bluuebunny/crossref_metadata_2025 huggingface dataset:
Luteolin Suppresses Sepsis-Induced Cold-Inducible RNA-Binding Protein Production and Lung Injury in Neonatal Mice
Authors: Zhang Yuanyuan , Zhang Jia , Ren Yifan , Li Teng , Bi Jianbin , Du Zhaoqing , Wu Rongqian
Published: July 2020

Neonatal sepsis is a life-threatening inflammatory condition. Extracellular cold-inducible RNA-binding protein (CIRP), a proinflammatory mediator, plays a critical role in the pathogenesis of sepsis-induced lung injury in neonates. Luteolin, a polyphenolic flavonoid, has potent anti-inflammatory properties. However, the effects of luteolin on CIRP production and neonatal sepsis-induced lung injury remained unknown. We therefore hypothesize that treatment with luteolin suppresses CIRP production and attenuates lung injury in neonatal sepsis. To study this, sepsis was induced in C57BL/6J mouse pups (5–7 days) by intraperitoneal cecal slurry injection (CSI). One hour after CSI, luteolin (10 mg/kg body weight) or vehicle (normal saline) was administered through intraperitoneal injection. CIRP mRNA and protein were determined and lung injury was assessed at 10 h after CSI. Our results showed that administration of luteolin decreased CIRP mRNA and protein, improved lung architecture, reduced lung edema, and apoptosis after CSI. To examine the direct effect of luteolin on CIRP production, peritoneal macrophages were isolated from neonatal mice and stimulated with 100 ng/mL LPS with or without the presence of luteolin. The result indicates that luteolin directly inhibited LPS-induced CIRP production in neonatal macrophages. In addition, luteolin also downregulated hypoxia-inducible factor-1α (HIF-1α) and NOD-like receptor 3 (NLRP3) expression in septic neonates and in LPS-stimulated neonatal macrophages. In conclusion, administration of luteolin suppresses CIRP production and attenuates lung injury in neonatal sepsis. The beneficial effect of luteolin may be related to downregulation of HIF-1α and NLRP3 expression in neonatal macrophages. Luteolin may be developed as an adjunctive therapy for neonatal sepsis.
Risk Factors Associated With Early and Late Posttraumatic Multiorgan Failure: An Analysis From RETRAUCI
Authors: Barea-Mendoza Jesús A. , Chico-Fernández Mario , Molina-Díaz Ismael , Moreno-Muñoz Gerard , Toboso-Casado José M. , Viña-Soria Lucía , Matachana-Martínez María , Freire-Aragón María D. , Pérez-Bárcena Jon , Llompart-Pou Juan A.
Published: July 2020

Objective:

To analyze factors associated with the development of early and late multiorgan failure (MOF) in trauma patients admitted to the intensive care unit (ICU).

Methods:

Spanish Trauma ICU Registry (RETRAUCI). Data collected from 52 trauma ICU between March 2015 and December 2019. We analyzed the incidence, outcomes, and the risk factors associated with early (< 72 h) or late (beyond 72 h) MOF in trauma ICU patients. Multiple logistic regression analysis was performed to analyze associated factors.

Results:

After excluding patients with incomplete data, 9,598 trauma ICU patients constituted the study population. Up to 965 patients (10.1%) presented with MOF, distributed by early MOF in 780 patients (8.1%) and late MOF in 185 patients (1.9%). The multivariate analysis showed that early MOF was associated with: ISS ≥ 16 (OR 2.80), hemodynamic instability (OR from 2.03 to 43.05), trauma-associated coagulopathy (OR 2.32), and acute kidney injury (OR 4.10). Late MOF was associated with: age > 65 years (OR 1.52), hemodynamic instability (OR from 1.92 to 9.94), acute kidney injury (OR 4.22), and nosocomial infection (OR 17.23). MOF was closely related to mortality (crude OR (95% CI) 4.77 (4.22–5.40)).

Conclusions:

Multiorgan failure was recorded in 10% of trauma ICU patients, with early MOF being the predominant form. Early and late MOF forms were associated with different risk factors, suggesting different pathophysiological pathways. Early MOF was associated with higher severity of injury and severe bleeding-related complications and late MOF with advanced age and nosocomial infection.
Breast Implant-associated Anaplastic Large Cell Lymphoma Incidence
Authors: Nelson Jonas A. , Dabic Stefan , Mehrara Babak J. , Cordeiro Peter G. , Disa Joseph J. , Pusic Andrea L. , Matros Evan , Dayan Joseph H. , Allen Robert J. , Coriddi Michelle , Polanco Thais O. , Shamsunder Meghana G. , Wiser Itay , Morrow Monica , Dogan Ahmet , Cavalli Michele R. , Encarnacion Elizabeth , Lee Meghan E. , McCarthy Colleen M.
Published: July 2020

Objective:

This study sought to estimate the incidence and incidence rate of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) at a high-volume single institution, which enables vigorous long-term follow-up and implant tracking for more accurate estimates.

Summary Background Data:

The reported incidence of BIA-ALCL is highly variable, ranging from 1 in 355 to 1 in 30,000 patients, demonstrating a need for more accurate estimates.

Methods:

All patients who underwent implant-based breast reconstruction from 1991 to 2017 were retrospectively identified. The incidence and incidence rate of BIA-ALCL were estimated per patient and per implant. A time-to-event analysis was performed using the Kaplan–Meier estimator and life table.

Results:

During the 26-year study period, 9373 patients underwent reconstruction with 16,065 implants, of which 9589 (59.7%) were textured. Eleven patients were diagnosed with BIA-ALCL, all of whom had a history of textured implants. The overall incidence of BIA-ALCL was 1.79 per 1000 patients (1 in 559) with textured implants and 1.15 per 1000 textured implants (1 in 871), with a median time to diagnosis of 10.3 years (range, 6.4–15.5 yrs). Time-to-event analysis demonstrated a BIA-ALCL cumulative incidence of 0 at up to 6 years, increasing to 4.4 per 1000 patients at 10 to 12 years and 9.4 per 1000 patients at 14 to 16 years, although a sensitivity analysis showed loss to follow-up may have skewed these estimates.

Conclusions:

BIA-ALCL incidence and incidence rates may be higher than previous epidemiological estimates, with incidence increasing over time, particularly in patients exposed to textured implants for longer than 10 years.
Development and Validation of an Image-based Deep Learning Algorithm for Detection of Synchronous Peritoneal Carcinomatosis in Colorectal Cancer
Authors: Yuan Zixu , Xu Tingyang , Cai Jian , Zhao Yebiao , Cao Wuteng , Fichera Alessandro , Liu Xiaoxia , Yao Jianhua , Wang Hui
Published: July 2020

Objective:

The aim of this study was to build a SVM classifier using ResNet-3D algorithm by artificial intelligence for prediction of synchronous PC.

Background:

Adequate detection and staging of PC from CRC remain difficult.

Methods:

The primary tumors in synchronous PC were delineated on preoperative contrast-enhanced computed tomography (CT) images. The features of adjacent peritoneum were extracted to build a ResNet3D + SVM classifier. The performance of ResNet3D + SVM classifier was evaluated in the test set and was compared to routine CT which was evaluated by radiologists.

Results:

The training set consisted of 19,814 images from 54 patients with PC and 76 patients without PC. The test set consisted of 7837 images from 40 test patients. The ResNet-3D spent only 34 seconds to analyze the test images. To increase the accuracy of PC detection, we have built a SVM classifier by integrating ResNet-3D features with twelve PC-specific features (P < 0.05). The ResNet3D + SVM classifier showed accuracy of 94.11% with AUC of 0.922 (0.912–0.944), sensitivity of 93.75%, specificity of 94.44%, positive predictive value (PPV) of 93.75%, and negative predictive value (NPV) of 94.44% in the test set. The performance was superior to routine contrast-enhanced CT (AUC: 0.791).

Conclusions:

The ResNet3D + SVM classifier based on deep learning algorithm using ResNet-3D framework has shown great potential in prediction of synchronous PC in CRC.
Pathological Regression of Lymph Nodes Better Predicts Long-term Survival in Esophageal Cancer Patients Undergoing Neoadjuvant Chemotherapy Followed by Surgery
Authors: Hagi Takaomi , Makino Tomoki , Yamasaki Makoto , Yamashita Kotaro , Tanaka Koji , Saito Takuro , Takahashi Tsuyoshi , Kurokawa Yukinori , Motoori Masaaki , Kimura Yutaka , Nakajima Kiyokazu , Morii Eiichi , Eguchi Hidetoshi , Doki Yuichiro
Published: July 2020

Objective:

To evaluate pathological response to NAC in metastatic LNs, and assess its clinical prognostic significance in patients with EC.

Summary of Background Data:

The pathological response to preoperative treatment is commonly evaluated in the PT. However, LN metastases strongly correlate with systemic micro-metastases. Thus, pathological evaluation of LN response could more accurately predict prognosis in EC patients undergoing NAC before surgery.

Methods:

We enrolled 371 consecutive patients who underwent triplet NAC followed by surgery for EC between January 2010 and December 2016. Pathological LN regression grade was defined by the proportion of viable tumor area within the whole tumor bed area for all metastatic LNs: grade I, >50%; II, 10%–50%; III, <10%; and IV, 0%. We analyzed the correlation of grade with clinico-pathological parameters.

Results:

Among 319 patients with clinically positive LNs, pathological LN regression grades were I/II/III/IV in 115/51/58/95 patients, and 191 patients (59.9%) showed discordance between the PT and LN pathological regression grades. LN regression grade significantly correlated with cN positive number, ypTNM, lymphovascular invasion, and clinical/pathological PT response. Multivariate analysis for recurrence-free survival revealed that LN regression grade [hazard ratio (HR) = 2.25, P < 0.001], ypT (HR = 1.65, P = 0.005), and ypT (HR = 1.62, P = 0.004) were independent prognostic factors, but not pathological PT regression grade (P = 0.67).

Conclusions:

Compared to PT response, pathological LN response better predicted long-term survival in EC patients who received NAC plus curative surgery.
Relation of Gastric Volume With Weight Loss After Sleeve Gastrectomy: Results of a Prospective Analysis
Authors: Pilone Vincenzo , Tramontano Salvatore , Cutolo Carmen , Griguolo Giulia , Di Spirito Federica , Pagano Antonio M. , Sbordone Ludovico
Published: July 2020

Background:

Postoperative sleeve volume (SV) is a key factor in evaluating the results of laparoscopic sleeve gastrectomy (LSG). An objective measurement of SV was obtained with 3-dimensional computed tomographic (3DCT) reconstruction. Several studies have compared SV with percent excess weight loss (%EWL), identifying an inverse relationship. We hypothesized that gastric capacity is one of the factors responsible for weight loss after LSG.

Objectives:

Outcomes of the study were the analysis of the inverse correlation between SV and weight loss (%EWL and body mass index) at the 12-month follow-up, and evaluation of SV in the group with %EWL >50%. In addition, the failure rate was quantified in the SV >180 mL group.

Materials and Methods:

This is a prospective study with the collection of data. All patients who received LSG from January to December 2017 were evaluated. Computed tomography was performed on the upper abdomen at 12 months postoperatively to measure the SV using a standardized technique involving gastric distension.

Results:

A total of 42 patients were considered for 3DCT evaluation at the 12-month follow-up. A significant linear inverse relation was reported between SV and %EWL (P<0.05); a similar trend, without significant results, was reported for body mass index loss. The entire cohort was subdivided according to %EWL. A %EWL<50% presented a significantly higher mean SV (P<0.01) than %EWL >50%. SV >180 mL was powerful in predicting abnormal gastric distension. Over this value, %EWL was lower than that in the remaining group (P<0.05, 31.9% vs. 51.8%).

Conclusions:

Our results confirmed a direct relation between SV and %EWL. Objective evaluation of gastric compliance obtained with 3DCT should be used intensively for LSG.
Treatment with AAV1-Rheb(S16H) provides neuroprotection in a mouse model of photothrombosis-induced ischemic stroke
Authors: Yoon Dongyeong , Jeon Min-Tae , Dong Woon Kim , Kim Sang Ryong
Published: July 2020

We recently reported that upregulation of the constitutively active ras homolog enriched in brain [Rheb(S16H)], which induces the activation of the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway, can protect adult neurons, mediated by the induction of neurotrophic factors, such as brain-derived neurotrophic factor (BDNF), in animal models of neurodegenerative diseases. Here we show that neuronal transduction of Rheb(S16H) using adeno-associated virus serotype 1 provides neuroprotection in a mouse model of photothrombosis-induced ischemic stroke. Rheb(S16H)-expressing neurons exhibited neurotrophic effects, such as mTORC1 activation, increases in neuronal size, and BDNF production, in mouse cerebral cortex. Moreover, the upregulation of neuronal Rheb(S16H) significantly attenuated ischemic damage and behavioral impairments as compared to untreated mice, suggesting that Rheb(S16H) upregulation in cortical neurons may be a useful strategy to treat ischemic stroke.
Visceral fat reduction and increase of intracellular fluid in weight loss participants on antihypertension medication
Authors: Dembrowski Gerald C. , Barnes Jessica W.
Published: July 2020

Objectives

Complex physiological interactions between hypertension and obesity contribute to and perpetuate a heightened morbidity and mortality. With the prevalence of both hypertension and obesity reaching epidemic proportions, we asked whether antihypertensive medications affect the ability of participants to achieve the same level of body composition improvements as other participants in a comprehensive weight loss program focused on reduction of visceral adipose tissue.

Methods

Data was analyzed from 2200 subjects completing a commercially available, expert supervised weight loss program including ~6 weeks of a proprietary, nutritionally complete, very low-calorie diet (VLCD) followed by a ~3-week structured transition back to a normal dietary intake. Overall, 33% of the subjects reported taking at least one prescription antihypertensive medication.

Results

Our data show participants in both groups (± antihypertensive drugs) achieved clinically relevant and statistically significant improvements in standard measures of weight loss and endpoints directly related to inflammation and hypertension.

Conclusion

A nonpharmacologic, nonsurgical VLCD-based weight loss and metabolic health program is capable of producing clinically meaningful improvements in body composition and physiological endpoints, including those linked to hypertension, cardiovascular disease and inflammation, and is as equally effective for adults taking prescription antihypertensives as it is for those participants who are not.
Coronary microvascular disease: current concepts of pathophysiology, diagnosis and management
Authors: Sinha Aish , Rahman Haseeb , Perera Divaka
Published: July 2020

Coronary microvascular disease (CMD) is present in 30% of patients with angina and is associated with increased morbidity and mortality. We now have an improved understanding of the pathophysiology of CMD and the invasive and noninvasive tests that can be used to make the diagnosis. Recent studies have shown that management of CMD guided by physiological testing yields better results than empirical treatment. Despite major advances in diagnosing and stratifying this condition, therapeutic strategies remain limited and poorly defined. This review article discusses recent advances in understanding the pathophysiology of CMD, the modalities that are available to diagnose it clinically, current management options and a look at what is in store for the future.
An unusual presentation of cutaneous histoplasmosis as a recurrent solitary and spontaneously healing lesion in an immunocompetent patient
Authors: Muldoon Jessica L. , Wysozan Timothy R. , Toubin Yulianna , Relich Ryan F. , Davis Thomas E. , Zhang Chen , Alomari Ahmed K.
Published: July 2020

Infection with Histoplasma capsulatum typically manifests as a self-limiting pulmonary disease in immunocompetent patients. Systemic symptoms such as cutaneous lesions are associated with immunodeficient states. Our patient was an immunocompetent 68-year-old male who presented with a plaque on his left infraorbital area that was concerning for malignancy. Histological examination of the lesion revealed granulomatous inflammation and small yeast forms suggestive of H. capsulatum. The lesion resolved spontaneously and recurred 1 year later. On recurrence, histological examination again revealed yeast forms consistent with H. capsulatum. Serum and urine testing for H. capsulatum antigen were negative. Next-generation sequencing detected H. capsulatum, which supported the diagnosis of a cutaneous infection. The patient was prescribed and started treatment with itraconazole for 1 year after recurrence of the lesion, and he has not reported further disease recurrence to date. This case is unique because of the presentation of a primary cutaneous recurrent H. capsulatum lesion, and it demonstrated the utility of laboratory testing in its diagnosis.
COVID-19 in patients undergoing renal replacement therapy in Scotland: findings and experience from the Scottish Renal Registry
Authors: Bell Samira , Campbell Jacqueline , McDonald Jackie , O’Neill Martin , Watters Chrissie , Buck Katharine , Cousland Zoe , Findlay Mark , Lone Nazir I , Metcalfe Wendy , Methven Shona , Peel Robert , Almond Alison , Sanu Vinod , Spalding Elaine , Thomson Peter C , Mark Patrick B , Traynor Jamie P
Published: July 2020

Introduction

Infection with the severe acute respiratory coronavirus 2 (SARS-CoV-2) has led to a worldwide pandemic with coronavirus disease 2019 (COVID-19), the disease caused by SARS-CoV-2, overwhelming healthcare systems globally. Preliminary reports suggest a high incidence of infection and mortality with SARS-CoV-2 in patients receiving renal replacement therapy (RRT). The aims of this study are to report characteristics, rates and outcomes of all patients affected by infection with SARS-CoV-2 undergoing RRT in Scotland.

Methods

Study design was an observational cohort study. Data were linked between the Scottish Renal Registry, Health Protection Scotland and the Scottish Intensive Care Society Audit Group national data sets using a unique patient identifier (Community Health Index (CHI)) for each individual by the Public Health and Intelligence unit of Public Health, Scotland. Descriptive statistics and survival analyses were performed.

Results

During the period 1stMarch 2020 to 31stMay 2020, 110 patients receiving RRT tested positive for SARS-CoV-2 amounting to 2% of the prevalent RRT population. Of those affected, 87 were receiving haemodialysis or peritoneal dialysis and 24 had a renal transplant. Patients who tested positive were older and more likely to reside in more deprived postcodes. Mortality was high at 26.7% in the dialysis patients and 29.2% in the transplant patients.

Conclusion

The rate of detected SARS-CoV-2 in people receiving RRT in Scotland was relatively low but with a high mortality for those demonstrating infection. Although impossible to confirm, it appears that the measures taken within dialysis units coupled with the national shielding policy, have been effective in protecting this population from infection.
Recruitment of Older African Americans in Alzheimer’s Disease Clinical Trials Using A Community Education Approach
Authors: Shaw Ashley R. , Perales-Puchalt Jaime , Moore Todd , Weatherspoon Patricia , Robinson Melissa , Hill Carl V. , Vidoni Eric D.
Published: July 2020

African Americans are disproportionately affected by Alzheimer’s disease and related dementias (ADRD) and are two times more likely to develop ADRD compared to their White counterparts. Despite the higher prevalence of ADRD among older African Americans, recent estimates suggest research enrollment by those who identify as African American remains limited. The purpose of the study is to 1) explore how a culturally tailored community education program impacts clinical trial interest and enrollment in ADRD research studies and to 2) identify how applicable the African American community perceived the culturally tailored curriculum. Using a community-engaged research approach, we collaborated with predominately African American serving community-based organizations to support content development and delivery of Aging with Grace (AWG), a culturally tailored ADRD educational curriculum. A total of five AWG presentations were given to 66 attendees. Most attendees (67%) expressed interest in participating in clinical trials after attending AWG. Enrollment increased within an observational study (84%) and lifestyle prevention clinical trials (52%) from 2018 to 2019. Attendees (32%) also perceived an increase in ADRD knowledge from attending AWG and 89.1% believed more African Americans should participate in research. Our work demonstrates the effectiveness of a culturally tailored community education program to enhance knowledge, clinical trial interest, and recruitment into observational studies and lifestyle ADRD clinical trials among older African Americans. Education programs developed in partnership with the community can serve as bridge to research participation for under-represented minorities in clinical research. Future studies should assess long-term retention of knowledge and research readiness.
Evaluation of the microbial community structure of potable water samples from occupied and unoccupied buildings using16S rRNA amplicon sequencing
Authors: Smith Kimothy L , Shuman Howard A , Findeisen Douglas
Published: July 2020

We conducted two studies of water samples from buildings with normal occupancy and water usage compared to water from buildings that were unoccupied with little or no water usage due to the COVID-19 shutdown. Study 1 had 52 water samples obtainedad hocfrom buildings in four metropolitan locations in different states in the US and a range of building types. Study 2 had 36 water samples obtained from two buildings in one metropolitan location with matched water sample types. One of the buildings had been continuously occupied, and the other substantially vacant for approximately 3 months. All water samples were analyzed using 16S rRNA amplicon sequencing with a MinION from Oxford Nanopore Technologies. More than 127 genera of bacteria were identified, including genera with members that are known to include more than 50 putative frank and opportunistic pathogens. While specific results varied among sample locations, 16S rRNA amplicon abundance and the diversity of bacteria were higher in water samples from unoccupied buildings than normally occupied buildings as was the abundance of sequenced amplicons of genera known to include pathogenic bacterial members. In both studiesLegionellaamplicon abundance was relatively small compared to the abundance of the other bacteria in the samples. Indeed, when present, the relative abundance ofLegionellaamplicons was lower in samples from unoccupied buildings.Legionelladid not predominate in any of the water samples and were found, on average, in 9.6% of samples in Study 1 and 8.3% of samples in Study 2.

Synopsis

Comparison of microbial community composition in the plumbing of occupied and unoccupied buildings during the COVID-19 pandemic shutdown.
A systematic review and meta-analysis on the rate of human schistosomiasis reinfection
Authors: Zacharia Abdallah , Mushi Vivian , Makene Twilumba
Published: July 2020

Background

While praziquantel mass drug administration is currently the most widely used method in the control of human schistosomiasis, it does not prevent subsequent reinfection hence persistent transmission. Towards schistosomiasis elimination, understanding the reinfection rate is crucial in planning for the future interventions. However, there is scarcity information on the global schistosomiasis reinfection rate.

Objective

This systematic review and meta-analysis aimed at summarizing studies that estimated the human schistosomiasis reinfection rate.

Materials and methods

The protocol for this review was prepared to guide authors throughout the process. However, registration was not sought. Three data bases (PubMed, Hinari and Google Scholar) were thoroughly searched to retrieve original research articles presenting data on human schistosomiasis reinfection rate. Study quality and risk of bias was assessed based on Joanna Briggs Institute critical appraisal checklist. Meta-analysis was conducted using statistical R version 3.6.2 and R Studio using “meta” and “metafor” packages. Heterogeneity and publication bias of the studies were determined using Q – test and Egger’s regression test respectively. Random effect model was employed to estimate pooled reinfection rates.

Results

A total of 29 studies met inclusion criteria to be included in this review. All studies had at least satisfactory (5 – 9 scores) quality. The overal calculated and pooled schistosomiasis reinfection rates were 36.1% (±23.3%) and 33.2% (95% CI, 26.5 – 40.5%) respectively. For intestinal schistosomiasis, the calculated and pooled reinfection rates were 43.9% (±20.6%) and 43.4% (95% CI, 35.8 – 51.4%), and that for urogenital schistosomiasis were 17.6% (±10.8%) and 19.4% (95% CI, 12.3% – 29.2%) respectively. Results of subgroup analysis showed that, the type of Schistosoma species, participants age group, sample size and geographical area had influence on disparity variation in Schistosomiasis reinfection rate (p < 0.05).

Conclusion

Despite the control measures in place, the re-infection rate was still high, specifically on intestinal schistosomiasis as compared to urogenital schistosomiasis. Achieving 2030 sustainable development goal 3 on good health and wellbeing through schistosomiasis elimination and intensive programmatic strategies should be implemented. Among such strategies to be used at national level are repeated mass drug administration at least every six month, intensive snails control and health education.
De novodesign of modular and tunable allosteric biosensors
Authors: Quijano-Rubio Alfredo , Yeh Hsien-Wei , Park Jooyoung , Lee Hansol , Langan Robert A. , Boyken Scott E. , Lajoie Marc J. , Cao Longxing , Chow Cameron M. , Miranda Marcos C. , Wi Jimin , Hong Hyo Jeong , Stewart Lance , Oh Byung-Ha , Baker David
Published: July 2020

Naturally occurring allosteric protein switches have been repurposed for developing novel biosensors and reporters for cellular and clinical applications1, but the number of such switches is limited, and engineering them is often challenging as each is different. Here, we show that a very general class of allosteric protein-based biosensors can be created by inverting the flow of information throughde novodesigned protein switches in which binding of a peptide key triggers biological outputs of interest2. Using broadly applicable design principles, we allosterically couple binding of protein analytes of interest to the reconstitution of luciferase activity and a bioluminescent readout through the association of designed lock and key proteins. Because the sensor is based purely on thermodynamic coupling of analyte binding to switch activation, only one target binding domain is required, which simplifies sensor design and allows direct readout in solution. We demonstrate the modularity of this platform by creating biosensors that, with little optimization, sensitively detect the anti-apoptosis protein Bcl-2, the hIgG1 Fc domain, the Her2 receptor, and Botulinum neurotoxin B, as well as biosensors for cardiac Troponin I and an anti-Hepatitis B virus (HBV) antibody that achieve the sub-nanomolar sensitivity necessary to detect clinically relevant concentrations of these molecules. Given the current need for diagnostic tools for tracking COVID-193, we use the approach to design sensors of antibodies against SARS-CoV-2 protein epitopes and of the receptor-binding domain (RBD) of the SARS-CoV-2 Spike protein. The latter, which incorporates ade novodesigned RBD binder, has a limit of detection of 15pM with an up to seventeen fold increase in luminescence upon addition of RBD. The modularity and sensitivity of the platform should enable the rapid construction of sensors for a wide range of analytes and highlights the power ofde novoprotein design to create multi-state protein systems with new and useful functions.
Clerodendrum Chinensis Extracts;AeC and EeC Exerts Rapid Antihypertensive Effects in L-NAME Hypertensive Experimental Models
Authors: Odimegwu Joy I. , Okanlawon Tolulope F. , Noel Obumneme , Ishola Ismail
Published: July 2020

Background

The rise in occurrence of hypertension, a non-communicable disease and a major factor for chronic renal failure, cardiovascular disease, and stroke, which most times lead to sudden death is worrisome. Resistant hypertension is more common and may have no symptoms at all for months or years, but then can cause heart attack, stroke, and vision and kidney damage. Prevention and quick management of hypertension are therefore essential in reducing the risk of these debilitating ailments. Aqueous and ethanolic extracts of the leaves ofClerodendrum chinensis (AeCandEeC) are used by local communities of West Africa as medicine for rapid antihypertensive actions. We aim to discover the scientific basis for the use of the herb as medicine.

Methods

This work investigates the antihypertensive effects ofAeCandEeCin L-Arginine Methyl Ester Hydrochloride (L-NAME)-induced hypertensive rats Acetylcholine, L-Arginine and Sodium Nitroprusside were used as standards. All results were expressed as means ± standard error of mean. Differences were considered significant at p <0.05.

Results

Intravenous administration of the extracts caused a significant decrease in the Mean Arterial Blood Pressure (MABP) in a dose-dependent manner.AeCat 100mg/kg caused a significant decline in blood pressure in a dose-related manner. Likewise at 100mg/kg,EeCreduced MABP steadily from 103.9± 2.55 to 34.1± 0.95mmHg. The two extracts; possess significant antihypertensive properties.

Conclusions

Both extracts show significant antihypertensive effects and at high doses could lead to hypotension and so should be used with care. Further research is necessary to determine safe dosage forms.
Learning the Mental Health Impact of COVID-19 in the United States with Explainable Artificial Intelligence
Authors: Jha Indra Prakash , Awasthi Raghav , Kumar Ajit , Kumar Vibhor , Sethi Tavpritesh
Published: July 2020

Importance

COVID-19 pandemic has deeply affected the health, economic, and social fabric of nations. Identification of individual-level susceptibility factors may help people in identifying and managing their emotional, psychological, and social well-being.

Objective

This work is focused on learning a ranked list of factors that could indicate a predisposition to a mental disorder during the COVID pandemic.

Data Sources and Study design

In this study, We have used a survey of 17764 adults in the USA at different age groups, genders, and socioeconomic statuses.

Methods

Through initial statistical analysis followed by Bayesian Network inference, we have identified key factors affecting Mental health during the COVID pandemic. Integrating Bayesian networks with classical machine learning approaches lead to effective modeling of the level of mental health.

Results

Overall, females are more stressed than males, and people of age-group 18-29 are more vulnerable to anxiety than other age groups. Using the Bayesian Network Model, we found that people with chronic medical condition of mental illness are more prone to mental disorders during the COVID age. The new realities of working from home, home-schooling, and lack of communication with family/friends/neighbors induces mental pressure. Financial assistance from social security helps in reducing mental stress during COVID generated economic crises. Finally, using supervised ML models, we predicted the most mentally vulnerable people with ~80% accuracy.

Question

What factors could affect mental health, and how could this level be predicted using the same factors during the of COVID-19?

Finding

In this survey-data based study, multiple factors such as Social isolation, digital communication, working, and schooling from home, were identified as crucial factors of mental illness during Covid-19. Interestingly, behavioral changes such as wearing a mask and avoiding restaurants and public places were not found to be associated with mental health.

Meaning

Regular non-virtual communication with friends and family, healthy social life and social security are key factors and especially taking care of people with mental disease history is even more important.
Estimating predator functional responses using the times between prey captures
Authors: Coblentz Kyle E. , DeLong John P.
Published: July 2020

Predator functional responses, which describe how predator feeding rates change with prey densities, are a core component of predator-prey theory. Given their importance, ecologists have measured thousands of predator functional responses. However, most of these studies have used a single standard experimental method that is ill-suited to address many current, pressing questions regarding functional responses.

We derive a new experimental design and statistical analysis that quantifies the parameters of predator functional responses by using the time between a predator’s feeding events and can be used with individual predators requiring only one or a few trials. We examine the feasibility of this experimental method and analysis by using simulations to examine the ability of the statistical model to estimate the ‘true’ functional response parameters from simulated data. We also perform a proof-of-concept experiment estimating the functional responses of two individual jumping spiders feeding on midges.

Our simulations show that the statistical method is capable of reliably estimating functional response parameters under a wide range of parameter values and sample sizes. Our proof-of-concept experiment illustrates that the experimental design and statistical method provided reasonable estimates of functional response parameters and good fits to the data for individual jumping spiders using only a few trials per individual.

By virtue of the fewer number of trials required to measure a functional response, the method derived here promises to expand the questions that can be addressed using functional response experiments and the systems for which functional responses can be measured. For example, this method is well-poised to address questions such as intraspecific variation in predator functional response parameters and the role of predator and prey traits and abiotic conditions on shaping functional responses. We hope, therefore, that this time-between-captures method will refine our understanding of functional responses and thereby our understanding of predator-prey interactions more generally.
Optogenetic activation of spinal microglia triggers chronic pain in mice
Authors: Yi Min-Hee , Liu Yong U. , Umpierre Anthony D. , Chen Tingjun , Ying Yanlu , Dheer Aastha , Bosco Dale B , Dong Hailong , Wu Long-Jun
Published: July 2020

Spinal microglia are highly responsive to peripheral nerve injury and are known to be a key player in neuropathic pain. However, there has not been any direct evidence showing selective microglial activation in vivo is sufficient to induce chronic pain. Here we used optogenetic approaches in microglia to address this question employing CX3CR1creER/+: R26LSL-ReaChR/+transgenic mice, in which red-activated channelrhodopsin (ReaChR) is inducibly and specifically expressed in microglia. We found that activation of ReaChR by red light in spinal microglia evoked reliable inward currents and membrane depolarization. In vivo optogenetic activation of microglial ReaChR in the spinal cord triggered chronic pain hypersensitivity lasting for 5-7 days. In addition, activation of microglial ReaChR upregulated neuronal c-fos expression and enhanced C-fiber responses. Mechanistically, ReaChR activation led to a reactive microglial phenotype with increased IL-1β production. IL-1 receptor antagonist was able to reverse the pain hypersensitivity and neuronal hyperactivity induced by microglial ReaChR activation.

Therefore, our work demonstrates that optogenetic activation of spinal microglia is sufficient to trigger chronic pain phenotypes by increasing neuronal activity via IL-1 signaling.
Evolution and genomic signatures of spontaneous somatic mutation inDrosophilaintestinal stem cells
Authors: Riddiford Nick , Siudeja Katarzyna , van den Beek Marius , Boumard Benjamin , Bardin Allison J.
Published: July 2020

Spontaneous mutations can alter tissue dynamics and lead to cancer initiation. While large-scale sequencing projects have illustrated processes that influence somatic mutation and subsequent tumour evolution, the mutational dynamics operating in the very early stages of cancer development are currently not well understood. In order to explore mutational dynamics in the early stages of cancer evolution we exploited neoplasia arising spontaneously in theDrosophilaintestine. We analysed whole-genome sequencing data through the development of a dedicated bioinformatic pipeline to detect structural variants, single nucleotide variants, and indels. We found neoplasia formation to be driven largely through the inactivation ofNotchby structural variants, many of which involve highly complex genomic rearrangements. Strikingly, the genome-wide mutational burden of neoplasia - at six weeks of age - was found to be similar to that of several human cancers. Finally, we identified genomic features associated with spontaneous mutation and defined the evolutionary dynamics and mutational landscape operating within intestinal neoplasia over the short lifespan of the adult fly. Our findings provide unique insight into mutational dynamics operating over a short time scale in the genetic model system,Drosophila melanogaster.
The change pattern and significance of IgM and IgG in the progress of COVID-19 disease
Authors: Qin Xuzhen , Shen Jun , Dai Erhei , Li Haolong , Tang Guodong , Zhang Lixia , Hou Xin , Lu Minya , Wu Xian , Duan Simeng , Zhang Jingjia , Li Yongzhe
Published: July 2020

Background

To investigate the significance of IgM and IgG in the progress of COVID-19.

Method

A multicenter cross-sectional study conducted in suspected and confirmed patients from four hospitals of China and a cohort study to identify the change pattern and significance in the process of COVID-19 disease.

Results

A total of 571 patients were enrolled in the cross-sectional study, including 235 confirmed SARS-CoV-2 infection with 91.9% patients IgG positive and 92.3% IgM positive. 30 patients diagnosed with SARS-CoV-2 infection were enrolled in the cohort study for flowing-up in 20 days. The peak of IgM and IgG reached in 10th and 20 th day separately after symptom onset. The relationship between clinical classification and serological antibodies were analysed. The positive rate of COVID-19 IgG and IgM increased along with the clinical classification and the delay of treatment time.

Conclusion

We demonstrated the kinetics of IgM and IgG SARS-CoV-2 antibody in COVID-19 patients, which may contribute to explain the results of IgM and IgG SARS-CoV-2 antibody test and predict the prognosis of COVID-19.
Host transcriptional response to TB preventive therapy differentiates two sub-groups of IGRA-positive individuals
Authors: Broderick Claire , Cliff Jacqueline M , Lee Ji-Sook , Kaforou Myrsini , Moore David AJ
Published: July 2020

We investigated the longitudinal whole blood transcriptional profile responses to tuberculosis preventive therapy of 18 IGRA-positive tuberculosis contacts and IGRA-negative, tuberculosis-unexposed healthy controls.

Longitudinal unsupervised clustering analysis with a subset of 474 most variable genes in antigen-stimulated blood separated the IGRA+ participants into two distinct subgroups, one of which clustered with the IGRA-negative controls. 117 probes were significantly differentially expressed over time between the two cluster groups, many of them associated with immunological pathways important in mycobacterial control.

We contend that the differential host RNA response reflects lack ofM.tuberculosis(Mtb) viability in the group that clustered with the IGRA-unexposed healthy controls, andMtbviability in the group (1/3 of IGRA-positives) that clustered away.

Gene expression patterns in the blood of IGRA+ individuals emerging during the course of PT, which reflectMtbviability, could have major implications in the identification of risk of progression, treatment stratification and biomarker development.
Ase1 domains dynamically slow anaphase spindle elongation and recruit Bim1 to the midzone
Authors: Thomas Ezekiel C. , Ismael Amber , Moore Jeffrey K.
Published: July 2020

How cells regulate microtubule crosslinking activity to control the rate and duration of spindle elongation during anaphase is poorly understood. In this study, we test the hypothesis that PRC1/Ase1 proteins use distinct microtubule-binding domains to control spindle elongation rate. Using budding-yeast Ase1, we identify unique contributions for the spectrin and carboxy-terminal domains during different phases of spindle elongation. We show that the spectrin domain uses conserved, basic residues to promote the recruitment of Ase1 to the midzone before anaphase onset and slow spindle elongation during early anaphase. In contrast, a partial Ase1 carboxy-terminal truncation fails to form a stable midzone in late anaphase, produces faster elongation rates after early anaphase, and exhibits frequent spindle collapses. We find that the carboxy-terminal domain interacts with the plus-end tracking protein EB1/Bim1 and recruits Bim1 to the midzone to maintain midzone length. Overall, our results suggest that the Ase1 domains provide cells with a modular system to tune midzone activity and control elongation rates.
Functional requirements of intentional control over the integrated cortico-thalamo-cortical and basal ganglia systems using neural computations
Authors: Naze Sébastien , Kozloski James
Published: July 2020

Large scale brain models encompassing cortico-cortical, thalamo-cortical and basal ganglia processing are fundamental to understand the brain as an integrated system in healthy and disease conditions but are complex to analyze and interpret. Neuronal processes are typically segmented by region and modality in order to explain an experimental observation at a given scale, but integrative frameworks linking scales and modalities are scarce. Here, we present a set of functional requirements used to evaluate the recently developed large-scale brain model against a learning task involving coordinated learning between cortical and sub-cortical systems. The original Information Based Exchange Brain model (IBEx) is decomposed into functionally relevant subsystems, and each subsystem is analyzed and tuned independently and with regard to its relevant functional requirements. Intermediate conclusions are made for each subsystems according to the constraints imposed by these requirements. Subsystems are then re-introduced into the global framework. The relationship between the global framework and phenotypes associated with Huntington’s disease is then discussed and the framework considered in the context of other state-of-the-art integrative brain models.
Brain Network Reconfiguration for Narrative and Argumentative Thought
Authors: Xu Yangwen , Vignali Lorenzo , Collignon Olivier , Crepaldi Davide , Bottini Roberto
Published: July 2020

Our brain constructs reality through narrative and argumentative thought. Some hypotheses argue that these two modes of cognitive functioning are irreducible, reflecting distinct mental operations underlain by separate neural bases; Others ascribe both to a unitary neural system dedicated to long-timescale information. We addressed this question by employing inter-subject measures to investigate the stimulus-induced neural responses when participants were listening to narrative and argumentative texts during fMRI. We found that following both kinds of texts enhanced functional couplings within the frontoparietal control system. However, while a narrative specifically implicated the default mode system, an argument specifically induced synchronization between the intraparietal sulcus in the frontoparietal control system and multiple perisylvian areas in the language system. Our findings reconcile the two hypotheses by revealing commonalities and differences between the narrative and the argumentative brain networks, showing how diverse mental activities arise from the segregation and integration of the existing brain systems.
Coronavirus surveillance in Congo basin wildlife detects RNA of multiple species circulating in bats and rodents
Authors: Kumakamba Charles , Niama Fabien R. , Muyembe Francisca , Mombouli Jean-Vivien , Kingebeni Placide Mbala , Nina Rock Aime , Lukusa Ipos Ngay , Bounga Gerard , N’Kawa Frida , Nkoua Cynthia Goma , Losoma Joseph Atibu , Mulembakani Prime , Makuwa Maria , Tamufe Ubald , Gillis Amethyst , LeBreton Matthew , Olson Sarah H. , Cameron Kenneth , Reed Patricia , Ondzie Alain , Tremeau-Bravard Alex , Smith Brett R. , Pante Jasmine , Schneider Bradley S. , McIver David J. , Ayukekbong James A. , Hoff Nicole A. , Rimoin Anne W. , Laudisoit Anne , Monagin Corina , Goldstein Tracey , Joly Damien O. , Saylors Karen , Wolfe Nathan D. , Rubin Edward M. , MPassi Romain Bagamboula , Tamfum Jean J. Muyembe , Lange Christian E.
Published: July 2020

Coronaviruses play an important role as pathogens of humans and animals, and the emergence of epidemics like SARS, MERS and COVID-19 is closely linked to zoonotic transmission events primarily from wild animals. Bats have been found to be an important source of coronaviruses with some of them having the potential to infect humans, with other animals serving as intermediate or alternate hosts or reservoirs. Host diversity may be an important contributor to viral diversity and thus the potential for zoonotic events. To date, limited research has been done in Africa on this topic, in particular in the Congo Basin despite frequent contact between humans and wildlife in this region. We sampled and, using consensus coronavirus PCR-primers, tested 3,561 wild animals for coronavirus RNA. The focus was on bats (38%), rodents (38%), and primates (23%) that posed an elevated risk for contact with people, and we found coronavirus RNA in 121 animals, of which all but two were bats. Depending on the taxonomic family, bats were significantly more likely to be coronavirus RNA-positive when sampled either in the wet (PteropodidaeandRhinolophidae) or dry season (Hipposideridae, Miniopteridae, Molossidae, andVespertilionidae). The detected RNA sequences correspond to 15 Alpha- and 6 Beta-coronaviruses, with some of them being very similar (>95% nucleotide identities) to known coronaviruses and others being more unique and potentially representing novel viruses. In seven of the bats, we detected RNA most closely related to sequences of the human common cold coronaviruses 229E or NL63 (>80% nucleotide identities). The findings highlight the potential for coronavirus spillover, especially in regions with a high diversity of bats and close human contact, and reinforces the need for ongoing surveillance.