bluuebunny/crossref_metadata_2025 huggingface dataset:
How does participation in a voluntary prize exam affect medical students’ knowledge and interest in ENT, plastic surgery, ophthalmology and dermatology?
Authors: Nour Razan , Jobling Kerry , Mayer Alasdair , Babikir Salma
Published: October 2020

Background

Otolaryngology (ENT), plastic surgery, ophthalmology and dermatology are medical specialties which tend to receive less coverage in UK medical school curricula compared to larger, generalist specialties. As a result, there are fewer opportunities for medical students to learn and to cultivate an interest. There are numerous papers that report concerns about junior doctors’ ability to manage conditions within these specialties, which may jeopardise patient safety. The aim of our pilot project was to increase medical students’ interest and knowledge of ENT, plastic surgery, ophthalmology and dermatology. In addition to describing our project, we present and discuss literature on UK undergraduate education in these specialties and its impact on preparedness of junior doctors and future career choices.

Methods

One hundred twelve final year medical students at Newcastle University were invited to take part in a voluntary two-part (written and clinical) exam, in which prizes could be won and all participants would receive a certificate of participation. We distributed two online surveys to the students, one administered before the exam and one afterwards. Data was collected regarding the students’ motivation for entering the prize exam and the students’ baseline interest and knowledge in these specialties before and after the prize exam. Free-text responses were collected about the students’ opinion of the project and whether participation was beneficial.

Results

Sixteen students participated in the exam. There was a statistically significant increase in the students’ knowledge in ENT (p < 0.000), plastic surgery (p < 0.000), ophthalmology (p < 0.028) and dermatology (p < 0.012) after participation in the exam, but not in their interest levels. ENT was the preferred specialty of our cohort. The students reported that they found participation beneficial to their learning, particularly receiving exam feedback and explanations to exam questions.

Conclusions

This pilot project was a useful intervention in increasing medical students’ knowledge in these specialties, but not in their levels of interest. It also demonstrates that medical students are willing to participate in voluntary initiatives (in their spare time) to gain more learning opportunities and that medical students value timely exam feedback to guide their revision.
Assessing and coping with the financial burden of computed tomography utilization in Limbe, Cameroon: a sequential explanatory mixed-methods study
Authors: Tambe Joshua , Mbuagbaw Lawrence , Ongolo-Zogo Pierre , Nguefack-Tsague Georges , Edjua Andrew , Mbome-Njie Victor , Ze Minkande Jacqueline
Published: October 2020

Background

There has been a significant increase in computed tomography (CT) utilization over the past two decades with the major challenges being a high exposure to ionizing radiation and rising cost. In this study we assess the risk of financial hardship after CT utilization and elaborate on how users adapt and cope in a sub-Saharan context with user fee for services and no national health insurance policy.

Methods

We carried out a sequential explanatory mixed methods study with a quantitative hospital-based survey of CT users followed by in-depth interviews of some purposively selected participants who reported risk of financial hardship after CT utilization. Data was summarized using frequencies, percentages and 95% confidence intervals. Logistic regression was used in multivariable analysis to determine predictors of risk of financial hardship. Identified themes from in-depth interviews were categorized. Quantitative and qualitative findings were integrated.

Results

A total of 372 participants were surveyed with a male to female sex ratio of 1:1.2. The mean age (standard deviation) was 52(17) years. CT scans of the head and facial bones accounted for 63% (95%CI: 59–68%) and the top three indications were suspected stroke (27% [95%CI: 22–32%]), trauma (14% [95%CI: 10–18%]) and persistent headaches (14% [95%CI: 10–18%]). Seventy-two percent (95%CI: 67–76%) of the respondents reported being at risk of financial hardship after CT utilization and predictors in the multivariable analysis were a low socioeconomic status (aOR: 0.19 [95%CI: 0.10–0.38]; p < 0.001), being unemployed or retired (aOR: 11.75 [95%CI: 2.59–53.18]; p = 0.001) and not having any form of health insurance (aOR: 3.59 [95%CI: 1.31–9.85]; p = 0.013). Coping strategies included getting financial support from family and friends, borrowing money and obtaining discounts from the hospital administration and staff.

Conclusion

No health insurance ownership, being unemployed or retired and a low socioeconomic status are associated with financial hardship after CT utilization. Diverse coping strategies are utilized to lessen the financial burden, some with negative consequences. Minimizing out-of-pocket payments and/or the direct cost of CT can reduce this financial burden and improve CT access.
Strengthening retina eye care services in Nepal: retina eye care of Nepal project
Authors: Shrestha Arjun , Shrestha Chunu , Karki Pratap , Gurung Hara Maya , Naito Takeshi
Published: October 2020

Background

Retinal diseases are very difficult to treat. So, early diagnoses and preventions are very important. But, few eye doctors can treat patients with retinal diseases in Nepal. Retina Eye Care of Nepal (RECON) project was designed to strengthen retina eye care services in Nepal.

Methods

RECON was implemented from May 2016 to February 2019 in Nepal. Four Master Eye Doctors (MED) received Training of Trainers (TOT) from Tokushima University, Japan. MEDs developed training materials for different cadres of ophthalmic human resources, enhanced retina eye care facilities, and conducted retina-screening camp in Nepal.

Results

Twenty ophthalmologists, 16 optometrists, 48 ophthalmic assistants and 17 ophthalmic nurses, 76 physicians and 28 health workers were trained in retina care. Eight outreach retina camps were conducted.

Conclusions

The project was a novel approach to strengthen retina services in Nepal. The aim of the project was accomplished with the ultimate benefits to the needy retina patients who otherwise were going to miss the retina services.
Involvement of NEK2 and its interaction with NDC80 and CEP250 in hepatocellular carcinoma
Authors: Zeng Lu , Fan Xiude , Wang Xiaoyun , Deng Huan , Zhang Xiaoge , Zhang Kun , He Shan , Li Na , Han Qunying , Liu Zhengwen
Published: October 2020

Background

NEK2 has an established involvement in hepatocellular carcinoma (HCC) but the roles of NEK2 and its interacting proteins in HCC have not been systematically explored.

Methods

This study examined NEK2 and its interacting proteins in HCC based on multiple databases.

Results

NEK2 mRNA was highly expressed in HCC tissues compared with normal liver tissues. The survival of HCC patients with high NEK2 mRNA expression was shorter than those with low expression. MAD1L1, CEP250, MAPK1, NDC80, PPP1CA, PPP1R2 and NEK11 were the interacting proteins of NEK2. Among them, NDC80 and CEP250 were the key interacting proteins of NEK2. Mitotic prometaphase may be the key pathway that NEK2 and its interacting proteins contributed to HCC pathogenesis. NEK2, NDC80 and CEP250 mRNAs were highly expressed in HCC tissues compared with normal liver tissues. The mRNA levels of NEK2 were positively correlated with those of NDC80 or CEP250. Univariate regression showed that NEK2, NDC80 and CEP250 mRNA expressions were significantly associated with HCC patients’ survival. Multivariate regression showed that NDC80 mRNA expression was an independent predictor for HCC patients’ survival. Methylations and genetic alterations of NEK2, NDC80 and CEP250 were observed in HCC samples. The alterations of NEK2, NDC80 and CEP250 genes were co-occurrence. Patients with high mRNA expression and genetic alterations of NEK2, NDC80 and CEP250 had poor prognosis.

Conclusions

NEK2 and its interacting proteins NDC80 and CEP250 play important roles in HCC development and progression and thus may be potentially used as biomarkers and therapeutic targets of HCC.
Identification of potential causal variants for premature ovarian failure by whole exome sequencing
Authors: Jin Haengun , Ahn JuWon , Park YoungJoon , Sim JeongMin , Park Han Sung , Ryu Chang Soo , Kim Nam Keun , Kwack KyuBum
Published: October 2020

Background

Premature ovarian failure (POF) is a highly heterogeneous disorder that occurs in 1% of women of reproductive age. Very few causative genes and variants contributing to POF have been detected, and the disease remains incompletely understood. In this study, we used whole exome sequencing (WES) to identify potential causal variants leading to POF.

Methods

WES was conducted to identify variants in 34 Korean patients with POF, alongside 10 normal controls. Detected variants were filtered using a range of characterized bioinformatics analyses, and the machine learning tools, CADD and VEST, were used to predict pathogenic variants that could cause disease. VarSome was used for a comprehensive interpretation of the variants. Potential causal variants finally screened by these analyses were confirmed using Sanger sequencing.

Results

We identified nine potential causative variants in genes previously associated with POF in 8 of 34 (24%) Korean patients by WES variant analysis. These potentially pathogenic variants included mutations in the MCM8, MCM9, and HFM1 genes, which are involved in homologous recombination, DNA repair, and meiosis, and are established as causing POF. Using a combination of CADD and VEST, 72 coding variants were also identified in 72 genes, including ADAMTSL1 and FER1L6, which have plausible functional links to POF.

Conclusions

WES is a useful tool to detect genetic variants that cause POF. Accumulation and systematic management of data from a number of WES studies in specialized groups of patients with POF (family data, severe case populations) are needed to better comprehend the genetic landscape underlying POF.
“Crazy person is crazy person. It doesn’t differentiate”: an exploration into Somali views of mental health and access to healthcare in an established UK Somali community
Authors: Linney Catherine , Ye Siyan , Redwood Sabi , Mohamed Abdi , Farah Abdullahi , Biddle Lucy , Crawley Esther
Published: October 2020

Background

Mental health conditions have been shown to disproportionately affect those from Black, Asian and Minority Ethnic (BAME) communities. Somali communities globally have relatively high levels of mental illness, but low levels of mental health service use, with numerous barriers to care identified.

This study was conducted in an established UK Somali community in the South West of England and aimed to explore community beliefs and views about the causes of mental illness, treatment for mental illness, and access to medical services in general. Participants were asked about how mental health and illness are understood and conceptualised, along with the cultural meaning of mental illness and its manifestations in relation to men, women and young people.

Design

Using a community-based participatory research design, in partnership with local Somali community organisations, the research team conducted four focus groups with a total of 23 participants aged over 18. Open-ended questions were used to facilitate discussion. Transcripts were analysed thematically.

Results

The participants discussed the role of migration and associated stress from the civil war and how that could contribute to mental illness.

Participants tended to view the symptoms of mental illness as physical manifestations such as headaches and to describe a strong community stigma where those with mental health conditions were viewed as “crazy” by others. Barriers to accessing healthcare included language barriers, waiting times and a mistrust of doctors. Various ideas for improvements were discussed, including ideas to reduce stigma and ideas for community initiatives.

Conclusion

Cultural considerations and reducing stigma are vital in improving understanding of mental illness and improving access to mental health services, along with building relationships and trust between the Somali community and health care workers.
Primary localized retroperitoneal sarcomas: report from Slovenian sarcoma referral center
Authors: Novak Marko , Perhavec Andraž , Kerin Povšič Milena , Arnuš Matej , Eržen Darja
Published: October 2020

Background

Sarcoma patients should be treated in high volume referral sarcoma centers. Compartmental resection is proposed as the best treatment option in retroperitoneal sarcoma patients.

Methods

Institute of Oncology Ljubljana is the only referral sarcoma center in Slovenia. Having a population of 2.1 million poses a unique situation. We manage all sarcoma patients in the country and operate on patients with soft tissue tumors of extremities, trunk, and abdomen. Data for all consecutive patients surgically treated from January 1999 to December 2018 for primary localized retroperitoneal sarcoma was extracted from a prospective surgical database. Data about the incidence of sarcoma patients in Slovenia was extracted from the Cancer Registry of Republic of Slovenia. Clinicopathologic variables and the outcome were analyzed.

Results

In total, 89 patients were included in the study. Median age was 62 years. Dedifferentiated liposarcoma was the most common histology (38.2%). Median tumor size was 21 cm. Compartmental resection was performed in 47.2% (42/89). Postoperative complication grade 3a or higher according to Clavien-Dindo classification had 30.3% (27/89) of patients. The 30-day and 90-day mortality rate was 2.2% and 5.6%. Median follow-up was 62.1 months. Corresponding 5-year overall survival was 67.2%, 5-year disease-specific survival was 72.6%, and 5-year local recurrence-free survival was 81.5%, respectively.

Conclusion

Results from our institution show that referral sarcoma centers may achieve very good results in management of retroperitoneal sarcoma patients, despite not meeting the criteria for high volume hospitals, as long as they have multidisciplinary team, appropriate facilities, and expertise.
The effect of tonsillectomy with adenoidectomy on medical services used in association with otitis media based on Korean national sample cohort data
Authors: Jeong Junhui , Choi Jung Kyu , Nam Jae Sung , Shin Hyang Ae , Chang Jung Hyun , Choi Hyun Seung
Published: October 2020

Background

The effect of tonsillectomy with adenoidectomy (T&A) on otitis media has been investigated, but there have been no reports of the relationship between T&A and medical services used in association with otitis media. We investigated the effect of T&A on otitis media with regard to the number and cost of medical services used.

Methods

From the National Health Insurance Service National Sample Cohort data in Korea, we selected patients 7 years old or younger in 2002 who had T&A in 2005 while between the ages of three and ten. A control group was established matching the patient group with similar propensities of demographic characteristics. The number and cost of medical services used in association with otitis media were analyzed for 3 years before T&A through 8 years after T&A.

Results

The total number of patients was 1,338, with 227 in the T&A group and 1,111 in the non-T&A group. The number of medical services used was not significantly different between the T&A and non-T&A groups before and after surgery. The cost of medical services used was significantly higher in the T&A group than in the non-T&A group one year before surgery. The cost of medical services used was not significantly different between the two groups after surgery.

Conclusions

There were no significant differences between the T&A and non-T&A groups in the number and cost of medical services used in association with otitis media after surgery.
JARID1B promotes colorectal cancer proliferation and Wnt/β-catenin signaling via decreasing CDX2 level
Authors: Huang Da , Xiao Fan , Hao Haibin , Hua Fuzhou , Luo Zhenzhong , Huang Zhaoxia , Li Qing , Chen Sha , Cheng Xiuzhi , Zhang Xinyue , Fang Weilan , Hu Xiaoyun , Liu Fanrong
Published: October 2020

Background

Jumonji AT-rich interactive domain 1B(JARID1B) has been shown to be upregulated in many human cancers and plays a critical role in the development of cancers cells. Nevertheless, its functional role in colorectal cancer (CRC) progression is not fully understood.

Methods

Herein, JARID1B expression levels were detected in clinical CRC samples by western blotting and qRT-PCR. DLD-1 cells with JARID1B knockdown or overexpression by stably transfected plasmids were used in vitro and in vivo study. Colony formation, 5-ethynyl-20-deoxyuridine (EdU) and Real Time Cellular Analysis (RTCA) assays were used to detect cell proliferation and growth. Transcriptome and CHIP assays were used to examine the molecular biology changes and molecular interaction in these cells. Nude mice was utilized to study the correlation of JARID1B and tumor growth in vivo.

Results

Here, we first observed that JARID1B was significantly upregulated in CRC tissue compared to adjacent normal tissues. In CRC patients, JARID1B high expression was positively relation with poor overall survival. Multivariate analyses revealed that high JARID1B expression was an independent predictive marker for the poor prognosis of CRC. In addition, we found that JARID1B promoted CRC cells proliferation by Wnt/β-catenin signaling pathway. Further studies demonstrated CDX2 as a downstream target of JARID1B, and our data demonstrated that CDX2 is crucial for JARID1B -mediated Wnt/β-catenin signaling pathway. Mechanistically, we demonstrated that JARID1B regulated CDX2 expression through demethylation of H3K4me3.

Conclusions

CDX2 inhibited by JARID1B-derived H3K4me3 methylation promoted cells proliferation of CRC via Wnt/β-catenin signaling pathway. Therefore, our studies provided a novel insight into the role of JARID1B in CRC cells proliferation and potential new molecular target for treating CRC.

Graphical abstract
Rapid, high efficiency virus-mediated mutant complementation and gene silencing in Antirrhinum
Authors: Tan Ying , Bukys Alfredas , Molnár Attila , Hudson Andrew
Published: October 2020

Background

Antirrhinum(snapdragon) species are models for genetic and evolutionary research but recalcitrant to genetic transformation, limiting use of transgenic methods for functional genomics. Transient gene expression from viral vectors and virus-induced gene silencing (VIGS) offer transformation-free alternatives. Here we investigate the utility of Tobacco rattle virus (TRV) for homologous gene expression inAntirrhinumand VIGS inAntirrhinumand its relativeMisopates.

Results

A. majusproved highly susceptible to systemic TRV infection. TRV carrying part of thePhytoene Desaturase(PDS) gene triggered efficientPDSsilencing, visible as tissue bleaching, providing a reporter for the extent and location of VIGS. VIGS was initiated most frequently in young seedlings, persisted into inflorescences and flowers and was not significantly affected by the orientation of the homologous sequence within the TRV genome. Its utility was further demonstrated by reducing expression of two developmental regulators that act either in the protoderm of young leaf primordia or in developing flowers. The effects of co-silencingPDSand the trichome-suppressingHairy(H) gene from the same TRV genome showed that tissue bleaching provides a useful marker for VIGS of a second target gene acting in a different cell layer. The ability of TRV-encoded H protein to complement thehmutant phenotype was also tested. TRV carrying the nativeHcoding sequence withPDSto report infection failed to complementhmutations and triggered VIGS ofHin wild-type plants. However, a sequence with 43% synonymous substitutions encoding H protein, was able to complement thehmutant phenotype when expressed without aPDSVIGS reporter.

Conclusions

We demonstrate an effective method for VIGS in the model genusAntirrhinumand its relativeMisopatesthat works in vegetative and reproductive tissues. We also show that TRV can be used for complementation of a loss-of-function mutation inAntirrhinum.These methods make rapid tests of gene function possible in these species, which are difficult to transform genetically, and opens up the possibility of using additional cell biological and biochemical techniques that depend on transgene expression.
Immune checkpoint inhibition in patients treated with stereotactic radiation for brain metastases
Authors: Kowalski Emily S. , Remick Jill S. , Sun Kai , Alexander Gregory S. , Khairnar Rahul , Morse Emily , Cherng Hua-Ren , Berg Lars J. , Poirier Yannick , Lamichhane Narottam , Becker Stewart , Chen Shifeng , Molitoris Jason K. , Kwok Young , Regine William F. , Mishra Mark V.
Published: October 2020

Purpose

Stereotactic radiation therapy (SRT) and immune checkpoint inhibitors (ICI) may act synergistically to improve treatment outcomes but may also increase the risk of symptomatic radiation necrosis (RN). The objective of this study was to compare outcomes for patients undergoing SRT with and without concurrent ICI.

Methods and materials

Patients treated for BMs with single or multi-fraction SRT were retrospectively reviewed. Concurrent ICI with SRT (SRT-ICI) was defined as administration within 3 months of SRT. Local control (LC), radiation necrosis (RN) risk and distant brain failure (DBF) were estimated by the Kaplan-Meier method and compared between groups using the log-rank test. Wilcoxon rank sum and Chi-square tests were used to compare covariates. Multivariate cox regression analysis (MVA) was performed.

Results

One hundred seventy-nine patients treated with SRT for 385 brain lesions were included; 36 patients with 99 lesions received SRT-ICI. Median follow up was 10.3 months (SRT alone) and 7.7 months (SRT- ICI) (p = 0.08). Lesions treated with SRT-ICI were more commonly squamous histology (17% vs 8%) melanoma (20% vs 2%) or renal cell carcinoma (8% vs 6%), (p < 0.001). Non-small cell lung cancer (NSCLC) compromised 60% of patients receiving ICI (n = 59). Lesions treated with SRT-ICI had significantly improved 1-year local control compared to SRT alone (98 and 89.5%, respectively (p = 0.0078). On subset analysis of NSCLC patients alone, ICI was also associated with improved 1 year local control (100% vs. 90.1%) (p = 0.018). On MVA, only tumor size ≤2 cm was significantly associated with LC (HR 0.38, p = 0.02), whereas the HR for concurrent ICI with SRS was 0.26 (p = 0.08). One year DBF (41% vs. 53%; p = 0.21), OS (58% vs. 56%; p = 0.79) and RN incidence (7% vs. 4%; p = 0.25) were similar for SRT alone versus SRT-ICI, for the population as a whole and those patients with NSCLC.

Conclusion

These results suggest SRT-ICI may improve local control of brain metastases and is not associated with an increased risk of symptomatic radiation necrosis in a cohort of predominantly NSCLC patients. Larger, prospective studies are necessary to validate these findings and better elucidate the impact of SRT-ICI on other disease outcomes.
Identifying and treating maternal mental health difficulties in Afghanistan: A feasibility study
Authors: Tomlinson Mark , Chaudhery Deepika , Ahmadzai Habibullah , Rodríguez Gómez Sofía , Bizouerne Cécile , van Heyningen Thandi , Chopra Mickey
Published: October 2020

Background

The disproportionately high burden of mental disorders in low- and middle-income countries, coupled with the overwhelming lack of resources, requires an innovative approach to intervention and response. This study evaluated the feasibility of delivering a maternal mental health service in a severely-resource constrained setting as part of routine service delivery.

Methods

This exploratory feasibility study was undertaken at two health facilities in Afghanistan that did not have specialist mental health workers. Women who had given birth in the past 12 months were screened for depressive symptoms with the PHQ9 and invited to participate in a psychological intervention which was offered through an infant feeding scheme.

Results

Of the 215 women screened, 131 (60.9%) met the PHQ9 criteria for referral to the intervention. The screening prevalence of postnatal depression was 61%, using a PHQ9 cut-off score of 12. Additionally, 29% of women registered as suicidal on the PHQ9. Several demographic and psychosocial variables were associated with depressive symptoms in this sample, including nutritional status of the infant, anxiety symptoms, vegetative and mood symptoms, marital difficulties, intimate partner violence, social isolation, acute stress and experience of trauma. Of the 47 (65%) women who attended all six sessions of the intervention, all had significantly decreased PHQ9 scores post-intervention.

Conclusion

In poorly resourced environments, where the prevalence of postnatal depression is high, a shift in response from specialist-based to primary health care-level intervention may be a viable way to provide maternal mental health care. It is recommended that such programmes also consider home-visiting components and be integrated into existing infant and child health programmes. Manualised, evidence-based psychological interventions, delivered by non-specialist health workers, can improve outcomes where resources are scarce.
Depression and experience of incarceration in North Central Nigeria: a situation analysis at Makurdi medium security prison
Authors: Nwefoh Emeka , Aguocha Chinyere M. , Ryan Grace , Ode Philip , Ighagbon Festus O. , Akinjola Oyedele , Omoi Samuel , Abdulmalik Jibril , Agbir Terkura M. , Obekpa Obekpa , Ogbole Samuel , Eaton Julian
Published: October 2020

Background

Human rights watchdogs have described conditions in Nigerian correctional facilities and detention centers as damaging to the physical and mental health of inmates. While the prevalence of mental disorders is high, access to appropriate healthcare is grossly inadequate. Understanding the current state of prison inmates’ mental health and well-being is an essential first step to addressing this important issue. This study aims to document the mental health and experiences of incarceration of inmates of the largest medium security prison in Nigeria’s Benue State.

Methods

A cross-sectional survey and descriptive analysis was carried out with a random sample of 381 prison inmates of Benue State Makurdi Medium Security Prison. Survey tools included: (1) a structured questionnaire on participants’ experiences in prison, and (2) the Patient Health Questionnaire (PHQ-9), a screening tool for depression.

Results

Most participants were young men (95.5%, mean age 27.95) and had completed secondary school (63.5%). While prison authorities had identified only 27 participants as having a mental disorder, 144 (37.8%) screened positive for depression. Twenty six had received professional counseling while in prison. Of the six participants who were already taking a psychotropic medication at the time of imprisonment, four received medication after being imprisoned. Approximately half, (52%) of participants were dissatisfied with prison health care.

Conclusions

Despite the high prevalence of depression among prison inmates, few cases are detected and treated. Prison staff may not recognize depression as a mental disorder, and the mental health care available is generally poor. Inadequate mental health and social care not only affects prison inmates’ well-being, but may also impact recidivism and health outcomes upon release. Prison inmates should be screened routinely for depression and other less-commonly recognized mental health conditions, and appropriate treatment made available.
Tyrosine kinase inhibitors for solid tumors in the past 20 years (2001–2020)
Authors: Huang Liling , Jiang Shiyu , Shi Yuankai
Published: October 2020

Tyrosine kinases are implicated in tumorigenesis and progression, and have emerged as major targets for drug discovery. Tyrosine kinase inhibitors (TKIs) inhibit corresponding kinases from phosphorylating tyrosine residues of their substrates and then block the activation of downstream signaling pathways. Over the past 20 years, multiple robust and well-tolerated TKIs with single or multiple targets including EGFR, ALK, ROS1, HER2, NTRK, VEGFR, RET, MET, MEK, FGFR, PDGFR, and KIT have been developed, contributing to the realization of precision cancer medicine based on individual patient’s genetic alteration features. TKIs have dramatically improved patients’ survival and quality of life, and shifted treatment paradigm of various solid tumors. In this article, we summarized the developing history of TKIs for treatment of solid tumors, aiming to provide up-to-date evidence for clinical decision-making and insight for future studies.
Italian inter-society expert panel position on radiological exposure in Neonatal Intensive Care Units
Authors: del Vecchio Antonella , Salerno Sergio , Barbagallo Massimo , Chirico Gaetano , Campoleoni Mauro , Cannatà Vittorio , Genovese Elisabetta , Granata Claudio , Magistrelli Andrea , Tomà Paolo
Published: October 2020

Background

In the recent years, clinical progress and better medical assistance for pregnant women, together with the introduction of new complex technologies, has improved the survival of preterm infants. However, this result requires frequent radiological investigations mostly represented by thoracic and abdominal radiographs in incubators. This document was elaborated by an expert panel Italian inter-society working group (Radiologists, Paediatricians, Medical Physicists) with the aim to assist healthcare practitioners in taking choices involving radiation exposures of new-born infants and to provide practical recommendations about justification and optimization in Neonatal Intensive Care Units. The adherence to these practice recommendations could ensure a high quality and patient safety. More complex and less common radiological practice, such as CT scan or fluoroscopy have been excluded.

Methods

The consensus was reached starting from current good practice evidence shared by four scientific societies panel: AIFM (Italian Association of Physics in Medicine), SIN (Italian Neonatology Society), SIP (Italian Paediatric Society), SIRM (Italian Medical Radiology Society) in order to guarantee good standard practices for every professional involved in Neonatal Intensive Care Units (NICU).

The report is divided into clinical and physical-dosimetric sections: clinical Indications, good practice in radiological exposures, devices, exposure parameters and modalities, patient positioning and immobilization, Reference Diagnostic Levels, operators and patient’s radiation protection.

Another important topic was the evaluation of the different incubators in order to understand if the consequences of the technological evolution have had an impact on the increase of the dose to the small patients, and how to choose the best device in terms of radiation protection.

At the end the working group faced the problem of setting up the correct communication between clinicians and parents following the most recent indications of the international paediatric societies.

Results

Taking into account the experience and expertise of 10 Italian Centres, the guideline sets out the criteria to ensure a high standard of neonatal care in NICU about procedures, facilities, recommended equipment, quality assurance, radiation protection measures for children and staff members and communication on radiation risk.

Conclusions

This document will allow a standardization of the approach to the exposures in NICU, although oriented to a flexible methodology.
Pubertal timing and breast cancer risk in the Sister Study cohort
Authors: Goldberg Mandy , D’Aloisio Aimee A. , O’Brien Katie M. , Zhao Shanshan , Sandler Dale P.
Published: October 2020

Background

Earlier age at menarche is an established risk factor for breast cancer. While age at menarche has been fairly stable over the past half-century, age at breast development (thelarche) has continued to decrease. Recently, earlier age at thelarche and a longer time between thelarche and menarche (pubertal tempo) were shown to be associated with increased breast cancer risk. Our objective was to examine how breast cancer risk was associated with pubertal timing and tempo in a prospective US cohort.

Methods

Women ages 35–74 years without a history of breast cancer, but who had a sister previously diagnosed with breast cancer, were enrolled in the Sister Study from 2003 to 2009 (N = 50,884). At enrollment, participants reported their ages at thelarche and menarche. Pubertal tempo was age at menarche minus age at thelarche. We estimated adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for each pubertal milestone and risk of breast cancer (invasive or ductal carcinoma in situ) using Cox proportional hazards regression. We examined whether associations between age at thelarche and breast cancer risk were modified by birth cohort, race/ethnicity, weight at age 10, and extent of breast cancer family history, as characterized by a Bayesian score based on first-degree family structure.

Results

During follow-up (mean = 9.3 years), 3295 eligible women were diagnosed with breast cancer. Early ages at thelarche (HR = 1.23, 95% CI 1.03–1.46 for < 10 vs. 12–13 years) and menarche (HR = 1.10, 95% CI 1.01–1.20 for < 12 vs. 12–13 years) were positively associated with breast cancer risk. Pubertal tempo was not associated with breast cancer risk (HR = 0.99, 95% CI 0.97–1.02 per 1-year longer tempo). When considering early thelarche (< 10 years) and early menarche (< 12 years) jointly, women with both had a 30% greater risk of breast cancer compared with women with neither risk factor (95% CI 1.07–1.57). The association between age at thelarche and breast cancer risk did not significantly vary by birth cohort, race/ethnicity, childhood weight, or Bayesian family history score.

Conclusions

Earlier ages at thelarche and menarche may enhance susceptibility to breast carcinogenesis. Age at thelarche is an important risk factor to consider given secular trends towards earlier development.
Discontinuing adalimumab in patients with controlled juvenile idiopathic arthritis-associated uveitis (ADJUST—Adalimumab in Juvenile Idiopathic Arthritis-associated Uveitis Stopping Trial): study protocol for a randomised controlled trial
Authors: Acharya Nisha R. , Ebert Caleb D. , Kelly Nicole K. , Porco Travis C. , Ramanan Athimalaipet V. , Arnold Benjamin F. ,   the ADJUST Research Group, Acharya Nisha R. , Porco Travis C. , Arnold Benjamin F. , Doan Thuy , Gonzales John A. , von Scheven Emily , Angeles-Han Shelia T. , Miraldi Utz Virginia , Vitale Albert T. , Hersh Aimee O. , Overbury Rebecca S. , Stahl Erin D. , Cooper Ashley M. , Lerman Melissa A. , Davidson Stefanie L. , Thorne Jennifer E. , Ogbu Ekemini A. , Nanda Kabita , Herlihy Erin P. , Cabrera Michelle T. , Dacey Mark S. , Moore Katharine F. , Guly Catherine , Dick Andrew D. , Petrushkin Harry , Moraitis Elena , Solebo Ameenat L. , Cleary Gavin , Gonzalez-Martin Jose A. , Jandial Sharmila , Clarke Michael P. , May Kristina , Leahy Alice , Choi Jessy , Hawley Daniel , Puvanachandra Narman , Armon Kate , Renton William D. , Troutbeck Robyn
Published: October 2020

Background

Juvenile idiopathic arthritis (JIA)-associated uveitis is a chronic paediatric ocular inflammatory condition that can result in visual impairment. Adalimumab, a tumour necrosis factor (TNF)-alpha inhibitor, effectively controls joint and eye inflammation; however, its long-term use may increase the risk of adverse health outcomes and place an undue financial burden on the patient and healthcare system given its high cost. There is great interest for patients to stop adalimumab following remission due to these reasons but there is a lack of information on the ability to maintain control after discontinuing adalimumab.

Methods

The Adalimumab in Juvenile Idiopathic Arthritis-associated Uveitis Trial (ADJUST) is a multicentred, international trial that will randomise 118 participants aged 2 years and older with controlled JIA-associated uveitis to either continue adalimumab or discontinue adalimumab and receive a placebo. The trial will compare the time to uveitis recurrence between the two groups over 12 months. All participants will receive the standard weight-based dose of adalimumab or placebo: 20 mg biweekly (if < 30 kg) or 40 mg biweekly (if ≥ 30 kg).

Discussion

This is the first randomised controlled trial to assess the efficacy of discontinuing adalimumab after demonstrating control of JIA-associated uveitis for at least 12 months. The results of ADJUST will provide information on clinical outcomes to guide clinicians in their decision-making regarding discontinuation of adalimumab.

Trial registration

ClinicalTrials.gov NCT03816397. Registered on 25 January 2019. EudraCT 2019-000412-29. Registered on 17 January 2019
Group Post-Admission Cognitive Therapy for Suicidality vs Individual Supportive Therapy for the prevention of repeat suicide attempts: a randomized controlled trial
Authors: Chaïb Laurent S. , Lopez-Castroman Jorge , Abbar Mocrane
Published: October 2020

Background

Suicide is a serious public health problem. The development and use of effective treatments for people hospitalized for suicide attempts remain a priority. Regarding psychosocial treatment, the evidence for treatments that effectively prevent suicide repetition of suicide attempts is extremely thin. There is some evidence that cognitive behavioural therapy may be effective for reducing suicide behaviour. The primary aim of this study is to compare Group Post-Admission Cognitive Therapy for Suicidality (GPACTS) versus Individual Supportive Therapy (IST) for preventing suicide.

Methods

In total, 240 participants with a high suicide risk score according to a Mini International Neuropsychiatric Interview (MINI) will be randomized to either GPACTS or IST. This is a multicentre, parallel group, randomized (1:1 ratio), two-tailed-superiority trial with endpoint-assessor blinding. Patients meeting inclusion criteria during a screening visit will be enrolled in the study and randomized into two groups: one group will undergo 6 weeks of GPACTS, and the second group will undergo 6 weeks of IST. Following 6 weeks of interventional therapy, patients are followed up for 12 months. Follow-up for both groups is identical and includes the administration of questionnaires at baseline and then within 10 days after the end of therapy sessions and then at 3, 6 and 12 months following the end of GPACTS/IST sessions.

Discussion

To our knowledge, this is the first RCT of its kind to be conducted in France, and so far, there are no studies in the literature on group psychotherapy for the treatment of individuals who have attempted suicide. The outcomes will provide clear guidance for professionals to apply psychological intervention with suicide attempts. The protocol respects ethical principles, and ethical approval was obtained from the local ethics committee. The results will be disseminated through an original research published as original research in peer-reviewed manuscript, through a therapist manual for cognitive therapy, and presentations at research conferences.

Trial registration

ClinicalTrials.gov NCT02664701. Registered on January 27, 2017.
Explaining the mixed findings of a randomised controlled trial of telehealth with centralised remote support for heart failure: multi-site qualitative study using the NASSS framework
Authors: Papoutsi Chrysanthi , A’Court Christine , Wherton Joseph , Shaw Sara , Greenhalgh Trisha
Published: October 2020

Background

The SUPPORT-HF2 randomised controlled trial compared telehealth technology alone with the same technology combined with centralised remote support, in which a clinician responds promptly to biomarker changes. The intervention was implemented differently in different sites; no overall impact was found on the primary endpoint (proportion of patients on optimum treatment). We sought to explain the trial’s findings in a qualitative evaluation.

Methods

Fifty-one people (25 patients, 3 carers, 18 clinicians, 4 additional researchers) were interviewed and observed in 7 UK trial sites in 2016–2018. We collected 110 pages of documents. The analysis was informed by the NASSS framework, a multi-level theoretical lens which considers non-adoption and abandonment of technologies by individuals and challenges to scale-up, spread and sustainability. In particular, we used NASSS to tease out why a ‘standardised’ socio-technical intervention played out differently in different sites.

Results

Patients’ experiences of the technology were largely positive, though influenced by the nature and severity of their illness. In each trial site, existing services, staffing levels, technical capacity and previous telehealth experiences influenced how the complex intervention of ‘telehealth technology plus centralised specialist remote support’ was interpreted and the extent to which it was adopted and used to its full potential. In some sites, the intervention was quickly mobilised to fill significant gaps in service provision. In others, it was seen as usefully extending the existing care model for selected patients. Elsewhere, the new model was actively resisted and the technology little used. In one site, centralised provision of specialist advice aligned awkwardly with an existing community-based heart failure support service.

Conclusions

Complex socio-technical interventions, even when implemented in a so-called standardised way with uniform inclusion and exclusion criteria, are inevitably implemented differently in different local settings because of how individual staff members interpret the technology and the trial protocol and because of the practical realities and path dependencies of local organisations. Site-specific iteration and embedding of a new technology-supported complex intervention may be required (in addition to co-design of the user interface) before such interventions are ready for testing in clinical trials.

Trial registration

BMC ISRCTN Registry 86212709. Retrospectively registered on 5 September 2014
Physiological characterization of a new thermotolerant yeast strain isolated during Brazilian ethanol production, and its application in high-temperature fermentation
Authors: Prado Cleiton D. , Mandrujano Gustavo P. L. , Souza Jonas. P. , Sgobbi Flávia B. , Novaes Hosana R. , da Silva João P. M. O. , Alves Mateus H. R. , Eliodório Kevy P. , Cunha Gabriel C. G. , Giudici Reinaldo , Procópio Diele P. , Basso Thiago O. , Malavazi Iran , Cunha Anderson F.
Published: October 2020

Background

The use of thermotolerant yeast strains can improve the efficiency of ethanol fermentation, allowing fermentation to occur at temperatures higher than 40 °C. This characteristic could benefit traditional bio-ethanol production and allow simultaneous saccharification and fermentation (SSF) of starch or lignocellulosic biomass.

Results

We identified and characterized the physiology of a new thermotolerant strain (LBGA-01) able to ferment at 40 °C, which is more resistant to stressors as sucrose, furfural and ethanol than CAT-1 industrial strain. Furthermore, this strain showed similar CAT-1 resistance to acetic acid and lactic acid, and it was also able to change the pattern of genes involved in sucrose assimilation (SUC2 and AGT1). Genes related to the production of proteins involved in secondary products of fermentation were also differentially regulated at 40 °C, with reduced expression of genes involved in the formation of glycerol (GPD2), acetate (ALD6 and ALD4), and acetyl-coenzyme A synthetase 2 (ACS2). Fermentation tests using chemostats showed that LBGA-01 had an excellent performance in ethanol production in high temperature.

Conclusion

The thermotolerant LBGA-01 strain modulates the production of key genes, changing metabolic pathways during high-temperature fermentation, and increasing its resistance to high concentration of ethanol, sugar, lactic acid, acetic acid, and furfural. Results indicate that this strain can be used to improve first- and second-generation ethanol production in Brazil.
Evaluation of a real-time PCR assay for diagnosis of schistosomiasis japonica in the domestic goat
Authors: Guo Qinghong , Chen Cheng , Zhou Keke , Li Yugang , Tong Laibao , Yue Yongcheng , Zhou Kerou , Liu Jinming , Fu Zhiqiang , Lin Jiaojiao , Zhao Jiaxi , Sun Pengxiang , Hong Yang
Published: October 2020

Background

Schistosomiasis japonica is an infectious disease caused by Schistosoma japonicum that seriously endangers human health. Domestic animals have important roles in disease transmission and goats are considered a primary reservoir host and source of infection. The prevalence and intensity of schistosomiasis infections have significantly decreased in China, and a more sensitive, specific detection method is urgently needed. The aim of this study was to develop a real-time PCR assay for accurate detection of S. japonicum infection in goats.

Methods

A real-time PCR method for detecting schistosomiasis japonica in goats was developed by amplification of a specific S. japonicum DNA fragment, and validated using a total of 94 negative and 159 positive plasma and serum samples collected in our previous study of S. japonicum infection. Both plasma and serum samples were evaluated by real-time PCR and enzyme-linked immunosorbent assay (ELISA). In addition, 120 goat plasma samples from an S. japonicum-endemic area (Wangjiang) and 33 from a non-endemic region (Weihai) were collected and evaluated using our method.

Results

The sensitivity and specificity of the real-time PCR for detecting infected samples were 98.74% (157/159, 95% CI: 95.53–99.85%) and 100% (94/94, 95% CI: 96.15–100%), respectively. For the ELISA, sensitivity and specificity were 98.11% (156/159, 95% CI: 94.59–99.61%) and 90.43% (85/94, 95% CI: 82.60–95.53%), respectively. Further, we found positivity rates for S. japonicum infection in Wangjiang and Weihai of 8.33% (10/120, 95% CI: 4.07–14.79%) and 0% (0/33, 95% CI: 0–10.58%), respectively.

Conclusions

The results of this study indicate that our real-time PCR method exhibits higher sensitivity and specificity than ELISA and is a useful method for detection of S. japonicum infection in goats.
Molecular detection of drug resistant polymorphisms in Plasmodium falciparum isolates from Southwest, Nigeria
Authors: Tola Monday , Ajibola Olumide , Idowu Emmanuel Taiwo , Omidiji Olusesan , Awolola Samson Taiwo , Amambua-Ngwa Alfred
Published: October 2020

Objective

Nigeria bears 25% of global malaria burden despite concerted efforts towards its control and elimination. The emergence of drug resistance to first line drugs, artemisinin combination therapies (ACTs), indicates an urgent need for continuous molecular surveillance of drug resistance especially in high burden countries where drug interventions are heavily relied on. This study describes mutations in Plasmodium falciparum genes associated with drug resistance in malaria; Pfk13, Pfmdr1, PfATPase6 and Pfcrt in isolates obtained from 83 symptomatic malaria patients collected in August 2014, aged 1–61 years old from South-west Nigeria.

Results

Two Pfmdr1, N86 and Y184 variants were present at a prevalence of 56% and 13.25% of isolates respectively. There was one synonymous (S679S) and two non-synonymous (M699V, S769M) mutations in the PATPase6 gene, while Pfcrt genotype (CVIET), had a prevalence of 45%. The Pfk13 C580Y mutant allele was suspected by allelic discrimination in two samples with mixed genotypes although this could not be validated with independent isolation or additional methods. Our findings call for robust molecular surveillance of antimalarial drug resistance markers in west Africa especially with increased use of antimalarial drugs as prophylaxis for Covid-19.