bluuebunny/crossref_metadata_2025 huggingface dataset:
Growth performance and nutrient digestibility of growing and finishing pigs fed multienzyme-supplemented low-energy and -amino acid diets
Authors: Jerez-Bogota Kevin , Sánchez Cristian , Ibagon Jimena , Jlali Maamer , Cozannet Pierre , Preynat Aurélie , Woyengo Tofuko A
Published: April 2020

A study was conducted to determine the effects of supplementing corn–soybean meal-based diets with a multienzyme on growth performance, bone mineralization, apparent ileal digestibility (AID) and apparent total tract digestibility (ATTD) of nutrients of growing pigs. A total of 276 pigs (body weight [BW] = 33.99 ± 4.3 kg) were housed by sex in 45 pens of 6 or 7 pigs and fed 5 diets (9 pens/diet) in a randomized complete block design. Diets were positive control (PC); and negative control 1 (NC1) or negative control 2 (NC2) without or with multienzyme. The multienzyme used supplied at least 1,800, 1,244, 6,600, and 1,000 units of xylanase, β-glucanase, arabinofuranosidase, and phytase per kilogram of diet, respectively. The PC diet was adequate in all nutrients according to NRC recommendations and had greater digestible P content than NC1 or NC2 diet by 0.134 percentage points. The PC diet had greater net energy (NE) and standardized ileal digestible amino acids (AA) content than NC1 diet by 3%, and than NC2 diet by 5%. The diets were fed in 4 phases based on BW: Phase 1: 34–50 kg; Phase 2: 50–75 kg; Phase 3: 75–100 kg; and Phase 4: 100–120 kg. Nutrient digestibility and bone mineralization were determined at the end of Phase 1. Overall (34–120 kg BW), pigs fed the PC and NC1 diets did not differ in average daily gain (ADG) and average daily feed intake. Pigs fed NC2 diet had lower (P < 0.05) ADG and gain-to-feed ratio (G:F) than those fed PC diet. Pigs fed PC diet had greater (P < 0.05) bone ash content and ATTD of P than those fed NC1 diet. The ATTD of GE for PC diet was greater (P < 0.05) than that for NC2 diet, and tended to be greater (P < 0.10) than that for NC1 diet. Multienzyme interacted (P < 0.05) with negative control diet type on overall ADG and AID of GE such that multienzyme did not affect overall ADG and AID of GE for the NC1 diet, but increased (P < 0.05) overall ADG and AID of GE for NC2 diet by 5.09 and 8.74%, respectively. Multienzyme did not interact with negative control diet type on overall G:F, bone ash content, AID of AA, and ATTD of nutrients. Multienzyme increased (P < 0.05) overall G:F, AID of methionine, ATTD of GE and P, and tended to increase (P = 0.056) bone ash content. The ADG, bone ash content, and ATTD of GE and P for the multienzyme-supplemented diets were similar to (P > 0.10) PC diet. Thus, NE and digestible AA and P can be lowered by ≤5% in multienzyme-supplemented diets without effects on growth performance and bone ash of pigs.
Egg yolk immunoglobulin Y as a promising tool to detect immune complexes in neurocysticercosis serum samples
Authors: Silva Gabriela B da , Faria Lucas S da , Lopes Camila A , Nunes Daniela S , Ribeiro Vanessa S , de Sousa José Eduardo N , Paiva Guilherme C M , Gonçalves-Pires Maria R F , Borges Isabela P , Santos Malú M , Ávila Veridiana M R , Júnior Álvaro Ferreira , Costa-Cruz Julia M
Published: April 2020

Background

Neurocysticercosis (NCC) is a neglected tropical disease and its diagnosis is still a challenge due to non-specific manifestations. Neuroimaging techniques are used in the diagnosis of NCC, however, due to the high cost of these methods and the advantages presented in the use of immunological tests, such as ease of performance and satisfactory results, immunoassays are commonly used to detect antibodies against Taenia sp. antigens. The aim of the present study was to produce, characterize and apply specific polyclonal immunoglobulin Y (IgY) anti-Taenia crassiceps extracted from egg yolk of hens immunized with T. crassiceps metacestodes.

Methods

Indirect enzyme-linked immunosorbent assay (ELISA), avidity ELISA, immunoblotting and indirect immunofluorescence tests were performed for characterization of IgY antibodies. Diagnostic performance was verified by ELISA for immune complex detection testing 90 serum samples.

Results

Values of sensitivity, specificity, positive and negative likelihood ratios (LR+/LR−) and area under the curve (AUC) were calculated and presented the following results: sensitivity 83.3%, specificity 96.7%, AUC 0.966, LR+ 25.0 and LR− 0.17.

Conclusions

Results of this pioneering and innovative study demonstrate that anti-T. crassiceps IgY antibodies present potential applicability and can be used as an efficient tool in human NCC serodiagnosis.
Consecutive 265 Profunda Artery Perforator Flaps: Refinements, Satisfaction, and Functional Outcomes
Authors: Haddock Nicholas T. , Teotia Sumeet S.
Published: April 2020

Introduction:

The ideal form of breast reconstruction provides total permanent restoration of the breast mound. When a deep inferior epigastric (DIEP) flap is not an option or does not provide significant volume, a secondary source must be considered. In our practice, the profunda artery perforator (PAP flap) from the thigh has emerged as a second choice. We present our experience with the first 265 PAP flaps used for breast reconstruction at our institution. We specifically focus on refinements, satisfaction, and functional outcomes.

Methods:

We conducted a retrospective review of the first 265 PAP flaps at our institution. Patient demographics, perioperative data, and postoperative complications were recorded and analyzed. The Breast Q and Lower Extremity Functional Scale (LEFS) were both implemented. Additionally, a satisfaction survey was performed, particularly focused on the donor site.

Results:

Two hundred sixty-five consecutive PAP flaps were used to reconstruct 244 breasts in 138 patients. The PAP flap was used for bilateral reconstruction (107 patients) and unilateral breast (30 patients). It was used in combination with a second flap as double PAP (21 patients) or combined with a DIEP (62 patients). Mean flap size was 403 g (range: 190–800 g) and mean patient body mass index was 26.5 (range: 18–43). Complications included total flap loss (3%), donor site cellulitis (4.9%), and significant donor site wound (6.8%). Currently, the PAP flap accounts for 16.9% of our autologous breast reconstruction and the DIEP flap accounts for 76.0%. Lower Extremity Functional Scale score was 75/80 (94%) by 6 months. Satisfaction with breast reconstruction was 78.9% and satisfaction with the thigh was 82.1%.

Conclusions:

The PAP flap is an excellent option for autologous breast reconstruction. Success rate and complications are similar to those of other options. There is no significant loss to lower extremity function and satisfaction with the reconstruction is comparable with other options.
Our Experiences with Plastic and Reconstructive Surgery Procedures during Coronavirus Disease 2019 Pandemic
Authors: Wang Zhichao , Wang Wei , Bai Ting , Di Meihua , Zan Tao , Gu Bin , Li Shengli , Li Qingfeng
Published: April 2020

Background:

The novel Coronavirus Disease 2019 (COVID-19) has rapidly become a health threat worldwide and has been declared global pandemic by the World Health Organization. Possible transmission routes, including respiratory droplets, close contact, and aerosol propagation, have put plastic and reconstructive healthcare professionals at high risk, especially during surgical procedures. The aim of this study was to summarize and share our experience of infection control measures and corresponding outcomes during the COVID-19 pandemic.

Methods:

Infection control measures, including workflow optimization, useful epidemiologic survey methods, and personal full protective clothing, were discussed. Characteristics and outcomes of emergency cases and elective cases under local and general anesthesia during the COVID-19 pandemic were summarized.

Results:

A hierarchy of interventions were applied mainly from 4 aspects. First, administration control and online consultation significantly decreased patient attendance. Second, a triage workflow was established to identify high-/low-risk patients, with clinical manifestations (fever, fatigue, cough, nasal discharge, etc), epidemiologic survey, blood test, chest computed tomographic scan, and coronavirus test if necessary. Third, strict environmental control was adopted using increasing ventilation, isolated room for inpatients, etc. Fourth, proper rotation of healthcare staff was ensured to reduce workload and minimize possible contact. A total of 904 emergency interventions, 2561 local anesthesia, and 570 general anesthesia were performed during this period, and none of the cases/healthcare professionals were found to be infected.

Conclusions:

Our experience could help global plastic and reconstructive healthcare professionals to get better preparation and continue to give qualified medical services during the COVID-19 pandemic. Proper adjustments should be taken according to their own clinical settings.
Candida Keratitis: Epidemiology, Management, and Clinical Outcomes
Authors: Qiao Grace L. , Ling Jennifer , Wong Titus , Yeung Sonia N. , Iovieno Alfonso
Published: April 2020

Purpose:

To examine the epidemiological characteristics, trends, risk factors, management strategies, and clinical outcomes ofCandida albicansand non-albicanskeratitis over a 15-year period in a tertiary Canadian eye center.

Methods:

In a retrospective observational case series ofCandidakeratitis from 2003 to 2017, demographics, risk factors, corrected distance visual acuity (CDVA) at initial and final consultations, medical and surgical management, and follow-up duration were recorded.

Results:

Twenty-one cases ofCandidakeratitis were identified (62.5% of total fungal keratitis; 10C. albicansand 11 non-albicans). The most commonly associated risk factors were topical steroid use (16 patients, 76%), ocular surface disease (15 patients, 71%), contact lens use (11 patients, 52%), and previous corneal surgery (8 patients, 38%); all patients had 2 or more combined risk factors. The number of patients with a visual acuity of 20/200 or better remained the same before and after the treatment (5/21, 24%). The mean duration of the antifungal treatment was 98 ± 126 days. Sixteen patients ultimately required surgical management (76%; 12 therapeutic keratoplasties, 3 enucleation, and 1 optical keratoplasty). When comparingC. albicanswith non-albicanskeratitis, we found no difference in presenting visual acuity, final visual acuity, or requirement for surgical management.

Conclusions:

Candidakeratitis accounts for the most identified fungal keratitis cases in this temperate climate area. An exposure to multiple risk factors appears necessary. A surgical intervention is required for the resolution of most cases. Different subspecies ofCandidaultimately resulted in similar clinical outcomes.
Endoscopic-Assisted Lateral Orbitotomy for Large Orbital Roof Dermoid Cysts With Dural Invasion
Authors: Kashkouli Mohsen Bahmani , Maleki Meysam , Khademi Behzad , Karimi Nasser , Hamami Parisa , Nadjafi-Semnani Fatemeh
Published: April 2020

Purpose:

To demonstrate the technique and report the results of endoscopic-assisted lateral orbitotomy for 6 patients with huge intraorbital dermoid cyst causing orbital roof bone erosion and dural invasion.

Methods:

Patients had unilateral cystic tumor with proptosis and hypoglobus for more than 6 months. There was no compressive optic neuropathy. Lateral orbitotomy procedure was performed from 2004 to 2016 by 1 surgeon. Cysts were dissected, and fluid content was aspirated to reduce the size. Solid contents were then suctioned, its cavity was repeatedly irrigated, and orbital part of epithelial lining was removed. The remained epithelial lining and keratinized content at the orbital roof (abutting the dura) were removed using the rigid endoscope lenses (4 mm, 0° and 30°) and curettage. Orbital tissue was pulled away from the roof (inferior) by an assistant surgeon to make a space for introducing the lens and curette. The surgical field was frequently irrigated. No orbital drain was used, and all the patients were discharged on the same day after 8–10 hours of observation. Skin sutures were removed 1 week later.

Results:

They were 4 men and 2 women with age range of 19–48 years. A large superolateral orbital tumor with roof erosion and dural invasion was observed on imaging. Procedures were performed uneventfully. Dermoid was the pathological diagnosis. While one patient lost to follow up after 1 week, others had 6–18 months follow-up time with no recurrence.

Conclusions:

Endoscopic-assisted lateral orbitotomy approach provided a good field of view, illumination, and magnification to totally remove all the content and epithelial lining of very large orbital roof dermoid cysts with dural invasion.
Occupational Quartz Exposure in a Population of Male Individuals—Association With Risk of Developing Atrial Fibrillation
Authors: Montén Adam , Bryngelsson Ing-Liss , Fornander Louise , Wiebert Pernilla , Vihlborg Per
Published: April 2020

Objective:

Occupational quartz exposure is a health risk, with increased risk of developing lung, autoimmune diseases, and elevated mortality in cardiovascular diseases.

Methods:

The population was obtained from the period 2005 to 2016 and consisted of 5237 cases of patients with atrial fibrillation (AF). Quartz exposure information was obtained through a Swedish job exposure matrix.

Results:

The risk of developing AF was increased for the quartz-exposed male population who were within a year of having commenced employment OR 1.54; (95% CI 1.06–2.24); this increased in the age group 20 to 55 (OR 2.05; CI 95% 1.02–4.10).

Conclusion:

Our main conclusion is that quartz dust exposure may be related to increased risk of AF in high exposed (above 0.05 mg/m3 mean quartz dust) in men aged 20 to 55 years.
Dual Airway and Esophageal Stenting in Advanced Esophageal Cancer With Lesions Near Carina
Authors: Khan Ajmal , Hashim Zia , Neyaz Zafar , Agarwal Aarti , Mohindra Samir , Nath Alok
Published: April 2020

Background:

Tracheobronchial stenting either alone or with esophageal stenting is often required for symptom palliation in obstructive or fistulous lesions of the airway due to esophageal cancer. There is limited evidence regarding dual stenting for lesions near the carina due to esophageal cancer. Hence, this study aims to evaluate the technical feasibility, outcomes, and complications of preplanned dual stenting in these patients.

Methods:

This is a prospective observational study carried out over a period of 4 years (January 2015 to July 2019). All patients undergoing dual stenting in the airway and esophagus with obstructive or fistulous lesions near the carina were included. The esophageal stent was placed within 24 hours. Prestenting and poststenting symptoms were compared using a symptom-based visual analog scale, Hugh Jones dyspnea scale and dysphagia scale.

Results:

Twenty-nine patients (20 males; mean±SD age, 55.3±12.2 y) underwent dual stenting. Twenty-four patients had central airway obstruction due to: infiltration in 20 (69%) and external compression in 4 (13.7%), respectively. Five (17.3%) patients had tracheoesophageal fistula with no airway obstruction. In 80% of the patients (n=23), silicone stents were placed. There was significant improvement in both dyspnea and dysphagia after dual stenting (P<0.001). Mucus plugging, lower respiratory infection, and granulation tissue were the main complications. Median survival after dual stent was 97 days (range, 17 to 297 d).

Conclusion:

Dual stenting within the airway and the esophagus is a safe and viable option for palliative relief of symptoms in patients with advanced esophageal cancer.
Events Associated With Changes in Reliance on the Veterans Health Administration Among Medicare-eligible Veterans
Authors: Hebert Paul L. , Wong Edwin S. , Reddy Ashok , Batten Adam , Gunnink Eric , Wagner Todd H. , Liu Chuan-Fen
Published: April 2020

Objectives:

We can learn something about how Veterans value the Veterans Health Administration (VHA) versus community providers by observing Veterans’ choices between VHA and Medicare providers after they turn 65. For a cohort of Veterans who were newly age-eligible for Medicare, we estimated the change in VHA reliance (VHA outpatient visits divided by total VHA and Medicare visits) associated with specific events: receiving a life-threatening diagnosis, having a Medicare-paid hospitalization, or moving further from the VHA.

Research Design:

A longitudinal cohort study of VHA and Medicare administrative data.

Subjects:

A total of 5932 VHA users who completed a health survey in 1999 and became age-eligible for Medicare from 1998 to 2000 were followed through 2016.

Principal Findings:

More Veterans chose to rely on the VHA than Medicare (64% vs. 36.%). For a VHA-reliant Veteran, a Medicare-paid hospital stay was associated with a decrease of 7.8 percentage points (pps) (P<0.001) in VHA reliance in the subsequent 12 months, but by 36 months reliance increased to near prehospitalization levels (−1.5 pps; P=0.138). Moving further from the VHA, or receiving a diagnosis of cancer, heart failure, or renal failure had no significant association with subsequent VHA reliance; however, a diagnosis of dementia was associated with a decrease in VHA reliance (−8.6 pps; P=0.026).

Conclusions:

A significant majority of newly Medicare-eligible VHA users voted with their feet in favor of sustaining the VHA as a provider of comprehensive medical care for Veterans. These VHA-reliant Veterans maintained their reliance even after receiving a life-threatening diagnosis, and after experiencing Medicare-provided hospital care.
Editorial Comment on Firth et al. (2019)
Authors: Kop Willem J. , Chapman Benjamin P.
Published: April 2020

This Editorial Comment addresses an article by Firth et al. published in the February issue of 2019.
HIV Prevalence Among Women Who Exchange Sex for Money or Drugs—4 U.S. Cities
Authors: Nerlander Lina M. , Handanagic Senad , Hess Kristen L. , Lutnick Alexandra , Agnew-Brune Christine B. , Hoots Brooke E. , Braunstein Sarah L. , Glick Sara Nelson , Higgins Emily , Padgett Paige , Schuette Stephanie M. , Broz Dita , Ivy Wade , Smith Amanda , Thorson Anna , Paz-Bailey Gabriela ,   for the NHBS High Risk Women Study Group
Published: April 2020

Background:

Limited data exist in the United States on the prevalence of HIV among women who exchange sex.

Setting:

We estimate HIV prevalence of women who exchange sex from a 2016 survey in Chicago, Detroit, Houston, and Seattle and compare it with the prevalence of HIV among women of low socioeconomic status (SES), who did not exchange sex, and women in the general population.

Methods:

Women who exchange sex were recruited via respondent-driven sampling among some cities participating in National HIV Behavioral Surveillance, interviewed, and offered HIV testing. We estimate HIV prevalence and, using prevalence ratios, compare it with the prevalence among women of low SES who did not exchange sex in the 2013 National HIV Behavioral Surveillance cycle, and to women in the general population estimated using 2015 National HIV Surveillance data.

Results:

One thousand four hundred forty women reported exchange sex in 2016. Aggregated HIV prevalence was 4.9% [95% confidence interval (CI): 2.7 to 7.1] among women who exchanged sex, 1.6% (95% CI: 0.3 to 2.8) among women of low SES who did not exchange sex, and 0.6% (95% CI: 0.5% to 0.6%) among women in the general population. HIV prevalence among women who exchanged sex was 3.1 times (95% CI: 1.6 to 5.9) as high as among women of low SES who did not exchange sex, and 8.8 times (95% CI: 7.0 to 11.1) as high as among women in the general population.

Conclusion:

HIV prevalence was significantly higher among women who exchanged sex compared with women in the general population and women of low SES who did not exchange sex.
Are White Matter Tract Integrities Different in Multiple Sclerosis Women With Voiding Dysfunction?
Authors: Tran Khue , Karmonik Christof , Boone Timothy B. , Khavari Rose
Published: April 2020

Objectives

Two white matter tracts (WMTs) are proposed to be involved in bladder function: anterior thalamic radiation and superior longitudinal fasciculus. Multiple sclerosis (MS) patients with voiding dysfunction (VD) may have distinct changes in these 2 WMTs. This study aims to compare the fractional anisotropy (FA) and mean diffusivity (MD) from diffusion tensor imaging of MS females with and without VD versus healthy controls (HCs).

Methods

Prospective observational cohorts of 28 female MS patients and 11 HCs were recruited. Multiple sclerosis patients were divided into 2 groups: voiders (patients without VD, n = 14) and VD (patients with VD, n = 14). Diffusion tensor imaging of each subject was obtained, from which FA and MD maps were generated. The mean FA and MD of each WMT on both sides were analyzed using one-way analysis of variance and pairwise comparison with adjusted P values.

Results

Overall MS patients had significantly lower mean FA (loss of coherence) and significantly higher mean MD (increased free diffusion) than HCs in both WMTs, indicating more damage. Furthermore, VD showed a trend of loss of integrity in both WMTs when compared with voiders with lower FA and higher MD.

Conclusions

There is damage reflected by lower FA and higher MD values in the proposed WMTs involved in bladder function in MS women. Voiding dysfunction in this patient population can be attributed to these damages considering women with VD demonstrated a trend of deterioration in these WMTs compared with women without VD. Future studies with larger sample sizes should be done to further confirm this correlation.
Renal Function Improvement Following ANG-3777 Treatment in Patients at High Risk for Delayed Graft Function After Kidney Transplantation
Authors: Bromberg Jonathan S. , Weir Matthew R. , Gaber A. Osama , Yamin Michael A. , Goldberg Itzhak D. , Mayne Tracy J. , Cal Weizhong , Cooper Matthew
Published: April 2020

Background.

Patients (20%–50%) undergoing renal transplantation experience acute kidney injury resulting in delayed graft function. ANG-3777 is an hepatocyte growth factor mimetic that binds to the c-MET receptor. In animal models, ANG-3777 decreases apoptosis, increases proliferation, and promotes organ repair and function.

Methods.

This was a randomized, double-blind, placebo-controlled, phase 2 trial of patients undergoing renal transplantation with <50 cc/h urine output for 8 consecutive hours over the first 24 hours posttransplantation, or creatinine reduction ratio <30% from pretransplantation to 24 hours posttransplantation. Subjects were randomized as 2:1 to 3, once-daily IV infusions of ANG-3777, 2 mg/kg (n = 19), or placebo (n = 9). Primary endpoint: time in days to achieve ≥1200 cc urine for 24 hours.

Results.

Patients treated with ANG-3777 were more likely to achieve the primary endpoint of 1200 cc urine for 24 hours by 28 days posttransplantation (83.3% versus 50% placebo; log-rank test: χ2 = 2.799, P = 0.09). Compared with placebo, patients in the ANG-3777 arm had larger increases in urine output; lower serum creatinine; greater reduction in C-reactive protein and neutrophil gelatinase-associated lipocalin; fewer dialysis sessions and shorter duration of dialysis; fewer hospital days; significantly less graft failure; and higher estimated glomerular filtration rate. Adverse events occurred in a similar percentage of subjects in both arms. Events per subject were twice as high in the placebo arm.

Conclusions.

There was an efficacy signal for improved renal function in subjects treated with ANG-3777 relative to placebo, with a good safety profile.
Paneth Cell Alterations During Ischemia-reperfusion, Follow-up, and Graft Rejection After Intestinal Transplantation
Authors: Kip Anna M. , Ceulemans Laurens J. , Hundscheid Inca H.R. , Canovai Emilio , Hartog Hermien , Brown Rachel M. , Corcos Olivier , Joly Francisca , De Hertogh Gert , Gupte Girish , Dejong Cornelis H.C. , Olde Damink Steven W.M. , Pirenne Jacques , Mirza Darius , Lenaerts Kaatje
Published: April 2020

Background.

Ischemia-reperfusion injury is inevitable during intestinal transplantation (ITx) and executes a key role in the evolution towards rejection. Paneth cells (PCs) are crucial for epithelial immune defense and highly vulnerable to ischemia-reperfusion injury. We investigated the effect of ITx on PC after reperfusion (T0), during follow-up, and rejection. Moreover, we investigated whether PC loss was associated with impaired graft homeostasis.

Methods.

Endoscopic biopsies, collected according to center protocol and at rejection episodes, were retrospectively included (n = 28 ITx, n = 119 biopsies) Biopsies were immunohistochemically co-stained for PC (lysozyme) and apoptosis, and PC/crypt and lysozyme intensity were scored.

Results.

We observed a decrease in PC/crypt and lysozyme intensity in the first week after ITx (W1) compared with T0. There was a tendency towards a larger decline in PC/crypt (P = 0.08) and lysozyme intensity (P = 0.08) in W1 in patients who later developed rejection compared with patients without rejection. Follow-up biopsies showed that the PC number recovered, whereas lysozyme intensity remained reduced. This persisting innate immune defect may contribute to the well-known vulnerability of the intestine to infection. There was no clear evidence that PCs were affected throughout rejection.

Conclusions.

This study revealed a transient fall in PC numbers in the early post-ITx period but a permanent reduction in lysozyme intensity following ITx. Further research is needed to determine the potential clinical impact of PC impairment after ITx.
Transient-mixed Chimerism With Nonmyeloablative Conditioning Does Not Induce Liver Allograft Tolerance in Nonhuman Primates
Authors: Chaudhry Sulemon , Kato Yojiro , Weiner Joshua , Alonso-Guallart Paula , Baker Sam , Woodland David C. , Lefkowitch Jay H. , Duran-Struuck Raimon , Sondermeijer Hugo P. , Zitsman Jonah , Sears Mallory L. , Wu Anette , Karolewski Brian , Houck Philipp J. , Martinez Mercedes , Kato Tomoaki , Sykes Megan , Griesemer Adam D.
Published: April 2020

Background.

Although short-term outcomes for liver transplantation have improved, patient and graft survival are limited by infection, cancer, and other complications of immunosuppression. Rapid induction of tolerance after liver transplantation would decrease these complications, improving survival and quality of life. Tolerance to kidneys, but not thoracic organs or islets, has been achieved in nonhuman primates and humans through the induction of transient donor chimerism. Since the liver is considered to be tolerogenic, we tested the hypothesis that the renal transplant transient chimerism protocol would induce liver tolerance.

Methods.

Seven cynomolgus macaques received immune conditioning followed by simultaneous donor bone marrow and liver transplantation. The more extensive liver surgery required minor adaptations of the kidney protocol to decrease complications. All immunosuppression was discontinued on postoperative day (POD) 28. Peripheral blood chimerism, recipient immune reconstitution, liver function tests, and graft survival were determined.

Results.

The level and duration of chimerism in liver recipients were comparable to those previously reported in renal transplant recipients. However, unlike in the kidney model, the liver was rejected soon after immunosuppression withdrawal. Rejection was associated with proliferation of recipient CD8 T effector cells in the periphery and liver, increased serum interleukin (IL)-6 and IL-2, but peripheral regulatory T cell (Treg) numbers did not increase. Antidonor antibody was also detected.

Conclusions.

These data show the transient chimerism protocol does not induce tolerance to livers, likely due to greater CD8 T cell responses than in the kidney model. Successful tolerance induction may depend on greater control or deletion of CD8 T cells in this model.
Accelerating surveillance and research of antimicrobial resistance – an online repository for sharing of antimicrobial susceptibility data associated with whole-genome sequences
Authors: Matamoros Sébastien , Hendriksen Rene S. , Pataki Bálint Ármin , Pakseresht Nima , Rossello Marc , Silvester Nicole , Amid Clara , Aarestrup Frank M. , Koopmans Marion , Cochrane Guy , Csabai Istvan , Lund Ole , Schultsz Constance ,   The COMPARE ML-AMR group
Published: April 2020

Antimicrobial resistance (AMR) is an emerging threat to modern medicine. Improved diagnostics and surveillance of resistant bacteria require the development of next-generation analysis tools and collaboration between international partners. Here, we present the ‘AMR Data Hub’, an online infrastructure for storage and sharing of structured phenotypic AMR data linked to bacterial whole-genome sequences. Leveraging infrastructure built by the European COMPARE Consortium and structured around the European Nucleotide Archive (ENA), the AMR Data Hub already provides an extensive data collection of more than 2500 isolates with linked genome and AMR data. Representing these data in standardized formats, we provide tools for the validation and submission of new data and services supporting search, browse and retrieval. The current collection was created through a collaboration by several partners from the European COMPARE Consortium, demonstrating the capacities and utility of the AMR Data Hub and its associated tools. We anticipate growth of content and offer the hub as a basis for future research into methods to explore and predict AMR.
Timing of antiviral treatment initiation is critical to reduce SARS-Cov-2 viral load
Authors: Gonçalves Antonio , Bertrand Julie , Ke Ruian , Comets Emmanuelle , de Lamballerie Xavier , Malvy Denis , Pizzorno Andrés , Terrier Olivier , Calatrava Manuel Rosa , Mentré France , Smith Patrick , Perelson Alan S , Guedj Jérémie
Published: April 2020

We modeled the viral dynamics of 13 untreated patients infected with SARS-CoV-2 to infer viral growth parameters and predict the effects of antiviral treatments. In order to reduce peak viral load by more than 2 logs, drug efficacy needs to be greater than 90% if treatment is administered after symptom onset; an efficacy of 60% could be sufficient if treatment is initiated before symptom onset. Given their pharmacokinetic/pharmacodynamic properties, current investigated drugs may be in a range of 6-87% efficacy. They may help control virus if administered very early, but may not have a major effect in severe patients.
Analysis and Applications of Adaptive Group Testing Methods for COVID-19
Authors: Mentus Cassidy , Romeo Martin , DiPaola Christian
Published: April 2020

Testing strategies for Covid-19 to maximize number of people tested are urgently needed. Recently, it has been demonstrated that RT-PCR has the sensitivity to detect one positive case in a mixed sample of 32 cases [12], In this paper we propose adaptive group testing strategies based on generalized binary splitting (CBS) [5], where we restrict the group test to the largest group that can be used. The method starts by choosing a group from the population to be tested, performing a test on the combined sample from the entire group, and progressively splitting the group further into subgroups. Compared to individual testing at 4% prevalence, we save 74%; at 1% we save 91%; and at .1% we save 98% of tests. We analyze the number of times each sample is used and show that the method is still efficient if we resort to testing a case individually if the sample is running low.

In addition we recommend clinical screening to filter out individuals with symptoms and show this leaves us with a population with lower prevalence. Our approach is particularly applicable to vulnerable confined populations such as nursing homes, prisons, military ships and cruise ships.
Multi-modal Nonlinear Optical and Thermal Imaging Platform for Label-Free Characterization of Biological Tissue
Authors: Adams Wilson R , Mehl Brian , Lieser Eric , Wang Manqing , Patton Shane , Throckmorton Graham A , Jenkins J Logan , Ford Jeremy B , Gautam Rekha , Brooker Jeff , Jansen E. Duco , Mahadevan-Jansen Anita
Published: April 2020

The ability to characterize the combined structural, functional, and thermal properties of biophysically dynamic samples is needed to address critical questions related to tissue structure, physiological dynamics, and disease progression. Towards this, we have developed an imaging platform that enables multiple nonlinear imaging modalities to be combined with thermal imaging on a common sample. Here we demonstrate label-free multimodal imaging of live cells, excised tissues, and live rodent brain models. While potential applications of this technology are wide-ranging, we expect it to be especially useful in addressing biomedical research questions aimed at the biomolecular and biophysical properties of tissue and their physiology.
The potential genetic network of human brain SARS-CoV-2 infection
Authors: Lapina Colline , Rodic Mathieu , Peschanski Denis , Mesmoudi Salma
Published: April 2020

The literature reports several symptoms of SARS-CoV-2 in humans such as fever, cough, fatigue, pneumonia, and headache. Furthermore, patients infected with similar strains (SARS-CoV and MERS-CoV) suffered testis, liver, or thyroid damage. Angiotensin-converting enzyme 2 (ACE2) serves as an entry point into cells for some strains of coronavirus (SARS-CoV, MERS-CoV, SARS-CoV-2). Our hypothesis was that as ACE2 is essential to the SARS-CoV-2 virus invasion, then brain regions where ACE2 is the most expressed are more likely to be disturbed by the infection. Thus, the expression of other genes which are also over-expressed in those damaged areas could be affected. We used mRNA expression levels data of genes provided by the Allen Human Brain Atlas (ABA), and computed spatial correlations with the LinkRbrain platform. Genes whose co-expression is spatially correlated to that of ACE2 were then clustered into 16 groups, depending on the organ in which they are the most expressed (as described by the NCBI genes database). The list of organs where genes sharing local over-expression with the ACE2 gene are the most expressed is astonishingly similar to the organs affected by Covid-19.
PARTITIONING AMONG NICHE AND NEUTRAL EXPLANATIONS FOR METACOMMUNITY PATTERNS IN CERRADO STREAM FISH COMMUNITIES
Authors: Vieira Thiago Bernardi , da Silva Liriann Chrisley Nascimento , Casatti Lilian , Romero Renato , Tejerina Garro Francisco Leonardo , Uchôa de Aquino Pedro De Podestà , Santos Pompeu Paulo dos , De Marco Paulo
Published: April 2020

The Species Sorting concept, one of the models developed to explain patterns in metacommunity structure, suggests that relationships between biological communities and environmental conditions is the basic means of the species selection processes. A second concept is neutral theory, and the idea of neutral dynamics underpinning metacommunity structure, cannot be overlooked. The third mechanism is the Mass Effect concept, that focuses on the interaction between environmental condition and neutral effects. In the present study, we partitioned fish communities in streams between niche and neutral theory concepts, identifying the best representation of metacommunity structure, and assessed if linear and hydrographic distance were equivalent in the representation of neutral processes. The result points to the importance of species sorting mechanisms in structuring fish communities with neutral processes best represented by the linear distances. On the other hand, the best representation of species’ niches was achieved with average values and variance of the local conditions.
PriSeT: EfficientDe NovoPrimer Discovery
Authors: Hoffmann Marie , Monaghan Michael T. , Reinert Knut
Published: April 2020

Motivation

DNA metabarcoding is a commonly applied technique used to infer the species composition of environmental samples. These samples can comprise hundreds of organisms that can be closely or very distantly related in the taxonomic tree of life. DNA metabarcoding combines polymerase chain reaction (PCR) and next-generation sequencing (NGS), whereby a short, homologous sequence of DNA is amplified and sequenced from all members of the community. Sequences are then taxonomically identified based on their match to a reference database. Ideally, each species of interest would have a unique DNAbarcode. This short, variable sequence needs to be flanked by relatively conserved regions that can be used as primer binding sites. Appropriate PCR primer pairs would match to a broad evolutionary range of taxa, such that we only need a few to achieve high taxonomic coverage. At the same time however, the DNA barcodes between primer pairs should be different to allow us to distinguish between species to improve resolution. This poses an interesting optimization problem. More specifically: Given a set of references ℛ = {R1,R2, …,Rm}, the problem is to find a primer setPbalancing both: high taxonomic coverage and high resolution. This goal can be captured by filtering for frequent primers and ranking by coverage or variation, i.e. the number of unique barcodes. Here we present the software PriSeT, an offline primer discovery tool that is capable of processing large libraries and is robust against mislabeled or low quality references. It tackles the computationally expensive steps with linear runtime filters and efficient encodings.

Results

We first evaluated PriSeT on references (mostly 18S rRNA genes) from 19 clades covering eukaryotic organisms that are typical for freshwater plankton samples. PriSeT recovered several published primer sets as well as additional, more chemically suitable primer sets. For these new sets, we compared frequency, taxon coverage, and amplicon variation with published primer sets. For 11 clades we foundde novoprimer pairs that cover more taxa than the published ones, and for six cladesde novoprimers resulted in greater sequence (i.e., DNA barcode) variation. We also applied PriSeT to 19 SARS-CoV-2 genomes and computed 114 new primer pairs with the additional constraint that the sequences have no co-occurrences in other taxa. These primer sets would be suitable for empirical testing.

Availability

https://github.com/mariehoffmann/PriSeT

Contact

marie.hoffmann@fu-berlin.de
Genetic similarity and facial cues for kin recognition in humans
Authors: Torosin Nicole S. , Ward Joshua , Bell Adrian V. , Knapp Leslie A.
Published: April 2020

Kin recognition is essential to the evolution of human cooperation, social organization, and altruistic behavior. However, the genetic underpinnings of kin recognition have been largely understudied. Facial resemblance is an important relatedness cue for humans and more closely related individuals are generally thought to share greater facial similarity. To evaluate the relationship between perceived self-resemblance and genetic similarity among biologically related and unrelated females, we administered facial self-recognition surveys to twenty-three sets of related females and genotyped three different genetic systems, human leukocyte antigens (HLA), neutral nuclear microsatellites and mitochondrial haplogroups, for each individual. Using these data, we examined the relationship between visual kin recognition and genetic similarity. We found that pairs of individuals identified as visually more similar had greater HLA allelic sharing when compared to less facially similar participants. We did not find the same relationship for microsatellite and mitochondrial similarity, suggesting that HLA allelic similarity increases the probability of perceived self-resemblance in humans while other genetic markers do not. Our results demonstrate that some genetic markers, such as HLA-DRB, may have significant influence on phenotype and that large scale surveys of HLA and facial feature morphology will yield valuable insight into the evolutionary biology of genotype-phenotype relationships and kin recognition.
Rapid Assessment of T-Cell Receptor Specificity of the Immune Repertoire
Authors: Lin Xingcheng , George Jason T. , Schafer Nicholas P. , Chau Kevin Ng , Birnbaum Michael E. , Clementi Cecilia , Onuchic José N. , Levine Herbert
Published: April 2020

Accurate assessment of TCR-antigen specificity at the whole immune repertoire level lies at the heart of improved cancer immunotherapy, but predictive models capable of high-throughput assessment of TCR-peptide pairs are lacking. Recent advances in deep sequencing and crystallography have enriched the data available for studying TCR-p-MHC systems. Here, we introduce a pairwise energy model, RACER, for rapid assessment of TCR-peptide affinity at the immune repertoire level. RACER applies supervised machine learning to efficiently and accurately resolve strong TCR-peptide binding pairs from weak ones. The trained parameters further enable a physical interpretation of interacting patterns encoded in each specific TCR-p-MHC system. When applied to simulate thymic selection of an MHC-restricted T-cell repertoire, RACER accurately estimates recognition rates for tumor-associated neoantigens and foreign peptides, thus demonstrating its utility in helping address the large computational challenge of reliably identifying the properties of tumor antigen-specific T-cells at the level of an individual patient’s immune repertoire.
The Tetrameric Structure of Nucleotide-regulated Pyrophosphatase and Its Modulation by Deletion Mutagenesis and Ligand Binding
Authors: Anashkin Viktor A. , Salminen Anu , Orlov Victor N. , Lahti Reijo , Baykov Alexander A.
Published: April 2020

A quarter of prokaryotic Family II inorganic pyrophosphatases (PPases) contain a regulatory insert comprised of two cystathionine β-synthase (CBS) domains and one DRTGG domain in addition to the two catalytic domains that form canonical Family II PPases. The CBS domain-containing PPases (CBS-PPases) are allosterically activated or inhibited by adenine nucleotides that cooperatively bind to the CBS domains. Here we use chemical cross-linking and analytical ultracentrifugation to show that CBS-PPases fromDesulfitobacterium hafnienseand four other bacterial species are active as 200–250-kDa homotetramers, which seems unprecedented among the four PPase families. The tetrameric structure is stabilized by Co2+, the essential cofactor, pyrophosphate, the substrate, and adenine nucleotides, including diadenosine tetraphosphate. The deletion variants ofdhPPase containing only catalytic or regulatory domains are dimeric. Co2+depletion by incubation with EDTA converts CBS-PPase into inactive tetrameric and dimeric forms. Dissociation of tetrameric CBS-PPase and its catalytic part by dilution renders them inactive. The structure of CBS-PPase tetramer was modelled from the structures of dimeric catalytic and regulatory parts. These findings signify the role of the unique oligomeric structure of CBS-PPase in its multifaced regulation.
Case reports of improvement in behaviour following switching of patients with intellectual disability and epilepsy from levetiracetam to brivaracetam
Authors: Baburaj Raghavendar , Dunstall Huw Morgan , Bright Catherine , Lawthom Charlotte
Published: April 2020

Purpose

Epilepsy is a chronic illness affecting around 50 million people worldwide. Levetiracetam is an effective novel antiepileptic drug but can cause behavioural adverse events. A total of 10-15 per cent people with intellectual disability (ID) already present with Behaviour that Challenges (BtC). Brivaracetam is postulated to have a distinct pharmacological profile compared with levetiracetam which may result in fewer behavioural adverse events.

Design/methodology/approach

This paper presents two cases of people with epilepsy and ID being switched from levetiracetam to brivaracetam for reported behaviour adverse events.

Findings

The cases support that people with epilepsy and ID who are experiencing behavioural adverse events from levetiracetam can safely be switched to brivaracetam, resulting in significant reductions in BtC and potentially improved seizure control. Nevertheless, these results must be interpreted with caution, as aetiology for BtC in people with ID is often multifactorial.

Originality/value

This is one of the first papers to date, according to the best of the authors’ knowledge, to describe improved behavioural profile in people with ID and epilepsy when switching from levetiracetam to brivaracetam.
The recursive interplay of capabilities and constraints amongst microfinance entrepreneurs
Authors: Kimmitt Jonathan , Dimov Dimo
Published: April 2020

Purpose

The purpose of this paper is to investigate, through practices and capabilities, how entrepreneurs use microfinance in a context of serious constraints.

Design/methodology/approach

The chosen methodology for this paper is longitudinal. A three-and-a-half-year study was conducted to be able to capture the entrepreneurial journeys of ten entrepreneurs at a micro-level in the developing economy of Ghana. This was augmented by a further 15 interviews with entrepreneurs and loan officers. This data is used to develop a theoretical model of entrepreneurial practices in this context.

Findings

The paper identifies two distinct pathways for understanding the recursive nature of entrepreneurial practices. It highlights how entrepreneurs generate capabilities through microfinance resources through convergent or divergent venturing in response to the serious constraints they face. This is identified as a generative recursive mechanism for the process, representing the “chain of actions” and how entrepreneurs engage with their “settings” and “intended relations” in practice.

Research limitations/implications

The research is limited by its focus on one nation in Sub-Saharan Africa and therefore how the findings may be transferred to other contexts.

Originality/value

The paper contributes to a practice approach in entrepreneurship by identifying how mechanisms of practice relate to entrepreneurial action in this context. It also provides an important contribution to discussion at the intersection of entrepreneurship and the capabilities approach by using Amartya Sen's concepts of process and opportunity freedom to understand practices.
A comparative study on the performance of rule engines in automated ontology learning: a case study with erythemato-squamous disease (ESD)
Authors: S Sivasankari , Punnoose Dinah , D Krishnamoorthy
Published: April 2020

Purpose

Erythemato-squamous disease (ESD) is one of the complex diseases related to the dermatology field. Due to common morphological features, the diagnosis of ESDs become stringent and leads to inconsistency. Besides, diagnosis has been done on the basis of inculcated visible symptoms pertinent with the expertise of the physician. Hence, ontology construction for ESD is essential to ensure credibility, consistency, to resolve lack of time, labor and competence and to diminish human error.

Design/methodology/approach

This paper presents the design of an automatic ontology framework through data mining techniques and subsequently depicts the diagnosis of ESD using the available knowledge- and rule-based system.

Findings

The rule language (Semantic Web Rule Language) and rule engine (Jess and Drools) have been integrated to explore the severity of the ESD and foresee the most appropriate class to be suggested.

Social implications

In this paper, the authors identify the efficiency of the rule engine and investigate the performance of the computational techniques in predicting ESD using three different measures.

Originality/value

Primarily, the approach assesses transfer time for total number of axioms exported to rule engine (Jess and Drools) while the other approach measures the number of inferred axioms (process time) using the rule engine while the third measure calculates the time to translate the inferred axioms to OWL knowledge (execution time).