bluuebunny/crossref_metadata_2025_split huggingface dataset:
Application of medical cannabis in unstable angina and coronary artery disease
Authors: Shaffer Brian L. , Davis Garrison M. , Incitti Marc A. , Piper Brian J. , Entler Brian V. 
Published: March 2021

Abstract

Rationale:
First discovered in 1990, the endocannabinoid system (ECS) was initially shown to have an intimate relationship with central areas of the nervous system associated with pain, reward, and motivation. Recently, however, the ECS has been extensively implicated in the cardiovascular system with contractility, heart rate, blood pressure, and vasodilation. Emerging data demonstrate modulation of the ECS plays an essential role in cardio metabolic risk, atherosclerosis, and can even limit damage to cardiomyocytes during ischemic events.

Patient Concerns:
This case describes a 63-year-old man who presented to a primary care physician for a medical cannabis (MC) consult due to unstable angina (UA) not relieved by morphine or cardiac medications; having failed all first- and second-line polypharmaceutical therapies. The patient reported frequent, unprovoked, angina and exertional dyspnea.

Diagnosis:
Having a complex cardiac history, the patient first presented 22 years ago after a suspected myocardial infarction. He re-presented in 2010 and underwent stent placement at that time for inoperable triple-vessel coronary artery disease (CAD) which was identified via percutaneous transluminal coronary angioplasty. UA developed on follow-up and, despite medical management over the past 6 years, became progressively debilitating.

Interventions and Outcomes:
In conjunction with his standard cardiac care, patient had a gradual lessening of UA-related pain, including frequency and character, after using an edible form of MC (1:1 cannabidiol:Δ9-tetrahydrocannabinol). Following continued treatment, he ceased long-term morphine treatment and described the pain as no longer crippling. As demonstrated by his exercise tolerance tests, the patient experienced an improved functional capacity and reported an increase in his daily functioning, and overall activity.

Lessons:
This case uniquely highlights MC in possibly reducing the character, quality, and frequency of UA, whereas concordantly improving functional cardiac capacity in a patient with CAD. Additional case reports are necessary to verify this.
Impact of COVID-19 on orthopaedic residents—an Indian perspective
Authors: Kumar GS Prasanna , Yadav Amit Kumar , Harsoor Abhishek , H Kantharaju , Mane Akash V , Palange Nikhil D. 
Published: March 2021

Abstract

Objectives:
The COVID-19 pandemic is a public health emergency causing a deleterious effect on the health system. It affected all the specialties and subspecialties in the medical field causing havoc in the health institutions. This pandemic affected both orthopaedic consultants and the residents who are under training. Our purpose was to study the impact of COVID-19 on orthopaedic residents in their professional life.

Method:
The study design was a computer-based digital online survey of the orthopaedic residents in India. The survey had 15 questions with multiple options related to the effect of COVID-19 on their orthopedic department, effect on teaching, surgical exposure, hands-on surgeries, the effect on workload, effect on mental stress, exposure to arthroplasty, arthroscopic surgeries, spine surgeries, and deformity correction surgeries.

Results:
Elective surgeries stopped in 91% of the hospitals, academic teaching stopped in 98% of the institutions. Eighty-six percent of the residents are not getting adequate surgical exposure, 73% of the residents are getting negligible hands-on surgical training. Residents are mentally stressed related to academic examinations, academic training, and also because of COVID 19 duties. Residents are getting the least exposure in subspecialties like arthroplasty, arthroscopy, and spine.

Conclusion:
The COVID-19 pandemic not only affected the orthopaedic consultants but also the orthopaedic residents to a great extent as residents are the backbone of any department/institution. The pandemic affected significantly resident's academic teaching, surgical exposure, hands-on training and mental stress related to COVID duties, academic training disturbance, and also academic examinations.
The Classification of Biliary Strictures in Patients With Right-Lobe Liver Transplant Recipients and Its Relation to Traversing the Stricture With a Guidewire
Authors: Parlak Erkan , Simsek Cem , Koksal Aydin Seref , Eminler Ahmet Tarik , Unal Emre , Ciftci Turkmen Turan , Akinci Devrim , Yilmaz Sezai 
Published: March 2021

Background.
Traversing the stricture with a guidewire is a prerequisite for the endoscopic treatment of biliary strictures after living donor liver transplantation. We aimed to evaluate the effect of variations in the biliary anastomosis and strictures on the success of endoscopic treatment and suggest a cholangiographic classification.

Methods.
The 125 strictures among the 104 patients with right-lobe living donor liver transplantation were reviewed. The strictures were classified by the anastomosis pattern according to the number (1, 2, or >2), location (common bile, hepatic, or cystic duct), the angle between the proximal and distal sites of the anastomosis, and the contrast enhancement pattern. The relationship between the success rate of traversing the anastomosis and the classification was evaluated.

Results.
Of the 125 biliary strictures, 86 (68.8%) could be passed via endoscopically. Thirty-three strictures were managed either percutaneously (n = 13) or by magnetic compression anastomosis (n = 20). Compared with the round, the triangular (odds ratio [OR], 6.5), the intermediate form (OR, 17.7), and the end-to-side anastomosis (OR, 5.1) were associated with an increased chance of traversing. The contrast enhancement pattern of the strictures and the bile ducts was also related to the successful rate of the endoscopic treatment (P < 0.001). The success rate was higher in the patients with the angle between the proximal and distal sites of the anastomosis approximated was small (0°–30° = 74%, 30°–60° = 69%, 60°–90° = 63%, >90° = 41%).

Conclusions.
The type of biliary anastomoses and stricture affect the success rate of endoscopic treatment. These data may play role in making decision about the type of anastomosis during the surgery.
A Multicenter Cohort Study From India of 75 Kidney Transplants in Recipients Recovered After COVID-19
Authors: Kute Vivek B. , Ray Deepak S. , Yadav Dinesh Kumar , Pathak Vivek , Bhalla Anil K. , Godara Suraj , Kumar Anil , Guleria Sandeep , Khullar Dinesh , Thukral Sharmila , Mondal Rabi Ranjan Sow , Jain Manish , Jha Pranaw Kumar , Hegde Umapati , Abraham M. Abi , Dalal Sonal , Patel Himanshu , Bahadur Madan M. , Shingare Ashay , Sharma Ashish , Kumar Sharma Raj , Anandh Urmila , Gulati Sanjeev , Gumber Manoj , Siddini Vishwanath , Deshpande Rushi , Kaswan Kamal , Varyani Umesh , Kakde Shailesh , Kenwar Deepesh B. , Shankar Meshram Hari , Kher Vijay 
Published: March 2021

Background.There is limited current knowledge on feasibility and safety of kidney transplantation in coronavirus disease-19 (COVID-19) survivors.Methods.We present a retrospective cohort study of 75 kidney transplants in patients who recovered from polymerase chain reaction (PCR)–confirmed COVID-19 performed across 22 transplant centers in India from July 3, 2020, to January 31, 2021. We detail demographics, clinical manifestations, immunosuppression regimen, laboratory findings, treatment, and outcomes. Patients with a previous diagnosis of COVID-19 were accepted after documenting 2 negative severe acute respiratory syndrome coronavirus 2 PCR tests, normal chest imaging with complete resolution of symptom for at least 28 d and significant social distancing for 14 d before surgery.Results.Clinical severity in patients ranged from asymptomatic (n = 17, 22.7%), mild (n = 36.48%), moderate (n = 15.20%), and severe (n = 7.9.3%) disease. Median duration between PCR positive to transplant was 60 d (overall) and increased significantly from asymptomatic, mild, moderate, and severe disease (49, 57, 83, 94 d,P0.019), respectively. All recipients and donors were asymptomatic with normal creatinine after surgery at a median (interquartile range) follow-up of 81 (56–117) d without any complications relating to surgery or COVID-19. Patient and graft survival was 100%, and acute rejection was reported in 6.6%.Conclusions.Prospective kidney transplant recipients post-COVID-19 can be considered for transplantation after comprehensive donor and recipient screening before surgery using a combination of clinical, radiologic, and laboratory criteria, careful pretransplant evaluation, and individualized risk-benefit analysis. Further large-scale prospective studies with longer follow-up will better clarify our initial findings. To date, this remains the first and the largest study of kidney transplantation in COVID-19 survivors.
Outcomes Following ATG Therapy for Chronic Lung Allograft Dysfunction
Authors: Kotecha Sakhee , Paul Eldho , Ivulich Steve , Fuller Jeremy , Paraskeva Miranda , Levvey Bronwyn , Snell Gregory , Westall Glen 
Published: March 2021

Background.
Chronic lung allograft dysfunction (CLAD) is the major factor limiting survival post lung transplantation (LTx) with limited effective therapeutic options. We report our 12-y experience of antithymocyte globulin (ATG) as second-line CLAD therapy.

Methods.
Clinical and lung function data were collected on LTx patients receiving ATG. Rate of FEV1 decline (mL/d) was calculated before and after ATG. Partial response to ATG was defined by rate of FEV1 decline improving 20%. Complete response was defined by an absolute improvement or stability in baseline FEV1.

Results.
Seventy-six patients received ATG for CLAD. Of these, 5 patients who had a clinical diagnosis of antibody-mediated rejection and were treated with plasmapheresis before or after ATG were excluded from analysis. Sixteen (23%) were complete responders, 29 (40%) were partial responders, and 26 (37%) did not respond. Those with CLAD stage 2 or 3 and younger age were more likely to respond. Partial responders had a 65% lower risk of death or retransplant (HR, 0.35; P = 0.003), whereas complete responders reduced their risk by 70% (HR, 0.30; P = 0.006).

Conclusions.
ATG appears to stabilize or attenuate lung function decline in CLAD, which may lead to improved retransplant-free survival. Although certain predictors of response have been identified in this large single-center review, these findings need to be confirmed by a multicenter randomized-controlled trial to determine predictors of response to ATG for CLAD.
Jannaschia marina sp. nov., isolated from the gut of a gastropod, Onchidium reevesii
Authors: Chen Si , He Mengyuan , Lai Qiliang , Xu Ying , Shang Chenjing 
Published: March 2021

A taxonomic study was carried out on strain SHC163T, which was isolated from the gut of Onchidium reevesii. The bacterium was Gram-stain-negative, oxidase-positive, catalase-negative and rod-shaped. Growth was observed at salinities of 0–4.0 % NaCl and at temperatures of 15–35 °C. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain SHC163T belonged to the genus

Jannaschia

, with the highest sequence similarity to

Jannaschia seosinensis

CL-SP26T (97.9%), followed by

Jannaschia faecimaris

DSM 100420T (97.8 %),

Jannaschia rubra

CECT 5088T (97.5%) and eight species of the genus

Jannaschia

(94.7−97.1 %). The average amino acid identity, average nucleotide identity and the digital DNA–DNA hybridization estimate values between strain SHC163T and the type strains of the genus

Jannaschia

were 64.33−79.78 %, 71.0−78.4 % and 19.2−21.0%, respectively. The principal fatty acids (>5 %) were summed feature 8 (C18 : 1
ω7c/C18 : 1
ω6c, 56.5 %), C18 : 1
ω7c 11-methyl (23.1 %), C18 : 0 (8.7 %). The G+C content of the chromosomal DNA was 67.8 mol%. The respiratory quinone was determined to be Q-10 (100 %). The polar lipids were phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, an unidentified phospholipid, an unidentified aminolipid and aminophospholipid. The combined genotypic and phenotypic data show that strain SHC163T represents a novel species within the genus

Jannaschia

, for which the name Jannaschia marina sp. nov. is proposed, with the type strain SHC163T (=MCCC 1K04032T=KCTC 72524T).
Targeting Lyn Kinase in Chorea-Acanthocytosis: A Translational Treatment Approach in an Ultra-Rare Disease
Authors: Peikert Kevin , Glaß Hannes , Federti Enrica , Matte Alessandro , Pelzl Lisann , Akgün Katja , Ziemssen Tjalf , Ordemann Rainer , Lang Florian ,   The Network for translational research for Neuroacanthocytosis Patients, Franceschi Lucia De , Hermann Andreas 
Published: March 2021

ABSTRACTBackgroundChorea-acanthocytosis (ChAc) is a neurodegenerative disease caused by mutations in the VPS13A gene. It is characterized by several neurological symptoms and the appearance of acanthocytes. Elevated tyrosine kinase Lyn activity has been recently identified as one of the key pathophysiological mechanisms and therefore represents a promising drug target.MethodsWe evaluated an individual off-label treatment with the FDA-approved tyrosine kinase inhibitor dasatinib (100 mg/d, 25.8-50.4 weeks) of three ChAc patients. Alongside with a thorough safety monitoring, we assessed motor and non-motor scales (e.g. MDS-UPDRS, UHDRS, quality of life) as well as routine and experimental laboratory parameters (e.g. serum neurofilament, Lyn kinase activity, actin cytoskeleton in red blood cells).ResultsDasatinib appeared to be reasonably safe. The clinical parameters remained stable without significant improvement or deterioration. Regain of deep tendon reflexes was observed in one patient. Creatine kinase, serum neurofilament levels and acanthocyte count did not reveal consistent effects. However, reduction of initially elevated Lyn kinase activity and accumulated autophagy markers as well as partial restoration of actin cytoskeleton was found in red blood cells.DiscussionWe report on the first treatment approach with disease-modifying intention in ChAc. The experimental parameters indicate target engagement in red blood cells, while clinical effects on the central nervous system could not be proven within a rather short treatment time. Limited knowledge on the natural history of ChAc and the lack of appropriate biomarkers remain major barriers for “clinical trial readiness”. Here, we suggest a panel of outcome parameters for future clinical trials in ChAc.
BNT162b2 mRNA COVID-19 vaccine induces antibodies of broader cross-reactivity than natural infection but recognition of mutant viruses is up to 10-fold reduced
Authors: Chang Xinyue , Augusto Gilles Sousa , Liu Xuelan , Kündig Thomas M , Vogel Monique , Mohsen Mona O. , Bachmann Martin F. 
Published: March 2021

AbstractBackgroundSeveral new variants of SARS-CoV-2 have emerged since fall 2020 which have multiple mutations in the receptor binding domain (RBD) of the spike protein.ObjectiveWe aimed to assess how mutations in RBD affected recognition of immune sera by antibodies induced by natural infection versus immunization with BNT162b2, a mRNA-based vaccine against COVID-19.MethodsWe produced SARS-CoV-2 RBD mutants with single mutations in the receptor binding domain (RBD) region (E484K, K417N, N501Y) or with all 3 mutations combined, as occurring in the newly emerged variants B.1.351 (South Africa) and P.1 (Brazil). Using standard and avidity ELISAs, we determined the binding capacities to mutant RBDs of antibodies induced by infection versus vaccination.ResultsThese binding assays showed that vaccination induced antibodies recognize both wildtype and mutant RBDs with higher avidities than those raised by infection. Nevertheless, recognition of mutants RBDK417Nand RBDN501Ywas 2.5-3-fold reduced while RBDE484Kand the triple mutant were 10-fold less well recognized, demonstrating that the mutation at position 484 was key for the observed loss in cross-reactivity.ConclusionOur binding data demonstrate improved recognition of mutant viruses by BNT162b2-induced antibodies compared to those induced by natural infection. Recognition may, however, be 10-fold reduced for the variants B.1.351/P.1, suggesting that the development of a new vaccine is warranted. The E484K mutation is an key hurdle for immune recognition, convalescent plasma and monoclonal antibody therapy as well as serological assays based on the wildtype sequence may therefore seriously impaired.Capsule summaryBNT162b2 mRNA COVID-19 vaccine-induced antibodies recognize mutant viruses with up to 10-fold lower efficiency
Structural insights into the role of Dicer-related helicase 3 in RNAi inCaenorhabditis elegans
Authors: Li Kuohan , Zheng Jie , Wirawan Melissa , Trinh Nguyen Mai , Fedorova Olga , Griffin Patrick , Pyle Anna Marie , Luo Dahai 
Published: March 2021

ABSTRACTDRH-3 belongs to the family of duplex RNA-dependent ATPases (DRAs), which include Dicer and RIG-I-like receptors (RLRs). DRH-3 is critically involved in germline development and RNAi-facilitated chromosome segregation via the 22G-siRNA pathway in C. elegans. The molecular understanding of DRH-3 and its function in endogenous RNAi pathways remains elusive. In this study, we solved the crystal structures of the DRH-3 N-terminal domain (NTD) and the C-terminal domains (CTDs) in complex with 5’-triphosphorylated RNAs. The NTD of DRH-3 adopts a distinct fold of tandem Caspase Activation and Recruitment Domains (CARDs) structurally similar to the CARDs of RIG-I and MDA5, suggesting a signaling function in the endogenous RNAi biogenesis. The CTD preferentially recognizes 5’-triphosphorylated double-stranded RNAs bearing the typical features of secondary siRNA transcripts. The full-length DRH-3 displays unique structural dynamics upon binding to RNA duplexes that differ from RIG-I or MDA5. These unique molecular features of DRH-3 help explain its function in RNAi in worms and the evolutionary divergence of the Dicer-like helicases.
Complex population dynamics in a spatial microbial ecosystem withPhysarum polycephalum
Authors: Epstein Leo , Dubois Zeth , Smith Jessica , Lee Yunha , Harrington Kyle 
Published: March 2021

AbstractThis research addresses the interactions between the unicellular slime moldPhysarum polycephalumand a red yeast in a spatial ecosystem over week-long imaging experiments. An inverse relationship between the growth rates of both species is shown, whereP. polycephalumhas positive growth when the red yeast has a negative growth rate and vice versa. The data also captures successional/oscillatory dynamics between both species. An advanced image analysis methodology for semantic segmentation is used to quantify population density over time, for all components of the ecosystem. We suggest thatP. polycephalumis capable of exhibiting a sustainable feeding strategy by depositing a nutritive slime trail, allowing yeast to serve as a periodic food source. This opens a new direction ofP. polycephalumresearch, where the population dynamics of spatial ecosystems can be readily quantified and complex ecological dynamics can be studied.
Chromosome counting in the mouse zygote using low-invasive super-resolution live-cell imaging
Authors: Hatano Yu , Mashiko Daisuke , Tokoro Mikiko , Yao Tatsuma , Yamagata Kazuo 
Published: March 2021

AbstractIn preimplantation embryos, an abnormal chromosome number causes developmental failure and a reduction in the pregnancy rate. Conventional chromosome testing methods requiring biopsy reduce the risk of associated genetic diseases; nevertheless, the reduction in cell number also reduces the pregnancy rate. Therefore, we attempted to count the chromosomes in mouse (Slc:ICR) embryos using super-resolution live-cell imaging as a new method of chromosome counting that does not reduce the cell number or viability. We counted the forty chromosomes at the first mitosis by injecting embryos with histone H2B-mCherry mRNA under conditions by which pups could be obtained; however, the results were often an underestimation of chromosome number and varied by embryo and time point. Therefore, we developed a method to count the chromosomes via CRISPR/dCas-mediated live-cell fluorescencein situhybridization targeting the sequence of the centromere region, enabling us to count the chromosomes more accurately in mouse embryos. The methodology presented here may provide useful information for assisted reproductive technologies, such as those used in livestock animals/humans, as a technique for assessing the chromosomal integrity of embryos prior to transfer.Impact StatementLow-toxic super-resolution observation enables chromosome counting in preimplantation embryos without cell collection.
Recurrent structural variations of lncRNA geneCCDC26in diffuse intrinsic pontine glioma
Authors: Zou Lihua 
Published: March 2021

AbstractWe report recurrent somatic structural variations (SVs) involving long noncoding RNA (lncRNA)CCDC26in 13% of Diffuse Intrinsic Pontine Glioma (DIPG) patients. We validate our findings using whole genome sequencing data from two independent patient cohorts.CCDC26SVs cause increased expression ofCCDC26gene in patients. In addition,CCDC26expression is associated with elevated expression ofMYCand proliferation signature. Our findings identifyCCDC26as a novel significantly mutated gene in DIPG and highlight the importance of structural variations in pediatric brain cancer.
Cytoplasmic forces functionally reorganize nuclear condensates in oocytes
Authors: Jord Adel Al , Letort Gaëlle , Chanet Soline , Tsai Feng-Ching , Antoniewski Christophe , Eichmuller Adrien , Da Silva Christelle , Huynh Jean-René , Gov Nir S. , Voituriez Raphaël , Terret Marie-Émilie , Verlhac Marie-Hélène 
Published: March 2021

AbstractCells remodel their cytoplasm with force-generating cytoskeletal motors1. Their activity generates random forces that stir the cytoplasm, agitating and displacing membrane-bound organelles like the nucleus in somatic2–4and germ5–7cells. These forces are transmitted inside the nucleus4,7, yet their consequences on liquid-like biomolecular condensates8–10residing in the nucleus remain unexplored. Here, we probe experimentally and computationally diverse nuclear condensates, that include nuclear speckles, Cajal bodies, and nucleoli, during cytoplasmic remodeling of female germ cells named oocytes. We discover that growing mammalian oocytes deploy cytoplasmic forces to timely impose multiscale reorganization of nuclear condensates for the success of meiotic divisions. These cytoplasmic forces accelerate nuclear condensate collision-coalescence and molecular kinetics within condensates. Inversely, disrupting the forces decelerates nuclear condensate reorganization on both scales, compromising condensate-associated mRNA processing and consequently hindering oocyte divisions that drive female fertility. We establish that cytoplasmic forces can reorganize nuclear condensates in an evolutionary conserved fashion in insects. Our work implies that cells evolved a mechanism, based on cytoplasmic force tuning, to functionally regulate a broad range of nuclear condensates across scales. This finding opens new perspectives when studying condensate-associated pathologies like cancer, neurodegeneration and viral infections11–13.