bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating the use of telemedicine in gynaecological practice: a systematic review
Authors: Murugesu Sughashini , Galazis Nicolas , Jones Benjamin P , Chan Maxine , Bracewell-Milnes Timothy , Ahmed-Salim Yousra , Grewal Karen , Timmerman Dirk , Yazbek Joseph , Bourne Tom , Saso Srdjan
Published: December 2020

Objectives

The aim of this systematic review is to examine the use of telemedicine in the delivery and teaching of gynaecological clinical practice. To our knowledge, no other systematic review has assessed this broad topic.

Design

Systematic review of all studies investigating the use of telemedicine in the provision of gynaecological care and education. The search for eligible studies followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and focused on three online databases: PubMed, Science Direct and SciFinder.

Eligibility criteria

Only studies within gynaecology were considered for this review. Studies covering only obstetrics and with minimal information on gynaecology, or clinical medicine in general were excluded. All English language, peer-reviewed human studies were included. Relevant studies published up to the date of final submission of this review were considered with no restrictions to the publication year.

Data extractions and synthesis

Data extracted included author details, year of publication and country of the study, study aim, sample size, methodology, sample characteristics, outcome measures and a summary of findings. Data extraction and qualitative assessment were performed by the first author and crossed checked by the second author. Quality assessment for each study was assessed using the Newcastle-Ottawa scale.

Results

A literature search carried out in August 2020 yielded 313 records published between 1992 and 2018. Following a rigorous selection process, only 39 studies were included for this review published between 2000 and 2018. Of these, 19 assessed gynaecological clinical practice, eight assessed gynaecological education, one both, and 11 investigated the feasibility of telemedicine within gynaecological practice. 19 studies were classified as good, 12 fair and eight poor using the Newcastle-Ottawa scale. Telecolposcopy and abortion care were two areas where telemedicine was found to be effective in potentially speeding up diagnosis as well as providing patients with a wide range of management options. Studies focusing on education demonstrated that telementoring could improve teaching in a range of scenarios such as live surgery and international teleconferencing.

Conclusions

The results of this review are promising and demonstrate that telemedicine has a role to play in improving clinical effectiveness and education within gynaecology. Its applications have been shown to be safe and effective in providing remote care and training. In the future, randomised controlled studies involving larger numbers of patients and operators with measurable outcomes are required in order to be able to draw reliable conclusions.
Baccalaureate nursing students’ experiences with high-fidelity simulation: protocol for a qualitative systematic review
Authors: Zhu Yuxuan , Geng Cong , Pei Xianbo , Chen Xiaoli
Published: December 2020

Introduction

High-fidelity simulation (HFS) can bridge the gap between theoretical knowledge and nursing practice and improve safety and quality of patient care in baccalaureate nursing education. Although inconsistent assessment instruments or lack of high-quality research designs affect the strength of the evidence and limit the generalisability of the results, quantitative studies generally demonstrate the effectiveness of HFS in baccalaureate nursing education. Synthesis of the existing evidence of baccalaureate nursing students’ experiences with HFS is crucial for the improvement and revision of simulation design and teaching.

Methods and analysis

A comprehensive search for qualitative studies on baccalaureate nursing students’ experiences with HFS will be conducted in the following databases: PubMed, Embase, CINAHL, ProQuest, Web of Science, PsycINFO, the Cochrane library, China Biology Medicine disc, China National Knowledge Infrastructure and VIP Database for Chinese Technical Periodicals. This review considered studies reported in English or Chinese, and studies that were conducted between January 2000 and December 2019 in view of the launch of International Nursing Association for Clinical Simulation and Learning. The literature search will be conducted by two independent reviewers, and any disagreement will be adjudicated by discussion or with a third reviewer. The two independent reviewers will use the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Qualitative Research to assess the methodological validity, following which the JBI standardised data extraction tools will be used to extract relevant data. The JBI meta-aggregation method will be subsequently used to synthesise the data, eventually forming themes, categories and synthesised findings. The final synthesised findings will establish confidence levels based on the JBI ConQual approach.

Ethics and dissemination

This review does not require formal ethical review since it is based on available published literature. Findings will be disseminated through publication in a peer-reviewed journal, and, if possible, presented in scientific conferences.
Enhancing community participation for stroke survivors with cognitive impairment: study protocol for a randomised controlled trial in Taiwan
Authors: Chang Feng-Hang , Chiu Valeria , Ni Pengsheng , Lin Yen-Nung , Kang Jiunn-Horng , Liou Tsan-Hon , Lu Lu , Han Der-Sheng , Skidmore Elizabeth R
Published: December 2020

Introduction

Stroke can lead to life-long disability and constitutes a huge financial burden on the family and society. Stroke survivors with cognitive impairment often experience considerable challenges in the process of recovery and returning to society. Interventions that effectively help individuals resume essential daily activities and return to active participation in their communities are lacking. This study examines the efficacy of a newly-developed intervention programme, the Optimising Participation after Stroke through Strategy-training (OPASS) programme, for improving community participation among stroke survivors with cognitive impairment.

Methods and analysis

A single-blind, parallel-group randomised controlled trial with allocation concealment and assessor blinding will be implemented to assess the efficacy of the OPASS programme. An expected 210 adults with cognitive impairment following stroke will be randomly assigned to either the experimental intervention (OPASS) group or the attention control group. In addition to their usual rehabilitation, both groups will receive 45 min sessions, twice weekly for a total of 12–15 sessions. The primary outcome is change in participation performance, which will be measured using the participation measure—three domains, four dimensions scale. Additional measures include the Activity Measure for Post-Acute Care generic outpatient short forms, Montreal Cognitive Assessment, Stroop Test, Trail Making Test and General Self-Efficacy Scale. These scales will be administered at baseline, post-intervention, 3-month follow-up, 6-month follow-up and 12-month follow-up. Their results will be analysed using multiple linear regression models and mixed-effects regression models. Further assessment of feasibility and acceptability of the intervention will be conducted through structured interviews with participants, caregivers and therapists. These interviews will be transcribed and thematically analysed.

Ethics and dissemination

Ethics approval was obtained from the Ethics Committee of Taipei Medical University (approval number: N201804055). The findings will be disseminated through presentations at scientific conferences and through publication in peer-reviewed journals.

Trial registration number

NCT03792061; pre-results.
Evidence of sociocultural factors influencing intimate partner violence among young women in sub-Saharan Africa: a scoping review
Authors: Maguele Maria Suzana , Taylor Myra , Khuzwayo Nelisiwe
Published: December 2020

Objective

This study carried out a scoping review of research on intimate partner violence to determine the extent to which studies on sociocultural factors influencing intimate partner violence among young women (15–24 years) have been conducted, and how different geographical areas are represented. It also considered whether the methodologies used were sufficient to describe the risk factors, prevalence and health outcomes associated with intimate partner violence among young women.

Study design

Scoping review.

Methods

Online databases were used to identify studies published between 2008 and 2019. The Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines by Arksey and O’Malley were used to select studies, and primary studies were assessed using the Mixed Method Appraisal Tool, V.2011. Thematic content analysis was used to summarise the findings of the scoping review.

Results

The majority of publications eight (61.5%) reported cross-sectional studies, while four (31.5%) were qualitative studies. One of the studies (7%) collected measured data. Overall, 13 (100%) of the publications examined factors influencing intimate partner violence.

Using a customised quality assessment instrument, 12 (92.3%) of studies achieved a ‘high’-quality ranking with a score of 100%, and 7.7% of studies achieved an ‘average’ quality ranking with a score of 75%.

Conclusions

While the quality of the studies is generally high, researches on sociocultural factors influencing intimate partner violence among young women would benefit from a careful selection of methods and reference standards, including direct measures of the violence affecting young women. Prospective cohort studies are required linking early exposure with individual, sociocultural and community factors, and detailing the abuse experienced from childhood, adolescence and youth.

PROSPERO registration number

CRD42018116463.

Scoping protocol publication

https://doi.org/10.1186/s13643-019-1234-y
Vitamin D supplementation prior to in vitro fertilisation in women with polycystic ovary syndrome: a protocol of a multicentre randomised, double-blind, placebo-controlled clinical trial
Authors: Hu Kai-Lun , Gan Kwanghann , Wang Rui , Li Wentao , Wu Qiongfang , Zheng Beihong , Zou Libo , Zhang Su , Liu Yifeng , Wu Yiqing , Chen Ruixue , Cao Wushuang , Yang Shuo , Liu Fen-Ting , Tian Lifeng , Zeng Han , Xu Huiling , Qiu Shumin , Yang Lihua , Chen Xiao , Pan Xiaoqin , Wu Xiaoyun , Mol Ben W , Li Rong , Zhang Dan
Published: December 2020

Introduction

Polycystic ovary syndrome (PCOS) is one of the leading causes of female infertility, affecting around 5% of women of childbearing age in China. Vitamin D insufficiency is common in women with PCOS and is associated with lower live birth rates. However, evidence regarding the effectiveness of vitamin D supplementation in women with PCOS is inconclusive. This multicentre randomised, double-blinded, placebo-controlled trial aims to evaluate the effectiveness of vitamin D supplementation prior to in vitro fertilisation (IVF) on the live birth rate in women with PCOS.

Methods and analysis

We plan to enrol women with PCOS scheduled for IVF. After informed consent, eligible participants will be randomised in a 1:1 ratio to receive oral capsules of 4000 IU vitamin D per day or placebo for around 12 weeks until the day of triggering. All IVF procedures will be carried out routinely in each centre. The primary outcome is live birth after the first embryo transfer. The primary analysis will be by intention-to-treat analysis. To demonstrate or refute that treatment with vitamin D results in a 10% higher live birth rate than treatment with placebo, we need to recruit 860 women (48% vs 38% difference, anticipating 10% loss to follow-up and non-compliance, significance level 0.05 and power 80%).

Ethics and dissemination

This study has been approved by the Ethics Committee in Women’s Hospital of Zhejiang University on 2 March 2020 (reference number: IRB-20200035-R). All participants will provide written informed consent before randomisation. The results of the study will be submitted to scientific conferences and a peer-reviewed journal.

Trial registration number

NCT04082650.
Senior ambulance officers in Swedish emergency medical services: a qualitative study of perceptions and experiences of a new management role in challenging incidents
Authors: Hylander Johan , Saveman Britt-Inger , Björnstig Ulf , Gyllencreutz Lina
Published: December 2020

Objectives

Increased demands are placed on emergency services and their role and ability to act in incidents in challenging environments, for example, road tunnels. Collaboration between officers from emergency services (fire brigade, police and ambulance services) is important for an effective rescue effort. In Gothenburg, Sweden, a position as a senior ambulance officer (SAO) within the emergency medical services (EMS) has been introduced to support the regular force during major incidents. The aim of this paper was to explore the perceptions and experiences of the SAO’s new management role in challenging incidents, such as those occurring in road tunnels.

Design

A qualitative interview study.

Setting

The study was carried out from February to June 2019 in Gothenburg, Sweden, which is a municipality with several road tunnels and a population of approximately 580 000 people. SAOs collaborate with the corresponding function within the police and fire brigade, both having senior officers at major incident sites.

Participants

Twelve SAOs.

Methods

The study used semistructured interviews. The collected data were analysed using qualitative content analysis.

Results

According to SAOs’ experience, prehospital medical management included not only leadership, but also planning, training and indepth knowledge of, for example, tunnel environments. Furthermore, SAOs adopted an encouraging and teaching role for their colleagues. SAOs’ responsibilities also included proactive planning together with the fire brigade and police, which was regarded as enhancing interorganisational collaboration. An overall theme emerged which the SAOs described as ‘A new holistic approach to EMS leadership and management’.

Conclusions

The participants considered that the new SAO role not only seems to improve the prehospital medical management, but also makes the EMS command structure during challenging incidents symmetrical with the fire brigade and police command structure. The implementation of national guidelines is desirable and is requested by the SAOs.
Epidemiological characterisation of asymptomatic carriers of COVID-19 in Colombia: a cross-sectional study
Authors: Teherán Aníbal A. , Camero Ramos Gabriel , Prado de la Guardia Ronald , Hernández Carolina , Herrera Giovanny , Pombo Luis M , Avila Albert Alejandro , Flórez Carolina , Barros Esther C , Perez-Garcia Luis , Paniz-Mondolfi Alberto , Ramírez Juan David
Published: December 2020

Introduction

Asymptomatic carriers (AC) of the new SARS-CoV-2 represent an important source of spread for COVID-19. Early diagnosis of these cases is a powerful tool to control the pandemic. Our objective was to characterise patients with AC status and identify associated sociodemographic factors.

Methods

Using a cross-sectional design and the national database of daily occurrence of COVID-19, we characterised both socially and demographically all ACs. Additional correspondence analysis and logistic regression model were performed to identify characteristics associated with AC state (OR, 95% CI).

Results

76.162 ACs (12.1%; 95% CI 12.0% to 12.2%) were identified, mainly before epidemiological week 35. Age≤26 years (1.18; 1.09 to 1.28), male sex (1.51; 1.40 to 1.62), cases imported from Venezuela, Argentina, Brazil, Germany, Puerto Rico, Spain, USA or Mexico (12.6; 3.03 to 52.5) and autochthonous cases (22.6; 5.62 to 91.4) increased the risk of identifying ACs. We also identified groups of departments with moderate (1.23; 1.13 to 1.34) and strong (19.8; 18.6 to 21.0) association with ACs.

Conclusion

Sociodemographic characteristics strongly associated with AC were identified, which may explain its epidemiological relevance and usefulness to optimise mass screening strategies and prevent person-to-person transmission.
Utility of established prognostic scores in COVID-19 hospital admissions: multicentre prospective evaluation of CURB-65, NEWS2 and qSOFA
Authors: Bradley Patrick , Frost Freddy , Tharmaratnam Kukatharmini , Wootton Daniel G
Published: December 2020

Introduction

The COVID-19 pandemic is ongoing, yet, due to the lack of a COVID-19-specific tool, clinicians must use pre-existing illness severity scores for initial prognostication. However, the validity of such scores in COVID-19 is unknown.

Methods

The North West Collaborative Organisation for Respiratory Research performed a multicentre prospective evaluation of adult patients admitted to the hospital with confirmed COVID-19 during a 2-week period in April 2020. Clinical variables measured as part of usual care at presentation to the hospital were recorded, including the Confusion, Urea, Respiratory Rate, Blood Pressure and Age Above or Below 65 Years (CURB-65), National Early Warning Score 2 (NEWS2) and Quick Sequential (Sepsis-Related) Organ Failure Assessment (qSOFA) scores. The primary outcome of interest was 30-day mortality.

Results

Data were collected for 830 people with COVID-19 admitted across seven hospitals. By 30 days, a total of 300 (36.1%) had died and 142 (17.1%) had been in the intensive care unit. All scores underestimated mortality compared with pre-COVID-19 cohorts, and overall prognostic performance was generally poor. Among the ‘low-risk’ categories (CURB-65 score<2, NEWS2<5 and qSOFA score<2), 30-day mortality was 16.7%, 32.9% and 21.4%, respectively. NEWS2≥5 had a negative predictive value of 98% for early mortality. Multivariable logistic regression identified features of respiratory compromise rather than circulatory collapse as most relevant prognostic variables.

Conclusion

In the setting of COVID-19, existing prognostic scores underestimated risk. The design of new prognostic tools should focus on features of respiratory compromise rather than circulatory collapse. We provide a baseline set of variables which are relevant to COVID-19 outcomes and may be used as a basis for developing a bespoke COVID-19 prognostication tool.
End-of-life care for older first-generation migrants: a scoping review
Authors: Gerber Katrin , Maharaj Emma , Brijnath Bianca , Antoniades Josefine
Published: December 2020

Background

The unprecedented scale of contemporary migration across countries over the last decade means that ageing and dying occur in a more globalised, multicultural context. It is therefore essential to explore the end-of-life experiences of older people from migrant backgrounds.

Methods

A scoping review of peer-reviewed articles published in English from 2008 to 2018. Included studies addressed end-of-life preferences, attitudes, values and beliefs of first-generation international migrants who were at least 50 years of age.

Results

Fifteen studies met the inclusion criteria for this review, which addressed six key themes: (1) the reluctance among older migrants and their families to talk about death and dying; (2) difficult communication in patient-clinician relationships; (3) the contrast between collectivistic and individualistic norms and its associated end-of-life preferences; (4) limited health literacy in older adults from migrant backgrounds; (5) experiences with systemic barriers like time pressure, inflexibility of service provision and lack of cultural sensitivity and (6) the need for care providers to appreciate migrants’ ‘double home experience’ and what this means for end-of-life decision-making regarding place of care and place of death.

Discussion

To respond effectively to an increasingly culturally diverse population, healthcare staff, researchers and policymakers need to invest in the provision of culturally sensitive end-of-life care. Areas for improvement include: (a) increased awareness of cultural needs and the role of family members; (b) cultural training for healthcare staff; (c) access to interpreters and translated information and (d) involvement of older migrants in end-of-life discussions, research and policymaking.
Abnormalities of the rib growth plate and the periphysis of previously healthy infants and toddlers dying suddenly and unexpectedly
Authors: Groff Elisa , Uday Suma , Zapata Vazquez Rita , Zainun Khairul , Cohen Marta C
Published: December 2020

Aims

Histological examination of the rib is of critical value in perinatal pathology and points to the health of the child preceding death. The rib is considered ideal because it is the most rapidly growing long bone in infants and demonstrates growth arrest at onset of the insult. We aimed to identify: (1) changes in the perichondrial ring (PR) in the rib of infants and children up to 16 months of age dying suddenly at our institution and (2) any association with presence of histological changes of vitamin D deficiency (VDD)/metabolic bone disease (MBD) in the growth plate.

Methods

Retrospective review of the PR histology and comparison with the presence or absence of histological features of VDD in the growth plate of 167 cases. The cases were anonymised and divided in six age/gender categories.

Results

Periphyseal abnormalities were only seen in 38% of the cases; of whom 33% had established and 67% had mild changes. Only 14.5% of cases with established histological appearance of VDD at the growth plate had significant PR abnormality; of whom majority (83%) were ≤3 months of age and none ≥9 months old, reflecting a temporal relation with birth and beyond the perinatal period.

Conclusion

The histological changes in the PR are significantly associated with histological changes of VDD/MBD at the rib growth plate with an OR of 3.04.
Gene of the month:DICER1:ruler and controller
Authors: Thunders Michelle , Delahunt Brett
Published: December 2020

DICER1 is a highly conserved RNaseIII endoribonuclease that has a critical role in the biogenesis of microRNAs (miRNAs). miRNAs are small regulatory RNAs responsible for post-transcriptional gene silencing, controlling more than half of human protein-coding genes. This is achieved through the targeting and regulation of complementary RNA transcripts and has a well-documented role in post-transcriptional gene regulation and transposon repression. DICER1 deficiency results in dysregulation of miRNAs, changing the expression of many genes. DICER1 syndrome represents a collection of benign and malignant tumours arising from an autosomally inherited germline mutation leading to an inherited predisposition to cancer. The syndrome represents an unusual form of Knudson’s two-hit hypothesis, where individuals with a pathogenic germlineDICER1variant acquire a second trans-somatic missenseDICER1mutation. This somatic mutation appears to have to occur in one of five hotspots codons and may contribute towards the incomplete penetrance observed within DICER1 syndrome families. In this case, DICER1 is haploinsuffcient with only one deletion required and partial loss of function being advantageous to tumours over complete loss of function. As increasing data emerge reaffirming the pivotal role of DICER1 in the maintenance of human physiology,DICER1is likely to become an increasingly attractive target for novel therapeutic strategies.
Body dissatisfaction predicts the onset of depression among adolescent females and males: a prospective study
Authors: Bornioli Anna , Lewis-Smith Helena , Slater Amy , Bray Isabelle
Published: December 2020

Rationale

Body dissatisfaction is prevalent in mid-adolescence and may be associated with the onset of depression.

Objective

The study assessed the influence of body dissatisfaction on the occurrence of later depressive episodes in a population-based sample of British adolescents.

Method

Participants were 2078 females and 1675 males from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. Logistic regression was used to test if body dissatisfaction at 14 years old predicted the onset of depressive episodes at 18 years old, controlling for baseline depression.

Results

Among females, body dissatisfaction predicted mild (OR=1.63, 95% CI=1.31, 2.04), moderate (OR=1.67, 95% CI=1.28, 2.18) and severe depressive episodes (OR=1.84, 95% CI=1.09, 3.12). Among males, body dissatisfaction predicted mild (OR=1.50, 95% CI=1.00, 2.25) and severe depressive episodes (OR=2.85, 95% CI=1.18, 6.87) at 18 years of age.

Conclusions

This is the first prospective study to demonstrate that body dissatisfaction in adolescence predicts the occurrence of later depressive episodes in a cohort born in the early 1990s. The findings highlight that body dissatisfaction is a public health concern.
Preschool attendance and developmental outcomes at age five in Indigenous and non-Indigenous children: a population-based cohort study of 100 357 Australian children
Authors: Falster Kathleen , Hanly Mark , Edwards Ben , Banks Emily , Lynch John W , Eades Sandra , Nickel Nathan , Goldfeld Sharon , Biddle Nicholas
Published: December 2020

Background

Policies to increase Australian Indigenous children’s participation in preschool aim to reduce developmental inequities between Indigenous and non-Indigenous children. This study aims to understand the benefits of preschool participation by quantifying the association between preschool participation in the year before school and developmental outcomes at age five in Indigenous and non-Indigenous children.

Methods

We used data from perinatal, hospital, birth registration and school enrolment records, and the Australian Early Development Census (AEDC), for 7384 Indigenous and 95 104 non-Indigenous children who started school in New South Wales, Australia in 2009/2012. Preschool in the year before school was recorded in the AEDC. The outcome was developmental vulnerability on ≥1 of five AEDC domains, including physical health, emotional maturity, social competence, language/cognitive skills and communication skills/general knowledge.

Results

5051 (71%) Indigenous and 68 998 (74%) non-Indigenous children attended preschool. Among Indigenous children, 33% of preschool attenders and 44% of the home-based care group were vulnerable on ≥1 domains, compared with 17% of preschool attenders and 33% in the home-based care group among non-Indigenous children. In the whole population model, the adjusted risk difference for developmental vulnerability among preschool attenders was −7.9 percentage points (95% CI, −9.8 to −6.1) in non-Indigenous children and −2.8 percentage points (95% CI −4.8 to −0.7) in Indigenous children, compared with Indigenous children in home-based care.

Conclusions

Our findings suggest a likely beneficial effect of preschool participation on developmental outcomes, although the magnitude of the benefit was less among Indigenous compared with non-Indigenous children.
Role of immunotherapy in Ewing sarcoma
Authors: Morales Erin , Olson Michael , Iglesias Fiorella , Dahiya Saurabh , Luetkens Tim , Atanackovic Djordje
Published: December 2020

Ewing sarcoma (ES) is thought to arise from mesenchymal stem cells and is the second most common bone sarcoma in pediatric patients and young adults. Given the dismal overall outcomes and very intensive therapies used, there is an urgent need to explore and develop alternative treatment modalities including immunotherapies. In this article, we provide an overview of ES biology, features of ES tumor microenvironment (TME) and review various tumor-associated antigens that can be targeted with immune-based approaches including cancer vaccines, monoclonal antibodies, T cell receptor-transduced T cells, and chimeric antigen receptor T cells. We highlight key reasons for the limited efficacy of various immunotherapeutic approaches for the treatment of ES to date. These factors include absence of human leukocyte antigen class I molecules from the tumor tissue, lack of an ideal surface antigen, and immunosuppressive TME due to the presence of myeloid-derived suppressor cells, F2 fibrocytes, and M2-like macrophages. Lastly, we offer insights into strategies for novel therapeutics development in ES. These strategies include the development of gene-modified T cell receptor T cells against cancer–testis antigen such as XAGE-1, surface target discovery through detailed profiling of ES surface proteome, and combinatorial approaches. In summary, we provide state-of-the-art science in ES tumor immunology and immunotherapy, with rationale and recommendations for future therapeutics development.
Combining inhibition of galectin-3 with and before a therapeutic vaccination is critical for the prostate-tumor-free outcome
Authors: Tiraboschi Carolina , Gentilini Lucas , Velazquez Carla , Corapi Enrique , Jaworski Felipe Martín , Garcia Garcia José Daniel , Rondón Yorfer , Chauchereau Anne , Laderach Diego José , Compagno Daniel
Published: December 2020

Background

Prostate cancer (PCa) is a major health problem worldwide. Taxol derivatives-based chemotherapies or immunotherapies are usually proposed depending on the symptomatic status of the patient. In the case of immunotherapy, tumors develop robust immune escape mechanisms that abolish any protective response, and to date why prostate cancer is one of the most resistant diseases remains unresolved.

Methods

By using a combination of clinical data to study the transcriptome of metastasis samples from patients with castration-refractory prostate cancer, and state of the art cellular and molecular biology assays in samples from tumor-bearing mice that have been submitted to surgical resection of the tumor before receiving a vaccination, we answered several essential questions in the field of immunotherapy for prostate cancer. We also used two different methods to inhibit the expression of galectin-3 (Gal-3) in tumor cells: a stable RNA interference method to control the expression of this galectin efficiently only in tumor cells, and low and non-cytotoxic doses of docetaxel to easily transfer our findings to clinical settings.

Results

Herein, we show for the first time that Gal-3 expressed by prostate tumor cells is the main immune checkpoint responsible for the failure of vaccine-based immunotherapy. Our results show that low and non-cytotoxic doses of docetaxel lead to the inhibition of Gal-3 expression in PCa cells as well as in clinical samples of patients with metastatic and castration-resistant PCa promoting a Th1 response. We thus optimized a prostate cancer animal model that undergoes surgical resection of the tumor to mimic prostatectomy usually performed in patients. Importantly, using Gal-3-knocked down-PCa cells or low and non-cytotoxic doses of taxane before vaccination, we were able to highly control tumor recurrence through a direct impact on the proliferation and infiltration of CD8+ cytotoxic T.

Conclusions

Thus, Gal-3 expression by PCa cells is a crucial inhibitor for the success of immunotherapy, and low doses of docetaxel with non-cytotoxic effect on leukocyte survival could be used before immunotherapy for all patients with PCa to reduce the expression of this critical negative immune checkpoint, pre-conditioning the tumor-microenvironment to activate an antitumor immune response and promote tumor-free outcome.
Ion availabilities in two forest soils amended with alkaline-treated biosolids, agricultural lime, and wood fly ash over a 10-week period
Authors: Keys Kevin , Burton David L. , Price G.W. , Duinker Peter N.
Published: December 2020

Two forest soil B-horizons were amended with alkaline-treated biosolids (ATB), powdered agricultural lime, and wood fly ash under controlled conditions to compare initial ion availabilities over a 10-week period. ATB was most effective in supplying available Ca2+but least effective in supplying available Mg2+, for which lime was most effective. Availability of K+and SO42–-S was greatest in fly ash amended soils because of high K and S loading rates and the high electrical conductivity of this amendment. Mineral N (NO3–-N + NH4+-N) availability increased in ATB amended soils, stayed the same in lime amended soils, and decreased in fly ash amended soils. Availability of PO43–-P was low in all soils but slightly enhanced in ATB amended soils. Fluxes of Cu2+, Pb2+, Zn2+, and Mn2+in amended soils generally decreased over time in association with increased soil pH. Fluxes of Cd2+were not affected by any treatment. Results suggest that ATB is equally as effective as or more effective than lime and fly ash at immediately supplying Ca2+, but less effective at supplying Mg2+because of low inputs and cation competition. This suggests that ATB amendments could be an alternative means of quickly adding available Ca2+to Ca-depleted forest soils as long as potential impacts on other nutrient base cations are considered.
Melatonin decreases circulating Trypanosoma cruzi load with no effect on tissue parasite replication
Authors: Providello Maiara Voltarelli , Portapilla Gisele Bulhões , Oliveira Pedro Alexandre Sampaio , da Silva Carla Brigagão Pacheco , Anchieta Naira Ferreira , Tirapelli Carlos Renato , de Albuquerque Sérgio
Published: December 2020

Cardiac damage during the acute phase of Chagas disease (CD) is associated with an increase in pro-inflammatory markers and oxidative stress. Melatonin (MEL) has emerged as a promising therapy for CD due to its antioxidant and immunomodulatory properties; however, the protective action of MEL in the cardiac tissue, as well as its direct action on the parasite cycle, is not fully understood. We investigated the effects of MEL on heart parasitism in mice infected with Trypanosoma cruzi and also its effects on the parasitic proliferation in vitro. Our in vivo study showed that MEL reduced circulating parasitemia load, but did not control tissue (heart, liver, and spleen) parasitism in mice. MEL did not prevent the redox imbalance in the left ventricle of infected mice. Our in vitro findings showed that MEL did not inhibit parasites replication within cells, but rather increased their release from cells. MEL did not control parasitism load in the heart or prevent the cardiac redox imbalance induced by acute T. cruzi infection. The hormone controlled the circulating parasitic load, but within cells MEL accelerated parasitic release, a response that can be harmful.
Top condensation model: a step towards the correct prediction of the Higgs mass
Authors: Osipov A. A. , Hiller B. , Blin A. H. , Palanca F. , Moreira J. , Sampaio M.
Published: December 2020

A realization of the composite Higgs scenario in the context of the effective model with the $$SU(2)_L\times U(1)_R$$

S
U

(
2
)

L

×
U

(
1
)

R

symmetric four-Fermi interactions proposed by Miransky, Tanabashi and Yamawaki is studied. The model implements Nambu’s mechanism of dynamical electroweak symmetry breaking leading to the formation of $${{\bar{t}}}t$$

t

¯

t

and $${{\bar{b}}}b$$

b

¯

b

quark condensates. We explore the vacuum structure and spectrum of the model by using the Schwinger proper-time method. As a direct consequence of this mechanism, the Higgs acquires a mass in accord with its experimental value. The present prediction essentially differs from the known overestimated value, $$m_\chi = 2m_t$$

m
χ

=
2

m
t

, making more favourable the top condensation scenario presented here. The mass formulas for the members of the second Higgs doublet are also obtained. The Nambu sum rule is discussed. It is shown that the anomalous $$U(1)_A$$

U

(
1
)

A

symmetry breaking modifies this rule at next to leading order in $$1/N_c$$

1
/

N
c

.
Synchronization of chaotic systems and long short-term memory networks by sharing a single variable
Authors: Zhang Kai , Chen Xiaolu , Weng Tongfeng , Wang Hao , Yang Huijie , Gu Changgui
Published: December 2020

We adopt long short-term memory (LSTM) networks to model and characterize chaotic systems rather than conventional dynamical equations. We find that a well-trained LSTM system can synchronize with its learned chaotic system via transmitting a common signal. In the same fashion, we show that when learning an identical chaotic system, the trained LSTM systems can also be synchronized. Remarkably, we find that a cascading synchronization will be achieved among chaotic systems and their trained LSTM systems in the same manner. We further validate that this synchronization behavior is robust even the transmitting signal is contaminated with relatively a high level of white noise. Our work reveals that synchronization is a common behavior linking chaotic systems and their learned LSTM networks.
The simplest equation approach for solving non-linear Tzitzéica type equations in non-linear optics
Authors: Zafar Asim , Rezazadeh Hadi , Reazzaq Waseem , Bekir Ahmet
Published: December 2020

The aim of this work is to investigate new exact solutions of Tzitzéica type equations. We utilize the Painlevé transformation to transform the aforesaid non-linear evolution equations into ordinary differential equations. Then, the simplest equation method is employed for securing some real and complex solutions of the Tzitzéica equation, the Tzitzéica–Dodd–Bullough equation and the Dodd–Bullough–Mikhailov equation. After the execution of the simplest equation method, we obtain many new results more simply and reliably than the other approaches executed on these equations. The solutions are obtained and verified through soft computations. Also, the dynamics of some solutions are presented via three types of graphs including 2D, 3D and contour graphs.
The Mechanosensory Transduction Machinery in Inner Ear Hair Cells
Authors: Zheng Wang , Holt Jeffrey R.
Published: December 2020

Sound-induced mechanical stimuli are detected by elaborate mechanosensory transduction (MT) machinery in highly specialized hair cells of the inner ear. Genetic studies of inherited deafness in the past decades have uncovered several molecular constituents of the MT complex, and intense debate has surrounded the molecular identity of the pore-forming subunits. How the MT components function in concert in response to physical stimulation is not fully understood. In this review, we summarize and discuss multiple lines of evidence supporting the hypothesis that transmembrane channel-like 1 is a long-sought MT channel subunit. We also review specific roles of other components of the MT complex, including protocadherin 15, cadherin 23, lipoma HMGIC fusion partner-like 5, transmembrane inner ear, calcium and integrin-binding family member 2, and ankyrins. Based on these recent advances, we propose a unifying theory of hair cell MT that may reconcile most of the functional discoveries obtained to date. Finally, we discuss key questions that need to be addressed for a comprehensive understanding of hair cell MT at molecular and atomic levels.
Ex Vivo Analysis of Primary Tumor Specimens for Evaluation of Cancer Therapeutics
Authors: Tognon Cristina E. , Sears Rosalie C. , Mills Gordon B. , Gray Joe W. , Tyner Jeffrey W.
Published: December 2020

The use of ex vivo drug sensitivity testing to predict drug activity in individual patients has been actively explored for almost 50 years without delivering a generally useful predictive capability. However, extended failure should not be an indicator of futility. This is especially true in cancer research, where ultimate success is often preceded by less successful attempts. For example, both immune- and genetic-based targeted therapies for cancer underwent numerous failed attempts before biological understanding, improved targets, and optimized drug development matured to facilitate an arsenal of transformational drugs. Similarly, directly assessing drug sensitivity of primary tumor biopsies—and the use of this information to help direct therapeutic approaches—has a long history with a definitive learningcurve. In this review, we survey the history of ex vivo testing and the current state of the art for this field. We present an update on methodologies and approaches, describe the use of these technologies to test cutting-edge drug classes, and describe an increasingly nuanced understanding of tumor types and models for which this strategy is most likely to succeed. We consider the relative strengths and weaknesses of predicting drug activity across the broad biological context of cancer patients and tumor types. This includes an analysis of the potential for ex vivo drug sensitivity testing to accurately predict drug activity within each of the biological hallmarks of cancer pathogenesis.
Small-Molecule Approaches to Targeted Protein Degradation
Authors: Faust Tyler B. , Donovan Katherine A. , Yue Hong , Chamberlain Philip P. , Fischer Eric S.
Published: December 2020

Many essential biological processes are regulated through proximity, from membrane receptor signaling to transcriptional activity. The ubiquitin-proteasome system controls protein degradation, with ubiquitin ligases as the rate-limiting step. Ubiquitin ligases are commonly controlled at the level of substrate recruitment and, therefore, by proximity. There are natural and synthetic small molecules that also operate through induced proximity. For example, thalidomide is effective in treating multiple myeloma and functions as a molecular glue that stabilizes novel protein-protein interactions between a ubiquitin ligase and proteins not otherwise targeted by the ligase, leading to neo-substrate degradation. Emerging data on new degrader molecules have uncovered diverse mechanisms distinct from molecular glues, which often mirror the regulatory mechanisms that control substrate-ligase proximity in nature. In this review, we summarize our current understanding of biological and synthetic regulation of protein degradation and share our view on how these diverse mechanisms have inspired novel therapeutic directions.
High TEC Copper to Connect Copper Bond Pads for Low Temperature Wafer Bonding
Authors: Tran Anh Van Nhat , Hirato Tetsuji , Kondo Kazuo
Published: December 2020

Copper to copper wafer hybrid bonding is the most promising technology for three-dimensional (3D) integration. In the hybrid bonding process, two silicon wafers are aligned and contacted. At room temperature (RT), these aligned copper pads contain radial-shaped nanometer-sized hollows due to the dishing effect induced by chemical-mechanical polishing (CMP). These wafers are annealed for copper to expand and connect upper and lower pads. This copper expansion is key to eliminate the radial-shaped hollows and make copper pads contacted. Therefore, in this research, we investigated the new high thermal expansion coefficient (TEC) electrodeposited copper to eliminate the dishing hollows at lower temperature than that with conventional copper using the combination of new additive A and low TEC additives. The TEC of new electrodeposited copper is 25.2 × 10−6 °C−1, 46% higher than conventional copper and the calculated contact area of copper surface at 250 °C with 5 nm dishing depth is 100%.
Tribological, Thermal, Kinetic, and Pad Micro-Textural Studies Using Polyphenylene Sulfide Retaining Rings in Interlayer Dielectric Chemical Mechanical Planarization
Authors: Philipossian Ara , Sampurno Yasa , Tustin Michael , Schranner Anton
Published: December 2020

We compared the long-term wear performance of 2 different PPS retaining ring materials (E-PPS and O-PPS) provided by 2 different suppliers. After 4 h of wear, O-PPS resulted in higher values of mean pad summit height as compared to E-PPS (26.4 ± 1 vs 23.9 ± 1 μm, respectively). We believed this was due to excessive pad fragment generation (confirmed by its associated higher level of pore obscuration) which caused the asperities to artificially appear taller. Regarding mean summit curvature, O-PPS did not sharpen the asperity tips beyond what had already been achieved through conditioning (341 ± 50 vs 352 ± 50 per μm2, respectively). On the other hand, E-PPS caused the tips to sharpen significantly (508 ± 50 per μm2). The pad-slurry-ring coefficient of friction (COF) was higher for E-PPS (0.69 vs 0.65). This was consistent with the higher observed pad surface temperature for E-PPS and its associated sharper pad asperities. Both rings showed similar tribological behaviors, and the contact mechanism was one of “boundary lubrication.” Both rings caused the pad to wear at comparable rates, but regarding ring wear rate, E-PPS seemed to wear about 30 percent faster than O-PPS. This was deemed to be inconsequential in IC manufacturing due to the estimated excessive life of the ring (regardless of which type of PPS material was used) compared to the useful life of the pad and other consumables such as filters and discs.
Joint Multifractal Analysis and Source Testing of River Level Records Based on Multifractal Detrended Cross-Correlation Analysis
Authors: Wu Liang , Wang Manling , Zhao Tongzhou
Published: December 2020

The joint multifractal analysis is usually conducted in two different variables for their cross-correlations but rarely used for two records of one variable collected at two different places. It is important for the detection of change in multifractality in space. Besides, the cross-correlations in two analyzed series make the analysis of sources of joint multifractality difficult. There are few studies on the source of joint multifractality. We focus on the two issues for two level records at pairs of adjacent sites along one river and carry out an extension of our previous work which is about the single multifractality of one record with the same data set. The data set is collected from 10 observation stations of a northern China river and contains about two million high-frequency river level records. Results of joint multifractal analysis via multifractal detrended cross-correlation analysis show that the change in joint multifractality at pairs of adjacent sites caused by weak cross-correlations can be detected by comparing the single generalized Hurst exponent with the joint scaling exponent function and reveal the effects of human activities on joint multifractality. This analysis provides an approach for detecting the change in multifractality. Following the idea of our previous work, two robust hypothesis tests via a set of pairs of surrogate series are proposed for the source testing of joint multifractality. The analysis of the effects of cross-correlations is carried out via a proposed simultaneously half-shifting technique which can both minimize the cross-correlations between original series and make full use of records. Results of source analysis show not only the effects of autocorrelations in series and probability distribution of river levels but also the effects of cross-correlations between series.