bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human genome editing: how to prevent rogue actors
Authors: Townsend Beverley A. 
Published: October 2020

Abstract
Background
Human genome editing technologies offer much potential benefit. However, central to any conversation relating to the application of such technologies are certain ethical, legal, and social difficulties around their application. The recent misuse, or inappropriate use, by certain Chinese actors of the application of genome editing technologies has been, of late, well noted and described. Consequently, caution is expressed by various policy experts, scientists, bioethicists, and members of the public with regard to the appropriate use of human germline genome editing and its possible future effect on future generations.

Main text
As concerns about the applications of heritable genome editing have grown, so too have the questions around what is to be done to curtail ‘rogue actors’. This paper explores various ways in which to regulate genomic editing that are socially beneficial, while being cognisant of legal and ethical principles and rights values. This is done by evolving regulatory frameworks across jurisdictions in an attempt to raise issues, address common principles, and set responsible standards for stewardship of the novel technology.

Conclusions
It is suggested that robust and concrete regulatory measures be introduced that are culturally and contextually sensitive, inclusive, appropriate, and trustworthy – and are based on public empowerment and human rights objectives. Doing so will ensure that we are perfectly positioned to harness and promote the benefits that novel technologies have to offer, while safeguarding public health and curtailing the ambitions of rogue actors. This it is acknowledged is no easy task, so, as a point of departure, this paper sets out a path forward by means of certain, practical recommendations – by constructing genome editing regulation in a manner that both fulfils the desire to better progress human health and that can withstand legal and ethical scrutiny.
The following observations and recommendations are made: Firstly, that a solution of effective, legitimate governance should consist of a combination of national and supranational legislative regulation or ‘hard’ law, in combination with ‘soft’ ethics, firmly anchored in and underpinned by human rights values. Second, that efforts to support legal and ethical solutions should be rigorous, practical, and robust, contribute to a reaffirmation of human rights in a contextually sensitive manner, and be transnational in reach. Lastly, that greater harmonisation across jurisdictions and increased public engagement be sought. This it is proposed will address the question of how to implement a normative framework which in turn can prevent future rogue actors.
Fraternal twins with Phelan-McDermid syndrome not involving the SHANK3 gene: case report and literature review
Authors: Li Shan , Xi Ke-wang , Liu Ting , Zhang Ying , Zhang Meng , Zeng Li-dong , Li Juan 
Published: October 2020

AbstractBackgroundPhelan-McDermid syndrome (PMS, OMIM#606232), or 22q13 deletion syndrome, is a rare genetic disorder caused by deletion of the distal long arm of chromosome 22 with a variety of clinical features that display considerably heterogeneous degrees of severity. TheSHANK3gene is understood to be the critical gene for the neurological features of this syndrome.Case presentationWe describe one pair of boy-girl twins with a 22q13 deletion not involving theSHANK3gene. Interestingly, the clinical and molecular findings of the two patients were identical, likely resulting from germline mosaicism in a parent. The boy-girl twins showed intellectual disability, speech absence, facial dysmorphism, cyanosis, large fleshy hands and feet, dysplastic fingernails and abnormal behaviors, and third-generation sequencing showed an identical de novo interstitial deletion of 6.0 Mb in the 22q13.31-q13.33 region.ConclusionsOur case suggests that prenatal diagnosis is essential for normal parents with affected children due to the theoretical possibility of parental germline mosaicism. Our results also indicated that other genes located in the 22q13 region may have a role in explaining symptoms in individuals with PMS. In particular, we propose that four candidate genes,CELSR1,ATXN10,FBLN1andWNT7B, may also be involved in the etiology of the clinical features of PMS. However, more studies of smaller interstitial deletions with 22q13 are needed to corroborate our hypothesis and better define the genotype-phenotype correlation. Our findings contribute to a more comprehensive understanding of PMS.
Functional relationships between recessive inherited genes and genes with de novo variants in autism spectrum disorder
Authors: Wang Lin , Zhang Yi , Li Kuokuo , Wang Zheng , Wang Xiaomeng , Li Bin , Zhao Guihu , Fang Zhenghuan , Ling Zhengbao , Luo Tengfei , Xia Lu , Li Yanping , Guo Hui , Hu Zhengmao , Li Jinchen , Sun Zhongsheng , Xia Kun 
Published: October 2020

Abstract
Background
Both de novo variants and recessive inherited variants were associated with autism spectrum disorder (ASD). This study aimed to use exome data to prioritize recessive inherited genes (RIGs) with biallelically inherited variants in autosomes or X-linked inherited variants in males and investigate the functional relationships between RIGs and genes with de novo variants (DNGs).

Methods
We used a bioinformatics pipeline to analyze whole-exome sequencing data from 1799 ASD quads (containing one proband, one unaffected sibling, and their parents) from the Simons Simplex Collection and prioritize candidate RIGs with rare biallelically inherited variants in autosomes or X-linked inherited variants in males. The relationships between RIGs and DNGs were characterized based on different genetic perspectives, including genetic variants, functional networks, and brain expression patterns.

Results
Among the biallelically or hemizygous constrained genes that were expressed in the brain, ASD probands carried significantly more biallelically inherited protein-truncating variants (PTVs) in autosomes (p = 0.038) and X-linked inherited PTVs in males (p = 0.026) than those in unaffected siblings. We prioritized eight autosomal, and 13 X-linked candidate RIGs, including 11 genes already associated with neurodevelopmental disorders. In total, we detected biallelically inherited variants or X-linked inherited variants of these 21 candidate RIGs in 26 (1.4%) of 1799 probands. We then integrated previously reported known or candidate genes in ASD, ultimately obtaining 70 RIGs and 87 DNGs for analysis. We found that RIGs were less likely to carry multiple recessive inherited variants than DNGs were to carry multiple de novo variants. Additionally, RIGs and DNGs were significantly co-expressed and interacted with each other, forming a network enriched in known functional ASD clusters, although RIGs were less likely to be enriched in these functional clusters compared with DNGs. Furthermore, although RIGs and DNGs presented comparable expression patterns in the human brain, RIGs were less likely to be associated with prenatal brain regions, the middle cortical layers, and excitatory neurons than DNGs.

Limitations
The RIGs analyzed in this study require functional validation, and the results should be replicated in more patients with ASD.

Conclusions
ASD RIGs were functionally associated with DNGs; however, they exhibited higher heterogeneity than DNGs.
Death of a neonate with suspected coronavirus disease 2019 born to a mother with coronavirus disease 2019 in Iran: a case report
Authors: Rashidian Tayebeh , Sharifi Nasibeh , Fathnezhad-Kazemi Azita , Mirzamrajani Fatemeh , Nourollahi Sajad , Ghaysouri Abas 
Published: October 2020

Abstract
Introduction
A novel coronavirus named severe acute respiratory syndrome coronavirus 2, was first reported in Wuhan, China, in December 2019. The virus, known as COVID-19, is recognized as a potentially life-threatening disease by causing severe respiratory disease. Since this virus has not previously been detected in humans, there is a paucity of information regarding its effects on humans. In addition, only limited or no information exists about its impact during pregnancy.

Case presentation
In the present case study, we report the death of a neonate born to a 32-year-old mother with coronavirus disease 2019 in Ilam, Iran, with Kurdish ethnicity. We report the infection and death of a neonate in Iran with a chest X-ray (CXR) marked abnormality 2 hours after birth demonstrating coronavirus disease 2019 disease. The neonate was born by elective cesarean section, the fetal health was assessed using fetal heart rate and a non-stress test before the birth, and there was no evidence of fetal distress. All the above-mentioned facts and radiographic abnormalities suggested that coronavirus disease 2019 is involved.

Conclusions
In this case study, we report the death of a neonate born to a mother with coronavirus disease 2019, 11 hours after birth. There is a paucity of data on the vertical transmission and the adverse maternal-fetal consequences of this disease, so vertical transmission from mother to child remains to be confirmed.
“Will you hear my voice?”: to engage older patients online, listen to them about their lives offline
Authors: Millenson Michael L. 
Published: October 2020

AbstractThe scope of health information and health care services available online is rapidly expanding. At the same time, COVID-19 is causing vulnerable elders to reconsider in-person provider visits. In that context, recently published research by Y. Mizrachi et al. examining obstacles to the use of online health services (OHS) among adults age 50 and up takes on new importance. An iconic Israeli song begins, “Will you hear my voice?” (Hebrew Songs. Zemer Nugeh (Hatishmah Koli), 2020). What makes Mizrachi et al.’s findings particularly intriguing, despite several caveats, is the manner in which they demonstrated a commitment to genuinely listen to individual voices. The researchers spoke “openly and bluntly” with interviewees as peers and were rewarded with “specific, well-defined and applicable answers with the potential to be used.” The most striking findings came in candid answers that went beyond the factors intrinsic to the online offerings and addressed important factors in what regular Internet users often refer to as IRL (“in real life”), such as support from family. The necessity of avoiding preconceptions about the most effective manner to engage patients underscores the importance of patient and family advisory councils (PFACs). PFACs, increasingly being adopted by health care organizations globally, provide an ongoing ability to listen and respond to the “patient voice.” Effectively addressing obstacles to older adults’ use of the full range of online health resources will require the involvement not just of health plans and government, but also of voluntary organizations, providers, families and others integral to users’ offline “real lives.” Sustained, focused listening must be a central part of that effort.
Reflections on the IJHPR’s article collection on dementia
Authors: Harrison Jill , Mor Vincent , Mitchell Susan , McCarthy Ellen P. 
Published: October 2020

AbstractAlzheimer’s disease and Alzheimer’s disease-related dementias (AD/ADRD) constitute a worldwide public health crisis. In light of the AD/ADRD epidemic now existing within the global COVID-19 pandemic, the need for global action to improve dementia care is greater than ever. The article collection “Dementia- an Interdisciplinary Approach,” in the Israeli Journal of Health Policy and Research (IJHPR) highlights the need for interprofessional approaches to improving outcomes for people living with dementia and their care partners, as well as the complexities of conducting dementia care research.
Primary non-adherence to inhaled medications measured with e-prescription data from Poland
Authors: Kardas Grzegorz , Panek Michał , Kuna Piotr , Kardas Przemysław 
Published: October 2020

Abstract

Background
Treatment adherence greatly influences the clinical outcomes in various fields of medicine, including management of asthma and COPD. With the recent implementation of a nationwide e-Health solutions in Poland, new and unique opportunities for studying primary non-adherence in asthma and COPD emerged. The aim was to study primary non-adherence to inhaled medications available in Poland indicated in asthma and/or COPD and analyse the impact of patients’ demographics and inhalers’ characteristics (dry powder inhalers (DPIs) vs metered dose inhalers (MDIs) and presence of a dosage counter) on primary non-adherence.

Methods
A retrospective analysis of all e-prescriptions issued in Poland in 2018 (n = 119,880) from the national e-prescription pilot framework.

Results
Primary non-adherence for inhalable medications reached 15.3%. It significantly differed among age groups—the lowest (10.8%) was in 75 + years-old patients, highest (18%) in 65–74 years-old patients. No gender differences in primary non-adherence were found. The highest non-adherence was observed for ICS + LABA combinations (18.86%). A significant difference was found between MDI and DPI inhalers and between inhalers with/without a dosage counter.

Conclusions
Out of e-prescriptions for inhaled medications issued in 2018 in Poland, 15.3% were not redeemed. The degree of primary non-adherence was influenced by age, but not gender. Significant differences between MDIs and DPIs and between inhalers with/without a dosage counter were observed.
Systematic review of therapeutic outcomes of multidrug resistant tuberculosis and their predictors in adults receiving integrated treatment of tuberculosis and human immuno-deficiency virus in low- and middle-income countries: a study protocol
Authors: Kadia Benjamin Momo , Aroke Desmond , Njefi Kevin Pene , Tochie Joel Noutakdie , Tianyi Frank-Leonel , Kadia Reine Suzanne , Dimala Christian Akem 
Published: October 2020

Abstract
Background
Programs that integrate tuberculosis (TB) and human immunodeficiency virus (HIV) treatment aim to provide efficient treatment services and maximize successful treatment outcomes through the delivery of both TB and HIV treatment by one provider at the same time and location. However, multi-drug resistant tuberculosis (MDR-TB) is more difficult to treat as compared to drug-sensitive TB, and in low- and middle-income countries (LMICs), the potential of programs integrating TB/HIV treatment to sustain favourable MDR-TB treatment outcomes is poorly elucidated. The objective of this review is to perform a systematic collection, critical appraisal and synthesis of existing evidence on therapeutic outcomes of MDR-TB and their predictors among adults receiving integrated treatment for TB/HIV in LMICs.

Methods
A systematic review of quantitative evidence from observational cohort studies will be performed. MEDLINE, Embase, and Global Health electronic databases will be searched for relevant studies published from March 2004 to December 2019. Two investigators will independently screen the search output, review the eligible studies, and assess the quality of the eligible studies using quality assessment tools of the National Heart Lung and Blood Institute. Random-effects meta-analysis will be used to obtain summary estimates. Heterogeneity across studies will be assessed using the I2 statistic. The confidence in the summary estimates will be rated using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. The final review will be reported following the guidelines of the Preferred Reporting System for Systematic Reviews and Meta-analysis, presented at scientific conferences and published in a peer-reviewed journal.

Discussion
This study is expected to report the performance of integrated TB/HIV treatment programs as regards their potential to uphold successful MDR-TB treatment outcomes in LMICs. Furthermore, the review will indicate patient-related and healthcare-related factors that should be addressed to improve on survival of patients with MDR-TB/HIV co-infection in LMICs.

Systematic review registration
This review has been registered with the International Prospective Register of Systematic Reviews and the reference ID is CRD42020159745
Decomposition of years of life lost due to premature death (YLL): a method for spatial and temporal comparative assessment
Authors: Saxena Nitya , Sethia Deepak 
Published: October 2020

AbstractBackgroundAcceptance of Disability-Adjusted Life Year (DALY) as a measure of health summary and progression has increased over the years, which in turn has instigated comparative analysis studies of DALY across time and geography. Thus, it is important to explore methodological underpinnings of comparative analysis.ResultsA crude comparison of disease burden across time or space may mislead the interpretation of the health system’s performance because the quantum and pattern of DALY can be influenced by the age structure of the society. A significant proportion of this burden is due to the Years of Life Lost (YLL) component. The paper proposes a mathematical exposition to decompose the change in YLL over time or region into burden attributed to a) population age structure, b) death rate, and c) age at death gradient.ConclusionWe reasoned that the death rate and age at death burden gradient signify the real contribution of the health systems. Hence, the method of decomposition can be utilized to measure the health service progression of a region in real terms.
Prospective outcomes following drainless superficial parotidectomy with sternocleidomastoid flap reconstruction
Authors: Melong Jonathan C. , Rigby Matthew H. , Corsten Martin , Trites Jonathan R. B. , Bulter Angela , Taylor S. Mark 
Published: October 2020

Background Patients undergoing superficial parotidectomy for benign parotid lesions are at risk of postoperative complications, most notably cosmetic complications such as facial paralysis and contour defects, and functional complications including Frey's syndrome. Traditionally, surgical drains have been placed at the end of surgery to prevent hematoma and sialocele formation. However, this can increase the risk of postoperative complications and contribute to a prolonged course in hospital. To try and prevent these risks and complications, we introduced a novel technique of a drainless parotidectomy by reconstructing the resulting parotid bed defect with a superiorly based sternocleidomastoid (SCM) rotational flap and by placement of gelfoam into the wound bed and a facelift dressing postoperatively to provide additional hemostasis and avoid drain placement. Methods All patients with benign parotid disease undergoing a drainless superficial parotidectomy and reconstruction with a superiorly based SCM rotational flap at our center were identified within a prospective cohort database between July 2010–2018. Primary outcomes included postoperative cosmetic and functional outcomes, complications and length of hospital stay. A secondary cost analysis was done to compare this novel technique to traditional superficial parotidectomy with surgical drain placement. Results Fifty patients were identified within the database and were included in the final analysis. The average length of hospital stay was 1.02 days. All patients were satisfied with their aesthetic outcome at 1 year. During long term follow-up, 63% of patients reported normal appearance of the operated side. Seven patient's (14%) developed temporary facial paresis following surgery. All patients had resultant normal facial function at follow-up in 1 year. No patients developed subjective Frey's Syndrome. Two patients (4%) developed a postoperative sialocele requiring drainage and one patient (2%) developed a hematoma on extubation requiring evacuation and drain placement. Cost analysis demonstrated a cost savings of approximately $975 per person following surgery. Conclusion In the current study, we introduced a novel approach of a drainless superficial parotidectomy using a superiorly based SCM flap, gelfoam and placement of a post-operative facelift dressing. This drainless approach was associated with good long-term cosmetic and functional outcomes with few postoperative complications. This new technique may also offer the potential for long-term savings to the health care system.
How do I keep myself safe? Patient perspectives on including reason for use information on prescriptions and medication labels: a qualitative thematic analysis
Authors: Whaley Colin , Bancsi Ashley , Ho Joanne Man-Wai , Burns Catherine M. , Grindrod Kelly 
Published: October 2020

Abstract

Background
Medications are crucial for maintaining patient wellness and improving health in modern medicine, but their use comes with risks. Helping patients to understand why they are taking medications is important for patient-centered care and facilitates patient adherence to prescribed medications. One strategy involves enhancing communication between patients, physicians, and pharmacists through the sharing of reason for use (RFU) information or the indication for medications.

Methods
Semi-structured interviews were conducted with 20 patients in Ontario, Canada, to gain perspectives on how patients currently store their medication information and benefits and disadvantages of adding RFU to prescriptions and medication labels. An interview guide was used by the two interviewers, and the interviews were recorded, transcribed, and thematically coded.

Results
The analysis yielded three main themes: patient decision making with RFU, RFU in modern, patient-centered care, and logistical aspects of communicating RFU. The patients that were interviewed expressed the value of having RFU when deciding if a medication was effective or to stop taking the medication. Patients felt comfortable with RFU being added to prescriptions and acknowledged the value in adding RFU to medication labels, helping patients and others identify and distinguish medications. Patients generally expressed interest in having RFU written in lay language and identified strengths and weaknesses of having access to RFU via a website or app.

Conclusions
Patients rated the importance of knowing RFU very highly, identified the value in sharing RFU with pharmacists on prescriptions, and in having RFU on medication labels. These results can be used to inform policy on the addition of RFU on prescriptions and medication labels and support improved communication between patients, pharmacists, and physicians about RFU.