bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased incidence of inflammatory bowel disease on etanercept in juvenile idiopathic arthritis regardless of concomitant methotrexate use
Authors: van Straalen Joeri W , Krol Roline M , Giancane Gabriella , Panaviene Violeta , Ailioaie Laura Marinela , Doležalová Pavla , Cattalini Marco , Susic Gordana , Sztajnbok Flavio R , Maritsi Despoina , Constantin Tamas , Sawhney Sujata , Rygg Marite , Oliveira Sheila Knupp , Nordal Ellen Berit , Saad-Magalhães Claudia , Rubio-Perez Nadina , Jelusic Marija , de Roock Sytze , Wulffraat Nico M , Ruperto Nicolino , Swart Joost F
Published: September 2021

Objective

To describe risk factors for IBD development in a cohort of children with JIA.

Methods

JIA patients who developed IBD were identified from the international Pharmachild register. Characteristics were compared between IBD and non-IBD patients and predictors of IBD were determined using multivariable logistic regression analysis. Incidence rates of IBD events on different DMARDs were calculated, and differences between therapies were expressed as relative risks (RR).

Results

Out of 8942 patients, 48 (0.54% ) developed IBD. These were more often male (47.9% vs 32.0%) and HLA-B27 positive (38.2% vs 21.0%) and older at JIA onset (median 8.94 vs 5.33 years) than patients without IBD development. They also had more often a family history of autoimmune disease (42.6% vs 24.4%) and enthesitis-related arthritis (39.6% vs 10.8%). The strongest predictors of IBD on multivariable analysis were enthesitis-related arthritis [odds ratio (OR): 3.68, 95% CI: 1.41, 9.40] and a family history of autoimmune disease (OR: 2.27, 95% CI: 1.12, 4.54). Compared with methotrexate monotherapy, the incidence of IBD on etanercept monotherapy (RR: 7.69, 95% CI: 1.99, 29.74), etanercept with methotrexate (RR: 5.70, 95% CI: 1.42, 22.77) and infliximab (RR: 7.61, 95% CI: 1.27, 45.57) therapy was significantly higher. Incidence on adalimumab was not significantly different (RR: 1.45, 95% CI: 0.15, 13.89).

Conclusion

IBD in JIA was associated with enthesitis-related arthritis and a family history of autoimmune disease. An increased IBD incidence was observed for etanercept therapy regardless of concomitant methotrexate use.
Sodium Tanshinone IIA Sulfonate Attenuates Cigarette Smoke Extract-Induced Mitochondrial Dysfunction, Oxidative Stress, and Apoptosis in Alveolar Epithelial Cells by Enhancing SIRT1 Pathway
Authors: Guan Ruijuan , Yao Hongwei , Li Ziying , Qian Jing , Yuan Liang , Cai Zhou , Ding Mingjing , Liu Wei , Xu Jingyi , Li Yuanyuan , Sun Dejun , Wang Jian , Lu Wenju
Published: September 2021

Emphysema is one of the most important phenotypes for chronic obstructive pulmonary disease (COPD). Apoptosis in alveolar epithelial cells (AECs) causes the emphysematous alterations in the smokers and patients with COPD. Sirtuin 1 (SIRT1) is able to attenuate mitochondrial dysfunction, oxidative stress, and to modulate apoptosis. It has been shown that sodium tanshinone IIA sulfonate (STS), a water-soluble derivative of tanshinone IIA, protects against cigarette smoke (CS)-induced emphysema/COPD in mice. However, the mechanisms underlying these findings remain unclear. Here, we investigate whether and how STS attenuates AEC apoptosis via a SIRT1-dependent mechanism. We found that STS treatment decreased CS extract (CSE)-induced apoptosis in human alveolar epithelial A549 cells. STS reduced oxidative stress, improved mitochondrial function and mitochondrial membrane potential (ΔΨm), and restored mitochondrial dynamics-related protein expression. Moreover, STS promoted mitophagy, and increased oxidative phosphorylation protein levels (complexes I–IV) in CSE-stimulated A549 cells. The protective effects of STS were associated with SIRT1 upregulation, because SIRT1 inhibition by EX 527 significantly attenuated or abolished the ability of STS to reverse the CSE-induced mitochondrial damage, oxidative stress, and apoptosis in A549 cells. In conclusion, STS ameliorates CSE-induced AEC apoptosis by improving mitochondrial function and reducing oxidative stress via enhancing SIRT1 pathway. These findings provide novel mechanisms underlying the protection of STS against CS-induced COPD.
Investigating Relationships Between Preparedness for Practice, Grade Point Average, and Demographic Correlates Among Prelicensure Nursing Students
Authors: Wu Tsu-Yin , Raghunathan Vedhika , Fox Diane Porretta
Published: September 2021

Understanding the factors contributing to the clinical preparedness of nursing students provides essential information for their successful transition into the workforce. The aims of this study were to examine preparedness for practice with demographic factors, grade point average, and taking care of multiple patient caseloads. This study used a correlational design with 185 prelicensure nursing students in the midwestern United States. The results showed that self-reported clinical preparedness was associated with program type and externship experience. The findings contribute to nursing education by bringing new information that contributes to the understanding of students’ preparedness for practice.
Connecting Evidence-Based Practice and Clinical Practice Guidelines With Bachelor of Science in Nursing Students
Authors: Key Betty , Owings Clara R. , Ford Cassandra , Graves Barbara Ann , Robinson Trent
Published: September 2021

Research has demonstrated the ability of evidence-based practice (EBP) to enhance quality and reliability of health care, improve health outcomes, and reduce cost and health disparities. Nursing curricula often lack best practices for teaching EBP, as well as actual EBP course content, objectives, and activities, to advance student understanding of EBP. The unfortunate results are nurse graduates who do not value or perceive that they can use EBP. This study implemented an EBP assignment assessing clinical practice guidelines as a means of improving EBP beliefs in senior-level nursing students.
Psychometric Testing of a Theory-Based Measure to Evaluate Clinical Performance of Nursing Students
Authors: El Hussein Mohamed , McLarnon Matthew , Fast Olive
Published: September 2021

AIM

The aim of this study was to psychometrically test a clinical evaluation tool that measures instructors’ gut feelings for placing students on a learning contract.

BACKGROUND

Evaluators feel unprepared or hesitant to fail students who do not meet professional and clinical expectations.

METHOD

A multiphase process was used to determine the reliability and validity of the Gut Feelings Scale. The first phase focused on item generation, the second phase focused on content validity and feedback from expert raters, and the third phase focused on psychometric evaluation to streamline the item pool and explore validity.

RESULTS

Correlations and descriptive statistics for each subscale were calculated. Reliability analyses revealed relatively strong estimates of internal consistency; specifically, the reliability estimates surpassed our criteria of >.70.

CONCLUSION

This pilot study established the validity and reliability of the scale and found it to be a reliable tool to guide instructors’ evaluative decision-making.
Beyond the Do-not-resuscitate Order: An Expanded Approach to Decision-making Regarding Cardiopulmonary Resuscitation in Older Surgical Patients
Authors: Allen Matthew B. , Bernacki Rachelle E. , Gewertz Bruce L. , Cooper Zara , Abrams Joshua L. , Peetz Allan B. , Bader Angela M. , Sadovnikoff Nicholas
Published: September 2021

American Society of Anesthesiologists guidelines recommend that anesthesiologists revisit do-not-resuscitate orders preoperatively and revise them if necessary based on patient preferences. In patients without do-not-resuscitate orders or other directives limiting treatment however, “full code” is the default option irrespective of clinical circumstances and patient preferences. It is time to revisit this approach based on (1) increasing understanding of the power of default options in healthcare settings, (2) changing demographics and growing evidence suggesting that an expanding subset of patients is vulnerable to poor outcomes after perioperative cardiopulmonary resuscitation (CPR), and (3) recommendations from multiple societies promoting risk assessment and goal-concordant care in older surgical patients. The authors reconsider current guidelines in the context of these developments and advocate for an expanded approach to decision-making regarding CPR, which involves identifying high-risk elderly patients and eliciting their preferences regarding CPR irrespective of existing or presumed code status.
Establishing Safety Parameters for Orthopaedic Cast Saw Blade Usage
Authors: McNeil Daniel S. , Trenholm J. Andrew I.
Published: September 2021

Background:

The incidence of injuries from cast saws during cast removal ranges from 0.12% to 4.3%. With 1 second or less of exposure time, a temperature of 65°C can cause partial thickness burns. Despite numerous studies that recommend avoiding the use of a dull blade, there is no objective measure of what defines dullness.

Methods:

Plaster and fiberglass casts were collected and measured after removal from patients in the clinic. A series of slabs were constructed based on these measurements. To simulate our emergency department setting, a Stryker 940 cast saw without an attached vacuum was used to split plaster slabs. A thermocouple was used to directly measure the 940-23 ion-nitride saw blade temperature after each use. To simulate our orthopaedic clinic setting, a Stryker 940 cast saw with an attached vacuum was used to split fiberglass and plaster slabs. Three blades were tested in each setting, bivalving 50 slabs each.

Results:

For the plaster slabs split without a vacuum, average blade temperature of the 3 blades reached 65°C on the 42nd cast. However, the individual blades exceeded 65°C on the 33rd, 31st, and 38th casts, respectively. For the fiberglass and plaster slabs split with a vacuum, average blade temperature reached a maximum of 57.5°C in the first 50 trials. Extrapolating from this data, the blade is predicted to exceed 65°C on the 104th cast.

Conclusions:

When a Stryker 940 cast saw without vacuum is used to cut plaster casts, the ion-nitride blade should be changed frequently, at minimum after 60 casts have been split, or 30 casts have been bivalved. When a Stryker 940 cast saw with vacuum is used to remove fiberglass and plaster casts, the ion-nitride blade should be changed after removing 103 casts. A cast saw with an attached vacuum should be used whenever possible to minimize the risk of burning patients.

Clinical Relevance:

Determine how often a cast saw blade should be changed to minimize risk of burning patients.
Surgical Treatment With Titanium Elastic Nail (TEN) for Failed Conservative Treatment of Acute Monteggia Lesions in Children
Authors: Ozturk Tahir , Erpala Firat , Zengin Eyup C. , Gedikbas Mete , Eren Mehmet B.
Published: September 2021

Background:

This study evaluated the results of intramedullary osteosynthesis with titanium elastic nail (TEN) in the surgical treatment of Monteggia lesions in children aged 12 and under.

Methods:

Patients who underwent surgery with the TEN method between 2013 and 2019 were screened retrospectively. The inclusion criteria were patients who failed conservative treatment, a history of acute trauma (<14 d after injury), age 12 years and under, patients who underwent intramedullary osteosynthesis with TEN when surgical treatment is required, a follow-up period of over 12 months, absence of congenital upper extremity and bone anomalies, and no history of trauma to the ipsilateral elbow. For functional classification, the Grace and Eversmann Criteria were used to evaluate union, pronation, and supination, while the Mayo Elbow Performance Score was used to assess overall elbow function and limitations.

Results:

Thirty-eight patients (26 male/12 female) were included in the study. The median age was 8.0 (6 to 10) years old and follow-up period was 26.0 (16 to 39) months. The mean value of the Mayo Elbow Performance Score was 97.1, 32 cases were excellent and 6 cases had good results. While the average age was 9.4 years in patients with mobility limitations, it was 7.1 years in patients without mobility limitations. Statistically, less movement restriction was observed in patients of younger age.

Conclusion:

Length unstable ulnar fracture pattern for Monteggia lesions and those with secondary loss of reduction, intramedullary stabilization of the ulna fracture with TEN helps to achieve good functional and radiologic outcomes.

Level of Evidence:

Level III.
Validity, Responsiveness, and Reliability of the ACL-QOL in an Adolescent Population
Authors: Marien Meaghan , Lafave Mark R. , Hiemstra Laurie A. , Heard Sydney Mark , Buchko Gregory M. , Kerslake Sarah
Published: September 2021

Background:

The anterior cruciate ligament quality of life (ACL-QOL) score is a disease-specific patient-reported outcome measure that assesses patients with ACL deficient and reconstructed knees. The ACL-QOL has demonstrated validity, responsiveness, and reliability in adult populations but has yet to be specifically evaluated in adolescent patients. The purpose of this study was to assess the validity, responsiveness, and reliability of the ACL-QOL in an adolescent population.

Methods:

Between 2010 and 2015, questionnaires from 294 consecutive adolescent patients consented for an ACL reconstruction were collected from an orthopaedic sport medicine clinic. The ACL-QOL was administered preoperatively, and at 6, 12, and 24 months following primary ACL reconstruction. To assess content validity, the Cronbach α and floor and ceiling effects were measured. Question reading level was measured with an online tool (https://readable.com/). Responsiveness was assessed with a 1-way analysis of variance to compare the preoperative and postoperative time periods. A test-retest strategy with completion of the ACL-QOL twice within 3 weeks was used to assess reliability using an intraclass correlation coefficient (ICC 2,k) and the SEM.

Results:

The ACL-QOL demonstrated high content validity with a Cronbach αbetween 0.93 and 0.97, with no evidence of floor or ceiling effects at any study time point. The mean readability grade level was calculated to be 6.9, along with a readability score of 68. The ACL-QOL scores revealed a statistically significant improvement over time (P<0.001) with a Cohen d of 0.56, indicating a large effect size. Test-retest reliability revealed an ICC (2,k) of 0.997 (95% confidence interval=0.992-0.999).

Conclusions:

The ACL-QOL demonstrated content validity, responsiveness to change, and reliability in an adolescent ACL reconstruction population. The readability of the ACL-QOL is acceptable for adolescents with an ACL injury. The ACL-QOL is a valid, responsive, and reliable patient-reported outcome measure that can be used in an adolescent population with ACL deficiency or following ACL reconstruction.

Level of Evidence:

Level III.
How Much Opioid Do Kids Actually Need? A Prospective Study of Analgesic Prescribing and Postdischarge Opioid Use Among Pediatric Patients With Operative Fractures
Authors: Keil Lukas G. , Sullivan Mikaela H. , Dadoo Sahil , Stillwagon Matthew R. , Vergun Anna D.
Published: September 2021

Background:

Analgesic guidelines are lacking for most operative pediatric fractures, and little is known about postdischarge opioid use or pain control. We hypothesized that opioid/acetaminophen/non-steroidal anti-inflammatory drugs (NSAID) prescribing would vary, pain would be well controlled, and postdischarge opioid use would be low.

Methods:

This prospective cohort study included nonpolytraumatized patients aged 17 years and below with operative fractures at a level 1 trauma center from August 1, 2019 to March 31, 2021. Supracondylar humerus fractures were excluded since they have been studied extensively. Information regarding injury/surgery/analgesics were collected. Discharged patients were called on postoperative days (POD) 1/3/5. Parents/guardians were asked about analgesic use and pain over the preceding 2 days. Complications, pain control, and opioid refills were recorded after first follow-up.

Results:

All 100 eligible patients were included. Mean age was 10.1 years (range: 1.8 to 17.8 y). Common fracture types were humeral condyle/epicondyle (28%), radius/ulna (15%), and femoral shaft (13%). Opioids were prescribed to 95% of patients with mean 14 doses (range: 2 to 45). Acetaminophen/NSAIDs were prescribed to 74% and 60% of patients, respectively. Eleven patients were excluded from telephone follow-up (7 non-English speaking, 3 prohibitive social situations, 1 inpatient POD1 to 5). Telephone follow-up was completed for 87/89 eligible patients (98%). Mean pain scores declined from 3.7/10 POD1 to 2.4/10 POD5. Opioids were taken by 50% POD1, 20% POD5. Acetaminophen/NSAID was given before opioid 82% of the time. By POD5, mean total doses of opioid taken postdischarge was 2.3; mean proportion of prescribed opioid doses taken was 22%; and 97% of patients took ≤8 opioid doses postdischarge. Two patients were evaluated early due to poor pain control which improved with cast changes. Pain was well controlled or absent at follow-up in 97% of patients.

Conclusions:

Pain is consistently well controlled after operative pediatric fractures. Nearly all were prescribed opioids, while acetaminophen/NSAIDs were inconsistently prescribed and used. Opioid prescriptions are written for 4 to 5 times the amount needed. Prescribing ≤8 doses of opioid is adequate for acute pain through POD5 in 97% of patients. Poorly controlled pain should prompt early evaluation for possible complications.

Level of Evidence:

Level II—prospective comparative study.
Organ Dose Reconstruction Applicable for a Japanese Nuclear Worker Cohort: J-EPISODE
Authors: Furuta Hiroshige , Sato Kaoru , Nishide Akemi , Kudo Shin’ichi , Saigusa Shin
Published: September 2021

An evaluation of cancer risk based on organ-absorbed dose is underway for the Japanese Epidemiological Study on Low-Dose Radiation Effects (J-EPISODE), which has analyzed health effects in association with radiation exposure evaluated with the personal dose equivalent H
p(10). Although the concept of effective dose and its operational definition of H
p(10) are widely used for radiological protection purposes, effective dose is not recommended for epidemiological evaluation. Organ-absorbed dose was instead adopted for the IARC 15-Country Collaborative study (15-Country study), the International Nuclear Workers Study (INWORKS), the Mayak worker study, and the Life Span Study (LSS) of atomic bomb survivors. The reconstruction method in J-EPISODE followed in principle the approach adopted in the 15-Country Study. As part of the approach of J-EPISODE, a conversion factor from photon dosimeter reading to air kerma was developed using dosimeter response data, which were measured by the experiment using an anthropomorphic phantom, and it was confirmed that the 15-Country study’s assumption of photon energy and geometry distribution in a work environment applied to Japanese nuclear workers. This article focuses on a method for reconstructing the conversion factor from photon dosimeter reading to organ-absorbed photon dose for a Japanese nuclear worker cohort. The model for estimating the conversion factor was defined under the assumption of a lognormal distribution from three concerned bias factors: (1) a dosimeter reading per air kerma, i.e., dosimeter response; (2) an organ-absorbed dose per air kerma; and (3) a factor relating to the differences in dose concepts and calibration practices between the roentgen dosimeter era and the present. Dosimeter response data were cited from the companion paper. Data on organ-absorbed photon dose per air kerma were estimated using a voxel phantom with the average Japanese adult male height and weight. The bias factor for the recorded dose in the roentgen era was defined, considering the backscatter radiation from the human body. The estimated values of organ-absorbed photon dose per air kerma were almost the same as those in ICRP Publication 116, revealing that the effect of differences in body size was almost negligible. The conversion factors from dosimeter reading to organ-absorbed dose were estimated by period (the roentgen era or from then), nuclear facility type (nuclear power plant or other), dosimeter type, and tissue or organ. The estimated conversion factors ranged from 0.7 to 0.9 (Gy Sv−1). The estimated cumulative organ-absorbed photon dose for the participants of J-EPISODE demonstrated that organ-absorbed dose values were approximately 0.8 times the recorded doses if neglecting dose-unit differences. J-EPISODE reconstructed an organ-absorbed dose conversion factor and will evaluate the risk of cancer mortality and morbidity using the organ-absorbed dose in the future.
Applications and Outcomes of Extracorporeal Life Support Use in Adult Liver Transplantation: A Case Series and Review of Literature
Authors: Park Jeieung , Lin Michael Y. , Wray Christopher L. , Kaldas Fady M. , Benharash Peyman , Gudzenko Vadim
Published: September 2021

The use of extracorporeal life support (ECLS) is increasingly reported in adult liver transplantation (LT). However, neither the role of ECLS in the perioperative setting for LT nor its outcomes has been well defined. We performed a retrospective chart review of all adult LT patients at our institution who received ECLS from 2004 to 2021. We also conducted a comprehensive literature search for adult LT cases that involved perioperative ECLS for respiratory or cardiac failure. Over the study period, 11 LT patients required ECLS at our institution, two for respiratory and nine for cardiac failure. Both patients with respiratory failure received ECLS as a bridge to LT and survived to discharge. Nine patients required ECLS for acute cardiac failure either intraoperatively or postoperatively, and two survived to discharge. In the literature, we identified 35 cases of respiratory failure in LT patients requiring perioperative ECLS. Applications included preoperative bridge to LT (n = 6) and postoperative rescue (n = 29), for which overall survival was 44%. We identified 31 cases of cardiac failure in LT patients requiring either ECLS or cardiopulmonary bypass for cardiac support or rescue for intraoperative or postoperative cardiac failure (n = 30). There is evidence for consideration of ECLS as a bridge to LT in patients with potentially reversible respiratory failure or as rescue therapy for respiratory failure in posttransplant patients. ECLS has a prohibitively high risk of futility in pretransplant patients with cardiac failure but may have a role in LT patients with a functioning graft and potentially reversible cardiac failure.
Fecal Microbiota Transplantation and Medical Therapy for Clostridium difficile Infection
Authors: Singh Tanveer , Bedi Prabhjot , Bumrah Karandeep , Gandhi Darshan , Arora Tanureet , Verma Nikita , Schleicher Mary , Rai Manoj P. , Garg Rajat , Verma Beni , Sanaka Madhusudhan R.
Published: September 2021

Goals:

The aim was to assess the effectiveness of fecal microbiota transplantation (FMT) against medical therapy (MT).

Background:

FMT has shown good outcomes in the treatment of Clostridium difficile infection (CDI). We aimed to conduct a systematic review and meta-analysis to compare the effectiveness of FMT versus MT for CDI.

Study:

We performed a comprehensive search to identify randomized controlled trials comparing FMT against MT in patients with CDI. Outcomes of interest were clinical cure as determined by the resolution of diarrhea and/or negative C. difficile testing. Primary CDI is defined as the first episode of CDI confirmed endoscopically or by laboratory analysis. Recurrent C. difficile infection (RCDI) is defined as laboratory or endoscopically confirmed episode of CDI after at least 1 course of approved antibiotic regimen.

Results:

A total of 7 studies with 238 patients were included in meta-analysis. Compared with MT, FMT did not have a statistically significant difference for clinical cure of combined primary and RCDI after first session [risk ratio (RR): 1.52, 95% confidence interval (CI): 0.90, 2.58; P=0.12; I
2=77%] and multiple sessions of FMT (RR: 1.68; CI: 0.96, 2.94; P=0.07; I
2=82%). On subgroup analysis, FMT has statistically higher rate of response than MT (RR: 2.41; CI: 1.20, 4.83; I
2=78%) for RCDI. However, for primary CDI there is no statistically significant difference between FMT and MT (RR: 1.00; CI: 0.72, 1.39; I
2=0%).

Conclusion:

As per our analysis, FMT should not be utilized for every patient with CDI. It is more effective in RCDI, but the results were not significant in patients with primary CDI.
Unexplained Distal Obstructive Biliary Dilatation
Authors: Zhu Yong , Jin Hailin , Mao Yingfan , Chen Jun , Qiu Yudong , Wang Zhongqiu , He Jian
Published: September 2021

Background:

The aim was to compare the differences of clinical-radiologic characteristics between malignant and benign causes of patients with unexplained distal obstructive biliary dilatation and to develop a logistic regression model (nomogram) based on those features to predict malignant causes preoperatively.

Patients and Methods:

Clinical-radiologic characteristics of 133 patients with unexplained distal obstructive biliary dilatation were analyzed. Multivariate logistic regression analysis was performed to construct a nomogram to predict malignant causes preoperatively. The developed nomograms were externally validated by assessing their predictive accuracy in an independent set of 90 patients.

Results:

Intrahepatic bile duct diameter, enlarged gallbladder, direct bilirubin, and carbohydrate antigen19-9 differed significantly between malignant and benign group. In the training set, the logistic regression model showed the discrimination between benign and malignant causes of distal obstructive biliary dilatation with an area under the curve of 0.965, an accuracy of 0.904, a sensitivity of 0.886, a specificity of 0.913. In the validation set, the model showed an area under the curve of 0.851, an accuracy of 0.837, a sensitivity of 0.897, a specificity of 0.750.

Conclusions:

Preoperative clinical-radiologic characteristics differed significantly between malignant and benign group. Nomogram based on those features performed well in predicting the malignant causes of patients with unexplained distal obstructive biliary dilatation.
Dental Therapists in the United States
Authors: Mertz Elizabeth , Kottek Aubri , Werts Miranda , Langelier Margaret , Surdu Simona , Moore Jean
Published: September 2021

Background:

Dental therapists (DTs) are primary care dental providers, used globally, and were introduced in the United States (US) in 2005. DTs have now been adopted in 13 states and several Tribal nations.

Objectives:

The objective of this study is to qualitatively examine the drivers and outcomes of the US dental therapy movement through a health equity lens, including community engagement, implementation and dissemination, and access to oral health care.

Methods:

The study compiled a comprehensive document library on the dental therapy movement including literature, grant documents, media and press, and gray literature. Key stakeholder interviews were conducted across the spectrum of engagement in the movement. Dedoose software was used for qualitative coding. Themes were assessed within a holistic model of oral health equity.

Findings:

Health equity is a driving force for dental therapy adoption. Community engagement has been evident in diverse statewide coalitions. National accreditation standards for education programs that can be deployed in 3 years without an advanced degree reduces educational barriers for improving workforce diversity. Safe, high-quality care, improvements in access, and patient acceptability have been well documented for DTs in practice.

Conclusion:

Having firmly taken root politically, the impact of the dental therapy movement in the US, and the long-term health impacts, will depend on the path of implementation and a sustained commitment to the health equity principle.
Catch it before it breaks!: managing metabolic bone disease of prematurity
Authors: Kehinde Folasade , Marinescu Andreea , Turchi Renee
Published: September 2021

Purpose of review

Metabolic bone disease of prematurity, commonly referred to as osteopenia of prematurity, remains prevalent in the neonatal intensive care unit (NICU) despite recent medical advances. It is estimated that up to 60% of extreme low birth weight and 20% of very low-birth-weight infants have metabolic bone disease of prematurity. Often silent, it typically presents with poor growth, increased ventilator dependency and fractures. Clinical sequalae, such as short stature can extend into young adulthood. There is no universal consensus by neonatal intensive care unit clinicians on the screening, diagnosis, or treatment for metabolic bone disease of prematurity. The disease is often diagnosed late by radiographs or incidentally in this highly fragile population.

Recent findings

Suggest screening using DEXA (dual-energy X-ray absorptiometry) scans or ultrasound, in combination with serum markers like alkaline phosphatase, phosphorous levels, parathyroid hormone, and tubular reabsorption of phosphate, might identify at-risk babies earlier. The use of protocol-based screenings may aid in early diagnosis.

We present a review of the risk factors, recent screening methods, diagnosis and management of this prevalent, clinically relevant diagnosis, as well as propose a protocol for the early screening and management of this silent disease.
Pulmonary “Inflammatory Leiomyosarcomas” Are Indolent Tumors With Diploid Genomes and No Convincing Rhabdomyoblastic Differentiation
Authors: Kao Yu-Chien , Kuo Chien-Tzu , Kuo Po-Yen , Huang Hsuan-Ying , Lu Tzu-Pin , Hsieh Tsung-Han , Fletcher Christopher D.M. , Lee Jen-Chieh
Published: September 2021

Inflammatory leiomyosarcoma is a rare myogenic tumor with striking inflammatory infiltrates and a specific genomic pattern of near-haploidization despite exception(s). Recent studies demonstrated that inflammatory leiomyosarcoma shares substantially overlapping features with histiocyte-rich rhabdomyoblastic tumor, including expression of rhabdomyoblastic markers such as myogenin, MyoD1, and PAX7 and a high prevalence of genomic near-haploidization, suggesting that they represent a unifying entity, for which the term inflammatory rhabdomyoblastic tumor was coined. In this study, we identified 4 pulmonary tumors histologically typical of inflammatory leiomyosarcomas, all in men (aged 26 to 49), presented as slow-growing well-defined nodules ranging from 1.4 to 3.5 cm, and following uneventful postoperative courses. All tumors were positive for desmin immunostaining, while only 1 and 2 were focally positive for smooth muscle actin and smooth muscle myosin heavy chain, respectively. They showed no expression of myogenin, MyoD1, or PAX7 by immunohistochemistry or RNA sequencing. Copy number analyses by whole-exome sequencing (N=1), OncoScan single-nucleotide polymorphism array (2), and fluorescence in situ hybridization (1) revealed/suggested diploid genomes. Together with a previously reported case, all these pulmonary “inflammatory leiomyosarcomas” seemed clinically, pathologically, and genomically alike. Despite a superficial resemblance to conventional inflammatory leiomyosarcoma in somatic soft tissues (now preferably termed inflammatory rhabdomyoblastic tumor), they differ in the lack of convincing rhabdomyoblastic differentiation and genomic near-haploidization. Therefore, we propose that these pulmonary tumors probably represent a distinct entity, for which the exact line of differentiation, and perhaps the most suitable terminology to better reflect its nature, remains to be determined. The term inflammatory rhabdomyoblastic tumor seems inappropriate for this group of tumors.
Novisyntrophococcus fermenticellae gen. nov., sp. nov., isolated from an anaerobic fermentation cellar of Chinese strong-flavour baijiu
Authors: Chai Li-Juan , Fang Guan-Yu , Xu Peng-Xiang , Zhang Xiao-Juan , Lu Zhen-Ming , Zhang Su-Yi , Wang Song-Tao , Shen Cai-Hong , Shi Jin-Song , Xu Zheng-Hong
Published: September 2021

A Gram-stain-negative, coccus-shaped, obligately anaerobic, non-motile and non-spore-forming bacterium, designated strain JN500902T, was isolated from the mud in a fermentation cellar used continuously over 30 years for Chinese strong-flavour baijiu production. Colonies were white, circular, convex and smooth-edged. Growth was observed at 20–40 °C (optimum, 37 °C), at pH 5.0–10 (optimum, pH 7.5), with 0–2 % (w/v) NaCl and with 0–4 % (v/v) ethanol. The Biolog assay demonstrated positive reactions of strain JN500902T in the metabolism of l-fucose and pyruvate. The predominant cellular fatty acids (>10 %) consisted of C16 : 0 and C14 : 0. The major end metabolites of strain JN500902T were acetic acid and ethanol when incubated anaerobically in liquid reinforced clostridial medium. Acetate was the major organic acid end product. The complete genome size of strain JN500902T was 3 420 321 bp with 3327 identified genes. The G+C content was 43.5 mol%. Phylogenetic analysis based on 16S rRNA gene sequences affiliated strain JN500902T with the family

Lachnospiraceae

, having low sequence similarity (92.8 %) to the nearest type strain,

Syntrophococcus sucromutans

DSM 3224T and forming a clearly distinct branch. Core genome phylogenetic analysis of the isolate and 134 strains belonging to the family

Lachnospiraceae

also revealed that strain JN500902T was well-separated from other genera of this family as a monophyletic clade. The average nucleotide identity and amino acid identity values between strain JN500902T and 134

Lachnospiraceae

strains were less than 74 and 65 %, respectively. Considering its polyphasic characteristics, strain JN500902T represents a novel genus and species within the family

Lachnospiraceae

, for which the name Novisyntrophococcus fermenticellae gen. nov., sp. nov. is proposed. The type strain is JN500902T (=CICC 24502T=JCM 33939T).
Metabolic and immune markers for precise monitoring of COVID-19 severity and treatment
Authors: Rendeiro André F. , Vorkas Charles Kyriakos , Krumsiek Jan , Singh Harjot , Kapatia Shashi , Cappelli Luca Vincenzo , Cacciapuoti Maria Teresa , Inghirami Giorgio , Elemento Olivier , Salvatore Mirella
Published: September 2021

Deep understanding of the SARS-CoV-2 effects on host molecular pathways is paramount for the discovery of early biomarkers of outcome of coronavirus disease 2019 (COVID-19) and the identification of novel therapeutic targets. In that light, we generated metabolomic data from COVID-19 patient blood using high-throughput targeted nuclear magnetic resonance (NMR) spectroscopy and high-dimensional flow cytometry. We find considerable changes in serum metabolome composition of COVID-19 patients associated with disease severity, and response to tocilizumab treatment. We built a clinically annotated, biologically-interpretable space for precise time-resolved disease monitoring and characterize the temporal dynamics of metabolomic change along the clinical course of COVID-19 patients and in response to therapy. Finally, we leverage joint immuno-metabolic measurements to provide a novel approach for patient stratification and early prediction of severe disease. Our results show that high-dimensional metabolomic and joint immune-metabolic readouts provide rich information content for elucidation of the host’s response to infection and empower discovery of novel metabolic-driven therapies, as well as precise and efficient clinical action.
Deep sampling of ancestral genetic diversity reveals Saccharomyces cerevisiae pre-domestication life histories
Authors: Lee Tracy J. , Liu Yu-Ching , Liu Wei-An , Lin Yu-Fei , Lee Hsin-Han , Ke Huei-Mien , Huang Jen-Pen , Lu Mei-Yeh Jade , Hsieh Chia-Lun , Chung Kuo-Fang , Liti Gianni , Tsai Isheng Jason
Published: September 2021

The ecology and genetic diversity of model yeast Saccharomyces cerevisiae prior to human domestication remain poorly understood. Taiwan is regarded as part of this yeast’s geographic birthplace where the most divergent natural lineage was discovered. Here, we deep sampled the broad-leaf forests across this continental island to probe the ancestral species diversity. We found that S. cerevisiae is distributed ubiquitously at low abundance in the forests. Whole-genome sequencing of 121 isolates revealed nine distinct lineages, the highest known in any region. Three lineages are endemic to Taiwan and six are widespread in Asia. Molecular dating placed the divergence of the Taiwanese and Asian lineages during the Pleistocene, when a transient continental shelf land bridge connected Taiwan to other major landmasses. Extensive historical and recent admixture events were detected between natural lineages. In particular, the genetic component from a lineage associated with fruits that spanned the widest geographical range was present in most admixed isolates. Collectively, Taiwanese isolates harbor genetic diversity comparable to that of the whole Asia continent, and different lineages have coexisted at a fine spatial scale even on the same tree. Patterns of variations within each lineage revealed that S. cerevisiae is highly clonal and predominantly reproduces asexually in nature. We detected prevalent purifying selection genome-wide, with lineage-specific signals of positive or directional selection independent between lineages. This study establishes that S. cerevisiae has rich natural diversity sheltered from human influences, making it a powerful model system in microbial ecology.
An individualized fMRI protocol to assess semantic congruency effects on episodic memory in an aging multilingual population
Authors: Perquin Magali , Viswanathan Shivakumar , Vaillant Michel , Risius Okka , Huiart Laetitia , Schmit Jean-Claude , Diederich Nico J. , Fink Gereon R. , Kukolja Juraj
Published: September 2021

The cognitive stimulation induced by multilingualism may slow down age-related memory impairment. However, a suitable neuroscientific framework to assess the influence of multilingualism on age-related memory processes is missing. We propose an experimental paradigm that assesses the effects of semantic congruency on episodic memory using functional magnetic resonance imaging (fMRI). To this end, we modified the picture-word interference (PWI) task to be suitable for the assessment of older multilingual subjects undergoing functional magnetic resonance imaging (fMRI). In particular, stimulus materials were prepared in multiple languages (French, German, Luxembourgish, English) and closely matched in semantic properties, thus enabling participants to perform the experiment in a language of their choice. This paradigm was validated in a group (n = 62) of healthy, older participants (over 64 years) who were multilingual, all practicing three or more languages. Consistent with the engagement of semantic congruency processes, we found that the encoding and recognition of semantically related vs. unrelated picture-word pairs evoked robust differences in behavior and the neural activity of parietal-temporal networks. These effects were negligibly modulated by the language used to perform the task. Based on this validation in a multilingual population, we conclude that the proposed paradigm will allow future studies to evaluate whether multilingualism aptitude engages neural systems in a manner that protects long-term memory from aging-related decline.
Unraveling the intracellular cross-talk governing the balance between TNFαmediated survival and apoptosis signaling
Authors: Biswas Sharmila , Tikader Baishakhi , Kar Sandip , Viswanathan Ganesh
Published: September 2021

Tumor necrosis factor alpha (TNFα), a pleiotropic cytokine, helps maintain a balance between proliferation and apoptosis in normal cells. This balance is often sacrificed in a diseased cell, such as that of a cancer, by preferring survival phenotype over apoptosis. Restoring this balance requires a detailed understanding of the causal intracellular mechanisms that govern TNFαstimulated apoptotic response. In this study, we use a systems biology approach to unravel the interplay between the intracellular signaling markers that orchestrate apoptosis levels. Our approach deciphered the synergism between the early intracellular markers phosphorylated JNK (pJNK) and phosphorylated AKT (pAKT) that modulate the activation of Caspase3, an important apoptotic regulator. We demonstrate that this synergism depends critically on the survival pathway signaling mediated by NFκB which plays a dominant role in controlling the extent of the overall apoptotic response. By systematic inhibition of the signaling markers, we establish that the dynamic cross-talk between the pJNK and pAKT transients directs the apoptosis phenotype via accumulated Caspase3 response. Interestingly, superposition of the semi-quantitative correlation between apoptosis and Caspase3 transient levels on the proposed TNFαnetwork model permits quantification of the dynamic apoptotic response under different stimulation conditions. Thus, the predictive model can be leveraged towards arriving at useful insights that can identify potential targeted therapeutic strategies for altering apoptotic response.
Supervised Promoter Recognition: A benchmark framework
Authors: Perez Martell Raul Ivan , Ziesel Alison , Jabbari Hosna , Stege Ulrike
Published: September 2021

Abstract

Deep learning has become a prevalent method in identifying genomic regulatory sequences such as promoters. In a number of recent papers, the performance of deep learning models have continually been reported as an improvement over alternatives for sequence-based promoter recognition. However, the performance improvements in these models do not account for the different datasets that models are being evaluated on. The lack of a consensus dataset and procedure for benchmarking purposes has made the comparison of each model’s true performance difficult to assess.

We present a framework called Supervised Promoter Recognition Framework (‘SUPR REF’) capable of streamlining the complete process of training, validating, testing, and comparing promoter recognition models in a systematic manner. SUPR REF includes the creation of biologically relevant benchmark datasets to be used in the evaluation process of deep learning promoter recognition models. We showcase this framework by comparing the models’ performance on alternative datasets, and properly evaluate previously published models on new benchmark datasets. Our results show that the reliability of deep learning ab initio promoter recognition models on eukaryotic genomic sequences is still not at a sufficient level, as precision is severely lacking. Furthermore, given the observational nature of these data, cross-validation results from small datasets need to be interpreted with caution.

Availability

Source code and documentation of the framework is available online at https://github.com/ivanpmartell/suprref
Identification of a stress-sensitive anorexigenic neurocircuit from medial prefrontal cortex to lateral hypothalamus
Authors: Clarke Rachel E , Voigt Katharina , Reichenbach Alex , Stark Romana , Bharania Urvi , Dempsey Harry , Lockie Sarah H , Mequinion Mathieu , Lemus Moyra , Wei Bowen , Reed Felicia , Rawlinson Sasha , Nunez-Iglesias Juan , Foldi Claire J. , Kravitz Alexxai V. , Verdejo-Garcia Antonio , Andrews Zane B.
Published: September 2021

By modeling neural network dynamics related to homeostatic state and BMI, we identified a novel pathway projecting from the medial prefrontal cortex (mPFC) to the lateral hypothalamus (LH) in humans. We then assessed the physiological role and dissected the function of this mPFC-LH circuit in mice. In vivo recordings of population calcium activity revealed that this glutamatergic mPFC-LH pathway is activated in response to acute stressors and inhibited during food consumption, suggesting a role in stress-related control over food intake. Consistent with this role, inhibition of this circuit increased feeding and sucrose seeking during mild stressors, but not under non-stressful conditions. Finally, chemogenetic or optogenetic activation of the mPFC-LH pathway is sufficient to suppress food intake and sucrose-seeking in mice. These studies identify a glutamatergic mPFC-LH as a novel stress-sensitive anorexigenic neural pathway involved in the cortical control of food intake.
EEG-Based Spectral Analysis Showing Brainwave Changes Related to Modulating Progressive Fatigue During a Prolonged Intermittent Motor Task
Authors: Suviseshamuthu Easter S. , Handiru Vikram Shenoy , Allexandre Didier , Hoxha Armand , Saleh Soha , Yue Guang H.
Published: September 2021

Repeatedly performing a submaximal motor task for a prolonged period of time leads to muscle fatigue comprising a central and peripheral component, which demands a gradually increasing effort. However, the brain contribution to the enhancement of effort to cope with progressing fatigue lacks a complete understanding. The intermittent motor tasks (IMTs) closely resemble many activities of daily living (ADL), thus remaining physiologically relevant to study fatigue. The scope of this study is therefore to investigate the EEG-based brain activation patterns in healthy subjects performing IMT until self-perceived exhaustion. Fourteen participants (median age 51.5 years; age range 26-72 years; 5 males) repeated elbow flexion contractions at 40% maximum voluntary contraction by following visual cues displayed on an oscilloscope screen until subjective exhaustion. Each contraction lasted for approximately 5 s with a 2-s rest between trials. The force, EEG, and surface EMG (from elbow joint muscles) data were simultaneously collected. After preprocessing, we selected a subset of trials at the beginning, middle, and end of the study session representing brain activities germane to mild, moderate, and severe fatigue conditions, respectively, to compare and contrast the changes in the EEG time-frequency (TF) characteristics across the conditions. The outcome of channel- and source-level TF analyses reveals that the theta, alpha, and beta power spectral densities vary in proportion to fatigue levels in cortical motor areas. We observed a statistically significant change in the band-specific spectral power in relation to the graded fatigue from both the steady- and post-contraction EEG data. The findings would enhance our understanding on the etiology and physiology of voluntary motor-action-related fatigue and provide pointers to counteract the perception of muscle weakness and lack of motor endurance associated with ADL. The study outcome would help rationalize why certain patients experience exacerbated fatigue while carrying out mundane tasks, evaluate how clinical conditions such as neurological disorders and cancer treatment alter neural mechanisms underlying fatigue in future studies, and develop therapeutic strategies for restoring the patients’ ability to participate in ADL by mitigating the central and muscle fatigue.