bluuebunny/crossref_metadata_2025 huggingface dataset:
A systematic scoping review of early interventions for parents of deaf infants
Authors: Wright B. , Hargate R. , Garside M. , Carr G. , Wakefield T. , Swanwick R. , Noon I. , Simpson P.
Published: October 2021

Background

Over 90% of the 50,000 deaf children in the UK have hearing parents, many of whom were not expecting a deaf child and may require specialist support. Deaf children can experience poorer long-term outcomes than hearing children across a range of domains. After early detection by the Universal Newborn Hearing Screening Programme, parents in the UK receive support from Qualified Teachers of the Deaf and audiologists but resources are tight and intervention support can vary by locality. There are challenges faced due to a lack of clarity around what specific parenting support interventions are most helpful.

Methods

The aim of this research was to complete a systematic scoping review of the evidence to identify early support interventions for parents of deaf infants. From 5577 identified records, 54 met inclusion criteria. Two reviewers screened papers through three rounds before completing data extraction and quality assessment.

Results

Identified parent support interventions included both group and individual sessions in various settings (including online). They were led by a range of professionals and targeted various outcomes. Internationally there were only five randomised controlled trials. Other designs included non-randomised comparison groups, pre / post and other designs e.g. longitudinal, qualitative and case studies. Quality assessment showed few high quality studies with most having some concerns over risk of bias.

Conclusion

Interventions commonly focused on infant language and communication followed by parental knowledge and skills; parent wellbeing and empowerment; and parent/child relationship. There were no interventions that focused specifically on parent support to understand or nurture child socio-emotional development despite this being a well-established area of poor outcome for deaf children. There were few UK studies and research generally was not of high quality. Many studies were not recent and so not in the context of recent healthcare advances. Further research in this area is urgently needed to help develop evidence based early interventions.
Color painting predicts clinical symptoms in chronic schizophrenia patients via deep learning
Authors: Shen Hui , Wang Shui-Hua , Zhang Yi , Wang Haixia , Li Feng , Lucas Molly V. , Zhang Yu-Dong , Liu Yan , Yuan Ti-Fei
Published: October 2021

Background

Individuals with psychiatric disorders perceive the world differently. Previous studies indicated impaired color vision and weakened color discrimination ability in psychotic patients. Examining the paintings from psychotic patients can measure the visual-motor function. However, few studies examined the potential changes in the color painting behavior in these individuals. The current study aims to discriminate schizophrenia patients from healthy controls (HCs) and predict PANSS scores of schizophrenia patients according to their paintings.

Methods

In the present study, we retrospectively analyzed the paintings colored by 281 chronic schizophrenia patients and 35 HCs. The images were scanned and processed using series of computational analyses.

Results

The results showed that schizophrenia patients tend to use less color and exhibit different strokes compared to HCs. Using a deep learning residual neural network (ResNet), we were able to discriminate patients from HCs with over 90% accuracy. Further, we developed a novel convolutional neural network to predict PANSS positive, negative, general psychopathology, and total scores. The Root Mean Square Error (RMSE) of the prediction was low, which indicates higher accuracy of prediction.

Conclusion

In conclusion, the deep learning paradigm showed the large potential to discriminate schizophrenia patients from HCs based on color paintings. Besides, this color painting-based paradigm can effectively predict clinical symptom severity for chronic schizophrenia patients. The color paintings by schizophrenia patients show potential as a tool for clinical diagnosis and prognosis. These findings show potential as a tool for clinical diagnosis and prognosis among schizophrenia patients.
Challenges to manage pandemic of coronavirus disease (COVID-19) in Iran with a special situation: a qualitative multi-method study
Authors: Khankeh Hamidreza , Farrokhi Mehrdad , Roudini Juliet , Pourvakhshoori Negar , Ahmadi Shokoufeh , Abbasabadi-Arab Masoumeh , Bajerge Nader Majidi , Farzinnia Babak , Kolivand Pirhossain , Delshad Vahid , Khanjani Mohammad Saeed , Ahmadi-Mazhin Sadegh , Sadeghi-Moghaddam Ali , Bahrampouri Saiedeh , Sack Ulrich , Stueck Marcus , Domres Bernd
Published: October 2021

Background

With the unprecedented expansion of COVID-19 in the world since December 2019, Iran’s health system, like other countries, faced various challenges in managing the disease, which led to numerous experiences and lessons learned. This study was conducted to identify these challenges regarding unique political, economic, and cultural issues, which could help other countries with similar situations.

Methods

The present study was performed using a qualitative multi-method approach with a content analysis method. The data were collected through in-depth and semi-structured interviews and focused group discussions with 60 key persons who were selected purposefully, including policymakers, health care workers, and affected people by the disease, and the review of all available national reports between February 21, 2020, and March 22, 2021. The data collection and analysis were done simultaneously.

Results

Identified critical challenges for the management of COVID-19 in the health system were limited evidence and scientific controversies, poor social prevention and social inequalities, burnout and sustained workload among healthcare workers, improper management of resources and equipment, the lack of a guideline for contact tracing, and patient flow management, and mental health problems in the community.

Conclusions

According to our results, measures should be taken to conduct a continuous comprehensive risk assessment and develop a national response plan with an emphasis on precise contact tracing, active screening, patient flow, paying attention to the psychological and social dimensions of the disease, and also transparency of social inequalities in the face of risk factors of the COVID-19. Also, the social protection programs should become a vital tool for policymakers and supporting the vulnerable groups using the capacity of the community and international cooperation to develop a vaccine, which is difficult to procure due to the sanctions.
Managing clinical uncertainty in older people towards the end of life: a systematic review of person-centred tools
Authors: Ellis-Smith Clare , Tunnard India , Dawkins Marsha , Gao Wei , Higginson Irene J. , Evans Catherine J. ,   on behalf of SPACE, Ellis-Smith  , Yi  , Gao  , Norton  , Marshall  , Banerjee  , Goodman  , Higginson  , Banerjee Sube , Dawkins Marsha , Ellis-Smith Clare , Evans Catherine J. , Goodman Claire , Higginson Irene J. , Maddocks Matthew , Norton Christine , Seamark David , Tunnard India , Vincent Colin , Wei Gao , Yi Deokhee
Published: October 2021

Background

Older people with multi-morbidities commonly experience an uncertain illness trajectory. Clinical uncertainty is challenging to manage, with risk of poor outcomes. Person-centred care is essential to align care and treatment with patient priorities and wishes. Use of evidence-based tools may support person-centred management of clinical uncertainty. We aimed to develop a logic model of person-centred evidence-based tools to manage clinical uncertainty in older people.

Methods

A systematic mixed-methods review with a results-based convergent synthesis design: a process-based iterative logic model was used, starting with a conceptual framework of clinical uncertainty in older people towards the end of life. This underpinned the methods. Medline, PsycINFO, CINAHL and ASSIA were searched from 2000 to December 2019, using a combination of terms: “uncertainty” AND “palliative care” AND “assessment” OR “care planning”. Studies were included if they developed or evaluated a person-centred tool to manage clinical uncertainty in people aged ≥65 years approaching the end of life and quality appraised using QualSyst. Quantitative and qualitative data were narratively synthesised and thematically analysed respectively and integrated into the logic model.

Results

Of the 17,095 articles identified, 44 were included, involving 63 tools. There was strong evidence that tools used in clinical care could improve identification of patient priorities and needs (n = 14 studies); that tools support partnership working between patients and practitioners (n = 8) and that tools support integrated care within and across teams and with patients and families (n = 14), improving patient outcomes such as quality of death and dying and satisfaction with care. Communication of clinical uncertainty to patients and families had the least evidence and is challenging to do well.

Conclusion

The identified logic model moves current knowledge from conceptualising clinical uncertainty to applying evidence-based tools to optimise person-centred management and improve patient outcomes. Key causal pathways are identification of individual priorities and needs, individual care and treatment and integrated care. Communication of clinical uncertainty to patients is challenging and requires training and skill and the use of tools to support practice.
Ultrasound-guided five-point injection of botulinum toxin for patients with trapezius hypertrophy
Authors: Chen Wanying , Zhang Xiaoyu , Xu Yingying , Xu Zemin , Qin Haiyan , Zhang Lianbo
Published: October 2021

Objectives

Our study aimed to explore the clinical therapeutic effects of ultrasound-guided five-point injection of botulinum toxin type A for patients with trapezius hypertrophy.

Methods

Twenty female patients diagnosed with trapezius hypertrophy were enrolled in this study. The thicknesses of the trapezius muscle were measured by using the ultrasound scanner to locate the thickest point of trapezius, followed by labelling the other four points around the first point. Botulinum toxin type A was injected bilaterally (50 IU/side, 5 points/side) in the trapezius muscle of these patients. The surgery effects were evaluated by thicknesses of the trapezius muscle, intramuscular needle electromyographic and electroneurographic examinations, appearance changes and patients’ satisfactions.

Results

Statistically significant differences in thicknesses of the trapezius muscle were observed at 4 weeks (p < 0.001), 12 weeks (p < 0.001), 20 weeks (p < 0.001), 28 weeks (p = 0.011), 36 weeks (p = 0.022), and 44 weeks (p = 0.032) after surgery. The latencies of trapezius muscle became longer at 12 weeks after surgery (left: 2.40 ms, right: 2.53 ms vs. left: 1.75 ms, right: 2.00 ms). Electroneurographic results showed amplitude reduction of compound muscle action potentials (CMAPs) at 12 weeks after surgery (left: 1.91 uV, right: 3.10 uV vs. left: 15.00 uV, right: 15.40 uV). Obvious appearance changes were revealed at 12 weeks after surgery. All of 80% patients were very satisfied, 15% patients were relatively satisfied, and 5% patients were not satisfied with the surgery.

Conclusion

Ultrasound-guided five-point injection of botulinum toxin type A might be effective for patients with trapezius hypertrophy.
Correction to: Embedding similarities between embryos and circulating tumor cells: fundamentals of abortifacients used for cancer metastasis chemoprevention
Authors: Wang Jie , Yu Xiaobo , Peng Huayi , Lu Yusheng , Li Shuhui , Shi Qing , Liu Jian , Dong Haiyan , Katanaev Vladimir , Jia Lee
Published: October 2021

An amendment to this paper has been published and can be accessed via the original article.
Engaging with selective dry cow therapy: understanding the barriers and facilitators perceived by Irish farmers
Authors: Huey Sarah , Kavanagh Michaela , Regan Aine , Dean Moira , McKernan Clare , McCoy Finola , Ryan Eoin G. , Caballero-Villalobos Javier , McAloon Catherine I.
Published: October 2021

Background

Selective dry cow therapy (SDCT) is widely promoted in dairy farming as a method to reduce antimicrobial usage. New legislation introduced by the European Union will restrict and regulate the prophylactic and metaphylactic use of antibiotics from January 2022. Blanket dry cow therapy continues to be a practice engaged in by many farmers in Ireland and for many of these farmers, moving towards SDCT would require a significant infrastructural, behavioural and/or cultural change on their farm. Existing research has reported the important need to understand farmers’ motivations to initiate any substantial behaviour change. However, it is currently unknown what farmers know, think and believe about SDCT in Ireland. The aim of this study was to use qualitative methods to explore what barriers and facilitators farmers perceived to exist with SDCT and explore if they had chosen to implement SDCT after voluntarily participating in a funded dry cow consult with a trained veterinarian, with the objective of maximising the dry period udder health performance and moving safely to SDCT.

Results

In this study, 19 farmers were contacted, and telephone interviews were conducted regarding farmers’ beliefs about the consequences of SDCT. Audio recordings were professionally transcribed verbatim and analysed qualitatively using an inductive thematic analysis. The analysis identified 6 barriers and 6 facilitators to implementing SDCT. A significant fear of increasing mastitis incidence was evident that caused reluctance towards SDCT and reliance on antibiotics. Mixed perceptions on SDCT, infrastructure limitations, a perceived lack of preventive advice as well as peer influence were presented as barriers to SDCT. Farmers can build confidence when a graded approach to SDCT is implemented, which could help overcome the fear of SDCT and reliance on antibiotics. Regulatory pressure, high standards of farm hygiene and use of targeted veterinary consults were found to facilitate SDCT. Education was suggested to motivate farmers in the future uptake of SDCT. Despite cited negative influences, peer influence can be utilised to encourage the farming community.

Conclusions

This study prioritises areas to facilitate the major behaviour change required as a dairy industry in order to move from blanket dry cow therapy to SDCT.
Bacterial metabolites and cardiovascular risk in children with chronic kidney disease
Authors: Schlender Julia , Behrens Felix , McParland Victoria , Müller Dominik , Wilck Nicola , Bartolomaeus Hendrik , Holle Johannes
Published: October 2021

Cardiovascular complications are the major cause of the marked morbidity and mortality associated with chronic kidney disease (CKD). The classical cardiovascular risk factors such as diabetes and hypertension undoubtedly play a role in the development of cardiovascular disease (CVD) in adult CKD patients; however, CVD is just as prominent in children with CKD who do not have these risk factors. Hence, the CKD-specific pathophysiology of CVD remains incompletely understood. In light of this, studying children with CKD presents a unique opportunity to analyze CKD-associated mechanisms of CVD more specifically and could help to unveil novel therapeutic targets.

Here, we comprehensively review the interaction of the human gut microbiome and the microbial metabolism of nutrients with host immunity and cardiovascular end-organ damage. The human gut microbiome is evolutionary conditioned and modified throughout life by endogenous factors as well as environmental factors. Chronic diseases, such as CKD, cause significant disruption to the composition and function of the gut microbiome and lead to disease-associated dysbiosis. This dysbiosis and the accompanying loss of biochemical homeostasis in the epithelial cells of the colon can be the result of poor diet (e.g., low-fiber intake), medications, and underlying disease. As a result of dysbiosis, bacteria promoting proteolytic fermentation increase and those for saccharolytic fermentation decrease and the integrity of the gut barrier is perturbed (leaky gut). These changes disrupt local metabolite homeostasis in the gut and decrease productions of the beneficial short-chain fatty acids (SCFAs). Moreover, the enhanced proteolytic fermentation generates unhealthy levels of microbially derived toxic metabolites, which further accumulate in the systemic circulation as a consequence of impaired kidney function. We describe possible mechanisms involved in the increased systemic inflammation in CKD that is associated with the combined effect of SCFA deficiency and accumulation of uremic toxins. In the future, a more comprehensive and mechanistic understanding of the gut–kidney–heart interaction, mediated largely by immune dysregulation and inflammation, might allow us to target the gut microbiome more specifically in order to attenuate CKD-associated comorbidities.
The dual-port endoscope-assisted cyst enucleation on the maxillofacial region
Authors: Choi Hyuk , Cho Gyu-Jang , Jung Ki-Hyun , Jeon Jae-Yun , Lim Seung-Weon , Park Chang-Joo , Hwang Kyung-Gyun
Published: October 2021

Background

Endoscope-assisted surgery is a surgical method that has been used in oral and maxillofacial surgical fields. It provides good illumination, clear, and magnified visualization of the operative field. The purpose of this article is to describe the early clinical experiences to conduct minimally invasive surgery with endoscope-assisted enucleation of cysts on the jaw. It appears that this approach may be a superior alternative to the conventional approach.

Methods

In this study, 24 patients (9 females, 15 males, average age 41.5) underwent endoscope-assisted cyst enucleation under general anesthesia. All operations were done by one surgeon. The cases were classified depending on whether bone penetration occurred at the cyst site. The cystic lesions were enucleated using an endoscope with a 0°, 1.9 mm diameter, or a 30°, 2.7 mm diameter. Two bony windows were used for the insertion of a syringe for irrigation, curettes, suction tips, sinus blades, surgical drills, and an endoscope. An additional small channel was made for the insertion of endoscopic instruments.

Results

The 24 patients who underwent cyst enucleation were regularly observed for 3 to 12 months to evaluate for complications. Although some patients experienced swelling and numbness, these symptoms did not persist, and the patients soon returned to normal and there was no sign of recurrence.

Conclusions

The results of this study have suggested the possibility of minimally invasive surgery with endoscopes when it comes to cyst removal in the oral and maxillofacial region. Nevertheless, this study has limitations designed as a preliminary report focusing on the feasibility of endoscope-assisted cyst enucleation in the oral and maxillofacial regions.
Acute cardiotoxicity after initiation of the novel tyrosine kinase inhibitor gilteritinib for acute myeloid leukemia
Authors: Kim Lisa , Fowler Brian , Campbell Courtney M. , Slivnick Jeremy , Nawaz Haseeb , Kaka Yaquta , Ruz Patrick , Vallakati Ajay , Baliga Ragavendra , Vasu Sumithira , Addison Daniel
Published: October 2021

Background

Gilteritinib is a novel FMS-like tyrosine kinase 3 inhibitor recently approved by the United States Food and Drug Administration in 2018 for relapsed or refractory acute myeloid leukemia. However, gilteritinib may be associated with underrecognized cardiotoxicities.

Case presentation

This case describes a patient with a history significant for hyperlipidemia who was diagnosed with relapsed acute myeloid leukemia. After four doses of gilteritinib monotherapy, she abruptly developed acute systolic heart failure with global hypokinesis and septal wall motion abnormalities. Two days after discontinuation, cardiac magnetic resonance imaging showed partial recovery of her left ventricular ejection fraction as well as myocardial edema and non-ischemic fibrosis suggestive of inflammatory cardiomyopathy. She underwent intravenous diuresis and eventually started guideline-directed heart failure therapy. Follow-up cardiac magnetic resonance imaging five months later showed improved ejection fraction with mild non-ischemic fibrosis and resolution of myocardial edema and inflammation. She later received an allogeneic stem cell transplant from a matched unrelated donor.

Conclusions

Gilteritinib may be associated with early cardiotoxicities, including non-ischemic cardiomyopathy and myocarditis. Cardiac magnetic resonance imaging can be an important modality to help differentiate or diagnose early cardiotoxicities associated with novel targeted therapies.
Erdheim–Chester disease: with neurological manifestation and multisystem involvement: case report and radiological review
Authors: Rangankar Varsha , Ajmera Pranav , Agarwal Neha , Kalekar Tushar , Yadav Pratiksha , Suhas M.
Published: October 2021

Background

Erdheim–Chester disease (ECD) is a rarely encountered idiopathic systemic form of non-Langerhans cell histiocytosis. The clinical manifestations of ECD are highly heterogeneous, ranging from unifocal forms to life-threatening multisystem involvement. Patients with CNS involvement often do not show clinical remission.

Case presentation

We present a case of a 60-year-old male patient with worsening complaints of loss of balance, involuntary jerky movements, emotional lability and scanning speech developing over a period of 5 years. Magnetic resonance imaging of the brain at present institute revealed signal abnormalities in the midbrain, pons, cerebellar peduncles and cerebellar white matter with mineral deposition and volume loss in the bilateral basal ganglia and midbrain. Positron emission tomography–computed tomography of chest and abdomen revealed 18-fluorodeoxyglucose avid soft tissues lesion in the retroperitoneum involving bilateral perinephric spaces with intra-renal sinus extension, in pre- and paraaortic regions with enlargement of both adrenal glands. The radiographs of the long bones revealed multiple areas of sclerosis. The suspected diagnosis of ECD was confirmed on histopathology. ECD is a rare disease and has a predilection towards middle-aged males and is usually diagnosed late after the onset of initial symptoms.

Conclusions

Our case was an atypical presentation of an extremely rare disease, presenting with ataxia and choreoathetoid movements linked to ferromagnetic deposition on brain scans. Multiple other imaging feature characteristics of the disease like the hairy kidney sign, coated aorta sign, skeletal, extra-skeletal and central nervous system manifestations were noted in this single patient.
Integrating deep neural networks with full-waveform inversion: Reparameterization, regularization, and uncertainty quantification
Authors: Zhu Weiqiang , Xu Kailai , Darve Eric , Biondi Biondo , Beroza Gregory C.
Published: October 2021

Full-waveform inversion (FWI) is an accurate imaging approach for modeling the velocity structure by minimizing the misfit between recorded and predicted seismic waveforms. However, the strong nonlinearity of FWI resulting from fitting oscillatory waveforms can trap the optimization in local minima. We have adopted a neural-network-based full-waveform inversion (NNFWI) method that integrates deep neural networks with FWI by representing the velocity model with a generative neural network. Neural networks can naturally introduce spatial correlations as regularization to the generated velocity model, which suppresses noise in the gradients and mitigates local minima. The velocity model generated by neural networks is input to the same partial differential equation (PDE) solvers used in conventional FWI. The gradients of the neural networks and PDEs are calculated using automatic differentiation, which back propagates gradients through the acoustic PDEs and neural network layers to update the weights of the generative neural network. Experiments on 1D velocity models, the Marmousi model, and the 2004 BP model determine that NNFWI can mitigate local minima, especially for imaging high-contrast features such as salt bodies, and it significantly improves the inversion in the presence of noise. Adding dropout layers to the neural network model also allows analyzing the uncertainty of the inversion results through Monte Carlo dropout. NNFWI opens a new pathway to combine deep learning and FWI for exploiting the characteristics of deep neural networks and the high accuracy of PDE solvers. Because NNFWI does not require extra training data and optimization loops, it provides an attractive and straightforward alternative to conventional FWI.
Assessment of landslides in Bosnia and Herzegovina and Serbia: A Geoscientists Without Borders project
Authors: Suto Koya , Komatina Snezana , Sugawara Jun , Aizawa Takao
Published: October 2021

A severe storm caused floods and landslides in the Balkan region in May 2014. In response to the disaster, geophysical and geotechnical surveys were organized as a Geoscientists Without Borders (GWB) project of SEG. It took place in eight landslide-prone areas in Serbia and Bosnia and Herzegovina in three phases in 2015 and 2016. The seismic and electric resistivity surveys were conducted, and the results were interpreted in conjunction with the geotechnical inspection. The surveys identified the size of a potential landslide layer by the S-wave velocity distribution and, in particular high-risk locations, by electric resistivity anomalies. This interpretation enhanced the geotechnical observation. From the result, several countermeasures were recommended to suit the budgetary restrictions of local governments. Among them, the survey results in the Lopare locality have been presented as an example. The project was organized by the Association of Geophysicists and Environmentalists of Serbia involving many scientists, engineers, students, government staff, and local communities. As well as technical achievements, the significance of the project included providing students with opportunities to have practical experience of geophysical surveys and to learn outside the classroom and bringing together participants from different racial, political, religious, and educational backgrounds. All were made aware of the importance of humanitarian expert work. We have assessed the effectiveness of the GWB project using the guidelines of the Organization for Economic Co-operation and Development, Development Assistance Committee. One important outcome of the assessment was that such a volunteer geoscientific survey cannot stand alone. It would be more effective if incorporated in overall recovery and prevention programs.
COVID-19 Pandemic Influence on Medical Oncology Provider Perceptions of Telehealth Video Visits
Authors: Handley Nathan R. , Heyer Arianna , Granberg Rachel E. , Binder Adam F. , Gentsch Alexzandra T. , Csik Valerie P. , Garber Gregory , Worster Brooke , Lopez Ana Maria , Rising Kristin L.
Published: October 2021

PURPOSE:

The COVID-19 pandemic necessitated a rapid expansion of telehealth use in oncology, a specialty in which prior utilization was low in part because of barriers perceived by providers. Understanding the changing perceptions of medical oncology providers during the pandemic is critical for continued expansion and improvement of telehealth in cancer care. This study was designed to identify medical oncology providers' perceptions of telehealth video visits as influenced by the COVID-19 pandemic.

METHODS:

We conducted semi-structured interviews with medical oncology providers from November 20, 2020, to January 27, 2021, at the Sidney Kimmel Cancer Center at Thomas Jefferson University, a National Cancer Institute–designated cancer center in an urban, academic health system in Philadelphia, PA. We assessed provider perceptions of the impact of the COVID-19 pandemic on (1) provider-level comfort and willingness for telehealth, (2) provider-perceived patient comfort and willingness to engage in telehealth, and (3) continued barriers to successful telehealth use.

RESULTS:

Volunteer and convenience sampling resulted in the participation of 25 medical oncology providers, including 18 physicians and seven advanced practice providers, in semi-structured interviews. Of the 25 participants, 13 (52%) were female and 19 (76%) were White, with an average age of 48.5 years (standard deviation = 12.6). Respondents largely stated an increased comfort level and willingness for use of video visits. In addition, respondents perceived a positive change in patient comfort and willingness, mostly driven by convenience, accessibility, and reduced risk of COVID-19 exposure. However, several reported technologic issues and limited physical examination capability as remaining barriers to telehealth adoption.

CONCLUSION:

The rapid adoption of telehealth necessitated by the COVID-19 pandemic has increased provider-level and provider-perceived patient comfort and willingness to engage in video visits for cancer care. As both providers and patients increasingly accept telehealth across many use cases, future work should focus on further addressing technology and physical examination barriers and ensuring continued reimbursement for telehealth as a routine part of covered care.
Tumor-Specific and Tumor-Agnostic Molecular Signatures Associated With Response to Immune Checkpoint Inhibitors
Authors: Schlauch Daniel , Fu Xiaotong , Jones Suzanne F. , Burris Howard A. , Spigel David R. , Reeves James , McKenzie Andrew J.
Published: October 2021

PURPOSE

Next-generation sequencing (NGS) testing is being incorporated into routine standard of care for patients with cancer. Immune checkpoint inhibitors (CPIs) are approved for use in both tumor-specific and tumor-agnostic indications. We sought to determine tumor type–specific or tumor-agnostic correlations between mutations detected by NGS and response to CPIs.

MATERIALS AND METHODS

A retrospective analysis of 26,004 patient records with NGS data available was conducted. Time to treatment failure and overall survival analyses were performed. Hazard ratios and associated statistics were computed in the R programming language. The study was considered exempt from internal review board review and data were considered nonhuman subjects.

RESULTS

Response to CPIs varied between tumor types with melanoma and lung cancer performing relatively better on CPIs than other tumor types. Within tumor types, response to CPIs was stratified by mutations in specific genes. Tumor-agnostic markers including high tumor mutation burden and microsatellite instability-high were also associated with longer time to treatment failure on CPIs. Importantly, within the high tumor mutation burden and microsatellite instability-high groups, mutations in individual genes correlate with response to CPIs.

CONCLUSION

The results from commercial NGS panels may be used to stratify patients for response to CPIs. In tumors where CPIs show relatively low efficacy, there may be distinct patient populations—based on gene mutation status—that are predicted to have better response to CPIs. Likewise, there may be distinct patient populations who do relatively worse on CPIs within tumor types known to respond well to CPIs.
Formal proof of the requirement of MESP1 and MESP2 in mesoderm specification and their transcriptional control via specific enhancers in mice
Authors: Ajima Rieko , Sakakibara Yuko , Sakurai-Yamatani Noriko , Muraoka Masafumi , Saga Yumiko
Published: October 2021

MESP1 and MESP2 are transcriptional factors involved in mesoderm specification, somite boundary formation and somite polarity regulation. However, Mesp quadruple mutant zebrafish displayed only abnormal somite polarity without mesoderm specification defects. In order to re-evaluate Mesp1/Mesp2 mutants in mice, Mesp1 and Mesp2 single knockouts (KOs), and a Mesp1/Mesp2 double KO were established using genome-editing techniques without introducing selection markers commonly used before. The Mesp1/Mesp2 double KO embryos exhibited markedly severe mesoderm formation defects that were similar to the previously reported Mesp1/Mesp2 double KO embryos, indicating species differences in the function of MESP family proteins. However, the Mesp1 KO did not display any phenotype, including heart formation defects, which have been reported previously. We noted upregulation of Mesp2 in the Mesp1 KO embryos, suggesting that MESP2 rescues the loss of MESP1 in mesoderm specification. We also found that Mesp1 and Mesp2 expression in the early mesoderm is regulated by the cooperation of two independent enhancers containing T-box- and TCF/Lef-binding sites. Deletion of both enhancers caused the downregulation of both genes, resulting in heart formation defects. This study suggests dose-dependent roles of MESP1 and MESP2 in early mesoderm formation.
Cooperation of membrane-translocated syntaxin4 and basement membrane for dynamic mammary epithelial morphogenesis
Authors: Hirose Yuina , Hirai Yohei
Published: October 2021

Mammary epithelia undergo dramatic morphogenesis after puberty. During pregnancy, luminal epithelial cells in ductal trees are arranged to form well-polarized cystic structures surrounded by a myoepithelial cell layer, an active supplier of the basement membrane (BM). Here, we identified a novel regulatory mechanism involved in this process by using a reconstituted BM-based three-dimensional culture and aggregates of a model mouse cell line, EpH4, that had either been manipulated for inducible expression of the t-SNARE protein syntaxin4 in intact or signal peptide-connected forms, or that were genetically deficient in syntaxin4. We found that cells extruded syntaxin4 upon stimulation with the lactogenic hormone prolactin, which in turn accelerated the turnover of E-cadherin. In response to extracellular expression of syntaxin4, cell populations that were less affected by the BM actively migrated and integrated into the cell layer facing the BM. Concurrently, the BM-facing cells, which were simultaneously stimulated with syntaxin4 and BM, acquired unique epithelial characteristics to undergo dramatic cellular arrangement for cyst formation. These results highlight the importance of the concerted action of extracellular syntaxin4 extruded in response to the lactogenic hormone and BM components in epithelial morphogenesis.
Pneumococcal carriage and antibiotic susceptibility patterns in mother-baby pairs in a rural community in Eastern Uganda: a cross-sectional study
Authors: Madut Akech Gabriel , Naloli Mercy , Sebwami Paul , Kazibwe Patrick , Atwikiriize Maureen , Onyait Julius , Oboth Paul , Nteziyaremye Julius , Nekaka Rebecca , Iramiot Jacob Stanley
Published: October 2021

Background: Pneumococcal carriage predisposes children to pneumonia. Pneumonia poses a significant threat to the lives of children below five years old worldwide, contributing to a high number of hospitalizations and death. Morbidity and morbidity are especially common in children under five and the elderly, although any age group can be affected. This study aimed to estimate pneumococcal carriage and determine antibiotic susceptibility patterns of the pneumococci isolated from mother-baby pairs in Ngora district after the rollout of the pneumococcal vaccine. We hypothesized that high carriage of Streptococcus pneumoniae in mothers leads to carriage in their babies and hence a greater chance of contracting pneumonia.

Methods: Consecutive sampling was used to select 152 mother-baby pairs from community visits and those seeking care at the health facility. We collected nasal swabs from both baby and mother for culture and sensitivity testing using Kirby-Bauer’s agar disc diffusion method. Data was also collected from the mothers who consented to take part in the study, using an interviewer-administered questionnaire.

Results: This study found that there was a low prevalence of pneumococcal carriage in the mother-baby pair in the Ngora district. Only one mother-baby pair (1/152) was found to be colonized with pneumococci in both mother and baby and the rest of S. pneumoniae colonized either the mother or baby. We also observed high rates of microbial resistance to penicillin, which is the first-line drug for the management of pneumonia in Uganda. Also, high resistance patterns were recorded with chloramphenicol (50%) and tetracycline (50%), whereas the lowest resistance was recorded in clindamycin (17%).

Conclusions: The relationship between pneumococcal carriage and immunization status suggests that the pneumococcal vaccine is protective against the pneumococcal carriage. Resistance of S. pneumoniae to commonly used antibiotics was high.
Optimal design for a psychosocial intervention on severely acute malnourished children in humanitarian settings: results of an expert survey
Authors: N'DIAYE Dieynaba S , Salpéteur Cécile , Bizouerne Cécile , Le Roch Karine
Published: October 2021

Background: Common psychosocial interventions focus on feeding, stimulation, emotional responsiveness and childcare and parenting. Inclusion of such a component in the outpatient management of severe acute malnutrition (SAM) children is recommended. However, clinical assessment of such interventions is tedious in humanitarian settings and modalities evidence on the impact of psychosocial interventions alongside nutrition protocol for SAM is scarce.  This survey aimed to gather expert opinions on the optimal design of a combined psychosocial and nutrition intervention feasible in humanitarian settings.

Methods: From March to May 2018, an online survey was emailed to international experts in nutrition and mental health and psychosocial support, mainly from academia and international non-governmental organisations (INGOs). It included multiple choices questions on the key components of an optimal combined intervention.

Results: Of the 76 experts targeted, 20 responded. 11 (55%) belonged to INGOs, 2 (10%) to academia, and 4 (20%) to international organizations and donors. For most respondents, a combined intervention should be provided in weekly 45-minuites counselling sessions, provided individually (rather than in a group) and at home (rather than at a health center). None of the proposed ideal duration (two, four or six months) gained the majority of votes. Experts thought that 35% staff training should be in “Active listening for psychosocial support”, and 30% in “Early child development”, 25% in “Maternal depression” and 9% in “Anthropometric measurements”. They estimated that a combined intervention could improve SAM recovery rate by 10% (min-max: 0-19%) vs. the nutritional protocol alone. Qualitative results highlighted the importance of tailoring the intervention to the individual, the population and the settings; as well as considering feasibility and scalability at the design stage.

Conclusion: These findings could guide further research on the impact of psychosocial interventions on SAM children’s health and development, and help designing innovative approaches to treat undernutrition.
Modelling mode I failure at crack tip with verifications using digital image correlation
Authors: Kok Chee Kuang , Koh Eric Ren Wei , Chen Gooi Mee
Published: October 2021

Background: Linear elastic fracture mechanics (LEFM) applies to sharp cracks, although crack sites such as holes and slots are often blunt cracks with nonzero widths. The advancement in finite element method (FEM) has enabled the calculation of stress intensity factor (SIF) for unstable crack growth prediction, regardless of crack shape and size, but the calculations often differ from contour to contour. Hence, the purpose of this work is to determine if SIFs computed using commercial FEM have experimentally verifiable advantages over the traditional stress-based modelling approaches in predicting Mode I brittle failure at blunt crack tip.

Methods: Experiments and simulations were conducted on brittle Poly(methyl methacrylate) (PMMA) plastic to compare the actual and predicted strain fields and SIFs at crack tip, and the critical force at which unstable crack growth initiates. A centrally straight cracked Brazilian disc made of PMMA was subjected to purely Mode I fracture. Its strain fields were measured from deformed speckle patterns using digital image correlation software. The same disc was modelled using plane stress model in FEM. By applying the critical force, SIFs were then computed using ANSYS pre-meshed crack method at different contours away from the crack tip. The effects of element type, mesh size and crack width on the simulated SIFs were investigated.

Results: It was found that the experimental critical load agreed well with LEFM prediction based on PMMA fracture toughness in published literature. Disc failure happened at the first sign of tensile yield at the crack tip in the finite element model with a triangle mesh. Digital image correlation clearly shows the occurrence of unstable crack growth at critical force. It also shows comparable far field strain responses to the FEM model.

Conclusions: The computed SIFs were inconsistent, and their usefulness in predicting unstable crack growth requires further investigation.
The genome sequence of the common frog, Rana temporaria Linnaeus 1758
Authors: Streicher Jeffrey W. ,   Wellcome Sanger Institute Tree of Life programme,   Wellcome Sanger Institute Scientific Operations: DNA Pipelines collective,   Tree of Life Core Informatics collective,   Darwin Tree of Life Consortium
Published: October 2021

We present a genome assembly from an individual female Rana temporaria (the common frog; Chordata; Amphibia; Anura; Ranidae). The genome sequence is 4.11 gigabases in span. The majority of the assembly is scaffolded into 13 chromosomal pseudomolecules. Gene annotation of this assembly by the NCBI Eukaryotic Genome Annotation Pipeline has identified 23,707 protein coding genes.
MathOptInterface: A Data Structure for Mathematical Optimization Problems
Authors: Legat Benoît , Dowson Oscar , Garcia Joaquim Dias , Lubin Miles
Published: October 2021

We introduce MathOptInterface, an abstract data structure for representing mathematical optimization problems based on combining predefined functions and sets. MathOptInterface is significantly more general than existing data structures in the literature, encompassing, for example, a spectrum of problems classes from integer programming with indicator constraints to bilinear semidefinite programming. We also outline an automated rewriting system between equivalent formulations of a constraint. MathOptInterface has been implemented in practice, forming the foundation of a recent rewrite of JuMP, an open-source algebraic modeling language in the Julia language. The regularity of the MathOptInterface representation leads naturally to a general file format for mathematical optimization we call MathOptFormat. In addition, the automated rewriting system provides modeling power to users while making it easy to connect new solvers to JuMP.

Summary of Contribution: This paper describes a new abstract data structure for representing mathematical optimization models with a corresponding file format and automatic transformation system. The advances are useful for algebraic modeling languages, allowing practitioners to model problems more naturally and more generally than before.
The Value of Health Information Technology Interoperability: Evidence from Interhospital Transfer of Heart Attack Patients
Authors: Li Yao , Lu Lauren Xiaoyuan , Lu Susan Feng , Chen Jian
Published: October 2021

Problem definition: Health information technology (HIT) interoperability refers to the ability of different electronic health record systems and software applications to communicate, exchange data, and use the information that has been exchanged. The U.S. Government has invested heavily to promote HIT interoperability in recent years in an attempt to improve patient outcomes and control healthcare expenditure. This study empirically assesses the value of HIT interoperability in the interhospital transfer process of heart attack patients. Academic/practical relevance: HIT interoperability is supposed to enable health information exchange between disparate providers. However, there exists little evidence about how it affects care delivery processes across providers. Methodology: Using transfer records of heart attack patients and HIT interoperability adoption records of hospitals in New York State between 2013 and 2015, we estimate the effect of HIT interoperability on care delivery process measures and patient outcome measures. We demonstrate the robustness of the results with alternative samples and model specifications, including the instrumental variable method, the propensity score matching method, the difference-in-differences method, and a falsification test. Results: We show that HIT interoperability shortens the throughput time of interhospital transfer by 45.6 minutes on average or 12.0%. Surprisingly, we find that HIT interoperability has little effect in reducing duplicate electrocardiogram (EKG) testing for transferred patients at receiving hospitals. When HIT interoperability is enabled through a common software vendor, it yields 15.6% more reduction in the throughput time than when it is enabled through different vendors, but it still has no significant effect on duplicate EKG testing. Furthermore, we find that HIT interoperability leads to a 3.0-percentage point decrease in the 30-day readmission rate of transferred patients, which can be explained by the reduction in the throughput time. Managerial implications: Our findings demonstrate the value of incentivizing HIT adoption and promoting widespread exchange of health information because HIT interoperability indeed improves the efficiency of healthcare delivery across providers, which ultimately translates to improved patient outcomes. Given the lack of reduction in duplicate testing in our study, we call for more provider effort toward realizing the full potential of HIT interoperability by minimizing the gap between technology adoption and utilization.
Problemistic Search of the Embedded Firm: The Joint Effects of Performance Feedback and Network Positions on Venture Capital Firms’ Risk Taking
Authors: Hu Songcui , Gu Qian (Cecilia) , Xia Jun
Published: October 2021

The Behavioral Theory of the Firm suggests that performance below aspirations triggers problemistic search that can lead to risk taking. This prediction has received empirical support from most studies on the topic. However, this literature has typically focused on the internal determinants of firm search and risk-taking behavior and given little attention to the influences of social networks in which firms are embedded. To this end, we incorporate the network embeddedness perspective regarding firms’ network positions and their roles in firm decision making. We suggest that a firm’s search behavior is jointly directed by its performance feedback and network positions. Specifically, network brokerage and centrality play important yet distinct roles in guiding firm search behavior by differentially shaping the direction of problemistic search: high brokerage directs problemistic search to high-risk solutions, whereas high centrality directs problemistic search to low-risk solutions. Our theoretical predictions receive general empirical support based on analyses using longitudinal data from the Chinese venture capital industry. Our approach incorporates the crucial role of network structures into the problemistic search model and works toward building a problemistic search theory of the embedded firm.