bluuebunny/crossref_metadata_2025 huggingface dataset:
Acitretin treatment in antimalarial-refractory/intolerant discoid lupus erythematosus: A prospective, open-label, uncontrolled study
Authors: Laosakul Kulwadee , Chiewchanvit Siri , Chuamanochan Mati , Tovanabutra Napatra
Published: March 2022

Background

The treatment of discoid lupus erythematosus (DLE) is often challenging, especially in patients who are refractory or intolerant to topical treatments and first-line systemic drugs, specifically antimalarial drugs. Although acitretin has been shown to be effective in patients with DLE in a few studies, there is no published study describing the long-term efficacy of acitretin with a validated score.

Objectives

To evaluate the efficacy and safety of acitretin in patients with antimalarial-refractory/intolerant DLE.

Methods

A prospective, open-label, uncontrolled study was conducted in patients with antimalarial-refractory/intolerant DLE. All patients were treated with an initial dosage of 10 mg acitretin daily. Clinical response was assessed using the Revised Cutaneous Lupus Erythematosus Disease Area and Severity Index (RCLASI) at weeks 4, 8, 12, and 24. Acitretin was increased to 25 mg daily unless an adequate response was achieved at week 8.

Results

Fourteen patients were recruited. Of these, 10 were antimalarial-refractory and four were antimalarial-intolerant. The acitretin therapy was discontinued in one patient after 20 weeks of treatment because of active systemic disease. Of the 13 remaining patients, the mean RCLASI activity scores declined from 21 ± 9 at baseline to 9 ± 4 at week 24. A significant reduction in RCLASI was initially observed at week four and consistently noted at each follow-up visit ( p ≤ 0.01). At the end of the study, a marked response was achieved in approximately 80% of patients. There were no statistically significant differences in the clinical response or in the requirement of the up-dosing of acitretin between the refractory and intolerance groups ( p = 0.88 and p = 0.326, respectively). Age ≥50 years old, female sex, and generalized DLE were the favorable prognostic factors. No serious adverse events were noted.

Conclusions

Acitretin appears to be an effective treatment with acceptable safety profiles for antimalarial-refractory/intolerant DLE.
Active Immunotherapy for Glioblastoma Treatment: A Systematic Review and Meta-Analysis
Authors: Wahyuhadi Joni , Immadoel Haq Irwan Barlian , Arifianto Muhammad Reza , Sulistyono Bagus , Meizikri Rizki , Rosada Atika , Sigit Prakoeswa Cita Rosita , Susilo Rahadian Indarto
Published: March 2022

Introduction

Glioblastoma multiforme (GBM) makes 60–70% of gliomas and 15% of primary brain tumors. Despite the availability of standard multimodal therapy, 2 years, 3 years, and 5 years survival rate of GBM are still low. Active immunotherapy is a relatively new treatment option for GBM that seems promising.

Methods

An electronic database search on PubMed, Cochrane, Scopus, and clinicaltrials.gov was performed to include all relevant studies. This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). Reported parameters are OS, PFS, AEs, post treatment KPS, and 2 year mortality.

Results

Active immunotherapy provided better OS (HR = .85; 95% CI = .71–1.01; P = .06) and PFS (HS = .83; 95% CI= .66 – 1.03; P = .11) side albeit not statistically significant. Active immunotherapy reduces the risk of 2 year mortality as much as 2.5% compared to control group (NNT and RRR was 56.7078 and 0,0258, respectively).

Conclusion

Active immunotherapy might be beneficial in terms of survival rate in patients with GBM although not statistically significant. It could be a treatment option for GBM in the future.
A Systematic Review Characterizing Psoriatic Arthritis Onset and Exacerbation in Patients Receiving Biologic Therapy
Authors: Sachdeva Muskaan , Abduelmula Abrahim , Mufti Asfandyar , Georgakopoulos Jorge R. , Lytvyn Yuliya , Yeung Jensen
Published: March 2022

Background

While biologic therapies revolutionized treatment of immune-mediated inflammatory diseases (IMIDs), some adverse effects have been noted. This includes the development and exacerbation of PsA in patients on biologic agents, however the outcomes were not extensively explored.

Objective

To perform a systematic review to characterize the outcomes of PsA onset or exacerbation secondary to biologic use.

Methods

MEDLINE and EMBASE search conducted on March 23, 2021 resulted in 18 studies comprised of 64 patients.

Results

Of the 64 patients, 57 (89.1%) experienced new-onset PsA and 7 (10.9%) experienced exacerbation of preexisting PsA following exposure to a biologic; most commonly a TNF-α inhibitor (42.2%, n = 27/64) and IL-12/23 inhibitors (39.1%, n = 25/64). The mean durations of biologic use before PsA onset and exacerbation were 14.8 months and 5.2 months, respectively. Twenty-four patients (44.4%) subsequently switched to an alternate biologic without further reports of PsA-related adverse events. All 64 patients reported a specific treatment for PsA; most commonly discontinuation of the associated biologic agent (32.8%, n = 21/64). Complete resolution of PsA was reported in 35.9% ( n = 23/64) of cases, of which 91.3% ( n = 21/23) resulted after discontinuation of biologic.

Conclusion

Although we characterized outcomes of PsA induction and exacerbation secondary to biologic use, large-scale studies are required.
Individuals with autism show non-adaptive relative weighting of perceptual prior and sensory reliability
Authors: Binur Nahal , Hel-Or Hagit , Hadad Bat-Sheva
Published: March 2022

Modulation in sensory-perceptual processing is a known characteristic of autism, although the underlying mechanism is debated. A prevailing account is formulated in Bayesian terms, where either a reduced prior or reduced noise in the measurement (sensory input) may account for the modulated perception as expressed by the posterior distribution. However, research has shown that individuals with autism use priors in some conditions, and to the same extent as neurotypicals, while other studies fail to show enhanced sensory sensitivity in these individuals. We asked whether the modulated prior effects on perception may arise from non-adaptive relative weighting of priors to sensory reliability. We employed a Two-alternative forced choice (2AFC) width discrimination task, using the width–height illusion, which is based on a long-term acquired bias, where a taller rectangle is typically perceived as thinner than a shorter one. The measurement was manipulated by adding Gaussian blur on the vertical edges of the rectangles. Typically developed individuals displayed the expected increase in bias as a function of noise in the measurement. High-functioning individuals with autism exhibited typical perceptual resolutions and similar susceptibility to the illusion. However, the relative weighting of the perceptual bias and the sensory input differed in their effect on the two groups. Individuals with autism showed a non-adaptive, consistent bias across the different degrees of sensory noise, while typically developed individuals displayed monotonically increasing biases. Cluster analyses showed that this difference in the relative weighting between the groups was preserved regardless of the overall illusion magnitude displayed by individuals in each cluster.

Lay abstract

Unique perceptual skills and abnormalities in perception have been extensively demonstrated in those with autism for many perceptual domains, accounting, at least in part, for some of the main symptoms. Several new hypotheses suggest that perceptual representations in autism are unrefined, appear less constrained by exposure and regularities of the environment, and rely more on actual concrete input. Consistent with these emerging views, a bottom-up, data-driven fashion of processing has been suggested to account for the atypical perception in autism. It is yet unclear, however, whether reduced effects of prior knowledge and top-down information, or rather reduced noise in the sensory input, account for the often-reported bottom-up mode of processing in autism. We show that neither is sufficiently supported. Instead, we demonstrate clear differences between autistics and neurotypicals in how incoming input is weighted against prior knowledge and experience in determining the final percept. Importantly, the findings tap central differences in perception between those with and without autism that are consistent across identified sub-clusters within each group.
MyCera. Application of mycelial growth within digitally manufactured clay structures
Authors: Jauk Julian , Gosch Lukas , Vašatko Hana , Christian Ingolf , Klaus Anita , Stavric Milena
Published: March 2022

In this paper we will demonstrate a digital workflow that includes a living material such as mycelium and makes the creation of structural designs possible. Our interdisciplinary research combines digital manufacturing with the use of mycelial growth, which enables fibre connections on a microscopic scale. We developed a structure that uses material informed toolpaths for paste-based extrusion, which are built on the foundation of experiments that compare material properties and growth observations. Subsequently, the tensile strength of 3D printed unfired clay elements was increased by using mycelium as an intelligently oriented fibre reinforcement. Assembling clay-mycelium composites in a living state allows force-transmitting connections within the structure. This composite has exhibited structural properties that open up the possibility of its implementation in the building industry. It allows the design and efficient manufacturing of lightweight ceramic constructions customised to this composite, which would not have been possible using conventional ceramics fabrication methods.
Robot-Assisted Liver Resection and Cholecystectomy Using Indocyanine-Green for Intrahepatic Cholangiocarcinoma, in a Very Rare Anatomical Anomaly of ‘Bipartite Liver’
Authors: Ceccarelli Graziano , Codacci-Pisanelli Massimo , De Rosa Michele , Mariani Lorenzo , Rocca Aldo , Mazzucca Daniele , Polistena Andrea
Published: March 2022

Robotic hepatobiliary surgery has significantly developed worldwide with substantial clinical results. Hepatobiliary anatomical anomalies increase the complexity of hepatobiliary resection with a relevant risk of iatrogenic lesions. Among congenital liver anomalies, the ‘bipartite liver’ is an extremely rare condition which might be associated with complex surgical dissection of the hepatic hilum. We herein report a rare case of congenital ‘bipartite liver’ associated with a cholangiocarcinoma of segment VI and calculous cholecystitis. The patient underwent robot-assisted segmentectomy and cholecystectomy with the use of indocyanine-green cholangiography and intraoperative ultrasound. A challenging hilar dissection was performed using this approach. To the best of our knowledge, this is the first case reported that describes a robot-assisted liver resection and cholecystectomy in a patient having a cholangiocarcinoma associated with this rare liver anomaly. The robotic approach was safe and effective and the 3D preoperative imaging, as well as the intraoperative green-indocyanine cholangiography was extremely useful, especially during hilar dissection and cholecystectomy.
The effect of reducing attentional resources on selective suppression in the Simon task
Authors: Grandjean Aurélie , Suarez Isabel , Casini Laurence
Published: March 2022

Studies using reaction times (RTs) distribution methods find that the Simon effect is greater for fast RTs and becomes smaller or reversed for slow RTs. However, the exact mechanisms responsible for this reduction are under debate. This study addressed the issue of whether attentional resources play a role in reduction of the Simon effect over time by investigating whether it is influenced by attentional constraints in a dual-task paradigm. Participants were instructed to perform a Simon task concurrently with a secondary task. Secondary task characteristics were manipulated by varying the overlap between the secondary task and the Simon task. Specifically, secondary tasks varied in their stimulus modality (auditory or visual) and/or response type (verbal or manual and lateralised or not). Distribution analyses of RTs, in the form of delta-plot functions, were performed for both the single- and dual-task conditions. Results showed that the more attention the secondary task demanded, the less the Simon effect was reduced, even for slower RTs. This suggests that the mechanisms responsible for the reduction of Simon effect over time are under top-down control.
Time to rehospitalization in involuntarily hospitalized individuals suffering from schizophrenia discharged on long-acting injectable antipsychotics or oral antipsychotics
Authors: Lin Ching-Hua , Chan Hung-Yu , Wang Fu-Chiang , Hsu Chun-Chi
Published: March 2022

Background:

Involuntarily hospitalized individuals suffering from schizophrenia often have a poorer prognosis after discharge.

Objective:

This study aimed to analyze time to rehospitalization within 6 months of discharge in involuntarily hospitalized individuals suffering from schizophrenia discharged on long-acting injectable antipsychotics (LAIs) or oral antipsychotics (OAPs). In addition, temporal trends in LAI use at discharge were explored.

Methods:

Involuntarily hospitalized individuals suffering from schizophrenia discharged from the study hospital between 2006 and 2019 ( n = 806) were included in the analysis. Survival analysis was used to compare time to rehospitalization within 6 months of discharge between individuals discharged on LAIs and OAPs, and between first-generation antipsychotic (FGA) LAIs and second-generation antipsychotic (SGA) LAIs. The Cochran–Armitage trend test was used to test whether a temporal trend existed for LAIs use at discharge during the study period.

Results:

The LAIs group ( n = 231) had a significantly lower rate of rehospitalization and a significantly longer time to rehospitalization than the OAPs group ( n = 575). Rehospitalization rate and time to rehospitalization were not significantly different between individuals discharged on FGA-LAIs and SGA-LAIs. LAIs use at discharge grew significantly from 16.77% in 2006 to 50.00% in 2019 ( Z = 6.81, p < 0.0001). Among all LAIs, only use of SGA-LAIs at discharge increased significantly ( Z = 5.74, p < 0.0001), but not FGA-LAIs.

Conclusions:

LAIs were superior to OAPs in preventing rehospitalization. However, SGA-LAIs were comparable with FGA-LAIs in reducing rehospitalization risk. Use of LAIs increased significantly in discharged involuntarily hospitalized individuals during the study period, especially SGA-LAIs.
Hierarchical representation for PPI sites prediction
Authors: Quadrini Michela , Daberdaku Sebastian , Ferrari Carlo
Published: March 2022

Background

Protein–protein interactions have pivotal roles in life processes, and aberrant interactions are associated with various disorders. Interaction site identification is key for understanding disease mechanisms and design new drugs. Effective and efficient computational methods for the PPI prediction are of great value due to the overall cost of experimental methods. Promising results have been obtained using machine learning methods and deep learning techniques, but their effectiveness depends on protein representation and feature selection.

Results

We define a new abstraction of the protein structure, calledhierarchical representations, considering and quantifyingspatial and sequential neighboringamong amino acids. We also investigate the effect of molecular abstractions using the Graph Convolutional Networks technique to classify amino acids as interface and no-interface ones. Our study takes into account three abstractions,hierarchical representations, contact map, and the residue sequence, and considers the eight functional classes of proteins extracted from the Protein–Protein Docking Benchmark 5.0. The performance of our method, evaluated using standard metrics, is compared to the ones obtained with some state-of-the-art protein interface predictors. The analysis of the performance values shows that our method outperforms the considered competitors when the considered molecules are structurally similar.

Conclusions

Thehierarchical representationcan capture the structural properties that promote the interactions and can be used to represent proteins with unknown structures by codifying only their sequential neighboring. Analyzing the results, we conclude that classes should be arranged according to their architectures rather than functions.
Clinical characteristics of Gram-negative and Gram-positive bacterial infection in acute cholangitis: a retrospective observational study
Authors: Tian Shijing , Li Kaili , Tang Hong , Peng Yan , Xia Liang , Wang Xi , Chen Xiaoying , Zhou Fachun
Published: March 2022

Background

To investigate the difference in the severity of illness, organ dysfunction, and prognosis of acute cholangitis due to different pathogenic bacterial infection types.

Methods

A retrospective observational study was performed. Patients who met the selection criteria according to blood culture and bile culture results of different pathogenic bacterial were divided into groups. The severity of illness, organ dysfunction, and prognosis of the groups were analyzed and compared comprehensively.

Results

A total of 424 patients were included, and no bacterial growth developed in 111 patients (26.2%). Among the 313 patients (73.8%) with bacterial growth, 155 patients had only Gram-negative bacteria cultured (49.5%), 48 patients had only Gram-positive bacteria cultured (15.3%), and 110 patients had both Gram-negative and Gram-positive bacteria cultured (35.1%). The proportion of Grade III patients and the APACHE II and SOFA scores of the mixed Gram-negative and positive group were the highest (p < 0.05); the intensive care unit admission day and hospital stay were longer, and the mortality rate were also higher 20/110 (18.2%) than the other two groups. Regression analysis showed that bacterial growth was an independent risk factor for organ dysfunction. The risks of an increased septic shock, neurological dysfunction, hepatic dysfunction, hematological dysfunction, and respiratory dysfunction in the mixed Gram-negative and positive group were higher than the Gram-negative group (P < 0.05). The Cox proportional hazards regression prompt showed that different culture results were independent risk factors for death. The mixed Gram-negative and positive group had increased hazard ratios and 95% CI of 7.30 (95% CI 1.55 to 34.38) compared with the Gram-negative group. There was no difference between the Gram-negative group and the Gram-positive group in the severity of illness, organ dysfunction, intensive care unit admission day, hospital stay, mortality rate, and risk of death (P > 0.05).

Conclusions

In acute cholangitis, mixed infection with Gram-negative and Gram-positive bacteria was more severe and was associated with a higher risk of death. There were no apparent differences between Gram-negative and Gram-positive bacterial infections.
Effectiveness of the BNT162b2 (Pfizer-BioNTech) and the ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vaccines for reducing susceptibility to infection with the Delta variant (B.1.617.2) of SARS-CoV-2
Authors: Pattni Karan , Hungerford Daniel , Adams Sarah , Buchan Iain , Cheyne Christopher P. , García-Fiñana Marta , Hall Ian , Hughes David M. , Overton Christopher E. , Zhang Xingna , Sharkey Kieran J.
Published: March 2022

Background

From January to May 2021 the alpha variant (B.1.1.7) of SARS-CoV-2 was the most commonly detected variant in the UK. Following this, the Delta variant (B.1.617.2) then became the predominant variant. The UK COVID-19 vaccination programme started on 8th December 2020. Prior to the Delta variant, most vaccine effectiveness studies focused on the alpha variant. We therefore aimed to estimate the effectiveness of the BNT162b2 (Pfizer-BioNTech) and the ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vaccines in preventing symptomatic and asymptomatic infection with respect to the Delta variant in a UK setting.

Methods

We used anonymised public health record data linked to infection data (PCR) using the Combined Intelligence for Population Health Action resource. We then constructed an SIR epidemic model to explain SARS-CoV-2 infection data across the Cheshire and Merseyside region of the UK. Vaccines were assumed to be effective after 21 days for 1 dose and 14 days for 2 doses.

Results

We determined that the effectiveness of the Oxford-AstraZeneca vaccine in reducing susceptibility to infection is 39% (95% credible interval [34, 43]) and 64% (95% credible interval [61, 67]) for a single dose and a double dose respectively. For the Pfizer-BioNTech vaccine, the effectiveness is 20% (95% credible interval [10, 28]) and 84% (95% credible interval [82, 86]) for a single-dose and a double dose respectively.

Conclusion

Vaccine effectiveness for reducing susceptibility to SARS-CoV-2 infection shows noticeable improvement after receiving two doses of either vaccine. Findings also suggest that a full course of the Pfizer-BioNTech provides the optimal protection against infection with the Delta variant. This reinforces the need to complete the full course programme to maximise individual protection and reduce transmission.
Developing new possibilities for interprofessional learning- students’ experience of learning together in the ambulance service
Authors: Conte Helen , Wihlborg Jonas , Lindström Veronica
Published: March 2022

Background

It is known that setting and context matters, and contextual factors influence interprofessional education (IPE). Activities developed in a new setting should therefore be evaluated to determine students’ experiences and learning. IPE in the ambulance service may present a new setting for interprofessional learning (IPL).

Aim

The aim of this study was to explore undergraduate students’ experiences of collaboration and learning together during their clinical rotation in the ambulance service.

Study design and method

A mixed convergent parallel design was used to describe nursing and medical students’ experiences of collaboration and learning together during their clinical rotation in the ambulance service during autumn 2019. Two group interviews with nursing students (n = 20; response rate 80%) were conducted and the medical students (n = 40; response rate 72.5%) answered a self-assessment questionnaire regarding their IPE. The group discussions were analysed using an inductive thematic analysis and descriptive statistics were used to describe the medical students’ self-assessed experiences and competencies in interprofessional collaboration.

Results

In the context of the ambulance service, some of the challenges included, the team vary daily, a context that can be unpredictable, and the team being required to make decisions in various situations with limited support. The context presented good opportunities to learn together, since they faced a broad variety of situations and had opportunities to follow patients through the chain of care.

Conclusion

The students’ experiences show that the ambulance service offers possibilities for IPL. The ambulance service enhanced the students’ learning in an unfamiliar environment, encouraging them to develop collaborative learning strategies and situational leadership regardless of established hierarchical structures and stereotypes that are sometimes present in other parts of the health care service.

Ethical approval

By the Swedish Ethical Review Authority. No: 2019–03595.
Association of gene polymorphisms in FBN1 and TGF-β signaling with the susceptibility and prognostic outcomes of Stanford type B aortic dissection
Authors: Sun Ling , Chang Yafei , Jiang Peipei , Ma Yitong , Yuan Qinghua , Ma Xiang
Published: March 2022

Background

This study is aimed at investigating the association of Fibrillin-1 (FBN1) and transforming growth factor β (TGF-β) signaling-related gene polymorphisms with the susceptibility of Stanford type B aortic dissection (AD) and its clinical prognostic outcomes.

Methods

Five single-nucleotide polymorphism (SNPs) (FBN1rs 145233125, rs201170905, rs11070646, TGFB1rs1800469, and TGFB2rs900) were analyzed in patients with Stanford type B AD (164) and healthy controls (317). Gene–gene and gene–environment interactions were assessed by generalized multifactor dimensionality reduction. A 4-year follow-up was performed for all AD patients.

Results

G carriers of FBN1 rs201170905 and TGFB1 rs1800469 have an increased risk of Stanford type B AD. The interaction of FBN1, TGFB1, TGFB2 and environmental promoted to the increased risk of type B AD (cross-validation consistency = 10/10, P = 0.001). Dominant models of FBN1rs145233125 TC + CC genotype (P = 0.028), FBN1 rs201170905 AG + GG (P = 0.047) and TGFB1 rs1800469 AG + GG (P = 0.052) were associated with an increased risk of death of Stanford type B AD. The recessive model of FBN1 rs145233125 CC genotype (P < 0.001), FBN1rs201170905 GG (P < 0.001), TGFB1 rs1800469 AG + GG genotype (P = 0.011) was associated with an increased risk of recurrence of chest pain in Stanford type B AD.

Conclusions

The interactions of gene–gene and gene–environment are related with the risk of Stanford type B AD. C carriers of rs145233125, G carriers of rs201170905 and G carriers of rs1800469 may be the poor clinical outcome indicators of mortality and recurrent chest pain in Stanford type B AD.
A mixed-methods study to determine the impact of COVID-19 on food security, food access and supply in regional Australia for consumers and food supply stakeholders
Authors: Godrich Stephanie Louise , Lo Johnny , Kent Katherine , Macau Flavio , Devine Amanda
Published: March 2022

Background

The COVID-19 pandemic has impacted the Australian food supply through changed consumer purchasing patterns, and potentially, household food security. The aim of this study was to determine the impact of COVID-19 on the prevalence of food insecurity and food supply issues, and perspectives of food supply stakeholders in regional Australia.

Methods

A mixed-methods consumer survey and in-depth interviews with food supply stakeholders were conducted in regional Australia, more specifically South West Western Australia between May and July 2020, immediately after the 1stwave of the pandemic.

Results

The prevalence of food insecurity was 21% among consumers, and significantly more prevalent for those aged less than 30 years and living with a disability. Most consumers (73%) agreed that the COVID-19 pandemic had impacted the food supply. Food insecure respondents were more likely to report that food was more expensive, resulting in changes to the types and quantities of food bought. Food supply stakeholders perceived that consumers increased their intention to buy locally grown produce. Panic buying temporarily reduced the availability of food for both food suppliers and consumers, regardless of their food security status.

Conclusions

This study provided novel insights from South West Australian consumer and food supply stakeholder perceptions. Food insecure consumers provided insights about the high cost of food and the subsequent adaptation of their shopping habits, namely type and amount of food purchased. Stakeholder perceptions largely focused on supply chain issues and corroborated consumer reports.
Expression and functions of adenylyl cyclases in the CNS
Authors: Devasani Karan , Yao Yao
Published: March 2022

Adenylyl cyclases (ADCYs), by generating second messenger cAMP, play important roles in various cellular processes. Their expression, regulation and functions in the CNS, however, remain largely unknown. In this review, we first introduce the classification and structure of ADCYs, followed by a discussion of the regulation of mammalian ADCYs (ADCY1-10). Next, the expression and function of each mammalian ADCY isoform are summarized in a region/cell-specific manner. Furthermore, the effects of GPCR-ADCY signaling on blood–brain barrier (BBB) integrity are reviewed. Last, current challenges and future directions are discussed. We aim to provide a succinct review on ADCYs to foster new research in the future.
Multi-patient dose synthesis of [18F]Flumazenil via a copper-mediated 18F-fluorination
Authors: Gendron Thibault , Destro Gianluca , Straathof Natan J. W. , Sap Jeroen B. I. , Guibbal Florian , Vriamont Charles , Caygill Claire , Atack John R. , Watkins Andrew J. , Marshall Christopher , Hueting Rebekka , Warnier Corentin , Gouverneur Véronique , Tredwell Matthew
Published: March 2022

Background

Flumazenil (FMZ) is a functionally silent imidazobenzodiazepine which binds to the benzodiazepine binding site of approximately 75% of the brain γ-aminobutyric acid-A receptors (GABAARs). Positron Emission Tomography (PET) imaging of the GABAARs with [11C]FMZ has been used to evidence alterations in neuronal density, to assess target engagement of novel pharmacological agents, and to study disorders such as epilepsy and Huntington’s disease. Despite the potential of FMZ PET imaging the short half-life (t1/2) of carbon-11 (20 min) has limited the more widespread clinical use of [11C]FMZ. The fluorine-18 (18F) isotopologue with a longer t1/2 (110 min) is ideally suited to address this drawback. However, the majority of current radiochemical methods for the synthesis of [18F]FMZ are non-trivial and low yielding. We report a robust, automated protocol that is good manufacturing practice (GMP) compatible, and yields multi-patient doses of [18F]FMZ.

Results

The fully automated synthesis was developed on the Trasis AllinOne (AIO) platform using a single-use cassette. [18F]FMZ was synthesized in a one-step procedure from [18F]fluoride, via a copper-mediated 18F-fluorination of a boronate ester precursor. Purification was performed by semi-preparative radio-HPLC and the collected fraction formulated directly into the final product vial. The overall process from start of synthesis to delivery of product is approximately 55 min. Starting with an initial activity of 23.6 ± 5.8 GBq (n = 3) activity yields of [18F]FMZ were 8.0 ± 1 GBq (n = 3). The synthesis was successfully reproduced at two independent sites, where the product passed quality control release criteria in line with the European Pharmacopoeia standards and ICH Q3D(R1) guidelines to be suitable for human use.

Conclusion

Reported is a fully automated cassette-based synthesis of [18F]FMZ that is Good Manufacturing Practice (GMP) compatible and produces multi-patient doses of [18F]FMZ.
Evaluation of antioxidant, phytochemicals and antibacterial potential of Mormordica charantia (Linn) against pathogenic bacteria isolated from ready to eat food sold in Akure Metropolis, Nigeria
Authors: Ibisanmi Tope Abraham , Aribisala Jamiu Olaseni
Published: March 2022

Background

Food hygiene and safety is of utmost importance for public health, as it helps to protect the health of consumers from foodborne illnesses. Although, hundreds of plant species have been screened and tested for antimicrobial properties, the vast majority of these plants have not been adequately screened and evaluated. Considering the vast potentiality of plants as sources for antimicrobial drugs, the present research aimed to evaluate antioxidant, phytochemicals and determine the antibacterial activity ofM. charantia(Linn)onpathogenic organism from Ready-to-eat food sold in Akure metropolis.

Results

Bacteria isolated from RTE food studied belong to the following genera;Staphylococcus, Streptococcus, Citrobacter, Pectobacterium, Klebsiella, Bacillus, Kocuria, Kluyveria, Serratia, Pantoea, Enterobacter and Salmonella. The antibiotic susceptibility pattern revealed that the Gram negative organisms were more susceptible to Gentamycin (30 µg) while Streptomycin (30 µg) was found to be more potent on Gram positive organisms. Water and ethanol extracts showed significant to moderate antibacterial activity toward all tested isolates except;Escherichia vulnerisandKluyveria intermediawhich are both resistant to the aqueous extracts ofM. charantiaand the latter which was resistant to the ethanoic extract. The highest inhibitory activity was observed forBacillus cereuswith zone of inhibition of diameters 28 ± 0.29l(mm), followed byEscherichia vulneris25 ± 0.29l(mm). DDPH% Inhibition has higher value in the water extract (69.21 ± 0.882a) while lower value was recorded in the ethanol extract (67.89 ± 0.155b). % Iron chelation has higher value in the ethanol extract (121.87 ± 0.882a) while lower value was recorded in the water extract (97.28 ± 0.155b). In all the concentration, vitamin C was higher in the ethanol extract than in the water extract.

Conclusions

The study revealed that all the Ready-to-eat food had a total bacterial count that are below potentially hazardous count although the presence of some microorganisms that are of health significance were observed. The study also confirmed thatM. charantia(Linn) extracts had antibacterial effect against tested isolates from Ready-to-eat food sold in Akure metropolis. Based on the findings of this great research work,Mormordica charantia(Linn) possesses antioxidant activity that could prevent oxidative stress and degenerative diseases.
Official position of the Brazilian Association of Bone Assessment and Metabolism (ABRASSO) on the evaluation of body composition by densitometry: part I (technical aspects)—general concepts, indications, acquisition, and analysis
Authors: Maeda Sergio Setsuo , Peters Barbara Santarosa Emo , Martini Lígia Araújo , Antunes Hannah Karen Moreira , Gonzalez Maria Cristina , Arantes Henrique Pierotti , Prado Carla M. , Pinto Camila Lemos , de Araújo Iana Mizumukai , de Paula Francisco José Albuquerque , Borges Joao Lindolfo Cunha , Albergaria Ben-Hur , Ushida Marcela , de Souza Guilherme Cardenaz , de Mendonça Laura Maria Carvalho , do Prado Mirley , de Medeiros Pinheiro Marcelo
Published: March 2022

Objective

To review the technical aspects of body composition assessment by dual-energy X-ray absorptiometry (DXA) and other methods based on the most recent scientific evidence.

Materials and methods

This Official Position is a result of efforts by the Scientific Committee of the Brazilian Association of Bone Assessment and Metabolism (Associação Brasileira de Avaliação Óssea e Osteometabolismo, ABRASSO) and health care professionals with expertise in body composition assessment who were invited to contribute to the preparation of this document. The authors searched current databases for relevant publications. In this first part of the Official Position, the authors discuss the different methods and parameters used for body composition assessment, general principles of DXA, and aspects of the acquisition and analysis of DXA scans.

Conclusion

Considering aspects of accuracy, precision, cost, duration, and ability to evaluate all three compartments, DXA is considered the gold-standard method for body composition assessment, particularly for the evaluation of fat mass. In order to ensure reliable, adequate, and reproducible DXA reports, great attention is required regarding quality control procedures, preparation, removal of external artifacts, imaging acquisition, and data analysis and interpretation.
Epidemiological studies on lower respiratory tract infection in children in the District Bannu, Khyber Pakhtunkhwa, Pakistan
Authors: Khan Muhammad Ashraf
Published: March 2022

Background

Lower respiratory tract infections are the leading cause of death in children globally and are transmitted by inhaling airborne droplets. The study demonstrated the prevalence of lower respiratory tract infections in children admitted to the Women and Children Hospital Bannu from February through November 2019. The cross-sectional study was conducted by obtaining indoor data from the official record maintained in the children’s wards.

Results

Males accounted for 649 (61.6%) and females 405 (38.4%) cases out of 1054 cases of the disease. Age group of ≤ 6 months showed 36.2% prevalence, followed by > 6 m ≤ 1 y (25.6%), > 1 y ≤ 2 y (17.1%), > 2 y ≤ 5 y (14.3%), > 5 ≤ 10 y (6.0%), and > 10 y ≤ 15 y (0.8%). Pediatric patients of age ≤ 2 y and ≤ 5 y contributed 78.9% and 93.3% to overall disease, respectively. The disease was at its peak in February (17.9%) while lowest in May (5.5%). The age group (≤ 6 m) was the dominant group in all months except August when replaced by the age group (> 6 m ≤ 1 y). The disease revealed higher prevalence during February-April and October-November.

Conclusions

Different age groups showed variation in the prevalence of the disease with an age group of ≤ 5 y contributing the largest share and seasonal peaks in the disease occurred. The present findings help in adopting strategies for effective control of the disease in different age groups of the children for their peak season.
Impact of sequential therapy with osimertinib on the overall survival in patients with EGFR-mutant non-small cell lung cancer
Authors: Inomata Minehiko , Matsumoto Masahiro , Mizushima Isami , Hayashi Kana , Seto Zenta , Tokui Kotaro , Taka Chihiro , Okazawa Seisuke , Kambara Kenta , Imanishi Shingo , Miwa Toshiro , Hayashi Ryuji , Matsui Shoko , Tobe Kazuyuki
Published: March 2022

Purpose

We conducted a retrospective analysis of the data of patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) to investigate the associations between clinical factors and the overall survival.

Methods

We retrieved the patient data from the medical charts. Patients who were diagnosed as having EGFR-mutant NSCLC and treated with EGFR-tyrosine kinase inhibitors (EGFR-TKIs) between 2007 and 2020 at our institution were included in the analysis.

Results

A total of 130 patients were included in the analysis. A log-rank test identified EGFR exon 19 deletion in the tumor, an Eastern Cooperative Oncology Group performance status of 0–1, serum lactate dehydrogenase level, local therapy for brain metastasis, and sequential osimertinib therapy for patients with the T790M mutation acquired after primary EGFR-TKI therapy as being significantly associated with a better overall survival. Analysis using a Cox proportional hazards model identified EGFR exon 19 deletion in the tumor, an Eastern Cooperative Oncology Group performance status of 0–1, serum lactate dehydrogenase level, local therapy for brain metastasis, and sequential therapy with osimertinib as being independently associated with a prolonged overall survival.

Conclusion

Our analysis suggested that EGFR mutation status, an Eastern Cooperative Oncology Group performance status, serum lactate dehydrogenase level, local therapy for brain metastasis, and sequential therapy with osimertinib were associated with overall survival in patients with EGFR-mutant NSCLC in clinical practice settings.
Reproductive problems and intensity of anxiety and depression in women treated for infertility
Authors: Wdowiak Artur , Makara-Studzińska Marta , Raczkiewicz Dorota , Cyranka Katarzyna
Published: March 2022

Cel pracy

Celem pracy była ocena nasilenia lęku i depresji u kobiet leczonych z powodu niepłodności w porównaniu z nasileniem tych parametrów klinicznych u kobiet bez problemów z rozrodem oraz ocena wpływu zaburzeń emocjonalnych na cykl owulacyjny.

Metoda

Owulację oceniano za pomocą badań hormonalnych i ultrasonograficznych. Stan emocjonalny został zbadany za pomocą Inwentarza Stanu i Cechu Lęku STAI oraz skali lęku i depresji HADS

Wyniki

Nasilenie lęku jako cechy i jako stanu oceniane przy pomocy STAI było znacznie wyższe u kobiet leczonych z powodu niepłodności niż u kobiet z potwierdzoną płodnością, a także wyższe u kobiet leczonych z powodu niepłodności, które nie zaszły w ciążę, niż u kobiet, które zaszły w ciążę. Nasilenie objawów lękowych i depresyjnych według HADS było znacznie wyższe u kobiet leczonych z powodu niepłodności niż u kobiet z potwierdzoną płodnością. Kobiety leczone z powodu niepłodności, które nie zaszły w ciążę, osiągnęły znacznie wyższe nasilenie objawów depresyjnych niż kobiety w ciąży. W surowicy kobiet leczonych z powodu niepłodności poziomy kortyzolu, zarówno podczas owulacji, jak i po niej, dodatnio korelowały z nasileniem lęku jako cechy i stanu, a także z depresją Te same korelacje stwierdzono w grupie kobiet z potwierdzoną płodnością (z wyjątkiem objawów lękowych).

Wnioski

1. Lęk i depresja związane są z problemami reprodukcyjnymi. Należy zbadać naturę i kierunek tego związku.
2. Zaburzenia emocjonalne niekorzystnie wpływają na wydzielanie hormonów cyklu płciowego i wzrost endometrium.
3. Pary z problemami reprodukcyjnymi wymagają wsparcia psychologicznego w celu poprawy efektów leczenia niepłodności.
A 45-year follow-up study of adolescent schizophrenia. Part II: Age of disease onset, type of onset of the disorder and presence of developmental burden in the context of disease course and long-term social functioning of patients
Authors: Ślosarczyk Mariusz , Ślosarczyk Katarzyna , Furgał Mariusz
Published: March 2022

Cel pracy

W literaturze przedmiotu rzadko spotyka się badania nad predyktorami przebiegu schizofrenii młodzieńczej, zwłaszcza oparte na danych pochodzących z długoterminowych katamnez. W naszej analizie badamy zależności pomiędzy wiekiem zachorowania, typem początku zaburzenia oraz obecnością obciążeń rozwojowych a wskaźnikami klinicznymi i społecznymi przebiegu choroby.

Metoda

69 pacjentów hospitalizowanych wieku średnio 16 lat (punkt 0) z powodu schizofrenii (rediagnozowanej retrospektywnie wg kryteriów ICD-10) i powtórnie zbadanych w 5 lat później (punkt 1 – badanie osobiste dotyczyło 41 osób) zostało po raz kolejny poddanych ocenie pod kątem parametrów klinicznych i społecznych w 45 lat po wyjściowej hospitalizacji (punkt 2 – badanie osobiste dotyczyło 21 osób). Poza badaniem osobistym korzystano także z innych metod zbierania danych, w tym także z kwerend szpitalnych.

Wyniki

Skryty typ początku schizofrenii ujawnił liczne i różnorodne korelacje zarówno z obrazem objawowym i klinicznym przebiegiem schizofrenii, jak i z odległym funkcjonowaniem społecznym badanych, przekładając się na klasycznie bleulerowski obraz objawowy, słabszą reakcję na leczenie oraz gorsze funkcjonowanie w życiu osobistym i zawodowym. Obecność istotnych separacji w dzieciństwie okazała się czynnikiem sprzyjającym wglądowi oraz mniejszemu nasileniu psychopatologii w odległym przebiegu schizofrenii. Rodzinne obciążenie schizofrenią korelowało z obrazem katatonicznym w przyszłości oraz z większą ilością hospitalizacji i wcześniejszą śmiercią.

Wnioski

Skryty typ początku schizofrenii jest najistotniejszym spośród badanych przez nas predyktorów jej późniejszego przebiegu.
Higher indexes of childhood trauma in borderline personality disorder compared with bipolar disorder
Authors: Jaworska-Andryszewska Paulina , Rybakowski Janusz
Published: March 2022

Cel pracy

Cel badań. Porównanie częstości traumatycznych wydarzeń w dzieciństwie w grupach chorych z chorobą afektywną dwubiegunową (ChAD), pacjentów z zaburzeniem osobowości typu borderline (borderline personality disorder - BPD) i osób zdrowych.

Metoda

Metody. Badaniem objęto 35 pacjentów (10 mężczyzn, 25 kobiet) z ChAD, hospitalizowanych w Klinice Psychiatrii Dorosłych UM w Poznaniu, Szpitalu Neuropsychiatrycznym w Kościanie oraz w Milickim Centrum Medycznym oraz 35 pacjentów (9 mężczyzn, 26 kobiet) z BPD pozostających pod opieką Szpitala im. Babińskiego w Krakowie. Grupę kontrolną stanowiło 71 zdrowych osób (22 mężczyzn, 49 kobiet). W badaniu użyto polskiej wersji Kwestionariusza Traumy Wczesnodziecięcej (CTQ).

Wyniki

Wyniki. W obu grupach klinicznych nie stwierdzono różnic między mężczyznami, a kobietami dotyczących wskaźników CTQ, natomiast pacjenci z tych grup istotnie częściej niż osoby z grupy kontrolnej doświadczali traumatycznych przeżyć w dzieciństwie. Pacjenci z BPD wykazywali istotnie wyższy poziom wskaźników mierzonych narzędziem CTQ w porównaniu z pacjentami z ChAD.

Wnioski

Wnioski. Uzyskane wyniki wskazują na istotnie częstsze doświadczanie w dzieciństwie traumatycznych przeżyć u osób z BPD w porównaniu z pacjentami z ChAD. Omawiane to jest w kontekście patogenezy obu tych chorób oraz sposobów ich leczenia. BPD należy prawdopodobnie do zaburzeń psychicznych, w patogenezie których trauma wczesnodziecięca odgrywa największą rolę.
Jordan in The Church of The Higher Hilbert Space: Entanglement and Thermal Fluctuations
Authors: Vedral Vlatko
Published: March 2022

I revisit Jordan's derivation of Einstein's formula for energy fluctuations in the black body in thermal equilibrium. This formula is usually taken to represent the unification of the wave and the particle aspects of the electromagnetic field since the fluctuations can be shown to be the sum of wave-like and particle-like contributions. However, in Jordan's treatment there is no mention of the Planck distribution and all averages are performed with respect to pure number states of radiation (mixed states had not yet been discovered!). The chief reason why Jordan does reproduce Einstein's result despite not using thermal states of radiation is that he focuses on fluctuations in a small (compared to the whole) volume of the black body. The state of radiation in a small volume is highly entangled to the rest of the black body which leads to the correct fluctuations even though the overall state might, in fact, be assumed to be pure (i.e. at zero temperature). I present a simple derivation of the fluctuations formula as an instance of mixed states being reductions of higher level pure states, a representation that is affectionately known as "Church of the Higher Hilbert Space". According to this view of mixed states, temperature is nothing but the amount of entanglement between the system and its environment.Quanta 2022; 11: 1–4.
Using Digital Platforms in Schools for Prevention and Health Promotion: A Scoping Review
Authors: Dagenais Christian , Proulx Michelle , McSween-Cadieux Esther
Published: March 2022

Objective: Digital platforms for prevention and health promotion (PHP) are now, more than ever, available for use by school professionals, including teachers. However, little is known about what motivates them to use such platforms. A scoping review (ScR) was conducted to identify conditions that promote use by school professionals, including teachers, of PHP digital platforms at schools. Methods: For our ScR, we accessed ERIC, Sociological Abstracts, MEDLINE, PubMed, and Web of Science databases (period 2000-2018) in 3 sectors: education, health, online technologies. For each study, we prepared and validated a summary sheet. Contents dealing with conditions for use were subjected to open coding, grouped into categories, and synthesized. Results: Of the 3639 articles captured, 17 studies were selected. Five conditions emerged: (1) ensuring that the digital platform becomes a reference for PHP activity in schools; (2) that the resources needed for its uptake are mobilized; (3) that it is user-friendly; (4) that the digital platform engages the participation of everyone involved; and (5) that it is linked to existing programs in the school. Conclusions: These results can guide the activities deployed in schools for optimal implementation of PHP programs from digital platforms.