bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristics and outcomes of patients with COVID-19 in Hainan, South China
Authors: Zheng Yamei , Gao Yunsuo , Wu Biao , Huang Linhui , Chen Yongxing , Cai Xingjun
Published: March 2021

As an international tourist center, Hainan province includes both imported and local COVID-19 cases. This study aimed to investigate the clinical characteristics and outcomes of COVID-19 patients in Hainan, China.

COVID-19 patients hospitalized in Hainan affiliated Hospital of Hainan Medical University in January to March 2020 were retrospectively assessed. Routine blood tests, blood gas analyses, and computed tomography imaging were performed within 24 hours. Virus nucleic acid was detected every other day. The patients were divided into local resident and traveler groups, and differences in clinical data as well as leukocyte, lymphocyte, and neutrophil levels were analyzed.

A total of 70 patients aged 51.23 ± 13.54 years were assessed, including 16 local residents and 54 travelers. Of these, 55 cases (78.6%) had fever, 47 (67.1%) had cough and sputum, and 9 (12.9%) had chest dyspnea; 60 and 10 cases were mild/common and severe/critical, respectively. Sex, basic diseases, smoking history and drinking history, Charlson Comorbidity Index, symptoms, time of onset to admission, clinical severity, white blood cell count, lymphocyte count, neutrophil count, oxygen inhalation, mechanical ventilation, glucocorticoid therapy, treatment, admission to ICU, hospital stay, and mortality were similar between the 2 groups.

The warm and humid climate of Hainan does not seem to significantly affect patient features and outcomes from COVID-19. Unnecessary travel to tourist areas should be avoided.
Efficacy and safety of Buzhong Yiqi decoction combined with western medicine in the treatment of myasthenia gravis
Authors: Zong Gang , Liu Shiliang , Chen Zunling , Hu Yulei
Published: March 2021

Background:

Myasthenia gravis is a common autoimmune disease in clinic. Although there are various ways and drugs for the treatment of myasthenia gravis in Western medicine, there are still a variety of adverse reactions. Studies have shown that Buzhong Yiqi decoction combined with Western medicine has a certain efficacy in the treatment of myasthenia gravis, but there is a lack of evidence-based medicine. The research carried out in this scheme is to systematically evaluate the efficacy and safety of Buzhong Yiqi decoction combined with Western medicine in the treatment of myasthenia gravis, and to provide reliable evidence for guiding clinical practice.

Methods:

English databases (the Cochrane Library, PubMed, Web of Science, Embase) and Chinese databases (China Biomedical Database, China Science and Technology Journal Database, China National Knowledge Infrastructure, Wanfang) will be searched by computer. In addition, Baidu Academic and Chinese Clinical Trial Registration Center will be searched manually. A randomized controlled clinical trial of Buzhong Yiqi decoction combined with Western medicine in the treatment of myasthenia gravis will be conducted from the establishment of the database to December 2020. The 2 researchers independently carry out data extraction and literature quality evaluation on the quality of the included study, and meta-analysis of the included literature will be carried out by using RevMan 5.3 software.

Results:

This study will evaluate the efficacy and safety of Buzhong Yiqi decoction combined with Western medicine in the treatment of myasthenia gravis by Quantitive MGscore, the number of Tregs cells and the content of anti-acetylcholine receptor antibody (AchR-Ab).

Conclusion:

This study will provide reliable evidence-based evidence for the clinical application of Buzhong Yiqi decoction combined with Western medicine in the treatment of myasthenia gravis.

Ethics and dissemination:

Private information from individuals will not be published. This systematic review also does not involve endangering participant rights. Ethical approval was not required. The results may be published in a peer-reviewed journal or disseminated at relevant conferences.

OSF Registration number:

DOI 10.17605/OSF.IO/MXUPK.
Irreducible Lisfranc injury by tibialis anterior tendon entrapment
Authors: Kim Do-Yeon , Kim Jong-Kil , Kim Min-Woo , Lee Kwang Bok
Published: March 2021

Rationale:

Lisfranc injuries are a dislocation of the metatarsal bones from the tarsal bone. Although closed reduction is possible in most cases of Lisfranc injury when attempted in the early stage, there are some rare cases for which open reduction is required. Herein we report a case of irreducible Lisfranc injury in a 34-year-old man who presented to our institution with painful swelling.

Patient concerns:

We report a 34-year-old man presented to our institution with painful swelling after a fall from 1.0 m height.

Diagnoses:

We diagnosed it as irreducible Lisfranc injury by tibialis anterior tendon entrapment through plain radiologic study and surgical findings.

Interventions:

Plain X-ray, C-arm fluoroscopy and open surgery were performed.

Outcomes:

We did a closed reduction under a C-arm fluoroscopic guide, but it was not successful. Thus, we had to do an open reduction of a Lisfranc dislocation. Upon exposure, we observed the entrapment of the tibialis anterior tendon between the medial and intermediate cuneiform bones.

Lessons:

Our report is valuable in that it can contribute to the diagnosis and suggest a clue to the treatment of such a rare pathology. The knowledge in the rare case of entrapment of the tibialis tendon and the understanding of management will be useful when a irreducible Lisfranc dislocation is unsuccessful after an attempt at closed reduction.
Digestive system symptoms and function in children with COVID-19
Authors: Wang Jiajia , Yuan Xiaofeng
Published: March 2021

The prevalence of children exhibiting coronavirus disease 2019 (COVID-19) with digestive system involvement remains unknown. Therefore, we aimed to quantify the impact of COVID-19 on the digestive system of children.

In this meta-analysis, we searched PubMed, Embase, and Web of Science from January 1, 2020, to June 31, 2020. We also searched for COVID-19 publications in specific journals for more comprehensive results. We included studies that reported the epidemiological and clinical characteristics of COVID-19, and we excluded duplicate publications, reviews, animal studies, case reports, publications without the full text, studies with incomplete information, and studies from which data extraction was impossible.

We conducted a meta-analysis of the incidence of gastrointestinal symptoms and changes in liver function involving 19 studies. The pooled prevalence of diarrhea was 10% (95% CI: 7–14; I
2 
= 84%), that of nausea or vomiting was 7% (95% CI: 5–11; I
2 
= 77%), and that of abdominal pain was 4% (95% CI: 2–9; I
2 
= 79%). In addition, the pooled incidence of increased alanine aminotransferase was 8% (95% CI: 5–15; I
2 
= 46%), and the pooled incidence of increased AST was 15% (95% CI: 9–26; I
2 
= 66%). The pooled rate of recovery was 97% (95% CI: 94–100; I
2 
= 86%), and the pooled rate of death, which was 1% (95% CI: 1–4; I
2 
= 48%), was much smaller than the recovery rate.

Our research shows that digestive system symptoms and function in children with COVID-19 are not uncommon. More attention should be paid to this unique group of patients.
Primary pulmonary lymphoepithelioma-like carcinoma
Authors: Zhang Liqin , Hao Tairan , Wei Yuqing , Dong Mo , Xiong Yuancheng
Published: March 2021

Rationale:

Primary pulmonary lymphoepithelioma-like carcinoma (PPLELC) is a rare subtype of non-small cell lung cancer (NSCLC). It is predominantly reported in East Asia and currently there is no standard treatment for this disease. We report a case of stage IV PPLELC that achieved pathological complete response (pCR) by neoadjuvant treatment.

Patient concerns:

The patient was a 46-year-old male who developed hemoptysis for about 20 ml of volume accompanied by cough and sputum after physical labor.

Diagnoses:

Contrast enhanced chest CT scanning showed occupation of left lower hilar area and left pleural effusion. Combined with medical history and auxiliary examination, the patient was formally diagnosed stage IV lymphoepithelioma-like carcinoma of the left lower lung (T3N0M1a pleura).

Interventions:

The patient was given Sintilimab combined with gemcitabine + nedaplatin chemotherapy (GP) regimen for four cycles with 3 weeks as a cycle, supplemented with antiemetics and stomach protection drugs to reduce chemotherapy-related side effects.

Outcomes:

After 4 cycles of treatment, the patient's left lung lesion has been markedly reduced and the left pleural effusion has also been significantly absorbed. Remarkably, surgical biopsies found no cancer cells in the lesion site and postoperative pathology showed complete pathological remission (pCR).

Lessons:

We reported a case of PPLELC that is sensitive to neoadjuvant treatment, showing excellent effectiveness and safety and achieving pCR.
PLCG2 as a potential indicator of tumor microenvironment remodeling in soft tissue sarcoma
Authors: Li Zhengtian , Zhao Rong , Yang Wenkang , Li Chan , Huang Jun , Wen Zhenpei , Du Gang , Jiang Lingling
Published: March 2021

The tumor microenvironment (TME) plays an important role in the occurrence and development of soft tissue sarcoma (STS). A number of studies have shown that to inhibit tumor growth, the TME can be remodeled into an environment unsuitable for tumor proliferation. However, a lack of understanding exists regarding the dynamic regulation of TME.

In this study, we used CIBERSORT and ESTIMATE calculation methods from the Cancer Genome Atlas (TCGA) database to calculate the proportion of tumor infiltrating immune cells (TICs) and the number of immune and stromal components in 263 STS samples. Differential expression genes (DEGs) shared by Immune Score and Stromal Score were obtained via difference analysis. Univariate Cox regression analysis and construction of protein–protein interaction (PPI) networks were applied to the DEGs.

Through intersection analysis of univariate COX and PPI, PLCG2 was determined as the indicator. Further analysis showed that PLCG2 expression was positively correlated with the survival of STS patients. Gene set enrichment analysis (GSEA) showed that genes in the highly expressed PLCG2 group were enriched in immune-related activities. In the low-expression PLCG2 group, genes were enriched in the E2F, G2M, and MYC pathways. Difference analysis and correlation analysis showed that CD8+ T cells, gamma delta T cells, monocytes, and M1 macrophages were positively correlated with PLCG2 expression, indicating that PLCG2 may represent the immune status of TME.

Therefore, the level of PLCG2 may aid in determining the prognosis of STS patients, especially the status of TME. These data provide additional insights into the remodeling of TME.
Phrenic nerve stimulation, a rare complication of pacemaker
Authors: Dalex Meddy , Malezieux Astrid , Parent Thibault , Zekry Dina , Serratrice Christine
Published: March 2021

Rationale:

The phrenic nerve stimulation (PNS) is a rare complication after pacemaker setting. We report a case report that describes this complication and how it can be resolved.

Patient concerns:

An 88-year-old man presented himself to the emergency geriatric unit with intermittent painless abdominal contraction due to phrenic nerve stimulation. He has a history of transcatheter aortic valve implantation with cardiac resynchronization therapy pacemaker due to persistent left bundle branch block.

Diagnoses:

All the usual causes for abdominal spasms were eliminated and the possibility of a link with the pacemaker was considered. The phrenic nerve stimulation is a rare complication of a pacemaker implantation. It can be clinically nonrelevant but challenging to diagnose for those not familiar with cardiac devices technology.

Interventions:

Initial setting was an axis of stimulation between distal left ventricular (LV) and right ventricular. It was changed to LV and D1-M2.

Outcomes:

This noninvasive procedure managed to eradicate the involuntary abdominal spasms.

Lessons:

PNS could be challenging to diagnose for those not familiar with cardiac devices technology but easy to manage with noninvasive methods.
The evaluation of oxidative stress parameters in breast and colon cancer
Authors: Kundaktepe Berrin Papila , Sozer Volkan , Durmus Sinem , Kocael Pinar Cigdem , Kundaktepe Fatih Orkun , Papila Cigdem , Gelisgen Remise , Uzun Hafize
Published: March 2021

Our aim in this study was to investigate the relationship between serum ischemia modified albumin (IMA) levels with oxidative stress parameters [protein carbonyl (PCO), advanced protein oxidation products (AOPPs), malondialdehyde (MDA), total nitric oxide (NOx), prooxidant-antioxidant balance (PAB), and ferric reducing of antioxidant power (FRAP)] in breast cancer (BC) and colon cancer (CC).

In total, 90 patients undergoing surgical treatment for BC (n = 45) or CC (n = 45) and 35 healthy controls were included in this cross-sectional study.

The serum PCO, AOPPs, MDA, NOx, PAB, and IMA levels were all statistically significantly higher in the cancer patients than in the control group. MDA, NOx, and PAB levels were significantly lower in the BC group than in the CC group. FRAP values were statistically significantly lower in both the CC group and the BC group compared to the control. IMA showed a weak positive correlation with CA-19.9 (r = 0.423 P = .007) but a moderate positive correlation with tumor size in the CC group. IMA showed a positive correlation with metastasis, grade, and HER2 and a negative correlation with ER and PR in the BC group.

Oxidative stress is a key player in the development of solid malignancies. Cancer development is a multistage process, and oxidative stress caused by the production of ROS/RNS in the breast and colon may predispose individuals to BC and CC. Patients with BC and CC had an impaired oxidative/antioxidant condition that favored oxidative stress. The ROC analysis indicated that IMA sensitivity above 80% could be used as a secondary biomarker in diagnosis.
A novel missense variant in TRAPPC2 causes X-linked spondyloepiphyseal dysplasia tarda
Authors: Zhang Li , Wang Jinling , Dong Guanping , Wu Dingwen , Wu Wei
Published: March 2021

Rationale:

X-linked spondyloepiphyseal dysplasia tarda (X-linked SEDT) is a rare hereditary cause in childhood short stature due to mutations in trafficking protein particle complex subunit 2 (TRAPPC2) gene located on chromosome Xp22. Several pathogenic variants in TRAPPC2 have been reported, but missense variants are rare.

Patient concerns:

A 13-year, 8-month-old Chinese Han boy presenting with short stature for the past 7 years.

Diagnosis:

X-linked SEDT was established by a combination of clinical and radiographic features, confirmed by targeted next-generation sequencing. Genetic testing of the TRAPPC2 gene revealed a novel missense variant with c.260A>C (p.H87P) hemizygote in exon5. The mother was found to be a heterozygous TRAPPC2 carrier, whereas the father was normal.

Interventions:

Patient was treated with recombinant human growth hormone daily. Patient's height, glucose level, and possible progressive joint and back pain with osteoarthritis were under intensive observation regularly.

Outcomes:

The patient achieved 2.1 cm height gain over the first 3 months’ recombinant human growth hormone treatment without joint or back pain. However, the therapy was terminated because of increased glucose level on follow-up.

Lessons:

The short stature is a noteworthy problem for X-linked SEDT cases. We report a novel missense variant site in TRAPPC2 treated with growth hormone in the literature. We do not recommend the use of recombinant human growth hormone on patients with X-linked SEDT for the concern of glucose homeostasis.
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

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

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.
Capillibacterium thermochitinicola gen. nov., sp. nov., a novel anaerobic thermophilic chitinolytic bacterium from compost
Authors: Ungkulpasvich Umbhorn , Baramee Sirilak , Uke Ayaka , Kosugi Akihiko
Published: March 2021

A novel Gram-negative, spore forming, obligately anaerobic, thermophilic, chitin-degrading bacterium, designated UUS1-1T, was isolated from compost on Ishigaki Island, Japan by enrichment culturing using chitin powder as the carbon source. The strain has unique, long, hair-like rod morphological features and exhibits strong degradation activity toward crystalline chitin under thermophilic conditions. Growth of the novel strain was observed at 45–65 °C (optimum, 55 °C) and pH 6.5–7.5 (optimum, pH 7.0). In addition to chitin, the strain utilized several other carbon sources, including N-acetylglucosamine, glucose, galactose, mannose, maltose, cellobiose, fructose and sucrose. The end products of chitin degradation were acetate, lactate, H2 and CO2. Phylogenetic tree analysis based on 16S rRNA gene sequences revealed a clear affiliation of the proposed bacterium to the phylum

Firmicutes

; the most closely related species were

Hydrogenispora ethanolica

LX-BT and

Desulfotomaculum thermobenzoicum

DSM6193T with similarities of 90.4 and 87.8 %, respectively. The G+C content of the genomic DNA was 52.1 mol%. The average nucleotide identity and digital DNA–DNA hybridization values between the genomes of UUS1-1T and

H. ethanolica

LX-BT were 65.5 and 21.0 %, respectively. The cellular fatty acid composition of the strain was C16 : 0, anteiso-C15 : 0, C14 : 0, C12 : 0 3-OH and dimethyl acetal-C13 : 0. Based on phenotypic, chemotaxonomic and genotypic analysis, strain UUS1-1T represents a novel genus and species, for which the name Capillibacterium thermochitinicola gen. nov., sp. nov. is proposed. The type strain is UUS1-1T (=JCM 33882T=DSM 111537T).
Kaistella flava sp. nov., isolated from Antarctic tundra soil, and emended descriptions of Kaistella yonginensis, Kaistella jeonii, Kaistella antarctica and Kaistella chaponensis
Authors: Peng Xiaoya , Zhang Yumin , Lu Yijing , Zhou Xueyin , Wei Zhourui , Sun Yulin , Kuang Chengjie , Lu Lu , Geng Yingchao , Qin Kun , Liu Jia , Peng Fang
Published: March 2021

A rod-shaped, yellow-pigmented, Gram-stain-negative, non-motile and aerobic bacterium, designated 7-3AT, was isolated from soil from King George Island, maritime Antarctica, and subjected to a polyphasic taxonomic study. Growth occurred at 4–37 °C (optimum, 20°C) and at pH 5.0–9.0 (optimum, pH 7.0–8.0). Tolerance to NaCl was up to 4 % (w/v) with optimum growth in the absence of NaCl. The results of phylogenetic analysis based on 16S rRNA gene sequences indicated that strain 7-3AT represented a member of the family

Flavobacteriaceae

. Strain 7-3AT showed the highest sequence similarities with

Kaistella yonginensis

HMD 1043T (96.65 %),

Kaistella carnis

NCTC 13525T (96.53 %),

Kaistella chaponensis

DSM 23145T (96.27 %),

Kaistella antarctica

LMG 24720T (96.13 %) and

Kaistella jeonii

DSM 17048T (96.06 %). A whole genome-level comparison of 7-3AT with

K. jeonii

DSM 17048T,

K. antarctica

LMG 24720T,

K. chaponensis

DSM 23145T, and

Kaistella palustris

DSM 21579T revealed average nucleotide identity (ANI) values of 79.03, 82.25, 78.12, and 74.42 %, respectively. The major respiratory isoprenoid quinone was identified as MK-6 and a few ubiquinones Q-10 were identified. In addition, flexirubin-type pigments were absent. The polar lipid profile of 7-3AT was found to contain one phosphatidylethanolamine, six unidentified aminolipids (AL) and two unidentified lipids (L). The G+C content of the genomic DNA was determined to be 34.54 mol%. The main fatty acids were iso-C15 : 0, summed feature 9 (comprising iso-C17 : 1ω9c and/or C16 : 0 10-methyl), anteiso-C15 : 0, iso-C13 : 0 and summed feature 3 (comprising C16 : 1ω7c and/or C16 : 1ω6c). On the basis of the evidence presented in this study, a novel species of the genus

Kaistella

, Kaistella flava sp. nov., is proposed, with the type strain 7-3AT (=CCTCC AB 2016141T= KCTC 52492T). Emended descriptions of

Kaistella yonginensis

,

Kaistella jeonii

,

Kaistella antarctica

and

Kaistella chaponensis

are also given.
Acidovorax antarcticus sp. nov., isolated from a soil sample of Collins Glacier front, Antarctica
Authors: Xu Qiang , Peng Xiaoya , Wang Yanhong , Lu Lu , Zhang Yongping , Qin Kun , Liu Jia , Peng Fang
Published: March 2021

A Gram-stain-negative, rod-shaped, and aerobic bacterium, strain 16-35-5T, was isolated from Collins Glacier front soil from the Fildes Peninsula, Antarctica. The bacterium grew optimally at 28 °C, pH 7.0 and in the presence of 0–4.0 % (w/v) NaCl. On the basis of the results of 16S rRNA gene sequence phylogenetic analyses, it was concluded that 16-35-5T represented a member of the genus

Acidovorax

and had the highest sequence similarities with

Acidovorax anthurii

CFBP 3232T (96.48 %). The genome of 16-35-5T is 4.2 Mb long with a DNA G+C content of 66.3 mol%. Average nucleotide identity (ANI) value between the genomes of 16-35-5T and

Acidovorax wautersii

DSM 27981T, was 85.29 %. Strain 16-35-5T had ubiquinone-8 (Q-8) as the respiratory ubiquinone. The polar lipids of 16-35-5T were consisted of phosphatidylethanolamine, diphosphatidylglycerol and phosphatidylglycerol. The main fatty acids were summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c, 25.2 %), summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c, 12.9 %), C16 : 0 (35.2 %), and C17 : 0 cyclo (19.0 %). On the basis of the evidence presented in this study, 16-35-5T should be classified as representing a novel species of the genus

Acidovorax

, for which the name Acidovorax antarcticus sp. nov., is proposed, with the type strain 16-35-5T (=CCTCC AB 2019325T=KCTC 72915T).
Lacticaseibacillus absianus sp. nov., isolated from the cecum of a mini-pig
Authors: Bai Lu , Paek Jayoung , Shin Yeseul , Park Ho-Yong , Chang Young Hyo
Published: March 2021

A rod-shaped, facultative anaerobic, Gram-stain-positive bacteria, isolated from the cecum of a mini-pig, was designated as strain YH-lac23T. Analysis of 16S rRNA gene sequences revealed that the strain was closely related to

Lacticaseibacillus daqingensis

JCM 33273T (97.9 %),

Lacticaseibacillus porcinae

KCTC 21027T (96.2 %) and

Lacticaseibacillus manihotivorans

KCTC 21010T (95.7 %). Analysis of housekeeping gene sequences (pheS and recA) revealed that the strain formed a sub-cluster with

L. daqingensis

. The average nucleotide identity value for YH-lac23T and its most closely related strain (

L. daqingensis

) is 80.7 %. The main fatty acids are C18 : 1ω9c and C16 : 0. The cell wall contains the peptidoglycan of meso-diaminopimelic acid. The G+C content of the genomic DNA is 59.8 mol%. In view of the chemotaxonomic, phenotypic and phylogenetic properties, YH-lac23T (=KCTC 25006=JCM 33998) represents a novel taxon. The name Lacticaseibacillus absianus sp. nov. is proposed.
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

Background

Chorea-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.

Methods

We 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).

Results

Dasatinib 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.

Discussion

We 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

Background

Several 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.

Objective

We 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.

Methods

We 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.

Results

These 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.

Conclusion

Our 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 summary

BNT162b2 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

DRH-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

This 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

In 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 Statement

Low-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

We 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

Cells 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.
Structural basis for late maturation steps of the human mitoribosomal large subunit
Authors: Cipullo Miriam , Gesé Genís Valentín , Khawaja Anas , Hällberg B. Martin , Rorbach Joanna
Published: March 2021

Mitochondrial ribosomes (mitoribosomes) synthezise a critical set of proteins essential for oxidative phosphorylation. Therefore, their function is vital to cellular energy supply and mitoribosomal defects give rise to a large and diverse group of human diseases1. The architecture of mitoribosomes is strikingly different from that of their bacterial and eukaryotic cytosolic counterparts and display high divergence between species2–6. Mitoribosome biogenesis follows distinct molecular pathways that remain poorly understood. Here, we determined the cryo-EM structures of mitoribosomes isolated from human cell lines with either depleted or overexpressed mitoribosome assembly factor GTPBP5. This allowed us to capture consecutive steps during mitoribosomal large subunit (mt-LSU) biogenesis that involve normally short-lived assembly intermediates. Our structures provide important insights into the last steps of 16S rRNA folding, methylation and peptidyl transferase centre (PTC) completion, which require the coordinated action of nine assembly factors. We show that mammalian-specific MTERF4 contributes to the folding of 16S rRNA, allowing 16S rRNA methylation by MRM2, while GTPBP5 and NSUN4 promote fine-tuning rRNA rearrangments leading to PTC formation. Moreover, our data reveal an unexpected role for the elongation factor mtEF-Tu in mt-LSU assembly, in which mt-EF-Tu interacts with GTPBP5 in a manner similar to its interaction with tRNA during translational elongation. Together, our approaches provide detailed understanding of the last stages of mt-LSU biogenesis that are unique to mammalian mitochondria.