bluuebunny/crossref_metadata_2025 huggingface dataset:
Accuracy of liver and spleen stiffness on magnetic resonance elastography for detecting portal hypertension: a systematic review and meta-analysis
Authors: Singh Ranjit , Wilson Mitchell P. , Katlariwala Prayash , Murad Mohammad H. , McInnes Matthew D.F. , Low Gavin
Published: April 2020

Introduction

The purpose of this systematic review and meta-analysis was to evaluate the diagnostic accuracy of liver and spleen stiffness on magnetic resonance elastography (MRE) for detecting clinically significant portal hypertension.

Methods

A systematic review of MEDLINE, EMBASE, Scopus, the Cochrane Library, and the Grey Literature through to 15 August 2019 was performed. Original articles with >10 patients evaluating liver and/or spleen stiffness on MRE using a reference standard of portal hypertension defined as intractable ascites, esophageal varices, encephalopathy and/or death were included in analysis. Patient, clinical, MRI, and diagnostic performance was independently acquired by two reviewers. Meta-analysis was performed using a bivariate mixed-effects regression model.

Results

Fourteen studies were included with 12 studies evaluating liver stiffness and eight studies evaluating spleen stiffness. The pooled and weighted sensitivity, specificity, and area under the curve (AUC) values for liver stiffness on MRE were 83% [95% confidence interval (CI) 72–90%], 80% (95% CI 70–88%), and 88% (95% CI 85–91%), respectively. The pooled and weighted sensitivity, specificity, and AUC values for spleen stiffness on MRE were 79% (95% CI 61–90%), 90% (95% CI 80–95%), and 92% (95% CI 89–94%), respectively. The liver and spleen stiffness sensitivity and specificity values were comparable when evaluating for esophageal varices only at of 80% (95% CI 66–89%) and 76% (95% CI 62–86%) for liver stiffness, and 75% (95% CI 52–90%) and 89% (95% CI 70–96%) for spleen stiffness.

Discussion

Liver and spleen stiffness on MRE can serve as a supplemental noninvasive assessment tools for detecting clinically significant portal hypertension. Spleen stiffness may be more specific and accurate than liver stiffness for detecting portal hypertension.
Needle-based confocal laser endomicroscopy in pancreatic cysts: a meta-analysis
Authors: Facciorusso Antonio , Buccino Vincenzo Rosario , Sacco Rodolfo
Published: April 2020

There is currently limited evidence supporting the use of needle-based confocal laser endomicroscopy in pancreatic cystic lesions. Aim of this study was to provide a pooled estimate of the diagnostic performance and safety profile of this technique in patients with pancreatic cysts. Computerized bibliographic search on the main databases was performed through November 2019. Pooled effects were calculated using a random-effects model by means of DerSimonian and Laird test. Primary endpoint was diagnostic accuracy. Secondary outcomes were pooled sensitivity, specificity, and mean procedural time. Ten studies enrolling 536 patients were included. Eight articles, of which five prospective series, compared confocal laser endomicroscopy to cytology/cystic fluid analysis. Most patients were female and body/tail was the most frequent location of pancreatic cysts. Mucinous cysts were prevalent in most of the included studies. Diagnostic accuracy with confocal laser endomicroscopy was 88.6% (83.7–93.4%) and sensitivity analysis according to study quality, design, and treatment arms confirmed the above reported result. Pooled sensitivity and specificity were 82.4% (74.7–90.1%) and 96.6% (94.3–99%), respectively. Both accuracy and sensitivity resulted higher in patients with mucinous cysts (91.4 and 94.9%, respectively). Confocal laser endomicroscopy clearly outperformed fine-needle aspiration in terms of diagnostic accuracy (odds ratio 3.94, 1.58–9.82; P = 0.003). A mean of 6.094 minutes (4.91–7.26) was needed to complete the procedure and no significant adverse event was registered. Our meta-analysis speaks in favor of the use of needle-based confocal laser endomicroscopy as a safe and effective tool in the diagnostic algorithm of pancreatic cysts.
The prevention and management of Crohn’s disease postoperative recurrence: results from the Y-ECCO/ClinCom 2019 Survey
Authors: Dragoni Gabriele , Ding Nik , Gecse Krisztina B. , Mansfield John C. , Kopylov Uri , Beaugerie Laurent , Bossuyt Peter , Sebastian Shaji , Milla Monica , Bagnoli Siro , Yassin Nuha A. , Bettenworth Dominik , Burisch Johan , Hedin Charlotte , Gisbert Javier P. , Ferrante Marc
Published: April 2020

Background:

Prevention and management of postoperative recurrence (POR) is a controversial field in Crohn’s disease. The aim of this survey was to report common practice in real-life settings.

Methods:

An 11-question survey was distributed among gastroenterologists attending the 14th European Crohn’s and Colitis Organisation (ECCO) congress.

Results:

Postoperative endoscopy to assess recurrence was routinely performed within 12 months by 87% of respondents. Forty-six percent of clinicians reported to maintain endoscopic assessment in routine follow-up even after first negative colonoscopy. Most respondents (60%) considered starting postoperative immunoprophylaxis in naïve patients if one or more known risk factors were present. The number of risk factors was an important driver for prescribing biologics over immunosuppressants for 60% of respondents.

In case of fistulizing phenotype, perianal disease, or concomitant colonic involvement, the majority of physicians reported to start an immediate prophylaxis in 85, 98 and 88% of patients, respectively. A significant percentage of clinicians were more prone to an endoscopy-driven treatment in long-standing disease after failure of thiopurines (51%) and elderly (43%).

Conclusion:

Endoscopy within the first year after surgery to assess POR has become routine in most centres. The high rate of early prophylaxis with expensive biologics despite missing solid evidence highlights the need for more randomized trials.
Small molecule drugs in the treatment of inflammatory bowel diseases: which one, when and why? – a systematic review
Authors: Lucaciu Laura A. , Seicean Radu , Seicean Andrada
Published: April 2020

In the ‘treat-to-target’ era of inflammatory bowel disease (IBD) management, small molecule drugs (SMDs) represent a promising alternative to biomolecular drugs. Moreover, increasing failure rates of anti-tumor necrosis factor α agents have contributed to the development of new molecules with different mechanisms of action and bioavailability. This review focuses on the positioning of new, orally targeted therapies in the treatment algorithm of both Crohn’s disease (CD) and ulcerative colitis (UC), with special consideration to their efficacy and safety. We performed a comprehensive search of PubMed and clinical trial registries to identify randomized controlled trials assessing SMDs in adult patients with moderate-to-severe IBD, irrespective of previous exposure to other biologics. In this review, we included 15 double-blind, placebo-controlled trials that assessed the efficacy and safety of Janus kinase inhibitors, sphingosine-1-phosphate modulators (S1P), SMAD blockers, phosphodiesterase 4 inhibitors and α-4 antagonists. The primary endpoints in UC were achieved for tofacitinib in the phase III OCTAVE study and AJM-300, with a favorable safety profile. S1P receptor agonists, such as etrasimod and ozanimod, demonstrated favorable results in induction studies. For CD, filgotinib and upadacitinib also met the primary outcome criteria. Available data have demonstrated so far that SMDs have an advantageous safety and efficacy profile. However, their use in a clinical setting will eventually require a personalized, mechanism-based therapeutic approach.
Comparison of the impact of tenofovir alafenamide and entecavir on declines of hepatitis B surface antigen levels
Authors: Kumada Takashi , Toyoda Hidenori , Tada Toshifumi , Yasuda Satoshi , Miyake Nozomi , Tanaka Junko
Published: April 2020

Objective:

Tenofovir alafenamide is a new prodrug of tenofovir that allows for the treatment of patients with hepatitis B virus (HBV) at a lower dose than with tenofovir disoproxil fumarate, due to the more efficient delivery of tenofovir to hepatocytes. In this study, we compared entecavir and tenofovir alafenamide in terms of their ability to reduce hepatitis B surface antigen (HBsAg) in the same group of patients with HBV infection.

Methods:

During March and June 2018, 129 patients who received entecavir were switched to tenofovir alafenamide. Every 3– 6 months for 1 year before and after switching to tenofovir alafenamide, all patients underwent measurements of HBsAg, hepatitis core-related antigen (HBcrAg), calcium (Ca), inorganic phosphorus, and estimated glomerular filtration rate (eGFR).

Results:

The percent decline rate during the entecavir and tenofovir alafenamide phases at 6 months were 2.38% (−3.57 to 0.00) and −3.57% (−7.14 to 0.00), respectively, and those at 12 months were 3.03% (−6.57 to 0.00) and −5.56% (−7.41 to −2.50), respectively. HBsAg levels were reduced significantly more during the tenofovir alafenamide phase than during the entecavir phase (P < 0.0001). There were no significant differences in the percent declines of HBcrAg, Ca, inorganic phosphorus, or eGFR during the entecavir and tenofovir alafenamide phases after 1 year.

Conclusion:

tenofovir alafenamide significantly decreased HBsAg levels compared to entecavir.
Platelet–lymphocyte ratio predicts survival in patients with hepatocellular carcinoma who receive lenvatinib: an inverse probability weighting analysis
Authors: Tada Toshifumi , Kumada Takashi , Hiraoka Atsushi , Michitaka Kojiro , Atsukawa Masanori , Hirooka Masashi , Tsuji Kunihiko , Ishikawa Toru , Takaguchi Koichi , Kariyama Kazuya , Itobayashi Ei , Tajiri Kazuto , Shimada Noritomo , Shibata Hiroshi , Ochi Hironori , Yasuda Satoshi , Toyoda Hidenori , Fukunishi Shinya , Ohama Hideko , Kawata Kazuhito , Nakamura Shinichiro , Nouso Kazuhiro , Tsutsui Akemi , Nagano Takuya , Itokawa Norio , Hayama Korenobu , Arai Taeang , Imai Michitaka , Joko Kouji , Koizumi Yohei , Hiasa Yoichi
Published: April 2020

Objective

Lenvatinib, a newly developed molecularly targeted agent, has become available as a first-line therapy in patients with unresectable hepatocellular carcinoma (HCC). The platelet-to-lymphocyte ratio (PLR) has been associated with poor outcome in various malignancies, including HCC. In this study, we investigated the ability of PLR to predict outcomes in patients with unresectable HCC who received lenvatinib.

Methods

Multivariate survival analysis was performed in 283 patients with unresectable HCC who received lenvatinib. In addition, the utility of PLR for predicting survival was clarified using an inverse probability weighting (IPW) analysis.

Results

Cumulative overall survival at 100, 200, 300, 400, and 500 days was 95.2, 83.8, 68.3, 60.3, and 49.9%, respectively. Multivariate analysis with Cox proportional hazards modeling showed that PLR (≥150) [hazard ratio, 1.588; 95% confidence interval (CI), 1.039–2.428; P = 0.033], α-fetoprotein level, and Barcelona clinic liver cancer stage were independently associated with overall survival. Cumulative overall survival differed significantly between patients with low versus high PLR (P = 0.029). In addition, univariate analysis with Cox proportional hazards modeling adjusted by IPW showed that PLR (≥150) (hazard ratio, 1.396; 95% CI, 1.051–1.855; P = 0.021) was significantly associated with overall survival. Conversely, univariate analysis with Cox proportional hazards modeling adjusted only by IPW showed that PLR (≥150) (hazard ratio, 1.254; 95% CI, 1.016–1.549; P = 0.035) was significantly associated with progression-free survival. PLR values were not independently associated with therapeutic responses before or after IPW-adjusted logistic regression analysis.

Conclusions

PLR predicted overall survival in patients with unresectable HCC who received lenvatinib.
Technical note on the administration of intravenous contrast media in hybrid imaging
Authors: Johnson Susan , Gulliver Nick , King Simon , Meadows Angela , do Mar Machado Joana
Published: April 2020

This article summarises the proceedings of a continuing professional development session on the use of intravenous contrast media in hybrid imaging for radiographers, technologists, and nurses. The session was jointly organised by the British Nuclear Medicine Society Radiographer, Technologist, and Nurses Group and the Society of Radiographers at the 47th Annual Spring Meeting of the British Nuclear Medicine Society held in Oxford, UK, on 1–3 April 2019.
Primary Renal Ewing Sarcoma in Children and Young Adults
Authors: Bradford Kathryn , Nobori Alexander , Johnson Brittany , Allen-Rhoades Wendy , Naik-Mathuria Bindi , Panosyan Eduard H. , Gotesman Moran , Lasky Joseph , Cheng Jerry , Ikeda Alan , Goldstein Jeffrey , Singh Arun , Federman Noah
Published: April 2020

The Ewing sarcoma family of tumors (ESFT) are high-grade small round blue cell malignancies traditionally presenting in children and adolescents. The most common site of primary disease is bone, though extraskeletal primary sites are well-recognized. We present 6 cases of primary ESFT of the kidney and 1 case of the adrenal gland. Patients were 11 to 18 years of age at diagnosis. Metastases at diagnosis were present in most cases (n=6). All patients underwent surgery, and most received radiation (n=5). Five patients relapsed after initial remission. Comprehensive review of the primary renal ESFT literature was used to analyze various factors, including age, sex, disease metrics, metastases at diagnoses, and overall survival in a total of 362 cases. Notably, while the general ESFT population has reported rates of metastasis at diagnosis of 20% to 25%, this rate in the renal ESFT population was 53% with a rate of 59% in adolescent and young-adult patients (11 to 24 y). Nodal disease at diagnosis was present in 24% of renal ESFT cases compared with 3.2% in patients with primary skeletal ESFT. While this malignant process may share histologic and molecular features with its bone and soft tissue counterparts, primary renal ESFT presentations seem to be more aggressive and have worse outcomes.
Prenatal Care for American Indian Women
Authors: Johnson Mary Beth
Published: April 2020

Early and regular prenatal care, which aims to prevent and identify complications associated with pregnancy, birth, and newborn health, is associated with improved health of pregnant women and their infants. American Indian/Alaska Native (AI/AN) women are at risk for pregnancy, birth, and newborn health complications associated with health disparities including poverty, lower educational levels, limited access to healthcare, and adverse childhood events. American Indian/Alaska Native women in the United States experience barriers specifically related to prenatal care, including lack of access, dissimilar communication styles, and inconsistent continuity of care. Culturally appropriate prenatal care should be provided to reduce maternal and newborn morbidity and mortality. Community-based interventions such as home visiting, that may potentially improve prenatal care, focusing on the American Indian tribes of the Northern Great Plains, specifically North Dakota, are discussed.
Follicular Thyroid Neoplasms
Authors: Cracolici Vincent , Ritterhouse Lauren L. , Segal Jeremy P. , Puranik Rutika , Wanjari Pankhuri , Kadri Sabah , Parilla Megan , Cipriani Nicole A.
Published: April 2020

In follicular thyroid neoplasms without invasion, a diagnosis of atypical adenoma (AA) (follicular tumor of uncertain malignant potential) may be rendered if atypical features (indefinite capsular/vascular invasion, necrosis, solid growth, increased mitoses) are present. This study compares clinical, histologic, and molecular features of patients with AAs (n=31), nonmetastatic follicular thyroid carcinoma (nmFTC) (n=18), and metastatic follicular thyroid carcinoma (mFTC) (n=38). Patients with mFTC were older. Mitotic activity in areas of solid growth was greatest in mFTC (P=0.05). Oncocytic tumors tended to show solid growth (P=0.04). The presence or frequency of capsular and/or vascular invasion was not different between nmFTC and mFTC. TERT promoter mutations were higher in patients with mFTC (50%) than nmFTC (25%) and AA (10%) (P=0.02). TERT promoter mutation was associated with necrosis (P=0.01) and solid growth plus increased mitoses (P=0.03). Necrosis and TERT promoter mutations were identified in all groups, most frequently in mFTC. The combination of solid growth with increased mitoses, necrosis, and TERT promoter mutation was only seen in follicular carcinomas. Poorly differentiated features, vascular invasion, and TERT promoter mutation correlated with metastasis in FTC. Given the low frequency of necrosis and TERT promoter mutation in AAs, close clinical follow-up is recommended in patients with these findings, especially if additional atypical features (such as solid growth plus mitoses) are present.
COVID-19 in Children in the United States: Intensive Care Admissions, Estimated Total Infected, and Projected Numbers of Severe Pediatric Cases in 2020
Authors: Pathak Elizabeth Barnett , Salemi Jason L. , Sobers Natasha , Menard Janelle , Hambleton Ian R.
Published: April 2020

Importance:

A surge in severe cases of COVID-19 (coronavirus disease 2019) in children would present unique challenges for hospitals and public health preparedness efforts in the United States.

Objective:

To provide evidence-based estimates of children infected with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) and projected cumulative numbers of severely ill pediatric COVID-19 cases requiring hospitalization during the US 2020 pandemic.

Design:

Empirical case projection study.

Main Outcomes and Measures:

Adjusted pediatric severity proportions and adjusted pediatric criticality proportions were derived from clinical and spatiotemporal modeling studies of the COVID-19 epidemic in China for the period January-February 2020. Estimates of total children infected with SARS-CoV-2 in the United States through April 6, 2020, were calculated using US pediatric intensive care unit (PICU) cases and the adjusted pediatric criticality proportion. Projected numbers of severely and critically ill children with COVID-19 were derived by applying the adjusted severity and criticality proportions to US population data, under several scenarios of cumulative pediatric infection proportion (CPIP).

Results:

By April 6, 2020, there were 74 children who had been reported admitted to PICUs in 19 states, reflecting an estimated 176 190 children nationwide infected with SARS-CoV-2 (52 381 infants and toddlers younger than 2 years, 42 857 children aged 2-11 years, and 80 952 children aged 12-17 years). Under a CPIP scenario of 5%, there would be 3.7 million children infected with SARS-CoV-2, 9907 severely ill children requiring hospitalization, and 1086 critically ill children requiring PICU admission. Under a CPIP scenario of 50%, 10 865 children would require PICU admission, 99 073 would require hospitalization for severe pneumonia, and 37.0 million would be infected with SARS-CoV-2.

Conclusions and Relevance:

Because there are 74.0 million children 0 to 17 years old in the United States, the projected numbers of severe cases could overextend available pediatric hospital care resources under several moderate CPIP scenarios for 2020 despite lower severity of COVID-19 in children than in adults.
Key Drivers in Reducing Hospital-acquired Pressure Injury at a Quaternary Children’s Hospital
Authors: Johnson Andrea K. , Kruger Jenna F. , Ferrari Sarah , Weisse Melissa B. , Hamilton Marie , Loh Ling , Chapman Amy M. , Taylor Kristine , Bargmann-Losche Jessey , Donnelly Lane F.
Published: April 2020

Introduction:

Despite being a participating Solutions for Patient Safety (SPS) children’s hospital and having attempted implementation of the SPS hospital-acquired pressure injuries (HAPIs) prevention bundle, our hospital remained at a HAPI rate that was 3 times the mean for SPS participating children’s hospitals. This performance led to the launch of an enterprise-wide HAPI reduction initiative in our organization. The purpose of this article is to describe the improvement initiative, the key drivers, and the resulting decrease in the SPS-reportable HAPI rate.

Methods:

We designed a hospital-wide HAPI reduction initiative with actions grouped into 3 key driver areas: standardization, data transparency, and accountability. We paused all individual hospital unit-based HAPI reduction initiatives. We calculated the rate of SPS-reportable HAPIs per 1,000 patient days during both the pre- and postimplementation phases and compared mean rates using a 2-sided t test assuming unequal variances.

Results:

The mean SPS-reportable HAPI rate for the preimplementation phase was 0.3489, and the postimplementation phase was 0.0609. The difference in rates was statistically significant (P < 0.00032). This result equates to an 82.5% reduction in HAPI rate.

Conclusions:

Having an institutional pause and retooled initiative to reduce HAPI with key drivers in the areas of standardization, data transparency, and accountability had a statistically significant reduction in our organization’s SPS-reportable HAPI rate.
Brief Report: Group Sex and Methamphetamine Use Fuel an Explosive Epidemic of Hepatitis C Among HIV-Infected Men Who Have Sex With Men in Bangkok, Thailand
Authors: Wansom Tanyaporn , Pinyakorn Suteeraporn , Kolsteeg Christy J. , Kroon Eugene , Sacdalan Carlo P. , Chomchey Nitiya , Ananworanich Jintanat , Vasan Sandhya , Phanuphak Nittaya , Colby Donn J.
Published: April 2020

Background:

Increased rates of hepatitis C virus (HCV) infection among HIV-infected men who have sex with men (MSM) and who deny injecting drugs have been reported in resource-rich settings.

Setting:

We measured HCV prevalence and incidence in a predominantly MSM cohort with acute HIV infection in Bangkok, Thailand.

Methods:

In 2009–2018, participants with acute HIV infection were enrolled into the SEARCH010/RV254 cohort. HCV antibody was measured at enrollment and at least once annually. Infection was confirmed with HCV RNA. Risk factors for HCV were analyzed by proportional hazards regression, with hazard ratios (HRs) calculated in a multivariable model.

Results:

Of 573 participants, 94% were MSM, with a median age of 26 years (range 18–70 years). The prevalence of HCV antibody was 9 of the 573, or 1.6% [95% confidence interval (CI): 0.7% to 3.0%]. In 1883 person-years (PY) of follow-up, 39 incident cases were identified (20.7 per 1000 PY, 95% CI: 15.1 to 28.3). All incident cases were identified from 2014 onward, and incidence rose from a range of 7.5–11.4 per 1000 PY between 2014 and 2016 to 44.8 per 1000 PY in 2018 (P = 0.001). Most cases (97.4%) were MSM and denied injecting drugs (37 of the 39, 94.5%). In multivariate analysis, methamphetamine use [adjusted HR 2.33 (95% CI: 1.13 to 4.8), P = 0.022], group sex [adjusted HR 2.54 (95% CI: 1.26 to 5.12), P = 0.009], and a history of positive Treponema pallidum hemagglutination or rapid plasma reagin [adjusted HR 2.43 (95% CI: 1.22 to 4.85), P = 0.012] were significantly associated with incident HCV.

Conclusion:

We report an HCV epidemic among this cohort of HIV-infected Bangkok-based MSM. Access to timely HCV diagnosis and treatment is needed to prevent morbidity and to decrease onward transmission.
Postoperative Dysphagia Following Magnetic Sphincter Augmentation for Gastroesophageal Reflux Disease
Authors: Tsai Catherine , Steffen Rudolf , Kessler Ulf , Merki Hans , Lipham John , Zehetner Joerg
Published: April 2020

The addition of posterior cruroplasty to magnetic sphincter augmentation (MSA-PC) has been shown to be effective in treating gastroesophageal reflux disease (GERD). This study evaluates the predictors of persistent postoperative dysphagia, one of the major complaints after MSA-PC. From August 2015 to February 2018 the medical records of 118 patients (male=59, female=59) receiving MSA-PC for GERD were reviewed. Postoperative dysphagia was present in 80 patients (67.8%), with 20 (16.9%) requiring dilation for persistent dysphagia. Three patients (2.5%) had the magnetic sphincter augmentation device removed for persistent dysphagia, one was converted to a Nissen fundoplication. The median number of dilations was 1, mean time from surgery to dilation was 5.6 months, and 15/20 (75%) had symptom resolution after 1 to 2 dilations. Dilated patients were more likely than nondilated patients to have atypical GERD symptoms preoperatively (70% vs. 44.7%, P=0.042). After dilation, 93.3% of patients reported a good quality of life.
Evaluation of Postpartum Pelvic Floor Physical Therapy on Obstetrical Anal Sphincter Injury: A Randomized Controlled Trial
Authors: Von Bargen Emily , Haviland Miriam J. , Chang Olivia H. , McKinney Jessica , Hacker Michele R. , Elkadry Eman
Published: April 2020

Objective

The aim of the study was to evaluate a short course of postpartum pelvic floor physical therapy (PFPT) on symptoms and quality of life after obstetrical anal sphincter injuries (OASIS).

Methods

This was a multicenter, randomized controlled trial. Adult women were eligible if they had a vaginal delivery complicated by OASIS and did not have a prior vaginal delivery after 24 weeks’ gestation. Participants were randomized to standard care plus PFPT or standard care alone. The primary outcome was change in the Pelvic Floor Distress Inventory (PFDI-20) at 12 weeks postpartum. Secondary outcomes included other validated questionnaires assessing pelvic floor symptoms and bother.

Results

We approached 89 eligible women; 50 were enrolled and randomized. We excluded 6 participants in the PFPT group and 1 in the standard care group who withdrew before study initiation or did not provide baseline data at 2 weeks postpartum. Thus, we analyzed 19 in the PFPT group and 24 in the standard care group. The groups were similar with regard to most baseline characteristics.

The PFPT group reported significant improvement in pelvic floor symptoms and bother compared with the standard care group, reflected by a decrease of 29.2 (interquartile range = −58.3 to −4.2) compared with 0.0 (interquartile range = −14.6 to 20.8) on the PFDI-20 from 2 to 12 weeks postpartum (P = 0.002). Significant differences also were observed for all PFDI-20 subscales (all P ≤ 0.02).

Conclusions

At 12 weeks postpartum, the PFPT group reported a significant improvement in pelvic floor symptoms and bother compared with the standard care group.
Convolvulus pluricaulis extract can modulate synaptic plasticity in rat brain hippocampus
Authors: Das Rishi , Sengupta Tathagata , Roy Shubhrajit , Chattarji Sumantra , Ray Jharna
Published: April 2020

The memory-boosting property of Indian traditional herb, Convolvulus pluricaulis, has been documented in literature; however, its effect on synaptic plasticity has not yet been reported. Two important forms of synaptic plasticity known to be involved in the processes of memory formation are long-term potentiation (LTP) and long-term depression (LTD). In the present study, the effect of C. pluricaulis plant extract on LTP and LTD were evaluated. The adult male Wistar rats were fed orally with 250, 500 and 1000 mg/kg of this extract for 4 weeks and the effect was determined on LTP and LTD in the Schaffer collaterals of the hippocampal cornu ammonis region CA1. We found that the 500 mg/kg dose of the extract could significantly enhance LTP compared to the vehicle treated ones. Moreover, the same dose could also reduce LTD while used in a separate set of animals. Also, a fresh group of animals treated with the effective dose (500 mg/kg) of plant extract were examined for memory retention in two behavioral platforms namely, contextual fear conditioning (CFC) and novel object recognition test (NORT). Increased fear response to the conditioned stimulus and enhanced recognition of objects were observed in CFC and NORT, respectively, both indicating strengthening of memory. Following up, ex-vivo electrophysiology experiments were performed with the active single molecule scopoletin, present in C. pluricaulis extract and similar patterns in synaptic plasticity changes were obtained. These findings suggest that prolonged treatment of C. pluricaulis extract, at a specific dose in healthy animals, can augment memory functions by modulating hippocampal plasticity.
Method for Active Pandemic Curve Management (MAPCM)
Authors: Odendaal Willem G.
Published: April 2020

The COVID-19 pandemic of 2020 prompted stringent mitigation measures to “flatten the curve” quickly leading to an asphyxiated US economy as a national side effect. There are severe drawbacks to this strategy. The resulting flattened curve remains exponential and always under utilizes available healthcare capacity with a chance of still overburdening it. Moreover, while a mitigation strategy involving isolation and containment can scale down infections, it not only prolongs the outbreak significantly, but also leaves a susceptible population in its wake that’s ripe for a secondary outbreak. Since economic activity is inversely proportional to mitigation, curtailing the outbreak with sustained mitigation can stifle the economy severely with disastrous repercussions. Full mitigation for the duration of an outbreak is therefore unsustainable and, overall, a poor solution with potentially catastrophic consequences that could’ve been avoided. A new strategy, coined a “Method for Active Pandemic Curve Management”, or MAPCM, presented herein can shape the outbreak curve in a controlled manner for optimal utilization of healthcare resources during the pandemic, while drastically shortening the outbreak duration compared to mitigation by itself without trading off lives. This method allows mitigation measures to be relaxed gradually from day one, which enables economic activity to resume gradually from the onset of a pandemic. Since outbreak curves (such as hospitalizations) can be programmed using this method, they can also be shaped to accommodate changing needs during the outbreak; and to build herd immunity without the damaging side effects. The method can also be used to ease out of containment. MAPCM is a method and not a model. It is compatible with any appropriate outbreak model; and herein it is illustrated in examples using a hybrid logistic model.
A novel culture-independent method to search unknown dominant bacterial groups and its application to microbial analysis of membrane bioreactors
Authors: Watanabe Katsuji , Horinishi Naoto
Published: April 2020

As we could not get numerical information for unknown unculturable microorganisms through conventional culture-independent analysis methods such as next-generation sequencing, or real time PCR, we developed an original culture-independent method, and searched the numerically dominant bacteria in three industrial membrane bioreactors for livestock farms.

AlthoughActinobacteriawas the numerically dominant phylum (9.3×105MPN/mL) on 6/August/2014 in the MBR of A farm, when a bacteria with the same genotype toArthrobactersp. (AF197047; 4.3×105MPN/mL), and those similar toBurkholderia sp. (AB299593; 4.3×105MPN/mL) were the numerically dominant, after about 13 months (24/October/2015) a number of theArthrobactergenotype increased to 930×105MPN (230 times) and become dominant, and those similar to theMicrobacteriumsp. (AM403628) increased to 92×105MPN, while that of theBurkholderia genotype disappeared. In the other MBR of B farm, bacteria having a similar genotype toEnshifersp. (AB195268, CP000738), orShinorhizobiumsp. (AF227755, AB195268), orMesorhizobiumsp. (BA000012, Mso.tians29), orAgrobacterium vitis(D12795) was dominant on 18/August/2015 (24×105MPN) and 30/August/2015 (15.5×105MPN). In the other MBR of C farm (9/October/2015), bacteria having a similar genotype to unculturedBetaproteobacteria(AY921864) was dominant (430×105MPN), followed by uncultured bacterium (74×105MPN ; AM268745), andMycobacteriaceae(AB298730), orPropionibacteriaceae(AB298731) (7.4 ×105MPN). There was no common bacterial groups among tested three MBRs. Present results indicated that different kinds of homogeneous bacteria were numerically dominant in the three tested membrane bioreactors, where their numbers and ratios were varied with the duration of the driving periods.

IMPORTANCE

Although the conventional molecular-based culture independent methods have been used in place of traditional culture-based methods for microbiological research and expanded information of unculturable low-abundance bacterial groups, not all of them were always highly active in the environment and it was difficult to search for microorganisms among them which were highly active and play an important role in the environment. As numerical data of each bacteria might become an important index to know their activity in environment, we had created a novel culture-independent enumeration method for numerically dominant unidentified bacteria. Through the method, we found that different kinds of homogeneous bacteria were numerically dominant in the three tested membrane bioreactors, whose numbers were high enough to affect the performance of the reactor as a single strain. The method was found useful to specify and trace unknown numerically dominant bacterial groups in a culture independent manner.
Insights on early mutational events in SARS-CoV-2 virus reveal founder effects across geographical regions
Authors: Farkas Carlos , Fuentes-Villalobos Francisco , Garrido José Luis , Haigh Jody J , Barría María Inés
Published: April 2020

Here we aim to describe early mutational events across samples from publicly available SARS-CoV-2 sequences from the sequence read archive repository. Up until March 27, 2020, we downloaded 53 illumina datasets, mostly from China, USA (Washington DC) and Australia (Victoria). Of 30 high quality datasets, 27 datasets (90%) contain at least a single founder mutation and most of the variants are missense (over 63%). Five-point mutations with clonal (founder) effect were found in USA sequencing samples. Sequencing samples from USA in GenBank present this signature with 50% allele frequencies among samples. Australian mutation signatures were more diverse than USA samples, but still, clonal events were found in those samples. Mutations in the helicase and orf1a coding regions from SARS-CoV-2 were predominant, among others, suggesting that these proteins are prone to evolve by natural selection. Finally, we firmly urge that primer sets for diagnosis be carefully designed, since rapidly occurring variants would affect the performance of the reverse transcribed quantitative PCR (RT-qPCR) based viral testing.
Proteogenomics analysis of non-coding region encoded peptides in normal tissues and five cancer types
Authors: Xiang Rong , Ma Leyao , Yang Mingyu , Zheng Zetian , Chen Xiaofang , Jia Fujian , Xie Fanfan , Li Fuqiang , Wu Kui , Zhu Yafeng
Published: April 2020

Previous proteogenomics studies have identified peptides encoded by non-coding sequences such as pseudogenes and long non-coding RNAs (lncRNAs) in healthy human tissues as well as in cancers. However, these studies are either limited to analyze only healthy or cancerous tissues, lacking direct comparison between them. In this study, we used an established proteogenomics analysis workflow to analyze proteomics data from 926 cancer samples of five cancer types and 31 different healthy human tissues. We observed the protein level expression of pseudogenes can be classified as ubiquitous or lineage expression. The ubiquitously translated pseudogenes are homologous to house-keeping genes. Our results suggest there is common mechanism underlying the translation of pseudogenes in both normal and tumors. Moreover, we discovered several translated non-coding genes such asDGCR5andRHOXF1P3that were up-regulated in tumors compared to normal. These translated pseudogenes imply the biological function of pseudogenes extends to protein level yet to be studied. Further, from the non-coding region encoded peptides specifically detected in tumors we have predicted a large number of potential neoantigens which can be developed as cancer vaccine.
In vivovisual screen for dopaminergicRab ↔ LRRK2-G2019Sinteractions inDrosophiladiscriminatesRab10fromRab3
Authors: Petridi Stavroula , Middleton C. Adam , Ugbode Chris , Fellgett Alison , Covill Laura , Elliott Christopher J. H.
Published: April 2020

LRRK2 mutations cause Parkinson’s, but the molecular link from increased kinase activity to pathological neurodegeneration remains undetermined. Previousin vitroassays indicate that LRRK2 substrates include at least 8 Rab GTPases. We have now examined this hypothesisin vivoin a functional, electroretinogram screen, expressing eachRabwith/withoutLRRK2-G2019Sin selectedDrosophiladopaminergic neurons. Our screen discriminated Rab10 from Rab3. The strongest Rab/LRRK2-G2019S interaction is with Rab10; the weakest with Rab3. Rab10 is expressed in a different set of dopaminergic neurons from Rab3. Thus, anatomical and physiological patterns of Rab10 are related. We conclude that Rab10 is a valid substrate of LRRK2 in dopaminergic neuronsin vivo. We propose that variations inRabexpression contribute to differences in the rate of neurodegeneration recorded in different dopaminergic nuclei in Parkinson’s.
Repurposing a digital kitchen scale for neuroscience research: a complete hardware and software cookbook for PASTA
Authors: Virag D , Homolak J , Kodvanj I , Babic Perhoc A , Knezovic A , Osmanovic Barilar J , Salkovic-Petrisic M
Published: April 2020

Widely available low-cost electronics encourage the development of open-source tools for neuroscientific research. In recent years, many neuroscientists recognized the open science movement for its potential to stimulate and encourage science that is less focused on money, and more on robustness, validity, questioning and understanding. Here, we wanted to contribute to this global community by creating a research platform based on a common digital kitchen scale. This everyday ordinary kitchen tool is sometimes used in neuroscience research in various ways; however, its use is limited by sampling rate and inability to store and analyze data. To tackle this problem we developed a Platform for Auditory STArtle or PASTA. This robust and simple platform enables users to obtain data from kitchen scale load cells at a high sampling rate, store it and analyze it. Here, we used it to analyze acoustic startle and prepulse inhibition sensorimotor gating in rats treated intracerebroventricularly with streptozotocin, but the system can be easily modified and upgraded for other purposes. In accordance with open science principles, we shared complete hardware design with instructions. Furthermore, we also disclose our software codes written for PASTA data acquisition (C++, Arduino) and acoustic startle experimental protocol (Python) and analysis (R-based Awesome Toolbox for PASTA, ratPASTA R package). To further encourage the development of our PASTA platform we demonstrate its sensitivity by using PASTA-gathered data to extract breathing patterns during rat freezing behavior in our experimental protocol.
STAT1 dissociates adipose tissue inflammation from insulin sensitivity in obesity
Authors: Cox Aaron R. , Chernis Natasha , Bader David A. , Saha Pradip K , Masschelin Peter M. , Felix Jessica , Lian Zeqin , Putluri Vasanta , Rajapakshe Kimal , Kim Kang Ho , Villareal Dennis T. , Armamento-Villareal Reina , Wu Huaizhu , Coarfa Cristian , Putluri Nagireddy , Hartig Sean M
Published: April 2020

Obesity fosters low-grade inflammation in white adipose tissue (WAT) that may contribute to the insulin resistance that characterizes type 2 diabetes mellitus (T2DM). However, the causal relationship of these events remains unclear. The established dominance of signal transducer and activator of transcription 1 (STAT1) function in the immune response suggests an obligate link between inflammation and the co-morbidities of obesity. To this end, we sought to determine how STAT1 activity in white adipocytes affects insulin sensitivity. STAT1 expression in WAT inversely correlated with fasting plasma glucose in both obese mice and humans. Metabolomic and gene expression profiling established STAT1 deletion in adipocytes (STAT1 fKO) enhanced mitochondrial function and accelerated TCA cycle flux coupled with subcutaneous WAT hyperplasia. STAT1 fKO reduced WAT inflammation, but insulin resistance persisted in obese mice. Rather, elimination of type I cytokine interferon gamma (IFNγ) activity enhanced insulin sensitivity in diet-induced obesity. Our findings reveal a permissive mechanism that bridges WAT inflammation to whole-body insulin sensitivity.
Perfusion bioreactor culture of adipose-derived stromal cells on decellularized adipose tissue scaffolds enhancesin vivoregeneration
Authors: Y. Han Tim Tian , E. Flynn Lauren
Published: April 2020

Adipose tissue engineering holds promise to address the unmet need in plastic and reconstructive surgery for strategies that promote the stable and predictable regeneration of adipose tissue for volume augmentation applications. Previous studies have demonstrated that decellularized adipose tissue (DAT) scaffolds can provide a pro-adipogenic microenvironment, and that seeding with adipose-derived stromal cells (ASCs) can enhancein vivoangiogenesis and adipogenesis within DAT implants. Recognizing that bioreactor systems can promote cell expansion and infiltration on tissue-engineered scaffolds, this study evaluated the effects of culturing human ASCs on DAT scaffolds within a perfusion bioreactor. Using this system, the impact of both shear stress stimulation and hypoxic preconditioning were exploredin vitroandin vivo. Initial studies compared the effects of 14 days of culture within the perfusion bioreactor under 2% O2or ~20% O2on human ASC expansion and hypoxia inducible factor 1 alpha (HIF-1α) expressionin vitrorelative to static cultured controls. The findings indicated that culturing within the bioreactor under 2% O2significantly increased ASC proliferation on the DAT, with a higher cell density observed in the scaffold periphery. HIF-1α expression was significantly higher when the scaffolds were cultured under 2% O2. Subsequent characterization in a subcutaneous implant model in athymic nude mice revealed thatin vivoangiogenesis and adipogenesis were markedly enhanced when the ASCs were cultured on the DAT within the perfusion bioreactor under 2% O2for 14 days prior to implantation relative to the other culture conditions, as well as additional freshly-seeded and unseeded DAT control groups. Overall, dynamic culture within the perfusion bioreactor system under hypoxia represents a promising approach for preconditioning ASCs on DAT scaffolds to enhance their capacity to stimulate blood vessel formation and infiltration, as well as host-derived adipose tissue regeneration.
Heme-Sensing Pathway Modulates Susceptibility of Poor Prognosis B-Lineage Acute Leukemia to BH3-Mimetics
Authors: Smith Kaitlyn H. , Budhraja Amit , Lynch John , Roberts Kathryn , Panetta John C. , Connelly Jon P. , Turnis Meghan E. , Pruett-Miller Shondra M. , Schuetz John D. , Mullighan Charles G. , Opferman Joseph T.
Published: April 2020

Anti-apoptoticMCL1is one of the most frequently amplified genes in human cancers and elevated expression confers resistance to many therapeutics including the BH3-mimetic agents ABT-199 and ABT-263. The anti-malarial, dihydroartemisinin (DHA) translationally represses MCL-1 and synergizes with BH3-mimetics. To explore how DHA represses MCL-1, a genome-wide CRISPR screen identified that loss of genes in the heme synthesis pathway renders mouse BCR-ABL+B-ALL cells resistant to DHA-induced death. Mechanistically, DHA disrupts the interaction between heme and the eIF2α kinase heme regulated inhibitor (HRI) triggering the integrated stress response. Genetic ablation ofEif2ak1, which encodes HRI, blocks MCL-1 repression in response to DHA treatment and represses the synergistic killing of DHA and BH3-mimetics compared to wild-type leukemia. Furthermore, BTdCPU, a small-molecule activator of HRI, similarly triggers MCL-1 repression and synergizes with BH3-mimetics in mouse and human leukemia including both Ph+and Ph-like B-ALL. Lastly, combinatorial treatment of leukemia bearing mice with both BTdCPU and a BH3-mimetic extended survival and repressed MCL-1in vivo. These findings reveal for the first time that the HRI-dependent cellular heme-sensing pathway can modulate apoptosis in leukemic cells by repressing MCL-1 and increasing their responsiveness to BH3-mimetics. This signaling pathway could represent a generalizable mechanism for repressing MCL-1 expression in malignant cells and sensitizing them to available therapeutics.
A Computational Approach to Design Potential siRNA Molecules as a Prospective Tool for Silencing Nucleocapsid Phosphoprotein and Surface Glycoprotein Gene of SARS-CoV-2
Authors: Chowdhury Umar Faruq , Shohan Mohammad Umer Sharif , Hoque Kazi Injamamul , Beg Mirza Ashikul , Siam Mohammad Kawsar Sharif , Moni Mohammad Ali
Published: April 2020

An outbreak, caused by a RNA virus, SARS-CoV-2 named COVID-19 has become pandemic with a magnitude which is daunting to all public health institutions in the absence of specific antiviral treatment. Surface glycoprotein and nucleocapsid phosphoprotein are two important proteins of this virus facilitating its entry into host cell and genome replication. Small interfering RNA (siRNA) is a prospective tool of the RNA interference (RNAi) pathway for the control of human viral infections by suppressing viral gene expression through hybridization and neutralization of target complementary mRNA. So, in this study, the power of RNA interference technology was harnessed to develop siRNA molecules against specific target genes namely, nucleocapsid phosphoprotein gene and surface glycoprotein gene. Conserved sequence from 139 SARS-CoV-2 strains from around the globe was collected to construct 78 siRNA that can inactivate nucleocapsid phosphoprotein and surface glycoprotein genes. Finally, based on GC content, free energy of folding, free energy of binding, melting temperature and efficacy prediction process 8 siRNA molecules were selected which are proposed to exerts the best action. These predicted siRNAs should effectively silence the genes of SARS-CoV-2 during siRNA mediated treatment assisting in the response against SARS-CoV-2
Holobiont Evolution: Population Theory for the Hologenome
Authors: Roughgarden Joan
Published: April 2020

This article develops mathematical theory for the population dynamics of microbiomes with their hosts and for holobiont evolution caused by holobiont selection. The objective is to account for the formation of microbiome-host integration.

Microbial population-dynamic parameters must mesh with the host’s for coexistence.

A horizontally transmitted microbiome is a genetic system with “collective inheritance”. The microbial source pool in the environment corresponds to the gamete pool for nuclear genes. Poisson sampling of the microbial source pool corresponds to binomial sampling of the gamete pool. However, holobiont selection on the microbiome does not lead to a counterpart of the Hardy-Weinberg Law nor to directional selection that always fixes microbial genes conferring the highest holobiont fitness.

A microbe might strike an optimal fitness balance between lowering its within-host fitness while increasing holobiont fitness. Such microbes are replaced by otherwise identical microbes that contribute nothing to holobiont fitness. This replacement can be reversed by hosts that initiate immune responses to non-helpful microbes. This discrimination leads to microbial species sorting. Host-orchestrated species sorting (HOSS) followed by microbial competition, rather than co-evolution or multi-level selection, is predicted to be the cause of microbiome-host integration.