bluuebunny/crossref_metadata_2025 huggingface dataset:
Final results from IMPROVE: a randomized, controlled, open-label, two-arm, cross-over phase IV study to determine patients’ preference for everolimus in combination with exemestane or capecitabine in combination with bevacizumab in advanced HR-positive, HER2-negative breast cancer
Authors: Decker Thomas , Söling Ulrike , Hahn Antje , Maintz Christoph , Kurbacher Christian Martin , Vehling-Kaiser Ursula , Sent Dagmar , Klare Peter , Hagen Volker , Chiabudini Marco , Falkenstein Julia , Indorf Martin , Runkel Eva , Potthoff Karin
Published: April 2020

Background

The objective of the IMPROVE study was patients’ preference for either endocrine-based therapy or combined chemo- and anti-angiogenic therapy in advanced HR-positive/HER2-negative breast cancer.

Methods

In this randomized, cross-over phase IV study, 77 patients were recruited in 26 sites in Germany. Patients were randomized 1:1 to receive either capecitabine plus bevacizumab (Cap+Bev) as first-line therapy followed by cross-over to everolimus plus exemestane (Eve+Exe) as second-line therapy (Arm A) or the reverse sequence (Arm B). The primary endpoint was patients’ preference for either regimen, assessed by the Patient Preference Questionnaire 12 weeks after cross-over. Key secondary endpoints included progression-free survival (PFS), overall survival (OS), safety, and quality of life (QoL).

Results

61.5% of patients preferred Cap+Bev (p = 0.1653), whereas 15.4% preferred Eve+Exe and 23.1% were indecisive. Physicians showed a similar tendency towards Cap+Bev (58.1%) as the preferred regimen versus Eve+Exe (32.3%). Median first-line PFS was longer for Cap+Bev than for Eve+Exe (11.1 months versus 3.5 months). Median second-line PFS was similar between Cap+Bev and Eve+Exe (3.6 months versus 3.7 months). Median OS was comparable between Arm A (28.8 months) and Arm B (24.7 months). 73.0% and 52.6% (first−/second-line, Cap+Bev) and 54.1% and 52.9% (first−/second-line, Eve+Exe) of patients experienced grade 3/4 TEAEs. No treatment-related deaths occurred. QoL and treatment satisfaction were not significantly different between arms or treatment lines.

Conclusions

Patients tended to favor Cap+Bev over Eve+Exe, which was in line with physicians’ preference. Cap+Bev showed superior first-line PFS, while QoL was similar in both arms. No new safety signals were reported.

Trial registration

EudraCT No: 2013–005329-22. Registered on 19 August 20
Trends in the epidemiology of young-onset colorectal cancer: a worldwide systematic review
Authors: Saad El Din Khalid , Loree Jonathan M. , Sayre Eric C. , Gill Sharlene , Brown Carl J. , Dau Hallie , De Vera Mary A.
Published: April 2020

Background

Recent data suggest that the risk of young-onset colorectal cancer (yCRC), in adults less than 50 years of age, is increasing. To confirm findings and identify contemporary trends worldwide, we conducted a systematic review of studies examining population-level trends in yCRC epidemiology.

Methods

We searched MEDLINE (1946–2018), EMBASE (1974–2018), CINAHL (1982–2018), and Cochrane Database of Systematic Reviews (2005–2018) for studies that used an epidemiologic design, assessed trends in yCRC incidence or prevalence, and published in English. Extracted information included country, age cut-off for yCRC, and reported trends in incidence or prevalence (e.g. annual percent change [APC]). We pooled similarly reported trend estimates using random effects models.

Results

Our search yielded 8695 articles and after applying our inclusion criteria, we identified 40 studies from 12 countries across five continents. One study assessed yCRC prevalence trends reporting an APCp of + 2.6 and + 1.8 among 20–39 and 40–49 year olds, respectively. 39 studies assessed trends in yCRC incidence but with substantial variability in reporting. Meta-analysis of the most commonly reported trend estimate yielded a pooled overall APCi of + 1.33 (95% CI, 0.97 to 1.68; p < 0.0001) that is largely driven by findings from North America and Australia. Also contributing to these trends is the increasing risk of rectal cancer as among 14 studies assessing cancer site, nine showed an increased risk of rectal cancer in adults less than 50 years with APCi up to + 4.03 (p < 0.001).

Conclusions

Our systematic review highlights increasing yCRC risk in North America and Australia driven by rising rectal cancers in younger adults over the past two decades.
Management and prognostic prediction of appendiceal mucinous adenocarcinoma with peritoneal metastasis: a single center study in China
Authors: Ma Ruiqing , Wang Bing , Zhai Xichao , Lu Yiyan , Xu Hongbin
Published: April 2020

Background

To investigate the clinical and pathological characteristics of appendiceal mucinous adenocarcinoma with peritoneal metastasis and analyze the prognostic factors.

Methods

A retrospective analyses of clinicopathological features of 50 patients with appendiceal mucinous adenocarcinoma with peritoneal metastasis from January, 2013 to December, 2017 in Aerospace Central Hospital, Beijing, China. Survival data calculation and comparison were respectively performed with the Kaplan-Meier method and the log-rank test. The Cox proportional hazards regression method was used for multivariate survival analyses.

Results

Cytoreduction for appendiceal mucinous adenocarcinoma was conducted on 50 patients (24 males and 26 females), with a median age of 52.5 years at the time of surgery (range 31–71 years). The median overall survival (OS) time was 24 months, with 2-,3- and 5-year survival rates of 53, 24 and 8%, respectively. At the last follow-up in December 2018, 13 patients were still alive. Multivariate analysis revealed that patients who had low Ki-67 expression (less than 50%) and CCR (completeness of cytoreduction) 0/1/2 score had significantly better OS rate than their respective counterparts.

Conclusions

Ki-67 expression statue and CCR score could be employed as the prognosis prediction in patients with appendiceal mucinous adenocarcinoma.
Racial differences in testicular cancer in the United States: descriptive epidemiology
Authors: Li Yang , Lu Qi , Wang Yu , Ma Shuangge
Published: April 2020

Background

Testicular cancer (TC) is the most common malignancy in young adult men, and in many countries the incidence rates of testicular cancer have been increasing since the middle of the twentieth century. Since disease presentation and tumor progression patterns are often heterogeneous across racial groups, there may be important racial differences in recent TC trends.

Methods

In this study, Surveillance, Epidemiology, and End Results (SEER) data on TC patients diagnosed between 1973 and 2015 were analyzed, including the following racial/ethnic groups: non-Hispanic whites (NHW), Hispanic whites (HW), blacks, and Asians and Pacific Islanders (API). Patient characteristics, age-adjusted incidence rates, and survival were compared across racial groups. A multivariate Cox model was used to analyze the survival data of TC patients, in order to evaluate racial differences across several relevant factors, including marital status, age group, histologic type, treatment, stage, and tumor location.

Results

NHWs had the highest incidence rates, followed by blacks, HWs, and APIs. There were significant survival differences among the racial groups, with NHWs having the highest survival rates and blacks having the lowest.

Conclusion

An analysis of SEER data showed that racial differences existed among TC patients in the United States with respect to patient characteristics, incidence, and survival. The results can be useful to stakeholders interested in reducing the burden of TC morbidity and mortality.
In vivo ultraosound elastographic evaluation of the age-related change of human lens nuclear stiffness
Authors: Zhou Haiyan , Yan Hong , Yan Weijia , Wang Xinchuan , Li Qiaoying
Published: April 2020

Background

To evaluate the age-related changes in the stiffness of the human lens nucleus in vivo.

Methods

A total of 78 volunteers with best-corrected visual acuity of 20/20with a mean ± standard deviation intraocular pressure (IOP) of 16 ± 2.5 mmHg were divided into 3 groups of 26. The mean ages of Groups A, B and C were 81 ± 5.5, 44 ± 3.2 and 21 ± 2.5 years, with mean axial lengths of 23.8 ± 0.5 mm, 23.8 ± 0.4 mm and 23.9 ± 0.3 mm, respectively. Using an elastographer, the ultrasound echolucency and elastic strain rate of the lens nucleus of one eye, selected randomly, of each subject were measured three times. The strain rate of the lens cortex could not be assessed. The qualitative differences in the strain rates across the groups were assessed, and differences in the strain rate ratios of the lens nuclei across groups were analysed by one-way ANOVA.

Results

The strain rates of the lens nuclei of Group A were much lower than those in Groups B and C, as assessed qualitatively; the elastograph images of the lens nuclei of the older group showed a blue colour.The strain rate ratios of the lens nuclei of Groups A, B and C were 0.02 ± 0.08, 0.69 ± 0.12 and 1.95 ± 0.85, respectively. The differences in the lens nucleus strain rate ratios across the groups were statistically significant, with p-values < 0.05.

Conclusions

Ultrasound elastography demonstrated in vivo that an older age is associated with a statistically significantly lower lens nucleus strain rate ratio and therefore a markedly higher lens nuclear stiffness.
Effect of a short-term vitamin E supplementation on oxidative stress in infertile PCOS women under ovulation induction: a retrospective cohort study
Authors: Chen Jie , Guo Qian , Pei Ying-hao , Ren Qing-ling , Chi Lei , Hu Rong-kui , Tan Yong
Published: April 2020

Background

Vitamin E, which is critically important in the whole process of reproduction, can antagonize the oxidative stress caused by the oxygen free radicals and antioxidant imbalance and regulate normal physiological function of the reproductive system. The effect of short-term supplementation of vitamin E on outcomes of infertile women with polycystic ovary syndrome (PCOS) when they underwent ovulation induction with clomiphene citrate (CC) and human menopausal gonadotropin (HMG) remains unknown.

Methods

This was a retrospective cohort clinical trial from October 2015 to April 2017. A total of 321 PCOS cases underwent ovulation induction with CC and HMG. Patients in group A (n = 110) did not receive vitamin E while patients in group B (n = 105) and group C (n = 106) received oral treatment of vitamin E at 100 mg/day during follicular phase and luteal phase, respectively.

Results

It was observed no significant differences of ovulation rate, clinical pregnancy rate, and ongoing pregnancy rate among the three groups. It was interesting that dosage of HMG were significant lower in group B compared with those in group A and group C (P<0.05).

Conclusions

A short-term supplementation of vitamin E can improve oxidative stress, and reduce exogenous HMG dosage to lower the economic cost with a similar pregnancy rate in the ovulation induction cycle. However, the supplementation does not alter the pregnancy rate in the ovulation induction cycle.

Trial registration

ChiCTR-OOC-14005389, 2014.
Cost analysis of depression using the national insurance system in South Korea: a comparison of depression and treatment-resistant depression
Authors: Shin Daun , Kim Nam Woo , Kim Min Ji , Rhee Sang Jin , Park Christopher Hyung Keun , Kim Hyeyoung , Yang Bo Ram , Kim Mi-sook , Choi Gum Jee , Koh Minjung , Ahn Yong Min
Published: April 2020

Background

The incidence and burden of depressive disorders are increasing in South Korea. There are many differences between pharmaceutically treated depression (PTD) and treatment-resistant depression (TRD), including the economic consequences; however, to our knowledge, the economic burden of depression is understudied in South Korea. Therefore, the objective of the present study was to calculate the different economic costs of PTD and TRD in South Korea, specifically by comparing several aspects of medical care.

Methods

This study comprised patients aged 18 and over who were newly prescribed antidepressants for more than 28 days with a depression code included from January 1, 2012, to December 31, 2012, by the Health Insurance Review and Assessment Service (HIRA). TRD was classified as more than two antidepressant regimen failures in PTD patients. The cost was calculated based on the cost reflected on the receipt registered with HIRA.

Results

Of the 834,694 patients with PTD, 34,812 patients (4.17%) were converted to TRD. The cost of medical care for TRD (6,610,487 KRW, 5881 USD) was approximately 5 times higher than the cost of non-TRD (1,273,045 KRW, 1133 USD) and was significantly higher for patients with or without depression and suicide codes. Medical expenses incurred by non-psychiatrists were roughly 1.7 times higher than those incurred by psychiatrists.

Conclusions

TRD patients had significantly higher healthcare costs than PTD patients. Identifying these financial aspects of care for depression can help to establish a more effective policy to reduce the burden on mentally ill patients.
Health care use and treatment-seeking for depression symptoms in rural India: an exploratory cross-sectional analysis
Authors: Roberts Tessa , Shidhaye Rahul , Patel Vikram , Rathod Sujit D.
Published: April 2020

Background

There is a large “treatment gap” for depression worldwide. This study aimed to better understand the treatment gap in rural India by describing health care use and treatment-seeking for depression.

Methods

Data were analysed from a two round cross-sectional community survey conducted in rural Madhya Pradesh between May 2013 and December 2016. We examined the proportion of individuals who screened positive for depression (≥10) on the Patient Health Questionnaire (PHQ-9) who sought treatment in different sectors, for depression symptoms and for any reason, and compared the latter with health service use by screen-negative individuals. We analysed the frequency with which barriers to healthcare utilisation were reported by screen-positive adults. We also analysed the association between seeking treatment for depression and various predisposing, enabling and need factors using univariable regression.

Results

86% of screen-positive adults reported seeking no depression treatment. However, 66% had used health services for any reason in the past 3 months, compared to 46% of screen-negative individuals (p < 0.0001). Private providers were most frequently consulted by screen-positive adults (32%), while only 19% consulted traditional providers. Structural barriers to healthcare use such as cost and distance to services were frequently reported (54 and 52%, respectively) but were not associated with treatment-seeking for depression. The following factors were found to be positively associated with treatment-seeking for depression: higher symptom severity; lack of energy, lack of interest/pleasure, low self-esteem, or slow movements/restlessness on more than 7 days in the past 2 weeks; being married; having discussed depression symptoms; and reporting problems with medication availability and supply as a barrier to healthcare. No evidence was found for an association between treatment-seeking for depression and most socio-economic, demographic or attitudinal factors.

Conclusions

These findings suggest that the majority of adults who screen positive for depression seek healthcare, although not primarily for depression symptoms, indicating the need to improve detection of depression during consultations about other complaints. Private providers may need to be considered in programmes to improve depression treatment in this setting. Further research should test the hypotheses generated in this descriptive study, such as the potential role of marriage in facilitating treatment-seeking.
Community engagement interventions for communicable disease control in low- and lower- middle-income countries: evidence from a review of systematic reviews
Authors: Questa K. , Das M. , King R. , Everitt M. , Rassi C. , Cartwright C. , Ferdous T. , Barua D. , Putnis N. , Snell A. C. , Huque R. , Newell J. , Elsey H.
Published: April 2020

Background

Community engagement (CE) interventions include a range of approaches to involve communities in the improvement of their health and wellbeing. Working with communities defined by location or some other shared interest, these interventions may be important in assisting equity and reach of communicable disease control (CDC) in low and lower-middle income countries (LLMIC). We conducted an umbrella review to identify approaches to CE in communicable disease control, effectiveness of these approaches, mechanisms and factors influencing success.

Methods

We included systematic reviews that: i) focussed on CE interventions; ii) involved adult community members; iii) included outcomes relevant to communicable diseases in LLMIC; iv) were written in English. Quantitative results were extracted and synthesised narratively. A qualitative synthesis process enabled identification of mechanisms of effect and influencing factors. We followed guidance from the Joanna Briggs Institute, assessed quality with the DARE tool and reported according to standard systematic review methodology.

Results

Thirteen systematic reviews of medium-to-high quality were identified between June and July 2017. Reviews covered the following outcomes: HIV and STIs (6); malaria (2); TB (1); child and maternal health (3) and mixed (1). Approaches included: CE through peer education and community health workers, community empowerment interventions and more general community participation or mobilisation. Techniques included sensitisation with the community and involvement in the identification of resources, intervention development and delivery. Evidence of effectiveness of CE on health outcomes was mixed and quality of primary studies variable. We found: i) significantly reduced neonatal mortality following women’s participatory learning and action groups; ii) significant reductions in HIV and other STIs with empowerment and mobilisation interventions with marginalised groups; iii) significant reductions in malaria incidence or prevalence in a small number of primary studies; iv) significant reductions in infant diarrhoea following community health worker interventions. Mechanisms of impact commonly occurred through social and behavioural processes, particularly: changing social norms, increasing social cohesion and social capacity. Factors influencing effectiveness of CE interventions included extent of population coverage, shared leadership and community control over outcomes.

Conclusion

Community engagement interventions may be effective in supporting CDC in LLMIC. Careful design of CE interventions appropriate to context, disease and community is vital.
Maternal and fetal exposures to fluoride during mid-gestation among pregnant women in northern California
Authors: Abduweli Uyghurturk Dawud , Goin Dana E. , Martinez-Mier Esperanza Angeles , Woodruff Tracey J. , DenBesten Pamela K.
Published: April 2020

Background

Previous studies have shown a correlation between fluoride concentrations in urine and community water fluoride concentrations. However, there are no studies of the relationship between community water fluoridation, urine, serum, and amniotic fluid fluoride concentrations in pregnant women in the US. The aim of this study was to determine the relationship between maternal urine fluoride (MUF), maternal urine fluoride adjusted for specific gravity (MUFSG), maternal serum fluoride (MSF), amniotic fluid fluoride (AFF) concentrations during pregnancy, and community water fluoridation in Northern California.

Methods

Archived samples of urine, serum and amniotic fluid collected from second trimester pregnant women in Northern California from 47 different communities in Northern California and one from Montana (n = 48), were analyzed for fluoride using an ion specific electrode following acid microdiffusion. Women’s addresses were matched to publicly reported water fluoride concentrations. We examined whether fluoride concentrations in biospecimens differed by fluoridation status of the community water, and determined the association between water fluoride concentrations and biospecimen fluoride concentrations using linear regression models adjusted for maternal age, smoking, Body Mass Index (BMI), race/ethnicity, and gestational age at sample collection.

Results

Fluoride concentrations in the community water supplies ranged from 0.02 to 1.00 mg/L. MUF, MSF , and AFF concentrations were significantly higher in pregnant women living in communities adhering to the U.S. recommended water fluoride concentration (0.7 mg/L), as compared with communities with less than 0.7 mg/L fluoride in drinking water. When adjusted for maternal age, smoking status, BMI, race/ethnicity, and gestational age at sample collection, a 0.1 mg/L increase in community water fluoride concentration was positively associated with higher concentrations of MUF (B = 0.052, 95% CI:0.019,0.085), MUFSG(B = 0.028, 95% CI: -0.006, 0.062), MSF (B = 0.001, 95% CI: 0.000, 0.003) and AFF (B = 0.001, 95% CI: 0.000, 0.002).

Conclusions

We found universal exposure to fluoride in pregnant women and to the fetus via the amniotic fluid. Fluoride concentrations in urine, serum, and amniotic fluid from women were positively correlated to public records of community water fluoridation. Community water fluoridation remains a major source of fluoride exposure for pregnant women living in Northern California.
Fetuin-a to adiponectin ratio is a sensitive indicator for evaluating metabolic syndrome in the elderly
Authors: Zhou Zhongwei , Sun Mingzhong , Jin Hao , Chen Hongmei , Ju Huixiang
Published: April 2020

Background

Fetuin-A and adiponectin present significant associations, supported by recent evidence, with metabolic syndrome (MS) featuring hyperglycemia, central obesity and insulin resistance as the main components, but their biological functions are opposite. The aim of this study was to verify whether fetuin-A/adiponectin ratio (F/A ratio) is a more sensitive indicator for evaluation of MS than either fetuin-A or adiponectin.

Methods

In this cross-sectional study, 465 elderly subjects were selected from the physical examination database. Serum levels of fetuin-A and adiponectin were measured using an enzyme-linked immunosorbent assay (ELISA) method. Spearman’s rank correlation coefficient, linear regression and logistic regression analysis were adopted to estimate the correlations of fetuin-A, adiponectin and F/A ratio with MS and its components, and receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive values of the aforesaid indices.

Results

Compared with fetuin-A or adiponectin, F/A ratio was significantly associated with all the components of MS, and this correlation was significant even after adjusting potential confounding factors (P < 0.05). Logistic regression analysis indicated that F/A ratio presented a stronger correlation with incident MS (adjusted OR: 1.466; 95% CI: 1.189–1.808) than fetuin-A (adjusted OR: 1.100; 95% CI: 1.020–1.186) and adiponectin (adjusted OR: 0.760; 95% CI: 0.664–0.871) alone. ROC analysis revealed that F/A ratio achieved a larger area under curve (AUC) than fetuin-A and adiponectin, with their AUC values of 0.755, 0.709 and 0.708, respectively.

Conclusion

F/A ratio is a more sensitive index for evaluating MS than either fetuin-A or adiponectin in the elderly.
RETRACTED ARTICLE: Serum sphingosine-1-phosphate levels and Sphingosine-1-Phosphate gene polymorphisms in acute respiratory distress syndrome: a multicenter prospective study
Authors: Zhao Jiangnan , Tan Yan , Wang Li , Su Xin , Shi Yi
Published: April 2020

Background

Sphingosine-1-phosphate (S1P) is a signaling phospholipid involved in pathophysiologic progression of acute respiratory distress syndrome (ARDS) through its roles in endothelial barrier function and immune modulation. We hypothesized that decreased serum S1P level is associated with the clinical outcomes of ARDS and polymorphisms in the S1P gene are associated with serum S1P levels.

Methods

This multicenter prospective study includes ARDS patients and healthy blood donors as controls. Serum S1P levels were quantified using enzyme-linked immunosorbent assays. Eight tag single nucleotide polymorphisms (SNPs) in the S1P gene were detected, and their associations with S1P levels were evaluated.

Results

A total of 121 ARDS patients and 100 healthy individuals were enrolled. Serum S1P levels were lower in ARDS patients than in controls (P < 0.001). Decreased S1P levels correlated with more organ dysfunction and higher Acute Physiology and Chronic Health Evaluation II scores. Changes in S1P levels in ARDS patients were associated with the clinical outcomes. The recessive model for SNP rs3743631 suggests that GG homozygote is associate with a higher risk for ARDS. The dominant model for SNP rs907045 suggests that AA or TA genotype might increase the risk for ARDS. In ARDS patients, the rs3743631 GG genotype showed lower S1P levels than those harboring AG and AA genotypes. The serum S1P levels of rs907045 AA or TA genotype patients were lower than those of TT genotype.

Conclusions

Serum S1P levels are dramatically decreased in ARDS patients. Reduced S1P levels are associated with worse clinical outcomes. There is a significant association between S1P rs3743631, rs907045 polymorphisms and susceptibility of ARDS.
Child and adolescent psychiatry training in Nepal: early career psychiatrists’ perspective
Authors: Karki Utkarsh , Rai Yugesh , Dhonju Gunjan , Sharma Eesha , Jacob Preeti , Kommu John Vijay Sagar , Seshadri Shekhar P.
Published: April 2020

Background

Nepal is a developing low-income country in Southeast Asia. There is a huge burden of child and adolescent mental health (CAMH) in Nepal which has a population of around 29 million and 40–50% of the population comprises of children and adolescents. Child and Adolescent Psychiatry (CAP) has not been formally recognized as a subspecialty in Nepal and there is no standardized curriculum for CAP training. The objectives of the survey were to identify the current status of training, shortfalls and to explore the training experiences of early career psychiatrists (ECPs) in Nepal.

Methods

The participants were ECPs in Nepal. An online questionnaire was created consisting of 20 questions including 3 questions requiring an answer indicating a level of agreement scored on a ten-point scale. Questionnaire using google form was e-mailed with the uniform resource locator (URL). Respondents anonymously answered the questions. The survey was open from 01/01/2019 to 01/04/2019.

Results

Response rate was 83.69%. Around 42% (n = 32) were trainees in Doctor of Medicine (MD) Psychiatry and 58% (n = 45) of respondents had completed their MD Psychiatry. More than half of the ECPs had not received formal training specific to CAP. Seventy percent (n = 54) ECPs reported that their current workplace did not have a specific unit to address psychological problems in children and adolescents. However, 62% (n = 48) of ECPs came across 10 CAP cases per week. On a ten-point scale, mean score of ECPs confidence in diagnosing, management and overall confidence in CAP cases were 5.18 ± 1.56, 4.58 ± 1.59 and 4.67 ± 1.62 respectively. Fifty-four percent (n = 42) of respondents rated their training as limited and 74% (n = 57) of them wanted additional training in CAP. Psychological intervention, psychotherapy and a fellowship course were the additional training most of the ECPs wanted to receive.

Conclusion

Despite significant exposure to CAP patients in daily practice, ECPs self-evaluated their training as inadequate and there is no standardized CAP training program in Nepal for ECPs. The desire of ECPs to receive additional training in CAP is highly encouraging and positive. We advocate for the development and incorporation of CAP training in current psychiatry training to fulfill these unmet training needs in Nepal.
Donald O. Hebb and the Organization of Behavior: 17 years in the writing
Authors: Brown Richard E.
Published: April 2020

The Organization of Behaviorhas played a significant part in the development of behavioural neuroscience for the last 70 years. This book introduced the concepts of the “Hebb synapse”, the “Hebbian cell assembly” and the “Phase sequence”. The most frequently cited of these is the Hebb synapse, but the cell assembly may be Hebb’s most important contribution. Even after 70 years, Hebb’s theory is still relevant because it is a general framework for relating behavior to synaptic organization through the development of neural networks.The Organization of Behaviorwas Hebb’s 40th publication. His first published papers in 1937 were on the innate organization of the visual system and he first used the phrase “the organization of behavior” in 1938. However, Hebb wrote a number of unpublished papers between 1932 and 1945 in which he developed the ideas published inThe Organization of Behavior. Thus, the concept of the neural organization of behavior was central to Hebb’s thinking from the beginning of his academic career. But his thinking about the organization of behavior in 1949 was different from what it was between 1932 and 1937. This paper examines Hebb’s early ideas on the neural basis of behavior and attempts to trace the rather arduous series of steps through which he developed these ideas into the book that was published asThe Organization of Behavior. Using the 1946 typescript and Hebb’s correspondence we can see a number of changes made in the book before it was published. Finally, a number of issues arising from the book, and the importance of the book today are discussed.
Everolimus versus alpelisib in advanced hormone receptor-positive HER2-negative breast cancer: targeting different nodes of the PI3K/AKT/mTORC1 pathway with different clinical implications
Authors: Vernieri Claudio , Corti Francesca , Nichetti Federico , Ligorio Francesca , Manglaviti Sara , Zattarin Emma , Rea Carmen G. , Capri Giuseppe , Bianchi Giulia V. , de Braud Filippo
Published: April 2020

Background

The PI3K/AKT/mTORC1 axis is implicated in hormone receptor-positive HER2-negative metastatic breast cancer (HR+ HER2− mBC) resistance to anti-estrogen treatments. Based on results of the BOLERO-2 trial, the mTORC1 inhibitor everolimus in combination with the steroidal aromatase inhibitor (AI) exemestane has become a standard treatment for patients with HR+ HER2− mBC resistant to prior non-steroidal AI therapy. In the recent SOLAR-1 trial, the inhibitor of the PI3K alpha subunit (p110α) alpelisib in combination with fulvestrant prolonged progression-free survival (PFS) when compared to fulvestrant alone in patients withPIK3CA-mutated HR+ HER2− mBC that progressed after/on previous AI treatment. Therefore, two different molecules targeting the PI3K/AKT/mTORC1 axis, namely everolimus and alpelisib, are available for patients progressing on/after previous AI treatment, but it is unclear how to optimize their use in the clinical practice.

Main body of the abstract

Here, we reviewed the available clinical evidence deriving from the BOLERO-2 and SOLAR-1 trials to compare efficacy and safety profiles of everolimus and alpelisib in advanced HR+ HER2− BC treatment. Adding either compound to standard endocrine therapy provided similar absolute and relative PFS advantage. In the SOLAR-1 trial, a 76% incidence of grade (G) 3 or 4 (G3/G4) adverse events was reported, while G3/G4 toxicities occurred in 42% of patients in the BOLERO-2 trial. While alpelisib was only effective in patients withPIK3CA-mutated neoplasms, retrospective analyses indicate that everolimus improves exemestane efficacy independently ofPIK3CAmutational status.

Conclusions

Based on the available efficacy and safety data, the “new” alpelisib may be burdened by higher incidence of severe adverse events, higher costs, and anticancer efficacy that is limited toPIK3CA-mutated tumors when compared to the “old” everolimus. Therefore, the everolimus-exemestane combination remains an effective and reasonably well-tolerated therapeutic option for HR+ HER2− mBC patients progressing after/on previous AI treatment, independently ofPIK3CAmutational status.
Multiphase CT-based prediction of Child-Pugh classification: a machine learning approach
Authors: Thüring Johannes , Rippel Oliver , Haarburger Christoph , Merhof Dorit , Schad Philipp , Bruners Philipp , Kuhl Christiane K. , Truhn Daniel
Published: April 2020

Background

To evaluate whether machine learning algorithms allow the prediction of Child-Pugh classification on clinical multiphase computed tomography (CT).

Methods

A total of 259 patients who underwent diagnostic abdominal CT (unenhanced, contrast-enhanced arterial, and venous phases) were included in this retrospective study. Child-Pugh scores were determined based on laboratory and clinical parameters. Linear regression (LR), Random Forest (RF), and convolutional neural network (CNN) algorithms were used to predict the Child-Pugh class. Their performances were compared to the prediction of experienced radiologists (ERs). Spearman correlation coefficients and accuracy were assessed for all predictive models. Additionally, a binary classification in low disease severity (Child-Pugh class A) and advanced disease severity (Child-Pugh class ≥ B) was performed.

Results

Eleven imaging features exhibited a significant correlation when adjusted for multiple comparisons with Child-Pugh class. Significant correlations between predicted and measured Child-Pugh classes were observed (ρLA = 0.35, ρRF = 0.32, ρCNN = 0.51, ρERs = 0.60; p < 0.001). Significantly better accuracies for the prediction of Child-Pugh classes versus no-information rate were found for CNN and ERs (p ≤ 0.034), not for LR and RF (p ≥ 0.384). For binary severity classification, the area under the curve at receiver operating characteristic analysis was significantly lower (p ≤ 0.042) for LR (0.71) and RF (0.69) than for CNN (0.80) and ERs (0.76), without significant differences between CNN and ERs (p = 0.144).

Conclusions

The performance of a CNN in assessing Child-Pugh class based on multiphase abdominal CT images is comparable to that of ERs.
Feasibility and impact of using an automated user interface for proton spectroscopy in multiparametric MRI of the prostate
Authors: Abd Ellah Mohamed M. H. , Kremser Christian , Judmaier Werner , Kiefer Berthold , Requardt Martin , Neji Radhouene , Kamel Hosam M. , Junker Daniel
Published: April 2020

Background

Multiparametric MRI including MR spectroscopy has recently gained much acceptance being a non-invasive imaging modality for the evaluation of prostate cancer. This study aimed to evaluate the reliability and effectiveness of an assisted workflow for guided and automated multiparametric MRI (mpMRI) of the prostate including MR spectroscopy (MRS) on a 3 T scanner.

Fifty-six consecutive patients (age range 44–73 years, mean 63 years) with suspected prostate cancer underwent mpMRI using a surface coil in a 3 T MR scanner. Thirty-eight patients were examined using a newly developed computer-assisted workflow and a control group of 18 randomly selected patients with the conventional technique. Overall examination time, spectral quality, saturation pulse positioning, and the outcome of automatic prostate segmentation were compared. A grading of 1 to 5 was used, where 1 represents the highest and 5 the lowest quality of the respective results.

Results

Both the conventional technique and the computer-assisted workflow provided good spectral quality. No significant differences were found regarding saturation pulse positioning and spectral quality (P > 0.05). However, a significant difference regarding overall examination time was found, 40.78 min versus 32.6 min for conventional and computer-assisted workflow respectively (P < 0.001). The automated scanning technique also showed satisfactory results for automated prostate segmentation.

Conclusions

The computer-assisted workflow achieved good spectral quality while reducing overall examination time. This time saving effect may allow the inclusion of MRS in clinical routine.
A fast and effective method for dissecting parasitic spores: myxozoans as an example
Authors: Guo Qingxiang , Liu Yang , Zhai Yanhua , Gu Zemao
Published: April 2020

Disassembling the parasitic spores and acquiring the main subunits is a prerequisite for deep understanding of the basic biology of parasites. Herein we present a fast and efficient method to dissect the myxospores in a few steps, which mainly involved sonication, sucrose density gradient and Percoll density gradient. We tested our method on three myxozoans species and demonstrated this method allows the dismembering of myxospores, isolation of intact and clean nematocysts and shell valves within 2h by low-cost. This new tool will facilitate subsequent analyses and enable a better understanding of the ecological and evolutionary significance of parasitic spores.
Wolbachia-infected ant colonies have increased reproductive investment and an accelerated life cycle
Authors: Singh Rohini , Linksvayer Timothy A.
Published: April 2020

Wolbachia is a widespread group of maternally-transmitted endosymbiotic bacteria that often manipulates the reproductive strategy and life history of its hosts to favor its own transmission. Wolbachia mediated phenotypic effects are well characterized in solitary hosts, but effects in social hosts are unclear. The invasive pharaoh ant, Monomorium pharaonis, shows natural variation in Wolbachia infection between colonies and can be readily bred under laboratory conditions. We previously showed that Wolbachia-infected pharaoh ant colonies had more queen-biased sex ratios than uninfected colonies, which is expected to favor the spread of maternally-transmitted Wolbachia. Here, we further characterize the effects of Wolbachia on the short- and longer-term reproductive and life history traits of pharaoh ant colonies. First, we characterized the reproductive differences between naturally infected and uninfected colonies at three discrete time points and found that infected colonies had higher reproductive investment (i.e. infected colonies produced more new queens), particularly when existing colony queens were three months old. Next, we compared the long-term growth and reproduction dynamics of infected and uninfected colonies across their whole life cycle. Infected colonies had increased colony-level growth and early colony reproduction, resulting in a shorter colony life cycle, when compared to uninfected colonies.
The Clinicopathological and Survival Profiles Comparison Across Primary Sites in Acral Melanoma
Authors: Wei Xiaoting , Wu Di , Li Hang , Zhang Rui , Chen Yu , Yao Hong , Chi Zhihong , Sheng Xinan , Cui Chuanliang , Bai Xue , Qi Zhonghui , Li Ke , Lan Shijie , Chen Lizhu , Guo Rui , Yao Xinyu , Mao Lili , Lian Bin , Kong Yan , Dai Jie , Tang Bixia , Yan Xieqiao , Wang Xuan , Li Siming , Zhou Li , Balch Charles M. , Si Lu , Guo Jun
Published: April 2020

Background

The clinicopathological and survival profiles across primary sites in acral melanoma (AM) are still controversial and unclear.

Methods

This is a multi-center retrospective study. Clinicopathological data of AM patients diagnosed between 1 January 2000 and 31 December 2017 from 6 large tertiary hospitals in China were extracted. Chi square tests were used to compare basic characteristics between primary sites of sole, palm and nail bed. Melanoma-specific survival (MSS) differences based on primary sites were compared by log-rank tests and multivariate Cox regressions were used to identify prognostic factors for MSS.

Results

In total, 1157 AM patients were included. The sole group had a more advanced initial stage, deeper Breslow thickness, higher recurrence rate and distant metastases risk (all P < 0.05). The proportion of age < 65 years and ulceration were statistically lower in nail bed and palm groups, respectively. A total of 294 patients underwent sentinel lymph node biopsy and rates of positive SLN status had no statistical difference across primary sites. Among 701 patients with genetic profiles, the mutational frequency of BRAF, C-KIT, and PDGFRA were similar except for NRAS (higher in sole group, P = 0.0102). The median MSS of sole, nail bed and palm patients were 65.0 months, 112.0 months, and not reached, respectively (log-rank P = 0.0053). In multivariate analyses, primary site, initial stage, ulceration and recurrence were the prognostic factors for MSS in overall population, but the statistical significance varied over primary sites.

Conclusions

Substantial clinicopathological and survival heterogeneities exist across different primary sites in the AM population. Sole melanoma has worse prognosis compared with palm and nail bed subtypes.
The Effects of Investigative Sanctioning Systems on Wrongdoing, Reporting, and Helping: A Multiparty Perspective
Authors: Chui Celia , Grieder Manuel
Published: April 2020

Over the past two decades, organizations have established sanctioning systems as an important component of their ethical infrastructures to detect and punish wrongdoing. However, empirical knowledge about the overall effectiveness of such systems remains limited. Existing studies have mostly adopted a single-party perspective even though many wrongdoing situations involve dynamic multiparty interactions between actors, recipients, and observers of wrongdoing. Moreover, most existing research has emphasized an economic perspective—that sanctioning systems only affect behavior because of economic considerations while crowding out ethical ones. In this research, we develop a moral and normative perspective of sanctioning systems. Using a novel experimental game design, our study focuses on the investigative dimension of sanctioning systems to examine their psychological and behavioral effects in actor–recipient–observer wrongdoing interactions. Findings reveal that investigative sanctioning systems influence wrongdoing, reporting, and helping behaviors as well as alter ethical and normative considerations, such that as systems become stronger, wrongdoing behaviors are judged as more unethical and perceived as less typical than when weaker systems are in place. These moral judgments and norm perceptions mediate the effect of investigative sanctioning system strength on wrongdoing behavior. Our research extends previous empirical and theoretical work on sanctioning systems by applying a more holistic perspective and by demonstrating that highly effective systems can serve as important behavioral guides because they activate and alter moral and normative considerations about wrongdoing.
Significant Medical Comorbidities Are Associated With Lower Causality Scores in Patients Presenting With Suspected Drug-Induced Liver Injury
Authors: Ghabril Marwan , Gu Jiezhun , Yoder Lindsay , Corbito Laura , Dakhoul Lara , Ringel Amit , Beyer Christian D. , Vuppalanchi Raj , Barnhart Huiman , Hayashi Paul H. , Chalasani Naga
Published: April 2020

INTRODUCTION:

Drug-induced liver injury (DILI) is a diagnosis of exclusion, and it can be challenging to adjudicate when there are multiple comorbidities and concomitant medications. In this study, we tested the hypothesis that comorbidity burden impacts the causality adjudication in patients with suspected DILI.

METHODS:

We studied consecutive patients with suspected DILI enrolled in the Drug-Induced Liver Injury Network Prospective Study at 2 centers between 2003 and 2017. The comorbidity burden at presentation was determined using the Charlson Comorbidity Index (CCI). We analyzed the association between significant comorbidity (CCI > 75th percentile) and (i) the adjudication of DILI by expert consensus as definite, highly likely, or probable (high-confidence DILI) and (ii) the Roussel Uclaf Causality Assessment Method (RUCAM) scores.

RESULTS:

Our cohort consisted of 551 patients who were classified as “no comorbidity” (54%, CCI = 0), “mild comorbidity” (29%, CCI = 1 or 2), and “significant comorbidity” (17%, CCI > 2). The probability of high-confidence DILI was significantly lower in patients with significant comorbidity compared with those with mild or no comorbidities (67% vs 76% vs 87%, respectively, P < 0.001). The mean RUCAM scores decreased with increasing comorbidity (no comorbidity 6.6 ± 2, mild comorbidity 6 ± 2.4, and significant comorbidity 5.6 ± 2.7, P < 0.001). In the multiple logistic regression, significant comorbidity had an independent inverse relationship with DILI (odds ratio: 0.37, 95% confidence interval: 0.2–0.69, P = 0.001).

DISCUSSION:

Higher comorbidity burden impacts the causality assessment in patients with suspected DILI. Further studies are needed to investigate the utility of comorbidity burden as a variable in the DILI causality instruments.
A distância é o que nos une
Authors: Coelho Marcelo , Faria Victor
Published: April 2020

Ainda hoje, algumas pessoas confundem ciência com opinião. Muito embora o direito à liberdade de pensamento e expressão seja garantido pelo artigo no13 da Constituição Federal, é preciso ter cautela em momentos delicados como o que vivemos. Já dizia o velho dito popular: “Contra fatos, não há argumentos; muito embora possa argumentar-se com os fatos”. Ciência é ciência. E ponto...
Análise da morfologia dos canais radiculares de pré-molares inferiores por meio da tomografia computadorizada de feixe cônico
Authors: Serqueira Stephânia Carolina , Lima Carolina , Devito Karina , Marion Jefferson , Prado Maíra , Campos Celso
Published: April 2020

O sucesso do tratamento endodôntico de- pende da limpeza e da modelagem dos canais radiculares. Para tanto, deve-se ter um conhecimento profundo sobre a anatomia do sistema de canais radiculares. No entanto, essa anatomia é complexa, com variações mor- fológicas em diferentes populações. Objetivo: O objetivo desse trabalho foi avaliar, em imagens de tomografia computadorizada de feixe cônico (TCFC), a anatomia dos canais radiculares de pré-molares (PM) inferiores de uma população brasileira. Métodos: Foram analisados 426 pré-molares inferiores nos cortes axiais, coronais e sagitais de TCFC. O número de raízes, canais radiculares e a classificação de Vertucci foram tabulados no programa Microsoft Excel. Associações entre o sexo, número de raízes e canais, e classificação de Vertucci foram avaliadas por meio do teste qui-quadrado (p<0,05). Resultados: dos 426 dentes avaliados, 224 (52,6%) foram 1oPM e 202 (47,4%), 2o PM. Os 1oPM apresentaram, em sua maioria, uma raiz (93,3%) e todos os 2oPM, apenas uma raiz. Nos dentes estudados, verificou-se classificação tipos I, II e V de Vertucci, sendo o tipo I o mais encontrado. O tipo V só esteve presente nos 1oPM com duas raízes (p<0,001). Não houve associação significativa entre o número de raízes e o sexo (p=0,182). Conclusão: A maioria dos pré-molares inferiores apresentou uma raiz com classificação tipo I de Vertucci, demonstrando uma baixa variação anatômica nos PM inferiores da população estudada. Não houve predileção por sexo, quanto ao número de raízes e à classificação do tipo de canal radicular.