bluuebunny/crossref_metadata_2025 huggingface dataset:
A deep generative model for multi-view profiling of single-cell RNA-seq and ATAC-seq data
Authors: Li Gaoyang , Fu Shaliu , Wang Shuguang , Zhu Chenyu , Duan Bin , Tang Chen , Chen Xiaohan , Chuai Guohui , Wang Ping , Liu Qi
Published: January 2022

Here, we present a multi-modal deep generative model, the single-cell Multi-View Profiler (scMVP), which is designed for handling sequencing data that simultaneously measure gene expression and chromatin accessibility in the same cell, including SNARE-seq, sci-CAR, Paired-seq, SHARE-seq, and Multiome from 10X Genomics. scMVP generates common latent representations for dimensionality reduction, cell clustering, and developmental trajectory inference and generates separate imputations for differential analysis and cis-regulatory element identification. scMVP can help mitigate data sparsity issues with imputation and accurately identify cell groups for different joint profiling techniques with common latent embedding, and we demonstrate its advantages on several realistic datasets.
Efficacy of repetitive transcranial magnetic stimulation (rTMS) for reducing consumption in patients with alcohol use disorders (ALCOSTIM): study protocol for a randomized controlled trial
Authors: Petit Benjamin , Soudry-Faure Agnès , Jeanjean Ludovic , Foucher Jack , Lalanne Laurence , Carpentier Maud , Jonval Lysiane , Allard Coralie , Ravier Mathilde , Mohamed Amine Ben , Meille Vincent , Trojak Benoit
Published: January 2022

Background

The number of people with an alcohol use disorder (AUD) was recently estimated to be 63.5 million worldwide. The global burden of disease and injury attributable to alcohol is considerable: about 3 million deaths, namely one in 20, were caused by alcohol in 2015. At the same time, AUD remains seriously undertreated.

In this context, alternative or adjunctive therapies such as brain stimulation could play an important role. The early results of studies using repetitive transcranial magnetic stimulation (rTMS) suggest that stimulations delivered to the dorsolateral prefrontal cortex significantly reduce cravings and improve decision-making processes in various addictive disorders. We therefore hypothesize that rTMS could lead to a decrease in alcohol consumption in patients with AUD.

Methods/design

We report the protocol of a randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the efficacy of rTMS on alcohol reduction in individuals diagnosed with AUD. The study will be conducted in 2 centers in France. Altogether, 144 subjects older than 18 years and diagnosed with AUD will be randomized to receive 5 consecutive twice-daily sessions of either active or sham rTMS (10 Hz over the right DLPFC, 2000 pulses per day). The main outcomes of the study will be changes in alcohol consumption within the 4 weeks after the rTMS sessions. Secondary outcome measures will include changes in alcohol consumption within the 24 weeks, alcohol cravings, clinical and biological improvements, effects on mood and quality of life, and cognitive and safety assessments, and, for smokers, an assessment of the effects of rTMS on tobacco consumption.

Discussion

Several studies have observed a beneficial effect of rTMS on substance use disorders by reducing craving, impulsivity, and risk-taking behavior and suggest that rTMS may be a promising treatment in addiction. However, to date, no studies have included sufficiently large samples and sufficient follow-up to confirm this hypothesis. The results from this large randomized controlled trial will give a better overview of the therapeutic potential of rTMS in AUD.

Trial registration

ClinicalTrials.gov NCT04773691. Registered on 26 February 2021

https://clinicaltrials.gov/ct2/show/NCT04773691?term=trojak&draw=2&rank=5.
Comparison of insertion time, pull-out strength, and screw-media interface area of customized pedicle screw with different core and thread design against commercial pedicle screw: a pilot study on Indonesian Population
Authors: Magetsari Rahadyan , Rukmoyo Tedjo , Saputra Marda Ade , Sakti Yudha Mathan
Published: January 2022

Objective

This research aimed to developing customized pedicle screw based on Indonesian vertebral anatomy and compare the insertion time, pull-out strength, and screw-media interface area of different screw design. We have developed 3 different types of pedicle screws (v-thread cylinder-core, square-thread cylinder-core and square-thread conical-core). The thread diameter was calculated from pedicle width of Indonesian population (6 mm). We used commercially available pedicle screw as control group (6.2 mm).

Result

The insertion time were significantly difference between v-thread cylinder-core pedicle screw (22.94 s) with commercially available pedicle screw (15.86 s) (p < 0.05). The pull-out strength was significantly difference between commercially available pedicle screw (408.60 N) with square-thread conical pedicle screw (836.60 N) (p < 0.05). The square-thread conical-core group have the highest interface area (1486.21 mm2). The data comparison showed that the square-thread conical-core customized pedicle screw group has comparable insertion time and has better pull-out strength than commercially available pedicle screw.
Improving low-resource Tibetan end-to-end ASR by multilingual and multilevel unit modeling
Authors: Qin Siqing , Wang Longbiao , Li Sheng , Dang Jianwu , Pan Lixin
Published: January 2022

Conventional automatic speech recognition (ASR) and emerging end-to-end (E2E) speech recognition have achieved promising results after being provided with sufficient resources. However, for low-resource language, the current ASR is still challenging. The Lhasa dialect is the most widespread Tibetan dialect and has a wealth of speakers and transcriptions. Hence, it is meaningful to apply the ASR technique to the Lhasa dialect for historical heritage protection and cultural exchange. Previous work on Tibetan speech recognition focused on selecting phone-level acoustic modeling units and incorporating tonal information but underestimated the influence of limited data. The purpose of this paper is to improve the speech recognition performance of the low-resource Lhasa dialect by adopting multilingual speech recognition technology on the E2E structure based on the transfer learning framework. Using transfer learning, we first establish a monolingual E2E ASR system for the Lhasa dialect with different source languages to initialize the ASR model to compare the positive effects of source languages on the Tibetan ASR model. We further propose a multilingual E2E ASR system by utilizing initialization strategies with different source languages and multilevel units, which is proposed for the first time. Our experiments show that the performance of the proposed method-based ASR system exceeds that of the E2E baseline ASR system. Our proposed method effectively models the low-resource Lhasa dialect and achieves a relative 14.2% performance improvement in character error rate (CER) compared to DNN-HMM systems. Moreover, from the best monolingual E2E model to the best multilingual E2E model of the Lhasa dialect, the system’s performance increased by 8.4% in CER.
Generalizations of the Jensen functional involving diamond integrals via Abel–Gontscharoff interpolation
Authors: Bibi Rabia , Nosheen Ammara , Bano Shanaz , Pečarić Josip
Published: January 2022

In this paper we obtain several refinements of the Jensen inequality on time scales by generalizing Jensen’s functional for n-convex functions. We also investigate the bounds for the identities related to the new improvements obtained.
Common deficiencies found in generic Finished Pharmaceutical Product (FPP) applications submitted for registration to the South African Health Products Regulatory Authority (SAHPRA)
Authors: Moeti Lerato , Litedu Madira , Joubert Jacques
Published: January 2022

Background

The aim of the study was to investigate the common deficiencies observed in the Finished Pharmaceutical Product (FPP) section of generic product applications submitted to SAHPRA. The study was conducted retrospectively over a 7-year period (2011–2017) for products that were finalised by the Pharmaceutical and Analytical pre-registration Unit.

Methods

There were 3148 finalised products in 2011–2017, 667 of which were sterile while 2089 were non-sterile. In order to attain a representative sample for the study, statistical sampling was conducted. Sample size was obtained using the statistical tables found in literature and confirmed by a sample size calculation with a 95% confidence level. The selection of the products was according to the therapeutic category using the multi-stage sampling method called stratified-systematic sampling. This resulted in the selection of 325 applications for non-sterile products and 244 applications for sterile products. Subsequently, all the deficiencies were collected and categorised according to Common Technical Document (CTD) subsections of the FPP section (3.2.P).

Results

A total of 3253 deficiencies were collected from 325 non-sterile applications while 2742 deficiencies were collected from 244 sterile applications. The most common deficiencies in the FPP section for non-sterile products were on the following sections: Specifications (15%), Description and Composition (14%), Description of the Manufacturing Process (13%), Stability Data (7.6%) and the Container Closure System (7.3%). The deficiencies applicable to the sterile products were quantified and the subsection, Validation and/or Evaluation (18%) has the most deficiencies. Comparison of the deficiencies with those reported by other agencies such as the USFDA, EMA, TFDA and WHOPQTm are discussed with similarities outlined.

Conclusions

The overall top five most common deficiencies observed by SAHPRA were extensively discussed for the generic products. The findings provide an overview on the submissions and regulatory considerations for generic applications in South Africa, which is useful for FPP manufacturers in the compilation of their dossiers and will assist in accelerating the registration process.
Comparative analysis of proficiencies of various textures and geometric features in breast mass classification using k-nearest neighbor
Authors: Singh Harmandeep , Sharma Vipul , Singh Damanpreet
Published: January 2022

This paper introduces a comparative analysis of the proficiencies of various textures and geometric features in the diagnosis of breast masses on mammograms. An improved machine learning-based framework was developed for this study. The proposed system was tested using 106 full field digital mammography images from the INbreast dataset, containing a total of 115 breast mass lesions. The proficiencies of individual and various combinations of computed textures and geometric features were investigated by evaluating their contributions towards attaining higher classification accuracies. Four state-of-the-art filter-based feature selection algorithms (Relief-F, Pearson correlation coefficient, neighborhood component analysis, and term variance) were employed to select the top 20 most discriminative features. The Relief-F algorithm outperformed other feature selection algorithms in terms of classification results by reporting 85.2% accuracy, 82.0% sensitivity, and 88.0% specificity. A set of nine most discriminative features were then selected, out of the earlier mentioned 20 features obtained using Relief-F, as a result of further simulations. The classification performances of six state-of-the-art machine learning classifiers, namely k-nearest neighbor (k-NN), support vector machine, decision tree, Naive Bayes, random forest, and ensemble tree, were investigated, and the obtained results revealed that the best classification results (accuracy = 90.4%, sensitivity = 92.0%, specificity = 88.0%) were obtained for the k-NN classifier with the number of neighbors having k = 5 and squared inverse distance weight. The key findings include the identification of the nine most discriminative features, that is, FD26 (Fourier Descriptor), Euler number, solidity, mean, FD14, FD13, periodicity, skewness, and contrast out of a pool of 125 texture and geometric features. The proposed results revealed that the selected nine features can be used for the classification of breast masses in mammograms.
Implementation of clinical audit to improve adherence to guideline-recommended therapy in acute coronary syndrome
Authors: George Nimmy Elizabeth , Shukkoor Aashiq Ahamed , Joseph Noel , Palanimuthu Ramasamy , Kaliappan Tamilarasu , Gopalan Rajendiran
Published: January 2022

Background

Despite global consensus on the management of acute coronary syndrome (ACS), implementation of strategies to improve adherence of guideline-directed medical therapy (GDMT) remains sub-optimal, especially in developing countries. Thus, we aimed to assess the effect of clinical pharmacist-led clinical audit to improve the compliance of discharge prescriptions in patients admitted with ACS. It is a prospective clinical audit of ACS patients which was carried out for 12 months. The discharge prescriptions were audited by clinical pharmacists for the appropriateness in the usage of statins, dual antiplatelet therapy (DAPT), beta-blockers, and angiotensin-converting enzyme inhibitors (ACE-I)/angiotensin receptor blocker (ARB). A feedback report was presented every month to the cardiologists involved in the patient care, and the trend in the adherence to GDMT was analyzed over 12 months.

Results

The discharge prescriptions of 1072 ACS patients were audited for the justifiable and non-justifiable omissions of mandated drugs. The first-month audit revealed unreasonable omissions of DAPT, statin, ACE-I/ARB, and beta-blockers in 1%, 0%, 14%, and 11% respectively, which reduced to nil by the end of the 11th month of the audit–feedback program. This improvement remained unchanged until the end of the 12th month.

Conclusions

The study revealed that periodic clinical audit significantly improves adherence to GDMT in patients admitted with ACS.
Knowledge, attitudes, and practices of cardiopulmonary rehabilitation among physiotherapists in Lebanon
Authors: Farah Rebecca , Groot Wim , Pavlova Milena
Published: January 2022

Background

Insufficient physical activity is one of the leading mortality risks worldwide for cardiovascular and pulmonary diseases. Physiotherapists (PT) are core healthcare professionals who play a major role in the prevention of disease complications and in inspiring a healthy lifestyle. To identify challenges in the promotion of cardiopulmonary rehabilitation (CR) in Lebanon, a survey was conducted among PT and physiotherapy students. The aim was to assess the knowledge, attitudes, and practices of CR in Lebanon.

Results

The response rate was 46.1% (N = 322). Results show that 24.5% of respondents have good to excellent knowledge about CR. More than 60% of the respondents indicate possible barriers to starting a CR program, and one of two respondents identify the absence of skills as a main barrier. Findings highlight the importance of the role of PT as a mediator to increase a healthy lifestyle among patients and to promote the prevention of cardiovascular diseases and pulmonary diseases in the country.

Conclusions and recommendations

Our results support the evidence and clinical guidelines that PT play a major role by increasing the participation of patients in CR. A cost-effective CR program needs to be covered by the private and public system in Lebanon.
Discriminative Capacity of CT Volumetry to Identify Autonomous Cortisol Secretion in Incidental Adrenal Adenomas
Authors: Olmos Roberto , Mertens Nicolás , Vaidya Anand , Uslar Thomas , Fernandez Paula , Guarda Francisco J , Zúñiga Álvaro , San Francisco Ignacio , Huete Alvaro , Baudrand René
Published: January 2022

Context

Incidentally discovered adrenal adenomas are common. Assessment for possible autonomous cortisol excess (ACS) is warranted for all adrenal adenomas, given the association with increased cardiometabolic disease.

Objective

To evaluate the discriminatory capacity of 3-dimensional volumetry on computed tomography (CT) to identify ACS.

Methods

Two radiologists, blinded to hormonal levels, prospectively analyzed CT images of 149 adult patients with unilateral, incidentally discovered, adrenal adenomas. Diameter and volumetry of the adenoma, volumetry of the contralateral adrenal gland, and the adenoma volume-to-contralateral gland volume (AV/CV) ratio were measured. ACS was defined as cortisol ≥ 1.8 mcg/dL after 1-mg dexamethasone suppression test (DST) and a morning ACTH ≤ 15. pg/mL.

Results

We observed that ACS was diagnosed in 35 (23.4%) patients. Cortisol post-DST was positively correlated with adenoma diameter and volume, and inversely correlated with contralateral adrenal gland volume. Cortisol post-DST was positively correlated with the AV/CV ratio (r = 0.46, P < 0.001) and ACTH was inversely correlated (r = −0.28, P < 0.001). The AV/CV ratio displayed the highest odds ratio (1.40; 95% CI, 1.18-1.65) and area under curve (0.91; 95% CI, 0.86-0.96) for predicting ACS. An AV/CV ratio ≥ 1 (48% of the cohort) had a sensitivity of 97% and a specificity of 70% to identify ACS.

Conclusion

CT volumetry of adrenal adenomas and contralateral adrenal glands has a high discriminatory capacity to identify ACS. The combination of this simple and low-cost radiological phenotyping can supplement biochemical testing to substantially improve the identification of ACS.
The Changing Face of Cystic Fibrosis: An Update for Anesthesiologists
Authors: Lee Amy J. , Huffmyer Julie L. , Thiele Eryn L. , Zeitlin Pamela L. , Chatterjee Debnath
Published: January 2022

Cystic fibrosis (CF) is the most common fatal genetic disease in North America. While CF is more common among Whites, it is increasingly being recognized in other races and ethnicities. Although there is no cure, life expectancy has steadily improved, with the median survival exceeding 46 years in the United States. There are now more adults than children with CF in the United States. CF is caused by mutations in a gene that encodes the cystic fibrosis transmembrane conductance regulator (CFTR) protein, expressed in many epithelial cells. More than 2100 CFTR mutations have been linked to CF, and newer CFTR modulator drugs are being used to improve the production, intracellular processing, and function of the defective CFTR protein. CF is a multisystem disease that affects primarily the lungs, pancreas, hepatobiliary system, and reproductive organs. Anesthesiologists routinely encounter CF patients for various surgical and medical procedures, depending on the age group. This review article focuses on the changing epidemiology of CF, advances in the classification of CFTR mutations, the latest innovations in CFTR modulator therapies, the impact of the coronavirus disease pandemic, and perioperative considerations that anesthesiologists must know while caring for patients with CF.
Varying Dosages of Subcutaneous Unfractionated Heparin and Activated Partial Thromboplastin Time in Hospitalized Antepartum Patients: A Retrospective Cohort Analysis
Authors: Elmofty Dalia H. , Tucker Andrew , Wuenstel Andrew M. , Cheng Paul K. , Fox Edward , Knoebel Randall , Liao Chuanghong , Scavone Barbara
Published: January 2022

BACKGROUND:

Venous thromboembolism (VTE) is a leading cause of maternal morbidity and mortality in the United States. Subcutanous unfractionated heparin (UFH) has been used for decades for VTE prophylaxis and under many obstetric quality of care initiatives, hospitalized antepartum patients now receive doses as high as 10,000 units every 12 hours. This practice increases the likelihood of UFH administration around the time that epidural labor analgesia is requested or neuraxial analgesia for cesarean delivery is needed. To clarify the effect of UFH on coagulation, we reviewed the care of hospitalized antepartum patients receiving VTE prophylaxis with UFH to determine the incidence of concurrent abnormal activated partial thromboplastin time (aPTT) values and associated risk factors.

METHODS:

This retrospective cohort study used data from the University of Chicago Pharmacy database to identify hospitalized antepartum patients receiving subcutaneous UFH from June 1, 2016 to July 1, 2019. Our institutional protocol states that all patients hospitalized for antepartum conditions should receive pharmacologic prophylaxis empirically unless contraindicated. For patients receiving UFH, dosing was based on gestational age: 5000 units every 12 hours for first trimester antepartum patients, 7500 units every 12 hours for second trimester patients, and 10,000 units every 12 hours for patients in the third trimester. As per protocol, aPTT values were obtained 2 hours after the third dose of heparin, and platelet counts after 4 days. Data collection included demographics, comorbidities, heparin doses, aPTT values, platelet counts, creatinine if available, and anesthetic type and complications. Logistic regression was performed to determine the association between elevated aPTT >40 seconds and study variables.

RESULTS:

Of the 321 antepartum patients who received subcutaneous UFH, 33 (10.3%) had an aPTT >40 seconds, 4 of those 33 patients (12.1%) received 5000 units every 12 hours, 14 (42.2%) received 7500 units every 12 hours, and 15 (45.5%) received 10,000 units every 12 hours. The likelihood of a patient having aPTT >40 seconds was 2.8% with 5000 units every 12 hours, 18.9% with 7500 units every 12 hours, and 14.6% with 10,000 units every 12 hours.

CONCLUSIONS:

Elevated aPTT values are likely with total daily doses of 15,000 or 20,000 units subcutaneous UFH in hospitalized antepartum patients.
The Association of Laryngeal Position on Videolaryngoscopy and Time Taken to Intubate Using Spatial Point Pattern Analysis of Prospectively Collected Quality Assurance Data
Authors: Miller Matthew R. , Gemal Hugo , Ware Sandra , Hayes-Bradley Clare
Published: January 2022

BACKGROUND:

During videolaryngoscopy (VL), the larynx appears within the defined area of the video screen, and its location can be measured as a point within this space. Spatial statistics offer methods to explore the relationship between location data and associated variables of interest. The aims of this study were to use spatial point pattern analysis to explore if the position of the larynx on VL is associated with longer times to intubate, increased risk of a needing >1 intubation attempt, or percentage of glottic opening.

METHODS:

Quality assurance data and clinical notes from all prehospital intubations using C-MAC Pocket Monitor with CMAC-4 blade (Karl Storz) from January 1, 2018, to July 31, 2020, were reviewed. We extracted 6 measurements corresponding to the time taken to obtain the initial and then best laryngeal view, time to manipulate a bougie, and time to place the endotracheal tube, as well a percentage of glottic opening and a number of intubation attempts. Larynx location was the middle of the base of glottis, in cm from the left and bottom on the C-MAC screen. Two plots were produced to summarize the base of glottis location and time to perform each time component of intubation. Next, a cross mark function and a maximum absolute deviation hypothesis test were performed to assess the null hypotheses that the spatial distributions were random. The association between glottis location and >1 intubation attempt was assessed by a spatial relative risk plot.

RESULTS:

Of 619 eligible intubations, 385 had a video for analysis. The following time variables had a nonrandom spatial distribution with a tendency for longer times when the larynx was off-center to the top or right of the screen: laryngoscope passing from teeth to glottis, glottis first view to best view of the larynx, time from bougie appearing to being placed in the cords, and overall time from teeth to endotracheal tube passing through cords. There was no increased relative risk for >1 intubation attempt.

CONCLUSIONS:

Spatial point pattern analysis identified a relationship between the position of the larynx during VL and prolonged intubation times. We did not find a relationship between larynx location and >1 attempt. Whether the location of the larynx on the screen is a marker for difficult VL or if optimizing the larynx position to the center of the screen improves intubation times would require further prospective studies.
Myotonic dystrophy type 1 embryonic stem cells show decreased myogenic potential, increased CpG methylation at the DMPK locus and RNA mis-splicing
Authors: Franck Silvie , Couvreu De Deckersberg Edouard , Bubenik Jodi L. , Markouli Christina , Barbé Lise , Allemeersch Joke , Hilven Pierre , Duqué Geoffrey , Swanson Maurice S. , Gheldof Alexander , Spits Claudia , Sermon Karen D.
Published: January 2022

Skeletal muscle tissue is severely affected in myotonic dystrophy type 1 (DM1) patients, characterised by muscle weakness, myotonia and muscle immaturity in the most severe congenital form of the disease. Previously, it was not known at what stage during myogenesis the DM1 phenotype appears. In this study we differentiated healthy and DM1 human embryonic stem cells to myoblasts and myotubes and compared their differentiation potential using a comprehensive multi-omics approach. We found myogenesis in DM1 cells to be abnormal with altered myotube generation compared to healthy cells. We did not find differentially expressed genes between DM1 and non-DM1 cell lines within the same developmental stage. However, during differentiation we observed an aberrant inflammatory response and increased CpG methylation upstream of the CTG repeat at the myoblast level and RNA mis-splicing at the myotube stage. We show that early myogenesis modelled in hESC reiterates the early developmental manifestation of DM1.
Non-Aqueous Liquid Phase Synthesis of Acetic Acid via Ionic Liquid Promoted Homogeneous Carbonylation of Methanol over Ir(III) Catalysts
Authors: Zhang Qiang , He Anbang , Xiao Wen , Du Jun , Liu Zuohua , Tao Changyuan
Published: January 2022

Carbonylation of methanol to acetic acid is an aqueous homogeneous catalytic process widely used in industry. In the existing methanol carbonylation industry, a large amount of water (14–15 wt.%) is required in the Monsanto process to inhibit catalyst deactivation, which also consumes a lot of energy to separate the water from the acetic acid product. Here, non-aqueous liquid phase synthesis of acetic acid was carried out by ionic liquid promoted homogeneous carbonylation of methanol over Ir(III) catalysts. It was found that 1-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide ([Bmim]Tf2N) and N-butyl pyridinium bis(trifluoromethanesulfonyl)imide ([BPy]Tf2N) could promote the acetic acid selectivity (>98%) and methanol conversion (>99%) under a relatively mild reaction condition of 160 °C and 3.0 MPa. In the reaction, Tf2N− formed an Ir*[Tf2N] complex with Ir to promote the stability of Ir and enhance the activation of CO. From DFT calculation results, the CO insertion was a rate controlling step on the Ir-base catalyst in the reaction cycle, determining the conversion and selectivity of the reaction. The oxygen and nitrogen groups from Tf2N− interacted with Ir to form an Ir*[Tf2N] complex, which could effectively reduce the energy barrier of the CO insertion step, enhancing the selectivity of HAc. Moreover, the catalyst system could be easily recycled and reused with the methanol conversion of 89.66% after five cycles. The methanol carbonylation based on the ionic liquid promoted catalyst is a promising non-aqueous liquid-phase sustainable process.
Sport-Related Concussion Preceding Adrenal Insufficiency and Hypopituitarism
Authors: Northam Weston T. , Alexander Andrew , Carneiro Kevin A.
Published: January 2022

A 49-year-old woman with a history of daily inhaled corticosteroid use for asthma presented to a concussion clinic 7 wk after sport-related head injury with headache, visual blurring, dizziness, nausea, fatigue, polydipsia, and polyuria. Examination revealed difficulty with vestibulo-occulomotor testing due to nausea and visual straining. Cranial CT/MR imaging was unremarkable. Laboratory testing revealed critically low serum cortisol, hypernatremia, and urine studies suggesting diabetes insipidus. The patient was referred to the emergency department. Intravenous fluid resuscitation, corticosteroids, and desmopressin led to significant symptomatic relief. She was maintained on oral hydrocortisone after cosyntropin test revealed adrenal insufficiency. Her clinical picture suggested chronic subclinical adrenal suppression from inhaled corticosteroids, which was exacerbated by hypopituitarism possibly from concussion combined with diabetes insipidus. Adrenal insufficiency should be considered in athletes with history of corticosteroid use and endocrine-related symptoms after concussion, because this can create significant morbidity and can mimic traditional symptoms of concussion.
Estimativa de Curvas e Greides para o Planejamento e Análise de Segurança a Partir de Dispositivos GIS E GPS
Authors: Riente de Andrade Gustavo
Published: January 2022

O perfil e alinhamento horizontal da rodovia são usados pelo Highway Safety Manual para estimar o efeito de greides e curvas no número previsto de acidentes. No entanto, nem sempre o projeto da via se encontra disponível aos planejadores de transporte. Além disso, a extração de parâmetros de geometria de forma convencional pode ser inviável em projetos em larga escala. Neste contexto, este artigo propõe um algoritmo capaz de extrair dados de geometria de bancos de dados geográficos ou dispositivos de GPS para uso em análises de segurança e operação. Em especial, o componente de análise de curvas horizontais foi desenvolvido de forma a identificar transições em espiral. Um algoritmo genético foi usado para calibrar o algoritmo de identificação e caracterização de curvas, de forma que os raios, desenvolvimentos e transição espiral reflitam as características reais da via. Uma rodovia de pista simples real foi usada para testar e calibrar o algoritmo proposto. Foram comparadas as características estimadas com o projeto as-built para 26 curvas horizontais. Todas as curvas foram identificadas pelo algoritmo, e todas as transições em espiral foram corretamente classificadas. Os raios estimados foram similares aos reais, indicando que o método proposto tem o potencial de ser validado e aplicado em outros locais em análises de planejamento.
Criação de valor na utilização da cabotagem no Brasil
Authors: MIGUEL PRISCILA LACZYNSKI DE SOUZA , GOMES DA CUNHA JÚNIOR GILBERTO
Published: January 2022

A cabotagem vem apresentando um crescimento constante em movimentação de contêineres nestes últimos anos, deixando de ser coadjuvante no setor de transporte nacional. O presente trabalho buscou identificar as vantagens, além da redução de custo de frete, que este modal proporciona aos seus usuários. Baseada em uma pesquisa qualitativa com 21 entrevistados, os resultados apontaram, como fatores que motivam a adoção deste modo de transporte, sua capacidade de transportar grandes volumes; estoque em trânsito; giro de frota dos caminhões próprios ou parceiros; capacidade de escoamento em regiões de difícil acesso via rodovia; pontualidade das entregas, possibilitando o uso do modal para realizar a entrega final com melhor assertividade e maior previsibilidade; lead time competitivo para cargas de grandes dimensões; utilização de contêineres para armazenagem ou antecipação de vendas a fim de otimizar seus espaços; possibilidade de revender o frete por um valor mais alto, sendo o frete considerado como receita, e não apenas custo.
CONFLITOS DE LEIS E JURISDIÇÕES NAS TRANSAÇÕES CELEBRADAS A PARTIR DA BLOCKCHAIN
Authors: Hastreiter Michele Alessandra , Ribeiro Marcia Carla Pereira
Published: January 2022

Contextualização: A tecnologia conhecida como blockchain permite a celebração de negócios jurídicos internacionais per se, uma vez que seu funcionamento se pauta na lógica descentralizada, na qual seus diferentes “nós” estão distribuídos em computadores de todo o mundo. No entanto, localizar uma transação feita através da blockchain por meio do raciocínio clássico do Direito Internacional Privado é tarefa desafiadora, o que traz questionamentos quanto à forma de solucionar o conflito de leis e jurisdições em relações jurídicas transnacionais.Objetivo: O objetivo deste artigo é apresentar as dificuldades para identificação da corte competente e do elemento de conexão aplicável aos conflitos internacionais potencialmente emergentes da tecnologia, bem como apontar possíveis caminhos para uma solução. Metodologia: A pesquisa utiliza-se do método dedutivo; quanto ao procedimento, é uma pesquisa bibliográfica que analisa estudos e artigos científicos sobre o tema.Resultados: A pesquisa conclui que a aplicação dos critérios clássicos para solucionar os conflitos de leis no espaço na tecnologia requer cuidados específicos e sugere que a própria tecnologia peer to peer pode trazer alternativas viáveis para uma maior segurança jurídica na solução de conflitos emergentes da tecnologia.
Novel antifungal agents in clinical trials
Authors: Jacobs Samantha E. , Zagaliotis Panagiotis , Walsh Thomas J.
Published: January 2022

Invasive fungal diseases due to resistant yeasts and molds are an important and increasing public health threat, likely due to a growing population of immunosuppressed hosts, increases in antifungal resistance, and improvements in laboratory diagnostics.  The significant morbidity and mortality associated with these pathogens bespeaks the urgent need for novel safe and effective therapeutics.  This review highlights promising investigational antifungal agents in clinical phases of development: fosmanogepix, ibrexafungerp, rezafungin, encochleated amphotericin B, oteseconazole (VT-1161), VT-1598, PC945, and olorofim.  We discuss three first-in-class members of three novel antifungal classes, as well as new agents within existing antifungal classes with improved safety and tolerability profiles due to enhanced pharmacokinetic and pharmacodynamic properties.
Factors Associated with Knowledge and Awareness of Stroke Among the Jordanian Population: A Cross-Sectional Study
Authors: Barakat Muna , A. AlSalamat Husam , Jirjees Feras , Al-Obaidi Hala , k. Hussain Zainab , El Hadidi Seif , Mansour Sara , Malaeb Diana , Hosseini Hassan
Published: January 2022

Background and objective: Stroke is the second leading cause of death in Jordan and over the world. Knowledge and awareness towards stroke play a crucial role in the management and prevention of its complications. This study aims to assess the knowledge and awareness about stroke among the Jordanian population and determine factors associated with stroke awareness.

Methods: This cross-sectional study through a web-based anonymous questionnaire that needed 10 minutes to be completed. It examined sociodemographic characteristics and recognition of the risk factors, warning signs, stroke consequences, and early response to stroke symptoms. Logistic regression analysis identified the factors associated with poor knowledge of stroke. 

Results: A total of 573 Jordanian adults participated in this study. The participant's ability to identify at least one early symptom of stroke and the proper response to the symptoms were significantly correlated with the educational level (OR of 3.4 and 2.5, respectively). At least one consequence of stroke was significantly associated with different demographic factors such as gender, socioeconomic income, females versus males and those with medium income versus low income had significantly higher odds (OR of 6.6 and 4.1, respectively).

Conclusion: This study revealed a good knowledge and awareness level about stroke among Jordanians correlated mainly with their educational level. Therefore, new strategies should be considered to decrease the prevalence of stroke in Jordan, including the need for engagement in enhanced awareness campaigns.
Sub-chronic effects of Baccharis dracunculifolia treatment on biochemical, oxidative, and histopathological parameters in diabetic rats
Authors: Pereira Ricardo Aparecido , Hey Albimara , de Carli Alexandre Lustoza , Sanches Camila Garcia Salvador , Bordion Jardel Cristiano , Iurckevicz Genice , Wouk Jessica , Almeida Pablo , da Silva Luiz Augusto , Penteado Rozilda , Prasniewski Anaclara , Oldoni Tatiane Luiza Cadorin , Dangui Anayana Zago , Malfatti Carlos Ricardo Maneck
Published: January 2022

Background: Oxidative stress and the mild inflammatory process present in diabetes play a critical role in the pathogenesis of the disease and its comorbidities. This understanding has opened new avenues and targets for developing improved treatments since the risk factors associated with diabetes may be reduced through non-pharmacological interventions. In this sense, plant extracts could be efficient in preventing or assisting these pathological conditions treatment.

Methods: Diabetes mellitus was induced in 24 rats, which were allocated in 4 groups: Control (CT), Control+Baccharis (CT-B), Diabetes (DB), and Diabetes+Baccharis (DB-B). For 28 days, the animals of CT-B and DB-B groups were treated, via gavage, with B. dracunculifolia extract at 50 mg.kg-1.

Results: The DB group presented higher values than the DB-B group on parameters such as creatinine (26.42%), urea (31.42%), and triglycerides (60.80%). Creatinine and triglycerides values of DB-B group (0.39±0.01 e 75.0±8.4, receptively) were equivalent to the values of CT group (0.32±0.01 e 71.7±5.4) and of CT-B group (0.39±0.01, and 58.8±4.5). The treatment with B. dracunculifolia improved the levels of fasting glucose and response of glucose tolerance (32%), insulin (52,17%) and lipid peroxidation (liver 33.33%, kidney 38.77%) when compared to the DB group.

Conclusions: The phenolic compounds and the anti-inflammatory activity of the extract of Baccharis dracunculifolia may be responsible for the hypoglycemic effect observed in the study.
Paradigm shift in medical education due to the COVID-19 pandemic: guidelines for developing a blended learning curriculum in medical education
Authors: Rafi Aisha , Anwar Muhammad Idrees , Younas Ayesha , Manzoor Shamaila
Published: January 2022

Background: The coronavirus disease 2019 (COVID-19) pandemic has transformed the world’s economy, health and education in a blink of an eye. Almost 1 billion learners have been affected across the globe. This has resulted in a paradigm shift to blended learning. Therefore, it was felt necessary to provide practical guidelines for the development of blended curriculum in medical education. It would help to overcome the challenges faced due to unprecedented transformation of medical education on account of pandemic.

Methods: Guidelines based on personal experience of the authors and literature search were developed using the complex adapted blended learning system (CALBS) framework. Seven experts developed these guidelines using the nominal group technique. The consent form and literature for CABLS framework was shared with experts. The experts developed the guidelines independently during phase one of the technique. After a given time, phase 2 started with moderator mediated discussion about the individual guidelines developed by the experts. After discussion and mutual consensus four types of guideline ideas were developed. During the third phase the experts ranked the guideline ideas on a scale of 1 to 5. The guideline idea that ranked highest was selected as a final guideline for developing a blended learning curriculum.

Results: The group consensus resulted in developing seven guidelines for a blended course or curriculum in medical education. These guidelines are based on a conceptual framework supplemented by expert’s own personal experience and current evidence from literature.

Conclusions: These guidelines would provide a comprehensive and systematic approach to develop a blended learning curriculum in medical education.
Positional weight matrices have sufficient prediction power for analysis of noncoding variants
Authors: Boytsov Alexandr , Abramov Sergey , Makeev Vsevolod J. , Kulakovskiy Ivan V.
Published: January 2022

The commonly accepted model to quantify the specificity of transcription factor binding to DNA is the position weight matrix, also called the position-specific scoring matrix. Position weight matrices are used in thousands of projects and computational tools in regulatory genomics, including prediction of the regulatory potential of single-nucleotide variants. Yet, recently Yan et al. presented new experimental method for analysis of regulatory variants and, based on its results, reported that "the position weight matrices of most transcription factors lack sufficient predictive power". Here, we re-analyze the rich experimental dataset obtained by Yan et al. and show that appropriately selected position weight matrices in fact can successfully quantify transcription factor binding to alternative alleles.
Modified poly(L-lysine)-based structures as novel antimicrobials for diabetic foot infections, an in-vitro study
Authors: Grace Alicia , Murphy Robert , Dillon Aoife , Smith Diarmuid , Cryan Sally-Ann , Heise Andreas , Fitzgerald-Hughes Deirdre
Published: January 2022

Background: Wound infections occur as sequelae to skin trauma and cause significant hospitalizations, morbidity and mortality. Skin traumas arise more frequently in those with diabetes or cardiovascular disease and in these settings, may be chronic with poorer outcomes including lower limb amputation. Treatment of chronic wound infection is challenging due to antibiotic resistance and biofilm formation by bacteria including S. aureus and P. aeruginosa, which are among the most frequent causative pathogens. Managing these challenging infections requires new molecules and modalities. Methods: We evaluated antimicrobial and anti-biofilm activity of star-shaped poly(L-lysine) (PLL) polymers against S. aureus and P. aeruginosa strains and clinical isolates recovered from wounds including diabetic foot wounds (DFW) in a Dublin Hospital in 2019. A star-shaped PLL polypeptide series, specifically G2(8)PLL20, G3(16)PLL10, G4(32)PLL5 with variation in polypeptide chain length and arm-multiplicity, were compared to a linear peptide, PLL160 with equivalent number of lysine residues. Results: All PLLs, including the linear polypeptide, were bactericidal at 1μM against S. aureus 25923 and P. aeruginosa PAO1, with log reduction in colony forming units/ml between 2.7-3.6. PLL160 demonstrated similar killing potency against 20 S. aureus and five P. aeruginosa clinical isolates from DFW, mean log reductions: 3.04 ± 0.16 and 3.96 ± 0.82 respectively after 1 hour incubation. Potent anti-biofilm activity was demonstrated against S. aureus 25923 but for clinical isolates, low to moderate loss of biofilm viability was shown using PLL160 and G3(16)PLL10 at 50 μM (S. aureus) and 200 μM (P. aeruginosa) with high inter-isolate variability. In the star-shaped architecture, antimicrobial activity was retained with incorporation of 5-mer hydrophobic amino-acid modifications to the arms of the polypeptides (series G3(16)PLL20-coPLT5, G3(16)PLL20-coPLI5, G3(16)PLL20-coPLP5). Conclusion: These polypeptides offer structural flexibility for clinical applications and have potential for further development, particularly in the setting of diabetic foot and other chronic wound infections.
Predictive potential for measuring motivational readiness for service in the internal affairs bodies of the Russian Federation
Authors: Krasnoshtanova Natal'ya , Pechenkova Elena
Published: January 2022

The article studies the components of the structure of the motivational sphere of the personality of employees of the internal affairs bodies of the Russian Federation. A theoretical and methodological analysis of the currently existing approaches to the study of the motivational sphere of a person's life is carried out and only those that are focused, to a greater extent, on the search and description of the dispositional (trait-like) foundations of motivation and the assessment of individual differences in the degree of their severity among employees are highlighted. ATS, to identify their deep motives and values that determine professional behavior and are able to predict it. One of the goals of the work was to create an original psychodiagnostic toolkit aimed at identifying the psychological characteristics of the professional motivation of candidates to enter the service in the internal affairs bodies, employees to be appointed to other positions in the internal affairs bodies and the choice of a certain direction of professional service by them. The novelty of the results lies in the fact that on the basis of the proposed structure and known methods and tests - questionnaires, a «Methodology for studying the professional motivation of candidates to enter the service in the internal affairs bodies, employees for appointment to other positions in the internal affairs bodies and the choice of a certain areas of professional service», which includes 12 basic scales: the need for achievement; the need for power; the need for security; the need for ownership; locus of control; hedonism / altruism; ambition; behavioral regulation; corruption resistance; conscientiousness; professional identity «I am a policeman» and a mandatory scale of «social desirability» and atypical responses. The developed methodology can be used in the activities of personnel departments to improve the professional psychological selection of candidates for entering the service in the internal affairs bodies, employees for appointment to other positions in the internal affairs bodies and the choice by them of a certain direction of professional service activity.
FORMATION OF MORAL CONSCIOUSNESS PRIMARY SCHOOL CHILDREN BASED ON COMPETENCE APPROACH
Authors: Vyalikova Galina , Finikova Julia , Hackalo Snezhana
Published: January 2022

The article examines some aspects of the formation of the moral consciousness of modern schoolchildren on the basis of one of the leading methodological principles - the competence-based approach.

Large-scale changes taking place in various spheres of society, new social and economic reality, developing market relations, digitalization, modernization of Russian education require a revision of the strategy and tactics of educating the younger generation in terms of solving the problems of forming high moral qualities of the personality of students, including primary school age. But is a modern teacher competent enough to successfully cope with the multitasking of real pedagogical reality, including the moral education of schoolchildren?

The study of the problem under consideration in theory and in practice shows that moral education is significant, first of all, because it permeates all aspects of education: mental, aesthetic, physical, labor, environmental, etc. Hence, its backbone nature is obvious. Any human action presupposes a moral aspect, including the regulatory function of morality.

All of the above served as the basis for choosing the topic of the article. According to the authors, the results and conclusion of this article can, to a certain extent, actualize the problem of the formation of the moral consciousness of primary schoolchildren from the standpoint of the competence-based approach and outline ways to solve it.