bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic and Therapeutic MicroRNAs in Primary Myelofibrosis
Authors: Manaila Roxana , Moisoiu Vlad , Knutsen Erik , Dragomir Mihnea P. , Calin George A.
Published: January 2021

Primary myelofibrosis (PMF) is a pluripotent hematopoietic stem cell-derived malignancy, included in the heterogeneous group of myeloproliferative neoplasms (MPNs). PMF diagnosis is based on a composite assessment of clinical and laboratory data. The three major diagnostic criteria are: screening for driver mutations, exclusion of other conditions that can cause myelofibrosis, and bone marrow biopsy displaying megakaryocyte changes and fibrosis. PMF treatment options are only partially disease-modifying and consist mainly of symptom control. Recently, a new targeted therapy was introduced for PMF patients, JAK-STAT inhibitors (i.e. ruxolitinib). However, specific subgroups of patients do not benefit from the JAK-STAT inhibitors: (1) those who are carrying JAK2 mutations, but ruxolitinib does not reduce the spleen size; (2) triple negative patients (no JAK2, CALR, or MPL mutations); and (3) those who discontinue JAK-STAT therapy because of side effects. These subgroups are in need of new therapeutic approaches. Mature microRNAs (miRNAs) range from 16 to 28 nucleotides (nt) in length and regulate specific messenger RNAs at the post-transcriptional level. Numerous in vitro and in vivo studies have reported specific miRNAs, as well as complex miRNA networks, to be dysregulated in PMF. Several of these miRNAs were shown to be implicated in essential events of PMF pathophysiology: increase of bone marrow fibrosis, progression to acute myeloid leukemia, resistance to JAK-STAT inhibitors, and activation of differentiation of hematopoietic stem/progenitor cells into megakaryocytes. Hence, we propose miRNAs as a potential minimally invasive diagnostic tool for PMF and as therapeutic targets that could address the unmet medical needs of these patients.
Multilateral Personal Portfolio Authentication System Based on Hyperledger Fabric
Authors: Jeong Junho , Kim Donghyo , Ihm Sun-Young , Lee Yangsun , Son Yunsik
Published: January 2021

Korean education-related evaluation agencies utilize a centralized system that directly manages learner data. This leaves the intellectual property of the organizations and the personal information of the students vulnerable to leakage should the central server be attacked. In this study, the researchers propose a multilateral personal portfolio authentication system that guarantees the reliability, integrity, and transparency of the data such as learner's schooling history. The system uses the features of blockchain in a distributed network wherein a learner submits schooling data to a peer in the network. The data is then verified through an agreement among the peers and recorded in a chronologically encrypted ledger. The proposed system is implemented based on Hyperledger Fabric and the analysis thereof conducted by evaluating its processing speed, capacity, and security. The analysis indicates that the system is able to successfully intercept the transactions of unvalidated users, thereby preventing the recording of incorrect data by an unauthorized user. Furthermore, it provides a record of previously made changes to a learner's profile, thus improving the integrity and reliability of the data. This system provides a platform to share learner information safely and promptly among schools, certification authorities, and higher learning institutions.
The Complete Mitochondrial Genome of the American Palm Cixiid, Haplaxius crudus (Hemiptera: Cixiidae)
Authors: Komondy Lidia , Huguet-Tapia Jose , Ascunce Marina S. , Helmick Ericka E. , Goss Erica M. , Bahder Brian W.
Published: January 2021

Haplaxius crudus Van Duzee is a pest of various economically important palms due to its ability to transmit lethal yellowing, a fatal phytoplasma infection. It is also the putative vector of lethal bronzing in Florida, another lethal phytoplasma disease causing significant economic losses. To date, no mitochondrial genomes for species in the family Cixiidae are sequenced. In this study, the complete mitochondrial genome of H. crudus was sequenced, assembled, and annotated from PacBio Sequel II long sequencing reads using the University of Florida’s HiPerGator. The mitogenome of H. crudus is 15,848 bp long and encodes 37 mitochondrial genes (including 13 protein-coding genes (PCGs), 22 tRNAs, and 2 rRNAs) in addition to a putative noncoding internal control region. The nucleotide composition of H. crudus is asymmetric with a bias toward A/T (44.8 %A, 13.4 %C, 8.5 %G, and 33.3 %T). Protein-coding genes (PCGs) possess the standard invertebrate mitochondrial start codons with few exceptions while the gene content and order of the H. crudus mitogenome is highly similar to most completely sequenced insect mitochondrial genomes. Phylogenetic analysis based on the entire mitogenome shows H. crudus resolving closely to Delphacidae, the accepted sister taxon of Cixiidae. These data provide a useful resource for developing novel primer sets that could aid in either phylogenetic studies or population genetic studies. As more full mitogenomes become available in the future for other planthopper species, more robust phylogenies can be constructed, giving more accurate perspectives on the evolutionary relationships within this fascinating and economically important group of insects.
The Role of CARD9 Deficiency in Neutrophils
Authors: Sheng Ruanmei , Zhong Xiaoming , Yang Zhiwen , Wang Xuemin
Published: January 2021

Neutrophils play a critical role in innate immune defense and directly contribute to infectious and autoimmune ailments. Great efforts are underway to better understand the nature of neutrophilic inflammation. Of note, CARD9, a myeloid cell-specific signaling protein that mainly expresses in macrophages and dendritic cells, is also present in neutrophils, emerging as a critical mediator for intercellular communication. CARD9–deficiency neutrophils display an increased susceptibility to fungal infection that primarily localize to the central nervous system, subcutaneous, and skin tissue. Additionally, CARD9–deficiency neutrophils are associated with some autoimmune diseases and even provide protection against a few bacteria. Here, the review summarizes recent preclinical and clinical advances that have provided a novel insight into the pathogenesis of CARD9 deficiency in neutrophils.
A Unique Case of Incomplete Bifid Ureter and Associated Arterial Variations
Authors: Ahuja Shivika , Sullivan Hannah , Noller Mark , Tan Yun , Daly Daniel
Published: January 2021

Introduction. Urogenital and vascular anomalies, including a left duplex kidney and a left aberrant renal artery that gave rise to the left ovarian artery, were observed in a 77-year-old female cadaver during a routine dissection. Description. A left aberrant renal artery, which gave rise to the left ovarian artery, was observed originating from the aorta 4 cm below the left renal artery. Two independent contributions to a bifid ureter were found originating from the hilum of the left kidney. These two contributions descended 12.4 cm and 10.6 cm, respectively, posterior to the left aberrant renal artery and lateral to the left ovarian artery before uniting anterior to the psoas major muscle to descend 12.7 cm to the bladder. Significance. While the duplex kidney is a relatively common congenital anomaly that can be asymptomatic, it can also potentially be associated with compression of renal vasculature or the ureter. Ureteral compression can then result in several pathologies including reflux, urinary tract infection (UTI), ureteropelvic junction obstruction, or hydronephrosis. Compression of renal and ovarian vasculature can result in altered blood flow to the kidney and ovary, potentially causing fibrosis, atrophy, or organ failure. Current imaging techniques alone are insufficient for correct diagnostics of such complications, and they must be supplemented with a thorough understanding of the respective anatomical variations.
Clinicopathological Characteristics of Breast Ductal Carcinoma In Situ: An Analysis of Chinese Population of 617 Patients
Authors: Mao Guangmin , Shi Xiu-hua , Wang Xiaofang , Zhang Xiaomeng , Chen Xingxing , Ma Jinli , Yu Xiaoli , Zhang Zhen , Guo Xiaomao
Published: January 2021

Background. The purpose of this study was to describe the clinicopathological characteristics of breast DCIS in Chinese women and compare with that of patients in western countries. Method. From December 2005 to December 2015, 617 women diagnosed with pure DCIS after surgery at our institution were enrolled, and the clinicopathological characteristics were described. Results. In this study, the percentage of patients detected on screening, diagnosed at ≤50 years of age, with tumor size ≤2.0 cm, and with low-intermediate grade was 39.4%, 56.7%, 72.6%, and 77.4%, respectively, as compared to 50–80%, 20–30%, 70–90%, and 40–60% in published reports from western countries. The percentage of ER-positive patients was 76.3% in this study, which is similar to the mean expression rate of ER (mean: 68.7%, range: 49–96.6%) reported previously. Conclusions. The clinicopathological characteristics of Chinese DCIS patients include less detection on screening, younger age at diagnosis, and more low-intermediate nuclear grade.
Use of neem (Azadirachta indica A. Juss) as a biopesticide in agriculture: A review
Authors: Adhikari Kripa , Bhandari Sudip , Niraula Dikshya , Shrestha Jiban
Published: January 2021

Neem (Azadirachta indica A. Juss) is a member of Meliaceae family, a fast-growing tropical evergreen plant whose products were found effective against economically important insect pests and diseases. All parts of this plant particularly leaf, bark, and root extracts have the biopesticidal activities. Azadirachtin, a biopesticide obtained from neem extract, can be used for con-trolling various insect pests in agriculture. It acts on insects by repelling them, by inhibiting feeding, and by disrupting their growth, and reproduction. Neem-based formulations do not usually kill insects directly, but they can alter their behavior in significant ways to reduce pest damage to crops and reduce their reproductive potential. The neem is considered as an eas-ily accessible, eco-friendly, biodegradable, cheap, and non-toxic biopesticide which control the target pests. Thus, this re-view highlighted the extract, byproducts and roles of neem that can be used as potential biopesticide in agriculture.
Multicohort Metabolomics Analysis Discloses 9‐Decenoylcarnitine to Be Associated With Incident Atrial Fibrillation
Authors: Lind Lars , Salihovic Samira , Sundström Johan , Broeckling Corey D. , Magnusson Patrik K. , Prenni Jessica , Fall Tove , Ärnlöv Johan
Published: January 2021

Background

The molecular mechanisms involved in atrial fibrillation are not well known. We used plasma metabolomics to investigate if we could identify novel biomarkers and pathophysiological pathways of incident atrial fibrillation.

Methods and Results

We identified 200 endogenous metabolites in plasma/serum by nontargeted ultra‐performance liquid chromatography coupled to time‐of‐flight mass spectrometry in 3 independent population‐based samples (TwinGene, n=1935, mean age 68, 43% females; PIVUS [Prospective Investigation of the Vasculature in Uppsala Seniors], n=897, mean age 70, 51% females; and ULSAM [Uppsala Longitudinal Study of Adult Men], n=1118, mean age 71, all males), with available data on incident atrial fibrillation during 10 to 12 years of follow‐up. A meta‐analysis of ULSAM and PIVUS was used as a discovery sample and TwinGene was used for validation. In PIVUS, we also investigated associations between metabolites of interest and echocardiographic indices of myocardial geometry and function. Genome‐wide association studies were performed in all 3 cohorts for metabolites of interest. In the meta‐analysis of PIVUS and ULSAM with 430 incident cases, 4 metabolites were associated with incident atrial fibrillation at a false discovery rate <5%. Of those, only 9‐decenoylcarnitine was associated with incident atrial fibrillation and replicated in the TwinGene sample (288 cases) following adjustment for traditional risk factors (hazard ratio, 1.24 per unit; 95% CI, 1.06–1.45,
P
=0.0061). A meta‐analysis of all 3 cohorts disclosed another 4 significant metabolites. In PIVUS, 9‐decenoylcarnitine was related to left atrium size and left ventricular mass. A Mendelian randomization analysis did not suggest a causal role of 9‐decenoylcarnitine in atrial fibrillation.

Conclusions

A nontargeted metabolomics analysis disclosed 1 novel replicated biomarker for atrial fibrillation, 9‐Decenoylcarnitine, but this acetylcarnitine is likely not causally related to atrial fibrillation.
Augustine on Active Perception, Awareness, and Representation
Authors: Nawar Tamer
Published: January 2021

It is widely thought that Augustine thinks perception is, in some distinctive sense, an active process and that he takes conscious awareness to be constitutive of perception. I argue that conscious awareness is not straightforwardly constitutive of perception and that Augustine is best understood as an indirect realist. I then clarify Augustine’s views concerning the nature and role of diachronically unified conscious awareness and mental representation in perception, the nature of the soul’s intentio, and the precise sense(s) in which perception is an active process.
The Aural Impact of Solecisms in Revelation
Authors: Best Garrett
Published: January 2021

Scholars have proposed as many as 232 solecisms (morpho-syntactical errors) within the Greek of the Apocalypse. One of the great paradoxes of the book is its astonishing complexity expressed in such irregular Greek. While numerous scholars have sought to account for and explain the solecisms in Revelation, few have explored the aural dimension. Since the book was designed to be read aloud to early churches in Asia, it is important to investigate how irregular grammar would have affected the first hearers. This paper attempts to fill this lacuna by examining how solecisms were viewed in the ancient world and how ancients responded when lectors made mistakes in reading. This paper will then draw on the insights of ancient rhetorical handbooks to provide new insight into the irregular grammar of Revelation.
Provenance and the Holy Grail of Purpose in Recent Markan Research
Authors: Jensen Morten Hørning
Published: January 2021

Since Willi Marxsen’s break with the consensus view that the Gospel of Mark was most probably written in Rome, the question of provenance has played a crucial role in discussions of Mark’s purpose. While several researchers (most notably Dwight Peterson) have pointed out how using provenance as the hermeneutical key to Mark may involve a risk of circular reasoning, recent contributions have tied discussions of Mark’s purpose ever more tightly to the question of where the gospel was written. After outlining these recent research developments, this article argues for an alternative way of handling the question of Mark’s provenance, one that emphasizes how the major themes of Mark’s gospel touch upon longstanding issues within Second Temple Judaism, which means that a particular provenance is not needed as a hermeneutical crutch for establishing Mark’s purpose.
Alessandro Bausani and ‘Muslim Languages’, Forty Years After
Authors: Rossi Adriano V.
Published: January 2021

Resorting to personal memories from the 1960s, 1970s and 1980s, the author, who defended in 1971 at the University of Rome a thesis entitled Iranian Elements in Brahui, under Prof. Bausani’s direction (later revised and published under the title Iranian lexical elements in Brāhūī [Naples: Istituto Universitario Orientale, 1979]), reconstructs the political and cultural climate in which – at the end of the 1970s – a major subject of enquiry was the problem of the nature of the national unity among the countries of the Arab world.

At the urging of Biancamaria Scarcia, Bausani decided to publish at the Institute of Islamic Studies of the University of Rome a volume of historical and linguistic essays coordinated by himself and B. Scarcia (Mondo islamico tra interazione e acculturazione [Roma: Istituto di studi islamici, 1981]). In this volume, Bausani published an essay on the concept of ‘Islamic language’ that took stock of his previous proposals made over more than twenty years (starting with his speech at the 1966 Ravello conference on a comparative history of the Islamic literatures).

The author demonstrates that notwithstanding his use of linguistic terminology, Bausani’s main interest has always been the investigation of the possibility of identifying minimum distinctive traits present in the different literary typologies of various countries of Islamic culture.
Styrax hwangiae (Styracaceae), a new species endemic to limestone areas of Guangxi, China
Authors: XU WEI-BIN , YANG PING , HUANG YU-SONG , ZHANG RUI , TANG MING
Published: January 2021

Styrax hwangiae, a new species with a narrow geographic distribution in limestone areas of Jingxi and Longzhou counties, Guangxi, China, is here described. The new species is similar to S. rugosus in habit, rugose leaves, shape of flowers and fruits, and to S. tonkinensis in habit and leaf shape, but it differs from S. rugosus by its longer petiole, paniculate or racemose inflorescence with more flowers, calyx abaxially tissue extend outward into many spires covered by many trichomes, flexuous longer filaments, and larger fruits with thicker pericarp, and from S. tonkinensis in its thickly leathery and rugose leaf blades, larger calyx and shorter peduncles. Colour plates of S. hwangiae, a distribution map and a table comparing the morphology of the three species are provided.
Comparison of adverse perinatal outcomes between Asians and Caucasians: a population-based retrospective cohort study in Ontario
Authors: Zeng Na , Erwin Erica , Wen Wendy , Corsi Daniel J. , Wen Shi Wu , Guo Yanfang
Published: January 2021

Background

Racial disparities in adverse perinatal outcomes have been studied in other countries, but little has been done for the Canadian population. In this study, we sought to examine the disparities in adverse perinatal outcomes between Asians and Caucasians in Ontario, Canada.

Methods

We conducted a population-based retrospective cohort study that included all Asian and Caucasian women who attended a prenatal screening and resulted in a singleton birth in an Ontario hospital (April 1st, 2015-March 31st, 2017). Generalized estimating equation models were used to estimate the independent adjusted relative risks and adjusted risk difference of adverse perinatal outcomes for Asians compared with Caucasians.

Results

Among 237,293 eligible women, 31% were Asian and 69% were Caucasian. Asians were at an increased risk of gestational diabetes mellitus, placental previa, early preterm birth (< 32 weeks), preterm birth, emergency cesarean section, 3rd and 4th degree perineal tears, low birth weight (< 2500 g, < 1500 g), small-for-gestational-age (<10th percentile, <3rd percentile), neonatal intensive care unit admission, and hyperbilirubinemia requiring treatment, but had lower risks of preeclampsia, macrosomia (birth weight > 4000 g), large-for-gestational-age neonates, 5-min Apgar score < 7, and arterial cord pH ≤7.1, as compared with Caucasians. No difference in risk of elective cesarean section was observed between Asians and Caucasians.

Conclusion

There are significant differences in several adverse perinatal outcomes between Asians and Caucasians. These differences should be taken into consideration for clinical practices due to the large Asian population in Canada.
The surgical treatment of non-metastatic melanoma in a Clinical National Melanoma Registry Study Group (CNMR): a retrospective cohort quality improvement study to reduce the morbidity rates
Authors:   on behalf of the Clinical National Melanoma Registry Study Group at the Italian Melanoma Intergroup (IMI), Vecchiato Antonella , Mocellin Simone , Del Fiore Paolo , Tosti Giulio , Ascierto Paolo A. , Corradin Maria Teresa , De Giorgi Vincenzo , Giudice Giuseppe , Queirolo Paola , Ferreli Caterina , Occelli Marcella , Giordano Monica , Trevisan Giusto , Mascheroni Luigi , Testori Alessandro , Spina Romina , Buja Alessandra , Cavallin Francesco , Caracò Corrado , Sommariva Antonio , Rossi Carlo Riccardo
Published: January 2021

Background

Reproducible, high-quality surgery is a key point in the management of cancer patients. Quality indicators for surgical treatment of melanoma has been presented with benchmarks but data on morbidity are still limited. This study presents the quality indicators on morbidity after surgical treatment for non-metastatic skin melanoma in an Italian registry.

Methods

Data were extracted from the Central National Melanoma Registry (CNMR) promoted by the Italian Melanoma Intergroup (IMI). All surgical procedures (WE, SNLB or LFND) for non-metastatic skin melanoma between January 2011 and February 2017 were evaluated for inclusion in the study. Only centers with adequate completeness of information (> 80%) were included in the study. Short-term complications (wound infection, dehiscence, skin graft failure and seroma) were investigated.

Results

Wound infection rate was 1.1% (0.4 to 2.7%) in WE, 1.3% (0.7 to 2.5%) in SLNB and 4.1% (2.1 to 8.0%) in LFND. Wound dehiscence rate was 2.0% (0.8 to 5.1%) in WE, 0.9% (0.2 to 3.0%) in SLNB and 2.8% (0.9 to 8.6%) in LFND. Seroma rate was 4.2% (1.5 to 11.1%) in SLNB and 15.1% (4.6 to 39.9%) in LFND. Unreliable information was found on skin graft failure.

Conclusions

Our findings contribute to available literature in setting up the recommended standards for melanoma centers, thus improving the quality of surgery offered to patients. A consensus on the core issues around surgical morbidity is needed to provide practical guidance on morbidity prevention and management.
MiR-608 overexpression in idiopathic pulmonary fibrosis (IPF)
Authors: Epstein Shochet Gali , Israeli-Shani Lilach , Kains Isabelle , Wand Ori , Shitrit David
Published: January 2021

Background

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease that causes scarring of the lungs. The disease is associated with the usual interstitial pneumonia pattern, which was not yet fully recapitulated by an animal model. Therefore, the disease is considered ‘human specific’. miRNA-608 is a primate specific miRNA with many potential targets, such CdC42 and Interlukin-6 (IL-6) that were previously implicated in IPF pathology.

Objective

To test miR-608 expression and its targets in IPF patient samples.

Methods

RNA was extracted from Formalin fixed paraffin embedded tissue sections (N = 18). miRNA-608 and Cdc42 and IL-6 levels were analyzed by qPCR. Acetylcholinesterase (AChE) is another target of miRNA-608. Its’ rs17228616 allele has a single-nucleotide polymorphism causing weakened miR-608 interaction (C2098A). Thus, DNA was extracted from whole blood samples from 56 subjects with fibrosing interstitial lung disease and this region was sequenced for assessment of rs17228616 allele polymorphism.

Results

miR-608 is significantly overexpressed in IPF samples in comparison with controls (p < 0.05). Cdc42 and IL-6 levels were lower in the IPF patient samples compared with control samples (p < 0.001 and p < 0.05, respectively). The frequency of the rs17228616 minor A-allele was 17/56 (30.4%) with all patients being heterozygous. This result is significant vs. the published Israeli cohort of healthy individuals, which reported 17% prevalence of this allele in healthy control volunteers (p = 0.01, OR = 2.1, CI 95% [1.19–3.9]).

Conclusion

miR-608 is overexpressed in IPF patients. While the exact mechanism remains to be discovered, it could potentially promote fibrotic disease.
Widespread occurrence of microRNA-mediated target cleavage on membrane-bound polysomes
Authors: Yang Xiaoyu , You Chenjiang , Wang Xufeng , Gao Lei , Mo Beixin , Liu Lin , Chen Xuemei
Published: January 2021

Background

Small RNAs (sRNAs) including microRNAs (miRNAs) and small interfering RNAs (siRNAs) serve as core players in gene silencing at transcriptional and post-transcriptional levels in plants, but their subcellular localization has not yet been well studied, thus limiting our mechanistic understanding of sRNA action.

Results

We investigate the cytoplasmic partitioning of sRNAs and their targets globally in maize (Zea mays, inbred line “B73”) and rice (Oryza sativa, cv. “Nipponbare”) by high-throughput sequencing of polysome-associated sRNAs and 3′ cleavage fragments, and find that both miRNAs and a subset of 21-nucleotide (nt)/22-nt siRNAs are enriched on membrane-bound polysomes (MBPs) relative to total polysomes (TPs) across different tissues. Most of the siRNAs are generated from transposable elements (TEs), and retrotransposons positively contributed to MBP overaccumulation of 22-nt TE-derived siRNAs (TE-siRNAs) as opposed to DNA transposons. Widespread occurrence of miRNA-mediated target cleavage is observed on MBPs, and a large proportion of these cleavage events are MBP-unique. Reproductive21PHAS(21-nt phasiRNA-generating) and24PHAS(24-nt phasiRNA-generating) precursors, which were commonly considered as noncoding RNAs, are bound by polysomes, and high-frequency cleavage of21PHASprecursors by miR2118 and24PHASprecursors by miR2275 is further detected on MBPs. Reproductive 21-nt phasiRNAs are enriched on MBPs as opposed to TPs, whereas 24-nt phasiRNAs are nearly completely devoid of polysome occupancy.

Conclusions

MBP overaccumulation is a conserved pattern for cytoplasmic partitioning of sRNAs, and endoplasmic reticulum (ER)-bound ribosomes function as an independent regulatory layer for miRNA-induced gene silencing and reproductive phasiRNA biosynthesis in maize and rice.
Crosstalk between codon optimality and cis-regulatory elements dictates mRNA stability
Authors: Medina-Muñoz Santiago Gerardo , Kushawah Gopal , Castellano Luciana Andrea , Diez Michay , DeVore Michelle Lynn , Salazar María José Blanco , Bazzini Ariel Alejandro
Published: January 2021

Background

The regulation of messenger RNA (mRNA) stability has a profound impact on gene expression dynamics during embryogenesis. For example, in animals, maternally deposited mRNAs are degraded after fertilization to enable new developmental trajectories. Regulatory sequences in 3′ untranslated regions (3′UTRs) have long been considered the central determinants of mRNA stability. However, recent work indicates that the coding sequence also possesses regulatory information. Specifically, translation in cis impacts mRNA stability in a codon-dependent manner. However, the strength of this mechanism during embryogenesis, as well as its relationship with other known regulatory elements, such as microRNA, remains unclear.

Results

Here, we show that codon composition is a major predictor of mRNA stability in the early embryo. We show that this mechanism works in combination with other cis-regulatory elements to dictate mRNA stability in zebrafish and Xenopus embryos as well as in mouse and human cells. Furthermore, we show that microRNA targeting efficacy can be affected by substantial enrichment of optimal (stabilizing) or non-optimal (destabilizing) codons. Lastly, we find that one microRNA, miR-430, antagonizes the stabilizing effect of optimal codons during early embryogenesis in zebrafish.

Conclusions

By integrating the contributions of different regulatory mechanisms, our work provides a framework for understanding how combinatorial control of mRNA stability shapes the gene expression landscape.
Disome-seq reveals widespread ribosome collisions that promote cotranslational protein folding
Authors: Zhao Taolan , Chen Yan-Ming , Li Yu , Wang Jia , Chen Siyu , Gao Ning , Qian Wenfeng
Published: January 2021

Background

The folding of proteins is challenging in the highly crowded and sticky environment of a cell. Regulation of translation elongation may play a crucial role in ensuring the correct folding of proteins. Much of our knowledge regarding translation elongation comes from the sequencing of mRNA fragments protected by single ribosomes by ribo-seq. However, larger protected mRNA fragments have been observed, suggesting the existence of an alternative and previously hidden layer of regulation.

Results

In this study, we performed disome-seq to sequence mRNA fragments protected by two stacked ribosomes, a product of translational pauses during which the 5′-elongating ribosome collides with the 3′-paused one. We detected widespread ribosome collisions that are related to slow ribosome release when stop codons are at the A-site, slow peptide bond formation from proline, glycine, asparagine, and cysteine when they are at the P-site, and slow leaving of polylysine from the exit tunnel of ribosomes. The structure of disomes obtained by cryo-electron microscopy suggests a different conformation from the substrate of the ribosome-associated protein quality control pathway. Collisions occurred more frequently in the gap regions between α-helices, where a translational pause can prevent the folding interference from the downstream peptides. Paused or collided ribosomes are associated with specific chaperones, which can aid in the cotranslational folding of the nascent peptides.

Conclusions

Therefore, cells use regulated ribosome collisions to ensure protein homeostasis.
Clostridium difficile appendicitis in an immunocompromised patient: a case report and review of the literature
Authors: Pham Charles Dac , Hua Duong Tommy
Published: January 2021

Background

Clostridium difficile (C. difficile) is a common cause of infectious colitis in individuals with prior antibiotic or hospital exposure. Extraintestinal manifestations of C. difficile infections, however, are rare. Here we present a case of C. difficile appendicitis in an immunocompromised patient.

Case presentation

A 53-year-old Caucasian male presented to the emergency room for two days of lower abdominal pain associated with nausea and subjective fevers. He otherwise denied having diarrhea or hematochezia. He did not have any recent hospitalizations, nursing home stays, or antibiotic exposure. His past medical history was notable for stage III tonsillar squamous cell carcinoma for which he was status post tonsillectomy, radiation therapy, and chemotherapy (cisplatin 4 days prior to presentation). He was afebrile with tenderness to palpation in the bilateral lower quadrants, right greater than left. His white blood cell (WBC) count was 15.6 × 103 cells/μL. Computed tomography (CT) of the abdomen and pelvis showed marked edema and inflammation of the cecum and ascending colon as well as an enlarged appendix with surrounding inflammatory changes with a small amount of free fluid in the right paracolic gutter. He was treated non-surgically with antibiotics. He did not clinically improve and on hospital day 3, he developed diarrhea for which C. difficile stool polymerase chain reaction was sent. Repeat CT of the abdomen and pelvis was performed which showed progression to pan-colitis and persistent appendicitis. C. difficile testing later resulted positive, for which oral vancomycin was started. The patient markedly improved with medical management alone and was subsequently discharged on oral vancomycin.

Conclusions

Our case highlights the importance of maintaining a high index of suspicion for C. difficile in a patient presenting with both appendicitis and colitis, with prompt diagnosis and treatment being essential.
Equipping community health workers with digital tools for pandemic response in LMICs
Authors: Feroz Anam Shahil , Khoja Adeel , Saleem Sarah
Published: January 2021

Background

Community health workers (CHWs) are well-positioned to play a pivotal role in fighting the pandemic at the community level. The Covid-19 outbreak has led to a lot of stress and anxiety among CHWs as they are expected to perform pandemic related tasks along with the delivery of essential healthcare services. In addition, movement restrictions, lockdowns, social distancing, and lack of protective gear have significantly affected CHWs’ routine workflow and performance. To optimize CHWs’ functioning, there is a renewed interest in supporting CHWs with digital technology to ensure an appropriate pandemic response.

Discussion

The current situation has necessitated the use of digital tools for the delivery of Covid-19 related tasks and other essential healthcare services at the community level. Evidence suggests that there has been a significant digital transformation to support CHWs in these critical times such as remote data collection and health assessments, the use of short message service and voice message for health education, use of digital megaphones for encouraging behavior change, and digital contract tracing. A few LMICs such as Uganda and Ethiopia have been successful in operationalizing digital tools to optimize CHWs’ functioning for Covid-19 tasks and other essential health services.

Conclusion

Yet, in most LMICs, there are some challenges concerning the feasibility and acceptability of using digital tools for CHWs during the Covid-19 pandemic. In most cases, CHWs find it difficult to adopt and use digital health solutions due to lack of training on new digital tools, weak technical support, issues of internet connectivity, and other administrative related challenges. To address these challenges, engaging governments would be essential for training CHWs on user-friendly digital health solutions to improve routine workflow of CHWs during the Covid-19 pandemic.
Diagnostic performance of high-resolution ultrasound in pre- and postoperative evaluation of the hand tendons injuries
Authors: Baz Ahmed Abdelrahman Mohamed , Hussien Aya Bahaa , Samad Hesham Mostafa Abdel , El-Azizi Hatem Mohamed Said
Published: January 2021

Background

Hand tendon injuries are recognized clinical entities that are frequently seen. Clinical examinations usually warrant radiological correlative studies for confirmation and as a postoperative screening test. Here is a prospective observational cohort study enrolling 30 patients who were diagnosed clinically to have hand tendon injuries either pre- or postoperative; their ages were ranging from 5 to 64 years with a mean ± SD of 31.43 ± 12.19 years; 23 male patients (76.7%) and 7 female patients (23.3%) were evaluated by high-resolution ultrasound examination and a correlative evaluation was done by either intra-operative assessment or MRI study as gold standards.

Results

High-resolution ultrasound (HRUS) findings were binned into seventeen cases (56%) that had tendon tears, of which 10 cases (33.3%) had a complete tear and 7 cases (23.3%) had a partial tear. Postoperative tendon integrity was present in 13 cases (43.3%), a tendon callus was found in 2 cases (6.66%), and a postoperative abnormal motion on the dynamic study was present in 15 cases (50%). Intra-tendinous foreign bodies were detected in two cases (6.66%), a gap between the torn ends was found in 10 cases (33.3%), and re-tear (rupture) of the repaired tendons was present in four cases (13.3%). Coexistent nerve injuries were seen in two cases (6.66%); for the forementioned findings, HRUS had gained high accuracy measures as correlated to the gold standards (100% sensitivity and 100% specificity).

Conclusion

High-resolution ultrasound serves as a highly accurate potential diagnostic modality for preoperative evaluation of hand tendon injuries and the postoperative follow-up.
Da constitucionalidade da prorrogação antecipada das concessões de serviço público
Authors: Montenegro Viviani Guimarães Felipe
Published: January 2021

Este artigo trata da prorrogação antecipada das concessões de serviço público. Ele justifica-se, entre outras razões, porque a prorrogação antecipada de inúmeras concessões foi autorizada recentemente no Brasil por diversos atos normativos, de modo que o interesse teórico e prático pelo tema realmente é muito grande neste momento em nosso país. Assim, o objetivo deste artigo é verificar se a prorrogação antecipada é, ou não, compatível com a Constituição da República. E a hipótese de pesquisa é que essa espécie de prorrogação é constitucional. O método de abordagem do tema é o dedutivo, e o método de pesquisa, o bibliográfico. Por fim, a principal conclusão deste artigo é que a prorrogação antecipada das concessões de serviço público é compatível com a Constituição da República, o que confirma a hipótese de pesquisa.
A interpretação da Lei de Improbidade Administrativa entre o interesse público e os direitos individuais de defesa
Authors: Luís Kanayama Rodrigo , Alberto Kanayama Ricardo
Published: January 2021

Desde a sua promulgação, a Lei de Improbidade Administrativa (LIA) divide os intérpretes. Partindo de tipos ideais que dividem a doutrina do direito administrativo em dois grupos (um que dá ênfase ao “interesse público” e outro que dá ênfase aos “direitos subjetivos”), a tese deste trabalho usa como objeto de análise a maneira como a doutrina tem interpretado o alcance das sanções previstas no art. 12, da LIA, uma vez que elas não têm contornos claros. Observa-se que a interpretação da LIA oscila entre uma visão ampliativa, que aumenta o espectro sancionatório, e uma visão restritiva, que diminui as hipóteses de incidência da sanção. Assim, enquanto a primeira teria por objetivo maior a proteção do chamadointeresse público, a segunda daria primazia aos direitos individuais de defesa.
Stroke in young adults – a challenge for etiology, treatment and rehabilitation
Authors: ROMAN-FILIP Corina , CATANĂ Maria-Gabriela
Published: January 2021

Strokes occur rarely in individuals under the age of 45 and are even more uncommon under the age of 30, the etiology of this pathology in young adults being generally related to unknown or unusual causes. We present the cases of three young adults that suffered strokes with three different unusual etiologies. The three men were 30, 36 and 43 years old, with no pathological antecedents, with neurological symptoms characteristic for stroke. Because the differential diagnostics are sometimes tricky, in all three cases imagery was very helpful. It is necessary to emphasize that in these cases one of the most important things to know is the etiology. It is very important to treat the effect too; this is the reason why we never miss an opportunity to use alteplase when all conditions are met. Common rehabilitation regimes for young adults, who have suffered a stroke, include a combination of physiotherapy, occupational therapy, speech-language therapy, and pharmacological therapy. Strategies to improve motor recovery in young patients include constraint-induced movement therapy, robot-aided rehabilitation, virtual reality training, functional electrical stimulation, increased exercise intensity, and acupuncture.

Keywords: stroke, young patients, etiology, thrombophilia, drugs abuse, artery dissection, rehabilitation,
The effect of the thrombolytic therapy on the early rehabilitation of patients with acute ischemic stroke – study report
Authors: MUTU Cătălin Cosmin , CEREI Larisa-Georgiana
Published: January 2021

Introduction. r-TPA intravenous thrombolytic therapy is a big step in acute management of ischemic stroke (IS) but is burdened by a small therapeutic window (max. 4.5 hours) that restricts patient access. NIH stroke scale (NIHSS) is the largest worldwide tool used by doctors in order to objectively quantify the severity of neurological impairment in acute IS, in the initial stage as well as in the subsequent stages. Material and method. The aim of this paper is to present the results of an observational, prospective, analytical study on a number of 110 patients with acute IS, hospitalized within two months in the Neurology Clinic of Sibiu (19 patients with thrombolytic therapy applied, 91 patients with classic therapy). NIHSS has been applied to all patients on the first day of the admission and at the discharge date. Results and discussions. The mean value of NIHSS at admission and at discharge (A/D) were 12,84/4.06 points for the patient with thrombolytic therapy and 7,73/4,45 points for the patients without thrombolytic therapy. In hospital NIHSS score reduction, meaning early recovery of patients, was consistent with type of applied therapy (8.78 vs3.28 points). The pattern of neurological impairment is specific for each subtype of IS. Conclusions. The degree of early recovery was superior for patients with versus without thrombolytic therapy (68.4% versus 42.4%). Average hospital care period was reduced with 8,33% for patients with thrombolytic therapy (11,4 versus 12,2 days care in hospital).

Keywords: ischemic stroke, early rehabilitation, NIH stroke scale, neurological pattern,
The ascent and decline of a great balneological resort: PUCIOASA
Authors: TEOIBAS-SERBAN Doroteea , IORDACHE Liviu , BLENDEA Dan
Published: January 2021

Introduction. Pucioasa is one of the greater and sadly, almost forgotten balneological resort of Romania. Known since the 18th century, where it was discovered a record of this area on the Austrian map in 1791 with sulphurous streams, the healing waters of the “Pe Pucioasa” hill enters the therapeutic balneological circle when the first water analysis occurred – 1821-1828 by Dr. Trangot von Schobel. In 1878, Ion Ghica, a prominent figure in Romania at that time initiated the exploitation of 14 wells from the 30 known streams of sulphurous and ferruginous waters, thus obtaining enough healing mineral water for a capacity of 60 beds of the balneological establishment. Since 1841, the Resort developed, transformed into a Rehabilitation Clinic (1969) and the number of patients treated there increased from 20 in the beginning to 1000 patient per day. Many of the patients included foreign elite society members who came regularly to benefit from the waters’ healing properties, both external and internal cures, setting Pucioasa on a high level of not only balneology treatment, but also of balneological tourism. Matherials and methods: Studying local industrializations and water analysis, we concluded that there were many factors that contributed to the decline of this great and international renowned balneological resort. The first wrong step in this direction was made when building and extending de gypsum carrier, the peek being between 1970 and 1975, when the industrial forging process made the sulphurous streams to migrate, and the waters from the wells diminished in its sulphur and iron concentration. Another possible factor for the decline can be the modernisation of the medical world, development of anti-inflammatory drugs and modern medical equipment which reduced the need for the elite society to come a long distance for the balneological treatment. Results: Whichever of the reasons, the once prosperous Balneological Resort of Pucioasa fell into an unknown, unimpressive place, known and frequented only by the locals. The Rehabilitation Clinic still has 60 beds, which are occupied to the maximum each month, it still prospers on a local level, but lost its glory from almost a century ago. Conclusions: The Romanian general population and the government must take an interest to one of the many once prosperous balneological resorts in order to revive the national treasure of Romania which is balneology, which many of the developed European countries only wish that they can possess.

Keywords: Balneary Resort, Pucioasa,
Testing the Process of Evacuation from the Passenger Aircraft with the Use of Computer Simulation
Authors: Jasztal Michał
Published: January 2021

Aim: The main aim of the study was to investigate the possibility to use the Pathfinder simulation software to determine the duration of an evacuation and to plan its course for various scenarios of evacuation organisation, for specific profiles and behaviours of passengers and on-board personnel, and for a specific geometrical arrangement of the passenger cabin of a selected passenger aircraft. In addition, the paper discusses selected factors that affect the evacuation from the passenger aircraft. Project and methods: The Pathfinder software used in the research has the graphical interface to create an evacuation simulation model (2D and 3D) as well as tools to visualise the results. Pathfinder is based on artificial intelligence algorithms, in which each passenger has a number of individual features that can influence his/her movements and decisions during the simulation. The simulation of people's movement is determined by their profiles and behaviours, the parameters of which can be entered by means of probability distributions, which makes it possible to take into account the stochastic nature of the evacuation process. Results: The Boeing 787 Dreamliner was selected for the study, for which six options for simulating the evacuation of 252 passengers and eight members of on-board personnel were conducted. The shortest evacuation time was achieved by changing the even distribution of the number of passengers to the individual emergency exits, thus avoiding congestions in sensitive areas of the passenger cabin. The increase in passengers' maximum speed has paradoxically increased evacuation times, as it has increased the intensity of passenger collisions. It was found that one of the key issues affecting the timing of an evacuation is the proper organisation of the evacuation by on-board personnel, who, by guiding passengers through the geometrically most advantageous passageways, results in the fastest possible evacuation. The simulations in variants five and six have achieved satisfactory evacuation times, which are within the emergency aircraft evacuation time limit required in a certification process. Conclusions: The presented simulation models, the results obtained, and the wide range of possibilities of three-dimensional visualisation of research results give a rational basis for the use of Pathfinder software for testing the evacuation process and thus: for the usage in the aircraft design process, for preparing aircrafts for tests, for shaping evacuation procedures, for on-board personnel training and for air accident investigation.
Prognostic factors for predicting health-related quality of life after intramedullary nailing of tibial fractures: a randomized controlled trial
Authors: Sprague Sheila , Heels-Ansdell Diane , Bzovsky Sofia , Zdero Radovan , Bhandari Mohit , Swiontkowski Marc , Tornetta Paul , Sanders David , Schemitsch Emil
Published: January 2021

Aims

Using tibial shaft fracture participants from a large, multicentre randomized controlled trial, we investigated if patient and surgical factors were associated with health-related quality of life (HRQoL) at one year post-surgery.

Methods

The Study to Prospectively Evaluate Reamed Intramedullary Nails in Patients with Tibial Fractures (SPRINT) trial examined adults with an open or closed tibial shaft fracture who were treated with either reamed or unreamed intramedullary nails. HRQoL was assessed at hospital discharge (for pre-injury level) and at 12 months post-fracture using the Short Musculoskeletal Functional Assessment (SMFA) Dysfunction, SMFA Bother, 36-Item Short Form 36 (SF-36) Physical, and SF-36 Mental Component scores. We used multiple linear regression analysis to determine if baseline and surgical factors, as well as post-intervention procedures within one year of fracture, were associated with these HRQoL outcomes. Significance was set at p < 0.01. We hypothesize that, irrespective of the four measures used, prognosis is guided by both modifiable and non-modifiable factors and that patients do not return to their pre-injury level of function, nor HRQoL.

Results

For patient and surgical factors, only pre-injury quality of life and isolated fracture showed a statistical effect on all four HRQoL outcomes, while high-energy injury mechanism, smoking, and race or ethnicity, demonstrated statistical significance for three of the four HRQoL outcomes. Patients who did not require reoperation in response to infection, the need for bone grafts, and/or the need for implant exchanges had statistically superior HRQoL outcomes than those who did require intervention within one year after initial tibial fracture nailing.

Conclusion

We identified several baseline patient factors, surgical factors, and post-intervention procedures within one year after intramedullary nailing of a tibial shaft fracture that may influence a patient’s HRQoL. Cite this article: Bone Jt Open 2021;2(1):22–32.