bluuebunny/crossref_metadata_2025 huggingface dataset:
Design and Implementation of Smart Energy Meter using LoRa-WAN and IoT Applications
Authors: Kanakaraja P , Upadhyay Sourabh , Kotamraju Sarat K , Venkata Sai Suneela G , Neelesh Rudra
Published: March 2021

In the day to day life in the present world where we are using vast technology, power is the most important term to deal for any Digital system to work, so it is as important to calculate the power we are consuming for our needs as anything over may drain one, so to know the power consumed from anywhere here we are dealing with smart energy meter using LoRa-WAN and IoT Applications, LoRa stands for Long Range, the name itself states that it deals with long range communication with the low power consumption working on batteries for years, In the IoT applications the range of the communication is the most important factor, as in IoT most of the Wi-Fi based systems needs to have many access points to cover the large area hence there is increment in the expenses for the system to integrate, by adding the unit of LoRa to the described design we can enhance the system to long range to several locations within that prescribed range as a LoRa can handle many nodes, the main theme of the LoRa is to promote the Bi-directional communication, all the data collected is stored in the Gateway and sent to the cloud server where you can access the data from anywhere through the mobile phone or PC and device, by installing the demanding version of software on your Gadget. AS we can see that in our real time we are using 4G network where transmitted bits or more, in the concept of LoRa the transmitted bits or less, by which we can overcome the disadvantage of the 4G/GSM networks, as of now as there is a huge loss to the telecommunication industries due to this they are switching to the LoRa.
Missing information in the Universe as a dark matter candidate based on the mass-energy-information equivalence principle
Authors: Džaferović-Mašić E
Published: March 2021

There are several theoretical models proposing dark matter candidates as well as different experimental searches for dark matter, collider, and non-collider ones. One of the most intriguing dark matter candidates is missing information in the cosmos. This is based on the mass-energy-information equivalence principle presented by M Vopson [1]. This review presents the historical development of this principle from its roots in the 1960s when Landauer principle was firstly presented to the latest data on the estimated value of the mass of one bit of information as well as data on missing energy as potential dark matter. Another theoretical discussion presented here is the reformulation of the second law of thermodynamics as a possible step to great unification. In addition to this theoretical postulation with a mathematical presentation focusing on statistics, we present some of the proposed experiments in this field. Two major proposals are in the direction of using an ultra-accurate balance with measurement uncertainty low enough to be comparable with proposed theoretical limits, and originally developed sensitive interferometer similar to the one in LIGO experiment.
Comparison of emission signals for different polarizations in femtosecond laser-induced breakdown spectroscopy
Authors: WANG Qiuyun , CHEN Anmin , LIU Miao , LIU Yitong , LI Qingxue , LI Suyu , JIANG Yuanfei , GAO Xun , JIN Mingxing
Published: March 2021

In this study, a femtosecond laser was focused to ablate brass target and generate plasma emission in air. The influence of lens to sample distance (LTSD) on spectral emission of brass plasma under linearly and circularly polarized pulses with different pulse energies was investigated. The results indicated that the position with the strongest spectral emission moved toward focusing lens with increasing the energy. At the same laser energy, the line emission under circularly polarized pulse was stronger compared with linearly polarized pulse for different LTSDs. Next, electron temperature and density of the plasma were obtained with Cu (I) lines, indicating that the electron temperature and density under circularly polarized pulse were higher compared to that under linearly polarized pulse. Therefore, changing the laser polarization is a simple and effective way to improve the spectral emission intensity of femtosecond laser-induced plasma.
The isoperimetric problem in the 2-dimensional Finsler space forms with 𝑘=0. II
Authors: Zhan Mengqing , Zhou Linfeng
Published: March 2021

This paper is a continuation of the second author’s previous work [Internat. J. Math. 30 (2019)]. We investigate the isoperimetric problem in the 2-dimensional Finsler space form

(

F
B

,

B
2

(
1
)
)

(F_B, B^2(1))

with

k
=
0

k=0

by using the Holmes-Thompson area and prove that the circle centered at the origin achieves the local maximum area of the isoperimetric problem.
Minimal free resolutions of ideals of minors associated to pairs of matrices
Authors: Lőrincz András
Published: March 2021

Consider the affine space consisting of pairs of matrices

(
A
,
B
)

(A,B)

of fixed size, and its closed subvariety given by the rank conditions

rank
⁡
A
≤
a
,

rank
⁡
B
≤
b

\operatorname {rank} A \leq a, \, \operatorname {rank} B \leq b

, and

rank
⁡
(
A
⋅
B
)
≤
c

\operatorname {rank} (A\cdot B) \leq c

, for three non-negative integers

a
,
b
,
c

a,b,c

. These varieties are precisely the orbit closures of representations for the equioriented

A

3

\mathbb {A}_3

quiver. In this paper we construct the (equivariant) minimal free resolutions of the defining ideals of such varieties. We show how this problem is equivalent to determining the cohomology groups of the tensor product of two Schur functors of tautological bundles on a 2-step flag variety. We provide several techniques for the determination of these groups, which is of independent interest.
Dietary Habits and Medications to Control Hypertension Among Women of Child-Bearing Age in the United States from 2001 to 2016
Authors: Kovell Lara C , Maxner Benjamin , Ayturk Didem , Moore Simas Tiffany A , Harrington Colleen M , McManus David D , Gardiner Paula , Aurigemma Gerard P , Juraschek Stephen P
Published: March 2021

Background

Hypertension (HTN) in pregnancy is a leading cause of maternal morbidity and mortality in the United States. Although the Dietary Approaches to Stop Hypertension (DASH) diet is recommended for all adults with HTN, rates of DASH adherence and antihypertensive medication use in women of child-bearing age are unknown. Our objectives were to determine DASH adherence and antihypertensive medication use in women of child-bearing age.

Methods

In the National Health and Nutrition Examination Surveys from 2001 to 2016, we estimated DASH adherence among women of child-bearing age (20–50 years). We derived a DASH score (0–9) based on 9 nutrients, with DASH adherence defined as DASH score ≥4.5. HTN was defined by blood pressure (BP) ≥130/80 mm Hg or antihypertensive medication use. DASH scores were compared across BP categories and antihypertensive medication use was categorized.

Results

Of the 7,782 women, the mean age (SE) was 32.8 (0.2) years, 21.4% were non-Hispanic Black, and 20.3% had HTN. The mean DASH score was 2.11 (0.06) for women with self-reported HTN and 2.40 (0.03) for women with normal BP (P < 0.001). DASH adherence was prevalent in 6.5% of women with self-reported HTN compared with 10.1% of women with normal BP (P < 0.05). Self-reported HTN is predominantly managed with medications (84.8%), while DASH adherence has not improved in these women from 2001 to 2016. Moreover, 39.5% of US women of child-bearing age are taking medications contraindicated in pregnancy.

Conclusions

Given the benefits of optimized BP during pregnancy, this study highlights the critical need to improve DASH adherence and guide prescribing among women of child-bearing age.
Clinical Evaluation of the Safety and Efficacy of a 1060-nm Diode Laser for Non-Invasive Fat Reduction of the Abdomen
Authors: Kislevitz Mikaela , Wamsley Christine , Kang Alison , Kilmer Suzanne , Hoopman John , Barillas Jennifer , Kenkel Jeffrey M
Published: March 2021

Background

Despite the proven efficacy of liposuction, there is a population of patients who prefer non-surgical alternatives. Laser hyperthermia-induced lipolysis has emerged as one non-invasive alternative to liposuction.

Objectives

The authors sought to evaluate the safety and efficacy of a 1060-nm (±10 nm) diode laser for non-invasive fat reduction of the abdomen.

Methods

This single-arm, 2-center study enrolled 30 patients. Patients received a 25-minute 1060-nm diode laser treatment on their abdomen. Ultrasound adipose measurements, body weight, and circumference were taken at baseline and at 6- and 12-week follow-up visits. Blinded evaluators identified “before” and “after” photos of each patient. A patient satisfaction questionnaire was completed by each patient at study exit.

Results

A total 29 patients completed all treatment and follow-up visits. Ultrasound images showed an adipose reduction of 8.55% at 12 weeks post-treatment (P < 0.0001). Blinded evaluators correctly identified 67% of the pre- and post-treatment images at site 01 (Sacramento, CA) and 56% at site 02 (Dallas, TX). Satisfaction was high, with 72% of patients reporting being either “satisfied” or “very satisfied” with their results on a 5-point Likert scale. Pain was rated as mild by 62% of patients, moderate by 38%, and severe by none on the Wong-Baker Scale.

Conclusions

These results indicate that a single treatment with a 1060-nm (±10 nm) diode laser, per the treatment protocol, is safe and effective in reducing unwanted fat in the abdomen as objectively measured employing ultrasound. The treatment was well-tolerated among all patients, with minimal discomfort reported and high patient satisfaction.

Level of Evidence: 4
KibioR & Kibio: a new architecture for next-generation data querying and sharing in big biology
Authors: Ongaro-Carcy Régis , Scott-Boyer Marie-Pier , Dessemond Adrien , Belleau François , Leclercq Mickael , Périn Olivier , Droit Arnaud
Published: March 2021

Motivation

The growing production of massive heterogeneous biological data offers opportunities for new discoveries. However, performing multi-omics data analysis is challenging, and researchers are forced to handle the ever-increasing complexity of both data management and evolution of our biological understanding. Substantial efforts have been made to unify biological datasets into integrated systems. Unfortunately, they are not easily scalable, deployable and searchable, locally or globally.

Results

This publication presents two tools with a simple structure that can help any data provider, organization or researcher, requiring a reliable data search and analysis base. The first tool is Kibio, a scalable and adaptable data storage based on Elasticsearch search engine. The second tool is KibioR, a R package to pull, push and search Kibio datasets or any accessible Elasticsearch-based databases. These tools apply a uniform data exchange model and minimize the burden of data management by organizing data into a decentralized, versatile, searchable and shareable structure. Several case studies are presented using multiple databases, from drug characterization to miRNAs and pathways identification, emphasizing the ease of use and versatility of the Kibio/KibioR framework.

Availabilityand implementation

Both KibioR and Elasticsearch are open source. KibioR package source is available at https://github.com/regisoc/kibior and the library on CRAN at https://cran.r-project.org/package=kibior.

Supplementary information

Supplementary data are available at Bioinformatics online.
SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study
Authors:   COVIDSurg Collaborative, GlobalSurg Collaborative
Published: March 2021

Background

Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling.

Methods

The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18–49, 50–69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty.

Results

NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year.

Conclusion

As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population.
The Prenatal Morphomechanic Impact of Agenesis of the Corpus Callosum on Human Brain Structure and Asymmetry
Authors: Schwartz Ernst , Diogo Mariana Cardoso , Glatter Sarah , Seidl Rainer , Brugger Peter C , Gruber Gerlinde M , Kiss Herbert , Nenning Karl-Heinz ,   IRC5 consortium, Langs Georg , Prayer Daniela , Kasprian Gregor
Published: March 2021

Genetic, molecular, and physical forces together impact brain morphogenesis. The early impact of deficient midline crossing in agenesis of the Corpus Callosum (ACC) on prenatal human brain development and architecture is widely unknown. Here we analyze the changes of brain structure in 46 fetuses with ACC in vivo to identify their deviations from normal development. Cases of complete ACC show an increase in the thickness of the cerebral wall in the frontomedial regions and a reduction in the temporal, insular, medial occipital and lateral parietal regions, already present at midgestation. ACC is associated with a more symmetric configuration of the temporal lobes and increased frequency of atypical asymmetry patterns, indicating an early morphomechanic effect of callosal growth on human brain development affecting the thickness of the pallium along a ventro–dorsal gradient. Altered prenatal brain architecture in ACC emphasizes the importance of conformational forces introduced by emerging interhemispheric connectivity on the establishment of polygenically determined brain asymmetries.
Did Lockdown Work? An Economist’s Cross-Country Comparison
Authors: Bjørnskov Christian
Published: March 2021

I explore the association between the severity of lockdown policies in the first half of 2020 and mortality rates. Using two indices from the Blavatnik Centre’s COVID-19 policy measures and comparing weekly mortality rates from 24 European countries in the first halves of 2017–2020, addressing policy endogeneity in two different ways, and taking timing into account, I find no clear association between lockdown policies and mortality development.
Rethinking Revisionism in World Politics
Authors: He Kai , Feng Huiyun , Chan Steve , Hu Weixing
Published: March 2021

Revisionism is an important concept in international relations discourse, and it is especially prevalent in discussions about relations between China and the United States in the context of a possible power transition. Yet, this concept has until recently not received the systematic research attention that it deserves. We present in this essay different strategies that a revisionist state may pursue. It builds on recent scholarship by other colleagues and is drawn from a larger project of ours to study revisionism historically and develop it conceptually. We argue that military conquest and subversion—or in our terminology, hard revisionism—have become less likely in today’s world compared to the past. Instead, different approaches of soft revisionism intended to advance institutional changes should be given more attention. We provide a typology of these soft revisionist strategies and offer examples from recent Chinese and US conduct to illustrate them.
‘These Discussions Aren’t Happening’: Experiences of People Living with Inflammatory Bowel Disease and Talking About Sexual Well-being with Health Care Professionals
Authors: Fourie Simona , Norton Christine , Jackson Debra , Czuber-Dochan Wladyslawa
Published: March 2021

Background

Inflammatory bowel disease [IBD] affects all aspects of life, yet little is known about the impact of the condition on intimacy and sexuality and if such concerns should be discussed with health care professionals. This hermeneutical phenomenological study aimed to explore the experiences of people living with inflammatory bowel disease and discussing their sexuality concerns with health care professionals.

Methods

Participants [n = 43] aged 17–64 years were recruited. Data were collected via in depth interviews and anonymous narrative accounts [Google Forms]. Thematic analysis was used to analyse the data.

Results

An overarching theme ‘These discussions aren’t happening’ with four main themes were generated. The main themes were: ‘I can’t image talking about sex’; ‘I am a person, not my IBD’; ‘We need to talk about sex’; and ‘Those who talked about sex, talked badly’. Participants described the lack of conversations with their health care professionals on sexual well-being issues, in spite of the importance they gave to the topic, and identified barriers to having such conversations. They made suggestions for future clinical practice that would better meet their needs. The few who had discussed sexual well-being issues with health care professionals reported negative experiences.

Conclusions

Patients’ needs and preferences, about addressing during clinical appointments concerns related to their sexual well-being, should be addressed routinely and competently by health care professionals. Understanding the implications of inflammatory bowel disease for intimate aspects of the lives of those living with the condition could improve the quality of the care provided.
Rimonabant potentiates the antifungal activity of amphotericin B by increasing cellular oxidative stress and cell membrane permeability
Authors: Zhang Ming , Lu Jinghui , Duan Ximeng , Chen Jinyao , Jin Xueyang , Lin Zhaomin , Pang Yingxin , Wang Xuexiang , Lou Hongxiang , Chang Wenqiang
Published: March 2021

Amphotericin B (AmB) is a very effective antifungal agent, and resistance in clinical isolates is rare. However, clinical treatment with AmB is often associated with severe side effects. Reducing the administration dose of AmB by combining it with other agents is a promising strategy to minimize this toxicity. In this study, we screened a small compound library and observed that the anti-obesity drug rimonabant exhibited synergistic antifungal action with AmB against Candida species and Cryptococcus neoformans. Moreover, the combination of AmB and rimonabant exhibited synergistic or additive effects against Candida albicans biofilm formation and cell viability in preformed biofilms. The effects of this combination were further confirmed in vivo using a murine systemic infection model. Exploration of the mechanism of synergy revealed that rimonabant enhances the fungicidal activity of AmB by increasing cellular oxidative stress and cell membrane permeability. These findings provide a foundation for the possible development of AmB–rimonabant polytherapies for fungal infections.
Re-expression of glucuronyl C5-epimerase in the mutant MEF cells increases heparan sulfate epimerization but has no influence on the Golgi localization and enzymatic activity of 2-O-sulfotransferase
Authors: Cui Hao , Wang Zhaoguang , Zhang Tianji , Li Jin-ping , Fang Jianping
Published: March 2021

Heparan sulfate (HS) is a linear and complex polysaccharide that modulates the biological activities through protein recognition and interaction. Evidence indicates that protein-binding properties of HS are largely dependent on distinctive sulfation and epimerization patterns that are modified by a series of Golgi-localized enzymes. In particular, the glucuronyl C5-epimerase (Hsepi) converts D-glucuronic acid (GlcA) residues to L-iduronic acid (IdoA) and 2-O-sulfotransferase (2OST) catalyzes sulfation at C2 position of IdoA and rarely GlcA residues. Mice lacking both Hsepi and 2OST display multiple development defects, indicating the importance of IdoA in HS. Here, to gain greater insights of HS structure–function relationships, as well as a better understanding of the regulatory mechanisms of Hsepi and 2OST, the fine structure and cellular signaling functions of HS were investigated after restoration of Hsepi in the mutant mouse embryonic fibroblast (MEF) cells. Introduction of Hsepi into the Hsepi mutant MEF cells led to robustly increased proportion of IdoA residues, which rescued the cell signaling in response to fibroblast growth factor 2. However, we found that Hsepi knockout had no influence on either cellular transport or enzymatic activity of 2OST in the MEF cells, which is not in accord with the findings suggesting that the enzymatic activity and cellular transport of 2OST and Hsepi might be differently regulated.
On the convergence of augmented Lagrangian strategies for nonlinear programming
Authors: Andreani Roberto , Ramos Alberto , Ribeiro Ademir A , Secchin Leonardo D , Velazco Ariel R
Published: March 2021

Augmented Lagrangian (AL) algorithms are very popular and successful methods for solving constrained optimization problems. Recently, global convergence analysis of these methods has been dramatically improved by using the notion of sequential optimality conditions. Such conditions are necessary for optimality, regardless of the fulfillment of any constraint qualifications, and provide theoretical tools to justify stopping criteria of several numerical optimization methods. Here, we introduce a new sequential optimality condition stronger than previously stated in the literature. We show that a well-established safeguarded Powell–Hestenes–Rockafellar (PHR) AL algorithm generates points that satisfy the new condition under a Lojasiewicz-type assumption, improving and unifying all the previous convergence results. Furthermore, we introduce a new primal–dual AL method capable of achieving such points without the Lojasiewicz hypothesis. We then propose a hybrid method in which the new strategy acts to help the safeguarded PHR method when it tends to fail. We show by preliminary numerical tests that all the problems already successfully solved by the safeguarded PHR method remain unchanged, while others where the PHR method failed are now solved with an acceptable additional computational cost.
Disease Burden Estimates of Respiratory Syncytial Virus related Acute Respiratory Infections in Adults With Comorbidity: A Systematic Review and Meta-Analysis
Authors: Shi Ting , Vennard Sophie , Jasiewicz Francis , Brogden Rory , Nair Harish ,   RESCEU Investigators, Nair Harish , Campbell Harry , Shi Ting , Li You , Openshaw Peter , Beutels Philippe , Bont Louis , Pollard Andrew , Molero Eva , Martinon-Torres Federico , Heikkinen Terho , Meijer Adam , Kølsen Fischer Thea , van den Berge Maarten , Giaquinto Carlo , Abram Michael , Swanson Kena , K Stoszek Sonia , Pircon Jean Yves , Gallichan Scott , Demont Clarisse , Aerssens Jeroen , Cheret Arnaud , Ispas Gabriela , Peeters Paul , Rosen Brian , Fuentes Robert , Falsey Ann , Mikolajczyk Rafael , Anderson Larry
Published: March 2021

Background

Respiratory syncytial virus related acute respiratory infection (RSV-ARI) constitutes a substantial disease burden in adults with comorbidities. We aimed to identify all studies investigating the disease burden of RSV-ARI in this group.

Methods

We estimated the incidence, hospitalization rate, and in-hospital case fatality ratio (hCFR) of RSV-ARI in adults with comorbidities based on a systematic review of studies published between January 1996 and March 2020. We also investigated the association between RSV-ARI and any comorbidity in adults. Meta-analyses based on random effects model were carried out.

Results

Overall, 20 studies were included. The annual incidence rate of RSV-ARI in adults with any comorbidity was 37.6 (95% confidence interval [CI], 20.1–70.3) per 1000 persons per year in industrialized countries and the seasonal incidence rate was 28.4 (11.4–70.9) per 1000 persons per season. The hCFR in industrialized countries was 11.7% (5.8%–23.4%). There were no studies in developing countries. There were insufficient data to generate the meta-estimate of hospitalization rate. The likelihood of experiencing RSV-ARI for those with any comorbidity compared to those without was estimated to be 4.1 (odds ratio [OR], 1.6–10.4) and 1.1 (OR, 0.6–1.8) from studies using univariable and multivariable analysis respectively.

Conclusion

The disease burden of RSV-ARI among adults with comorbidity is substantial with limited data available.
Emergence of a Neisseria gonorrhoeae clone with reduced cephalosporin susceptibility between 2014 and 2019 in Amsterdam, The Netherlands, revealed by genomic population analysis
Authors: de Korne-Elenbaas Jolinda , Bruisten Sylvia M , de Vries Henry J C , Van Dam Alje P
Published: March 2021

Background

Emerging resistance to cephalosporins in Neisseria gonorrhoeae (Ng) is a major public health threat, since these are considered antibiotics of last resort. Continuous surveillance is needed to monitor the circulation of resistant strains and those with reduced susceptibility.

Objectives

For the purpose of epidemiological surveillance, genomic population analysis was performed on Ng isolates from Amsterdam with a focus on isolates with reduced susceptibility to ceftriaxone.

Methods

WGS data were obtained from 318 isolates from Amsterdam, the Netherlands between 2014 and 2019. Isolates were typed according to MLST, Ng Multi-Antigen Sequence Typing (NG-MAST) and Ng Sequence Typing for Antimicrobial Resistance (NG-STAR) schemes and additional resistance markers were identified. Phylogenetic trees were created to identify genetic clusters and to compare Dutch and non-Dutch MLST7827 isolates.

Results

MLST7363 and MLST1901 were the predominant strains having reduced susceptibility to ceftriaxone during 2014–16; MLST7827 emerged and dominated during 2017–19. NG-STAR38 and NG-MAST2318/10386 were predominant among MLST7827 isolates. MLST7827 reduced susceptibility isolates carried a non-mosaic 13.001 penA allele with an A501V mutation and porB1b G120K/A121D mutations, which were lacking in susceptible MLST7827 isolates. Phylogenetic analysis of all publicly available MLST7827 isolates showed strong genetic clustering of Dutch and other European MLST7827 isolates.

Conclusions

MLST7827 isolates with reduced ceftriaxone susceptibility have emerged during recent years in Amsterdam. Co-occurrence of penA A501V and porB1b G120K/A121D mutations was strongly associated with reduced susceptibility to ceftriaxone. Genetic clustering of Dutch and other European MLST7827 isolates indicates extensive circulation of this strain in Europe. Close monitoring of the spread of this strain having an alarming susceptibility profile is needed.
Characterization of the aberrant splicing of MAP3K7 induced by cancer-associated SF3B1 mutation
Authors: Li Zhuang , Zhao Bo , Shi Yueru , Liang Yuqi , Qian Rui , Wan Youzhong
Published: March 2021

SF3B1, an essential RNA splicing factor, is frequently mutated in various types of cancers, and the cancer-associated SF3B1 mutation causes aberrant RNA splicing. The aberrant splicing of several transcripts, including MAP3K7, promotes tumorigenesis. Here, we identify a premature termination codon in the aberrantly spliced transcript of MAP3K7. Treatment of HEK293T cells transfected with the K700E-mutated SF3B1 with cycloheximide leads to increased accumulation of the aberrant spliced transcript of MAP3K7, demonstrating that the aberrantly spliced transcript of MAP3K7 is targeted by nonsense-mediated decay. The aberrantly spliced MAP3K7 transcript uses an aberrant 3ʹ splice sites and an alternative branchpoint sequence. In addition, the aberrant splicing of MAP3K7 requires not only the polypyrimidine tract associated with normal splicing but also an alternative polypyrimidine tract upstream of the aberrant 3ʹ splice site. Other cancer-associated SF3B1 mutations also cause the aberrant splicing of MAP3K7, which depends on the same sequence features. Our data provide a further understanding of the mechanisms underlying aberrant splicing induced by cancer-associated SF3B1 mutation, and reveal an important role of alternative polypyrimidine tract in diseases.
Penicillium chrysogenum polypeptide extract protects tobacco plants from tobacco mosaic virus infection through modulation of ABA biosynthesis and callose priming
Authors: Li Yu , Jiao Mengting , Li Yingjuan , Zhong Yu , Li Xiaoqin , Chen Zhuangzhuang , Chen Suiyun , Wang Jianguang
Published: March 2021

The polypeptide extract of the dry mycelium of Penicillium chrysogenum (PDMP) can protect tobacco plants from tobacco mosaic virus (TMV), although the mechanism underlying PDMP-mediated TMV resistance remains unknown. In our study, we analysed a potential mechanism via RNA sequencing (RNA-seq) and found that the abscisic acid (ABA) biosynthetic pathway and β-1,3-glucanase, a callose-degrading enzyme, might play an important role in PDMP-induced priming of resistance to TMV. To test our hypothesis, we successfully generated a Nicotiana benthamiana ABA biosynthesis mutant and evaluated the role of the ABA pathway in PDMP-induced callose deposition during resistance to TMV infection. Our results suggested that PDMP can induce callose priming to defend against TMV movement. PDMP inhibited TMV movement by increasing callose deposition around plasmodesmata, but this phenomenon did not occur in the ABA biosynthesis mutant; moreover, these effects of PDMP on callose deposition could be rescued by treatment with exogenous ABA. Our results suggested that callose deposition around plasmodesmata in wild-type plants is mainly responsible for the restriction of TMV movement during the PDMP-induced defensive response to TMV infection, and that ABA biosynthesis apparently plays a crucial role in PDMP-induced callose priming for enhancing defence against TMV.
Myeloid Sarcoma Expressing Keratins and Mimicking Carcinoma—Case Report and Literature Review
Authors: Dayton Vanessa J , Beckman Amy , Linden Michael
Published: March 2021

Unusual presentations of otherwise common hematopoietic neoplasms are a well-recognized diagnostic challenge. Herein, we present a case study of a previously healthy 64 year old woman with myeloid sarcoma whose diagnosis was delayed by an unusual immunohistochemical staining pattern, including cytokeratin expression, by the neoplastic cells and by possible anchoring bias introduced by radiographic and flow cytometric immunophenotyping reports. This case study emphasizes the need to integrate clinical, radiographic, histologic, and immunophenotyping data for rapid and accurate tissue diagnoses while being wary of the lack of specificity for many common immunophenotypic markers.
Multiplex indexing approach for the detection of DNase I hypersensitive sites in single cells
Authors: Gao Weiwu , Ku Wai Lim , Pan Lixia , Perrie Jonathan , Zhao Tingting , Hu Gangqing , Wu Yuzhang , Zhu Jun , Ni Bing , Zhao Keji
Published: March 2021

Single cell chromatin accessibility assays reveal epigenomic variability at cis-regulatory elements among individual cells. We previously developed a single-cell DNase-seq assay (scDNase-seq) to profile accessible chromatin in a limited number of single cells. Here, we report a novel indexing strategy to resolve single-cell DNase hypersensitivity profiles based on bulk cell analysis. This new technique, termed indexing single-cell DNase sequencing (iscDNase-seq), employs the activities of terminal DNA transferase (TdT) and T4 DNA ligase to add unique cell barcodes to DNase-digested chromatin ends. By a three-layer indexing strategy, it allows profiling genome-wide DHSs for >15 000 single-cells in a single experiment. Application of iscDNase-seq to human white blood cells accurately revealed specific cell types and inferred regulatory transcription factors (TF) specific to each cell type. We found that iscDNase-seq detected DHSs with specific properties related to gene expression and conservation missed by scATAC-seq for the same cell type. Also, we found that the cell-to-cell variation in accessibility computed using iscDNase-seq data is significantly correlated with the cell-to-cell variation in gene expression. Importantly, this correlation is significantly higher than that between scATAC-seq and scRNA-seq, suggesting that iscDNase-seq data can better predict the cellular heterogeneity in gene expression compared to scATAC-seq. Thus, iscDNase-seq is an attractive alternative method for single-cell epigenomics studies.
Growth and Nitrate Reductase Activity Are Impaired in Rice Osnlp4 Mutants Supplied with Nitrate
Authors: Wang Mengyao , Hasegawa Takahiro , Beier Marcel , Hayashi Makoto , Ohmori Yoshihiro , Yano Kenji , Teramoto Shota , Kamiya Takehiro , Fujiwara Toru
Published: March 2021

Nitrate is an important nutrient and signaling molecule in plants, which modulates the expression of many genes and regulates plant growth. In paddy-grown rice (Oryza sativa), nitrogen is mostly supplied in the form of ammonium but can also be supplied in the form of nitrate. Several nitrogen transporters and nitrate assimilation enzymes have been identified and functionally characterized in rice. However, little is known regarding the nitrate sensing system in rice, and the regulatory mechanisms of nitrate-related genes remain to be elucidated. In recent years, NIN-like proteins (NLPs) have been described as key transcription factors of nitrogen responses in Arabidopsis thaliana, which implies that OsNLP4 is involved in the regulation of nitrate assimilation and nitrogen use efficiency in rice. Here, we show that OsNLP4 can influence plant growth by affecting nitrate reductase (NR) activity. The growth of OsNLP4 knockdown mutants was reduced when nitrate was supplied, but not when ammonium was supplied. The nitrate concentration was significantly reduced in osnlp4 mutants. Furthermore, the concentrations of iron and molybdenum, essential elements for NR activity, were reduced in OsNLP4 knockdown mutants. We propose that, in addition to the regulation of gene expression within the nitrate signaling pathway, OsNLP4 can affect the NR activity and nitrate-dependent growth of rice. Our results support a working model for the role of OsNLP4 in the nitrate signaling pathway.
Unicompartmental versus total knee arthroplasty for knee osteoarthritis: a systematic review and meta-analysis of randomized controlled trial
Authors: Wang Huan , Ma Qiong , Ma Baoan
Published: March 2021

Objective:

To evaluate the operative time, intraoperative blood loss, incision length, length of hospital stay, postoperative joint function recovery, and complications of unicompartmental knee arthroplasty (UKA) and total knee replacement (total knee arthroplasty, TKA) in order to compare the differences between the 2 methods in the treatment of single-compartment knee osteoarthritis.

Materials and methods:

Computer retrieval Pubmed, Embase, the Cochrane, Sinomed, CNKI, WangFang, and VIP database of UKA and TKA osteoarthritis knee single room curative effect comparison, retrieval time limit for a library to November 2020, consult the reference index can be obtained at the same time. Two researchers independently screened the retrieved literature according to the established inclusion and exclusion criteria. Operative time, incision length, intraoperative blood loss, length of hospital stay, postoperative hospital for special surgery score, American knee society knee score, and excellent rateof pain relief were used as the main evaluation indexes, postoperative flexion degree, postoperative visual analogue scale score, time required for active kneeling to 90 degrees, and hemoglobin decrease in 72 hours and postoperative complications were used as secondary evaluation indexes. The methodological quality was evaluated and meta-analysis was performed using Stata 16.0 software.

Results:

A total of 54 articles were included, including a total of 4577 patients. Meta-analysis results showed that the UKA group was superior to the TKA group in terms of early postoperative knee function score, postoperative pain relief, hemoglobin reduction at 72 hours and complications, and the differences were statistically significant (P<0.05). At the same time, the amount of intraoperative blood loss, length of hospital stay, operative time, incision length and the time required for active kneeling to 90 degrees in the UKA group were less than those in the TKA group, and the differences were statistically significant (P<0.05). The UKA group had fewer early complications but higher long-term revision rate than the TKA group.

Conclusion:

UKA is superior to TKA in the treatment of single-compartment knee osteoarthritis during surgery and in early stage patients, but patients with UKA are at high risk of long-term revision.
Women with Type 1 diabetes (T1D) experience a shorter reproductive period compared with nondiabetic women: the Pittsburgh Epidemiology of Diabetes Complications (EDC) study and the Study of Women's Health Across the Nation (SWAN)
Authors: Yi Yan , El Khoudary Samar R. , Buchanich Jeanine M. , Miller Rachel G. , Rubinstein Debra , Matthews Karen , Orchard Trevor J. , Costacou Tina
Published: March 2021

Objective:

Evidence suggests that insulin deficiency and hyperglycemia may disrupt the female reproductive system's normal function, leading to delayed menarche and premature ovarian aging. We thus compared the length of the reproductive period of women with type 1 diabetes (T1D) to women without diabetes.

Methods:

Women with childhood-onset T1D (diagnosed in 1950-80) from the prospective Epidemiology of Diabetes Complications (EDC) study and nondiabetic women from the Pittsburgh site of the Study of Women's Health Across the Nation (SWAN) were studied. Exclusion criteria comprised not having reached natural menopause, hysterectomy/oophorectomy before menopause, and sex hormone therapy during the menopausal transition. Reproductive history was self-reported. The historical and Women's Ischemia Syndrome Evaluation hormonal algorithms were also used to assess menopause status.

Results:

Women in the T1D cohort (n = 105) were younger, more likely to be White, never smokers, with lower BMI and higher high-density lipoprotein cholesterol levels (all P values < 0.05) compared with women without diabetes (n = 178). After covariate adjustment, T1D women were also older at menarche (0.5-y delay, P = 0.002) but younger at natural menopause (−2.0 y, P < 0.0001). Women with T1D thus experienced 2.5 fewer reproductive years compared to those without diabetes (P < 0.0001). These findings were restricted to the subgroup of women who were diagnosed with T1D before reaching menarche (n = 80).

Conclusion:

Women with T1D onset before menarche have a shorter reproductive period compared with nondiabetic women, exhibiting delayed menarche and earlier natural menopause. Factors that may be related to a shorter reproductive period in T1D should be investigated.
Improving Diabetic Retinopathy Screening Among Patients With Diabetes Mellitus Using the Define, Measure, Analyze, Improve, and Control Process Improvement Methodology
Authors: Kollipara Usha , Varghese Shilu , Mutz Jackie , Putra Joseph , Bajaj Puneet , Mirfakhraee Sasan , Tessnow Alex , Fish Jason , Ali Sadia
Published: March 2021

Diabetic retinopathy, a complication of diabetes mellitus (DM), is the leading cause of blindness in the United States. Early detection and appropriate timely treatment would result in 50–70% reduction in blindness due to DM, with a positive economic impact on patients and the healthcare system. The purpose of our project is to improve screening rates for retinopathy among patients with DM seen in a large endocrinology clinic applying the Lean Six Sigma Define, Measure, Analyze, Improve, and Control project framework and clinical decision support tools embedded in the electronic health record (EHR). Retinopathy screening rates improved from 49% to 72% by the end of the project. Interventions included identifying care gaps using a population registry, patient outreach through the electronic medical record patient portal, placing referrals to ophthalmology, improving documentation in health maintenance, and tracking improvement for sustainability. Our results demonstrate that process improvement methodologies and EHR tools can be successfully applied to improve care and clinical outcomes in patients with DM.
The clinical black, white, and gray lessons
Authors: Pulipati Vishnu Priya , Davidson Michael H.
Published: March 2021

Purpose of review

This review examines recent contradictory large, well-controlled randomized control trials assessing the effects of omega-3 fatty acids and colchicine on cardiovascular (CV) outcomes.

Recent findings

The Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial (REDUCE-IT) and Statin Residual Risk Reduction with Epanova in high Cardiovascular Risk patients with Hypertriglyceridemia (STRENGTH) trial assessed the CV outcomes using high-dose omega-3 fatty acids in statin-treated patients with moderate hypertriglyceridemia and high-risk for CV disease with differing results. Similarly, Colchicine Cardiovascular Outcomes trial, (COLCOT) second Low Dose Colchicine (LoDoCo2), and Colchicine in patients with Acute Coronary Syndrome (COPS) assessed the CV outcomes using low-dose colchicine in patients with coronary artery disease with inconsistent results. These contradictory findings among studies assessing similar questions with the same drug or a drug within the same class challenge the scientific validity and clinical applicability of the derived conclusions.

A comprehensive review revealed many differences between the trials, which could have contributed to observed divergent results. Consistent findings across multiple trials help strengthen the evidence for specific endpoints or sub-populations, and these findings must be included in guidelines. Large prospective cohort studies with diligent study protocols are warranted in the future to resolve unanswered dilemmas.
Reassessing the July Effect: 30 Years of Evidence Show No Difference in Outcomes
Authors: Zogg Cheryl K. , Metcalfe David , Sokas Claire M. , Dalton Michael K. , Hirji Sameer A. , Davis Kimberly A. , Haider Adil H. , Cooper Zara , Lichtman Judith H.
Published: March 2021

Objective:

The aim of this study was to critically evaluate whether admission at the beginning versus end of the academic year is associated with increased risk of major adverse outcomes.

Summary Background Data:

The hypothesis that the arrival of new residents and fellows is associated with increases in adverse patient outcomes has been the subject of numerous research studies since 1989. Methods: We conducted a systematic review and random-effects meta-analysis of July Effect studies published before December 20, 2019, looking for differences in mortality, major morbidity, and readmission. Given a paucity of studies reporting readmission, we further analyzed 7 years of data from the Nationwide Readmissions Database to assess for differences in 30-day readmission for US patients admitted to urban teaching versus nonteach-ing hospitals with 3 common medical (acute myocardial infarction, acute ischemic stroke, and pneumonia) and 4 surgical (elective coronary artery bypass graft surgery, elective colectomy, craniotomy, and hip fracture) conditions using risk-adjusted logistic difference-in-difference regression.

Results:

A total of 113 studies met inclusion criteria; 92 (81.4%) reported no evidence of a July Effect. Among the remaining studies, results were mixed and commonly pointed toward system-level discrepancies in efficiency. Metaanalyses of mortality [odds ratio (95% confidence interval): 1.01 (0.98–1.05)] and major morbidity [1.01 (0.99–1.04)] demonstrated no evidence of a July Effect, no differences between specialties or countries, and no change in the effect over time. A total of 5.98 million patient encounters were assessed for readmission. No evidence of a July Effect on readmission was found for any of the 7 conditions.

Conclusion:

The preponderance of negative results over the past 30 years suggests that it might be time to reconsider the need for similarly-themed studies and instead focus on system-level factors to improve hospital efficiency and optimize patient outcomes.
Outcomes of 100 Patients More Than 4 Years After POEM for Achalasia
Authors: Campagna Ryan A. J. , Cirera Arturo , Holmstrom Amy L. , Triggs Joseph R. , Teitelbaum Ezra N. , Carlson Dustin A. , Pandolfino John E. , Hungness Eric S.
Published: March 2021

Objective:

We aim to describe the long-term follow-up data from our institution's POEM experience.

Summary Background Data:

Per-oral endoscopic myotomy (POEM) is a well-established endoscopic therapy for achalasia with excellent short-term efficacy, but long-term outcomes data are limited.

Methods:

Patients older than 4 years removed from POEM for treatment of achalasia were studied. Clinical success was defined as an Eckardt Symptom (ES) score ≤3 and freedom from reintervention for achalasia. Patients underwent esophagogastroduodenoscopy (EGD), high-resolution manometry, impedance planimetry, and timed barium esophagram (TBE) preoperatively and at least 4 years postoperatively. Objective gastroesophageal reflux disease (GERD) was defined LA Grade B or worse esophagitis on EGD.

Results:

One hundred and nineteen consecutive patients were included. Five patients died or had catastrophic events unrelated to achalasia or POEM. One hundred of the remaining patients (88%, 100/114) had long-term data available. Clinical follow-up for all patients was greater than 4 years postoperatively and the mean was 55 months. Mean current ES was significantly improved from preop (n = 100, 1 ± 1 vs 7 ± 2, P < 0.001). Overall clinical success was 88% and 92%. Five patients had a current ES >3 and 4 patients required procedural reintervention on the lower esophageal sphincter. Reinterventions were successful in 75% of patients (3/4), with current ES ≤3. The rate of objective GERD was 33% (15/45). Esophageal physiology was improved with a decrease in median integrated relaxation pressure (11 ± 4 vs 33 ± 15 mm Hg, P < 0.001), a decrease in median TBE column height (3 ± 3 vs 13 ± 8 cm, P < 0.001), and an increase in median distensibility index (5.1 ± 2 vs 1.1 ± 1 mm2/mm Hg, P < 0.001).

Conclusions:

POEM provides durable symptom relief and improvement in physiologic esophagogastric junction relaxation parameters over 4.5 years postoperatively. Reinterventions are rare and effective.