bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acceptability of donor breastmilk banking among health workers: a cross-sectional survey in Zimbabwean urban settings
Authors: Chagwena Dexter T. , Mugariri Felistas , Sithole Bhekimpilo , Mataga Steady Faith , Danda Ruvimbo , Matsungo Tonderayi M. , Maponga Charles C. 
Published: May 2020

Abstract
Background
The World Health Organization (WHO) recommends that donor human milk is superior to artificial infant formula in situations where the baby cannot feed on the mother’s breastmilk. The purpose of this study was to determine the acceptability of donor human milk banking among health workers in Zimbabwean urban settings.

Methods
A cross sectional study was conducted among 535 health workers and 15 key informants. Three referral hospitals were purposively selected and systematic random sampling was used to select the health workers. The study was conducted between October 2017 and October 2018.

Results
The concept of donor human milk banking was acceptable among health workers. One-third (31%) of the study participants reported that they would accept donor breastmilk for their children while 56% of them would encourage their clients to donate breastmilk. Acceptance of donor human milk banking was associated with a high level of knowledge on breastmilk banks (p = 0.009) and the study participants’ health profession (p = 0.001). Clinical staff were more receptive to donor human milk banking compared to non-clinical health workers. Donor human milk banking was not associated with religion (p = 0.498) or marital status (p = 0.714).

Conclusions
The results showed that health workers and policy informers would accept the establishment of breastmilk banks subject to resource availability. Commitment to the establishment of breastmilk banks was moderately acceptable among opinion leaders responsible for spearheading health and nutrition policies.
High-throughput three-dimensional visualization of root system architecture of rice using X-ray computed tomography
Authors: Teramoto Shota , Takayasu Satoko , Kitomi Yuka , Arai-Sanoh Yumiko , Tanabata Takanari , Uga Yusaku 
Published: May 2020

Abstract
Background
X-ray computed tomography (CT) allows us to visualize root system architecture (RSA) beneath the soil, non-destructively and in a three-dimensional (3-D) form. However, CT scanning, reconstruction processes, and root isolation from X-ray CT volumes, take considerable time. For genetic analyses, such as quantitative trait locus mapping, which require a large population size, a high-throughput RSA visualization method is required.

Results
We have developed a high-throughput process flow for the 3-D visualization of rice (Oryza sativa) RSA (consisting of radicle and crown roots), using X-ray CT. The process flow includes use of a uniform particle size, calcined clay to reduce the possibility of visualizing non-root segments, use of a higher tube voltage and current in the X-ray CT scanning to increase root-to-soil contrast, and use of a 3-D median filter and edge detection algorithm to isolate root segments. Using high-performance computing technology, this analysis flow requires only 10 min (33 s, if a rough image is acceptable) for CT scanning and reconstruction, and 2 min for image processing, to visualize rice RSA. This reduced time allowed us to conduct the genetic analysis associated with 3-D RSA phenotyping. In 2-week-old seedlings, 85% and 100% of radicle and crown roots were detected, when 16 cm and 20 cm diameter pots were used, respectively. The X-ray dose per scan was estimated at < 0.09 Gy, which did not impede rice growth. Using the developed process flow, we were able to follow daily RSA development, i.e., 4-D RSA development, of an upland rice variety, over 3 weeks.

Conclusions
We developed a high-throughput process flow for 3-D rice RSA visualization by X-ray CT. The X-ray dose assay on plant growth has shown that this methodology could be applicable for 4-D RSA phenotyping. We named the RSA visualization method ‘RSAvis3D’ and are confident that it represents a potentially efficient application for 3-D RSA phenotyping of various plant species.
Surgical repair for persistent truncus arteriosus in neonates and older children
Authors: Alamri Rawan M. , Dohain Ahmed M. , Arafat Amr A. , Elmahrouk Ahmed F. , Ghunaim Abdullah H. , Elassal Ahmed A. , Jamjoom Ahmed A. , Al-Radi Osman O. 
Published: May 2020

Abstract
Objectives
Persistent truncus arteriosus represents less than 3% of all congenital heart defects. We aim to analyze mid-term outcomes after primary Truncus arteriosus repair at different ages and to identify the risk factors contributing to mortality and the need for intervention after surgical repair.

Methods
This retrospective cohort study included 36 children, underwent repair of Truncus arteriosus in the period from January 2011 to December 2018 in two institutions. We recorded the clinical and echocardiographic data for the patients preoperatively, early postoperative, 6 months postoperative, then every year until their last documented follow-up appointment.

Results
Thirty-six patients had truncus arteriosus repair during the study period. Thirty-one patients had open sternum post-repair, and two patients required extracorporeal membrane oxygenation. Bleeding occurred in 15 patients (41.67%), and operative mortality occurred in 5 patients (14.7%). Patients with truncus arteriosus type 2 (p = 0.008) and 3 (p = 0.001) and who were ventilated preoperatively (p < 0.001) had a longer hospital stay. Surgical re-intervention was required in 8 patients (22.86%), and 11 patients (30.56%) had catheter-based reintervention. Freedom from reintervention was 86% at 1 year, 75% at 2 years and 65% at 3 years. Survival at 1 year was 81% and at 3 years was 76%. High postoperative inotropic score predicted mortality (p = 0.013).

Conclusion
Repair of the truncus arteriosus can be performed safely with low morbidity and mortality, both in neonates, infants, and older children. Re-intervention is common, preferably through a transcatheter approach.
1-O-Acetylgeopyxin A, a derivative of a fungal metabolite, blocks tetrodotoxin-sensitive voltage-gated sodium, calcium channels and neuronal excitability which correlates with inhibition of neuropathic pain
Authors: Zhou Yuan , Cai Song , Gomez Kimberly , Wijeratne E. M. Kithsiri , Ji Yingshi , Bellampalli Shreya S. , Luo Shizhen , Moutal Aubin , Gunatilaka A. A. Leslie , Khanna Rajesh 
Published: May 2020

AbstractChronic pain can be the result of an underlying disease or condition, medical treatment, inflammation, or injury. The number of persons experiencing this type of pain is substantial, affecting upwards of 50 million adults in the United States. Pharmacotherapy of most of the severe chronic pain patients includes drugs such as gabapentinoids, re-uptake blockers and opioids. Unfortunately, gabapentinoids are not effective in up to two-thirds of this population and although opioids can be initially effective, their long-term use is associated with multiple side effects. Therefore, there is a great need to develop novel non-opioid alternative therapies to relieve chronic pain. For this purpose, we screened a small library of natural products and their derivatives in the search for pharmacological inhibitors of voltage-gated calcium and sodium channels, which are outstanding molecular targets due to their important roles in nociceptive pathways. We discovered that the acetylated derivative of the ent-kaurane diterpenoid, geopyxin A, 1-O-acetylgeopyxin A, blocks voltage-gated calcium and tetrodotoxin-sensitive voltage-gated sodium channels but not tetrodotoxin-resistant sodium channels in dorsal root ganglion (DRG) neurons. Consistent with inhibition of voltage-gated sodium and calcium channels, 1-O-acetylgeopyxin A reduced reduce action potential firing frequency and increased firing threshold (rheobase) in DRG neurons. Finally, we identified the potential of 1-O-acetylgeopyxin A to reverse mechanical allodynia in a preclinical rat model of HIV-induced sensory neuropathy. Dual targeting of both sodium and calcium channels may permit block of nociceptor excitability and of release of pro-nociceptive transmitters. Future studies will harness the core structure of geopyxins for the generation of antinociceptive drugs.
Treatment of relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma with the BTK inhibitor zanubrutinib: phase 2, single-arm, multicenter study
Authors: Xu Wei , Yang Shenmiao , Zhou Keshu , Pan Ling , Li Zengjun , Zhou Jianfeng , Gao Sujun , Zhou Daobin , Hu Jianda , Feng Ru , Huang Haiwen , Ji Meng , Guo Haiyi , Huang Jane , Novotny William , Feng Shibao , Li Jianyong 
Published: May 2020

Abstract
Background
Bruton tyrosine kinase (BTK) inhibitors have demonstrated a high degree of efficacy in the treatment of B cell malignancies characterized by constitutive B cell receptor activation, including chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).

Methods
The efficacy and safety of zanubrutinib, an investigational highly selective BTK inhibitor, was evaluated in this single-arm, phase 2 study of Chinese patients with relapsed/refractory CLL/SLL. The primary endpoint was overall response rate as assessed by an independent review committee.

Results
Of the 91 evaluable patients, 77 (84.6%) achieved a response, with three (3.3%), 54 (59.3%), and 20 (22%) patients achieving a complete response, partial response, and partial response with lymphocytosis, respectively, after a median follow-up of 15.1 months. The estimated 12-month event-free rate for duration of response was 92.9%. The most commonly reported grade ≥ 3 adverse events (AEs) were neutropenia (44%), thrombocytopenia (15.4%), lung infection/pneumonia (13.2%), upper respiratory tract infection (9.9%), and anemia (8.8%). The 12-month overall survival rate was 96%. Eight (9.0%) patients discontinued zanubrutinib due to AEs, and seven (8.0%) patients required at least one dose reduction.

Conclusion
Treatment of patients with relapsed/refractory CLL/SLL with zanubrutinib was generally well tolerated and resulted in a high overall response rate, thereby conferring a favorable benefit-risk profile.

Trial registration
Prospectively registered in China public registry (CTR20160890) on December 7, 2016: http://www.chinadrugtrials.org.cn/. Retrospectively registered in ClinicalTrials.gov (NCT03206918) on July 2, 2017.
Jaffe-Campanacci syndrome or neurofibromatosis type 1: a case report of phenotypic overlap with detection of NF1 gene mutation in non-ossifying fibroma
Authors: Vannelli Silvia , Buganza Raffaele , Runfola Federica , Mussinatto Ilaria , Andreacchio Antonio , de Sanctis Luisa 
Published: May 2020

AbstractBackgroundJaffe-Campanacci syndrome is characterized by multiple non-ossifying fibromas, café-au-lait macules and giant cell granulomas of the jaw. Even if the association between all these peculiar features and neurofibromatosis type 1 have been described, it has not yet been clarified whether Jaffe-Campanacci syndrome represents a distinct entity or it can be regarded as a neurofibromatosis type 1 subtype.Case presentationThe patient here described is a young boy, who fulfilled the clinical diagnostic criteria for both syndromes. He had a complex clinical history with café-au-lait macules, axillary and inguinal freckling, multiple non-ossifying fibromas, giant-cell granuloma of the jaw, neurofibromas, plexiform fibroma, ocular Lisch nodules, optic chiasmatic- hypothalamic glioma, pseudarthrosis, scoliosis, short stature, vascular anomalies, seizures. Molecular analysis of the NF1 gene both on blood cells and non-ossifying fibroma’s biopsy tissue allowed the detection of a novel variant within the coding region, NM_000267.3:c.2789_2791delATC(p.Tyr930_Pro931delinsSer), with loss of heterozygosity (second hit mutation) in the non-ossifying fibroma.ConclusionThis result indicates that every patient with clinical features of Jaffe-Campanacci syndrome should be further evaluated to detect features related to neurofibromatosis type 1 and genetically investigated for mutations in the NF1 gene, since this could lead to a definite diagnosis, but also could clarify and quantify the real genotype-phenotype overlap between neurofibromatosis type 1 and Jaffe-Campanacci syndrome.
Preparing your intensive care unit for the COVID-19 pandemic: practical considerations and strategies
Authors: Goh Ken Junyang , Wong Jolin , Tien Jong-Chie Claudia , Ng Shin Yi , Duu Wen Sewa , Phua Ghee Chee , Leong Carrie Kah-Lai 
Published: May 2020

AbstractThe coronavirus disease 2019 (COVID-19) has rapidly evolved into a worldwide pandemic. Preparing intensive care units (ICU) is an integral part of any pandemic response. In this review, we discuss the key principles and strategies for ICU preparedness. We also describe our initial outbreak measures and share some of the challenges faced. To achieve sustainable ICU services, we propose the need to 1) prepare and implement rapid identification and isolation protocols, and a surge in ICU bed capacity; (2) provide a sustainable workforce with a focus on infection control; (3) ensure adequate supplies to equip ICUs and protect healthcare workers; and (4) maintain quality clinical management, as well as effective communication.
Defining the relative and combined contribution of CTCF and CTCFL to genomic regulation
Authors: Nishana Mayilaadumveettil , Ha Caryn , Rodriguez-Hernaez Javier , Ranjbaran Ali , Chio Erica , Nora Elphege P. , Badri Sana B. , Kloetgen Andreas , Bruneau Benoit G. , Tsirigos Aristotelis , Skok Jane A. 
Published: May 2020

Abstract
Background
Ubiquitously expressed CTCF is involved in numerous cellular functions, such as organizing chromatin into TAD structures. In contrast, its paralog, CTCFL, is normally only present in the testis. However, it is also aberrantly expressed in many cancers. While it is known that shared and unique zinc finger sequences in CTCF and CTCFL enable CTCFL to bind competitively to a subset of CTCF binding sites as well as its own unique locations, the impact of CTCFL on chromosome organization and gene expression has not been comprehensively analyzed in the context of CTCF function. Using an inducible complementation system, we analyze the impact of expressing CTCFL and CTCF-CTCFL chimeric proteins in the presence or absence of endogenous CTCF to clarify the relative and combined contribution of CTCF and CTCFL to chromosome organization and transcription.

Results
We demonstrate that the N terminus of CTCF interacts with cohesin which explains the requirement for convergent CTCF binding sites in loop formation. By analyzing CTCF and CTCFL binding in tandem, we identify phenotypically distinct sites with respect to motifs, targeting to promoter/intronic intergenic regions and chromatin folding. Finally, we reveal that the N, C, and zinc finger terminal domains play unique roles in targeting each paralog to distinct binding sites to regulate transcription, chromatin looping, and insulation.

Conclusion
This study clarifies the unique and combined contribution of CTCF and CTCFL to chromosome organization and transcription, with direct implications for understanding how their co-expression deregulates transcription in cancer.
Frequency of KCNQ1 variants causing loss of methylation of Imprinting Centre 2 in Beckwith-Wiedemann syndrome
Authors: Eßinger Carla , Karch Stephanie , Moog Ute , Fekete György , Lengyel Anna , Pinti Eva , Eggermann Thomas , Begemann Matthias 
Published: May 2020

AbstractBackgroundBeckwith-Wiedemann syndrome (BWS) is an imprinting disorder caused by disturbances of the chromosomal region 11p15.5. The most frequent molecular finding in BWS is loss of methylation (LOM) of the Imprinting Centre 2 (IC2) region on the maternal allele, which is localised in intron 10 of theKCNQ1gene. In rare cases, LOM of IC2 has been reported in families withKCNQ1germline variants which additionally cause long-QT syndrome (LQTS). Thus, a functional link between disruptedKCNQ1transcripts and altered IC2 methylation has been suggested, resulting in the co-occurrence of LQTS and BWS in case of maternal inheritance. Whereas these cases were identified by chance or in patients with abnormal electrocardiograms, a systematic screen forKCNQ1variants in IC2 LOM carriers has not yet been performed.ResultsWe analysed 52 BWS patients with IC2 LOM to determine the frequency of germline variants inKCNQ1by MLPA and an amplicon-based next generation sequencing approach. We identified one patient with a splice site variant causing premature transcription termination ofKCNQ1.ConclusionsOur study strengthens the hypothesis that properKCNQ1transcription is required for the establishment of IC2 methylation, but thatKCNQ1variants cause IC2 LOM only in a small number of BWS patients.
DNA methylation changes during preimplantation development reveal inter-species differences and reprogramming events at imprinted genes
Authors: Ivanova Elena , Canovas Sebastian , Garcia-Martínez Soledad , Romar Raquel , Lopes Jordana S. , Rizos Dimitrios , Sanchez-Calabuig Maria J. , Krueger Felix , Andrews Simon , Perez-Sanz Fernando , Kelsey Gavin , Coy Pilar 
Published: May 2020

AbstractPreimplantation embryos experience profound resetting of epigenetic information inherited from the gametes. Genome-wide analysis at single-base resolution has shown similarities but also species differences between human and mouse preimplantation embryos in DNA methylation patterns and reprogramming. Here, we have extended such analysis to two key livestock species, the pig and the cow. We generated genome-wide DNA methylation and whole-transcriptome datasets from gametes to blastocysts in both species. In oocytes from both species, a distinctive bimodal methylation landscape is present, with hypermethylated domains prevalent over hypomethylated domains, similar to human, while in the mouse the proportions are reversed.An oocyte-like pattern of methylation persists in the cleavage stages, albeit with some reduction in methylation level, persisting to blastocysts in cow, while pig blastocysts have a highly hypomethylated landscape. In the pig, there was evidence of transient de novo methylation at the 8–16 cell stages of domains unmethylated in oocytes, revealing a complex dynamic of methylation reprogramming. The methylation datasets were used to identify germline differentially methylated regions (gDMRs) of known imprinted genes and for the basis of detection of novel imprinted loci. Strikingly in the pig, we detected a consistent reduction in gDMR methylation at the 8–16 cell stages, followed by recovery to the blastocyst stage, suggesting an active period of imprint stabilization in preimplantation embryos. Transcriptome analysis revealed absence of expression in oocytes of both species of ZFP57, a key factor in the mouse for gDMR methylation maintenance, but presence of the alternative imprint regulator ZNF445. In conclusion, our study reveals species differences in DNA methylation reprogramming and suggests that porcine or bovine models may be closer to human in key aspects than in the mouse model.
Longitudinal trajectories of Alzheimer’s ATN biomarkers in elderly persons without dementia
Authors:   Alzheimer’s Disease Neuroimaging Initiative, Tan Meng-Shan , Ji Xi , Li Jie-Qiong , Xu Wei , Wang Hui-Fu , Tan Chen-Chen , Dong Qiang , Zuo Chuan-Tao , Tan Lan , Suckling John , Yu Jin-Tai 
Published: May 2020

Abstract
Background
Models of Alzheimer’s disease (AD) pathophysiology posit that amyloidosis [A] precedes and accelerates tau pathology [T] that leads to neurodegeneration [N]. Besides this A-T-N sequence, other biomarker sequences are possible. This current work investigates and compares the longitudinal trajectories of Alzheimer’s ATN biomarker profiles in non-demented elderly adults from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort.

Methods
Based on the ATN classification system, 262 individuals were identified before dementia diagnosis and accompanied by baseline and follow-up data of ATN biomarkers (CSF Aβ42, p-tau, and FDG-PET). We recorded the conversion processes in ATN biomarkers during follow-up, then analyzed the possible longitudinal trajectories and estimated the conversion rate and temporal evolution of biomarker changes. To evaluate how biomarkers changed over time, we used linear mixed-effects models.

Results
During a 6–120-month follow-up period, there were four patterns of longitudinal changes in Alzheimer’s ATN biomarker profiles, from all negative to positive through the course of the disease. The most common pattern is that A pathology biomarker first emerges. As well as the classical A-T-N sequence, other “A-first,” “T-first,” and “N-first” biomarker pathways were found. The N-A-T sequence had the fastest rate of pathological progression (mean 65.00 months), followed by A-T-N (mean 67.07 months), T-A-N (mean 68.85 months), and A-N-T sequences (mean 98.14 months).

Conclusions
Our current work presents a comprehensive analysis of longitudinal trajectories of Alzheimer’s ATN biomarkers in non-demented elderly adults. Stratifying disease into subtypes depending on the temporal evolution of biomarkers will benefit the early recognition and treatment.
Exploring the mechanisms underlying excitation/inhibition imbalance in human iPSC-derived models of ASD
Authors: Culotta Lorenza , Penzes Peter 
Published: May 2020

AbstractAutism spectrum disorder (ASD) is a range of neurodevelopmental disorders characterized by impaired social interaction and communication, and repetitive or restricted behaviors. ASD subjects exhibit complex genetic and clinical heterogeneity, thus hindering the discovery of pathophysiological mechanisms. Considering that several ASD-risk genes encode proteins involved in the regulation of synaptic plasticity, neuronal excitability, and neuronal connectivity, one hypothesis that has emerged is that ASD arises from a disruption of the neuronal network activity due to perturbation of the synaptic excitation and inhibition (E/I) balance. The development of induced pluripotent stem cell (iPSC) technology and recent advances in neuronal differentiation techniques provide a unique opportunity to model complex neuronal connectivity and to test the E/I hypothesis of ASD in human-based models. Here, we aim to review the latest advances in studying the different cellular and molecular mechanisms contributing to E/I balance using iPSC-based in vitro models of ASD.