bluuebunny/crossref_metadata_2025 huggingface dataset:
Amylin: new insight into pathogenesis, diagnosis, and prognosis of non-insulin-dependent diabetes-mellitus-related cardiomyopathy
Authors: Xie Jiaying , Tong Zhoujie , Shen Longfei , Shang Yuanyuan , Li Yulin , Lu Bin , Ma Weixuan , Zhang Wei , Zhong Ming
Published: January 2022

Co-secretion with insulin, highly amyloidogenic human amylin is considered to contribute to the initiation and progression of diabetic heart complications, despite other situations such as hypertension and atherosclerosis. In response to insulin resistance, hyperinsulinemia, and consequently hyperamylinemia, is common in prediabetic patients, where highly concentrated amylin is prone to form amylin oligomers, which further assemble into fibrils and amyloids with high β-sheet content. The infusion and deposition of oligomeric amylin in myocytes cause a series of consequences, including cytosolic Ca2+ dysregulation, calmodulin activation, myocyte hypertrophy, and ventricular stiffness, eventually leading to heart failure. In this review, we present the latest reports of amylin-related heart complications, provide new insights, and state the underlying pathogenesis, diagnosis, possible treatment, and prevention of diabetic cardiomyopathy.
Cost Utility of Schlemm’s Canal Microstent Injection With Cataract Surgery for Open-angle Glaucoma in the US Medicare System
Authors: Atik Alp , Rhodes Lindsay A. , Samuels Brian C. , Mennemeyer Stephen T. , Girkin Christopher A.
Published: January 2022

Précis:

Hydrus microstent (HMS) implantation at the time of cataract surgery appears to be cost-effective in mild-to-moderate glaucoma. However, long-term follow-up is essential for a full assessment of device performance, safety and cost-effectiveness.

Purpose:

The aim was to assess the societal cost-utility to the US Medicare system of implanting HMS with cataract surgery versus cataract surgery alone in patients with open-angle glaucoma.

Patients:

Markov model cohort of patients with mild-to-moderate open-angle glaucoma and visually significant cataract.

Methods:

Patients received HMS during cataract surgery versus cataract surgery alone, in a deterministic model over a 2-year horizon using TreeAge software. Both arms received additional ocular hypotensive agents to control intraocular pressure. Treatment effect of HMS was measured as mean number of ocular hypotensive medications and intraocular pressure, which directly impacted transition probabilities. Health states included the Hodapp-Parrish-Anderson glaucoma stages (mild, moderate, advanced, blind) and death. One-way sensitivity and probabilistic sensitivity analyses were conducted on device efficacy and longer time horizons.

Results:

At 2 years, HMS with cataract surgery in mild glaucoma had an incremental cost-utility ratio of USD 38,346.43 per utility gained, compared with cataract surgery alone. Probabilistic sensitivity analysis was cost-effective in 61.4% of iterations for HMS+cataract surgery. The probability of side-effects with eye drops, utility decrement with side-effects, cost of the HMS and real-world efficacy rate had the greatest impact on model outcomes. HMS must be 85.60% as effective as published data to maintain cost-effectiveness at a willingness-to-pay threshold of USD 50,000. The incremental cost-utility ratio of HMS with cataract surgery in moderate glaucoma was USD 42,895.38.

Conclusions:

HMS implantation during cataract surgery appears to be cost-effective for patients with mild-to-moderate glaucoma. Nevertheless, more long-term safety and efficacy data are required.
Acute Respiratory Failure and Mechanical Ventilation in Women With COVID-19 During Pregnancy
Authors: Troiano Nan H. , Richter Amber , King Cecilia
Published: January 2022

Symptomatic pregnant women with coronavirus disease-2019 (COVID-19) are at increased risk of severe disease and death compared with symptomatic nonpregnant females of reproductive age. Among those who become critically ill, profound acute hypoxemic respiratory failure is the dominant finding. Significant morbidity and mortality from COVID-19 are largely due to acute viral pneumonia that evolves to acute respiratory distress syndrome. Admission of these patients with critical disease to an intensive care unit and initiation of invasive mechanical ventilation may be indicated. Effective ventilatory support can be challenging in the COVID-19 patient population, even more so when the need occurs in a woman during pregnancy. Key respiratory changes during pregnancy are reviewed. Principles related to maternal-fetal oxygen transport, assessment of ventilation and oxygenation status, and oxygenation goals are also reviewed. Selected concepts related to mechanical ventilatory support for the woman with COVID-19 and acute respiratory failure during pregnancy are presented including indications for ventilatory support, noninvasive support, and invasive ventilator management. Challenges in providing care to this patient population are identified as well as strategies to address them going forward.
Restricted use of copy and paste in electronic health records potentially improves healthcare quality
Authors: Cheng Chun-Gu , Wu Ding-Chung , Lu Jui-Cheng , Yu Chia-Peng , Lin Hong-Ling , Wang Mei-Chuen , Cheng Chun-An
Published: January 2022

The copy-and-paste feature is commonly used for clinical documentation, and a policy is needed to reduce overdocumentation. We aimed to determine if the restricted use of copy and paste by doctors could improve inpatient healthcare quality.

Clinical documentation in an inpatient dataset compiled from 2016 to 2018 was used. Copied-and-pasted text was detected in word templates using natural language programming with a threshold of 70%. The prevalence of copying and pasting after the policy introduction was accessed by segmented regression for trend analysis. The rate of readmission for the same disease within 14 days was assessed to evaluate inpatient healthcare quality, and the completion of discharge summary notes within 3 days was assessed to determine the timeliness of note completion. The relationships between these factors were used cross-correlation to detect lag effect. Poisson regression was performed to identify the relative effect of the copy and paste restriction policy on the 14-day readmission rate or the discharge note completion rate within 3 days.

The prevalence of copying and pasting initially decreased, then increased, and then flatly decreased. The cross-correlation results showed a significant correlation between the prevalence of copied-and-pasted text and the 14-day readmission rate (P < .001) and a relative risk of 1.105 (P < .005), with a one-month lag. The discharge note completion rate initially decreased and not affected long term after restriction policy.

Appropriate policies to restrict the use of copying and pasting can lead to improvements in inpatient healthcare quality. Prospective research with cost analysis is needed.
The effect of acupuncture on condition being studied emotional disorders in patients with postpartum
Authors: Luo Ning , Wang Yiyi , Xia Yunfan , Tu Mingqi , Wu Xiaoting , Shao Xiaomei , Fang Jianqiao
Published: January 2022

Background:

As one of the common postpartum diseases, postpartum emotional disorders (PEDs) mainly include postpartum depression, postpartum anxiety, posttraumatic stress disorder, and obsessive-compulsive disorder, which significantly affect the patient's quality of life. Acupuncture has been widely used as a popular alternative complementary therapy for the treatment of PEDs. Nevertheless, its effectiveness and safety remain uncertain. Hence, the first systematic review and meta-analysis will be urgently executed to explore the effectiveness and safety of acupuncture in the treatment of PEDs.

Methods:

Eight databases will be searched, including the PubMed, Web of Science, EMBASE, the Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, Wanfang Database, and Technology Periodical Database. Only randomized controlled trials of acupuncture for PEDs will be considered. The languages are limited to English and Chinese. All publications were retrieved by 2 researchers independently. Assessment of the Edinburgh Postpartum Depression Scale will be dedicated as a primary outcome, and secondary outcomes include the Hamilton Anxiety Inventory, the Hamilton Depression Inventory, the Orientation to Life Questionnaire (sense of coherence 29-item scale), and adverse effects of acupuncture. The Cochrane Risk of Bias tool will be used to assess the quality of the eligible publications. Additionally, the level of evidence for results will be evaluated by using the Grades of Recommendation, Assessment, Development, and Evaluation method. All data will be analyzed statistically by using RevMan V.5.3 software.

Results:

This study will provide a high level of the evidence-based basis for the effectiveness and safety of acupuncture in the treatment of PEDs.

Conclusion:

The findings of this study will assess the safety, efficacy, and adverse effects of acupuncture in the treatment of PEDs.

Ethics and dissemination:

No ethical approval is required as patient data will not be collected. In addition, the results of this meta-analysis will be disseminated through publication in peer-reviewed scholarly journals or relevant academic conferences.

Registration number:

INPLASY 2021120091.
Assessing Depressive Symptoms in Patients With Cancer Treated With Interleukin-2
Authors: McClintock Shawn M. , Dail Robin B. , Howe-Martin Laura S. , Mann Tara K. , Bailey Donald E.
Published: January 2022

Background

High-dose interleukin-2 is a therapy available for individuals with renal cell carcinoma; however, it can produce adverse effects, specifically depressive symptoms. There is limited information regarding the trajectory of depressive symptoms and measurement-based care assessment of depressive symptoms.

Objective

The purpose was to describe the trajectory of depressive symptoms and compare 2 depression measures.

Methods

A descriptive, mixed-method case study approach was used to describe the longitudinal trajectory of depressive symptoms The qualitative assessment included a journal entry and an interview. The quantitative depression symptom severity measures included the 8-item self-report Patient-Reported Outcomes Measurement Information System Depression and the 30-item Inventory of Depressive Symptomatology–Clinician Rated (IDS-C).

Results

Ten cases were enrolled. The maximum number of interleukin-2 doses that any patient received within a single hospitalization ranged from 4 to 12. Mean scores on the 8-item Patient-Reported Outcomes Measurement Information System Depression showed no changes in depressive symptoms from pretreatment to posttreatment, nor across hospitalizations. Mean total scores on the IDS-C increased from “normal” to “mild severity” depressive symptom range across all treatment cycles, suggesting transient depressive symptoms within hospitalizations. Qualitative data from the case supported the IDS-C increase, suggesting that the patient developed depressive symptoms pretreatment to posttreatment.

Conclusions

Understanding the trajectory of depressive symptoms allows for the identification of critical time points when depressive symptoms present and change across treatment. It is critical to use measurement-based care using validated measures to assess for the presence and changes in depressive symptoms.

Implications for Practice

Validated self-report or clinician-rated depression symptom measures should be used to document the presence or absence of depressive symptoms in this population.
The Effectiveness of a Self-management Program of Bowel Dysfunction in Patients With Mid and Low Rectal Cancer After Sphincter-Preserving Surgery
Authors: Li Cong , Li Zhao-Yu , Lu Qian , Zhou Yu-Jie , Qin Xue-Ying , Wu Ai-Wen , Pang Dong
Published: January 2022

Background

Most patients with mid and low rectal cancer passively react to bowel symptoms after sphincter-preserving surgery (SPS), and their self-management behaviors are scarce in the Chinese patient population.

Objective

The aim of this study was to evaluate the effect of a self-management program for bowel symptoms in patients with mid and low rectal cancer after SPS.

Methods

A convenient sampling method was used to recruit patients with mid and low rectal cancer after SPS in gastric wards from 2 tertiary hospitals in Beijing, China. Ninety-five patients (intervention, n = 47; control, n = 48) were recruited. The intervention group received a predetermined self-management program plus routine postoperative care; the control group received only routine care in the ward. Data on patients’ bowel symptoms, quality of life, and bowel symptom self-management behaviors were collected at baseline and at 3 and 6 months postoperatively using questionnaires. A generalized estimating equation was adopted to examine group effect and time effect.

Results

Bowel symptoms and quality of life in both the intervention and control groups of patients improved significantly 6 months after SPS compared with baseline (time effect, P < .001). The total score of patients’ bowel symptom self-management behaviors and the score of the therapeutic domain increased significantly in the intervention group compared with those in the control group (group effect, P = .009).

Conclusions

Self-management programs could help prompt patients’ self-management behaviors, but the extent to which they impact patients’ bowel symptoms requires further investigation.

Implications for Practice

The bowel dysfunction self-management program could alter the behavior of patients. It also effectively improves self-management strategies for bowel symptoms.
A 10-Year Retrospective before-and-after Study of Lipedema Surgery: Patient-Reported Lipedema-Associated Symptom Improvement after Multistage Liposuction
Authors: Kruppa Philipp , Georgiou Iakovos , Schmidt Jeremias , Infanger Manfred , Ghods Mojtaba
Published: January 2022

Background:

Despite an increasing demand for surgical treatment of lipedema, the evidence for liposuction is still limited. Little is known about the influence of disease stage, patient age, body mass index, or existing comorbidities on clinical outcomes. It was hypothesized that younger patients with lower body mass index and stage would report better results.

Methods:

This retrospective, single-center, noncomparative study included lipedema patients who underwent liposuction between July of 2009 and July of 2019. After a minimum of 6 months since the last surgery, all patients completed a disease-related questionnaire. The primary endpoint was the need for complex decongestive therapy based on a composite score. Secondary endpoints were the severity of disease-related complaints measured on a visual analogue scale.

Results:

One hundred six patients underwent a total of 298 large-volume liposuctions (mean lipoaspirate, 6355 ± 2797 ml). After a median follow-up of 20 months, a median complex decongestive therapy score reduction of 37.5 percent (interquartile range, 0 to 88.8 percent; p < 0.0001) was observed. An improvement in lipedema-associated symptoms was also observed (p < 0.0001). The percentage reduction in complex decongestive therapy scores was greater in patients with a body mass index less than or equal to 35 kg/m2 (p < 0.0001) and in stage I and II patients (p = 0.0019).

Conclusion:

Liposuction reduces the severity of symptoms and the need for conservative treatment in lipedema patients, especially if it is performed in patients with a body mass index below 35 kg/m2 at an early stage of the disease.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
A Symbolic Regression Approach to Hepatocellular Carcinoma Diagnosis Using Hypermethylated CpG Islands in Circulating Cell-Free DNA
Authors: Goyal Rushank
Published: January 2022

Purpose

Hepatocellular carcinoma is the most common primary liver cancer, accounting for 90% of cases, and a major cause of death worldwide. Despite this, alpha-fetoprotein tests are the only blood-based diagnostic tools available, and their use is limited by their low sensitivity. DNA methylation changes, which have been implicated in a majority of cancers, offer an alternative method of diagnosis through measuring such changes in circulating cell-free DNA present in blood plasma.

Method

A genetic programming-based symbolic regression approach was applied to gain the benefits of machine learning while avoiding the opacity drawbacks of “black box” models. The data included plasma samples from 36 patients with hepatocellular carcinoma as well as a control group of 55 that contained patients with and without cirrhosis. A 75-25 train-test splitting was done before training.

Results

The symbolic regression methodology developed an equation utilizing the methylation levels of three biomarkers, with an accuracy of 91.3%, a sensitivity of 100%, and a specificity of 87.5% on the test data. The performance matches prior research while providing the added benefits of transparency.

Conclusion

Circulating cell-free DNA presents opportunities for minimally invasive early diagnosis of hepatocellular carcinoma, and utilizing transparent machine learning approaches like symbolic regression can allow accurate diagnosis by combining biological and mathematical principles. Future validation of the model obtained here on a larger and more diverse dataset can reveal the potential for such approaches in cancer diagnosis and pave the way for further research.
Immunogenicity of COVID-19 mRNA Vaccines in Patients with Acute Myeloid Leukemia and Myelodysplastic Syndrome
Authors: Helfgott David C. , Racine-Brzostek Sabrina , Short Kelsey J. , Zhao Zhen , Christos Paul , Nino Itzel , Niu Tina , Contreras Jorge , Ritchie Ellen K. , Desai Pinkal , Samuel Michael , Roboz Gail J.
Published: January 2022

Immunocompromised patients are particularly susceptible to serious complications from infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Two mRNA vaccines, BNT162b2 and mRNA-1273, have been shown to have excellent clinical efficacy in immunocompetent adults, but diminished activity in immunocompromised patients. In this study, we measured anti-spike SARS-CoV-2 antibody response, avidity, and surrogate neutralizing antibody activity in Coronavirus Disease 2019 (COVID-19) vaccinated patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Anti-spike SARS-CoV-2 antibody was present in 89% of AML and 88% of MDS patients, but median antibody levels for were lower than in healthy controls (p=0.001 and p=0.04, respectively). SARS-CoV-2 antibody avidity and neutralizing antibody activity from AML patients were significantly lower than controls (p=0.028 and p=0.002, respectively). There was a trend toward higher anti-spike SARS-CoV-2 antibody levels after mRNA-1273 vaccination. Antibody avidity was greater in patients after mRNA-1273 versus BNT162b2 (p=0.01) and there was a trend toward greater neutralizing antibody activity after mRNA-1273 versus BNT162b2 vaccination.
The P132H mutation in the main protease of Omicron SARS-CoV-2 decreases thermal stability without compromising catalysis or small-molecule drug inhibition
Authors: Sacco Michael D , Hu Yanmei , Gongora Maura V , Meilleur Flora , Kemp M Trent , Zhang Xiujun , Wang Jun , Chen Yu
Published: January 2022

The ongoing SARS-CoV-2 pandemic continues to be a significant threat to global health. First reported in November 2021, the Omicron variant (B.1.1.529) is more transmissible and can evade immunity better than previous SARS-CoV-2 variants, fueling an unprecedented surge in cases. To produce functional proteins from this polyprotein, SARS-CoV-2 relies on the cysteine proteases Nsp3/papain-like protease (PLpro) and Nsp5/Main Protease (Mpro)/3C-like protease to cleave at three and more than 11 sites, respectively.1 Therefore, Mpro and PLpro inhibitors are considered to be some of the most promising SARS-CoV-2 antivirals. On December 22, 2021, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for PAXLOVID, a ritonavir-boosted formulation of nirmatrelvir. Nirmatrelvir is a first-in-class orally bioavailable SARS-CoV-2 Mpro inhibitor.2 Thus, the scientific community must vigilantly monitor potential mechanisms of drug resistance, especially because SARS-CoV-2 is naïve to Mpro inhibitors. Mutations have been well identified in variants to this point.3 Notably, Omicron Mpro (OMpro) harbors a single mutation– P132H. In this study we characterize the enzymatic activity, drug inhibition, and structure of OMpro while evaluating the past and future implications of Mpro mutations.
B-cell epitope mapping of TprC and TprD variants ofTreponema pallidumsubspecies
Authors: Molini Barbara , Fernandez Mark C. , Godornes Charmie , Vorobieva Anastassia , Lukehart Sheila A. , Giacani Lorenzo
Published: January 2022

Several recent studies have focused on the identification, functional analysis, and structural characterization of outer membrane proteins (OMPs) ofTreponema pallidum(Tp). TheTpspecies encompasses the highly relatedpallidum,pertenue,andendemicumsubspecies of this pathogen, known to be the causative agents of syphilis, yaws, and bejel, respectively. These studies highlighted the importance of identifying surface-exposed OMP regions and the identification of B-cell epitopes that could be protective and used in vaccine development efforts. We previously reported that the TprC and TprD OMPs ofTpare predicted to contain external loops scattered throughout the entire length of the proteins, several of which show a low degree of sequence variability among strains and subspecies. In this study, these models were corroborated using AlphaFold2, a state-of-the-art protein structure modeling software. Here, we identified B-cell epitopes across the full-length TprC and TprD variants using the Geysan pepscan mapping approach with antisera from rabbits infected with syphilis, yaws, and bejel strains and from animals immunized with refolded recombinant TprC proteins from three syphilis strains. Our results show that the humoral response is primarily directed to sequences predicted to be on surface-exposed loops of TprC and TprD proteins, and that the magnitude of the humoral response to individual epitopes differs among animals infected with various syphilis strains andTpsubspecies. Rather than exhibiting strain-specificity, antisera showed various degrees of cross-reactivity with variant sequences from other strains. The data support the further exploration of TprC and TprD as vaccine candidates.
Immune checkpoint blockade induces gut microbiota translocation that augments extraintestinal anti-tumor immunity
Authors: Choi Yongbin , Gao Yajing , Coughlin Laura A. , Poulides Nicole , Kim Jiwoong , Zhan Xiaowei , Hooper Lora V. , Pasare Chandrashekhar , Koh Andrew Y.
Published: January 2022

Gut microbiota are critical for effective immune checkpoint blockade therapy (ICT) for cancer. The mechanisms by which gut microbiota augment extraintestinal anti-cancer immune responses, however, are largely unknown. Here, we find that ICT induces translocation of specific endogenous gut microbiota into secondary lymphoid organs and subcutaneous melanoma tumors. Mechanistically, gut microbiota activated dendritic cells (DCs) traffic a selective subset of gut bacteria to mesenteric lymph nodes (MLN) and promote optimal anti-tumor T-cell responses in both the tumor draining lymph nodes (TDLN) and the primary tumor. Antibiotic treatment resulted in decreased gut microbiota translocation into MLN and TDLN, diminished polyfunctional effector CD8+ T cell responses, and attenuated response to ICT. Our findings illuminate a key mechanism by which gut microbiota promote extraintestinal anti-cancer immunity.

One sentence summary

Following immune checkpoint blockade therapy, dendritic cells traffic gut microbiota into secondary lymphoid organs, promoting optimal extraintestinal anti-cancer immunity.
Accurate strain-level microbiome composition analysis from short reads
Authors: Liao Herui , Ji Yongxin , Sun Yanni
Published: January 2022

Because bacterial strains can exhibit different biological properties, strain-level composition analysis plays a vital role in understanding the functions and dynamics of microbial communities. Metagenomic sequencing has become the major means for probing the microbial composition in host-associated or environmental samples. Despite a plethora of composition analysis tools, they are not optimized to address the challenges in strain-level analysis: a reference database with highly similar reference strain genomes and the presence of multiple strains under one species in a sample. In this work, we present a new strain-level composition analysis tool named StrainScan that employs a novel tree-based k-mer indexing structure to strike a balance between the strain identification accuracy and the computational complexity. We rigorously tested StrainScan on many simulated and real sequencing data and benchmarked StrainScan with popular strain-level analysis tools including Krakenuniq, StrainSeeker, Pathoscope2, Sigma, StrainGE, and Strainest. The results show that StrainScan has higher accuracy and resolution than the the state-of-the-art tools on strain-level composition analysis. It improves the F1-score by 20% in identifying multiple strains with at least 99.89% average nucleotide identity. StrainScan takes short reads and a set of reference strains as input and its source codes are freely available at https://github.com/liaoherui/strainScan.
CyclinD2-mediated regulation of neurogenic output from the retinal ciliary margin is perturbed in albinism
Authors: Slavi Nefeli , Balasubramanian Revathi , Lee Melissa A. , Liapin Michael , Oaks-Leaf Rachel , Peregrin John , Potenski Anna , Troy Carol , Ross M. Elizabeth , Herrera Eloisa , Kosmidis Stylianos , John Simon W. M. , Mason Carol A.
Published: January 2022

In albinism, aberrations in the ipsi-/contralateral retinal ganglion cell (RGC) ratio compromise the functional integrity of the binocular circuit. We focus here on the mouse ciliary margin zone (CMZ), a neurogenic niche at the embryonic peripheral retina, to investigate developmental processes regulating RGC neurogenesis and identity acquisition. We found that the mouse ventral CMZ has the competence to generate predominantly ipsilaterally-projecting RGCs, but this competence is altered in the albino visual system due to CyclinD2 downregulation and disturbed temporal control of the cell cycle. Consequently, albino as well as CyclinD2-deficient pigmented mice exhibit a diminished ipsilateral retinogeniculate projection and compromised depth perception. Pharmacological stimulation of calcium channels in albino mice, known to upregulate CyclinD2 in other cell types, augmented CyclinD2-dependent neurogenesis of ipsilateral RGCs, and improved stereopsis. Together, these results implicate CMZ neurogenesis and its regulators as critical for the formation and function of the mammalian binocular circuit.

Highlights

The mouse ventral CMZ produces predominantly ipsilateral RGCs.

In the albino visual system, CyclinD2 downregulation leads to delayed G1/S transition toward mitotic exit of CMZ progenitors.

Perturbations in the temporal control of cell cycle by CyclinD2 lead to reduced Zic2+ RGCs and consequently, a diminished ipsilateral retinogeniculate projection and compromised depth perception.

Calcium channel modulation during embryogenesis normalizes the levels of CyclinD2 and restores binocular vision in albino mice.
cir-DNA sequencing revealed the landscape of extrachromosomal circular DNA in articular cartilage and the potential roles in osteoarthritis
Authors: Xiang Wei , Zhang Tongyi , Li Song , Gong Yunquan , Luo Xiaoqing , Yuan Jing , Wu Yaran , Yan Xiaojing , Xiong Yan , Lian Jiqin , Zhao Guangyu , Gao Changyue , Kuang Liang , Ni Zhenhong
Published: January 2022

Objective

Extrachromosomal circular DNA (eccDNA) has been shown to be involved in several physiological and pathological processes including immunity, inflammation, aging and tumor. However, the expression of eccDNA in cartilage has been not reported until now. In this study, we aimed to investigate the landscape of eccDNA in articular cartilage and analyze the potential roles in Osteoarthritis (OA).

Methods

The samples of articular cartilage were obtained from total knee arthroplasty (TKA) donors with OA. The mtDNAs (mitochondrial DNA) and the linear DNAs from chondrocytes of articular cartilage were removed. Then the eccDNAs were enriched for cir-DNA sequencing. After quality control evaluation, we systematically revealed the identified eccDNA data including size distribution, the size range and sequence pattern. Moreover, we explored and disscussed the potential roles of eccDNA in OA via motif analysis and GO/KEGG pathways analysis.

Results

The chondrocytes from OA cartilage contained an abundance of eccDNAs, which was termed as OC-eccDNAs (OA Cartilage-derived eccDNA). The characteristics of OC-eccDNAs were tissue specific, including the distribution, the size range and sequence pattern. Moreover, the functional analysis indicated that eccDNA may be involved in the homeostasis maintenance of chondrocytes and participated in the process of OA.

Conclutions

Our data firstly showed the landscape of eccDNA in articular cartilage, and preliminarily indicated the potential roles of eccDNA in OA.
FRIENDLY (FMT) is an RNA binding protein associated with cytosolic ribosomes at the mitochondrial surface
Authors: Hemono Mickaele , Salinas-Giegé Thalia , Roignant Jeanne , Vingadassalon Audrey , Hammann Philippe , Ubrig Elodie , Ngondo Patryk , Duchêne Anne-Marie
Published: January 2022

The spatial organization of protein synthesis in the eukaryotic cell is essential for maintaining the integrity of the proteome and the functioning of the cell. Translation on free polysomes or on ribosomes associated with the endoplasmic reticulum has been studied for a long time. More recent data have revealed selective translation of mRNAs in other compartments, in particular at the surface of mitochondria. Although these processes have been described in many organisms, in particular in plants, the mRNA targeting and localized translation mechanisms remain poorly understood.

Here, the Arabidopsis thaliana Friendly (FMT) protein is shown to be a cytosolic RNA binding protein that associates with cytosolic ribosomes at the surface of mitochondria. Its knockdown delays seedling development and causes mitochondrial clustering. The mutation also disrupts the mitochondrial proteome and the localization of nuclear transcripts on the surface of mitochondria. These data indicate that FMT participates in the localization of mRNAs and their translation at the surface of mitochondria.
Decidual innate immune cell kinetics following lipopolysaccharide challenge
Authors: St-Germain Lauren E. , Castellana Barbara , Baltayeva Jennet , Beristain Alexander G.
Published: January 2022

In early pregnancy, macrophages (Mφ) and natural killer cells (NK) infiltrate and expand within the decidua to comprise 30% of all cellular content. These immune cell populations coordinate angiogenic and tissue remodeling processes that are needed for a healthy pregnancy. Importantly, decidual tissue-resident macrophages (trMφ) and uterine NK retain immunosurveillance properties that facilitate the targeting of infections (e.g., viral, bacterial). The timing and severity of these infections, as well as the resulting immune response, can dictate pregnancy outcome. However, little is known about the kinetics and activities of uterine myeloid and NK populations following infections. To address this knowledge gap, we defined the stepwise changes of uterine myeloid and NK subpopulations following lipopolysaccharide (LPS) challenge in a mouse model of early pregnancy. Low (25 µg/kg), moderate (50 µg/kg), and high (200 µg/kg) doses of LPS resulted in dose-dependent increases in peripheral and uterine inflammation, as well as a dose-dependent increase in the rate of fetal resorption. Compared with saline controls, mice exposed to LPS showed higher frequencies of immature monocytes, decreased TNFα-producing monocytes and Mφ, and increased conventional (c)NK expression of granzyme B in the uterus. These changes were followed by alterations in overall uterine (u)NK frequencies with increased cNK and decreased tissue resident (tr)NK. Together, this work describes how discrete levels of LPS-induced inflammation shape the innate immune cell landscape of the decidua. These findings establish insight into the stepwise immunological changes following endotoxin challenge and provide a better understanding of how inflammation controls the activity of key decidual leukocytes.

Summary sentence

Graded LPS challenge in early pregnancy leads to a stepwise increase in fetal resorption and associates with distinct alterations in frequencies and activities of uterine immune cells.
Tissue-specific and repeat length-dependent somatic instability of the X-linked dystonia parkinsonism-associated CCCTCT repeat
Authors: Campion Lindsey N. , Maza Alan Mejia , Yadav Rachita , Penney Ellen B. , Murcar Micaela G. , Correia Kevin , Gillis Tammy , Fernandez-Cerado Cara , Velasco-Andrada M. Salvie , Legarda G. Paul , Ganza-Bautista Niecy G. , Lagarde J. Benedict B. , Acuña Patrick J. , Multhaupt-Buell Trisha , Aldykiewicz Gabrielle , Supnet Melanie L. , De Guzman Jan K. , Go Criscely , Sharma Nutan , Munoz Edwin L. , Ang Mark C. , Diesta Cid Czarina E. , Bragg D. Cristopher , Ozelius Laurie J. , Wheeler Vanessa C.
Published: January 2022

X-linked dystonia-parkinsonism (XDP) is a progressive adult-onset neurodegenerative disorder caused by insertion of a SINE-VNTR-Alu (SVA) retrotransposon in the TAF1 gene. The SVA retrotransposon contains a CCCTCT hexameric repeat tract of variable length, whose length is inversely correlated with age at onset. This places XDP in a broader class of repeat expansion diseases, characterized by the instability of their causative repeat mutations. Here, we observe similar inverse correlations between CCCTCT repeat length with age at onset and age at death and no obvious correlation with disease duration. To gain insight into repeat instability in XDP we performed comprehensive quantitative analyses of somatic instability of the XDP CCCTCT repeat in blood and in seventeen brain regions from affected males. Our findings reveal repeat length-dependent and expansion-based instability of the XDP CCCTCT repeat, with greater levels of expansion in brain than in blood. The brain exhibits regional-specific patterns of instability that are broadly similar across individuals, with cerebellum exhibiting low instability and cortical regions exhibiting relatively high instability. The spectrum of somatic instability in the brain includes a high proportion of moderate repeat length changes of up to 5 repeats, as well as expansions of ∼20->100 repeats and contractions of ∼20-40 repeats at lower frequencies. Comparison with HTT CAG repeat instability in postmortem Huntington’s disease brains reveals similar brain region-specific profiles, indicating common trans-acting factors that contribute to the instability of both repeats. Analyses in XDP brains of expansion of a different SVA-associated CCCTCT located in the LIPG gene, and not known to be disease-associated, reveals repeat length-dependent expansion at overall lower levels relative to the XDP CCCTCT repeat, suggesting that expansion propensity may be modified by local chromatin structure. Together, the data support a role for repeat length-dependent somatic expansion in the process(es) driving the onset of XDP and prompt further investigation into repeat dynamics and the relationship to disease.
Self-assembled DNA nanostructures promote cell migration & differentiation of human umbilical vein endothelial cells
Authors: Gada Anjali Rajwar , Vaswani Payal , Bhatia Dhiraj
Published: January 2022

DNA nanostructures have been explored for capabilities to influence cellular behavior and its functions. Recent times have seen the development of new emergent functionalities of DNA nanodevices as class of biomaterials with immense capacity to interface with biological systems and having vast potential in disease diagnosis and therapeutics. Being chemically robust and biocompatible in nature, DNA nanostructures have been surface modified and structurally fine-tuned to find emerging applications in the field of stem cell therapy and tissue regeneration. DNA nanostructures can be utilized for therapeutic angiogenesis that involves induction of blood vessel formation and can be used to treat ischemic diseases like stroke or heart failure. This work addresses the effect of DNA nanostructures’ structural topology in their capacity to stimulate endothelial cells angiogenesis. We tested a panel of four geometries of DNA nanostructure and checked their potential on the differentiation of human umbilical vein endothelial cells (HUVECs). While different DNA nanostructure geometries showed successful angiogenesis induction and cell migration in HUVECs, tetrahedral DNA cages showed the maximum uptake and angiogenesis potential indicating that not only the composition of materials, but also the 3D arrangement of ligands might also play role in stimulating the angiogenesis process.
Inherited and de novo variants extend the etiology of TAOK1-associated neurodevelopmental disorder
Authors: Hunter Jesse M , Massingham Lauren J , Manickam Kandamurugu , Bartholomew Dennis , Williamson Rachel K , Schwab Jennifer L , Marhabaie Mohammad , Siemon Amy , de los Reyes Emily , Reshmi Shalini C , Cottrell Catherine E , Wilson Richard K , Koboldt Daniel C
Published: January 2022

Alterations in the TAOK1 gene have recently emerged as the cause of developmental delay with or without intellectual impairment or behavioral abnormalities (MIM #619575). The thirty-two cases currently described in the literature have predominantly de novo alterations in TAOK1 and a wide spectrum of neurodevelopmental abnormalities. Here, we report four patients with novel pathogenic TAOK1 variants identified by research genome sequencing, clinical exome sequencing, and international matchmaking. The overlapping clinical features of our patients are consistent with the emerging core phenotype of TAOK1-associated syndrome: facial dysmorphism, feeding difficulties, global developmental delay, joint laxity, and hypotonia. However, behavioral abnormalities and gastrointestinal issues are more common in our cohort than previously reported. Two patients have de novo TAOK1 variants (one missense, one splice site) consistent with most known alterations in this gene. However, we also report the first sibling pair who both inherited a TAOK1 frameshift variant from a mildly affected mother. Our findings suggest that incomplete penetrance and variable expressivity are relatively common in TAOK1-associated syndrome, which holds important implications for clinical genetic testing.
The willingness to offer livestock insurance in rural China: a discrete choice experiment among Chinese insurance agents
Authors: Yang Youwei , Long Wenjun , Turvey Calum G.
Published: January 2022

Purpose

This paper investigates Chinese agricultural insurance agents willingness to offer (WTO) livestock insurance based on the variations of eight main attributes of livestock insurance.

Design/methodology/approach

This study implements discrete choice experiments (DCE) with actual insurance agents who design, sell and operate livestock insurance in China. The choice experiment of this study is based on the D-optimal approach, a six-block design, with 15 cards per block and two choices per card. The sample size was 211. Econometrics results are based on conditional and mixed logit models.

Findings

The authors find that the subsidy effect is enormous; a one level increase of subsidy leads to 3.166 times higher probability to offer. This subsidy effect is important as it confirms the endogenous structure between price and quantity in insurance offering, where subsidy does not only incentivize demand but also the supply. Another main factor of insurance investigated is the impact of different coverage types on agents' WTO. The authors find that agents prefer mortality insurance the most, followed by revenue insurance and profit insurance, while Index-Based Livestock Insurance (IBLI) is the least preferred to offer. Agents' knowledge about these newer types of insurance supports their WTO as well; thus, proper education is necessary to promote the more advanced types of livestock insurance.

Research limitations/implications

A limitation is that in the presence of COVID 19, and administrative issues at the local level, the sample was not randomly drawn. Nonetheless, the authors believe that there is enough diversity across participants, insurers and provinces and have done sufficient robustness checks to support results and conclusions.

Practical implications

This study provides further validation for the DCE research method that could potentially be applied to different analyses: using choice experiments to study insurers and reveal their preferences, through combinations of various levels of core attributes for insurance products. The findings and contribution are critical to the reform and improvement of livestock insurance in China and for insurance markets more broadly. The authors find that insurers do not place equal weights or values on insurance product attributes and do not view types of insurance equally. In other words, while farmers may hold different preferences about the type of insurance they demand, the results suggest that insurers also hold preferences in the type of insurance they sell.

Originality/value

So far as the authors are aware, this is the first DCE designed around the supply of insurance products with the subjects being insurance agents, marketers and executives.
Skilling the Indian youth: a State-level analysis
Authors: Ghosh Piyali , Goel Geetika , Bhongade Ankita
Published: January 2022

Purpose

Market-driven skill development initiatives are essential in India as a large segment of its educated workforce is unemployed or unemployable, with little or no job skills. The “Skill India Mission” aims at endowing the youth with skills that can increase their employability and productivity in jobs. The success of the Mission depends on State-level initiatives in tandem with the Mission. This paper analyzes the impact of job offers extended to the youth of Jharkhand State as an outcome of State-level skill development initiatives. Its broad objective is to assist the Government in the delivery of skill-based training programs.

Design/methodology/approach

Data were collected through a structured questionnaire administered across various districts of Jharkhand to capture the perceptions of trainees and training centers. The final sample of 498 had attended training in apparel, retail, security, automotive, food and beverage service, IT/ITES, electronics and construction.

Findings

Statistical analysis reveals a significant increase in the economic status of trainees after joining jobs. Other findings include apathy toward migration, a mismatch between skills gained and jobs, and a dearth of qualified trainers.

Practical implications

The authors recommend counseling and attitudinal restructuring of the youth, designing multi-skill training programs and promoting entrepreneurial spirit. The authors also propose a stakeholder-based approach for curriculum development to fill the demand–supply gap of training and ensure better trainee retention. The Government could benefit by focusing the skilling programs on the career adaptability of trainees. Skill development and vocational education and training may not operate in silos. Training programs could be planned to be conducted jointly through ITIs and State-level training institutions under the Skill India Mission.

Originality/value

This research could increase the effectiveness of skill development initiatives across India, thereby improving the socioeconomic status of the youth thus trained. The authors emphasize developing a people-centric perspective in skilling, shifting attention from the existing industry-driven approach, to strike a balance between the demand and supply sides. This perspective can optimize skill development initiatives by reducing the gap between employment demand and skill development.
Survival of the fittest: the multiple paths of entrepreneurial leadership driving adaptive innovation in uncertain environment
Authors: Lin Qin , Yi Lingfeng
Published: January 2022

Purpose

This study aims to investigate the multiple influence paths or underlying mechanisms of entrepreneurial leadership (EL) on adaptive innovation from the perspectives of organizational learning and resource management, drawing on complex adaptive system theory.

Design/methodology/approach

With a questionnaire survey of 317 senior and middle managers from different firms in China, structural equation modeling was used to test the hypothesized conceptual model, and bootstrapping method was employed to examine the multiple mediating effects.

Findings

Results indicate that EL has a significant and positive effect on adaptive innovation. This relationship is partially mediated through exploitative learning, exploratory learning, resource bricolage and boundary-spanning integration, respectively. The impact of EL on adaptive innovation is also sequentially transmitted through exploitative learning and resource bricolage or exploratory learning and boundary-spanning integration.

Originality/value

Adaptive innovation has become a firm competition strategy to cope with dynamic changes in current uncertain environment where EL can play its effectiveness to engage firms in such innovation activities. However, the question of why and how EL drives adaptive innovation has yet to be discussed. This study highlights the innovation effectiveness of EL and the triggering process of adaptive innovation, and contributes to several countermeasures for firms to implement leadership and innovation practices responding to uncertain environment.
Corporate environmental responsibility and innovation: empirical evidence from Vietnam
Authors: Nguyen Van Ha , Vu Nam Hoang
Published: January 2022

Purpose

This study aims to examine the relationship between corporate environmental responsibility (CER) practices and different types of innovation carried out by small- and medium-sized enterprises (SMEs) in Vietnam.

Design/methodology/approach

The authors employ the bivariate probit model and the two-stage least squares regression model to estimate the effects of CER on process innovation and product innovation of SMEs.

Findings

The findings show that while CER is not significantly related to product innovation, it has a positive and significant effect on process innovation. Further analysis indicates that CER engagement increases labor productivity and financial performance of SMEs.

Practical implications

Corporate managers should view implementation of environmental responsibility practices as a strategy to foster process innovation and boost labor productivity and financial performance. For policy makers, government support for firms proactively engaging in CER practices could encourage firms to pursue innovative activities, which are vital to their long-term success as well as to the society's prosperity.

Originality/value

This study makes several important contributions. First, the authors provide new empirical evidence regarding the different effects of engaging in environmentally friendly practices on firm innovation in an under-examined emerging market setting. Second, the authors enrich our understanding of potential benefits of CER implementation. Third, the findings suggest that firm innovation may play a mediating role in the CER–firm performance association.