bluuebunny/crossref_metadata_2025 huggingface dataset:
Music Theory in Retirement Centers
Authors: Peebles Crystal
Published: June 2022

This chapter addresses the challenges of creating music theory programming for older adults living in retirement centers. The first challenge is accessibility. Accessible programming delivers music theory content that engages a musically diverse audience while using a modality open to various physical capabilities. The second challenge is connecting content to an individual’s musical experience. Active learning experiences, like performance, moving to music, composition, discussion, and sharing musical examples, encourage participants to think critically about music using concepts and tools from music theory. This chapter describes three types of music theory programming designed for older adults: stand-alone lectures, class series, and intergenerational collaborations with college students in the context of a service-learning project. Each type of programming upholds the ideals of accessible and active music theory learning.
Face Processing and TMS
Authors: Pitcher David
Published: June 2022

Faces are rich sources of social information that simultaneously convey someone’s identity, attentional focus, and emotional state. Humans process this wealth of socially relevant information in a network of face-selective regions distributed across the brain. This chapter reviews studies that have used transcranial magnetic stimulation (TMS) to study the cognitive operations and functional connections of the face network. TMS has been used to disrupt brain areas contributing to the processing of facial identity, facial expression, eye-gaze direction, head direction, trustworthiness, and the auditory-visual integration of speech. TMS has also been combined with neuroimaging to map how transient disruption of a targeted face area impacts connectivity across the face network. I also review chronometric TMS studies that have established when faces are processed across different brain areas down to a millisecond resolution.
Site of service of irrigation and debridement of open finger and hand fractures: a retrospective review of trends and outcomes
Authors: Wadhwa Harsh , Zhuang Thompson , Shapiro Lauren M. , Welch Jessica M. , Richard Marc J. , Kamal Robin N.
Published: June 2022

Background:

Irrigation and debridement (I&D) of open finger and hand fractures can be performed in the emergency department as opposed to the operating room (OR), though reports of postoperative infection rates vary greatly. The authors hypothesized that I&D of open finger and hand fractures in the OR would decrease over time. They also describe rates of postoperative infection, reoperation, readmission, and costs.

Methods:

A large nationwide administrative claims dataset was retrospectively reviewed to identify patients who underwent I&D after open finger and hand fractures from 2007 to 2016. The incidence of I&D procedures performed outside the OR was reported and trends over the study period were assessed.

Results:

The proportion of open finger and hand fractures that underwent I&D outside the OR did not change significantly over time. Rates of postoperative surgical site infection, readmission, and reoperation were higher in the OR cohort at 90 days after the index stay. The OR cohort had greater total costs and out-of-pocket costs for the index stay. At 90 days, the OR cohort had greater total cost, but out-of-pocket costs were similar.

Conclusions:

Site of service for treatment of open finger and hand fractures has not significantly changed from 2007 to 2016. Given that total costs are significantly greater among patients undergoing I&D in the OR, prospective trials are needed to assess the safety of treating open finger and hand fractures outside of the OR to optimize management of these injuries.

Level of Evidence:

Level III.
Cervical Paraspinal Muscle Fatty Infiltration is Directly Related to Extension Reserve in Patients With Cervical Spine Pathology
Authors: Virk Sohrab , Lafage Renaud , Elysee Jonathan , Passias Peter , Kim Han Jo , Qureshi Sheeraz , Lafage Virginie
Published: June 2022

Study Design/Setting:

Retrospective review of a prospectively collected database.

Objective:

The objective of this study was to determine the relationship between paracervical muscle area, density, and fat infiltration and cervical alignment among patients presenting with cervical spine pathology.

Background Context:

The impact of cervical spine alignment on clinical outcomes has been extensively studied, but little is known about the association between spinal alignment and cervical paraspinal musculature.

Methods:

We examined computed tomography scans and radiographs for patients presenting with cervical spine pathology. The posterior paracervical muscle area, density, and fat infiltration was calculated on axial slices at C2, C4, C6, and T1. We measured radiographic parameters including cervical sagittal vertical axis, cervical lordosis, T1 slope (T1S), range of motion of the cervical spine. We performed Pearson correlation tests to determine if there were significant relationships between muscle measurements and alignment parameters.

Results:

The study included 51 patients. The paracervical muscle area was higher for males at C2 (P=0.005), C4 (P=0.001), and T1 (P=0.002). There was a positive correlation between age and fat infiltration at C2, C4, C6, and T1 (all P<0.05). The cervical sagittal vertical axis positively correlated with muscle cross-sectional area at C2 (P=0.013) and C4 (P=0.013). Overall cervical range of motion directly correlated with muscle density at C2 (r=0.48, P=0.003), C4 (r=0.41, P=0.01), and C6 (r=0.53. P<0.001) and indirectly correlated with fat infiltration at C2 (r=−0.40, P=0.02), C4 (r=−0.32, P=0.04), and C6 (r=−0.35, P=0.02). Muscle density correlated directly with reserve of extension at C2 (r=0.57, P=0.009), C4 (r=0.48, P=0.037), and C6 (r=0.47, P=0.033). Reserve of extension indirectly correlated with fat infiltration at C2 (r=0.65, P=0.006), C4 (r=0.47, P=0.037), and C6 (r=0.48, P=0.029).

Conclusions:

We have identified specific changes in paracervical muscle that are associated with a patient’s ability to extend their cervical spine.
The Influence of Presenting Physical Function on Postoperative Patient Satisfaction and Clinical Outcomes Following Minimally Invasive Lumbar Decompression
Authors: Jacob Kevin C. , Patel Madhav R. , Park Grant A. , Gheewala Jessica R. , Vanjani Nisheka N. , Pawlowski Hanna , Prabhu Michael C. , Singh Kern
Published: June 2022

Study Design:

The study of retrospective cohort.

Objective:

The aim was to compare patient-reported outcome measures (PROMs), satisfaction, and minimum clinically important difference (MCID) achievement following minimally invasive lumbar decompression (MIS-LD) in patients stratified by the preoperative patient-reported outcomes measurement information system physical function (PROMIS-PF) score.

Summary of Background Data:

Although prior studies have assessed the predictive utility of preoperative PROMIS-PF scores on patient outcomes in spinal fusion, its utility has not been studied for patients undergoing MIS-LD.

Methods:

Primary, single/multilevel MIS-LD procedures were identified. PROMs were administered at preoperative/6-week/12-week/6-month/1-year/2-year time points and included PROMIS-PF/visual analog scale (VAS) back and leg/Oswestry Disability Index (ODI). Satisfaction scores were collected postoperatively. The patients were grouped by preoperative PROMIS-PF score (≤35, >35), with higher scores indicating improved physical function. Demographic/perioperative characteristics were compared using χ2/Student t test. Mean PROMs/postoperative satisfaction was compared utilizing 2-sample t test. Postoperative PROM improvement from preoperative was calculated with paired t tests. MCID achievement rates were compared using simple logistic regression.

Results:

Two hundred and sixteen patients were included, 58 PROMIS-PF≤35 and 158 PROMIS-PF>35. Ethnicity/insurance differed (P≤0.004, all). Hospital length of stay was greater for PROMIS-PF>35 (P=0.042). All preoperative mean PROMs significantly differed except for VAS Back. Several postoperative mean PROMs differed: PROMIS-PF at 6 weeks/12 weeks/6 months/1 year, SF-12 PCS at 6 weeks/12 weeks/1 year, VAS Back at 6 weeks/12 weeks, VAS leg at 6 weeks/12 weeks, and ODI at 6 weeks/12 weeks (P<0.050, all). All PROMs significantly improved from preoperative at all postoperative time points (P<0.003, all). The MCID achievement rates differed only for VAS back for 6 weeks, favoring PROMIS-PF>35 cohort (P=0.001). Postoperative satisfaction was greater in PROMIS-PF>35 cohort for VAS leg at 6 weeks/12 weeks/6 months/2 years, VAS back at 6-weeks/12-weeks, and ODI at all time points (P<0.037, all). Postoperative satisfaction was greater in PROMIS-PF>35 cohort for individual ODI categories: sleep at 6-weeks/12-weeks/1-year/2-years, lifting, walking, standing, and travel at all time points, and sexual at 6-weeks/12-weeks/1-year/2-years (P<0.030, all).

Conclusion:

Poorer preoperative PROMIS-PF scores were associated with worse postoperative clinical outcomes and satisfaction. By stratifying patients with preoperative PROMIS-PF scores, surgeons may better predict postoperative clinical improvement and seek to manage patient expectations.
The national major trauma system within the United Kingdom: inclusive regionalized networks of care
Authors: Cole Elaine
Published: June 2022

The United Kingdom has a population of 67 million people and is divided into 4 nations: England, Wales, Scotland, and the North of Ireland. Healthcare is provided free to all within each nation via the National Health Service (NHS), which is funded by taxes and national insurance payments. Each year, there are approximately 22,000 cases of “major trauma” in the UK across the four nations. Prior to 2010, trauma patients in the UK were managed at any acute hospital with an Emergency Department, irrespective of resource availability or clinical experience and expertise. In the late 2000s, national reports identified significant variation or serious failings in the organization of UK trauma care. These reports, together with political drivers for centralized services, led to the formation of the national major trauma system made up of regional trauma networks. England was the first nation to implement the system in 2012 and this re-organization of major trauma care was associated with a 19% increase in the odds of survival for patients who reached hospital alive. This paper will provide an overview of the positive attributes and challenges within 6 key components of the national trauma system: pre-hospital care, facility-based care, trauma networks, the trauma registries, rehabilitation and governance, financing, and quality assurance.
Microcirculatory tissue perfusion during general anaesthesia and noncardiac surgery
Authors: Flick Moritz , Schreiber Tim-Henrik , Montomoli Jonathan , Krause Linda , de Boer Hans D. , Kouz Karim , Scheeren Thomas W.L. , Ince Can , Hilty Matthias P. , Saugel Bernd
Published: June 2022

BACKGROUND

Handheld vital microscopy allows direct observation of red blood cells within the sublingual microcirculation. Automated analysis allows quantifying microcirculatory tissue perfusion variables – including tissue red blood cell perfusion (tRBCp), a functional variable integrating microcirculatory convection and diffusion capacities.

OBJECTIVE

We aimed to describe baseline microcirculatory tissue perfusion in patients presenting for elective noncardiac surgery and test that microcirculatory tissue perfusion is preserved during elective general anaesthesia for noncardiac surgery.

DESIGN

Prospective observational study.

SETTING

University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

PATIENTS

120 elective noncardiac surgery patients (major abdominal, orthopaedic or trauma and minor urologic surgery) and 40 young healthy volunteers.

MAIN OUTCOME MEASURES

We measured sublingual microcirculation using incident dark field imaging with automated analysis at baseline before induction of general anaesthesia, under general anaesthesia before surgical incision and every 30 min during surgery. We used incident the dark field imaging technology with a validated automated analysis software.

RESULTS

A total of 3687 microcirculation video sequences were analysed. Microcirculatory tissue perfusion variables varied substantially between individuals – but ranges were similar between patients and volunteers. Under general anaesthesia before surgical incision, there were no important changes in tRBCp, functional capillary density and capillary haematocrit compared with preinduction baseline. However, total vessel density was higher and red blood cell velocity and the proportion of perfused vessels were lower under general anaesthesia. There were no important changes in any microcirculatory tissue perfusion variables during surgery.

CONCLUSION

In patients presenting for elective noncardiac surgery, baseline microcirculatory tissue perfusion variables vary substantially between individuals – but ranges are similar to those in young healthy volunteers. Microcirculatory tissue perfusion is preserved during general anaesthesia and noncardiac surgery – when macrocirculatory haemodynamics are maintained.
Factors associated with noncompliance to diabetes medication in a rapidly urbanizing region in Ghana: a mixed-methods study
Authors: Berkoh Dorice A. , Owiredu William B. K. A. , Gyasi Samuel F. , Donkoh Emmanuel T. , Ngala Robert A.
Published: June 2022

Background:

Failure to achieve adequate glycemic control can lead to debilitating complications for diabetics. Strict compliance to prescribed diet, lifestyle, and medication can prevent complications.

Methods:

In order to examine factors accompanying noncompliance behavior to diabetes medication in a rapidly urbanizing region of Ghana, a mixed approach was adopted. Study subjects (N: 160, mean age: 58.3) were interviewed at the diabetic clinic of the Brong-Ahafo Regional Hospital, Sunyani. Compliance to diabetes treatment was evaluated with an adapted Morisky Medication Adherence Scale (MMAS). Face-to-face interviews of 20 subjects allowed for more personalized exploration of psychosocial aspects of noncompliance. The interviews were audio recorded, transcribed verbatim, and coded using the Nvivo software. Qualitative data was processed and subjected to inductive thematic analysis.

Results:

Majority of study participants reported an optimum (n = 121, 75.6%) level of compliance to diabetes medication, although some also reported poor compliance (n = 39, 24.4%). Qualitative responses received during interviews suggest that poor compliance may be attributable to misconceptions about religious beliefs and practices. Psychosocial factors relating to felt stress, the inevitability of fate, and compliance fatigue were also discovered to undermine compliance. Noncompliance behavior was also explained by socioeconomic status and barriers to health-seeking behavior.

Conclusion:

Reported medication compliance was among the highest in out-patient settings in Ghana. However, contextual determinants of noncompliance have to be addressed. Efforts to improve compliance to diabetic medication could benefit from interventions that address superstition, target psychological aspects of chronic disease management, and remove operational barriers to healthcare delivery such as transportation costs and long waiting times.
Biomechanical Effects of Prophylactic Knee Bracing on Anterior Cruciate Ligament Injury Risk: A Systematic Review
Authors: Tuang Brian H. H. , Ng Zheng Qin , Li Joshua Z. , Sirisena Dinesh
Published: June 2022

Objective:

Prophylactic knee braces (PKBs) are widely used by athletes in pivoting and landing sports and have the potential to influence knee movement and alignment, thus modulating anterior cruciate ligament (ACL) injury risk. This systematic review analyses current evidence on the biomechanical effects that PKBs have in the prevention of ACL injuries.

Data sources:

The review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Searches were conducted on PubMed, Web of Science, Scopus, Ovid MEDLINE, EMBASE, Cochrane, and CINAHL for studies published from inception until May 31, 2021. Included studies assessed the effects of PKBs on biomechanical variables associated with ACL injuries in landing or pivoting tasks, comparing between braced and unbraced conditions.

Main results:

A total of 234 articles were identified; from which, 14 controlled, laboratory, biomechanical studies were included in this review. The effects of PKBs on knee biomechanics could be divided into kinematic variables in the coronal, sagittal, and transverse planes; and common kinetic variables, such as ground reaction force (GRF) and ACL load/strain. Also, PKBs were found to have protective effects in coronal and transverse plane kinematics, but results in the sagittal plane were inconclusive. Assessing knee kinetics, PKBs were advantageous in decreasing ACL load/strain but had no significant effect on GRF.

Conclusions:

Prophylactic knee braces may serve to reduce ACL injury risk by modulating knee coronal and transverse plane movements and ACL load/strain during high-risk maneuvres. Precise recommendations are limited by study heterogeneity. More prospective studies are needed to assess ACL injury risk during high-risk sports using specific PKBs.
Assessment of left main coronary artery disease: a comparison between invasive and noninvasive
Authors: Alalawi Luay H. , Dookhan Christina M. , Verghese Dhiran , Manubolu Venkat S. , Aldana-Bitar Jairo , Lakshmanan Suvasini , Ahmad Khadije , Shafter Ahmad , Alchokhachi Zahra , Ghanem Ahmed , Golub Ilana S. , Budoff Matthew , Roy Sion
Published: June 2022

Left main coronary artery disease has significant therapeutic as well as prognostic implications. The presence of left main coronary artery stenosis is strongly associated with poor short- and long-term prognoses. Accurate identification of left main stenosis is extremely important since it would be the main factor to guide management. There are several modalities used to determine the presence of atherosclerosis and the degree of stenosis in a left main coronary artery. Newer modalities allow for an accurate evaluation of left main stenosis and atherosclerosis. In this review, we go through different invasive and noninvasive modalities to diagnose left main stenosis, shedding more light into coronary computed tomography angiography, and its accuracy in this specific diagnosis.
Correlation of computed tomography quantitative parameters with tumor invasion and Ki-67 expression in early lung adenocarcinoma
Authors: Dong Hao , Yin Lekang , Lou Cuncheng , Yang Junjie , Wang Xinbin , Qiu Yonggang
Published: June 2022

The purpose of the study is to investigate the correlation of computed tomography (CT) quantitative parameters with tumor invasion and Ki-67 expression in early lung adenocarcinoma.

The study involved 141 lesions in 141 patients with early lung adenocarcinoma. According to the degree of tumor invasion, the lesions were assigned into (adenocarcinoma in situ + minimally invasive adenocarcinoma) group and invasive adenocarcinoma (IAC) group. Artificial intelligence-assisted diagnostic software was used to automatically outline the lesions and extract corresponding quantitative parameters on CT images. Statistical analysis was performed to explore the correlation of these parameters with tumor invasion and Ki-67 expression.

The results of logistic regression analysis showed that the short diameter of the lesion and the average CT value were independent predictors of IAC. Receiver operating characteristic curve analysis identified the average CT value as an independent predictor of IAC with the best performance, with the area under the receiver operating characteristic curve of 0.893 (P < .001), and the threshold of –450 HU. Besides, the predicted probability of logistic regression analysis model was detected to have the area under the curve of 0.931 (P < .001). The results of Spearman correlation analysis showed that the expression level of Ki-67 had the highest correlation with the average CT value of the lesion (r = 0.403, P < .001).

The short diameter of the lesion and the average CT value are independent predictors of IAC, and the average CT value is significantly positively correlated with the expression of tumor Ki-67.
Impact of phase angle and sarcopenia estimated by bioimpedance analysis on clinical prognosis in patients undergoing hemodialysis
Authors: Bae Eunjin , Lee Tae Won , Bae Wooram , Kim Seongmin , Choi Jungyoon , Jang Ha Nee , Chang Se-Ho , Park Dong Jun
Published: June 2022

Bioimpedance analysis (BIA) has been widely used in the evaluation of body composition in patients undergoing maintenance hemodialysis. We conducted this study to evaluate impact of phase angle (PA) and sarcopenia measured by BIA on clinical prognosis in these patients.

This longitudinal retrospective study enrolled patients who underwent hemodialysis between January 2016 and March 2019. The patients were stratified into higher (> 4°) and lower (≤ 4.0°) PA groups. Sarcopenia was defined when the appendicular skeletal muscle mass was < 20 kg in men and < 15 kg in women.

Of the 191 patients, 63.4% were men. The mean age was 64.2 ± 12.4 years. The lower PA group was older, had a higher proportion of women, a lower body mass index, lower albumin, cholesterol, uric acid, and phosphorus levels, and a higher incidence of history of coronary artery disease than the higher PA group. Linear regression analysis revealed that PA was significantly associated with body mass index (B = 0.18, P = .005), serum albumin (B = 0.23, P = .001), and creatinine levels (B = 0.32, P < .001). During a median follow-up of 16.7 months, 14.1% (n = 27) of patients experienced major adverse cardiovascular events and 11.0% (n = 21) died. Kaplan–Meier survival analysis showed that the higher PA group had significantly better survival, regardless of sarcopenia. Multivariate Cox analyses revealed that lower PA (0.51 [0.31–0.85], P = .010), higher IDWG (1.06 [1.01–1.12], P = .028) and C-reactive protein level (1.01 [1.01–1.02], P < .001), and a history of coronary artery disease (3.02 [1.04–8.77], P = .042) were significantly related to all-cause mortality after adjusting for other covariates.

PA measured by BIA was an independent factor in the prediction of mortality in maintenance hemodialysis patients, regardless of sarcopenia. Intervention studies are needed to confirm if the improvement in PA is associated with better clinical outcome.
IL-31 expression in HIV-infected patients with different routes of disease transmission
Authors: Yan Changxin , Xu Huafeng , Rong Chunli , Cao Meilin , Miao Zhuo , Zhou Haizhou
Published: June 2022

Acquired immunodeficiency syndrome (AIDS) is caused by the human immunodeficiency virus (HIV). AIDS is characterized by an impaired immune system and low cellular immunity. The main manifestation of AIDS is a reduction in the number of CD4+ T cells and alteration in cytokine concentration. The present work aimed to explore the expression of IL-31 in HIV infection and disease progression.

Serum samples were collected from HIV-infected patients with different routes of disease transmission. The subjects included 24 patients who were infected with HIV upon blood transmission and 36 patients who had acquired the disease through sexual transmission (21 cases of homosexual transmission and 15 cases of heterosexual transmission). In addition, 20 normal healthy individuals were included to serve as the control group. The levels of IL-31 in the collected serum samples were estimated using the human IL-31 Platinum ELISA kit.

The serum analysis results revealed that the concentration of IL-31 in the serum samples for the blood transmission, sexually transmission, and normal group patients was 4.07 ± 1.63 pg/L, 7.43 ± 1.15 pg/L, and 2.87 ± 1.04 pg/L, respectively. The statistical analysis revealed that the concentration of IL-31 in HIV-1 infection was higher than that in the normal control. In addition, the expression of IL-31 was significantly higher in the sexual transmission group compared to the blood transmission group (P < .05).

IL-31 could have an important role in HIV infection, although the role of IL-31 in disease progression in HIV-infected individuals requires further research.
A Study of Postoperative Complications Occurring at Home With Pediatric Gastrostomy Feeding Tubes
Authors: Aedla Mihika , Zhou Anson , Sompel Kevin , Hu Katherine , Cheng Charlotte , Hsu Jocelyn , Qian Jason , Zhang Siya , Ho Anthony , Slagle Jacob , Logsdon Elizabeth A. , Sharma Karun V. , Weiss Clifford R.
Published: June 2022

Objective:

Gastrostomy tubes (G-tubes) provide long-term feeding assistance to children with severe feeding dysfunction. Although there are a host of complications that occur at home with current pediatric G-tube feeding, their prevalences and outcomes remain relatively unstudied. This study aims to identify and describe such complications.

Methods:

A dual-round survey was administered to 98 participants through the Feeding Tube Awareness Foundation, a 501(c)(3) organization that supports parents and caretakers of G-tube-fed children. Information was collected broadly regarding G-tube complications, causes, and attitudes toward such complications.

Results:

Infection (56%), itching/irritation/redness (52%), and leakage (51%) were the leading G-tube related complications. The average time that G-tubes were replaced was 3.4 ± 1.2 months as compared to the typical recommended period of up to 6 months. Of the caretakers who had not experienced G-tube displacement, 7.9% wanted to see a change in current G-tubes to address the issue, compared with 75% of those who had experienced displacement. This 67.1% differential in caretakers’ attitudes toward G-tubes based on their prior experience with a particular complication was the largest gap among all other listed complications.

Conclusions:

G-tube complications are prevalent and varied. A sizable portion of G-tube users experience complications severe enough to require intervention. Of these, G-tube displacement is particularly critical and frequently precedes other prevalent complications, namely gastric leakage, infection, and tissue granulation.
Autoimmune Antibodies in Children and Adolescents With Nonalcoholic Fatty Liver Disease
Authors: Kohut Taisa , Shah Amit , Russo Pierre , Panganiban Jennifer
Published: June 2022

Objectives:

The clinical significance of autoantibody positivity in nonalcoholic fatty liver disease (NAFLD) in the absence of autoimmune hepatitis (AIH) remains uncertain. We aimed to determine the prevalence of autoantibodies in a pediatric cohort with biopsy-proven NAFLD and investigate the association between autoantibodies and NAFLD histologic grade.

Methods:

Single-center, retrospective study of patients ≤21 years with biopsy-proven NAFLD from 2014 to 2019. Clinical and laboratory data were obtained within 90 days of liver biopsy. Autoantibody positivity was defined as serum titer ≥1:80 or units ≥20. Liver biopsies were evaluated for features of AIH, then scored for steatosis, hepatocyte ballooning, lobular inflammation, and NAFLD activity score (NAS) was calculated. Portal inflammation and fibrosis were scored separately. Multivariable logistic regression was used for continuous and binary outcomes.

Results:

Sixty-seven subjects met inclusion criteria. Positive antinuclear antibody (ANA), antismooth muscle antibody (ASMA), antineutrophil cytoplasmic antibody (ANCA), anti-F-actin antibody (F-actin), anti-liver kidney microsomal (LKM) antibody, or any combination was observed in 43%, 39%, 19%, 13%, 0%, and 66% of subjects, respectively. After controlling for confounders, positive ANA and alanine aminotransferase (ALT) >80 had 4.6 greater odds of having an NAS ≥5 (P = 0.035; 95% confidence interval [CI], 1.12–19.01). Autoantibody positivity resolution occurred in 10%–50% who underwent serial monitoring.

Conclusions:

Autoantibodies, except LKM, were frequently encountered in our pediatric NAFLD cohort in the absence of AIH. ANA positivity with ALT may help clinically stratify pediatric patients with suspected NAFLD targeting those at greater risk for nonalcoholic steatohepatitis (NASH).
Methotrexate for Primary Maintenance Therapy in Mild-to-Moderate Crohn Disease in Children
Authors: Baldwin Katherine , Goldfarb Alexa , Brimacombe Michael , Hopkins Dena , Hyams Jeffrey S.
Published: June 2022

Objectives:

Despite limited data, methotrexate (MTX) is often used as primary maintenance therapy in pediatric Crohn disease (CD). We sought to assess the effectiveness of MTX as “initial” primary maintenance therapy in newly diagnosed mild/moderate pediatric CD and ascertain baseline predictive factors.

Methods:

Single-center 10-year retrospective review of newly diagnosed CD patients treated with MTX as primary maintenance therapy. We compared baseline characteristics of those patients with sustained response/clinical remission to those patients who escalated to anti-TNF therapy within 1 year. Pediatric Crohn Disease Activity Index (PCDAI) ≤ 10 defined remission.

Results:

We identified 65 patients (mean age, 11.8 years; 72 % male; mean ± SD PCDAI, 17.8 ± 10.5) who started MTX ≤4 months of diagnosis as their primary maintenance therapy. Initial therapy prior to MTX was corticosteroids (CS) (54/65), defined diet (4/65), and combination CS/diet (6/65). Oral dosing was used in 55%; mean dose was 11.4 mg/m2 orally and 12.5 mg/m2 subcutaneously. At 1 year, 36 of 65 (55%) were on MTX monotherapy, and of those, 32 of 36 were in clinical remission; 81% were in steroid-free remission for the year following induction. For the 36 patients on MTX at 1 year, 14 (39%) had gross mucosal healing (22% of the original cohort). Ten additional patients had mucosal improvement (37% of total healed/improved). Fifteen patients (23%) were early failures, transitioning to anti-TNF ≤4 months. Baseline PCDAI, hemoglobin, ESR, albumin, and route of administration were not predictive of outcome. MTX was well tolerated in our cohort, with only 1 patient stopping due to elevated aminotransferases. No patient required CD surgery in the 1-year follow-up.

Conclusions:

MTX may have a primary maintenance role in mild/moderate CD.
Indirect and Out-of-Pocket Disease-associated Costs in Pediatric Inflammatory Bowel Disease: A Cross-sectional Analysis
Authors: El-Matary Wael , Witt Julia , Bernstein Charles N. , Jacobson Kevan , Mack David , Otley Anthony , Walters Thomas D. , Huynh Hien Q. , deBruyn Jennifer , Griffiths Anne M. , Benchimol Eric I.
Published: June 2022

Objectives:

Data on pediatric inflammatory bowel disease (IBD)-associated indirect and out-of-pocket (OOP) costs are limited. We aimed to estimate indirect (lost work hours and productivity) and OOP pediatric IBD-associated costs in Canada.

Methods:

In a nation-wide cross-sectional analysis, caregivers of children with IBD were invited to complete a questionnaire on lost work hours and OOP costs related to IBD in the 4 weeks prior to the survey. Participants were reinvited to periodically answer the same questionnaire every 3–9 months for 2 years. Lost productivity was calculated using the Human Capital method. Costs were reported in 2018 inflation-adjusted Canadian dollars. Predictors of high cost users (top 25%) were examined using binary logistic regression.

Results:

Consecutive 243 (82 incident cases) of 262 (92.7%) approached participants completed the first survey with a total of 450 surveys longitudinally completed over 2 years. The median annual indirect cost per patient was $5966 (IQR $1809–$12,676), with $5721 (IQR $1366–$11,545) for Crohn’s disease (CD) and $7007 (IQR $2428–$14,057) for ulcerative colitis (UC) (P= 0.11). The annual median per patient OOP costs were $4550 with $4550 for CD and $5038 for UC (P= 0.53). Longer travel distance to clinic was associated with higher OOP costs (odds ratio = 4.55;P< 0.0001; 95% confidence interval: 1.99–10.40).

Conclusions:

Indirect and OOP IBD-associated costs are substantial and more likely to affect families living in remote communities.
An agonistic monoclonal antibody targeting cMet attenuates inflammation and upregulates collagen synthesis and angiogenesis in Type 2 diabetic mouse wounds
Authors: Choi Min-Ha , Jang Tae-Sik , Kim Hyeonwoo , Ku Inhoe , Lee Junghun , Jeong Jae-Gyun , Kim Sunyoung , Park Ji-Ung
Published: June 2022

Background:

Diabetic wounds account for 25%–50% of total diabetic healthcare costs annually, and present overall healing rates of less than 50%. Since delayed diabetic wound healing is associated with impaired fibroblast function, we hypothesize that tyrosine kinase Met (cMet) agonistic monoclonal antibody (mAb) will promote diabetic wound healing via stable activation of HGF/cMet signaling.

Methods:

Two 6 mm dorsal wounds were created in each mice (6-week-old, male BKS.Cg-Dock7m+/+Leprdb/J, n=5). After subcutaneous injections of agonist (20 mg/kg) at 0 and 72h, the wound sizes were measured at days 0, 1, 3, 6, and 10. Histological and immunohistochemical analyses were performed at day 10 (cMet, α-SMA, CD68, and TGF-β). In vitro cytotoxicity and migration tests with diabetic fibroblasts were performed with/without agonist treatment (1 or 10 nM). cMet pathway activation of fibroblasts was confirmed through p-p44/42MAPK, p-mTOR, p-cMet, and ROCK-1 expression.

Results:

cMet agonistic mAb-treated group showed 1.60-fold lower wound area (p=0.027), 1.54-fold higher collagen synthesis (p=0.001), and 1.79-fold lower inflammatory cell infiltration (p=0.032) than the saline-treated control. The agonist increased cMet (1.86-fold, p=0.029), α-SMA (1.20-fold, p=0.018), and VEGF (1.68-fold, p=0.029) expression but suppressed CD68 (1.25-fold, p=0.043), TFG-β (1.25-fold, p=0.022), and MMP-2 (2.59-fold, p=0.029) expression. In vitro agonist treatment (10 nM) of diabetic fibroblasts increased their migration by 8.98-fold (p=0.029) and activated HGF/cMet pathway.

Conclusions:

cMet agonistic mAb treatment improved diabetic wound healing in mice and reduced wound-site inflammatory cell infiltration. These results need to be validated in large animals before piloting human trials.
Impact of Ischemia Duration on Lower Limb Salvage in Combat Casualties
Authors: Perkins Zane B. , Kersey Alexander J. , White Joseph M. , Lauria Alexis L. , Propper Brandon W. , Tai Nigel R.M. , Rasmussen Todd E.
Published: June 2022

Introduction:

The 6-hour threshold to revascularization of an ischemic limb is ubiquitous in the trauma literature, however, contemporary evidence suggests that this threshold should be less. This study aims to characterize the relationship between the duration of limb ischemia and successful limb salvage following lower extremity arterial trauma.

Methods:

This is a cohort study of the United States and UK military service members injured while serving in Iraq or Afghanistan between 2003 and 2013. Consecutive patients who sustained iliac, femoral, or popliteal artery injuries, and underwent surgery to attempt revascularization, were included. The association between limb outcome and the duration of limb ischemia was assessed using the Kaplan-Meier method.

Results:

One hundred twenty-two patients (129 limbs) who sustained iliac (2.3%), femoral (56.6%), and popliteal (41.1%) arterial injuries were included. Overall, 87 limbs (67.4%) were successfully salvaged. The probability of limb salvage was 86.0% when ischemia was ≤1 hour; 68.3% when between 1 and 3 hours; 56.3% when between 3 and 6 hours; and 6.7% when >6 hours (P<0.0001). Shock more than doubled the risk of failed limb salvage [hazard ratio=2.42 (95% confidence interval: 1.27–4.62)].

Conclusions:

Limb salvage is critically dependent on the duration of ischemia with a 10% reduction in the probability of successful limb salvage for every hour delay to revascularization. The presence of shock significantly worsens this relationship. Military trauma systems should prioritize rapid hemorrhage control and early limb revascularization within 1 hour of injury.
Ecological complexity and the biosphere: the next 30 years
Authors: Solé Ricard , Levin Simon
Published: June 2022

Global warming, habitat loss and overexploitation of limited resources are leading to alarming biodiversity declines. Ecosystems are complex adaptive systems that display multiple alternative states and can shift from one to another in abrupt ways. Some of these tipping points have been identified and predicted by mathematical and computational models. Moreover, multiple scales are involved and potential mitigation or intervention scenarios are tied to particular levels of complexity, from cells to human–environment coupled systems. In dealing with a biosphere where humans are part of a complex, endangered ecological network, novel theoretical and engineering approaches need to be considered. At the centre of most research efforts is biodiversity, which is essential to maintain community resilience and ecosystem services. What can be done to mitigate, counterbalance or prevent tipping points? Using a 30-year window, we explore recent approaches to sense, preserve and restore ecosystem resilience as well as a number of proposed interventions (from afforestation to bioengineering) directed to mitigate or reverse ecosystem collapse. The year 2050 is taken as a representative future horizon that combines a time scale where deep ecological changes will occur and proposed solutions might be effective.

This article is part of the theme issue ‘Ecological complexity and the biosphere: the next 30 years’.
Is the genomics ‘cart’ before the restoration ecology ‘horse’? Insights from qualitative interviews and trends from the literature
Authors: Mohr Jakki J. , Harrison Peter A. , Stanhope Jessica , Breed Martin F.
Published: June 2022

Harnessing new technologies is vital to achieve global imperatives to restore degraded ecosystems. We explored the potential of genomics as one such tool. We aimed to understand barriers hindering the uptake of genomics, and how to overcome them, via exploratory interviews with leading scholars in both restoration and its sister discipline of conservation—a discipline that has successfully leveraged genomics. We also conducted an examination of research trends to explore some insights that emerged from the interviews, including publication trends that have used genomics to address restoration and conservation questions. Our qualitative findings revealed varied perspectives on harnessing genomics. For example, scholars in restoration without genomics experience felt genomics was over-hyped. Scholars with genomics experience emphatically emphasized the need to proceed cautiously in using genomics in restoration. Both genomics-experienced and less-experienced scholars called for case studies to demonstrate the benefits of genomics in restoration. These qualitative data contrasted with our examination of research trends, which revealed 70 restoration genomics studies, particularly studies using environmental DNA as a monitoring tool. We provide a roadmap to facilitate the uptake of genomics into restoration, to help the restoration sector meet the monumental task of restoring huge areas to biodiverse and functional ecosystems.

This article is part of the theme issue ‘Ecological complexity and the biosphere: the next 30 years’.
Complexity–biodiversity relationships on marine urban structures: reintroducing habitat heterogeneity through eco-engineering
Authors: Bishop Melanie J. , Vozzo Maria L. , Mayer-Pinto Mariana , Dafforn Katherine A.
Published: June 2022

Urbanization is leading to biodiversity loss through habitat homogenization. The smooth, featureless surfaces of many marine urban structures support ecological communities, often of lower biodiversity, distinct from the complex natural habitats they replace. Eco-engineering (design for ecological co-benefits) seeks to enhance biodiversity and ecological functions on urban structures. We assessed the benefits to biodiversity of retrofitting four types of complex habitat panels to an intertidal seawall at patch (versus flat control panels) and site (versus unmodified control seawalls and reference rocky shores) scales. Two years after installation, patch-scale effects of complex panels on biodiversity ranged from neutral to positive, depending on the protective features they provided, though all but one design (honeycomb) supported unique species. Water-retaining features (rockpools) and crevices, which provided moisture retention and cooling, increased biodiversity and supported algae and invertebrates otherwise absent. At the site scale, biodiversity benefits ranged from neutral at the high- and mid-intertidal to positive at the low-intertidal elevation. The results highlight the importance of matching eco-engineering interventions to the niche of target species, and environmental conditions. While species richness was greatest on rockpool and crevice panels, the unique species supported by other panel designs highlights that to maximize biodiversity, habitat heterogeneity is essential.

This article is part of the theme issue ‘Ecological complexity and the biosphere: the next 30 years’.
Arginase 1 is a key driver of immune suppression in pancreatic cancer
Authors: Menjivar Rosa E. , Nwosu Zeribe C. , Du Wenting , Donahue Katelyn L. , Espinoza Carlos , Brown Kristee , Velez-Delgado Ashley , Yan Wei , Lima Fatima , Bischoff Allison , Kadiyala Padma , Salas-Escabillas Daniel , Crawford Howard , Bednar Filip , Carpenter Eileen , Zhang Yaqing , Halbrook Christopher J. , Lyssiotis Costas A. , Pasca di Magliano Marina
Published: June 2022

An extensive fibroinflammatory stroma rich in macrophages is a hallmark of pancreatic cancer. In this disease, it is well appreciated that macrophages are immunosuppressive and contribute to the poor response to immunotherapy; however, the mechanisms of immune suppression are complex and not fully understood. Immunosuppressive macrophages are classically defined by expression of the enzyme Arginase 1 (Arg1), which we demonstrated is potently expressed in pancreatic tumor associated macrophages from both human patients and mouse models. While routinely used as a polarization marker, Arg1 also catabolizes arginine, an amino acid required for T cell activation and proliferation. To investigate this metabolic function, we used a genetic and a pharmacologic approach to target Arg1 in pancreatic cancer. Genetic inactivation of Arg1 in macrophages, using a dual recombinase genetically engineered mouse model of pancreatic cancer, delayed formation of invasive disease, while increasing CD8+ T cell infiltration. Treatment of established tumors with the arginase inhibitor CB-1158 exhibited further increased CD8+ T cell infiltration, beyond that seen with the macrophage-specific knockout, and sensitized the tumors to anti-PD1 immune checkpoint blockade. Thus, our data demonstrate that Arg1 is more than simply a marker of macrophage function. Rather, Arg1 is also a driver of immune suppression and represents a promising immunotherapeutic target for pancreatic cancer.
Linking microenvironment modification to species interactions and demography in an alpine plant community
Authors: Ray Courtenay A. , Kapas Rozalia E. , Opedal Øystein H. , Blonder Benjamin W.
Published: June 2022

Individual plants can modify the microenvironment within their spatial neighborhood. However, the consequences of microenvironment modification for demography and species interactions remain unclear at the community scale. In a study of co-occurring alpine plants, we (1) determined the extent of species-specific microclimate modification by comparing temperature and soil moisture between vegetated and non-vegetated microsites for several focal species. We (2) determined how vital rates (survival, growth, fecundity) of all species varied in response to aboveground and belowground vegetative overlap with inter- and intraspecific neighbors as proxies for microenvironment modification. For (1), surface temperatures were buffered (lower maximums and higher minimums) and soil moisture was higher below the canopies of most species compared to non-vegetated areas. For (2), vegetative overlap predicted most vital rates, although the effect varied depending on whether aboveground or belowground overlap was considered. Vital rate response to microenvironment-modification proxies (vegetative overlap) was also frequently context dependent with respect to plant size and macroclimate. Microenvironment modification and spatial overlapping of individuals are key drivers of demography and species interactions in this alpine community.
A disease model for Diffuse Intrinsic Pontine Glioma (DIPG) with mutations in TP53 and its application for drug repurposing
Authors: Yuryev Anton , Nesterova Anastasia , Sozhin Sergey , Shkrob Maria
Published: June 2022

1.1

Brain cancers are ones of most aggressive and difficult to treat cancers. Despite numerous studies of the cellular mechanisms of gliomas, it is difficult to stop tumor growth. A complex genetic and epigenetic nature of many gliomas and poorly known pathways of human neuron precursors maturation suggest turning to big data analysis to find new insights and directions for drug development. We developed in silico molecular models and predicted molecular switches in signaling cascades that maintain multipotency of neuronal precursor cells in diffuse intrinsic pontine glioma (DIPG) driven by the H3K27M mutation and mutations in the TP53 gene. Oncogenes and biomarkers were predicted based on transcriptomics and mutational genomics data from a cohort of 30 patients with DIPG analyzed using Elsevier artificial intelligence methods and a collection of manually curated cancer hallmark pathways. The molecular models of DIPG with mutations in TP53 and histone 3 gene describe the mechanism of oligodendrocyte dedifferentiation due to activation of transcriptional factors OLIG2, SOX2 and POU5F1, epithelial-to-mesenchymal transition via strong EGFR and TGFR signaling, enhanced cell response to hypoxia via HIF1A signaling, and enhanced angiogenesis by VEGFA overexpression. Using in silico analysis, we identified drugs capable of inhibiting mutant TP53: vorinostat, cisplatin, paclitaxel, and statins were top ranked drugs. The predicted drugs and oncogenes had individual patient-level differences that can be visualized with created DIPG model and may be useful for future research in the field of personalized medicine.
Efficacy and safety of ensitrelvir in patients with mild-to-moderate COVID-19: the phase 2b part of a randomized, placebo-controlled, phase 2/3 study
Authors: Mukae Hiroshi , Yotsuyanagi Hiroshi , Ohmagari Norio , Doi Yohei , Sakaguchi Hiroki , Sonoyama Takuhiro , Ichihashi Genki , Sanaki Takao , Baba Keiko , Tsuge Yuko , Uehara Takeki
Published: June 2022

This phase 2b part of a randomized phase 2/3 study assessed the efficacy and safety of ensitrelvir for mild-to-moderate coronavirus disease 2019 (COVID-19). Patients were randomized (1:1:1) to orally receive ensitrelvir fumaric acid 125 mg (375 mg on day 1; n=140) or 250 mg (750 mg on day 1; n=140) or placebo (n=141) once daily for 5 days. Compared with placebo, the change from baseline in severe acute respiratory syndrome coronavirus 2 titer (measured as log10 50% tissue-culture infectious dose) on day 4 was significantly greater with ensitrelvir 125 mg and 250 mg (differences from placebo: −0.41, P<0.0001 for both). The total score of predefined 12 COVID-19 symptoms showed an improving trend with ensitrelvir treatment without a significant intergroup difference. Most adverse events were mild in severity. Ensitrelvir treatment demonstrated a favorable antiviral efficacy and potential clinical benefit with an acceptable safety profile. (Japan Registry of Clinical Trials identifier: jRCT2031210350)