bluuebunny/crossref_metadata_2025 huggingface dataset:
Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) participant’s profile regarding self-rated health: a multiple correspondence analysis
Authors: Lopes de Oliveira Thaís , Oliveira Raquel Vasconcellos Carvalhaes de , Griep Rosane Harter , Moreno Arlinda B. , Almeida Maria da Conceição Chagas de , Almquist Ylva Brännström , Fonseca Maria de Jesus Mendes da
Published: September 2021

Background

Self-rated health (SRH) - one of the most common health indicators used to verify health conditions - can be influenced by several types of socioeconomic conditions, thereby reflecting health inequalities. This study aimed to evaluate the participant profiles regarding the association between self-rated health and social and occupational characteristics of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

Methods

Cross-sectional design, including 11,305 individuals. Self-rated health was categorized as good, fair, and poor. The relationship between socio-demographic, psychosocial work environment, health-related variables, and self-rated health was analyzed by multiple correspondence analysis (stratified by age: up to 49 years old and 50 years old or more).

Results

For both age strata, group composition was influenced by socioeconomic conditions. Poor SRH was related to lower socioeconomic conditions, being women, black self-declared race/ethnicity, being non-married/non-united, low decision authority, low skill discretion, and obesity.

Conclusion

To promote health, interventions should focus on reducing existing socioeconomic, race, and gender inequalities in Brazil.
The water incident database (WAID) 2012 to 2019: a systematic evaluation of the documenting of UK drownings
Authors: Hills Samuel P. , Hobbs Matthew , Tipton Michael J. , Barwood Martin J.
Published: September 2021

Background

Death by drowning is a leading cause of accidental death in the United Kingdom (UK) and worldwide. The World Health Organization (WHO) states that effective documentation of drowning is required to describe drowning frequency and to underpin effective drowning prevention intervention, thus improving the quality of data describing drowning frequency represents a key initiative. The water incident database (WAID) has been used to document UK fatal and non-fatal water-based incidents since 2009. WAID has not undergone a systematic evaluation of its data or data collection procedures to establish if the database meets the WHO requirements. The present study investigated the characteristics of UK fatal drowning incidents and audited current WAID data capture procedures.

Methods

Data for the fatal drowning cases recorded between 2012 and 2019 were reviewed. Descriptive data were generated 1) to describe fatal drownings in the UK’s WAID in this period; 2) a sub-set of drownings were audited i) for completeness of data entry and, based on source documents, ii) for quality of data entry; 3) these processes were used to make recommendations for onward revisions to WAID.

Results

A total of 5051 fatalities were recorded between 2012 and 2019. Drowning was most frequent amongst males aged 35 to 60 years (n = 1346), whilst suspected accidents and suicides accounted for 44 and 35% of fatalities. Suicide by drowning was at a peak in the most recent year of data analysed (i.e., 2019; 279 cases) highlighting an urgent need for targeted intervention. Audit part 2i) indicated that 16% of all fields were incomplete, thus indicating potential redundancy, duplication, or the need for onward review. Audit part 2ii) indicated high levels of agreement (80 ± 12%) between audited cases and the ‘true’ WAID entries.

Conclusions

This study confirms WAID as a rigorous, transparent and effective means of documenting UK drownings thereby meeting WHO requirements for data quality; yet future improvements are recommended. Such findings allow researchers and policy makers to use WAID to further investigate UK drowning with a view to improving public safety measures and drowning prevention interventions. Observations alongside several expert recommendations have informed a revised version of WAID.
Prevalence of depression and its associated factors in bronchiectasis: findings from KMBARC registry
Authors: Lee Ji-Ho , Lee Won-Yeon , Yong Suk Joong , Kim Woo Jin , Sin Sooim , Lee Chang Youl , Kim Youlim , Jung Ji Ye , Kim Sang-Ha ,   the KMBARC, Oh Yeon-Mok , Lee Hyun , Choi Hayoung , Sim Yun Su , Yoo Kwang Ha , Lee Seung Jun , Kim Tae-Hyung , Yang Bumhee , Jeong Ina , Um Soo-Jung , Kim Deog Kyeom , Lee Ji-Hyun , Kwon Byoung Soo , Cho Young-Jae , Lee Chang-Hoon , Rhee Chin Kook , Lee Sang Haak , Na Ju-Ok , Jang An-Soo , Kim Changhwan , Kim Hyun Kuk , Park Hye Yun , Lee Jae Seung , Lee Sei Won , Ra Seung Won , Kang Sung-Yoon , Kim Yee Hyung , Park Yong Bum , Park So-Young , Kim Junghyun , Yoon Young-Soon , Jeong Yun Jeong , Lee Jung-Kyu , Kim Ki Uk , Lee Hyun-Kyung , Kim Eun Kyung , Lee Se Hee , Choi Jae Sung , Kang Hyung Koo , Kwon Yong-Soo , Lee Jae Ha
Published: September 2021

Background

With the emergence of bronchiectasis as a common respiratory disease, epidemiological data have accumulated. However, the prevalence and impact of psychological comorbidities were not sufficiently evaluated. The present study examined the prevalence of depression and its associated factors in patients with bronchiectasis.

Methods

This study involved a multicenter cohort of bronchiectasis patients recruited from 33 pulmonary specialist hospitals. The baseline characteristics and bronchiectasis-related factors at enrollment were analyzed. Depressive symptoms were assessed using the Patient Health Questionnaire (PHQ-9).

Results

Of the 810 patients enrolled in the study, 168 (20.7%) patients had relevant depression (PHQ-9 score ≥ 10), and only 20 (11.9%) patients had a diagnosis of depression. Significant differences were noted in the depressive symptoms with disease severity, which was assessed using the Bronchiectasis Severity Index and E-FACED (all p < 0.001). Depressive symptoms inversely correlated with quality-of-life (r = − 0.704, p < 0.001) and positively correlated with fatigue severity score (r = 0.712, p < 0.001). Multivariate analysis showed that depression was significantly associated with the modified Medical Research Council dyspnea scale ≥ 2 (OR 2.960, 95% CI 1.907–4.588, p =  < 0.001) and high number of exacerbations (≥ 3) in the previous year (OR 1.596, 95% CI 1.012–2.482, p = 0.041).

Conclusions

Depression is common, but its association with bronchiectasis was underrecognized. It negatively affected quality-of-life and presented with fatigue symptoms. Among the bronchiectasis-related factors, dyspnea and exacerbation were closely associated with depression. Therefore, active screening for depression is necessary to optimize the treatment of bronchiectasis.

Trial registration

The study was registered at Clinical Research Information Service (CRiS), Republic of Korea (KCT0003088). The date of registration was June 19th, 2018.
Orthodontic emergencies and mental state of Chinese orthodontic patients during the COVID-19 pandemic
Authors: Quan Shuqi , Guo Yutong , Zhou Jiawei , Zhang Guanning , Xing Ke , Mei Hongxiang , Li Juan
Published: September 2021

Background

The ongoing COVID-19 pandemic postponed routine follow-up visits of many orthodontic patients, which compromised their treatment process and mental states. This study was aimed to assess orthodontic emergency occurrence and psychological states of Chinese orthodontic patients during this pandemic.

Methods

Orthodontic patients in China were invited to answer an anonymous online questionnaire from February 20, 2020 to March 5, 2020, when routine dental care was suspended in China. The questionnaire included self-assessment of oral hygiene and compliance, orthodontic emergencies, perceptions and feelings about COVID-19 and anxiety self-rating scale, etc. Collected data was statistically analyzed with Chi-square, independent t test and univariable generalized estimating equations regression analysis.

Results

A total of 1078 respondents (292 male; 786 female) from 30 provinces of China were included in this study. About one-third (33.67%) of patients reported that they encountered orthodontic problems during the pandemic. Patients with clear aligners reported fewer orthodontic problems than those with fixed appliances or removable appliances. Female patients, elder patients and patients who encountered orthodontic emergencies were more anxious than other patients.

Conclusions

The compliance and occurrence of orthodontic emergencies differed in patients with different orthodontic appliances. Patients with orthodontic emergencies exhibited higher anxiety states.
Attitude towards migration of psychiatric trainees and early career psychiatrists in Iran
Authors: Eissazade Negin , Hemmati Dina , Ahlzadeh Niloofar , Shalbafan Mohammadreza , Askari-Diarjani Adeleh , Mohammadsadeghi Homa , Pinto da Costa Mariana
Published: September 2021

Introduction

Migration of medical professionals has been rapidly increasing in the past decades and it strongly affects origin and destination countries.

Objectives

We aimed to explore the extent and the reasons of migration among psychiatric trainees and early career psychiatrists in Iran.

Methods

Our semi-structured 61-items questionnaire inquired participants’ demographics, experiences of short-term mobility (from 3 months to 1 year), long-term migration (more than 1 year) and attitudes towards migration (current and future plans).

Results

A total of 184 responses were received. Most (73.4 %) participants were female, and within the age range of 25–65 (Mean: 34.9). Only 15.2 % had a short-term mobility experience, mostly due to academic reasons (35.7 %). Most (75 %) stated that this short-term mobility experience influenced them in favor of migration. The majority (83.7 %) had ‘ever’ considered leaving Iran, and more than half (57.3 %) stated they ‘strongly agree’ or ‘agree’ to leaving the country ‘now’ (at the time of the study). The main reason to migrate from Iran was first political, followed by work, financial, social, religious, academic, and cultural reasons, and the least ranked were personal reasons. In relation to their 5-year plans, 67.3 % saw themselves in the country they currently live in, Iran. The main features reported for an attractive job were ‘pleasant work environment’ (97.3 %), ‘good welfare and social security’ (96.7 %) and ‘high salary ‘(96.2 %).

Conclusions

This study calls for more support of psychiatric trainees and early career psychiatrists in Iran. Improvements in the political context, work conditions and finances might lower the rate of migratory intention and brain drain.
Development of a valid and reliable pterygium surgery assessment scale for ophthalmology residents
Authors: Zhang Zhihua , Qian Tianwei , Zhu Bijun , Liu Haiyun , Sun Xiaodong , Xu Xun
Published: September 2021

Background

Microsurgery training has become an important part of ophthalmology teaching and one of the main topics of examination. Accurate and effective evaluation of microsurgery skills is vital for the training and teaching of residents. In this study, we aimed to establish a pterygium surgery assessment scale for use by ophthalmic residents and evaluate its reliability and validity.

Methods

Based on a literature search, experienced pterygium surgeons developed the preliminary scale according to the standard surgical procedure. The preliminary scale and a questionnaire were sent to teaching and research experts in the field for feedback. Face and content validity and reliability of the scale were determined by rounds of modifications based on expert feedback. For construct validity, existing assessment scales were obtained and a range of factors were tested.

Results

Nineteen expert surgeons completed the questionnaire and modifications were made until all surgeons agreed on the final scale. Good construct validity was found by evaluation against 257 existing scales. For reliability, 280 evaluation scales were completed. Inter- and intra-rater reliability analysis both found Intraclass Correlation Coefficient (ICC) > 0.8 for all items and total scores.

Conclusion

The pterygium surgery assessment scale developed in this study has good reliability and validity, and is an effective measurement tool for the evaluation of ophthalmology residents’ pterygium surgical skills.
“Petal-like” size-tunable gold wrapped immunoliposome to enhance tumor deep penetration for multimodal guided two-step strategy
Authors: Li Yanan , Song Wenting , Hu Yumin , Xia Yun , Li Zhen , Lu Yang , Shen Yan
Published: September 2021

Background

Breast cancer is the fastest-growing cancer among females and the second leading cause of female death. At present, targeted antibodies combined with hyperthermia locally in tumor has been identified as a potential combination therapy to combat tumors. But in fact, the uniformly deep distribution of photosensitizer in tumor sites is still an urgent problem, which limited the clinical application. We reported an HER2-modified thermosensitive liposome (immunoliposome)-assisted complex by reducing gold nanocluster on the surface (GTSL-CYC-HER2) to obtain a new type of bioplasma resonance structured carrier. The HER2 decoration on the surface enhanced targeting to the breast cancer tumor site and forming irregular, dense, "petal-like" shells of gold nanoclusters. Due to the good photothermal conversion ability under near-infrared light (NIR) irradiation, the thermosensitive liposome released the antitumor Chinese traditional medicine, cyclopamine, accompanied with the degradation of gold clusters into 3–5 nm nanoparticles which can accelerate renal metabolism of the gold clusters. With the help of cyclopamine to degrade the tumor associated matrix, this size-tunable gold wrapped immunoliposome was more likely to penetrate the deeper layers of the tumor, while the presence of gold nanoparticles makes GTSL-CYC-HER2 multimodal imaging feasible.

Results

The prepared GTSL-CYC-HER2 had a size of 113.5 nm and displayed excellent colloidal stability, photo-thermal conversion ability and NIR-sensitive drug release. These GTSL-CYC-HER2 were taken up selectively by cancer cells in vitro and accumulated at tumour sites in vivo. As for the in vivo experiments, compared to the other groups, under near-infrared laser irradiation, the temperature of GTSL-CYC-HER2 rises rapidly to the phase transition temperature, and released the cyclopamine locally in the tumor. Then, the released cyclopamine destroyed the stroma of the tumor tissue while killing the tumor cells, which in turn increased the penetration of the liposomes in deep tumor tissues. Moreover, the GTSL-CYC-HER2 enhanced the performance of multimodal computed tomography (CT) and photothermal (PT) imaging and enabled chemo-thermal combination therapy.

Conclusions

This optically controlled biodegradable plasmonic resonance structures not only improves the safety of the inorganic carrier application in vivo, but also greatly improves the anti-tumor efficiency through the visibility of in vivo CT and PT imaging, as well as chemotherapy combined with hyperthermia, and provides a synergistic treatment strategy that can broaden the conventional treatment alone.

Graphic Abstract
Low postoperative blood platelet count may be a risk factor for 3-year mortality in patients with acute type A aortic dissection
Authors: Liu Guangyu , Wang Hongbai , Luo Qipeng , Cao Liang , Yang Lijing , Yu Cuntao , Yan Fuxia , Yuan Su
Published: September 2021

Background

Mortality and complications remain high after acute type A aortic dissection (ATAAD) open surgery and are associated with coagulation dysfunction. Platelets play an important role in the process of coagulation. This study explored the relationship between postoperative platelet counts and 3-year mortality after operation in patients with ATAAD undergoing open aortic repair surgery.

Methods

Patients with ATAAD who underwent Total Arch Replacement and Frozen Elephant Trunk in Fuwai Hospital from 2011 to 2015 were selected for this study. The perioperative data were collected and sorted through the electronic clinical case system. Multivariate Logistic regression was used to analyze the risk factors for death within three years after surgery.

Results

A total of 495 patients were included in the analysis. After correction for confounding factors, decreased postoperative platelet count remained an independent factor that was associated with lower mortality (OR = 0.918, 95% CI 0.853–0.988, P = 0.023).

Conclusions

The study indicated that decreased postoperative platelet count may lead to increased 3-year mortality, in patients with ATAAD who underwent open aortic repair surgery.
Cultural adaptation of a scalable psychological intervention for Burundian refugee adolescents in Tanzania: a qualitative study
Authors: Singh Aneeha , Nemiro Ashley , Malik Aiysha , Guimond Marie-France , Nduwimana Estella , Likindikoki Samuel , Annan Jeannie , Tol Wietse A.
Published: September 2021

Background

There is an urgent need for evidence-based, scalable, psychological interventions to improve the mental health of adolescents affected by adversity in low-resource settings. Early Adolescents Skills for Emotions (EASE) was developed by the WHO as a brief, transdiagnostic, group intervention for early adolescents exhibiting internalising problems, delivered by trained and supervised lay providers. This study describes the cultural adaptation of EASE for Burundian adolescents living in Mtendeli refugee camps in Tanzania.

Methods

A phased approach to adaptation of the EASE intervention and its implementation, was adopted and comprised of: (1) a desk review to synthesize existing research on mental health issues in conflict-affected Burundian communities, (2) a rapid qualitative assessment involving free listing and key informant interviews with multiple stakeholders, (3) cognitive interviews with end users, and (4) a two-part adaptation workshop involving the implementing partner staff, members of the refugee community and mental health experts. We applied the Bernal framework to systematically document and track adaptations across eight dimensions of the intervention.

Results

Problems associated with worry, stress, sadness, shame and fear were identified as amongst the most critical mental health concerns, alongside a range of experiences of different forms of violence (such as gender-based violence, violence when fleeing from their homes) and associated problems. Problems associated with violence that included past experiences of fleeing as well as ongoing problems of gender-based violence in the camp. The most significant adaptations that were required included providing options for low literacy of participants, safety planning to address the high prevalence of sexual violence, simplification of strategies for the benefit of the end users and of lay facilitators, and implementation changes to consider involvement of refugee incentive workers. A majority of changes were across dimensions of language, people, metaphors, content, methods and context, while there were fewer changes regarding the goals and concepts of EASE.

Conclusions

The approach to adaptation of a psychological intervention suggested both minor and major required changes. Adaptations based on the findings of this study are anticipated to enhance relevance and acceptability of the EASE intervention and its delivery for camp-residing Burundian refugees in Tanzania.
SIRPα-αCD123 fusion antibodies targeting CD123 in conjunction with CD47 blockade enhance the clearance of AML-initiating cells
Authors: Tahk Siret , Vick Binje , Hiller Björn , Schmitt Saskia , Marcinek Anetta , Perini Enrico D. , Leutbecher Alexandra , Augsberger Christian , Reischer Anna , Tast Benjamin , Humpe Andreas , Jeremias Irmela , Subklewe Marion , Fenn Nadja C. , Hopfner Karl-Peter
Published: September 2021

Background

Acute myeloid leukaemia (AML) stem cells (LSCs) cause disease relapse. The CD47 “don’t eat me signal” is upregulated on LSCs and contributes to immune evasion by inhibiting phagocytosis through interacting with myeloid-specific signal regulatory protein alpha (SIRPα). Activation of macrophages by blocking CD47 has been successful, but the ubiquitous expression of CD47 on healthy cells poses potential limitations for such therapies. In contrast, CD123 is a well-known LSC-specific surface marker utilized as a therapeutic target. Here, we report the development of SIRPα-αCD123 fusion antibodies that localize the disruption of CD47/SIRPα signalling to AML while specifically enhancing LSC clearance.

Methods

SIRPα-αCD123 antibodies were generated by fusing the extracellular domain of SIRPα to an αCD123 antibody. The binding properties of the antibodies were analysed by flow cytometry and surface plasmon resonance. The functional characteristics of the fusion antibodies were determined by antibody-dependent cellular phagocytosis and antibody-dependent cellular cytotoxicity assays using primary AML patient cells. Finally, an in vivo engraftment assay was utilized to assess LSC targeting.

Results

SIRPα-αCD123 fusion antibodies exhibited increased binding and preferential targeting of CD123+ CD47+ AML cells even in the presence of CD47+ healthy cells. Furthermore, SIRPα-αCD123 fusion antibodies confined disruption of the CD47-SIRPα axis locally to AML cells. In vitro experiments demonstrated that SIRPα-αCD123 antibodies greatly enhanced AML cell phagocytosis mediated by allogeneic and autologous macrophages. Moreover, SIRPα-αCD123 fusion antibodies efficiently targeted LSCs with in vivo engraftment potential.

Conclusions

SIRPα-αCD123 antibodies combine local CD47 blockade with specific LSC targeting in a single molecule, minimize the risk of targeting healthy cells and efficiently eliminate AML LSCs. These results validate SIRPα-αCD123 antibodies as promising therapeutic interventions for AML.
Transcriptome analysis of heterogeneity in mouse model of metastatic breast cancer
Authors: Ionkina Anastasia A. , Balderrama-Gutierrez Gabriela , Ibanez Krystian J. , Phan Steve Huy D. , Cortez Angelique N. , Mortazavi Ali , Prescher Jennifer A.
Published: September 2021

Background

Cancer metastasis is a complex process involving the spread of malignant cells from a primary tumor to distal organs. Understanding this cascade at a mechanistic level could provide critical new insights into the disease and potentially reveal new avenues for treatment. Transcriptome profiling of spontaneous cancer models is an attractive method to examine the dynamic changes accompanying tumor cell spread. However, such studies are complicated by the underlying heterogeneity of the cell types involved. The purpose of this study was to examine the transcriptomes of metastatic breast cancer cells using the well-established MMTV-PyMT mouse model.

Methods

Organ-derived metastatic cell lines were harvested from 10 female MMTV-PyMT mice. Cancer cells were isolated and sorted based on the expression of CD44low/EpCAMhigh or CD44high/EpCAMhigh surface markers. RNA from each cell line was extracted and sequenced using the NextSeq 500 Illumina platform. Tissue-specific genes were compared across the different metastatic and primary tumor samples. Reads were mapped to the mouse genome using STAR, and gene expression was quantified using RSEM. Single-cell RNA-seq (scRNA-seq) was performed on select samples using the ddSeq platform by BioRad and analyzed using Seurat v3.2.3. Monocle2 was used to infer pseudo-time progression.

Results

Comparison of RNA sequencing data across all cell populations produced distinct gene clusters. Differential gene expression patterns related to CD44 expression, organ tropism, and immunomodulatory signatures were observed. scRNA-seq identified expression profiles based on tissue-dependent niches and clonal heterogeneity. These cohorts of data were narrowed down to identify subsets of genes with high expression and known metastatic propensity. Dot plot analyses further revealed clusters expressing cancer stem cell and cancer dormancy markers. Changes in relevant genes were investigated across pseudo-time and tissue origin using Monocle2. These data revealed transcriptomes that may contribute to sub-clonal evolution and treatment evasion during cancer progression.

Conclusions

We performed a comprehensive transcriptome analysis of tumor heterogeneity and organ tropism during breast cancer metastasis. These data add to our understanding of metastatic progression and highlight targets for breast cancer treatment. These markers could also be used to image the impact of tumor heterogeneity on metastases.
Single-dose HPV vaccination efficacy among adolescent girls and young women in Kenya (the KEN SHE Study): study protocol for a randomized controlled trial
Authors: Barnabas Ruanne V. , Brown Elizabeth R. , Onono Maricianah , Bukusi Elizabeth A. , Njoroge Betty , Winer Rachel L. , Donnell Deborah , Galloway Denise , Cherne Stephen , Heller Kate , Leingang Hannah , Morrison Susan , Rechkina Elena , McClelland R. Scott , Baeten Jared M. , Celum Connie , Mugo Nelly ,   for the KEN SHE Study Team
Published: September 2021

Background

HPV infection is the primary cause of cervical cancer, a leading cause of cancer among women in Kenya and many sub-Saharan African countries. High coverage of HPV vaccination is a World Health Organization priority to eliminate cervical cancer globally, but vaccine supply and logistics limit widespread implementation of the current two or three dose HPV vaccine schedule.

Methods

We are conducting an individual randomized controlled trial to evaluate whether a single dose of the bivalent (HPV 16/18) or nonavalent (HPV 16/18/31/33/45/52/58/6/11) HPV vaccine prevents persistent HPV infection, a surrogate marker for precancerous lesions and cervical cancer. The primary objective is to compare the efficacy of immediate, single-dose bivalent or nonavalent vaccination with delayed HPV vaccination. Kenyan women age 15–20 years old are randomized to immediate bivalent HPV and delayed meningococcal vaccine (group 1), immediate nonavalent HPV vaccine and delayed meningococcal vaccine (group 2), or immediate meningococcal vaccine and delayed HPV vaccine (group 3) with 36 months of follow-up. The primary outcome is persistent vaccine-type HPV infection by month 18 and by month 36 for the final durability outcome. The secondary objectives include to (1) evaluate non-inferiority of antibody titers among girls and adolescents (age 9 to 14 years) from another Tanzanian study, the DoRIS Study (NCT02834637), compared to KEN SHE Study participants; (2) assess the memory B cell immune response at months 36 and 37; and (3) estimate cost-effectiveness using the trial results and health economic models.

Discussion

This study will evaluate single-dose HPV vaccine efficacy in Africa and has the potential to guide public health policy and increase HPV vaccine coverage. The secondary aims will assess generalizability of the trial results by evaluating immunobridging from younger ages, durability of the immune response, and the long-term health benefits and cost of single-dose HPV vaccine delivery.

Trial registration

ClinicalTrials.govNCT03675256. Registered on September 18, 2018
Natural vs. programmed cycles for frozen embryo transfer: study protocol for an investigator-initiated, randomized, controlled, multicenter clinical trial
Authors: Baksh Sheriza , Casper Anne , Christianson Mindy S. , Devine Kate , Doody Kevin J. , Ehrhardt Stephan , Hansen Karl R. , Lathi Ruth B. , Timbo Fatmata , Usadi Rebecca , Vitek Wendy , Shade David M. , Segars James , Baker Valerie L. ,   NatPro Study Group, Aghajanova Lusine , Alvero Ruben , Andrews Mary , Arevalo Diego , Barnard Emily , Casillas Aracely , Copeland Morgan , Craig La Tasha B. , Doody Kathleen M. , Eskew Ashley , Gonzalez Alma , Hoelscher Gretchen , Vaught Arthur Jason , Kochman Lynda , Lears Andie , Murugappan Gaya , Nackley Anna C. , Newsome Tasha , Quintana Natalie , Singh Bhuchitra , Sokalska Anna , Starkey-Scruggs Michelle , Thomas Robin L. , Toney Deveine , Trueheart Irene , Turner Kisha , Usadi Rebecca , Villalobos Sally , Wignarajah Anjali , Winn Virginia , Zones Christy
Published: September 2021

Background

Randomized trials of assisted reproductive technology (ART) have been designed for outcomes of clinical pregnancy or live birth and have not been powered for obstetric outcomes such as preeclampsia, critical for maternal and fetal health. ART increasingly involves frozen embryo transfer (FET). Although there are advantages of FET, multiple studies have shown that risk of preeclampsia is increased with FET compared with fresh embryo transfer, and the reason for this difference is not clear. NatPro will compare the proportion of preeclampsia between two commonly used protocols for FET,modified natural and programmed cycle.

Methods

In this two-arm, parallel-group, multi-center randomized trial, NatPro will randomize 788 women to either modified natural or programmed FET and follow them for up to three FET cycles. Primary outcome will be the proportion of preeclampsia in women with a viable pregnancy assigned to a modified natural cycle FET (corpus luteum present) protocol compared to the proportion of preeclampsia in pregnant women assigned to a programmed FET (corpus luteum absent) protocol. Secondary outcomes will compare the proportion of live births and the proportion of preeclampsia with severe features between the protocols.

Conclusion

This study has a potential significant impact on millions of women who pursue ART to build their families. NatPro is designed to provide clinically relevant guidance to inform patients and clinicians regarding maternal risk with programmed and modified natural cycle FET protocols. This study will also provide accurate point estimates regarding the likelihood of live birth with programmed and modified natural cycle FET.

Trial registration

ClinicalTrials.govNCT04551807. Registered on September 16, 2020
Full-length transcriptome analysis and identification of transcript structures in Eimeria necatrix from different developmental stages by single-molecule real-time sequencing
Authors: Gao Yang , Suding Zeyang , Wang Lele , Liu Dandan , Su Shijie , Xu Jinjun , Hu Junjie , Tao Jianping
Published: September 2021

Background

Eimeria necatrix is one of the most pathogenic parasites, causing high mortality in chickens. Although its genome sequence has been published, the sequences and complete structures of its mRNA transcripts remain unclear, limiting exploration of novel biomarkers, drug targets and genetic functions in E. necatrix.

Methods

Second-generation merozoites (MZ-2) of E. necatrix were collected using Percoll density gradients, and high-quality RNA was extracted from them. Single-molecule real-time (SMRT) sequencing and Illumina sequencing were combined to generate the transcripts of MZ-2. Combined with the SMRT sequencing data of sporozoites (SZ) collected in our previous study, the transcriptome and transcript structures of E. necatrix were studied.

Results

SMRT sequencing yielded 21,923 consensus isoforms in MZ-2. A total of 17,151 novel isoforms of known genes and 3918 isoforms of novel genes were successfully identified. We also identified 2752 (SZ) and 3255 (MZ-2) alternative splicing (AS) events, 1705 (SZ) and 1874 (MZ-2) genes with alternative polyadenylation (APA) sites, 4019 (SZ) and 2588 (MZ-2) fusion transcripts, 159 (SZ) and 84 (MZ-2) putative transcription factors (TFs) and 3581 (SZ) and 2039 (MZ-2) long non-coding RNAs (lncRNAs). To validate fusion transcripts, reverse transcription-PCR was performed on 16 candidates, with an accuracy reaching up to 87.5%. Sanger sequencing of the PCR products further confirmed the authenticity of chimeric transcripts. Comparative analysis of transcript structures revealed a total of 3710 consensus isoforms, 815 AS events, 1139 genes with APA sites, 20 putative TFs and 352 lncRNAs in both SZ and MZ-2.

Conclusions

We obtained many long-read isoforms in E. necatrix SZ and MZ-2, from which a series of lncRNAs, AS events, APA events and fusion transcripts were identified. Information on TFs will improve understanding of transcriptional regulation, and fusion event data will greatly improve draft versions of gene models in E. necatrix. This information offers insights into the mechanisms governing the development of E. necatrix and will aid in the development of novel strategies for coccidiosis control.

Graphical Abstract
Deep learning in cancer diagnosis, prognosis and treatment selection
Authors: Tran Khoa A. , Kondrashova Olga , Bradley Andrew , Williams Elizabeth D. , Pearson John V. , Waddell Nicola
Published: September 2021

Deep learning is a subdiscipline of artificial intelligence that uses a machine learning technique called artificial neural networks to extract patterns and make predictions from large data sets. The increasing adoption of deep learning across healthcare domains together with the availability of highly characterised cancer datasets has accelerated research into the utility of deep learning in the analysis of the complex biology of cancer. While early results are promising, this is a rapidly evolving field with new knowledge emerging in both cancer biology and deep learning. In this review, we provide an overview of emerging deep learning techniques and how they are being applied to oncology. We focus on the deep learning applications for omics data types, including genomic, methylation and transcriptomic data, as well as histopathology-based genomic inference, and provide perspectives on how the different data types can be integrated to develop decision support tools. We provide specific examples of how deep learning may be applied in cancer diagnosis, prognosis and treatment management. We also assess the current limitations and challenges for the application of deep learning in precision oncology, including the lack of phenotypically rich data and the need for more explainable deep learning models. Finally, we conclude with a discussion of how current obstacles can be overcome to enable future clinical utilisation of deep learning.
Searching for synergy: combining systemic daptomycin treatment with localised phage therapy for the treatment of experimental pneumonia due to MRSA
Authors: Valente Luca G. , Federer Lea , Iten Manuela , Grandgirard Denis , Leib Stephen L. , Jakob Stephan M. , Haenggi Matthias , Cameron David R. , Que Yok-Ai , Prazak Josef
Published: September 2021

Objective

Bacteriophages (or phages) are viruses which infect and lyse bacteria. The therapeutic use of phages (phage therapy) has regained attention in the last decades as an alternative strategy to treat infections caused by antimicrobial-resistant bacteria. In clinical settings it is most likely that phages are administered adjunct to antibiotics. For successful phage therapy it is therefore crucial to investigate different phage-antibiotic combinations in vivo. This study aimed to elucidate the combinatorial effects of systemic daptomycin and nebulised bacteriophages for the treatment of experimental pneumonia due to methicillin-resistant Staphylococcus aureus (MRSA).

Results

Using a rat model of ventilator-associated pneumonia caused by MRSA, the simultaneous application of intravenous daptomycin and nebulised phages was not superior to aerophage therapy alone at improving animal survival (55% vs. 50%), or reducing bacterial burdens in the lungs, or spleen. Thus, this combination does not seem to be of benefit for use in patients with MRSA pneumonia.
The Nereid on the rise: Platynereis as a model system
Authors: Özpolat B. Duygu , Randel Nadine , Williams Elizabeth A. , Bezares-Calderón Luis Alberto , Andreatta Gabriele , Balavoine Guillaume , Bertucci Paola Y. , Ferrier David E. K. , Gambi Maria Cristina , Gazave Eve , Handberg-Thorsager Mette , Hardege Jörg , Hird Cameron , Hsieh Yu-Wen , Hui Jerome , Mutemi Kevin Nzumbi , Schneider Stephan Q. , Simakov Oleg , Vergara Hernando M. , Vervoort Michel , Jékely Gáspár , Tessmar-Raible Kristin , Raible Florian , Arendt Detlev
Published: September 2021

The Nereid Platynereis dumerilii (Audouin and Milne Edwards (Annales des Sciences Naturelles 1:195–269, 1833) is a marine annelid that belongs to the Nereididae, a family of errant polychaete worms. The Nereid shows a pelago-benthic life cycle: as a general characteristic for the superphylum of Lophotrochozoa/Spiralia, it has spirally cleaving embryos developing into swimming trochophore larvae. The larvae then metamorphose into benthic worms living in self-spun tubes on macroalgae. Platynereis is used as a model for genetics, regeneration, reproduction biology, development, evolution, chronobiology, neurobiology, ecology, ecotoxicology, and most recently also for connectomics and single-cell genomics. Research on the Nereid started with studies on eye development and spiralian embryogenesis in the nineteenth and early twentieth centuries. Transitioning into the molecular era, Platynereis research focused on posterior growth and regeneration, neuroendocrinology, circadian and lunar cycles, fertilization, and oocyte maturation. Other work covered segmentation, photoreceptors and other sensory cells, nephridia, and population dynamics. Most recently, the unique advantages of the Nereid young worm for whole-body volume electron microscopy and single-cell sequencing became apparent, enabling the tracing of all neurons in its rope-ladder-like central nervous system, and the construction of multimodal cellular atlases. Here, we provide an overview of current topics and methodologies for P. dumerilii, with the aim of stimulating further interest into our unique model and expanding the active and vibrant Platynereis community.
Spectral CT of the abdomen: Where are we now?
Authors: Adam Sharon Z. , Rabinowich Aviad , Kessner Rivka , Blachar Arye
Published: September 2021

Spectral CT adds a new dimension to radiological evaluation, beyond assessment of anatomical abnormalities. Spectral data allows for detection of specific materials, improves image quality while at the same time reducing radiation doses and contrast media doses, and decreases the need for follow up evaluation of indeterminate lesions. We review the different acquisition techniques of spectral images, mainly dual-source, rapid kV switching and dual-layer detector, and discuss the main spectral results available. We also discuss the use of spectral imaging in abdominal pathologies, emphasizing the strengths and pitfalls of the technique and its main applications in general and in specific organs.
Large-vessel vasculitis in graft-versus-host disease: a case report
Authors: Al-Heilfi Anmar , Nataraja Champa , Cooley Helen , Batt Tracey
Published: September 2021

Background

Graft-versus-host disease is a common complication seen with allogenic stem cell transplant, which is used to treat a variety of hematological malignancies. Graft-versus-host disease is an allogenic syndrome and can present in a variety of ways, including symptoms mimicking various autoimmune diseases; however, it is quite rare to see graft-versus-host disease affecting the vascular system and causing vasculitis.

Case presentation

We describe a case of a 59-year-old Caucasian man with follicular lymphoma and diffuse large B-cell transformation who developed graft-versus-host disease post allogenic hematopoietic stem cell transplantation and later progressed to neurological complication foot drop and large-vessel vasculitis.

Conclusion

The life-threatening vascular complications associated with large-vessel vasculitis include arterial aneurysms and dissections, and ischemic or hemorrhagic stroke. Thus, this rare immunological association needs to be recognized and treated in a timely manner to prevent the long-term complications.
Management of toxic optic neuropathy via a combination of Wharton’s jelly-derived mesenchymal stem cells with electromagnetic stimulation
Authors: Özmert Emin , Arslan Umut
Published: September 2021

Purpose

To investigate the effect of the combination of Wharton's jelly derived mesenchymal stem cells (WJ-MSC) and high frequency repetitive electromagnetic stimulation (rEMS) in the therapy of toxic optic neuropathies with severe symptoms after the available current therapy modalities which were unsucessful.

Material and methods

This prospective, open-label clinical phase-3 study was conducted at Ankara University Faculty of Medicine, Department of Ophthalmology between April 2019 and April 2021. Thirty-six eyes of 18 patients with toxic optic neuropathy (TON) were included in the study. Within 1–3 months after the emergency interventions, patients with various degrees of sequela visual disturbances were studied in this clinical trial. The cases were divided into three groups according to similar demographic characteristics. Group 1: Consists of 12 eyes of 12 patients treated with the WJ-MSC and rEMS combination in one eye. Group 2: Consists of 12 eyes of 12 patients treated with only rEMS in one eye. Group 3: Consists of 12 eyes of six patients treated with only WJ-MSC in both eyes. The course was evaluated by comparing the quantitive functional and structural assessment parameters measured before and at the fourth month of applications in each group.

Results

The mean best corrected visual acuity (BCVA) delta change percentages of the groups can be ranked as: Group 1 (47%) > Group 3 (32%) > Group 2 (21%). The mean fundus perimetry deviation index (FPDI) delta change percentages of the groups can be ranked as: Group 1 (95%) > Group 2 (33%) > Group 3 (27%). The mean ganglion cell complex (GCC) thickness delta change (decrease in thickness) percentages can be ranked as: Group 1 (− 21%) > Group 3 (− 15%) > Group 2 (− 13%). The visual evoked potential (VEP) P100 latency delta change percentages of the groups can be ranked as: Group 1 (− 18%) > Group 3 (− 10%) > Group 2 (− 8%). The P100 amplitude delta change percentages of the groups can be ranked as: Group 1 (105%) > Group 3 (83%) > Group 2 (24%).

Conclusion

Toxic optic neuropathies are emergent pathologies that can result in acute and permanent blindness. After poisoning with toxic substances, progressive apoptosis continues in optic nerve axons and ganglion cells. After the proper first systemic intervention in intensive care clinic, the WJ-MSC and rEMS combination seems very effective in the short-term period in cases with TON. To prevent permanent blindness, a combination of WJ-MSC and rEMS application as soon as possible may increase the chance of success in currently untreatable cases.

Trial RegistrationClinicalTrials.gov ID: NCT04877067.
Relationship between epicardial fat volume measured by multi-detector computed tomography and coronary artery disease
Authors: Taha Doaa Ashour , El Shafey Rasha Ahmed Ali , Hamesa Manal Fathy , Abu-Dewan Khaled Abd El-Wahab , Nagy Hanan Ahmad
Published: September 2021

Background

The association between epicardial fat thickness and coronary artery disease (CAD) has been evaluated previously using echocardiography. Recently, multidetector computed tomography (MDCT), as a valuable tool in cardiovascular CT imaging, can improve characterization of CAD and give a more accurate volumetric quantitation of EF. The purpose of our study was to evaluate the relationship between the epicardial fat volume and CAD using multi-detector row CT.

Results

Out of the studied 120 patients, 22 patients were negative for CAD, while 98 patients had positive CAD. There was significant difference between both groups as regard epicardial fat volume (p < 0.001), and good relation was found between the amount of epicardial fat volume and coronary calcium score, number of affected vessel, plaque burden and degree of stenosis (p =  < 0.001).

Conclusion

EAT volume was larger in the presence of obstructive CAD and atheromatous plaques. These data suggest that EAT is associated with the development of coronary atherosclerosis and potentially the most dangerous types of plaques.
CT of cardiac and extracardiac vascular anomalies: embryological implications
Authors: Kamel Dalia Wageeh , Abdelhameed Abeer Maghawry , Mohammad Shaimaa Abdelsattar , Abbas Sherif Nabil
Published: September 2021

Background

Congenital heart disease (CHD) is the most common neonatal anomaly. Extracardiac findings are commonly associated with CHD. It is mandatory to evaluate extracardiac structures for potential associated abnormalities that might impact the surgical planning for these patients. The purpose of this study was to determine the extracardiac abnormalities that could associate cardiac anomalies and to give insights into their embryological aberrations.

Results

Thirty-two pediatric patients (22 males and 10 females) underwent CT angiography to assess CHD. Diagnosis of the CHD and associated extracardiac findings were recorded and tabulated by organ system and type of CHD. Retrospective ECG-gated low-peak kilovoltage (80Kvp) technique was used on 128MDCT GE machine. Patients were diagnosed according to their CHD into four groups: chamber anomalies 90%, septal anomalies 81.3%, conotruncal anomalies 59.4%, and valvular anomalies 59.4%. Extracardiac findings were found in 28 patients (87.5%) with a total of 76 findings. Vascular findings were the most prevalent as 50 vascular findings were observed in 28 patients. Aortic anomalies were the commonest vascular anomalies. Fourteen thoracic findings were observed in 12 patients; of them lung consolidation patches were the most common and 12 abdominal findings were found in seven patients, most of findings were related to situs abnormalities.

Conclusion

Extracardiac abnormalities especially vascular anomalies are commonly associating CHD. Along with genetic basis, aberrations in dynamics of blood flow could represent possible causes of this association.
Pregnancy Outcome in Women With APECED (APS-1): A Multicenter Study on 43 Females With 83 Pregnancies
Authors: Laakso Saila , Holopainen Elina , Betterle Corrado , Saari Viivi , Vogt Elinor , Schmitt Monica M , Winer Karen K , Kareva Maria , Sabbadin Chiara , Husebye Eystein S , Orlova Elizaveta , Lionakis Michail S , Mäkitie Outi
Published: September 2021

Context

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED; also known as autoimmune polyendocrine syndrome type 1) has a severe, unpredictable course. Autoimmunity and disease components may affect fertility and predispose to maternal and fetal complications, but pregnancy outcomes remain unknown.

Objective

To assess fetal and maternal outcomes and course of clinical APECED manifestations during pregnancy in women with APECED.

Design and Setting

A multicenter registry-based study including 5 national patient cohorts.

Patients

321 females with APECED.

Main Outcome Measure

Number of pregnancies, miscarriages, and deliveries.

Results

Forty-three patients had altogether 83 pregnancies at median age of 27 years (range, 17–39). Sixty (72%) pregnancies led to a delivery, including 2 stillbirths (2.4%) and 5 (6.0%) preterm livebirths. Miscarriages, induced abortions, and ectopic pregnancies were observed in 14 (17%), 8 (10%), and 1 (1.2%) pregnancies, respectively. Ovum donation resulted in 5 (6.0%) pregnancies. High maternal age, premature ovarian insufficiency, primary adrenal insufficiency, or hypoparathyroidism did not associate with miscarriages. Women with livebirth had, on average, 4 APECED manifestations (range 0-10); 78% had hypoparathyroidism, and 36% had primary adrenal insufficiency. APECED manifestations remained mostly stable during pregnancy, but in 1 case, development of primary adrenal insufficiency led to adrenal crisis and stillbirth. Birth weights were normal in >80% and apart from 1 neonatal death of a preterm baby, no serious perinatal complications occurred.

Conclusions

Outcome of pregnancy in women with APECED was generally favorable. However, APECED warrants careful maternal multidisciplinary follow-up from preconceptual care until puerperium.