bluuebunny/crossref_metadata_2025_split huggingface dataset:
A collaborative clinical case conference model for teaching social and behavioral science in medicine: an action research study
Authors: Miyachi Junichiro , Iida Junko , Shimazono Yosuke , Nishigori Hiroshi 
Published: November 2021

Abstract
Background
Effective social and behavioral sciences teaching in medical education requires integration with clinical experience, as well as collaboration between social and behavioral sciences experts and clinical faculty. However, teaching models for achieving this integration have not been adequately established, nor has the collaboration process been described. This study aims to propose a collaborative clinical case conference model to integrate social and behavioral sciences and clinical experience. Additionally, we describe how social and behavioral science experts and clinical faculty collaborate during the development of the teaching method.

Methods
A team of medical teachers and medical anthropologists planned for the development of a case conference based on action research methodology. The initial model was planned for a 3-h session, similar to a Clinicopathological Conference (CPC) structure. We evaluated each session based on field notes taken by medical anthropologists and post-session questionnaires that surveyed participants’ reactions and points of improvement. Based on the evaluation, a reflective meeting was held to discuss revisions for the next trial. We incorporated the development process into undergraduate medical curricula in clinical years and in a postgraduate and continuous professional development session for residents and certified family physicians in Japan. We repeated the plan-act-observe-reflection process more than 15 times between 2015 and 2018.

Results
The development of the collaborative clinical case conference model is summarized in three phases: Quasi-CPC, Interactive, and Co-constructive with unique structures and underlying paradigms. The model successfully contributed to promoting the participants’ recognition of the clinical significance of social and behavioral sciences. The case preparation entailed unique and significant learning of how social and behavioral sciences inform clinical practice. The model development process promoted the mutual understanding between clinical faculty and anthropologists, which might function as faculty development for teachers involved in social and behavioral sciences teaching in medical education.

Conclusions
The application of appropriate conference models and awareness of their underlying paradigms according to educational situations promotes the integration of social and behavioral sciences with clinical medicine education. Faculty development regarding social and behavioral sciences in medical education should focus on collaboration with scholars with different paradigmatic orientations.
Sequencing the CaSR locus in Pakistani stone formers reveals a novel loss-of-function variant atypically associated with nephrolithiasis
Authors: Ullah Ihsan , Ottlewski Isabel , Shehzad Wasim , Riaz Amjad , Ijaz Sadaqat , Tufail Asad , Ammara Hafiza , Mane Shrikant , Shril Shirlee , Hildebrandt Friedhelm , Zahoor Muhammad Yasir , Majmundar Amar J. 
Published: November 2021

Abstract
Background
Nephrolithiasis (NL) affects 1 in 11 individuals worldwide and causes significant morbidity and cost. Common variants in the calcium sensing receptor gene (CaSR) have been associated with NL. Rare inactivating CaSR variants classically cause hyperparathyroidism, hypercalcemia and hypocalciuria. However, NL and familial hypercalciuria have been paradoxically associated with select inactivating CaSR variants in three kindreds from Europe and Australia.

Methods
To discover novel NL-associated CaSR variants from a geographically distinct cohort, 57 Pakistani families presenting with pediatric onset NL were recruited. The CaSR locus was analyzed by directed or exome sequencing.

Results
We detected a heterozygous and likely pathogenic splice variant (GRCh37 Chr3:122000958A>G; GRCh38 Chr3:12228211A>G; NM_000388:c.1609-2A>G) in CaSR in one family with recurrent calcium oxalate stones. This variant would be predicted to cause exon skipping and premature termination (p.Val537Metfs*49). Moreover, a splice variant of unknown significance in an alternative CaSR transcript (GRCh37 Chr3:122000929G>C; GRCh38 Chr3:122282082G >C NM_000388:c.1609-31G >C NM_001178065:c.1609-1G >C) was identified in two additional families.

Conclusions
Sequencing of the CaSR locus in Pakistani stone formers reveals a novel loss-of-function variant, expanding the connection between the CaSR locus and nephrolithiasis.
Long-term visual pathway alterations after elemental mercury poisoning: report of a series of 29 cases
Authors: Pastor-Idoate Salvador , Coco-Martin Rosa M. , Zabalza Iratxe , Lantigua Yrbani , Fernández Itziar , Pérez-Castrillón Jose L. , Cuadrado Ruben , de Lazaro Jose A. , Morejon Angela , Dueñas-Laita Antonio , Pastor Jose C. 
Published: November 2021

Abstract
Background
There are few clinical data on retinal involvement after acute exposure to high concentrations mercury and the available reports are based on a small number of patients suffering chronic exposure. The purpose of this paper is to report findings in workers acutely exposed to very high concentrations of mercury vapor with the aim of providing data on a possible direct retinal involvement.

Methods
Twenty-nine patients and 16 controls were evaluated in a comparative case series. Mercury levels in blood and urine samples, visual acuity (VA), contrast sensitivity (CS), visual field (VF), color discrimination and optical coherence tomography (OCT) were recorded. The pattern reversal visual-evoked potentials (PRVEP), full-field and multifocal electroretinography (ffERG/mfERG), pattern electroretinography (PERG), systemic symptoms, presence of erethism, and electromyography (EMG) were also gathered. A descriptive analysis was performed. The correlations between variables also were studied.
In addition, electrophysiological data from those patients with deeper VF defects (group 1) were compared with a normal control group.

Results
Twenty-six workers exhibited symptoms of erethism. The EMG showed sensorimotor polyneuropathy and multiple mononeuropathy. The VA was slightly affected in 48.27% (n = 14) of subjects. Loss of CS in at least one of four spatial frequencies and color vision alterations occurred in 96.5% (n = 28) and 44.8% (n = 13), respectively. VF alterations were identified in 72.4% (n = 21) patients. No morphologic changes were seen in the OCT scans. Latencies over 100 milliseconds and reduced amplitudes of P100 were found in the PRVEP (p < 0.05). The reduced amplitude of the b wave at the ffERG, of the P50 at the PERG and of the P1 wave at the mfERG results (p < 0.05) suggested that the outer retina was involved. Significant negative correlations among blood mercury levels, VA, and ffERG were observed.

Conclusions
In this case series, showed that acute exposure to mercury vapor had a hazardous effect on the visual system. Although neurologic and visual pathway involvement was clearly demonstrated, the differences found compared to control support the existence of a direct functional retinal damage and participation in impaired vision in mercury poisoning.
Revision arthroplasty after unicompartimental knee arthroplasty
Authors: Walter Nike , Weber Johannes , Kerschbaum Maximilian , Lau Edmund , Kurtz Steven M. , Alt Volker , Rupp Markus 
Published: November 2021

Abstract
Background
Unicompartimental knee arthroplasty (UKA) is a promising and increasing application to treat unicompartimental knee osteoarthritis. However, revision arthroplasty numbers after UKA are unknown. Therefore, aim of this study was to determine the nationwide burden of revision after UKA by answering the following questions: (1) How did numbers of revision UKA procedures developed over the last decade as a function of age and gender? (2) How high is the percentage of revision UKA procedures due to infection? (3) Which therapy strategy was chosen for surgical treatment of aseptic revision UKA?

Methods
Revision arthroplasty rates as a function of age, gender, infection and type of prosthesis were quantified based on Operation and Procedure Classification System codes using revision knee arthroplasty data from 2008 to 2018, provided by the Federal Statistical Office of Germany (Destatis).

Results
Over the last decade, revision UKA increased by 46.3% up to 3105 procedures in 2018. A trend towards higher numbers in younger patients was observed. Septic interventions constituted 5.7% of all revisions, whereby total procedures increased by 67.1% from 2008 through 2018. The main treatment strategy was an exchange to a bicondylar surface replacement prosthesis, which was done in 63.70% of all cases, followed by exchange to a femoral and tibial shaft-anchored (16.2% of all revisions).

Conclusion
The increasing number of revision arthroplasty after UKA in Germany, especially in younger patients and due to infection, underlines the need for future efforts to improve treatment strategies beyond UKA to delay primary arthroplasty and avoid periprosthetic joint infection.
MiR-497-5p down-regulates CDCA4 to restrains lung squamous cell carcinoma progression
Authors: Hu Jiangwei , Xiang Xinqin , Guan Wei , Lou Weihua , He Junming , Chen Jian , Fu Yin , Lou Guoliang 
Published: November 2021

Abstract
Background
So far, few have concerned miR-497-5p in lung squamous cell carcinoma (LUSC).

Methods
MiR-497-5p expression in LUSC was measured by qRT-PCR. Its impacts on tumor-related cell behaviors were investigated by CCK8 assay, scratch healing assay, flow cytometry and Transwell invasion methods. In addition, interaction between miR-497-5p and CDCA4 in LUSC was also elucidated through rescue experiment, western blot, dual-luciferase, and bioinformatics analysis.

Results
Low level of miR-497-5p was confirmed in LUSC tissue and cells. Overexpressed miR-497-5p markedly inhibited cancer progression. miR-497-5p restrained CDCA4 expression. Rescue assay showed that overexpressing miR-497-5p eliminated effect of overexpressed CDCA4.

Conclusion
By targeting CDCA4, miR-497-5p restrained development of LUSC.
Improving phenylalanine and micronutrients status of children with phenylketonuria: a pilot randomized study
Authors: Zamani Reza , Karimi-Shahanjarini Akram , Tapak Leili , Moeini Babak 
Published: November 2021

Abstract
Background
Children with Phenylketonuria (PKU) need a special diet to avoid a variety of physical and psychological complications. The aim of this study was to compare and assess the effects of two interventions on and levels of phenylalanine and micronutrients in children with PKU.

Methods
Forty-six children with PKU (ages 1–12 years) and their caregivers were randomly assigned to one of two 10-week interventions: a caregiver educational intervention based on the Integrative Model of Behvioral Prediction (IMBP) and supplementary low-protein-modified foods. Outcomes consisted of Children's plasma phenylalanine and micronutrients (i.e., vitamin B12, vitamin D3, and zinc) and hemoglobin levels. To assess the sustainability of outcomes, we also compared the children’s phenylalanine level at five-time points including baseline and 10-week, 6 months, 12 months, and 24 months follow-ups. In addition, caregivers of both groups were asked to complete a questionnaire to assess how well the interventions were implemented as well as satisfaction with interventions.

Results
While a large percentage of children had phenylalanine levels out of range indicating non-adherence (69.6% and 81% in the educational and food items group, respectively), micronutrient deficiencies were not prevalent in the patient cohort. The levels of phenylalanine in both groups decreased significantly over time. However, conducting a repeated-measures ANOVA to evaluating the change in groups across five-time points, revealed a significant difference between groups (F = 4.68, p = 0.03). That is, the educational intervention was more effective in lowering the children's phenylalanine level. At 24-month follow-up, the percentage of children with a normal range of phenylalanine level in the educational and food items groups increased to 73.9 and 57.1 percent, respectively, from 26 and 38 percent at baseline. There were no significant changes in children's micronutrients level following the interventions, except in the hemoglobin. In this way, at 10-week follow-up, the mean hemoglobin of children in the educational group reduced significantly (P = 0.041). However, there was no significant difference between the two groups. In general, all caregivers completed the process evaluation checklist, the feedback was largely positive.

Conclusions
The results of this study demonstrated that both educational and providing food item interventions resulted in a significant reduction in phenylalanine levels. Empowering caregivers of patients, creating and fortifying social networks, providing favorable social supports, and providing access to special food items may be effective in controlling PKU.
Clinical trial registration: Iranian Registry of Clinical Trials (IRCT20180506039548N1). Registered 6th Jun 2018, https://www.irct.ir/trial/30977.
The impact of Mediterranean diet on coronary plaque vulnerability, microvascular function, inflammation and microbiome after an acute coronary syndrome: study protocol for the MEDIMACS randomized, controlled, mechanistic clinical trial
Authors: Fernández Ana I. , Bermejo Javier , Yotti Raquel , Martínez-Gonzalez Miguel Ángel , Mira Alex , Gophna Uri , Karlsson Roger , Al-Daccak Reem , Martín-Demiguel Irene , Gutiérrez-Ibanes Enrique , Charron Dominique , Fernández-Avilés Francisco ,   on behalf of the MEDIMACS research team, Fernández Ana I. , Bermejo Javier , Yotti Raquel , Gutierrez-Ibanes Enrique , Gabaldón-Badiola Álvaro , Martín-Demiguel Irene , Sanz Ricardo , Martínez-Legazpi Pablo , Elízaga Jaime , Fernández-Avilés Francisco , Jurado Elena , Martínez-Gonzalez Miguel Ángel , Razquin Cristina , Vázquez-Ruiz Zenaida , Mira Alex , López Aránzazu , Ferrer Maria D. , Gophna Uri , Reshef Leah , Karlsson Roger , Moore Edward , Karlsson Göran , Winqvist Anna , Al-Daccak Reem , Charron Dominique 
Published: November 2021

Abstract
Background
Primary prevention trials have demonstrated that the traditional Mediterranean diet is associated with a reduction in cardiovascular mortality and morbidity. However, this benefit has not been proven for secondary prevention after an acute coronary syndrome (ACS). We hypothesized that a high-intensity Mediterranean diet intervention after an ACS decreases the vulnerability of atherosclerotic plaques by complex interactions between anti-inflammatory effects, microbiota changes and modulation of gene expression.

Methods
The MEDIMACS project is an academically funded, prospective, randomized, controlled and mechanistic clinical trial designed to address the effects of an active randomized intervention with the Mediterranean diet on atherosclerotic plaque vulnerability, coronary endothelial dysfunction and other mechanistic endpoints. One hundred patients with ACS are randomized 1:1 to a monitored high-intensity Mediterranean diet intervention or to a standard-of-care arm. Adherence to diet is assessed in both arms using food frequency questionnaires and biomarkers of compliance. The primary endpoint is the change (from baseline to 12 months) in the thickness of the fibrous cap of a non-significant atherosclerotic plaque in a non-culprit vessel, as assessed by repeated optical coherence tomography intracoronary imaging. Indices of coronary vascular physiology and changes in gastrointestinal microbiota, immunological status and protein and metabolite profiles will be evaluated as secondary endpoints.

Discussion
The results of this trial will address the key effects of dietary habits on atherosclerotic risk and will provide initial data on the complex interplay of immunological, microbiome-, proteome- and metabolome-related mechanisms by which non-pharmacological factors may impact the progression of coronary atherosclerosis after an ACS.

Trial registration
ClinicalTrials.govNCT03842319. Registered on 13 May 2019
Partial oral antibiotic treatment for bacterial brain abscess: an open-label randomized non-inferiority trial (ORAL)
Authors: Bodilsen Jacob , Brouwer Matthijs C. , van de Beek Diederik , Tattevin Pierre , Tong Steven , Naucler Pontus , Nielsen Henrik 
Published: November 2021

Abstract
Background
The advised standard treatment for bacterial brain abscess following surgery is 6 to 8 weeks of intravenous (IV) antibiotic treatment, but an early switch to oral antibiotic treatment has been suggested to be equally effective.

Methods
This investigator-initiated, international, multi-center, parallel group, open-label, randomized (1:1 allocation) controlled trial will examine if oral treatment after 2 weeks of IV antibiotic therapy is non-inferior to standard 6–8 weeks of IV antibiotics for bacterial brain abscess in adults (≥ 18 years of age). The study will be conducted at hospitals across Denmark, the Netherlands, France, Australia, and Sweden. Exclusion criteria are severe immunocompromise or impaired gastro-intestinal absorption, pregnancy, device-related brain abscesses, and brain abscess caused by nocardia, tuberculosis, or Pseudomonas spp. The primary objective is a composite endpoint at 6 months after randomization consisting of all-cause mortality, intraventricular rupture of brain abscess, unplanned re-aspiration or excision of brain abscess, relapse, or recurrence. The primary endpoint will be adjudicated by an independent blinded endpoint committee. Secondary outcomes include extended Glasgow Outcome Scale scores and all-cause mortality at end of treatment as well as 3, 6, and 12 months since randomization, completion of assigned treatment, IV catheter associated complications, durations of admission and antibiotic treatment, severe adverse events, quality of life scores, and cognitive evaluations. The planned sample size is 450 patients for a one-sided alpha of 0.025 and a power of 90% to exclude a difference in favor of standard treatment of more than 10%. Date of initiation of first study center was November 3, 2020, with active recruitment for 3 years and follow-up for 1 year of all patients.

Discussion
The results of this study may guide future recommendations for treatment of bacterial brain abscess. If early transition to oral antibiotics proves non-inferior to standard IV treatment, this will provide considerable health and costs benefits.

Trial registration
ClinicalTrials.gov NCT04140903, first registered 28.10.2019. EudraCT number: 2019-002845-39, first registered 03.07.2019
The invasive Korean bush mosquito Aedes koreicus (Diptera: Culicidae) in Germany as of 2020
Authors: Hohmeister Nicolas , Werner Doreen , Kampen Helge 
Published: November 2021

Abstract
Background
The Korean bush mosquito Aedes koreicus was recently reported to have established a population in western Germany (Wiesbaden) in 2016. The species is difficult to distinguish morphologically from its close relative, the invasive Japanese bush mosquito Ae. japonicus, which is already widely distributed in many parts of Germany, including the area colonised by Ae. koreicus. Genetic confirmation of morphologically identified “Ae. japonicus” collection material, however, had only been done exceptionally before the German Ae. koreicus population became known.

Methods
Dried archived “Ae. japonicus” specimens both from the municipality of Wiesbaden and from deliberately and randomly selected distribution sites all over Germany were re-examined morphologically and genetically for admixture by Ae. koreicus. Moreover, cemeteries in the greater Wiesbaden area were sampled in 2019 and 2020 to check for Ae. koreicus spread. Korean and Japanese bush mosquitoes submitted to the German citizen science mosquito monitoring scheme “Mueckenatlas” in 2019 and 2020 were also subjected to particularly thorough species identification. The ND4 DNA sequences generated in this study in the context of species identification were phylogenetically compared to respective GenBank entries of Ae. koreicus. As a by-product, several genetic markers were evaluated for their suitability to identify Ae. koreicus.

Results
Aedes koreicus specimens could be identified in mosquito collection material and submissions from Wiesbaden from 2015 onwards, suggesting establishment to have happened in the same year as Ae. japonicus establishment. Detections of Ae. koreicus from 2019 and 2020 in Wiesbaden indicate a negligible enlargement of the populated area as described for 2018. Two Ae. koreicus specimens were also submitted from the city of Munich, southern Germany, in 2019 but further specimens could not be identified during immediate local inspections. Comparison of ND4 sequences generated in this and other studies demonstrate a high degree of homology, suggesting that this DNA region is not informative enough for clarification of origins and relationships of Ae. koreicus populations. For genetic identification of Ae. koreicus, PCR primers used for classical CO1 barcoding were found to lead to mismatches and produce no or incorrect amplicons. Alternative CO1 primers or a validated ND4 marker should be used instead.

Conclusions
Aedes koreicus is probably introduced into Germany every now and then but rarely succeeds in becoming established. As with most European populations, the German population is characterised by a limited expansion tendency. Since Ae. koreicus is a potential vector, however, Asian bush mosquitoes found at new places should be examined quite carefully and known distribution areas of Ae. japonicus regularly checked for the presence of Ae. koreicus.

Graphical Abstract
In vivo human molecular neuroimaging of dopaminergic vulnerability along the Alzheimer’s disease phases
Authors: Sala Arianna , Caminiti Silvia Paola , Presotto Luca , Pilotto Andrea , Liguori Claudio , Chiaravalloti Agostino , Garibotto Valentina , Frisoni Giovanni Battista , D’Amelio Marcello , Paghera Barbara , Schillaci Orazio , Mercuri Nicola , Padovani Alessandro , Perani Daniela 
Published: November 2021

Abstract
Background
Preclinical and pathology evidence suggests an involvement of brain dopamine (DA) circuitry in Alzheimer’s disease (AD). We in vivo investigated if, when, and in which target regions [123I]FP-CIT-SPECT regional binding and molecular connectivity are damaged along the AD course.

Methods
We retrospectively selected 16 amyloid-positive subjects with mild cognitive impairment due to AD (AD-MCI), 22 amyloid-positive patients with probable AD dementia (AD-D), and 74 healthy controls, all with available [123I]FP-CIT-SPECT imaging. We tested whether nigrostriatal vs. mesocorticolimbic dopaminergic targets present binding potential loss, via MANCOVA, and alterations in molecular connectivity, via partial correlation analysis. Results were deemed significant at p < 0.05, after Bonferroni correction for multiple comparisons.

Results
We found significant reductions of [123I]FP-CIT binding in both AD-MCI and AD-D compared to controls. Binding reductions were prominent in the major targets of the ventrotegmental-mesocorticolimbic pathway, namely the ventral striatum and the hippocampus, in both clinical groups, and in the cingulate gyrus, in patients with dementia only. Within the nigrostriatal projections, only the dorsal caudate nucleus showed reduced [123I]FP-CIT binding, in both groups. Molecular connectivity assessment revealed a widespread loss of inter-connections among subcortical and cortical targets of the mesocorticolimbic network only (poor overlap with the control group as expressed by a Dice coefficient ≤ 0.25) and no alterations of the nigrostriatal network (high overlap with controls, Dice coefficient = 1).

Conclusion
Local- and system-level alterations of the mesocorticolimbic dopaminergic circuitry characterize AD, already in prodromal disease phases. These results might foster new therapeutic strategies for AD. The clinical correlates of these findings deserve to be carefully considered within the emergence of both neuropsychiatric symptoms and cognitive deficits.