bluuebunny/crossref_metadata_2025 huggingface dataset:
The joint role of HRM and leadership for teleworker well-being: An analysis during the COVID-19 pandemic
Authors: Günther Niklas , Hauff Sven , Gubernator Philip
Published: March 2022

The sudden and extensive implementation of teleworking in the beginning of the COVID-19 pandemic has threatened employees’ well-being. Based on the challenges that particularly threatened such well-being in the beginning of the pandemic, we identify sets of telework-specific HRM practices and leadership behaviors, and examine their joint relationships with teleworkers’ happiness well-being in terms of work engagement and job satisfaction. Thus, we also consider the mediating roles of social isolation (as an indicator of social well-being) and psychological strain (as an indicator of health well-being). We also expect that HRM and leadership should interact and reinforce each other. Our analyses are based on data from German teleworkers at two consecutive points in time. Our findings reveal differentiated and complementary effects of telework-oriented HRM and leadership. In particular, we identified the provision of health care to contribute most to telework-oriented HRM’s relationship with social isolation and happiness well-being. Telework-oriented leadership mainly affected teleworkers’ happiness well-being via strain by ensuring communication and information exchanges between teleworkers.
Key determinants of particulate matter 2.5 concentrations in urban environments with scenario analysis
Authors: Chun Bumseok , Choi Kwangyul , Pan Qisheng
Published: March 2022

Particulate matter (PM) 2.5 generates a variety of negative effects on health, such as heart and lung disease, asthma, and respiratory symptoms. The pollutants in the atmosphere primarily result from human activities, and, in urban settings, increases in traffic volume and higher building density can elevate the level of PM2.5. Building on previous research, this study primarily focuses on two highly developed urban areas in the Texas Triangle region: Travis County in the Austin Metropolitan Area and Harris County in the Greater Houston Area. It explores different types of urban features, such as urban structures, land use/land cover, traffic volume, and distance from roads, that affect the PM2.5 concentration in urban environments at the local scale. Throughout this study, we use various research methods, including geographically weighted regression, to estimate the PM2.5 concentrations at local scales, 3D city models to derive urban characteristics, and the random forest algorithm to predict the effects of urban features on PM2.5 concentrations. Our findings suggest that developed land use, tall buildings in dense areas, and major traffic networks are the key contributors to PM2.5. However, we also find that tree canopy cover can significantly reduce PM2.5 concentrations.
Kaleidoscope visualisation of China’s internal migration, 1985–2020
Authors: Gu Hengyu , Xu Zhibin
Published: March 2022

In migration networks, the origin-destination (OD) bilateral flows and each site’s in- and outflow volumes are like two sides of the same coin; though popular visualisation approaches such as the chord diagram excel in describing the former, the latter mostly remains less depicted aspect. By applying the Voronoi-based migration Kaleidoscope diagram and integrating it with the sunburst treemap, the article visualises China’s interprovincial migration from 1985 to 2020 with the latest data and focalises on the relative status of each migration body as origin or destination. By attributing different colours to China’s four economic-geographical regions and differentiating in- and outflows with deep and light shades, information about each province’s weight in the migration network is gained from their size in the diagrams, and variable as well as invariable patterns are observed from the trends. Possible social and economic causes in shaping the diagrams are discussed, and the potential for the migration Kaleidoscope pertaining to other migration data is examined.
Density of Health Workforce Correlates to Disease Outcomes: Evidence From Global Data in Otolaryngology
Authors: Stanford‐Moore Gaelen Britton , Cahill Gabrielle , Raj Ankit , Irakoze Pacifique , Alkire Blake , Bhutta Mahmood F.
Published: March 2022

Objective

To better understand the impact of the otolaryngology‐specific workforce on the burden of related diseases.

Study Design

Retrospective analysis of existing workforce density data as compared with the incidence, mortality, and morbidity data for 4 otolaryngologic diseases.

Setting

An overall 138 countries with known otolaryngology–head and neck surgery workforce and epidemiologic data.

Methods

We obtained raw data on workforce estimates of ear, nose, and throat surgical specialists from the World Health Organization. Disease burdens for 4 conditions were estimated via 2 ratios, the mortality:incidence ratio (MIR) and YLD:incidence ratio (years lost to disability), as specified in the Global Burden of Disease database. These were correlated to country‐specific otolaryngologist density data in univariate and multivariate analyses.

Results

Increased density of the ear, nose, and throat workforce correlated with better outcomes for otolaryngologic‐treated surgical diseases. A 10% increase in otolaryngology workforce density was associated with a 0.27% reduction in YLD:incidence ratio for chronic otitis media, a 0.94% reduction in MIR for lip and oral cavity cancer, a 1.46% reduction in MIR for laryngeal cancer, and a 1.34% reduction in MIR for pharyngeal cancer (all P <. 001)—an effect that remained after adjustment for health systems factors for all conditions but chronic otitis media.

Conclusion

The density of the surgical workforce is assumed to affect disease outcomes, but ours is the first analysis to show that increased workforce density for a specific surgical specialty correlates with improved disease outcomes. While there is a consensus to increase access to health care providers, quantifying the effect on disease outcomes is an important metric for those performing health economics modeling, particularly where resources are limited.
Navigating together without a map: Metaphors for making Geography’s future
Authors: Castree Noel
Published: March 2022

This article sets the scene for the 10 papers comprising the special issue ‘‘Geographical research for the 21st century: trajectories and possibilities’. It asks the hoary question, ‘by what means, and to what ends, should Geography be directed?’. It does not, however, venture a substantive response because there is no single answer that will suffice. Instead, the article offers resources for those seeking to respond to this question. It identifies 12 parameters that define the ‘operating space’ that most geographers worldwide now have to act within, like it or not. These parameters not only impose constraints but also offer opportunities. The article then focuses on metaphors that might help us better understand who we are as a research and teaching community: after all, metaphors can distil the essence of our ongoing preoccupations. I venture a ‘new ecological’ metaphor that might enable accuracy and hope in our self-understanding as we enter the third decade of an already extraordinary century. It may seem paradoxical to say, but we can navigate forward purposefully without a map, avoiding the polar opposites of an infeasible disciplinary unity and an undesirable Balkanisation of our activities.
How might values in mathematics learning affect the development of beliefs: An exploratory study with Chinese elementary students
Authors: Seah Wee Tiong , Pan Yichen , Zhong Juan
Published: March 2022

258 Grade 3 students in a suburban primary school located in Chengdu, China responded to an open-ended questionnaire item regarding their beliefs about mathematics. The traditional beliefs attracted the most number of students, followed by integral, feeling good, and constructivist beliefs. Since the questionnaire also identified the students’ values in relation to positive mathematical wellbeing, it was additionally found that students who valued engagement highly were more likely to hold constructivist beliefs and less likely to hold traditional beliefs, compared to peers who did not value engagement as highly. Also, students who valued perseverance highly were more likely to hold integral beliefs.
A framework for operationalizing the assessment of post-earthquake functional recovery of buildings
Authors: Cook Dustin T , Liel Abbie B , Haselton Curt B , Koliou Maria
Published: March 2022

Building damage after an earthquake, or other hazard event, can interrupt businesses, displace households, and significantly disrupt a community for years. As a result, policymakers and engineers are working toward new design guidelines and policies that reduce the vulnerability of the built environment through improved building functional recovery performance. This study proposes a method for assessing post-earthquake building performance states of function and reoccupancy within the architecture of performance-based earthquake engineering, targeted at US construction, making use of Federal Emergency Management Agency (FEMA) P-58 fragility and consequence models. This is accomplished by mapping component damage states to systems-level operational performance, and then to building-level performance states, through a series of fault trees. The study also proposes a repair scheduling algorithm to estimate the time taken to restore building reoccupancy or function, considering impeding factors that delay the start of repairs. The result is a probabilistic approach that extends the performance-based engineering framework to explicitly quantify post-earthquake building function performance states, thus facilitating design and mitigation decisions for recovery-based performance objectives.
Single cell lineage reconstruction using distance-based algorithms and the R package, DCLEAR
Authors: Gong Wuming , Kim Hyunwoo J. , Garry Daniel J. , Kwak Il-Youp
Published: March 2022

Background

DCLEAR is an R package used for single cell lineage reconstruction. The advances of CRISPR-based gene editing technologies have enabled the prediction of cell lineage trees based on observed edited barcodes from each cell. However, the performance of existing reconstruction methods of cell lineage trees was not accessed until recently. In response to this problem, the Allen Institute hosted the Cell Lineage Reconstruction Dream Challenge in 2020 to crowdsource relevant knowledge from across the world. Our team won sub-challenges 2 and 3 in the challenge competition.

Results

The DCLEAR package contained the R codes, which was submitted in response to sub-challenges 2 and 3. Our method consists of two steps: (1) distance matrix estimation and (2) the tree reconstruction from the distance matrix. We proposed two novel methods for distance matrix estimation as outlined in the DCLEAR package. Using our method, we find that two of the more sophisticated distance methods display a substantially improved level of performance compared to the traditional Hamming distance method. DCLEAR is open source and freely available from R CRAN and from under the GNU General Public License, version 3.

Conclusions

DCLEAR is a powerful resource for single cell lineage reconstruction.
Determining the applicability of the RSNA radiology lexicon (RadLex) in high-grade glioma MRI reporting—a preliminary study on 20 consecutive cases with newly diagnosed glioblastoma
Authors: Huckhagel Torge , Stadelmann Christine , Abboud Tammam , Riedel Christian
Published: March 2022

Background

The implementation of a collective terminology in radiological reporting such as the RSNA radiological lexicon (RadLex) yields many benefits including unambiguous communication of findings, improved education, and fostering data mining for research purposes. While some fields in general radiology have already been evaluated so far, this is the first exploratory approach to assess the applicability of the RadLex terminology to glioblastoma (GBM) MRI reporting.

Methods

Preoperative brain MRI reports of 20 consecutive patients with newly diagnosed GBM (mean age 68.4 ± 10.8 years; 12 males) between January and October 2010 were retrospectively identified. All terms related to the tumor as well as their frequencies of mention were extracted from the MRI reports by two independent neuroradiologists. Every item was subsequently analyzed with respect to an equivalent RadLex representation and classified into one of four groups as follows: 1. verbatim RadLex entity, 2. synonymous/multiple equivalent(s), 3. combination of RadLex concepts, or 4. no RadLex equivalent. Additionally, verbatim entities were categorized using the hierarchical RadLex Tree Browser.

Results

A total of 160 radiological terms were gathered. 123/160 (76.9%) items showed literal RadLex equivalents, 9/160 (5.6%) items had synonymous (non-verbatim) or multiple counterparts, 21/160 (13.1%) items were represented by means of a combination of concepts, and 7/160 (4.4%) entities could not eventually be transferred adequately into the RadLex ontology.

Conclusions

Our results suggest a sufficient term coverage of the RadLex terminology for GBM MRI reporting. If applied extensively, it may improve communication of radiological findings and facilitate data mining for large-scale research purposes.
Determining factors of functioning in hemodialysis patients using the international classification of functioning, disability and health
Authors: Santos Luciana M. M. , Figueiredo Pedro Henrique S. , Silva Ana C. R. , Campos Patrícia C. , Gonçalves Gabriele T. , de Paula C Freitas Jaqueline , da Silva Junior Fidelis Antônio , Santos Jousielle Márcia , Alves Frederico L. , Rodrigues Vanessa G. B. , Maciel Emílio Henrique B. , Prates Maria Cecília S. M. , Sañudo Borja , Taiar Redha , Bernardo-Filho Mario , Lima Vanessa P. , Costa Henrique S. , Mendonça Vanessa A. , Lacerda Ana Cristina R.
Published: March 2022

Background

Hemodialysis (HD) treatment affects functioning, physical activity level, clinical biomarkers, and body composition. However, the association between these variables with functioning, considering International Classification of Functioning, Disability and Health (ICF) domains remains unclear. Thus, the aim of this study was to investigate the possible association between physical activity, biomarkers, and body composition with functioning in HD patients in reference to the ICF.

Methods

Eighty HD patients performed different tests grouped according to ICF domain: Body structure and function – handgrip strength (HS), 5-repetition sit-to-stand test, and 60-s sit-to-stand test (5-STS, 60-STS, respectively); Activity – short physical performance battery (SPPB); and Participation – participation scale questionnaire. Physical activity [Human Activity Profile questionnaire (HAP)], body composition (Dual-energy X-ray absorptiometry), Parathormone (PTH), and alkaline phosphatase were analyzed as possible variables associated with ICF domains. Data analyses were performed using simple and multiple regression models adjusted for age, duration of HD, and diuresis volume.

Results

In the body structure and function domain, appendicular lean mass, PTH level, and age were associated with HS (R2 = 0.558); HAP and PTH were associated with 5-STS (R2 = 0.263); and HAP, PTH, duration of HD, and age were associated with 60-STS (R2 = 0.337). In the activity domain, HAP, PTH, alkaline phosphatase, duration of HD, age, and body fat were associated with SPPB (R2 = 0.689). Finally, only HAP was associated with the participation scale (R2 = 0.067).

Conclusion

Physical activity and PTH levels are determinant protagonists of functioning in all ICF domains in hemodialysis patients.
An integrated modelling methodology for estimating global incidence and prevalence of hereditary spastic paraplegia subtypes SPG4, SPG7, SPG11, and SPG15
Authors: Vander Stichele Geert , Durr Alexandra , Yoon Grace , Schüle Rebecca , Blackstone Craig , Esposito Giovanni , Buffel Connor , Oliveira Inês , Freitag Christian , van Rooijen Stephane , Hoffmann Stéphanie , Thielemans Leen , Cowling Belinda S.
Published: March 2022

Background

Hereditary spastic paraplegias (HSPs) are progressively debilitating neurodegenerative disorders that follow heterogenous patterns of Mendelian inheritance. Available epidemiological evidence provides limited incidence and prevalence data, especially at the genetic subtype level, preventing a realistic estimation of the true social burden of the disease. The objectives of this study were to (1) review the literature on epidemiology of HSPs; and (2) develop an epidemiological model of the prevalence of HSP, focusing on four common HSP genetic subtypes at the country and region-level.

Methods

A model was constructed estimating the incidence at birth, survival, and prevalence of four genetic subtypes of HSP based on the most appropriate published literature. The key model parameters were assessed by HSP clinical experts, who provided feedback on the validity of assumptions. A model was then finalized and validated through comparison of outputs against available evidence. The global, regional, and national prevalence and patient pool were calculated per geographic region and per genetic subtype.

Results

The HSP global prevalence was estimated to be 3.6 per 100,000 for all HSP forms, whilst the estimated global prevalence per genetic subtype was 0.90 (SPG4), 0.22 (SPG7), 0.34 (SPG11), and 0.13 (SPG15), respectively. This equates to an estimated 3365 (SPG4) and 872 (SPG11) symptomatic patients, respectively, in the USA.

Conclusions

This is the first epidemiological model of HSP prevalence at the genetic subtype-level reported at multiple geographic levels. This study offers additional data to better capture the burden of illness due to mutations in common genes causing HSP, that can inform public health policy and healthcare service planning, especially in regions with higher estimated prevalence of HSP.
Neuroimaging appearance of hypothalamic hamartomas in monozygotic twins with Pallister-Hall syndrome: case report and review of the literature
Authors: Consales Alessandra , Ardemani Giulia , Cinnante Claudia Maria , Catalano Mariana Rita , Giavoli Claudia , Villa Roberta , Iascone Maria , Fontana Camilla , Bedeschi Maria Francesca , Fumagalli Monica
Published: March 2022

Background

Pallister-Hall syndrome (OMIM #146510) is a rare autosomal dominant condition caused by a mutation in the GLI3 gene. The cardinal feature of Pallister-Hall syndrome is the presence of hypothalamic hamartomas, which may manifest with seizures, panhypopituitarism and visual impairment. In Pallister-Hall syndrome, dysplastic histogenetic processes responsible for hypothalamic hamartomas are thought to disrupt early craniofacial development. The clinical presentation of Pallister-Hall syndrome may include: characteristic facies (low-set and posteriorly angulated ears, short nose with flat nasal bridge), cleft palate and uvula, bifid epiglottis and laryngotracheal cleft, limb anomalies (e.g., polysyndactyly, short limbs and nail dysplasia), anal atresia, genitourinary abnormalities and congenital heart defects.

Case presentation

We report the case of two monochorionic diamniotic twins diagnosed with Pallister-Hall syndrome during the neonatal period, after the identification of a hypothalamic hamartoma on day 1 by cerebral ultrasound scan, later confirmed by brain magnetic resonance imaging. Cerebral ultrasound and magnetic resonance imaging presentations were identical in both twins.

Discussion and conclusions

We review previously published cases (four reports) of hypothalamic hamartomas identified via cerebral ultrasound and compare reported ultrasonographic features. Main differential diagnoses based on cerebral ultrasound findings are discussed. Full description of typical magnetic resonance imaging appearance is also provided. This is the first case reported in the literature of monochorionic diamniotic twins affected by genetically confirmed Pallister-Hall syndrome with identical hypothalamic hamartomas at cerebral ultrasound and magnetic resonance imaging. Moreover, this paper adds to the existing literature on the sonographic appearance of hypothalamic hamartomas. Considering the consistency in hypothalamic hamartomas’ sonographic appearance, we support the use of cerebral ultrasound as a first-line neuroimaging modality in case of clinical suspicion of Pallister-Hall syndrome.

Graphical Abstract
Clinic and genetic similarity assessments of atypical carcinoid, neuroendocrine neoplasm with atypical carcinoid morphology and elevated mitotic count and large cell neuroendocrine carcinoma
Authors: Zhang Ying , Wang Weiya , Hu Qianrong , Liang Zuoyu , Zhou Ping , Tang Yuan , Jiang Lili
Published: March 2022

Background

Pulmonary neuroendocrine neoplasms can be divided into typical carcinoid, atypical carcinoid, large cell neuroendocrine carcinoma, and small cell (lung) carcinoma. According to the World Health Organization, these four neoplasms have different characteristics and morphological traits, mitotic counts, and necrotic status. Importantly, “a grey-zone” neoplasm with an atypical carcinoid-like morphology, where the mitotic rate exceeds the criterion of 10 mitoses per 2 mm2, have still not been well classified. In clinical practice, the most controversial area is the limit of 11 mitoses to distinguish between atypical carcinoids and large cell neuroendocrine carcinomas.

Methods

Basic and clinical information was obtained from patient medical records. A series of grey-zone patients (n = 8) were selected for exploring their clinicopathological features. In addition, patients with atypical carcinoids (n = 9) and classical large cell neuroendocrine carcinomas (n = 14) were also included to compare their similarity to these neoplasms with respect to tumour morphology and immunohistochemical staining.

Results

We found that these grey-zone tumour sizes varied and affected mainly middle-aged and older men who smoked. Furthermore, similar gene mutations were found in the grey-zone neoplasms and large cell neuroendocrine carcinomas, for the mutated genes of these two are mainly involved in PI3K-Akt signal pathways and Pathways in cancer, including a biallelic alteration of TP53/RB1 and KEAP1.

Conclusions

Our findings indicate that neuroendocrine neoplasm with atypical carcinoid morphology and elevated mitotic counts is more similar to large cell neuroendocrine carcinoma than atypical carcinoid. Furthermore, this study may help improve diagnosing these special cases in clinical practice to avoid misdiagnosis.
Serum untargeted lipidomics by UHPLC-ESI-HRMS aids the biomarker discovery of colorectal adenoma
Authors: Zhou Hailin , Nong Yanying , Zhu Yifan , Liang Yunxiao , Zhang Jiahao , Chen Hongwei , Zhu Pingchuan , Zhang Qisong
Published: March 2022

Background

Colorectal adenoma (CA) is an important precancerous lesion and early screening target of colorectal cancer (CRC). Lipids with numerous physiological functions are proved to be involved in the development of CRC. However, there is no lipidomic study with large-scale serum samples on diagnostic biomarkers for CA.

Methods

The serum lipidomics of CA patients (n = 50) and normal control (NR) (n = 50) was performed by ultra high performance liquid chromatography-high resolution mass spectrometry with electrospray ionization (UHPLC-ESI-HRMS). Univariate and multivariate statistical analyses were utilized to screen the differential lipids between groups, and combining the constituent ratio analysis and diagnostic efficiency evaluation by receiver operating characteristic (ROC) curve disclosed the potential mechanism and biomarkers for CA.

Results

There were obvious differences in serum lipid profiles between CA and NR groups. Totally, 79 differential lipids were selected by criterion of P < 0.05 and fold change > 1.5 or < 0.67. Triacylglycerols (TAGs) and phosphatidylcholines (PCs) were the major differential lipids with ratio > 60%, indicating these two lipid metabolic pathways showed evident disequilibrium, which could contribute to CA formation. Of them, 12 differential lipids had good diagnostic ability as candidate biomarkers for CA (AUC ≥ 0.900) by ROC analysis.

Conclusions

To our knowledge, this is the first attempt to profile serum lipidomics and explore lipid biomarkers of CA to help early screening of CRC. 12 differential lipids are obtained to act as potential diagnostic markers of CA. PCs and fatty acids were the main dysregulated biomarkers for CA in serum.
Pre-diagnostic faecal calprotectin levels in patients with colorectal cancer: a retrospective study
Authors: Blad Nathalie , Palmqvist Richard , Karling Pontus
Published: March 2022

Background

Faecal calprotectin (FC) is a potential biomarker for colorectal cancer (CRC) screening. There is uncertainty if tumor characteristics are associated with FC levels. We investigated how tumor stage and tumor localization influence the extent of FC levels in patients with CRC in clinical practice.

Methods

In two cohorts of patients with CRC, we retrospectively analyzed FC tests (CALPRO®) performed within three months prior to diagnosis. One hundred twenty-four patients with CRC were included (mean age 68 years, 44% women).

Results

Ninety-eight patients with CRC (79%) had a FC ≥ 50 µg/g. FC correlated positively with tumor stage (UICC based on WHO TNM classification) (rs 0.24; p = 0.007) and with CRP levels (rs 0.31, p = 001), and a negatively with B-haemoglobin (rs -0.21; p = 0.019). The patients with right-sided CRC had significantly more often a FC ≥ 50 µg/g than patients with left-sided CRC (92% vs 74% p = 0.027). In a binary logistic regression analysis, tumor stage III/IV (adjusted OR 3.47; CI 1.27–9.42) and right-sided tumor localization (adjusted OR 3.80; CI 1.01–14.3) were associated with FC ≥ 50 µg/g. Tumor stage III/IV (adjusted OR 2.30; CI 1.04–5.10) and acetylsalicylic use (adjusted OR 3.54; CI 1.03–12.2) were associated with FC ≥ 100 µg/g. In a cox regression analysis, a FC ≥ 100 µg/g was not associated with survival (Hazard OR 0.61; CI 0.24–1.52).

Conclusions

Elevated pre-diagnostic FC levels were common in patients with CRC in close proximity to diagnosis. Right-sided localization and tumor stage were significantly associated with a rise in FC levels.
Spontaneous closure of a chronic full-thickness idiopathic macular hole after Irvine-Gass syndrome resolution
Authors: da Costa Douglas Rodrigues , Braga Pedro Gomes Oliveira , Ariello Leonardo Eleuterio , Zacharias Leandro Cabral
Published: March 2022

Background

Full-thickness idiopathic macular hole (IMH) usually causes serious visual deformities and visual acuity loss. Pseudophakic cystic macular edema, also known as Irvine-Gass syndrome, is another entity that causes visual disturbances, and occurs mainly after cataract extraction. We present a case report of a patient that was diagnosed with a full-thickness macular hole that spontaneously closed after the resolution of an Irvine-Gass syndrome, which occurred after an uneventful cataract extraction.

Case presentation

A 75 years-old female presented with the complaints of decreased visual acuity and color contrast sensitivity on both eyes (OU) and central visual field deformations on her left eye (LE). She was diagnosed with a full-thickness IMH on her LE, and cataract on OU. After an uneventful cataract extraction via phacoemulsification, she developed an Irvine-Gass syndrome at her LE, which was treated topically. The IMH closed spontaneously after the resolution of the Irvine-Gass syndrome, and the patient is being followed with no further complaints.

Conclusion

The exact mechanism for spontaneous closure of full-thickness idiopathic macular holes is still not completely understood. In this case, we hypothesize that the coalesced intraretinal cysts caused by the Irvine-Gass syndrome formed a bridge-like structure connecting the inner walls of the macular hole, thus connecting the remnants of the Muller cells which enabled the full recovery of the normal foveal structure.
Comparing a mindfulness- and CBT-based guided self-help Internet- and mobile-based intervention against a waiting list control condition as treatment for adults with frequent cannabis use: a randomized controlled trial of CANreduce 3.0
Authors: Dey Michelle , Wenger Andreas , Baumgartner Christian , Herrmann Ute , Augsburger Mareike , Haug Severin , Malischnig Doris , Schaub Michael P.
Published: March 2022

Background

Though Internet- and mobile-based interventions (IMIs) and mindfulness-based interventions (generally deliveredin-situ) appear effective for people with substance use disorders, IMIs incorporating mindfulness are largely missing, including those targeting frequent cannabis use.

Methods

This paper details the protocol for a three-arm randomized controlled trial comparing a mindfulness-based self-help IMI (arm 1) and cognitive-behavioral therapy (CBT)-based self-help IMI (arm 2) versus being on a waiting list (arm 3) in their effectiveness reducing cannabis use in frequent cannabis users. Predictors of retention, adherence and treatment outcomes will be identified and similarities between the two active intervention arms explored. Both active interventions last six weeks and consist of eight modules designed to reduce cannabis use and common mental health symptoms. With a targeted sample size ofn = 210 per treatment arm, data will be collected at baseline immediately before program use is initiated; at six weeks, immediately after program completion; and at three and six months post baseline assessment to assess the retention of any gains achieved during treatment.

The primary outcome will be number of days of cannabis use over the preceding 30 days. Secondary outcomes will include further measures of cannabis use and use of other substances, changes in mental health symptoms and mindfulness, client satisfaction, intervention retention and adherence, and adverse effects. Data analysis will follow ITT principles and primarily employ (generalized) linear mixed models.

Discussion

This RCT will provide important insights into the effectiveness of an IMI integrating mindfulness to reduce cannabis use in frequent cannabis users.

Trial registration

International Standard Randomized Controlled Trial Number Registry:ISRCTN14971662; date of registration: 09/09/2021.
One year monitoring of SARS-CoV-2 prevalence in a German cohort of patients with cystic fibrosis
Authors: Jaudszus Anke , Pavlova Mariya , Rasche Marius , Baier Michael , Moeser Anne , Lorenz Michael
Published: March 2022

Background

In Germany, the first case of coronavirus disease 2019 (COVID-19) was registered on 28 January 2020. By February 2021, the third wave of the pandemic began. So far, only few data are available on the SARS-CoV-2 prevalence and the clinical impact of an infection in patients with cystic fibrosis (CF).

Methods

From February 2020 until March 2021, we screened 156 CF patients for anti-SARS-CoV-2 IgG antibodies (serology) and the presence of SARS-CoV-2 in deep throat saliva or nasopharyngeal swabs (molecular testing). From patients with confirmed SARS-CoV-2 infection, we recorded symptoms and collected clinical data.

Results

In total, 13 patients (8.3%) were tested positive for SARS-CoV-2 infection, most of them during the second and the beginning third wave of the pandemic. Ten positive tested patients described symptoms linked to COVID-19. The most common symptom was cough followed by fatigue and headache. SARS-CoV-2 infection did not impair lung function. No positive tested patient needed to be hospitalized.

Conclusions

SARS-CoV-2 infections in patients with CF are not as rare as initially anticipated, as frequent testing revealed. However, infected patients did not experience more severe clinical courses or worse clinical outcome. Our observation is in line with published reports indicating that individuals with CF are not at higher risk for severe COVID-19.
Discomfort, pain and stiffness: what do these terms mean to patients? A cross-sectional survey with lexical and qualitative analyses
Authors: Funabashi Martha , Wang Simon , Lee Alexander D , C. K. Duarte Felipe , Budgell Brian , Stilwell Peter , Hogg-Johnson Sheilah
Published: March 2022

Background

While pain is often the focus of clinical interventions, other clinical outcomes (e.g., discomfort, stiffness) might also contribute to patients’ functionality and well-being. Although researchers and clinicians may view discomfort, pain and stiffness as different constructs, it remains unclear how patients perceive and differentiate between these constructs. Therefore, the purpose of this study was to explore patients’ perceptions of pain, discomfort, and stiffness.

Methods

Chiropractic patients were invited to complete an online cross-sectional survey and describe what ‘discomfort’, ‘pain’ and ‘stiffness’ meant to them using their own words. Lexical and inductive qualitative content analyses were conducted independently and then triangulated.

Results

Fifty-three chiropractic patients (47.2% female, mean age: 39.1 ± 15.1 years) responded. The most common combinations of words to describe discomfort were “can be ignored” and “less severe than”. “Cannot be ignored” and “sharp shooting” were used to describe pain. “Limited range of motion” was used to describe stiffness. Qualitatively, five themes were developed: impact, character, feeling, intensity and temporality. Stiffness was described as limited movement/mobility. Although discomfort and stiffness impacted patients’ activities, patients remained functional; pain was described as stopping/limiting activities. Discomfort was described as dull and tingling, pain as sharp and shooting, and stiffness as tight and restricted. Patients felt displeased and annoyed when experiencing discomfort and stiffness but hurt and in danger of harm when experiencing pain. Discomfort and stiffness were described as less intense than pain, with shorter/intermittent duration; however, all constructs could be experienced constantly.

Conclusion

Patients perceived discomfort, pain and stiffness as different, yet overlapping constructs. This preliminary work advances our knowledge of how patients conceptualize these constructs, contributing to better understanding of what patients mean when reporting these experiences, potentially improving the clinician-patient communication.
A copper switch for inducing CRISPR/Cas9-based transcriptional activation tightly regulates gene expression in Nicotiana benthamiana
Authors: Garcia-Perez Elena , Diego-Martin Borja , Quijano-Rubio Alfredo , Moreno-Giménez Elena , Selma Sara , Orzaez Diego , Vazquez-Vilar Marta
Published: March 2022

Background

CRISPR-based programmable transcriptional activators (PTAs) are used in plants for rewiring gene networks. Better tuning of their activity in a time and dose-dependent manner should allow precise control of gene expression. Here, we report the optimization of a Copper Inducible system called CI-switch for conditional gene activation in Nicotiana benthamiana. In the presence of copper, the copper-responsive factor CUP2 undergoes a conformational change and binds a DNA motif named copper-binding site (CBS).

Results

In this study, we tested several activation domains fused to CUP2 and found that the non-viral Gal4 domain results in strong activation of a reporter gene equipped with a minimal promoter, offering advantages over previous designs. To connect copper regulation with downstream programmable elements, several copper-dependent configurations of the strong dCasEV2.1 PTA were assayed, aiming at maximizing activation range, while minimizing undesired background expression. The best configuration involved a dual copper regulation of the two protein components of the PTA, namely dCas9:EDLL and MS2:VPR, and a constitutive RNA pol III-driven expression of the third component, a guide RNA with anchoring sites for the MS2 RNA-binding domain. With these optimizations, the CI/dCasEV2.1 system resulted in copper-dependent activation rates of 2,600-fold and 245-fold for the endogenous N. benthamiana DFR and PAL2 genes, respectively, with negligible expression in the absence of the trigger.

Conclusions

The tight regulation of copper over CI/dCasEV2.1 makes this system ideal for the conditional production of plant-derived metabolites and recombinant proteins in the field.
The relationships between women’s reproductive factors: a Mendelian randomisation analysis
Authors: Prince Claire , Sharp Gemma C. , Howe Laura D. , Fraser Abigail , Richmond Rebecca C.
Published: March 2022

Background

Women’s reproductive factors include their age at menarche and menopause, the age at which they start and stop having children and the number of children they have. Studies that have linked these factors with disease risk have largely investigated individual reproductive factors and have not considered the genetic correlation and total interplay that may occur between them. This study aimed to investigate the nature of the relationships between eight female reproductive factors.

Methods

We used data from the UK Biobank and genetic consortia with data available for the following reproductive factors: age at menarche, age at menopause, age at first birth, age at last birth, number of births, being parous, age first had sexual intercourse and lifetime number of sexual partners. Linkage disequilibrium score regression (LDSC) was performed to investigate the genetic correlation between reproductive factors. We then applied Mendelian randomisation (MR) methods to estimate the causal relationships between these factors. Sensitivity analyses were used to investigate directionality of the effects, test for evidence of pleiotropy and account for sample overlap.

Results

LDSC indicated that most reproductive factors are genetically correlated (rg range: |0.06–0.94|), though there was little evidence for genetic correlations between lifetime number of sexual partners and age at last birth, number of births and ever being parous (rg < 0.01). MR revealed potential causal relationships between many reproductive factors, including later age at menarche (1 SD increase) leading to a later age at first sexual intercourse (beta (B) = 0.09 SD, 95% confidence intervals (CI) = 0.06,0.11), age at first birth (B = 0.07 SD, CI = 0.04,0.10), age at last birth (B = 0.06 SD, CI = 0.04,0.09) and age at menopause (B = 0.06 SD, CI = 0.03,0.10). Later age at first birth was found to lead to a later age at menopause (B = 0.21 SD, CI = 0.13,0.29), age at last birth (B = 0.72 SD, CI = 0.67, 0.77) and a lower number of births (B = −0.38 SD, CI = −0.44, −0.32).

Conclusion

This study presents evidence that women’s reproductive factors are genetically correlated and causally related. Future studies examining the health sequelae of reproductive factors should consider a woman’s entire reproductive history, including the causal interplay between reproductive factors.
Diversity and pathogenesis of Staphylococcus aureus from bovine mastitis: current understanding and future perspectives
Authors: Campos Bruno , Pickering Amy C. , Rocha Lis Souza , Aguilar Ananda Pereira , Fabres-Klein Mary Hellen , de Oliveira Mendes Tiago Antônio , Fitzgerald J. Ross , de Oliveira Barros Ribon Andrea
Published: March 2022

Staphylococcus aureus is a leading cause of bovine mastitis worldwide. Despite some improved understanding of disease pathogenesis, progress towards new methods for the control of intramammary infections (IMI) has been limited, particularly in the field of vaccination. Although herd management programs have helped to reduce the number of clinical cases, S. aureus mastitis remains a major disease burden. This review summarizes the past 16 years of research on bovine S. aureus population genetics, and molecular pathogenesis that have been conducted worldwide. We describe the diversity of S. aureus associated with bovine mastitis and the geographical distribution of S. aureus clones in different continents. We also describe studies investigating the evolution of bovine S. aureus and the importance of host-adaptation in its emergence as a mastitis pathogen. The available information on the prevalence of virulence determinants and their functional relevance during the pathogenesis of bovine mastitis are also discussed. Although traits such as biofilm formation and innate immune evasion are critical for the persistence of bacteria, the current understanding of the key host-pathogen interactions that determine the outcome of S. aureus IMI is very limited. We suggest that greater investment in research into the genetic and molecular basis of bovine S. aureus pathogenesis is essential for the identification of novel therapeutic and vaccine targets.
Protein interaction networks provide insight into fetal origins of chronic obstructive pulmonary disease
Authors: Röhl Annika , Baek Seung Han , Kachroo Priyadarshini , Morrow Jarrett D. , Tantisira Kelan , Silverman Edwin K. , Weiss Scott T. , Sharma Amitabh , Glass Kimberly , DeMeo Dawn L.
Published: March 2022

Background

Chronic obstructive pulmonary disease (COPD) is a leading cause of death in adults that may have origins in early lung development. It is a complex disease, influenced by multiple factors including genetic variants and environmental factors. Maternal smoking during pregnancy may influence the risk for diseases during adulthood, potentially through epigenetic modifications including methylation.

Methods

In this work, we explore the fetal origins of COPD by utilizing lung DNA methylation marks associated with in utero smoke (IUS) exposure, and evaluate the network relationships between methylomic and transcriptomic signatures associated with adult lung tissue from former smokers with and without COPD. To identify potential pathobiological mechanisms that may link fetal lung, smoke exposure and adult lung disease, we study the interactions (physical and functional) of identified genes using protein–protein interaction networks.

Results

We build IUS-exposure and COPD modules, which identify connected subnetworks linking fetal lung smoke exposure to adult COPD. Studying the relationships and connectivity among the different modules for fetal smoke exposure and adult COPD, we identify enriched pathways, including the AGE-RAGE and focal adhesion pathways.

Conclusions

The modules identified in our analysis add new and potentially important insights to understanding the early life molecular perturbations related to the pathogenesis of COPD. We identify AGE-RAGE and focal adhesion as two biologically plausible pathways that may reveal lung developmental contributions to COPD. We were not only able to identify meaningful modules but were also able to study interconnections between smoke exposure and lung disease, augmenting our knowledge about the fetal origins of COPD.
Construction of cell factory capable of efficiently converting l-tryptophan into 5-hydroxytryptamine
Authors: Wang Yingying , Chen Xueman , Chen Qiaoyu , Zhou Ning , Wang Xin , Zhang Alei , Chen Kequan , Ouyang Pingkai
Published: March 2022

Background

l-Tryptophan (l-Trp) derivatives such as 5-hydroxytryptophan (5-HTP) and 5-hydroxytryptamine (5-HT), N-Acetyl-5-hydroxytryptamine and melatonin are important molecules with pharmaceutical interest. Among, 5-HT is an inhibitory neurotransmitter with proven benefits for treating the symptoms of depression. At present, 5-HT depends on plant extraction and chemical synthesis, which limits its mass production and causes environmental problems. Therefore, it is necessary to develop an efficient, green and sustainable biosynthesis method to produce 5-HT.

Results

Here we propose a one-pot production of 5-HT from l-Trp via two enzyme cascades for the first time. First, a chassis cell that can convert l-Trp into 5-HTP was constructed by heterologous expression of tryptophan hydroxylase from Schistosoma mansoni (SmTPH) and an artificial endogenous tetrahydrobiopterin (BH4) module. Then, dopa decarboxylase from Harminia axyridis (HaDDC), which can specifically catalyse 5-HTP to 5-HT, was used for 5-HT production. The cell factory, E. coli BL21(DE3)△tnaA/BH4/HaDDC-SmTPH, which contains SmTPH and HaDDC, was constructed for 5-HT synthesis. The highest concentration of 5-HT reached 414.5 ± 1.6 mg/L (with conversion rate of 25.9 mol%) at the optimal conditions (substrate concentration,2 g/L; induced temperature, 25℃; IPTG concentration, 0.5 mM; catalysis temperature, 30℃; catalysis time, 72 h).

Conclusions

This protocol provided an efficient one-pot method for converting. l-Trp into 5-HT production, which opens up possibilities for the practical biosynthesis of natural 5-HT at an industrial scale.
The molecular mechanism of METTL3 promoting the malignant progression of lung cancer
Authors: Ma Chao , Ma Rui-Jie , Hu Kang , Zheng Qi-Ming , Wang Ye-Peng , Zhang Nan , Sun Zhi-Gang
Published: March 2022

Lung cancer remains one of the major causes of cancer-related death globally. Recent studies have shown that aberrant m6A levels caused by METTL3 are involved in the malignant progression of various tumors, including lung cancer. The m6A modification, the most abundant RNA chemical modification, regulates RNA stabilization, splicing, translation, decay, and nuclear export. The methyltransferase complex plays a key role in the occurrence and development of many tumors by installing m6A modification. In this complex, METTL3 is the first identified methyltransferase, which is also the major catalytic enzyme. Recent findings have revealed that METTL3 is remarkably associated with different aspects of lung cancer progression, influencing the prognosis of patients. In this review, we will focus on the underlying mechanism of METT3 in lung cancer and predict the future work and potential clinical application of targeting METTL3 for lung cancer therapy.
Biochemical but not imaging parameters are predictive of outcome in septic shock: a pilot study
Authors: Belli Oriana E. , Campolo Jonica , Vallerio Paola , Musca Francesco , Moreo Antonella , Maloberti Alessandro , Parolini Marina , Bonacchini Luca , Monti Gianpaola , De Gasperi Andrea , Fumagalli Roberto , Giannattasio Cristina
Published: March 2022

Background

Septic shock is a severe form of sepsis marked by hypotension with an ominous outcome despite the introduction of modern intensive care. The aim of the present study is to obtain a panel with biomarkers, echocardiographic and vascular parameters to better risk stratify patients and identify those at higher risk of ominous outcome.

Methods

Between May 2013 and April 2016, 35 consecutive patients admitted at the Intensive Care Unit (ICU) of ASST Great Metropolitan Hospital Niguarda with the diagnosis of severe sepsis or septic shock were enrolled. All patients underwent rest echocardiography and several circulating biomarkers of myocardial damage or oxidative stress.

Results

The multivariate Cox’s proportional hazard model showed that the only independent prognostic predictor for 30-day mortality was the angiopoietin-2, (HR 1.017, 95% CI 1.000–1.034; P = 0.049). An angiopoietin-2 concentrations ≥ of 33,418 pg/mL was identified as the optimal threshold for the discrimination between survivors and non survivors at the time of admission in ICU, with a sensitivity of 80% and a specificity of 68%.

Conclusions

Septic shock has a poor in-hospital outcome even when the best of care is implemented. Among the biochemical parameters angiopoietin was able to identify patients at risk of death. The lowest the value at admission, the highest the risk of in-hospital death. No echocardiographic nor vascular parameter was able to predict outcome in this setting.