bluuebunny/crossref_metadata_2025 huggingface dataset:
Utility of post-liver transplantation MELD and delta MELD in predicting early and late mortality
Authors: Zakareya Talaat , Abbasy Mohammed , Abdel-Razek Wael , Elsiesy Hussein , Abal Khail Faisal , Al Sebayel Mohammed , Waked Imam
Published: September 2017

Introduction

The performance of early post-liver transplantation (post-LT) model for end-stage liver disease (MELD) or even its dynamic changes over time (ΔMELD) in predicting the mortality after LT is still controversial.

Aim

The aim of this study was to assess the ability of absolute and ΔMELD calculated at days 7 and 30 after LT to predict 1- and 5-year mortality.

Patients and methods

Data of 209 consecutive patients who underwent LT in two centers were reviewed. Patients who received LT for hepatocellular carcinoma were excluded, as well as those who did not survive for at least 1 month. MELD and ∆MELD were calculated for each patient at 7 and 30 days after LT.

Results

One hundred fifty-six patients were included, mostly male [104 (66.7%)] with a mean age of 51.9±8.8 years. The main indications for transplantation were decompensated hepatitis C virus-related liver cirrhosis [138 (88.5%)] and hepatitis C and B virus co-infection [10 (6.4%)]. Grafts were obtained from 104 living donors and 52 deceased donors. Survival at 1 and 5 years was 89.7 and 85.9%, respectively, with a mean survival of 52.3±1.5 months. In univariate analysis, both absolute and ΔMELD at postoperative days 7 and 30 significantly predicted 1- and 5-year post-LT mortality. In multivariate analysis, MELD at postoperative day 30 was significantly associated with 1- (odds ratio: 1.24, 95% confidence interval: 1.14–1.35, P<0.0001) and 5-year mortality (odds ratio: 1.23, 95% confidence interval: 1.14–1.33, P<0.0001). The area under the curve for MELD at 30 days post-LT in the prediction of mortality was 0.823 (P=0.01) at 1 year and 0.812 (P<0.001) at 5 years. A cutoff of post-LT day 30 MELD less than 10 could predict mortality with a sensitivity and specificity of 90 and 68.1% at 1 year and 81.3 and 69.7% at 5 years, respectively.

Conclusion

Failure of the MELD score to decline over the first postoperative month to less than 10 is a significant predictor of both early and late post-LT mortality.
Comparison of correlations between lipid profile and different computed tomography fatty liver criteria in the setting of incidentally noted fatty liver on computed tomography examinations
Authors: Jawahar Anugayathri , Gonzalez Beverly , Balasubramanian Neelam , Adams William , Goldberg Ari
Published: September 2017

Purpose

The aim of this study was to compare the correlations between computed tomography (CT) criteria for hepatic steatosis and lipid profile values when hepatic steatosis is incidentally detected.

Participants and methods

This is an institutional Review Board-approved, HIPPA-compliant, retrospective study of abdominal CT scans in 200 randomly selected patients who had either nonenhanced CT (NECT) or contrast-enhanced CT (CECT) studies with reported fatty liver. The participants were matched for age, sex, and ethnicity with 200 patients with nonfatty liver. For NECT, four different criteria have been proposed in the literature to diagnose fatty liver: (i) liver Hounsfield Units (HU) less than 48 HU, (ii) ratio of liver to spleen HU less than 0.8, (iii) HU difference between liver and spleen less than −10, and (iv) hepatic vessel HU greater than or equal to liver HU. For CECT, the criteria was attenuation difference between liver and spleen HU, in the portal venous phase of up to −20 to −25 HU. Laboratory results (low-density lipoprotein, high-density lipoprotein, triglycerides) were documented. Matched analyses and conditional logistic regression analysis were carried out for matched variables.

Results

There were statistically significant differences in triglyceride values, between the cases and controls (P=0.02), when all criteria were considered. Also, statistically significant differences were found between cases and controls on the basis of NECT criterion 2 and high-density lipoprotein (P=0.04), as well as CECT criteria and triglyceride levels (P=0.02). In addition, the data indicate that criteria for steatosis on CECT may be more broad than traditionally utilized.

Conclusion

Incidental reporting of fatty liver on NECT/CECT should prompt consideration of clinical follow-up and lipid profile testing in an otherwise asymptomatic patient. Additional metrics for the diagnosis of steatosis in CECT exam should also be considered.
Triglyceride-lowering trials
Authors: Keech Anthony C. , Jenkins Alicia J.
Published: September 2017

Purpose of review

We provide an overview of current evidence about the independent role of high triglyceride levels for cardiovascular risk and for acute pancreatitis.

Recent findings

Natural experiments of Mendelian randomization have given us a deeper understanding about the molecular pathways involved in triglyceride metabolism. Individuals with low-triglyceride levels generally have lower rates of cardiovascular disease (CVD). There has been a significant growth in the development of new agents that modulate enzymes involved in a variety of aspects of triglyceride packaging into VLDL or chylomicron particles, and triglyceride catabolism. Antisense inhibitors of apolipoprotein CIII are being tested, as are a variety of agents designed to increase lipoprotein lipase activity. Large-scale trials are underway with purified fatty acid (FA) formulations in over 20 000 individuals in aggregate. A large study of a new fibrate is underway.

A focus on patients with elevated triglyceride levels is a new paradigm not previously the focus of large trials. Clinical outcome data on cardiovascular risk reductions remains sparse. Some drugs are already approved for use in rare inherited disorders predisposing to severe hypertriglyceridaemia and acute pancreatitis. Safety and costs issues are critical.
Developing operational items for the International Classification of Functioning, Disability and Health Rehabilitation Set: the experience from China
Authors: Gao Yan , Yan Tiebin , You Liming , Li Kun
Published: September 2017

The International Classification of Functioning, Disability and Health (ICF) Rehabilitation Set is proposed as a tool to measure functioning among a clinical population in Chinese rehabilitation services. It needs to be applied in a transparent and reliable way and considered from a measurement perspective. The aim of this study was to develop items operationalizing the ICF Rehabilitation Set to enhance the standardized and unified assessment in varied clinical settings. A list of proposed operational items was generated by (i) linking the items of four standard assessment instruments; (ii) literature review; and (iii) self-development. The candidate operational items were then evaluated by Chinese experts in rehabilitation medicine. One hundred and sixty-six operational items were generated using the three approaches and 54 were evaluated in the formal expert survey. Finally, 30 experts validated nine items from the assessment instruments, two found in the literature and 19 self-developed items for operationalizing the ICF Rehabilitation Set. The 30 operational items validated could potentially facilitate the implementation of the ICF Rehabilitation Set in clinical settings and provide a reference point for future research.
The Relation Between Mastery, Anticipated Stigma and Depression Among Older Adults in a Primary Care Setting
Authors: Raeifar Elmira , Halkett Ashley , Lohman Matthew C. , Sirey Jo Anne
Published: September 2017

The current study evaluates the interaction between mastery, depression, and psychological barriers to care among older adults in a primary care setting, including the longitudinal effects of anticipated stigma and mastery on depressive symptoms. The sample was composed of 70 depressed older adults (age ≥ 60) who were newly recommended antidepressant treatment by their physicians. This cohort is part of a larger study examining the usefulness of the Treatment Initiation and Participation program to improve medication adherence. Anticipated stigma significantly predicted greater depression among older adults with low mastery, but not among those with high mastery. Mastery was found to moderate the relationship between anticipated stigma and depressive symptoms among older adults. Increased mastery over 28 weeks was also associated with greater reductions in depressive symptoms at follow-up, controlling for antidepressant strength and adherence. Bolstering older adults' sense of mastery in treatment could provide a source of resilience for older adults facing depression.
Bipolar Disorder and Cognitive Dysfunction
Authors: Cipriani Gabriele , Danti Sabrina , Carlesi Cecilia , Cammisuli Davide Maria , Di Fiorino Mario
Published: September 2017

The aim of this article was to describe the current evidence regarding phenomenon of cognitive functioning and dementia in bipolar disorder (BD). Cochrane Library and PubMed searches were conducted for relevant articles, chapters, and books published before 2016. Search terms used included “bipolar disorder,” “cognitive dysfunction,” and “dementia.” At the end of the selection process, 159 studies were included in our qualitative synthesis. As result, cognitive impairments in BD have been previously considered as infrequent and limited to the affective episodes. Nowadays, there is evidence of stable and lasting cognitive dysfunctions in all phases of BD, including remission phase, particularly in the following domains: attention, memory, and executive functions. The cause of cognitive impairment in BD raises the question if it subtends a neurodevelopmental or a neurodegenerative process. Impaired cognitive functioning associated with BD may contribute significantly to functional disability, in addition to the distorted affective component usually emphasized.
Food Gums
Authors: Clemens Roger , Pressman Peter
Published: September 2017

Food scientists use hundreds of ingredients to assure the safety, stability, and nutritional quality of the food supply. Many of these ingredients with a rich history of safe use and consumption are now the target of consumer skepticism. Among those ingredients is carrageenan, the safety of which has been supported by numerous global regulatory agencies. Despite the demonstrated safety of carrageenan, some recent reports suggest the contrary. This brief review provides the scientific context of carrageenan use and safety. The preponderance of evidence indicates that, when carrageenan is used and consumed as intended, there are no any health risks, even when consumed by infants.
Classification of Thinness, Overweight, and Obesity as a Function of the Body Mass Index and Fat Percentiles in Preschool and Primary School Children
Authors: Rodrigues Jessica , Rocha Ada
Published: September 2017

Introduction

Portugal is one of the European countries showing an increase in mortality and morbidity associated with chronic diseases, presenting one of the highest prevalence rates of overweight and obesity among children.

Objective

The aim of this study was to evaluate the prevalence of thinness, overweight, and obesity as a function of the body mass index (BMI) and fat percentiles in preschool and primary school children in a municipality of the center region of Portugal.

Methods

A total of 901 children were evaluated between November 2014 and March 2015. Evaluation included weight, height, waist circumference, and body fatness (total and trunk). Nutritional status was classified based on the Centers for Disease Control and Prevention, BMI percentile by age and gender, and the International Obesity TaskForce (IOTF) cutoff values of BMI.

Results

Of the children evaluated, according to the Centers for Disease Control and Prevention cutoff values, 32.3% were overweight or obese, and from those, 16.2% were obese. According to the fat percentile, the prevalence of overweight was 18.0%, corresponding 6.6% to obese children. Total body fat percentage and trunk fat percentage were 23.5% and 17.8%, respectively.

Conclusion

The prevalences found were quite different depending on the method used. To allow comparisons and more accurately determine prevalence rates of thinness, overweight, and obesity in children, it is necessary to standardize methodologies between studies and between countries.
Effects of Lens-Care Solutions on Hydrogel Lens Performance
Authors: Kitamata-Wong Britney , Yuen Tiffany , Li Wing , Svitova Tatyana , Zhou Yixiu , Lin Meng C.
Published: September 2017

SIGNIFICANCE

Lens care multipurpose solutions (MPSs) can have varying effects on contact lens (CL) surface properties and the corneal epithelium.

PURPOSE

The aim of this study was to investigate the short-term effects of newer MPS on CL comfort and dryness, prelens tear-film stability, and ocular-surface health.In vitrostudy was also performed to assess the effect of MPSs on CL surface properties.

METHODS

Acuvue 2 CLs were soaked in control solution, Clear Care (CC), or test solutions: PureMoist, Biotrue, RevitaLens (RL), or saline solution (SS). Over four visits, subjects were exposed to control solution in one eye and to test solution in the contralateral eye for 2 hours using presoaked CLs. Contact lens comfort and dryness, ocular-surface health assessment, prelens noninvasive tear breakup time, and corneal epithelial permeability measured with fluorometry were assessed. Captive-sessile bubble technique evaluated CL wettability and viscous dragin vitro.

RESULTS

At 10 minutes, mean comfort ± SD with PureMoist (76 ± 22) was lower than CC (86 ± 15,P= .02), Biotrue (92 ± 9,P< .005), RL (90 ± 13,P< .005), and SS (90 ± 14,P< .005). No other difference in comfort or dryness was noted. RevitaLens was associated with greater corneal epithelial permeability than CC (P= .020) and increased corneal staining compared with all MPSs (P< .005 for all). RevitaLens was also associated with longer prelens noninvasive tear breakup than CC (P< .005).In vitroresults agreed with clinical findings of tear-film stability as RL reduced viscous drag. Contact lens surface wettability was enhanced by all MPSs in comparison to SS.

CONCLUSIONS

Differences of MPSs on the ocular surface were foundin vivoandin vitro. RL caused the greatest corneal epithelium disruption but also associated with higher tear-film stability. The effect of MPSs on CL surface propertiesin vitroseems to reflect how MPSs altered prelens tear stability.
Neurobiological Mediators of Squalor-dwelling Behavior
Authors: GUPTA MANAN , BISHNOI RAM J. , SCHILLERSTROM JASON E.
Published: September 2017

Squalor-dwelling behavior has been characterized as living in conditions so unsanitary that feelings of revulsion are elicited among visitors. This behavior is commonly associated with an insensitivity to distress/disgust and a failure to understand the direness of one’s living situation, which leads to social isolation and impairment in quality of life. Etiologically, several associations have been described in the literature, including age-related decline, lower socioeconomic status, and rural dwelling status. Primary neuropsychiatric disorders, such as psychosis, alcoholism, dementia, personality disorders, developmental delays, and learning or physical disabilities are frequently seen in squalor-dwelling individuals. However, none of these disorders seems to be necessary or sufficient to explain the behavior. Neurobiologically, squalor-dwelling behavior has been associated with frontal lobe dysfunction as evidenced by executive dysfunction; however, cognitive impairments also fail to completely explain this behavior. The purpose of this report is to describe a typical case of squalor-dwelling behavior and use it as an example to illustrate the complexity of uncovering the neurobiological basis for this maladaptive personal and public health threat. Neuroimaging findings from our case and a review of the literature point toward decreased activity in the insular cortex and the amygdala as a unifying biological explanation for squalor-dwelling behaviors.
An Unusual Case of Acute Psychosis With Obsessive-Compulsive Features Following Arsenic Poisoning
Authors: WU HANJING E. , ABDEL-GAWAD NOHA M. , GHARBAOUI YASMINE , TEIXEIRA ANTONIO L. , PIGOTT TERESA A.
Published: September 2017

Arsenic exposure, particularly the chronic type, can lead to poisoning with manifestations presenting in multiple organ systems. However, acute psychosis is not a commonly described manifestation of arsenic exposure. In this report, we present the case of a patient who developed acute psychosis with hallucinations, disorganized thinking, and obsessive-compulsive symptoms following chronic occupational arsenic exposure. The patient was treated with the combination of an antipsychotic and an antidepressant and he responded well with significant improvement in both the acute psychosis and obsessive-compulsive symptoms. The authors concluded that patients can develop atypical symptoms, including acute psychosis, following arsenic poisoning. In the case described in this report, the patient also presented with a new onset of obsessive-compulsive symptoms. Given this rare manifestation of arsenic poisoning for which there is no clearly defined treatment regimen, this case suggests that the use of a combination of an antipsychotic and an antidepressant may be considered in the rare event of psychosis with obsessive-compulsive features following arsenic poisoning.
Bias Toward Psychodynamic Therapy: Framing the Problem and Working Toward a Solution
Authors: ABBASS ALLAN , LUYTEN PATRICK , STEINERT CHRISTIANE , LEICHSENRING FALK
Published: September 2017

Although psychodynamic therapy (PDT) is an evidence-based intervention for a broad spectrum of psychiatric conditions, there is often notable bias in the way PDT is depicted both in the popular media and in the scientific literature. This has contributed to a negative view of PDT, which hampers both patient access to this treatment and researcher access to funding for further research on PDT. The adverse effects of these distortions and biases are detrimental not only to PDT but also to the overall field of psychotherapy, raising questions about its credibility. Here we summarize current evidence for PDT, describe existing biases, and formulate a set of recommendations to foster a more balanced perspective on PDT.
Bias Toward Psychodynamic Therapy: Framing the Problem and Working Toward a Solution
Authors: PLAKUN ERIC M.
Published: September 2017

Although psychodynamic therapy (PDT) is an evidence-based intervention for a broad spectrum of psychiatric conditions, there is often notable bias in the way PDT is depicted both in the popular media and in the scientific literature. This has contributed to a negative view of PDT, which hampers both patient access to this treatment and researcher access to funding for further research on PDT. The adverse effects of these distortions and biases are detrimental not only to PDT but also to the overall field of psychotherapy, raising questions about its credibility. Here we summarize current evidence for PDT, describe existing biases, and formulate a set of recommendations to foster a more balanced perspective on PDT.
Neurobiological Mediators of Squalor-dwelling Behavior
Authors: KAHN DAVID A.
Published: September 2017

Squalor-dwelling behavior has been characterized as living in conditions so unsanitary that feelings of revulsion are elicited among visitors. This behavior is commonly associated with an insensitivity to distress/disgust and a failure to understand the direness of one’s living situation, which leads to social isolation and impairment in quality of life. Etiologically, several associations have been described in the literature, including age-related decline, lower socioeconomic status, and rural dwelling status. Primary neuropsychiatric disorders, such as psychosis, alcoholism, dementia, personality disorders, developmental delays, and learning or physical disabilities are frequently seen in squalor-dwelling individuals. However, none of these disorders seems to be necessary or sufficient to explain the behavior. Neurobiologically, squalor-dwelling behavior has been associated with frontal lobe dysfunction as evidenced by executive dysfunction; however, cognitive impairments also fail to completely explain this behavior. The purpose of this report is to describe a typical case of squalor-dwelling behavior and use it as an example to illustrate the complexity of uncovering the neurobiological basis for this maladaptive personal and public health threat. Neuroimaging findings from our case and a review of the literature point toward decreased activity in the insular cortex and the amygdala as a unifying biological explanation for squalor-dwelling behaviors.
Factors Associated With Poor Linkage to HIV Care in South Africa: Secondary Analysis of Data From the Thol'impilo Trial
Authors: Dorward Jienchi , Mabuto Tonderai , Charalambous Salome , Fielding Katherine L. , Hoffmann Christopher J.
Published: September 2017

Background:

Poor linkage to HIV care is impeding achievement of the Joint United Nations Programme on HIV and AIDS (UNAIDS) 90-90-90 targets. This study aims to identify risk factors for poor linkage-to-care after HIV counseling and testing, thereby informing strategies to achieve 90-90-90.

Setting:

The Thol'impilo trial was a large randomized controlled trial performed between 2012 and 2015 in South Africa, comparing different strategies to improve linkage-to-care among adults aged ≥18 years who tested HIV-positive at mobile clinic HIV counseling and testing.

Methods:

In this secondary analysis, sociodemographic factors associated with time to linkage-to-care were identified using Cox regression.

Results:

Of 2398 participants, 61% were female, with median age 33 years (interquartile range: 27–41) and median CD4 count 427 cells/mm3 (interquartile range: 287–595). One thousand one hundred one participants (46%) had clinic verified linkage-to-care within 365 days of testing HIV-positive. In adjusted analysis, younger age [≤30 vs >40 years: adjusted hazard ratio (aHR): 0.58, 95% CI: 0.50 to 0.68; 31–40 vs >40 years: aHR: 0.81, 95% CI: 0.70 to 0.94, test for trend P < 0.001], being male (aHR: 0.86, 95% CI: 0.76 to 0.98, P = 0.028), not being South African (aHR: 0.79, 95% CI: 0.66 to 0.96, P = 0.014), urban district (aHR: 0.82, 95% CI: 0.73 to 0.93, P = 0.002), being employed (aHR: 0.81, 95% CI: 0.72 to 0.92, P = 0.001), nondisclosure of HIV (aHR: 0.63, 95% CI: 0.56 to 0.72, P < 0.001), and having higher CD4 counts (test for trend P < 0.001) were all associated with decreased hazard of linkage-to-care.

Conclusion:

Linkage-to-care was low in this relatively large cohort. Increasing linkage-to-care requires innovative, evidence-based interventions particularly targeting individuals who are younger, male, immigrant, urban, employed, and reluctant to disclose their HIV status.
The Effect of PrEP on HIV Incidence Among Men Who Have Sex With Men in the Context of Condom Use, Treatment as Prevention, and Seroadaptive Practices
Authors: LeVasseur Michael T. , Goldstein Neal D. , Tabb Loni P. , Olivieri-Mui Brianne L. , Welles Seth L.
Published: September 2017

Background:

HIV preexposure prophylaxis (PrEP) is an effective tool in preventing HIV infection among high-risk men who have sex with men (MSM). It is unknown how effective PrEP is in the context of other implemented HIV prevention strategies, including condom use, seroadaption, and treatment as prevention (TasP). We evaluate the impact of increasing uptake of PrEP in conjunction with established prevention strategies on HIV incidence in a high-risk population of MSM through simulation.

Methods:

Agent-based simulation models representing the sexual behavior of high-risk, urban MSM in the United States over the period of 1 year were used to evaluate the effect of PrEP on HIV infection rates. Simulations included data for 10,000 MSM and compared increasing rates of PrEP uptake under 8 prevention paradigms: no additional strategies, TasP, condom use, seroadaptive behavior, and combinations thereof.

Results:

We observed a mean of 103.2 infections per 10,000 MSM in the absence of any prevention method. PrEP uptake at 25% without any additional prevention strategies prevented 30.7% of infections. In the absence of PrEP, TasP, condom use, and seroadaptive behavior independently prevented 27.1%, 48.8%, and 37.7% of infections, respectively, and together prevented 72.2%. The addition of PrEP to the 3 aforementioned prevention methods, at 25% uptake, prevented an additional 5.0% of infections.

Conclusions:

To achieve a 25% reduction in HIV infections by 2020, HIV prevention efforts should focus on significantly scaling up access to PrEP in addition to HIV testing, access to antiretroviral therapy, and promoting condom use.
Surgical Outcome of Simplified Horse-Shoe Technique With the Traditional Procedure in Children With Trigonocephaly
Authors: Kalantar Hormozi Abdoljalil , Dastgerdi Vahid , Ghalambor Abdolazim
Published: September 2017

Trigonocephaly is one of the most common types of craniosynostosis leading to triangular-shaped head and neurodevelopmental complications. Several surgical techniques have been suggested for its correction, but the newly suggested technique seems to have optimal outcomes compared with the traditional methods. Thus, the authors retrospectively evaluated the outcomes of the simplified horse-shoe technique with previous procedures performed on 169 children severe trigonocephaly during 1996 to 2015 at Mofid Hospital, Tehran, Iran. Demographic data of the patients and the surgical outcomes and complications and the need for reoperation were recorded and scored using the Whitaker system. The male-to-female ratio was 2.75:1. The mean ±  standard deviation age of all the patients at the time of surgery was 7.09 ± 7.5, 9.95 ± 7.71, 10.53 ± 6.57, and 10.59 ± 7.96 months for the traditional, horse-shoe, and simplified horse-shoe techniques, respectively. The total reoperation rate was 6.5% (4.7% in the traditional technique, 1.2% in the horse-shoe, and 0.6% in the simplified horse-shoe technique) (P < 0.001). The main reason for reoperation was hardware removal (in the traditional technique). Whitaker scoring showed no patients of class IV in any of the groups and no patients of class III and IV in simplified horse-shoe technique, but the difference in the Whitaker scores among the 3 groups was not statistically significant (P = 1.176). The new surgical technique is easier and simpler with fewer complications than the traditional technique and is suggested to be recommended for surgical treatment in children with trigonocephaly, especially in younger children.
Multidimensional Fatigue Inventory in People With Hepatitis B Infection
Authors: Saffari Mohsen , Naderi Maryam K. , Piper Crystal N. , Koenig Harold G.
Published: September 2017

There is no valid and well-established tool to measure fatigue in people with chronic hepatitis B. The aim of this study was to translate the Multidimensional Fatigue Inventory (MFI) into Persian and examine its reliability and validity in Iranian people with chronic hepatitis B. The demographic questionnaire and MFI, as well as Chronic Liver Disease Questionnaire and EuroQol-5D (to assess criterion validity), were administered in face-to-face interviews with 297 participants. A forward–backward translation method was used to develop a culturally adapted Persian version of the questionnaire. Cronbach's α was used to assess the internal reliability of the scale. Pearson correlation was used to assess criterion validity, and known-group method was used along with factor analysis to establish construct validity. Cronbach's α for the total scale was 0.89. Convergent and discriminant validities were also established. Correlations between the MFI and the health-related quality of life scales were significant (p < .01). The scale differentiated between subgroups of persons with the hepatitis B infection in terms of age, gender, employment, education, disease duration, and stage of disease. Factor analysis indicated a four-factor solution for the scale that explained 60% of the variance. The MFI is a valid and reliable instrument to identify fatigue in Iranians with hepatitis B.
What is next after anamorelin?
Authors: Garcia Jose M.
Published: September 2017

Purpose of review

In spite of its relevance, treatments for the cancer anorexia and cachexia syndrome (CACS) are not available. One of the agents that recently reached phase III clinical trials is anamorelin. Its development, along with that of other agents for this indication, will be reviewed here, with a focus on the gaps in the current knowledge and future directions.

Recent findings

In spite of several targets showing promising results in early development, their difficulties obtaining regulatory approval underscore the need to reconsider the current strategies in drug development and the challenges in the field of CACS.

Further research is needed in order to meet the challenges of developing treatments for CACS. Preclinical studies should expand our understanding about key regulators of appetite, muscle, and energy metabolism in this setting using models that can be translated reliably to humans. Clinical research efforts should focus on validating the entry criteria, endpoints, outcomes, and the potential synergistic effects and interaction between different targets, nutrition, and exercise interventions. Clinical meaningfulness and significance should be taken into account in the design of clinical trials. It is essential that all key stakeholders are included in the design of future strategies.
Practical approaches to managing cancer patients with weight loss
Authors: Del Fabbro Egidio , Orr Tamara A. , Stella Susan M.
Published: September 2017

Purpose of review

Poor appetite and weight loss are a source of family conflict, psychological distress, and associated with poor tolerance to chemotherapy, impaired quality of life, and decreased survival. Despite clinicians’ concern about the effect of cachexia on their patients, few oncological professional organizations provide guidelines for the treatment of cancer-related weight loss.

Recent findings

Recent publications indicate there is an unmet need for addressing cachexia in patients with cancer. Studies also reveal that patients are often consuming inadequate calories and protein. Inadequate oral intake may be mitigated by a multimodal interdisciplinary approach that uses pharmacological and nonpharmacological measures such as exercise and counseling. Other positive clinical outcomes include decreased symptom burden, improved quality of life, and enhanced physical performance.

Experience from specialist cachexia clinics and published literature indicates that simple assessments and interventions can be applied more broadly in clinical practice and that the interdisciplinary multimodal approach is important for achieving successful outcomes. The positive influence of this approach on clinical outcomes also has to be considered in clinical trial design.
Research priorities in cancer cachexia: The University of Rochester Cancer Center NCI Community Oncology Research Program Research Base Symposium on Cancer Cachexia and Sarcopenia
Authors: Dunne Richard F. , Mustian Karen M. , Garcia Jose M. , Dale William , Hayward Reid , Roussel Breton , Buschmann Mary M. , Caan Bette J. , Cole Calvin L. , Fleming Fergal J. , Chakkalakal Joe V. , Linehan David C. , Hezel Aram F. , Mohile Supriya G.
Published: September 2017

Purpose of review

Cancer cachexia remains understudied and there are no standard treatments available despite the publication of an international consensus definition and the completion of several large phase III intervention trials in the past 6 years. In September 2015, The University of Rochester Cancer Center NCORP Research Base led a Symposium on Cancer Cachexia and Sarcopenia with goals of reviewing the state of the science, identifying knowledge gaps, and formulating research priorities in cancer cachexia through active discussion and consensus.

Recent findings

Research priorities that emerged from the discussion included the implementation of morphometrics into clinical decision making, establishing specific diagnostic criteria for the stages of cachexia, expanding patient selection in intervention trials, identifying clinically meaningful trial endpoints, and the investigation of exercise as an intervention for cancer cachexia.

Standardizing how we define and measure cancer cachexia, targeting its complex biologic mechanisms, enrolling patients early in their disease course, and evaluating exercise, either alone or in combination, were proposed as initiatives that may ultimately result in the improved design of cancer cachexia therapeutic trials.
Reconstruction of developmental landscapes by optimal-transport analysis of single-cell gene expression sheds light on cellular reprogramming
Authors: Schiebinger Geoffrey , Shu Jian , Tabaka Marcin , Cleary Brian , Subramanian Vidya , Solomon Aryeh , Liu Siyan , Lin Stacie , Berube Peter , Lee Lia , Chen Jenny , Brumbaugh Justin , Rigollet Philippe , Hochedlinger Konrad , Jaenisch Rudolf , Regev Aviv , Lander Eric S.
Published: September 2017

Understanding the molecular programs that guide cellular differentiation during development is a major goal of modern biology. Here, we introduce an approach, WADDINGTON-OT, based on the mathematics of optimal transport, for inferring developmental landscapes, probabilistic cellular fates and dynamic trajectories from large-scale single-cell RNA-seq (scRNA-seq) data collected along a time course. We demonstrate the power of WADDINGTON-OT by applying the approach to study 65,781 scRNA-seq profiles collected at 10 time points over 16 days during reprogramming of fibroblasts to iPSCs. We construct a high-resolution map of reprogramming that rediscovers known features; uncovers new alternative cell fates including neuraland placental-like cells; predicts the origin and fate of any cell class; highlights senescent-like cells that may support reprogramming through paracrine signaling; and implicates regulatory models in particular trajectories. Of these findings, we highlightObox6, which we experimentally show enhances reprogramming efficiency. Our approach provides a general framework for investigating cellular differentiation.
No evidence that inbreeding avoidance is up-regulated during the ovulatory phase of the menstrual cycle
Authors: Holzleitner Iris J. , Driebe Julie C. , Arslan Ruben C. , Hahn Amanda C. , Lee Anthony J. , O’Shea Kieran J. , Gerlach Tanja M. , Penke Lars , Jones Benedict C. , DeBruine Lisa M.
Published: September 2017

Mate preferences and mating-related behaviors are hypothesized to change over the menstrual cycle in ways that function to increase reproductive fitness. Results of recent large-scale studies suggest that many of these hormone-linked behavioral changes are less robust than was previously thought. One specific hypothesis that has not yet been subject to a large-scale test is the proposal that women’s preference for associating with male kin is down-regulated during the ovulatory (high-fertility) phase of the menstrual cycle. Consequently, we used a longitudinal design to investigate the relationship between changes in women’s steroid hormone levels and their perceptions of faces experimentally manipulated to possess kinship cues (Study 1). Analyses suggested that women viewed men’s faces displaying kinship cues more positively (i.e., more attractive and trustworthy) when estradiol-to-progesterone ratio was high. Since estradiol-to-progesterone ratio is positively associated with conception risk during the menstrual cycle, these results directly contradict the hypothesis that women’s preference for associating with male kin is down-regulated during the ovulatory (high-fertility) phase of the menstrual cycle. Study 2 employed a daily diary approach and found no evidence that women reported spending less time in the company of male kin or thought about male kin less often during the fertile phase of the menstrual cycle. Thus, neither study found evidence that inbreeding avoidance is up-regulated during the ovulatory phase of the menstrual cycle.
Estimation of genetic correlation using linkage disequilibrium score regression and genomic restricted maximum likelihood
Authors: Ni Guiyan , Moser Gerhard ,   Schizophrenia Working Group of the Psychiatric Genomics Consortium, Wray Naomi R. , Lee S. Hong
Published: September 2017

Genetic correlation is a key population parameter that describes the shared genetic architecture of complex traits and diseases. It can be estimated by current state-of-art methods, i.e. linkage disequilibrium score regression (LDSC) and genomic restricted maximum likelihood (GREML). The massively reduced computing burden of LDSC compared to GREML makes it an attractive tool, although the accuracy (i.e., magnitude of standard errors) of LDSC estimates has not been thoroughly studied. In simulation, we show that the accuracy of GREML is generally higher than that of LDSC. When there is genetic heterogeneity between the actual sample and reference data from which LD scores are estimated, the accuracy of LDSC decreases further. In real data analyses estimating the genetic correlation between schizophrenia (SCZ) and body mass index, we show that GREML estimates based on ~150,000 individuals give a higher accuracy than LDSC estimates based on ~400,000 individuals (from combined meta-data). A GREML genomic partitioning analysis reveals that the genetic correlation between SCZ and height is significantly negative for regulatory regions, which whole genome or LDSC approach has less power to detect. We conclude that LDSC estimates should be carefully interpreted as there can be uncertainty about homogeneity among combined meta-data sets. We suggest that any interesting findings from massive LDSC analysis for a large number of complex traits should be followed up, where possible, with more detailed analyses with GREML methods, even if sample sizes are lesser.
A preliminary analysis of the association between perceived stigma and HIV-related pain
Authors: Wadley Antonia L , Pincus Tamar , Evangeli Michael
Published: September 2017

Objective

HIV stigma remains common and has been associated with severity of HIV-related symptoms. Associations between HIV stigma and HIV-related pain, one of the most common symptoms in HIV, have not been investigated however. Data from low back pain populations suggest that stigma associates with worse pain intensity and so we hypothesised that the same would be the case in HIV. In a small pilot study we assessed the association between HIV stigma and pain intensity in PLWH with chronic pain while controlling for depression, a well-established correlate of pain.

Methods

Mediation analysis was used to assess the effect of depression on the relationship between stigma and pain intensity in a cross-sectional cohort of 50 PLWH and chronic pain (pain most days of the week for > 3 months) recruited in Johannesburg, South Africa. All participants were assessed using: HIV/AIDS stigma instrument – PLWA (HASI-P), 11-point numerical pain rating scale, and the Beck Depression Inventory II.

Results

88% (44/50) of participants reported experiencing some form of HIV stigma (HIV stigma scale score ≥ 1). Worst pain intensity and depressive symptoms individually correlated with total stigma score (Spearman’s r = 0.33, p = 0.02 for both). The mediation analysis highlighted that mediation of the relationship by depression was equivocal (b = −0.002, bootstrapped CI −0.02 to 0.00).

Conclusions

Whilst these preliminary data are marginal, they do suggest that associations between HIV stigma and HIV-related pain warrant further investigation. Future study should also include potential mechanisms, which may include mediation through depression.
Hydrogel encapsulation of living organisms for long-term microscopy
Authors: Burnett Kyra , Edsinger Eric , Albrecht Dirk R.
Published: September 2017

Imaging living organisms at high spatial resolution requires effective and innocuous immobilization. Long-term imaging, across development or behavioral states, places further demands on sample mounting with minimal perturbation of the organism. Here we present a simple and inexpensive method for rapid encapsulation of small animals of any developmental stage within a photocrosslinked polyethylene glycol (PEG) hydrogel, gently restricting movement within their confined spaces. Immobilized animals maintained a normal, uncompressed morphology in a hydrated environment and could be exposed to different aqueous chemicals. We focus in particular on the nematodeC. elegans, an organism that is typically viewed with paralyzing reagents, nanobeads, adhesives, or microfluidic traps. The hydrogel is optically clear, non-autofluorescent, and nearly index-matched with water for use with light-sheet microscopy. We captured volumetric images of optogenetically-stimulated responses in multiple sensory neurons over 14 hours using a diSPIM light-sheet microscope, and immobilized worms were recoverable and viable after 24 hours encapsulation. We further imaged living pygmy squid hatchlings to demonstrate size scalability, characterized immobilization quality for various crosslinking parameters and identified paralytic-free conditions suitable for high-resolution single cell imaging. PEG hydrogel encapsulation enables continuous observation for hours of small living organisms, from yeast to zebrafish, and is compatible with multiple microscope mounting geometries.
Low cost and open source multi-fluorescence imaging system for teaching and research in biology and bioengineering
Authors: Isaac Nuñez , Tamara Matute , Roberto Herrera , Juan Keymer , Tim Marzullo , Tim Rudge , Fernán Federici
Published: September 2017

The advent of easy-to-use open source microcontrollers, off-the-shelf electronics and customizable manufacturing technologies has facilitated the development of inexpensive scientific devices and laboratory equipment. In this study, we describe an imaging system that integrates low-cost and open-source hardware, software and genetic resources. The multi-fluorescence imaging system consists of readily available 470 nm LEDs, a Raspberry Pi camera and a set of filters made with low cost acrylics. This device allows imaging in scales ranging from single colonies to entire plates. We developed a set of genetic components (e.g. promoters, coding sequences, terminators) and vectors following the standard framework of Golden Gate, which allowed the fabrication of genetic constructs in a combinatorial, low cost and robust manner. In order to provide simultaneous imaging of multiple wavelength signals, we screened a series of long stokes shift fluorescent proteins that could be combined with cyan/green fluorescent proteins. We found CyOFP1, mBeRFP and sfGFP to be the most compatible set for 3-channel fluorescent imaging. We developed open source Python code to operate the hardware to run time-lapse experiments with automated control of illumination and camera and a Python module to analyze data and extract meaningful biological information. To demonstrate the potential application of this integral system, we tested its performance on a diverse range of imaging assays often used in disciplines such as microbial ecology, microbiology and synthetic biology. We also assessed its potential for STEM teaching in a high school environment, using it to teach biology, hardware design, optics, and programming. Together, these results demonstrate the successful integration of open source hardware, software, genetic resources and customizable manufacturing to obtain a powerful, low cost and robust system for STEM education, scientific research and bioengineering. All the resources developed here are available under open source licenses.
Arabidopsis phenotyping through Geometric Morphometrics
Authors: Manacorda Carlos A. , Asurmendi Sebastian
Published: September 2017

In recent years, much technical progress has been done regarding plant phenotyping including the model speciesArabidopsis thaliana. With automated, high-throughput platforms and the development of improved algorithms for the rosette segmentation task, it is now possible to massively extract reliable shape and size parameters for genetic, physiological and environmental studies. The development of low-cost phenotyping platforms and freeware resources make it possible to widely expand phenotypic analysis tools for Arabidopsis. However, objective descriptors of shape parameters that could be used independently of platform and segmentation software used are still lacking and shape descriptions still rely onad hocor even sometimes contradictory descriptors, which could make comparisons difficult and perhaps inaccurate. Modern geometric morphometrics is a family of methods in quantitative biology proposed to be the main source of data and analytical tools in the emerging field of phenomics studies. It has been used for taxonomists and paleontologists for decades and is now a mature discipline. By combining geometry, multivariate analysis and powerful statistical techniques, it offers the possibility to reproducibly and accurately account for shape variations amongst groups. Based on the location of homologous landmarks points over photographed or scanned specimens, these tools could identify the existence and degree of shape variation and measure them in standard units. Here, it is proposed a particular scheme of landmarks placement on Arabidopsis rosette images to study shape variation in the case study of viral infection processes. Several freeware-based geometric morphometric tools are applied in order to exemplify the usefulness of this approach to the study of phenotypes in this model plant. These methods are concisely presented and explained. Shape differences between controls and infected plants are quantified throughout the infectious process and visualized with the appealing graphs that are a hallmark of these techniques and render complex mathematical analysis simple outcomes to interpret. Quantitative comparisons between two unrelated ssRNA+ viruses are shown and reproducibility issues are assessed. Combined with the newest automatons and plant segmentation procedures, geometric morphometric tools could boost phenotypic features extraction and processing in an objective, reproducible manner.