bluuebunny/crossref_metadata_2025 huggingface dataset:
Locomotor sensitization in male Sprague-Dawley rats following repeated concurrent treatment with 4-methylmethcathinone and 3,4-methylenedioxymethamphetamine
Authors: Bullock Trent A. , Berquist Michael D. , Baker Lisa E.
Published: July 2019

Recreational abuse of illicit synthetic cathinones is an ongoing public health concern. Recent studies indicate that the methcathinone derivative 4-methylmethcathinone (4-MMC) produces behavioral and neurochemical effects similar to the entactogen 3,4-methylenedioxymethamphetamine (MDMA). Whereas polysubstance abuse is common, most preclinical studies of drug abuse liability only evaluate the effects of single drugs. Utilizing the locomotor sensitization paradigm, the present study assessed the combined locomotor stimulant effects of 4-MMC and MDMA for induction of sensitization following repeated administration and for expression of sensitization to a challenge dose of either substance alone after a 10-day period of drug abstinence. Male Sprague-Dawley rats received once daily intraperitoneal injections of saline, 4-MMC (1.0 mg/kg or 5.0 mg/kg), MDMA (3.0 mg/kg), or a mixture containing 4-MMC (1.0 mg/kg or 5.0 mg/kg) + MDMA (3.0 mg/kg) for 7 consecutive days. Following a 10-day drug-free period, rats were given a single intraperitoneal injection of either saline, 4-MMC (1.0 or 5.0 mg/kg), or 3.0 mg/kg MDMA. Activity was recorded for 1 h immediately before and 1 h immediately after injections on days 1, 7, and 17. 4-MMC treatment failed to induce locomotor sensitization, but, when combined with MDMA, sensitization was induced to a greater extent than with MDMA alone. Furthermore, the expression of sensitization to a subsequent challenge dose of MDMA was observed only in animals previously exposed to MDMA or a 5.0 mg/kg 4-MMC + MDMA mixture. In consideration of these findings along with the fact that 4-MMC has similar neurochemical actions to MDMA, further research may be warranted to determine the abuse liability of drug mixtures including 4-MMC and MDMA.
Depressive symptoms and associated factors among Iranian women at midlife: a community-based, cross-sectional study
Authors: Azizi Marzieh , Fooladi Ensieh , Bell Robin J. , Elyasi Forouzan , Masoumi Maryam , Davis Susan R.
Published: July 2019

Objective:

Little is known of depressive symptoms in Iranian women at midlife. This population-based study was undertaken to document the prevalence of, and factors associated with, depressive symptoms using validated questionnaires.

Methods:

A total of 1,520 community-dwelling women, aged 40 to 64 years, residing in Sari, Northern Iran, were recruited, using multistage cluster sampling, to this cross-sectional study, between October 2016 and April 2017. Participants completed the Menopause Quality of Life Questionnaire, the Beck Depression Inventory-II, and the World Health Organization Well-being Index.

Results:

Participants’ mean age was 49.1 (7.0) years and 88.7% were married. Overall, 167 (11%) women had moderate–severe depressive symptoms, 837 (55.1%) had low psychological well-being, and 172 (11.3%) reported taking psychotropic medication in the prior month. Factors independently associated with moderate–severe depressive symptoms included moderate–severe vasomotor symptoms (VMS) (adjusted odds ratio [AOR] 2.6, 95% CI, 1.5-4.6; P = 0.001), age 60 years or older (AOR = 1.9, 95% CI, 1.1-3.5; P = 0.03), body mass index 30 to 39 kg/m2 (AOR = 1.8, 95% CI, 1.0-3.1; P = 0.04), and housing insecurity (AOR = 5.6, 95% CI, 3.7-8.3; P < 0.001). Education beyond high school was associated with a lower risk (AOR = 0.5, 95% CI, 0.3-0.9; P = 0.04). Women reporting low marital satisfaction (19.2% of married women) were more likely than women who were very satisfied to have moderate–severe depressive symptoms (AOR = 27.9, 95% CI, 10.5-74.2; P < 0.001).

Conclusions:

Marital relationship dissatisfaction, reported by one in five women, was strongly associated with moderate–severe depressive symptoms in women at midlife in Iran, in addition to moderate–severe VMS, housing insecurity, obesity, and older age.
A Prediction Model for Uncontrolled Type 2 Diabetes Mellitus Incorporating Area-level Social Determinants of Health
Authors: Basu Sanjay , Narayanaswamy Rajiv
Published: July 2019

Background:

Social determinants of health (SDH) at the area level are understood to influence the likelihood of having poor glycemic control for patients with type 2 diabetes mellitus (T2DM).

Objectives:

To develop a model for predicting whether a person with T2DM has uncontrolled diabetes (hemoglobin A1c ≥9%), incorporating individual and area-level (census tract) covariates.

Research Design:

Development and validation of machine learning models.

Subjects:

Total of N=1,015,808 privately insured persons in claims data with T2DM.

Measures:

C-statistic, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy.

Results:

A standard logistic regression model selecting among the available individual-level covariates and area-level SDH covariates (at the census tract level) performed poorly, with a C-statistic of 0.685, sensitivity of 25.6%, specificity of 90.1%, positive predictive value of 56.9%, negative predictive value of 70.4%, and accuracy of 68.4% on a 25% held-out validation subset of the data. By contrast, machine learning models improved upon risk prediction, with the highest performance from a random forest algorithm with a C-statistic of 0.928, sensitivity of 68.5%, specificity of 94.6%, positive predictive value of 69.8%, negative predictive value of 94.3%, and accuracy of 90.6%. SDH variables alone explained 16.9% of variation in uncontrolled diabetes.

Conclusions:

A predictive model developed through a machine learning approach may assist health care organizations to identify which area-level SDH data to monitor for prediction of diabetes control, for potential use in risk-adjustment and targeting.
Comparing Resource Use in Medical Admissions of Children With Complex Chronic Conditions
Authors: Silber Jeffrey H. , Rosenbaum Paul R. , Pimentel Samuel D. , Calhoun Shawna , Wang Wei , Sharpe James E. , Reiter Joseph G. , Shah Shivani A. , Hochman Lauren L. , Even-Shoshan Orit
Published: July 2019

Background:

Children with complex chronic conditions (CCCs) utilize a disproportionate share of hospital resources.

Objective:

We asked whether some hospitals display a significantly different pattern of resource utilization than others when caring for similar children with CCCs admitted for medical diagnoses.

Research Design:

Using Pediatric Health Information System data from 2009 to 2013, we constructed an inpatient Template of 300 children with CCCs, matching these to 300 patients at each hospital, thereby performing a type of direct standardization.

Subjects:

Children with CCCs were drawn from a list of the 40 most common medical principal diagnoses, then matched to patients across 40 Children’s Hospitals.

Measures:

Rate of intensive care unit admission, length of stay, resource cost.

Results:

For the Template-matched patients, when comparing resource use at the lower 12.5-percentile and upper 87.5-percentile of hospitals, we found: intensive care unit utilization was 111% higher (6.6% vs. 13.9%, P<0.001); hospital length of stay was 25% higher (2.4 vs. 3.0 d/admission, P<0.001); and finally, total cost per patient varied by 47% ($6856 vs. $10,047, P<0.001). Furthermore, some hospitals, compared with their peers, were more efficient with low-risk patients and less efficient with high-risk patients, whereas other hospitals displayed the opposite pattern.

Conclusions:

Hospitals treating similar patients with CCCs admitted for similar medical diagnoses, varied greatly in resource utilization. Template Matching can aid chief quality officers benchmarking their hospitals to peer institutions and can help determine types of their patients having the most aberrant outcomes, facilitating quality initiatives to target these patients.
Diagnostic and Management Challenges in Vasoactive Intestinal Peptide Secreting Tumors
Authors: Angelousi Anna , Koffas Apostolos , Grozinsky-Glasberg Simona , Gertner Julian , Kassi Eva , Alexandraki Krystallenia , Caplin Martyn E. , Kaltsas Grigorios , Toumpanakis Christos
Published: July 2019

Objectives

Vasoactive intestinal peptide–secreting tumors (VIPomas) are rare functioning neuroendocrine tumors often characterized by a difficult-to-control secretory syndrome and high potential to develop metastases. We hereby present the characteristics of 15 cases of VIPomas and provide a recent literature review.

Methods

This was a retrospective data analysis of 15 patients with VIPoma from 3 different centers and literature research through PubMed database during the last 10 years.

Results

Fifteen patients with VIPomas (9 with hepatic metastases at diagnosis) with watery diarrhea and raised VIP levels were studied. Ten patients (67%) had grade 2 tumors, 6 of 15 had localized disease and underwent potentially curative surgery, whereas the remaining 9 received multiple systemic therapies; 3 patients died during follow-up. The median overall survival was 71 months (range, 41–154 months). Patients who were treated with curative surgery (n = 7) had longer median overall survival compared with patients who were treated with other therapeutic modalities (44 vs 33 months).

Conclusions

The management of VIPomas is challenging requiring the application of multiple treatment modalities. Patients who underwent surgical treatment with curative intent appear to have higher survival rate. Central registration and larger prospective studies are required to evaluate the effect of currently employed therapies in these patients.
Impact of Changes in the American Joint Committee on Cancer Staging Manual, Eighth Edition, for Pancreatic Ductal Adenocarcinoma
Authors: Kassardjian Ari , Stanzione Nicholas , Donahue Timothy R. , Wainberg Zev A. , Damato Lauren , Wang Hanlin L.
Published: July 2019

Objective

Consistent and reliable tumor staging is a critical factor in determining treatment strategy, selection of patients for adjuvant therapy, and for therapeutic clinical trials. The aim of this study was to evaluate the number and extent of pancreatic ductal adenocarcinoma (PDAC) cases that would have a different pT, pN, and overall stages based on the new eighth edition American Joint Committee on Cancer staging system when compared with the seventh edition.

Methods

Patients diagnosed with PDAC who underwent pancreaticoduodenectomy, total pancreatectomy, or distal pancreatectomy from 2007 to 2017 were retrospectively reviewed. A total of 340 cases were included.

Results

According to the seventh edition, the vast majority of tumors in our cohort were staged as pT3 tumors (88.2%). Restaging these cases with the new size-based pT system resulted in a more equal distribution among the 3 pT categories, with higher percentage of pT2 cases (55%).

Conclusions

The newly adopted pT stage protocol for PDAC is clinically relevant, ensures a more equal distribution among different stages, and allows for a significant prognostic stratification. In contrast, the new pN classification (pN1 and pN2) based on the number of positive lymph nodes failed to show survival differences and remains controversial.
Acute Recurrent and Chronic Pancreatitis as Initial Manifestations of Cystic Fibrosis and Cystic Fibrosis Transmembrane Conductance Regulator–Related Disorders
Authors: Baldwin Christina , Zerofsky Melissa , Sathe Meghana , Troendle David M. , Perito Emily R.
Published: July 2019

Objectives

Recurrent pancreatitis is considered a rare manifestation of cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction; this case series highlights that pancreatitis can be a presenting symptoms of cystic fibrosis (CF) or a CFTR-related disorder (CFTR-RD).

Methods

Retrospective review of patients younger than 30 years diagnosed as having acute recurrent pancreatitis (ARP) or chronic pancreatitis (CP) and subsequently diagnosed as having CF or CFTR-RD.

Results

Among 18 patients, median time from diagnosis of ARP/CP to diagnosis of CF was 0.4 years (range, 0–33 years). Eight were classified as having CF by elevated sweat chloride testing (SCT). Five had intermediate SCT (30–59 mmol/L) with 2 pathogenic mutations. Five had CFTR-RD with intermediate SCT and 0 to 1 pathogenic mutations. Eight patients (44%) had exocrine pancreatic insufficiency, and pancreatic fluid collections were more common in this group. Based on the CFTR mutation, 6 patients were eligible for CFTR potentiator therapy, although none received it during the study period. Nine of the 18 had ≥1 other likely CF manifestations, including sinusitis (33%), nasal polyps (11%), pneumonia (22%), and gallbladder disease (22%).

Conclusions

Cystic fibrosis or CFTR-RD can present as ARP/CP. Complete diagnostic testing for CFTR-RD in patients with ARP/CP will broaden treatment options and help to identify comorbid illness.
Induction Therapy in Localized Pancreatic Cancer
Authors: Shaib Walid L. , Sayegh Layal , Zhang Chao , Belalcazar Astrid , Ip Andrew , Alese Olatunji B. , Akce Mehmet , Wu Christina , Qu Yuesheng , Maithel Shishir K. , Kooby David , Cardona Kenneth , Sarmeinto Juan M. , El-Rayes Bassel F.
Published: July 2019

Objectives

Pancreatic cancer (PDAC) with localized stage includes resectable (RPC), borderline resectable (BRPC), or locally advanced unresectable (LAPC). Standard of care for RPC is adjuvant chemotherapy. There are no prospective randomized trials for best treatment of BRPC and LAPC. We evaluate the impact of induction chemotherapy on localized PDAC.

Methods

Charts of PDAC patients treated at Emory University between 2009 and 2016 were reviewed. The primary end point was overall survival (OS).

Results

A total of 409 localized PDACs were identified. Resectability was prospectively determined at a multidisciplinary tumor conference. Median age was 67 years (range, 30–92 years), 49% were male, 66% were white, 171 had RPC, 131 had BRPC, and 107 had LAPC. Median OSs for RPC, BRPC, and LAPC were 19.5, 16.1, and 12.7 months, respectively. Type of chemotherapy and age were predictors of OS. Induction chemotherapy was used in 106 with BRPC (81%) and 74 with RPC (56.5%); patients with BRPC who received combination chemotherapy and resection had a median OS of 31.5 compared with 19.5 months in patients with RPC (P = 0.0049). Patients with LAPC had a median OS of 12.7 months.

Conclusions

In patients with BRPC who undergo resection after induction treatment, the OS was significantly better than in patients with RPC. Neoadjuvant treatment should be considered for all localized PDACs.
Correlation of DOTATOC Uptake and Pathologic Grade in Neuroendocrine Tumors
Authors: Chan Hilary , Moseley Christian , Zhang Li , Bergsland Emily K. , Pampaloni Miguel Hernandez , Van Loon Katherine , Hope Thomas A.
Published: July 2019

Objectives

68Gallium (Ga)–DOTATOC is a somatostatin analog used to detect neuroendocrine tumors (NETs). Ki-67 proliferation index (Ki-67 PI) has been established as a prognostic factor in NETs. We aimed to evaluate whether a correlation exists between Ki-67 PI and somatostatin receptor positron emission tomography (SSTR-PET) uptake.

Methods

We retrospectively reviewed 238 DOTATOC PET scans between 2014 and 2016. Patients were excluded if DOTATOC PET was performed more than 365 days from the date of biopsy. Maximum standardized uptake values (SUVmax) of SSTR-PET from biopsied lesions were measured and correlated with Ki-67 PI using the Pearson correlation coefficient.

Results

Among 110 lesions from 90 patients, DOTATOC PET had 92.7% sensitivity and 100% specificity (102 true positives, 8 false negatives) for detection of NETs. Among 63 lesions from 54 patients with Ki-67 PI available, there were 27 grade 1 lesions [median Ki-67 PI, 1.0%; interquartile range (IQR), 1.0–2.0], 30 grade 2 lesions (median, Ki-67 PI 7.5%; IQR, 5–10), and 6 grade 3 lesions (median Ki-67 PI, 30%; IQR, 26–34). There was a correlation between Ki-67 PI and SUVmax (r
2 = −0.3, P = 0.018).

Conclusions

Our analysis demonstrates an inverse correlation between Ki-67 PI and SUVmax in NETs. Somatostatin receptor–PET provides additional information that can help guide management of NETs.
New-Onset Diabetes Mellitus After Chronic Pancreatitis Diagnosis
Authors: Zhu Xiangyun , Liu Dechen , Wei Qiong , Lin Hao , Zhi Mengmeng , Chen Yuling , Qi Liang , Waldron Richard T. , Lugea Aurelia , Pandol Stephen J. , Li Ling
Published: July 2019

Objectives

The aim of this study was to assess the occurrence of new-onset diabetes mellitus (DM) after chronic pancreatitis (CP) diagnosis via systematic review and meta-analysis.

Methods

A systematic review of literature and meta-analysis of relevant reports were performed. The primary outcome measures studied were newly diagnosed DM and DM treated with insulin. For the binary outcomes, pooled prevalence and 95% confidence interval (CI) were calculated.

Methods

Fifteen studies involving 8970 patients were eligible. The incidence of new-onset DM after CP diagnosis was 30% (95% CI, 27%–33%). Among all patients, 17% (95% CI, 13%–22%) developed insulin-dependent new-onset DM. The prevalence of newly diagnosed DM after CP diagnosis increased from 15% within 36 months to 33% after 60 months. The proportion of alcoholic CP, sex, age, and body mass index had minimal effect on the studied outcomes.

Conclusions

This systematic review identified a clinically relevant risk of new-onset DM after CP diagnosis. Therefore, patients should be informed of the risk of DM and monitored.
The Importance of a Conjoint Analysis of Tumor-Associated Macrophages and Immune Checkpoints in Pancreatic Cancer
Authors: Xu Jun-Ying , Wang Wang-Sheng , Zhou Jing , Liu Chao-Ying , Shi Jing-Ling , Lu Pei-Hua , Ding Jun-Li
Published: July 2019

Objectives

Tumor-associated macrophages are dominant players in establishing the inmmunosuppressive microenvironment in pancreatic ductal adenocarcinoma (PDAC). Immune checkpoint inhibitor monotherapy has achieved limited clinical effectiveness. To date, the interaction of macrophages and checkpoint regulators and their correlation with clinicopathologic characteristics in PDAC have been largely unavailable.

Methods

Macrophages and immune checkpoint expression were assessed by immunohistochemistry from 80 PDAC samples. Clinicopathologic features and the prognostic value of each marker were evaluated. In vitro changes in the expression of immune markers in cocultured macrophages and PDAC cells were detected by Western blot and immunosorbance assays.

Results

The macrophages marker CD163 and the checkpoint marker programmed death-ligand 1 (PD-L1) remained as the independent prognostic factors for overall survival (hazard ratio, 2.543; P = 0.017 and hazard ratio, 2.389; P = 0.021). Furthermore, integrated analysis of CD163 and PD-L1 served as more optimal indicators of survival (P = 0.000). In vitro coculture of macrophages and PDAC cells significantly increased the expression of CD163 and PD-L1, compared with monocultured counterpart (P < 0.05).

Conclusions

Combined analysis of CD163 and PD-L1 was enhanced indicators of survival in PDAC patients. The interaction of macrophages and immune checkpoints implied the value of the combination therapy.
Using the Delphi Technique to Determine Core Components of a Nurse Competency Program
Authors: Boyer Susan , Mann-Salinas Elizabeth , Valdez-Delgado Krystal , VanFosson Christopher
Published: July 2019

This modified Delphi study determined consensus on core nurse competency program components that apply across the continuum of transition to initial practice, to new specialty practice, to a new role, or within general nursing orientation. The literature review found no published agreement on support and systems for universal transition programs. This broad-based study addressed this gap by identifying core elements within a competency or transition program and then ranking their importance within program structure.
Get In, Get Tested, Get Care: STD Services in Urban Urgent Care Centers
Authors: Williams Samantha P. , Kinsey Jennine , Carry Monique G. , Terry Latasha , Wells Joy , Kroeger Karen
Published: July 2019

Background

Recent evidence indicates increased use of urgent care centers (UCCs) for sexually transmitted disease (STD) testing. We sought to learn more about STD services in UCCs in a large metropolitan area.

Method

Using a modified rapid gap assessment approach, we interviewed staff from 19 UCCs in metro Atlanta, GA. The UCCs were identified using two online search engines. We focused on a 50-mile radius around Atlanta. We then excluded duplicates and closed UCCs, and the ones outside Atlanta's five contiguous counties. Using a prioritization process, we visited UCCs in or adjacent to areas with mid to high local STD morbidity, or facilities from which STD cases were reported the year prior. We collected checklist-based data on STD testing, treatment, and preventive services, as well as supportive services (eg, substance use/mental health referrals). Checklist data, notes, and open-ended questions were summarized and analyzed descriptively.

Results

All UCCs (n = 19) reported offering basic to comprehensive STD testing. Although most could treat on-site for chlamydia and gonorrhea, most relied on referrals, or prescriptions and “return to facility” practices to treat syphilis. Sources for STD information/management included the health department/Centers for Disease Control and Prevention, online medical sites, and electronic medical record embedded information. Challenges UCCs acknowledged included staying up-to-date with treatment guidance and laboratory reporting requirements, inadequate time for sexual risk reduction counseling, and linking patients with extended care needs (eg, HIV+ case management, supportive services), or following up with patients.

Conclusions

Urgent cares are STD testing resources. Service availability varies, but opportunities exist to enhance STD services in UCC settings and in communities.
The Effect of Levosimendan Versus Milrinone on the Occurrence Rate of Acute Kidney Injury Following Congenital Heart Surgery in Infants: A Randomized Clinical Trial*
Authors: Thorlacius Elin M. , Suominen Pertti K. , Wåhlander Håkan , Keski-Nisula Juho , Vistnes Maria , Ricksten Sven-Erik , Synnergren Mats , Romlin Birgitta S. , Castellheim Albert
Published: July 2019

Objectives:

It has been shown that, in contrast to other inotropic agents, levosimendan improves glomerular filtration rate after adult cardiac surgery. The aim of this study was to investigate the efficacy of levosimendan, compared with milrinone, in preventing acute kidney dysfunction in infants after open-heart surgery with cardiopulmonary bypass.

Design:

Two-center, double-blinded, prospective, randomized clinical trial.

Setting:

The study was performed in two tertiary pediatric centers, one in Sweden (Gothenburg) and one in Finland (Helsinki).

Patients:

Infants between 1 and 12 months old, diagnosed with Tetralogy of Fallot, complete atrioventricular septal defect or nonrestrictive ventricular septal defect, undergoing total corrective cardiac surgery with cardiopulmonary bypass.

Interventions:

Seventy-two infants were randomized to receive a perioperative infusion of levosimendan (0.1 µg/kg/min) or milrinone (0.4 µg/kg/min). The infusion was initiated at the start of cardiopulmonary bypass and continued for 26 hours.

Measurements and Main Results:

The primary outcome variable was the absolute value of serum creatinine data on postoperative day 1. Secondary outcomes included the following: 1) acute kidney injury according to the serum creatinine criteria of the Kidney Diseases: Improving Global Outcomes; 2) acute kidney injury with serum creatinine corrected for fluid balance; 3) plasma neutrophil gelatinase-associated lipocalin; 4) cystatin C; 5) urea; 6) lactate; 7) hemodynamic variables; 8) use of diuretics in the PICU; 9) need of dialysis; 10) length of ventilator therapy; and 11) length of PICU stays. There was no significant difference in postoperative serum creatinine between the treatment groups over time (p = 0.65). The occurrence rate of acute kidney injury within 48 hours was 46.9% in the levosimendan group and 39.5% in the milrinone group (p = 0.70). There were no significant differences in other secondary outcome variables between the groups.

Conclusions:

Levosimendan compared with milrinone did not reduce the occurrence rate of acute kidney injury in infants after total corrective heart surgery for atrioventricular septal defect, ventricular septal defect, or Tetralogy of Fallot.
Correlation Between Apparent Diffusion Coefficient Values of the Renal Parenchyma and Estimated Glomerular Filtration Rates on 3-T Diffusion-Weighted Echo-Planar Magnetic Resonance Imaging
Authors: Thiravit Shanigarn , Suwanchatree Paphatsanan , Skulratanasak Peenida , Thiravit Phakphoom , Suvannarerg Voraparee
Published: July 2019

Objective

To evaluate the relationship between the apparent diffusion coefficient (ADC) values of renal parenchyma and estimated glomerular filtration rates (eGFR).

Methods

Data on 216 patients examined by 3-T magnetic resonance imaging for various reasons were retrospectively collected.

Results

There was a significant linear correlation between the ADC values and eGFRs (r = 0.254, P < 0.001). The ADC values in patients with an eGFR of less than 60 mL/min per 1.73 m2 were significantly lower than those with an eGFR of 60 mL/min per 1.73 m2 or greater. The mean ADC value of patients with grouped stage 2 disease was significantly higher than those with grouped stage 3 of chronic kidney disease (P < 0.01).

Conclusions

The ADC value of renal parenchyma may be a promising marker for the determination of patients with normal to mild reduction in renal function (eGFR ≥60 mL/min per 1.73 m2) versus those with a moderate to severe reduction in renal function (eGFR <60 mL/min per 1.73 m2).
Computed Tomography–based Body Composition Analysis and Its Role in Lung Cancer Care
Authors: Troschel Amelie S. , Troschel Fabian M. , Best Till D. , Gaissert Henning A. , Torriani Martin , Muniappan Ashok , Van Seventer Emily E. , Nipp Ryan D. , Roeland Eric J. , Temel Jennifer S. , Fintelmann Florian J.
Published: July 2019

Body composition analysis, also referred to as analytic morphomics, morphomics, or morphometry, describes the measurement of imaging biomarkers of body composition such as muscle and adipose tissue, most commonly on computed tomography (CT) images. A growing body of literature supports the use of such metrics derived from routinely acquired CT images for risk prediction in various patient populations, including those with lung cancer. Metrics include cross-sectional area and attenuation of skeletal muscle and subcutaneous, visceral, and intermuscular adipose tissue. The purpose of this review is to provide an overview of the concepts, definitions, assessment tools, segmentation techniques and associated pitfalls, interpretation of those measurements on chest and abdomen CT, and a discussion of reported outcomes associated with body composition metrics in patients with early-stage and advanced lung cancer.
Recent research on the social network concept and cancer
Authors: Jones Eric C. , Storksdieck Martin
Published: July 2019

Purpose of review

This review covers articles in 2018 and early 2019 that employed the concept of networks and social interactions in research on how patients with cancer cope, receive and respond to medical treatment and allied support. The use of social aspects, and more formally the method of social network analysis for research on social aspects of cancer is quite new. Although we paid special attention to articles that used formal social network analysis, we noted that those articles cover just over a quarter of the material we reviewed. Most articles that incorporated social aspects of cancer did not intend to formalize those aspects but treated the network concept as a way to characterize social support, social influence, or social responsibilities.

Recent findings

We identified 74 recent articles that mentioned the network concept for research about cancer, excluding gene interaction networks. Of those 74 articles, 21 measured specific relationships between individuals or organizations and/or attributes of those individuals or organizations connected to participants or to others. Primary foci of the network analysis and nonnetwork analysis studies were breast cancer, social support for patients, and they usually at least considered sex and age of the cancer patients/survivors. Social media received some attention, and there were some studies considering quality of life and mental health. Among network analysis studies, size of network and number of people providing emotional/informational/instrumental support occurred in more than a couple studies but not the majority. There was little similarity among studies – whether using network analysis or not – suggesting that theory building and methodological development are in early stages.

Implications of the review include opportunities for more systematic research using the network concept to understand people's experience of cancer as well as research on cancer. Researchers can make considerable contributions at this stage in the field's development, and practitioners can help develop interventions that make fuller use of the insights of social network analysis.
Gaussian process emulation to accelerate parameter estimation in a mechanical model of the left ventricle: a critical step towards clinical end-user relevance
Authors: Noè Umberto , Lazarus Alan , Gao Hao , Davies Vinny , Macdonald Benn , Mangion Kenneth , Berry Colin , Luo Xiaoyu , Husmeier Dirk
Published: July 2019

In recent years, we have witnessed substantial advances in the mathematical modelling of the biomechanical processes underlying the dynamics of the cardiac soft-tissue. Gao
et al.
(Gao
et al.
2017
J. R. Soc. Interface
14
, 20170203 (
doi:10.1098/rsif.2017.0203
)) demonstrated that the parameters underlying the biomechanical model have diagnostic value for prognosticating the risk of myocardial infarction. However, the computational costs of parameter estimation are prohibitive when the goal lies in building real-time clinical decision support systems. This is due to the need to repeatedly solve the mathematical equations numerically using finite-element discretization during an iterative optimization routine. The present article presents a method for accelerating the inference of the constitutive parameters by using statistical emulation with Gaussian processes. We demonstrate how the computational costs can be reduced by about three orders of magnitude, with hardly any loss in accuracy, and we assess various alternative techniques in a comparative evaluation study based on simulated data obtained by solving the left ventricular model with the finite-element method, and real magnetic resonance images data for a human volunteer.
Digital gene expression analyses of mammary glands from meat ewes naturally infected with clinical mastitis
Authors: Li Taotao , Gao Jianfeng , Zhao Xingxu , Ma Youji
Published: July 2019

Clinical mastitis in sheep has gravely restrained production performance for a long time. Knowledge of mechanisms of its pathogenesis and resistance in meat sheep mammary gland with clinical mastitis are not yet understood, especially for clinical mastitis caused by natural infection. In this work, RNA-sequencing was firstly used to screen the differentially expressed genes (DEGs) in clinical mastitic mammary tissues (CMMTs) when compared with healthy mammary tissues (HMTs) from meat sheep flocks. We identified 420 DEGs including 316 upregulated and 104 downregulated genes in CMMTs. Gene ontology annotation revealed these DEGs were mainly engaged in immune response and inflammation response. Pathway enrichment showed they were primarily enriched in pathways relevant to inflammation, immune response and metabolism. Alternative splicing analysis showed most common differential splicing genes in CMMTs and HMTs were implicated in immune response. Immunostaining for three immune response-related proteins encoded by DEGs were mainly observed in mammary epithelium from both CMMTs and HMTs, and their positive signals were more intensive in CMMTs than those in HMTs. These findings provide experimental basis and reference for further researching the molecular genetic mechanisms, particularly immune defence mechanisms, of sheep mammary gland during clinical mastitis.
The bold and the sperm: positive association between boldness and sperm number in the guppy
Authors: Gasparini Clelia , Speechley Elizabeth M. , Polverino Giovanni
Published: July 2019

Assessing the consequences of personality traits on reproductive success is one of the most important challenges in personality studies and critical to understand the evolutionary implications of behavioural variability among animals. Personality traits are typically associated with mating acquisition in males, and, hence, linked to variation in their reproductive success. However, in most species, sexual selection continues after mating, and sperm traits (such as sperm number and quality) become very important in determining post-mating competitive success. Here, we investigate whether variation in personality traits is associated with variation in sperm traits using the guppy (Poecilia reticulata), a species with high levels of sperm competition. We found a positive association between boldness and sperm number but not sperm velocity, suggesting that bolder males have increased post-copulatory success than shyer individuals. No association was found between exploration and sperm traits. Our work highlights the importance of considering post-copulatory traits when investigating fitness consequences of personality traits, especially in species with high levels of female multiple matings and hence sperm competition.
Framework for rational donor selection in fecal microbiota transplant clinical trials
Authors: Duvallet Claire , Zellmer Caroline , Panchal Pratik , Budree Shrish , Osman Majdi , Alm Eric
Published: July 2019

Early clinical successes are driving enthusiasm for fecal microbiota transplantation (FMT), the transfer of healthy gut bacteria through whole stool, as emerging research is linking the microbiome to many different diseases. However, preliminary trials have yielded mixed results and suggest that heterogeneity in donor stool may play a role in patient response. Thus, clinical trials may fail because an ineffective donor was chosen rather than because FMT is not appropriate for the indication. Here, we describe a conceptual framework to guide rational donor selection to increase the likelihood that FMT clinical trials will succeed. We argue that the mechanism by which the microbiome is hypothesized to be associated with a given indication should inform how healthy donors are selected for FMT trials, categorizing these mechanisms into four disease models and presenting associated donor selection strategies. We next walk through examples based on previously published FMT trials and ongoing investigations to illustrate how donor selection might occur in practice. Finally, we show that typical FMT trials are not powered to discover individual taxa mediating patient responses, suggesting that clinicians should develop targeted hypotheses for retrospective analyses and design their clinical trials accordingly. Moving forward, developing and applying novel clinical trial design methodologies like rational donor selection will be necessary to ensure that FMT successfully translates into clinical impact.
The effectiveness of digital technology interventions to reduce loneliness in adult people: A protocol for a systematic review and meta-analysis
Authors: Shah Syed Ghulam Sarwar , Nogueras David , van Woerden Hugo Cornelis , Kiparoglou Vasiliki
Published: July 2019

Introduction

Loneliness is an emerging public health problem, which is associated with social, emotional, mental and physical health issues. The application of digital technology (DT) interventions to reduce loneliness has increased in recent years. The effectiveness of DT interventions needs to be assessed systematically.

Methods and analysis

Aim

To undertake a systematic review and meta-analysis on the effectiveness of digital technology interventions to reduce loneliness among adult people.

Design

systematic review and meta-analysis.

Data sources

Five leading online bibliographic databases: PubMed, Medline, CINAHL, EMBASE, and Web of Science.

Publication period

1 January 2010 to 30 April 2019.

Inclusion criteria

Primary studies involving the application of digital technology interventions to reduce loneliness, involving adult participants (aged 18 years and more) and published in the English language.

Search strategy

Literature searches using a priory list of keywords, involvement of two independent researchers in article screening, short listing and data extraction using a predefined template based on the population, intervention(s), comparator(s) and outcome(s) (PICO) framework.

Synthesis and meta-analysis

A narrative summary of the characteristics of included studies, findings by the type of DT intervention, and the age, gender and ethnicity of participants. A meta-analysis by the type of DT intervention and determination of effect sizes.

Quality of evidence and bias

Quality of evidence assessed the RoB 2.0 (revised tool for Risk of Bias in randomized trials) and ROBINS-I (Risk Of Bias in Non-randomized Studies - of Interventions) tools for randomized control trials and non-randomized studies respectively. Heterogeneity between studies determined by the I2 and Cochran’s Q statistics and publication bias checked with funnel plots and the Egger’s test.

Patients and public involvement

None

Ethics and dissemination

Ethics approval was not required for writing this protocol. The findings will be disseminated through the publication of research articles and conference presentations.

PROSPERO Registration Number

CRD42019131524.

Article Summary

Strengths and limitations of this study

The main strength of this study includes a systematic assessment of evidence on the effectiveness of digital technology interventions to reduce loneliness, which is imperative from the health and social care and public health perspectives.

Another strength of the study is the involvement of two independent researchers (and a third researcher as an arbitrator) involved in the identification, screening, inclusion and extraction of on a predefined template using the PICO framework.

Limitations may include missing identification of additional relevant studies due to the application of selection filters such as the publication years and English as the publication language.
Robotic middle ear access for cochlear implantation: first in man
Authors: Caversaccio Marco , Wimmer Wilhelm , Anso Juan , Mantokoudis Georgios , Gerber Nicolas , Rathgeb Christoph , Schneider Daniel , Hermann Jan , Wagner Franca , Scheidegger Olivier , Huth Markus , Anschuetz Lukas , Kompis Martin , Williamson Tom , Bell Brett , Gavaghan Kate , Weber Stefan
Published: July 2019

To demonstrate the feasibility of robotic middle ear access in a clinical setting, nine adult patients with severe-to-profound hearing loss indicated for cochlear implantation were included in this clinical trial. A keyhole access tunnel to the tympanic cavity and targeting the round window was planned based on preoperatively acquired computed tomography image data and robotically drilled to the level of the facial recess. Intraoperative imaging was performed to confirm sufficient distance of the drilling trajectory to relevant anatomy. Robotic drilling continued toward the round window. The cochlear access was manually created by the surgeon. Electrode arrays were inserted through the keyhole tunnel under microscopic supervision via a tympanomeatal flap. All patients were successfully implanted with a cochlear implant. In 9 of 9 patients the robotic drilling was planned and performed to the level of the facial recess. In 3 patients, the procedure was reverted to a conventional approach for safety reasons. No change in facial nerve function compared to baseline measurements was observed. Robotic keyhole access for cochlear implantation is feasible. Further improvements to workflow complexity, duration of surgery, and usability including safety assessments are required to enable wider adoption of the procedure.
The chromatin remodeler SMARCD3 regulates cell cycle progression and its expression predicts survival outcome in ER+ breast cancer
Authors: Tropée Romain , de la Peña Avalos Bárbara , Gough Madeline , Snell Cameron , Duijf Pascal H.G. , Dray Eloïse
Published: July 2019

Chromatin remodeling plays an essential role in regulating transcriptional networks and timing of gene expression. Chromatin remodelers such as SWItch/Sucrose Non-Fermentable (SWI/SNF) harbor many protein components, with the catalytic subunit providing ATPase activity to displace histones along or from the DNA molecules, and associated subunits ensuring tissue specificity and transcriptional or co-transcriptional activities. Mutations in several of the SWI/SNF subunits have been linked to cancer. Here, we describe how SMARCD3/Baf60c expression is associated with hormone positive (ER+) breast cancer. The level SMARCD3, as detected by immunohistochemistry in breast cancer patient samples, is correlated with differential long-term disease-free survival. In contrast, the expression level of SMARCD1/Baf60a and SMARCD2/Baf60b, which are mutually exclusive within the SWI/SNF complex and have a partially redundant function, lacks predictive value in breast cancer patient samples. Lower proliferation rates are observed in SMARCD3 depleted cells, which reflects a failure to fully progress through G2/M, and an increase in endoreplication. In the absence of SMARCD3, p21 accumulates in cells but does not halt the cell cycle, and DNA damage accumulates and remains unrepaired. Taken together, our data begin to explain why ER+ breast cancer patients with low SMARCD3 expressing tumors exhibit reduced survival rates compared to patients expressing normal or higher levels of SMARCD3. SMARCD3 might act as a tumor suppressor role through regulation of cell cycle checkpoints and could be a reliable and specific breast cancer prognostic biomarker.

Significance

Mutations in chromatin remodelers are a leading cause of cancer. Estrogen Receptor positive (ER+) breast cancers represent approximately 80% of all cases diagnosed. Although these tumors can be treated with hormone therapy, most breast cancer fatalities occur in ER+ breast cancer patients, due to metastasis. Low expression of SMARCD3 in ER+ cancer is associated with diminished survival rates. As such, SMARCD3 could be used as a predictive biomarker for survival. In addition, we have identified a role for SMARCD3 in the cell cycle, which could at least partially explain its protective role in breast cancer. While catalytic subunits are often viewed as the major components in chromatin remodeling function, we show here new evidence that mutations or silencing of SMARCD3 may also contribute to genomic instability and thus development of breast cancer.
Conformity to Bergmann’s rule in birds depends on nest design and migration
Authors: Mainwaring Mark C. , Street Sally E.
Published: July 2019

Species’ geographic ranges and range limits are thought to be determined by climate, and across climatic gradients the morphology of populations varies non-randomly. Ecogeographic rules seek to characterise such variation, with Bergmann’s rule positing that organisms inhabiting colder environments are typically larger-bodied than those inhabiting warmer environments. While Bergmann’s rule has been supported across a range of taxonomic groups, how organisms’ behaviour may moderate its effect remains unclear. Here we investigate whether conformity to Bergmann’s rule among birds of the Western Palearctic varies in relation to nest design and migratory behaviour, using phylogenetic comparative analyses. We test predictions using data on nest structure and location, migration, body mass, latitudinal distribution, annual mean temperature and phylogenetic relatedness for a sample of >500 species. We find that conformity to Bergmann’s rule depends strongly on migratory behaviour: non-migratory species breeding at colder, more northerly latitudes are larger-bodied, while body mass is unaffected by climate in short- and long-distance migrants. Among non-migratory species, conformity to Bergmann’s rule depends, further, on nest design: species with more open nests, who are thus most exposed to adverse climatic conditions while breeding, conform most strongly to Bergmann’s rule. Our findings suggest that enclosed nesting and migration allow smaller bodied species to breed in colder environments than their body size would otherwise allow. Therefore, we conclude that organisms’ behaviour can strongly affect exposure to environmental selection pressures.
IsoSeq transcriptome assembly of C3panicoid grasses provides tools to study evolutionary change in the Panicoideae
Authors: Carvalho Daniel S. , Schnable James C.
Published: July 2019

The number of plant species with genomic and transcriptomic data has been increasing rapidly. The grasses – Poaceae – have been well represented among species with published reference genomes. However, as a result the genomes of wild grasses are less frequently targeted by sequencing efforts. Sequence data from wild relatives of crop species in the grasses can aid the study of domestication, gene discovery for breeding and crop improvement, and improve our understanding of the evolution of C4photosynthesis. Here we used long read sequencing technology to characterize the transcriptomes of three C3panicoid grass species:Dichanthelium oligosanthes, Chasmanthium laxum, andHymenachne amplexicaulis. Based on alignments to the sorghum genome we estimate that assembled consensus transcripts from each species capture between 54.2 and 65.7% of the conserved syntenic gene space in grasses. Genes co-opted into C4were also well represented in this dataset, despite concerns that, because these genes might play roles unrelated to photosynthesis in the target species, they would be expressed at low levels and missed by transcript-based sequencing. A combined analysis using syntenic orthologous genes from grasses with published reference genomes and consensus long read sequences from these wild species was consistent with previously published phylogenies. It is hoped that this data, targeting under represented classes of species within the PACMAD grasses – wild species and species utilizing C3photosynthesis – will aid in futurue studies of domestication and C4evolution by decreasing the evolutionary distance between C4and C3species within this clade, enabling more accurate comparisons associated with evolution of the C4pathway.