bluuebunny/crossref_metadata_2025 huggingface dataset:
The clinical effect of traditional chinese medicine on middle-aged women with Interstitial Cystitis
Authors: Liu Yahong , Zhang Pingan , Liu Mengyu , Liu Xiaohe , Liu Ruijia , Yu Xudong , Deng Sheng , Si Hongmei , Sun Bei
Published: April 2020

Introduction:

Interstitial cystitis (IC), as a common disease in urology, is prolonged and repeated. IC has caused great harm to the patient's physical and psychological. Traditional Chinese medicine (TCM) is characterized by overall concepts and dialectical treatment. It provides clinicians with safer and more reliable alternatives in terms of clinical prescriptions and prepared medicines, and also improves the quality of life of patients with IC. Therefore, in this study, we will use the research method of randomized controlled trials to explore the effects of TCM combined with western medicine on renal function and urine metabolism on middle-aged women with IC.

Methods/design:

Use randomized controlled trials. According to the proposed diagnostic, inclusion, and exclusion criteria. Sixty patients with interstitial bladder inflammation that met the criteria were randomized into a treatment group and a control group of 30 cases each. The intervention group was treated with integrated traditional Chinese and western medicine. The control group was given conventional Western medicine treatment. The course of treatment is 8 weeks. Interstitial bladder inflammation symptoms score (ICS worker), problem score (worker CPI), pelvic pain and urinary urgency symptoms, and urodynamics were used as the evaluation criteria.

Discussion:

This trial may provide evidence regarding the clinical effectiveness, safety, and cost-effectiveness of TCM for patients with IC.

Trial registration:

ClinicalTrials.gov, ChiCTR2000029971, Registered on 17 February 2020
Comparative effectiveness and safety of direct-acting oral anticoagulants (DOACS) for the reduction of recurrent venous thromboembolism in cancer patients
Authors: Danjuma Mohammed ibn-Mas’ud , Mohamed Mouhand F.H. , ElShafei Mohamad Nabil , Fatima Haajra , Shokri Shaikha Al , Mohamed Sara , Abubeker Ibrahim Yusuf , Kartha Anand , Elzouki Abdel-Naser , Mohamedali Mohamed Gaafar Hussein , Mahgboub Yahya , Bidmos Mubarak
Published: April 2020

Background:

There has been a significant improvement in both our understanding and therapeutic choices available to clinicians for the management of cancer associated thrombosis (CAT). Even with the recent publication of a systematic review and landmark trials demonstrating the non-inferiority of DOACS-based anticoagulation strategy compared to the standard of care in patients with CAT, there is unresolved uncertainty regarding the exact hierarchy of risks and effectiveness of various DOAC analogues in these cohorts of patients.

Method:

We will carry out a network meta-analyses, utilizing a novel generalized pairwise methodology to generate direct and indirect comparisons between the various DOAC analogues. We will search the following databases for studies that satisfies pre-specified inclusions criteria; these include PubMed, EMBASE, Cochrane library, Clinicaltrials.gov, conference abstracts among other sources. The primary efficacy and safety outcomes are recurrent VTE and major hemorrhagic events, respectively. Two reviewers will Search the databases independently with the view to identify studies that meet eligibility criteria. The methodological quality of the included studies will be determined using a recently validated risk of bias assessment tool.

Results:

We expect that the result of this review will ascertain the hierarchy of risks and effectiveness of various DOAC analogues in patients with CAT.

Conclusion:

Results of this review will assist in informed decisions making regarding therapeutic guidelines of DOAC in CAT.
Effect of auriculotherapy on chronic low back pain
Authors: Zhang Guilong , Zhang Leixiao , Deng Yanli , Shen Yuquan , Wang Xinling , Yu Yang
Published: April 2020

Background:

Chronic low back pain (CLBP) is a clinically common and recurrent disease. However, many trials have shown that auriculotherapy (AT) can effectively treat CLBP. There are currently no systematic reviews of this therapy. The plan aims to evaluate the effectiveness and safety of this treatment in patients with CLBP.

Methods:

This systematic evaluation will entail an electronic and manual search of all AT for CLBP from inception to January 31, 2020, regardless of the publication status or language. Databases include PubMed, Excerpt Medica Database, Springer, Web of Science, the Cochrane Library, the World Health Organization International Clinical Trial Registration Platform, the Chinese Medicine Database, the China National Knowledge Infrastructure, the Chinese Biomedical Literature Database, the China Science Journal Database, and the Wanfang Database. Other sources of information, including bibliographies and meeting minutes for identified publications, will also be searched. A manual search for grey literature, including unpublished conference articles will be performed. Additionally, any clinical randomized controlled trials related to AT for CLBP, regardless of the publication status and language limitations, will be included in the study. Study selection, data extraction, and research quality assessments will be conducted independently by 2 researchers. The main result was the use of a visual analog scale, a short pain scale, or other effective scale. Secondary outcomes included effectiveness, Oswestry dysfunction index, self-rating anxiety scale, self-depression rating scale, Pittsburgh sleep quality index, follow-up relapse rate, and adverse events. The system searches for randomized controlled trials of this therapy for CLBP. Implement the Cochrane RevMan V5.3 bias assessment tool to assess bias risk, data integration risk, meta-analysis risk, and subgroup analysis risk (if conditions are met). Mean difference, standard mean deviation, and binary data will be used to represent continuous results.

Results:

This study will provide a comprehensive review and evaluation of the available evidence for the treatment of CLBP using this therapy.

Conclusion:

This study will provide new evidence to evaluate the effectiveness and side effects of AT on CLBP. Because the data is not personalized, no formal ethical approval is required.

PROSPERO registration number:

CRD42020151584.
Esophageal foreign bodies: observational cohort study and factors associated with recurrent impaction
Authors: Ferrari Davide , Siboni Stefano , Riva Carlo Galdino , Aiolfi Alberto , Panici Tonucci Tommaso , Asti Emanuele , Bonavina Luigi
Published: April 2020

Background and aim

Esophageal foreign bodies, including food bolus impaction, represent a common clinical problem. The prevalence of underlying esophageal disease depends on study design and degree of suspicion of a structural or functional esophageal abnormality. Aim of this study was to analyze factors associated with recurrent impaction.

Methods

The prospectively collected database at a University Hospital and Swallowing Center was reviewed from January 2012 to June 2019 to identify all patients admitted for esophageal foreign bodies. Patients who underwent an emergency endoscopic procedure represented the final study sample. Patient characteristics, including history of previous esophageal foreign bodies, and type of endoscopic procedure were collected.

Results

Sixty-five patients, 41 males and 24 females with a median age of 59 years, underwent emergency endoscopy for esophageal foreign bodies during the study period. Food bolus was the most common foreign body (n = 43, 66%). Flexible endoscopy was successful in retrieving or pushing the foreign bodies in the stomach in 91% of patients. In 54% of patients, impaction was secondary to an underlying esophageal disorder, which was previously unrecognized in half of them. Recurrent impaction was more common in patients with esophageal disease (P < 0.011). Surgical therapy was required in 4 patients (6.1%).

Conclusions

Food bolus impaction is a common sentinel event in patients with underlying esophageal disease and is associated with recurrent impaction. Diagnostic endoscopy with biopsies should possibly be performed at the first episode of impaction. Patients with negative biopsies should undergo barium swallow study and high-resolution esophageal manometry.
The Adoption of Oncoplastic Surgery Using Breast Reduction or Mastopexy Techniques in an Academic Breast Cancer Center Program Can Increase Breast Conservation Rates
Authors: Sekigami Yurie , Chowdhury Ritam , Char Sydney , Radparvar Jacob , Chen Lilian , Parsons Susan K. , Chatterjee Abhishek
Published: April 2020

Background

Interest in oncoplastic surgery (OPS), a form of breast conservation surgery (BCS), has grown in the United States over the last decade. Oncoplastic surgery allows for the removal of larger tumors without compromising esthetic outcome or oncologic safety. One of the quality measures on which breast cancer centers in the United States are evaluated is rate of BCS. The purpose of this study was to investigate whether the adoption of OPS increases BCS rates and decreases mastectomy rates at the institutional level.

Methods

Clinicopathologic data were retrospectively collected for breast cancer patients in a single institution database. Rates of BCS vs mastectomy and partial mastectomy versus OPS were measured between 2012 and 2018 to capture 3 years before and 3 years after the hiring of an oncoplastic surgeon in 2015 with subsequent practice adoption of oncoplastic techniques. We compared the 2 periods using χ2 and Fisher exact test for categorical variables. Rates of breast conservation and mastectomy were further stratified by tumor stage.

Results

Four hundred sixty-eight patients underwent breast cancer surgery at Tufts Medical Center between 2012 and 2018.

Patients who underwent surgery between 2012–2015 and 2016–2018 were similar in terms of age, histological type, tumor size, receipt of neoadjuvant therapy, receptor status, and Charlson Comorbidity Index. There was a statistically significant (P < 0.0001) increase in BCS rate after 2015 attributable to the practice adoption of OPS. The proportion of patients who were recommended reexcision did not significantly increase with the introduction of OPS suggesting an appropriate and safe patient selection process for patients undergoing these breast conservation techniques. When stratified by T stage (tumor size), rates of mastectomy for T2 tumors (greater than 2 cm but less than 5 cm) decreased precipitously after 2015 and BCS increased proportionately. The rate of BCS for T1 tumors also increased but less drastically.

Conclusions

The adoption of OPS in an academic breast cancer center can result in significantly higher rates of BCS, particularly for those with larger tumors (T2). Academic breast cancer centers should strongly consider incorporating OPS to their treatment paradigm to provide patients with the option to avoid mastectomy.
Clinical Outcomes After Hematoma Development
Authors: Rogoff Hunter , Marquez Jocellie E. , Ghosh Kanad , Jou Christopher , McAuliffe Phoebe , Rathi Sourish , Monroig Kaitlin , Medrano Christopher , Marmor William A. , Ferrier Austin , Kapadia Kailash , Klein Gabriel , Huston Tara L. , Ganz Jason , Dagum Alexander B. , Khan Sami , Bui Duc
Published: April 2020

Background

Hematomas after tissue expander immediate breast reconstruction (TE-IBR) pose a significant challenge during the recovery period. In this study, we aim to evaluate whether hematoma formation leads to subsequent complications and how management can impact final reconstructive goals.

Methods

A single-institution retrospective review of TE-IBRs from 2001 to 2018 was performed using an established breast reconstruction database. Demographics, medications, comorbidities, and complications were identified. Implant loss was defined as removal of the tissue expander/implant without immediate reimplantation during that operation. Hematoma size, management, transfusion requirement, reoperations, and final outcome were recorded. Reconstructive failure was defined as an implant loss that was not replaced with another implant or required secondary autologous reconstruction.

Results

Six hundred twenty-seven TE-IBR patients were analyzed. Postoperative hematoma (group 1) occurred in 4.1% (n = 26) of TE-IBRs and did not develop in 95.9% (group 2: n = 601). Group 2 had a higher mean body mass index (24.5 vs 27.3 kg/m2, P = 0.018); however, there were no significant differences in smoking status, preoperative/postoperative radiation/chemotherapy, or other comorbidities. Group 1 was found to have increased rates of implant loss (15.4% vs 3.7%, P = 0.0033) and reconstructive failure (11.5% vs 2.8%, P = 0.0133) compared with group 2.

Eighteen hematomas (69.2%) underwent surgical intervention (group 1a) compared with 30.8% (n = 8) that were clinically managed (group 1b). Group 1a had statistically significant lower rates of subsequent complications (22.2% vs 62.5%, P = 0.046) and reoperations (5.6% vs 27.5%, P = 0.037) than did group 1b, respectively.

Lastly, 23.1% (n = 6) of patients who developed a hematoma were on home antithrombotics (group 1c) compared with 76.9% (n = 20) of patients with no antithrombotics (group 1d). There were statistically significant differences in transfusion rates (50% vs 0%, P = 0.001) between groups 1c and 1d, respectively. Differences in hematoma volume (330 vs 169.3 mL, P = 0.078) and reconstructive failure (33.3% vs 5%, P = 0.057) approached significance between both groups.

Conclusions

Hematoma after TE-IBR should be monitored closely, as it may play a role in jeopardizing reconstruction success. Patients on home antithrombotic medication may be at increased risk of larger-volume hematomas and reconstruction failure. Plastic surgeons should consider aggressive surgical evacuation of postoperative TE-IBR hematomas to reduce subsequent complications and reoperations, thus optimizing reconstructive outcomes.
Repair of Massive Bone Defects of the Proximal Femur Using Iliac Bone Flaps of the Ascending Branch of the Lateral Circumflex Femoral Artery
Authors: Li Zonghuan , Yu Aixi , Yu Guorong , Tao Shengxiang , Qi Baiwen
Published: April 2020

Background and Objective

The management of bone defects is still a difficult problem. Local vascularized bone grafts represent an efficient and widely used method. In this retrospective report, iliac bone flaps of the ascending branch of the lateral circumflex femoral artery were used for the management of proximal femur bone defects.

Patients and Methods

The hospital information system and clinical data collected by surgeons were retrospectively reviewed. Patients with massive bone defects of the proximal femur reconstructed with iliac bone flaps of the ascending branch of the lateral circumflex femoral artery were included. Relevant data, including general information, perioperative treatment, and imaging data during follow-up, were retrieved for analysis. Five patients (4 males and 1 female) aged 18 to 42 years were included in this report. All patients were diagnosed with proximal femoral bone defects. The sizes of the bone defects ranged from 5 ×4 cm to 8 × 5 cm. Harris hip score was adopted to evaluate the functional outcomes. The adverse events were recorded. The mean follow-up time was 6.3 years.

Results

Iliac bone flaps of the ascending branch of the lateral circumflex femoral artery were transferred locally for the 5 patients. Bone flaps were fixed with plates in 4 cases and Kirschner wires in 1 case. The hospital stay was 12 to 27 days, with an average of 19.4 days. All cases achieved bony healing after 3 to 6 months postoperatively. The Harris hip scores ranged from 87 to 95 at final follow-up. All patients achieved good to excellent functional outcomes. One superficial infection occurred. No other adverse events or serious adverse events were noted.

Conclusions

Local transfer of iliac bone flaps of the ascending branch of the lateral circumflex femoral artery represents a safe and effective method for the reconstruction of massive bone defects of the proximal femur.
Comparing Prepectoral Versus Subpectoral Tissue Expander Placement Outcomes in Delayed-Immediate Autologous Breast Reconstruction
Authors: Patel Ashraf A. , Borrelli Mimi R. , Cai Lawrence , Moshrefi Shawn , Sando Ian C. , Lee Gordon K. , Nazerali Rahim S.
Published: April 2020

Background

Delayed-immediate breast reconstruction has traditionally involved placement of tissue expanders (TE) in the subpectoral (SP) position. Development of acellular dermal matrices has renewed interest in the prepectoral (PP) pocket, which avoids extensive muscle manipulation. We compare complication rates between PP and SP TE placement in autologous delayed-immediate breast reconstruction.

Methods

A retrospective chart review of patients undergoing autologous, delayed-immediate breast reconstruction at our institution (June 2009 to December 2018) was performed. Demographics, comorbidities, perioperative information, and complication incidence ≤12 months' follow-up were collected from first- and second-stage surgeries. Complications were modeled using univariable and multivariable binary logistic regressions.

Results

A total of 89 patients met the inclusion criteria, and data from 125 breast reconstructions were evaluated. Complication rates following TE placement trended lower in the PP cohort (28.8% vs 37%, P = 0.34). Overall complication rates following autologous reconstruction were significantly lower for PP reconstructions (7.7% vs 23.3%, P = 0.02). Multivariable regression showed TE position (P = 0.01) was a significant predictor of ≥1 complication following autologous reconstruction. Time delay between first- and second-stage surgeries was greater for SP reconstructions (199.7 vs 324.8 days, P < 0.001). Postoperative drains were removed earlier in the PP cohort (8.6 vs 12.0 days, P < 0.001). Mean follow-up time was 331.3 days.

Conclusions

Prepectoral reconstruction in the delayed-immediate autologous reconstruction patient leads to significantly lower complication rates, shorter duration between first- and second-stage surgeries, and shorter times before removal of breast drains compared with SP reconstructions.
Morphological and molecular characterization of Orbilia pseudopolybrocha and O. tonghaiensis, two new species of Orbiliaceae from China
Authors: Zhang Ying , Qiao Min , Baral H.O. , Xu Jianping , Zhang Ke-Qin , Yu Ze-Fen
Published: April 2020

This study examined over 20 fungal specimens of the Orbiliaceae (Orbiliomycetes) from different regions in China. Our analyses based on morphological traits and the ITS rDNA sequences revealed two new Orbilia species with drechslerella-like asexual morphs. These new species are able to trap nematodes with constricting rings. In addition, Orbilia cf. orientalis is reported as a new cryptic Chinese variant of European collections of O. orientalis. All three species are described and illustrated in detail in this paper. Their phylogenetic relationships with other orbiliaceous species were identified based on their ITS sequences.
Fulvivirga aurantia sp. nov. and Xanthovirga aplysinae gen. nov., sp. nov., marine bacteria isolated from the sponge Aplysina fistularis, and emended description of the genus Fulvivirga
Authors: Goldberg Stacey R. , Correa Hebelin , Haltli Brad A. , Kerr Russell G.
Published: April 2020

Two Gram-stain-negative, strictly aerobic, marine bacteria, designated as strains RKSG066T and RKSG123T, were isolated from a sponge Aplysina fistularis collected at a depth of 15 m off the west coast of San Salvador, The Bahamas. Investigation of nearly full-length 16S rRNA gene and whole genome-based phylogenies revealed that both strains belong to the order

Cytophagales

within the class

Cytophagia

and phylum

Bacteroidetes

. Strain RKSG066T formed a monophyletic clade with described members of the genus

Fulvivirga

, while strain RKSG123T formed a well-supported paraphyletic branch apart from this and other related genera within the family

Flammeovirgaceae

. For both RKSG066T and RKSG123T, optimal growth parameters were 30–37 °C, pH 7–8 and 2–3 % (w/v) NaCl; cells were catalase- and oxidase-positive, and flexirubin-type pigments were absent. The predominant fatty acids were iso-C15 : 0, C16 : 0, C18 : 0, iso-C17 : 0 3-OH, C16 : 1 ω5c, iso-C15 : 0 3-OH, C18 : 1 ω9c and iso-C15 : 1 G for RKSG066T, and iso-C17 : 0 3-OH, C16 : 1 ω5c, iso-C15 : 0, C16 : 0 3-OH and summed feature 4 (iso-C17 : 1 I and/or anteiso-C17 : 1 B) for RKSG123T. Menaquinone-7 was the major respiratory quinone for both strains. The DNA G+C contents of RKSG066T and RKSG123T were 39.5 and 36.7 mol%, respectively. On the basis of phylogenetic distinctiveness and polyphasic analysis, the type strain RKSG066T (=TSD-73T=LMG 29870T) is proposed to represent a novel species of the genus

Fulvivirga

, for which the name Fulvivirga aurantia sp. nov. is proposed. The type strain RKSG123T (=TSD-75T=LMG 30075T) is proposed to represent the type species of a novel genus and species with the proposed name Xanthovirga aplysinae gen. nov., sp. nov. Additionally, the genus

Fulvivirga

is emended to include strains of orange-pigmented colonies that contain the predominant cellular fatty acids C16 : 0, C18 : 0, C16  :  1
ω5c and C18  :  1
ω9c.
Cellulomonas endophytica sp. nov., isolated from Gastrodia elata Blume
Authors: Li Yan-Qiong , Zhang Hui , Xiao Min , Dong Zhou-Yan , Zhang Jing-Yi , Narsing Rao Manik Prabhu , Li Wen-Jun
Published: April 2020

A Gram-stain-positive, facultatively anaerobic and non-motile strain, designated SYSUP0004T, was isolated from the tubers of Gastrodia elata Blume collected from Yunnan Province, PR China. The 16S rRNA gene sequence result showed that the strain SYSUP0004T shared low similarity (97.7 %) with the type strain of

Cellulomonas marina

. SYSUP0004T grew at pH 6.0–9.0 (optimum, pH 8.0), temperature 4–30 °C (optimum, 28 °C) and could tolerate NaCl up to 4 % w/v (optimum in the absence of NaCl). The cell-wall peptidoglycan type was A4β with an interpeptide bridge l-ornithine–d-glutamic acid. Cell-wall sugars were mannose, ribose, glucose, galactose and fucose. The menaquinone was MK-9(H4). The major fatty acids were anteiso-C15:0, anteiso-C15 : 1 A, C16 : 0 and anteiso-C17 : 0. The polar lipids of SYSUP0004T were diphosphatidylglycerol, unidentified phosphoglycolipid, phosphatidylinositol mannosides and unidentified glycolipid. The genomic DNA G+C content was 76.5 %. The average nucleotide identity values between SYSUP0004T and members of the genus

Cellulomonas

were below the cut-off level (95–96 %) recommended as the ANI criterion for interspecies identity. Thus, based on the above results strain SYSUP0004T represents a novel species of the genus

Cellulomonas

, for which the name Cellulomonas endophytica sp. nov. is proposed. The type strain, SYSUP0004T (=KCTC 49025T=CGMCC 1.16405T).
A systematic, unbiased mapping of CD8+and CD4+T cell epitopes in Yellow Fever vaccinees
Authors: Stryhn Anette , Kongsgaard Michael , Rasmussen Michael , Harndahl Mikkel Nors , Østerbye Thomas , Bassi Maria Rosaria , Thybo Søren , Gabriel Mette , Hansen Morten Bagge , Nielsen Morten , Christensen Jan Pravsgaard , Thomsen Allan Randrup , Buus Soren
Published: April 2020

1.

Examining CD8+and CD4+T cell responses after primary Yellow Fever vaccination in a cohort of 210 volunteers, we have identified and tetramer-validated 92 CD8+and 50 CD4+T cell epitopes, many inducing strong and prevalent (i.e. immunodominant) T cell responses. Restricted by 40 and 14 HLA-class I and II allotypes, respectively, these responses have wide population coverage and might be of considerable academic, diagnostic and therapeutic interest. The broad coverage of epitopes and HLA overcame the otherwise confounding effects of HLA diversity and non-HLA background providing the first evidence of T cell immunodomination in humans. Also, double-staining of CD4+T cells with tetramers representing the same HLA-binding core, albeit with different flanking regions, demonstrated an extensive diversification of the specificities of many CD4+T cell responses. We suggest that this could reduce the risk of pathogen escape, and that multi-tetramer staining is required to reveal the true magnitude and diversity of CD4+T cell responses. Our T cell epitope discovery approach uses a combination of 1) overlapping peptides representing the entire Yellow Fever virus proteome to search for peptides containing CD4+and/or CD8+T cell epitopes, 2) predictors of peptide-HLA binding to suggest epitopes and their restricting HLA allotypes, 3) generation of peptide-HLA tetramers to identify T cell epitopes, and 4) analysis ofex vivoT cell responses to validate the same. This approach is systematic, exhaustive, and can be done in any individual of any HLA haplotype. It is all-inclusive in the sense that it includes all protein antigens and peptide epitopes, and encompasses both CD4+and CD8+T cell epitopes. It is efficient and, importantly, reduces the false discovery rate. The unbiased nature of the T cell epitope discovery approach presented here should support the refinement of future peptide-HLA class I and II predictors and tetramer technologies, which eventually should cover all HLA class I and II isotypes. We believe that future investigations of emerging pathogens (e.g. SARS-CoV-2) should include population-wide T cell epitope discovery using blood samples from patients, convalescents and/or long-term survivors, who might all hold important information on T cell epitopes and responses.
Entraining movement-related brain oscillations using rhythmic median nerve stimulation
Authors: Maiquez Barbara Morera , Jackson Georgina M. , Jackson Stephen R.
Published: April 2020

Non-invasive brain stimulation techniques delivered to cortical motor areas have been shown previously to: modulate cortical motor excitability; entrain brain oscillations; and influence motor behavior; and have therefore attracted considerable interest as potential therapeutic approaches targeted for the treatment of movement disorders. However, these techniques are most often not suitable for treatment outside of the clinic, or for use with young children. We therefore investigated directly whether rhythmic pulses of median nerve stimulation (MNS) could be used to entrain brain oscillations linked to the suppression of movement. Using electroencephalography techniques together with concurrent MNS we demonstrate that 10 pulses of rhythmic MNS, delivered at 19Hz, is sufficient to entrain Beta-band brain oscillations within the contralateral sensorimotor cortex, whereas 10-pulse trains of arrhythmic MNS does not. This approach has potential in our view to be developed into a non-drug therapeutic device suitable for use outside of the research laboratory or the clinic with brain health conditions associated by excessive movements.
Post-transcriptional regulation of human endogenous retroviruses by RNA-Binding Motif Protein 4, RBM4
Authors: Foroushani Amir K. , Chim Bryan , Wong Madeline , Rastegar Andre , Barbian Kent , Martens Craig , Hafner Markus , Muljo Stefan A.
Published: April 2020

The human genome encodes for over 1,500 RNA-binding proteins (RBPs), which coordinate regulatory events on RNA transcripts (Gerstbergeret al., 2014). Most studies of RBPs concentrate on their action on mRNAs that encode protein, which constitute a minority of the transcriptome. A widely neglected subset of our transcriptome derives from integrated retroviral elements termed endogenous retroviruses (ERVs) that comprise ~8% of the human genome. Some ERVs have been shown to be transcribed under physiological and pathological conditions suggesting that sophisticated regulatory mechanisms to coordinate and prevent their ectopic expression exist. However, it is unknown whether RBPs and ERV transcripts directly interact to provide a post-transcriptional layer of regulation. Here, we implemented a computational pipeline to determine the correlation of expression between individual RBPs and ERVs from single-cell or bulk RNA sequencing data. One of our top candidates for an RBP negatively regulating ERV expression was RNA-Binding Motif Protein 4 (RBM4). We used PAR-CLIP to demonstrate that RBM4 indeed bound ERV transcripts at CGG consensus elements. Loss of RBM4 resulted in elevated transcript level of bound ERVs of the HERV-K and -H families, as well as increased expression of HERV-K envelope protein. We pinpointed RBM4 regulation of HERV-K to a CGG-containing element that is conserved in the long terminal repeats (LTRs) of HERV-K-10 and -K-11, and validated the functionality of this site using reporter assays. In summary, we identified RBPs as potential regulators of ERV function and demonstrate a new role for RBM4 in controlling ERV expression.

Significance Statement

The expression of endogenous retroviruses (ERVs) appears to have broad impact on human biology. Nevertheless, only a handful of transcriptional regulators of ERV expression are known and to our knowledge no RNA-binding proteins (RBPs) were yet implicated in positive or negative post-transcriptional regulation of ERVs. We implemented a computational pipeline that allowed us to identify RBPs that modulate ERV expression levels. Experimental validation of one of the prime candidates we identified, RBM4, showed that it indeed bound RNAs made from ERVs and negatively regulated the levels of those RNAs. We hereby identify a new layer of ERV regulation by RBPs.
Covid-19 Outbreak Progression in Italian Regions: Approaching the Peak by March 29th
Authors: Distante Cosimo , Piscitelli Prisco , Miani Alessandro
Published: April 2020

Background

Italy and especially the Lombardy region is experiencing a heavy burden of Covid-19 infection. The peak of the epidemics has not yet been reached and it is expected to be delayed in Central and Southern Italian regions compared to Northern ones. We have modeled the Covid-19 outbreak progression in Italian Regions vs. Lombardy.

Methods

In our models, we have estimated the basic reproduction number (R0) -which represents the average number of people that can be infected by a person who has already acquired the infection - both by fitting the exponential growth rate of the infection across a 1-month period and also by using day by day assessment, based on single observations. We used the susceptible–exposed–infected–removed (SEIR) compartment model to predict the spreading of the pandemic in Italy.

Results

The two methods provide agreements of values, although the first method based on exponential fit should provide a better estimation, being computed on the entire time series. Taking into account the growth rate of the infection across a 1-month period, in Lombardy each infected person has involved other 5 people (4.94 base on data of March 22nd vs. 5.07 based on data of March 19th) compared to a value of R0 = 2.68 reported in the Chinese city of Whuan. According to our model and Piedmont, Veneto, Emilia Romagna, Tuscany and Marche reach an R0 value up to 4. The R0 is 3.7 for Lazio and 3.6 for Campania region, where this latter shows the highest value among the Southern Italian regions, followed by Apulia (3.5), Sicily (3.4), Abruzzo (3.4), Calabria (3.1), Basilicata (2.5) and Molise (2.4). The value of R0 is decreasing in Lombardy and Northern Regions, while it is increasing in Central and Southern Regions.

Conclusion

The expected peak of SEIR model can be forecast by the last week of March at national level, and by the first weeks of April in Southern Italian Regions. These kind of models can be useful for adoption of all the possible preventive measures, and to assess the epidemics progression across Southern regions as opposed to the Northern ones.
Population based estimates of comorbidities affecting risk for complications from COVID-19 in the US
Authors: Adams Mary L. , Katz David L. , Grandpre Joseph
Published: April 2020

We used 2017 Behavioral Risk Factor Surveillance System (BRFSS) data (N=444,649) to estimate the proportion of US adults who report comorbidities that suggest heightened risk of complications from COVID-19. Co-morbidities included cardiovascular disease, chronic obstructive pulmonary disease (COPD), diabetes, asthma, hypertension, and/or cancer other than skin, based on data from China. Overall 45.4% (95% CI 45.1-45.7) of adults reported any of the 6 comorbidities, increasing from 19.8% (19.1-20.4) for ages 18-29 years to 80.7% (79.5-81.8) for ages 80+ years. State rates ranged from 37.3% (36.2-38.5) in Utah to 58.7% (57.0-60.4) in West Virginia. Rates also varied by race/ethnicity, health insurance status, and employment. Excluded were residents of nursing homes or assisted living facilities. Although almost certainly an underestimate of all adults at risk due to these exclusions, these results should help in estimating healthcare needs for adults with COVID-19 complications living in the community.

Article Summary Line

Overall, 45.4% of US adults were estimated to be at heightened risk of COVID-19 complications due to co-morbidities, increasing from 19.8% for ages 18-29 years to 80.7% for ages 80+ years, with state-to-state variation.
Growth rate and acceleration analysis of the COVID-19 pandemic reveals the effect of public health measures in real time
Authors: Utsunomiya Yuri Tani , Utsunomiya Adam Taiti Harth , Torrecilha Rafaela Beatriz Pintor , de Cássia Paula Silvana , Milanesi Marco , Garcia José Fernando
Published: April 2020

Background

Ending the COVID-19 pandemic is arguably one of the most prominent challenges in recent human history. Following closely the growth dynamics of the disease is one of the pillars towards achieving that goal.

Objective

We aimed at developing a simple framework to facilitate the analysis of the growth rate (cases/day) and growth acceleration (cases/day2) of COVID-19 cases in real-time.

Methods

The framework was built using the Moving Regression (MR) technique and a Hidden Markov Model (HMM). The dynamics of the pandemic was initially modeled via combinations of four different growth stages: lagging (beginning of the outbreak), exponential (rapid growth), deceleration (growth decay) and stationary (near zero growth). A fifth growth behavior, namely linear growth (constant growth above zero), was further introduced to add more flexibility to the framework. AnR Shinyapplication was developed, which can be accessed athttp://www.theguarani.com.br/covid-19or downloaded fromhttps://github.com/adamtaiti/SARS-CoV-2. The framework was applied to data from the European Center for Disease Prevention and Control (ECDC), which comprised 853,200 cases reported worldwide as of April 2nd2020.

Results

We found that the impact of public health measures on the prevalence of COVID-19 could be perceived in seemingly real-time by monitoring growth acceleration curves. Restriction to human mobility produced detectable decline in growth acceleration within few days, deceleration within ∼2 weeks and near-stationary growth within ∼6 weeks. Countries exhibiting different permutations of the five growth stages indicated that the evolution of COVID-19 prevalence is more complex and dynamic than previously appreciated.

Conclusions

These results corroborate that mass social isolation is a highly effective measure against the dissemination of SARS-CoV-2, as previously suggested. Apart from the analysis of prevalence partitioned by country, the proposed framework is easily applicable to city, state, region and arbitrary territory data, serving as an asset to monitor the local behavior of COVID-19 cases.
Molecular Basis for ADP-ribose Binding to the Macro-X Domain of SARS-CoV-2 Nsp3
Authors: Frick David N. , Virdi Rajdeep S. , Vuksanovic Nemanja , Dahal Narayan , Silvaggi Nicholas R.
Published: April 2020

The virus that causes COVID-19, SARS-CoV-2, has a large RNA genome that encodes numerous proteins that might be targets for antiviral drugs. Some of these proteins, such as the RNA-dependent RNA polymers, helicase and main protease, are well conserved between SARS-CoV-2 and the original SARS virus, but several others are not. This study examines one of the proteins encoded by SARS-CoV-2 that is most different, a macrodomain of nonstructural protein 3 (nsp3). Although 26% of the amino acids in this SARS-CoV-2 macrodomain differ from those seen in other coronaviruses, biochemical and structural data reveal that the protein retains the ability to bind ADP-ribose, which is an important characteristic of beta coronaviruses, and potential therapeutic target.
Behavioral and neural decomposition of skull-induced death awareness
Authors: Gao Tianyu , Pu Yue , Zhou Jingyi , Zheng Guo , Zhou Yuqing , Han Shihui
Published: April 2020

Death awareness influences multiple aspects of human lives, but its psychological constructs and underlying brain mechanisms remain unclear. We address these by measuring behavioral and brain responses to images of human skulls. We show that skulls relative to control stimuli delay responses to life-related words but speed responses to death-related words. Skulls compared to the control stimuli induce early deactivations in the posterior ventral temporal cortex followed by activations in the posterior and anterior ventral temporal cortices. The early and late neural modulations by perceived skulls respectively predict skull-induced changes of behavioral responses to life- and death-related words and the early neural modulation further predicts death anxiety. Our findings decompose skull-induced death awareness into two-stage neural processes of a lifeless state of a former life.

One sentence summary

Behavioral and brain imaging findings decompose skull-induced death awareness into two-stage neural processes of a lifeless state of a former life.
Cost-effectiveness of genetic and clinical predictors for choosing combined psychotherapy and pharmacotherapy in major depression
Authors: Fabbri Chiara , Kasper Siegfried , Zohar Joseph , Souery Daniel , Montgomery Stuart , Albani Diego , Forloni Gianluigi , Ferentinos Panagiotis , Rujescu Dan , Mendlewicz Julien , Serretti Alessandro , Lewis Cathryn M.
Published: April 2020

Background

Predictors of treatment outcome in major depressive disorder (MDD) could contribute to evidence-based therapeutic choices. This study tested the cost-effectiveness of a pharmacogenetic and clinical predictive model (PGx-CL-R) vs a clinical risk (CL-R) predictive model in guiding the assignment of combined pharmacotherapy and psychotherapy vs pharmacotherapy in MDD.

Methods

We hypothesized that the prescription of combined treatment, a strategy with evidence of increased efficacy vs pharmacotherapy, may be optimized based on the baseline risk of pharmacotherapy resistance, estimated through PGx-CL-R or CL-R predictive models. Both strategies were compared to standard care (ST, pharmacotherapy to all subjects). Treatment effects, costs and utilities (quality adjusted life years, QALYs) were based on the literature and included in a three-years Markov model.

Results

CL-R was cost-effective compared to PGx-CL-R, with ICER (incremental cost effect ratio) of £2341 (CL-R) and £3937 (PGx-CL-R) per QALY compared to ST. PGx-CL-R had similar or better ICER compared to ST only when 1) the cost of genotyping was £100 per subject or less or 2) the sensitivity of the PGx-CL-R test was at least 0.90 and the specificity at least 0.85. CL-R had ICER of £3664 and of £4110 when the CL-R model was tested in two independent samples.

Limitations

lack of validation in clinical trial.

Conclusions

Prediction of pharmacotherapy resistance according to clinical risk might be a cost-effective strategy if confirmed on large samples from the general population. Combined treatment with drugs having a very good tolerability profile could be a cheaper alternative to psychotherapy.
Blood glucose levels in elderly subjects with type 2 diabetes during COVID-19 outbreak: a retrospective study in a single center
Authors: Xue Ting , Li Qianwen , Zhang Qiongyao , Lin Wei , Wen Junping , Li Li , Chen Gang
Published: April 2020

Aims

Ideal glycemic control is of great importance for diabetic patients during public health emergencies of infectious diseases as long-term hyperglycemic are not only associated with chronic complications but also vital drivers of common and life-threatening infections. The present study was designed to investigate the changes of blood glucose levels in elderly subjects with type 2 diabetes(T2D) during COVID-19 outbreak.

Methods

This retrospective study focused on the T2D outpatients at Fujian Provincial Hospital aged 65 years old and above who received baseline test for fasting plasma glucose and/or glycated hemoglobin (HbA1c) between January 1, 2019 and March 8, 2019 and were followed up on fasting plasma glucose and/or HbA1c in the same period in 2020. The baseline and follow-up data were analyzed with the paired-samples T-test.

Results

A total of 135 elderly subjects with T2D with baseline and follow-up fasting plasma glucose and 50 elderly subjects with T2D with baseline and follow-up HbA1c were analyzed, respectively. The baseline and follow-up fasting plasma glucose were 7.08 ± 1.80 and 7.48±2.14 mmol/L, respectively (P=0.008). The baseline and follow-up HbA1c were 7.2±1.7% and 7.4±1.8%, respectively (P=0.158).

Conclusions

Elderly subjects with T2D had higher fasting plasma glucose levels during COVID-19 outbreak. We should pay more attension to the management of diabetics during public health emergencies.
Association of extended dosing intervals or delays in pembrolizumab-based regimens with survival outcomes in advanced non-small cell lung cancer
Authors: Sehgal Kartik , Bulumulle Anushi , Brody Heather , Gill Ritu R. , Macherla Shravanti , Qilleri Aleksandra , McDonald Danielle C. , Cherry Cynthia R. , Shea Meghan , Huberman Mark S. , VanderLaan Paul A. , Weiss Glen J. , Walker Paul R. , Costa Daniel B. , Rangachari Deepa
Published: April 2020

Background

Besides modeling/simulation-based analysis, no post-approval studies have evaluated optimal administration frequency of pembrolizumab in non-small cell lung cancer (NSCLC).

Patients and Methods

We performed a multicenter retrospective cohort study to evaluate association between survival outcomes and treatment extensions/delays of pembrolizumab-based regimens in advanced NSCLC patients. Those who had received at least four cycles in routine practice were divided into two groups: non-standard (Non-Std: ≥2 cycles at intervals >3weeks ±3days) and standard (Std: all cycles every 3weeks or 1 cycle >3weeks ±3days).

Results

Among 150 patients, 92 (61%) were eligible for the study (Non-Std:27, Std:65). Reasons for patients with extensions/delays in the Non-Std group included: immune-related adverse events (irAEs,33%), non-irAE-related medical issues (26%), and patient-physician preference (41%). Non-Std group was more likely to have higher PD-L1 tumor proportion score, higher number of treatment cycles and pembrolizumab monotherapy. Univariate and 6-month landmark analyses showed longer median overall survival (OS) and progression-free survival (PFS) in Non-Std group compared to the Std group. After multivariable adjustment for confounding factors, there was no significant difference in OS [HR 1.1 (95%C.I.: 0.3–4.7), p=0.874] or PFS [HR 2.7 (95%C.I.: 0.8–8.8), p=0.094] between the two groups.

Conclusion

Our study shows that a significant proportion of advanced NSCLC patients receive pembrolizumab-based regimens with extended intervals or delays in routine clinical practice and with similar outcomes to those receiving treatment at label-specified 3-week intervals. Given the durability of benefit seen and the potential for cost reduction and decreased infusion frequency in these patients, this requires validation in prospective trials.

MicroAbstract

The most cost-effective administration frequency of pembrolizumab in advanced non-small cell lung cancer (NSCLC) is unknown. We found that a significant proportion of these patients receive pembrolizumab-based regimens with extended intervals or delays in routine practice, with similar outcomes to those on label-specified 3-week interval treatments. Prospective evaluation of alternative dosing strategies is warranted to develop a more fiscally viable and patient-centered model.
Differences in power-law growth over time and indicators of COVID-19 pandemic progression worldwide
Authors: Merrin Jack
Published: April 2020

1

An automated statistical and error analysis of 45 countries or regions with more than 1000 cases of COVID-19 as of March 28, 2020, has been performed. This study reveals differences in the rate of disease spreading rate over time in different countries. This survey observes that most countries undergo a beginning exponential growth phase, which transitions into a power-law phase, as recently suggested by Ziff and Ziff. Tracking indicators of growth, such as the power-law exponent, are a good indication of the relative danger different countries are in and show when social measures are effective towards slowing the spread. The data compiled here are usefully synthesizing a global picture, identifying country to country variation in spreading, and identifying countries most at risk. This analysis may factor into how best to track the effectiveness of social distancing policies and quarantines in real-time as data is updated each day.
Phenotypic Associations and Shared Genetic Etiology between Bipolar Disorder and Cardiometabolic Traits
Authors: Fürtjes Anna E. , Coleman Jonathan R.I. , Tyrrell Jess , Lewis Cathryn M. , Hagenaars Saskia P.
Published: April 2020

Background

People with bipolar disorder (BPD) are more likely to die prematurely, which is partly attributed to comorbid cardiometabolic traits. BPD has a bidirectional relationship with cardiometabolic traits, but their shared etiology is poorly understood. This study aimed to examine the phenotypic associations and shared genetic etiology between BPD and various cardiometabolic traits.

Methods

In a subset of the UK Biobank sample (N = 67,317) we investigated phenotypic associations between BPD (n = 4,155) and cardiometabolic traits, represented by biomarkers, anthropometric traits and cardiometabolic diseases. To determine the shared genetic etiology, polygenic risk scores and genetic correlations were calculated between BPD and these traits.

Results

Several cardiometabolic traits were significantly associated with increased risk for BPD, namely low total cholesterol, low high-density lipoprotein cholesterol, high triglycerides, high glycated haemoglobin (HbA 1c), low systolic blood pressure, high body mass index, high waist-to-hip ratio, as well as stroke, coronary artery disease and type 2 diabetes diagnosis. Polygenic risk score regressions showed that higher polygenic risk for triglycerides, waist-to-hip ratio, coronary artery disease, and type 2 diabetes was associated with increased risk for bipolar disorder. These associations were not replicated when using genetic correlations.

Conclusions

This large study identified phenotypic cardiometabolic risk factors for BPD. Moreover, it found that comorbidities between BPD and waist-to-hip ratio, triglycerides, type 2 diabetes and coronary artery disease may be based on shared genetic etiology. These results provide a better understanding of the phenotypic and genetic comorbidity between BPD and cardiometabolic traits.