bluuebunny/crossref_metadata_2025 huggingface dataset:
Valuable Hospital and Laboratory Practice in an Integrated Medical System for HIV Infection Prevention Interventions at a Veteran Affairs Medical Center (VAMC)
Authors: Petersen J M , Jhala D
Published: October 2020

Introduction/Objective

Patient focused integrated health systems have been described in the literature as being more likely to obtain positive health outcomes in their patient populations. This has particularly been the case for screenings with follow-up interventions as necessary. The usefulness of an Integrated Medical System in optimizing quality medical care for HIV infection and in monitoring patients already on Pre-Exposure Prophylaxis (PrEP) has been previously discussed in the literature. However, when it comes to the screening and initial identification of HIV- negative patients who may benefit from HIV preventive therapies such as PrEP, the literature is sparse. Here we report the useful initial identification of potential patients in a VAMC.

Methods

As part of a quality assurance/improvement project, a search in Vista/Fileman from June 2018 to February 2020 was performed for all patients with a positive sexually transmitted disease (STD) test result - PCR testing for gonorrhea/chlamydia and RPR - during this time period. A medical chart review was performed to determine the HIV status of the patient, and if negative for HIV, whether PrEP was discussed with the patient by the clinical primary care team or the infectious disease consult. The number of patients who ultimately began PrEP as a result of this initial identification was tabulated.

Results

A total of 58 unique patients who tested positive for an STD were successfully identified as being potential candidates for PrEP by the clinical primary care teams or the infectious disease consult in the Integrated Medical System, and as a result the possibility of PrEP was discussed with all 58. In the end, 28 of these patients started PrEP interventions after discussion with their clinical providers. In all patients, these patients were initially identified by a positive STD test result. This is out of a total of 220 HIV negative patients that had been reviewed by their respective clinical providers upon being alerted by the computerized patient record system.

Conclusion

The Integrated Medical System at the VAMC successfully screened and identified patients who may benefit from PrEP. This is a significant example of an integrated medical system successfully screening and providing quality care for identified patients who otherwise would not have had this health preserving intervention.
Resistant Bacteria Isolated from Blood Culture of Febrile Neutropenic Cancer Patients
Authors: Abdelmonem M , Gad AlKarim A , Eissa S , Boraik A , Shedid M
Published: October 2020

Introduction/Objective

Bacteremia is one of the major causes of life-threatening complications in patients with cancer. Significant changes in the spectrum of microorganisms isolated from blood culture BC have been reported in cancer patients over the past years.

This study aimed to determine the predominant bacterial species causing bacteremia among febrile neutropenic FN cancer patients at the National Cancer Institute in Egypt (NCI).

Methods

A total of 300 BC collected from 300 FN cancer patients at NCI, Cairo. All cases were in patients with a mean age of 51 years, 158 patients were male (53%) while 142 patients were females (47%). BC was collected for microbiological investigations. Identification of the isolated organisms by the cultural characters (Morphological of bacterial isolates, Gram stain reaction, motility test, and biochemical tests) for each organism using standard semi- automated techniques.

Results

68 (22.6%) BC were positive while 232 (77.4%) BC were negative. Gram-negative bacteria isolated and identified in 11 blood cultures (16.17%), while gram-positive isolates identified in 57 BC (83.8%). Among the Gram- negative organisms, 4 (5.8%) were Pseudomonas aeruginosa, 4 (5.8%) were E. coli, 1 (1.5%) was Klebssila pneumoni, 1 (1.5%) was Acintobacter and 1 (1.5%) was Citrobacter frenudiri. Among the Gram-positive organisms, Coagulase-negative Staphylococci CNS were most predominant in most cases 35 (61.4%). 7 (12%) were S. aureus, 5 (8%) were S. epidermises, 5 (8%) were Streptococcus spp., 1 (1.5%) were Listeria spp., 4 (5.88%) Achromobacter spp., 4 (5.88%) were Gram-Positive Cocci and 1(1.5%) Micrococcus spp. The study of R-factor in all positive BC showed the resistant bacterial isolates to the commonly used antimicrobial agents, especially to ampicillin and penicillin.

Conclusion

This study showed that patients with febrile neutropenia are vulnerable to developing bacteremia. the prevalence rate of bacteremia in post-chemotherapy FN in our center is relatively high compared to the national rate. Multidrug-resistant are the main cause of bacteremia in febrile cancer patients in Egypt. There is a need for ongoing antimicrobial surveillance to guide antimicrobial therapy and support the development of infection control programs in Egypt
Improved Across the Board Access to SARS-CoV-2 Laboratory Testing in an Integrated Medical System; the Veteran Affairs Medical Center (VAMC) Experience
Authors: Petersen J M , Dalal S , Jhala D
Published: October 2020

Introduction/Objective

Due to the spread of SARS-CoV-2 – the causative pathogen behind COVID-19, a significant impact on society including significant death, morbidity, strain on the nation’s medical systems, and an economic shutdown of many sectors has come to pass. While society has been affected by this virus, it has also been documented in the mainstream news that this pandemic has disproportionately affected non-white minority groups, and that access to testing for vulnerable populations have been limited. Similarly, previously published epidemiological data by Zuvekas et al. show that populations with health insurance, higher socioeconomic class, and white in race have received significantly better access to private health care resources. As veterans represent a vulnerable population, as part of quality assurance, testing data was reviewed to verify that this trend was not also affecting the VAMC.

Methods

As part of a quality assurance/quality improvement project, a retrospective manual review of all SARS-CoV- 2 RT-PCR tests performed at the VAMC from March 11th, 2020 to April 13th, 2020. These tests were reviewed within the computerized medical record system to determine the age, gender, and ethnicity of the patients. The demographic data from this search was compared with the population statistics of the major metropolitan city that the VAMC is located in.

Results

Out of 571 patients who were tested for SARS-CoV-2, 264 (46%) had an ethnic African-Americans background, 135 (24%) had an ethnic Caucasian or white background, 8 had an ethnic Hispanic background, 3 had an ethnic native Hawaiian or other Pacific Islander background, 2 had an ethnic Asian background (0.4%), and 1 had an ethnic American Indian or Alaskan Native background. The rest had left ethnicity unanswered or was unknown/declined to state. The majority of those tested were males (392 or 69%). Ages of patients tested ranged from 24 to 98 years of age. The ethnic distribution of those tested was like the ethnic distribution within the city where the VAMC was located.

Conclusion

Quality healthcare to the entire population also means that healthcare should be accessible to all members who require it. The VAMC offers broad access for testing to all its patients of all ethnicities. This demonstrates, in the changing healthcare landscape, one of the many advantages of the Veteran Affairs system.
Decreasing Extra Tube Collections in a Healthcare System
Authors: Evans K M
Published: October 2020

Introduction/Objective

To determine a mechanism for obtaining and utilizing data on extra specimens collected that were not used, monitoring collections and decreasing the need to collect these specimens in order to save the patient’s blood from being wasted, as well as the resources used to collect and house the extra specimens.

Methods

Internal database, Sunquest, and Tableau

Results

Starting in early 2017, statistics were pulled and analyzed by our Phlebotomy Best Practice committee in order to obatin a solid basis to review all extra specimens being collected (excluding blue, lavender, and lithium herparin tubes) by phlebotomy in order to save teh patient’s blood from being disposed of without being used for testing, continue to look for ways to maintain blood conservation and collections, cost effectiveness due to not having to use the supplies, as well as store the specimens that were not being used for testing.

Conclusion

As of January 2020, there has been a 30% decrease in collections (yearly - over 3 years), and a maximum 45% decrease in cost (thus far) of supplies and waste. It has been a larage patient and upper management satisfier; patient’s don’t question the number of tubes being taken, and the decrease in spending makes the VP happy!
B-Cell/Mixed Phenotype Acute Leukemia Following Lenalidomide Maintenance For Multiple Myeloma: A Study Of Two Cases
Authors: Fei F , Reddy V , Rosenblum F
Published: October 2020

Introduction/Objective

The incidence of patients with multiple myeloma (MM) followed by hematologic malignancies as second primary malignancy is around 0.8 – 3.1%. The majority of cases are myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), however, acute lymphoblastic or mixed phenotype leukemia can be rarely observed.

Methods

A retrospective chart review was performed for patients diagnosed with acute lymphoblastic or mixed phenotype leukemia from January 2009 through February 2020. Two patients were identified and the corresponding clinical data were reviewed.

Results

Case 1 was a 74-year old male diagnosed with pre-B ALL 5 years after an IgG Lambda MM. His MM therapy included Bortezomib-based chemotherapy followed by Lenalidomide maintenance. Pre-B diagnosis was confirmed on a pelvic lesion biopsy with sheets of intermediate sized cells (CD45+, PAX5+, CD34+, CD43+, CD10+, BCL6+ and BCL2+). The patient had 4 cycles of HyperCVAD chemotherapy, followed by Blinatumomab and Inotuzumab treatment. Unfortunately, the patient was referred to hospice 2 years after the diagnosis of ALL. Case 2 was a 69-year old male diagnosed with mixed phenotype acute leukemia 8 years after an lgA Lambda MM with del 13q and Trisomy 11. The patient was treated with Bortezomib-based chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HSCT) and Lenalidomide maintenance. Bone marrow biopsy showed around 79% blasts (CD34+, PAX-5+, CD79a+ and MPO+). Flow cytometry from bone marrow showed 90% precursor B cells, however MPO was negative. Furthermore, a DNTM3A p.T835M missense variant (25-30% fraction) was identified by next generation sequencing (NGS). The patient was scheduled for Hyper-CVAD chemotherapy.

Conclusion

Lenalidomide maintenance following auto-HSCT is considered a standard therapy for MM patients. Recent studies indicate that Lenalidomide maintenance is associated with an increased risk of second primary hematologic malignancies. Although AML and MDS are more commonly seen, ALL and rarely mixed phenotype leukemias can occur.
A Rare Case of Acute Interstitial Pneumonia Diagnosed at Autopsy
Authors: Conner E , Troxclair D , Khokhar H , Beversdorf W
Published: October 2020

Introduction/Objective

Acute interstitial pneumonia (AIP) is a rare disease clinically characterized by rapidly progressing respiratory failure in individuals with no history of respiratory illness or other inciting factors. While most often diagnosed in middle-aged adults, it may present in any age group. Initial presentation is described as influenza- like, and respiratory failure requiring ventilatory support often progresses within weeks to months. Prognosis is poor, with an estimated mortality rate approaching 80% without treatment.

Methods

We present the case of a 44-year-old male nonsmoker with no significant medical history, who presented in 2018 with 1.5 months of dyspnea and headache initially diagnosed as atypical pneumonia. Chest imaging revealed bilateral opacities; however, microbial workup revealed no evidence of infectious etiology. Autoimmune serology studies were likewise unrevealing. Despite aggressive supportive and medical management, he deteriorated to respiratory failure and succumbed.

Results

At autopsy, the lungs were symmetrically congested and edematous (combined weight 2,340 g) but free of evident consolidation or discrete lesions. Microscopic examination revealed diffuse alveolar damage with extensive hyaline membrane formation, interstitial edema, and fibroblastic proliferation. The vasculature was severely congested, and the alveoli contained hemorrhage and scattered macrophages. No fungal or mycobacterial elements were identified by staining. Based on the histologic features and clinical context, the diagnosis of AIP was made.

Conclusion

AIP is a rare, aggressive, and diagnostically challenging disease that includes a broad range of both clinical and histologic differentials. Timely recognition and intervention with aggressive respiratory support and high- dose glucocorticoids are the mainstays of clinical management. The diagnostic role of histology is significant, but hinges on early clinical consideration of AIP as disease progression may later preclude the biopsy procedure. We share this case to raise awareness of this rapidly progressive and diagnostically troubling interstitial lung disease while emphasizing the importance of clinicopathologic correlation.
Heterogeneity and Geographical Patterns of PD-L1 Positive Tumor Infiltrating Immune Cells in Colonic Adenocarcinoma
Authors: Messersmith L , Williams G , Broadwater` D R , Brady R
Published: October 2020

Introduction/Objective

Programmed death-ligand 1 (PD-L1) status is an important prognostic and predictive biomarker. PD-L1 status is difficult to accurately assess in tumor cells (TCs) due to tumor heterogeneity and lack of standardized histologic evaluation. PD-L1 expression by tumor infiltrating immune cells (TIICs) is an independent prognostic marker and may provide fewer diagnostic challenges, as TIICs appear less heterogeneous. We examined the geographical patterns of PD-L1 expression in TCs and TIICs in order to evaluate heterogeneity and ease of histological evaluation.

Methods

197 blocks of colonic adenocarcinoma from 33 patients were retrospectively reviewed and stained for PD- L1. PD-L1 was interpreted as positive or negative in the TCs and TIICs. Geographical patterns of expression were recorded for the TCs and the TIICs at the surface, center of tumor, and invasive margin. Geographical patterns were compared using a chi-square test.

Results

56% of blocks had PD-L1 positive TCs. 42.7% showed positive TCs at the invasive margin. 38.2% had positive TCs at the invasive margin and surface. No blocks had positive TCs at the center of the tumor. 79% of blocks had PD-L1 positive TIICs. 20% showed positive TIICs at the invasive margin. 37.4% had positive TIICs at the surface and invasive margin. 15.5% of TIICs expressed PD-L1 throughout the tumor. There was a statistically significant difference in PD-L1 expression on TCs versus TIICs in 4 of the 7 geographic patterns.

Conclusion

PD-L1 expression on TCs of colonic adenocarcinoma is more heterogeneous than PD-L1 expression by TIICs. TIICs express PD-L1 more consistently throughout the tumor and are easier to identify and report. PD-L1 expression by TIICs is an independent prognostic indicator and may be more useful than TCs when evaluating the tumor microenvironment and determining PD-L1 status.
Diagnostic Challenges And Clinical Implications For Systemic EBV-Associated T-Cell Lymphoproliferative Disorders Of Childhood
Authors: Yasa Benkli C , Marcogliese A , Elghetany M , Punia J , Fisher K , Curry C , El-Mallawany N , Allen C , McClain K , John T , Gaikwad A
Published: October 2020

Introduction/Objective

Systemic EBV-associated T-cell lymphoproliferative disorders of childhood (S-EBV-T-LPD) comprise three major forms: EBV-positive hemophagocytic lymphohistiocytosis (EBV-HLH), systemic EBV-positive T- cell lymphoma (S-EBV-TCL), and systemic T-cell chronic active EBV infection (S-T-CAEBV). These disorders are rare in children and young adults in Western countries and are associated with poor outcomes. Frequently patients were treated initially for EBV-HLH and subsequently found to have relapsed/refractory EBV-HLH vs S-EBV-TCL or overt EBV+ TCL, the latter of which requires different therapy than EBV-HLH. We report the clinicopathologic findings of 13 cases, including 8 previously reported. (PMID: 31099136)

Methods

Thirteen cases of S-EBV-T-LPD were identified at Texas Children’s Hospital from 1990 to 2020. Clinicopathologic and relevant laboratory parameters were recorded.

Results

Patients included six females and seven males of Hispanic (n=6), Asian (4), and Caucasian origins (3) ages 1-22 years (median 2). All had fever, hepatosplenomegaly, cytopenias, abnormal EBV serologies, and significantly elevated peripheral blood EBV- DNA load by quantitative PCR. Histologic features were variable ranging from EBV+ T-cell infiltrates with subtle architectural distortion and mild atypia to overt morphologic appearance of lymphoma.

Consistent findings were aberrant T-cell populations identified by immunohistochemistry (n=4) or bone marrow flow cytometry (n=9, 1-50%, mean 16%). Five patients were classified as overt EBV+ TCL with abnormal karyotyping identified in 3. Seven patients had pathology findings indistinguishable between EBV-HLH and S-EBV-TCL and were classified as EBV-HLH/S-EBV-TCL. One patient had S-T-CAEBV. Outcomes were dismal after HLH-directed immuno/chemotherapy protocols with/without bone marrow transplant as only three EBV-HLH/S-EBV-TCL patients were alive at 1.5, 2.5 months, and 9 years follow-up.

Conclusion

This series from North America demonstrate challenges in the diagnosis and management of S-EBV-T- LPD cases. Particularly, EBV-HLH and S-EBV-TCL, which require vastly different treatment strategies, may initially present with overlapping clinicopathological features. Further studies are needed to address clear diagnostic criteria to guide appropriate management.
Blood Provision for Cardiac Ablation (CA) Procedures in the Catheterization Laboratory; a Veteran Affairs Medical Center (VAMC) Experience in a Non-Trauma Center Setting
Authors: Petersen J M , Patel V , Jhala D
Published: October 2020

Introduction/Objective

Cardiac perforation is a life-threatening complication (~1% risk, with reported rates between 0.2% to 5%) of CA procedures. As cardiac perforation may lead to extensive bleeding, it would be reasonable for a medical center carrying out CA to be capable of arranging for a massive transfusion protocol and for surgical repair as required. However, there is sparse literature to guide a non-trauma medical center implementing a CA program on what the number of red blood cell (RBC) units for crossmatch should be for each case.

Methods

In interdisciplinary collaborative meetings, the CA program logistics were agreed to between the multiple clinical services. Given the case series on the amount of drained blood in complicated cases, there was agreement that three units of RBCs would be crossmatched for each case. Education was provided on the massive transfusion protocol and on blood bank procedures. As part of quality assurance/quality improvement, records were reviewed from the beginning of the CA program (10/1/2019) to 1/31/2019 to determine number of patient cases, crossmatched units, and transfused units for quality assurance purposes.

Results

A total of fifteen patients underwent CA procedures, for which three units were crossmatched for each patient. As there were no cardiac perforations with the cardiac ablation procedures so far, no units were transfused. The organized approach for ensuring adequate blood bank support and education led to the reassurance, alleviation of clinical anxiety, and building of a successful CA program. Education sessions completed with thorough understanding of blood bank procedures including the massive transfusion protocol, labeling of blood bank specimens, and on ordering of blood for crossmatch.

Conclusion

This study provides a reference that may provide helpful guidance to other blood banks on what the number of RBCs to be crossmatched prior to each CA procedure. Multidisciplinary collaborative meetings in advance are an essential component for ensuring adequate support for CA procedures or any new service that requires blood product support. Thorough education of clinical staff on blood bank procedures particularly the massive transfusion protocol is also recommended. This procedure for massive transfusion should be available to be referred to in real time.
Blood Requests and Utilization in Elective Surgical Patients in a Nigerian Teaching Hospital
Authors: Olatinwo A T , Bolarinwa A , Adeyemo T
Published: October 2020

Introduction/Objective

Although requesting for blood is a very common practice for patients for surgical interventions, the average requirement for a particular procedure is usually based on subjective anticipation of blood loss rather than on evidence based estimates. Over-ordering of blood components results in wasting of technical time, reagents and imposes extra cost on patients.

The objective of this study is to assess blood ordering and utilization in a Nigerian Tertiary Hospital.

Methods

A review of one year data collected from the records of all discharged surgical patients and blood bank registers was done. Blood utilization was calculated using crossmatch to transfusion ratio (C/T), transfusion probability (%T), and transfusion index (TI).

Results

A crossmatch request for 1,228 units for 569 patients was made. Requests was higher for gynaecological cases (24.8 %) followed by orthopaedic procedures and least for cardiothoracic and urological surgeries (1.4 % each). Out of the crossmatched units, 880 units was transfused for 373 patients. The overall of C/T, %T, and TI were 1.4, 65.6%, and 1.55 respectively. The highest C/T was observed in elective caesarean sections (2.25) and

neurosurgeries (2.2) while the lowest C/T was observed in oral maxillofacial surgeries (1.09)

Conclusion

Unnecessary crossmatching with minimal transfusion practice was observed in many elective surgical cases. Blood request pattern for elective surgeries needs to be revised and unnecessary requests minimized. There is a need for a Hospital blood transfusion committee which should come up with blood request policies and transfusion guidelines for elective surgical procedures and also conduct regular blood transfusion service audits.
FR-Match: robust matching of cell type clusters from single cell RNA sequencing data using the Friedman–Rafsky non-parametric test
Authors: Zhang Yun , Aevermann Brian D , Bakken Trygve E , Miller Jeremy A , Hodge Rebecca D , Lein Ed S , Scheuermann Richard H
Published: October 2020

Single cell/nucleus RNA sequencing (scRNAseq) is emerging as an essential tool to unravel the phenotypic heterogeneity of cells in complex biological systems. While computational methods for scRNAseq cell type clustering have advanced, the ability to integrate datasets to identify common and novel cell types across experiments remains a challenge. Here, we introduce a cluster-to-cluster cell type matching method—FR-Match—that utilizes supervised feature selection for dimensionality reduction and incorporates shared information among cells to determine whether two cell type clusters share the same underlying multivariate gene expression distribution. FR-Match is benchmarked with existing cell-to-cell and cell-to-cluster cell type matching methods using both simulated and real scRNAseq data. FR-Match proved to be a stringent method that produced fewer erroneous matches of distinct cell subtypes and had the unique ability to identify novel cell phenotypes in new datasets. In silico validation demonstrated that the proposed workflow is the only self-contained algorithm that was robust to increasing numbers of true negatives (i.e. non-represented cell types). FR-Match was applied to two human brain scRNAseq datasets sampled from cortical layer 1 and full thickness middle temporal gyrus. When mapping cell types identified in specimens isolated from these overlapping human brain regions, FR-Match precisely recapitulated the laminar characteristics of matched cell type clusters, reflecting their distinct neuroanatomical distributions. An R package and Shiny application are provided at https://github.com/JCVenterInstitute/FRmatch for users to interactively explore and match scRNAseq cell type clusters with complementary visualization tools.
Psoriasis-like skin disorder in transgenic mice expressing a RIG-I Singleton–Merten syndrome variant
Authors: Abu Tayeh Ahmed , Funabiki Masahide , Shimizu Shota , Satoh Saya , Sumin Lee , Iwakura Yoichiro , Kato Hiroki , Fujita Takashi
Published: October 2020

Mutations in DDX58 (DExD/H-box helicase 58), which encodes the cytoplasmic RNA sensor retinoic acid-inducible gene I (RIG-I), were recently identified in the rare autoimmune disease Singleton–Merten syndrome (SMS). We report the spontaneous development of psoriasis-like skin lesions as an SMS-like symptom in transgenic mice harboring one of the RIG-I SMS variants, E373A. Histological analysis revealed typical characteristics of psoriasis, including the abnormal proliferation and differentiation of keratinocytes leading to epidermal hyperplasia, and infiltrates consisting of neutrophils, dendritic cells and T cells. Levels of the IL-23/IL-17 immune axis cytokines were high in the skin lesions. Rag2−/− transgenic mice showed partial amelioration of the phenotype, with down-regulation of inflammatory cytokines, including IL-17A, suggesting the importance of lymphocytes for the pathogenesis similar to that of human psoriasis. Of note, IL-17A deficiency abolished the skin phenotype, and treatment using the JAK inhibitor tofacitinib not only prevented onset, but also improved the skin manifestations even after onset. Our study provides further evidence for the involvement of RIG-I activation in the onset and progression of psoriasis via type I interferon signaling and the IL-23/IL-17 axis.
An observational cohort study of bacterial co-infection and implications for empirical antibiotic therapy in patients presenting with COVID-19 to hospitals in North West London
Authors: Wang Liyang , Amin Amit K , Khanna Priya , Aali Adnan , McGregor Alastair , Bassett Paul , Gopal Rao Guduru
Published: October 2020

Objectives

To describe the prevalence and nature of bacterial co-infections in COVID-19 patients within 48 hours of hospital admission and assess the appropriateness of empirical antibiotic treatment they received.

Methods

In this retrospective observational cohort study, we included all adult non-pregnant patients who were admitted to two acute hospitals in North West London in March and April 2020 and confirmed to have COVID-19 infection within 2 days of admission. Results of microbiological specimens taken within 48 hours of admission were reviewed and their clinical significance was assessed. Empirical antibiotic treatment of representative patients was reviewed. Patient age, gender, co-morbidities, inflammatory markers at admission, admission to ICU and 30 day all-cause in-hospital mortality were collected and compared between patients with and without bacterial co-infections.

Results

Of the 1396 COVID-19 patients included, 37 patients (2.7%) had clinically important bacterial co-infection within 48 hours of admission. The majority of patients (36/37 in those with co-infection and 98/100 in selected patients without co-infection) received empirical antibiotic treatment. There was no significant difference in age, gender, pre-existing illnesses, ICU admission or 30 day all-cause mortality in those with and without bacterial co-infection. However, white cell count, neutrophil count and CRP on admission were significantly higher in patients with bacterial co-infections.

Conclusions

We found that bacterial co-infection was infrequent in hospitalized COVID-19 patients within 48 hours of admission. These results suggest that empirical antimicrobial treatment may not be necessary in all patients presenting with COVID-19 infection, although the decision could be guided by high inflammatory markers.
Bioavailability of the calcium salt of dl-methionine hydroxy analog compared with dl-methionine for nitrogen retention and the preference of nursery pigs for diets based on the 2 forms of methionine
Authors: Wang Minqi Q , Huyen La T T , Lee Jung W , Ramos Sheila H , Htoo John K , Kinh La V , Lindemann Merlin D
Published: October 2020

Experiments were conducted to determine the relative bioavailability (RBV) of the calcium salt of the hydroxy analog of dl-methionine (MHA-Ca, 84%) to dl-methionine (dl-Met, 99%) as Met sources fed to pigs. In experiment 1, 42 crossbred barrows (initial BW of 15.0 ± 0.7 kg) were allotted to 7 treatments in an N-balance study. The basal diet (BD) was formulated to contain 15.4% CP and 0.22% Met (70% of requirement). Diets included (1) BD, (2) BD + 0.025% dl-Met, (3) BD + 0.050% dl-Met, (4) BD + 0.075% dl-Met, (5) BD + 0.038% MHA-Ca, (6) BD + 0.077% MHA-Ca, and (7) BD + 0.115% MHA-Ca. An increase in dietary inclusion rates of both Met sources linearly increased (P < 0.01) N retained (g/d) and N retention (% of intake). Using linear slope-ratio regression, the RBV value of MHA-Ca to dl-Met for N retained (g/d) was 63.0% on a product-to-product basis (75.0% on an equimolar basis). In experiment 2, 40 crossbred barrows (initial BW of 15.5 ± 1.5 kg) were allotted to 5 treatments in another N-balance study. The BD was formulated to contain 17.0% CP and 0.22% Met (70% of requirement). Diets included (1) BD, (2) BD + 0.030% dl-Met, (3) BD + 0.060% dl-Met, (4) BD + 0.046% MHA-Ca, and (5) BD + 0.092% MHA-Ca. Increasing levels of dl-Met or MHA-Ca increased N retained (g/d) and N retention (% of intake) linearly (P < 0.001) and quadratically (P < 0.05). Using linear slope-ratio regression, a product-to-product RBV value of MHA-Ca to dl-Met was 68.4% (81.4% on an equimolar basis) for N retained (g/d). In experiment 3, 276 pigs (12 barrow and 11 gilt replicates; initial BW of 7.09 ± 1.1 kg) were used in 3 diet preference studies. Pigs were randomly allotted to 1 of 3 treatment comparisons of feed choice: (1) BD (0.23% Met) or BD + 0.07% dl-Met; (2) BD or BD + 0.0825% MHA-Ca, and (3) BD + 0.07% dl-Met or BD + 0.0825% MHA-Ca. Pigs consumed a higher percentage (55 vs. 45%; P = 0.008) of their total feed intake from the diet supplemented with 0.07% dl-Met in Comparison 1, but a lower percentage (45 vs. 55%; P = 0.003) of their total feed intake from the diet supplemented with 0.0825% MHA-Ca in Comparison 2. There was no diet preference for dl-Met or MHA-Ca in Comparison 3. The observed Met source preference differences occurred in the barrow replicates but not in the gilt replicates. These results demonstrated the mean RBV of MHA-Ca to dl-Met of 65.7% on a product-to-product (wt/wt) basis or 78.2% on an equimolar basis and that a preference for Met sources was observed in barrows but not in gilts.
The COVID-19 Pandemic and Ecological Connectivity
Authors: Clark Janine Natalya
Published: October 2020

The ongoing COVID-19 pandemic has affected multiple aspects of our lives. This interdisciplinary article reflects on the significance of the pandemic from a largely unexplored angle, through a focus on the key concept of ecological connectivity, which broadly refers to the inter-connections between diffe-Srent elements of an ecosystem. Examining the pandemic through the lens of ecological connectivity, the article also theorizes it (and zoonotic diseases more generally) as a violation of this connectivity. It uses this idea as a core thread for linking COVID-19, international criminal law and transitional justice. Its key argument in this regard is that war crimes and human rights violations can themselves be viewed, in part, as violations of ecological connectivity. This theorization, in turn, provides a novel basis for thinking about the wider ecological dimensions and legacies of war crimes and gross violations of human rights, and, by extension, the potential role of international criminal law and transitional justice in helping to restore damaged connectivities through a relational approach to justice.
Orbital eccentricity–multiplicity correlation for planetary systems and comparison to the Solar system
Authors: Bach-Møller Nanna , Jørgensen Uffe G
Published: October 2020

The orbit eccentricities of the Solar system planets are unusually low compared to the average of known exoplanetary systems. A power-law correlation has previously been found between the multiplicity of a planetary system and the orbital eccentricities of its components, for systems with multiplicities above two. In this study we investigate the correlation for an expanded data sample by focusing on planetary systems as units (unlike previous studies that have focused on individual planets). Our full data sample contains 1171 exoplanets, in 895 systems, and the correlation between eccentricity and multiplicity is found to follow a clear power law for all multiplicities above one. We discuss the correlation for several individual subsamples and find that all samples consistently follow the same basic trend regardless of e.g. planet types and detection methods. We find that the eccentricities of the Solar system fit the general trend and suggest that the Solar system might not show uncommonly low eccentricities (as often speculated) but rather uncommonly many planets compared to a ‘standard’ planetary system. The only outlier from the power-law correlation is, consistently in all the samples, the one-planet systems. It has previously been suggested that this may be due to additional unseen exoplanets in the observed one-planet systems. Based on this assumption and the power-law correlation, we estimate that the probability of a system having eight planets or more is of the order of 1 per cent, in good agreement with recent predictions from analyses based on independent arguments.
Cleaning our own dust: simulating and separating galactic dust foregrounds with neural networks
Authors: Aylor K , Haq M , Knox L , Hezaveh Y , Perreault-Levasseur L
Published: October 2020

Separating galactic foreground emission from maps of the cosmic microwave background (CMB) and quantifying the uncertainty in the CMB maps due to errors in foreground separation are important for avoiding biases in scientific conclusions. Our ability to quantify such uncertainty is limited by our lack of a model for the statistical distribution of the foreground emission. Here, we use a deep convolutional generative adversarial network (DCGAN) to create an effective non-Gaussian statistical model for intensity of emission by interstellar dust. For training data we use a set of dust maps inferred from observations by the Planck satellite. A DCGAN is uniquely suited for such unsupervised learning tasks as it can learn to model a complex non-Gaussian distribution directly from examples. We then use these simulations to train a second neural network to estimate the underlying CMB signal from dust-contaminated maps. We discuss other potential uses for the trained DCGAN, and the generalization to polarized emission from both dust and synchrotron.
Fast radio bursts: do repeaters and non-repeaters originate in statistically similar ensembles?
Authors: Cui Xiang-Han , Zhang Cheng-Min , Wang Shuang-Qiang , Zhang Jian-Wei , Li Di , Peng Bo , Zhu Wei-Wei , Wang Na , Strom Richard , Ye Chang-Qing , Wang De-Hua , Yang Yi-Yan
Published: October 2020

Fast radio bursts (FRBs) are the short, strong radio pulses lasting several milliseconds. They are subsequently identified, for the most part, as emanating from unknown objects at cosmological distances. At present, over 100 FRBs have been verified, and they are classified into two groups: repeating bursts (20 samples) and apparently non-repeating bursts (91 samples). Their origins, however, are still hotly debated. Here, we investigate the statistical classifications for the two groups of samples to see if the non-repeating and repeating FRBs have different origins by employing Anderson–Darling (A–D) test and Mann–Whitney–Wilcoxon (M–W–W) test. First, by taking the pulse width as a statistical variant, we found that the repeating samples do not follow the Gaussian statistics (may belong to a χ-square distribution), although the overall data and non-repeating group do follow the Gaussian. Meanwhile, to investigate the statistical differences between the two groups, we turn to M–W–W test and notice that the two distributions have different origins. Secondly, we consider the FRB radio luminosity as a statistical variant, and find that both groups of samples can be regarded as the Gaussian distributions under the A–D test, although they have different origins according to M–W–W tests. Therefore, statistically, we can conclude that our classifications of both repeaters and non-repeaters are plausible, that the two FRB classes have different origins, or that each has experienced distinctive phases or been subject to its own physical processes.
Final design and on-sky testing of the iLocater SX acquisition camera: broad-band single-mode fibre coupling
Authors: Crass J , Bechter A , Sands B , King D , Ketterer R , Engstrom M , Hamper R , Kopon D , Smous J , Crepp J R , Montoya M , Durney O , Cavalieri D , Reynolds R , Vansickle M , Onuma E , Thomes J , Mullin S , Shelton C , Wallace K , Bechter E , Vaz A , Power J , Rahmer G , Ertel S
Published: October 2020

Enabling efficient injection of light into single-mode fibres (SMFs) is a key requirement in realizing diffraction-limited astronomical spectroscopy on ground-based telescopes. SMF-fed spectrographs, facilitated by the use of adaptive optics (AO), offer distinct advantages over comparable seeing-limited designs, including higher spectral resolution within a compact and stable instrument volume, and a telescope independent spectrograph design. iLocater is an extremely precise radial velocity (EPRV) spectrograph being built for the Large Binocular Telescope (LBT). We have designed and built the front-end fibre injection system, or acquisition camera, for the SX (left) primary mirror of the LBT. The instrument was installed in 2019 and underwent on-sky commissioning and performance assessment. In this paper, we present the instrument requirements, acquisition camera design, as well as results from first-light measurements. Broad-band SMF coupling in excess of 35 per cent (absolute) in the near-infrared (0.97–1.31 ${\mu {\rm m}}$) was achieved across a range of target magnitudes, spectral types, and observing conditions. Successful demonstration of on-sky performance represents both a major milestone in the development of iLocater and in making efficient ground-based SMF-fed astronomical instruments a reality.
Photoionization feedback in turbulent molecular clouds
Authors: Sartorio Nina S , Vandenbroucke Bert , Falceta-Goncalves Diego , Wood Kenneth
Published: October 2020

We present a study of the impact of photoionization feedback from young massive stars on the turbulent statistics of star-forming molecular clouds. This feedback is expected to alter the density structure of molecular clouds and affect future star formation. Using the AMUN-Rad code, we first generate a converged isothermal forced turbulent density structure inside a periodic box. We then insert an ionizing source in this box and inject photoionization energy using a two-temperature pseudo-isothermal equation of state. We study the impact of sources at different locations in the box and of different source luminosities. We find that photoionization has a minor impact on the 2D and 3D statistics of turbulence when turbulence continues to be driven in the presence of a photoionizing source. Photoionization is only able to disrupt the cloud if the turbulence is allowed to decay. In the former scenario, the presence of an H ii region inside our model cloud does not lead to a significant impact on observable quantities, independent of the source parameters.
RBP2GO: a comprehensive pan-species database on RNA-binding proteins, their interactions and functions
Authors: Caudron-Herger Maiwen , Jansen Ralf E , Wassmer Elsa , Diederichs Sven
Published: October 2020

RNA–protein complexes have emerged as central players in numerous key cellular processes with significant relevance in health and disease. To further deepen our knowledge of RNA-binding proteins (RBPs), multiple proteome-wide strategies have been developed to identify RBPs in different species leading to a large number of studies contributing experimentally identified as well as predicted RBP candidate catalogs. However, the rapid evolution of the field led to an accumulation of isolated datasets, hampering the access and comparison of their valuable content. Moreover, tools to link RBPs to cellular pathways and functions were lacking. Here, to facilitate the efficient screening of the RBP resources, we provide RBP2GO (https://RBP2GO.DKFZ.de), a comprehensive database of all currently available proteome-wide datasets for RBPs across 13 species from 53 studies including 105 datasets identifying altogether 22 552 RBP candidates. These are combined with the information on RBP interaction partners and on the related biological processes, molecular functions and cellular compartments. RBP2GO offers a user-friendly web interface with an RBP scoring system and powerful advanced search tools allowing forward and reverse searches connecting functions and RBPs to stimulate new research directions.
HP1γ regulates H3K36 methylation and pluripotency in embryonic stem cells
Authors: Zaidan Nur Zafirah , Sridharan Rupa
Published: October 2020

The heterochromatin protein 1 (HP1) family members are canonical effectors and propagators of gene repression mediated by histone H3 lysine 9 (H3K9) methylation. HP1γ exhibits an increased interaction with active transcription elongation-associated factors in embryonic stem cells (ESCs) compared to somatic cells. However, whether this association has a functional consequence remains elusive. Here we find that genic HP1γ colocalizes and enhances enrichment of transcription elongation-associated H3K36me3 rather than H3K9me3. Unexpectedly, sustained H3K36me3 deposition is dependent on HP1γ. HP1γ-deleted ESCs display reduced H3K36me3 enrichment, concomitant with decreased expression at shared genes which function to maintain cellular homeostasis. Both the H3K9me3-binding chromodomain and histone binding ability of HP1γ are dispensable for maintaining H3K36me3 levels. Instead, the chromoshadow together with the hinge domain of HP1γ that confer protein and nucleic acid-binding ability are sufficient because they retain the ability to interact with NSD1, an H3K36 methyltransferase. HP1γ-deleted ESCs have a slower self-renewal rate and an impaired ability to differentiate towards cardiac mesoderm. Our findings reveal a requirement for HP1γ in faithful establishment of transcription elongation in ESCs, which regulates pluripotency.
Sequence dependent phase separation of protein-polynucleotide mixtures elucidated using molecular simulations
Authors: Regy Roshan Mammen , Dignon Gregory L , Zheng Wenwei , Kim Young C , Mittal Jeetain
Published: October 2020

Ribonucleoprotein (RNP) granules are membraneless organelles (MLOs), which majorly consist of RNA and RNA-binding proteins and are formed via liquid–liquid phase separation (LLPS). Experimental studies investigating the drivers of LLPS have shown that intrinsically disordered proteins (IDPs) and nucleic acids like RNA and other polynucleotides play a key role in modulating protein phase separation. There is currently a dearth of modelling techniques which allow one to delve deeper into how polynucleotides play the role of a modulator/promoter of LLPS in cells using computational methods. Here, we present a coarse-grained polynucleotide model developed to fill this gap, which together with our recently developed HPS model for protein LLPS, allows us to capture the factors driving protein-polynucleotide phase separation. We explore the capabilities of the modelling framework with the LAF-1 RGG system which has been well studied in experiments and also with the HPS model previously. Further taking advantage of the fact that the HPS model maintains sequence specificity we explore the role of charge patterning on controlling polynucleotide incorporation into condensates. With increased charge patterning we observe formation of structured or patterned condensates which suggests the possible roles of polynucleotides in not only shifting the phase boundaries but also introducing microscopic organization in MLOs.
Discovery and characterization of a fourth class of guanidine riboswitches
Authors: Lenkeit Felina , Eckert Iris , Hartig Jörg S , Weinberg Zasha
Published: October 2020

Riboswitches are RNAs that specifically sense a small molecule and regulate genes accordingly. The recent discovery of guanidine-binding riboswitches revealed the biological significance of this compound, and uncovered genes related to its biology. For example, certain sugE genes encode guanidine exporters and are activated by the riboswitches to reduce toxic levels of guanidine in the cell. In order to study guanidine biology and riboswitches, we applied a bioinformatics strategy for discovering additional guanidine riboswitches by searching for new candidate motifs associated with sugE genes. Based on in vitro and in vivo experiments, we determined that one of our six best candidates is a new structural class of guanidine riboswitches. The expression of a genetic reporter was induced 80-fold in response to addition of 5 mM guanidine in Staphylococcus aureus. This new class, called the guanidine-IV riboswitch, reveals additional guanidine-associated protein domains that are extremely rarely or never associated with previously established guanidine riboswitches. Among these protein domains are two transporter families that are structurally distinct from SugE, and could represent novel types of guanidine exporters. These results establish a new metabolite-binding RNA, further validate a bioinformatics method for finding riboswitches and suggest substrate specificities for as-yet uncharacterized transporter proteins.
PD-1+ Monocytes Mediate Cerebral Vasospasm Following Subarachnoid Hemorrhage
Authors: Jackson Christopher M , Choi John , Routkevitch Denis , Pant Ayush , Saleh Laura , Ye Xiaobu , Caplan Justin M , Huang Judy , McDougall Cameron G , Pardoll Drew M , Brem Henry , Tamargo Rafael J , Lim Michael
Published: October 2020

BACKGROUND

Cerebral vasospasm is a major source of morbidity and mortality following aneurysm rupture and has limited treatment options.

OBJECTIVE

To evaluate the role of programmed death-1 (PD-1) in cerebral vasospasm.

METHODS

Endovascular internal carotid artery perforation (ICAp) was used to induce cerebral vasospasm in mice. To evaluate the therapeutic potential of targeting PD-1, programmed death ligand-1 (PD-L1) was administered 1 h after ICAp and vasospasm was measured histologically at the level of the ICA bifurcation bilaterally. PD-1 expressing immune cell populations were evaluated by flow cytometry. To correlate these findings to patients and evaluate the potential of PD-1 as a biomarker, monocytes were isolated from the peripheral blood and analyzed by flow cytometry in a cohort of patients with ruptured cerebral aneurysms. The daily frequency of PD-1+ monocytes in the peripheral blood was correlated to transcranial Doppler velocities as well as clinical and radiographic vasospasm.

RESULTS

We found that PD-L1 administration prevented cerebral vasospasm by inhibiting ingress of activated Ly6c+ and CCR2+ monocytes into the brain. Human correlative studies confirmed the presence of PD-1+ monocytes in the peripheral blood of patients with ruptured aneurysms and the frequency of these cells corresponded with cerebral blood flow velocities and clinical vasospasm.

CONCLUSION

Our results identify PD-1+ monocytes as mediators of cerebral vasospasm and support PD-1 agonism as a novel therapeutic strategy.