bluuebunny/crossref_metadata_2025 huggingface dataset:
The distribution and function of GDE2, a regulator of spinal motor neuron survival, are disrupted in Amyotrophic Lateral Sclerosis
Authors: Westerhaus Anna , Joseph Thea , Meyers Alison J. , Jang Yura , Na Chan Hyun , Cave Clinton , Sockanathan Shanthini
Published: May 2022

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that affects the viability of upper and lower motor neurons. Current options for treatment are limited, necessitating deeper understanding of the mechanisms underlying ALS pathogenesis. Glycerophosphodiester phosphodiesterase 2 (GDE2 or GDPD5) is a six-transmembrane protein that acts on the cell surface to cleave the glycosylphosphatidylinositol (GPI)-anchor that tethers some proteins to the membrane. GDE2 is required for the survival of spinal motor neurons but whether GDE2 neuroprotective activity is disrupted in ALS is not known. We utilized a combination of mouse models and patient post-mortem samples to evaluate GDE2 functionality in ALS. Haplogenetic reduction of GDE2 exacerbated motor neuron degeneration and loss in SOD1G93A mice but not in control SOD1WT transgenic animals, indicating that GDE2 neuroprotective function is diminished in the context of SOD1G93A. In tissue samples from patients with ALS, total levels of GDE2 protein were equivalent to healthy controls; however, membrane levels of GDE2 were substantially reduced. Indeed, GDE2 was found to aberrantly accumulate in intracellular compartments of ALS motor cortex, consistent with a disruption of GDE2 function at the cell surface. Supporting the impairment of GDE2 activity in ALS, tandem-mass-tag mass spectrometry revealed a pronounced reduction of GPI-anchored proteins released into the CSF of patients with ALS compared with control patients. Taken together, this study provides cellular and biochemical evidence that GDE2 distribution and activity is disrupted in ALS, supporting the notion that the failure of GDE2-dependent neuroprotective pathways contributes to neurodegeneration and motor neuron loss in disease. These observations highlight the dysregulation of GPI-anchored protein pathways as candidate mediators of disease onset and progression and accordingly, provide new insight into the mechanisms underlying ALS pathogenesis.
Real-time automatic prediction of treatment response to transcatheter arterial chemoembolization in patients with hepatocellular carcinoma using deep learning based on digital subtraction angiography videos
Authors: Zhang Lu , Jiang Yicheng , Jin Zhe , Jiang Wenting , Zhang Bin , Wang Changmiao , Wu Lingeng , Chen Luyan , Chen Qiuying , Liu Shuyi , You Jingjing , Mo Xiaokai , Liu Jing , Xiong Zhiyuan , Huang Tao , Yang Liyang , Wan Xiang , Wen Ge , Han Xiao Guang , Fan Weijun , Zhang Shuixing
Published: May 2022

Background

Transcatheter arterial chemoembolization (TACE) is the mainstay of therapy for intermediate-stage hepatocellular carcinoma (HCC); yet its efficacy varies between patients with the same tumor stage. Accurate prediction of TACE response remains a major concern to avoid overtreatment. Thus, we aimed to develop and validate an artificial intelligence system for real-time automatic prediction of TACE response in HCC patients based on digital subtraction angiography (DSA) videos via a deep learning approach.

Methods

This retrospective cohort study included a total of 605 patients with intermediate-stage HCC who received TACE as their initial therapy. A fully automated framework (i.e., DSA-Net) contained a U-net model for automatic tumor segmentation (Model 1) and a ResNet model for the prediction of treatment response to the first TACE (Model 2). The two models were trained in 360 patients, internally validated in 124 patients, and externally validated in 121 patients. Dice coefficient and receiver operating characteristic curves were used to evaluate the performance of Models 1 and 2, respectively.

Results

Model 1 yielded a Dice coefficient of 0.75 (95% confidence interval [CI]: 0.73–0.78) and 0.73 (95% CI: 0.71–0.75) for the internal validation and external validation cohorts, respectively. Integrating the DSA videos, segmentation results, and clinical variables (mainly demographics and liver function parameters), Model 2 predicted treatment response to first TACE with an accuracy of 78.2% (95%CI: 74.2–82.3), sensitivity of 77.6% (95%CI: 70.7–84.0), and specificity of 78.7% (95%CI: 72.9–84.1) for the internal validation cohort, and accuracy of 75.1% (95% CI: 73.1–81.7), sensitivity of 50.5% (95%CI: 40.0–61.5), and specificity of 83.5% (95%CI: 79.2–87.7) for the external validation cohort. Kaplan-Meier curves showed a significant difference in progression-free survival between the responders and non-responders divided by Model 2 (p = 0.002).

Conclusions

Our multi-task deep learning framework provided a real-time effective approach for decoding DSA videos and can offer clinical-decision support for TACE treatment in intermediate-stage HCC patients in real-world settings.
Role of IL-17 family cytokines in the progression of IPF from inflammation to fibrosis
Authors: Nie Yun-Juan , Wu Shuo-Hua , Xuan Ying-Hua , Yan Gen
Published: May 2022

Idiopathic pulmonary fibrosis (IPF) is a fatal chronic interstitial lung disease with no established treatment and is characterized by progressive scarring of the lung tissue and an irreversible decline in lung function. Chronic inflammation has been demonstrated to be the pathological basis of fibrosis. Emerging studies have revealed that most interleukin-17 (IL-17) isoforms are essential for the mediation of acute and chronic inflammation via innate and adaptive immunity. Overexpression or aberrant expression of IL-17 cytokines contributes to various pathological outcomes, including the initiation and exacerbation of IPF. Here, we aim to provide an overview of IL-17 family members in the pathogenesis of IPF.
Beyond the snapshot: identification of the timeless, enduring indicator microbiome informing soil fertility and crop production in alkaline soils
Authors: Zhang Jianwei , Dolfing Jan , Liu Wenjing , Chen Ruirui , Zhang Jiabao , Lin Xiangui , Feng Youzhi
Published: May 2022

Background

Microorganisms are known to be important drivers of biogeochemical cycling in soil and hence could act as a proxy informing on soil conditions in ecosystems. Identifying microbiomes indicative for soil fertility and crop production is important for the development of the next generation of sustainable agriculture. Earlier researches based on one-time sampling have revealed various indicator microbiomes for distinct agroecosystems and agricultural practices as well as their importance in supporting sustainable productivity. However, these microbiomes were based on a mere snapshot of a dynamic microbial community which is subject to significant changes over time. Currently true indicator microbiomes based on long-term, multi-annual monitoring are not available.

Results

Here, using samples from a continuous 20-year field study encompassing seven fertilization strategies, we identified the indicator microbiomes ecophysiologically informing on soil fertility and crop production in the main agricultural production base in China. Among a total of 29,184 phylotypes in 588 samples, we retrieved a streamlined consortium including 2% of phylotypes that were ubiquitously present in alkaline soils while contributing up to half of the whole community; many of them were associated with carbon and nutrient cycling. Furthermore, these phylotypes formed two opposite microbiomes. One indicator microbiome dominated byBacillus asahii, characterized by specific functional traits related to organic matter decomposition, was mainly observed in organic farming and closely associated with higher soil fertility and crop production. The counter microbiome, characterized by known nitrifiers (e.g.,Nitrosospira multiformis) as well as plant pathogens (e.g.,Bacillus anthracis) was observed in nutrient-deficit chemical fertilizations. Both microbiomes are expected to be valuable indictors in informing crop yield and soil fertility, regulated by agricultural management.

Conclusions

Our findings based on this more than 2-decade long field study demonstrate the exciting potential of employing microorganisms and maximizing their functions in future agroecosystems. Our results report a “most-wanted” or “most-unwanted” list of microbial phylotypes that are ready candidates to guide the development of sustainable agriculture in alkaline soils.
A practical guide for translating in-person simulation curriculum to telesimulation
Authors: Cruz-Panesso Ilian , Perron Roger , Chabot Valérie , Gauthier Frédérique , Demers Marie-Michèle , Trottier Roxane , Soulières Francis , Juste Laetitia , Gharavi Shiva , MacDonald Nathalie , Richard Amélie , Boivin Audrey , Deligne Benoit , Bouillon Karine , Drolet Pierre
Published: May 2022

This article provides a road map, along with recommendations, for the adoption and implementation of telesimulation at a large scale. We provide tools for translating an in-presence simulation curriculum into a telesimulation curriculum using a combination off-the-shelf telecommunication platform. We also describe the roles and tasks that emerged within the simulation team when planning and delivering a telesimulation curriculum.
The effects of community clustering on under-five mortality in India: a parametric shared frailty modelling approach
Authors: Meitei Wahengbam Bigyananda , Singh Abhishek , Ladusingh Laishram
Published: May 2022

The study of the effect of community clustering of under-five mortality has its implications in both research and policy. Studies have shown the contribution of community factors on under-five mortality. However, these studies did not account for censoring. We examine the presence of community dependencies and determine the risk factors of under-five mortality in India and its six state-regions by employing a Weibull hazard model with gamma shared frailty. We considered every possible way to ensure that the frailty models used in the study are not merely a consequence of how the data are organized rather than representing a substantive assumption about the source of the frailty. Data from the fourth round of the National Family Health Survey has been used. The study found that except for south India, children born in the same community in India and the other five state-regions shared similar characteristics of under-five mortality. The risk of under-five mortality decreased with an increase in mother’s schooling. Except for northern region, female births were less likely to die within first five years of life. We found a U-shaped relationship between preceding birth interval and under-five mortality. History of sibling’s death, multiple births and low-birthweight significantly increases the risk of under-five mortality in all the six state-regions. The Hindu–Muslim mortality gaps and Scheduled Caste or Tribe’s mortality disadvantage is diminishing. Since the factors associated with under-five mortality were not necessarily the same across the six state-regions of India, adopting a uniform approach in dealing with under-five mortality in India may not benefit all the regions equally.
How history trails and set size influence detection of hostile intentions
Authors: Patton Colleen E. , Wickens Christopher D. , Clegg Benjamin A. , Noble Kayla M. , Smith C. A. P.
Published: May 2022

Previous research suggests people struggle to detect a series of movements that might imply hostile intentions of a vessel, yet this ability is crucial in many real world Naval scenarios. To investigate possible mechanisms for improving performance, participants engaged in a simple, simulated ship movement task. One of two hostile behaviors were present in one of the vessels: Shadowing—mirroring the participant’s vessel’s movements; and Hunting—closing in on the participant’s vessel. In the first experiment, history trails, showing the previous nine positions of each ship connected by a line, were introduced as a potential diagnostic aid. In a second experiment, the number of computer-controlled ships on the screen also varied. Smaller set size improved detection performance. History trails also consistently improved detection performance for both behaviors, although still falling well short of optimal, even with the smaller set size. These findings suggest that working memory plays a critical role in performance on this dynamic decision making task, and the constraints of working memory capacity can be decreased through a simple visual aid and an overall reduction in the number of objects being tracked. The implications for the detection of hostile intentions are discussed.
Development of the SF-6Dv2 health utility survey: comprehensibility and patient preference
Authors: Broderick Lynne , Bjorner Jakob B. , Lauher-Charest Miranda , White Michelle K. , Kosinski Mark , Mulhern Brendan , Brazier John
Published: May 2022

Background

The SF-6Dv2 classification system assesses health states in six domains—physical functioning, role function, bodily pain, vitality, social functioning, and mental health. Scores have previously been derived from the SF-36v2® Health Survey. We aimed to develop a six-item stand-alone SF-6Dv2 Health Utility Survey (SF-6Dv2 HUS) and evaluate its comprehensibility.

Methods

Two forms of a stand-alone SF-6Dv2 HUS were developed for evaluation. Form A had 6 questions with 5–6 response choices, while Form B used 6 headings and 5–6 statements describing the health levels within each domain. The two forms were evaluated by 40 participants, recruited from the general population. Participants were randomized to debrief one form of the stand-alone SF-6Dv2 HUS during a 75-min interview, using think-aloud techniques followed by an interviewer-led detailed review. Participants then reviewed the other form of SF-6Dv2 and determined which they preferred. Any issues or confusion with items was recorded, as was as overall preference. Data were analyzed using Microsoft Excel and NVivo Software (v12).

Results

Participants were able to easily complete both forms. Participant feedback supported the comprehensibility of the SF-6Dv2 HUS. When comparing forms, 25/40 participants preferred Form A, finding it clearer and easier to answer when presented in question/response format. The numbered questions and underlining of key words in Form A fostered quick and easy comprehension and completion of the survey. However, despite an overall preference for Form A, almost half of participants (n = 19) preferred the physical functioning item in Form B, with more descriptive response choices.

Conclusion

The results support using Form A, with modifications to the physical functioning item, as the stand-alone SF-6Dv2 HUS. The stand-alone SF-6Dv2 HUS is brief, easy to administer, and comprehensible to the general population.
Training second-grade dyslexic students using a computerized program in Asyut, Egypt
Authors: Farghaly W. M. , El Tallawy S. H. , Ramadan A. S. , Abdelrasol R. B. , Omar M. S. , Eltallawy H. N. , Mohamed K. O.
Published: May 2022

Background

Dyslexia is characterized by difficulties in spelling and reading. The aim of this study is to identify domains of cognitive strength and weakness of students with dyslexia and to study the effect of an especially designed computerized training program on their reading abilities. This study was conducted on 2nd-grade primary school students in Asyut city, Egypt (n = 560). Identification of students with dyslexia was done using Arabic Reading Achievement test and a newly constructed computerized Arabic Cognitive Abilities diagnostic battery for Reading (CADB-R). Training was applied using a newly constructed Computerized Cognitive abilities training battery for reading (CATB-R).

Results

The prevalence of dyslexia was 13.9% (N = 52/373), and it was higher among girls (15.8%) than boys (11.7%). After application of the training program, there was a significant increase in post-training mean scores of CADB-R score in their total and all sub-items.

Conclusions

All struggling readers should be included in well-tailored research-based rehabilitation programs.

Clinical trial registration Training Second-grade Dyslexic Students Using a Computerized Program in Assiut, Egypt (Dyslexia), NCT04642859, 12 November 2020. URL: https://register.clinicaltrials.gov/prs/app/action/Status?uid=U000495F&ts=10&sid=S000AD3G&cx=20acrp
Potential role of recombinant growth differentiation factor 11 in Alzheimer’s disease treatment
Authors: de Liyis Bryan Gervais , Halim Wilson , Widyadharma I. Putu Eka
Published: May 2022

Alzheimer's disease (AD) is a neurodegenerative disease closely related to the accumulation of beta-amyloid (Aβ) plaques. Growth differentiation factor 11 (GDF11) is one of the proteins that play a role in the aggravation of AD. Decreased concentration of GDF11 disrupts regenerative nervous system, blood vessels, and various vital systems. Low levels of GDF11 with age can be overcome with recombinant GDF11 (rGDF11) to rejuvenate the regenerative effect. Based on research results, rGDF11 enhance the proliferation rate of neuronal precursor cells as well as angiogenesis. rGDF11 can replace lost levels of GDF11, overcome astrogliosis and activation of nerve cell microglia. Therapeutic effect of rGDF11 leads to an improved prognosis in AD patients by neurogenesis and angiogenesis. The prospects of rGDF11 in the treatment of AD have great potential for further research in the future.
Dramatic increase in volume versus length of invasive ductal carcinoma mimicking intramammary lymph node in a small nodular lesion
Authors: Aladag Kurt Seda , Celik Varol
Published: May 2022

Background

The tumor growth pattern in breast cancer appears to be variable and unpredictable. A minor increase in size in a pre-existing lesion, especially under 1 cm, corresponds to a more pronounced increase in volume.

Case presentation

We report a 63-year-old woman with a nodular density mimicking intramammary lymph node, diagnosed as invasive carcinoma of luminal B subtype. The lesion increased size and density over time in following mammograms until having indistinct margins. While the tumor volume was 12.7 mm3 at the first observation on mammography, it has increased approximately 6.7 times to reach 85.7 mm3 in four years. Finally, the patient diagnosed with early-stage breast cancer (T1N0M0) was treated with breast-conserving surgery.

Conclusions

Minor changes in size, density, and margin status of a lesion on serial mammograms are warning for breast cancer. Withal, a slight increase in lesion size in two dimensions can result in significant differences in volume. Therefore, comparative evaluation with previous mammograms and observing any difference in morphological features by screening are crucial for early diagnosis and optimal management of the disease.
Biosynthesis and optimization of highly stable gold nanoparticles, nanoconjugates, nanodrug conjugates and chitosan nanoconjugates using medicinal plants
Authors: Priya M. R. Kamala , Iyer Priya R.
Published: May 2022

Background

In the present study, the medicinal plants were exclusively selected based on their significant anti-HIV and anticancer activities. The green synthesis of gold nanoparticles was carried out using the 15 medicinal plant extracts on reduction with chloroauric acid. The present study also focused on a novel pharmacognostic approach over the usage of plants source. The nanoparticle synthesized through medicinal plants possessed the potential therapeutic properties of the plants. The resultant nanoparticle carried the attributes of a nanomaterial alongside the phytoactivity.

Results

Initially, individual nanoparticle (NP) was synthesized through a single plant extract and studied for its effective anti-HIV and anticancer activity. Finally, a nanoconjugate (NC) comprising of the 3 extracts (trio extract) in one nanoparticle was synthesized. The nanoparticles which exhibited comparatively high anti-HIV and anticancer activity were chosen for the synthesis of nanoconjugate, thereby achieving a synergistic anticancer and anti-HIV activity. Further, a nanodrug conjugate (NDC) was prepared in combination of AuNPs and the chemotherapeutic drug, doxorubicin (Dox) for cancer and AuNPs with antiretroviral drug azidothymidine (AZT) for HIV.

Conclusions

A nanodrug conjugate helps to enhance the efficiency of the drug. The nanodrug conjugate brings about a combinatorial effect of the nanomaterials and the drug. Further, a biocompatible nanocarrier was developed as a conjugate with chitosan and gold nanoparticles using STPP as gelating agent for the drug doxorubicin. The synthesis reaction was optimized under various underlying parameters. The gold nanoparticles proved to be stable at high temperature and different buffers and ensured to be a safe option for bioassays and in vivo applications. Upon storing the synthesized AuNPs at different storage conditions, the nanoparticles were observed to be highly stable for a period of more than 48 months. The present study resulted in biosynthesis of highly stable gold nanoparticles using medicinal plant extracts as reducing and stabilizing agents.
Systemic necrosis induced by overexpression of wheat yellow mosaic virus 14K suppresses the replication of other viruses in Nicotiana benthamiana
Authors: Zhang Yan , Zhang Chuanxi , Li Junmin , Chen Jianping , Lu Gang
Published: May 2022

Systemic necrosis, induced by plant virus-derived elicitors, is considered as one of the most severe symptoms. It has never been reported that the elicitors encoded by wheat yellow mosaic virus (WYMV) can induce systemic necrosis in plant. In this study, we discovered that the WYMV-encoded 14K protein localized to the endoplasmic reticulum (ER) membrane and triggered a necrotic symptom in Nicotiana benthamiana at 5 days post-infiltration (dpi). Meanwhile, overexpression of WYMV 14K suppressed the replication of tobacco rattle virus (TRV) and potato virus X (PVX). Additionally, deletion of the transmembrane domain and substitution of two non-conserved regions in 14K resulted in the loss of the ability of this protein to induce systemic necrosis. Moreover, the 14K homologous proteins of other bymoviruses failed to induce systemic necrosis. Our results, for the first time, reveal that WYMV 14K induces systemic necrosis and suppresses the replication of other viruses.
RETRACTED ARTICLE: Toward a characterization of Ecuadorian ceviche: much more than shrimp
Authors: Duarte-Casar Rodrigo , Robalino-Vallejo Jessica , Buzetta-Ricaurte María Fernanda , Rojas-Le-Fort Marlene
Published: May 2022

Ceviche is present in all the Pacific coast of Latin America. Its origin and history are still debated. The consensus is that it arises from creolization between local and Eurasian ingredients and techniques. Ecuadorian ceviche is both traditional and iconic, present in one form or another in its twenty-four provinces, adapting to the availability of products and becoming part of the identity of regions, parishes, and cities. The objective of this work is to confirm ceviche as a traditional Ecuadorian dish, to assess the most popular types of Ecuadorian ceviche, condiments and sides, and also to glimpse the wide variety of preparations that appear through adaptation to ingredient availability and food customs. We performed a review of both scientific and gray literature, a relative search volume analysis and a survey among culinary professionals (n = 403). The most popular in Ecuador is shrimp (Litopenaeus vannamei) ceviche with 54% of the responses, followed by fish, regardless of species (29%), and both lupin (Lupinus mutabilis) and black clam (Anadara tuberculosa) with 5%. The most utilized condiments are onion, lemon juice and cilantro a “holy trinity” with more than 90% usage. These results are in good agreement with those provided by Web search volumes. The variety of main ingredients, condiments and sides is ample, though, and suggests further research. Sustainability concerns related to ceviche are the sustainability of shrimp farming and fish capture, and the preservation of mollusks and their ecosystems.
Characterization of chronic relapsing antibody mediated arthritis in mice with a mutation in Ncf1 causing reduced oxidative burst
Authors: Liang Peibin , Li Yanpeng , Xu Rui , Nandakumar Kutty Selva , Stawikowska Roma , Fields Gregg B. , Holmdahl Rikard
Published: May 2022

Rheumatoid arthritis (RA) is a chronic autoimmune disorder affecting joints with a hallmark of autoantibody production. Mannan-enhanced collagen type II (COL2) antibody induced arthritis (mCAIA) in neutrophil cytosolic factor 1(Ncf1) mutation mouse is a chronic disease model imitating RA in mice. In this study, we characterize the chronic phase of mCAIA in Ncf1 mutated (BQ.Ncf1m1j/m1j) mice. Arthritis was induced by an intravenous injection of anti-COL2 monoclonal antibodies on day 0 followed by intra-peritoneal injections of mannan (from Saccharomyces cerevisiae) on days 3 and 65 in BQ.Ncf1m1j/m1j and BQ mice. Bone erosion was analysed by computed tomography (CT) and blood cell phenotypes by flow cytometry. Cytokines and anti-COL2 antibodies were analyzed with multiplex bead-based assays. The arthritis in the Ncf1m1j/m1j mice developed with a chronic and relapsing disease course, which was followed for 200 days and bone erosions of articular joints were evaluated. An increased number of circulating CD11b+ Ly6G+ neutrophils were observed during the chronic phase, together with a higher level of G-CSF (granulocyte colony-stimulating factor) and TNF-α. In conclusion, the chronic relapsing arthritis of mCAIA in the Ncf1m1j/m1j mice develop bone erosions associated with a sustained neutrophil type of inflammatory responses.
Prevalence of mental disorders in defendants at criminal court
Authors: Brown Penelope , Bakolis Ioannis , Appiah-Kusi Elizabeth , Hallett Nicholas , Hotopf Matthew , Blackwood Nigel
Published: May 2022

Background

Psychiatric morbidity in prisons and police custody is well established, but little is known about individuals attending criminal court. There is international concern that vulnerable defendants are not identified, undermining their right to a fair trial.

Aims

To explore the prevalence of a wide range of mental disorders in criminal defendants and estimate the proportion likely to be unfit to plead.

Method

We employed two-stage screening methodology to estimate the prevalence of mental illness, neurodevelopmental disorders and unfitness to plead, in 3322 criminal defendants in South London. Sampling was stratified according to whether defendants attended court from the community or custody. Face-to-face interviews, using diagnostic instruments and assessments of fitness to plead, were administered (n = 503). Post-stratification probability weighting provided estimates of the overall prevalence of mental disorders and unfitness to plead.

Results

Mental disorder was more common in those attending court from custody, with 48.5% having at least one psychiatric diagnosis compared with 20.3% from the community. Suicidality was frequently reported (weighted prevalence 71.2%; 95% CI 64.2–77.3). Only 16.7% of participants from custody and 4.6% from the community were referred to the liaison and diversion team; 2.1% (1.1–4.0) of defendants were estimated to be unfit to plead, with a further 3.2% (1.9–5.3) deemed ‘borderline unfit’.

Conclusions

The prevalence of mental illness and neurodevelopmental disorders in defendants is high. Many are at risk of being unfit to plead and require additional support at court, yet are not identified by existing services. Our evidence challenges policy makers and healthcare providers to ensure that vulnerable defendants are adequately supported at court.
Impact of Polymorphism in the β2-Receptor Gene on Metabolic Responses to Repeated Hypoglycemia in Healthy Humans
Authors: Rokamp Kim Zillo , Holst Jens Juul , Olsen Niels V , Dela Flemming , Secher Niels H , Juul Anders , Faber Jens , Wiberg Sebastian , Thorsteinsson Birger , Pedersen-Bjergaard Ulrik
Published: May 2022

Context

The Arg16 variant in the β2-receptor gene is associated with increased risk of severe hypoglycemia in subjects with type 1 diabetes mellitus.

Objective

We hypothesized that the Arg16 variant is associated with decreased metabolic and symptomatic responses to recurrent hypoglycemia.

Methods

Twenty-five healthy male subjects selected according to ADRB2 genotype and being homozygous for either Arg16 (AA; n = 13) or Gly16 (GG; n = 12) participated in 2 consecutive trial days with 3 periods of hypoglycemia (H1-H3) induced by a hyperinsulinemic hypoglycemic clamp. The main outcome measure was mean glucose infusion rate (GIR) during H1-H3.

Results

During H1-H3, there was no difference between AA or GG subjects in GIR, counter-regulatory hormones (glucagon, epinephrine, cortisol, growth hormone), or substrate levels of lactate, glycerol, and free fatty acids (FFAs), and no differences in symptom response score or cognitive performance (trail making test, Stroop test). At H3, lactate response was reduced in both genotype groups, but AA subjects had decreased response (mean ± standard error of the mean of area under the curve) of glycerol (–13.1 ± 3.8 μmol L–1 hours; P = .0052), FFA (–30.2 ± 11.1 μmol L–1 hours; P = .021), and β-hydroxybutyrate (–0.008 ± 0.003 mmol L–1 hour; P = .027), while in GG subjects alanine response was increased (negative response values) (–53.9 ± 20.6 μmol L–1 hour; P = .024).

Conclusion

There was no difference in GIR between genotype groups, but secondary outcomes suggest a downregulation of the lipolytic and β-hydroxybutyrate responses to recurrent hypoglycemia in AA subjects, in contrast to the responses in GG subjects.
Non-Iodine-Avid Disease Is Highly Prevalent in Distant Metastatic Differentiated Thyroid Cancer With Papillary Histology
Authors: Soe Myat Han , Chiang Janet M , Flavell Robert R , Khanafshar Elham , Mendoza Laura , Kang Hyunseok , Liu Chienying
Published: May 2022

Context

Patients with radioactive iodine (RAI) refractory metastatic differentiated thyroid cancer (DTC) have poor prognosis. Early identification of RAI refractoriness may improve care.

Objective

This work aimed to characterize DTC patients with distant metastases (DM) at diagnosis who presented with non–iodine-avid disease.

Methods

Retrospective analyses of DTC patients with DM at diagnosis who presented between 2012 and 2020 were performed. Iodine uptake in DM was correlated with tumor histology and mutational profile. The difference in uptake between BRAFV600E-like (BVL) and RAS-like (RL) cancers based on insights from The Cancer Genome Atlas was evaluated.

Results

Among 78 patients, 48.7% had negative uptake in DM on the first posttherapy scan. Negative scans were highly prevalent in papillary thyroid carcinoma (PTC) with papillary architecture, PTC with BRAFV600E mutation, and PTC with both BRAFV600E and TERT promoter mutations (71.1%, 80.9%, and 100%, respectively). BVL and RL tumors exhibited distinct uptake patterns with negative scan prevalence of 76.9% and 14.3% (P = .005). Multivariate logistical regression confirmed high odds of negative uptake in BVL tumors with either BVL mutations or papillary architecture, 19.8 (95% CI, 2.72-144), and low odds of negative uptake in RL tumors with either RL mutations or follicular architecture, 0.048 (95% CI, 0.006-0.344), after adjusting for age, sex, race, RAI preparation method, bone metastases, and RAI dose. Patients with negative scans were significantly older (62.4 vs 47.0 years, P = .03).

Conclusion

Among DTC patients with DM at diagnosis, non–iodine-avid disease is highly prevalent in patients with BVL cancers, particularly with BRAFV600E and TERT promoter mutations, and is associated with an older age. Better strategies are needed to improve RAI treatment response for these patients.
Comparison of Antinociceptive Properties Between Sevoflurane and Desflurane Using Pupillary Dilation Reflex Under Equivalent Minimum Alveolar Concentration: A Randomized Controlled Trial
Authors: Kim Soo Yeon , Kim Ji-Yoon , Kim Jonghae , Yu Seungcheol , Lee Kwang Hyun , Lee Hyeon Seok , Oh Min Seok , Kim Eugene
Published: May 2022

BACKGROUND:

The pupillary dilation reflex (PDR), the change in pupil size after a nociceptive stimulus, has been used to assess antinociception during anesthesia. The aim of this study was to compare the antinociceptive properties of sevoflurane and desflurane by measuring the PDR amplitude.

METHODS:

Seventy patients between 20 and 55 years of age were randomly allocated to receive either sevoflurane or desflurane. The PDR amplitude after an electrical standardized noxious stimulation (SNT) was measured using an infrared pupillometer under 1.0 minimum alveolar concentration (MAC). The pupil diameter was measured from 5 seconds before to 5 minutes after the SNT. The mean arterial pressure (MAP), heart rate (HR), and bispectral index (BIS) were also measured immediately before and after SNT as well as 1 minute and 5 minutes after SNT. The primary outcome was the maximum percent increase from the prestimulation value of the pupil diameter, and the secondary outcomes were the maximum percent increase from the prestimulation value of the MAP, HR, and BIS after SNT.

RESULTS:

The maximum percent increase of the pupil diameter after SNT was not different between the 2 groups (median [first quartile to third quartile], 45.1 [29.3–80.3] vs 43.4 [27.0–103.1]; median difference, −0.3 [95% confidence interval, −16.0 to 16.5]; P = .986). Before SNT, the MAP was higher under 1.0 MAC of sevoflurane than desflurane; however, the maximum percent increase of MAP, HR, and BIS was not different between the 2 groups.

CONCLUSIONS:

The amount of change in the PDR amplitude, MAP, and HR after SNT was not different between sevoflurane and desflurane anesthesia. This result might suggest that sevoflurane and desflurane may not have different antinociceptive properties at equivalent MAC.
The extra-embryonic space and the local contour are crucial geometric constraints regulating cell arrangement
Authors: Seirin-Lee Sungrim , Yamamoto Kazunori , Kimura Akatsuki
Published: May 2022

In multicellular systems, cells communicate with adjacent cells to determine their positions and fates, an arrangement important for cellular development. Orientation of cell division, cell-cell interactions (i.e. attraction and repulsion) and geometric constraints are three major factors that define cell arrangement. In particular, geometric constraints are difficult to reveal in experiments, and the contribution of the local contour of the boundary has remained elusive. In this study, we developed a multicellular morphology model based on the phase-field method so that precise geometric constraints can be incorporated. Our application of the model to nematode embryos predicted that the amount of extra-embryonic space, the empty space within the eggshell that is not occupied by embryonic cells, affects cell arrangement in a manner dependent on the local contour and other factors. The prediction was validated experimentally by increasing the extra-embryonic space in the Caenorhabditis elegans embryo. Overall, our analyses characterized the roles of geometrical contributors, specifically the amount of extra-embryonic space and the local contour, on cell arrangements. These factors should be considered for multicellular systems.
Functional Resistance Training Improves Thigh Muscle Strength after ACL Reconstruction: A Randomized Clinical Trial
Authors: PALMIERI-SMITH RIANN M. , BROWN SCOTT R. , WOJTYS EDWARD M. , KRISHNAN CHANDRAMOULI
Published: May 2022

Purpose

Quadriceps weakness is common after anterior cruciate ligament (ACL) reconstruction, resulting in prolonged disability and increased risk for reinjury and osteoarthritis. Functional resistance training (FRT) combines resistance training with task-specific training and may prove beneficial in restoring quadriceps strength. The primary purpose of this study was to determine if a walking-specific FRT program (e.g., resisted walking) improves knee strength in individuals after ACL reconstruction.

Methods

Thirty participants were randomized into one of three groups: 1) FRT with a customized knee BRACE applied to the ACL leg, 2) FRT with elastic BAND tethered to the ankle of the ACL leg, or 3) a TARGET MATCH condition where no resistance was externally applied. Participants in all groups received training while walking on a treadmill 2–3 times per week for 8 wk. Isometric knee extension and flexion strength were measured before the start of the intervention, after the intervention (POST), and 8 wk after intervention completion (POST-2).

Results

The BRACE group had greater knee extensor strength compared with the TARGET MATCH group at POST and POST-2 (P < 0.05). The BRACE group had greater knee flexor strength than the TARGET MATCH group at POST and POST-2 (P < 0.05) and the BAND group at POST (P < 0.05).

Conclusions

FRT applied via a customized knee brace results in improvements in knee extensor and flexor strength after ACL reconstruction. FRT is a beneficial adjuvant to ACL rehabilitation and leads to better strength compared with standard of care.
Case Report: Open biopsy and drainage for breast abscess caused by cholesterol granuloma is beneficial rather than breast core biopsy
Authors: Halim Freda , Hanafi Ricarhdo Valentino , Wahjoepramono Eka Julianta
Published: May 2022

Cholesterol granuloma is a rare non-infectious disease. Currently, there are no established guidelines, leaving the clinician to decide the best practice for each patient. A 43-year-old woman presented to the Surgery Clinic at Siloam General Hospital, Tangerang, Banten, Indonesia, with the primary complaint of a painful mass located in her left breast over the previous week before being admitted to the hospital. The mass was found abruptly and was accompanied by severe pain and fever. On inspection, peau d’orange, nipple retraction, tenderness, and warmth of the skin were observed. Ultrasonography suggested a malignant mass. The primary diagnosis was breast cancer, with a secondary differential diagnosis of breast abscess. An open biopsy was chosen because a breast abscess was the possible diagnosis. The biopsy results showed characteristics of cholesterol granuloma. Following the operation, the pain score was notably reduced as the operation showed a satisfactory result. The primary purpose of this case report was to illustrate a case of breast abscess caused by cholesterol granuloma, in which open excisional biopsy and drainage was superior for pain reduction and faster recovery.
Current practices of physiotherapists in Switzerland regarding fall risk-assessment for community-dwelling older adults: A national cross-sectional survey
Authors: Duc Morgane , Mittaz Hager Anne-Gabrielle , Zemp Damiano , Roulet Guillaume , Bridel Alice , Hilfiker Roger
Published: May 2022

Background: Falls can strongly impact older people’s quality of life, health, and lifestyle. Multifactorial assessment can determine an individual’s risk of falling as the first step for fall prevention intervention. Physiotherapists have an essential role to play in assessing fall risk by older adults living in the community. In the absence of published data on this topic in Switzerland, this study investigated the current practices of physiotherapists to determine whether those are in line with recommendations.

Methods: An anonymous cross-sectional survey was undertaken among physiotherapists practising in Switzerland between the 21st of November and the 31st of December 2020. A priori and exploratory hypotheses were tested. Responses to open-ended questions were grouped into themes for analysis. 

Results: A total of 938 questionnaires from all three language regions of Switzerland was analysed. Participants worked in different settings, with a higher representation of private practice self-employees (56%). Standardised fall risk assessments or instruments were used by 580 (62%) participants, while 235 (25%) preferred subjective assessment of fall risk only. Differences in fall risk assessment were observed according to the workplace setting (adjusted OR 1.93, 95% CI 1.37 to 2.7) and education level (trend test, p<0.001). The standardised assessments most frequently employed were the Berg Balance Scale (57.5%), the Timed-Up-and-Go (56.5%) and the Tinetti Balance Assessment tool (46.7%). Risk factors for falls were frequently queried, particularly history of falls (88.3%), home hazards (84.1%), and functional ability (81%). Technical resources (39.8%), knowledge (30.3%), and time (22.2%) were common barriers to implement a systematic fall risk assessment.

Conclusions: This study provides an overview of the current practices of physiotherapists in Switzerland in fall risk assessment. There is still room to optimise the standardisation and systematisation of this assessment to implement a best practice strategy and prevent avoidable falls.
MindKind: A mixed-methods protocol for the feasibility of global digital mental health studies in young people
Authors:   The MindKind Consortium
Published: May 2022

Background: While an estimated 14-20% of young adults experience mental health conditions worldwide, the best strategies for prevention and management are not fully understood. The ubiquity of smartphone use among young people makes them excellent candidates for collecting data about lived experiences and their relationships to mental health. However, not much is known about the factors affecting young peoples’ willingness to share information about their mental health.

Objective: We aim to understand the data governance and engagement strategies influencing young peoples’ (aged 16-24) participation in app-based studies of mental health. We hypothesize that willingness to participate in research is influenced by involvement  in how their data is collected, shared, and used.

Methods: Here, we describe the MindKind Study, which employs mixed methods to understand the feasibility of global, smartphone-based studies of youth mental health. A pilot 12-week app-based substudy will query participants’ willingness to engage with remote mental health studies. Participants will be randomized into one of four different data governance models designed to understand their preferences, as well as the acceptability of models that allow them more or less control over how their data are accessed and used. Enrolees will receive one of two different engagement strategies. A companion qualitative study will employ a deliberative democracy approach to examine the preferences, concerns and expectations of young people, with respect to remote mental health research. We also detail our engagement with young people as co-researchers in this study. This pilot study is being conducted in India, South Africa and the United Kingdom.

Conclusions: This study is expected to generate new insights into the feasibility of, and best practices for, remote smartphone-based studies of mental health in youth and represents an important step toward understanding which approaches could help people better manage their mental health.
Nurse staffing and patient care outcomes: protocol for an umbrella review to identify evidence gaps for low and middle-income countries in global literature
Authors: Imam Abdulazeez , Obiesie Sopuruchukwu , Aluvaala Jalemba , Maina Michuki , Gathara David , English Mike
Published: May 2022

Background: Adequate staffing is key to the delivery of nursing care and thus to improved inpatient and health service outcomes. Several systematic reviews have addressed the relationship between nurse staffing and these outcomes. Most primary studies within each systematic review are likely to be from high-income countries which have different practice contexts to low and middle-income countries (LMICs), although this has not been formally examined. We propose conducting an umbrella review to characterise the existing evidence linking nurse staffing to key outcomes and explicitly aim to identify evidence gaps in nurse staffing research in LMICs.

Methods and analysis: This protocol was developed using the Preferred Reporting Items for Systematic Reviews and Meta-analysis Protocols (PRISMA-P). Literature searching will be conducted across Ovid Medline, Embase and EBSCO Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases. Two independent reviewers will conduct searching and data abstraction and discordance will be handled by discussion between both parties. The risk of bias of the individual studies will be performed using the AMSTAR-2.

Ethics and dissemination: Ethical permission is not required for this review as we will make use of already published data. We aim to publish the findings of our review in peer-reviewed journals.

PROSPERO registration number: CRD42021286908
Obesity treatment - overview of pharmacological and surgical methods
Authors: Osiak Joanna , Mikut Karolina , Wijata Aleksandra , Kędziora-Kornatowska Kornelia
Published: May 2022

Introduction and purpose of the work: Obesity is a chronic disease that leads to many complications. Almost a third of the world's population is now classified as overweight or obese. This is a huge global problem. The base of treatment is diet and physical activity, but fortunately nowadays we also have pharmacological and surgical treatment - which are increasingly used. The aim of this study is to draw attention to obesity disease which may lead to serious complications and compare available pharmacological and surgical treatment.

State of knowledge (brief description): Treating obesity is a difficult and often multidisciplinary challenge. Currently many drugs with different mechanisms and different efficiencies has been approved for treatment. All of them show efficiency, but the available studies show that surgical treatment produces better results than pharmacological treatment. 

Summary: We currently have a huge range of obesity treatment options available. Surgical treatment produces better results than pharmacological treatment. Nevertheless, not every patient qualifies for bariatric surgery. Pharmacological methods are also effective. The treatment method should be individually selected for the patient.
A Branch-and-Cut Algorithm for Submodular Interdiction Games
Authors: Tanınmış Kübra , Sinnl Markus
Published: May 2022

Many relevant applications from diverse areas such as marketing, wildlife conservation, and defending critical infrastructure can be modeled as interdiction games. In this work, we introduce interdiction games whose objective is a monotone and submodular set function. Given a ground set of items, the leader interdicts the usage of some of the items of the follower in order to minimize the objective value achievable by the follower, who seeks to maximize a submodular set function over the uninterdicted items subject to knapsack constraints. We propose an exact branch-and-cut algorithm for this kind of interdiction game. The algorithm is based on interdiction cuts, which allow the leader to capture the follower’s objective function value for a given interdiction decision of the leader and exploit the submodularity of the objective function. We also present extensions and liftings of these cuts and discuss additional preprocessing procedures. We test our solution framework on the weighted maximal covering interdiction game and the bipartite inference interdiction game. For both applications, the improved variants of our interdiction cut perform significantly better than the basic version. For the weighted maximal covering interdiction game for which a mixed-integer bilevel linear programming (MIBLP) formulation is available, we compare the results with those of a state-of-the-art MIBLP solver. Whereas the MIBLP solver yields a minimum of 54% optimality gap within one hour, our best branch-and-cut setting solves all but four of 108 instances to optimality with a maximum of 3% gap among unsolved ones.