bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic accuracy and feasibility of a rapid SARS-CoV-2 antigen test in general practice – a prospective multicenter validation and implementation study
Authors: Rohde Jörn , Himmel Wolfgang , Hofinger Clemens , Lâm Thiên-Trí , Schrader Hanna , Wallstabe Julia , Kurzai Oliver , Gágyor Ildikó
Published: June 2022

Background

PCR testing is considered the gold standard for SARS-CoV-2 diagnosis but its results are earliest available hours to days after testing. Rapid antigen tests represent a diagnostic tool enabling testing at the point of care. Rapid antigen tests have mostly been validated by the manufacturer or in controlled laboratory settings only. External validation at the point of care, particularly in general practice where the test is frequently used, is needed. Furthermore, it is unclear how well point of care tests are accepted by the practice staff.

Methods

In this prospective multicenter validation study in primary care, general practitioners included adult individuals presenting with symptoms suggesting COVID-19. Each patient was tested by the general practitioner, first with a nasopharyngeal swab for the point of care test (Roche SARS-CoV-2 Rapid Antigen Test) and then with a second swab for PCR testing. Using the RT-PCR result as a reference, we calculated specificity, sensitivity, positive predictive value and negative predictive value, with their 95% confidence intervals. General practitioners and medical assistants completed a survey to assess feasibility and usefulness of the point of care tests.

Results

In 40 practices in Würzburg, Germany, 1518 patients were recruited between 12/2020 and 06/2021. The point of care test achieved a sensitivity of 78.3% and a specificity of 99.5% compared to RT-PCR. With a prevalence of 9.5%, the positive predictive value was 93.9% and the negative predictive value was 97.8%. General practitioners rated the point of care test as a helpful tool to support diagnostics in patients with signs and symptoms suggestive for infection, particularly in situations where decision on further care is needed at short notice.

Conclusion

The point of care test used in this study showed a sensitivity below the manufacturer’s specification (Sensitivity 96.25%) in the practice but high values for specificity and high positive predictive value and negative predictive value. Although widely accepted in the practice, measures for further patient management require a sensitive interpretation of the point of care test results.
Development and application of an electronic synoptic report for reporting and management of low-dose computed tomography lung cancer screening examination
Authors: Tremblay Alain , Ezer Nicole , Burrowes Paul , MacGregor John Henry , Lee Andrew , Armstrong Gavin A. , Pereira Raoul , Bristow Michael , Taylor Jana L. , MacEachern Paul , Taghizadeh Niloofar , Koetzler Rommy , Bedard Eric
Published: June 2022

Background

Interpretation of Low Dose CT scans and protocol driven management of findings is a key aspect of lung cancer screening program performance. Reliable and reproducible methods are needed to communicate radiologists’ interpretation to the screening program or clinicians driving management decision.

Methods

We performed an audit of a subset of dictated reports from the PANCAN study to assess for omissions. We developed an electronic synoptic reporting tool for radiologists embedded in a clinical documentation system software. The tool was then used for reporting as part of the Alberta Lung Cancer Screening Study and McGill University Health Centre Pilot Lung Cancer Screening Program.

Results

Fifty reports were audited for completeness. At least one omission was noted in 30 (70%) of reports, with a major omission (missing lobe, size, type of nodule in report or actionable incidental finding in recommendation section of report) in 24 (48%). Details of the reporting template and functionality such as automated nodule cancer risk assessment, Lung-RADS category assignment, auto-generated narrative type report as well as personalize participant results letter is provided. A description of the system’s performance in its application in 2815 CT reports is then summarized.

Conclusions

We found that narrative type radiologist reports for lung cancer screening CT examinations frequently lacked specific discrete data elements required for management. We demonstrate the successful implementation of a radiology synoptic reporting system for use in lung cancer screening, and the use of this information to drive program management and communications.
Serum biomarkers of neuroinflammation and blood-brain barrier leakage in amyotrophic lateral sclerosis
Authors: Cao Maize C. , Cawston Erin E. , Chen Grace , Brooks Collin , Douwes Jeroen , McLean Dave , Graham E. Scott , Dragunow Mike , Scotter Emma L.
Published: June 2022

Amyotrophic lateral sclerosis (ALS) is an incurable and rapidly progressive neurological disorder. Biomarkers are critical to understanding disease causation, monitoring disease progression and assessing the efficacy of treatments. However, robust peripheral biomarkers are yet to be identified. Neuroinflammation and breakdown of the blood-brain barrier (BBB) are common to familial and sporadic ALS and may produce a unique biomarker signature in peripheral blood. Using cytometric bead array (n = 15 participants per group (ALS or control)) and proteome profiling (n = 6 participants per group (ALS or control)), we assessed a total of 106 serum cytokines, growth factors, and BBB breakdown markers in the serum of control and ALS participants. Further, primary human brain pericytes, which maintain the BBB, were used as a biosensor of inflammation following pre-treatment with ALS serum. Principal components analysis of all proteome profile data showed no clustering of control or ALS sera, and no individual serum proteins met the threshold for statistical difference between ALS and controls (adjustedPvalues). However, the 20 most changed proteins between control and ALS sera showed a medium effect size (Cohen’s d = 0.67) and cluster analysis of their levels together identified three sample subsets; control-only, mixed control-ALS, and ALS-only. These 20 proteins were predominantly pro-angiogenic and growth factors, including fractalkine, BDNF, EGF, PDGF, Dkk-1, MIF and angiopoietin-2. S100β, a protein highly concentrated in glial cells and therefore a marker of BBB leakage when found in blood, was unchanged in ALS serum, suggesting that serum protein profiles were reflective of peripheral rather than CNS biofluids. Finally, primary human brain pericytes remained proliferative and their secretome was unchanged by chronic exposure to ALS serum. Our exploratory study suggests that individual serum cytokine levels may not be robust biomarkers in small studies of ALS, but that larger studies using multiplexed analysis of pro-angiogenic and growth factors may identify a peripheral signature of ALS pathogenesis.
Gardnerella vaginalis purulent meningitis in an adolescent male: a case report
Authors: Lu Hongji , Du Yaming , Pan Tao , Lou Zheng , Li Huiping , Liao Yingdi , Wang Lixin
Published: June 2022

Background

We report a rare case of Gardnerella vaginalis found in the cerebrospinal fluid of a young boy.

Case presentation

A 14-year-old boy was admitted to hospital with headache, vomiting, fever, drowsiness and positive meningeal irritation signs on examination. Cerebrospinal fluid (CSF) shows white blood cell and protein were elevated, and glucose was low. Traditional aerobic and anaerobic culture of CSF did not grow any organisms. However, metagenomic next-generation sequencing (mNGS) reveals G. vaginalis in his CSF. The patient was diagnosed with purulent meningitis, and treated with intravenous meropenem and linezolid for a week, followed by oral administration of amoxicillin for two weeks. He recovered without sequelae.

Conclusions

Purulent meningitis caused by Gardnerella vaginalis is extremely rare. Metagenomic next-generation sequencing of CSF should be highlighted for early diagnosis. With effective antibiotic treatment, the prognosis was excellent.
Development and validation of a prognostic scoring system for patients with colorectal cancer hepato-pulmonary metastasis: a retrospective study
Authors: Deng Shenghe , Jiang Zhenxing , Cao Yinghao , Gu Junnan , Mao Fuwei , Xue Yifan , Qin Le , Liu Ke , Wang Jiliang , Wu Ke , Cai Kailin
Published: June 2022

Background

Hepato-pulmonary metastasis of colorectal cancer (CRC) is a rare disease with poor prognosis. This study aims to establish a highly efficient nomogram model to predict overall survival (OS) and cancer-specific survival (CSS) in patients with colorectal cancer hepato-pulmonary metastasis (CRCHPM).

Methods

We retrospectively analyzed the data of patients with CRCHPM from SEER database and Wuhan Union Hospital Cancer Center (WUHCC). A total of 1250 CRCHPM patients were randomly assigned to the training, internal validation, and external validation cohorts from 2010 to 2016.Univariate and multivariate cox analysis were performed to identify independent clinicopathological predictors of OS and CSS, and a nomogram was constructed to predict OS and CSS in CRCHPM patients.

Results

A nomogram of OS was constructed based on seven independent predictors of age, degree of differentiation, T stage, chemotherapy, number of lsampled lymph nodes, number of positive lymph nodes, and tumor size. Nomogram showed favorable sensitivity in predicting OS at 1, 3 and 5 years, with area under the receiver operating characteristic curve (AUROC) values of 0.802, 0.759 and 0.752 in the training cohort;0.814, 0.769 and 0.716 in the internal validation cohort;0.778, 0.756 and 0.753 in the external validation cohort, respectively. A nomogram of CSS was constructed based on three independent predictors of T stage, chemotherapy, and tumor size. The AUROC values of 1, 3 and 5 years were 0.709,0.588,0.686 in the training cohort; 0.751, 0.648,0.666 in the internal validation cohort;0.781,0.588,0.645 in the external validation cohort, respectively. Calibration curves, Concordance index (C-index), and decision curve analysis (DCA) results revealed that using our model to predict OS and CSS is more efficient than other single clinicopathological characteristics.

Conclusion

A nomogram of OS and CSS based on clinicopathological characteristics can be conveniently used to predict the prognosis of CRCHPM patients.
The relationship between corneal biomechanical parameters and treatment outcomes of orthokeratology lenses
Authors: Li Xia , Xu Jianjiang , Hong Jiaxu , Yao Jing
Published: June 2022

Background

To evaluate changes in corneal biomechanical properties after long-term orthokeratology (OK) treatment and the factors affecting treatment outcomes.

Methods

Twenty-four myopic teenagers who wore OK lenses for more than 1 year were included. Twenty-three individuals of the same age and with the same spherical equivalent wearing single-vision spectacles (SVS) were enrolled as controls. After routine eye examinations, corneal biomechanical properties and axial length were measured. Parameters were compared between groups.

Results

Less axial elongation (AE) occurred in the OK group (P= 0.021). The OK group experienced a statistically significant decrease in the A1 deformation amplitude (P= 0.02), whole eye movement maximum (P= 0.026), and Ambrósio’s relational thickness to the horizontal profile (ARTh) (P< 0.001), and a statistically significant increase in the pachyslope (P< 0.001) and Corvis biomechanical index (P< 0.001). Smaller ARTh and a larger highest concavity deflection area resulted in a better refractive state. The inhibitory effect of AE was better for older patients with smaller ARTh.

Conclusions

Long-term OK treatment slowed myopia progression by reshaping the cornea. Smaller ARTh after OK lens wear indicated a better refractive state and slower AE and could predict OK lens treatment outcomes.
Respiratory viruses dynamics and interactions: ten years of surveillance in central Europe
Authors: Horemheb-Rubio Gibran , Eggeling Ralf , Schmeiβer Norbert , Pfeifer Nico , Lengauer Thomas , Gärtner Barbara C. , Prifert Christiane , Kochanek Matthias , Scheid Christoph , Adams Ortwin , Kaiser Rolf ,   Respiratory Virus Network, Kaiser Rolf , C. Gärtner Barbara , Weissbrich Benedikt , Adams Ortwin , Berger Annemarie , Palupsky Katrin , Huzly Daniela , Tiemann Carsten , Borena Wegene , Lindauer Andreas , Liebert Uwe Gerd , Siemens Hans-Joachim , Hofmann Jörg , Eis-Hübinger Anna-Maria , Grundmann Hajo , Kehlen Astrid , Oehme Albrecht , Schnitzler Paul , Kühn Joachim , Heim Albert , Sauerbrei Andreas , Schmidt Barbara , Beck Robert , Hoffmann Dieter , Michel Detlef , Nitschko Hans , Aepinus Christian , Dreier Jens , Puchhammer-Stoeckl Elisabeth , Kaup Theresa Popow , Redlberger Monika , Kessler Harald , Obermeier Martin , Weise Kerstin , Bartsch Patricia , Devide Annette , Niesters Bert , Kleines Michael , Krumbholz Andi , Meyer Thomas , Gohl Peter , G. Schüttler Christian , Gorgievski Meri , Pagarolas Andres Anton , Gulich Wolfgang , Ziegler Thomas , Wintsche Babett , Griego Marcena , Bossart Walter
Published: June 2022

Background

Lower respiratory tract infections are among the main causes of death. Although there are many respiratory viruses, diagnostic efforts are focused mainly on influenza. The Respiratory Viruses Network (RespVir) collects infection data, primarily from German university hospitals, for a high diversity of infections by respiratory pathogens. In this study, we computationally analysed a subset of the RespVir database, covering 217,150 samples tested for 17 different viral pathogens in the time span from 2010 to 2019.

Methods

We calculated the prevalence of 17 respiratory viruses, analysed their seasonality patterns using information-theoretic measures and agglomerative clustering, and analysed their propensity for dual infection using a new metric dubbed average coinfection exclusion score (ACES).

Results

After initial data pre-processing, we retained 206,814 samples, corresponding to 1,408,657 performed tests. We found that Influenza viruses were reported for almost the half of all infections and that they exhibited the highest degree of seasonality. Coinfections of viruses are frequent; the most prevalent coinfection was rhinovirus/bocavirus and most of the virus pairs had a positive ACES indicating a tendency to exclude each other regarding infection.

Conclusions

The analysis of respiratory viruses dynamics in monoinfection and coinfection contributes to the prevention, diagnostic, treatment, and development of new therapeutics. Data obtained from multiplex testing is fundamental for this analysis and should be prioritized over single pathogen testing.
Differential effect of prenatal exposure to the Great Ethiopian Famine (1983–85) on the risk of adulthood hypertension based on sex: a historical cohort study
Authors: Abate Kalkidan Hassen , Arage Getachew , Hassen Habtamu , Abafita Jemal , Belachew Tefera
Published: June 2022

Background

The consequence of the Great Ethiopian Famine (1983–1985) on mortality had been well documented. However, the long term assaults of the famine on adulthood health, particularly on the risk of hypertension, has never been documented. The aim of this study was twofold: to examine the association of prenatal-exposure to the Great Ethiopian Famine and hypertension in adulthood and investigate if there existed sex difference in the risk estimate.

Methods

Participants were recruited using multistage stratified random sampling and grouped as prenatal famine exposed and non-exposed cohorts based on their reported date of birth and current age. Independent sample T test was employed to compare continuous outcomes between the groups. A multivariable logistic regression was used to examine the association between prenatal famine exposure and risk of hypertension in adults.

Results

Compared to the non-exposed groups, prenatal famine exposed cohorts had higher systolic blood pressure by 1.05 mmHg, (95% CI 0.29, 4.42) and diastolic by 2.47 mmHg (95% CI 1.01, 3.95). In multivariable logistic regression analysis, both unadjusted (COR = 2.50; 1.575, 3.989) and adjusted model for covariates (OR: 2.306 95% CI (1.426, 3.72) indicated a positive association between prenatal famine exposure and the risk of adult hypertension. However, in sex disaggregated analysis, the positive association was only significant in females (AOR = 3.95 95% CI 1.76, 8.85) indicating nearly four folds of odds of hypertension among females, while the corresponding figure for males was not significant (AOR = 1.201 (0.69, 2.07).

Conclusions

Famine exposure during prenatal period could have differential impact on the development of hypertension based on sex, where adult exposed females had higher risk of hypertension as compared to males. Contextualized primary prevention programs with special focus on gender is critical undertaking in hunger spots and regions with historical famine.
One in ten ever-married women who visited health facilities for various reasons have pelvic organ prolapse in Harari regional state, Eastern Ethiopia
Authors: Abebe Dawit , Kure Mohammed Abdurke , Demssie Enku Afework , Mesfin Sinetibeb , Demena Melake , Dheresa Merga
Published: June 2022

Background

Pelvic organ prolapse remains a neglected public health problem in developing countries. The burden of pelvic organ prolapse varies by region and ranges from 9 to 20%. It poses an impact on women’s quality of life and affects their role at the community and family level. Although it has negative consequences and extensive burden, the true feature of pelvic organ prolapse is not well known among ever-married women attending health facilities for various reasons in the study area. Therefore, this study was aimed to assess the magnitude of pelvic organ prolapse and associated factors among ever-married women attending health care services in public Hospitals, Eastern Ethiopia.

Methods

A facility-based cross-sectional study design was conducted from March 4th to April 5th, 2020 among 458 ever-married women attending public Hospitals in Harar town, Eastern Ethiopia. The study subjects were selected through systematic sampling. The data were collected using a structured questionnaire through face-to-face interviews. Data were analyzed using SPSS version 22 (IBM SPSS Statistics, 2013). The prevalence was reported by proportion and summary measures. Predictors were assessed using a multivariable logistic regression analysis model and reported using an adjusted odds ratio with 95% CI. Statistical significance was declared at p-value < 0.05.

Result

Of 458 women enrolled in the study, 10.5% of them had pelvic organ prolapse based on women’s reporting of symptoms. History of lifting heavy objects [AOR = 3.22, 95% CI (1.56, 6.67)], history of chronic cough [AOR = 2.51, 95% CI (1.18, 5.31)], maternal age of greater than or equal to 55 years [AOR = 3.51, 95% CI (1.04, 11.76)], history chronic constipation (AOR = 3.77, 95% CI (1.54, 9.22) and no history of contraceptive utilization [AOR = 2.41, 95% CI (1.13, 5.05)] were significantly associated with pelvic organ prolapse.

Conclusion

In this study, one in ten ever-married women who visited health facilities for various reasons have pelvic organ prolapse. Modifiable and non-modifiable risk factors were identified. This result provides a clue to give due consideration to primary and secondary prevention through various techniques.
A qualitative enquiry into dental students’ perceptions of dentistry as a career choice in the State of Qatar
Authors: Daud Alaa , Matoug-Elwerfelli Manal , Du Xiangyun , Ali Kamran
Published: June 2022

Background

Career choice is a complex, multifaceted process affecting all aspects of life. Motivational factors of aspiring dentists are crucial to inform institutions and aid with the admission process. The aim of this study was to explore undergraduate dental students’ perceived motivation for their career choice in the first dental institution in the State of Qatar to bridge the gap in knowledge in this area.

Methods

Homogeneous purposive sampling technique was employed to collect data from all year 2 and year 3 undergraduate dental students to gain a deeper insight into their motivation of career choice. An explorative qualitative method using face-to-face focus group sessions were utilized. All focus groups were conducted in English and contained a moderator and observer. A topic guide was used to ensure data collection standardization. Participants’ views were recorded and filed notes obtained. Data was transcribed and analysis performed utilizing an inductive thematic approach.

Results

A total of 34 students (89.5%) from year 2 and 3 participated in the focus groups. Data analysis revealed six main themes emerging from this study namely; altruism and patient care, family influence factors, childhood aspirations, hands-on practical skills, professional and social status, and the opportunity to reconsider and transfer. Based on frequency, altruism, opportunities to learn hands-on practical skills and professional status appeared to be the main drivers influencing students’ choice of dentistry as a professional career.

Conclusion

This qualitative study presents the first national study providing insightful information regarding current undergraduate dental students’ decision process in relation to their profession selection, and shows that opportunities to provide patient care seems to be the key to motivation. There was also a strong inclination towards performing hands-on practical tasks as a dentist, and developing a professional status. Interestingly, financial reward did not feature as a motivational factor in this study. The study highlights the influence of socio-cultural and economic factors on choosing dentistry as a career. This data could help dental institutions better understand future applicant’s motivations to join dentistry and assist with the academic recruitment/admission process and targeting students with a potential to excel in the profession.
COVID-19 infection control education for medical students undergoing clinical clerkship: a mixed-method approach
Authors: Kasai Hajime , Saito Go , Ito Shoichi , Kuriyama Ayaka , Kawame Chiaki , Shikino Kiyoshi , Takeda Kenichiro , Yahaba Misuzu , Taniguchi Toshibumi , Igari Hidetoshi , Sakao Seiichiro , Suzuki Takuji
Published: June 2022

Background

Coronavirus disease (COVID-19) has induced an urgent need to train medical students not only in infection prevention control but also in the treatment of infectious diseases, including COVID-19. This study evaluates the impact of simulated clinical practice with peer role-plays and a lecture on clinical education for COVID-19.

Methods

The sample for the study included 82 fourth- and fifth-year medical students undergoing clinical clerkship in respiratory medicine. They answered questionnaires and participated in semi-structured focus group interviews (FGIs) regarding the advantages of simulated clinical practice with peer role-plays and lectures on clinical education for COVID-19.

Results

A total of 75 students participated in the COVID-19 education program between January and November 2021. The responses to the questionnaire revealed that the satisfaction level of students with COVID-19 education was high. No significant change was found among students concerning fear of COVID-19 before and after the program. The degree of burden of handling information on COVID-19 reduced significantly, while the degree with respect to the use of personal protective equipment (PPE), including appropriate wearing and removing of PPE, and care of patients with confirmed COVID-19 while taking steps to prevent infection, exhibited a decreasing trend. Nine FGIs were conducted (n = 74). The advantages of simulated clinical practice were segregated into five categories (infection prevention control, educational methods, burden on healthcare providers, self-reflection, and fear of COVID-19); and that of the lecture were segregated into four categories (information literacy, knowledge of COVID-19, educational methods, and self-reflection).

Conclusions

Simulated clinical practice with peer role-plays and the lecture pertaining to COVID-19 can prove to be efficient and safe methods for learning about COVID-19 infection and prevention control for medical students. They can reduce the burden of COVID-19 patients’ care. Moreover, they can also provide an opportunity for self-reflection, realize the burden of medical care, and acquire relevant information.
One-year follow-up healthcare costs of patients diagnosed with skin cancer in Germany: a claims data analysis
Authors: Speckemeier Christian , Pahmeier Kathrin , Trocchi Pietro , Schuldt Katrin , Lax Hildegard , Nonnemacher Michael , Dröge Patrik , Stang Andreas , Wasem Jürgen , Neusser Silke
Published: June 2022

Background

Routine skin cancer screening (SCS) is covered by the German statutory health insurance (SHI) since 2008. The objective of this study was to compare direct healthcare costs between patients in whom skin cancer was detected by routine SCS and patients in whom skin cancer was not detected by routine SCS.

Methods

A retrospective observational study of administrative claims data from a large German SHI was performed. Patients with a diagnosis of malignant melanoma (MM) or non-melanoma skin cancer (NMSC) diagnosed in 2014 or 2015 were included. Costs were obtained for one year before and one year after diagnosis and analyzed in a difference-in-differences approach using regression models. Frequency matching was applied and risk adjustment was performed. Additional analyses were conducted, separately for specific age groups, excluding persons who died during the observation period and without taking costs for screening into consideration.

Results

A total of 131,801 patients were included, of whom 13,633 (10.3%) had a diagnosis of MM and 118,168 (89.7%) had a diagnosis of NMSC. The description of total costs (without risk adjustment) shows lower mean total costs among patients whose skin cancer was detected via routine SCS compared to patients in whom skin cancer was not detected by routine SCS (MM: €5,326 (95% confidence interval (CI) €5,073; €5,579) vs. €9,038 (95% CI €8,629; €9,448); NMSC: €4,660 (95% CI €4,573; €4,745) vs. €5,890 (95% CI €5,813; €5,967)). Results of the regression analysis show cost savings of 18.8% (95% CI -23.1; -8.4) through routine SCS for patients with a diagnosis of MM. These cost savings in MM patients were more pronounced in patients younger than 65 years of age. For patients with a diagnosis of NMSC, the analysis yields a non-substantial increase in costs (2.5% (95% CI -0.1; 5.2)).

Conclusion

Cost savings were detected for persons with an MM diagnosed by routine SCS. However, the study could not detect lower costs due to routine SCS in the large fraction of persons with a diagnosis of NMSC. These results offer important insights into the cost structure of the routine SCS and provide opportunities for refinements.
Lipid droplet dynamics in healthy and pyometra-affected canine endometrium
Authors: Leitner Natascha , Hlavaty Juraj , Heider Susanne , Ertl Reinhard , Gabriel Cordula , Walter Ingrid
Published: June 2022

Background

Accumulation of lipid droplets (LDs) was recently observed in pyometra-affected uteri. As data about their nature and function are missing we intended to compare the localization, quality and quantity of LDs in canine healthy and pyometra-affected tissues and in an in vitro model.

Methods and results

We characterized LDs in healthy and pyometra uterine tissue samples as well as in canine endometrial epithelial cells (CEECs) in vitro by means of histochemistry, immunohistochemistry, transmission electron microscopy, western blot, and RT-qPCR. Oil Red O (ORO) staining and quantification as well as p-phenylenediamine staining showed a higher number of LDs in epithelial cells of pyometra samples. Immunohistochemistry revealed that the amount of LDs coated by perilipin2 (PLIN2) protein was also higher in pyometra samples. Transmission electron microscopy showed an increase of LD size in surface and glandular epithelial cells of pyometra samples. In cell culture experiments with CEECs, supplementation with oleic acid alone or in combination with cholesterol lead to an increased LD accumulation. The expression of PLIN2 at protein and mRNA level was also higher upon oleic acid supplementation. Most LDs were double positive for ORO and PLIN2. However, ORO positive LDs lacking PLIN2 coating or LDs positive for PLIN2 but containing a lipid class not detectable by ORO staining were identified.

Conclusions

We found differences in the healthy and pyometra-affected endometrium with respect to LDs size. Moreover, several kinds of LDs seem to be present in the canine endometrium. In vitro studies with CEECs could show their responsiveness to external lipids. Since epithelial cells reacted only to oleic acid stimulation, we assume that the cyclic lipid accumulation in the canine endometrium is based mainly on triglycerides and might serve as energy provision for the developing early embryo. Further studies are necessary to verify the complex role of lipids in the healthy and pyometra-affected canine endometrium.
How has mass drug administration with dihydroartemisinin-piperaquine impacted molecular markers of drug resistance? A systematic review
Authors: Moss Sophie , Mańko Emilia , Krishna Sanjeev , Campino Susana , Clark Taane G. , Last Anna
Published: June 2022

The World Health Organization (WHO) recommends surveillance of molecular markers of resistance to anti-malarial drugs. This is particularly important in the case of mass drug administration (MDA), which is endorsed by the WHO in some settings to combat malaria. Dihydroartemisinin-piperaquine (DHA-PPQ) is an artemisinin-based combination therapy which has been used in MDA. This review analyses the impact of MDA with DHA-PPQ on the evolution of molecular markers of drug resistance. The review is split into two parts. Section I reviews the current evidence for different molecular markers of resistance to DHA-PPQ. This includes an overview of the prevalence of these molecular markers in Plasmodium falciparum Whole Genome Sequence data from the MalariaGEN Pf3k project. Section II is a systematic literature review of the impact that MDA with DHA-PPQ has had on the evolution of molecular markers of resistance. This systematic review followed PRISMA guidelines. This review found that despite being a recognised surveillance tool by the WHO, the surveillance of molecular markers of resistance following MDA with DHA-PPQ was not commonly performed. Of the total 96 papers screened for eligibility in this review, only 20 analysed molecular markers of drug resistance. The molecular markers published were also not standardized. Overall, this warrants greater reporting of molecular marker prevalence following MDA implementation. This should include putative pfcrt mutations which have been found to convey resistance to DHA-PPQ in vitro.
Treatment-seeking behaviour, awareness and preventive practice toward malaria in Abu Ushar, Gezira state, Sudan: a household survey experience from a rural area
Authors: Hasabo Elfatih A. , Khalid Rawan I. , Mustafa Ghassan E. , Taha Ruaa E. , Abdalla Riham S. , Mohammed Reham A. , Haroun Mazin S. , Adil Rawaa , Khalil Riham A. , Mansour Rawaa M. , Mohamed Reham K. , Awadalla Heitham
Published: June 2022

Background

Usage of mosquito bed nets and the practice of other prevention methods are essential for the prevention of malaria in endemic areas. Proper community knowledge about malaria and prompt treatment-seeking behaviour for early diagnosis and treatment are crucial for eliminating the disease. This study aimed to assess the awareness, treatment-seeking behaviour, and prevention practices towards malaria in Abu Ushar, Gezira State, Sudan.

Methods

A community-based, cross-sectional study was conducted in March 2021, including 310 households in Abu Ushar, Aljazeera, Sudan. Data were collected through face-to-face interviews with head of the household using an interviewer-administered questionnaire. Data were entered and analysed using R software.

Results

A total of 310 households were enrolled in this study. Sixty per cent had children under the age of 5 years. The majority of these households (94.8%) had a history of malaria in the past 12 months. Overall, awareness of malaria was good; 197 (63.5%) households had bed nets in their houses; 75.8% of total households identified fever with shivering as a symptom of malaria. Regarding treatment-seeking behaviour, 77.9% seek treatment from the nearby primary health centre, and 60% seek treatment within the first day. Only 45.3% stated that everyone in the household sleeps under bed nets.

Conclusion

High awareness about malaria and preventive measures was found among participants in households. Most households had previous infections with malaria. Therefore, an interventional programme should be established in this area to reduce this high rate of malaria.
A pump-free and high-throughput microfluidic chip for highly sensitive SERS assay of gastric cancer-related circulating tumor DNA via a cascade signal amplification strategy
Authors: Cao Xiaowei , Ge Shengjie , Hua Weiwei , Zhou Xinyu , Lu Wenbo , Gu Yingyan , Li Zhiyue , Qian Yayun
Published: June 2022

Circulating tumour DNA (ctDNA) has emerged as an ideal biomarker for the early diagnosis and prognosis of gastric cancer (GC). In this work, a pump-free, high-throughput microfluidic chip coupled with catalytic hairpin assembly (CHA) and hybridization chain reaction (HCR) as the signal cascade amplification strategy (CHA–HCR) was developed for surface-enhanced Raman scattering (SERS) assays of PIK3CA E542K and TP53 (two GC-related ctDNAs). The chip consisted of six parallel functional units, enabling the simultaneous analysis of multiple samples. The pump-free design and hydrophilic treatment with polyethylene glycol (PEG) realized the automatic flow of reaction solutions in microchannels, eliminating the dependence on external heavy-duty pumps and significantly improving portability. In the reaction region of the chip, products generated by target-triggered CHA initiated the HCR, forming long nicked double-stranded DNA (dsDNA) on the Au nanobowl (AuNB) array surface, to which numerous SERS probes (Raman reporters and hairpin DNA-modified Cu2O octahedra) were attached. This CHA–HCR strategy generated numerous active “hot spots” around the Cu2O octahedra and AuNB surface, significantly enhancing the SERS signal intensity. Using this chip, an ultralow limit of detection (LOD) for PIK3CA E542K (1.26 aM) and TP53 (2.04 aM) was achieved, and the whole process was completed within 13 min. Finally, a tumour-bearing mouse model was established, and ctDNA levels in mouse serum at different stages were determined. To verify the experimental accuracy, the gold-standard qRT–PCR assay was utilized, and the results showed a high degree of consistency. Thus, this rapid, sensitive and cost-effective SERS microfluidic chip has potential as an ideal detection platform for ctDNA monitoring.
Is letrozole during ovarian stimulation useful in breast cancer patients undergoing fertility preservation to reduce early luteal progesterone levels following GnRH-agonist trigger?
Authors: Lalami Imane , Labrosse Julie , Cedrin-Durnerin Isabelle , Comtet Marjorie , Vinolas Claire , Krief Fabien , Sifer Christophe , Peigne Maeliss , Grynberg Michael
Published: June 2022

Background

In absence of contraindication, breast cancer patients of reproductive age can undergo fertility preservation with controlled ovarian stimulation for oocyte/embryo cryopreservation before the administration of potentially gonadotoxic treatments. High hormonal levels induced by ovarian stimulation might have an adverse impact on hormone-positive breast cancer. Whether letrozole supplementation during ovarian stimulation (COSTLES) reduces serum progesterone levels after GnRHa trigger remains unknown. We aimed to determine whether COSTLES might be useful for breast cancer patients undergoing fertility preservation to reduce early luteal progesterone levels following GnRH-agonist (GnRHa)trigger.

Methods

All women who underwent COS with GnRH antagonist protocol with GnRHa trigger were included. Serum progesterone level measured 12 h after GnRHa trigger was compared between patients undergoing COS with letrozole supplementation (COSTLES group) and patients undergoing COS without letrozole (Control group) for fertility preservation purposes.

Results

A total of 246 patients were included, of which 84 patients (34.1%) in the COSTLES group and 162 patients (65.6%) in the Control group. All patients in the COSTLES group were BC patients (n = 84, 100%), while the Control group included 77 BC patients (47.5%). Patients in the two groups were comparable. The mean number of oocytes recovered and vitrified at metaphase 2 stage did not significantly differ between the two groups. Serum progesterone levels on the day after GnRHa trigger were significantly lower in the COSTLES group (8.6 ± 0.7 vs. 10.5 ± 0.5 ng/mL, respectively, p < 0.03), as well as serum E2 levels (650.3 ± 57.7 vs. 2451.4.0 ± 144.0 pg/mL, respectively, p < 0.01). However, the GnRHa-induced LH surge was significantly higher in in the COSTLES group (71.9 ± 4.6 vs. 51.2 ± 2.6 UI/L, respectively, p < 0.01).

Conclusions

Our results show that COSTLES for fertility preservation in breast cancer patients using GnRHa trigger reduces serum progesterone levels compared to ovarian stimulation without letrozole. These findings encourage the use of COSTLES in this context to decrease the potential deleterious effect of elevated hormonal levels on hormone-positive breast cancer.
Clinical applications of machine learning in the survival prediction and classification of sepsis: coagulation and heparin usage matter
Authors: Guo Fei , Zhu Xishun , Wu Zhiheng , Zhu Li , Wu Jianhua , Zhang Fan
Published: June 2022

Background

Sepsis is a life-threatening syndrome eliciting highly heterogeneous host responses. Current prognostic evaluation methods used in clinical practice are characterized by an inadequate effectiveness in predicting sepsis mortality. Rapid identification of patients with high mortality risk is urgently needed. The phenotyping of patients will assistant invaluably in tailoring treatments.

Methods

Machine learning and deep learning technology are used to characterize the patients’ phenotype and determine the sepsis severity. The database used in this study is MIMIC-III and MIMIC-IV (‘Medical information Mart for intensive care’) which is a large, public, and freely available database. The K-means clustering is used to classify the sepsis phenotype. Convolutional neural network (CNN) was used to predict the 28-day survival rate based on 35 blood test variables of the sepsis patients, whereas a double coefficient quadratic multivariate fitting function (DCQMFF) is utilized to predict the 28-day survival rate with only 11 features of sepsis patients.

Results

The patients were grouped into four clusters with a clear survival nomogram. The first cluster (C_1) was characterized by low white blood cell count, low neutrophil, and the highest lymphocyte proportion. C_2 obtained the lowest Sequential Organ Failure Assessment (SOFA) score and the highest survival rate. C_3 was characterized by significantly prolonged PTT, high SIC, and a higher proportion of patients using heparin than the patients in other clusters. The early mortality rate of patients in C_3 was high but with a better long-term survival rate than that in C_4. C_4 contained septic coagulation patients with the worst prognosis, characterized by slightly prolonged partial thromboplastin time (PTT), significantly prolonged prothrombin time (PT), and high septic coagulation disease score (SIC). The survival rate prediction accuracy of CNN and DCQMFF models reached 92% and 82%, respectively. The models were tested on an external dataset (MIMIC-IV) and achieved good performance. A DCQMFF-based application platform was established for fast prediction of the 28-day survival rate.

Conclusion

CNN and DCQMFF accurately predicted the sepsis patients’ survival, while K-means successfully identified the phenotype groups. The distinct phenotypes associated with survival, and significant features correlated with mortality were identified. The findings suggest that sepsis patients with abnormal coagulation had poor outcomes, abnormal coagulation increase mortality during sepsis. The anticoagulation effects of appropriate heparin sodium treatment may improve extensive micro thrombosis-caused organ failure.
Evaluation of the value of conventional and unconventional lipid parameters for predicting the risk of diabetes in a non-diabetic population
Authors: Sheng Guotai , Kuang Maobin , Yang Ruijuan , Zhong Yanjia , Zhang Shuhua , Zou Yang
Published: June 2022

Background

Conventional and unconventional lipid parameters are associated with diabetes risk, the comparative studies on lipid parameters for predicting future diabetes risk, however, are still extremely limited, and the value of conventional and unconventional lipid parameters in predicting future diabetes has not been evaluated. This study was designed to determine the predictive value of conventional and unconventional lipid parameters for the future development of diabetes.

Methods

The study was a longitudinal follow-up study of 15,464 participants with baseline normoglycemia. At baseline, conventional lipid parameters such as low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) were measured/calculated, and unconventional lipid parameters such as non-HDL-C, remnant cholesterol (RC), LDL/HDL-C ratio, TG/HDL-C ratio, non-HDL/HDL-C ratio, TC/HDL-C ratio and RC/HDL-C ratio were calculated. Hazard ratio (HR) and 95% confidence interval (CI) were estimated by Cox proportional hazard regression adjusting for demographic and diabetes-related risk factors. The predictive value and threshold fluctuation intervals of baseline conventional and unconventional lipid parameters for future diabetes were evaluated by the time-dependent receiver operator characteristics (ROC) curve.

Results

The incidence rate of diabetes was 3.93 per 1000 person-years during an average follow-up period of 6.13 years. In the baseline non-diabetic population, only TG and HDL-C among the conventional lipid parameters were associated with future diabetes risk, while all the unconventional lipid parameters except non-HDL-C were significantly associated with future diabetes risk. In contrast, unconventional lipid parameters reflected diabetes risk better than conventional lipid parameters, and RC/HDL-C ratio was the best lipid parameter to reflect the risk of diabetes (HR: 6.75, 95% CI 2.40–18.98). Sensitivity analysis further verified the robustness of this result. Also, time-dependent ROC curve analysis showed that RC, non-HDL/HDL-C ratio, and TC/HDL-C ratio were the best lipid parameters for predicting the risk of medium-and long-term diabetes.

Conclusions

Unconventional lipid parameters generally outperform conventional lipid parameters in assessing and predicting future diabetes risk. It is suggested that unconventional lipid parameters should also be routinely evaluated in clinical practice.
Persistent cortical and white matter inflammation after therapeutic hypothermia for ischemia in near-term fetal sheep
Authors: Zhou Kelly Q. , Bennet Laura , Wassink Guido , McDouall Alice , Curtis Maurice A. , Highet Blake , Stevenson Taylor J. , Gunn Alistair J. , Davidson Joanne O.
Published: June 2022

Background

Therapeutic hypothermia significantly improves outcomes after moderate–severe hypoxic-ischemic encephalopathy (HIE), but it is partially effective. Although hypothermia is consistently associated with reduced microgliosis, it is still unclear whether it normalizes microglial morphology and phenotype.

Methods

Near-term fetal sheep (n = 24) were randomized to sham control, ischemia-normothermia, or ischemia-hypothermia. Brain sections were immunohistochemically labeled to assess neurons, microglia and their interactions with neurons, astrocytes, myelination, and gitter cells (microglia with cytoplasmic lipid granules) 7 days after cerebral ischemia. Lesions were defined as areas with complete loss of cells. RNAscope® was used to assess microglial phenotype markers CD86 and CD206.

Results

Ischemia-normothermia was associated with severe loss of neurons and myelin (p < 0.05), with extensive lesions, astrogliosis and microgliosis with a high proportion of gitter cells (p < 0.05). Microglial wrapping of neurons was present in both the ischemia groups. Hypothermia improved neuronal survival, suppressed lesions, gitter cells and gliosis (p < 0.05), and attenuated the reduction of myelin area fraction. The “M1” marker CD86 and “M2” marker CD206 were upregulated after ischemia. Hypothermia partially suppressed CD86 in the cortex only (p < 0.05), but did not affect CD206.

Conclusions

Hypothermia prevented lesions after cerebral ischemia, but only partially suppressed microglial wrapping and M1 marker expression. These data support the hypothesis that persistent upregulation of injurious microglial activity may contribute to partial neuroprotection after hypothermia, and that immunomodulation after rewarming may be an important therapeutic target.
Intermittent theta-burst stimulation improves motor function by inhibiting neuronal pyroptosis and regulating microglial polarization via TLR4/NFκB/NLRP3 signaling pathway in cerebral ischemic mice
Authors: Luo Lu , Liu Meixi , Fan Yunhui , Zhang Jingjun , Liu Li , Li Yun , Zhang Qiqi , Xie Hongyu , Jiang Congyu , Wu Junfa , Xiao Xiao , Wu Yi
Published: June 2022

Background

Neuronal pyroptosis and neuroinflammation with excess microglial activation are widely involved in the early pathological process of ischemic stroke. Repetitive transcranial magnetic stimulation (rTMS), as a non-invasive neuromodulatory technique, has recently been reported to be anti-inflammatory and regulate microglial function. However, few studies have elucidated the role and mechanism of rTMS underlying regulating neuronal pyroptosis and microglial polarization.

Methods

We evaluated the motor function in middle cerebral artery occlusion/reperfusion (MCAO/r) injury mice after 1-week intermittent theta-burst rTMS (iTBS) treatment in the early phase with or without depletion of microglia by colony-stimulating factor 1 receptor (CSF1R) inhibitor treatment, respectively. We further explored the morphological and molecular biological alterations associated with neuronal pyroptosis and microglial polarization via Nissl, EdU, TTC, TUNEL staining, electron microscopy, multiplex cytokine bioassays, western blot assays, immunofluorescence staining and RNA sequencing.

Results

ITBS significantly protected against cerebral ischemia/reperfusion (I/R) injury-induced locomotor deficits and neuronal damage, which probably relied on the regulation of innate immune and inflammatory responses, as evidenced by RNA sequencing analysis. The peak of pyroptosis was confirmed to be later than that of apoptosis during the early phase of stroke, and pyroptosis was mainly located and more severe in the peri-infarcted area compared with apoptosis. Multiplex cytokine bioassays showed that iTBS significantly ameliorated the high levels of IL-1β, IL-17A, TNF-α, IFN-γ in MCAO/r group and elevated the level of IL-10. ITBS inhibited the expression of neuronal pyroptosis-associated proteins (i.e., Caspase1, IL-1β, IL-18, ASC, GSDMD, NLRP1) in the peri-infarcted area rather than at the border of infarcted core. KEGG enrichment analysis and further studies demonstrated that iTBS significantly shifted the microglial M1/M2 phenotype balance by curbing proinflammatory M1 activation (Iba1+/CD86+) and enhancing the anti-inflammatory M2 activation (Iba1+/CD206+) in peri-infarcted area via inhibiting TLR4/NFκB/NLRP3 signaling pathway. Depletion of microglia using CSF1R inhibitor (PLX3397) eliminated the motor functional improvements after iTBS treatment.

Conclusions

rTMS could alleviate cerebral I/R injury induced locomotor deficits and neuronal pyroptosis by modulating the microglial polarization. It is expected that these data will provide novel insights into the mechanisms of rTMS protecting against cerebral I/R injury and potential targets underlying neuronal pyroptosis in the early phase of stroke.