bluuebunny/crossref_metadata_2025 huggingface dataset:
Can TSH level and premenstrual spotting constitute a non-invasive marker for the diagnosis of endometriosis?
Authors: Birke Lena , Baston-Büst Dunja M. , Kruessel Jan-Steffen , Fehm Tanja N. , Bielfeld Alexandra P.
Published: September 2021

Background

To date, there is no reliable non-invasive marker for the early detection and diagnosis of endometriosis available possibly resulting in a delayed diagnosis and consequently an unnecessary long ordeal for the individual woman. Therefore, the primary objective of the current study was to evaluate whether the combination of a thyroid-stimulating hormone (TSH) level > 2.5 µlU/ml and premenstrual spotting could serve as non-invasive markers of endometriosis. A secondary objective was to determine whether typical symptoms of endometriosis like dysmenorrhea and/or dyspareunia could increase the diagnostic reliability.

Methods

We conducted a retrospective, case–control study with 167 female patients at the Department of OB/GYN and REI (UniKiD) of the medical center of the University of Düsseldorf, between January 2015 and December 2016. 107 women with surgically confirmed endometriosis were compared to 60 without endometriosis (controls). To evaluate the diagnostic accuracy, we considered sensitivity, specificity and predictive values. In order to assess the association between the non-invasive markers and endometriosis an odds ratio (OR) with a 95% confidence interval was calculated.

Results

In our cohort, diagnosis of endometriosis with non-invasive markers according to their sensitivity yielded the following ranking: increased TSH level, premenstrual spotting, combination of both previous parameters, addition of dysmenorrhea, addition of dyspareunia and combination of all parameters.

Conclusion

The existence of endometriosis should be taken into consideration when a patient suffers from thyroid dysfunction and premenstrual spotting. Apart from an increased TSH level, the presence of premenstrual spotting underlines the possible diagnosis of endometriosis with non-invasive markers and therefore, the patient´s history needs to be taken into account carefully.

Trial registration The retrospective study was approved by the Ethics Committee of the medical faculty of the Heinrich-Heine University, Düsseldorf, Germany, Registration number Düsseldorf: 5371R (approved: April 04th, 2016). Since the design of the study was retrospective no written informed consent was necessary.
Variation in referrals from primary care to scheduled paediatric services in North and East Scotland -a cross-sectional study
Authors: Dick Smita , Crabb Ryen , McFaul Claire , MacRae Clare , Wilson Philip , Turner Steve
Published: September 2021

Background

Factors contributing to decisions to refer children for scheduled appointments at medical paediatric outpatient clinics are not well understood. Our aim was to describe practice-level characteristics associated with referrals to general paediatric clinics.

Methods

In this cross-sectional study the setting was general practices in three health boards in Scotland, NHS Grampian, NHS Highland and NHS Tayside The outcome was average annual number of referrals per 1000 children between 2011 and 2017. Univariate and multivariate analyses related the outcome to practice characteristics. For each practice the following characteristics were determined: distance from hospital; area deprivation; number of children registered; presence of ≥ 1 general practitioner with a child health interest and practice ownership.

Results

There were 62 practices in NHS Grampian, 63 in NHS Highland, and 65 in NHS Tayside; representative annual number of referrals to paediatric clinics per capita were 22, 34, and 35/1000 respectively. In the multivariate model, the number of referrals was inversely related to number of children in the practice (0.8 % fall per 1000 children [95 % confidence interval, CI, 0.5, 1.1]) and was higher from practices in the more deprived areas by a mean 55 % [95 % CI 9, 121] compared to less deprived areas. The number of referrals from a practice rose by 0.91 % [95 % CI 0.86, 0.97] for each additional partner in the practice.

Conclusion

Some practice-level characteristics were related to the standardised number of referrals, and associations differed between regions.
Synthesis of (−)−deoxypodophyllotoxin and (−)−epipodophyllotoxin via a multi-enzyme cascade in E. coli
Authors: Decembrino Davide , Raffaele Alessandra , Knöfel Ronja , Girhard Marco , Urlacher Vlada B.
Published: September 2021

Background

The aryltetralin lignan (−)−podophyllotoxin is a potent antiviral and anti-neoplastic compound that is mainly found in Podophyllum plant species. Over the years, the commercial demand for this compound rose notably because of the high clinical importance of its semi-synthetic chemotherapeutic derivatives etoposide and teniposide. To satisfy this demand, (−)−podophyllotoxin is conventionally isolated from the roots and rhizomes of Sinopodophyllum hexandrum, which can only grow in few regions and is now endangered by overexploitation and environmental damage. For these reasons, targeting the biosynthesis of (−)−podophyllotoxin precursors or analogues is fundamental for the development of novel, more sustainable supply routes.

Results

We recently established a four-step multi-enzyme cascade to convert (+)−pinoresinol into (−)−matairesinol in E. coli. Herein, a five-step multi-enzyme biotransformation of (−)−matairesinol to (−)−deoxypodophyllotoxin was proven effective with 98 % yield at a concentration of 78 mg/L. Furthermore, the extension of this cascade to a sixth step leading to (−)−epipodophyllotoxin was evaluated. To this end, seven enzymes were combined in the reconstituted pathway involving inter alia three plant cytochrome P450 monooxygenases, with two of them being functionally expressed in E. coli for the first time.

Conclusions

Both, (−)−deoxypodophyllotoxin and (−)−epipodophyllotoxin, are direct precursors to etoposide and teniposide. Thus, the reconstitution of biosynthetic reactions of Sinopodophyllum hexandrum as an effective multi-enzyme cascade in E. coli represents a solid step forward towards a more sustainable production of these essential pharmaceuticals.
The pattern of romantic and sexual related experiences among Chinese young adolescents: an exploration with multi-group latent class analysis
Authors: Yu Chunyan , Lou Chaohua , Lian Qiguo , Tu Xiaowen , Zhang Jiashuai , Zuo Xiayun
Published: September 2021

Background

Studies on very young adolescents’ romantic and sexual experiences would help inform the context in which early sex arises. However, such studies are scant in China due to sparse data and cultural issues.

Method

This study used the GEAS baseline data conducted among1776 adolescents in Shanghai. Multi-group latent class analysis was used to explore adolescents’ romantic and sexual experiences patterns and subgroups. Multi-nominal logistic regression was performed to identify the factors distinguishing different subgroups subsequently.

Results

There were gender differences in the lifetime prevalence for very young adolescents’ romantic and sexual-related behaviors. The Multi-group latent class analysis indicated that the participants could be classified into three classes: general group, early romance group, and sex exploratory group. Multi-nominal logistic regression showed youth in the early romance group were more likely to had friends of both gender, ever had a romantic relationship, and had more autonomy in deciding where to go than the general group; while male respondents in the sex exploratory group were older, ever had a romantic relationship, believed that boys should be more sexually active and more proactive than girls, had more autonomy on deciding where to go, and perceived less school connection and neighborhood cohesion. Female respondents in the sex exploratory group were older and less empowered in decision-making than the general group.

Conclusions

The result provides a picture of romantic and sexual behavior patterns among both gender of very young adolescents in China. Current sex education needs not only to be culturally appropriate but also to address the harm of gender inequality and stereotypes, as well as to provide accessible and supportive services to help young adolescents personalize their received information and strengthen their skills in communication, decision making, and critical thinking.
Investigating receptor-mediated antibody transcytosis using blood–brain barrier organoid arrays
Authors: Simonneau Claire , Duschmalé Martina , Gavrilov Alina , Brandenberg Nathalie , Hoehnel Sylke , Ceroni Camilla , Lassalle Evodie , Kassianidou Elena , Knoetgen Hendrik , Niewoehner Jens , Villaseñor Roberto
Published: September 2021

Background

The pathways that control protein transport across the blood–brain barrier (BBB) remain poorly characterized. Despite great advances in recapitulating the human BBB in vitro, current models are not suitable for systematic analysis of the molecular mechanisms of antibody transport. The gaps in our mechanistic understanding of antibody transcytosis hinder new therapeutic delivery strategy development.

Methods

We applied a novel bioengineering approach to generate human BBB organoids by the self-assembly of astrocytes, pericytes and brain endothelial cells with unprecedented throughput and reproducibility using micro patterned hydrogels. We designed a semi-automated and scalable imaging assay to measure receptor-mediated transcytosis of antibodies. Finally, we developed a workflow to use CRISPR/Cas9 gene editing in BBB organoid arrays to knock out regulators of endocytosis specifically in brain endothelial cells in order to dissect the molecular mechanisms of receptor-mediated transcytosis.

Results

BBB organoid arrays allowed the simultaneous growth of more than 3000 homogenous organoids per individual experiment in a highly reproducible manner. BBB organoid arrays showed low permeability to macromolecules and prevented transport of human non-targeting antibodies. In contrast, a monovalent antibody targeting the human transferrin receptor underwent dose- and time-dependent transcytosis in organoids. Using CRISPR/Cas9 gene editing in BBB organoid arrays, we showed that clathrin, but not caveolin, is required for transferrin receptor-dependent transcytosis.

Conclusions

Human BBB organoid arrays are a robust high-throughput platform that can be used to discover new mechanisms of receptor-mediated antibody transcytosis. The implementation of this platform during early stages of drug discovery can accelerate the development of new brain delivery technologies.
Research led by people who use drugs: centering the expertise of lived experience
Authors: Salazar Zach R. , Vincent Louise , Figgatt Mary C. , Gilbert Michael K. , Dasgupta Nabarun
Published: September 2021

Background

Research collaborations between people who use drugs (PWUD) and researchers are largely underutilized, despite the long history of successful, community-led harm reduction interventions and growing health disparities experienced by PWUD. PWUD play a critical role in identifying emerging issues in the drug market, as well as associated health behaviors and outcomes. As such, PWUD are well positioned to meaningfully participate in all aspects of the research process, including population of research questions, conceptualization of study design, and contextualization of findings.

Main body

We argue PWUD embody unparalleled and current insight to drug use behaviors, including understanding of novel synthetic drug bodies and the dynamics at play in the drug market; they also hold intimate and trusting relationships with other PWUD. This perfectly situates PWUD to collaborate with researchers in investigation of drug use behaviors and development of harm reduction interventions. While PWUD have a history of mistrust with the medical community, community-led harm reduction organizations have earned their trust and are uniquely poised to facilitate research projects. We offer the North Carolina Survivors Union as one such example, having successfully conducted a number of projects with reputable research institutions. We also detail the fallacy of meaningful engagement posed by traditional mechanisms of capturing community voice. As a counter, we detail the framework developed and implemented by the union in hopes it may serve as guidance for other community-led organizations. We also situate research as a mechanism to diversify the job opportunities available to PWUD and offer a real-time example of the integration of these principles into public policy and direct service provision.

Conclusion

In order to effectively mitigate the risks posed by the fluid and volatile drug market, research collaborations must empower PWUD to play meaningful roles in the entirety of the research process. Historically, the most effective harm reduction interventions have been born of the innovation and heart possessed by PWUD; during the current overdose crisis, there is no reason to believe they will not continue to be.
Acute Toxic Effects of the New Psychoactive Substance “Voodoo” among Patients presented to the Poison Control Center of Ain Shams University Hospitals (PCC-ASUH), Egypt, during 2017
Authors: Hussien Rania , El-Setouhy Maged , Shinawi Mohamed El , El-Hariri Hazem Mohamed , Hirshon Jon Mark
Published: September 2021

Background

Voodoo is a heterogeneous mixture of psychoactive substances that has recently grown in popularity among youth in Egypt. Patients can present with a variety of manifestations that may lead to death in some cases. This study assessed the acute toxic effects of voodoo among patients presented to the Poison Control Center of Ain Shams University Hospitals (PCC-ASUH) during a one year period.

Methods

This is a retrospective study of all patients presented with voodoo intoxication at the PCC-ASUH from 1 January 2017 to 31 December 2017. Clinical data, routine laboratory findings, and ECG results as well as duration of hospitalization and outcome were compiled from hospital records.

Results

Seventy-one voodoo intoxication cases meeting the inclusion criteria were analyzed (mean age: 25.19 ± 9.54 years, range: 15–50 years, 97.2 % male). Pulse, blood pressure, and respiratory rate were normal in more than half of all patients. Neurological abnormalities including agitation, hallucinations, disturbance of consciousness were the most frequent manifestations. Respiratory acidosis was the most common laboratory finding (54.9 %), followed by increased serum urea (43.6 %), hypokalemia (33.8 %), hyperglycemia (28.1 %), and leukocytosis (26.7 %). The most common ECG finding was sinus tachycardia (31 %), followed by QT prolongation (15.4 %). More than half of the studied patients (53.5 %) co-administered other illicit substances, most frequently cannabis and tramadol. Most patients recovered fully and were discharged, but death occurred in two cases.

Conclusions

Voodoo toxicity can manifest with many presentations, hampering timely diagnosis. Clinicians should consider possible voodoo poisoning in patients presenting with a history of drug use with neurological symptoms, and they should conduct follow-up arterial blood gases, electrolytes and ECG as voodoo may contain potentially fatal psychoactive substances.
Patient positioning and immobilization procedures for hybrid MR-Linac systems
Authors: Cuccia Francesco , Alongi Filippo , Belka Claus , Boldrini Luca , Hörner-Rieber Juliane , McNair Helen , Rigo Michele , Schoenmakers Maartje , Niyazi Maximilian , Slagter Judith , Votta Claudio , Corradini Stefanie
Published: September 2021

Hybrid magnetic resonance (MR)-guided linear accelerators represent a new horizon in the field of radiation oncology. By harnessing the favorable combination of on-board MR-imaging with the possibility to daily recalculate the treatment plan based on real-time anatomy, the accuracy in target and organs-at-risk identification is expected to be improved, with the aim to provide the best tailored treatment. To date, two main MR-linac hybrid machines are available, Elekta Unity and Viewray MRIdian. Of note, compared to conventional linacs, these devices raise practical issues due to the positioning phase for the need to include the coil in the immobilization procedure and in order to perform the best reproducible positioning, also in light of the potentially longer treatment time. Given the relative novelty of this technology, there are few literature data regarding the procedures and the workflows for patient positioning and immobilization for MR-guided daily adaptive radiotherapy. In the present narrative review, we resume the currently available literature and provide an overview of the positioning and setup procedures for all the anatomical districts for hybrid MR-linac systems.
Effects of postoperative radiotherapy on cardiovascular-pulmonary disease mortality in patients with stage IIIA-N2 resected NSCLC: analysis of the SEER database
Authors: Wang Xia , Song Jiaqi , Long Jie , Zeng Zhimin , Liu Anwen
Published: September 2021

Background

The role of postoperative radiotherapy (PORT) in cardiovascular-pulmonary disease mortality in patients with stage IIIA-N2 resected non-small cell lung cancer (NSCLC) remains uncertain. The purpose of this population-based analysis was to explore the effect of PORT on cardiovascular-pulmonary disease mortality in these patients.

Methods

Patients aged ≥ 18 years with stage IIIA-N2 resected NSCLC were identified in the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2015 and were grouped according to the use of PORT. Propensity score matching (PSM) was used to account for differences in baseline characteristics between the Non-PORT and PORT groups. The cumulative risk for cardiovascular-pulmonary disease death was estimated using the cumulative incidence curve. Competing risk regression was used to run univariate and multivariate analyses to evaluate risk factors.

Results

A total of 3981 patients were included in the study population. Among them, 1446 patients received PORT, and 2535 did not. A total of 1380 patients remained in each group after PSM, and the baseline characteristics were not significantly different between the two groups. The cumulative incidence of cardiovascular-pulmonary mortality was 10.93% in the Non-PORT group compared with 9.85% in the PORT group. There was no significant difference in the cumulative risk between the two groups (HR 1.07, 95% CI 0.77–1.48, p = 0.703). Multivariate analysis indicated that PORT had no significant impact on increased risk, with an HR of 1.18 (p = 0.377).

Conclusions

No significant differences between the PORT and Non-PORT groups were found in cardiovascular-pulmonary-specific modalities in this study. Further studies are required to validate these results. This study highlights the importance of long-term surveillance for NSCLC patients.
Scaling up care for perinatal depression for improved maternal and infant health (SPECTRA): protocol of a hybrid implementation study of the impact of a cascade training of primary maternal care providers in Nigeria
Authors: Gureje Oye , Oladeji Bibilola , Ayinde Olatunde Olayinka , Kola Lola , Abdulmalik Jibril , Abass Waheed Akinola Lanre , Faregh Neda , Zelkowitz Phyllis
Published: September 2021

Background

The large treatment gap for mental disorders in low- and middle-income countries (LMIC) necessitates task-sharing approaches in scaling up care for mental disorders. Previous work have shown that primary health care workers (PHCW) can be trained to recognize and respond to common mental disorders but there are lingering questions around sustainable implementation and scale-up in real world settings.

Method

This project is a hybrid implementation-effectiveness study guided by the Replicating Effective Programmes Framework. It will be conducted in four overlapping phases in maternal care clinics (MCC) in 11 local government areas in and around Ibadan metropolis, Nigeria. In Phase I, engagement meetings with relevant stake holders will be held. In phase II, the organizational and clinical profiles of MCC to deliver chronic depression care will be assessed, using interviews and a standardized assessment tool administered to staff and managers of the clinics. To ascertain the current level of care, 167 consecutive women presenting for antenatal care for the first time and who screened positive for depression will be recruited and followed up till 12 months post-partum. In phase III, we will design and implement a cascade training programme for PHCW, to equip them to identify and treat perinatal depression. In phase IV, a second cohort of 334 antenatal women will be recruited and followed up as in Phase I, to ascertain post-training level of care. The primary implementation outcome is change in the identification and treatment of perinatal depression by the PHCW while the primary effectiveness outcome is recovery from depression among the women at 6 months post-partum. A range of mixed-method approaches will be used to explore secondary implementation outcomes, including fidelity and acceptability. Secondary effectiveness outcomes are measures of disability and of infant outcomes.

Discussion

This study represents an attempt to systematically assess and document an implementation strategy that could inform the scaling up of evidence based interventions for perinatal depression using the WHO mhGAP-IG in LMIC.

Trial registration This study was registered on 03 December, 2019. https://doi.org/10.1186/ISRCTN94230307.
STAT: a fast, scalable, MinHash-based k-mer tool to assess Sequence Read Archive next-generation sequence submissions
Authors: Katz Kenneth S. , Shutov Oleg , Lapoint Richard , Kimelman Michael , Brister J. Rodney , O’Sullivan Christopher
Published: September 2021

Sequence Read Archive submissions to the National Center for Biotechnology Information often lack useful metadata, which limits the utility of these submissions. We describe the Sequence Taxonomic Analysis Tool (STAT), a scalable k-mer-based tool for fast assessment of taxonomic diversity intrinsic to submissions, independent of metadata. We show that our MinHash-based k-mer tool is accurate and scalable, offering reliable criteria for efficient selection of data for further analysis by the scientific community, at once validating submissions while also augmenting sample metadata with reliable, searchable, taxonomic terms.
Aspirin as secondary prevention in colorectal cancer liver metastasis (ASAC trial): study protocol for a multicentre randomized placebo-controlled trial
Authors: Yaqub Sheraz , Bjørnbeth Bjørn Atle , Angelsen Jon-Helge , Fristrup Claus Wilki , Grønbech Jon Erik , Hemmingsson Oskar , Isaksson Bengt , Juel Ingebjørg Soterud , Larsen Peter Nørgaard , Lindell Gert , Mortensen Frank Viborg , Mortensen Kim Erlend , Rizell Magnus , Sandström Per , Sandvik Oddvar Mathias , Sparrelid Ernesto , Taflin Helena , Taskén Kjetil ,   The ASAC study group, Brudvik Kristoffer W. , Fretland Åsmund A. , Horn Arild , Kleive Dyre , Labori Knut J. , Lassen Kristoffer , Røsok Bård I. , Søreide Jon A. , Tholfsen Tore , Villanger Olaug , Waage Anne
Published: September 2021

Background

Colorectal cancer is one the most common cancers in the western world with increasing incidence. Approximately 50% of the patients develop liver metastases. Resection of liver metastases is the treatment of choice although almost half of the resected patients get recurrence in the liver.

Methods

The ASAC trial is a Scandinavian, multicentre, double-blinded, randomized, placebo-controlled study to determine whether adjuvant treatment with low-dose aspirin (acetylsalicylic acid (ASA)) can improve disease-free survival in patients treated for colorectal cancer liver metastases (CRCLM). Up to 800 patients operated for CRCLM will be randomized to Arm#1 ASA 160 mg once daily or Arm#2 Placebo, for a period of 3 years or until disease recurrence. The patients will be recruited at all major hepatobiliary surgical units in Norway, Sweden and Denmark and have follow-up according to standard of care and the National Guidelines.

Discussion

The ASAC trial will be the first clinical interventional trial to assess the potential beneficial role of ASA in recurrence of CRCLM and survival. ASA is an inexpensive, well-tolerated and easily accessible drug that will be highly potential as adjuvant drug in secondary prevention of CRCLM if the study shows a beneficial effect. We will also determine the effect of ASA as adjuvant treatment on Health-Related Quality of Life and the cost-effectiveness.

Trial registration

ClinicalTrials.gov NCT03326791. Registered on 31 October 2017.
Safety and preliminary efficacy of sequential multiple ascending doses of solnatide to treat pulmonary permeability edema in patients with moderate-to-severe ARDS—a randomized, placebo-controlled, double-blind trial
Authors: Schmid Benedikt , Kredel Markus , Ullrich Roman , Krenn Katharina , Lucas Rudolf , Markstaller Klaus , Fischer Bernhard , Kranke Peter , Meybohm Patrick , Zwißler Bernhard , Frank Sandra ,   and the Solnatide Collaborators Group
Published: September 2021

Background

Acute respiratory distress syndrome (ARDS) is a complex clinical diagnosis with various possible etiologies. One common feature, however, is pulmonary permeability edema, which leads to an increased alveolar diffusion pathway and, subsequently, impaired oxygenation and decarboxylation. A novel inhaled peptide agent (AP301, solnatide) was shown to markedly reduce pulmonary edema in animal models of ARDS and to be safe to administer to healthy humans in a Phase I clinical trial. Here, we present the protocol for a Phase IIB clinical trial investigating the safety and possible future efficacy endpoints in ARDS patients.

Methods

This is a randomized, placebo-controlled, double-blind intervention study. Patients with moderate to severe ARDS in need of mechanical ventilation will be randomized to parallel groups receiving escalating doses of solnatide or placebo, respectively. Before advancing to a higher dose, a data safety monitoring board will investigate the data from previous patients for any indication of patient safety violations. The intervention (application of the investigational drug) takes places twice daily over the course of 7 days, ensued by a follow-up period of another 21 days.

Discussion

The patients to be included in this trial will be severely sick and in need of mechanical ventilation. The amount of data to be collected upon screening and during the course of the intervention phase is substantial and the potential timeframe for inclusion of any given patient is short. However, when prepared properly, adherence to this protocol will make for the acquisition of reliable data. Particular diligence needs to be exercised with respect to informed consent, because eligible patients will most likely be comatose and/or deeply sedated at the time of inclusion.

Trial registration

This trial was prospectively registered with the EU Clinical trials register (clinicaltrialsregister.eu). EudraCT Number: 2017-003855-47.
Assessing the fidelity of a peer-led chronic pain management program (PAP)
Authors: Tse Mimi M. Y. , Tang Shuk Kwan , Ng Shamay , Li Yajie , Cheung Daphne Sze Ki , Kwan Rick Yiu Cho
Published: September 2021

Background

Intervention fidelity is the core component of a well-designed clinical trial and processes that are used to ensure that the study intervention is delivered as planned. It affects the design and implementation of a study as well as the analysis of the results and interpretation of the findings. The objectives of this study are (a) to describe the methods of assessing the intervention fidelity used in the peer-led chronic pain management program (PAP) and (b) to report the findings on the PAP’s intervention fidelity.

Methods

To optimize fidelity to the intervention, we used various strategies and measured them in a continuous process using several different approaches: (a) peer volunteer (PV) training workshop, (b) biweekly meetings with the research team, (c) a detailed teaching manual, (d) a fidelity checklist, (e) on-site visits and direct observations, and (f) semi-structured interview.

Results

The PVs’ attendance was high, and most of them achieved a high level of implementation in following the fidelity checklist. As part of a large clustered RCT, the fidelity assessment was carried out to help determine the effectiveness of the intervention.

Conclusions

Overall, the PVs successfully delivered the intervention, and the results of the study indicate the effectiveness of the PAP.

Trial registration

ClinicalTrials.govNCT03823495. Registered on 30 January 2019.
ssvQC: an integrated CUT&RUN quality control workflow for histone modifications and transcription factors
Authors: Boyd Joseph , Rodriguez Princess , Schjerven Hilde , Frietze Seth
Published: September 2021

Objective

Among the different methods to profile the genome-wide patterns of transcription factor binding and histone modifications in cells and tissues, CUT&RUN has emerged as a more efficient approach that allows for a higher signal-to-noise ratio using fewer number of cells compared to ChIP-seq. The results from CUT&RUN and other related sequence enrichment assays requires comprehensive quality control (QC) and comparative analysis of data quality across replicates. While several computational tools currently exist for read mapping and analysis, a systematic reporting of data quality is lacking. Our aims were to (1) compare methods for using frozen versus fresh cells for CUT&RUN and (2) to develop an easy-to-use pipeline for assessing data quality.

Results

We compared a workflow for CUT&RUN with fresh and frozen samples, and present an R package called ssvQC for quality control and comparison of data quality derived from CUT&RUN and other enrichment-based sequence data. Using ssvQC, we evaluate results from different CUT&RUN protocols for transcription factors and histone modifications from fresh and frozen tissue samples. Overall, this process facilitates evaluation of data quality across datasets and permits inspection of peak calling analysis, replicate analysis of different data types. The package ssvQC is readily available at https://github.com/FrietzeLabUVM/ssvQC.
A hybrid framework for improving uncertainty quantification in deep learning-based QSAR regression modeling
Authors: Wang Dingyan , Yu Jie , Chen Lifan , Li Xutong , Jiang Hualiang , Chen Kaixian , Zheng Mingyue , Luo Xiaomin
Published: September 2021

Reliable uncertainty quantification for statistical models is crucial in various downstream applications, especially for drug design and discovery where mistakes may incur a large amount of cost. This topic has therefore absorbed much attention and a plethora of methods have been proposed over the past years. The approaches that have been reported so far can be mainly categorized into two classes: distance-based approaches and Bayesian approaches. Although these methods have been widely used in many scenarios and shown promising performance with their distinct superiorities, being overconfident on out-of-distribution examples still poses challenges for the deployment of these techniques in real-world applications. In this study we investigated a number of consensus strategies in order to combine both distance-based and Bayesian approaches together with post-hoc calibration for improved uncertainty quantification in QSAR (Quantitative Structure–Activity Relationship) regression modeling. We employed a set of criteria to quantitatively assess the ranking and calibration ability of these models. Experiments based on 24 bioactivity datasets were designed to make critical comparison between the model we proposed and other well-studied baseline models. Our findings indicate that the hybrid framework proposed by us can robustly enhance the model ability of ranking absolute errors. Together with post-hoc calibration on the validation set, we show that well-calibrated uncertainty quantification results can be obtained in domain shift settings. The complementarity between different methods is also conceptually analyzed.
A visual fingerprint update algorithm based on crowdsourced localization and deep learning for smart IoV
Authors: Yin Xiliang , Ma Lin , Sun Ping , Tan Xuezhi
Published: September 2021

Recently, deep learning and vision-based technologies have shown their great significance for the prospective development of smart Internet of Vehicle (IoV). When the smart vehicle enters the indoor parking of a shopping mall, the vision-based localization technology can provide reliable parking service. As known, the vision-based technique relies on a visual map without a change in the position of the reference object. Although, some researchers have proposed a few automatic visual fingerprinting (AVF) methods, which are aiming at reducing the cost of building the visual map database. However, the AVF method still costs too much under such a situation, since it is impossible to determine the specific location of the displaced object. Given the smart IoV and the development of deep learning approach, we propose an algorithm for solving the problem based on crowdsourcing and deep learning in this paper. Firstly, we propose a Region-based Fully Convolutional Network (R-FCN) based method with the feedback of crowdsourced images to locate the specific displaced object in the visual map database. Secondly, we propose a method based on quadratic programming (QP) for solving the translation vector of the displaced objects, which finally solves the problem of updating the visual map database. The simulation results show that our method can provide a higher detection sensitivity and correction accuracy as well as the relocation results. It means that our proposed algorithm outperforms the compared one, which is verified by both synthetic and real data simulation.
Trophic level drives the host microbiome of soil invertebrates at a continental scale
Authors: Zhu Dong , Delgado-Baquerizo Manuel , Ding Jing , Gillings Michael R. , Zhu Yong-Guan
Published: September 2021

Background

Increasing our knowledge of soil biodiversity is fundamental to forecast changes in ecosystem functions under global change scenarios. All multicellular organisms are now known to be holobionts, containing large assemblages of microbial species. Soil fauna is now known to have thousands of species living within them. However, we know very little about the identity and function of host microbiome in contrasting soil faunal groups, across different terrestrial biomes, or at a large spatial scale. Here, we examined the microbiomes of multiple functionally important soil fauna in contrasting terrestrial ecosystems across China.

Results

Different soil fauna had diverse and unique microbiomes, which were also distinct from those in surrounding soils. These unique microbiomes were maintained within taxa across diverse sampling sites and in contrasting terrestrial ecosystems. The microbiomes of nematodes, potworms, and earthworms were more difficult to predict using environmental data, compared to those of collembolans, oribatid mites, and predatory mites. Although stochastic processes were important, deterministic processes, such as host selection, also contributed to the assembly of unique microbiota in each taxon of soil fauna. Microbial biodiversity, unique microbial taxa, and microbial dark matter (defined as unidentified microbial taxa) all increased with trophic levels within the soil food web.

Conclusions

Our findings demonstrate that soil animals are important as repositories of microbial biodiversity, and those at the top of the food web harbor more diverse and unique microbiomes. This hidden source of biodiversity is rarely considered in biodiversity and conservation debates and stresses the importance of preserving key soil invertebrates.
A qualitative study of perspectives on access to tuberculosis health services in Xigaze, China
Authors: Haldane Victoria , Zhang Zhitong , Ma Qi , Yin Tingting , Zhang Bei , Li Yinlong , Pan Qiuyu , Dainty Katie N. , Rea Elizabeth , Pasang Pande , Wei Xiaolin , Hu Jun
Published: September 2021

Background

Tuberculosis (TB) is a major global health threat and the leading infectious disease cause of death worldwide. Access to and retention in TB care remains a challenge for patients, particularly those living in rural and remote settings. This qualitative study explored barriers and facilitators to accessing and maintaining contact with TB care services in communities in Xigaze (Shigatse) prefecture, Xizang Autonomous Region (Tibet Autonomous Region), China from the perspective of persons impacted by TB.

Methods

We conduced in-depth interviews with 23 participants impacted by TB in four rural districts in Xigaze prefecture, Xizang Autonomous Region, China between April 2019 and November 2020. Interviews were conducted in Tibetan and Mandarin, transcribed in Mandarin and translated into English. Transcripts were checked against recordings by native Tibetan and Mandarin speakers. QSR NVivo12 software was used for framework analysis guided by an access to care conceptual framework by Levesque et al.

Results

Overall patients reported low awareness of and an indifferent attitude towards TB, although all reported understanding the need to adhere to treatment. Participants reported complex pathways to care, often requiring visits to multiple healthcare facilities. Some participants reported visiting traditional Tibetan medicine (TTM) providers. Participants reported various barriers to accessing care including challenges physically reaching care, out-of-pocket payments for tests, diagnostics and transport. Barriers to maintaining care included medication side effects and worry about treatment effectiveness. Enablers to accessing care identified included knowledge or past experience with TB, integrated models of TTM and western care, supportive village doctors who conducted home visits, free TB treatment and other subsidies, as well as having family support with care and social support as barriers and facilitators to maintaining treatment.

Conclusions

We identified barriers and facilitators to accessing services in rural communities in Xigaze from the perspective of persons impacted by TB. Challenges include complex pathways to care, travel distances, wait times and low awareness. Tuberculosis care in the region could be strengthened by ongoing culturally tailored educational campaigns to increase awareness, partnerships with TTM providers, providing comprehensive treatment subsidies and strengthening the role of family members in comprehensive TB care.

Graphic abstract
WS2–WC–WO3 nano-hollow spheres as an efficient and durable catalyst for hydrogen evolution reaction
Authors: Van Nguyen Tuan , Do Ha Huu , Tekalgne Mahider , Van Le Quyet , Nguyen Thang Phan , Hong Sung Hyun , Cho Jin Hyuk , Van Dao Dung , Ahn Sang Hyun , Kim Soo Young
Published: September 2021

Transition metal dichalcogenides (TMDs), transition metal carbides (TMCs), and transition metal oxides (TMOs) have been widely investigated for electrocatalytic applications owing to their abundant active sites, high stability, good conductivity, and various other fascinating properties. Therefore, the synthesis of composites of TMDs, TMCs, and TMOs is a new avenue for the preparation of efficient electrocatalysts. Herein, we propose a novel low-cost and facile method to prepare TMD–TMC–TMO nano-hollow spheres (WS2–WC–WO3 NH) as an efficient catalyst for the hydrogen evolution reaction (HER). The crystallinity, morphology, chemical bonding, and composition of the composite material were comprehensively investigated using X-ray diffraction, Raman spectroscopy, field emission scanning electron microscopy, and X-ray photoelectron spectroscopy. The results confirmed the successful synthesis of the WS2–WC–WO3 NH spheres. Interestingly, the presence of nitrogen significantly enhanced the electrical conductivity of the hybrid material, facilitating electron transfer during the catalytic process. As a result, the WS2–WC–WO3 NH hybrid exhibited better HER performance than the pure WS2 nanoflowers, which can be attributed to the synergistic effect of the W–S, W–C, and W–O bonding in the composite. Remarkably, the Tafel slope of the WS2–WC–WO3 NH spheres was 59 mV dec−1, which is significantly lower than that of the pure WS2 NFs (82 mV dec−1). The results also confirmed the unprecedented stability and superior electrocatalytic performance of the WS2–WC–WO3 NH spheres toward the HER, which opens new avenues for the preparation of low-cost and highly effective materials for energy conversion and storage applications.
Image-guided confirmation of a precision pull-through procedure during laparoscopically assisted anorectoplasty in an open MRI operating theater: first application in an infantile case with anorectal malformation
Authors: Onishi Shun , Kedoin Chihiro , Murakami Masakazu , Higa Nayuta , Yoshida Akihiro , Onitsuka Kazutoshi , Moriyama Takahiro , Yoshimoto Koji , Ieiri Satoshi
Published: September 2021

Background

Image-guided surgery with an open magnetic resonance imaging (MRI) system is applied for brain tumors in the neurosurgery field, but has rarely been reported in pediatric surgery. We report our initial experience of intraoperative confirmation of precision rectal pull-through during laparoscopically assisted anorectoplasty (LAARP) in an open MRI operating theater for pediatric patients with anorectal malformation (ARM).

Case presentation

A 3.0 kg term male neonate was delivered with anorectal malformation. An invertogram revealed the intermediate type. Transverse colostomy was made on the left upper abdomen. The recto-bulbar urethral fistula (RBUF) was diagnosed by a distal colostogram and voiding cystourethrogram. LAARP was planned at 6 months of age. Because this was the first procedure in which the pediatric abdomen had been scanned in an open MRI operating theater in our institution, we scanned his pelvic floor under sedation 3 weeks before the operation using the open MRI system in our operation room. We performed the operation with 4 trocars. The peritoneal reflection was carefully incised and the rectum was dissected. The RBUF was resected. The center of the muscle complex was detected at the perineal skin with an electrical nerve stimulator, and a 7-mm longitudinal skin incision was made on the perineal lesion for anoplasty. The muscle complex and the pubo-rectal sling were confirmed laparoscopically using a 3.5-mm bipolar forceps connected to the electrical nerve stimulator. Anoplasty was performed between the rectal stump and perineal skin. After anoplasty, the patient was scanned with open MRI under general anesthesia. We attached the quadrature-detection (QD) head coil around the patient’s pelvis and inserted him in the gantry. A 0.45-T open MRI clearly revealed that the pulled through rectum was located in the center of the muscle complex on T2-weighted images. The postoperative course was uneventful. Oral intake was started on post-operative day 1. Postoperative dynamic urography showed no complication (e.g., leakage or residual fistula).

Conclusions

We successfully performed LAARP for ARM, with intraoperative confirmation of precision rectal pull-through in an open MRI operating theater. Further cases are required to evaluate the application of open MRI systems in pediatric surgery.
Role of 99mTc sulphur colloid lymphoscintigraphy in a rare case of chylothorax and lymphocele formation post esophageal duplication cyst excision
Authors: Yadav Naveen , Taywade Sameer , Kumar Rajesh , Prashanth Arun , Saxena Rahul
Published: September 2021

We report a rare case of chylothorax with lymphocele formation post esophageal duplication cyst (EDC) excision in a 2 year old male child. Patient developed chylothorax after excision of EDC. Pleural fluid cytology showed increased triglycerides and cholesterol levels. Filtered Tc-99m Sulphur colloid lymphoscintigraphy showed abnormal radiotracer uptake in the lower thoracic region on right side corresponding to lymphocele on SPECT-CT images with possible site of leak medially. In addition, Tc-99m pertechnetate scan was done to rule out possibility of residual duplication cyst revealed no abnormality. Patient underwent open and en-masse ligation of the duct. Patient recovered completely post-surgery. This case highlights the importance of lymphoscintigraphy with SPECT-CT in the evaluation of patients with post-operative complications of chylothorax with detection of site of chyle leak.
Outcome of ductus arteriosus stenting including vertical tubular and convoluted tortuous ducts with emphasis on technical considerations
Authors: Bahaidarah Saud , Al-Ata Jameel , Alkhushi Naif , Azhar Ahmad , Zaher Zaher , Alnahdi Bayan , Abdelsalam Mohamed , Elakaby Ahmed , Dohain Ahmed , Abdelmohsen Gaser
Published: September 2021

Background

Ductal stenting is the preferred method of securing adequate pulmonary blood flow in patients with duct-dependent pulmonary circulation. The main limitation in most centers is the difficult vertical tubular or convoluted ducts that represent real challenges to interventional pediatric cardiologists. We present our experience in patent ductus arteriosus (PDA) stenting with some technical tips to overcome difficulties, especially in stenting tortuous or long tubular ducts. This study was conducted on all patients with cyanotic congenital heart disease who underwent PDA stenting between January 2011 and December 2018.

Results

We attempted to stent the PDA in 43 patients, with a success rate of 93% (40 patients) and only one procedural mortality. There was also one stent migration that needed to be treated with urgent surgery. Three-fourths of the patients had difficult ductal morphology and origin. One stent was used to cover the PDA in 27 patients (62.8%), two stents were used in 13 (30.2%), and three stents were used in 2 patients (4.6%). In-stent stenosis rate was 12.5% (5 patients) and the development of progressive left pulmonary artery stenosis was seen in two patients (5%). Pulmonary artery growth was adequate in all patients.

Conclusions

PDA stenting is an effective method of palliation for patients with duct-dependent pulmonary circulation. It has low morbidity and mortality rates. Stenting difficult ducts have become more feasible with evolving materials and techniques.
The role of California sea lion (Zalophus californianus) hindflippers as aquatic control surfaces for maneuverability
Authors: Leahy Ariel M. , Fish Frank E. , Kerr Sarah J. , Zeligs Jenifer A. , Skrovan Stefani , Cardenas Kaitlyn L. , Leftwich Megan C.
Published: September 2021

California sea lions (Zalophus californianus) are a highly maneuverable species of marine mammal. During uninterrupted, rectilinear swimming, sea lions oscillate their foreflippers to propel themselves forward without aid from the collapsed hindflippers, which are passively trailed. During maneuvers such as turning and leaping (porpoising), the hindflippers are spread into a delta-wing configuration. There is little information defining the role of otarrid hindflippers as aquatic control surfaces. To examine Z. californianus hindflippers during maneuvering, trained sea lions were video recorded underwater through viewing windows performing porpoising behaviors and banking turns. Porpoising by a trained sea lion was compared with sea lions executing the maneuver in the wild. Anatomical points of reference (ankle and hindflipper tip) were digitized from videos to analyze various performance metrics and define the use of the hindflippers. During a porpoising bout, the hindflippers were considered to generate lift when surfacing with a mean angle of attack of 14.6±6.3 deg. However, while performing banked 180 deg turns, the mean angle of attack of the hindflippers was 28.3±7.3 deg, and greater by another 8-12 deg for the maximum 20% of cases. The delta-wing morphology of the hindflippers may be advantageous at high angles of attack to prevent stalling during high-performance maneuvers. Lift generated by the delta-shaped hindflippers, in concert with their position far from the center of gravity, would make these appendages effective aquatic control surfaces for executing rapid turning maneuvers.