bluuebunny/crossref_metadata_2025_split huggingface dataset:
Were SARS-CoV-2 self-tests used for their intended purpose? The experience in Belgium
Authors: Lafort Yves , Cornelissen Laura , Van Cauteren Dieter , Verboven Barbara , Drieskens Sabine , Couvreur Simon , Hermans Lize , Straetmans Koen , Lernout Tinne 
Published: June 2023

Abstract
Background
Self-testing has been promoted as a means of increasing COVID-19 test coverage. In Belgium, self-testing was recommended as a complement to the formal, provider-administered indications, such as out of courtesy before meeting others and when feared to be infected. More than a year after the introduction of self-testing their place in the test strategy was evaluated.

Methods
We assessed trends in the number of self-tests sold, the number of positive self-tests reported, the proportion sold self-tests/total tests, and the proportion of all positive tests that were confirmed self-tests. To evaluate the reason why people use self-tests, we used the results of two online surveys among members of the general population: one among 27,397 people, held in April 2021, and one among 22,354 people, held in December 2021.

Results
The use of self-tests became substantial from end 2021 onwards. In the period mid-November 2021 – end-of-June 2022, the average proportion of reported sold self-tests to all COVID-19 tests was 37% and 14% of all positive tests were positive self-tests. In both surveys, the main reported reasons for using a self-test were having symptoms (34% of users in April 2021 and 31% in December 2021) and after a risk contact (27% in both April and December). Moreover, the number of self-tests sold, and the number of positive self-tests reported closely followed the same trend as the provider-administered tests in symptomatic people and high risk-contacts, which reinforces the hypothesis that they were mainly used for these two indications.

Conclusions
From end 2021 onwards, self-testing covered a significant part of COVID-19 testing in Belgium, which increased without doubt the testing coverage. However, the available data seem to indicate that self-testing was mostly used for indications outside of official recommendations. If and how this affected the control of the epidemic remains unknown.
DNA replication stress and mitotic catastrophe mediate sotorasib addiction in KRASG12C-mutant cancer
Authors: Chiou Li-Wen , Chan Chien-Hui , Jhuang Yu-Ling , Yang Ching-Yao , Jeng Yung-Ming 
Published: June 2023

Abstract
Background
Sotorasib is the first KRASG12C inhibitor approved by the US Food and Drug Administration for treating KRASG12C-mutant non-small-cell lung cancer (NSCLC). Clinical trials on the therapeutic use of sotorasib for cancer have reported promising results. However, KRASG12C-mutant cancers can acquire resistance to sotorasib after treatment. We incidentally discovered that sotorasib-resistant (SR) cancer cells are addicted to this inhibitor. In this study, we investigated the mechanisms underlying sotorasib addiction.

Methods
Sotorasib-resistant cells were established using KRASG12C-mutant pancreatic cancer and NSCLC cell lines. Cell viability in the presence or absence of sotorasib and in combination with multiple inhibitors was assessed through proliferation assay and annexin V/propidium iodide (PI) flow cytometry assays. The mechanisms underlying drug addiction were elucidated through 5-bromo-2′-deoxyuridine (BrdU) incorporation assay, immunofluorescence staining, time-lapse microscopy, and comet assay. Furthermore, a subcutaneous xenograft model was used to demonstrate sotorasib addiction in vivo.

Results
In the absence of sotorasib, the sotorasib-resistant cells underwent p21Waf1/Cip1-mediated cell cycle arrest and caspase-dependent apoptosis. Sotorasib withdrawal resulted in robust activation of mitogen-activated protein kinase (MAPK) pathway, inducing severe DNA damage and replication stress, which activated the DNA damage response (DDR) pathway. Persistent MAPK pathway hyperactivation with DDR exhaustion led to premature mitotic entry and aberrant mitosis, followed by micronucleus and nucleoplasmic bridge formation. Pharmacologic activation of the MAPK pathway with a type I BRAF inhibitor could further enhance the effects of sotorasib withdrawal on sotorasib-resistant cancer cells both in vitro and in vivo.

Conclusions
We elucidated the mechanisms underlying the sotorasib addiction of cancer cells. Sotorasib addiction appears to be mediated through MAPK pathway hyperactivity, DNA damage, replication stress, and mitotic catastrophe. Moreover, we devised a therapeutic strategy involving a type I BRAF inhibitor to strengthen the effects of sotorasib addiction; this strategy may provide clinical benefit for patients with cancer.
The use of sodium-glucose co-transporter-2 inhibitors or glucagon-like peptide-1 receptor agonists versus sulfonylureas and the risk of lower limb amputations: a nation-wide cohort study
Authors: Werkman Nikki C. C. , Driessen Johanna H. M. , Stehouwer Coen D. A. , Vestergaard Peter , Schaper Nicolaas C. , van den Bergh Joop P. , Nielen Johannes T. H. 
Published: June 2023

Abstract
Background
Numerous studies have investigated the potential association of sodium-glucose co-transporter-2 inhibitors (SGLT2-Is) with an increased risk of lower limb amputations (LLAs), but have produced conflicting results. Particularly studies comparing SGLT2-Is to glucagon-like peptide-1 receptor agonists (GLP1-RAs) seem to find a higher LLA risk with SGLT2-I use. This raises the question whether the results are driven by a protective GLP1-RA-effect rather than a harmful SGLT2-I-effect. GLP1-RAs could promote wound healing and therefore reduce the risk of LLAs, but the associations between both drug classes and LLA remain uncertain. Therefore, the aim of the current study was to investigate the risk of LLA and diabetic foot ulcer (DFU) with SGLT2-I use and GLP1-RA use versus sulfonylurea use.

Methods
A retrospective population-based cohort study was conducted using data from the Danish National Health Service (2013–2018). The study population (N = 74,475) consisted of type 2 diabetes patients aged 18 + who received a first ever prescription of an SGLT2-I, GLP1-RA or sulfonylurea. The date of the first prescription defined the start of follow-up. Time-varying Cox proportional hazards models estimated the hazard ratios (HRs) of LLA and DFU with current SGLT2-I use and GLP1-RA use versus current SU use. The models were adjusted for age, sex, socio-economic variables, comorbidities and concomitant drug use.

Results
Current SGLT2-I use was not associated with a higher risk of LLA versus sulfonylureas {adjusted HR 1.10 [95% confidence interval (CI) 0.71–1.70]}. Current GLP1-RA use, on the other hand, was associated with a lower risk of LLA [adjusted HR 0.57 (95%CI 0.39–0.84)] compared to sulfonylureas. The risk of DFU was similar to that with sulfonylureas with both exposures of interest.

Conclusion
SGLT2-I use was not associated with a higher risk of LLA, but GLP1-RAs with a lower risk of LLA. Previous studies reporting a higher risk of LLA with SGLT2-I use compared to GLP1-RA use might have been looking at a protective GLP1-RA effect, rather than a harmful SGLT2-I effect.
Association between non-insulin-based insulin resistance indices and cardiovascular events in patients undergoing percutaneous coronary intervention: a retrospective study
Authors: Zhang Zenglei , Zhao Lin , Lu Yiting , Meng Xu , Zhou Xianliang 
Published: June 2023

Abstract
Background
Insulin resistance (IR) has been confirmed that getting involved in the pathophysiological process of cardiovascular diseases (CVD). Recently, increasing evidence suggests metabolic score for insulin resistance (METS-IR), triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, triglyceride and glucose (TyG) index, triglyceride glucose-body mass (TyG-BMI) index are simple and reliable surrogates for IR. However, their abilities in predicting cardiovascular outcomes in patients undergoing percutaneous coronary intervention (PCI) are not well explored. Therefore, this study aimed to investigate the association and evaluate the predictive performance of each index.

Methods
A total of 2533 consecutive participants undergoing PCI were included in this study, and the data from 1461 patients were used to determine the correlation of these non-insulin-based IR indices with major adverse cardiac and cerebrovascular events (MACCEs) via performing the multivariate logistic models and restricted cubic splines (RCS).

Results
During a median of 29.8 months follow-up, 195 cases of 1461 patients experienced incident MACCEs. In the overall population, both univariate and multivariate logistic regression analyses indicated no statistically significant connection between these IR indices and MACCEs. Subgroup analyses revealed significant interactions between age subgroups and TyG-BMI index, as well as METS-IR, and between sex subgroups and TyG index. In elderly patients, per 1.0-SD increment in TyG-BMI index and METS-IR had a significant association with MACCEs, with odds ratios (ORs) [95% confidence interval (CI)] of 1.24 (1.02–1.50) and 1.27 (1.04–1.56), respectively (both P < 0.05). Moreover, in female patients, all the IR indices showed significant associations with MACCEs. Multivariable-adjusted RCS curves demonstrated a linear relationship between METS-IR and MACCEs in elderly and female patients, respectively. However, all the IR indices failed to enhance the predictive performance of the basic risk model for MACCEs.

Conclusion
All the four IR indices showed a significant association with MACCEs in female individuals, whereas only TyG-BMI index and METS-IR showed associations in elderly patients. Although the inclusion of these IR indices did not improve the predictive power of basic risk model in either female or elderly patients, METS-IR appears to be the most promising index for secondary prevention of MACCEs and risk stratification in patients undergoing PCI.
Pilot-scale bioethanol production from the starch of avocado seeds using a combination of dilute acid-based hydrolysis and alcoholic fermentation by Saccharomyces cerevisiae
Authors: Caballero-Sanchez Luis , Lázaro-Mixteco Pedro E. , Vargas-Tah Alejandra , Castro-Montoya Agustín J. 
Published: June 2023

Abstract
Background
A processing methodology of raw starch extraction from avocado seeds (ASs) and a sequential hydrolysis and fermentation bioprocess in just a few steps was successfully obtained for the bioethanol production by a single yeast Saccharomyces cerevisiae strain and this research was also to investigate the optimum conditions for the pretreatment of biomass and technical procedures for the production of bioethanol. It successfully resulted in high yields and productivity of all the experiments from the laboratory scale and the pilot plant. Ethanol yields from pretreated starch are comparable with those in commercial industries that use molasses and hydrolyzed starch as raw materials.

Results
Before the pilot-scale bioethanol production, studies of starch extraction and dilute sulfuric acid-based pretreatment was carefully conducted. The amount of starch extracted from dry and fresh avocado seed was 16.85 g ± 0.34 g and 29.79 ± 3.18 g of dry starch, representing a yield of ∼17% and 30%, respectively. After a dilute sulfuric acid pretreatment of starch, the released reducing sugars (RRS) were obtained and the hydrolysate slurries containing glucose (109.79 ± 1.14 g/L), xylose (0.99 ± 0.06 g/L), and arabinose (0.38 ± 0.01 g/L). The efficiency of total sugar conversion was 73.40%, with a productivity of 9.26 g/L/h. The ethanol fermentation in a 125 mL flask fermenter showed that Saccharomyces cerevisiae (Fali, active dry yeast) produced the maximum ethanol concentration, pmax at 49.05 g/L (6.22% v/v) with a yield coefficient, Yp/s of 0.44 gEthanol/gGlucose, a productivity or production rate, rp at 2.01 g/L/h and an efficiency, Ef of 85.37%. The pilot scale experiments of the ethanol fermentation using the 40-L fermenter were also successfully achieved with essentially good results. The values of pmax,Yp/s, rp, and Ef of the 40-L scale were at 50.94 g/L (6.46% v/v), 0.45 gEthanol/gGlucose, 2.11 g/L/h, and 88.74%, respectively. Because of using raw starch, major by-products, i.e., acetic acid in the two scales were very low, in ranges of 0.88–2.45 g/L, and lactic acid was not produced, which are less than those values in the industries.

Conclusions
The sequential hydrolysis and fermentation process of two scales for ethanol production using the combination of hydrolysis by utilizing dilute sulfuric acid-based pretreatment and fermentation by a single yeast Saccharomyces cerevisiae strain is practicable and feasible for realistic and effective scale-up strategies of bioethanol production from the starch of avocado seeds.
Effect measure modification of the association between short-term exposures to PM2.5 and hospitalizations by long-term PM2.5 exposure among a cohort of people with Chronic Obstructive Pulmonary Disease (COPD) in North Carolina, 2002–2015
Authors: Cowan Kristen N. , Wyatt Lauren H. , Luben Thomas J. , Sacks Jason D. , Ward-Caviness Cavin , Rappazzo Kristen M. 
Published: June 2023

Abstract
Background
Approximately nine million adults in the United States are living with chronic obstructive pulmonary disease (COPD), and positive associations between short-term air pollution exposure and increased risk of COPD hospitalizations in older adults are consistently reported. We examined the association between short-term PM2.5 exposure and hospitalizations and assessed if there is modification by long-term exposure in a cohort of individuals with COPD.

Methods
In a time-referent case-crossover design, we used a cohort of randomly selected individuals with electronic health records from the University of North Carolina Healthcare System, restricted to patients with a medical encounter coded with a COPD diagnosis from 2004–2016 (n = 520), and estimated ambient PM2.5 concentrations from an ensemble model. Odds ratios and 95% confidence intervals (OR (95%CI)) were estimated with conditional logistic regression for respiratory-related, cardiovascular (CVD), and all-cause hospitalizations. Exposures examined were 0–2 and 0–3 day lags of PM2.5 concentration, adjusting for daily census-tract temperature and humidity, and models were stratified by long-term (annual average) PM2.5 concentration at the median value.

Results
We observed generally null or low-magnitude negative associations with short-term PM2.5 exposure and respiratory-related (OR per 5 µg/m3 increase in 3-day lag PM2.5: 0.971 (0.885, 1.066)), CVD (2-day lag: 0.976 (0.900, 1.058) and all-cause (3 day lag: 1.003 (0.927, 1.086)) hospitalizations. Associations between short-term PM2.5 exposure and hospitalizations were higher among patients residing in areas with higher levels of annual PM2.5 concentrations (OR per 5 µg/m3 in 3-day lag PM2.5 for all-cause hospitalizations: 1.066 (0.958, 1.185)) than those in areas with lower annual PM2.5 concentrations (OR per 5 µg/m3 in 3-day lag PM2.5 for all-cause hospitalizations: 0.914 (0.804, 1.039)).

Concluisons
Differences in associations demonstrate that people in areas with higher annual PM2.5 exposure may be associated with higher risk of hospitalization during short-term increases in PM2.5 exposure.
Community-based respondent-driven sampling as a strategy for drug use surveillance in a large French urban area
Authors: Donnadieu Hélène , Quillet Catherine , D’Ottavi Morgana , Castellani Joëlle , Debellefontaine Anne , Guichard Sylvain , Baglioni René , Langendorfer Nicolas , Faucherre Vincent , Hanslik Bertrand , Tuaillon Edouard , Laureillard Didier , Nagot Nicolas 
Published: June 2023

Abstract
Background
Understanding drug use and behavior within the PWUD population is crucial to adapt harm reduction and prevention strategies, and provide improved addiction and medical treatment. However, in most countries such as France, the knowledge of drug use behaviors is likely biased as it originates from addiction centers which are attended by only an unknown proportion of PWUD. The objectives of this study were to describe drug use behavior in a population of active PWUD in the urban area of Montpellier, South of France.

Methods
We implemented a community-based respondent-driven sampling survey (RDSS), a validated strategy to obtain a representative sample of a population, to recruit PWUD in the city. Adult individuals reporting frequent psychoactive drug use other than cannabis, with confirmation by urine test, were eligible. Beside HCV and HIV testing, trained peers interviewed participants on their drug consumption and behavior using standardized questionnaires. Fifteen seeds launched the RDSS.

Results
During the 11 weeks of the RDSS, 554 actives PWUD were consecutively included. They were mostly men (78.8%), had a median age of 39 years, and only 25.6% had a stable living place. On average, participants consumed 4.7 (± 3.1) different drugs, and 42.6% smoked free-base cocaine. Unexpectedly, heroin and methamphetamine were consumed by 46.8% and 21.5% of participants, respectively. Among the 194 participants injecting drugs, 33% declared sharing their equipment.

Conclusion
This RDSS highlighted a high consumption of heroin, crack and methamphetamine in this PWUD population. These unexpected results can be explained by low attendance to addiction centers, the source of drug use reports. Despite free care and risk reduction equipment in the city, sharing was very frequent among injectors, challenging the current program of harm reduction.
A rapid assay for assessing bacterial effects on Arabidopsis thermotolerance
Authors: Lee Jun Hyung , Burdick Leah H. , Piatkowski Bryan , Carrell Alyssa A. , Doktycz Mitchel J. , Pelletier Dale A. , Weston David J. 
Published: June 2023

Abstract
Background
The role of beneficial microbes in mitigating plant abiotic stress has received considerable attention. However, the lack of a reproducible and relatively high-throughput screen for microbial contributions to plant thermotolerance has greatly limited progress in this area, this slows the discovery of novel beneficial isolates and the processes by which they operate.

Results
We designed a rapid phenotyping method to assess the effects of bacteria on plant host thermotolerance. After testing multiple growth conditions, a hydroponic system was selected and used to optimize an Arabidopsis heat shock regime and phenotypic evaluation. Arabidopsis seedlings germinated on a PTFE mesh disc were floated onto a 6-well plate containing liquid MS media, then subjected to heat shock at 45 °C for various duration. To characterize phenotype, plants were harvested after four days of recovery to measure chlorophyll content. The method was extended to include bacterial isolates and to quantify bacterial contributions to host plant thermotolerance. As an exemplar, the method was used to screen 25 strains of the plant growth promoting Variovorax spp. for enhanced plant thermotolerance. A follow-up study demonstrated the reproducibility of this assay and led to the discovery of a novel beneficial interaction.

Conclusions
This method enables rapid screening of individual bacterial strains for beneficial effects on host plant thermotolerance. The throughput and reproducibility of the system is ideal for testing many genetic variants of Arabidopsis and bacterial strains.
Ideal entry point and direction of retrograde intramedullary nailing of the tibia
Authors: He Min , Jiang Ziyu , Tan Wenfu , Li Zhengmao , Peng Bin 
Published: June 2023

Abstract
Purpose
To determine the ideal entry point and direction of retrograde intramedullary nailing of the tibia.

Methods
The imaging data of patients with distal tibial fractures from June 2020 to December 2021 in our hospital were collected, and computer-aided design was performed. The relevant data were imported into the software for processing, so as to obtain a distal tibial fracture model and simulate the retrograde intramedullary nail placement in the tibia. The entry points and angles at which the intramedullary nail could be inserted successfully and the fracture could be maintained in good alignment were overlapped and counted to obtain the safe entry range and angle. The center of this safe range is the ideal entry point for retrograde intramedullary nailing of the tibia, and the mean value of the angle is the ideal direction of entry.

Results
The ideal entry point of the retrograde intramedullary nailing was located at the midpoint of the medial malleolus in the C-arm fluoroscopic anteroposterior (AP) and lateral view. The ideal nail entry direction was located at the anatomic axis of the medial malleolus in the AP position and at the anatomic axis of the distal tibial metaphysis in the lateral position.

Conclusion
The ideal point and direction of nail insertion for retrograde tibial intramedullary nailing is a "double midpoint, double axis" approach.
Preoperative simulated surgery on 3D model assists osteotomy feasibility verification and surgical guidance for patients with cubitus valgus/varus deformity: a retrospective observational study
Authors: Xue Kai-Xiao , Zheng Xing-Guo , Qiao Chang , Fang Jia-Hu 
Published: June 2023

Abstract
Background
As the common delayed complication of supracondylar fractures in children, cubitus valgus/varus deformity might lead to pain and loss of motion of the elbow. The current corrective treatment might not be accurate enough and even contribute to postoperative deformity. This study retrospectively analyzed the clinical value of preoperative simulated surgery on 3D model-assisted osteotomy feasibility verification and surgical guidance for cubitus valgus/varus deformity.

Methods
Seventeen patients were selected from January 2017 and November 2019. Deformities were analyzed from imaging data and 3D models and corrected after the simulated operations. The radiographic evaluation comprised osseous union, carrying angle, and anteversion angle of the distal humerus. The clinical evaluation was performed according to the Hospital for Special Surgery (HSS) scoring system.

Results
All patients underwent the operation successfully and had no postoperative deformity. The carrying angle was significantly improved postoperatively (P < 0.001). The anteversion angle of the distal humerus did not change significantly (P > 0.05). The HSS score rose after surgery (P < 0.001). The function of the elbow joint was excellent in seven cases and good in ten cases.

Conclusion
Simulated surgery on 3D model plays an important role in osteotomy plan and surgical guidance, contributing to good surgical efficacy.