bluuebunny/crossref_metadata_2025_split huggingface dataset:
Placental Mammals Acquired Functional Sequences in NRK for Regulating the CK2–PTEN–AKT Pathway and Placental Cell Proliferation
Authors: Lestari Beni , Naito Satomi , Endo Akinori , Nishihara Hidenori , Kato Akira , Watanabe Erika , Denda Kimitoshi , Komada Masayuki , Fukushima Toshiaki 
Published: January 2022

Abstract
The molecular evolution processes underlying the acquisition of the placenta in eutherian ancestors are not fully understood. Mouse NCK-interacting kinase (NIK)-related kinase (NRK) is expressed highly in the placenta and plays a role in preventing placental hyperplasia. Here, we show the molecular evolution of NRK, which confers its function for inhibiting placental cell proliferation. Comparative genome analysis identified NRK orthologs across vertebrates, which share the kinase and citron homology (CNH) domains. Evolutionary analysis revealed that NRK underwent extensive amino acid substitutions in the ancestor of placental mammals and has been since conserved. Biochemical analysis of mouse NRK revealed that the CNH domain binds to phospholipids, and a region in NRK binds to and inhibits casein kinase-2 (CK2), which we named the CK2-inhibitory region (CIR). Cell culture experiments suggest the following: 1) Mouse NRK is localized at the plasma membrane via the CNH domain, where the CIR inhibits CK2. 2) This mitigates CK2-dependent phosphorylation and inhibition of PTEN and 3) leads to the inhibition of AKT signaling and cell proliferation. Nrk deficiency increased phosphorylation levels of PTEN and AKT in mouse placenta, supporting our hypothesis. Unlike mouse NRK, chicken NRK did not bind to phospholipids and CK2, decrease phosphorylation of AKT, or inhibit cell proliferation. Both the CNH domain and CIR have evolved under purifying selection in placental mammals. Taken together, our study suggests that placental mammals acquired the phospholipid-binding CNH domain and CIR in NRK for regulating the CK2–PTEN–AKT pathway and placental cell proliferation.
The scaffolding protein DLG5 promotes glioblastoma growth by controlling Sonic Hedgehog signaling in tumor stem cells
Authors: Kundu Somanath , Nandhu Mohan S , Longo Sharon L , Longo John A , Rai Shawn , Chin Lawrence S , Richardson Timothy E , Viapiano Mariano S 
Published: January 2022

Abstract

Background
Tumor invasion, a hallmark of malignant gliomas, involves reorganization of cell polarity and changes in the expression and distribution of scaffolding proteins associated with polarity complexes. The scaffolding proteins of the DLG family are usually downregulated in invasive tumors and regarded as tumor suppressors. Despite their important role in regulating neurodevelopmental signaling, the expression and functions of DLG proteins have remained almost entirely unexplored in malignant gliomas.

Methods
Western blot, immunohistochemistry, and analysis of gene expression were used to quantify DLG members in glioma specimens and cancer datasets. Over-expression and knockdown of DLG5, the highest-expressed DLG member in glioblastoma, were used to investigate its effects on tumor stem cells and tumor growth. qRT-PCR, Western blotting, and co-precipitation assays were used to investigate DLG5 signaling mechanisms.

Results
DLG5 was upregulated in malignant gliomas compared to other solid tumors, being the predominant DLG member in all glioblastoma molecular subtypes. DLG5 promoted glioblastoma stem cell invasion, viability, and self-renewal. Knockdown of this protein in vivo disrupted tumor formation and extended survival. At the molecular level, DLG5 regulated Sonic Hedgehog (Shh) signaling, making DLG5-deficient cells insensitive to Shh ligand. Loss of DLG5 increased the proteasomal degradation of Gli1, underlying the loss of Shh signaling and tumor stem cell sensitization.

Conclusions
The high expression and pro-tumoral functions of DLG5 in glioblastoma, including its dominant regulation of Shh signaling in tumor stem cells, reveal a novel role for this protein that is strikingly different from its proposed tumor-suppressor role in other solid tumors.
A Phase II Study of Pembrolizumab in Combination with Capecitabine and Oxaliplatin with Molecular Profiling in Patients with Advanced Biliary Tract Carcinoma
Authors: Monge Cecilia , Pehrsson Erica C , Xie Changqing , Duffy Austin G , Mabry Donna , Wood Bradford J , Kleiner David E , Steinberg Seth M , Figg William D , Redd Bernadette , Budhu Anuradha , Wang Sophie , Tandon Mayank , Ma Lichun , Wei Wang Xin , Greten Tim F 
Published: January 2022

Abstract

Background
We conducted a phase II study of the combination of pembrolizumab with capecitabine and oxaliplatin (CAPOX) in patients with advanced biliary tract carcinoma (BTC) to assess response rate and clinical efficacy. Exploratory objectives included correlative studies of immune marker expression, tumor evolution, and immune infiltration in response to treatment.

Patients and Methods
Adult patients with histologically confirmed BTC were enrolled and received oxaliplatin and pembrolizumab on day 1 of cycles 1-6. Capecitabine was administered orally twice daily as intermittent treatment, with the first dose on day 1 and the last dose on day 14 of cycles 1-6. Starting on cycle 7, pembrolizumab monotherapy was continued until disease progression. The primary endpoint was progression-free survival (PFS). Secondary endpoints were safety, tolerability, feasibility, and response rate. Immunohistochemistry (IHC) for PD-L1 and immune infiltrates was analyzed in paired tumor biopsies, as well as bulk transcriptome and exome profiling for five patients and single-cell RNA sequencing for one partial responder.

Results
Eleven patients enrolled, three of whom had received no prior systemic therapy. Treatment was well tolerated, and the most common treatment-related grade 3 or 4 adverse events were lymphocytopenia, anemia, and decreased platelet count. Three patients (27.3%) achieved a partial response, and six (54%) had stable disease. The disease control rate was 81.8%. The median PFS was 4.1 months with a 6-month PFS rate of 45.5%. Molecular profiling suggests qualitative differences in immune infiltration and clonal evolution based on response.

Conclusion
Capecitabine and oxaliplatin in combination with pembrolizumab is tolerable and a potentially effective treatment for refractory advanced BTC. This study highlights a design framework for the precise characterization of individual BTC tumors.

Trial Registration
This study was registered in ClinicalTrials.gov (NCT03111732).
Writing the History of Endemic Viral Disease: The Case of Bovine Viral Diarrhoea, c.1945–1980
Authors: Woods Abigail 
Published: January 2022

Summary
In Western countries during the post-World War II decades, endemic viral diseases were increasingly important to health. Such diseases have attracted limited historical attention. Due to changing methods of livestock production, they were particularly prevalent on the farm. This article uses a case study of the cattle disease, bovine viral diarrhoea (BVD), to demonstrate their historical significance. Spanning North America, the UK and Australia, it reveals the complex nature of BVD, and how and why its clinical, aetiological, epidemiological and host species identities evolved over time. This analysis sheds new light on how endemic viral diseases of livestock were experienced, understood and distributed in this period, and the influence exerted by changing agricultural practices, concerns about biological warfare and the development of virology as applied to veterinary medicine.
Leaving the Pervasive Barrio: Gang Disengagement under Criminal Governance
Authors: Cruz José Miguel , Rosen Jonathan D 
Published: January 2022

Abstract
Is it possible to disengage from street gangs in communities and districts where gang organizations rule? We argue that disengagement is possible when this process does not alter the social order that allows street gangs to continue controlling and establishing the rules that govern economic activities and relationships in the barrios they control. We explore the process of gang disengagement under criminal governance in El Salvador, a country plagued by the powerful MS-13 and Barrio 18 gangs. We conducted a survey with nearly 1,200 people with a history of gang membership and 25 in-depth interviews with former gang members. We find that disengagement through religious conversion allows the gang to continue exerting power over the deserters, while at the same time enforcing religious commitment to the congregation. The religious community provides the normative framework that reassures the gang that its former associates will not act against it, consolidating its local authority.
The protective impacts of Spirulina platensis against cisplatin-induced renal injury through the regulation of oxidative stress, pro-inflammatory cytokines and Bax/Bcl2
Authors: Abouzed Tarek Kamal , Soliman Mohamed Mohamed , Khatab Shymaa A , Gouda Wael M , Eldomany Ehab B , Dorghamm Doaa Abdullah 
Published: January 2022

Abstract
One of the main antineoplastic chemotherapy medications is cisplatin, of which nephropathy is a major side effect. In this current study, we aim to investigate the molecular protective effect of Spirulina platensis (SP) on cisplatin-induced nephrotoxicity. In total, 48 healthy male albino rats were allocated into 4 groups. Group 1 received saline intraperitoneally (IP) twice per week (normal rats). Group 2 received SP (100 mg/kg BW orally). Group 3 were injected with cisplatin (1.5 mg/kg IP) twice per week. Group 4 received SP and on the 4th day received cisplatin (1.5 mg/kg IP) for 21 days. After 3 weeks of experiment, blood and renal tissues were taken for serum analysis, gene expression using qRT-polymerase chain reaction, and renal histopathology. As per our findings, it was found that SP significantly ameliorated the alterations in body weight, relative kidney weight, and the disturbance in examined renal markers. Furthermore, SP recovered and restored cisplatin-induced oxidative stress biomarkers (MDA and NO) and antioxidant activity (SOD and GSH) and cisplatin-induced upregulation in the gene expression of TNF-α, inducible nitric oxide synthase, TGF1-β, IL-1β, and IL-6. Interestingly, these gene expressions were ameliorated by the SP pre-administration. Furthermore, cisplatin upregulated pro-apoptotic gene Bax, whereas it downregulated anti-apoptotic gene Bcl2. Interestingly, SP mitigated this alteration in apoptosis and anti-apoptotic associated genes. Renal histopathology revealed the protective impacts of SP against cisplatin-induced severe glomerular congestion, hemorrhage, inflammatory cell infiltration, degeneration, and severe necrosis in renal glomeruli and tubules. In conclusion, SP has a protective effect against cisplatin-induced renal damage through modulating oxidative stress and anti-inflammatory, anti-necrotic, and anti-apoptotic-associated genes.
Mapping of Crown Rust (Puccinia coronataf. sp.avenae) Resistance GenePc54and a Novel Quantitative Trait Locus Effective Against Powdery Mildew (Blumeria graminisf. sp.avenae) in the Oat (Avena sativa) Line Pc54
Authors: Admassu-Yimer Belayneh , Klos Kathy Esvelt , Griffiths Irene , Cowan Alexander , Howarth Catherine 
Published: January 2022

The Pc54 oat line carries the crown rust resistance gene Pc54 and an unknown gene effective against powdery mildew. In this study, two recombinant inbred line (RIL) populations were developed to identify the genomic locations of the two genes and produce lists of molecular markers with a potential for marker-assisted selection. The RILs and parents were phenotyped for crown rust and powdery mildew in a controlled environment. They were also genotyped using the 6K Illumina Infinium iSelect oat single nucleotide polymorphism (SNP) chip. Multiple interval mapping placed Pc54 on the linkage group Mrg02 (chromosome 7D) and the novel powdery mildew quantitative trait locus (QTL) QPm.18 on Mrg18 (chromosome 1A) both in mapping and in the validating populations. A total of 9 and 31 significant molecular markers were identified linked with the Pc54 gene and QPm.18, respectively. Reactions to crown rust inoculations have justified separate identities of Pc54 from other genes and QTLs that have previously been reported on Mrg02 except for qPCRFd. Pm3 is the only powdery mildew resistance gene previously mapped on Mrg18. However, the pm3 differential line, Mostyn, was susceptible to the powdery mildew race used in this study, suggesting that Pm3 and QPm.18 are different genes. Determining the chromosomal locations of Pc54 and QPm.18 is helpful for better understanding of the molecular mechanism of resistance to crown rust and powdery mildew in oats. Furthermore, SNPs and single sequence repeats that are closely linked with the genes could be valuable for developing PCR-based molecular markers and facilitating the utilization of these genes in oat breeding programs.[Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Professional Roles of Oncologic Specialty Physical Therapists in the United States
Authors: Stout Nicole L. , Pfalzer Lucinda , Drouin Jacqueline S , Litterini Amy , Tible Amy , Demarse Elizabeth 
Published: January 2022

Background:
Oncologic specialty physical therapists (OncPTs) are a growing discipline in the cancer workforce. The complexities of cancer care delivery and the multidimensional nature of cancer care teams require oncology providers to serve in professional roles beyond clinical care. This project aims to assess the professional roles that OncPTs play in cancer care delivery.

Methods:
A 27-item survey was developed by the Oncologic Specialty Council of the American Board of Physical Therapy Specialties and sent electronically to board-certified oncologic clinical specialists in the United States. The survey was open for 45 days. Demographics of the population and frequency data were analyzed in Qualtrics.

Results:
Fifty-seven complete surveys were received out of 106 eligible specialists (response rate 53%). Respondents were predominantly female (91%) and White (78%). Fifty-six percent (n = 32) had greater than 15 years of practice experience and 68% (n = 39) held DPTs. Seventy-three percent reported greater than 50% of their work week dedicated to oncology practice and 52.6% reported providing consultations or treatment in the physical space of a cancer center. All respondents have been board-certified OncPTs for at least 1 year. Providing clinical care accounted for 71% of the cohorts' work time and 14% was spent in program development (outside of clinical care). Specialists reported oncology-specific program development responsibilities across 3 themes: workforce development (mentoring and teaching peers and staff), establishing clinical practice standards (standardizing assessment tools and clinical pathways), and program assessment (quality improvement and research). The OncPT professional roles included leadership responsibilities within their health system (n = 24) and leadership or committee roles in rehabilitation-specific professional organizations (n = 55). No respondents reported serving in roles regarding research mentorship or advising on state policy or payer issues, and 1 respondent identified a role in advising on federal policy issues.

Conclusion:
Oncologic specialty physical therapists primarily serve clinical patient care roles. Aside from clinical practice, program development roles focus on rehabilitation-centric staff and student education and clinical pathways for rehabilitation care delivery. However, at the cancer care delivery system level, participation in professional roles beyond the rehabilitation clinic is less frequent. Gaps in participation are identified at the societal level with no representation from this cohort in payment and policy initiatives at the state and federal levels. We provide a roadmap to action that describes multilevel interventions to improve the integration of OncPTs into cancer care delivery. These findings may inform competencies for clinical specialists and guide residency program development.
Concise Definitive Review for Reinitiation of Antidepressants, Antipsychotics, and Gabapentinoids in ICU Patients
Authors: Cucci Michaelia D. , Chester Katleen W. , Hamilton Leslie A. 
Published: January 2022

OBJECTIVE:
Concise definitive review of the reinitiation of prior-to-admission neuropsychiatric medications (NPMs) in ICU patients.

DATA SOURCES:
Available literature on PubMed and MEDLINE databases.

STUDY SELECTION:
Available clinical trials and observational studies addressing the reinitiation of select NPMs (antidepressants, antipsychotics, and gabapentinoids) on various outcomes were included.

DATA EXTRACTION:
Eligible studies were identified by authors, and recommendations were summarized.

DATA SYNTHESIS:
Agitation and delirium are recognized as common complications of patients in the ICU. While there is literature that suggests patients can acutely withdraw from opioids, less data are known about withdrawal from NPM such as antidepressants, antipsychotics, and gabapentinoids. However, there is some literature that suggests reinitiating some NPMs may lead to reductions in agitation, delirium, and hospital and ICU length of stay.

CONCLUSIONS:
Additional larger studies are needed to evaluate the safety and efficacy of reinitiation of select prior-to-admission NPM to prevent agitation and delirium in ICU patients. Multiple factors for NPM reinitiation should be considered, such as reason for admission, organ dysfunction, available route of administration to provide prior-to-admission NPM, concomitant additional medications for agitation and delirium, and safety of these medications for patients in the ICU.
Hidden Telltale Signs in Hyperacute Ischemic Stroke Caused by Aortic Dissection
Authors: Ge Beihai , Wei Ninglin , Mo Yun , Qin Guangping , Li Huiyue , Xu Guolong 
Published: January 2022

Introduction:
Rapid identification of hidden telltale signs in hyperacute ischemic stroke caused by aortic dissection (AD) is challenging, mainly owing to the narrow time window for bridging therapy.

Case Report:
A 63-year-old man was referred for sudden right-side weakness accompanied by a decreased level of consciousness for almost 1 hour and 37 minutes. He had a history of hypertension. His skin was clammy, and on physical examination, there was involuntary chest thumping in the left upper limb. Hyperacute cerebral infarction was considered after no bleeding was observed on emergency head computed tomography, and intravenous thrombolysis with alteplase was administered immediately after. The patient was then taken to the catheter room, ready for endovascular thrombectomy. Stanford type A AD was found by cerebral angiography before endovascular thrombectomy. The infusion of alteplase was stopped immediately during cerebral angiography, but the patient’s blood pressure, heart rate, and blood oxygen were still declining progressively, and the degree of consciousness disturbance deepened. The patient died after the combined but failed rescue attempts of multiple departments.

Conclusion:
Hyperacute ischemic stroke caused by AD often hides some telltale signs. Clinicians should master basic clinical skills to exclude AD by looking for these telltale signs hidden in hyperacute ischemic stroke to avoid the fatal consequences of intravenous thrombolysis and/or cerebral angiography within the narrow window of time.
Postoperative Acute Kidney Injury in Williams Syndrome Compared With Matched Controls
Authors: Yokota Rumi , Kwiatkowski David M. , Journel Chloe , Adamson Greg T. , Zucker Evan , Suarez Geovanna , Lechich Kirstie M. , Chaudhuri Abanti , Collins R. Thomas 
Published: January 2022

OBJECTIVES:
Cardiovascular manifestations occur in over 80% of Williams syndrome (WS) patients and are the leading cause of morbidity and mortality. One-third of patients require cardiovascular surgery. Renal artery stenosis (RAS) is common in WS. No studies have assessed postoperative cardiac surgery–related acute kidney injury (CS-AKI) in WS. Our objectives were to assess if WS patients have higher risk of CS-AKI postoperatively than matched controls and if RAS could contribute to CS-AKI.

DESIGN:
This was a retrospective study of all patients with WS who underwent cardiac surgery at our center from 2010 to 2020. The WS study cohort was compared with a group of controls matched for age, sex, weight, and surgical procedure.

SETTING:
Patients underwent cardiac surgery and postoperative care at Lucile Packard Children’s Hospital Stanford.

PATIENTS:
There were 27 WS patients and 43 controls (31% vs 42% female; p = 0.36). Median age was 1.8 years (interquartile range [IQR], 0.7–3.8 yr) for WS and 1.7 years (IQR, 0.8–3.1 yr) for controls.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
Postoperative hemodynamics, vasopressor, total volume input, diuretic administration, and urine output were collected in the first 72 hours. Laboratory studies were collected at 8-hour intervals. Multivariable analysis identified predictors of CS-AKI.
Controlled for renal perfusion pressure (RPP) and vasoactive inotrope score (VIS), compared with controls, the odds ratio (OR) of CS-AKI in WS was 4.2 (95% CI, 1.1–16; p = 0.034). Higher RPP at postoperative hours 9–16 was associated with decreased OR of CS-AKI (0.88 [0.8–0.96]; p = 0.004). Increased VIS at hour 6 was associated with an increased OR of CS-AKI (1.47 [1.14–1.9]; p = 0.003). Younger age was associated with an increased OR of CS-AKI (1.9 [1.13–3.17]; p = 0.015).

CONCLUSIONS:
The OR of CS-AKI is increased in pediatric patients with WS compared with controls. CS-AKI was associated with VIS at the sixth postoperative hour. Increases in RPP and mean arterial pressure were associated with decreased odds of CS-AKI.
Comparison of infectious SARS-CoV-2 from the nasopharynx of vaccinated and unvaccinated individuals
Authors: Peña-Hernández Mario A. , Klein Jon , Malik Amyn A. , Coppi Andreas , Kalinich Chaney , Vogels Chantal B. F. , Silva Julio ,   Yale SARS-CoV-2 Genomic Surveillance Initiative, Peaper David R. , Landry Marie-Louise , Wilen Craig , Grubaugh Nathan D. , Schulz Wade , Omer Saad B. , Iwasaki Akiko 
Published: January 2022

ABSTRACTThe frequency of SARS-CoV-2 breakthrough infections in fully vaccinated individuals increased with the emergence of the Delta variant, particularly with longer time from vaccine completion. However, whether breakthrough infections lead to onward transmission remains unclear. Here, we conducted a study involving 125 patients comprised of 72 vaccinated and 53 unvaccinated individuals, to assess the levels of infectious virus in vaccinated and unvaccinated individuals. Quantitative plaque assays showed no significant differences in the titers of virus between these cohorts. However, the proportion of nasopharyngeal samples with culturable virus was lower in the vaccinated patients relative to unvaccinated patients (21% vs. 40%). Finally, time-to-event analysis with Kaplan-Myer curves revealed that protection from culturable infectious virus waned significantly starting at 5 months after completing a 2-dose regimen of mRNA vaccines. These results have important implications in timing of booster dose to prevent onward transmission from breakthrough cases.