bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of transcript-deleterious variants in Mendelian disorders: implications for RNA-based diagnostics
Authors: Maddirevula Sateesh , Kuwahara Hiroyuki , Ewida Nour , Shamseldin Hanan E. , Patel Nisha , Alzahrani Fatema , AlSheddi Tarfa , AlObeid Eman , Alenazi Mona , Alsaif Hessa S. , Alqahtani Maha , AlAli Maha , Al Ali Hatoon , Helaby Rana , Ibrahim Niema , Abdulwahab Firdous , Hashem Mais , Hanna Nadine , Monies Dorota , Derar Nada , Alsagheir Afaf , Alhashem Amal , Alsaleem Badr , Alhebbi Hamoud , Wali Sami , Umarov Ramzan , Gao Xin , Alkuraya Fowzan S. 
Published: June 2020

Abstract
Background
At least 50% of patients with suspected Mendelian disorders remain undiagnosed after whole-exome sequencing (WES), and the extent to which non-coding variants that are not captured by WES contribute to this fraction is unclear. Whole transcriptome sequencing is a promising supplement to WES, although empirical data on the contribution of RNA analysis to the diagnosis of Mendelian diseases on a large scale are scarce.

Results
Here, we describe our experience with transcript-deleterious variants (TDVs) based on a cohort of 5647 families with suspected Mendelian diseases. We first interrogate all families for which the respective Mendelian phenotype could be mapped to a single locus to obtain an unbiased estimate of the contribution of TDVs at 18.9%. We examine the entire cohort and find that TDVs account for 15% of all “solved” cases. We compare the results of RT-PCR to in silico prediction. Definitive results from RT-PCR are obtained from blood-derived RNA for the overwhelming majority of variants (84.1%), and only a small minority (2.6%) fail analysis on all available RNA sources (blood-, skin fibroblast-, and urine renal epithelial cells-derived), which has important implications for the clinical application of RNA-seq. We also show that RNA analysis can establish the diagnosis in 13.5% of 155 patients who had received “negative” clinical WES reports. Finally, our data suggest a role for TDVs in modulating penetrance even in otherwise highly penetrant Mendelian disorders.

Conclusions
Our results provide much needed empirical data for the impending implementation of diagnostic RNA-seq in conjunction with genome sequencing.
Statistical analysis plan for a cluster-randomised trial assessing the effectiveness of implementation of a bedside evidence-based checklist for clinical management of brain-dead potential organ donors in intensive care units: DONORS (Donation Network to Optimise Organ Recovery Study)
Authors: Giordani Natalia Elis , Robinson Caroline Cabral , Westphal Glauco Adrieno , Rosa Regis Goulart , Sganzerla Daniel , Cavalcanti Alexandre Biasi , Machado Flávia Ribeiro , Azevedo Luciano Cesar Pontes , Bozza Fernando Augusto , Teixeira Cassiano , de Andrade Joel , Franke Cristiano Augusto , Guterres Cátia Moreira , Madalena Itiana Cardoso , Rohden Adriane Isabel , da Silva Sabrina Souza , Andrighetto Luiza Vitelo , Rech Gabriela Soares , Gimenes Bruna dos Passos , Hammes Luciano Serpa , Pontes Daniela Ferreira Salomão , Meade Maureen O. , Falavigna Maicon 
Published: June 2020

Abstract
Background
The quality of clinical care of brain-dead potential organ donors may help reduce donor losses caused by irreversible or unreversed cardiac arrest and increase the number of organs donated. We sought to determine whether an evidence-based, goal-directed checklist for donor management in intensive care units (ICUs) can reduce donor losses to cardiac arrest.

Methods/design
The DONORS study is a multicentre, cluster-randomised controlled trial with a 1:1 allocation ratio designed to compare an intervention group (goal-directed checklist for brain-dead potential organ donor management) with a control group (standard ICU care). The primary outcome is loss of potential donors due to cardiac arrest. Secondary outcomes are the number of actual organ donors and the number of solid organs recovered per actual donor. Exploratory outcomes include the achievement of relevant clinical goals during the management of brain-dead potential organ donors. The present statistical analysis plan (SAP) describes all primary statistical procedures that will be used to evaluate the results and perform exploratory and sensitivity analyses of the trial.

Discussion
The SAP of the DONORS study aims to describe its analytic procedures, enhancing the transparency of the study. At the moment of SAP subsmission, 63 institutions have been randomised and were enrolling study participants. Thus, the analyses reported herein have been defined before the end of the study recruitment and database locking.

Trial registration
ClinicalTrials.gov, NCT03179020. Registered on 7 June 2017.
Salivary β2-microglobulin levels in patients with erosive oral lichen planus and squamous cell carcinoma
Authors: Nosratzehi Fatemeh , Nosratzehi Tahereh , Alijani Ebrahim , Rad Soha Saberi 
Published: June 2020

AbstractObjectivesβ2 microglobulin, as a biomarker, is used for the diagnosis of oral malignant and pre-malignant lesions. The components of the microglobulin system can directly or indirectly help grow and develop tumors. The present study aims to compare beta-2 microglobulin levels in patients with lichen planus of the esophagus, oral squamous cell carcinoma, and healthy individuals. Further, it evaluated the salivary β2-microglobulin level in malignant and pre-malignant lesions. Oral lichen planus (OLP) is a chronic skin-mucus disorder. Of the total 75 patients referred to Oral Medicine at Dentistry School of Zahedan University of Medical Sciences, 25 were healthy and 25 had oral lichen planus (OLP) and the rest had squamous cell carcinoma (SCC). To collect the saliva samples, unstimulated spitting was used. They were collected between 9 and 12 a.m. Salivary beta2 microglobulin was recorded based on the factory instructions by ELISA optical density method with 450 nm wavelength for each sample. The data were analyzed using descriptive, Kruskal–Wallis and Mann–Whitney and Pearson’s correlation coefficient (SPSS 21).ResultsThe salivary β2 microglobulin level in patients with squamous cell carcinoma (SCC) and oral lichen plan (OLP) is significantly higher than that in healthy group. Thus, this index is used for assessing early malignant transformation and oral pre-malignant lesion.
Epigenetic silencing of AATK in acinar to ductal metaplasia in murine model of pancreatic cancer
Authors: Ding Li-Yun , Hou Ya-Chin , Kuo I-Ying , Hsu Ting-Yi , Tsai Tsung-Ching , Chang Hsiu-Wei , Hsu Wei-Yu , Tsao Chih-Chieh , Tian Chung-Chen , Wang Po-Shun , Wang Hao-Chen , Lee Chung-Ta , Wang Yi-Ching , Lin Sheng-Hsiang , Hughes Michael W. , Chuang Woei-Jer , Lu Pei-Jung , Shan Yan-Shen , Huang Po-Hsien 
Published: June 2020

Abstract
Background
Cancer subtype switching, which involves unclear cancer cell origin, cell fate decision, and transdifferentiation of cells within a confined tumor microenvironment, remains a major problem in pancreatic cancer (PDA).

Results
By analyzing PDA subtypes in The Cancer Genome Atlas, we identified that epigenetic silencing of apoptosis-associated tyrosine kinase (AATK) inversely was correlated with mRNA expression and was enriched in the quasi-mesenchymal cancer subtype. By comparing early mouse pancreatic lesions, the non-invasive regions showed AATK co-expression in cells with acinar-to-ductal metaplasia, nuclear VAV1 localization, and cell cycle suppression; but the invasive lesions conversely revealed diminished AATK expression in those with poorly differentiated histology, cytosolic VAV1 localization, and co-expression of p63 and HNF1α. Transiently activated AATK initiates acinar differentiation into a ductal cell fate to establish apical-basal polarization in acinar-to-ductal metaplasia. Silenced AATK and ectopically expressed p63 and HNF1α allow the proliferation of ductal PanINs in mice.

Conclusion
Epigenetic silencing of AATK regulates the cellular transdifferentiation, proliferation, and cell cycle progression in converting PDA-subtypes.
Long noncoding RNA LINC00314 facilitates osteogenic differentiation of adipose-derived stem cells through the hsa-miR-129-5p/GRM5 axis via the Wnt signaling pathway
Authors: Shi Zheng-liang , Zhang Hua , Fan Zhi-yong , Ma Wei , Song Yong-zhou , Li Ming , Li Tong-qiu , Cao Shu-xing , Feng Guo-jun 
Published: June 2020

Abstract
Background
Many studies have shown that long noncoding RNAs (lncRNAs) are closely related to the stimulation of osteogenic differentiation of adipose-derived stem cells (ADSCs) and the prevention of osteoporosis. Current research aimed to investigate the novel lncRNA and explored the function and molecular mechanism of the LINC00314/miR-129-5p/GRM5 axis in regulating osteogenic differentiation of ADSCs.

Methods
LncRNA and miRNA sequencing was performed in normal and osteogenic differentiation-induced ADSCs (osteogenic group). Abnormally expressed lncRNAs and miRNAs were obtained by the R software and the relative expression of LINC00314, miR-129-5p, and GRM5 during osteogenic induction was measured by RT-PCR. ADSCs were then transfected with pcDNA3.1-sh-LINC00314 and agomiR-129-5p. Alizarin red staining (ARS) and alkaline phosphatase (ALP) staining were performed to identify the mechanism of the LINC00314/miR-129-5p/GRM5 axis in regulating osteogenic differentiation of ADSCs.

Results
LINC00314 was significantly upregulated in the group of osteogenic-induced ADSCs. LINC00314 and GRM5 mimics increased the early and late markers of osteogenic differentiation, which manifest in not only the markedly increased ALP activity but also higher calcium deposition, while miR-129-5p mimic had the opposite effects. LINC00314 directly targeted miR-129-5p through luciferase reporter assay, and miR-129-5p suppressed GRM5 expression. Moreover, the LINC00314/miR-129-5p/GRM5 regulatory axis activated the Wnt/β-catenin signaling pathway.

Conclusions
LINC00314 confers contributory function in the osteogenic differentiation of ADSCs and thus the LINC00314/miR-129-5p/GRM5 axis may be a novel mechanism for osteogenic-related disease.
A centennial-resolution terrestrial climatostratigraphy and Matuyama–Brunhes transition record from a loess sequence in China
Authors: Hyodo Masayuki , Banjo Kenta , Yang Tianshui , Katoh Shigehiro , Shi Meinan , Yasuda Yuki , Fukuda Jun-ichi , Miki Masako , Bradák Balázs 
Published: June 2020

AbstractTerrestrial records of the last geomagnetic reversal often have few age constraints. Chronostratigraphy using suborbital-scale paleoceanic events during marine isotope stage 19 may contribute to solving this problem. We applied the method to an 8 m long, high-resolution paleomagnetic record from a loess sequence in China and revealed millennial-to-sub-centennial scale features of the Matuyama–Brunhes (MB) transition. All samples were subjected to progressive thermal demagnetization with 14–15 steps up to 650–680 °C. As a result, 96% of the samples yielded a high-quality remanent magnetization. The MB transition terminated with a 75 cm thick zone with nine polarity flips. The polarity flip zone, dated at about 779–777 ka, began between the warm events “I” and “J” and terminated at the end of the cooling event coincident with the lowest axial-dipole strength interval. Most polarity flips occurred within 70 years. The virtual geomagnetic poles (VGPs) in the upper polarity flip zone clustered in the SW Pacific region, where the MB transitional VGPs from lavas of the Hawaiian and Canary Islands and lacustrine deposits of Java also clustered. These sites were probably dominated by dipolar fields. The absence of transitional fields across polarity flips implies a short time span for averaging fields due to a thin loess-magnetization lock-in zone. The reverse-to-normal polarity reversal dated at about 778 ka in Lingtai occurred at the end of the SW Pacific VGP zone, an important key bed for MB transition stratigraphy. The reversal is a good candidate for the main MB boundary. We found an excursion at about 766 ka spanning about 1 ka.
Nutritional status and the associated factors among people living with HIV: an evidence from cross-sectional survey in hospital based antiretroviral therapy site in Kathmandu, Nepal
Authors: Khatri Samip , Amatya Archana , Shrestha Binjwala 
Published: June 2020

AbstractBackgroundNutritional status is the key concern among the people living with HIV but this issue has been failed to be prioritized in HIV strategic plan of Nepal. This study aims to assess the nutritional status among people living with HIV and determine their associated factors.MethodsA hospital based cross-sectional study was conducted where 350 people living with HIV attending the ART clinic were selected using systematic random sampling technique. Nutritional status among people living with HIV was assessed through anthropometry, body mass index; Underweight (body mass index < 18.5 kg/m2) and overweight/obesity (body mass index > 23 kg/m2). HIV related clinical factors such CD4 count, WHO stage, opportunistic infection, antiretroviral therapy regimen etc. were collected from the medical records. Socio-demographic data were collected using pretested structured questionnaire through interview technique. Multiple linear regression method was employed to determine the association between different independent factors and body mass index score.ResultsThe prevalence of underweight was found to be 18.3% (95% CI: 14.3–22.6). Most of the study participants were overweight/obese (39.1%). After subjection to multiple linear regression analysis, it was found that age, being male, being married, being in business occupation, smoking, hemoglobin level and antiretroviral therapy duration were significantly associated with body mass index score. Majority of the participants in our study lacked diversified food (62.3%).ConclusionOverweight/obesity is an emerging problem among people living with HIV. This group of participants should be screened for the presence of non-communicable disease. This study also highlights the importance of nutritional program being an integral part of HIV/AIDS continuum of care. Therefore, an effort should be made to address the burden of malnutrition by addressing the identified determinants.
Application of machine learning to microseismic event detection in distributed acoustic sensing data
Authors: Stork Anna L. , Baird Alan F. , Horne Steve A. , Naldrett Garth , Lapins Sacha , Kendall J.-Michael , Wookey James , Verdon James P. , Clarke Andy , Williams Anna 
Published: June 2020

This study presents the first demonstration of the transferability of a convolutional neural network (CNN) trained to detect microseismic events in one fiber-optic distributed acoustic sensing (DAS) data set to other data sets. DAS increasingly is being used for microseismic monitoring in industrial settings, and the dense spatial and temporal sampling provided by these systems produces large data volumes (approximately 650 GB/day for a 2 km long cable sampling at 2000 Hz with a spatial sampling of 1 m), requiring new processing techniques for near-real-time microseismic analysis. We have trained the CNN known as YOLOv3, an object detection algorithm, to detect microseismic events using synthetically generated waveforms with real noise superimposed. The performance of the CNN network is compared to the number of events detected using filtering and amplitude threshold (short-term average/long-term average) detection techniques. In the data set from which the real noise is taken, the network is able to detect >80% of the events identified by manual inspection and 14% more than detected by standard frequency-wavenumber filtering techniques. The false detection rate is approximately 2% or one event every 20 s. In other data sets, with monitoring geometries and conditions previously unseen by the network, >50% of events identified by manual inspection are detected by the CNN.
The biomechanics of knuckle-walking: 3-D kinematics of the chimpanzee and macaque wrist, hand and fingers
Authors: Thompson Nathan E. 
Published: June 2020

ABSTRACT
The origin and evolution of knuckle-walking has long been a key focus in understanding African ape, including human, origins. Yet, despite numerous studies documenting morphological characteristics potentially associated with knuckle-walking, little quantitative three-dimensional (3-D) data exist of forelimb motion during knuckle-walking. Nor do any comparative 3-D data exist for hand postures used during quadrupedalism in monkeys. This lack of data has limited the testability of proposed adaptations for knuckle-walking in African apes. This study presents the first 3-D kinematic data of the wrist, hand and metacarpophalangeal joints during knuckle-walking in chimpanzees and in macaques using digitigrade and palmigrade hand postures. These results clarify the unique characteristics of, and commonalities between, knuckle-walking and digitigrady/palmigrady in multiple planes of motion. Notably, chimpanzees utilized more wrist ulnar deviation than any macaque hand posture. Maximum extension of the chimpanzee wrist was slight (5–20 deg) and generally overlapped with macaque digitigrady. Metacarpophalangeal joint motion displayed distinct differences between digits in both species, likely related to the timing of force application. These data also reveal that maximum metacarpophalangeal extension angles during knuckle-walking (26–59 deg) were generally higher than previously considered. In macaques, maximum metacarpophalangeal extension during digitigrady and palmigrady overlapped for most digits, highlighting additional complexity in the interpretation of skeletal features that may be related to limiting metacarpophalangeal motion. Most importantly, however, these new 3-D data serve as a fundamental dataset with which evaluation of proposed musculoskeletal adaptations for knuckle-walking can be tested.
Structure- and Functionality-Based Molecular Design of Azoles and Thiophenes
Authors: Mori Atsunori 
Published: June 2020

Abstract
Heteroaromatic structures are widely found in a variety of organic molecules such as π-extended oligomers/polymers, pharmaceutical drugs, agrochemicals, etc. Considerable efforts have been made for the wide use of heteroaromatic compounds. It is therefore of great interest to develop efficient and practical synthetic methodology in organic chemistry. In this account, the focus is on the molecular design of five-membered heteroaromatic compounds such as azoles and thiophenes covering transition metal-catalyzed carbon–carbon and carbon–heteroatom bond formation at the C–H bond, polymerization reactions employing coupling reactions, and a new class of structural design of heterobiaryls showing molecular asymmetry.
The interface of psychiatry and COVID-19: Challenges for management of psychiatric patients
Authors: Javed Afzal , Mohandas E. , De Sousa Avinash 
Published: June 2020

COVID-19 is a viral infection that has multisystemic physical and psychological complications. The following paper looks at the various challenges seen while treating psychiatric patients during the COVID pandemic. There is a need for physician to be aware of the drug interactions between psychiatric medications and the medications used routinely in the management of COVID. There is also the concern of psychiatric side effects of medications used to manage COVID and medical complications caused by some side effects of psychiatric drugs. The telepsychiatry and telemedicine paradigm has made it mandatory for physicians to be vigilant of the same.
doi: https://doi.org/10.12669/pjms.36.5.3073
How to cite this:Javed A, Mohandas E, De-Sousa A. The interface of psychiatry and COVID-19: Challenges for management of psychiatric patients. Pak J Med Sci. 2020;36(5):1133-1136. doi: https://doi.org/10.12669/pjms.36.5.3073
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Anatomy: learning the language
Authors: Peate Ian 
Published: June 2020

This article is the first in a series that focuses on anatomy and physiology. Human anatomy, just like any other technical subject, has its own vocabulary. When learning anatomy for the first time, it can sometimes feel like you are learning a new language. This article provides the reader with an understanding of the language used when discussing various anatomical concepts. The healthcare assistant and assistant practitioner (HCA and AP) will need to understand anatomical terminology accurately, so as to provide care that is safe and effective. The article addresses roots, prefixes and suffixes, anatomical position, regional terms, directional terms, body planes and body cavities. Each article in the series ends with a glossary of terms helping readers understand some of the terminology that has been used. A series of ‘test yourself’ questions is also provided.
How Islamic Finance can affect the Financial Stability?
Authors: Mohamed Taher Sassi , Kinski Marius 
Published: June 2020

Abstract
The subprime mortage crisis during the years 2007-2010 demonstrated the weaknesses of the conventional system of finance. The inherent speculative element of this system, which is fueled through the logic of interest additionally, brought attention to alternative approaches in order to recover control over the financial system. Islamic finance, a system relatively young in practice, contributed its part to the ongoing discussion on financial stability and has to present its own tools for this huge task. This paper wants to outline the ongoing theoretical discussion and empirical evidence concerning the question of financial stability and the role of Islamic finance in it. Main results found was Islamic finance has contributed to the overall financial stability. The survival of this financial system through the crisis of 2007-2008 has made it more and more interesting to investigate and to develop. The question of tradeoff between stability and profitability of this financial system remains under investigation as the conventional financial sector continues to be more profitable but less stable. The new avenue of the research channel in the financial sector could measure this tradeoff taking into account the future challenges.
Lower Gastrointestinal Hemorrhage Caused by Superior Rectal Artery Pseudoaneurysm
Authors: Nguyen Christopher , Baliss Michelle , Tayyem Obada , Merwat Shehzad 
Published: June 2020

ABSTRACT
Acute lower gastrointestinal (GI) bleeding is self-limiting and managed conservatively. Ongoing bleeding from a lower GI source and hemodynamic instability can create difficult diagnostic and therapeutic dilemmas. The severity of bleeding can necessitate emergent diagnostic and therapeutic interventions. Diverticulosis and angiodysplasias are the most common causes of massive lower GI hemorrhage. Other etiologies that can lead to life-threatening hemorrhage are important to recognize. We present a rare case of massive lower GI hemorrhage attributable to a superior rectal artery pseudoaneurysm. The absence of a preceding traumatic or iatrogenic cause distinguishes this case from other reports in the literature.