bluuebunny/crossref_metadata_2025 huggingface dataset:
Infinitival Clauses in the Romance Languages
Authors: Mensching Guido
Published: September 2021

“Infinitival clauses” are constructions with a clausal status whose predicate is an infinitive. Romance infinitive clauses are mostly dependent clauses and can be divided into the following types: argumental infinitival clauses (such as subject and object clauses, the latter also including indirect interrogatives), predicative infinitival clauses, infinitival adjunct clauses, infinitival relative clauses, and nominalized infinitive clauses (with a determiner). More rarely, they appear as independent (main) clauses (root infinitival clauses) of different types, which usually have a marked character.

Whereas infinitival adjunct clauses are generally preceded by prepositions, which can be argued to be outside the infinitival clause proper (i.e., the clause is part of a prepositional phrase), Romance argumental infinitive clauses are often introduced by complementizers that are diachronically derived from prepositions, mostly de/di and a/à. In most Romance languages, the infinitive itself is morphologically marked by an ending containing the morpheme {r} but lacks tense and agreement morphemes. However, some Romance languages have developed an infinitive that can be inflected for subject agreement (which is found in Portuguese, Galician, and Sardinian and also attested in Old Neapolitan).

Romance languages share the property of English and other languages to leave the subject of infinitive clauses unexpressed (subject/object control, arbitrary control, and optional control) and also have raising and accusative-and-infinitive constructions. A special property of many Romance languages is the possibility of overtly expressing a nominative subject in infinitival clauses, mostly in postverbal position. The tense of the infinitive clause is usually interpreted as simultaneous or anterior to that of the matrix clause, but some matrix predicates and infinitive constructions trigger a posteriority/future reading. In addition, some Romance infinitive clauses are susceptible to constraints concerning aspect and modality.
Compounding: From Latin to Romance
Authors: Rainer Franz
Published: September 2021

Compounding in the narrow sense of the term, that is, leaving aside so-called syntagmatic compounds like pomme de terre ‘potato’, is a process of word formation that creates new lexemes by combining more than one lexeme according to principles different from those of syntax. New lexemes created according to ordinary syntactic principles are by some called syntagmatic compounds, also juxtapositions in the Romance tradition since Darmesteter. In a diachronically oriented article such as this one, it is convenient to take into consideration both types of compounding, since most patterns of compounding in Romance have syntactic origins. This syntactic origin is responsible for the fact that the boundaries between compounding and syntax continue to be fuzzy in modern Romance varieties, the precise delimitation being very much theory-dependent (for a discussion based on Portuguese, cf. Rio-Torto & Ribeiro, 2009). Whether some Latin patterns of compounding might, after all, have come down to the Romance languages through the popular channel of transmission continues to be controversial. There can be no doubt, however, that most of them were doomed.
Case-Marking in the Romance Languages
Authors: Nicolae Alexandru
Published: September 2021

Case-marking is subject to several important developments in the passage from Latin to the Romance languages. With respect to synthetic marking, nouns and adjectives witness considerable simplification, leading (with some exceptions, i.e., the binary case systems) to the almost complete disappearance of inflectional case-marking, while pronouns continue to show consistent inflectional case-marking. In binary case systems, case distinctions are also marked in the inflection of determiners. Inflectional simplification is compensated for by the profusion of analytic and mixed case-marking strategies and by alternative strategies of encoding grammatical relations.
The Zoom Effect: A Google Trends Analysis
Authors: Thawanyarat Kometh , Francis Shannon , Kim Trudy , Arquette Connor , Morrison Shane , Nazerali Rahim
Published: September 2021

Background

Increased video-chatting, stimulated by the COVID-19 pandemic, has been correlated with increased appearance concerns. Initial lockdown restrictions correlated with a decrease in aesthetic/cosmetic plastic surgery case volumes.

Objectives

The authors aimed to delineate public interest in aesthetic procedures surrounding the COVID-19 pandemic via Google Trends. They hypothesized that because of the pandemic, public interest in plastic surgery procedures increased, especially localized above the shoulder.

Methods

Trends in the United States for given search terms and volumes were gathered via Google Trends between January 2015 and March 2021. The search volumes were normalized, and a bivariate regression analysis of panel data was then applied to the aggregate trendlines to determine if a statistically significant change in search volume occurred following the stay-at-home orders.

Results

The following search terms had statistically significant (P < 0.000) increases in search volumes after February 2020: blepharoplasty, Botox, brachioplasty, breast implant removal, breast reduction, brow lift, buccal fat removal, hair transplantation, lip augmentation, mentoplasty, otoplasty, platysmaplasty, rhinoplasty, and thighplasty. Chi-squared analysis demonstrated a statistically significant association (chi-squared = 4.812, P = 0.028) between increases in search volume and above-the-shoulder procedures.

Conclusions

Public interest in above-the-shoulder surgical procedures statistically significantly increased following February 2020 compared with below-the-shoulder procedures. Continued examination of specific procedure trends and determining correlations with more accurate procedural datasets will provide increased insight into consumers’ mindsets and to what extent video conferencing plays a role in the public’s interest in pursuing aesthetic surgery.
Capn4 aggravates angiotensin II-induced cardiac hypertrophy by activating the IGF-AKT signalling pathway
Authors: Cao Yuanping , Wang Qun , Liu Caiyun , Wang Wenjun , Lai Songqing , Zou Huaxi , Tao Ende , Wang Fudong , Wan Li
Published: September 2021

Capn4 belongs to a family of calpains that participate in a wide variety of biological functions, but little is known about the role of Capn4 in cardiac disease. Here, we show that the expression of Capn4 was significantly increased in Angiotensin II (Ang II)-treated cardiomyocytes and Ang II-induced cardiac hypertrophic mouse hearts. Importantly, in agreement with the Capn4 expression patterns, the maximal calpain activity measured in heart homogenates was elevated in Ang II-treated mice and oral coadministration of SNJ-1945 (calpain inhibitor) attenuated the total calpain activity measured in vitro. Functional assays indicated that overexpression of Capn4 obviously aggravated Ang II-induced cardiac hypertrophy, whereas Capn4 knockdown resulted in the opposite phenotypes. Further investigation demonstrated that Capn4 maintained the activation of the insulin-like growth factor (IGF)-AKT signalling pathway in cardiomyocytes by increasing c-Jun expression. Mechanistic investigations revealed that Capn4 directly bound and stabilized c-Jun and knockdown of Capn4 increased the ubiquitination level of c-Jun in cardiomyocytes. Additionally, our results demonstrated that the antihypertrophic effect of Capn4 silencing was partially dependent on the inhibition of c-Jun. Overall, these data suggested that Capn4 contributes to cardiac hypertrophy by enhancing the c-Jun-mediated IGF-AKT signalling pathway and could be a potential therapeutic target for hypertrophic cardiomyopathy.
Nonpharmacologic approaches to pain management
Authors: Nathenson Prem Paul , Nathenson Sophie
Published: September 2021

This article discusses nonpharmacologic pain management interventions for alternative or concomitant use with nonopioid medications. Potential barriers as well as facilitators to integrating nonpharmacologic interventions are discussed as they relate to nursing practice.
Multisystem inflammatory syndrome in children
Authors: Greenway Andrew , Macklay Holly , Xuereb Kevin , Gibbons Linda
Published: September 2021

Multisystem inflammatory syndrome in children is a previously unrecognized and potentially catastrophic illness that appears in children who have been exposed to or diagnosed with COVID-19. As healthcare agents and members of the community, nurses are positioned to assist in identifying children who may experience previously unrecognized complications of infection from the SARS-CoV-2 virus.
The impact of COVID-19 on patient safety attendant use
Authors: Shields Lisa B.E. , Lawson Tiffany P. , Flanders Kimberly
Published: September 2021

Patient safety attendants (PSAs) provide constant direct observation to patients who have cognitive impairments or thoughts. Some estimates report that an acute care hospital in the United States may spend more than $1 million annually on PSAs, an expenditure often not reimbursed. With no national defined standards to regulate or monitor PSA use, this study sought to determine the impact of COVID-19 on a PSA reduction program in a large Midwestern healthcare system.
Therapeutic alliance in mental health care
Authors: Martinez Angel Johann Solorzano
Published: September 2021

The field of psychiatric nursing provides unique opportunities for nurse-patient interactions. Nurses working in inpatient psychiatric settings face constant challenges that may hinder the development of meaningful nurse-patient interactions. Peplau's theory of interpersonal relations emphasized the importance of nurse-patient relationships in nursing care. Therapeutic alliance can help promote nurse-patient relationships and may help nurses and patients achieve their goals. This article presents several phases of a concept-building process that illustrates the importance of therapeutic alliance and its application in mental health care.
COVID-19 in complex common variable immunodeficiency patients affected by lung diseases
Authors: Milito Cinzia , Soccodato Valentina , Auria Stefania , Pulvirenti Federica , Quinti Isabella
Published: September 2021

Purpose of review

In the general population, the risk of severe COVID-19 is associated with old age, male sex, hypertension, obesity and chronic diseases. Chronic lung diseases are listed as additional risk factors for hospitalization and ICU admission. The purpose of this review is to define whether chronic lung diseases, such as bronchiectasis and interstitial diseases, represent a risk for a severe SARS-CoV-2 infection in patients affected by common variable immunodeficiency (CVID), the most common symptomatic primary antibody defect.

Recent findings

CVID patients with SARS-CoV-2 infection have been reported since the beginning of the pandemic with a wide range of clinical presentations ranging from asymptomatic to mild/moderate and severe COVID-19. The meta-analysis of 88 CVID cases described in large cohorts and case reports demonstrated that CVID patients with chronic lung involvement have an increased risk for severe COVID-19 in comparison to CVID without lung diseases (50 vs. 28%, relative risk 1.75, 95% confidence interval 1.04--2.92, P = 0.043). Differently from the general population, age and metabolic comorbidities did not represent a risk factor for severe course in this patient's population.

Underlying chronic lung diseases but not age represent a risk factor for severe COVID-19 in CVID. Prompt therapeutic intervention should be adopted in SARS-CoV-2 positive CVID patients with chronic lung diseases independently of their age.
Home Auditory Environments of Children With Cochlear Implants and Children With Normal Hearing
Authors: Wang Yuanyuan , Cooke Molly , Reed Jessa , Dilley Laura , Houston Derek M.
Published: September 2021

Objectives:

Early home auditory environment plays an important role in children’s spoken language development and overall well-being. This study explored differences in the home auditory environment experienced by children with cochlear implants (CIs) relative to children with normal hearing (NH).

Design:

Measures of the child’s home auditory environment, including adult word count (AWC), conversational turns (CTs), child vocalizations (CVs), television and media (TVN), overlapping sound (OLN), and noise (NON), were gathered using the Language Environment Analysis System. The study included 16 children with CIs (M = 22.06 mo) and 25 children with NH (M = 18.71 mo). Families contributed 1 to 3 daylong recordings quarterly over the course of approximately 1 year. Additional parent and infant characteristics including maternal education, amount of residual hearing, and age at activation were also collected.

Results:

The results showed that whereas CTs and CVs increased with child age for children with NH, they did not change as a function of age for children with CIs; NON was significantly higher for the NH group. No significant group differences were found for the measures of AWC, TVN, or OLN. Moreover, measures of CTs, CVs, TVN, and NON from children with CIs were associated with demographic and child factors, including maternal education, age at CI activation, and amount of residual hearing.

Conclusions:

These findings suggest that there are similarities and differences in the home auditory environment experienced by children with CIs and children with NH. These findings have implications for early intervention programs to promote spoken language development for children with CIs.
A New Trick for an Old Dog: L-Epinephrine Delivered Continuously in the Vapor Phase
Authors: Winter Meredith C. , Newth Christopher J. L. , Castro Cristina , Hotz Justin C. , Ross Patrick A.
Published: September 2021

OBJECTIVES:

Inhaled L-epinephrine is a known treatment of severe croup and postextubation upper airway obstruction. L-epinephrine can be delivered continuously in the vapor phase, but the indications, safety, and efficacy of this novel practice have yet to be evaluated. Theoretical risks are tachycardia, hypertension, and dysrhythmias. The study objective was to describe patient characteristics and vital sign changes related to continuous vaporized L-epinephrine use in critically ill children with the hypothesis that it can be practically and safely administered to children with subglottic edema and lower airway obstruction.

DESIGN:

Retrospective cohort study.

SETTING:

PICU and cardiothoracic ICU in a tertiary academic children’s hospital.

PATIENTS:

Patients age 0–21 years treated with continuous vaporized L-epinephrine from 2013 to 2019.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Continuous vaporized L-epinephrine was administered 140 times to 129 subjects via a high-flow nasal oxygen device. The median age was 10.6 months (1.3; interquartile range, 4.8–17.1 mo). The most common indications were lower respiratory tract obstruction (45%), postextubation subglottic edema (31%), and croup (16%). Eighty-eight percent had no escalation of respiratory support within 24 hours of initiation of continuous vaporized L-epinephrine, 5% progressed to require endotracheal intubation, and 3% were reintubated within 24 hours of initiation of continuous vaporized L-epinephrine following an extubation attempt. After starting continuous vaporized L-epinephrine, 85% of subjects had a decrease in heart rate and 80% had a decrease in respiratory rate. Six subjects had an increase in heart rate, and eight had an increase in blood pressure of more than 20% from baseline. These subjects did not receive interventions specific to these vital sign changes, including discontinuation of continuous vaporized L-epinephrine.

CONCLUSIONS:

Continuous vaporized L-epinephrine was safely administered to critically ill children with most subjects demonstrating a decrease in heart rate, blood pressure, and respiratory rate.
The Effectiveness of High-Flow Nasal Cannula in Coronavirus Disease 2019 Pneumonia: A Retrospective Cohort Study
Authors: Burnim Michael S. , Wang Kunbo , Checkley William , Nolley Eric P. , Xu Yanxun , Garibaldi Brian T.
Published: September 2021

OBJECTIVES:

High-flow nasal cannula is widely used in acute hypoxemic respiratory failure due to coronavirus disease 2019, yet data regarding its effectiveness is lacking. More evidence is needed to guide patient selection, timing of high-flow nasal cannula initiation, and resource allocation. We aimed to assess time to discharge and time to death in severe coronavirus disease 2019 in patients treated with high-flow nasal cannula compared with matched controls. We also evaluated the ability of the respiratory rate-oxygenation ratio to predict progression to invasive mechanical ventilation.

DESIGN:

Time-dependent propensity score matching was used to create pairs of individuals who were then analyzed in a Cox proportional-hazards regression model to estimate high-flow nasal cannula’s effect on time to discharge and time to death. A secondary analysis excluded high-flow nasal cannula patients intubated within 6 hours of admission. A Cox proportional-hazards regression model was used to assess risk of invasive mechanical ventilation among high-flow nasal cannula patients stratified by respiratory rate-oxygenation.

SETTING:

The five hospitals of the Johns Hopkins Health System.

PATIENTS:

All patients who were admitted with a laboratory-confirmed diagnosis of coronavirus disease 2019 were eligible for inclusion.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

High-flow nasal cannula was associated with longer median time to discharge: 10.6 days (interquartile range, 7.1–15.8 d) versus 7.8 days (interquartile range, 4.9–12.1 d). Respiratory rate-oxygenation index performed poorly in predicting ventilation or death. In the primary analysis, there was no significant association between high-flow nasal cannula and hazard of death (adjusted hazard ratio, 0.79; 95% CI, 0.57–1.09). Excluding patients intubated within 6 hours of admission, high-flow nasal cannula was associated with reduced hazard of death (adjusted hazard ratio, 0.67; 95% CI, 0.45–0.99).

CONCLUSIONS:

Among unselected patients with severe coronavirus disease 2019 pneumonia, high-flow nasal cannula was not associated with a statistically significant reduction in hazard of death. However, in patients not mechanically ventilated within 6 hours of admission, high-flow nasal cannula was associated with a significantly reduced hazard of death.
Association Between Urine Output and Mortality in Critically Ill Patients: A Machine Learning Approach
Authors: Heffernan Aaron J. , Judge Stephanie , Petrie Stephen M. , Godahewa Rakshitha , Bergmeir Christoph , Pilcher David , Nanayakkara Shane
Published: September 2021

OBJECTIVES:

Current definitions of acute kidney injury use a urine output threshold of less than 0.5 mL/kg/hr, which have not been validated in the modern era. We aimed to determine the prognostic importance of urine output within the first 24 hours of admission to the ICU and to evaluate for variance between different admission diagnoses.

DESIGN:

Retrospective cohort study.

SETTING:

One-hundred eighty-three ICUs throughout Australia and New Zealand from 2006 to 2016.

PATIENTS:

Patients greater than or equal to 16 years old who were admitted with curative intent who did not regularly receive dialysis. ICU readmissions during the same hospital admission and patients transferred from an external ICU were excluded.

MEASUREMENTS AND MAIN RESULTS:

One hundred and sixty-one thousand nine hundred forty patients were included with a mean urine output of 1.05 mL/kg/hr and an overall in-hospital mortality of 7.8%. A urine output less than 0.47 mL/kg/hr was associated with increased unadjusted in-hospital mortality, which varied with admission diagnosis. A machine learning model (extreme gradient boosting) was trained to predict in-hospital mortality and examine interactions between urine output and survival. Low urine output was most strongly associated with mortality in postoperative cardiovascular patients, nonoperative gastrointestinal admissions, nonoperative renal/genitourinary admissions, and patients with sepsis.

CONCLUSIONS:

Consistent with current definitions of acute kidney injury, a urine output threshold of less than 0.5 mL/kg/hr is modestly predictive of mortality in patients admitted to the ICU. The relative importance of urine output for predicting survival varies with admission diagnosis.
Poor Reliability of Common Measures of Anticoagulation in Pediatric Extracorporeal Membrane Oxygenation
Authors: Rabinowitz Edon J. , Ouyang Amy , Armstrong Dustin R. , Wallendorf Michael , Said Ahmed S.
Published: September 2021

Anticoagulation management in pediatric extracorporeal membrane oxygenation (ECMO) is challenging with multiple laboratory measures utilized across institutions without consensus guidelines. These include partial thromboplastin time (PTT), thromboelastography (TEG), and antifactor Xa (aXa). We aimed to evaluate the consistency of TEG R-time, PTT, and aXa correlation to bivalirudin and heparin dosing. We conducted a single-center restrospective review of pediatric ECMO cases from 2018 to 2020 anticoagulated with bivalirudin or heparin. We collected up to 14 serial simultaneous TEG R-time, PTT, and aXa measurements over a 7 day ECMO course with corresponding bivalirudin or heparin dosing. We analyzed the correlation between bivalirudin, heparin, and the three measurements of anticoagulation. A total of 67 ECMO runs, 32 bivalirudin, and 35 heparin, and more than 1,500 laboratory values, of which >80% simultaneous, were analyzed. When assessing correlations at the individual patient level, there was no consistent correlation between dosing and at least one laboratory parameter in the majority of patients. Furthermore, 44% of the bivalirudin cohort and 37% of the heparin cohort exhibited no correlation with any parameters. There were statistically significant correlations only between bivalirudin and heparin dosing and the sum total of the different laboratory tests. These inconsistencies highlight the importance of multimodality testing of anticoagulation in the management of pediatric ECMO anticoagulation and cannot be relied on in isolation from bedside clinical judgment.
The Advanced Practitioner Certification in Clinical Nutrition Provides Opportunities for Validation and Career Advancement for Registered Dietitians
Authors: Stevens Jason R. , Rothpletz-Puglia Pamela , Brody Rebecca A.
Published: September 2021

This qualitative study explored career impacts of the Advanced Practitioner Certification in Clinical Nutrition (RD-AP) from the perspective of credentialed dietitians. Twelve geographically dispersed RD-APs participated in semistructured interviews ranging from 38 to 67 minutes. Interview data were analyzed using conventional content analysis with an inductive approach. All reported intrinsic benefits of increased confidence, validation, and personal satisfaction, which drove some extrinsic career benefits, including enhanced quality of patient care. The RD-AP credential is an opportunity for career advancement for advanced-level dietitians; however, increased recognition of the credential by stakeholders is needed for the continued growth of the certification program.
Zinc Level in Pathogenesis of Inflammatory Bowel Disease
Authors: Zhang Mingqiang , Yi Zongyan , Ma Liyan , Li Shaoshu , Han Long , Cao Qi
Published: September 2021

This study aimed to investigate the relationship between serum zinc levels (SZL) and inflammatory bowel disease (IBD) risk via a meta-analysis. Human studies that have reported SZL in patients with IBD and healthy controls were retrieved from different databases. Of the 123 identified articles, only 16 met our criteria and were examined for data extraction and analysis. Our analysis demonstrated a significant relationship between SZL and Crohn's disease. There was no significant relationship between SZL and ulcerative colitis. In conclusion, the results of the meta-analysis indicate a significant association between low SZL and the risk of Crohn's disease, but not ulcerative colitis.
Decreased Dietary Diversity Is a Predictor of Metabolic Syndrome Among Adults
Authors: Hamedi-Shahraki Soudabeh , Norouzadeh Mostafa , Amirkhizi Farshad
Published: September 2021

This cross-sectional study assessed the relationship between the dietary diversity score (DDS) and metabolic syndrome (MetS) among 410 Iranian adults aged 20 to 60 years. Dietary intake was evaluated using a validated semiquantitative food frequency questionnaire and the DDS was calculated for each participant. The probability of having MetS (P for trend = .042) and some of its components such as abdominal adiposity (P for trend = .036), high blood pressure (P for trend = .029), and high serum triglycerides (P for trend = .038) decrease with enhancing quartile of the DDS. The increased diversity score of diets may be useful in preventing MetS and its metabolic features.
Cancer stem cells in gliomas: evolving concepts and therapeutic implications
Authors: Alcantara Llaguno Sheila , Parada Luis F.
Published: September 2021

Purpose of review

Cancer stem cells (CSCs) have been implicated in the hierarchical heterogeneity and treatment resistance of hematologic and solid tumor malignancies, including gliomas, for several decades now but their therapeutic targeting has not been fully realized. Recent studies have uncovered deeper layers of CSC complexity, related to developmental origins, plasticity, cellular states, and interface with the microenvironment.

Recent findings

Sequencing and in-vivo lineage-tracing studies in mouse and patient-derived models show evidence of stem and progenitor origin of glioma, at the same time that genomic studies show a relatedness of glioma CSCs with radial glia. The spate of single-cell sequencing analyses demonstrates the diversity of transcriptional cellular states, which are susceptible to transitions, indicating the plasticity of glioma CSCs. The evolution of glioma CSCs and their interactions with niche cells play important roles in CSC treatment resistance and immune evasion, with epigenetic modulation as one of the emerging mechanisms.

To harness the potential of CSCs for clinical application, there is urgent need to investigate their complex nature and myriad interactions, to better understand the contribution of these self-renewing, stem-like cancer cells in the pathogenesis and therapy resistance of malignant brain tumors.
OUTCOME AND ASSOCIATED FACTORS AMONG ROAD TRAFFIC ACCIDENT VICTIMS AT WOLAITA SODDO CHRISTIAN HOSPITAL, WOLAITA SODDO, SOUTH ETHIOPIA 2020, INSTITUTION-BASED CROSS-SECTIONAL STUDY
Authors: Hizkel Asrat , Gebru Teklemichael , Yisihak Eshetu , Markos Desta
Published: September 2021

Background

In today’ s world road traffic accident victims are treated as a major epidemic of non-communicable disease. Road traffic accidents caused numerous family tragedies such as serious economic loss to the community and the death of young people. The problem is more severe in low and middle-income countries. In Ethiopia, the largest proportion of series injuries comes from road traffic accidents and become major causes of death in the emergency room. Despite this, only a little is known about treatment outcomes of road traffic accident victims and its associated factors in Ethiopia.

Method

An institution-based Cross-sectional study design was conducted at Wolaita Soddo Christian hospital with a sample of 400 road traffic accidents. The medical record was selected using a systematic sampling method. Data was entered using Epi-data version 4.1 and was exported to and analyzed using SPSS version 23. A multivariable logistic regression model was used to assess the association between the independent variables and dependent variables.

RESULT

The overall death rate was 9.5%. Being out of hospital catchment area [AOR= 2.16, 95% CI= (1.01-4.70)] presence of co-morbid condition [AOR= 6.77 95% CI= (2.44-18.81)] lack of first aid help [AOR= 2.77 95% CI= (1.17-6.52)] and severity of the injury [AOR= 3.85 95% CI= (1.50-9.89)] were found to be significantly associated with outcome of road traffic accident victims.

Conclusion

The study shows that the death rate from road traffic accidents was high. Therefore, designing strategies to decrease death from road traffic accidents by giving great emphasis to road traffic accident victims with co-morbid conditions and severe injury and focusing on the availability and accessibility of pre-hospital care service.
Analysis of modular gene co-expression networks reveals molecular pathways underlying Alzheimer’s disease and progressive supranuclear palsy
Authors: Carvalho Lukas Iohan , Lambert Jean-Charles , Costa Marcos R.
Published: September 2021

A comprehensive understanding of the pathological mechanisms involved at different stages of neurodegenerative diseases is key for the advance of preventive and disease-modifying treatments. Gene expression alterations in the diseased brain is a potential source of information about biological processes affected by pathology. In this work, we performed a systematic comparison of gene expression alterations in the brains of human patients diagnosed with Alzheimer’s disease (AD) or Progressive Supranuclear Palsy (PSP) and animal models of amyloidopathy and tauopathy. Using a systems biology approach to uncover biological processes associated with gene expression alterations, we could pinpoint processes more strongly associated with tauopathy/PSP and amyloidopathy/AD. We show that gene expression alterations related to immune-inflammatory responses preponderate in younger, whereas those associated to synaptic transmission are mainly observed in older AD patients. In PSP, however, changes associated with immune-inflammatory responses and synaptic transmission overlap. These two different patterns observed in AD and PSP brains are fairly recapitulated in animal models of amyloidopathy and tauopathy, respectively. Moreover, in AD, but not PSP or animal models, gene expression alterations related to RNA splicing are highly prevalent, whereas those associated with myelination are enriched both in AD and PSP, but not in animal models. Finally, we identify 12 AD and 4 PSP genetic risk factors in cell-type specific co-expression modules, thus contributing to unveil the possible role of these genes to pathogenesis. Altogether, this work contributes to unravel the potential biological processes affected by amyloid versus tau pathology and how they could contribute to the pathogenesis of AD and PSP.
Improved survival byHelicobacter pylori-modulated immunity in gastric cancer patients with S-1 adjuvant chemotherapy
Authors: Koizumi Yuka , Ahmad Sheny , Ikeda Miyuki , Yashima-Abo Akiko , Espina Ginny , Sugimoto Ryo , Sugai Tamotsu , Iwaya Takeshi , Koeda Keisuke , Liotta Lance A. , Takahashi Fumiaki , Nishizuka Satoshi S.
Published: September 2021

Background

Paradoxically,Helicobacter pylori-positive (HP+) advanced gastric cancer patients have a better prognosis than those who are HP-negative (HP-). Immunologic and statistical analyses can be used to verify whether systematic mechanisms modulated by HP are involved in this more favorable outcome.

Methods

A total of 658 advanced gastric cancer patients who underwent gastrectomy were enrolled. HP infection, mismatch repair, programmed death-ligand 1 (PD-L1), and CD4/CD8 proteins, and microsatellite instability were analyzed. Overall survival (OS) and relapse free survival (RFS) rates were analyzed after stratifying clinicopathological factors. Cox proportional hazards regression analysis was performed to identify independent prognostic factors.

Results

Among 491 cases that were analyzed, 175 (36%) and 316 (64%) cases were HP+and HP−, respectively. Analysis of RFS indicated an interaction of HP status among the subgroups for S-1 Dose (P=0.0487) and PD-L1 (P=0.016). HP+patients in the PD-L1 group had significantly higher five-year OS and RFS than HP-patients (81% vs. 68%;P=0.0011; HR 0.477; and 76% vs. 63%;P=0.0011; HR 0.508, respectively). The five-year OS and RFS was also significantly higher for HP+compared to HP-patients in the PD-L1-/S-1-reduced group (86% vs. 46%;p=0.0014; HR 0.205; 83% vs. 34%;p=0.001; HR 0.190, respectively). Thus, HP status was identified as one of the most potentially important independent factors to predict prolonged survival.

Conclusion

Modulation of host immune system function by HP may contribute to prolonged survival in the absence of immune escape mechanisms of gastric cancer.
CNN for a Connectivity Based Epilepsy Diagnosis with Resting-state EEG
Authors: Rijnders Berjo , Korkmaz Emin Erkan , Yildirim Funda
Published: September 2021

Objective

This study investigates the performance of a CNN algorithm on epilepsy diagnosis. Without pathology, diagnosis involves long and costly electroencephalographic (EEG) monitoring. Novel approaches may overcome this by comparing brain connectivity using graph metrics. This study, however, uses deep learning to learn connectivity patterns directly from easily acquired EEG data.

Methods

A convolutional neural network (CNN) algorithm was applied on directed Granger causality (GC) connectivity measures, derived from 50 seconds of resting-state surface EEG recordings from 30 subjects with epilepsy and a 30 subject control group.

Results

The learned CNN filters reflected reduced delta band connectivity in frontal regions and increased left lateralized frontal-posterior gamma band connectivity. A diagnosis accuracy of 85% (F1-score 85%) was achieved by an ensemble of CNN models, each trained on differently prepared data from different electrode combinations.

Conclusions

Appropriate preparation of connectivity data enables generic CNN algorithms to be used for detection of multiple discriminative epileptic features. Differential patterns revealed in this study may help to shed light on underlying altered cognitive abilities in epilepsy patients.

Significance

The accuracy achieved in this study shows that, in combination with other methods, this approach could prove a valuable clinical decision support system for epilepsy diagnosis.
The mathematics of erythema: Development of machine learning models for artificial intelligence assisted measurement and severity scoring of radiation induced dermatitis
Authors: Ranjan Rahul , Partl Richard , Erhart Ricarda , Kurup Nithin , Schnidar Harald
Published: September 2021

Although significant advancements in computer-aided diagnostics using artificial intelligence (AI) have been made, to date, no viable method for radiation-induced skin reaction (RISR) analysis and classification is available. The objective of this single-center study was to develop machine learning and deep learning approaches using deep convolutional neural networks (CNNs) for automatic classification of RISRs according to the Common Terminology Criteria for Adverse Events (CTCAE) grading system. Scarletred® Vision, a novel and state-of-the-art digital skin imaging method capable of remote monitoring and objective assessment of acute RISRs was used to convert 2D digital skin images using the CIELAB color space and conduct SEV* measurements. A set of different machine learning and deep convolutional neural network-based algorithms has been explored for the automatic classification of RISRs. A total of 2263 distinct images from 209 patients were analyzed for training and testing the machine learning and CNN algorithms. For a 2-class problem of healthy skin (grade 0) versus erythema (grade ≥ 1), all machine learning models produced an accuracy of above 70%, and the sensitivity and specificity of erythema recognition were 67-72% and 72-83%, respectively. The CNN produced a test accuracy of 74%, sensitivity of 66%, and specificity of 83% for predicting healthy and erythema cases. For the severity grade prediction of a 3-class problem (grade 0 versus 1 versus 2), the overall test accuracy was 60-67%, and the sensitivities were 56-82%, 35-59%, and 65-72%, respectively. For estimating the severity grade of each class, the CNN obtained an accuracy of 73%, 66%, and 82%, respectively. Ensemble learning combines several individual predictions to obtain a better generalization performance. Furthermore, we exploited ensemble learning by deploying a CNN model as a meta-learner. The ensemble CNN based on bagging and majority voting shows an accuracy, sensitivity and specificity of 87%, 90%, and 82% for a 2-class problem, respectively. For a 3-class problem, the ensemble CNN shows an overall accuracy of 66%, while for each grade (0, 1, and 2) accuracies were 76%, 69%, and 87%, sensitivities were 70%, 57%, and 71%, and specificities were 78%, 75%, and 95%, respectively. This study is the first to focus on erythema in radiation-dermatitis and produces benchmark results using machine learning models. The outcome of this study validates that the proposed system can act as a pre-screening and decision support tool for oncologists or patients to provide fast, reliable, and efficient assessment of erythema grading.
DAVI: a tool for clustering and visualising protein domain architectures
Authors: Saighi Paul , Jaouadi Chadi , Vieira Fabio R.J , Bernardes Juliana Silva
Published: September 2021

The characterization of protein functions is one of the main challenges in bioinformatics. Proteins are often composed of individual units termed domains, motifs that can evolve independently. The domain architecture of a given protein is the particular order and the content of its numerous domains. Some computational approaches predict the most likely domain architecture for a set of proteins. However, a few numbers of visualization tools exist, and most of them are unavailable. Here we present DAVI, an efficient and user-friendly web server for protein domain architecture clustering and visualization. DAVI accepts the output of most used domain architecture prediction tools and also produces domain architectures for a set of protein sequences. It provides a rich visualization for comparing, analyzing, and visualizing domain architectures.

Availability

http://genome.lcqb.upmc.fr/Domain-Architecture-Viewer
Characterization of cutaneous sex steroid hormone production through analysis of skin secretions
Authors: Pineider Juliana , Eckert Kaitlyn , McDonald Jeffrey , Harris-Tryon Tamia
Published: September 2021

Importance

Systemic sex steroid hormone aberrations often manifest in skin disease. The sebaceous, apocrine, and eccrine glands all play an important role in the response and production of these hormones in the skin. However, our ability to quantify hormonal secretions at the skin surface is limited.

Objective

Our study aims to characterize the hormonal landscape of the skin at different anatomical sites and between the sexes through analysis of skin secretions.

Design

In this observational pilot study, we collected skin secretions from twelve male and ten female control subjects using commercially available, Sebutape®, from the antecubital fossa, forehead, back, and axilla. We then developed a method to extract and quantify the amount of sex steroid hormones from these secretions through liquid chromatography tandem mass spectrometry (LC-MS/MS).

Setting

Outpatient clinic

Participants

34 participants were enrolled in the study, with 22 participants meeting criteria. Eligibility criteria included age of 18 to 40 and BMI between 15-35. Exclusion criteria included participants outside the ages of 18 to 40, use of antibiotics in the last 6 months, history of hormonal aberrations or chronic skin disorders, and use of hormone altering medications (except oral contraception).

Results

Our study detected anatomical site differences most notably in elevated dehydroepiandrosterone in the axilla and androstenedione in the forehead. Several hormonal differences were also detected between male and females consistent with known systemic hormone differences between the sexes.

Conclusions

We developed a method to quantify the hormonal levels in skin secretions using Sebutape®. Our approach found that hormonal composition varies based on sex and anatomical site. Additional studies will need to be completed to determine relevant hormonal shifts in clinical skin conditions.

KEY POINTS

Sex steroid hormones of skin secretions varies between males and females

Dehydroepiandrosterone is produced in elevated amounts in the axilla

Androstenedione is produced in elevated amounts in the forehead
Generation of realistic synthetic data using multimodal neural ordinary differential equations
Authors: Wendland Philipp , Birkenbihl Colin , Gomez-Freixa Marc , Sood Meemansa , Kschischo Maik , Fröhlich Holger
Published: September 2021

Individual organizations, such as hospitals, pharmaceutical companies and health insurance providers are currently limited in their ability to collect data that is fully representative of a disease population. This can in turn negatively impact the generalization ability of statistical models and scientific insights. However, sharing data across different organizations is highly restricted by legal regulations. While federated data access concepts exist, they are technically and organizationally difficult to realize. An alternative approach would be to exchange synthetic patient data instead. In this work, we introduce the Multimodal Neural Ordinary Differential Equations (MultiNODEs), a hybrid, multimodal AI approach, which allows for generating highly realistic synthetic patient trajectories on a continuous time scale, hence enabling smooth interpolation and extrapolation of clinical studies. Our proposed method can integrate both static and longitudinal data, and implicitly handles missing values. We demonstrate the capabilities of MultiNODEs by applying them to real patient-level data from two independent clinical studies and simulated epidemiological data of an infectious disease.
COVID-19 Vaccination Strategies Considering Hesitancy Using Particle-Based Epidemic Simulation
Authors: Karabay Aknur , Kuzdeuov Askat , Varol Huseyin Atakan
Published: September 2021

Vaccine hesitancy is one of the critical factors in achieving herd immunity and suppressing the COVID-19 epidemic. Many countries face this as an acute public health issue that diminishes the efficacy of their vaccination campaigns. Epidemic modeling and simulation can be used to predict the effects of different vaccination strategies. In this work, we present an open-source particle-based COVID-19 simulator with a vaccination module capable of taking into account the vaccine hesitancy of the population. To demonstrate the efficacy of the simulator, we conducted extensive simulations for the province of Lecco, Italy. The results indicate that the combination of both high vaccination rate and low hesitancy leads to faster epidemic suppression.
Compartment-specific tuning of hippocampal dendritic feature selectivity by intracellular Ca2+ release
Authors: O’Hare Justin K. , Hirabayashi Yusuke , Hewitt Victoria L. , Blockus Heike , Szoboszlay Miklos , Rolotti Sebi V. , Geiller Tristan C. , Negrean Adrian , Chelur Vikas , Losonczy Attila , Polleux Franck
Published: September 2021

Dendritic Ca2+ signaling is central to neural plasticity mechanisms allowing animals to adapt to the environment. Intracellular Ca2+ release (ICR) from endoplasmic reticulum has long been thought to shape these mechanisms. However, ICR has not been investigated in mammalian neurons in vivo. We combined electroporation of single CA1 pyramidal neurons, simultaneous imaging of dendritic and somatic activity during spatial navigation, optogenetic place field induction, and acute genetic augmentation of ICR cytosolic impact to reveal that ICR supports the establishment of dendritic feature selectivity and shapes integrative properties determining output-level receptive fields. This role for ICR was more prominent in apical than in basal dendrites. Thus, ICR cooperates with circuit-level architecture in vivo to promote the emergence of behaviorally-relevant plasticity in a compartment-specific manner.
OnePetri: accelerating common bacteriophage Petri dish assays with computer vision
Authors: Shamash Michael , Maurice Corinne F.
Published: September 2021

Introduction

Bacteriophage plaque enumeration is a critical step in a wide array of protocols. The current gold standard for plaque enumeration on Petri dishes is through manual counting. This approach is time-intensive, has low-throughput, is limited to Petri dishes which have a countable number of plaques, and can have variable results upon recount due to human error.

Methods

We present OnePetri, a collection of trained machine learning models and open-source mobile application for the rapid enumeration of bacteriophage plaques on circular Petri dishes.

Results

When compared against the current gold standard of manual counting, OnePetri was significantly faster, with minimal error. Compared against two other similar tools, Plaque Size Tool and CFU.AI, OnePetri had higher plaque recall and reduced detection times on most test images.

Conclusions

The OnePetri application can rapidly enumerate phage plaques on circular Petri dishes with high precision and recall.
Targeting interactions between the Galectin-3 intrinsically disordered and structured domains based on long time-scale accelerated molecular dynamics
Authors: Bhattacharya Supriyo , Zhang Mingfeng , Hu Weidong , Qi Tong , Heisterkamp Nora
Published: September 2021

Intrinsically disordered regions (IDRs) are common and important functional domains in many proteins. However, IDRs are difficult to target for drug development due to the lack of defined structures which would facilitate the identification of possible drug-binding pockets. Galectin-3 is a carbohydrate-binding protein of which overexpression has been implicated in a wide variety of disorders including cancer and inflammation. Apart from its carbohydrate recognition/binding domain (CRD), Galectin-3 also contains a functionally important disordered N-terminal domain (NTD) that contacts the C-terminal domain (CTD) and could be a target for drug development. To overcome challenges involved in inhibitor design due to lack of structure and the highly dynamic nature of the NTD, we used a novel protocol combining nuclear magnetic resonance data from recombinant Galectin-3 with accelerated molecular dynamics (MD) simulations. This approach identified a pocket in the CTD with which the NTD makes frequent contact. In accordance with this model, mutation of residues L131 and L203 in this pocket caused loss of Galectin-3 agglutination ability, signifying the functional relevance of the cavity. In-silico screening was used to design candidate inhibitory peptides targeting the newly discovered cavity and experimental testing of only 3 of these yielded one peptide that inhibits the agglutination promoted by wild type Galectin-3. NMR experiments further confirmed that this peptide indeed binds to a cavity in the CTD not within the actual CRD. Our results show that it is possible to apply a combination of MD simulations and NMR experiments to precisely predict the binding interface of a disordered domain with a structured domain, and furthermore use this predicted interface for designing inhibitors. This procedure can be potentially extended to many other targets in which similar IDR interactions play a vital functional role.