bluuebunny/crossref_metadata_2025 huggingface dataset:
Spectroscopy of an extreme [O iii] emitting active galactic nucleus at
z
= 3.212: implications for the reionization era
Authors: Tang Mengtao , Stark Daniel P , Ellis Richard S , Charlot Stéphane , Feltre Anna , Shapley Alice E , Endsley Ryan
Published: November 2021

Reionization-era galaxies often display intense nebular emission lines, both in rest-frame optical ([O iii] + H β) and ultraviolet (UV; C iii], C iv). How such strong nebular emission is powered remains unclear, with both active galactic nuclei (AGNs) and hot stars considered equally viable. The UV continuum slopes of these early systems tend to be very blue (β < −2), reflecting minimal dust obscuration, young ages, and low metallicities. This contrasts with narrow-lined AGNs at $z$ ∼ 2−3, whose UV slopes are significantly redder (β > −1) than typical star-forming systems in the reionization era. To investigate the properties of AGNs in the reionization era, we have conducted a search for potential examples of rare analogues with blue continua at intermediate redshift ($z$ ∼ 2−3). Our goals are to determine whether AGNs with intense line emission and blue continua exist and thereby to establish the range of rest-frame UV and optical line ratios in this population. In this paper, we report the detection of an X-ray luminous AGN at $z$ = 3.21 (UDS-24561) with extreme [O iii] + H β line emission (equivalent width = 1300 Å) and a blue UV continuum slope (β = −2.34). MMT/Binospec and Keck/MOSFIRE spectra indicate rest-frame UV line ratios consistent with AGN photoionization models and rest-frame optical lines with both a narrow component [full width at half-maximum (FWHM) $=154\, {\rm km\, s}^{-1}$] and extended broad wings (FWHM $=977\, {\rm km\, s}^{-1}$), consistent with outflowing gas. We describe how such objects can be identified in future James Webb Space Telescope emission line surveys in the reionization era, thereby providing a valuable census of AGN activity at $z$ > 6 and understanding their contribution to cosmic reionization.
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

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.
The Compositional Turnover of Grapevine-Associated Plant Pathogenic Fungal Communities Is Greater Among Intraindividual Microhabitats andTerroirsthan Among Healthy and Esca-Diseased Plants
Authors: Geiger Adrienn , Karácsony Zoltán , Golen Richard , Váczy Kálmán Zoltán , Geml József
Published: November 2021

Grapevine trunk diseases (GTDs) are a major threat to the wine industry, causing yield loss and dieback of grapevines. While the increasing damage caused by GTDs in recent decades have spurred several studies on grapevine-associated pathogenic fungi, key questions about the emergence and severity of GTDs remain unanswered, including possible differences in plant pathogenic fungal communities in asymptomatic and symptomatic grapevines. We generated fungal DNA metabarcoding data from soil, bark, and perennial wood samples from asymptomatic and symptomatic grapevines sampled in three terroirs. We observed larger compositional differences in plant pathogenic fungi among different plants parts within grapevine plants than among individual grapevines. This is driven by the dominance of GTD-associated fungi in perennial wood and non-GTD pathogens in soil, as well as by the lack of significant differences among asymptomatic and Esca symptomatic grapevines. These results suggest that fungi generally associated with Esca disease belong to the core grapevine microbiome and likely are commensal endophytes and/or latent saprotrophs, some of which can act as opportunistic pathogens on stressed plants. In addition, we found significant compositional differences among sampling sites, particularly in soil, which suggest a certain influence of local edaphic and mesoclimatic factors on plant pathogenic fungal communities. Furthermore, the observed differences among terroirs in plant pathogenic fungal communities in grapevine woody parts indicate that environmental factors likely are important for the development of Esca disease and further studies are needed to investigate the abiotic conditions on fungal compositional dynamics in Esca-affected plants.
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.
An Adolescent with Chanarin-Dorfman Syndrome Presenting with Ichthyosis and Hepatic Steatosis
Authors: Habash Nawras , Wang Yaohong , Morava Eva , Ibrahim Samar H.
Published: November 2021

Chanarin-Dorfman syndrome also known as neutral lipid storage disease is a rare multisystemic autosomal recessive disorder. It is mostly encountered in patients of Mediterranean and Middle Eastern origin. Most patients are brought to medical attention secondary to dermatological manifestations namely ichthyosis. Here, we report a 10-year-old Kurdish male patient with ichthyosis, who was referred to pediatric liver clinic for transaminase elevation of unknown etiology despite elaborate workup. Histological findings on liver biopsy were consistent with nonalcoholic steatohepatitis. Genetic testing identified homozygous mutation C.776G>A (p.G259D) in the Abhydrolase domain containing 5 gene on chromosome 3 described in patients with Chanarin-Dorfman syndrome. After the initiation of a diet with high medium chain triglycerides/long chain triglycerides ratio, aerobic exercise, and vitamin E, the patient liver enzymes improved. Due to debilitating ichthyosis, he was started on acitretin therapy that was discontinued due to transaminases elevation. Patient is currently stable and doing well.
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.

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.
Physicochemical properties and antioxidant activities of ginger
(Zingiber officinale Roscoe) slices according to
temperature and duration of hot water treatment
Authors: Choi Ji-Young , Lee Yeong-Min , Kim Jiyoon , Kim Jungsoo , Jeong Saeul , Park Sanghyeok , Kim Minhyun , Moon Kwang-Deog
Published: November 2021

This study was conducted to determine the optimal hydrothermal pretreatment
conditions for manufacturing processed ginger products. Ginger slices heated at
different temperatures (60-100°C for 1 h) for varying durations (1-5 h at
80°C) were compared in terms of their physiochemical properties,
antioxidant activities, and functional compound contents. The pH and soluble
solid content decreased with increasing hydrothermal treatment temperature.
Browning occurred at temperatures > 80°C. The
2,2-diphenyl-1-picrahydrazyl and
2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging were
highest after heating at 80°C for 1 h, and the total phenolic compound
content showed a similar trend. As the hydrothermal treatment temperature and
duration increased, the 6-gingerol content decreased and the 6-shogaol content
generally increased. Based on sensory testing of ginger jeonggwa (with sugar
syrup) prepared using hot water-treated ginger slices, the optimal hot water
treatments were conducted at 70 and 80°C for 1 h, with no significant
difference between these temperatures in terms of smell, taste, and texture.
Therefore, hydrothermal treatment of ginger at 70-80°C for 1 h was a
suitable to improve the functionality and antioxidant ability while maintaining
the sensory quality. Therefore, this may be used in the production of processed
ginger.
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

δ 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

Polygenic 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

In 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

With 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

Background

Multiple 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.

Methods

The 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.

Results

A 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.

Conclusions

The 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

Covid-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

T 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.
SARS-CoV-2 triggered excessive inflammation and abnormal energy metabolism in gut microbiota
Authors: Zhou Tuoyu , Zeng Yufei , Wu Jingyuan , Li Junfeng , Yan Jun , Meng Wenbo , Han Hawen , Feng Fengya , He Jufang , Zhao Shuai , Zhou Ping , Wu Ying , Yang Yanling , Han Rong , Jin Weiling , Li Xun , Yang Yunfeng , Li Xiangkai
Published: November 2021

Specific roles of gut microbes in COVID-19 progression are critical. However, the circumstantial mechanism remains elusive. In this study, shotgun metagenomic or metatranscriptomic sequencing were performed on fecal samples collected from 13 COVID-19 patients and controls. We analyzed the structure of gut microbiota, identified the characteristic bacteria and selected biomarkers. Further, GO, KEGG and eggNOG annotation were employed to correlate the taxon alteration and corresponding functions. The gut microbiota of COVID-19 patients was characterized by the enrichment of opportunistic pathogens and depletion of commensals. The abundance of Bacteroides spp. displayed an inverse relationship to COVID-19 severity, whereas Actinomyces oris, Escherichia coli, and Gemmiger formicilis were positively correlated with disease severity. The genes encoding oxidoreductase were significantly enriched in SARS-CoV-2 infection. KEGG annotation indicated that the expression of ABC transporter was up regulated, while the synthesis pathway of butyrate was aberrantly reduced. Furthermore, increased metabolism of lipopolysaccharide, polyketide sugar, sphingolipids and neutral amino acids was found. These results suggested the gut microbiome of COVID-19 patients was correlated with disease severity and in a state of excessive inflammatory response. Healthy gut microbiota may enhance antiviral defenses via butyrate metabolism, whereas the accumulation of opportunistic and inflammatory bacteria may exacerbate the disease progression.
Prevalent mouse phenotypes in the unexplored druggable genome
Authors: Gulyaeva Olga , Hu Zicheng , Oprea Tudor , Lloyd K. C. Kent , Gomez Shawn , Roth Bryan L , McManus Michael T
Published: November 2021

Among the estimated ~23,000 protein encoding human genes, the class of ‘druggable genes’– defined by their ability to bind drug-like compounds– represents an enticing collection of targets for clinical intervention. Yet many if not most of these genes remain poorly understood and understudied. Here we evaluate three major classes of druggable genes (GPCRs, ion channels, and kinases) and found that a third of these remain largely ignored yet display significant mouse phenotypes upon genetic ablation. We show that both well-studied and understudied druggable genes share a similar number and spectrum of phenotypes. Moreover, many of the mouse phenotypes arising from the ablation of both well-studied and understudied druggable genes show similarities with symptoms in rare human diseases. Collectively these data diminish the notion that most poorly studied genes may not be especially ‘important’ and highlight therapeutic opportunities and potential disease models among poorly characterized druggable genes.
Egr3/Pilot, a zinc finger transcription factor, is rapidly regulated by activity in brain neurons and colocalizes with Egr1/zif268.
Authors: Yamagata K , Kaufmann W E , Lanahan A , Papapavlou M , Barnes C A , Andreasson K I , Worley P F
Published: November 2021

Programs of gene activation may underlie long-term adaptive cellular responses to extracellular ligands. We have used a differential cDNA cloning strategy to identify genes that are strongly induced by excitatory stimuli in the adult rat hippocampus. Here, we report the rat cDNA sequence of a zinc-finger transcription factor, Egr3/Pilot, and characterize its regulated mRNA expression in brain. Egr3 mRNA is rapidly and transiently induced in neurons of the hippocampus and cortex by electroconvulsive seizure. mRNA levels peak 2 hr after the seizure and remain elevated for as long as 8 hr. Egr3 mRNA is also rapidly induced in granule cells of the dentate gyrus by synaptic NMDA receptor activation elicited by patterned stimulation of the perforant pathway and by drugs that alter dopamine neurotransmission in the striatum. Basal levels of Egr3 mRNA in the cortex appear to be driven by natural synaptic activity because monocular deprivation rapidly decreases Egr3 mRNA in the deafferented visual cortex. Aspects of the protein structure, sequence-specific DNA binding, transcriptional activity, and regulation of Egr3 are highly similar to another zinc-finger transcription factor, Egr1/zif268. Moreover, we demonstrate colocalization of Egr3 and zif268 mRNAs in neurons of normal and stimulated cortex. Our studies suggest that interactions between these coregulated transcription factors may be important in defining long-term, neuroplastic responses.
How and when economic policy uncertainty influences firms' strategic change: the role of CEO turnover and organizational inertia
Authors: Zhong Xi , Chen Weihong , Ren Ge
Published: November 2021

Purpose

Many studies have examined the antecedents of firms' strategic change on a micro and meso level, but few studies have explored it from the macrolevel (e.g. economic policy uncertainty) perspective. This research draws attention to the impact of economic policy uncertainty on firms' strategic change.

Design/methodology/approach

This research empirically tests hypotheses based on a sample of listed firms in China during the period between 2010 and 2017.

Findings

Based on real options theory, the authors theorize and find that economic policy uncertainty will negatively affect firms' strategic change through the mediating effect of CEO turnover. Moreover, organizational inertia will strengthen the negative impact of economic policy uncertainty on CEO turnover and will weaken the positive impact of CEO turnover on firms' strategic change.

Originality/value

First, this research contributes to the strategic change literature by demonstrating the important impact of economic policy uncertainty on firms' strategic change. Second, this research expands the literature on the economic consequences of economic policy uncertainty. Third, this research clarifies the path and boundary conditions of economic policy uncertainty affecting strategic change by introducing the mediating effects of CEO turnover and the moderating effects of organizational inertia.
Antecedents of the attitude toward the athlete celebrities' human brand extensions
Authors: Koo Jakeun
Published: November 2021

Purpose

The present study aims to examine how consumers evaluate the extended human brands of athlete celebrities beyond their unique brand personality associated with sports. Athlete celebrities' unique image in sports is used as a human brand, and attitude toward the athlete brand extensions is investigated when the athlete's name is included in a new non-sport brand. The concepts of brand extensions were employed to develop the ideas of human brand extensions.

Design/methodology/approach

In total, 198 participants answered online survey questions before and after being informed of athlete brand extensions. Partial least squares structural equation modeling is utilized to test the hypotheses.

Findings

The survey results indicated that athlete–product fit and image transfer positively influenced attitude toward the extension. In addition, attitude toward the athlete brand extensions was significantly influenced by consumers' pre-existing attitude toward the celebrity; however, not by celebrity's expertise.

Originality/value

The research findings imply that some brand extension concepts are applicable to human brands to understand the effectiveness of athlete brand extensions for non-sport products.
Cantilever enhanced based photoacoustic detection of SF6 decomposition component SO2 using UV LED
Authors: Chen Tunan , Ma Fengxiang , Zhao Yue , Liao Zhenghai , Qiu Zongjia , Zhang Guoqiang
Published: November 2021

Purpose

This paper aims to establish a photoacoustic detection system for SO2 using UV-LED and testify its feasibility for sensitive measurement. The work in this paper can avoid potential crossover interference in infrared (IR) range and also balance the capability and cost of feasible excitation for photoacoustic detection system.

Design/methodology/approach

In this experimental work, a cantilever-enhanced–based photoacoustic SO2 detection system using an ultraviolet (UV) LED light source with a light power of 4 mW as the excitation was established.

Findings

A feasible photoacoustic detection system for SO2 using UV-LED was established. Experimental results demonstrate that the detection limit of the system can reach the level of 0.667 ppm, which can serve as a reference for the application of PAS in insulation fault diagnosis.

Originality/value

This work investigated the potential of using ultraviolet photoacoustic spectroscopy to detect trace SO2, which provided an ideal replacement of infrared-laser-based detection system. In this paper, a photoacoustic detection system using LED with a low light power was established. Low light power requirement can expand the options of light sources accordingly. In this paper, the absorption characteristics of SO2 in the presented detection system and ultraviolet range were studied. And the detection limit of the presented system was given. Both of which can provide reference to SO2 detection in ambient SF6.
Prefrontal cortex pyramidal neurons express functional Nav1.8 tetrodotoxin‐resistant sodium currents
Authors: Szulczyk Bartłomiej , Pasierski Michał , Gawlak Maciej
Published: November 2021

It has been repeatedly proved that Nav1.8 tetrodotoxin (TTX)‐resistant sodium currents are expressed in peripheral sensory neurons where they play important role in nociception. There are very few publications that show the presence of TTX‐resistant sodium currents in central neurons. The aim of this study was to assess if functional Nav1.8 TTX‐resistant sodium currents are expressed in prefrontal cortex pyramidal neurons. All recordings were performed in the presence of TTX in the extracellular solution to block TTX‐sensitive sodium currents. The TTX‐resistant sodium current recorded in this study was mainly carried by the Nav1.8 sodium channel isoform because the Nav1.9 current was inhibited by the −65 mV holding potential that we used throughout the study. Moreover, the sodium current that we recorded was inhibited by treatment with the selective Nav1.8 inhibitor A‐803467. Confocal microscopy experiments confirmed the presence of the Nav1.8 α subunit in prefrontal cortex pyramidal neurons. Activation and steady state inactivation properties of TTX‐resistant sodium currents were also assessed in this study and they were similar to activation and inactivation properties of TTX‐resistant sodium currents expressed in dorsal root ganglia (DRG) neurons. Moreover, this study showed that carbamazepine (60 µM) inhibited the maximal amplitude of the TTX‐resistant sodium current. Furthermore, we found that carbamazepine shifts steady state inactivation curve of TTX‐resistant sodium currents toward hyperpolarization. This study suggests that the Nav1.8 TTX‐resistant sodium channel is expressed not only in DRG neurons, but also in cortical neurons and may be molecular target for antiepileptic drugs such as carbamazepine.
Determination of stable nitrogen isotopic ratios of nitrate ions in ammonium nitrate
Authors: Hu Can , Huang Yang , Mei Hongcheng , Guo Hongling , Liu Zhanfang , Zhu Jun
Published: November 2021

Ammonium nitrate (AN) is one of the most commonly used explosives in criminal cases. The comparison and source‐tracing of AN is important for investigation of attribution and fingerprinting of an explosive used at different events. The stable isotope signature of AN is an important index for comparison and tracing. However, the characteristics of the stable nitrogen isotopic ratios of AN (δ15NNH4NO3) alone are not sufficient to achieve a fine comparison between different AN samples. To increase the comparison index and further improve the discriminability between stable nitrogen isotopic ratios of different ANs, a method of isolation and analysis of nitrate ions in AN was established using stable‐isotope‐ratio mass spectrometry (IRMS). The method was based on the principle that strong alkali react with AN to produce ammonia and nitrate. After the isolation, stable nitrogen isotopes of nitrate ions (δ15NNO3) were obtained using IRMS, and then the stable nitrogen isotopes of ammonium ions from AN (δ15NNH4) was calculated according to the principle of mass balance. The results show that the method is effective for the isolation of nitrate ions without notable isotope fractionation. The developed method was applied to analyze and discriminate AN samples from eight different cities in China. Three samples out of the initial eight AN samples with similar δ15NNH4NO3 values were further distinguished by their δ15NNH4 and δ15NNO3 values. The isolation and stable‐nitrogen isotopic analysis method developed for nitrate ions in AN is simple and effective, thereby increasing the discriminability of the stable isotope ratios in AN.
Estimation of body weight in captive Amur tigers (Panthera tigris altaica)
Authors: WANG Qi , SHI Chunmei , LIU Dan , JIANG Guangshun
Published: November 2021

So far, there has been no safe and convenient method to weigh the large fierce animals, like Amur tigers. To address this problem, we built models to predict the body weight of Amur tigers based on the fact that body weight is proportional to body measurements or age. Using the method of body measurements, we extracted the body measurements from 4 different kinds of the lateral body image of tigers, that is, total lateral image, central lateral image, ellipse fitting image, and rectangle fitting image, and then we respectively used artificial neural network (ANN) and power regression model to analyze the predictive relationships between body weight and body measurements. Our results demonstrated that, among all ANN models, the model built with rectangle fitting image had the smallest mean square error. Comparatively, we screened power regression models which had the smallest Akakai information criteria (AIC). In addition, using the method of age, we fitted nonlinear regression models for the relationship between body weight and age and found that, for male tigers, logistic model had the smallest AIC. For female tigers, Gompertz model had the smallest AIC. Consequently, this study could be applied to estimate body weight of captive, or even wild, Amur tigers safely and conveniently, helping to monitor individual health and growth of the Amur tiger populations.
miR‐125a‐5p increases cellular DNA damage of aging males and perturbs stage‐specific embryo development via Rbm38‐p53 signaling
Authors: Liang Kuan , Yao Liangyu , Wang Shuxian , Zheng Lu , Qian Zhang , Ge Yifeng , Chen Li , Cheng Xi , Ma Rujun , Li Chuwei , Jing Jun , Yang Yang , Yu Wanwan , Xue Tongmin , Chen Qiwei , Cao Siyuan , Ma Jinzhao , Yao Bing
Published: November 2021

An increasing number of men are fathering children at an older age than in the past. While advanced maternal age has long been recognized as a risk factor for adverse reproductive outcomes, the influence of paternal age on reproduction is incompletely comprehended. Herein, we found that miR‐125a‐5p was upregulated in the sperm of aging males and was related to inferior sperm DNA integrity as an adverse predictor. Moreover, we demonstrated that miR‐125a‐5p suppressed mitochondrial function and increased cellular DNA damage in GC2 cells. We also found that miR‐125a‐5p perturbed embryo development at specific morula/blastocyst stages. Mechanistically, we confirmed that miR‐125a‐5p disturbed the mitochondrial function by targeting Rbm38 and activating the p53 damage response pathway, and induced a developmental delay in a p21‐dependent manner. Our study revealed an important role of miR‐125a‐5p in sperm function and early embryo development of aging males, and provided a fresh view to comprehend the aging process in sperm.
Effects of competing food desert policies on store format choice among SNAP participants
Authors: Cuffey Joel , Beatty Timothy K. M.
Published: November 2021

We measure how Supplemental Nutrition Assistance Program (SNAP) participants respond to policies designed to improve access to retail food store formats that stock healthy foods, specifically grocery stores. Supply‐side policies seek to increase the supply of grocery stores by subsidizing store openings. Demand‐side policies seek to increase the demand for food from grocery stores by, for example, increasing benefits. Unique SNAP administrative data allow us to estimate and compare impacts of grocery store openings and a SNAP benefit increase at a fine geographic scale. We find both policies increase shopping at grocery stores relative to other store formats but observe substantive impacts for grocery store openings only among households in very close proximity to the opening. Furthermore, we find that the impacts are mediated by car ownership and food desert status. In particular, households without cars in food deserts exhibit the largest impact. Grocery store openings decrease SNAP spending shares primarily at ethnic stores, whereas benefit increases decrease SNAP spending shares at convenience stores. Neither policy decreases total SNAP spending at convenience stores. The spillover effects on shopping at other store formats therefore make the potential effect on access to healthy food ambiguous.