bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemical Exposure-Induced Developmental Neurotoxicity in Head-Regenerating Schmidtea mediterranea
Authors: Morris Johnathan , Bealer Elizabeth J , Souza Ivan D S , Repmann Lauren , Bonelli Hannah , Stanzione III Joseph F , Staehle Mary M 
Published: November 2021

Abstract
The growing number of commercially used chemicals that are under-evaluated for developmental neurotoxicity (DNT) combined with the difficulty in describing the etiology of exposure-related neurodevelopmental toxicity has created a reticent threat to human health. Current means of screening chemicals for DNT are limited to expensive, time-consuming, and labor-intensive traditional laboratory animal models. In this study, we hypothesize that exposed head-regenerating planarian flatworms can effectively and efficiently categorize DNT in known developmental neurotoxins (ethanol and bisphenol A [BPA]). Planarian flatworms are an established alternative animal model for neurodevelopmental studies and have remarkable regenerative abilities allowing neurodevelopment to be induced via head resection. Here, we observed changes in photophobic behavior and central nervous system (CNS) morphology to evaluate the impact of exposure to low concentrations of ethanol, BPA, and BPA industry alternatives bisphenol F, and bisguaiacol on neurodevelopment. Our studies show that exposure to 1% v/v ethanol during regeneration induces a recoverable 48-h delay in the development of proper CNS integrity, which aligns with behavioral assessments of cognitive ability. Exposure to BPA and its alternatives induced deviations to neurodevelopment in a range of severities, distinguished by suppressions, delays, or a combination of the 2. These results suggest that quick and inexpensive behavioral assessments are a viable surrogate for tedious and costly immunostaining studies, equipping more utility and resolution to the planarian model for neurodevelopmental toxicity in the future of mass chemical screening. These studies demonstrate that behavioral phenotypes observed following chemical exposure are classifiable and also temporally correlated to the anatomical development of the CNS in planaria. This will facilitate and accelerate toxicological screening assays with this alternative animal model.
Impact of a Procalcitonin-Based Protocol on Antibiotic Exposure and Costs in Critically Ill Patients
Authors: Chow Jarva , Markossian Talar W. , Albarillo Fritzie S. , Donahey Elisabeth E. , Bobay Kathleen L. 
Published: November 2021

OBJECTIVES:
To examine the impact before and after adoption of a procalcitonin-based protocol to guide sepsis management has on antibiotic use, care costs, and outcomes of critically ill patients.

DESIGN:
Before-after study.

SETTING:
ICU of an academic tertiary care center.

PATIENTS:
Adults over 18 years old admitted to the ICU from January 1, 2017, to January 31, 2020.

INTERVENTIONS:
In this before-after study, we compared the use of medications, outcomes, and overall cost before and after the introduction of a procalcitonin-based protocol for evaluation and treatment of sepsis.

MEASUREMENTS AND MAIN RESULTS:
The final study cohort consisted of 1,793 patients admitted to the ICU, 776 patients pre-procalcitonin and 1,017 patients in the post-procalcitonin period. Patients were not different in the pre-procalcitonin adoption period compared with post-procalcitonin adoption with regard to gender, age (62.0 vs 62.6), race, or comorbidities. Patients admitted during the post-procalcitonin adoption period were less likely to receive the examined broad-spectrum antibiotics (odds ratio, –0.58; CI, –0.99 to –0.17; p < 0.01) than patients during the pre-procalcitonin adoption period. The odds of inhospital death did not differ after procalcitonin adoption when compared with before (0.87; CI, 0.70–1.09; p = 0.234). Total charges for each admission were significantly less in the post-procalcitonin adoption period $3,834.99 compared with pre-procalcitonin adoption $4,429.47 (p < 0.05). Patients post-procalcitonin adoption incurred $1,127.18 per patient less in total charges (–1,127.18; CI, –2,014.74 to –239.62; p = 0.013) after controlling for relevant factors.

CONCLUSIONS:
In critically ill patients in a large U.S. tertiary care hospital, the adoption of a procalcitonin-based protocol for evaluation and treatment of sepsis may be associated with decreased antibiotic use and significant cost savings, with no change in mortality.
Liposomal Bupivacaine Suspension for Pain Control Following Ocular Evisceration Surgery
Authors: Cox Shannon G. , Vicinanzo Matthew G. , Jacobs Sarah M. , Scruggs Jennifer , Long John A. 
Published: November 2021

Purpose:
To determine the effectiveness of retrobulbar liposomal bupivacaine for controlling postoperative pain following evisceration, compared with 0.75% bupivacaine.

Methods:
Randomized controlled trial, in which the postoperative pain scores from 24 patients who had retrobulbar liposomal bupivacaine after an evisceration were compared with the pain scores from 24 patients eviscerated using 0.75% bupivacaine.

Results:
Patients who received liposomal bupivacaine reported significantly less pain at 24 hours (2.0 out of 10, p = 0.01) and 48 hours (2.2 out of 10, p = 0.01) after surgery than patients who received 0.75% bupivacaine (5.7, and 5.0, respectively). The postoperative pain scores at 1 hour and at 7 days did not significantly differ between the 2 groups. Significantly, fewer patients who received liposomal bupivacaine (0%) than patients who received 0.75% bupivacaine (16.7%) returned emergently during the postoperative period for uncontrolled pain (p ≤ 0.001).

Conclusions:
Retrobulbar liposomal bupivacaine is more effective than 0.75% bupivacaine for controlling pain during the first 2 days after evisceration and should be considered for patients undergoing this procedure.
Laser Speckle Contrast Imaging of the Blood Perfusion in Glabellar Flaps Used to Repair Medial Canthal Defects
Authors: Berggren Johanna V. , Tenland Kajsa , Sheikh Rafi , Hult Jenny , Engelsberg Karl , Lindstedt Sandra , Malmsjö Malin 
Published: November 2021

Background:
The glabellar flap is a common technique for surgical repair after tumor excision in the medial canthal area. However, the outcome may be affected by partial flap necrosis. Little is known about the impact of surgery on blood perfusion and the postoperative course of reperfusion due to the absence of reliable and noninvasive perfusion monitoring techniques. The aim of this study was to use a modern imaging technique to assess blood perfusion in glabellar flaps.

Methods:
Glabellar flaps were used to repair medial canthal defects following tumor excision in 7 patients. Blood perfusion was monitored using laser speckle contrast imaging: during surgery, immediately postoperatively (0 weeks), and at follow-up, 1, 3, and 6 weeks after surgery.

Results:
Perfusion decreased gradually along the length of the flap, and reached a minimum 15 mm from the flap base. Perfusion in the proximal 20 mm of the flap was completely restored after 1 week, while the distal part of the flap was gradually reperfused over 6 weeks. Both the functional and esthetic surgical outcomes were excellent.

Conclusions:
The rapid reperfusion of the glabellar flap may be explained by its connection to the vascular network via the flap pedicle. In flaps longer than 20 mm, the distal part can be considered a free skin transplant, and a combination of a glabellar flap and a free skin graft could then be considered.
Long noncoding RNA KIF9-AS1 promotes cell apoptosis by targeting the microRNA-148a-3p/suppressor of cytokine signaling axis in inflammatory bowel disease
Authors: Yao Jun , Gao Ruoyu , Luo Minghan , Li Defeng , Guo Liliangzi , Yu Zichao , Xiong Feng , Wei Cheng , Wu Benhua , Xu Zhenglei , Zhang Dingguo , Wang Jianyao , Wang Lisheng 
Published: November 2021

Objective
Inflammatory bowel disease (IBD) is a chronic intestinal disease. This study was attempted to investigate the effects of long noncoding RNA KIF9-AS1 (KIF9-AS1) on the development of IBD and its underlying mechanism of action.

Methods
Quantitative real time PCR (qRT-PCR) was implemented to examine the expression of KIF9-AS1 and microRNA-148a-3p (miR-148a-3p). The IBD mouse model was induced by dextran sulfate sodium (DSS). The body weight, disease activity index (DAI) score, colon length and histological injury were used to evaluate the colon injury. The levels of proinflammatory cytokines were measured by ELISA. In vitro, IBD was simulated by DSS treatment in colonic cells. Then the apoptosis of colonic cells was detected by flow cytometry assay. Furthermore, a dual-luciferase reporter assay was used to demonstrate the interactions among KIF9-AS1, miR-148a-3p and suppressor of cytokine signaling (SOCS3).

Results
KIF9-AS1 expression was upregulated in IBD patients, DSS-induced IBD mice and DSS-induced colonic cells, whereas miR-148a-3p expression was downregulated. KIF9-AS1 silencing attenuated the apoptosis of DSS-induced colonic cells in vitro and alleviated colon injury and inflammation in DSS-induced IBD mice in vivo. Additionally, the mechanical experiment confirmed that KIF9-AS1 and SOCS3 were both targeted by miR-148a-3p with the complementary binding sites at 3′UTR. Moreover, miR-148a-3p inhibition or SOCS3 overexpression reversed the suppressive effect of KIF9-AS1 silencing on the apoptosis of DSS-induced colonic cells.

Conclusion
KIF9-AS1 silencing hampered the colon injury and inflammation in DSS-induced IBD mice in vivo, and restrained the apoptosis of DSS-induced colonic cells by regulating the miR-148a-3p/SOCS3 axis in vitro, providing a new therapeutic target for IBD.
Activation of Human Pancreatic Proteolytic Enzymes: The Role of Enteropeptidase and Trypsin
Authors: Freiburghaus Andreas U. , Roduner Jürg , Hadorn Hans Beat 
Published: November 2021

Objective:
The role of enteropeptidase and trypsin in the process by which pancreatic proteolytic zymogens are converted into active enzymes has been investigated in the past, using purified enzymes and proenzymes of animal origin. In the present study, we wanted to study this process under conditions which come near to the physiological situation, which prevails in the human duodenum and upper small intestine.

Patients and Methods:
Duodenal contents were collected from 2 patients with intestinal enteropeptidase deficiency. The samples expressed no tryptic activity and were used as the source of zymogens. Enteropeptidase or trypsin was added to these samples and the process of zymogen activation was followed by measuring trypsin and chymotrypsin activities.

Results:
When exogenous trypsin was added to the duodenal contents of patients with enteropeptidase deficiency, having no tryptic activity, activation of intrinsic trypsinogen was not observed. When purified porcine or human enteropeptidase was added to the same samples of duodenal contents, this resulted in a rapid, dose-dependent activation of trypsinogen followed by the activation of chymotrypsinogen.

Conclusion:
The study underlines the key role of enteropeptidase in the cascade process, which leads to the presence of active proteolytic enzymes in the human small intestine. The results also explain why patients with congenital deficiency of enteropeptidase are unable to activate trypsinogen by alternative pathways and therefore suffer from a severe disturbance of protein digestion with failure to thrive at young age, hypoproteinemia, and anemia.
Echocardiography and FDG-PET/CT scan in Gram-negative bacteremia and cardiovascular infections
Authors: Dahl Anders , Hernandez-Meneses M. , Perissinotti A. , Vidal B. , Quintana E. , Miro Jose M. 
Published: November 2021

Purpose of review
Current evidence on cardiovascular infections in Gram-negative blood stream infections (GNBSI) with focus on the use of transesophageal echocardiography (TEE) and 18F-Fluorodeoxyglucose - positron emission tomography/Computed tomography (FDG-PET/CT) in the diagnostic workup.

Recent findings
Most evidence focuses on characteristics of diagnosed cardiovascular infections and the proportion caused by GNBSI. These proportions are low (1–5%) when it comes to native and prosthetic valve endocarditis as well as cardiac implantable electronic device (CIED) infections whereas the proportion of vascular graft infections caused by GNBSI seems substantially higher (30–40%). Information on the prevalence of cardiovascular infection in patients with GNBSI is limited to a few studies finding around 3% endocarditis in patients with GNBSI and a prosthetic heart valve and 4–16% device-related infection in patients with CIED and GNBSI.

Summary
Patients with GNBSI and native or prosthetic valves should only undergo work-up for endocarditis (TEE and FDG-PET/CT) if they present GNBSI relapse or signs suggestive of endocarditis. CIED patients with GNBSI with Pseudomonas or Serratia spp. should undergo TEE and PET/CT because of the high prevalence of device-related infection. In other GNBs without IE suggestive signs, normal BSI treatment is reasonable and only cases with relapse need work-up. GNBSI in patients with vascular grafts should lead to consideration of PET/CT.
δ subvariants of SARS-COV-2 in Israel, Qatar and Bahrain: Optimal vaccination as an effective strategy to block viral evolution and control the pandemic
Authors: Yang Xiang-Jiao 
Published: November 2021

ABSTRACTδ variant has rapidly become the predominant pandemic driver and yielded four subvariants (δ1, δ2, δ3 and δ4). Among them, δ1 has been mainly responsible for the latest COVID-19 waves in India, Southeast Asia, Europe and the USA. A relevant question is how δ subvariants may have driven the pandemic in the rest of the world. In both Israel and Qatar, mRNA-based vaccination has been rolled out competitively, but the outcomes are quite different in terms of controlling the recent waves resulting from δ variant. This raises the question whether δ subvariants have acted differently in Israel and Qatar. In both countries, δ variant was first identified in April 2021 and δ1 subvariant constituted ∼50% δ genomes from April to May 2021. But the situation started to diverge in June 2021: In Israel, δ1 variant was encoded by 92.0% δ genomes, whereas this fraction was only 43.9% in Qatar. Moreover, a δ1 sublineage encoding spike T791I was identified in Israel but not Qatar. This sublineage accounted for 31.8% δ genomes sequenced in June 2021 and declined to 13.3% in October 2021. In August 2021, δ1 also became dominant in Qatar and a major sublineage encoding spike D1259H emerged. This sublineage has evolved further and acquired additional spike substitutions, including K97E, S255F, I693S, I712S, I1104L, E1258D and/or V1177I, in Qatar and other countries, such as Czech Republic, France and Mexico. Monthly distribution of the above sublineages suggests that the one from Qatar is much more of concern than that from Israel. Different from what was in Israel and Qatar, δ2 subvariant has also been important in Bahrain, whereas a δ2 sublineage encoding spike V1264L and A1736V of NSP3 was dominant in June 2021, but was gradually taken over by δ1 subvariant. These results suggest that δ1 and δ2 subvariants continue their evolution in different countries. The recent successful pandemic control in Israel, Qatar and Bahrain supports that δ1 and δ2 subvariants are still sensitive to timed vaccination, thereby urging the use of optimal immunity as a strategy to block SARS-COV-2 evolution and control the pandemic.
A combined polygenic score of 21,293 rare and 22 common variants significantly improves diabetes diagnosis based on hemoglobin A1C levels
Authors: Dornbos Peter , Koesterer Ryan , Ruttenburg Andrew , Cole Joanne B. ,   AMP-T2D-GENES Consortia, Leong Aaron , Meigs James B. , Florez Jose C. , Rotter Jerome I. , Udler Miriam S. , Flannick Jason 
Published: November 2021

AbstractPolygenic scores (PS), constructed from the combined effects of many genetic variants1, have been shown to predict risk or treatment strategies for certain common diseases2–6. As most PS to date are based on common variants7, the benefit of adding rare variation to PS remains largely unknown and methodically challenging. We developed and validated a method for constructing a rare variant PS and applied it to a previously identified clinical scenario, in which genetic variants modify the hemoglobin A1C (HbA1C) threshold recommended for type 2 diabetes (T2D) diagnosis6, 8–10. The resultant rare variant PS is highly polygenic (21,293 variants across 144 genes), depends on ultra-rare variants (72.7% of variants observed in <3 people), and identifies significantly more undiagnosed T2D cases than expected by chance (OR=2.71, p=1.51×10-6). A model combining the rare variant PS with a previously published common variant PS6 is expected to identify 4.9M misdiagnosed T2D cases in the USA, nearly 1.5-fold more than the common variant PS alone. These results provide a method for constructing complex trait PS from rare variants and suggest that rare variants will augment common variants in precision medicine approaches for common disease.
Immunity to COVID-19 in India through vaccination and natural infection
Authors: Sarraf Tresa Rani , Maity Shreyasi , Ghosh Arjun , Bhattacharjee Suchandan , Pani Arijit , Saha Kaushik , Chattopadhyay Dhrubajoyti , Ghosh Gourisankar , Sen Malini 
Published: November 2021

AbstractIn India, Corona Virus-2 Disease-2019 (COVID-19) continues to this day, although with subdued intensity, following two major waves of viral infection. Despite ongoing vaccination drives to curb the spread of COVID-19, the potential of the administered vaccines to render immune protection to the general population, and how this compares with the immune potential of natural infection remain unclear. In this study we examined correlates of immune protection (humoral and cell mediated) induced by the two vaccines Covishield and Covaxin, in individuals living in and around Kolkata, India. Additionally, we compared the vaccination induced immune response profile with that of natural infection, evaluating thereby if individuals infected during the first wave retained virus specific immunity. Our results indicate that while Covaxin generates better cell-mediated immunity toward the Delta variant of SARS-CoV-2 than Covishield, Covishield is more effective than Covaxin in inducing humoral immunity. Both Covishield and Covaxin, however, are more effective toward the wild type virus than the Delta variant. Moreover, the overall immune response resulting from natural infection in and around Kolkata is not only to a certain degree better than that generated by vaccination, especially in the case of the Delta variant, but cell mediated immunity to SARS-CoV-2 also lasts for at least ten months after the viral infection.
Evaluating the impact of RSV immunisation strategies on antibiotic use in England
Authors: Atkins Katherine E. , Hodgson David , Jit Mark , Davies Nicholas G. 
Published: November 2021

AbstractWith a sizable fraction of primary care antibiotics prescribing attributable to RSV, the promising suite of prophylactic pharmaceuticals against could reduce the need for antibiotics in addition to controlling respiratory disease. To assess the potential impact of RSV vaccines on the reduction in primary care antibiotic prescribing in England, we integrate results from a dynamic transmission model of RSV and a statistical attribution framework. Under base case assumptions, targeting children aged 5-14 years reduces antibiotic prescribing by 10.9 (8.0-14.2) antibiotic courses per 10,000 person years. This reduction in antibiotic use would gain 128 DALYs and avert 51,000 GBP associated with infections caused by drug resistant bacteria. Seasonally administering monoclonal antibodies (mAbs) to high risk infants under 6 months is the most efficient strategy (reducing per person year antibiotic prescribing by 2.6 (1.9-3.3) antibiotic courses per 1,000 mAb courses).
Development of a Decision Support Tool for Acute Appendicitis
Authors: Rosen Joshua E. , Liao Joshua M. , Flum David R. , Kohler Jonathan E. , Davidson Giana H. 
Published: November 2021

AbstractBackgroundMultiple randomized controlled trials have shown that it is safe and effective to treat appendicitis with antibiotics or surgery. There are no tools available to assist surgeons and their patients in choosing the optimal treatment for each individual patient. Here we describe the development of a new decisions support tool (DST) for acute appendicitis and place it in the context of international guidelines for decision aid development.MethodsThe stakeholder engagement and development process for the DST is described. The DST and its development process are placed in the context of the International Patient Decision Aid Standards (IPDAS) and the DEVELOPTOOLS checklist for a user-centered design process.ResultsA diverse group of over 60 stakeholders were involved in the needs-assessment, development, and evaluation of the DST. The development process met 11/11 of the scored items on the DEVELOPTOOLS checklist. Of the 34 applicable IPDAS items, the current version of the DST meets 31 of them including 6/6 qualifying criteria, 6/6 certification criteria, and 18/22 quality criteria.ConclusionsThe novel appendicitis DST was developed with the input of multiple stakeholders. The development process and the tool itself complies with best practices recommended by the IPDAS.
A mathematical model for repetitive behaviors of Covid-19
Authors: Nishimoto Yoshiro , Inoue Kenichi 
Published: November 2021

AbstractCovid-19 pandemic waves have been hitting us again and again in the past couple years in many countries, while the reason why they come in such repetitive manners remains unexplained, which have brought us with lingering anxieties and economic stagnations.We proposed a mathematical model to describe the mechanism of the repetitive appearance of the number of new cases based upon the SIQR model in which Q (quarantined infectors) were distinguished from I (un-quarantined ones). The repetitive behavior of the pandemic was simulated by an activator-inhibitor system around a fixed point in a phase space as a kind of self-organized oscillations. Periods between each wave were confirmed to be approximately similar. Repetitive behaviors were also observed in actual Covid-19 data.Practical policies and actions were discussed on the ways to effectively control the repetition of pandemic, and proactive PCR test especially after the peak-out stage is highly recommended.
Oncogenic and Tumor Suppressor Functions for Lymphoid Enhancer Factor 1 in a Murine Model of T Acute Lymphoblastic Leukemia
Authors: Carr Tiffany , McGregor Stephanie , Dias Sheila , Verykokakis Mihalis , LeBeau Michelle M. , Xue Hai-Hui , Bartom Elizabeth T. , Kee Barbara L. 
Published: November 2021

AbstractT lymphocyte acute lymphoblastic leukemia (T-ALL) is a heterogeneous disease affecting T cells at multiple stages of their development and is characterized by frequent genomic alterations. The transcription factor LEF1 is inactivated through mutation in a subset of T-ALL cases but elevated LEF1 expression and activating mutations have also been identified in this disease. Here we show, in a murine model of T-ALL, that the developmental timing of Lef1 mutation impacts its ability to function as a cooperative tumor suppressor or oncogene. T cell transformation in the presence of LEF1 allows leukemic cells to become addicted to its presence. In contrast, deletion prior to transformation both accelerates leukemogenesis and results in leukemic cells with altered expression of genes controlling receptor signaling pathways. Our data demonstrate that the developmental timing of Lef1 mutations impact its apparent oncogenic or tumor suppressive characteristics and demonstrate the utility of mouse models for understanding the cooperation and consequence of mutational order in leukemogenesis.