bluuebunny/crossref_metadata_2025 huggingface dataset:
Catalyst-free synthesis of tetrahydrodipyrazolopyridines via an one-pot tandem and green pseudo-six-component reaction in water
Authors: Keihanfar Mina , Mirjalili Bi Bi Fatemeh
Published: March 2022

Background

A new, green and environmentally friendly protocol has been developed for the synthesis of tetrahydrodipyrazolopyridine derivatives. The structures of these products were determined in terms of melting point, FTIR, NMR and Mass spectroscopy.

Results

The tetrahydrodipyrazolopyridine derivatives were synthesized in water through a catalyst-free pseudo-six-component reaction of hydrazine hydrate, ethyl acetoacetate, ammonium acetate and aldehyde at room temperature.

Conclusions

This novel procedure has some advantages such as aqueous media, high yield and simple work-up.

Graphical Abstract
Growth in diagnosis and treatment of primary immunodeficiency within the global Jeffrey Modell Centers Network
Authors: Quinn Jessica , Modell Vicki , Orange Jordan S. , Modell Fred
Published: March 2022

Background

Primary immunodeficiencies (PI), which include more than 450 single-gene inborn errors of immunity and may affect up to 1% of the population, are genetic disorders that impair the immune system. If not properly identified and treated, individuals with PI are subject to serious, prolonged, and sometimes life-threatening infections or autoimmunity. Despite advancements, awareness of PI remains a critical issue for physicians and the public alike, as this leads to the enhanced and expedited management of these conditions. To address this critical issue, the Jeffrey Modell Foundation (JMF) formed a global network of specialized centers. The goal of this endeavor was to raise awareness of PI to better identify, diagnose, and treat patients, reducing associated mortality and morbidity and improving quality of life (QOL). For more than two decades, the Jeffrey Modell Centers Network (JMCN) has served as the foundation upon which these goals have been pursued. The JMCN currently includes 909 Expert Physicians at 400 institutions, in 316 cities, and 86 countries spanning six continents.

Methods

A survey was developed by JMF for members of the JMCN, following the most recent Classification of PI from the IUIS Expert Committee, to periodically describe the patient population, including treatment modalities and demographics. Physician-reported data from 2021 was compared to that from 2018 and 2013. Physicians in the JMCN also reported on select outcomes of their PI patients one year prior to and one year following diagnosis.

Results

A total of 300 JMF Physician Surveys from 681 physicians were included in this analysis. This is a 75% physician response rate. From 2013 to 2021, there was a 96.3% increase in patients followed in the US and an 86.1% increase globally. During the same period, patients identified with a specific PI defect increased by 46.6% in the US and 47.9% globally. Patients receiving IgG and HSCT increased by 110% and 201% respectfully since 2013. Early diagnosis led to reported decreased morbidity and mortality and reduced calculated healthcare costs.

Conclusions

This global analysis of physician-reported data on patients with PI demonstrates an increase in both diagnosed and treated patients. This substantial increase from within the JMCN is a testament to its impact. In addition to building an extensive global patient database, the expanding JMCN serves as a unique and critical resource, providing the infrastructure for earliest diagnosis, optimized treatments, and implementation of standard-of-care and best practices. The JMCN provides a critical platform that facilitates the education of physicians and patients, awareness initiatives, and research advances, through collaboration and connectivity, ultimately resulting in improved outcomes and QOL for patients with PI. The JMCN has steadily and substantially grown for more than two decades and continues to substantively impact the field of Immunology globally.
The assessment of image quality and diagnostic value in X-ray images: a survey on radiographers’ reasons for rejecting images
Authors: Kjelle Elin , Chilanga Catherine
Published: March 2022

Background

Assessing the quality of diagnostic images is subjective and influenced by factors such education, skills, and experience of the assessor. This study aims to explore the radiographers’ assessments of medical usefulness or rejection of X-ray images in specific cases.

Results

Eighty-one radiographers from different countries responded to the questionnaire distributed online at the EFRS research HUB at ECR 2020 (a 15% response rate). Forty-two percent of the respondents practiced in the UK and Ireland. In addition to rejecting or keeping images in the presented 30 cases and giving a main reason for the images rejected, the participants explained their choice using comments, 1176 comments were obtained. Sixty percent of the comments were on kept images. The respondents kept on average 63% of the images. In the “Keep”, “Could keep”, and “Reject” categories on average 84%, 63% and 43% of images were kept respectively. The most common reasons given for rejecting an image were suboptimal positioning and centering. Potential diagnostic value and radiation protection were indicated as reasons to keep an image perceived as of low quality reported in n = 353 and n = 33 comments respectively.

Conclusions

There is an agreement internationally on what makes a good quality X-ray image. However, the opinion on medical usefulness of images of low or poor quality compared to image criteria varies. Diagnostic capability and radiation protection was the rationale used for keeping images not fulfilling image criteria. There seems to be a need for diagnostic quality to be included in image assessment in clinical practice.
Target occupancy study and whole-body dosimetry with a MAGL PET ligand [11C]PF-06809247 in non-human primates
Authors: Arakawa Ryosuke , Takano Akihiro , Nag Sangram , Jia Zhisheng , Amini Nahid , Maresca Kevin P. , Zhang Lei , Keliher Edmund J. , Butler Christopher R. , Piro Justin R. , Samad Tarek A. , Smith Deborah , Nason Deane , O’Neil Steve , Trapa Patrick , Fonseca Kari R. , Litchfield John , McCarthy Timothy , Carson Richard E. , Halldin Christer
Published: March 2022

Background

Monoacylglycerol lipase (MAGL) is a key serine hydrolase which terminates endocannabinoid signaling and regulates arachidonic acid driven inflammatory responses within the central nervous system. To develop [11C]PF-06809247 into a clinically usable MAGL positron emission tomography (PET) radioligand, we assessed the occupancy of MAGL by an inhibitor in the non-human primate (NHP) brain. Additionally, we measured the whole-body distribution of [11C]PF-06809247 in NHP and estimated human effective radiation doses.

Methods

Seven cynomolgus monkeys were enrolled for brain PET measurements. Two PET measurements along with arterial blood sampling were performed in each NHP: one baseline and one pretreatment condition with intravenous administration of PF-06818883, a pro-drug of a selective MAGL inhibitor (total of seven doses between 0.01 and 1.27 mg/kg). Kinetic parameters K1, k2 and k3 were estimated by a two tissue compartment (2TC) model using metabolite corrected plasma radioactivity as the input function. k4 was set as 0 according to the irreversible binding of [11C]PF-06809247. Ki by 2TC and Patlak analysis were calculated as the influx constant. The target occupancy was calculated using Ki at baseline and pretreatment conditions. Two cynomolgus monkeys were enrolled for whole-body PET measurements. Estimates of the absorbed radiation dose in humans were calculated with OLINDA/EXM 1.1 using the adult male reference model.

Results

Radioactivity retention was decreased in all brain regions following pretreatment with PF-06818883. Occupancy was measured as 25.4–100.5% in a dose dependent manner. Whole-body PET showed high radioactivity uptake values in the liver, small intestine, kidney, and brain. The effective dose of [11C]PF-06809247 was calculated as 4.3 μSv/MBq.

Conclusions

[11C]PF-06809247 is a promising PET ligand for further studies of MAGL in the human brain.
Explaining external economic support inequality among households affected by HIV/AIDS in Tanzania: an Oaxaca Blinder decomposition analysis
Authors: Guets Wilfried , Ameyaw Edward Kwabena , Yaya Sanni
Published: March 2022

Background

HIV/AIDS remains the leading cause of death in sub-Saharan Africa. Due to multiple constraints experienced by households that seem to be disproportionally affected, families generally seek assistance from the community and external economic support. Previous researchers studied socioeconomic and gender inequality in HIV/AIDS prevalence in sub-Saharan African countries. However, very few researchers have paid attention to the external economic support for HIV/AIDS affected households in Tanzania. This study investigates the difference in economic support among households affected or not affected by the HIV/AIDS epidemic in Tanzania.

Methods

Data used stemmed from the Tanzania HIV Impact Survey 2016–2017 (THIS) of the Population-based HIV Impact Assessment (PHIA) project, collected between 2016 and 2017 in Tanzania. The study population were the heads of households (adults) with age greater than 15. The dependent variable for the study was economic support. This consisted of both material and non-material assistance obtained from outside the household. Socio-demographic (economics) characteristics constituted the predictors of the study. Descriptive statistics and econometric modelling were used to analyse determinants associated with external economic support. Oaxaca-Blinder decomposition method was also performed to investigate the difference in economic support depending on households’ serological status in Tanzania.

Results

A total of 12,008 households were included. Almost 11% of the household heads indicated that their households received economic support. HIV/AIDS affected 7% of households. The mean age of the household heads was 45 years (SD ± 15) with a range of 16–80. The majority of household heads were men (72%). Being a household head affected by HIV/AIDS increases the probability to receive external economic support (p < 0.05). The difference in external economic support between the two groups (HIV/AIDS and no- HIV/AIDS households) was - 0.032 (p < 0.01). This gap was observed to favour households affected by HIV/AIDS. Almost 72% (− 0.023/− 0.032) of this difference was explained by characteristics such as the wealth index (p < 0.01), residence area (urban) (p < 0.01), marital status (widowed (p < 0.05) and divorced or separated) (p < 0.1) and age (p < 0.01).

Conclusion

The difference in economic support across households affected or not affected by HIV/AIDS was explained by wealth index, residence area, marital status and age. These findings represent important implications for health policy regarding future economic support strategies for HIV/AIDS-affected households.
Image denoising based on global image similar patches searching and HOSVD to patches tensor
Authors: Guo Jiye , Chen Huayan , Shen Zhengwei , Wang Ziqing
Published: March 2022

Nonlocal self-similarity of natural image is an essential property for image processing. But how to measure the similarity between different patches and how to better exploit the similarity of patches are two crucial problems for image denoising. In this article, we establish a novel image denoising method based on a global image similar patches searching method and the similar patches tensor high-order singular value decomposition theory. Particularly, in order to find the reasonable similar patches to a reference, a variant of Gaussian mixture model (GMM) global similar patches searching method is proposed, and the graph process unit-based GMM model training method is performed to speed up the training process. Furthermore, the k-means and the local inter-class searching are used to improve on the similarity measure between patches. To better exploit the similarity of patches to image denoising, we rearrange similar patches to a tensor for each reference, and an iterative adaptive weighted tensor low-rank approximation method is established to perform image denoising. Experimental results clearly show that the proposed method is comparable to many recent denoising algorithms from the PNSR, SSIM and NCC viewpoint. For higher noise level (e.g., $$sigma=50$$

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i
g
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), the performance of our proposed algorithm evinces a 0.06-unit, 0.05-unit and 0.12-unit improvement in the PNSR, SSIM and NCC score, respectively, when compared to state-of-the-art.
The impact of wait time on patient outcomes in knee and hip replacement surgery: a scoping review protocol
Authors: Dawson E. , Neufeld M. E. , Schemitsch E. , John-Baptiste A.
Published: March 2022

Background

Total hip and total knee replacement surgery are in high demand, leading to long wait times for many patients. While on the waiting list, patients may experience worsening pain, reduced mobility, and deteriorating health. Given that long wait times are common for lower joint replacement surgery, it is important to understand how patient health changes during the wait period and whether this impacts patient outcomes after surgery. The aim of this scoping review will be to identify and describe the evidence regarding the impact of wait time on patient outcomes for patients who undergo total knee and total hip replacement surgery.

Methods

This scoping review was designed with guidance from the Joanna Briggs Institute Manual for Evidence Synthesis, and results will be reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews. EMBASE, Medline, PubMed, Scopus, CINAHL, and Cochrane electronic databases will be searched for English language articles published after 1999. Studies of adult patients with osteoarthritis undergoing primary knee or hip replacement surgery, which measure patient outcomes over the wait period for surgery, will be included. Two independent reviewers will screen titles and abstracts followed by full article review. Data will be extracted by two reviewers using a standardized form. Outcomes assessed during the wait period will be identified and described in tables. Factors associated with changes in health status during the wait period will be qualitatively described.

Discussion

This review will map the evidence regarding wait times for lower extremity joint replacement surgery. Better understanding of how the impact of wait times on patient health status is measured over the perioperative period will inform future research on wait times.

Scoping review registration

Registered with Open Science Framework, Feb 14, 2021 DOI: 10.17605/OSF.IO/MV4FS
Increased TOX expression associates with exhausted T cells in patients with multiple myeloma
Authors: Zhao Yujie , Liao Pengjun , Huang Shuxin , Deng Tairan , Tan Jiaxiong , Huang Youxue , Zhan Huien , Li Yangqiu , Chen Shaohua , Zhong Liye
Published: March 2022

Previous studies have shown increased aberrant expression of immune checkpoint (IC) proteins, such as programmed cell death receptor-1 (PD-1) and T cell immunoglobulin mucin-domain-containing-3 (Tim-3) on T cells from patients with multiple myeloma (MM), which result in T cell exhaustion and dysfunction. However, little is known about the mechanism regulating aberrant IC protein expression. In this study, we analyzed the expression of TOX (thymocyte selection-associated HMG BOX), a crucial transcription factor involved in T cell exhaustion, and its co-expression with PD-1, Tim-3, and CD244 in T cell subsets by multi-color fluorescent flow cytometry in peripheral blood (PB) and bone marrow (BM) samples from patients with MM. Significantly, the percentage of TOX + CD3 +/CD4 +/CD8 + T cells was increased, and similarly, higher numbers of TOX co-expression with PD-1, Tim-3, and CD244 on CD3 +/CD4 +/CD8 + T cells were found. Interestingly, the numbers of TOX +, TOX + PD-1 +, and TOX + Tim-3 + regulatory T (Treg) cells also significantly increased in both the PB and BM of MM patients. In summary, we for the first time observed increased TOX expression concurrent with PD-1, Tim-3, and CD244 on T cells, which may contribute to T cell exhaustion and impair their function in MM. Thus, TOX may be considered a potential target for reversing T cell exhaustion and improving T cell function in MM.
Epidemiological characteristics of imported respiratory infectious diseases in China, 2014‒2018
Authors: Wang Jin-Long , Chen Tao , Deng Le-Le , Han Ya-Jun , Wang Da-Yan , Wang Li-Ping , He Guang-Xue
Published: March 2022

Background

With the progress of globalization, international mobility increases, greatly facilitating cross-border transmission of respiratory infectious diseases (RIDs). This study aimed to analyze the epidemiological characteristics and factors influencing imported RIDs, with the goal of providing evidence to support adoption of high-tech, intelligent methods to early find imported RIDs and prevent their spread in China.

Methods

We obtained data of imported RIDs cases from 2014 to 2018 from the Inbound Sentinel Network of Customs and the National Notifiable Diseases Reporting System in China. We analyzed spatial, temporal, and population distribution characteristics of the imported RIDs. We developed an index to describe seasonality. Pearson correlation coefficients were used to examine associations between independent variables and imported cases. Data analyses and visualizations were conducted with R software.

Results

From a total of 1 409 265 253 inbound travelers, 31 732 (2.25/100 000) imported RIDs cases were reported. RIDs cases were imported from 142 countries and five continents. The incidence of imported RIDs was nearly 5 times higher in 2018 (2.81/100 000) than in 2014 (0.58/100 000). Among foreigners, incidence rates were higher among males (5.32/100 000), 0–14-year-olds (15.15/100 000), and cases originating in Oceania (11.10/100 000). The vast majority (90.3%) of imported RIDs were influenza, with seasonality consistent with annual seasonality of influenza. The spatial distribution of imported RIDs was different between Chinese citizens and foreigners. Increases in inbound travel volume and the number of influenza cases in source countries were associated with the number of imported RIDs.

Conclusions

Our study documented importation of RIDs into China from 142 countries. Inbound travel poses a significant risks bringing important RIDs to China. It is urgent to strengthen surveillance at customs of inbound travelers and establish an intelligent surveillance and early warning system to prevent importation of RIDs to China for preventing further spread within China.

Graphical Abstract
Coordinated control by ADRC strategy for a wind farm based on SCIG considering low voltage ride-through capability
Authors: Laghridat Hammadi , Essadki Ahmed , Nasser Tamou
Published: March 2022

Wind farms are integrated with the power grid system to provide active and reactive power. Because in a wind farm, wind turbines (WTs) are highly coupled to their operating conditions, a central wind farm supervisory unit must take into account these conditions when producing power control references for each WT. The aim of this paper is to manage and control the active and reactive power of wind farms based on squirrel cage induction generators and back-to-back converters. The proportional distribution algorithm is used for distributing wind farm power to individual WTs. In addition, we consider the development of a local power management and control units for WTs. This is in order to extract the maximum available power from the wind, and to provide the active and reactive power predetermined by the transmission system operator, or to satisfy the grid code requirements considering Low Voltage Ride-through capability. The power dispatch strategy is to be used on all WTs using the distribution algorithm while ensuring the control loops using the proposed Active Disturbance Rejection Control strategy. The results demonstrate that the proposed strategies are efficient and can guarantee the safe integration of wind farms into the grid while respecting grid code requirements and power system stability.
Ultrasound-guided quadratus lumborum block versus transversus abdominis plane block in patients undergoing total abdominal hysterectomy
Authors: Alansary Amin M. , Kamaly Ayman M. , Abdel Hamid Hatem S. , Aboelanean Yassmin M. , Ezzat Ahmed W.
Published: March 2022

Background

Ultrasound (US)-guided quadratus lumborum block (QLB) and transversus abdominis plane block (TAP) are used as a part of multimodal analgesia for postoperative pain after abdominal procedures, as they improve postoperative pain.

Results

QLB group showed significantly better visual analog score (VAS) scores from 6 h till 24 h postoperative. Time for the first request for pethidine was significantly longer in the QLB group (398.3 ± 23.7 min) than in the TAP group (80.3 ± 20.7 min), (p < 0.0001 and its total consumption was significantly lesser (p = 0.007) in the QLB group (68.33 ± 66.28) than in TAP group (120.0 ± 76.11). Also, the sensory level was higher in the QLB group (8.3 ± 0.63 segments) than in the TAP group (6.2 ± 0.79 segments), (p < 0.001). Moreover, only 2 patients (6.67%) in the QLB group experienced nausea and/or vomiting versus 9 (30%) in TAP group with significant value.

Conclusions

QLB was more effective in providing visceral and somatic pain analgesia after total abdominal hysterectomy (TAH) in comparison to TAP block, QLB resulted in wider sensory blockade compared to TAP block with less incidence of postoperative nausea and/or vomiting.
Effect of partial substitution of wheat flour with Moringa oleifera leaf powder on physical, nutritional, antioxidant and antidiabetic properties of cookies
Authors: Fapetu Aanuoluwapo Patricia , Karigidi Kayode Olayele , Akintimehin Emmanuel Sina , Olawuwo Tomilayo , Adetuyi Foluso Olutope
Published: March 2022

Background

Moringa oleifera leaf is a prominent leaf in folk medicine used to treat many diseases including diabetes mellitus. This study is aimed at determining the effects of substitution of wheat flour with Moringa oleifera leaf powder (MOLP) on physical, nutritional, bioactive, antioxidant and antidiabetic properties of cookies. Wheat flour was substituted with MOLP (2.5%, 5% and 10%) in the baking of the cookies (C1, C2 and C3, respectively), and its effects were evaluated on proximate, bioactive compounds, antioxidant, physical and inhibitory properties against α-amylase and α-glucosidase enzymes using standard methods. Also, sensory attributes of the cookies were determined using 9-point hedonic point.

Results

The results showed thickness were significantly (p < 0.05) reduced while diameter and spread ratio of the cookies increased as the level of MOLP increases. The inclusion of MOLP in the cookies led to significant (p < 0.05) enhancement in the bioactive compound, antioxidant and inhibitory properties of MOLP-substituted cookies. Also protein, ash, fat and fibre contents were significantly (p < 0.05) increased in MOLP-substituted cookies while carbohydrate and energy value reduced. The sensory evaluation revealed that MOLP-substituted cookies at the level of 2.5% were more acceptable than other MOLP-substituted cookies.

Conclusion

With the higher bioactive, antioxidant and inhibitory abilities against α-amylase and α-glucosidase enzymes and enhanced protein content of MOLP-substituted cookies, MOLP poses as a potential functional ingredient in baking of cookies.
Implant survivorship, functional outcomes and complications with the use of rotating hinge knee implants: a systematic review
Authors: Xu Joshua , von Fritsch Lennart , Sabah Shiraz A. , Price Andrew J. , Alvand Abtin
Published: March 2022

Background

With more complex primary and revision total knee arthroplasty procedures there is often the need to use more constrained prostheses. This study aims to investigate patient-relevant outcomes following primary and revision rotating-hinged total knee arthroplasty.

Methods

Electronic searches were performed using four databases from their date of inception to January 2021. Relevant studies were identified, with data extracted and analysed using PRIMSA guidelines.

Results

Nineteen studies were included, producing a cohort of 568 primary and 413 revision rotating hinge total knee arthroplasties (TKAs). Survival was assessed at 1-, 5-, and 10-year post-implantation. Sensitivity analyses based on person-time incidence ratios (PTIRs) were prespecified for studies not reporting survival at these timepoints. From the primary hinge TKA cohort, the median survival at 1 year was 93.4% and at 10 years it was 87%. The PTIR at long-term follow-up of this primary cohort was 1.07 (95% CI 0.4–1.7) per 100 person-years. From the revision hinge TKA cohort, the median survival at 1 year was 79.6%, and at 10 years it was 65.1%. The PTIR at long term-follow-up of this revision cohort was 1.55 (95% CI 0.9–2.3) per 100 person-years. Post-operative flexion range of motion (ROM) was 110° for primary hinge TKA and 103° for revision hinge TKA. Compared with baseline, the Knee Society Score (KSS) and Knee Society Function Score (KSFS) improved for both groups post-operatively (primary: KSS 17 to 86, KSFS 28 to 58; revision: KSS 37 to 82, KSFS 34 to 61).

Conclusion

The quality of the evidence for patient-relevant outcomes following hinged knee arthroplasty was limited. While there is the potential for high early revision rates, where successful, large functional benefits may be achieved.
SARS-CoV-2 origin, myths and diagnostic technology developments
Authors: Wambani Josephine , Okoth Patrick
Published: March 2022

Background

After the first case of COVID-19 being announced in China in December 2019, various diagnostic technologies have been developed at unprecedented pace with the aim of providing a basis for accurate clinical intervention. However, some assays including CRISPR-based diagnostics and loop-mediated isothermal amplification (LAMP) have been less explored. As new COVID-19 technologies emerge, there is need for them to be assessed, validated and improved upon. Moreover, there is paucity of data on the essential factors governing the selection of an appropriate diagnostic approach within the correct timeframe. Myths and origin of SARS-CoV-2 remain to be controversial. Consequently, this review aims at exploring the current COVID-19 diagnostic technologies, performance evaluation, principles, suitability, specificity, sensitivity, successes and challenges of the technologies for laboratory and bedside testing.

Main Body

To date, there exist more publications on COVID-19 diagnostics as compared to the Zika virus. The SARS-CoV-2 virus genome profiles were readily available by 31st of December 2019. This was attributed to the fast-paced sharing of the epidemiological and diagnostics data of COVID-19. Timely profiling of the virus genome accelerated the development of diagnostic technologies. Furthermore, the rapid publication of studies that evaluated several diagnostic methods available provided baseline information on how the various technologies work and paved way for development of novel technologies.

Conclusion

Up to date, RT-PCR is the most preferred as compared to the other assays. This is despite the repeated false negatives reported in many of the study findings. Considering that COVID-19 has caused devastating effects on the economy, healthcare systems, agriculture and culture, timely and accurate detection of the virus is paramount in the provision of targeted therapy hence reducing chances of drug resistance, increased treatment costs and morbidity. However, information on the origin of SARS-CoV-2 still remains elusive. Furthermore, knowledge and perception of the patients toward management of SARS-CoV-2 are also paramount to proper diagnosis and management of the pandemic. Future implications of the misperceptions are that they may lead to increased non-compliance to SARS-CoV-2-related World Health Organization (WHO) policies and guidelines.
Reflections on mental healthcare for an asylum seeker population caught in limbo on the Greek island of Samos
Authors: Solera-Deuchar Lindsay
Published: March 2022

A psychiatry trainee reflects on a period of work on the Greek island of Samos with the international medical non-governmental organisation Medécins Sans Frontières/Doctors Without Borders, providing mental health and psychosocial support to asylum seekers. The clinic provided services to asylum seekers who were living in a crowded refugee camp, many of whom were experiencing symptoms of severe mental illness. The author reflects on the nature and severity of these presentations, and questions the role of psychiatry in treating mental illness that is clearly exacerbated by circumstances resulting from European asylum policies.
The G209R mutant mouse as a model for human PCSK1 polyendocrinopathy
Authors: Shakya Manita , Gahlot Surbhi , Martin Nicolle K , Arunagiri Anoop , Martin Martin G , Arvan Peter , Low Malcolm J , Lindberg Iris
Published: March 2022

PCSK1 encodes an enzyme required for prohormone maturation into bioactive peptides. A striking number of SNPs and rare mutations in PCSK1 are associated with a range of clinical phenotypes. Infants bearing two copies of a catalytically inactivating mutation, such as G209R, exhibit life-threatening chronic diarrhea and subsequently develop systemic endocrinopathies. Using CRISPR/Cas9 technology, we have engineered a mouse model bearing a G209R missense mutation in exon 6 of the murine Pcsk1 locus. Most pups homozygous for the G209R mutation succumbed by day 2, and surviving pups were severely dwarfed. In homozygous (but not heterozygous) pups, blood glucose levels were significantly lower, accompanied by elevated plasma insulin-like immunoreactivity and accumulation of large quantities of unprocessed proinsulin in the pancreas. Peptide hormone processing was also aberrant in G209R mouse pituitary, with mature ACTH levels markedly reduced in homozygotes, accompanied by a significant accumulation of POMC. We also observed a significant reduction in PC1/3 protein in the brains of G209R homozygous mice by Western blotting, while PC2 levels remained unaffected. Most likely due to the continued presence of PC2, pituitary and brain levels of α-MSH were not impaired. Analysis of intestinal cell types indicated a modest reduction of enteroendocrine cells in G209R homozygotes. We suggest that the G209R Pcsk1 mouse model recapitulates many of the dramatic neonatal deficiencies of human patients with this homozygous mutation.
Success and Time to Oxygen Delivery for Scalpel-Finger-Cannula and Scalpel-Finger-Bougie Front-of-Neck Access: A Randomized Crossover Study With a Simulated “Can’t Intubate, Can’t Oxygenate” Scenario in a Manikin Model With Impalpable Neck Anatomy
Authors: Zhang Jinbin , Ong Shimin , Toh Han , Chew Meifang , Ang Hope , Goh Stacey
Published: March 2022

BACKGROUND:

Emergency front-of-neck access (FONA) is particularly challenging with impalpable neck anatomy. We compared 2 techniques that are based on a vertical midline neck incision, followed by finger dissection and then either a cannula or scalpel puncture to the cricothyroid membrane.

METHODS:

A manikin simulation scenario of impalpable neck anatomy and bleeding was created. Sixty-five anesthesiologists undergoing cricothyrotomy training performed scalpel-finger-cannula (SFC) and scalpel-finger-bougie (SFB) cricothyrotomy in random order. Primary outcomes were time to oxygen delivery and first-attempt success; data were analyzed using multilevel mixed-effects models.

RESULTS:

SFC was associated with a shorter time to oxygen delivery on univariate (median time difference, −61.5 s; 95% confidence interval [CI], −84.7 to −38.3; P < .001) and multivariable (mean time difference, −62.1 s; 95% CI, −83.2 to −41.0; P < .001) analyses. Higher first-attempt success was reported with SFC than SFB (47 of 65 [72.3%] vs 18 of 65 [27.7%]). Participants also had higher odds at achieving first-attempt success with SFC than SFB (odds ratio [OR], 10.7; 95% CI, 3.3–35.0; P < .001). Successful delivery of oxygen after the “can’t intubate, can’t oxygenate” (CICO) declaration within 3 attempts and 180 seconds was higher (84.6% vs 63.1%) and more likely with SFC (OR, 5.59; 95% CI, 1.7–18.9; P = .006). Analyzing successful cases only, SFC achieved a shorter time to oxygen delivery (mean time difference, −24.9 s; 95% CI, −37.8 to −12.0; P < .001), but a longer time to cuffed tube insertion (mean time difference, +56.0 s; 95% CI, 39.0–73.0; P < .001). After simulation training, most participants preferred SFC in patients with impalpable neck anatomy (75.3% vs 24.6%).

CONCLUSIONS:

In a manikin simulation of impalpable neck anatomy and bleeding, the SFC approach demonstrated superior performance in oxygen delivery and was also the preferred technique of the majority of study participants. Our study findings support the use of a cannula-based FONA technique for achieving oxygenation in a CICO situation, with the prerequisite that appropriate training and equipment are available.
Intermittent Legitimacy: Hans Blumenberg and Artificial Intelligence
Authors: Weatherby Leif
Published: March 2022

Hans Blumenberg’s only known treatment of the topic of artificial intelligence comes in the form of a fragmentary meditation on the first chatbot, Joseph Weizenbaum’s ELIZA. Blumenberg compares this program to the philosophy of Edmund Husserl, arguing that both AI and phenomenology make a false assumption about intelligence or consciousness. This article argues that Blumenberg’s brush with digital systems is crucial in updating our own critique of AI as it proliferates in a new, dynamic form today. Drawing on and shifting the account of technology in the phenomenological tradition, Blumenberg includes machines in the constitution of meaning through rhetoric and points the way to a new wave of digital critique.
A Well-Tempered Modernist
Authors: Lang Colin
Published: March 2022

In the vast archive of literature from, and on, Hans Blumenberg, there are few mentions of theories of modern or contemporary art. Two exceptions exist, which both took place in 1966. One deals with the topic more obliquely: a lecture on Paul Valéry given at the Akademie der Künste in West Berlin. The second takes the topic of pop and op art head-on in a discussion led by Blumenberg for the research group Poetik und Hermeneutik. In neither does Blumenberg offer anything like a working theory of contemporary art, but his lecture enacts a performative contemporary reading of Valéry’s attempt to make Leonardo da Vinci relevant for the French poet’s age. Comparing Blumenberg’s comments on contemporary art with those in US formalist art criticism (Clement Greenberg, Michael Fried) provides a unique constellation of later modernist thinking on the plastic arts (painting and sculpture, chiefly). This article attempts to read Blumenberg as a contemporary thinker for art, an attempt that revisits the provocation that Blumenberg set for himself in 1966 when considering the stakes for contemporary art forms. Can one say that Blumenberg was himself a modernist?
Retreatment of Residual and Recurrent Aneurysms After Embolization With the Woven EndoBridge Device: Multicenter Case Series
Authors: Srinivasan Visish M. , Dmytriw Adam A. , Regenhardt Robert W. , Vicenty-Padilla Juan , Alotaibi Naif M. , Levy Elad , Waqas Muhammad , Cherian Jacob , Johnson Jeremiah N. , Jabbour Pascal , Sweid Ahmad , Gross Bradley , Starke Robert M. , Puri Ajit , Massari Francesco , Griessenauer Christoph J. , Catapano Joshua S. , Rutledge Caleb , Tanweer Omar , Yashar Parham , Cortez Gustavo M. , Aziz-Sultan Mohammad A. , Patel Aman B. , Ducruet Andrew F. , Albuquerque Felipe C. , Hanel Ricardo A. , Lawton Michael T. , Kan Peter
Published: March 2022

BACKGROUND:

The Woven EndoBridge (WEB) device (Terumno Corp. [parent company of Microvention]) was approved by the U.S. Food and Drug Administration as the first intrasaccular device for intracranial aneurysm treatment in December 2018. Its use has become more common since then, but both trial results and postmarket experiences have raised questions about the efficacy in achieving complete aneurysm obliteration. Retreatment after WEB embolization has not been extensively discussed.

OBJECTIVE:

To discuss the incidence and retreatment of aneurysms after initial WEB embolization.

METHODS:

Retrospective review across 13 institutions identified all occurrences of WEB retreatment within neurovascular databases. Details regarding demographics, aneurysm characteristics, treatment considerations, clinical outcomes, and aneurysm occlusion were obtained and analyzed.

RESULTS:

Thirty aneurysms were retreated in 30 patients in a cohort of 342 WEB-treated aneurysms. The retreatment rate was 8.8%. Endovascular methods were used for 23 cases, and 7 were treated surgically. Two aneurysms presented with rehemorrhage after initial WEB embolization. Endovascular treatments included stent-assisted coiling (12), flow diversion (7), coiling (2), PulseRider (Johnson & Johnson)–assisted coiling (1), and additional WEB placement (1). Surgical treatments included primary clipping (6) and Hunterian ligation (1). There were no major complications within the study group.

CONCLUSION:

WEB retreatments were successfully performed by a variety of techniques, including stent-assisted coiling, clipping, and flow diversion as the most common. These procedures were performed safely with subsequent obliteration of most aneurysms. The potential need for retreatment of aneurysms should be considered during primary WEB treatments.
Carbon-Bridged Oligo(phenylenevinylene)s that Reveal Cryogenic Phenomena at Room Temperature
Authors: Tsuji Hayato
Published: March 2022

We have developed carbon-bridged oligo(phenylenevinylene)s (COPVs), in which the molecular structure of the phenylenevinylenes is constricted via intramolecular bridging by carbon atoms, or more specifically, substituted methylene groups. COPVs are characterized by their rigid planar molecular structure, which is ideal for the expansion of π-conjugation, and leads to excellent functionality and high stability. Most importantly, COPVs exhibit some phenomena at room temperature that conventional molecules only demonstrate at cryogenic temperatures. In this account, the features of COPVs will be outlined together with research background on structural control using carbon bridges.
A 2x2 randomised factorial SWAT of the use of a pen and small, financial incentive to improve recruitment in a randomised controlled trial of yoga for older adults with multimorbidity
Authors: Fairhurst Caroline , Roche Jenny , Bissell Laura , Hewitt Catherine , Hugill-Jones Jess , Howsam Jenny , Maturana Camila S , Corbacho Martin Belen , Paul Shirley-Anne S , Rose Fi , Torgerson David J , Ward Lesley , Wiley Laura , Tew Garry A
Published: March 2022

Background: Monetary and other incentives may increase recruitment to randomised controlled trials.

Methods: 2x2 factorial ‘study within a trial’ of including a pen and/or £5 (GBP) in cash with a postal recruitment pack to increase the number of participants randomised into the host trial (‘Gentle Years Yoga’) for older adults with multimorbidity. Secondary outcomes: return, and time to return, of screening form, and the cost per additional participant randomised. Binary data were analysed using logistic regression and time to return using Cox proportional hazards regression. 

Results: 818 potential host trial participants were included. Between those sent a pen (n=409) and not sent a pen (n=409), there was no evidence of a difference in the proportion of participants randomised (15 (3.7%) versus 11 (2.7%); OR 1.38, 95% CI 0.63–3.04), in returning a screening form (66 (16.1%) versus 61 (14.9%); OR 1.10, 95% CI 0.75–1.61) nor in time to return the screening form (HR 1.09, 95% CI 0.77–1.55). Between those sent £5 (n=409) and not sent £5 (n=409), there was no evidence of increased randomisation (14 (3.4%) versus 12 (2.9%); OR 1.18, 95% CI 0.54–2.57), but more screening forms were returned (77 (18.8%) versus 50 (12.2%); OR 1.67, 95% CI 1.13–2.45) and there was decreased time to return screening form (HR 1.56, 95% CI 1.09–2.22). No significant interaction between the interventions was observed. The cost per additional participant randomised was £32 and £1000 for the pen and £5, respectively.

Conclusion: A small, monetary incentive did not result in more participants being randomised into the host trial but did encourage increased and faster response to the recruitment invitation. Since it is relatively costly, we do not recommend this intervention for use to increase recruitment in this population. Pens were cheaper but did not provide evidence of benefit.
The phenomenon of workplace bullying among nurses
Authors: Tomaszewska Katarzyna , Majchrowicz Bożena , Norek Karolina
Published: March 2022

Introduction The problem of workplace bullying, which carries several pathologies, is becoming a more and more common phenomenon in the work environment. Regardless of the form of aggression or its causes in the workplace, it always significantly affects the employee, causing a number of consequences, ranging from health and psychological to social and professional. The aim of the study was to assess the prevalence of workplace bullying among nurses. Material & methods: The study involved 120 nurses, including 110 women and 10 men. The survey was conducted anonymously, with the consent of the respondents. A proprietary questionnaire was used as the research tool and the NAQ questionnaire was used to assess the workplace bullying phenomenon. A diagnostic survey was used as the research method. Results: In the studied group, the presence of workplace bullying was found in more than half of the nursing staff (54.2%), so it occurred more often than it was absent, but no statistically significant differences were found between the number of respondents affected or not by workplace bullying (p=0.180), it was therefore found that this problem was as common as its absence. Moreover, it was shown that among the respondents with the shortest work experience, workplace bullying was the least frequent. Conclusions: Workplace bullying among nursing staff is a common phenomenon, while respondents with longer work experience are more exposed to these activities. Workplace bullying activities are rarely applied to people with higher education, but to a greater extent they are related to the competences, and therefore directed at work, rather than at the private sphere.
New mothers' mental health needs
Authors: Donaghy Miriam
Published: March 2022

Miriam Donaghy, the CEO and founder of MumsAid, discusses the charity's work delivering services that support the mental health needs of new mothers
Improving care for new mothers with postnatal morbidity in Ireland
Authors: Brophy Caroline , Doherty Jean , Coughlan Barbara , Sheehy Lucille , Folan Margaret , O'Brien Laoise , Brosnan Mary
Published: March 2022

Background

Pathways to dedicated clinics for women in Ireland who experience morbidity during the antenatal, intrapartum or postnatal periods are lacking. In view of this, a postnatal morbidity clinic was set up and an evaluation was conducted with clinic attendees with the aim of improving the service by using the results to guide the expansion and improvements.

Methods

A survey was developed using two validated questionnaires of women who were discharged from the clinic over 6 months. Surveys were self-completed and returned by 92 women, then analysed using descriptive statistics for quantitative data and thematic analysis for qualitative data.

Results

Several areas were highlighted for improvement, such as expanding debriefing services, making a more precise plan of action upon discharge and improving continuity of care.

Conclusions

Postnatal morbidities exert a considerable toll on new mothers. Listening to women's experiences of attending the clinic guided the successful expansion of advanced midwife practitioner-led supports and improved efficiencies within the clinic as well as highlighting the importance of such a service for all women.
Offering vaginal examinations
Authors: Franks Sophie
Published: March 2022

Sophie Franks reflects on her experiences on a labour ward and women's right not to consent to a vaginal examination
Diagnosis and management of arterial injuries associated with limb fracture or dislocation
Authors: Hussain SA , Walters S , Ahluwalia A , Trompeter A
Published: March 2022

An arterial injury is a time-critical emergency and, when associated with a fracture or dislocation, its management requires joint specialist input from orthopaedic and vascular or plastic surgeons. Initial management involves haemorrhage control and stabilisation of the patient, reduction and splinting of the limb and careful reassessment. With ongoing vascular compromise, urgent surgery is indicated to restore arterial flow and stabilise the skeleton, and this should be performed at a centre with appropriate expertise. This article provides an evidence-based review of the British Orthopaedic Association Standards for Trauma for the diagnosis and management of arterial injuries associated with extremity fractures and dislocations.
Innovative utilization of compact disc for measuring fast neutron generated from a 10 MV medical linear accelerator
Authors:   Department of Radiologic Technology, Faculty of Associated Medical Science, Chiang Mai University, Chiang Mai Province, Thailand, Thepsiri Porama , Phruksarojanakun Phiphat ,   Office of Atoms for Peace, Ministry of Higher Education, Science, Research and Innovation, Bangkok, Thailand, Rattanarungruangchai Natch ,   Department of Radiation Dose Measurement and Assessment, Nuclear Technology Service Center, Thailand Institute of Nuclear Technology (Public Organization), Bangkok, Thailand, Rungseesumran Thiti ,   Department of Radiation Dose Measurement and Assessment, Nuclear Technology Service Center, Thailand Institute of Nuclear Technology (Public Organization), Bangkok, Thailand, Dachviriyakij Tanapol ,   Office of Atoms for Peace, Ministry of Higher Education, Science, Research and Innovation, Bangkok, Thailand, Jumpee Chayanit ,   Department of Radiologic Technology, Faculty of Associated Medical Science, Chiang Mai University, Chiang Mai Province, Thailand
Published: March 2022

Background: High-energy photons produced from a medical linear accelerator (LINAC) have long been used as one of the most effective ways for treating cancers. During the treatment process, some photo neutrons are unavoidably created by [γ,n] reactions, imposing additional and undesirable dose on a patient. This amount of unplanned dose from photo neutrons can potentially harm the patient as well as medical personnel during the treatment. This study is aimed to develop a methodology for measuring fast neutron dose generated from 10 MV LINAC by employing polycarbonate from base material of compact disk (CDs) and a fast neutron converter. Materials and methods: The polycarbonate base layer of CDs has been applied to fast neutron dosimetry with nuclear track method by combining with polymethyl methacrylate (PMMA) converter for fast neutrons. A number of CDs badges were irradiated with high energy photon from 10 MV Elekta Synergy LINAC in the solid water phantom at depth of 0, 2.5, 5, 10, 15 and 20 cm then etched with potassium hydroxide ethanol water (PEW) solution that containing with potassium hydroxide, ethanol and water with ratio of 15:45:40. The optimal condition for the chemical etching were found at 60±2 °C, for 14 hr. Results: Comparison of neutron equivalent doses from measurement of CD track detector and CR-39 track detector has shown that the maximum fast neutron dose equivalent was at depth of 5 cm of phantom. This agreement has confirmed that the CD track detector can be employed to measure fast neutron doses produced from LINAC in an accurate and affordable fashion. Conclusion: It is confirmed that the CD track detector can be employed to measure fast neutron doses produced from LINAC in an accurate and affordable fashion.