bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

Abstract
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

AbstractThe 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

Abstract
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

AbstractCirculating 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

Abstract
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

AbstractBackgroundSepsis 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.MethodsMachine 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.ResultsThe 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.ConclusionCNN 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

AbstractBackgroundConventional 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.MethodsThe 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.ResultsThe 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.ConclusionsUnconventional 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

Abstract
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.