bluuebunny/crossref_metadata_2025_split huggingface dataset:
Timing and severity of COVID-19 during pregnancy and risk of preterm birth in the International Registry of Coronavirus Exposure in Pregnancy
Authors: Smith Louisa H. , Dollinger Camille Y. , VanderWeele Tyler J. , Wyszynski Diego F. , Hernández-Díaz Sonia 
Published: October 2022

Abstract
Background
Studies of preterm delivery after COVID-19 are often subject to selection bias and do not distinguish between early vs. late infection in pregnancy, nor between spontaneous vs. medically indicated preterm delivery. This study aimed to estimate the risk of preterm birth (overall, spontaneous, and indicated) after COVID-19 during pregnancy, while considering different levels of disease severity and timing.

Methods
Pregnant and recently pregnant people who were tested for or clinically diagnosed with COVID-19 during pregnancy enrolled in an international internet-based cohort study between June 2020 and July 2021. We used several analytic approaches to minimize confounding and immortal time bias, including multivariable regression, time-to-delivery models, and a case-time-control design.

Results
Among 14,264 eligible participants from 70 countries who did not report a pregnancy loss before 20 gestational weeks, 5893 had completed their pregnancies and reported delivery information; others were censored at time of their last follow-up. Participants with symptomatic COVID-19 before 20 weeks’ gestation had no increased risk of preterm delivery compared to those testing negative, with adjusted risks of 10.0% (95% CI 7.8, 12.0) vs. 9.8% (9.1, 10.5). Mild COVID-19 later in pregnancy was not clearly associated with preterm delivery. In contrast, severe COVID-19 after 20 weeks’ gestation led to an increase in preterm delivery compared to milder disease. For example, the risk ratio for preterm delivery comparing severe to mild/moderate COVID-19 at 35 weeks was 2.8 (2.0, 4.0); corresponding risk ratios for indicated and spontaneous preterm delivery were 3.7 (2.0, 7.0) and 2.3 (1.2, 3.9), respectively.

Conclusions
Severe COVID-19 late in pregnancy sharply increased the risk of preterm delivery compared to no COVID-19. This elevated risk was primarily due to an increase in medically indicated preterm deliveries, included preterm cesarean sections, although an increase in spontaneous preterm delivery was also observed. In contrast, mild or moderate COVID-19 conferred minimal risk, as did severe disease early in pregnancy.
Do coagulation or fibrinolysis reflect the disease condition in patients with soft tissue sarcoma?
Authors: Asanuma Kunihiro , Nakamura Tomoki , Okamoto Takayuki , Hagi Tomohito , Kita Kouji , Nakamura Koichi , Matsuyama Yumi , Yoshida Keisuke , Asanuma Yumiko , Sudo Akihiro 
Published: October 2022

AbstractBackgroundCoagulation and fibrinolysis are distinct processes that are highly correlated. Cells control coagulation and fibrinolysis by expression of tissue factor and urokinase-type plasminogen activator receptor on their surface. Tumor cells express these proteins, adjust their microenvironment and induce tumor exacerbation. We hypothesized that the expression of plasma markers for coagulation and fibrinolysis in patients with soft tissue sarcomas (STSs) was dependent on the level of tumor malignancy. To elucidate which markers are predictive of recurrence, metastasis and prognosis, coagulation or fibrinolysis, we analyzed the correlation between plasma levels of thrombin-antithrombin III complex (TAT), soluble fibrin (SF), plasmin-α2 plasmin inhibitor complex (PIC), D-dimer (DD) and clinical parameters in patients with STSs.MethodsTAT, SF, PIC or DD were measured in pre-treatment blood samples from 64 patients with primary STSs and analyzed with clinicopathological parameters, and 5-year recurrence free survival (RFS), 5-year metastasis free survival (MFS) and 5-year overall survival (OS) were evaluated.ResultsThe metastasis group had significantly higher DD (p = 0.0394), PIC (p = 0.00532) and SF (p = 0.00249) concentrations than the group without metastasis. The group that died of disease showed significantly higher DD (p = 0.00105), PIC (p = 0.000542), SF (p = 0.000126) and TAT (p = 0.0373) than surviving patients. By dividing the patients into low and high groups, the group with high DD, PIC, SF and TAT showed significantly lower 5-year MFS and 5-year OS than the corresponding low group. Furthermore, in multivariate COX proportional hazard analysis of continuous variables for 5-year MFS, only PIC was found to be a significant factor (HR: 2.14).ConclusionFibrinolysis was better than coagulation at reflecting the disease condition of patients with STS. Notably, PIC levels ≥ 1.1 can not only predict the risk of metastasis and poor prognosis, but also increasing PIC levels correspond to further increases in risks of metastasis and poor prognosis.
Loss to follow-up of HIV-exposed infants for confirmatory HIV test under Early Infant Diagnosis program in India: analysis of national-level data from reference laboratories
Authors: Gawde Nilesh , Kamble Suchit , Goel Noopur , Nikhare Kalyani , Bembalkar Shilpa , Thorwat Mohan , Jagtap Dhanashree , Kurle Swarali , Yadav Neeru , Verma Vinita , Kapoor Neha , Das Chinmoyee 
Published: October 2022

Abstract
Background
Early Infant Diagnosis was launched in India in 2010 and its effect on the diagnosis of HIV-exposed infants needs to be assessed. The present study was done to find out the median age at DBS sample collection for early infant diagnosis and its trend over years, the median age at diagnosis of HIV among the HIV-exposed infants with DNA PCR tests, and the proportion of infants who completed testing cascades after detection of HIV-1 in a sample.

Methods
DNA PCR data (from 2013 to 2017) maintained at all regional reference laboratories in India was collated with each infant identified by a unique code. Cohort analysis of the infant data was used to find the median age at sample collection and diagnosis. The outcomes of testing in each cascade and the overall outcomes of testing for infants were prepared.

Results
The median age at sample collection for the four years combined at all India level was 60 days (48–110 days). The median age at diagnosis of HIV was 285 days (174–418 days). HIV-1 was detected in samples of 1897 (6.3%) infants out of 30,216 infants who had a DNA PCR test, out of whom 1070 (56.4%) completed the testing cascade and the rest were lost to follow-up.

Conclusion
The data highlights delay in diagnosis; both due to delay in sample collection and turn-around-times. Loss to follow-up of HIV-exposed infants with virus detection is a significant concern to the Early Infant Diagnosis and tracking systems need to be strengthened.
Analysing the role of sleep quality, functional limitation and depressive symptoms in determining life satisfaction among the older Population in India: a moderated mediation approach
Authors: Banerjee Shreya , Boro Bandita 
Published: October 2022

Abstract
Background:
Life satisfaction (LS), a useful construct in the study of psycho-social well-being, is an important indicator of healthy aging. With a view to investigate whether the improved longevity in India is accompanied by commensurate levels of well-being and contentment among the older adults , this study aimed to examine (1) the association between LS and sleep quality among older Indian adults aged 60 years and above (2) the mediating role of depression that accounts for the association and (3) the moderating role of functional limitation in this mediation.

Methods:
Cross-sectional data from the Longitudinal Ageing Study in India (LASI), Wave-1 (2017-18) was used. Pearson’s correlation coefficients were calculated to investigate the pair-wise relationship between sleep quality, depressive symptoms, functional limitation, and LS. Structural Equation Model was employed to analyse the moderated-mediated association between sleep quality and the level of LS.

Results:
Sleep quality had a direct effect (β=-0.12) as well as an indirect effect (β=-0.024) via depressive symptoms on LS, accounting for 83.6 and 16.4 per cent of the total effects, respectively. Also, the interaction term between poor seep quality and functional limitation was positive (β = 0.03, p < 0.001) in determining depressive symptoms, suggesting that higher level of functional limitation aggravated the indirect effect of poor sleep quality on LS.

Conclusion:
The findings of the study suggested that ensuring both the physical as well as the mental well-being of the population during the life course may confer in later life the desired level of life satisfaction.
Role of community pharmacy professionals in child health service provision in Ethiopia: a cross-sectional survey in six cities of Amhara regional state
Authors: Ayele Asnakew Achaw , Cosh Suzanne , Islam Md Shahidul , East Leah 
Published: October 2022

AbstractBackgroundCommunity pharmacy professionals have great potential to deliver various public health services aimed at improving service access, particularly in countries with a shortage of health professionals. However, little is known about their involvement in child health service provision in Ethiopia.ObjectiveThe purpose of this study was to evaluate the level of involvement of community pharmacy professionals in child health service provision within Ethiopia.MethodsA multi-center cross-sectional survey was conducted among 238 community pharmacy professionals from March to July 2020 in Amhara regional state of Ethiopia. Independent samples t-test and one way Analysis of Variance (ANOVA) was used to test the mean difference.ResultsMost community pharmacy professionals were ‘involved’ in providing child health services related to‘advice about vitamins/supplements’(46.6%),‘advice about infant milk/formulas’(47.1%) and‘responding to minor symptoms’(50.8%) for children. The survey revealed that, community pharmacy professionals were less frequently involved in providing childhood‘vaccination’services. Further, level of involvement of community pharmacy professionals differed according to participants’ licensure level, setting type, responsibility in the facility and previous training experience in child health services.ConclusionCommunity pharmacy professionals have been delivering various levels of child health services, demonstrating ability and capacity in improving access to child health services in Ethiopia. However, there is a need for training and government support to optimize pharmacist engagement and contribution to service delivery.
Characteristics of events in which police responded to overdoses: an examination of incident reports in Rhode Island
Authors: Macmadu Alexandria , Yolken Annajane , Frueh Lisa , Toussaint Jai’el R. , Newman Roxxanne , Jacka Brendan P. , Collins Alexandra B. , Marshall Brandon D. L. 
Published: October 2022

Abstract
Background
Narrow or non-existent Good Samaritan Law protections and harsh drug selling statutes in the USA have been shown to deter bystanders from seeking medical assistance for overdoses. Additionally, little is known about the actions that police take when responding to overdose events. The objectives of this study were to assess the prevalence and correlates of naloxone administration by police, as well as to examine overdose events where arrests were made and those in which the person who overdosed was described as combative.

Methods
We analyzed incident reports of police responding to an overdose between September 1, 2019, and August 31, 2020 (i.e., 6 months prior to and during the COVID-19 pandemic), from a city in Rhode Island. We examined characteristics of incidents, as well as individual characteristics of the person who overdosed. Correlates of police naloxone administration were assessed using Wilcoxon rank sum tests and Fisher’s exact tests, and we examined incidents where arrests occurred and incidents in which the person who overdosed was described as combative descriptively.

Results
Among the 211 incidents in which police responded to an overdose during the study period, we found that police administered naloxone in approximately 10% of incidents. In most incidents, police were the last group of first responders to arrive on scene (59%), and most often, naloxone was administered by others (65%). Police were significantly more likely to administer naloxone when they were the first professionals to arrive, when naloxone had not been administered by others, and when the overdose occurred in public or in a vehicle. Arrests at overdose events were rarely reported (1%), and people who overdosed were rarely (1%) documented in incident reports as being ‘combative.’

Conclusions
Considering these findings, ideally, all jurisdictions should have sufficient first responder staffing and resources to ensure a rapid response to overdose events, with police rarely or never dispatched to respond to overdoses. However, until this ideal can be achieved, any available responders should be dispatched concurrently, with police instructed to resume patrol once other professional responders arrive on scene; additionally, warrant searches of persons on scene should be prohibited.
SARS-CoV-2 variants of concern and spike protein mutational dynamics in a Swedish cohort during 2021, studied by Nanopore sequencing
Authors: Mannsverk Steinar , Bergholm Julia , Palanisamy Navaneethan , Ellström Patrik , Kaden René , Lindh Johan , Lennerstrand Johan 
Published: October 2022

Abstract
Background
Since the beginning of the COVID-19 pandemic, new variants of significance to public health have emerged. Consequently, early detection of new mutations and variants through whole-genome sequencing remains crucial to assist health officials in employing appropriate public health measures.

Methods
We utilized the ARTIC Network SARS-CoV-2 tiled amplicon approach and Nanopore sequencing to sequence 4,674 COVID-19 positive patient samples from Uppsala County, Sweden, between week 15 and 52 in 2021. Using this data, we mapped the circulating variants of concern (VOC) in the county over time and analysed the Spike (S) protein mutational dynamics in the Delta variant throughout 2021.

Results
The distribution of the SARS-CoV-2 VOC matched the national VOC distribution in Sweden, in 2021. In the S protein of the Delta variant, we detected mutations attributable to variants under monitoring and variants of interest (e.g., E484Q, Q613H, Q677H, A222V and Y145H) and future VOC (e.g., T95I and Y144 deletion, which are signature mutations in the Omicron variant). We also frequently detected some less well-described S protein mutations in our Delta sequences, that might play a role in shaping future emerging variants. These include A262S, Q675K, I850L, Q1201H, V1228L and M1237I. Lastly, we observed that some of the Delta variant’s signature mutations were underrepresented in our study due to artifacts of the used bioinformatics tools, approach and sequencing method. We therefore discuss some pitfalls and considerations when sequencing SARS-CoV-2 genomes.

Conclusion
Our results suggest that genomic surveillance in a small, representative cohort can be used to make predictions about the circulating variants nationally. Moreover, we show that detection of transient mutations in currently circulating variants can give valuable clues to signature mutations of future VOC. Here we suggest six such mutations, that we detected frequently in the Delta variant during 2021. Lastly, we report multiple systematic errors that occurred when following the ARTIC Network SARS-CoV-2 tiled amplicon approach using the V3 primers and Nanopore sequencing, which led to the masking of some of the important signature mutations in the Delta sequences.
An area under the concentration–time curve threshold as a predictor of efficacy and nephrotoxicity for individualizing polymyxin B dosing in patients with carbapenem-resistant gram-negative bacteria
Authors: Yang Jing , Liu Shaohua , Lu Jingli , Sun Tongwen , Wang Peile , Zhang Xiaojian 
Published: October 2022

Abstract
Background
Evidence supports therapeutic drug monitoring of polymyxin B, but clinical data for establishing an area under the concentration–time curve across 24 h at steady state (AUCss,24 h) threshold are still limited. This study aimed to examine exposure–response/toxicity relationship for polymyxin B to establish an AUCss,24 h threshold in a real-world cohort of patients.

Methods
Using a validated Bayesian approach to estimate AUCss,24 h from two samples, AUCss,24 h threshold that impacted the risk of polymyxin B-related nephrotoxicity and clinical response were derived by classification and regression tree (CART) analysis and validated by Cox regression analysis and logical regression analysis.

Results
A total of 393 patients were included; acute kidney injury (AKI) was 29.0%, clinical response was 63.4%, and 30-day all-cause mortality was 35.4%. AUCss,24 h thresholds for AKI of > 99.4 mg h/L and clinical response of > 45.7 mg h/L were derived by CART analysis. Cox and logical regression analyses showed that AUCss,24 h of > 100 mg h/L was a significant predictor of AKI (HR 16.29, 95% CI 8.16–30.25, P < 0.001) and AUCss,24 h of ≥ 50 mg h/L (OR 4.39, 95% CI 2.56–7.47, P < 0.001) was independently associated with clinical response. However, these exposures were not associated with mortality. In addition, the correlation between trough concentration (1.2–2.8 mg/L) with outcomes was similar to AUCss,24 h.

Conclusions
For critically ill patients, AUCss,24 h threshold of 50–100 mg h/L was associated with decreased nephrotoxicity while assuring clinical efficacy. Therapeutic drug monitoring is recommended for individualizing polymyxin B dosing.
Elevated NRAS expression during DCIS is a potential driver for progression to basal-like properties and local invasiveness
Authors: Zheng Ze-Yi , Elsarraj Hanan , Lei Jonathan T. , Hong Yan , Anurag Meenakshi , Feng Long , Kennedy Hilda , Shen Yichao , Lo Flora , Zhao Zifan , Zhang Bing , Zhang Xiang H.-F. , Tawfik Ossama W. , Behbod Fariba , Chang Eric C. 
Published: October 2022

Abstract
Background
Ductal carcinoma in situ (DCIS) is the most common type of in situ premalignant breast cancers. What drives DCIS to invasive breast cancer is unclear. Basal-like invasive breast cancers are aggressive. We have previously shown that NRAS is highly expressed selectively in basal-like subtypes of invasive breast cancers and can promote their growth and progression. In this study, we investigated whether NRAS expression at the DCIS stage can control transition from luminal DCIS to basal-like invasive breast cancers.

Methods
Wilcoxon rank-sum test was performed to assess expression of NRAS in DCIS compared to invasive breast tumors in patients. NRAS mRNA levels were also determined by fluorescence in situ hybridization in patient tumor microarrays (TMAs) with concurrent normal, DCIS, and invasive breast cancer, and association of NRAS mRNA levels with DCIS and invasive breast cancer was assessed by paired Wilcoxon signed-rank test. Pearson’s correlation was calculated between NRAS mRNA levels and basal biomarkers in the TMAs, as well as in patient datasets. RNA-seq data were generated in cell lines, and unsupervised hierarchical clustering was performed after combining with RNA-seq data from a previously published patient cohort.

Results
Invasive breast cancers showed higher NRAS mRNA levels compared to DCIS samples. These NRAShigh lesions were also enriched with basal-like features, such as basal gene expression signatures, lower ER, and higher p53 protein and Ki67 levels. We have shown previously that NRAS drives aggressive features in DCIS-like and basal-like SUM102PT cells. Here, we found that NRAS-silencing induced a shift to a luminal gene expression pattern. Conversely, NRAS overexpression in the luminal DCIS SUM225 cells induced a basal-like gene expression pattern, as well as an epithelial-to-mesenchymal transition signature. Furthermore, these cells formed disorganized mammospheres containing cell masses with an apparent reduction in adhesion.

Conclusions
These data suggest that elevated NRAS levels in DCIS are not only a marker but can also control the emergence of basal-like features leading to more aggressive tumor activity, thus supporting the therapeutic hypothesis that targeting NRAS and/or downstream pathways may block disease progression for a subset of DCIS patients with high NRAS.
StOP? II trial: cluster randomized clinical trial to test the implementation of a toolbox for structured communication in the operating room—study protocol
Authors: Keller Sandra , Tschan Franziska , Semmer Norbert K. , Trelle Sven , Manser Tanja , Beldi Guido 
Published: October 2022

Abstract
Background
Surgical care, which is performed by intensely interacting multidisciplinary teams of surgeons, anesthetists, and nurses, remains associated with significant morbidity and mortality. Intraoperative communication has been shown to be associated with surgical outcomes, but tools ensuring efficient intraoperative communication are lacking. In a previous study, we developed the StOP?-protocol that fosters structured intraoperative communication. Before the critical phases of the operation, the responsible surgeon initiates and leads one or several StOP?s. During a StOP?, the surgeon informs about the progress of the operation (status), next steps and proximal goals (objectives), and possible problems (problems) and encourages all team members to voice their observations and ask questions (?). In a before-after study performed mainly in visceral surgery, we found effects of the StOP?-protocol on mortality, length of hospital stay, and reoperation. We intend to assess the impact of the StOP?-protocol in a cluster randomized trial, in a wider variety of surgical specialties (i.e., general, visceral, thoracic, vascular surgery, surgical urology, and gynecology). The primary hypothesis is that the consistent use of the StOP?-protocol by the main surgeon reduces patient mortality within 30 days after the operation. The secondary hypothesis is that the consistent use of the StOP?-protocol by the main surgeon reduces unplanned reoperations, length of hospital stay, and unplanned hospital readmissions.

Methods
This study is designed as a multicenter, cluster-randomized parallel-group trial. Board-certified surgeons of participating clinical departments will be randomized 1:1 to the StOP? intervention group or to the standard of care (control) group. The intervention group will undergo a training to use the StOP?-protocol and receive regular feedback on their compliance with the protocol. The surgeons in the control group will communicate as usual during their operations. The unit of observation will be operations performed by cluster surgeons. Consecutive patients will be enrolled over 4 months per cluster. A total of 400 surgeons will be recruited, and we expect to collect patient outcome data for 14,000 surgical procedures.

Discussion
The StOP?-protocol was designed as a tool to structure communication during surgical procedures. Testing its effects on patient outcomes will contribute to implementing evidenced-based interventions to reduce surgical complications.

Trial registration
ClinicalTrials.gov NCT05356962. Registered on May 2, 2022