bluuebunny/crossref_metadata_2025_split huggingface dataset:
Problem-based learning in medical degree teaching: a scoping review
Authors: Trullas Joan Carles , Blay Carles , Sarri Elisabet , Pujol Ramon 
Published: May 2021

Abstract
Problem-based learning (PBL) is a pedagogical approach that shifts the role of the teacher to the student (student-centred) and is based on self-directed learning. Although PBL has been adopted in undergraduate and postgraduate medical education, the effectiveness of the method is still under discussion. We employed a scoping review to appraise available international evidence concerning to the effectiveness and usefulness of PBL methodology in undergraduate medical teaching programs. We applied the Arksey and O’Malley framework to undertake a scoping review. A search of literature published in English and Spanish identified one hundred and twenty four publications eligible for this review. Despite the fact that this review includes many studies, their design is heterogeneous and only a few provide a high scientific evidence methodology (randomized design and/or systematic review with meta-analysis). Furthermore, most are single-center experiences with small sample size and there are no large multi-center studies. PBL methodology obtains a high level of satisfaction, especially among students. It is more effective than other more traditional (or lecture-based methods) at improving social and communication skills, problem-solving and self-learning skills. Knowledge retention and academic performance are no worse (and in many studies are better) than with traditional methods. PBL is not universally widespread, probably because it requires greater human resources and continuous training for its implementation. More comparative and randomized studies and/or other systematic reviews and meta-analysis are required to determine which educational strategies are the most suitable for training the doctors of the future.
Pre-lacteal Feeding Among Infants Within the First Week of Birth in Eastern Uganda: Evidence From a Health Facility-based Cross-sectional Study
Authors: Akello Rachael , Kimuli Derrick , Okoboi Stephen , Komuhangi Alimah , Izudi Jonathon 
Published: May 2021

Abstract
Background: Pre-lacteal feeding hinders early initiation of breastfeeding and exclusive breastfeeding but is understudied in Uganda. We examined the prevalence and factors associated with pre-lacteal feeding among postpartum mothers in Kamuli district in rural eastern Uganda.Methods: We conducted a cross-sectional study at four large healthcare facilities and randomly sampled mother-baby pairs attending postnatal care clinics. Pre-lacteal feeding was defined as giving anything to eat or drink to a newborn other than breast milk within the first 0-3 days of life. Data were collected using a researcher-administered questionnaire and summarized using frequencies and percentages. The Chi-squared, Fisher’s exact, and Student’s t-tests were used for comparison while the factors independently associated with pre-lacteal feeding were determined using modified Poisson regression analysis, reported as adjusted prevalence risk ratio (aPRR) with corresponding 95% confidence intervals (CI). Results: Of 875 participants enrolled, 319 (36.5%) practiced pre-lacteal feeding. Pre-lacteal feeding was associated with being unemployed (aPRR, 0.70; 95% CI, 0.50-0.91), married (aPRR, 0.71; 95% CI, 0.58-0.87), receiving health education on infant feeding practices (aPRR, 0.72; 95% CI, 0.60-0.86), spontaneous vaginal delivery (aPRR, 0.76; 95% CI, 0.61-0.95), health facility delivery (aPRR, 0.73; 95% CI, 0.60-0.89), knowing that pre-lacteal feeding could lead to difficulties in breathing (aPRR, 0.70; 95% CI0.57-0.86), attendance of antenatal care at public health facility (aPRR, 2.41; 95% CI, 1.71-3.39), and a travel distance of 5 km or beyond from home to health facility (aPRR, 1.46; 95% CI, 1.23-1.72).Conclusion: We observed a high prevalence of pre-lacteal feeding among postpartum mothers in rural eastern Uganda. Pre-lacteal feeding is less likely among the unemployed and married mothers, those who received health education on infant feeding practices, had a spontaneous vaginal delivery, had delivered in a health facility, and knew that pre-lacteal feeding could lead to breathing difficulties in the newborn. Conversely, pre-lacteal feeding is more likely among mothers who attend antenatal care visits at public health facilities and those who travel 5 km or beyond to access health facilities.
Cathelicidin Protects the Brain from Mitochondrial DNA Damage in Health, but not Following Septic Shock
Authors: barbeiro Denise Frediani , Ariga Suely Kubo , Barbeiro Hermes Vieira , Souza-Pinto Nadja C , Silva Fabiano Pinheiro da 
Published: May 2021

Abstract
Recent discoveries have demonstrated that mitochondria play a critical role in innate immune signaling. By the other hand, immune responses may lead to mitochondrial deregulation. Cathelicidins play a critical role in innate immunity, promoting poorly understood cellular responses that may enhance or inhibit several signaling pathways, depending on the health conditions and subjacent microenvironment.Here, we investigated the role of CRAMP, the murine cathelicidin, in healthy mice and following experimental sepsis. We found that sepsis induces significant mitochondrial DNA damage in the prefrontal cortex and that cathelicidin protects the brain from this kind of damage in healthy animals, but not following septic shock.
Ursolic acid reverses liver fibrosis by inhibiting NOX4/NLRP3 inflammasome pathways and bacterial dysbiosis
Authors: Liu Qi , Nie Yuan , Zhang Wang , Wan Yipeng , Huang Chenkai , Zhu Xuan 
Published: May 2021

Abstract
IntroductionActivation of the NOX4/NLRP3 inflammasome pathway has been associated with fibrosis in other organs. An imbalance in intestinal bacteria is an important driving factor of liver fibrosis through the liver-gut axis. This study aimed to explore whether the effect of ursolic acid (UA) on liver fibrosis was associated with the NOX4/NLRP3 inflammasome pathways and intestinal bacteriaMethodsWild-type (WT), NLRP3−/−, and NOX4−/− mice and AP-treated mice were injected with CCL4 and treated with or without UA.ResultUA alleviated liver fibrosis and the expression of NOX4 and NLRP3 was significantly inhibited by UA treatment. Even after CCL4 injection, liver damage and fibrosis-related factors were significantly decreased in NLRP3−/−, NOX4−/−, and AP-treated mice. Importantly, the expression of NLRP3 was obviously inhibited in NOX4−/− and AP-treated mice. In addition, the diversity of intestinal bacteria and the abundance of probiotics in NLRP3−/− and NOX4−/− mice was significantly higher than those in WT mice.ConclusionThe NOX4/NLRP3 inflammasome pathway plays a crucial role in liver fibrosis and is closely associated with the beneficial effect of UA. The mechanism by which the NOX4/NLRP3 pathway is involved in liver fibrosis may be associated with disordered intestinal bacteria.
Gm12664-201, A Pseudogene-Transcribed RNA Promotestriglyceride Accumulation Via Activating Endoplasmic Reticulum Stress Pathway in Hepatocytes
Authors: Zhao Yanhe , Tian Zhen , Jia Yubing , Shi Dan , Wang Xinyue , Sun Changhao , na lixin 
Published: May 2021

Abstract
Background: Typical pseudogenes expressions have been reported to been associated with liver diseases. However, whether pseudogenes contribute to non-alcoholic fatty liver disease (NAFLD) and triglyceride (TG) accumulation and the underlying molecular mechanisms are poorly understood. We aimed to elucidate the role of Gm12664-201 in TG accumulation and the potential mechanism.Method and Results: We identified Gm12664-01 in high-fat diet (HFD) fed mice using microarray and confirmed its expression in both vivo and vitro high fat models with quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Then changed the level of Gm12664-201 in vitro to determine the role of it in TG accumulation, which evaluated by Oil red O staining and enzymatic method. The underlying mechanisms of Gm12664-01 in TG accumulation were investigated by detecting signaling markers BiP, PERK, ATF6, CHOP, eIF2α, XBP1 and ATF4 with qRT-PCR and western blotting. We found that Gm12664-201 was markedly increased in liver tissue of HFD mice and steric acid (SA) incubated AML-12 cells. Gm12664-201 overexpression rendered AML-12 cells susceptible to triglyceride (TG) accumulation, and silencing pseudogene Gm12664-201 expression efficiently alleviated SA-induced TG accumulation. Further studies revealed that Gm12664-201 regulates endoplasmic reticulum stress signaling markers BiP, PERK, ATF6, CHOP, eIF2α, XBP1 and ATF4 expression, which may be responsible for increased TG accumulation in hepatocytes.Conclusions: Upregulation of pseudogene Gm12664-201 induced by HFD promotes triglyceride accumulation and activates ER stress pathway in hepatocytes.
A molecularly engineered, broad-spectrum anti-coronavirus lectin inhibits SARS-CoV-2 and MERS-CoV infection in vivo
Authors: Markovitz David , Chan Jasper , Oh Yoo Jin , Yuan Shuofeng , Chu Hin , Yeung Man Lung , Canena Daniel , Chan Chris , Poon Vincent , Chan Chris , Zhang Jinxia , Cai Jian-Piao , Wen Lei , Chik Kenn Ka Heng , Shuai Huiping , Wang Yixin , Hou Yuxin , Luo Cuiting , Chan Wan-Mui , Sit Ko-Yung , Au Wing-Kuk , Legendre Maureen , Zhu Rong , Hain Lisa , To Kelvin , Chan Kwok-Hung , Thomas Dafydd , Klausberger Miriam , Stadlmann Johannes , Penninger Josef , Oostenbrink Chris , Hinterdorfer Peter , Yuen Kwok-Yung 
Published: May 2021

Abstract
Coronaviruses have repeatedly crossed species barriers to cause epidemics1. “Pan-coronavirus” antivirals targeting conserved viral components involved in coronavirus replication, such as the extensively glycosylated spike protein, can be designed. Here we show that the rationally engineered H84T-banana lectin (H84T-BanLec), which specifically recognizes high-mannose found on viral proteins but seldom on healthy human cells2, potently inhibits the highly virulent MERS-CoV, pandemic SARS-CoV-2 and its variants, and other human-pathogenic coronaviruses at nanomolar concentrations. MERS-CoV-infected human DPP4-transgenic mice treated by H84T-BanLec have significantly higher survival, lower viral burden, and reduced pulmonary damage. Similarly, prophylactic or therapeutic H84T-BanLec is effective against SARS-CoV-2 in hamsters. Importantly, intranasally and intraperitoneally administered H84T-BanLec are comparably effective. Time-of-drug-addition assay shows that H84T-BanLec targets virus entry. Real-time structural analysis with high-speed atomic force microscopy depicts multi-molecular associations of H84T-BanLec dimers with the SARS-CoV-2 spike trimer. Single-molecule force spectroscopy demonstrates binding of H84T-BanLec to multiple SARS-CoV-2 spike mannose sites with high affinity, and that H84T-BanLec competes with SARS-CoV-2 spike for binding to cellular ACE2. Modelling experiments identify distinct high-mannose glycans in spike recognized by H84T-BanLec. The multiple H84T-BanLec binding sites on spike likely account for the activity against SARS-CoV-2 variants and the lack of resistant mutants. The broad-spectrum H84T-BanLec should be clinically evaluated in respiratory viral infections including COVID-19.
Procalcitonin Predicts Intensive Care Unit Admission and Mortality in Patients With a COVID-19 Infection in the Emergency Department
Authors: Tong-Minh Kirby , Does Yuri van der , Engelen Susanna , de Jong Evelien , Ramakers Christian , Gommers Diederik , Gorp Eric van , Endeman Henrik 
Published: May 2021

Abstract
IntroductionPatients with a severe COVID-19 infection often require admission at an intensive care unit (ICU) when they develop acute respiratory distress syndrome (ARDS). Hyperinflammation plays an important role in the development of ARDS in COVID-19. Procalcitonin (PCT) is a biomarker which may be a predictor of hyperinflammation. When patients with COVID-19 are in the emergency department (ED), PCT could be a predictor of severe COVID-19 infection. The goal of this study is to investigate the predictive value of PCT on severe COVID-19 infections in the ED. MethodsThis was a retrospective cohort study including patients with confirmed COVID-19 infection who visited the ED of Erasmus Medical Center in Rotterdam, the Netherlands, between March and December 2020. The primary endpoint was a severe COVID-19 infection, which was defined as patients who required ICU admission, in-hospital mortality and 30-day mortality after hospital discharge. PCT levels were measured during the ED visit. We used logistic regression to calculate the odds ratio (OR) of PCT on a severe COVID-19 infection, adjusting for bacterial coinfections, age, gender and comorbidities. ResultsA total of 332 patients were included in the final analysis of this study, of which 105 patients reached the composite endpoint of a severe COVID-19 infection. PCT showed an unadjusted OR of 4.19 (CI: 2.52-7.69) on a severe COVID-19 infection. Corrected for bacterial coinfection, the OR of PCT was 4.05 (2.45 – 7.41). Adjusted for gender, bacterial coinfection, age and comorbidities, PCT was still an independent predictor of severe COVID-19 infection with an adjusted OR of 3.82 (CI: 2.26-7.48).ConclusionPCT is a predictor of severe COVID-19 infections in patients with a COVID-19 infection in the ED. The routine measurement of PCT in patients with a COVID-19 infection in the ED may assist physicians in the clinical decision making process regarding ICU disposition when PCT levels are elevated.
WITHDRAWN: Nomegestrol Acetate or Chlormadinone Acetate Progestative Treatment in Women: Meningioma Behavior at Treatment Discontinuation
Authors: Florea Simona Mihaela , Boissonneau Sebastien , Passeri Thibault , Bernat Anne Laure , Mandonnet Emmanuel , Dufour Henry , Graillon Thomas , Froelich Sebastien 
Published: May 2021

Abstract
Background: Associations between progestins and meningiomas is now well established. While the link between cyproterone acetate (CA) and meningioma was thoroughly studied, there is far less available data regarding the link between chlormadinone acetate (CHA) or nomegestrol acetate (NA) and risk of intracranial meningiomaMethods: We are presenting a series of 28 patients diagnosed with single or multiple meningiomas while treated with CHA-NA, in which the clinical and radiological course were analyzed after treatment discontinuation.Results: 28 women, with a mean age of 56 years old, were diagnosed with one or multiple meningioma while being treated with either CHA or NA. After stopping treatment, 89.3% showed either tumor shrinkage or tumor stabilization on follow-up MRIs. Multiple meningiomas were more likely observed in patients with long periods of treatment (>10 years, p 0.03) and seem to have a better clinical course (p 0.01). Most of the lesions were located on the skull base (55.4%). Four patients with multiple meningiomas showed discordant tumors evolution, with some tumors growing while others were decreasing. Most of the growing meningiomas were either convexity or midline lesions and more posteriorly located. Conclusion: Our study demonstrated a significant percentage of tumor diminution or stabilization after NA and CHA discontinuation. Therefore, treatment discontinuation with close monitoring should be the first measure taken if urgent surgery is not indicated. However, our results seem to be less encouraging than previously described in patients treated by CA, with more patients showing tumor growth despite treatment discontinuation. Further studies are needed to differentiate the effect of the different progestins treatment on meningiomas.
18F-Fluorocholine-PET/CT for Localizing Hyperfunctioning Parathyroid Glands and Optimizing Surgical Treatment in Patients With Hyperparathyroidism
Authors: Gass Jörn-Markus , Wicke Corinna , Mona Carolina , Strobel Klaus , Müller Werner , Metzger Jürg , Suter-Widmer Isabelle , Henzen Christoph , Fischli Stefan 
Published: May 2021

Abstract
PurposeHyperparathyroidism (HPT) is a common disorder. Cure can only be achieved by removal of all diseased glands. Exact localization of hyperfunctioning glands is of importance to prevent extensive surgical exploration. The number of false negative/inconclusive results in standard imaging techniques is high. We aimed to evaluate the diagnostic accuracy of 18F-Fluorocholine-PET/CT (FCH-PET/CT) and its sensitivity in patients with primary, secondary/tertiary and familial HPT with negative and/or discordant findings in ultrasound and/or 99mTc-sestamibi scintigraphy/SPECT/CT.Methods96 patients with HPT and negative/equivocal conventional imaging were referred for FCH-PET/CT. 69 patients who have undergone surgery and histopathologic workup were analyzed in this retrospective single institution study. 60 patients suffered from primary HPT, 4 from secondary or tertiary HPT and 5 from familial HPT. Sensitivities, positive predictive values, and accuracies were calculated.ResultsAll patients showed normalized serum calcium levels in the postoperative period. The follow-up rate was 97%. 58 of 60 patients with primary HPT and 4 of 4 patients with secondary/tertiary HPT showed normal calcium- and PTH-levels after 6 months and were cured. 4 of 5 patients with familial HPT were cured. Sensitivity/positive predictive value (PPV) per lesion for primary HPT was 87.5/98.3%, for secondary/tertiary HPT 75/100% and for familial HPT 14.6/100%, respectively. Sensitivity/PPV per patient was 91.5/98.2% for primary HPT, 100/100% for secondary/tertiary HPT and 50/100% for familial HPT, respectively.ConclusionDiagnostic accuracy of 18F-Fluorocholine-PET/CT for patients with pHPT is excellent. 18F-Fluorocholine-PET/CT is a valuable tool for endocrine surgeons to optimize the surgical treatment of patients with hyperparathyroidism.
Sustainable Polyhydroxyalkanoates (PHA) Extraction Protocol Selection Using AHP-GRA
Authors: Requiso Princess , Nayve Fidel Rey P. , Ventura Jey-R Sabado 
Published: May 2021

Abstract
In this study, a sustainable protocol for PHA extraction was methodically selected using two (2) multi-criteria decision analysis (MCDA) tools, the analytic hierarchy process (AHP) and grey relational analysis (GRA). AHP was first used to evaluate the proposed criteria categorized into technical, economic, and environmental aspects using a collected survey of pairwise comparisons. Based on the results of AHP, it was identified that both environmental and economic aspects were given higher priorities. Among the criteria, hazards and risks has the highest overall importance, followed by extraction cost and purity. Using GRA, twelve (12) protocol alternatives categorized into solvent extraction and precipitation, non-PHA cell mass (NPCM) digestion, and assisted extraction methods were graded according to the criteria. Overall, the highest priority weights were given to NPCM digestion protocols including sodium hydroxide, sodium hydroxide + sodium dodecyl sulfate, and ammonia water. The reagents involved in these protocols are ecologically benign and cheaper compared to other solvents; hence, the higher grades in the environmental and economic aspect. Sensitivity analysis also proved that these protocols are excellent, particularly if extraction cost is given a higher priority. However, if hazards and risks and purity were given more importance, butyl acetate is preferable than sodium hydroxide. Further investigations such as the validation and optimization of protocols, together with feasibility studies and life cycle analyses may be integrated with the results of this study to comprehensively determine a sustainable PHA extraction protocol.
Improvement of Inflammation and Pain After Three Months’ Exclusion Diet in Rheumatoid Arthritis Patients
Authors: Teresa Guagnano Maria , Chiara D’Angelo , Daniela Caniglia , Eleonora Celletti , Sabatini Emanuela , Lorenza Speranza , Marco Bucci , Francesco Cipollone , Paganelli Roberto 
Published: May 2021

Abstract
Introduction: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease affecting the synovial joints and causing severe disability. Environmental and lifestyle factors, including diet, have been proposed to play a role in the onset and severity of RA. Dietary manipulation may help, to manage the symptoms of RA, by lowering inflammation, and potentially decreasing pain.Methods: In 40 patients with long standing RA, with stable symptoms, and treated with conventional (c-) and biological (b-) Disease modifying anti-rheumatic drugs (DMARDs), the effect of 3-months’ diet avoiding meat, gluten, and lactose (privative diet) was evaluated in comparison with a control balanced diet including those foods. Patients choosing the exclusion diet were followed in parallel to an equal number of patients on their normal diet, and RA was clinically assessed at Time 0 (T0), through the Visual Analogue Scale (VAS), for pain, and the Disease Activity Score of 28 joints (DAS 28) for RA activity. Patients were also administered the Short Form Health survey (SF-36) and the Health Assessment Questionnaire (HAQ). At T0 a blood sample was collected for laboratory tests, and anthropometric measurements were recorded. These evaluations were repeated at the end of the 3 months’dietary regimens.Results: A significant decrease in VAS and the improvement of the overall state of physical and mental health, assessed through SF-36, was observed in patients following the avoidance diet. Both dietary regimens resulted in the improvement of quality of life compared to baseline values, however the change was significant only for the exclusion diet. With either diet, patients showed significant decreases of body weight and body mass index (BMI), with a reduction of waist and hips circumferences, lower basal glucose and circulating leptin levels. Exclusion diet was also able to significantly reduce systolic (SYS) (p=0.002) and diastolic (DIA) (p=0.027) arterial pressure. The number of circulating leukocytes and neutrophils, and the level of hs-C-Reactive Protein (CRP) were also significantly decreased after 3 months of the meat-, lactose, and gluten-free diet.Conclusions: Our results suggest that an exclusion diet can result in a better control of inflammation and pain in RA patients under stable optimized drug treatment.