bluuebunny/crossref_metadata_2025 huggingface dataset:
Cannabis and its derivatives for the use of motor symptoms in Parkinson’s disease: a systematic review and meta-analysis
Authors: Thanabalasingam Susan J. , Ranjith Brandan , Jackson Robyn , Wijeratne Don Thiwanka
Published: May 2021

Background:

Recent changes to the legal status of cannabis across various countries have renewed interest in exploring its use in Parkinson’s disease (PD). The use of cannabinoids for alleviation of motor symptoms has been extensively explored in pre-clinical studies.

Objective:

We aim to systematically review and meta-analyze literature on the use of medical cannabis or its derivatives (MC) in PD patients to determine its effect on motor function and its safety profile.

Methods:

We reviewed and analyzed original, full-text randomized controlled trials (RCTs) and observational studies. Primary outcomes were change in motor function and dyskinesia. Secondary outcomes included adverse events and side effects. All studies were analyzed for risk of bias.

Results:

Fifteen studies, including six RCTs, were analyzed. Of these, 12/15 (80%) mention concomitant treatment with antiparkinsonian medications, most commonly levodopa. Primary outcomes were most often measured using the Unified Parkinson Disease Rating Scale (UPDRS) among RCTs and patient self-report of symptom improvement was widely used among observational studies. Most of the observational data lacking appropriate controls had effect estimates favoring the intervention. However, the controlled studies demonstrated no significant motor symptom improvement overall. The meta-analysis of three RCTs, including a total of 83 patients, did not demonstrate a statistically significant improvement in UPDRS III score variation (MD −0.21, 95% CI −4.15 to 3.72; p = 0.92) with MC use. Only one study reported statistically significant improvement in dyskinesia ( p < 0.05). The intervention was generally well tolerated. All RCTs had a high risk of bias.

Conclusion:

Although observational studies establish subjective symptom alleviation and interest in MC among PD patients, there is insufficient evidence to support its integration into clinical practice for motor symptom treatment. This is primarily due to lack of good quality data.
Harnessing the epigenome to boost immunotherapy response in non-small cell lung cancer patients
Authors: Gkountakos Anastasios , Delfino Pietro , Lawlor Rita T. , Scarpa Aldo , Corbo Vincenzo , Bria Emilio
Published: May 2021

The introduction of immune checkpoint inhibitor (ICI)-based therapy for non-oncogene addicted non-small cell lung cancer (NSCLC) has significantly transformed the treatment landscape of the disease. Inhibitors of the programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) immune checkpoint axis, which were initially considered as a late-line treatment option, gradually became the standard of care as first-line treatment for subgroups of NSCLC patients. However, a significant fraction of patients either fails to respond or progresses after a partial response to ICI treatment. Thus, the identification of mechanisms responsible for innate and acquired resistance to immunotherapy within a rapidly evolving tumor microenvironment (TME) is urgently required, as is the identification of reliable predictive biomarkers beyond PD-L1 expression. The deregulation of the epigenome is a key driver of cancer initiation and progression, and it has also been shown to drive therapeutic resistance. Tumor education of infiltrating myeloid cells towards an immuno-suppressive phenotype as well as induction of T-cell dysfunction in the TME is also driven by epigenome reprogramming. As it stands and, given their dynamic nature, epigenetic changes in cancer and non-cancer cells represent an attractive target to increase immunotherapy activity in NSCLC. Accordingly, clinical trials of combinatorial immuno-epigenetic drug regimens have been associated with tumor response in previously immunotherapy-resistant NSCLC patients irrespective of their PD-L1 status. Moreover, epigenetic signatures might represent valuable theragnostic biomarkers as they can be assayed easily in liquid biopsy and provide multiple layers of information. In this review, we discuss the current knowledge regarding the dysregulated epigenetic mechanisms contributing to immunotherapy resistance in NSCLC. Although the clinical data are still maturing, we highlight the attractive perspective that the synergistic model of immuno-epigenetic strategies might overcome the current limitations of immunotherapy alone and will be translated into durable clinical benefit for a broader NSCLC population.
Hyperuricemia, urate-lowering therapy, and kidney outcomes: a systematic review and meta-analysis
Authors: Sharma Gaurav , Dubey Abhishek , Nolkha Nilesh , Singh Jasvinder A.
Published: May 2021

Background:

Contradictory evidence exists for association of hyperuricemia and kidney function. To investigate the association of hyperuricemia and kidney function decline (hyperuricemia question) and effect of urate-lowering therapies (ULTs) on kidney function (ULT question), we performed a systematic review and meta-analysis.

Methods:

MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and CINAHL were searched from inception to July 2020. We selected observational studies for the hyperuricemia question and controlled trials for the ULT question. Two investigators independently assessed study eligibility and abstracted the data. Risk of bias was assessed using the Newcastle–Ottawa Scale and Cochrane risk of bias tool. Meta-analysis was done using the inverse variance method and random effect model. We estimated odds ratio (OR), hazard ratio (HR), risk ratio (RR), and the mean difference (MD). Evidence certainty was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system.

Results:

Of 12,037 studies screened, 131 studies with 3,414,226 patients were included. Hyperuricemia was associated with a significant risk of rapid estimated glomerula filtration rate (eGFR) decline ⩾3 ml/min per 1.73 m2 per year (OR 1.38, 95% CI 1.20–1.59; low certainty), albuminuria (OR/HR 1.94, 95% CI 1.34–2.79; very low certainty), chronic kidney disease (OR/HR 2.13, 95% CI 1.74–2.61; very low certainty), and kidney failure (HR 1.53, 95% CI 1.18–1.99; very low certainty). Compared with control, ULT use for ⩾1 year was associated with significantly more improved eGFR (MD 1.81 ml/min per 1.73 m2, 95% CI 0.26–3.35; very low certainty), serum creatinine (MD −0.33 mg/dl, 95% CI −0.47 to −0.19; low certainty), and proteinuria (MD −5.44 mg/day, 95% CI −8.49 to −2.39; low certainty), but no difference in kidney failure.

Conclusion:

Hyperuricemia is associated with worsening eGFR, albuminuria, chronic kidney disease, and kidney failure. ULT use for ⩾1 year may improve kidney function.

Registration:

The protocol was registered at PROSPERO database, CRD42015013859.
An uncommon case of bioprosthetic mitral valve thrombosis with subsequent prosthesis dehiscence
Authors: Raja Shariff Raja Ezman Faridz , Kasim Sazzli
Published: May 2021

Bioprosthetic valve thrombosis (BVT) is uncommon. An 82-year-old gentleman presented following a cardioembolic stroke due to a mitral valve infective endocarditis. The patient underwent bioprosthetic mitral valve replacement. Following discharge, he re-presented with weakness due to a new left-sided stroke and right-sided occipital intracerebral haemorrhage. Both transthoracic and transoesophageal echocardiography revealed BVT on the anterior portion of the prosthesis. Following a multidisciplinary team discussion, it was felt that thrombolytics and anticoagulation would be detrimental. The patient continued to worsen and eventually succumbed to congestive cardiac failure. BVT is uncommon, and patients often present with signs and symptoms of heart failure, shock or embolism. There are no guidelines available on managing BVT in patients with concurrent intracerebral haemorrhage, highlighting the importance of multidisciplinary efforts and patient inclusivity in decision making.
Eye Placement Bias Is Remarkably Robust
Authors: Smith Kirsten , Kempe Vera , Wood Lara
Published: May 2021

When drawing faces, people show a systematic bias of placing the eyes higher up the head than they are placed in reality. This study investigated the development of this phenomenon while removing the potential confound of drawing ability. Participants ( N = 124) in three age groups (3–5 yo, 10–11 yo, and adults) reconstructed two foam faces: one from observation and one from memory. The high eye placement bias was remarkably robust with mean eye placement in every condition significantly higher than the original faces. The same bias was not shown for mouth placement. Eye placement was highest for the youngest participants and for the memory conditions. The results suggest that an eye placement bias is not caused by the motor skill demands required for drawing and lend evidence to the suggestion that an eye placement bias is caused by perceptual and decision-making processes.
Promoting the Musical Engagement of Autistic Children in the Early Years Through a Program of Parental Support: An Ecological Research Study
Authors: Lisboa Tania , Shaughnessy Caitlin , Voyajolu Angela , Ockelford Adam
Published: May 2021

Some autistic children display an intuitive capacity to reproduce and restyle the musical stimuli that they encounter in their environments. Music also offers a safe space for the development of social competencies and, across the spectrum, musical interventions are regarded as an effective way of promoting engagement with others. Yet, there is a lack of empirically researched music programs for parents and carers of children with autism. In this study, 11 families with autistic children incorporated music making into everyday life, supported by researcher-practitioners and framed by resources outlining musical activities based on the Sounds of Intent in the Early Years framework. Assessment of video data and interviews revealed that the new resources were flexible enough to be adapted to each child and they helped parents to build confidence to engage with their children musically. It was found that children had an increased interest and engagement in music as well as in joint play, which impacted positively on their musical and social development. The interpersonal music spaces created by the parents provided opportunities for unlocking expressiveness and interactive behavior, which in turn supported verbal development, emotional regulation and social interaction. These findings have implications for arts-in-health research and highlight the potentially crucial role of parents as mentors for their child’s musical development. The study further demonstrates that specialist musical training is not a requirement to develop parent–child engagement in music making at home.
Music, Selves and Societies: Respondent Paper
Authors: Robertson Craig
Published: May 2021

Researchers working within the field of music and society often comment that they wish to use their research for the betterment of society and individuals, wherever possible. In many cases, this process of betterment requires some sort of behavioral change—whether this is changing poor habits to promote healthy living and thinking or changing destructive behavior in order to lead more productive and connected lives. It can increasingly be seen in the world today that social behavior has a complex array of influences and motivations and rarely is empirical evidence one of them. No amount of thoroughly researched evidence or logically developed arguments influences this behavior. Brexit and the Trump administration are two examples of this phenomenon. What seems to influence this seemingly bizarre social behavior is a collective belief in a narrative. The narrative needs to speak to common emotions, senses of identities and memories, but it does not need to necessarily be supported by empirical evidence to be effective. There is a need to understand this power of narrative in the public discourse if we are to truly influence how public policy engages with music.
Swallowing Problems among Community-Dwelling Elderly in Northeastern Thailand
Authors: Chaleekrua Sarintip , Janpol Kanya , Wattanapan Pattra
Published: May 2021

Introduction/objectives

Aging brings deterioration in many organs involving in swallowing, such as, oropharyngeal muscle weakness, decreased salivation, multiple teeth loss, decreased oral sensation, and delayed swallowing response. There are no official statistics and systematic records of swallowing problems in Thailand’s healthy elder populations. Therefore, this study aimed to determine the prevalence of swallowing problems among a Thai healthy elder population.

Methods

A survey of 874 elders was conducted at Community Hospitals in region 7 of the Thai National Health Security Office from September to November 2019. All participants were interviewed using a questionnaire focused on, screening for swallowing problems using a 10-item Eating Assessment Tool (EAT-10) and questions about participants’ physical and oral health behaviors.

Results

Sixty-six percent of the participants were women and 34% were males, with mean age 69.70 ± 6.79 years. Of these, 11.4% had swallowing problems. The most common swallowing problems were food sticking in the throat, effort on swallowing and choking. Age and having an underlying disease were found to be statistically significantly associated with dysphagia, whereas gender was not associated with dysphagia.

Conclusions

The prevalence of swallowing problems among Thai healthy community-dwelling elders was assessed as about 11%. Early identification and early intervention for swallowing problem is necessary for promoting health and quality of life of our growing elderly population.
Health Consciousness, Food Safety Concern, and Consumer Purchase Intentions Toward Organic Food: The Role of Consumer Involvement and Ecological Motives
Authors: Iqbal Jawad , Yu Donglei , Zubair Maria , Rasheed Muhammad Imran , Khizar Hafiz Muhammad Usman , Imran Muhammad
Published: May 2021

The organic food market is speedily growing in the current era; organizations in this industry, therefore, need to understand consumer motivations, perceptions, attitudes, and behavioral intentions of purchasing organic food. Based on a survey of 268 respondents, we investigated the relationships between individuals’ food safety concerns and health consciousness with their purchase intentions of organic food. The findings of our study reveal that individuals’ health consciousness and food safety concerns are positively related to their intentions of purchasing organic food products through consumer involvement. In addition, consumers’ ecological motive has been found as a boundary condition on the direct and indirect relationships described above such that the associations are stronger at the higher levels of ecological motive.
Identifying the Strategic Priorities of the Technical Factors for the Sustainable Low Carbon Industry Based on Macroeconomic Conditions
Authors: Shang Haiyang , Su Fang , Yüksel Serhat , Dinçer Hasan
Published: May 2021

This study aims to find out the strategic priorities of the technical factors to have sustainable low carbon industry. For this purpose, a hybrid multi-criteria decision-making (MCDM) is proposed that contains three different stages. First, the economic criteria required for sustainable development and the technical needs of the low carbon industry are defined by making a comprehensive literature review. After that, economic criteria are weighted by using the fuzzy decision-making trial and evaluation laboratory (DEMATEL) methodology. Finally, technical factors are ranked with the help of the fuzzy technique for order preference by similarity to ideal solution (TOPSIS) approach. Moreover, another analysis is also performed by considering fuzzy Vise Kriterijumska Optimizacija I Kompromisno Resenje (VIKOR) to evaluate the consistency of the analysis results. The main motivation of this study is to define the primary technical factors to minimize carbon emission problem by proposing a hybrid MCDM model. The findings indicate that research and development for renewable sources has the greatest importance for low-carbon industry. In addition, the analysis results of fuzzy TOPSIS and fuzzy VIKOR are quite similar. This situation demonstrates the consistency and coherency of the ranking results. Hence, it is recommended that countries should mainly give importance to the research and development investments so that the costs of renewable energy problems can be minimized. This situation can attract the attentions of the companies to invest in these projects. In this way, it will be possible to use a cleaner energy in industrial production.
Acupuncture Intervention Protocol: Consensus Process for a Pragmatic Randomized Controlled Trial of Acupuncture for Management of Chronic Low Back Pain in Older Adults: An NIH HEAL Initiative Funded Project
Authors: Nielsen Arya , Ocker Laura , Majd Iman , Draisin Jeff A , Taromina Katherine , Maggenti Marjorie T , Long Jaimie , Nolting Mark , Sherman Karen J
Published: May 2021

Objective

The aim of this article is to describe the consensus process used to develop an acupuncture intervention protocol for an NIH-funded pragmatic randomized controlled trial (PRCT) of acupuncture for the management of chronic low back (cLBP) in older adults (BackInAction).

Background

CLBP is among leading causes of disability worldwide: almost 33% of US adults 65 and older experience LBP. Acupuncture is effective for cLBP but there is no specific data on older adults. The National Institutes for Health (NIH) funded a PRCT of acupuncture needling for this population. An essential trial milestone was development of a consensus intervention protocol.

Methods

An Acupuncture Advisory Panel (AAP) was formed with nine members: two physician-acupuncturists, six licensed acupuncturists representing diverse work backgrounds, and an acupuncture researcher. We used a modified Delphi process that included provision of acupuncture trial data, survey data describing how each expert treats cLBP, three conference calls, and between-call email discussion.

Results

Lively and professional discussions led to a consensus intervention protocol for the BackInAction trial that included steps/staging of care, recommendations for parameters of care session length, number of needle insertion sites, insertion depths, needle retention times, recommended types of needles, both local and distal areas of the body to be treated, acupuncture point options, auricular point options, self-care options, and minimum number of sessions considered ideal.

Conclusion

Using a modified Delphi process, an expert AAP created a consensus intervention protocol for the PRCT of acupuncture needling for cLBP in patients 65 and older.
Aeromonas hydrophilia-infected nonunion of a closed tibial fracture in a healthy adolescent: A case report
Authors: Hsu Wei-Kuo , Chou Yi-Chuan , Chuang Chang-Han , Li Chia-Lung , Wu Po-Ting
Published: May 2021

Aeromonas hydrophilia can cause soft tissue infection in both immunocompromised and healthy persons. A healthy 15-year-old adolescent fell into a ditch after a scooter accident and sustained a right distal tibial shaft closed fracture, a right femoral shaft closed fracture, and a dirty laceration over the medial aspect of the distal thigh above the right knee. After empiric antibiotics and radical debridement of the contaminated wound, a femoral interlocking nail and tibial external fixator were applied. However, acute osteomyelitis later presented in his femur and tibia, and Aeromonas hydrophilia grew in cultures from the knee wound and the fracture sites. During the follow-up, his tibia became an infected nonunion, and was successfully treated with the induced membrane technique. In an otherwise healthy patient with a closed fracture, Aeromonas hydrophilia can cause acute osteomyelitis and necrotizing fasciitis by spreading from a nearby contaminated wound. Exposure to water is a risk factor for Aeromonas hydrophilia infection.
Navigating the Crises of COVID-19: Human Resource Professionals Battle Against the Pandemic
Authors: Adikaram Arosha S. , Priyankara H. P. R. , Naotunna N. P. G. S. I.
Published: May 2021

This article aims to examine the experiences of human resource professionals (HRPs) in managing crises posed by the COVID-19 pandemic. Employing qualitative research methodology, in-depth interviews with 24 HRPs of different industries were carried out. The findings indicate how the HRPs have navigated through five phases of the crisis as (a) anticipatory; (b) crisis; (c) adjustment; (d) rebounding; (e) continuance or reverting to old ways, struggling with many decisions and actions. The periods that companies took to navigate these different stages and the success of how they faced the crises posed by the pandemic mainly depend on factors such as the level of preparedness, nature of the industry, availability of resources, and role of the HRPs. The learning from the experiences of the HRPs and the phases they have navigated through will help to successfully manage similar crises in the future.
Distinct Coagulopathy With Myocardial Injury and Pulmonary Embolism in COVID-19
Authors: Fath Ayman R. , Aglan Amro , Varkoly Kyle S. , Eldaly Abdullah S. , Beladi Roxana N. , Forlemu Arnold , Mihyawi Nawfal , Solsi Anup , Israr Sharjeel , Lucas Alexandra R.
Published: May 2021

In this article, we report a case of a 61-year-old male who was diagnosed with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), presenting with acute respiratory distress syndrome requiring intubation and hemodynamic support, marked D-Dimer and troponin I elevation, worsening ST-elevation myocardial infarction on repeat electrocardiograms, and a negative coronary angiogram ruling out a coronary artery thrombosis or occlusion. With worsening diffuse ST-segment elevation on electrocardiograms and reduced ejection fraction on echocardiography in the setting of systemic inflammation, fulminant myocarditis was highly suspected. Despite optimal medical treatment, the patient’s condition deteriorated and was complicated by cardiac arrest that failed resuscitation. Although myocarditis was initially suspected, the autopsy revealed no evidence of myocarditis or pericarditis but did demonstrate multiple microscopic sites of myocardial ischemia together with thrombi in the left atrium and pulmonary vasculature. Additionally, scattered microscopic cardiomyocyte necrosis with pathological diagnosis of small vessel micro-thrombotic occlusions. These findings are potentially exacerbated by inflammation-induced coagulopathy, hypoxia, hypotension, and stress, that is, a multifactorial etiology. Further research and an improved understanding are needed to define the precise pathophysiology of the coagulopathic state causing widespread micro-thrombosis with subsequent myocardial and pulmonary injury.
Tolerable Suboptimization: Racial Consequences of Defunding Public Universities
Authors: Hamilton Laura T. , Nielsen Kelly , Lerma Veronica
Published: May 2021

We argue that the public defunding of public higher education and turn to private revenue streams—for example, non-resident tuition, grants, philanthropy, and corporate sponsorship—generates organizational racial resource disparities. We draw on a year-long qualitative case study of a University of California campus with a majority Latinx and low-income student body, including ethnographic observations and interviews with administrators, staff, and students, to argue that these disparities may impede majority-marginalized universities’ abilities to serve their student body. Our data demonstrate how limited organizational resources impact the provision of academic advising, mental health, and cultural programming for racially marginalized students. We articulate a racial neoliberal cycle of resource allocation: Colorblind constructs of “merit” lead to racial segregation and generate racialized organizational hierarchies that result in unequal organizational access to private resources. University leadership at resourced-starved majoritymarginalized universities may respond to fiscal constraints by accepting and normalizing suboptimal support for students—what we refer to as “tolerable suboptimization.” Tolerable suboptimization may also be unevenly applied within universities, such that supports accessed or needed by marginalized students are the most impacted. As a consequence, institutional racism can take on the appearance of financial necessity.
Test Score Gaps in Higher Order Thinking Skills: Exploring Instructional Practices to Improve the Skills and Narrow the Gaps
Authors: Mitani Hajime
Published: May 2021

Today’s economy demands higher order thinking skills (HOTS), and the public education system has a critical role in supporting students’ acquisition of HOTS. Yet, numerous studies documented inequity in access to higher quality instruction that promotes HOTS, which could result in wide test score gaps in HOTS. In this study, I examined test score gaps in HOTS and explored instructional practices associated with HOTS, particularly among low-performing students, using large-scale international assessment data from the 2015 Trends in Mathematics and Science Study. I found wide test score gaps in HOTS in mathematics between the lowest and highest socioeconomic status students and between White students and students of color. Instructional practices such as the same ability group work, asking students to work on problems with teacher guidance, and working on problems with no immediately obvious method of solution were found positively associated with the test scores.
(Re)contextualizing the Trauma to Prevent or Treat PTSD-Related Hypermnesia
Authors: Desmedt Aline
Published: May 2021

A cardinal feature of Post-traumatic stress-related disorder (PTSD) is a paradoxical memory alteration including both intrusive emotional hypermnesia and declarative/contextual amnesia. Most preclinical, but also numerous clinical, studies focus almost exclusively on the emotional hypermnesia aiming at suppressing this recurrent and highly debilitating symptom either by reducing fear and anxiety or with the ethically questionable idea of a rather radical erasure of traumatic memory. Of very mixed efficacy, often associated with a resurgence of symptoms after a while, these approaches focus on PTSD-related symptom while neglecting the potential cause of this symptom: traumatic amnesia. Two of our preclinical studies have recently demonstrated that treating contextual amnesia durably prevents, and even treats, PTSD-related hypermnesia. Specifically, promoting the contextual memory of the trauma, either by a cognitivo-behavioral, optogenetic or pharmacological approach enhancing a hippocampus-dependent memory processing of the trauma normalizes the fear memory by inducing a long-lasting suppression of the erratic traumatic hypermnesia.
Investigation of deformation behavior of PETG-FDM-printed metamaterials with pantographic substructures based on different slicing strategies
Authors: Özen Arda , Ganzosch Gregor , Barchiesi Emilio , Auhl Dietmar W , Müller Wolfgang H
Published: May 2021

Based on the progress and advances of additive manufacturing technologies, design and production of complex structures became cheaper and therefore rather possible in the recent past. A promising example of such complex structure is a so-called pantographic structure, which can be described as a metamaterial consisting of repeated substructure. In this substructure, two planes, which consist of two arrays of beams being orthogonally aligned to each other, are interconnected by cylinders/pivots. Different inner geometries were taken into account and additively manufactured by means of fused deposition modeling technique using polyethylene terephthalate glycol (PETG) as filament material. To further understand the effect of different manufacturing parameters on the mechanical deformation behavior, three types of specimens have been investigated by means of displacement-controlled extension tests. Different slicing approaches were implemented to eliminate process-related problems. Small and large deformations are investigated separately. Furthermore, 2D digital image correlation was used to calculate strains on the outer surface of the metamaterial. Two finite-element simulations based on linear elastic isotropic model and linear elastic transverse isotropic model have been carried out for small deformations. Standardized extension tests have been performed on 3D-printed PETG according to ISO 527-2. Results obtained from finite-element method have been validated by experimental results of small deformations. These results are in good agreement with linear elastic transverse isotropic model (up to about [Formula: see text] of axial elongation), though the response of large deformations indicates a nonlinear inelastic material behavior. Nevertheless, all samples are able to withstand outer loading conditions after the first rupture, resulting in resilience against ultimate failure.
A procedure for matching the near-fault ground motions based on spectral accelerations and instantaneous power
Authors: Zengin Esra , Abrahamson Norman A
Published: May 2021

Selection of ground motions for use in nonlinear dynamic analysis is one of the most critical steps for both code-based design and probabilistic seismic risk assessment of structures. In practice, time-domain spectrum-matching methods, which add wavelet functions to an initial acceleration time series, have been widely used to obtain a record whose response spectrum closely matches the desired target spectrum. Although the spectral shape is known to be a good predictor of structural response, it does not represent the critical aspects of the velocity pulses, such as pulse amplitude and pulse period for near-fault ground motions. The Instantaneous Power ( IP( T1)), defined as the maximum rate of change of energy of the bandpass-filtered velocity time series over a short time interval given by half of the structural period, has been shown to be an effective alternative parameter to capture effects of the presence of a velocity pulse and the pulse period in near-fault record selection. We introduce an approach to modify time series so as to simultaneously match a target response spectrum and IP spectrum over a specified period interval. We demonstrate that the records modified using the proposed approach produce results comparable to those obtained using unscaled records, and prevent potential bias in structural response, relative to results when matching is performed without consideration of IP.
Patient-reported outcomes and patient-reported outcome measures in interstitial lung disease: where to go from here?
Authors: Kalluri Meena , Luppi Fabrizio , Vancheri Ada , Vancheri Carlo , Balestro Elisabetta , Varone Francesco , Mogulkoc Nesrin , Cacopardo Giulia , Bargagli Elena , Renzoni Elisabetta , Torrisi Sebastiano , Calvello Mariarosaria , Libra Alessandro , Pavone Mauro , Bonella Francesco , Cottin Vincent , Valenzuela Claudia , Wijsenbeek Marlies , Bendstrup Elisabeth
Published: May 2021

Patient-reported outcome measures (PROMs), tools to assess patient self-report of health status, are now increasingly used in research, care and policymaking. While there are two well-developed disease-specific PROMs for interstitial lung diseases (ILD) and idiopathic pulmonary fibrosis (IPF), many unmet and urgent needs remain. In December 2019, 64 international ILD experts convened in Erice, Italy to deliberate on many topics, including PROMs in ILD. This review summarises the history of PROMs in ILD, shortcomings of the existing tools, challenges of development, validation and implementation of their use in clinical trials, and the discussion held during the meeting. Development of disease-specific PROMs for ILD including IPF with robust methodology and validation in concordance with guidance from regulatory authorities have increased user confidence in PROMs. Minimal clinically important difference for bidirectional changes may need to be developed. Cross-cultural validation and linguistic adaptations are necessary in addition to robust psychometric properties for effective PROM use in multinational clinical trials. PROM burden of use should be reduced through appropriate use of digital technologies and computerised adaptive testing. Active patient engagement in all stages from development, testing, choosing and implementation of PROMs can help improve probability of success and further growth.
Performance of alternative COPD case-finding tools: a systematic review and meta-analysis
Authors: Schnieders Elena , Ünal Elyesa , Winkler Volker , Dambach Peter , Louis Valérie R. , Horstick Olaf , Neuhann Florian , Deckert Andreas
Published: May 2021

Rationale

Guidelines recommend pre-/post-bronchodilator spirometry for diagnosing COPD, but resource constraints limit the availability of spirometry in primary care in low- and middle-income countries. Although spirometry is the diagnostic gold standard, we shall assess alternative tools for settings without spirometry.

Methods

A systematic literature review and meta-analysis was conducted, utilising Cochrane, CINAHL, Google Scholar, PubMed and Web of Science (search cut-off was May 01, 2020). Published studies comparing the accuracy of diagnostic tools for COPD with post-bronchodilator spirometry were considered. Studies without sensitivity/specificity data, without a separate validation sample and outside of primary care were excluded. Sensitivity, specificity and area under the curve (AUC) were assessed.

Results

Of 7578 studies, 24 were included (14 635 participants). Hand devices yielded a larger AUC than questionnaires. The meta-analysis included 17 studies and the overall AUC of micro-spirometers (0.84, 95% CI 0.80–0.89) was larger when compared to the COPD population screener (COPD-PS) questionnaire (0.77, 95% CI 0.63–0.85) and the COPD diagnostic questionnaire (CDQ) (0.72, 95% CI 0.64–0.78). However, only the difference between micro-spirometers and the CDQ was significant.

Conclusions

The CDQ and the COPD-PS questionnaire were approximately equally accurate tools. Questionnaires ensured testing of symptomatic patients, but micro-spirometers were more accurate. A combination could increase accuracy but was not evaluated in the meta-analysis.
Fully integrating pathophysiological insights in COPD: an updated working disease model to broaden therapeutic vision
Authors: Walters E. Haydn , Shukla Shakti D. , Mahmood Malik Q. , Ward Chris
Published: May 2021

Our starting point is that relatively new findings into the pathogenesis and pathophysiology of airway disease in smokers that lead to chronic obstructive pulmonary disease (COPD) need to be reassessed as a whole and integrated into “mainstream” thinking along with traditional concepts which have stood the test of time. Such a refining of the accepted disease paradigm is urgently needed as thinking on therapeutic targets is currently under active reconsideration. We feel that generalised airway wall “inflammation” is unduly over-emphasised, and highlight the patchy and variable nature of the pathology (with the core being airway remodelling). In addition, we present evidence for airway wall disease in smokers/COPD as including a hypocellular, hypovascular, destructive, fibrotic pathology, with a likely spectrum of epithelial–mesenchymal transition states as significant drivers of this remodelling. Furthermore, we present data from a number of research modalities and integrate this with the aetiology of lung cancer, the role of chronic airway luminal colonisation/infection by a specific group of “respiratory” bacteria in smokers (which results in luminal inflammation) and the central role for oxidative stress on the epithelium. We suggest translation of these insights into more focus on asymptomatic smokers and early COPD, with the potential for fresh preventive and therapeutic approaches.
A workflow to identify novel proteins based on the direct mapping of peptide-spectrum-matches to genomic locations
Authors: Anders John , Petruschke Hannes , Jehmlich Nico , Haange Sven-Bastiaan , von Bergen Martin , Stadler Peter F
Published: May 2021

Background

Small Proteins have received increasing attention in recent years. They have in particular been implicated as signals contributing to the coordination of bacterial communities. In genome annotations they are often missing or hidden among large numbers of hypothetical proteins because genome annotation pipelines often exclude short open reading frames or over-predict hypothetical proteins based on simple models. The validation of novel proteins, and in particular of small proteins (sProteins), therefore requires additional evidence. Proteogenomics is considered the gold standard for this purpose. It extends beyond established annotations and includes all possible open reading frames (ORFs) as potential sources of peptides, thus allowing the discovery of novel, unannotated proteins. Typically this results in large numbers of putative novel small proteins fraught with large fractions of false-positive predictions.

Results

We observe that number and quality of the peptide-spectrum matches (PSMs) that map to a candidate ORF can be highly informative for the purpose of distinguishing proteins from spurious ORF annotations. We report here on a workflow that aggregates PSM quality information and local context into simple descriptors and reliably separates likely proteins from the large pool of false-positive, i.e., most likely untranslated ORFs. We investigated the artificial gut microbiome model SIHUMIx, comprising eight different species, for which we validate 5114 proteins that have previously been annotated only as hypothetical ORFs. In addition, we identified 37 non-annotated protein candidates for which we found evidence at the proteomic and transcriptomic level. Half (19) of these candidates have close functional homologs in other species. Another 12 candidates have homologs designated as hypothetical proteins in other species. The remaining six candidates are short (< 100 AA) and are most likely bona fide novel proteins.

Conclusions

The aggregation of PSM quality information for predicted ORFs provides a robust and efficient method to identify novel proteins in proteomics data. The workflow is in particular capable of identifying small proteins and frameshift variants. Since PSMs are explicitly mapped to genomic locations, it furthermore facilitates the integration of transcriptomics data and other sources of genome-level information.
Genetic interaction network has a very limited impact on the evolutionary trajectories in continuous culture-grown populations of yeast
Authors: Klim Joanna , Zielenkiewicz Urszula , Skoneczny Marek , Skoneczna Adrianna , Kurlandzka Anna , Kaczanowski Szymon
Published: May 2021

Background

The impact of genetic interaction networks on evolution is a fundamental issue. Previous studies have demonstrated that the topology of the network is determined by the properties of the cellular machinery. Functionally related genes frequently interact with one another, and they establish modules, e.g., modules of protein complexes and biochemical pathways. In this study, we experimentally tested the hypothesis that compensatory evolutionary modifications, such as mutations and transcriptional changes, occur frequently in genes from perturbed modules of interacting genes.

Results

Using Saccharomyces cerevisiae haploid deletion mutants as a model, we investigated two modules lacking COG7 or NUP133, which are evolutionarily conserved genes with many interactions. We performed laboratory evolution experiments with these strains in two genetic backgrounds (with or without additional deletion of MSH2), subjecting them to continuous culture in a non-limiting minimal medium. Next, the evolved yeast populations were characterized through whole-genome sequencing and transcriptome analyses. No obvious compensatory changes resulting from inactivation of genes already included in modules were identified. The supposedly compensatory inactivation of genes in the evolved strains was only rarely observed to be in accordance with the established fitness effect of the genetic interaction network. In fact, a substantial majority of the gene inactivations were predicted to be neutral in the experimental conditions used to determine the interaction network. Similarly, transcriptome changes during continuous culture mostly signified adaptation to growth conditions rather than compensation of the absence of the COG7, NUP133 or MSH2 genes. However, we noticed that for genes whose inactivation was deleterious an upregulation of transcription was more common than downregulation.

Conclusions

Our findings demonstrate that the genetic interactions and the modular structure of the network described by others have very limited effects on the evolutionary trajectory following gene deletion of module elements in our experimental conditions and has no significant impact on short-term compensatory evolution. However, we observed likely compensatory evolution in functionally related (albeit non-interacting) genes.
Genetic analysis of three maize husk traits by QTL mapping in a maize-teosinte population
Authors: Zhang Xiaolei , Lu Ming , Xia Aiai , Xu Tao , Cui Zhenhai , Zhang Ruiying , Liu Wenguo , He Yan
Published: May 2021

Background

The maize husk consists of numerous leafy layers and plays vital roles in protecting the ear from pathogen infection and dehydration. Teosinte, the wild ancestor of maize, has about three layers of small husk outer covering the ear. Although several quantitative trait loci (QTL) underlying husk morphology variation have been reported, the genetic basis of husk traits between teosinte and maize remains unclear.

Results

A linkage population including 191 BC2F8 inbred lines generated from the maize line Mo17 and the teosinte line X26–4 was used to identify QTL associated with three husk traits: i.e., husk length (HL), husk width (HW) and the number of husk layers (HN). The best linear unbiased predictor (BLUP) depicted wide phenotypic variation and high heritability of all three traits. The HL exhibited greater correlation with HW than HN. A total of 4 QTLs were identified including 1, 1, 2, which are associated with HL, HW and HN, respectively. The proportion of phenotypic variation explained by these QTLs was 9.6, 8.9 and 8.1% for HL, HN and HW, respectively.

Conclusions

The QTLs identified in this study will pave a path to explore candidate genes regulating husk growth and development, and benefit the molecular breeding program based on molecular marker-assisted selection to cultivate maize varieties with an ideal husk morphology.
Clinical indications of premenstrual disorders and subsequent risk of injury: a population-based cohort study in Sweden
Authors: Yang Qian , Sjölander Arvid , Li Yuchen , Viktorin Alexander , Bertone-Johnson Elizabeth R. , Ye Weimin , Fang Fang , Valdimarsdóttir Unnur A. , Lu Donghao
Published: May 2021

Background

Premenstrual disorders, including premenstrual syndrome and premenstrual dysphoric disorder, are suggested to be correlated with suicidal behavior and accidents in cross-sectional and retrospective studies. However, prospective data are still lacking.

Methods

We performed a population-based cohort study including 1,472,379 Swedish women of reproductive age who were followed from 2001 to 2012. Within the cohort, we also performed a sibling analysis where we compared the rates of injury between full sisters. By linking to the Patient and the Prescribed Drug Registers, we identified 18,628 women with any clinical indications for premenstrual disorders in the cohort (population analysis) and 7674 women in the sibling analysis. Any injury, primarily suicidal behavior (completed suicide and suicide attempt) or accidents (e.g., fall and transportation accidents), was identified through the Patient and Causes of Death Registers as the primary outcome. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) of these outcomes among women with premenstrual disorders in both population and sibling analyses using multivariable Cox proportional hazards regression.

Results

During a maximal follow-up of 12 years (mean 9.55 years), we identified 2390 women with premenstrual disorders with any injury; 216 through suicidal behavior and 2191 through accidents. Compared to women without premenstrual disorders, women with premenstrual disorders were at increased risk of any injury (HR 1.37, 95% CI 1.31–1.42), particularly suicidal behavior (HR 2.26, 95% CI 1.97–2.59) and accidents (HR 1.32, 95% CI 1.27–1.38). Such associations somewhat attenuated yet remained significant in the sibling analysis (HRs: 1.31 for any injury, 1.86 for suicidal behavior, and 1.29 for accidents). Additional adjustment for psychiatric comorbidities minimally altered the associations with any injury and accidents in both population and sibling analyses, whereas the association with suicidal behavior was considerably attenuated to non-significance in the sibling analysis. Such risks were particularly strong within 2 years after receiving the diagnosis of premenstrual disorders and were evident among women with premenstrual disorders with and without psychiatric comorbidities.

Conclusions

Our findings suggest that women with a clinical indication of premenstrual disorders are at increased subsequent risk of injury, particularly accidents within the first 2 years after diagnosis.
Effects of increasing intake of soybean oil on synthesis of testosterone in Leydig cells
Authors: Su Yu , Tian Zhenhua , Qi Xiangyu , Luo Dandan , Liu Luna , Liu Shuang , Zheng Dongmei , Wei Fang , He Zhao , Guan Qingbo
Published: May 2021

Background

Soybean oil is a very common edible oil in daily life. With the changes in the dietary composition, the intake of soybean oil increased. However, the effects of dietary intake of soybean oil on testosterone production are still unclear.

Methods

In order to study the effects of increasing intake of soybean oil on the synthesis of testosterone in Leydig cells, we fed male C57BL/6 mice on the diet which added 20% soybean salad oil (SOY group). We detected the hormone levels by enzyme-linked immunosorbent assay (ELISA) kits and serum fatty acid composition by gas chromatography, and analyzed the expression of steroidogenic enzymes by Real-Time PCR or immunoblotting analysis.

Results

After the 16-week feeding period, serum linoleic acid (LA) and α-linolenic acid (ALA) significantly increased and serum palmitic acid (PA) significantly decreased in SOY group mice. Compared to the normal diet (ND group), increasing intake of soybean oil raised the luteinizing hormone (LH) levels and up-regulated luteinizing hormone/chorionic gonadotropin receptor (LHCGR), steroidogenic acute regulatory protein (StAR) and cytochrome P450 family 11 subfamily A member I (CYP11A1). Testosterone levels in SOY group were higher than that in the ND group, and significantly difference showed.

Conclusions

Increasing intake of soybean oil could raise the serum LA and ALA levels and decrease serum PA levels. This could activate the LH/LHCGR pathway and improve the function of steroid synthesis in Leydig cells, and finally lead to the elevated testosterone levels.