bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between non-alcoholic fatty liver and acute cerebral infarction: a protocol of systematic review and meta-analysis
Authors: Zhang Ya-Juan , Liu Wen-Juan
Published: June 2020

Background:

This study will systematically synthesize the evidence on the potential association between non-alcoholic fatty liver (NAFL) and acute cerebral infarction (ACI).

Methods:

We will propose literature search in electronic databases (MEDLINE, EMBASE, Cochrane Library, Scopus, Web of Science, WANGFANG, and China National Knowledge Infrastructure) from the source to March 1, 2020. There are no restrictions related to the language and publication status. Two review authors will separately carry out records selection, data extraction and study quality assessment. Any divisions will be solved by discussion with consulting a third review author. We will use RevMan 5.3 software to perform data analysis.

Results:

The present study will afford additional insight into the investigation the association between NAFL and ACI.

Conclusion:

The results of this study will provide helpful evidence to explore the association between NAFL and ACI.

Study registration number: INPLASY202040102.
Developing a template matching algorithm for benchmarking hospital performance in a diverse, integrated healthcare system
Authors: Molling Daniel , Vincent Brenda M. , Wiitala Wyndy L. , Escobar Gabriel J. , Hofer Timothy P. , Liu Vincent X. , Rosen Amy K. , Ryan Andrew M. , Seelye Sarah , Prescott Hallie C.
Published: June 2020

Template matching is a proposed approach for hospital benchmarking, which measures performance based on matching a subset of comparable patient hospitalizations from each hospital. We assessed the ability to create the required matched samples and thus the feasibility of template matching to benchmark hospital performance in a diverse healthcare system.

Nationwide Veterans Affairs (VA) hospitals, 2017.

Observational cohort study.

We used administrative and clinical data from 668,592 hospitalizations at 134 VA hospitals in 2017. A standardized template of 300 hospitalizations was selected, and then 300 hospitalizations were matched to the template from each hospital.

There was substantial case-mix variation across VA hospitals, which persisted after excluding small hospitals, hospitals with primarily psychiatric admissions, and hospitalizations for rare diagnoses. Median age ranged from 57 to 75 years across hospitals; percent surgical admissions ranged from 0.0% to 21.0%; percent of admissions through the emergency department, 0.1% to 98.7%; and percent Hispanic patients, 0.2% to 93.3%. Characteristics for which there was substantial variation across hospitals could not be balanced with any matching algorithm tested. Although most other variables could be balanced, we were unable to identify a matching algorithm that balanced more than ∼20 variables simultaneously.

We were unable to identify a template matching approach that could balance hospitals on all measured characteristics potentially important to benchmarking. Given the magnitude of case-mix variation across VA hospitals, a single template is likely not feasible for general hospital benchmarking.
Impressive long-term response with chemo-endocrine therapy in a premenopausal patient with metastatic breast cancer
Authors: Maltoni Roberta , Palleschi Michela , Gallerani Giulia , Bravaccini Sara , Cecconetto Lorenzo , Melegari Elisabetta , Altini Mattia , Rocca Andrea
Published: June 2020

Rationale:

Patients with, or who develop, metastatic breast cancer have a 5-year relative survival of about 25%. Endocrine therapy clearly improves outcomes in patients with estrogen receptor-positive breast cancer. In the metastatic setting, the primary goal of treatment is to maintain long-term disease control with good quality of life. Rarely, exceptional responders achieve durable disease control, and potential cures cannot be ruled out.

Patient Concerns:

We report the case of a 39-year-old woman with primary breast cancer and associated synchronous bone metastases, who experienced a disease response of 12 years with hormonal therapy as maintenance after first line chemotherapy, with a good toxicity profile.

Diagnosis:

The patient was diagnosed with estrogen receptor + human epidermal growth factor receptor 2 (HER2)− metastatic breast cancer with synchronous bone metastases.

Interventions:

This patient was treated with chemotherapy for 6 cycles as a first-line therapy following by endocrine treatment given as a maintenance therapy.

Outcomes:

Our patient experienced a progression-free survival >12 years with an exceptionally good quality of life.

Lessons:

Our anecdotal experience highlights the existence of exceptional responders among patients with hormone receptor-positive metastatic breast cancer, who achieve clinical remission and durable disease control with endocrine therapy. Being able to identify these patients could help in the selection of the best treatment option among the many available.
The brain structure and function alterations in tension-type headache
Authors: Zhou Jun , Cheng Shirui , Yang Han , Lan Lei , Chen Yijia , Xu Guixing , Yin Zihan , Li Zhengjie , Liu Mailan
Published: June 2020

Objective:

The aim of this systematic review and meta-analysis is to improve the understanding of the pathophysiology of tension-type headache (TTH), as well as propose avenues for future neuroimaging studies of TTH.

Methods:

From the inception dates to May 1, 2020, a systematic literature will search in Medline (Ovid SP), Embase (Ovid SP), Cochrane Central Register of Controlled Trials, Web of Science, and 4 Chinese databases without limitation on language or publication. Additionally, International Clinical Trials Registry Platform , reference lists, and relevant gray literatures will be searched. After screening of eligible references, included studies will be determined according to included criteria, and then data extraction and a methodological quality assessment with a customized checklist will be conducted. Each process will be independently implemented by 2 reviewers, any disagreement will be resolved by consensus to the third researcher. If the extracted data is feasible, anisotropic effect-size version of signed differential mapping will be conducted to perform the meta-analysis of the structural and functional brain alterations in TTH patients.
The efficacy and safety of Jinhua Qinggan granule (JHQG) in the treatment of coronavirus disease 2019 (COVID-19)
Authors: Zhang Qiongshuai , Cao Fang , Wang Yufeng , Xu Xiaohong , Sun Yihan , Li Jiannan , Qi Xun , Sun Shaoqian , Ji Guangcheng , Song Bailin
Published: June 2020

Background:

Currently, the global number of infected novel coronavirus has exceeded 2.6 million and the death toll has exceeded 170,000, but the specific drug for the treatment of COVID-19 has been not appears. In the process of fighting COVID-19 in China, JHQG has been promoted by the Chinese government and widely used in the treatment of COVID-19. The purpose of this study is to systematically evaluate the efficacy and safety of JHQG for COVID-19.

Methods:

We are going to search the electronic databases: PubMed, EMBASE, Cochrane library, Web of Science (WOS), Google scholar, China National Knowledge Infrastructure (CNKI), Chinese Biomedical literature Database (CBM), Chinese Scientific and Journal Database (VIP), Wan Fang database (Wanfang) for published clinical trails and search clinical trials register platforms of Chinese Clinical Trial Registry (ChiCTR) and ClinicalTrials.gov (www.ClinicalTrials.gov/) for ongoing trials of Jinhua Qinggan granule for COVID-19. The primary outcomes of the included studies contain Clinical symptom disappearance rate and the secondary outcomes obtain: TCM syndrome scale score, Hamilton anxiety scale score, and adverse events. We will use RevMan V5.3 software to perform the calculations. PRISMA-P checklist was used in writing this report.

Results:

The study results will be submitted to a peer-reviewed journal for publication.

Conclusion:

This study will provide a high-quality evidence of the efficacy and safety of Jinhua Qinggan granule on patients with COVID-19.

PROSPERO registration number:

CRD42020181919.
Retinal blood oxygen saturation and vascular endothelial growth factor-A in early diabetic retinopathy
Authors: Qiu Xianliang , Wang Xian , Hong Peipei , Liu Min , Wen Qing , Chen Qiu
Published: June 2020

Background:

Diabetic retinopathy (DR) remains the most common microvascular complication of diabetes; both its high prevalence and associated high risk of vision loss lead it to the major global health burden. Despite significant research efforts, there still remains much of the underlying pathology not fully understand. In the past studies, inner retinal blood flow disturbances are widely assessed as a potential biomarker of DR. However, the results have been variable and even contradictory. Improved methods to figure out the metabolic disturbances associated with DR are essential. Some research showed that both vascular endothelial growth factor-A and blood oxygen saturation are higher in DR patients and correlated with disease severity. Therefore, we decided to conduct a systematic review and meta-analysis to find out the connection of them and provide robust evidence on the mechanism underlying this connection to help us better understand the pathophysiology behind the hypoxic retina and find better ways to treat DR.

Methods:

This study will be conducted according to Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. We will do electronic searches from PubMed, EMBASE, Web of Science, Cochrane Library, Wanfang database, CNKI, and VIP database. Two reviewers will screen all the references independently and any disagreement will be solved by the third involvement. All data will be extracted by 2 independent reviewers according to a standardized data extraction sheet. Based on the type of studies, 2 reviewers will independently use different scales to assess the risk of bias. Any disagreements and conflicts will be resolved by discussing it with a third reviewer. We will conduct a random-effects meta-analysis. Individual and pooled odds ratios/relative risks and associated 95% confidence intervals will be calculated as well as between-study heterogeneity. The potential for publication bias will also be evaluated. If possible, we will explore reasons for potential between-study heterogeneity.

Results:

This study is a protocol for systematic review and meta-analysis without results. Associated data analysis will be carried out after the protocol.

Conclusion:

The protocol aims to guide a meta-analysis whose purpose is investigating the association between retinal blood oxygen saturation and vascular endothelial growth factors in patients with early DR and trying to find out the mechanism that the changing of retinal oxygen saturation in patients with DR.

INPLASY registration number:

INPLASY202040161
Efficacy and safety of Jinhua Qinggan granules for coronavirus disease 2019 (COVID-19)
Authors: Chen Hao , Song Yan-Ping , Gao Kai , Zhao Lin-Tao , Ma Li
Published: June 2020

Background:

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome (SARS)-COV2 and represents the causative agent of a potentially fatal disease. Jinhua Qinggan granules has definite effect in treating COVID-19 patients, but it has not been systematically evaluated for efficacy and safety.

Methods:

Retrieved the database, including the China National Knowledge Infrastructure (CNKI), Chinese Biomedical literature Database (CBM), Chinese Scientific and Journal Database (VIP), Wan Fang database, PubMed, and EMBASE. Evaluate methodological quality and judge risk of bias through the Cochrane manual. RevMan 5.3 and STATA 16.0 software were used to perform the meta-analysis.

Results:

This study will provide high-quality evidence of Jinhua Qinggan granules for COVID-19.

Conclusion:

The conclusion of this study will provide evidence to determine whether Jinhua Qinggan granules is an effective treatment for COVID-19.

PROSPERO Registration Number:

CRD42020182373.
Efficacy and safety of ramucirumab treatment in patients with advanced colorectal cancer
Authors: Ju Man , Cheng Honggang , Qu Kai , Lu Xiangqian
Published: June 2020

Background:

vascular endothelial growth factor receptor 2 (VEGFR-2) has an important role in colorectal cancer pathogenesis and progression. The aim of our study is to provide a protocol for assessing the efficacy and safety of ramucirumab (a monoclonal antibody VEGFR-2 antagonist) for the treatment of advanced colorectal cancer.

Methods:

The systematic review will be reported according to the preferred reporting items for systematic reviews and meta-analyses protocols. Relevant randomized controlled trials were searched from PubMed, Cochrane Library, Web of Science, Excerpt Medica Database, China National Knowledge Infrastructure, and Wanfang Database. Papers in English or Chinese published from their inception to February 2020 will be included without any restrictions.

Study selection and data extraction will be performed independently by 2 investigators. The clinical outcomes including overall response rate, complete response rate (disease control rate), overall survival, progression-free survival, quality of life, immune function, and adverse events, were systematically evaluated. Review Manager 5.3 and Stata 14.0 were used for data analysis, and a fixed or random-effect model of meta-analysis will be used depending upon the heterogeneity observed between studies. Subgroup analysis will be carried out depending on the availability of sufficient clinical data.

Results and Conclusion:

The findings of this systematic review and meta-analysis will be published in a peer-reviewed journal, and provide more evidence-based guidance in clinical practice.

PROSPERO registration number:

CRD42020165683.
Higher serum uric acid levels are associated with reduced risk of hip osteoporosis in postmenopausal women with rheumatoid arthritis
Authors: Lee Han-Na , Kim Aran , Kim Yunkyung , Kim Geun-Tae , Sohn Dong Hyun , Lee Seung-Geun
Published: June 2020

Although the positive correlation between serum uric acid (UA) levels and bone mineral density (BMD) has been reported in the general population, there are little data regarding the effect of serum UA levels on bone loss in patients with rheumatoid arthritis (RA).

We investigated whether increased serum UA levels were associated with a reduced risk of osteoporosis in postmenopausal women with RA.

In this retrospective cross-sectional study, 447 postmenopausal female patients with RA and 200 age-matched, postmenopausal healthy controls underwent BMD examination by dual energy x-ray absorptiometry and serum UA levels measurement. Osteoporosis was diagnosed when the T-score was <−2.5.

The median UA level in postmenopausal RA patients was found to be significantly lower than that in the healthy women (4 vs 4.1 mg/dL, P = .012) and the frequency of osteoporosis incidence in the lumbar spine, hip, and either site in RA patients was 25.5%, 15.9%, and 32.5%, respectively; the values were significantly higher than those of the controls. After adjusting for confounding factors, a significantly lower risk for osteoporosis of the hip in RA patients was observed within the highest quartile (odds ratio [OR] = 0.37, 95% confidence interval [CI] = 0.16–0.72, P = .021) and the second highest quartile (OR = 0.44, 95% CI = 0.2–0.95, P = .038) of serum UA levels as compared with the lowest quartile, but this association was not found to be consistent with respect to the lumbar spine. Serum UA levels also showed an independently positive correlation with femoral neck BMD (β = 0.0104, P = .01) and total hip BMD (β = 0.0102, P = .017), but not with lumbar BMD.

Our data suggest that UA may exert a protective effect on bone loss in RA, especially in the hip.
The efficacy of ketamine in total knee arthroplasty: a randomized controlled trial protocol
Authors: Chen Jing , Hu Wei , Li Shu-Ming , Li Xiao-Lin , Yang Zhan-Min
Published: June 2020

Background:

Appropriate pain management is essential to improve the postoperative recovery after total knee arthroplasty (TKA). There is a paucity of literature on ketamine for TKA procedures. The aim of this study was to evaluate the analgesic efficacy of ketamine in patients undergoing primary TKA.

Methods:

This study was designed as a prospective, double blind, single center, randomized controlled trial. The participants were randomly assigned to either the ketamine or placebo groups, using a set of random numbers for the allocation sequence. All patients underwent TKA without patella resurfacing under spinal anesthesia. Preoperative workup, surgical technique, and postoperative management were standardized for all the patients. The primary outcome of this noninferiority study is opioid consumption within the first 24 hours following surgery, pain scores, distance ambulated, patient satisfaction, length of hospital stay, and complications.

Results:

The results of this study were expected to provide useful information on the effectiveness and safety of ketamine for immediate postoperative analgesia after TKA surgery.

Trial registration:

This study protocol was registered in Research Registry (researchregistry5575).
Acupuncture for the treatment of radiation-induced xerostomia among patients with cancer
Authors: Chen Rumeng , Gao Yang , Qiu Xianliang , Hong Peipei , Zhou Dongqi , Chen Qiu
Published: June 2020

Background:

With the number of cancer patients growing, radiotherapy and chemotherapy have been a necessary treatment. Unfortunately, there are many side effects after radiation and chemotherapy, one of which is xerostomia that always harasses patients. Although there are many ways of treatment of xerostomia, they have many disadvantages. With the rare side effects and the excellent effect, acupuncture has been widely applied to dry mouth after radiotherapy, but it has not been recognized as the standard treatment. Because acupuncture prescription is mostly different and the sample size of studies is small, we need more high-quality meta-analysis to provide relatively reliable evidence for the treatment of radiation-induced xerostomia. The objective of this study is to assess the curative effect of acupuncture treatment of cancer patients after radiotherapy and provide more reliable evidence for acupuncture treatment of xerostomia after radiotherapy for cancer patients.

Methods:

We will search the following databases: CENTRAL (The Cochrane Central Register of Controlled Trials), MEDLINE, EMBASE, PubMed, CNKI (China National Knowledge Infrastructure), VIP (China Science and Technology Journal Database), Wan Fang Data Knowledge Service Platform. At any rate, 2 review authors will assess all randomized controlled trials (RCTs), seemingly conformance to the inclusion criteria, to confirm qualification, determine the risk of bias and extract data using a running data extraction form. The revolution of disagreements is a discussion. We will use the approach recommended by Cochrane reviews to assess the bias in studies. Risk ratios (RR) and 95% confidence intervals (CIs) will be used to assess the treatment effects of an intervention for dichotomous results. We will use mean differences (MD) and standard deviation (SD) to aggregate the data of every trial for continuous results. The heterogeneity test of Cochran and quantification of the I
2 statistic will be used to assess the variation of treatment effects. Only if there are studies of semblable comparisons reporting the same results, we will conduct a meta-analysis.

Results:

From the study, we will evaluate the efficacy of acupuncture for xerostomia patients who has cancer and been treated by radiation.

Conclusion:

The conclusion of this study will be the evidence, which can ensure the efficacy of acupuncture for cancer patients with radiation-evoked xerostomia among and provide guidance for the treatment of xerostomia.

INPLASY registration number:

INPLASY202040211.
Serum vitamin D levels and type 2 diabetic erectile dysfunction
Authors: Li Fuhao , Qiu Xianliang , Yao Hangyu , Chang Degui
Published: June 2020

Introduction:

Diabetic erectile dysfunction (DED) has gradually become a worldwide problem. Due to the mechanism of DED is not clear, it is impossible to treat it pertinently. Recently, some studies have shown that vitamin D is associated with DED, type 2 diabetes mellitus (T2DM) and erectile dysfunction (ED), but there is no systematic review and meta-analysis on the relationship between vitamin D and DED.

Methods and analysis:

The databases of English databases (PubMed, MEDLINE, EMBASE, Web of Science, Cochrane Library) and Chinese databases (China National Knowledge Infrastructure, China Biology Medicine Database, Wanfang Database, VIP Database) will be retrieved. The search strategy that will be run in the PubMed and tailored to the other database when necessary is presented in Table 1

JOURNAL/medi/04.03/00005792-202006120-00065/table1/v/2023-09-15T184520Z/r/image-tiff

. RevMan 5.3 and Stata 11.0 will be used for Systematic Review and Meta-analysis. This protocol reported under the Preferred Reporting ltems for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) statement, and we will report the systematic review by following the PRISMA statement.

Results:

Through a systematic review, and meta-analysis when necessary, we can obtain the relationship between vitamin D and DED. We will share our findings in the third quarter of 2021.

Conclusion:

The association between serum vitamin D levels and type 2 diabetic erectile dysfunction will be assessed. Besides, the results of this review may provide some help for clinicians to make decisions.

Ethics and dissemination:

Ethical approval is not required as the review is a secondary study based on published literature. The results will be published in a public issue journal to provide evidence-based medical evidence for urologists and andrologists to make better clinical decisions.

Protocol registration number:

INPLASY202040164.
Late presenting congenital diaphragmatic hernia misdiagnosed as a pleural effusion
Authors: Shin Hyun Beak , Jeong Yeon-Jun
Published: June 2020

Rationale:

Late presenting congenital diaphragmatic hernia (CDH) that develops after the neonatal period has various clinical manifestations and can often be misdiagnosed as pleural effusion, pneumonia, or pneumothorax. We report an adolescent case who was transferred to our hospital after iatrogenic gastric perforation during chest tube thoracotomy caused by misdiagnosis of pleural effusion.

Patient concerns:

A 13-year-old boy with no medical history of conditions relevant to CDH and traumatic events visited a community hospital complaining of left upper quadrant abdominal pain and vomiting over the previous 3 days. The initial chest x-ray looked like pleural effusion at a cursory glance, so a chest tube thoracotomy was performed, upon insertion food-like materials drained through the tube.

Diagnosis:

CDH and iatrogenic gastric perforation by chest tube were diagnosed by chest computed tomography scan.

Interventions:

The patient was transferred to our hospital immediately, and emergent operation was performed. There was a large hernial defect on the left posterolateral side of the diaphragm and various intra-abdominal organs, including the stomach, had been displaced into the thoracic cavity. After manual reduction, stomach perforation by chest tube was identified. Wedge resection of the gastric perforation site was performed and the hernial defect in the diaphragm was closed with Gore-Tex mesh and nonabsorbable sutures.

Outcomes:

The patient was discharged without complication on the postoperative 15th day.

Lessons:

Late presenting CDH can be misdiagnosed as pleural effusion on chest x-ray, so special attention should be given to a differential diagnosis to avoid any serious complications.
Gene expression and prognosis of sirtuin family members in ovarian cancer
Authors: Zeng Zhenguo , Huang Yiming , Li Yanshu , Huang Shuying , Wang Jiao , Tang Yunliang , Jiang Yanxia
Published: June 2020

Sirtuins (SIRTs), a class of nicotinamide-adenine dinucleotide (NAD)+-dependent deacetylases, involve in modulating carcinogenesis and progression of various malignancies through their regulation of the cancer metabolism. However, the expression profiles and prognostic roles of SIRTs in ovarian cancer (OC) remain unclear. We underscore the transcriptional expression and prognostic significance of SIRTs in OC patients using online databases. Gene Expression Profiling Interactive analysis (GEPIA) was applied to analyze mRNA expression, and Kaplan–Meier plotter was used to evaluate prognostic value. In patients with OC, SIRT1/2/3 were significantly down-regulated, while rest of SIRTs were not significantly changed. High SIRT2/5/6/7 expression was correlated with favorable overall survival (OS), while high SIRT1/4 expression was correlated with poor OS. Additionally, aberrant SIRTs mRNA levels were related to the prognosis of OC patients with different clinicopathological characteristics. This is the first study to integrate bioinformatics approaches intended to identify the expression profiles and prognostic value of SIRTs in OC. These results suggest that SIRTs is related to the prognosis of OC and may be the potential therapeutic interventions in OC.
Efficacy of intra-articular polynucleotides associated with hyaluronic acid vs hyaluronic acid alone in the treatment of knee osteoarthritis
Authors: Zhang Lei , Lei Ningbo , Chang Ruilong , Yang Chenxu , Li Qiang , Zuo Ning , Gu Yubiao
Published: June 2020

Background:

The reduced range of motion and pain are the most characteristic clinical features of osteoarthritis (OA). Hyaluronic acid (HA), which is one of the infiltrative therapies for OA treatment, and polynucleotides (PNs), which is a DNA-derived macromolecule favored cell growth and collagen production, are an ongoing debate in clinical effectiveness.

Methods:

We plan to perform a systematic review and meta-analysis of randomized clinical trial to evaluate efficacy of intra-articular polynucleotides associated with hyaluronic acid versus hyaluronic acid alone in the treatment of knee osteoarthritis. We will search PubMed, EMBASE, Cochrane Library using a comprehensive strategy. The related conference proceedings and reference lists of the included studies will also be checked to identify additional studies. Two reviewers will screen retrieved records, extract information and assess the risk of bias independently. Stata v15.1 software will be used to conduct data synthesis.

Results:

This study will be submitted to a peer-reviewed journal for publication.

Conclusion:

We hope it will provide a relatively comprehensive reference for clinical practice and future relevant clinical trials.

Ethics and dissemination:

Ethics approval and patient consent are not required, as this study is a systematic review and meta-analysis.

PROSPERO registration number:

CRD42020167678
Safety of implantable Collamer lens implantation without ophthalmic viscosurgical device
Authors: Peng Manqiang , Tang Qiongyan , Zhao Libei , Khan Muhanmad Ahmad , Lin Ding
Published: June 2020

To compare the safety of implantable Collamer lens (ICL) implantation with and without ophthalmic viscosurgical device (OVD).

A total of 148 eyes underwent a conventional ICL implantation with OVD (OVD group), and 112 eyes underwent a modified ICL implantation without OVD (OVD-free group). The balanced salt solution was used to load ICL and maintain the anterior chamber in the OVD-free group. The surgical time, postoperative uncorrected distance visual acuity, intraocular pressure, endothelial cell density (ECD), and percentage of hexagonal cells were compared between the OVD and the OVD-free groups.

No significant differences were detected in uncorrected distance visual acuity, intraocular pressure, ECD, and percentage of hexagonal cells at any time post-surgery between the 2 groups (P > .05). The mean ECD loss was 1.9% in the OVD-free group and 2.3% in the OVD group at 2 years post-surgery (P = .680). The surgical time was much shorter in the OVD-free group than that in the OVD group (P ≤ .001). None of the following occurred at any time during the 2-year follow-up period in both groups: cataract formation, macular degeneration, or any other vision-threatening complications.

OVD-free ICL implantation presented satisfactory results for safety. Compared to OVD, the OVD-free technique had the advantages of decreased surgical time, increased efficiency, and reduced cost.
HIV Lymphoma and Burkitts Lymphoma
Authors: Noy Ariela
Published: June 2020

Despite widely available antiretroviral therapy, lymphoma remains the leading cause of death for human immunodeficiency virus (HIV)–infected persons in economically developed countries. Even a few months of drug interruptions can lead to drops in the CD4 cell count, HIV viremia, and an increased risk of lymphoma. Currently, good HIV control facilitates intensive therapies appropriate to the lymphoma, including autologous and even allogeneic hematopoietic stem cell transplantation. Nonetheless, HIV-related lymphomas have unique aspects, including pathogenetic differences driven by the presence of HIV and often coinfection with oncogenic viruses. Future therapies might exploit these differences. Lymphoma subtypes also differ in the HIV-infected population, and the disease has a higher propensity for advanced-stage, aggressive presentation and extranodal disease. Other unique aspects include the need to avoid potential interactions between antiretroviral therapy and chemotherapeutic agents and the need for HIV-specific supportive care such as infection prophylaxis. Overall, the care of these patients has progressed sufficiently that recent guidelines from the American Society of Clinical Oncology advocate the inclusion of HIV-infected patients alongside HIV-negative patients in cancer clinical trials when appropriate. This article examines HIV lymphoma and includes Burkitt lymphoma in the general population.
Survival and selection biases in early animal evolution and a source of systematic overestimation in molecular clocks
Authors: Budd Graham E. , Mann Richard P.
Published: June 2020

Important evolutionary events such as the Cambrian Explosion have inspired many attempts at explanation: why do they happen when they do? What shapes them, and why do they eventually come to an end? However, much less attention has been paid to the idea of a ‘null hypothesis’—that certain features of such diversifications arise simply through their statistical structure. Such statistical features also appear to influence our perception of the timing of these events. Here, we show in particular that study of unusually large clades leads to systematic overestimates of clade ages from some types of molecular clocks, and that the size of this effect may be enough to account for the puzzling mismatches seen between these molecular clocks and the fossil record. Our analysis of the fossil record of the late Ediacaran to Cambrian suggests that it is likely to be recording a true evolutionary radiation of the bilaterians at this time, and that explanations involving various sorts of cryptic origins for the bilaterians do not seem to be necessary.
Quantitative PCR for cannabis flower containing SARs-CoV-2
Authors: McKernan Kevin J. , Kane Liam T. , Helbert Yvonne
Published: June 2020

In January of 2020, COVID-19 became a worldwide pandemic. As many industries shutdown to comply with social distancing measures, the cannabis industry was deemed an essential business in most U.S. jurisdictions. Cannabis is manually farmed, trimmed and packaged. Employees and trimmers in cannabis grows have been reported to test qPCR positive for SARs-CoV-2 and as a result cannabis flower can be a potential inhaled SARs-CoV-2 fomite. Many of the comorbidities described in COVID-19 are also qualifying conditions for medical cannabis access. Bat guano has been identified as a rich source for novel coronavirus discovery and it is also a common fertilizer in the cannabis field. To better assess cannabis fomite risk we developed a SARs-CoV-2 quantitative PCR assay optimized to operate with a hemp flower background matrix. This assay was utilized to estimate the stability of gamma irradiated SARs-CoV-2 as a hemp flower fomite.
Seeing Nemo: molecular evolution of ultraviolet visual opsins and spectral tuning of photoreceptors in anemonefishes (Amphiprioninae)
Authors: Mitchell Laurie J. , Cheney Karen L. , Chung Wen-Sung , Marshall N. Justin , Michie Kyle , Cortesi Fabio
Published: June 2020

Many animals can see ultraviolet (UV) light (shorter than 400 nm) undetectable to human vision. UV vision may have functional importance in many taxa including for foraging and communication in birds, reptiles, insects and teleost fishes. Shallow coral reefs transmit a broad spectrum of light and are rich in UV; driving the evolution of diverse spectral sensitivities in teleost reef fishes, including UV-sensitivity. However, the identities and sites of the specific visual genes that underly vision in reef fishes remain elusive and are useful in determining how molecular evolution has tuned vision to meet the ecological demands of life on the reef. We investigated the visual systems of eleven anemonefish (Amphiprioninae) species, specifically probing for the molecular pathways that facilitate UV-sensitivity. Searching the genomes of anemonefishes, we identified a total of seven functional visual genes from all five vertebrate opsin gene subfamilies. We found rare instances of UV-sensitiveSWS1opsin gene duplications, that produced two functional paralogs (SWS1αandSWS1β) and a pseudogene. We also found separateRH2Aopsin gene duplicates not yet reported in the family Pomacentridae. Finally, we report on both qualitative and quantitative aspects of opsin gene expression found in the adult retina of the false clown anemonefish (Amphiprion ocellaris), and their photoreceptor spectral sensitivities measured using microspectrophotometry.
A Mesoscale Finite Element Modelling Approach for Understanding Brain Morphology and Material Heterogeneity Effects in Chronic Traumatic Encephalopathy
Authors: Bakhtairydavijani A. , Khalid G. , Murphy M.A. , Johnson K.L. , Peterson L. E. , Jones M. , Horstemeyer M.F. , Dobbins A.C. , Prabhu R. K.
Published: June 2020

Chronic Traumatic Encephalopathy (CTE) affects a significant portion of athletes in contact sports but is difficult to quantify using clinical examinations and modelling approaches. We use anin silicoapproach to quantify CTE biomechanics using mesoscale Finite Element (FE) analysis that bridges with macroscale whole head FE analysis. The sulci geometry produces complex stress waves that interact with each another to create increased shear stresses at the sulci depth that are significantly larger than in analyses without sulci (from 0.5 kPa to 18.0 kPa). Also, Peak sulci stresses are located where CTE has been experimentally observed in the literature.

Highlights

3 to 5 bullet points 85 characters max

Sulci introduce stress localizations at their depth in the gray matter

Sulci stress fields interact to produce stress concentration sites in white matter

Differentiating brain tissue properties did not significantly affect peak stresses
Spatiotemporal sequence of mesoderm and endoderm lineage segregation during mouse gastrulation
Authors: Probst Simone , Sagar  , Tosic Jelena , Schwan Carsten , Grün Dominic , Arnold Sebastian J.
Published: June 2020

Anterior mesoderm (AM) and definitive endoderm (DE) progenitors represent the earliest embryonic cell types that are specified during germ layer formation at the primitive streak (PS) of the mouse embryo. Genetic experiments indicate that both lineages segregate fromEomesexpressing progenitors in response to different NODAL signaling levels. However, the precise spatiotemporal pattern of the emergence of these cell types and molecular details of lineage segregation remain unexplored. We combined genetic fate labeling and imaging approaches with scRNA-seq to follow the transcriptional identities and define lineage trajectories ofEomesdependent cell types. All cells moving through the PS during the first day of gastrulation expressEomes. AM and DE specification occurs before cells leave the PS from discrete progenitor populations that are generated in distinct spatiotemporal patterns. Importantly, we don’t find evidence for the existence of progenitors that co-express markers of both cell lineages suggesting an immediate and complete separation of AM and DE lineages.

Summary statement

Cells lineages are specified in the mouse embryo already within the primitive streak whereMesp1+ mesoderm andFoxa2+ endoderm are generated in a spatial and temporal sequence from unbiased progenitors.
Estimating daily intakes of manganese due to breast milk, infant formulas, or young child nutritional beverages in the United States and France: Comparison to sufficiency and toxicity thresholds
Authors: Mitchell Erika J. , Frisbie Seth H. , Roudeau Stéphane , Carmona Asuncion , Ortega Richard
Published: June 2020

Background

Although manganese (Mn) is an essential nutrient, recent research has revealed that excess Mn in early childhood may have adverse effects on neurodevelopment.

Methods

We estimated daily total Mn intake due to breast milk at average body weights by reviewing reported concentrations of breast milk Mn and measurements of body weight and breast milk intake at 3 weeks, 4.25 months, 7 months, and 18 months. We compared these figures to the Mn content measured in 44 infant, follow-up, and toddler formulas purchased in the United States and France. We calculated Mn content of formula products made with ultra-trace elemental analysis grade water (0 µg Mn/L) and with water containing 250 µg Mn/L, a concentration which is relatively high but less than the World Health Organization Health-based value of 400 µg Mn/L or the United States Environmental Protection Agency Health Advisory of 350 µg Mn/L.

Results

Estimated mean daily Mn intake from breast milk ranged from 1.2 µg Mn/kg/day (3 weeks) to 0.16 µg Mn/kg/day (18 months), with the highest intakes at the youngest age stage we considered, 3 weeks. Estimated daily Mn intake from formula products reconstituted with 0 µg Mn/L water ranged from 130 µg Mn/kg/day (3 weeks) to 4.8 µg Mn/kg/day (18 months) with the highest intakes at 3 weeks. Formula products provided 28 to 520 times greater than the mean daily intake of Mn from breast milk for the 4 age stages that we considered. Estimated daily Mn intake from formula products reconstituted with water containing 250 µg Mn/L ranged from 12 µg Mn/kg/day to 170 µg Mn/kg/day, which exceeds the United States Environmental Protection Agency Reference Dose of 140 µg Mn/kg/day for adults.

Conclusions

Mn deficiency is highly unlikely with exclusive breast milk or infant formula feeding, but established tolerable daily intake levels for Mn may be surpassed by some of these products when following labeled instructions.

Highlights

Mn deficiency is unlikely with exclusive breast milk or infant formula feeding.

Breast milk Mn mean intake is 1.2 µg/kg/day (3 weeks)-0.16 µg/kg/day (18 months).

Formula Mn intake range is 130 µg/kg/day (3 weeks)-4.8 µg/kg/day (18 months).

Formula products reconstituted with 250 µg Mn/L water may exceed 140 µg Mn/kg/day.

Formula products may surpass regulatory tolerable daily intake levels for Mn.
V-pipe: a computational pipeline for assessing viral genetic diversity from high-throughput sequencing data
Authors: Posada-Céspedes Susana , Seifert David , Topolsky Ivan , Metzner Karin J. , Beerenwinkel Niko
Published: June 2020

High-throughput sequencing technologies are used increasingly, not only in viral genomics research but also in clinical surveillance and diagnostics. These technologies facilitate the assessment of the genetic diversity in intra-host virus populations, which affects transmission, virulence, and pathogenesis of viral infections. However, there are two major challenges in analysing viral diversity. First, amplification and sequencing errors confound the identification of true biological variants, and second, the large data volumes represent computational limitations. To support viral high-throughput sequencing studies, we developed V-pipe, a bioinformatics pipeline combining various state-of-the-art statistical models and computational tools for automated end-to-end analyses of raw sequencing reads. V-pipe supports quality control, read mapping and alignment, low-frequency mutation calling, and inference of viral haplotypes. For generating high-quality read alignments, we developed a novel method, calledngshmmalign, based on profile hidden Markov models and tailored to small and highly diverse viral genomes. V-pipe also includes benchmarking functionality providing a standardized environment for comparative evaluations of different pipeline configurations. We demonstrate this capability by assessing the impact of three different read aligners (Bowtie 2, BWA MEM, ngshmmalign) and two different variant callers (LoFreq, ShoRAH) on the performance of calling single-nucleotide variants in intra-host virus populations. V-pipe supports various pipeline configurations and is implemented in a modular fashion to facilitate adaptations to the continuously changing technology landscape. V-pipe is freely available athttps://github.com/cbg-ethz/V-pipe.
Digital twinning of Cellular Capsule Technology: emerging outcomes from the perspective of porous media mechanics
Authors: Stéphane Urcun , Pierre-Yves Rohan , Wafa Skalli , Pierre Nassoy , Bordas Stéphane P.A. , Giuseppe Sciumè
Published: June 2020

Spheroids encapsulated within alginate capsules are emerging as suitablein vitrotools to investigate the impact of mechanical forces on tumor growth since the internal tumor pressure can be retrieved from the deformation of the capsule. Here we focus on the particular case of Cellular Capsule Technology (CCT).

We show in this contribution that a modeling approach accounting for the triphasic nature of the spheroid (extracellular matrix, tumor cells and interstitial fluid) offers a new perspective of analysis revealing that the pressure retrieved experimentally cannot be interpreted as a direct picture of the pressure sustained by the tumor cells and, as such, cannot therefore be used to quantify the critical pressure which induces stress-induced phenotype switch in tumor cells.

The proposed multiphase reactive poro-mechanical model was cross-validated. Parameter sensitivity analyses on the digital twin revealed that the main parameters determining the encapsulated growth configuration are different from those driving growth in free condition, confirming that radically different phenomena are at play. Results reported in this contribution support the idea that multiphase reactive poro-mechanics is an exceptional theoretical framework to attain an in-depth understanding of CCT experiments, to confirm their hypotheses and to further improve their design.
Swan: a library for the analysis and visualization of long-read transcriptomes
Authors: Reese Fairlie , Mortazavi Ali
Published: June 2020

Motivation

Long-read RNA-sequencing technologies such as PacBio and Oxford Nanopore have discovered an explosion of new transcript isoforms that are difficult to visually analyze using currently available tools. We introduce the Swan Python library, which is designed to analyze and visualize transcript models.

Results

Swan finds 4,909 differentially expressed transcripts between cell lines HepG2 and HFFc6, including 279 that are differentially expressed even though the parent gene is not. Additionally, Swan discovers 1,021 reproducible exon skipping and 73 intron retention events not recorded in the GENCODE v29 annotation.

Availability

The Swan library for Python 3 is available on PyPi and on GitHub athttps://pypi.org/project/swan-vis/1.0/andhttps://github.com/mortazavilab/swan_paper.
MethylationToActivity: a deep-learning framework that reveals promoter activity landscapes from DNA methylomes in individual tumors
Authors: Williams Justin , Xu Beisi , Putnam Daniel , Thrasher Andrew , Li Chunliang , Yang Jun , Chen Xiang
Published: June 2020

Although genome-wide DNA methylomes have demonstrated their clinical value as reliable biomarkers for tumor detection, subtyping, and classification, their direct biological impacts at the individual gene level remain elusive. Here we present MethylationToActivity (M2A), a machine learning framework that uses convolutional neural networks to infer promoter activities (H3K4me3 and H3K27ac enrichment) from DNA methylation patterns for individual genes. Using publicly available datasets in real-world test scenarios, we demonstrate that M2A is highly accurate and robust in revealing promoter activity landscapes in various pediatric and adult cancers, including both solid and hematologic malignant neoplasms.
Differential expression of COVID-19-related genes in European Americans and African Americans
Authors: Singh Urminder , Wurtele Eve Syrkin
Published: June 2020

The Coronavirus disease 2019 (COVID-19) pandemic has affected African American populations disproportionately in regards to both morbidity and mortality. A multitude of factors likely account for this discrepancy. Gene expression represents the interaction of genetics and environment. To elucidate whether levels of expression of genes implicated in COVID-19 vary in African Americans as compared to European Americans, we re-mine The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) RNA-Seq data. Multiple genes integral to infection, inflammation and immunity are differentially regulated across the two populations. Most notably, F8A2 and F8A3, which encode the HAP40 protein that mediates early endosome movement in Huntington’s Disease, are more highly expressed by up to 24-fold in African Americans. Such differences in gene expression can establish prognostic signatures and have critical implications for precision treatment of diseases such as COVID-19. We advocate routine inclusion of information such as postal code, education level, and profession (as a proxies for socioeconomic condition) and race in the metadata about each individual sampled for sequencing studies. This relatively simple change would enable large-scale data-driven approaches to dissect relationships among race, socio-economic factors, and disease.