, 50.4% of the patients had uncontrolled asthma status. More than two number of trigger factors (AOR=1.88; 95%CI:1.09-2.01), cold weather (AOR=2.11;95%CI: 1.51-2.42), exacerbations of asthma in the last 12 months (AOR=2.01;95%CI:1.39-2.32), moderate persistent asthma (AOR=3.47;95%CI:1.75-5.13), severe persistent asthma (AOR=2.90;95%CI:2.56-3.98) and Salbutamol Puff alone regimen (AOR=2.30;95%CI:2.01-2.76) use were significantly associated with uncontrolled asthma.ConclusionMore than half of asthmatic patients had uncontrolled asthma treatment outcome. This indicates the need to give due attention to asthma patients with uncontrolled status particularly to those with identified risk factors. Health care providers should work in creating patient awareness on appropriate use of their prescribed medications, avoidance of asthma triggering factors for decreasing the progression of the disease and better asthma control.
Factors associated with adherence to HIV testing guidelines among HIV negative female sex workers in Kampala Uganda
Authors: Atuhaire Lydia , Shumba Constance S , Mapahla Lovemore , Maposa Innocent , Nyasulu Peter S 
Published: January 2022

AbstractBackgroundFrequent HIV testing at intervals of every three to six months is recommended among HIV negative female sex workers as the first entry point to HIV prevention and treatment. In this study, we examined the extent to which HIV negative female sex workers adhere to the testing guidelines by measuring the frequency of testing in the last 12 months and identified associated factors among female sex workers in Kampala Uganda.MethodsWe conducted a cross-sectional study using structured questionnaires. Using equal probability selection method, 12 hotspots were selected, and 200 participants interviewed based on proportional allocation in each hotspot. We used descriptive statistics to describe female sex workers’ characteristics, and multivariable logistic regression model to determine the factors associated with their adherence to the HIV testing guidelines. Adherence to the HIV testing guidelines was defined as having tested three or more times in the last 12 months. Factors with p-value ≤0.05 significance level were considered statistically significant.ResultsFrom the 200 study participants, 43% were aged 25-30 years, joined sex work between the ages of 18 to 24 years, 49% had attained primary and 41% secondary school respectively. 88% reported HIV testing status, of which 56% had tested three or more times in the 12 months preceding the survey. Attaining secondary education, was independently associated with adherence to the HIV testing guidelines (OR 1.86, 95% CI: 1.01 - 3.44, p=0.047). Those that had tested for STIs in the last three months (OR= 2.13, 95% CI: 0.95 - 4.74, p=0.065) and accessed HIV testing in a drop-in centre (OR= 5.90, 95% CI: 0.71 - 49.1, p=0.101) had higher odds of adhering to the HIV testing guidelinesConclusionThis study found suboptimal adherence to the HIV testing guidelines among HIV negative female sex workers. Interventions such as HIV self-testing that improve access to, and frequency of HIV testing need to be taken to scale. There is need for rigorous behaviour change program evaluation to continually refine understanding of the message mix, to ensure simplified and easy to comprehend awareness messages are designed for female sex workers with no formal education.
Synaptic and intrinsic potentiation in O-LM interneurons is induced by theta patterns of stimulation
Authors: Sammari Malika , Inglebert Yanis , Ankri Norbert , Russier Michaël , Incontro Salvatore , Debanne Dominique 
Published: January 2022

AbstractOriens lacunosum-moleculare (O-LM) interneurons display a non-conventional form of long-term synaptic potentiation (LTP) conferred by calcium-permeable AMPA receptors (CP-AMPAR). So far, this form of LTP has been induced in O-LM cells by physiologically unrealistic protocols. We report here the induction of both synaptic and intrinsic potentiation in O-LM interneurons following stimulation of afferent glutamatergic inputs in the theta (θ) frequency range. LTP is induced by synaptic activation of CP-AMPAR whereas long-term potentiation of intrinsic excitability (LTP-IE) results from the mGluR1-dependent down-regulation of Kv7 voltage-dependent potassium channel and hyperpolarization activated and cyclic nucleotide-gated (HCN) channel through the depletion of phosphatidylinositol-4,5-bi-phosphate (PIP2). LTP and LTP-IE are reversible, demonstrating that both synaptic and intrinsic changes are bidirectional in O-LM cells. We conclude that physiological stimuli such as θ patterns induce synaptic and intrinsic potentiation in O-LM interneurons.
Multiomic Body Mass Index signatures in blood reveal clinically relevant population heterogeneity and variable responses to a healthy lifestyle intervention
Authors: Watanabe Kengo , Wilmanski Tomasz , Diener Christian , Earls John C. , Zimmer Anat , Lincoln Briana , Hadlock Jennifer J. , Lovejoy Jennifer C. , Gibbons Sean M. , Magis Andrew T. , Hood Leroy , Price Nathan D. , Rappaport Noa 
Published: January 2022

AbstractMultiomic profiling can reveal population heterogeneity for both health and disease states. Obesity drives a myriad of metabolic perturbations in individuals and is a risk factor for multiple chronic diseases. Here, we report a global atlas of cross-sectional and longitudinal changes in 1,111 blood analytes associated with variation in Body Mass Index (BMI), as well as the multiomic associations with host polygenic risk scores and gut microbiome composition, from a cohort of 1,277 individuals enrolled in a wellness program. Machine learning model predictions of BMI from blood multiomics captured heterogeneous phenotypic states of host metabolism and gut microbiome composition, better than classically-measured BMI. Moreover, longitudinal analyses identified variable BMI trajectories for different omics measures in response to a healthy lifestyle intervention; metabolomics-inferred BMI decreased to a greater extent than actual BMI, while proteomics-inferred BMI exhibited greater resistance to change. Our analyses further revealed blood analyte–analyte associations that were significantly modified by metabolomics-inferred BMI and partially reversed in the metabolically obese population during the intervention. Taken together, our findings provide a blood atlas of the molecular perturbations associated with changes in obesity status, serving as a valuable resource to robustly quantify metabolic health for predictive and preventive medicine.
SARS-CoV-2 Viral Genes Compromise Survival and Functions of Human Pluripotent Stem Cell-derived Cardiomyocytes via Reducing Cellular ATP Level
Authors: Liu Juli , Zhang Yucheng , Wu Shiyong , Han Lei , Wang Cheng , Liu Sheng , Simpson Ed , Liu Ying , Wang Yue , Shou Weinian , Liu Yunlong , Rubart-von der Lohe Michael , Wan Jun , Yang Lei 
Published: January 2022

AbstractCardiac manifestations are commonly observed in COVID-19 patients and prominently contributed to overall mortality. Human myocardium could be infected by SARS-CoV-2, and human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) are susceptible to SARS-CoV-2 infection. However, molecular mechanisms of SARS-CoV-2 gene-induced injury and dysfunction of human CMs remain elusive. Here, we find overexpression of three SARS-CoV-2 coding genes, Nsp6, Nsp8 and M, could globally compromise transcriptome of hPSC-CMs. Integrated transcriptomic analyses of hPSC-CMs infected by SARS-CoV-2 with hPSC-CMs of Nsp6, Nsp8 or M overexpression identified concordantly activated genes enriched into apoptosis and immune/inflammation responses, whereas reduced genes related to heart contraction and functions. Further, Nsp6, Nsp8 or M overexpression induce prominent apoptosis and electrical dysfunctions of hPSC-CMs. Global interactome analysis find Nsp6, Nsp8 and M all interact with ATPase subunits, leading to significantly reduced cellular ATP level of hPSC-CMs. Finally, we find two FDA-approved drugs, ivermectin and meclizine, could enhance the ATP level, and ameliorate cell death and dysfunctions of hPSC-CMs overexpressing Nsp6, Nsp8 or M. Overall, we uncover the global detrimental impacts of SARS-CoV-2 genes Nsp6, Nsp8 and M on the whole transcriptome and interactome of hPSC-CMs, define the crucial role of ATP level reduced by SARS-CoV-2 genes in CM death and functional abnormalities, and explore the potentially pharmaceutical approaches to ameliorate SARS-CoV-2 genes-induced CM injury and abnormalities.