bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mammary Tumors Growing in the Absence of Growth Hormone Are More Sensitive to Doxorubicin Than Wild-Type Tumors
Authors: Lantvit Daniel D , Unterberger Christopher J , Lazar Michelle , Arneson Paige D , Longhurst Colin A , Swanson Steven M , Marker Paul C 
Published: January 2021

AbstractPreviously, we reported that N-methyl-N-nitrosourea (MNU)-induced mammary tumors could be established in mutant spontaneous dwarf rats (SDRs), which lack endogenous growth hormone (GH) by supplementing with exogenous GH, and almost all such tumors regressed upon GH withdrawal. When the highly inbred SDR line was outcrossed to wild-type (WT) Sprague-Dawley rats, MNU-induced mammary tumors could still be established in resulting outbred SDRs by supplementing with exogenous GH. However, unlike tumors in inbred SDRs, 65% of mammary tumors established in outbred SDRs continued growth after GH withdrawal. We further tested whether these tumors were more sensitive to doxorubicin than their WT counterparts. To accomplish this, MNU-induced mammary tumors were established in WT rats and in SDRs supplemented with exogenous GH. Once mammary tumors reached 1 cm3 in size, exogenous GH was withdrawn from SDRs, and the subset that harbored tumors that continued or resumed growth in the absence of GH were selected for doxorubicin treatment. Doxorubicin was then administered in 6 injections over 2 weeks at 2.5 mg/kg or 1.25 mg/kg for both the WT and SDR groups. The SDR mammary tumors that had been growing in the absence of GH regressed at both doxorubicin doses while WT tumors continued to grow robustly. The regression of SDR mammary tumors treated with 1.25 mg/kg doxorubicin was accompanied by reduced proliferation and dramatically higher apoptosis relative to the WT mammary tumors treated with 1.25 mg/kg doxorubicin. These data suggest that downregulating GH signaling may decrease the doxorubicin dose necessary to effectively treat breast cancer.
EFA6A, an exchange factor for Arf6, regulates early steps in ciliogenesis
Authors: Partisani Mariagrazia , Baron Carole L. , Ghossoub Rania , Fayad Racha , Pagnotta Sophie , Abélanet Sophie , Macia Eric , Brau Frédéric , Lacas-Gervais Sandra , Benmerah Alexandre , Luton Frédéric , Franco Michel 
Published: January 2021

ABSTRACT
Ciliogenesis is a coordinated process initiated by the recruitment and fusion of pre-ciliary vesicles at the distal appendages of the mother centriole through mechanisms that remain unclear. Here, we report that EFA6A (also known as PSD), an exchange factor for the small G protein Arf6, is involved in early stage of ciliogenesis by promoting the fusion of distal appendage vesicles forming the ciliary vesicle. EFA6A is present in the vicinity of the mother centriole before primary cilium assembly and prior to the arrival of Arl13B-containing vesicles. During ciliogenesis, EFA6A initially accumulates at the mother centriole and later colocalizes with Arl13B along the ciliary membrane. EFA6A depletion leads to the inhibition of ciliogenesis, the absence of centrosomal Rab8-positive structures and the accumulation of Arl13B-positive vesicles around the distal appendages. Our results uncover a novel fusion machinery, comprising EFA6A, Arf6 and Arl13B, that controls the coordinated fusion of ciliary vesicles docked at the distal appendages of the mother centriole.
Sexual organ-sparing with hydrogel spacer injections for rectal cancer radiotherapy: a feasibility pilot study
Authors: Achard Vérane , Ris Frederic , Rouzaud Michel , Puppa Giacomo , Buchs Nicolas C , De Perrot Thomas , Koessler Thibaud , Picardi Cristina , Zilli Thomas 
Published: January 2021

Objectives:
The aim of this pilot study was to investigate in two rectal cancer patients undergoing neoadjuvant chemo-radiotherapy (nCRT) the implant feasibility and dosimetric benefit in sexual organ-sparing of an injectable, absorbable, radiopaque hydrogel spacer.

Methods:
Two rectal cancer patients (one male and one female) underwent hydrogel implant between rectum and vagina/prostate before nCRT and curative surgery. A CT scan was performed before and after injection and a comparative dosimetric study was performed testing a standard (45/50 Gy) and a dose escalated (46/55.2 Gy) schedule.

Results:
In both patients, the spacer implant in the recto-prostatic or recto-vaginal space was feasible and well tolerated. For the male, the dosimetric benefit with spacer was minimal for sexual organs. For the female however, doses delivered to the vagina were significantly reduced with spacer with a mean reduction of more than 5 Gy for both regimens.

Conclusions:
For organ preservation protocols and selected sexually active female patients, use of hydrogel spacers can be considered to spare sexual organs from the high radiotherapy dose levels.

Advances in knowledge:
For females with advanced rectal tumor, a spacer implant between the rectum and the vagina before nCRT is feasible and reduces doses delivered to the vagina.
netDx: Software for building interpretable patient classifiers by multi-'omic data integration using patient similarity networks
Authors: Pai Shraddha , Weber Philipp , Isserlin Ruth , Kaka Hussam , Hui Shirley , Shah Muhammad Ahmad , Giudice Luca , Giugno Rosalba , Nøhr Anne Krogh , Baumbach Jan , Bader Gary D. 
Published: January 2021

Patient classification based on clinical and genomic data will further the goal of precision medicine. Interpretability is of particular relevance for models based on genomic data, where sample sizes are relatively small (in the hundreds), increasing overfitting risk netDx is a machine learning method to integrate multi-modal patient data and build a patient classifier. Patient data are converted into networks of patient similarity, which is intuitive to clinicians who also use patient similarity for medical diagnosis. Features passing selection are integrated, and new patients are assigned to the class with the greatest profile similarity. netDx has excellent performance, outperforming most machine-learning methods in binary cancer survival prediction. It handles missing data – a common problem in real-world data – without requiring imputation. netDx also has excellent interpretability, with native support to group genes into pathways for mechanistic insight into predictive features. The netDx Bioconductor package provides multiple workflows for users to build custom patient classifiers. It provides turnkey functions for one-step predictor generation from multi-modal data, including feature selection over multiple train/test data splits. Workflows offer versatility with custom feature design, choice of similarity metric; speed is improved by parallel execution. Built-in functions and examples allow users to compute model performance metrics such as AUROC, AUPR, and accuracy. netDx uses RCy3 to visualize top-scoring pathways and the final integrated patient network in Cytoscape. Advanced users can build more complex predictor designs with functional building blocks used in the default design. Finally, the netDx Bioconductor package provides a novel workflow for pathway-based patient classification from sparse genetic data.
IMPORTANCE trial: a provisional study-design of a single-center, phase II, double-blinded, placebo-controlled, randomized, 4-week study to compare the efficacy and safety of intranasal esketamine in chronic opioid refractory pain
Authors: Fernandes Mauricio , Schelotto Magdalena , Doldi Philipp Maximilian , Milani Giovanna , Ariza Manzano Abul Andrés , Perera Valdivia Doriam , Winter Matos Alexandra Marie , Hamdy Abdelrahim Yasmin , Hamad Bek Shaza Ahmed , Benitez Benito K. , Romanelli Tavares Vanessa Luiza , Basendwah Abdulrahim M. , Albuquerque Sousa Luis Henrique , Xavier Naiara Faria , Zertuche Maldonado Tania , Toyomi de Oliveira Sarah , Chaker Melisa , Menon Miyake Michelle , Uygur Kucukseymen Elif , Waqar Kinza , Alkhozondar Ola M.J. , Bernardo da Silva Ricardo , Droppelmann Guilhermo , Vaz de Macedo Antonio , Nakamura Rui , Fregni Felipe 
Published: January 2021

Background: Cancer is the second leading cause of death globally. Up to 86% of advanced cancer patients experience significant pain, while 10-20% live in chronic pain. Besides, increasing prescription of opioids resulted in 33,000 deaths in the US in 2015. Both reduce patients’ functional status and quality of life. While cancer survival rates are increasing, therapeutic options for chronic opioid refractory pain are still limited. Esketamine is the s-enantiomer of ketamine, with superior analgesic effect and less psychotomimetic side effects. Intranasal esketamine was approved by the FDA for treatment-resistant depression. However, its use in chronic cancer pain has never been tested. Therefore, we propose a phase II, randomized, placebo-controlled trial to evaluate the efficacy and safety of intranasal esketamine in chronic opioid refractory cancer pain. Methods and analysis: We will recruit 120 subjects with chronic opioid refractory pain, defined as pain lasting more than 3 months despite optimal therapy with high dose opioids (>60 mg morphine equivalent dose/day) and optimal adjuvant therapy. Subjects will be randomized into two groups: intranasal esketamine (56mg) and placebo. Treatment will be administered twice a week for four consecutive weeks. The primary outcome is defined as reduction in the Numeric Pain Rating Scale (NPRS) after first application. Secondary outcomes include NPRS reduction after four weeks, the number of daily morphine rescue doses, functional status and satisfaction, and depression. Conclusion: This study may extend therapeutic options in patients with chronic pain, thus improving their quality of life and reducing opioid use. Trial registration: Clinical Trials.gov, NCT04666623. Registered on 14 December 2020
6th European Student Council Symposium (ESCS): overcoming obstacles to enhance virtuality, connectivity, inclusivity and community engagement
Authors: Olguín-Orellana Gabriel J. , Papadimitriou Sofia , Langtry Yáñez Alberto , Eranti Pradeep , Flores-Vallejo Rosario del Carmen , Castillo-Orozco Ana I. , Mayoral-Peña Kalaumari , Parra R. Gonzalo 
Published: January 2021

This editorial summarises the organisation, activities, and scientific content of the 6th European Student Council Symposium (ESCS) organised by the International Society for Computational Biology Student Council (ISCB-SC). The event was held on September 6, 2020, as a satellite event preceding the ISCB’s 19th European Conference in Computational Biology. Both events were first planned to be held in-person in Sitges, Spain, but moved virtually as a strategy to face the SARS-CoV2 sanitary crisis. This completely unforeseen situation has posed several challenges that have been successfully addressed thanks to the robust ISCB Student Council community structure and the strong commitment of the organisers. Despite all the obstacles and challenges, we have found that virtuality has several advantages that can continue to be kept to improve in-person meetings in the future and make conferences more inclusive allowing a larger audience to participate.
Dielectric Properties of Switchgrass and Corn Stover in the Radio Frequency Range
Authors: Souza Augusto M. , Birrell Stuart J. , Steward Brian L. 
Published: January 2021

HighlightsDielectric permittivities of switchgrass and corn stover in the radio frequency range were calculated.Prediction models achieved R2 &gt; 0.9, except for the switchgrass loss factor for the material in motion.The loss factors were different when static and in motion, but the dielectric constants were similar.Abstract. The dielectric properties of biological materials are relevant when developing moisture content sensors. However, little is known about the permittivities of switchgrass and corn stover in a wider frequency range. The goal of this research was to determine their dielectric constants and loss factors at different moisture contents across a frequency range of 5 Hz to 13 MHz and with the material static and in motion inside a sample container. The permittivity of these materials was calculated by measuring their admittance in a test fixture using an impedance analyzer at three different moisture levels (9.0% to 30.5%). Overall, the materials’ dielectric properties increased with moisture but decreased with frequency. Prediction models were developed using the data in a frequency range of 10 kHz to 5 MHz. Model coefficients of determination were higher than 0.90 in general, except for the model measuring the loss factor of switchgrass in motion. Additionally, the dielectric constant was not different with the materials static or in motion, but the loss factor values were distinct. This work can be used for the development of electrical moisture content sensors for switchgrass and corn stover. Keywords: Corn stover, Dielectric constant, Loss factor, Moisture content, Permittivity, Switchgrass.
When evidence alone is not enough: the problem, policy and politics of water fluoridation in England
Authors: Lowery Gary , Flinders Matthew , Gibson Barry J. 
Published: January 2021

Background: Tooth extractions are the most common cause of hospital admissions for children in England. Water fluoridation has the potential to reduce this number by 60%, is backed by the scientific and public health communities, and yet is currently consumed by only 10% of the population.
Aims and objectives: This ‘evidence-policy gap’ is explored through Kingdon’s ‘multi-streams approach’ which provides insights into the circumstances under which water fluoridation has made it onto the political agenda, the rationale underpinning opponent and advocate policy positions, and the role of the political arena in fostering or hindering policy action.
Methods: Over 100 primary documents were reviewed to develop an understanding of the scientific and ethical arguments for and against water fluoridation, as well as to identify how they have all historically sought to mobilise their policy preferences. Eleven consultations were also conducted with stakeholders as part of the knowledge exchange process.
Findings: The key finding of this research is that evidence is only likely to trigger policy change if it emerges into a receptive sociopolitical context. In substantiating this claim we identify evidence not of an ‘evidence-policy gap’ but of a more complex and multidimensional ‘evidence-policy-politics gap’.
Discussion and conclusions: The findings contribute to a range of debates in relation to: (1) the apparent irreconcilability of background ideas about what ought to form the basis of public health policymaking; (2) the presence of differing evidential standards that create an uneven playing field; and (3) the central underpinning role of politics in public health policymaking.
Diagnosis of soil-transmitted helminths using the Kato-Katz technique: What is the influence of stirring, storage time and storage temperature on stool sample egg counts?
Authors: Bosch Felix , Palmeirim Marta S. , Ali Said M. , Ame Shaali M. , Hattendorf Jan , Keiser Jennifer 
Published: January 2021

Background
Soil-transmitted helminths infect about one fifth of the world’s population and have a negative impact on health. The Kato-Katz technique is the recommended method to detect soil-transmitted helminth eggs in stool samples, particularly in programmatic settings. However, some questions in its procedure remain. Our study aimed to investigate the effect of storage time, storage temperature and stirring of stool samples on fecal egg counts (FECs).

Methodology/Principal findings
In the framework of a clinical trial on Pemba Island, United Republic of Tanzania, 488 stool samples were collected from schoolchildren. These samples were evaluated in three experiments. In the first experiment (n = 92), two Kato-Katz slides were prepared from the same stool sample, one was stored at room temperature, the other in a refrigerator for 50 hours, and each slide was analyzed at nine time points (20, 50, 80, 110, 140 minutes, 18, 26, 42 and 50 hours). In the second experiment (n = 340), whole stool samples were split into two, one part was stored at room temperature, and the other part was put in a refrigerator for 48 hours. From each part one Kato-Katz slide was prepared and analyzed at three time points over two days (0, 24 and 48 hours). In the third experiment (n = 56), whole stool samples where stirred for 15 seconds six times and at each time point a Kato-Katz slide was prepared and analyzed.
Mean hookworm FECs of Kato-Katz slides stored at room temperature steadily decreased following slide preparation. After two hours, mean hookworm FECs decreased from 22 to 16, whereas no reduction was observed if Kato-Katz slides were stored in the refrigerator (19 vs 21). The time x storage interaction effect was statistically significant (coefficient 0.26, 95% CI: 0.17 to 0.35, p < 0.0001). After 24 hours mean hookworm FECs dropped close to zero, irrespective of the storage condition. Whole stool samples stored at room temperature for one day resulted in a mean hookworm FEC decrease of 23% (p < 0.0001), compared to a 13% reduction (p < 0.0001) if samples were stored in the refrigerator. Fecal egg counts of A. lumbricoides and T. trichiura remained stable over time regardless of storage temperature of whole stool samples. Finally, we found a significant reduction of the variation of hookworm and T. trichiura eggs with increasing rounds of stirring the sample, but not for A. lumbricoides. For hookworm we observed a simultaneous decrease in mean FECs, making it difficult to draw recommendations on stirring samples.

Conclusions/Significance
Our findings suggest that stool samples (i) should be analyzed on the day of collection and (ii) should be analyzed between 20–30 minutes after slide preparation; if that is not possible, Kato-Katz slides can be stored in a refrigerator for a maximum of 110 minutes.
The Good Enough Parenting early intervention schema therapy based program: Participant experience
Authors: Louis John Philip , Ortiz Vida , Barlas Joanna , Lee Joyce Sue , Lockwood George , Chong Wayne Freeman , Louis Karen McDonald , Sim Patricia 
Published: January 2021

Background and objectives
Schema therapy (ST) has become a mainstream therapy for the treatment of psychopathology and has been validated through a series of large scale, international randomized control trials. Among other things, schema therapy emphasizes the meeting of core emotional needs in children by primary caregivers as these unmet needs continue to adversely affect their lives into adulthood. An early intervention parenting program has been developed to help parents meet these core emotional needs in order to prevent the development of psychopathology in the first place. The program, Good Enough Parenting, is equally focused on reducing problems and strengthening parenting practices, regardless of where the child is on the “disordered to well-being continuum”. This study aims to explore “patient experience” by users of this program. Best clinical research guidelines advocate that participants should be used as collaborators rather than pure recipients; this process should predate large scale trials.

Design
An exploratory qualitative study with 55 parent-participants of Good Enough Parenting was conducted.

Methods
One-to-one interviews were conducted with participants, using critical incident technique and guided by semi-structured interview schedule, to explore their experiences with the program. Transcripts were then analyzed using thematic analysis.

Results
Coding showed a high degree of inter-rater reliability (kappa value of 0.78). The themes that emerged were Cultivating Awareness of Parents’ Own Schemas, Cultivating Intentionality, Working through Developmental Issues, Responses to Challenges at Home, Performing Multiple Roles, and the Learning Process. Participants overwhelmingly reported satisfaction within these key themes.

Conclusions
The results support the development of the program and the choice of “participant reported outcome measures” for use in subsequent randomized controlled trials.
Integrated psychosocial, economic strengthening, and clinical service-delivery to improve health and resilience of adolescents living with HIV and their caregivers: Findings from a prospective cohort study in Zambia
Authors: Rosen Joseph G. , Phiri Lyson , Chibuye Mwelwa , Namukonda Edith S. , Mbizvo Michael T. , Kayeyi Nkomba 
Published: January 2021

Background
Children and youth are profoundly impacted groups in Zambia’s HIV epidemic. To evaluate delivery of integrated psychosocial, economic strengthening, and clinical services to HIV-affected households through the Zambia Family (ZAMFAM) Project, a prospective cohort study compared socio-economic, psychosocial, and health outcomes among ZAMFAM beneficiaries to non-beneficiaries.

Methods
In July–October 2017, 544 adolescents living with HIV (ALHIV) aged 5–17 years and their adult caregivers were recruited from Central (ZAMFAM implementation sites) and Eastern (non-intervention sites) Provinces. Structured interviews at baseline and one-year follow-up assessed household characteristics, socio-economic wellbeing, and health service utilization. Poisson regression with generalized estimating equations measured one-year changes in key health and socio-economic indicators, comparing ZAMFAM beneficiaries to non-beneficiaries.

Results
Overall, 494 households completed two rounds of assessment (retention rate: 91%) Among ALHIV, improvements in current antiretroviral therapy use over time (Adjusted Prevalence Rate Ratio [aPRR] = 1.06, 95% Confidence Interval [95% CI]: 1.01–1.11) and reductions in non-household labor (aPRR = 0.44, 95% CI: 0.20–0.99) were significantly larger among ZAMFAM beneficiaries than non-beneficiaries. For caregivers, receiving ZAMFAM services was associated with significant reductions in HIV-related stigma (aPRR = 0.49, 95% CI: 0.28–0.88) and perceived negative community attitudes towards HIV (aPRR = 0.77, 95% CI: 0.62–0.96). Improvements in caregiver capacity to pay for unexpected (aPRR = 1.54, 95% CI: 1.17–2.04) and food-related expenses (aPRR = 1.48, 95% CI: 1.16–1.90), as well as shared decision-making authority in household spending (aPRR = 1.41, 95% CI: 1.04–1.93) and self-reported good or very good health status (aPRR = 1.46, 95% CI: 1.14–1.87), were also significantly larger among ZAMFAM beneficiaries.

Conclusions
Significant improvements in caregivers’ financial capacity were observed among households receiving ZAMFAM services, with few changes in health or wellbeing among ALHIV. Integrated service-delivery approaches like ZAMFAM may yield observable socio-economic improvements in the short-term. Strengthening community-based delivery of psychosocial and health support to ALHIV is encouraged.