bluuebunny/crossref_metadata_2025 huggingface dataset:
The standardization of clinical ethics consultation and technique’s “long encirclement” of humanity: a response to Brummett and Muaygil
Authors: Parks Benjamin N. , Mason Jordan
Published: October 2021

In their recent article, Brummett and Muaygil reject Bishop et al.’s framing of the debate over standardization in clinical ethics consultation (CEC) “as one between pro-credentialing procedural and anti-credentialing phenomenological,” claiming that this framing “amounts to a false dichotomy between two extreme approaches to CEC.” Instead of accepting proceduralism and phenomenology as a binary, Brummett and Muaygil propose that these two views should be seen as the extreme ends of a spectrum upon which CEC should be done. However, as evidenced by several inconsistencies within their article, they have failed to fully appreciate the concern animating Bishop et al.’s proposal. Additionally, because of this failure, they do not seem to realize that credentialing ethicists for CEC will only create different problems in Saudi Arabia even as it possibly solves some of the current problems they identify. In this commentary, we highlight and clarify Brummet and Muaygil’s five misunderstandings of Bishop et al. This leads us to conclude that while they claim to be advocating a middle way between proceduralism and phenomenology, in fact they would like for us to standardize another proceduralism, albeit one that incorporates some of the “qualitative” values of American bioethics.
Personalized analysis of minimal residual cancer cells in peritoneal lavage fluid predicts peritoneal dissemination of gastric cancer
Authors: Zhao Dongbing , Yue Pinli , Wang Tongbo , Wang Pei , Song Qianqian , Wang Jingjing , Jiao Yuchen
Published: October 2021

Peritoneal dissemination (PD) is a major type of gastric cancer (GC) recurrence and leads to rapid death. Current approaches cannot precisely determine which patients are at high risk of PD to provide early intervention. In this study, we developed a technology to detect minimal residual cancer cells in peritoneal lavage fluid (PLF) samples with a personalized assay profiling tumor-specific mutations. In a prospective cohort of 104 GC patients, the technology detected all the cases that developed PD with 100% sensitivity and 85% specificity. The minimal residual cancer cells in PLF were associated with a significantly increased risk of PD (HR = 145.13; 95% CI 20.20–18,435.79; p < 0.001), which was the strongest independent predictor over pathologic diagnosis and cytological diagnosis. In pathologically high-risk (pT4) patients, the PLF mutation profiling model exhibited a greater specificity of 91% and a positive predictive value of 88% while retaining a sensitivity of 100%. This approach may help in the postsurgical management of GC patients by detecting PD far before metastatic lesions grow to a significant size detectable by conventional methods such as MRI and CT scanning.
Differences between intrinsic and acquired nucleoside analogue resistance in acute myeloid leukaemia cells
Authors: Rothenburger Tamara , Thomas Dominique , Schreiber Yannick , Wratil Paul R. , Pflantz Tamara , Knecht Kirsten , Digianantonio Katie , Temple Joshua , Schneider Constanze , Baldauf Hanna-Mari , McLaughlin Katie-May , Rothweiler Florian , Bilen Berna , Farmand Samira , Bojkova Denisa , Costa Rui , Ferreirós Nerea , Geisslinger Gerd , Oellerich Thomas , Xiong Yong , Keppler Oliver T. , Wass Mark N. , Michaelis Martin , Cinatl Jindrich
Published: October 2021

Background

SAMHD1 mediates resistance to anti-cancer nucleoside analogues, including cytarabine, decitabine, and nelarabine that are commonly used for the treatment of leukaemia, through cleavage of their triphosphorylated forms. Hence, SAMHD1 inhibitors are promising candidates for the sensitisation of leukaemia cells to nucleoside analogue-based therapy. Here, we investigated the effects of the cytosine analogue CNDAC, which has been proposed to be a SAMHD1 inhibitor, in the context of SAMHD1.

Methods

CNDAC was tested in 13 acute myeloid leukaemia (AML) cell lines, in 26 acute lymphoblastic leukaemia (ALL) cell lines, ten AML sublines adapted to various antileukaemic drugs, 24 single cell-derived clonal AML sublines, and primary leukaemic blasts from 24 AML patients. Moreover, 24 CNDAC-resistant sublines of the AML cell lines HL-60 and PL-21 were established. The SAMHD1 gene was disrupted using CRISPR/Cas9 and SAMHD1 depleted using RNAi, and the viral Vpx protein. Forced DCK expression was achieved by lentiviral transduction. SAMHD1 promoter methylation was determined by PCR after treatment of genomic DNA with the methylation-sensitive HpaII endonuclease. Nucleoside (analogue) triphosphate levels were determined by LC-MS/MS. CNDAC interaction with SAMHD1 was analysed by an enzymatic assay and by crystallisation.

Results

Although the cytosine analogue CNDAC was anticipated to inhibit SAMHD1, SAMHD1 mediated intrinsic CNDAC resistance in leukaemia cells. Accordingly, SAMHD1 depletion increased CNDAC triphosphate (CNDAC-TP) levels and CNDAC toxicity. Enzymatic assays and crystallisation studies confirmed CNDAC-TP to be a SAMHD1 substrate. In 24 CNDAC-adapted acute myeloid leukaemia (AML) sublines, resistance was driven by DCK (catalyses initial nucleoside phosphorylation) loss. CNDAC-adapted sublines displayed cross-resistance only to other DCK substrates (e.g. cytarabine, decitabine). Cell lines adapted to drugs not affected by DCK or SAMHD1 remained CNDAC sensitive. In cytarabine-adapted AML cells, increased SAMHD1 and reduced DCK levels contributed to cytarabine and CNDAC resistance.

Conclusion

Intrinsic and acquired resistance to CNDAC and related nucleoside analogues are driven by different mechanisms. The lack of cross-resistance between SAMHD1/ DCK substrates and non-substrates provides scope for next-line therapies after treatment failure.
Under-nutrition and associated factors among children on ART in Southern Ethiopia: a facility-based cross-sectional study
Authors: Tiruneh Chalie Marew , Walle Belete Gelaw , Emiru Tigabu Desie , Tibebu Nigusie Selomon , Abate Moges Wubneh , Nigat Adane Birhanu , Belete Amsalu , Alem Eyasu , Lankrew Tadele , Eshetu Kirubel
Published: October 2021

Background

Malnutrition is very common in HIV-infected individuals. Even though data from different settings are necessary to tackle it, pieces of evidence are limited especially in the case of the nutritional status of HIV-infected children. Hence, this study aims to assess the nutritional status and associated factors among children on antiretroviral therapy.

Methods

An institutional-based cross-sectional study was conducted among 383 HIV-positive children in Southern Ethiopia. Data were collected using an interviewer-administered questionnaire and anthropometry measurement. Data were coded and entered into Epi-Data Version 3.1 and analyzed using SPSS Version 25. Bi-variable and multi-variable binary logistic regression models were used to identify factors associated with nutritional status and variables with p-values <0.05 in multi-variable logistic regression were considered as statistically significant.

Results

The prevalence of wasting among HIV-positive children in Southern Ethiopiaselected Hospitals was 36.3% (95% CI, 31.6–41.0) while stunting on the same study population was 5.5% (95% CI, 3.4–7.8). Rural residence, lack of maternal education, low CD4 counts (< 500), using an unprotected water source, having a non-biological mother and recurrent oral lesion were significantly associated with wasting. Furthermore, history of hospital admission, recurrent oral lesion, low CD4 counts (< 500), advanced WHO clinical stage were statically associated with stunting with p-value < 0.05.

Conclusion

This study found that the prevalence of under-nutrition among HIV-positive children in Ethiopia was significantly high. Therefore, timely identification and monitoring of nutritional problems should be necessary to enhance the effectiveness of ART treatment and to prevent further related complications.
Breastfeeding technique and associated factors among lactating mothers visiting Gondar town health facilities, Northwest Ethiopia: observational method
Authors: Safayi Boko Loka , Assimamaw Nega Tezera , Kassie Destaye Guadie
Published: October 2021

Background

The breastfeeding technique is explained positioning, attachment, and suckling during breastfeeding. Ineffective breast feeding technique is one of the factors leading to premature discontinuation of breastfeeding and malnutrition. There is a limited study on the assessments of BFT and associated factors among lactating mothers in the study area. Therefore, the study aimed to assess breastfeeding technique and the associated factors among lactating mothers visiting Gondar town health facilities, Northwest Ethiopia.

Methods

An institution-based cross-sectional study was conducted from February 20 to March 20, 2020. An observational checklist and structured interviewer-administered questionnaire were applied to collect the data. The data were entered into Epi-Data 4.6 version and transferred to analyzed using SPSS version 20. Bi-variable and multivariable logistic regressions were performed to identify the association. The strength of association was identified using odds ratio with a 95% confidence interval (), and a p-value of 0.05 was declare as statistically significant.

Results

The proportion of effective BFT was 48% (95%, CI: 43.0–53.0%). The likelihood of applying proper BFT among age group of 18–20 years was 70% lower than (AOR = 0.3; 95% CI: 0.11–0.83) age group > 30 years. The odds of effective BFT in primipara mothers were 49% (AOR = 0.51; 95% CI: 0.32–0.82) lower compared to multiparous mothers. Likewise, the provability of effective BFT was 55% (AOR = 0.45; 95% CI: 0.29–0.70) times lower in women who had no counseling immediately after delivery compared to their counterparts. Moreover, effective breast feeding technique mothers who have breast problem was 78% lower than (AOR = 0.22; 95% CI: 0.07–0.68) mothers who have no breast problem. And mothers who had counselling of BFT during ANC follow up was 55% (AOR = 0.45; 95% CI: 0.29, 0.70) lower than mothers who had no counseling.

Conclusion

Just under half of the women in the study area applied proper breast feeding technique Younger and primipara mothers poorly performed to effective BFT. But women having counseling during antenatal care follow-up and immediately after delivery and not having breast problems applied BFT effectively. Hence, special emphasis have to give for younger and primipara mothers. Besides, educate the mother for preventing breast problems and working on enhancing counseling at postnatal clinic.
Targeting PDZ domains as potential treatment for viral infections, neurodegeneration and cancer
Authors: Nardella Caterina , Visconti Lorenzo , Malagrinò Francesca , Pagano Livia , Bufano Marianna , Nalli Marianna , Coluccia Antonio , La Regina Giuseppe , Silvestri Romano , Gianni Stefano , Toto Angelo
Published: October 2021

The interaction between proteins is a fundamental event for cellular life that is generally mediated by specialized protein domains or modules. PDZ domains are the largest class of protein–protein interaction modules, involved in several cellular pathways such as signal transduction, cell–cell junctions, cell polarity and adhesion, and protein trafficking. Because of that, dysregulation of PDZ domain function often causes the onset of pathologies, thus making this family of domains an interesting pharmaceutical target. In this review article we provide an overview of the structural and functional features of PDZ domains and their involvement in the cellular and molecular pathways at the basis of different human pathologies. We also discuss some of the strategies that have been developed with the final goal to hijack or inhibit the interaction of PDZ domains with their ligands. Because of the generally low binding selectivity of PDZ domain and the scarce efficiency of small molecules in inhibiting PDZ binding, this task resulted particularly difficult to pursue and still demands increasing experimental efforts in order to become completely feasible and successful in vivo.
Personalized versus standard cognitive behavioral therapy for fear of cancer recurrence, depressive symptoms or cancer-related fatigue in cancer survivors: study protocol of a randomized controlled trial (MATCH-study)
Authors: Harnas Susan J. , Knoop Hans , Bennebroek Evertsz Floor , Booij Sanne H. , Dekker Joost , van Laarhoven Hanneke W. M. , van der Lee Marije , Meijer Ellen , Sharpe Louise , Sprangers Mirjam A. G. , van Straten Annemieke , Zweegman Sonja , Braamse Annemarie M. J.
Published: October 2021

Background

Fear of cancer recurrence, depressive symptoms, and cancer-related fatigue are prevalent symptoms among cancer survivors, adversely affecting patients’ quality of life and daily functioning. Effect sizes of interventions targeting these symptoms are mostly small to medium. Personalizing treatment is assumed to improve efficacy. However, thus far the empirical support for this approach is lacking. The aim of this study is to investigate if systematically personalized cognitive behavioral therapy is more efficacious than standard cognitive behavioral therapy in cancer survivors with moderate to severe fear of cancer recurrence, depressive symptoms, and/or cancer-related fatigue.

Methods

The study is designed as a non-blinded, multicenter randomized controlled trial with two treatment arms (ratio 1:1): (a) systematically personalized cognitive behavioral therapy and (b) standard cognitive behavioral therapy. In the standard treatment arm, patients receive an evidence-based diagnosis-specific treatment protocol for fear of cancer recurrence, depressive symptoms, or cancer-related fatigue. In the second arm, treatment is personalized on four dimensions: (a) the allocation of treatment modules based on ecological momentary assessments, (b) treatment delivery, (c) patients’ needs regarding the symptom for which they want to receive treatment, and (d) treatment duration. In total, 190 cancer survivors who experience one or more of the targeted symptoms and ended their medical treatment with curative intent at least 6 months to a maximum of 5 years ago will be included. Primary outcome is limitations in daily functioning. Secondary outcomes are level of fear of cancer recurrence, depressive symptoms, fatigue severity, quality of life, goal attainment, therapist time, and drop-out rates. Participants are assessed at baseline (T0), and after 6 months (T1) and 12 months (T2).

Discussion

To our knowledge, this is the first randomized controlled trial comparing the efficacy of personalized cognitive behavioral therapy to standard cognitive behavioral therapy in cancer survivors. The study has several innovative characteristics, among which is the personalization of interventions on several dimensions. If proven effective, the results of this study provide a first step in developing an evidence-based framework for personalizing therapies in a systematic and replicable way.

Trial registration

The Dutch Trial Register (NTR) NL7481 (NTR7723). Registered on 24 January 2019.
In-season monotony, strain and acute/chronic workload of perceived exertion, global positioning system running based variables between player positions of a top elite soccer team
Authors: Oliveira Rafael , Martins Alexandre , Nobari Hadi , Nalha Matilde , Mendes Bruno , Clemente Filipe Manuel , Brito João Paulo
Published: October 2021

Background

The interpretation of the load variations across a period seems important to control the weekly progression or variation of the load, or to identify within- micro and mesocycle variations. Thus, the aim of this study was to describe the in-season variations of training monotony, training strain, and acute: chronic workload ratio (ACWR) through session rating of perceived exertion (s-RPE), total distance and high-speed running (HSR) according to playing positions in an elite soccer team.

Methods

Seventeen professional players from an European First League team participated in this study. They were divided four central defenders (CD), three wide defenders (WD), four central midfielders (CM), three wide midfielders (WM) and three strikers (ST). The players were monitored daily over a 41-week period of competition where 52 matches occurred during the 2015–2016 in-season. Through the collection of s-RPE, total distance and HSR, training monotony, training strain and ACWR were calculated for each measure, respectively. Data were analysed across ten mesocycles (M: 1–10).

Results

The main results showed significant differences (p < 0.05) for TMs-RPE between CD vs. ST (moderate effect) in M2; between CD vs. CM (moderate effect) for TS of s-RPE; between CD vs. ST moderate effect) in M6 for ACWR of s-RPE. In addition, there was significant difference between CM vs. ST (moderate effect) in M2 for TS of TD; between WD vs. ST (moderate effect) in M3 for ACWR of TD. Moreover, there were significant differences for TM of HSR between CD vs. WD (very large effect); CD vs. WD (moderate effect) in M4 for TS of HSR.

Conclusions

The present study presents new insights to coaches and technical staff about the variation profiling of TM, TS, and ACWR calculated with internal and external load measures, between player positions during 10 mesocycles.
On interpolative contractions that involve rational forms
Authors: Fulga Andreea
Published: October 2021

The aim of this paper is to investigate the interpolative contractions involving rational forms in the framework of b-metric spaces. We prove the existence of a fixed point of such a mapping with different combinations of the rational forms. A certain example is considered to indicate the validity of the observed result.
Oral self-care behavior and its influencing factors in a sample of school children from Central Iran
Authors: Zareban Iraj , Karimy Mahmood , Araban Marzieh , Delaney Daniel
Published: October 2021

Background

Oral health is an important part of public health and crucial to health promotion and enhancing the quality of life. This research examined childhood oral self-care behavior and their related factors using extended Theory of Planned Behavior (TPB).

Method

This cross-sectional study was conducted on 368 sixth-grade elementary school students in Saveh city, Iran, in 2019. The students were selected using a random multi-stage sampling method. The instrument included the socio-demographic questions, TPB constructs, and action and coping plan items. Data were analyzed by SPSS software (Version 21) at alpha levelp ≤ 0.05.

Result

Overall, 24 (6.6%) students have never used toothbrushes, 222 (62.7%) have never used dental floss, and 298 (82.7%) students have never used mouthwash. The stepwise multiple linear regression analysis results indicated that the TPB with action and coping planning constructs had better predictive power than the original model. In the final model, coping planning (β = .28), intention (β = .24), action planning (β = .23), and perceived behavior control (β = .15) were the most important predictors of oral self-care behavior.

Conclusion

The results indicated that the oral self-care behavior status in Iranian elementary students was not favorable, and the extended model of the TPB with action and coping plan constructs were significant predictors of self-care behavior. Therefore, these findings emphasize the need for expanding educational interventions based on the extended model of the TPB to improve the oral self-care behavior of students.
A meta-analysis study of the robustness and universality of gut microbiome-metabolome associations
Authors: Muller Efrat , Algavi Yadid M. , Borenstein Elhanan
Published: October 2021

Background

Microbiome-metabolome studies of the human gut have been gaining popularity in recent years, mostly due to accumulating evidence of the interplay between gut microbes, metabolites, and host health. Statistical and machine learning-based methods have been widely applied to analyze such paired microbiome-metabolome data, in the hope of identifying metabolites that are governed by the composition of the microbiome. Such metabolites can be likely modulated by microbiome-based interventions, offering a route for promoting gut metabolic health. Yet, to date, it remains unclear whether findings of microbially associated metabolites in any single study carry over to other studies or cohorts, and how robust and universal are microbiome-metabolites links.

Results

In this study, we addressed this challenge by performing a comprehensive meta-analysis to identify human gut metabolites that can be predicted based on the composition of the gut microbiome across multiple studies. We term such metabolites “robustly well-predicted”. To this end, we processed data from 1733 samples from 10 independent human gut microbiome-metabolome studies, focusing initially on healthy subjects, and implemented a machine learning pipeline to predict metabolite levels in each dataset based on the composition of the microbiome. Comparing the predictability of each metabolite across datasets, we found 97 robustly well-predicted metabolites. These include metabolites involved in important microbial pathways such as bile acid transformations and polyamines metabolism. Importantly, however, other metabolites exhibited large variation in predictability across datasets, suggesting a cohort- or study-specific relationship between the microbiome and the metabolite. Comparing taxonomic contributors to different models, we found that some robustly well-predicted metabolites were predicted by markedly different sets of taxa across datasets, suggesting that some microbially associated metabolites may be governed by different members of the microbiome in different cohorts. We finally examined whether models trained on a control group of a given study successfully predicted the metabolite’s level in the disease group of the same study, identifying several metabolites where the model was not transferable, indicating a shift in microbial metabolism in disease-associated dysbiosis.

Conclusions

Combined, our findings provide a better understanding of the link between the microbiome and metabolites and allow researchers to put identified microbially associated metabolites within the context of other studies.
Recovery of strain-resolved genomes from human microbiome through an integration framework of single-cell genomics and metagenomics
Authors: Arikawa Koji , Ide Keigo , Kogawa Masato , Saeki Tatsuya , Yoda Takuya , Endoh Taruho , Matsuhashi Ayumi , Takeyama Haruko , Hosokawa Masahito
Published: October 2021

Background

Obtaining high-quality (HQ) reference genomes from microbial communities is crucial for understanding the phylogeny and function of uncultured microbes in complex microbial ecosystems. Despite improvements in bioinformatic approaches to generate curated metagenome-assembled genomes (MAGs), existing metagenome binners obtain population consensus genomes but they are nowhere comparable to genomes sequenced from isolates in terms of strain level resolution. Here, we present a framework for the integration of single-cell genomics and metagenomics, referred to as single-cell (sc) metagenomics, to reconstruct strain-resolved genomes from microbial communities at once.

Results

Our sc-metagenomics integration framework, termed SMAGLinker, uses single-cell amplified genomes (SAGs) generated using microfluidic technology as binning guides and integrates them with metagenome-assembled genomes (MAGs) to recover improved draft genomes. We compared sc-metagenomics with the metagenomics-alone approach using conventional metagenome binners. The sc-metagenomics approach showed precise contig binning and higher recovery rates (>97%) of rRNA and plasmids than conventional metagenomics in genome reconstruction from the cell mock community. In human microbiota samples, sc-metagenomics recovered the largest number of genomes with a total of 103 gut microbial genomes (21 HQ, with 65 showing >90% completeness) and 45 skin microbial genomes (10 HQ, with 40 showing >90% completeness), respectively. Conventional metagenomics recovered one Staphylococcus hominis genome, whereas sc-metagenomics recovered two S. hominis genomes from identical skin microbiota sample. Single-cell sequencing revealed that these S. hominis genomes were derived from two distinct strains harboring specifically different plasmids. We found that all conventional S. hominis MAGs had a substantial lack or excess of genome sequences and contamination from other Staphylococcus species (S. epidermidis).

Conclusions

SMAGLinker enabled us to obtain strain-resolved genomes in the mock community and human microbiota samples by assigning metagenomic sequences correctly and covering both highly conserved genes such as rRNA genes and unique extrachromosomal elements, including plasmids. SMAGLinker will provide HQ genomes that are difficult to obtain using metagenomics alone and will facilitate the understanding of microbial ecosystems by elucidating detailed metabolic pathways and horizontal gene transfer networks. SMAGLinker is available at https://github.com/kojiari/smaglinker.
Transmission of amyloid-beta and tau pathologies is associated with cognitive impairments in a primate
Authors: Lam Suzanne , Petit Fanny , Hérard Anne-Sophie , Boluda Susana , Eddarkaoui Sabiha , Guillermier Martine ,   The Brain Bank Neuro-C. E. B. Neuropathology Network, Letournel Franck , Martin-Négrier Marie-Laure , Faisant Maxime , Godfraind Catherine , Boutonnat Jean , Maurage Claude-Alain , Deramecourt Vincent , Duchesne Mathilde , Meyronet David , Fenouil Tanguy , de Paula André Mauès , Rigau Valérie , Vandenbos-Burel Fanny , Seilhean Danielle , Duyckaerts Charles , Boluda Susana , Plu Isabelle , Chiforeanu Dan Christian , Laquerrière Annie , Marguet Florent , Lannes Béatrice , Lhermitte Benoît , Buée Luc , Duyckaerts Charles , Haïk Stéphane , Picq Jean-Luc , Dhenain Marc
Published: October 2021

Amyloid-β (Aβ) pathology transmission has been described in patients following iatrogenic exposure to compounds contaminated with Aβ proteins. It can induce cerebral Aβ angiopathy resulting in brain hemorrhages and devastating clinical impacts. Iatrogenic transmission of tau pathology is also suspected but not experimentally proven. In both scenarios, lesions were detected several decades after the putatively triggering medico-surgical act. There is however little information regarding the cognitive repercussions in individuals who do not develop cerebral hemorrhages. In the current study, we inoculated the posterior cingulate cortex and underlying corpus callosum of young adult primates (Microcebus murinus) with either Alzheimer’s disease or control brain extracts. This led to widespread Aβ and tau pathologies in all of the Alzheimer-inoculated animals following a 21-month-long incubation period (n = 12) whereas none of the control brain extract-inoculated animals developed such lesions (n = 6). Aβ deposition affected almost all cortical regions. Tau pathology was also detected in Aβ-deposit-free regions distant from the inoculation sites (e.g. in the entorhinal cortex), while some regions adjacent, but not connected, to the inoculation sites were spared (e.g. the occipital cortex). Alzheimer-inoculated animals developed cognitive deficits and cerebral atrophy compared to controls. These pathologies were induced using two different batches of Alzheimer brain extracts. This is the first experimental demonstration that tau can be transmitted by human brain extracts inoculations in a primate. We also showed for the first time that the transmission of widespread Aβ and tau pathologies can be associated with cognitive decline. Our results thus reinforce the need to organize a systematic monitoring of individuals who underwent procedures associated with a risk of Aβ and tau iatrogenic transmission. They also provide support for Alzheimer brain-inoculated primates as relevant models of Alzheimer pathology.
Topography modulates effects of nitrogen deposition on microbial resource limitation in a nitrogen-saturated subtropical forest
Authors: Chen Hao , Tang Junjie , Sun Xibin , Ma Kayan , Chen Huaihai , Li Dejun
Published: October 2021

Background

Nitrogen (N) saturation theory proposes that an ecosystem might switch from N limitation to carbon (C), phosphorus (P), or other nutrient limitations if it receives continuous N input. Yet, after N limitation is removed, which nutrient is the most limited and whether topography modulates such change is rarely tested at a microbial level. Here, we conducted a two-year N addition experiment under two different topography positions (i.e. a slope and a valley) in a N-saturated subtropical forest. Soil enzyme activity was measured, and ecoenzymatic stoichiometry indexes were calculated as indicators of microbial resource limitation.

Results

In the valley, two-year N addition changed the activity of all studied enzymes to various degrees. As a result, microbial C limitation was aggravated in the valley, and consequently microbial decomposition of soil labile organic C increased, but microbial P limitation was alleviated due to the stoichiometry balance. On the slope, however, N addition did not significantly change the activity of the studied enzymes, and did not alter the status of microbial resource limitation.

Conclusions

These results indicate that C is a more limited element for microbial growth than P after removing N limitation, but we also highlight that topography can regulate the effect of N deposition on soil microbial resource limitation in subtropical forests. These findings provide useful supplements to the N saturation theory.
How much do social connections matter in fundraising outcomes?
Authors: Guo Lihuan , Wang Wei , Wu Yenchun Jim , Goh Mark
Published: October 2021

This study examines the role of social connections and network centrality in attracting funders to crowdfunding campaigns. We classify social connections as either external (e.g., Facebook) or internal (e.g., investing in online platforms through resource exchange). Drawing from the 108,463 crowdfunding campaigns on the online platform Kickstarter from April 21, 2009, to July 24, 2019, we apply external linkages and online followers to estimate the effect of external social connections. We construct a digraph network for the internal social connections and use PageRank, HITS, and centrality to obtain the weights of the nodes. Next, we compare the performance change of several prediction algorithms by feeding social connection-related variables. This study has several findings. First, for external social connections, having more online followers improves the funding success rate of a campaign. Second, for internal social connections, only authority and degree in centrality positively affect the number of funders and the campaign’s financing progress among the weights of the nodes. Third, using social connection variables improves the prediction algorithms for funding outcomes. Fourth, external social connections exert greater funding outcomes than internal social connections. Fourth, entrepreneurs should extend their external social connections to their internal social connections, and network centrality expedites project financing. Fifth, the effect of social connections on fundraising outcomes varies among the campaign categories. Fundraisers who are online influencers should leverage their online social connections, notably for the project categories that matter.
The use of patient-reported outcome measures in primary care: applications, benefits and challenges
Authors: Brower Krista , Schmitt-Boshnick Margo , Haener Michel , Wilks Shea , Soprovich Allison
Published: October 2021

PROMs use in primary care has expanded from simply describing patient populations to contributing to decision-making, in response to the increasingly complex, ever-changing healthcare environment. In Alberta, primary care is organized into primary care networks (PCNs), where family physicians are grouped geographically and supported by allied health professionals. PCNs implement programs and services in response to local population health needs with frequent evaluation, often incorporating PROMs for this purpose. As PCN programs and services vary greatly across Alberta, so do their use of PROMs. An area of commonality is the use of the EQ-5D-5L instrument; 29 out of 41 PCNs are registered and licensed to use the instrument. It is often administrated by paper, pre- and post-program, and in combination with other specific measures, depending on the program or target population. Some PCNs share programming and therefore outcome measurement, but often the selection, implementation (including training and administration procedures) and evaluation/reporting of PROMs are unique to the PCN. As well, data analysis is largely dependent on the size and capacity of the PCN. Using PROMs for PCN program evaluation supports clinical understanding and complements clinical outcomes. PROMs describe the population attending a program, as well as provide an element of consistency when examining trends across multiple programs or timepoints. This contributes to inquiries and decisions around program development, components, administrative features, resource allocation and delivery. Challenges of PROMs use in primary care include the absence of cohesive data capture technology. This limits data capabilities and presents difficulties with data fidelity, storage, export, and analysis. Additionally, this real-world application lacks a control arm and presents methodological challenges for comparative research purposes. Furthermore, capturing long term patient outcomes poses administrative challenges of multiple follow ups. More research is required into best reporting mechanisms to ensure the data is used to its full potential. To overcome these challenges, leadership and clinician engagement are key. As well, determining consistent PCN PROM reporting requirements will ensure data are comparable across PCNs and contribute to provincial level evaluations, further supporting the movement towards overall health system quality improvement.
Utilizing Patient Reported Outcome Measures (PROMs) in ambulatory oncology in Alberta: Digital reporting at the micro, meso and macro level
Authors: Watson Linda , Delure Andrea , Qi Siwei , Link Claire , Chmielewski Lindsi , Photitai Éclair , Smith Louise
Published: October 2021

Cancer patients experience numerous distressing symptoms and concerns across the course of their illness, which negatively influence their quality of life. Regardless of cancer type, unmanaged symptoms can lead to adverse downstream consequences. Patient Reported Outcome Measures (PROMs) can be used to inform patient care and lead to targeted symptom management but simply gathering this information does not improve outcomes for the patient. Patient generated information must be easy for the clinicians to access and interpret if it is to be used to inform care delivery in ambulatory oncology facilities. This pragmatic work responded to this need. One Canadian provincial ambulatory oncology jurisdiction implemented digital tracking of PROMs over time in the provincial Electronic Medical Record (EMR) to support full integration of PROMs into standard care workflows and processes. Due to an inability within the EMR for direct patient entry, a hybrid data-entry was designed where the patient completes a paper-based PROM in the waiting room, and after clinical review, a clinician documents this along with their clinical assessment in the EMR. Several digital dashboards were developed which report PROMs data at the micro (individual), meso (clinic) and macro (program) levels. Using PROMs routinely in these provincial practice settings has numerous benefits including enhanced patient-clinician communication, assisting with problem detection, management of symptoms, and improving outcomes for patients. There are over 60,000 unique patients represented in our PROMs database, and over 300,000 unique screening events captured. The PROMs data is now used at all levels of the provincial cancer jurisdiction to provide targeted person centred care (micro), to staff appropriately at a clinic or program level (meso), and for capacity planning for provincial programs (macro). A new provincial EMR is currently being implemented which has an associated patient portal. Based on the success of this work, integration of direct entry of PROMs by the patient prior to the appointment and an associated workflow for symptom management is underway in this jurisdiction.
Thoracic esophageal perforation by the use of Magill forceps in infant, success with non-operative treatment: case report
Authors: Bori Bata Abdel-Kémal , Gbénou Antoine Séraphin , Akodjènou Joseph , Kpossou Aboudou Raïmi , Noukpozoukou Bruno , Fiogbe Armand Michel
Published: October 2021

Background

Esophageal perforation is a rare surgical pathology in children. Thoracic esophageal perforation is more severe than cervical esophageal perforation. Iatrogenic cause, mainly by endoscopy, is the most common in esophageal perforation. However, perforation induced by “Magill forceps” is exceptional.

Case presentation

A systematic physical examination revealed pyrexia severe respiratory distress and right-sided pleural effusion.

We report the success of non-operative treatment applied to thoracic esophageal perforation due to Magill forceps in a 24-month-old male infant. The immediate and short-term outcomes were excellent.

Conclusions

Non-operative treatment is possible in iatrogenic perforation of thoracic esophageal in infants. This treatment delivers excellent outcome in carefully selected patients.
Investigating dizziness symptom in adult cases with Crimean-Congo hemorrhagic fever using various scales
Authors: Bora Adem , Büyüktuna Seyit Ali , Durmuş Kasım , Demirkıran Berat Baturay , Aslan Yasin , Oksüz Caner , Altuntas Emine Elif
Published: October 2021

Background

This study was to investigate the frequency of self-reported dizziness symptom in cases with Crimean-Congo hemorrhagic fever (CCHF) and the severity of dizziness, if any, by using various scales. The frequency and severity of the self-reported dizziness symptom of CCHF patients, level of disability caused by dizziness, and to what extent vestibular symptoms affected activities of daily living were assessed by various scales. The frequency and severity of the self-reported dizziness symptom of CCHF patients, level of disability caused by dizziness, and to what extent vestibular symptoms affected activities of daily living were assessed by various scales.

Results

The frequency of dizziness in CCHF cases included in the study was 11.11% and all the cases were involved in the mild category in terms of disease severity. When the results of the scales applied to all of the cases were evaluated in general, it was seen that there was no vertigo or dizziness.

Conclusion

According to the results of the present study, we consider that multicenter studies with large series investigating pathophysiological mechanisms underlying these clinical symptoms are needed in order to evaluate dizziness symptom and to make definitive interpretations in CCHF disease.
Parsimonious truncated Newton method for time-domain full-waveform inversion based on the Fourier-domain full-scattered-field approximation
Authors: Yong Peng , Brossier Romain , Métivier Ludovic
Published: October 2021

To exploit Hessian information in full-waveform inversion (FWI), the matrix-free truncated Newton method can be used. In such a method, Hessian-vector product computation is one of the major concerns due to the huge memory requirements and demanding computational cost. Using the adjoint-state method, the Hessian-vector product can be estimated by zero-lag crosscorrelation of the first-/second-order incident wavefields and the second-/first-order adjoint wavefields. Different from the implementation in frequency-domain FWI, Hessian-vector product construction in the time domain becomes much more challenging because it is not affordable to store all of the time-dependent wavefields. The widely used wavefield recomputation strategy leads to computationally intensive tasks. We have developed an efficient alternative approach to computing the Hessian-vector product for time-domain FWI. In our method, discrete Fourier transform is applied to extract frequency-domain components of involved wavefields, which are used to compute wavefield crosscorrelation in the frequency domain. This makes it possible to avoid reconstructing the first- and second-order incident wavefields. In addition, a full-scattered-field approximation is proposed to efficiently simplify the second-order incident and adjoint wavefield computation, which enables us to refrain from repeatedly solving the first-order incident and adjoint equations for the second-order incident and adjoint wavefields (re)computation. With our method, the computational time can be reduced by 70% and 80% in viscous media for Gauss-Newton and full-Newton Hessian-vector product construction, respectively. The effectiveness of our method is also verified in the frame of a 2D multiparameter inversion, in which our method almost reaches the same iterative convergence of the conventional time-domain implementation.
A new method of mineral inversion based on error analysis and static response equation error: A case study of a shale gas reservoir in the Wufeng-Longmaxi Formation
Authors: Liu Weinan , Zhang Chaomo , Zhang Zhansong , Li Jun , Zhu Linqi , Hu Song , Zhou Xueqing
Published: October 2021

The accurate quantitative calculation of mineral components is very important and basic work in formation evaluation. Using well-log data to estimate mineralogy and porosity is a mainstream method with core measurements often used. However, in shale reservoirs, there are many mineral components, such as organic matter and pyrite. In addition, the pore structure is complex, and gas exists in the pores as free state, adsorbed state, and dissolved state. These factors make the logging response characteristics more complex and thus the estimation of the mineral components more difficult. To address this problem, we have adopted a mineral inversion method based on error analysis and response equation error. Based on the error analysis of the mineral inversion method, we first establish a technique to obtain interpretation parameters and the function of the response equation error combined with the core data. Then, based on the weighted total least-squares method, we construct the objective function, and we use the improved krill herd algorithm to solve the problem. Finally, we estimate the mineral component volume. The calculated results indicate that the method can accurately determine the clay, quartz + feldspar, carbonate contents, and porosity by conventional logging data. Compared to the traditional mineral inversion method, the average relative error is reduced by 11.1%. The method has high applicability to shale reservoirs and can supply the basic parameters for formation evaluation.
Optimal Endocrine Therapy in Premenopausal Women: A Pragmatic Approach to Unanswered Questions
Authors: Sella Tal , Ruddy Kathryn J. , Carey Lisa A. , Partridge Ann H.
Published: October 2021

Recent epidemiologic data show an increasing incidence of breast cancer among premenopausal women in many higher-income countries. Among premenopausal women, those diagnosed under age 40 years experience inferior long-term outcomes, particularly in the setting of hormone receptor–positive, human epidermal growth factor receptor 2–negative disease. In addition to more advanced disease presentation and/or less favorable disease biology, suboptimal adjuvant endocrine therapy (ET) has emerged as an important driver of this age-related disparity. Historically, young women have been excluded from treatment with aromatase inhibitors (AIs), attained low rates of chemotherapy-related amenorrhea, and exhibited low adherence to ET. Recently, several studies have demonstrated treatment with ovarian function suppression (OFS) during the first 5 years postdiagnosis to be associated with improvements in breast cancer recurrence and mortality, with additional benefits achieved from pairing OFS with an AI. As the first 5 years of ET for premenopausal women has been transformed, extended ET, administered in years 5-10 postdiagnosis, has also become more common. However, the only studies of extending ET in premenopausal women have tested an additional 5 years of tamoxifen following an initial 5 years of tamoxifen and studies of AIs in the second 5 years have been limited to postmenopausal women. Herein, we review available data concerning potential benefits and risks to be considered when counseling premenopausal women on extended ET, including the continuation of OFS. We offer a pragmatic framework to support decision making given the current body of knowledge and call out the need for additional research into this issue.
Development of a Controlled Continuous Low-Dose Feeding Process
Authors: Fathollahi Sara , Kruisz Julia , Sacher Stephan , Rehrl Jakob , Escotet-Espinoza M. Sebastian , DiNunzio James , Glasser Benjamin J. , Khinast Johannes G.
Published: October 2021

This paper proposes a feed rate control strategy for a novel volumetric micro-feeder, which can accomplish low-dose feeding of pharmaceutical raw materials with significantly different powder properties. The developed feed-forward control strategy enables a constant feed rate with a minimum deviation from the set-point, even for materials that are typically difficult to accurately feed (e.g., due to high cohesion or low density) using conventional continuous feeders. Density variations observed during the feeding process were characterized via a displacement feed factor profile for each powder. The characterized effective displacement density profile was applied in the micro-feeder system to proactively control the feed rate by manipulating the powder displacement rate (i.e., computing the feed rate from the powder displacement rate). Based on the displacement feed factor profile, the feed rate can be predicted during the feeding process and at any feed rate set-point. Three pharmaceutically relevant materials were used for the micro-feeder evaluation: di-calcium phosphate (large-particle system, high density), croscarmellose sodium (small-particle system, medium density), and barium sulfate (very small-particle <10 μm, high density). A significant improvement in the feeding performance was achieved for all investigated materials. The feed rate deviation from the set-point and its relative standard deviation were minimal compared to operations without the control strategy.